Journal of Cosmetic Dermatology, EarlyView.
Παρασκευή 31 Αυγούστου 2018
Novel ethosomal gel of clove oil for the treatment of cutaneous candidiasis
Sweet's syndrome associated with Talaromyces marneffei and Mycobacterium abscessus infection due to anti-interferon-gamma autoantibodies
Hongyan Xu, Donghua Liu, Xiaoyue He, Dongyan Zheng, Yan Deng
Indian Journal of Dermatology 2018 63(5):428-430
Indian Journal of Dermatology 2018 63(5):428-430
Three sequential lymphomatous tumors in a patient
Ellie Choi, Sam Yang, Kong Bing Tan, Derrick Aw, Nisha Suyien Chandran
Indian Journal of Dermatology 2018 63(5):443-444
Indian Journal of Dermatology 2018 63(5):443-444
Estimation of zinc and iron levels in the serum and hair of women with androgenetic alopecia: Case–control study
Samer A Dhaher, Abdulla A Yacoub, Ausama Ayob Jacob
Indian Journal of Dermatology 2018 63(5):369-374
Background: Although female androgenetic alopecia (FAGA) occurs in genetically susceptible women, some trace elements may play an important role. Aim of the Study: This study aimed to evaluate serum and hair zinc and iron levels in patients with FAGA and to compare the findings with normal controls. Patients and Methods: A case–control study that was conducted at Dermatology Clinic in Basra General Hospital, Basra, Iraq. The participants were divided into two groups: The first group consisted of 27 women with FAGA and the second was age-matched 28 healthy women control group. The serum and hair zinc and iron assays were done for all participants. Results: Both hair and serum zinc levels in FAGA group were significantly lower than that in the control (103.4±25.5 ppm vs. 143.5±33.1 ppm for hair and 65.6±14.2 μg/dl vs. 128.4±41.4 μg/dl for serum). Hair iron level in FAGA was significantly lower than in control (17.9±3.8 ppm vs. 26.9±7.4 ppm, P>0.05). Serum iron level in FAGA group was lower than in the control, but it was not significant statistically (88.9±22.3 μg/dl vs. 100.9±18.9 μg/dl). Except for the hair iron, there was no significant correlation between zinc and iron concentrations in hair and serum with severity of alopecia. Conclusions: Zinc and iron levels in serum and hair were lower in FAGA compared to that of normal individuals indicating that trace elements might play an important role in the etiopathogenesis of FAGA.
Indian Journal of Dermatology 2018 63(5):369-374
Background: Although female androgenetic alopecia (FAGA) occurs in genetically susceptible women, some trace elements may play an important role. Aim of the Study: This study aimed to evaluate serum and hair zinc and iron levels in patients with FAGA and to compare the findings with normal controls. Patients and Methods: A case–control study that was conducted at Dermatology Clinic in Basra General Hospital, Basra, Iraq. The participants were divided into two groups: The first group consisted of 27 women with FAGA and the second was age-matched 28 healthy women control group. The serum and hair zinc and iron assays were done for all participants. Results: Both hair and serum zinc levels in FAGA group were significantly lower than that in the control (103.4±25.5 ppm vs. 143.5±33.1 ppm for hair and 65.6±14.2 μg/dl vs. 128.4±41.4 μg/dl for serum). Hair iron level in FAGA was significantly lower than in control (17.9±3.8 ppm vs. 26.9±7.4 ppm, P>0.05). Serum iron level in FAGA group was lower than in the control, but it was not significant statistically (88.9±22.3 μg/dl vs. 100.9±18.9 μg/dl). Except for the hair iron, there was no significant correlation between zinc and iron concentrations in hair and serum with severity of alopecia. Conclusions: Zinc and iron levels in serum and hair were lower in FAGA compared to that of normal individuals indicating that trace elements might play an important role in the etiopathogenesis of FAGA.
Use of an anal retractor device for excision in patients with perianal extramammary paget's disease
Yuichi Yoshida, Hiroyuki Goto, Reiko Tsutsumi, Osamu Yamamoto
Indian Journal of Dermatology 2018 63(5):435-437
Indian Journal of Dermatology 2018 63(5):435-437
Topical steroid damaged/dependent face (TSDF): A study from a tertiary care hospital in Eastern India
Dayamay Pal, Projna Biswas, Sudip Das, Abhishek De, Nidhi Sharma, Asad Ansari
Indian Journal of Dermatology 2018 63(5):375-379
Background: Awareness against abuse of topical corticosteroids (TC), especially over the face, has been going on for last 5 years in India. In spite of that we are getting lots of cases in our hospitals. Aims: The aims of this study were to ascertain the demographics, magnitude and clinical features of TC misuse on the face among the dermatology outpatient department (OPD) attendees and to analyze its causes. Methods: This study was conducted in a tertiary care medical center of eastern India. Patients with relevant facial dermatoses were asked about their current use of topical formulations and confirmed to be TSDF were included in the study. Results: A total of 748 patients with facial dermatoses were screened, of which 271 (36.22%) were using TC. Of them mostly young adults between 20 and 29 years (37.10%) were using TC. Average duration between starting of use of medication and the onset of symptoms was 5 months. Ninety-eight (36.16%) patients were using topical corticosteroid for the treatment of acne and 74 (27.30%) were using as depigmenting cream. About 108 (39.85%) patients bought medicine over the counter being recommended by pharmacist/shop owner. Rosacea like features with photosensitivity was the most common adverse effect found in 79 (29.15%) patients whereas comedonal acne/acne exacerbation were found in 68 (25.09%) patients. Most of them (227, 83.76%) were unaware about the side effects of steroids. Conclusions: TC misuse in patients with facial dermatoses is still quite common even after efforts to grow the awareness among population.
Indian Journal of Dermatology 2018 63(5):375-379
Background: Awareness against abuse of topical corticosteroids (TC), especially over the face, has been going on for last 5 years in India. In spite of that we are getting lots of cases in our hospitals. Aims: The aims of this study were to ascertain the demographics, magnitude and clinical features of TC misuse on the face among the dermatology outpatient department (OPD) attendees and to analyze its causes. Methods: This study was conducted in a tertiary care medical center of eastern India. Patients with relevant facial dermatoses were asked about their current use of topical formulations and confirmed to be TSDF were included in the study. Results: A total of 748 patients with facial dermatoses were screened, of which 271 (36.22%) were using TC. Of them mostly young adults between 20 and 29 years (37.10%) were using TC. Average duration between starting of use of medication and the onset of symptoms was 5 months. Ninety-eight (36.16%) patients were using topical corticosteroid for the treatment of acne and 74 (27.30%) were using as depigmenting cream. About 108 (39.85%) patients bought medicine over the counter being recommended by pharmacist/shop owner. Rosacea like features with photosensitivity was the most common adverse effect found in 79 (29.15%) patients whereas comedonal acne/acne exacerbation were found in 68 (25.09%) patients. Most of them (227, 83.76%) were unaware about the side effects of steroids. Conclusions: TC misuse in patients with facial dermatoses is still quite common even after efforts to grow the awareness among population.
Metastatic dermatosis in breast carcinoma on adjuvant trastuzumab: Is skin a sanctuary site in human epidermal growth factor receptor-2-amplified disease?
Amit Sehrawat, Sumedha A Kotwal, KM Parthasarathy
Indian Journal of Dermatology 2018 63(5):424-426
Cutaneous metastasis (CM) from internal malignancies is commonly seen. Sometimes, skin metastases can be the first sign of advanced cancer or an indicator of cancer recurrence. Cases of breast cancer with cutaneous progression after or during trastuzumab therapy have been described in the past, frequently associated with systemic disease progression. However, CM during adjuvant trastuzumab therapy is very rare. It has been hypothesized that cancer cells located in the skin survive and take proliferative advantage by virtue of an immune-tolerance mechanism that hampers trastuzumab-mediated antibody-dependent cell-mediated cytotoxicity. We describe a case of human epidermal growth factor receptor-2-overexpressing breast cancer presenting with diffuse CM during adjuvant trastuzumab therapy.
Indian Journal of Dermatology 2018 63(5):424-426
Cutaneous metastasis (CM) from internal malignancies is commonly seen. Sometimes, skin metastases can be the first sign of advanced cancer or an indicator of cancer recurrence. Cases of breast cancer with cutaneous progression after or during trastuzumab therapy have been described in the past, frequently associated with systemic disease progression. However, CM during adjuvant trastuzumab therapy is very rare. It has been hypothesized that cancer cells located in the skin survive and take proliferative advantage by virtue of an immune-tolerance mechanism that hampers trastuzumab-mediated antibody-dependent cell-mediated cytotoxicity. We describe a case of human epidermal growth factor receptor-2-overexpressing breast cancer presenting with diffuse CM during adjuvant trastuzumab therapy.
Comparison of efficacy of doxycycline and isotretinoin on cutaneous human beta-defensin-1 and -2 levels in acne vulgaris
Gulhan Aksoy, Esra Adisen, Ozlem Erdem, Ahmet Burhan Aksakal
Indian Journal of Dermatology 2018 63(5):380-385
Background: Recent studies have shown that human beta-defensin-1 (hBD-1) and (human beta-defensin-2 hBD-2), which are antimicrobial peptides produced by the skin, play a role in the pathogenesis of acne vulgaris (AV). Objective: The aim of this study was to determine the role of antimicrobial peptides in the pathogenesis of AV and enlighten the effects of doxycycline and isotretinoin in the expression of these defensins in AV. Materials and Methods: A total of 44 patients (22 patients in each group) with Grade 6 and 8 AV who were indicated doxycycline or isotretinoin for their treatment, and 20 healthy volunteers were included in this study. Pretreatment cutaneous samples were obtained from pustular lesions and uninvolved skin of AV patients and were repeated after the treatment. Only one biopsy was obtained from controls. Results: Cutaneous levels of hBD-1 and hBD-2 were significantly increased in AV patients when compared with healthy controls (P<0.05). Doxycycline therapy achieved a decrease in hBD-1 levels (P<0.05), whereas isotretinoin therapy achieved a reduction in hBD-2 levels when compared with pretreatment levels (P<0.05). Posttreatment hBD-1 and hBD-2 levels were not different between doxycycline and isotretinoin groups (P>0.05). Conclusion: In the light of these results, it was reasonable to assume the role of hBD-1 and hBD-2 in the pathogenesis of AV. Our results showing a significant reduction in hBD-1 staining with doxycycline treatment and in hBD-2 with isotretinoin suggested that some part of their anti-acne effect worked through these mechanisms.
Indian Journal of Dermatology 2018 63(5):380-385
Background: Recent studies have shown that human beta-defensin-1 (hBD-1) and (human beta-defensin-2 hBD-2), which are antimicrobial peptides produced by the skin, play a role in the pathogenesis of acne vulgaris (AV). Objective: The aim of this study was to determine the role of antimicrobial peptides in the pathogenesis of AV and enlighten the effects of doxycycline and isotretinoin in the expression of these defensins in AV. Materials and Methods: A total of 44 patients (22 patients in each group) with Grade 6 and 8 AV who were indicated doxycycline or isotretinoin for their treatment, and 20 healthy volunteers were included in this study. Pretreatment cutaneous samples were obtained from pustular lesions and uninvolved skin of AV patients and were repeated after the treatment. Only one biopsy was obtained from controls. Results: Cutaneous levels of hBD-1 and hBD-2 were significantly increased in AV patients when compared with healthy controls (P<0.05). Doxycycline therapy achieved a decrease in hBD-1 levels (P<0.05), whereas isotretinoin therapy achieved a reduction in hBD-2 levels when compared with pretreatment levels (P<0.05). Posttreatment hBD-1 and hBD-2 levels were not different between doxycycline and isotretinoin groups (P>0.05). Conclusion: In the light of these results, it was reasonable to assume the role of hBD-1 and hBD-2 in the pathogenesis of AV. Our results showing a significant reduction in hBD-1 staining with doxycycline treatment and in hBD-2 with isotretinoin suggested that some part of their anti-acne effect worked through these mechanisms.
Cyclosporine in generalized bullous-fixed drug eruption
Ranjana Beniwal, Lalit Kumar Gupta, Ashok Kumar Khare, Asit Mittal, Sharad Mehta, Manisha Balai
Indian Journal of Dermatology 2018 63(5):432-433
Indian Journal of Dermatology 2018 63(5):432-433
Pathogenic yeasts recovered from acne vulgaris: Molecular characterization and antifungal susceptibility pattern
Ayatollah Nasrollahi Omran, Alinaghi Ghiasi Mansori
Indian Journal of Dermatology 2018 63(5):386-390
Context: Acne vulgaris is a disorder showing persistent inflammation in the pilosebaceous follicles. It is one of the most prevalent dermatoses that millions of people suffer from globally. Aim: The aim of this study was to identify Candida species from patients with acne and to determine their drugs susceptibility. Subjects and Methods: A total of 70 cutaneous samples from acne vulgaris patients suspected to have Candida infections were collected. Macroscopic and microscopic morphology were recorded followed by polymerase chain reaction-sequencing of ITS regions, using universal primers. In vitro antifungal susceptibility was performed using Clinical and Laboratory Standards Institute method. Results: Overall, 11 Candida species including Candida parapsilosis 8 (72.73%), Candida krusei 1 (12.5%), Candida lusitaniae 1 (12.5%), Candida kefyr 1 (12.5%), and a Trichosporon asahi out of the collected clinical materials were isolated and identified. C. parapsilosis isolates susceptibility to diverse concentrations of the antifungal agents to isolate Cp1 study indicated that the isolated Cp8 and Cp5 with minimal inhibitory concentration (MIC) 50 = 32, 0.5, 0.25 and MIC 90 of <64, <1, <0.5 μg/ml fluconazole, itraconazole, and ketoconazole were resistant, respectively. Some of the isolates having relative strength, almost all other species of C. parapsilosis isolates were susceptible to these drugs. Conclusion: C. parapsilosis was the most prevalent Candida species in acne vulgaris samples which had higher in vitro susceptibility for antifungals.
Indian Journal of Dermatology 2018 63(5):386-390
Context: Acne vulgaris is a disorder showing persistent inflammation in the pilosebaceous follicles. It is one of the most prevalent dermatoses that millions of people suffer from globally. Aim: The aim of this study was to identify Candida species from patients with acne and to determine their drugs susceptibility. Subjects and Methods: A total of 70 cutaneous samples from acne vulgaris patients suspected to have Candida infections were collected. Macroscopic and microscopic morphology were recorded followed by polymerase chain reaction-sequencing of ITS regions, using universal primers. In vitro antifungal susceptibility was performed using Clinical and Laboratory Standards Institute method. Results: Overall, 11 Candida species including Candida parapsilosis 8 (72.73%), Candida krusei 1 (12.5%), Candida lusitaniae 1 (12.5%), Candida kefyr 1 (12.5%), and a Trichosporon asahi out of the collected clinical materials were isolated and identified. C. parapsilosis isolates susceptibility to diverse concentrations of the antifungal agents to isolate Cp1 study indicated that the isolated Cp8 and Cp5 with minimal inhibitory concentration (MIC) 50 = 32, 0.5, 0.25 and MIC 90 of <64, <1, <0.5 μg/ml fluconazole, itraconazole, and ketoconazole were resistant, respectively. Some of the isolates having relative strength, almost all other species of C. parapsilosis isolates were susceptible to these drugs. Conclusion: C. parapsilosis was the most prevalent Candida species in acne vulgaris samples which had higher in vitro susceptibility for antifungals.
Dermatofibrosarcoma protuberans secondary to a decorative tattoo: An Isotattootopic Response?
Irene Lastrucci, Susanna Gunnella, Alessandro Pileri, Vincenza Maio, Vieri Grandi
Indian Journal of Dermatology 2018 63(5):439-440
Indian Journal of Dermatology 2018 63(5):439-440
Sensitization to fungi in atopic dermatitis patients 14 year and older – Association with other atopic diseases and parameters
Jarmila Celakovska, Bukac Josef, Karel Ettler, Jaroslava Vaneckova, Kvetuse Ettlerova, Krejsek Jan
Indian Journal of Dermatology 2018 63(5):391-398
Background: Fungi as a source of allergen are still largely neglected in basic research as well as in clinical practice. This study aimed to highlight the impact of fungal allergens in a group of patients suffering from atopic dermatitis (AD). Aims and Objectives: The evaluation of the sensitization to fungi in AD patients aged 14 year and older and the evaluation of the relation of fungal sensitization to the occurrence of other atopic diseases and parameters. Materials and Methods: All patients satisfying inclusion criteria attending our hospital between 2008 and 2017 were included in the study. The complete dermatological and allergological examinations were performed in all included patients including examination of specific immunoglobulin E, skin prick test to mixture of fungi and inhalant allergens, evaluation of asthma bronchiale, rhinitis, onset of AD, family history about atopy, duration of eczematous lesions, severity of AD. Pairs of these categories were entered in the contingency tables and the Chi-square test for relationship of these variables was performed with the level of significance set below 5%. Results: Three hundred and thirty-one patients were included in the study; the average age was 26.8 years. The sensitization to fungi was recorded in 100 patients (30%). In these patients, the occurrence of asthma bronchiale, rhinitis, family history about atopy, sensitization to grass and trees was significantly higher than in patients without sensitization to fungi. We did not find any significant relation between the sensitization to fungi and the severity of AD, no relation was also found between the sensitization to fungi and sensitization to mites, animal dander, bird feather, and dust. Conclusion: The occurrence of asthma bronchiale, rhinitis, family history about atopy, sensitization to grass and trees was significantly higher in AD patients with sensitization to fungi. No relation was found between the severity of AD and the sensitization to fungi.
Indian Journal of Dermatology 2018 63(5):391-398
Background: Fungi as a source of allergen are still largely neglected in basic research as well as in clinical practice. This study aimed to highlight the impact of fungal allergens in a group of patients suffering from atopic dermatitis (AD). Aims and Objectives: The evaluation of the sensitization to fungi in AD patients aged 14 year and older and the evaluation of the relation of fungal sensitization to the occurrence of other atopic diseases and parameters. Materials and Methods: All patients satisfying inclusion criteria attending our hospital between 2008 and 2017 were included in the study. The complete dermatological and allergological examinations were performed in all included patients including examination of specific immunoglobulin E, skin prick test to mixture of fungi and inhalant allergens, evaluation of asthma bronchiale, rhinitis, onset of AD, family history about atopy, duration of eczematous lesions, severity of AD. Pairs of these categories were entered in the contingency tables and the Chi-square test for relationship of these variables was performed with the level of significance set below 5%. Results: Three hundred and thirty-one patients were included in the study; the average age was 26.8 years. The sensitization to fungi was recorded in 100 patients (30%). In these patients, the occurrence of asthma bronchiale, rhinitis, family history about atopy, sensitization to grass and trees was significantly higher than in patients without sensitization to fungi. We did not find any significant relation between the sensitization to fungi and the severity of AD, no relation was also found between the sensitization to fungi and sensitization to mites, animal dander, bird feather, and dust. Conclusion: The occurrence of asthma bronchiale, rhinitis, family history about atopy, sensitization to grass and trees was significantly higher in AD patients with sensitization to fungi. No relation was found between the severity of AD and the sensitization to fungi.
Antifungal resistance in dermatology
Varadraj Pai, Ajantha Ganavalli, Naveen Narayanshetty Kikkeri
Indian Journal of Dermatology 2018 63(5):361-368
Cutaneous fungal infections affect more than one-fourth of world's population. The pathogenesis and severity of fungal infection depend on various immunological and nonimmunological factors. The rampant use of antifungal therapy in immunocompromised individuals marked the onset of antifungal drug resistance. Fungal resistance can be microbiological or clinical. Microbiological resistance depends on various fungal factors which have established due to genetic alteration in the fungi. Clinical resistance is due to host- or drug-related factors. All these factors may cause fungal resistance individually or in tandem. In addition to standardized susceptibility testing and appropriate drug dosing, one of the ways to avoid resistance is the use of combinational antifungal therapy. Combination therapy also offers advantages in increased synergistic action with enhanced spectrum activity. Newer insights into mechanisms of drug resistance will help in the development of appropriate antifungal therapy.
Indian Journal of Dermatology 2018 63(5):361-368
Cutaneous fungal infections affect more than one-fourth of world's population. The pathogenesis and severity of fungal infection depend on various immunological and nonimmunological factors. The rampant use of antifungal therapy in immunocompromised individuals marked the onset of antifungal drug resistance. Fungal resistance can be microbiological or clinical. Microbiological resistance depends on various fungal factors which have established due to genetic alteration in the fungi. Clinical resistance is due to host- or drug-related factors. All these factors may cause fungal resistance individually or in tandem. In addition to standardized susceptibility testing and appropriate drug dosing, one of the ways to avoid resistance is the use of combinational antifungal therapy. Combination therapy also offers advantages in increased synergistic action with enhanced spectrum activity. Newer insights into mechanisms of drug resistance will help in the development of appropriate antifungal therapy.
Impact on quality of life in vitiligo patients treated with narrowband ultraviolet B phototherapy
Yatendra S Chahar, Pramod Kumar Singh, Vijay Kumar Sonkar, Inder Rajani, Mohammad Adil
Indian Journal of Dermatology 2018 63(5):399-402
Context: Vitiligo is a psychosocial problem which significantly affects quality of life in Indian scenario. Aims: The purpose of this study was to compare the changes in quality of life in patients of vitiligo before and after treatment with narrowband ultraviolet B (NBUVB) phototherapy. Subjects and Methods: A total of 54 patients had completed the study. The age ranged between 16 and 70 years with a mean age of 26.77±14.2 years. The initial dose of NBUVB was 300 mJ/cm2 in adults and 150 mJ/cm2 in children twice weekly with 20% dose increment on subsequent visits. It was given for a maximum period of 6 months and was followed up for another 6 months to determine stability of repigmentation. Results: The average number of exposure given to the patients was 45.63±12.74 while the mean irradiation cumulative dose was 39.8 J/cm2. Mean Dermatology Life Quality Index (DLQI) of the vitiligo patients was 8.64±4.32 while those patients with acrofacial vitiligo had a mean DLQI of 11.78±5.61. After treatment with NBUVB, mean DLQI of all vitiligo patients was significantly reduced to 5.86±2.15 (P<0.01). Conclusions: This study showed that phototherapy had a positive therapeutic outcome in vitiligo, especially in younger patients. Even a small, depigmented lesion in a child could be psychosocially devastating.
Indian Journal of Dermatology 2018 63(5):399-402
Context: Vitiligo is a psychosocial problem which significantly affects quality of life in Indian scenario. Aims: The purpose of this study was to compare the changes in quality of life in patients of vitiligo before and after treatment with narrowband ultraviolet B (NBUVB) phototherapy. Subjects and Methods: A total of 54 patients had completed the study. The age ranged between 16 and 70 years with a mean age of 26.77±14.2 years. The initial dose of NBUVB was 300 mJ/cm2 in adults and 150 mJ/cm2 in children twice weekly with 20% dose increment on subsequent visits. It was given for a maximum period of 6 months and was followed up for another 6 months to determine stability of repigmentation. Results: The average number of exposure given to the patients was 45.63±12.74 while the mean irradiation cumulative dose was 39.8 J/cm2. Mean Dermatology Life Quality Index (DLQI) of the vitiligo patients was 8.64±4.32 while those patients with acrofacial vitiligo had a mean DLQI of 11.78±5.61. After treatment with NBUVB, mean DLQI of all vitiligo patients was significantly reduced to 5.86±2.15 (P<0.01). Conclusions: This study showed that phototherapy had a positive therapeutic outcome in vitiligo, especially in younger patients. Even a small, depigmented lesion in a child could be psychosocially devastating.
A case of bullous pemphigoid associated with lichen sclerosus et atrophicus
Asuka Yoshifuku, Aoi Okubo, Nozomi Jimura, Kazuyasu Fujii, Yuko Higashi, Takuro Kanekura
Indian Journal of Dermatology 2018 63(5):427-428
Indian Journal of Dermatology 2018 63(5):427-428
A comparative study of combined dermaroller and platelet-rich plasma versus dermaroller alone in acne scars and assessment of quality of life before and after treatment
Shefali Porwal, Yatendra Singh Chahar, Pramod Kumar Singh
Indian Journal of Dermatology 2018 63(5):403-408
Background: Scarring due to acne is a frequently encountered problem in dermatological outpatient department. Microneedling has been a well-accepted modality for the treatment of atrophic acne scars. Platelet-rich plasma (PRP) is a newer option to investigate. Aims: The aims of this study were (1) to compare the efficacy of combined dermaroller and PRP therapy with dermaroller alone in facial acne scars and (2) to assess the psychosocial impact due to acne scars and its treatment. Methods: A total of 55 patients were included in the study and randomly divided into two groups, Group A: 28 and Group B: 27. Proper counseling was done, and detailed clinical findings were recorded. Patients in Group A were treated with dermaroller alone while Group B patients underwent treatment with a combination of dermaroller and intradermal PRP injections. A total of three sitting were done at monthly interval. Final response was assessed at 1 month after the last sitting. Criteria of evaluation included Goodman and Baron's quantitative scale, visual analog score, and dermatology life quality index scores. Side effects were noted. Results were analyzed using Chi-square test and t-test. Results: Significant percentage improvement was noted in both the groups. However, Group B treated with both modalities had better results when compared with that in the Group A. Conclusion: A combination approach using dermaroller and PRP was a safe and better option than using dermaroller alone in atrophic acne scars for clinical improvement as well as for improvement in dermatology life quality index score.
Indian Journal of Dermatology 2018 63(5):403-408
Background: Scarring due to acne is a frequently encountered problem in dermatological outpatient department. Microneedling has been a well-accepted modality for the treatment of atrophic acne scars. Platelet-rich plasma (PRP) is a newer option to investigate. Aims: The aims of this study were (1) to compare the efficacy of combined dermaroller and PRP therapy with dermaroller alone in facial acne scars and (2) to assess the psychosocial impact due to acne scars and its treatment. Methods: A total of 55 patients were included in the study and randomly divided into two groups, Group A: 28 and Group B: 27. Proper counseling was done, and detailed clinical findings were recorded. Patients in Group A were treated with dermaroller alone while Group B patients underwent treatment with a combination of dermaroller and intradermal PRP injections. A total of three sitting were done at monthly interval. Final response was assessed at 1 month after the last sitting. Criteria of evaluation included Goodman and Baron's quantitative scale, visual analog score, and dermatology life quality index scores. Side effects were noted. Results were analyzed using Chi-square test and t-test. Results: Significant percentage improvement was noted in both the groups. However, Group B treated with both modalities had better results when compared with that in the Group A. Conclusion: A combination approach using dermaroller and PRP was a safe and better option than using dermaroller alone in atrophic acne scars for clinical improvement as well as for improvement in dermatology life quality index score.
Familiar manifestations of unfamiliar selenium toxicity
Banashree Majumdar, Nirmala Saini, Shweta Agrawal, Chiatra Prakash
Indian Journal of Dermatology 2018 63(5):430-431
Indian Journal of Dermatology 2018 63(5):430-431
Idiopathic eruptive macular pigmentation - uncommon presentation of an uncommon condition
Resham Jayvant Vasani
Indian Journal of Dermatology 2018 63(5):409-411
Idiopathic eruptive macular pigmentation (IEMP) is an asymptomatic condition with dark brown, nonconfluent lesions chiefly occurring in children and adolescents. The usual sites involved are face, trunk, extremities, and the lesions resolve over few months to years. We report an unusual presentation of this uncommon condition. A 22-year-old male presented with multiple dark-colored asymptomatic lesions on the scalp and forehead for the past 3 years. There was no history of preceding symptoms, drug, or applications, past or family history of such lesions. Examination revealed multiple hyperpigmented macules and barely elevated nonscaly plaques with a velvety feel akin to acanthosis nigricans (AN). Dermoscopy was similar to AN. Blood sugar, thyroid, and lipid profiles were normal. Histology showed "pigmented papillomatosis" concluding the final diagnosis of IEMP. Confluence of lesions is a rarely described phenomenon, with the scalp being a hitherto unreported site. The velvety feel of lesions, the dermoscopic, and histopathological findings further substantiate the hypothesis of this entity being an eruptive variant of AN.
Indian Journal of Dermatology 2018 63(5):409-411
Idiopathic eruptive macular pigmentation (IEMP) is an asymptomatic condition with dark brown, nonconfluent lesions chiefly occurring in children and adolescents. The usual sites involved are face, trunk, extremities, and the lesions resolve over few months to years. We report an unusual presentation of this uncommon condition. A 22-year-old male presented with multiple dark-colored asymptomatic lesions on the scalp and forehead for the past 3 years. There was no history of preceding symptoms, drug, or applications, past or family history of such lesions. Examination revealed multiple hyperpigmented macules and barely elevated nonscaly plaques with a velvety feel akin to acanthosis nigricans (AN). Dermoscopy was similar to AN. Blood sugar, thyroid, and lipid profiles were normal. Histology showed "pigmented papillomatosis" concluding the final diagnosis of IEMP. Confluence of lesions is a rarely described phenomenon, with the scalp being a hitherto unreported site. The velvety feel of lesions, the dermoscopic, and histopathological findings further substantiate the hypothesis of this entity being an eruptive variant of AN.
Kaposi's varicelliform eruption in a patient with darier's disease
Irene Garcia-Morales, Sandra Case-Mérida, Jerónimo Escudero
Indian Journal of Dermatology 2018 63(5):434-435
Indian Journal of Dermatology 2018 63(5):434-435
A distinct clinicopathological presentation of cutaneous dermatophytosis mimicking autoimmune blistering disorder
Jignaben Krunal Padhiyar, Nayankumar Harshadkumar Patel, Trusha Gajjar, Bhagirath Patel, Aseem Chhibber, Mansi Buch
Indian Journal of Dermatology 2018 63(5):412-414
Infectious diseases can clinically present as vesiculobullous disorders. Direct immunofluorescence (DIF) study of skin biopsy helps distinguish true autoimmune blistering disorders from other conditions. In many situations, even DIF findings in infections disorders imitate autoimmune process. Here, we describe a case of 29-year-old female with extensive dermatophytosis having presentation mimicking bullous pemphigoid both clinically and histopathologically including DIF findings.
Indian Journal of Dermatology 2018 63(5):412-414
Infectious diseases can clinically present as vesiculobullous disorders. Direct immunofluorescence (DIF) study of skin biopsy helps distinguish true autoimmune blistering disorders from other conditions. In many situations, even DIF findings in infections disorders imitate autoimmune process. Here, we describe a case of 29-year-old female with extensive dermatophytosis having presentation mimicking bullous pemphigoid both clinically and histopathologically including DIF findings.
A bibliometric evaluation of global productivity of teledermatology publications between 1975 and 2017 with a 3-year update
Engin Senel, Emre Demir, Refika Ferda Artüz
Indian Journal of Dermatology 2018 63(5):437-439
Indian Journal of Dermatology 2018 63(5):437-439
BLIMP1 transcriptionally induced by EGFR activation and post-translationally regulated by proteasome and lysosome is involved in keratinocyte differentiation, migration and inflammation
B lymphocyte-induced maturation protein-1 (BLIMP1) encoded by the PRDM1 gene belongs to the PRDM family of transcription repressor. BLIMP1 lacks intrinsic histone methyltransferase activity and serves as a scaffold for numerous epigenetic regulators to modulate DNA binding, gene silencing and chromatin reorganization [1,2]. Beside the well-known master regulator of B lymphocyte differentiation, BLIMP1 controls the development of various immune cells [3–7]. Thus, BLIMP1 is critical in maintenance of immune homeostasis, and dysfunction of BLIMP1 may contribute to autoimmune disorders.
NEUTROPHILS CONTRIBUTE TO VASCULITIS BY INCREASED RELEASE OF NEUTROPHIL EXTRACELLULAR TRAPS IN BEHÇET’S DISEASE
Bechet's disease (BD) is an inflammatory multi-system disorder causing recurrent oral and genital ulcers, uveitis, and vasculitis, in addition to cutaneous, neurological, gastrointestinal, articular and pulmonary manifestations [1]. Mild cases are treated with Colchicine, an anti-inflammatory drug. Severe cases can be life threatening and require systemic steroids, anti-TNFα drugs and immunosuppressants. Its pathophysiology is poorly known. Genetic studies identified several susceptibility loci implicating MHC1 and innate immunity genes namely HLA-B51, ERAP1, IL10, IL23R-IL12RB2, and IL1 A-IL1B [2–4].
Low-dose UVB therapy is comparable with conventional UVB phototherapy for treatment of vitiligo: A pilot study
UVB phototherapy is currently considered as the treatment of choice for vitiligo [1]. UVB is also used for treating inflammatory conditions including psoriasis. Although the major goals for treating vitiligo and psoriasis are different: one aims to bio-stimulate while the other aims to immune modulate, respectively, the protocols of phototherapy are surprisingly similar. More specifically, for narrow-band UVB (NBUVB) treatment of vitiligo, lesion repigmentation is associated with melanocyte precursor cell activation [2].
Non‐healing herpes zoster ophthalmicus
JDDG: Journal der Deutschen Dermatologischen Gesellschaft, EarlyView.
Dissecting folliculitis (dissecting cellulitis) of the scalp: a 66‐patient case series and proposal of classification
JDDG: Journal der Deutschen Dermatologischen Gesellschaft, EarlyView.
Antibacterial Effectiveness of Rice Water (Starch) Capped Silver Nanoparticles Fabricated Rapidly in Presence of Sunlight
Photochemistry and Photobiology, Volume 0, Issue ja, -Not available-.
Assessment of endothelial function during the loading phase of infliximab in psoriasis: a potential predictor of its drug survival
International Journal of Dermatology, EarlyView.
Basal cell carcinoma treated with Mohs micrographic surgery in young Ibero‐American patients
International Journal of Dermatology, EarlyView.
Autoimmune skin disease among dermatology outpatients in Botswana: a retrospective review
International Journal of Dermatology, EarlyView.
Controversies in off‐label prescriptions in dermatology: the perspective of the patient, the physician, and the pharmaceutical companies
International Journal of Dermatology, EarlyView.
Specific foot health‐related quality‐of‐life impairment in patients with type II versus type I diabetes
International Wound Journal, EarlyView.
The first ever reported case of malignant fibrous histiocytoma of the scalp
International Wound Journal, EarlyView.
Secondary‐intention healing following Mohs micrographic surgery for squamous cell carcinoma of a finger
International Wound Journal, EarlyView.
Prevention of hypergranulation tissue after gastrostomy tube placement: A randomised controlled trial of hydrocolloid dressings
International Wound Journal, EarlyView.
Percutan nasal septal retraction technique for dorsal cartilagenous deviations
Clinical Otolaryngology, Volume 0, Issue ja, -Not available-.
The Effect of Ventilation Tube Insertion to the Health‐Related Quality of Life in a Group of Children in Southeast Anatolia
Clinical Otolaryngology, Volume 0, Issue ja, -Not available-.
Fluoroscopic Balloon Diameter Measurement at Different Pressures during Eustachian Balloon Dilation
Clinical Otolaryngology, Volume 0, Issue ja, -Not available-.
Atopic Dermatitis and Cancer in Solid Organs: a Systematic Review and Meta‐Analysis
Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.
Creation and pilot test results of the dermatology‐specific proxy instrument the Infants and Toddlers Dermatology Quality of Life
Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.
Evaluation of a non‐ablative, fractional 1565 nm laser for the improvement of striae distensae albae
Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.
Investigation of the Predisposing Factor of Pemphigus and its clinical subtype through a Genome‐wide association and next generation sequence analysis
Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.
Chromoblastomycosis: an autochthonous case of a tropical disease
Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.
Bier's spots
Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.
The impact of atopic dermatitis on sexual health
Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.
Manipulating mindsets to improve patient outcomes: Is it ethical? Can it be avoided?
Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.
Does the Dermatology Life Quality Index (DLQI) underestimate the disease‐specific burden of psoriasis patients?
Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.
Terminal osseous dysplasia presenting with intracytoplasmic inclusion bodies in digital fibromas
Pediatric Dermatology, EarlyView.
Vancomycin‐induced red man syndrome presentation in a preterm infant
Pediatric Dermatology, EarlyView.
The value of full‐body skin examination: Poland syndrome diagnosed as an incidental finding
Pediatric Dermatology, EarlyView.
An atypical presentation of herpes simplex virus infection in Harlequin ichthyosis
Pediatric Dermatology, EarlyView.
Localized infantile hemangiomas of the face and scalp: Predilection for the midline and periorbital and perioral skin
Pediatric Dermatology, EarlyView.
Ulcerated congenital plexiform fibrohistiocytic tumor: Case report and literature review
Pediatric Dermatology, EarlyView.
Chronic urticaria in infants as the first manifestation of autoinflammatory disease
Pediatric Dermatology, EarlyView.
Pediatric ocular lichen planus and lichen planopilaris: One new case and a review of the literature
Pediatric Dermatology, EarlyView.
Prolonged migraine aura: new insights from a prospective diary-aided study
There is limited literature on prolonged aura (PA - defined as an aura including at least one symptom for > 1 h and
Effect of exogenous estrogens and progestogens on the course of migraine during reproductive age: a consensus statement by the European Headache Federation (EHF) and the European Society of Contraception and Reproductive Health (ESCRH)
We systematically reviewed data about the effect of exogenous estrogens and progestogens on the course of migraine during reproductive age. Thereafter a consensus procedure among international experts was unde...
New CACNA1A deletions are associated to migraine phenotypes
Familial hemiplegic migraine type 1 (FHM1) is a form of migraine with aura caused by heterozygous mutations in 4 genes: CACNA1A, ATP1A2, SNC1A and PRRT2, but further heterogeneity is expected. Here have been desc...
A Milroy case with FLT4/VEGFR3 mutation and an unusual skin biopsy
British Journal of Dermatology, Volume 0, Issue ja, -Not available-.
Fatigue and the wear‐off effect in adult patients with common variable immunodeficiency
Clinical &Experimental Immunology, Volume 0, Issue ja, -Not available-.
Perfused 3D angiogenic sprouting in a high-throughput in vitro platform
Abstract
Angiogenic sprouting, the growth of new blood vessels from pre-existing vessels, is orchestrated by cues from within the cellular microenvironment, such as biochemical gradients and perfusion. However, many of these cues are missing in current in vitro models of angiogenic sprouting. We here describe an in vitro platform that integrates both perfusion and the generation of stable biomolecular gradients and demonstrate its potential to study more physiologically relevant angiogenic sprouting and microvascular stabilization. The platform consists of an array of 40 individually addressable microfluidic units that enable the culture of perfused microvessels against a three-dimensional collagen-1 matrix. Upon the introduction of a gradient of pro-angiogenic factors, the endothelial cells differentiated into tip cells that invaded the matrix. Continuous exposure resulted in continuous migration and the formation of lumen by stalk cells. A combination of vascular endothelial growth factor-165 (VEGF-165), phorbol 12-myristate 13-acetate (PMA), and sphingosine-1-phosphate (S1P) was the most optimal cocktail to trigger robust, directional angiogenesis with S1P being crucial for guidance and repetitive sprout formation. Prolonged exposure forces the angiogenic sprouts to anastomose through the collagen to the other channel. This resulted in remodeling of the angiogenic sprouts within the collagen: angiogenic sprouts that anastomosed with the other perfusion channel remained stable, while those who did not retracted and degraded. Furthermore, perfusion with 150 kDa FITC-Dextran revealed that while the angiogenic sprouts were initially leaky, once they fully crossed the collagen lane they became leak tight. This demonstrates that once anastomosis occurred, the sprouts matured and suggests that perfusion can act as an important survival and stabilization factor for the angiogenic microvessels. The robustness of this platform in combination with the possibility to include a more physiological relevant three-dimensional microenvironment makes our platform uniquely suited to study angiogenesis in vitro.
Removal of hexavalent chromium from water by modified sponge iron particles and insights into mechanism
Abstract
Sponge iron particles modified with expanded graphite and Cu were used to purify solutions contaminated with aqueous Cr(VI). A removal mechanism that involved physical adsorption and a redox reaction is proposed. The reaction, which consisted of rapid adsorption, a desorption stage, and an adsorption–desorption equilibrium stage, corresponded to a first-order kinetic model. The properties of the adsorption materials before and after use were investigated by X-ray diffraction, scanning electron microscopy–energy-dispersive spectroscopy, Fourier-transform infrared spectroscopy, energy-dispersive X-ray fluorescence spectroscopy, and surface area measurements. Changes in the surface properties, e.g., attachment of material to the surface and filling of pores with Cr, were clearly observed. The Langmuir model best described Cr(VI) adsorption on the sponge iron and its modified particles. Removal efficiencies of 98.7, 98.8, and 100% were achieved in 7 h at a Cr(VI) dosage of 10 mg/L. Sponge iron particles are therefore potential adsorbents and after modification give good removal of Cr(VI) ions from contaminated water.
Familial acanthosis nigricans with the FGFR3 mutation: Differences of pigmentation between male and female patients
The Journal of Dermatology, EarlyView.
Efficiency of methylene blue mediated photodynamic therapy versus intense pulsed light in the treatment of onychomycosis in the toenails
Photodermatology, Photoimmunology &Photomedicine, Volume 0, Issue ja, -Not available-.
Diagnostic ultrasonography in a child with eosinophilic fasciitis
Clinical and Experimental Dermatology, EarlyView.
Πέμπτη 30 Αυγούστου 2018
Filamentous Organisms in a Blood Culture
A 79-year-old male presented to our institution with a fever of 100.9oF, shaking, chills, altered mental status, and 2 episodes of seizures. His prior medical history is significant for dementia, myasthenia gravis, type 2 diabetes mellitus, hypertension, right frontal hemorrhagic stroke, benign prostatic hyperplasia, and 2 simple kidney cysts. He was diagnosed 6 weeks earlier with an Escherichia coli bacteremia with no known source and with acute cystitis and hematuria caused by Klebsiella pneumoniae. Both organisms were pansensitive, and he was treated for 4 days with piperacillin–tazobactam and for 10 days with cefdinir. Follow-up blood cultures after 2 days showed no growth. His current urinalysis results showed negative nitrite, positive leukocyte esterase, and the presence of both red and white blood cells (WBC >50 and RBC >50/high-powered field). Blood and urine cultures were sent to the laboratory. The patient was started on empiric vancomycin and piperacillin–tazobactam but expired less than 24 hours later. The anaerobic blood culture bottle flagged positive after 98 hours of incubation, with the Gram stain showing long, gram-variable filaments containing bulbous inclusions (Figure 1).
Erratum
An error appeared in the 15 January 2017 issue of the journal [Lockhart S.R., Etienne K.A., Vallabhaneni S., et al. Simultaneous Emergence of Multidrug-Resistant Candida auris on 3 Continents by Whole-Genome Sequencing and Epidemiological Analyses. Clin Infect Dis 2017; 64(2):134–40. https://doi.org/10.1093/cid/ciw691]. The Erg11 amino acid substitution associated with South African isolates is F126L, not F126T, as originally stated. The authors regret this error.
A Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2018 Update by the Infectious Diseases Society of America and the American Society for Microbiologya
Abstract
The critical nature of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician/advanced practice provider and the microbiologists who provide enormous value to the healthcare team. This document, developed by experts in laboratory and adult and pediatric clinical medicine, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. This document presents a system-based approach rather than specimen-based approach, and includes bloodstream and cardiovascular system infections, central nervous system infections, ocular infections, soft tissue infections of the head and neck, upper and lower respiratory infections, infections of the gastrointestinal tract, intra-abdominal infections, bone and joint infections, urinary tract infections, genital infections, and other skin and soft tissue infections; or into etiologic agent groups, including arthropod-borne infections, viral syndromes, and blood and tissue parasite infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. In addition, the pediatric needs of specimen management are also emphasized. There is intentional redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a guidance for physicians in choosing tests that will aid them to quickly and accurately diagnose infectious diseases in their patients.Erratum
An error appeared in the 1 February 2018 issue of the journal [Muñoz L, Santin M, Alcaide F, et al. QuantiFERON-TB Gold In-Tube as a Confirmatory Test for Tuberculin Skin Test in Tuberculosis Contact Tracing: A Noninferiority Clinical Trial. Clin Infect Dis 2018; 66(3):396–403. https://ift.tt/2MIeTIs]. A Biostatistics Unit – IDIBELL team member (Cristian Tebé) name was inadvertently omitted. In the Appendix, after "Department of Microbiology: Fernando Alcaide, Raquel Moure." should appear the following "Biostatistics Unit, Bellvitge Biomedical Research Institute (IDIBELL): Cristian Tebé Codormi." The authors regret this error.
Drawing Inferences: Thinking with 6B (and Sketching Paper)
Abstract
This article discusses the epistemology of design as a process, arguing specifically that sketching and drawing are essential modes of thinking and reasoning. It demonstrates that the commonly accepted notion of a spontaneous and intuitive vision in the mind's eye—encapsulated in the cliché of the napkin sketch—obscures the exploratory inferences that are made while scribbling with a pencil on a sheet of paper. The draughtsperson, along with their work tools (such as the 6B), modes of notation, specific techniques, and epistemic strategies as well as the resulting design artefacts form milieus of reflection that facilitate complex processes of exploration. Case studies, including the genesis of the Mini by Alec Issigonis, samples of work by Alvar Aalto, and a reinterpretation of student sketches from a classical design study by Gabriela Goldschmidt, serve to illustrate how drawing inferences with pencil and paper occurs.
Dominant dystrophic epidermolysis bullosa pruriginosa with a COL7A1 exon 87 c.6898C>T mutation
Clinical and Experimental Dermatology, EarlyView.
Subacute cutaneous lupus erythematosus and systemic lupus erythematosus associated with abatacept
Subacute cutaneous lupus erythematosus (SCLE) is a subtype of cutaneous lupus erythematosus (CLE) with distinct clinical and immunologic features. It can be associated with Sjogren syndrome and rheumatoid arthritis (RA) as well as several classes of medications. Here we present a patient with new-onset SCLE and systemic lupus erythematosus (SLE) after treatment with abatacept. There is one other case of SCLE and one of SLE associated with abatacept described in the literature.1,2
The impact of diaper design on mitigating known causes of diaper dermatitis
Pediatric Dermatology, EarlyView.
Balance of tofacitinib efficacy and disease flare in the treatment of alopecia universalis: A case report and review of the literature
Alopecia areata (AA) is one of the most prevalent autoimmune diseases with 1.7% lifetime risk.1 AA is a nonscarring hair loss, typified by alopecic patches that can encompass the entire scalp in alopecia totalis (AT) or body in alopecia universalis (AU). The cause of AA is multifactorial, including an immune-mediated destruction of hair follicles2 in conjunction with genetic predisposition.3 There are currently no US Food and Drug Administration–approved treatments for alopecia areata, and treatment regimens are empiric, although topical, intralesional, and systemic steroids are commonly offered.
Reticular rash in drug reaction with eosinophilia and systemic symptoms syndrome: A clue to parvovirus B19 reactivation?
The term drug reaction with eosinophilia and systemic symptoms (DRESS) refers to a complex syndrome characterized by cutaneous lesions, eosinophilia, and systemic symptoms that may be triggered by different medications. The reaction takes place 2 to 6 weeks after the initial exposure to the culprit drug.1 Even after appropriate diagnosis and treatment have been conducted, patients may experience isolated or sequential relapses and slow clinical resolution that may be associated with viral reactivations of herpesvirus.
A case of subungual tumors of incontinentia pigmenti: A rare manifestation and association with bipolar disease
Incontinentia pigmenti (IP), or Bloch-Sulzberger syndrome, is an X-linked dominant disorder with male lethality caused by mutations in the IKBKG gene (also known as IKK-γ or NEMO), which is essential for nuclear factor-κB (NF-κB) activation and protects cells against tumor necrosis factor-α–induced apoptosis.1 In addition to the 4 cutaneous stages of IP (vesiculo-bullous, verrucous, hyperpigmented, and atrophic/hypopigmented), IP is also associated with ectodermal abnormalities, such as pegged teeth, alopecia, and anodontia as well as neurologic and ocular abnormalities.
Generalized familial benign chronic pemphigus (Hailey-Hailey disease) treated successfully with low-dose naltrexone
Familial benign chronic pemphigus or Hailey-Hailey disease (HHD) is an autosomal dominant genodermatosis with complete penetrance that was initially described by dermatologists and brothers Howard and Hugh Hailey.1 This disorder results from mutations in the ATP2C1 gene on chromosome 3q21, which encodes the Golgi-associated Ca2+ ATPase. Mutations in this gene lead to abnormal intracellular Ca2+ signaling leading to impaired processing of junctional proteins needed for cell-cell adhesion.
Subclinical granulomas in benign skin lesions heralding the onset of BRAF and MEK inhibitor–associated granulomatous dermatitis in a patient with metastatic melanoma
A 48 year-old white woman presented with melanoma, metastatic to the mediastinum. The primary lesion was ulcerated with a Breslow depth of 2.6 mm. The lesion was excised with appropriate margins. Right axillary sentinel lymph node biopsy was positive in 1 node, whereas a full lymph node dissection failed to find additional nodal involvement. She was treated with adjuvant interferon-β2, which was poorly tolerated and discontinued after 2 weeks. One year later, she presented with a 1-cm subcutaneous nodule above the excision scar, a biopsy of which confirmed metastatic melanoma.
Pancreatic acinar cell carcinoma–induced panniculitis
Pancreatic cancer is the fourth most common cause of cancer-related death among men and women in the United States. Every year, an estimated 43,090 people die of pancreatic cancer nationally.1 Pancreatic acinar cell carcinoma (ACC) is a rare form of pancreatic cancer that accounts for 1% to 2% of all pancreatic neoplasms.2 ACCs are generally asymptomatic and may be discovered incidentally when patients undergo work-up for general complaints such as abdominal pain. In the literature, investigators have reported a variety of systemic presentations of ACC.
Dehydrated human amnion/chorion membrane allograft as an aid for wound healing in patients with full-thickness scalp defects after Mohs micrographic surgery
Large surgical defects after Mohs micrographic surgeries (MMS) often require rotation or advancement flaps, skin grafts, or delayed reconstruction after use of tissue expanders. For patients with limited tissue redundancy, wounds may also heal by secondary intention. Elderly patients undergoing MMS with full-thickness defects exposing bone pose a unique set of healing barriers, such as immunosuppression, increased infection risk, poor tolerance to bone chiseling for exposing pinpoint bleeding, and difficulty in reaching wounds to apply dressings successfully.
Giant condyloma acuminatum of the vulva: Successful management with imiquimod
Giant condyloma acuminata (GCA) is a large condyloma of the anogenital region with a cauliflowerlike appearance. The tumor is extremely rare and is related to human papilloma virus (HPV) infection (HPV type 6 and 11 in 90% of cases).1 The definitive treatment is wide surgical excision, but topical medical treatment can be effective in selected cases.2,3 Here we report the first case, to our knowledge, of complete regression of vulvar GCA after treatment with topical imiquimod (5% cream) therapy, with no recurrence reported over a 3-year follow-up period.
Cutaneous metastases of malignant peripheral nerve sheath tumor: Ineffectiveness of intralesional methotrexate
Malignant peripheral nerve sheath tumor (MPNST) is an uncommon, aggressive sarcoma that arises from peripheral nerves and metastasizes hematogenously, most often to lung and bone.1 Approximately half of MPNSTs arise from plexiform neurofibromas in patients with neurofibromatosis type I (NF1).1 The remaining half occur sporadically, 10% of which arise from previously irradiated tissue.1 The epithelioid variant of MPNST is uncommon, accounting for less than 5% of cases.1 The most important aspect of treatment for MPNST is achieving clear surgical margins, as survival decreases dramatically with positive margins.
Successful treatment of cutaneous metastatic breast cancer with topical treatments that potentially synergize with systemic therapy: A case series
Breast cancer is the second most common malignancy after melanoma to metastasize to skin.1 Approximately 30% of individuals with metastatic breast cancer (MBC) go on to have cutaneous metastases, frequently presenting as firm nodules, diffuse infiltrative or ulcerative lesions, often in proximity to an old mastectomy scar.2,3 Cutaneous metastases of breast cancer (CMOBC) is a therapeutic challenge and is associated with increased morbidity. Progression of disease often results in severe pain, chest wall ulceration, bleeding, and superinfection.
Multiple reactive keratoacanthomas treated with zinc oxide wraps and intralesional corticosteroids
Keratoacanthoma (KA), a neoplasm of epidermal cells from the hair follicle unit,1 is often present on chronic sun-exposed skin.2 Many facets of this neoplasm are controversial, including its epidemiology, etiology, and biologic behavior, including malignant potential and recommendations for treatment.2 This case presents a treatment option for multiple reactive KAs that is both conservative and noninvasive.
Multiple acantholytic dyskeratotic acanthomas in an organ transplant recipient
Organ transplant recipients are known for carrying a high risk of various benign and malignant tumor development, particularly of the skin. Therapeutic immunosuppression in association with a variety of (co-)carcinogenic factors are held responsible for the high tumor incidence.
Pure testicular choriocarcinoma presenting as a friable hemorrhagic nodule on the lip
Here we present a case of metastatic cutaneous choriocarcinoma presenting as a lesion on the upper lip. This report briefly discusses choriocarcinoma, cutaneous manifestations, and prognosis.
Hepatitis C mixed cryoglobulinemia with undetectable viral load: A case series
Mixed cryoglobulinemic vasculitis is caused by circulating cold-precipitable immunoglobulins, or cryoglobulins, composed of monoclonal (type II) or polyclonal (type III) IgM directed against a polyclonal IgG. It causes palpable purpura and has long been associated with hepatitis C virus (HCV) infection. The initial theory regarding the new antiviral medications, which have been so successful in treating hepatitis C, was that once the HCV was treated, the mixed cryoglobulinemic vasculitis would also resolve.
Erythrodermic presentation of psoriasis in a patient treated with dupilumab
Dupilumab is an interleukin (IL)-4 receptor α (IL-4Rα) antagonist that inhibits IL-4 and IL-13 signaling, key mediators of T-helper (Th)2-mediated inflammation.1 Whereas an immune shift toward Th2 drives atopic dermatitis and thus a blockade in the Th2 inflammatory cascade is an effective treatment, the opposing shift toward Th1 and Th17 cells is implicated in the pathogenesis of psoriasis.2 We present an erythrodermic presentation of psoriasis in a patient treated with dupilumab for a dermatitis that was clinically diagnosed as atopic dermatitis.
Checkpoint inhibitor–associated cutaneous small vessel vasculitis
Under physiologic conditions, immune checkpoints provide negative signals to control T-cell activation and prevent inflammation-associated tissue destruction. Cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4), a principal negative regulator of T-cell activation, binds to CD80/CD86 on antigen-presenting cells, dampening the stimulatory signal of CD28 on T cells. Programmed cell death 1 receptor (PD-1) is another inhibitive co-regulator of the CD28/CTLA4 pathway. Excessive activity of either of these checkpoints is one of the underlying mechanisms for cancers, such as melanoma, to evade the immune system.
Neglected basal cell carcinoma presenting with diffuse skeletal metastases
Metastatic basal cell carcinoma (mBCC) is exceedingly rare, with an estimated incidence of 0.0028% to 0.55%.1 Although the behavior of mBCC is poorly understood, the primary tumor typically exhibits aggressive histopathology, such as morpheaform, infiltrating, or basosquamous features. Basal cell carcinoma (BCC) usually metastasizes to regional lymph nodes (53%), lungs (33%), and bone (20%). Until a few years ago, the median survival after diagnosis was only 8 to 10 months. After the demonstration that more than 90% of BCC expressed abnormal Hedgehog signaling, 2 Hedgehog pathway inhibitors, vismodegib and sonidegib, were approved for advanced BCC.
Potential for overlooked melanoma in solid organ donors with a severely dysplastic nevus
Current or recent malignancy is a contraindication to organ donation because of the risk of transmission. Given the profound organ shortage in the United States, transplant surgeons frequently consider potential deceased organ donors with a remote history of malignancy. However, a diagnosis of melanoma, at any time, is an absolute contraindication to organ donation.1 Melanoma is one of the cancers most commonly transmitted from donor to recipient, which is likely related to its pathophysiology. The behavior of melanoma can be modulated by immunity; melanoma can remain dormant in the donor and then reactivate in the recipient because of the intense immunosuppression required to prevent rejection.
Negative Predictive Value of NI-RADS Category 2 in the First Posttreatment FDG-PET/CT in Head and Neck Squamous Cell Carcinoma [HEAD & NECK]
BACKGROUND AND PURPOSE:
FDG PET/CT has a high negative predictive value in patients with head and neck squamous cell carcinoma who responds completely to non-operative therapy. However, the treatment failure rate in patients with a partial but incomplete response is unclear. Our aim was to investigate the negative predictive value of the first posttreatment FDG-PET/CT in patients with head and neck squamous cell carcinoma with incomplete response interpreted as Neck Imaging Reporting and Data System (NI-RADS) category 2.
MATERIALS AND METHODS:We retrospectively identified patients with head and neck squamous cell carcinoma treated with chemoradiation or radiation therapy with curative intent in our institution between 2008 and 2016. We included patients whose first posttreatment FDG-PET/CT was interpreted as showing marked improvement of disease but who had a mild residual mass or FDG avidity in either the primary tumor bed or lymph nodes (NI-RADS 2). The negative predictive value of FDG-PET/CT was calculated, including the 95% CI, using the Newcombe method. Two-year disease-free survival was the reference standard.
RESULTS:Seventeen of 110 patients (15%) experienced locoregional treatment failure within 2 years of completing treatment, yielding a negative predictive value of 85% (95% Cl, 77%–90%). The most common location of tumor recurrence was the cervical lymph nodes (59%). The median time interval between completion of therapy and treatment failure was 10 months (range, 5–24 months).
CONCLUSIONS:In patients with an incomplete response after treatment of head and neck squamous cell carcinoma, the negative predictive value of the first posttreatment FDG-PET/CT was 85%, which is lower than the 91% negative predictive value of FDG-PET/CT in patients with an initial complete response. Patients with an incomplete response (NI-RADS 2) should undergo more frequent clinical and imaging surveillance than patients with an initial complete response (NI-RADS 1).
Multiple Brain Developmental Venous Anomalies as a Marker for Constitutional Mismatch Repair Deficiency Syndrome [PEDIATRICS]
BACKGROUND AND PURPOSE:
Biallelic constitutional mutations in DNA mismatch repair genes cause a distinct syndrome, constitutional mismatch repair deficiency syndrome (CMMRD), characterized by cancers from multiple organs, most commonly brain tumors, during childhood. Surveillance protocols include total and brain MR imaging among other modalities to enable early detection of tumors. Brain surveillance scans revealed prominent brain developmental venous anomalies (DVAs) in some patients. DVAs are benign vascular anomalies, and their incidence in the general population is 2.6%–6.4%. Most developmental venous anomalies are asymptomatic and are found incidentally. Our purpose was to assess the prevalence of DVAs in CMMRD patients and describe their phenotype.
MATERIALS AND METHODS:A retrospective descriptive analysis of brain MR imaging studies from 10 patients from 3 families with CMMRD was performed. Analysis included the number of developmental venous anomalies, location, draining vessels, and associated vascular anomalies (ie, cavernomas), with clinical correlation of symptoms and tumors.
RESULTS:All 10 patients had ≥2 developmental venous anomalies, and 2 had, in addition, non-therapy-induced cavernomas. There was no clinically symptomatic intracranial bleeding from developmental venous anomalies. Six patients had malignant brain tumors. The location of brain tumors was not adjacent to the developmental venous anomalies. No new developmental venous anomalies developed during follow-up.
CONCLUSIONS:The occurrence of multiple developmental venous anomalies in all our patients with CMMRD suggests that developmental venous anomalies may be a characteristic of this syndrome that has not been previously described. If confirmed, this quantifiable feature can be added to the current scoring system and could result in early implementation of genetic testing and surveillance protocols, which can be life-saving for these patients.
Radiologic-Pathologic Correlation of Tumor Thickness and Its Prognostic Importance in Squamous Cell Carcinoma of the Oral Cavity: Implications for the Eighth Edition Tumor, Node, Metastasis Classification [HEAD & NECK]
BACKGROUND AND PURPOSE:
Addressing the performance of an imaging-based parameter compared to a "gold standard" pathologic measurement is essential to achieve accurate clinical T-classification. Our aim was to determine the radiologic-pathologic tumor thickness correlation and its prognostic value in oral squamous cell carcinoma.
MATERIALS AND METHODS:All pathologic T1–T3 (seventh edition of the Cancer Staging Manual of the American Joint Committee on Cancer) oral squamous cell carcinomas diagnosed between 2010 and 2015 were reviewed. Radiologic tumor thickness was measured on preoperative CT or MR imaging blinded to pathology. The radiologic-pathologic tumor thickness correlation was calculated. The impact of the imaging-to-surgery time interval and imaging technique on the correlation was explored. Intra-/interrater reliability on radiologic tumor thickness was calculated. The correlation of radiologic-versus-pathologic tumor thickness and its performance as the seventh edition T-category modifier was evaluated. Multivariable analysis assessed the prognostic value of the radiologic tumor thickness for overall survival adjusted for age, seventh edition T-category, and performance status.
RESULTS:For 354 consecutive patients, the radiologic-pathologic tumor thickness correlation was similar for the image-to-surgery interval of ≤4.0 weeks ( = 0.76) versus 4–8 weeks ( = 0.80) but lower in those with more than an 8-week interval ( = 0.62). CT and MR imaging had similar correlations (0.76 and 0.80). Intrarater and interrater reliability was excellent (0.88 and 0.84). Excluding 19 cases with an imaging-to-surgery interval of >8 weeks, 335 patients were eligible for further analysis. The radiologic-pathologic tumor thickness correlation was 0.78. The accuracy for upstaging the T-classification based on radiologic tumor thickness was 83% for pathologic T1 and 74% for pathologic T2 tumors. Multivariable analysis confirmed the prognostic value of radiologic tumor thickness (hazard ratio = 1.5, P = .02) for overall survival.
CONCLUSIONS:This study demonstrates a good radiologic-pathologic tumor thickness correlation. Intrarater and interrater reliability for radiologic tumor thickness was excellent. Radiologically thicker tumor was predictive of inferior survival.
Thrombus Permeability on Dynamic CTA Predicts Good Outcome after Reperfusion Therapy [INTERVENTIONAL]
BACKGROUND AND PURPOSE:
Thrombus permeability assessed on conventional CTA is associated with neurologic outcome in patients with acute ischemic stroke. We aimed to investigate whether dynamic CTA can improve the accuracy of thrombus permeability assessment and its predictive value for outcome.
MATERIALS AND METHODS:We reviewed consecutive patients with acute ischemic stroke who had occlusion of the M1 segment of the middle artery cerebral artery and underwent pretreatment perfusion CT. Thrombus permeability, determined by thrombus attenuation increase (TAI), was assessed on 26-phase dynamic CTA derived from perfusion CT. TAImax was defined as the maximum TAI among phases; TAIpeak, as TAI of peak arterial phase; TAIcon, as TAI on phase 13. Good outcome was defined as a 3-month mRS score of ≤2.
RESULTS:One hundred four patients were enrolled in the final analysis. The median TAImax, TAIpeak, and TAIcon were 30.1 HU (interquartile range, 13.0–50.2 HU), 9.5 HU (interquartile range, –1.6–28.7 HU), and 6.6 HU (interquartile range, –5.1–24.4 HU), respectively. Multivariable regression analyses showed that TAImax (OR = 1.027; 95% CI, 1.007–1.048; P = .008), TAIpeak (OR = 1.029; 95% CI, 1.005–1.054; P = .020), and TAIcon (OR = 1.026; 95% CI, 1.002–1.051; P = .037) were independently associated with good outcome. The areas under the ROC curve of TAImax, TAIpeak, and TAIcon in predicting good outcome were 0.734, 0.701, and 0.658, respectively.
CONCLUSIONS:Thrombus permeability assessed on dynamic CTA could be a better predictor of outcome after reperfusion therapy than that assessed on conventional single-phase CTA.
Reasons for Reperfusion Failures in Stent-Retriever-Based Thrombectomy: Registry Analysis and Proposal of a Classification System [INTERVENTIONAL]
BACKGROUND AND PURPOSE:
In 5%–10% of patients with acute ischemic stroke with an intention to treat with mechanical thrombectomy, no reperfusion can be achieved (Thrombolysis in Cerebral Infarction score = 0/1). Purpose of this analysis was a systematic assessment of underlying reasons for reperfusion failures.
MATERIALS AND METHODS:An intention-to-treat single-center cohort (n = 592) was re-evaluated for all patients in whom no reperfusion could be achieved (n = 63). Baseline characteristics of patients were compared between patients with and without reperfusion failures. After qualitative review of all cases with reperfusion failures, a classification system was proposed and relative frequencies were reported. In a second step, occurrence of delayed recanalization at 24 hours after reperfusion failure and dependency on IV-tPA were evaluated.
RESULTS:In 63/592 patients with an intention to perform stent-retriever thrombectomy, no reperfusion was achieved (TICI 0/1, 10.6%, 95% CI, 8.2%–13.1%). Older patients (adjusted OR per yr = 1.03; 95% CI, 1.01–1.05) and patients with M2 occlusion (adjusted OR = 3.36; 95% CI, 1.82–6.21) were at higher risk for reperfusion failure. In most cases, no reperfusion was a consequence of technical difficulties (56/63, 88.9%). In one-third of these cases, reperfusion failures were due to the inability to reach the target occlusion (20/63, 31.7%), while "stent-retriever failure" occurred in 39.7% (25/63) of patients. Delayed recanalization was very rare (18.2%), without dependence on IV-tPA pretreatment status.
CONCLUSIONS:Reasons for reperfusion failure in stent-retriever thrombectomy are heterogeneous. The failure to establish intracranial or cervical access is almost as common as stent-retriever failure after establishing intracranial access. Systematic reporting standards of reasons may help to further estimate relative frequencies and thereby guide priorities for technical development and scientific effort.
Comparison of Advanced Imaging Resources, Radiology Workforce, and Payment Methodologies between the United States and Canada [PRACTICE PERSPECTIVES]
SUMMARY:
The purpose of this Practice Perspectives was to review the United States and Canadian approaches to health care access and payment for advanced imaging. The historical background, governmental role, workforce, coding, payment, radiologic challenges, cost, resource intensity, and overall outcomes in longevity are reviewed.
Identification of Hostile Hemodynamics and Geometries of Cerebral Aneurysms: A Case-Control Study [INTERVENTIONAL]
BACKGROUND AND PURPOSE:
Hostile hemodynamic conditions and geometries are thought to predispose aneurysms for instability and rupture. This study compares stable, unstable, and ruptured aneurysms while controlling for location and patient characteristics.
MATERIALS AND METHODS:The hemodynamics and geometries of 165 stable, 65 unstable, and 554 ruptured aneurysms were compared. Hemodynamics was modeled using image-based computational fluid dynamics. Case-control pairs were selected matching aneurysm location, patient age, and sex. Paired Wilcoxon tests were used to compare hemodynamic and geometric variables among different aneurysm groups. The pairing was repeated 100 times, and the combined P values were calculated and adjusted for multiple testing.
RESULTS:Ruptured aneurysms had lower minimum wall shear stress (P = .03), higher maximum wall shear stress (P = .03), more concentrated (P = .03) and mean oscillatory shear stress (P = .03), higher maximum velocity (P = .03), and more complex flows (vortex core-line length, P = .03) than stable aneurysms. Similarly, unstable aneurysms had more concentrated shear stress (P = .04) and more complex flows (vortex core-line length, P = .04) than stable aneurysms. Compared with stable aneurysms, ruptured aneurysms were larger (size ratio, aneurysm size/vessel size, P = .03), more elongated (aspect ratio, P = .03), and irregular (nonsphericity index, P = .03). Similarly, unstable aneurysms were larger (size ratio, P = .04), more elongated (aspect ratio, P = .04), and irregular (bulge location, P = .04; area-weighted Gaussian curvature; P = .04) than stable aneurysms. No significant differences were found between unstable and ruptured aneurysms.
CONCLUSIONS:Unstable and ruptured aneurysms have more complex flows with concentrated wall shear stress and are larger, more elongated, and irregular than stable aneurysms, independent of aneurysm location and patient sex and age.
Teaching with Stories: Ecology, Haraway, and Pedagogical Practice
Abstract
Haraway foregrounds many stories that we, in a late capitalist era, tell ourselves in order to justify, or not even notice, actions that are harmful to all living things. While I am mindful of Haraway's excellent attention to the ways that 'stories tell stories, thoughts think thoughts, and knots knot knots,' I argue that we must take great care when we, as educators, blur the lines between facts and fiction; reality and art. When everything becomes a story—with some stories simply being more compelling than other stories—we run the risk of contributing to the very sense of unmooring (from each other, from all living, from the earth) that has led us to the status quo where arctic icecaps are melting, living things are becoming extinct, and humans are suffering from man-made pollution. In this paper, I trouble the use of stories to draw attention to the ecological harm we have done to our earth. While stories can be powerful, there are risks associated with how we tell stories; and particular risks when we blur the lines between critical storytelling and the idea of something as 'factual'. Storytelling, and blurring the lines between stories and facts, can have negative implications for our quest to generate a sense of 'response-ability' for our planet and all who live on it. In order to make that argument, I first talk about my own story and the ways that I have used stories in the classroom. I then touch on Haraway and her particular use of (and argument for the use of) stories. I then foreground the practice of telling truths with stories by exploring the use of critical fiction and narrative inquiry. I conclude with implications for pedagogy.
Exploring an Alternative Justification for the Importance of Curiosity in Education: Social Curiosity and Løgstrup’s Sovereign Expression of Life
Abstract
There seems to be a broad agreement that curiosity is important in education. However, current research often seeks to answer the question of how best to nurture curiosity and fails to ask the normative question of why this should be done. A closer look reveals that the reasons for justifying the importance of curiosity vary, with some theorists pointing to its role in cognitive development as a starting point for learning, and others praising it as an element of democracy and a child's right to participation. Most of these approaches understand curiosity as an individual urge or desire for knowledge. In contrast, this article will examine a relational understanding of the concept by focussing on social curiosity. Instead of following a cognitive developmentalist, intellectual virtue or emancipatory approach to valuing curiosity, I will employ relational ethical theory. The argument then explores a possible analogy between social curiosity and the concept of sovereign expressions of life, as developed by the Danish philosopher and theologian K.E. Løgstrup. By drawing on his relational ethics, the article aims to expand the theoretical grounds on which curiosity can be normatively legitimised in education. With children spending longer and longer hours in educational, structured and adult-led settings, I conclude with a twofold normative claim: Social curiosity should be a part of all relations in education and its absence should lead to an ethical demand. In addition, an awareness of the actual deeds through which social curiosity is realised is also a topic that must be addressed by educators.
Topical 3-bromopyruvate is a novel targeted therapy for melanoma in a preclinical model
Targeting cancer metabolism is a promising strategy in improving cancer treatment.
Treatment of alopecia universalis with topical Janus kinase inhibitors – a double blind, placebo, and active controlled pilot study
International Journal of Dermatology, EarlyView.
Three-dimensional analysis of cutaneous nervous system in pruritic atopic dermatitis and psoriasis skin
Introduction: Intraepidermal nerve fiber (IENF) count in skin biopsies has been used as a reflection of the innervation density of itch-transmitting C nerve fibers in the skin. Changes in IENF densities in pruritic conditions such as eczema and psoriasis has been studied previously, but conflicting results have been reported. In these studies, IENF count is defined as the number of PGP9.5-positive nerve fibers crossing the basement membrane per unit length in 50-μm-thick histologic sections. However, this 2-dimensional approach is limited by the thickness of the section examined.
Introduction: Allergy Special Issue
Vascular wall imaging in reversible cerebral vasoconstriction syndrome – a 3-T contrast-enhanced MRI study
Limited histopathology studies have suggested that reversible cerebral vasoconstriction syndromes (RCVS) does not present with vascular wall inflammation. Previous vascular imaging studies have had inconsisten...
Satisfying your neuro-oncologist: a fast approach to routine molecular glioma diagnostics
Diffuse gliomas are the most common primary brain tumors in adults. Discrimination between astrocytic and oligodendroglial lineage differentiation has been subject to substantial intra- and interobserver variability, impairing prognostic and predictive stratification. Therefore, the 2016 WHO Classification of Tumors of the Central Nervous System introduced molecular markers, notably isocitrate dehydrogenase (IDH) mutation and loss of heterozygosity 1p/19q status, to reduce diagnostic bias.1 Nevertheless, standardized protocols for diagnostic (eg, IDH1/2 mutation, loss of heterozygosity 1p/19q) and predictive markers (eg, O6-methylguanine-DNA methyltransferase [MGMT] promoter methylation) are lacking. In addition, practical implementation of routine molecular workup of these tumors may be compromised by impractically long turnaround times and economic restraints, including lack of required equipment.
Facial Animation Surgery for Long-standing Facial Palsy: Opportunities for Shared Decision Making
This Viewpoint discusses the shared patient-physician decision-making process and suggests a 6-step approach for implementing the practice before surgical treatment of long-standing facial palsy in adults and children.
Anesthesia Duration Does Not Exist in a Surgical Vacuum
To the Editor Brady et al performed a novel retrospective investigation into outcomes after prolonged, otherwise intermediate-risk surgery. We take issue with the wording of their conclusion. From our perspective, they studied duration of surgery not anesthesia duration because it is for the prolonged surgery that prolonged anesthesia was administered. Obviously having a control group for similar surgery and similar duration without anesthesia would be practically impossible. One possible imaginary control group would be being anesthetized for a similarly prolonged number of hours without any surgery. From practical experience we can say with almost absolute certainty that the imaginary control group is very unlikely to see any complications. It is well established that perioperative entities like MINS (myocardial injury after noncardiac surgery) can affect mortality and outcome, especially after longer surgeries, from the extreme inflammation and prothrombogenic processes getting stimulated exits. Although the authors reported the incidence of myocardial infarction (MI), MINS is diagnosed using a high-sensitivity troponin assay, and most likely was not recorded in the National Surgical Quality Improvement Program database. Other studies have associated blood loss and blood transfusion with an increased risk of cardiac complications after surgery. In our experience, when we provide anesthesia for these patients it is often a vexing problem to maintain an adequate blood pressure for graft perfusion given the slow but persisting blood loss while simultaneously trying to avoid transfusion. To us, this is one more of the several studies showing that a prolonged surgical procedure, compounded by anesthesia and ongoing inflammatory processes may contribute to increased complications as observed in this study.
Anesthesia Duration Does Not Exist in a Surgical Vacuum
To the Editor In a recent retrospective database analysis, Brady et al dramatically opined in the title and repeatedly in the article that anesthesia duration is directly associated with several adverse outcomes in patients undergoing microvascular reconstruction procedures. This is a misleading and alarming claim which may lead to physician and lay public misunderstanding of the effects of general anesthesia.
Health Utility of Facial Palsy and Facial Reanimation
This survey study examines the societal perception of facial deformities and surgical facial reanimation.
The calcium-binding type III repeats domain of thrombospondin-2 binds to fibroblast growth factor 2 (FGF2)
Abstract
Thrombospondin (TSP)-1 and TSP-2 share similar structures and functions, including a remarkable antiangiogenic activity. We have previously demonstrated that a mechanism of the antiangiogenic activity of TSP-1 is the interaction of its type III repeats domain with fibroblast growth factor-2 (FGF2), affecting the growth factor bioavailability and angiogenic activity. Since the type III repeats domain is conserved in TSP-2, this study aimed at investigating whether also TSP-2 retained the ability to interact with FGF2. The FGF2 binding properties of TSP-1 and TSP-2 and their recombinant domains were analyzed by solid-phase binding and surface plasmon resonance assays. TSP-2 bound FGF2 with high affinity (Kd = 1.3 nM). TSP-2/FGF2 binding was inhibited by calcium and heparin. The FGF2-binding domain of TSP-2 was located in the type III repeats and the minimal interacting sequence was identified as the GVTDEKD peptide in repeat 3C, corresponding to KIPDDRD, the active sequence of TSP-1. A second putative FGF2 binding sequence was also identified in repeat 11C of both TSPs. Computational docking analysis predicted that both the TSP-2 and TSP-1-derived heptapeptides interacted with FGF2 with comparable binding properties. Accordingly, small molecules based on the TSP-1 active sequence blocked TSP-2/FGF2 interaction. Binding of TSP-2 to FGF2 impaired the growth factor ability to interact with its cellular receptors, since TSP-2-derived fragments prevented the binding of FGF2 to both heparin (used as a structural analog of heparan sulfate proteoglycans) and FGFR-1. These findings identify TSP-2 as a new FGF2 ligand that shares with TSP-1 the same molecular requirements for interaction with the growth factor and a comparable capacity to block FGF2 interaction with proangiogenic receptors. These features likely contribute to TSP-2 antiangiogenic and antineoplastic activity, providing the rationale for future therapeutic applications.
Understanding the evolving phenotype of vascular complications in telomere biology disorders
Abstract
Vascular complications such as bleeding due to gastrointestinal telangiectatic anomalies, pulmonary arteriovenous malformations, hepatopulmonary syndrome, and retinal vessel abnormalities are being reported in patients with telomere biology disorders (TBDs) more frequently than previously described. The international clinical care consortium of telomere-associated ailments and family support group Dyskeratosis Congenita Outreach, Inc. held a workshop on vascular abnormalities in the TBDs at the National Cancer Institute in October 2017. Clinicians and basic scientists reviewed current data on vascular complications, hypotheses for the underlying biology and developed new collaborations to address the etiology and clinical management of vascular complications in TBDs.
Angiogenesis in pancreatic cancer: current research status and clinical implications
Abstract
Pancreatic cancer is one of the most lethal malignancies worldwide. Although the standard of care in pancreatic cancer has improved, prognoses for patients remain poor with a 5-year survival rate of < 5%. Angiogenesis, namely, the formation of new blood vessels from pre-existing vessels, is an important event in tumor growth and hematogenous metastasis. It is a dynamic and complex process involving multiple mechanisms and is regulated by various molecules. Inhibition of angiogenesis has been an established therapeutic strategy for many solid tumors. However, clinical outcomes are far from satisfying for pancreatic cancer patients receiving anti-angiogenic therapies. In this review, we summarize the current status of angiogenesis in pancreatic cancer research and explore the reasons for the poor efficacy of anti-angiogenic therapies, aiming to identify some potential therapeutic targets that may enhance the effectiveness of anti-angiogenic treatments.
L’album des résultats
Publication date: Available online 30 August 2018
Source: Annales de Chirurgie Plastique Esthétique
Author(s): C. Bruant Rodier, F. Bodin, C. Huttin, V. Duquennoy, E. Delay, C. Dissaux
Résumé
Cet album est à l'usage du chirurgien pour faciliter l'information de la patiente. Des résultats cliniques y sont présentés, déclinés en fonction de la technique de reconstruction envisagée ; reconstruction prothétique, mixte ou autologue, par lambeau ou lipomodelage et en prenant en compte des femmes de morphologies diverses. Sans constituer un catalogue, ni une promesse de résultat, le but de cet album est d'assister le chirurgien et sa patiente dans un choix avisé de l'indication technique par le biais d'un support visuel.
Summary
This document is meant to be a practical guide for the surgeon, to assist him in informing the patient more easily. Different clinical results with different reconstructive techniques and different morphologies are presented. This document is not meant to be a catalogue, or to guarantee any result to the patient, but truly to assist as best as it can the surgeon and the patient in choosing together the most appropriate techniques on a visual basis.
Sentinel lymph node biopsy in melanoma: Which hot nodes should be harvested and is blue dye really necessary?
Publication date: September 2018
Source: Journal of Plastic, Reconstructive & Aesthetic Surgery, Volume 71, Issue 9
Author(s): JM Ranson, NM Pantelides, D Gharpuray Pandit, JKG Laitung
Abstract
Objectives
The '10% rule' has become widely accepted by surgeons performing sentinel lymph node biopsy (SLNB) for melanoma. The purpose of this study was to compare the '10% rule' with alternative node harvesting criteria. In particular, we were interested to see whether the use of blue dye had any impact on the sensitivity of the test and whether it is necessary to remove all hot nodes.
Methods
We reviewed 537 SLNBs performed for primary melanoma from 2009–2015. SLNB was offered to all patients with 1–4 mm Breslow thickness melanoma and sentinel nodes were harvested according to the '10% rule'.
Results
One hundred sixteen patients (22%) had at least one positive sentinel node and there were 45 positive nodal basins from which more than one sentinel node had been harvested. Excluding blue dye and sampling only hot nodes would have enabled a 5% reduction in nodes harvested, without any compromise in the sensitivity of the test. However, applying harvesting criteria whereby not all hot nodes are taken was associated with a loss of sensitivity, with positive sentinel nodes being missed and patients understaged.
Conclusions
Our data do not support the continued use of blue dye in SLNB for melanoma, as it does not improve the sensitivity of the test. This series adds to growing evidence, suggesting that the '10% rule' with the inclusion of blue nodes should be reconsidered and that radiocolloid tracer alone is sufficient for sentinel node localisation.
The Effect of Endothelial Cells on UVB‐induced DNA Damage and Transformation of Keratinocytes In 3D Polycaprolactone Scaffold Co‐culture System
Photochemistry and Photobiology, Volume 0, Issue ja, -Not available-.
De novo design of biosynthetic pathways for bacterial production of bulk chemicals and biofuels
Abstract
Recent advances in DNA synthesis and computer science have enabled the de novo design of biosynthetic pathways. Numerous computational tools are currently available for searching biosynthetic pathways and ranking them on the basis of multiple criteria for installation into microbial chassis strains. This new framework allows the design of artificial biosynthetic pathways without expert knowledge of the specific biochemical reactions involved. Moreover, genetic apparatuses with quantitative and predictable properties enable rational construction of gene circuits. Thus, our ability to construct microbial cells specialized for bio-production is accelerating. However, many synthetic biology tools have not yet been fully applied to metabolic engineering owing to the lack of interdisciplinary collaboration between metabolic engineers and synthetic biologists. Therefore, we have focused on discussing how synthetic biology tools can be applied to de novo design of biosynthetic pathways.RpoS controls the expression and the transport of the AlgE1-7 epimerases in Azotobacter vinelandii
Abstract
Azotobacter vinelandii produces differentiated cells, called cysts, surrounded by two alginate layers, which are necessary for their desiccation resistance. This alginate contains variable proportions of guluronate residues, resulting from the activity of seven extracytoplasmic epimerases, AlgE1-7. These enzymes are exported by a system secretion encoded by the eexDEF operon; mutants lacking the AlgE1-7 epimerases, the EexDEF or the RpoS sigma factor produce alginate, but are unable to form desiccation resistant cysts. Herein, we found that RpoS was required for full transcription of the algE1-7 and eexDEF genes. We found that the AlgE1-7 epimerases proteins were diminished in the rpoS mutant strain. In addition, the alginate produced in the absence of RpoS was more viscous in the presence of proteases, a phenotype similar to that of the eexD mutant. Primer extension analysis located two promoters for the eexDEF operon, one of them RpoS dependent. Thus, during encysting conditions, RpoS coordinates the expression of both the AlgE1-7 epimerases and the EexDEF protein complex responsible for their transport.Lactic acid bacteria: from starter cultures to producers of chemicals
Abstract
Lactic acid bacteria constitute a diverse group of industrially significant, safe microorganisms that are primarily used as starter cultures and probiotics, and are also being developed as production systems in industrial biotechnology for biocatalysis and transformation of renewable feedstocks to commodity- and high value chemicals, and health products. Development of strains, which was initially based mainly on natural approaches, is also achieved by metabolic engineering that has been facilitated by the availability of genome sequences and genetic tools for transformation of some of the bacterial strains. The aim of this paper is to provide a brief overview of the potential of lactic acid bacteria as biological catalysts for production of different organic compounds for food and non-food sectors based on their diversity, metabolic- and stress tolerance features, as well as the use of genetic/metabolic engineering tools for enhancing their capabilities.Utility of a sensor‐based technology to assist in the prevention of pressure ulcers: A clinical comparison
International Wound Journal, EarlyView.
Surgery, radiotherapy or a combined modality for jugulotympanic paraganglioma of Fisch class C and D
Clinical Otolaryngology, Volume 0, Issue ja, -Not available-.
Foreign body granuloma treatment with 22‐MHz ultrasound‐guided corticoid infiltration
Journal of Cosmetic Dermatology, EarlyView.
Effects of four soaps on skin trans‐epidermal water loss and erythema index
Journal of Cosmetic Dermatology, EarlyView.
Τετάρτη 29 Αυγούστου 2018
Chronic ulcerative stomatitis: case series of an under‐recognized entity
Journal of Cutaneous Pathology, Volume 0, Issue ja, -Not available-.
Two‐phase delivery using a horse oil and adenosine‐loaded dissolving microneedle patch for skin barrier restoration, moisturization, and wrinkle improvement
Journal of Cosmetic Dermatology, EarlyView.
Septo‐columelloplasty ‐ anchoring the caudal septum to anterior nasal spine using a hypodermic needle as a trocar
Clinical Otolaryngology, Volume 0, Issue ja, -Not available-.
A case of cutaneous lymphoid hyperplasia after hyaluronic acid filler injection and fat grafting
Australasian Journal of Dermatology, EarlyView.
Characteristic features of neck skin aging in Chinese women
Journal of Cosmetic Dermatology, EarlyView.
A Case of Muckle‐Wells Syndrome due to novel NLRP3 mutation
JDDG: Journal der Deutschen Dermatologischen Gesellschaft, EarlyView.
A female newborn with papulovesicular lesions
JDDG: Journal der Deutschen Dermatologischen Gesellschaft, EarlyView.
Issue Information
Immunity, Inflammation and Disease, Volume 6, Issue 3, Page 371-373, September 2018.
Efficacy responses with tildrakizumab in moderate-to-severe chronic plaque psoriasis patients with previous exposure to apremilast: Results of a pooled analysis of reSURFACE 1 and reSURFACE 2
Background: Tildrakizumab (TIL) is a high-affinity anti–IL-23p19 monoclonal antibody for the treatment of chronic plaque psoriasis. We assessed a subgroup of chronic plaque psoriasis patients who reported previous treatment with apremilast (APT), a phosphodiesterase 4 inhibitor, to evaluate its potential influence on efficacy in two large, phase 3 clinical studies of tildrakizumab.
Modified purse string closure for excisional biopsy of pigmented lesions on extremities
Proper selection of biopsy technique is imperative, especially when approaching a suspicious pigmented lesion on the extremity. When possible, a complete excisional biopsy with narrow margins is preferred to prevent partial sampling and inadequate evaluation of a lesion. A vertically oriented fusiform excisional biopsy is often selected for biopsy as it preserves lymphatics and prevents circumferential scarring. In this communication, we highlight possible pitfalls of selecting a fusiform ellipse for potential melanomas and provide a patient centered step-by-step guide to the use of narrow excisional biopsy with modified purse string closure.
Impact of palmoplantar psoriasis on clinical and patient-reported outcomes: Results from the Corrona Psoriasis Registry
Objective: Palmoplantar psoriasis (PPP) is associated with a profound negative impact on patients' quality of life and is difficult to treat. The objective of this study was to assess the impact of PPP on clinical and patient reported outcomes (PROs) among patients enrolled in the Corrona Psoriasis (Pso) Registry.
Cutaneous complications associated with intraosseous access placement: A retrospective cohort study
Purpose: Intraosseous (IO) access can provide a lifesaving means of vascular access in emergency settings. Insertion sites include the tibia, humerus, and sternum. IO access allows the administration of large volumes of fluids, vasopressors, blood products and other medications at flow rates of up to 125 mL/min using a 15 or 18 gauge needle. An additional benefit of IO access is the rare incidence of complications, with many recent studies revealing rates of <1%. The most common cited complications include compartment syndrome, osteomyelitis, traumatic bone fracture, and epiphyseal plate damage.
Laterality of skin cancer in the Utah population
Background: Previous retrospective studies have reported increased frequency of both malignant melanoma (MM, using population-based SEER data) and nonmelanoma skin cancer (NMSC) on the left side of the body. Population-based studies for basal and squamous cell carcinoma (BCC and SCC) have been very difficult as a database similar to SEER does not exist for NMSC, resulting in inferences from smaller retrospective cohorts to assess laterality. As Utah has one of the highest incidences of both MM and NMSC, we explored this question for both skin cancer types using a large database of all biopsies read by the University of Utah Dermatopathology Lab over the past decade.
Fibroadenoma of ectopic breast tissue masquerading as an axillary lipoma
Fibroadenoma of the breast is the most common benign breast condition found in up to 33% of women aged 35-50. Clinically, these are firm, mobile growths within the breast measuring 1-2 cm. The differential diagnosis include cysts, tubular adenoma and phyllodes tumors. The American College of Obstetricians and Gynecologists (ACOG) notes that fibroadenoma of the breast is associated with an elevated risk factor of 1.76 for future breast cancer. The clinician can differentiate between these growths using mammography and ultrasound.
Differential facial esthetic treatment considerations for African-American, Asian, and Hispanic skin color populations
Background: By 2050, more than half the U.S. population will be African American, Asian, or Hispanic. The unique anatomic needs, esthetic goals, and cultural considerations for these growing patient populations should be evaluated to optimize treatment expectations and outcomes. A study was performed to gain insights into areas of esthetic concern, prioritization of treatment areas, and barriers to receiving injectables among these populations.
Man with a perianal ulcer, what to think?
Perianal ulcers imply a vast differential diagnosis, including in the first place squamous cell carcinoma, follow by others such as Bowen's disease, Paget disease, acuminated condyloma, metastatic gastrointestinal carcinoma, Crohn's disease, and others. We present the case of a 51-year-old man that came to the emergency room with a 5-year-evolution perianal ulcer. He referred that it started as a perianal abscess that did not improve over the time and came progressively bigger. It was always asymptomatic and did not give him any problem until 2 weeks before the consultation when it started to hurt and had some episodes of diarrhea, what motivated the consultation.
Influence of mycosis fungoides immunophenotype on prognosis, a retrospective cohort study of 160 patients
Background: Mycosis fungoides (MF) typically has a CD4+CD8− T-cell phenotype. Rare cases of CD4-CD8+, CD4-CD8− or CD4+CD8+ immunophenotypes have been described. Little is known about the impact of MF immunophenotypes on disease behavior.
Health care delivery model effects on access to dermatologic care
Introduction: In contrast to direct access (DA) health care models, gatekeeper (GK) models require a referral for specialist evaluation. Upon dermatologist evaluation, a skin biopsy may be necessary. Under the gatekeeper model, preauthorization is required to perform this procedure. This entails that the patient visit his primary care provider (PCP) to obtain authorization and a following appointment for dermatologic biopsy. This introduces a waiting time to diagnosis and treatment. This is of concern in patients with melanoma, where staging correlates with survival.
Erythema nodosum–like eruption in the setting of sorafenib therapy
Background: Sorafenib, a small molecule inhibitor of RAF kinase and VEGFR-2/PDGFR-beta, is approved for use in several cancers. Numerous cutaneous adverse events from sorafenib therapy have been reported. To the best of our knowledge, we report the first case of erythema nodosum (EN)–like eruption concurrent with sorafenib therapy.
Effectiveness of a nature-based sensitive skin regimen (NBSSR) compared with a synthetic dermatologist-recommended control regimen (CR) in subjects with clinically diagnosed sensitive skin
Background: Sensitive skin is associated with complaints of discomfort and may result from epidermal barrier impairment. An NBSSR is formulated to be safe and effective for sensitive skin.
Definition and classification of chronic prurigo: First expert consensus
Pruriginous conditions may have numerous different causes and manifest with a wide range of clinical presentations, ranging from papules to large plaques. Owing to these characteristics, a plethora of terms have been associated with prurigo without clear criteria, leading to confusion among clinicians, researchers and patients. To address this issue, specialists of the Task Force Pruritus of the European Academy of Dermatology and Venereology gathered with the aim of reaching a clear definition and classification for chronic prurigo.
Comparison of the real-world costs associated with different treatment patterns in adults initiating apremilast or biologics for the treatment of psoriasis
Background: Apremilast, an oral, nonbiologic medication, was approved by the U.S. FDA in 2014 for the treatment of adult patients with active psoriatic arthritis and patients with moderate to severe plaque psoriasis. Treatment patterns in patients with psoriasis initiating apremilast or biologics are well described in the literature. However, cost differences associated with different treatment patterns have not been described in biologic-naive patients initiating apremilast compared with biologics for treatment of psoriasis.
Combined treatment of striae using calcium hydroxylapatite, ascorbic acid delivered by microneedling, and microfocused ultrasound
Background and objective: Striae (i.e., stretch marks) are associated with the loss of collagen and reduced fibrillin and elastin in the skin. Currently available treatments are less than optimal. The objective of this retrospective study was to evaluate improvements in straie appearance after combined treatment with microneedling, topical ascorbic acid, calcium hydroxylapatite (CaHA; Merz North America), and microfocused ultrasound with visualization (MFU-V; Ulthera).
Melanoma follow-up and mortality: A large-scale study of Medicare patients
Background: Cutaneous melanoma is one of the fastest growing skin cancers in the United States, yet is highly curable when detected early. Despite the growing impact of melanoma in the United States, current research on assessing how well patients follow-up and how follow-up and socioeconomic factors affect mortality in patients with melanoma has been limited.
Long-term incidence and geographic trends of follicular lymphoma in Canada: A population-based study
Rationale: Follicular lymphoma is the most common indolent lymphoma and the second most common non-Hodgkin lymphoma. Follicular lymphoma accounts for 10%-20% of all lymphomas in the Western world. Primary cutaneous follicular B-cell lymphoma arises in the skin, while the systemic extranodal follicular lymphoma often involves the skin. Epidemiology and geographic trends of follicular lymphoma have not been investigated in Canada. Our study's objective is to analyze incidence and geographic characteristics of follicular lymphoma in Canada.
Itching for answers: Prevalence and severity of pruritus in psoriasis
Introduction: Psoriasis is a very common skin pathology worldwide. Pruritus is the most frequently reported bothersome complaint or symptom for psoriasis patients. Despite the morbidity associated with pruritus in psoriasis there are few studies evaluating the prevalence of itch in psoriasis in the current context of biologic agents. The aims of this study were to ascertain the severity, characteristics and aggravators of itch in psoriasis.
Improving stratum corneum cell cohesion and skin appearance through an advanced ultramild lamellar cleanser comprising dual lipids with triglycerides and glyceryl monooleate
Background: The introduction of moisturizing liquid cleanser is one of the most significant changes to affect the personal cleansing market in recent years. A key factor contributing to the popularity of these products is that the advanced lipid-containing cleaner can be designed to deliver significant skin care benefits over the ordinary personal cleansing products.
Hypertrophic lichen planus–like eruption secondary to pembrolizumab for metastatic melanoma
A 52-year-old man presented with a new skin eruption primarily affecting the chest, upper extremities, palms, and soles. He previously received pembrolizumab for 3 months for metastatic melanoma, the last infusion of which coincided with the onset of rash. Physical examination revealed scaly, annular erythematous to violaceous plaques predominantly located on the forearms, hands, and feet, with lesser involvement on the chest. Small white papules were present on the buccal mucosa. A punch biopsy was obtained from the left arm.
Patch testing with meropenem following a severe cutaneous adverse drug reaction
Contact Dermatitis, EarlyView.
Brainstem Steering of Locomotor Activity in the Newborn Rat
Control of locomotion relies on motor loops conveying modulatory signals between brainstem and spinal motor circuits. We investigated the steering control of the brainstem reticular formation over the spinal locomotor networks using isolated brainstem–spinal cord preparations of male and female neonatal rats. First, we performed patch-clamp recordings of identified reticulospinal cells during episodes of fictive locomotion. This revealed that a spinal ascending phasic modulation of reticulospinal cell activity is already present at birth. Half of the cells exhibited tonic firing during locomotion, while the other half emitted phasic discharges of action potentials phase locked to ongoing activity. We next showed that mimicking the phasic activity of reticulospinal neurons by applying patterned electrical stimulation bilaterally at the ventral caudal medulla level triggered fictive locomotion efficiently. Moreover, the brainstem stimuli-induced locomotor rhythm was entrained in a one-to-one coupling over a range of cycle periods (2–6 s). Additionally, we induced turning like motor outputs by either increasing or decreasing the relative duration of the stimulation trains on one side of the brainstem compared to the other. The ability of the patterned descending command to control the locomotor output depended on the functional integrity of ventral reticulospinal pathways and the involvement of local spinal central pattern generator circuitry. Altogether, this study provides a mechanism by which brainstem reticulospinal neurons relay steering and speed commands to the spinal locomotor networks.
SIGNIFICANCE STATEMENT Locomotor function allows the survival of most animal species while sustaining the expression of fundamental behaviors. Locomotor activities adapt from moment to moment to behavioral and environmental changes. We show that the brainstem can control the spinal locomotor network outputs through phasic descending commands that alternate bilaterally. Manipulating the periodicity and/or the relative durations of the left and right descending commands at the brainstem level is efficient to set the locomotor speed and sustain directional changes.
Persistent Sodium Current Drives Excitability of Immature Renshaw Cells in Early Embryonic Spinal Networks
Spontaneous network activity (SNA) emerges in the spinal cord (SC) before the formation of peripheral sensory inputs and central descending inputs. SNA is characterized by recurrent giant depolarizing potentials (GDPs). Because GDPs in motoneurons (MNs) are mainly evoked by prolonged release of GABA, they likely necessitate sustained firing of interneurons. To address this issue we analyzed, as a model, embryonic Renshaw cell (V1R) activity at the onset of SNA (E12.5) in the embryonic mouse SC (both sexes). V1R are one of the interneurons known to contact MNs, which are generated early in the embryonic SC. Here, we show that V1R already produce GABA in E12.5 embryo, and that V1R make synaptic-like contacts with MNs and have putative extrasynaptic release sites, while paracrine release of GABA occurs at this developmental stage. In addition, we discovered that V1R are spontaneously active during SNA and can already generate several intrinsic activity patterns including repetitive-spiking and sodium-dependent plateau potential that rely on the presence of persistent sodium currents (INap). This is the first demonstration that INap is present in the embryonic SC and that this current can control intrinsic activation properties of newborn interneurons in the SC of mammalian embryos. Finally, we found that 5 μm riluzole, which is known to block INaP, altered SNA by reducing episode duration and increasing inter-episode interval. Because SNA is essential for neuronal maturation, axon pathfinding, and synaptogenesis, the presence of INaP in embryonic SC neurons may play a role in the early development of mammalian locomotor networks.
SIGNIFICANCE STATEMENT The developing spinal cord (SC) exhibits spontaneous network activity (SNA) involved in the building of nascent locomotor circuits in the embryo. Many studies suggest that SNA depends on the rhythmic release of GABA, yet intracellular recordings of GABAergic neurons have never been performed at the onset of SNA in the SC. We first discovered that embryonic Renshaw cells (V1R) are GABAergic at E12.5 and spontaneously active during SNA. We uncover a new role for persistent sodium currents (INaP) in driving plateau potential in V1R and in SNA patterning in the embryonic SC. Our study thus sheds light on a role for INaP in the excitability of V1R and the developing SC.
Beyond Trial-Based Paradigms: Continuous Behavior, Ongoing Neural Activity, and Natural Stimuli
The vast majority of experiments examining perception and behavior are conducted using experimental paradigms that adhere to a rigid trial structure: each trial consists of a brief and discrete series of events and is regarded as independent from all other trials. The assumptions underlying this structure ignore the reality that natural behavior is rarely discrete, brain activity follows multiple time courses that do not necessarily conform to the trial structure, and the natural environment has statistical structure and dynamics that exhibit long-range temporal correlation. Modern advances in statistical modeling and analysis offer tools that make it feasible for experiments to move beyond rigid independent and identically distributed trial structures. Here we review literature that serves as evidence for the feasibility and advantages of moving beyond trial-based paradigms to understand the neural basis of perception and cognition. Furthermore, we propose a synthesis of these efforts, integrating the characterization of natural stimulus properties with measurements of continuous neural activity and behavioral outputs within the framework of sensory-cognitive-motor loops. Such a framework provides a basis for the study of natural statistics, naturalistic tasks, and/or slow fluctuations in brain activity, which should provide starting points for important generalizations of analytical tools in neuroscience and subsequent progress in understanding the neural basis of perception and cognition.
The Drosophila Receptor Tyrosine Kinase Alk Constrains Long-Term Memory Formation
In addition to mechanisms promoting protein-synthesis-dependent long-term memory (PSD-LTM), the process appears to also be specifically constrained. We present evidence that the highly conserved receptor tyrosine kinase dAlk is a novel PSD-LTM attenuator in Drosophila. Reduction of dAlk levels in adult α/β mushroom body (MB) neurons during conditioning elevates LTM, whereas its overexpression impairs it. Unlike other memory suppressor proteins and miRNAs, dAlk within the MBs constrains PSD-LTM specifically but constrains learning outside the MBs as previously shown. Dendritic dAlk levels rise rapidly in MB neurons upon conditioning, a process apparently controlled by the 3'UTR of its mRNA, and interruption of the 3'UTR leads to enhanced LTM. Because its activating ligand Jeb is dispensable for LTM attenuation, we propose that postconditioning elevation of dAlk within α/β dendrites results in its autoactivation and constrains formation of the energy costly PSD-LTM, acting as a novel memory filter.
SIGNIFICANCE STATEMENT In addition to the widely studied molecular mechanisms promoting protein-synthesis-dependent long-term memory (PSD-LTM), recent discoveries indicate that the process is also specifically constrained. We describe a role in PSD-LTM constraint for the first receptor tyrosine kinase (RTK) involved in olfactory memory in Drosophila. Unlike other memory suppressor proteins and miRNAs, dAlk limits specifically PSD-LTM formation as it does not affect 3 h, or anesthesia-resistant memory. Significantly, we show conditioning-dependent dAlk elevation within the mushroom body dendrites and propose that its local abundance may activate its kinase activity, to mediate imposition of PSD-LTM constraints through yet unknown mechanisms.
Identification of VAPA and VAPB as Kv2 Channel-Interacting Proteins Defining Endoplasmic Reticulum-Plasma Membrane Junctions in Mammalian Brain Neurons
Membrane contacts between endoplasmic reticulum (ER) and plasma membrane (PM), or ER-PM junctions, are ubiquitous in eukaryotic cells and are platforms for lipid and calcium signaling and homeostasis. Recent studies have revealed proteins crucial to the formation and function of ER-PM junctions in non-neuronal cells, but little is known of the ER-PM junctions prominent in aspiny regions of mammalian brain neurons. The Kv2.1 voltage-gated potassium channel is abundantly clustered at ER-PM junctions in brain neurons and is the first PM protein that functions to organize ER-PM junctions. However, the molecular mechanism whereby Kv2.1 localizes to and remodels these junctions is unknown. We used affinity immunopurification and mass spectrometry-based proteomics on brain samples from male and female WT and Kv2.1 KO mice and identified the resident ER vesicle-associated membrane protein-associated proteins isoforms A and B (VAPA and VAPB) as prominent Kv2.1-associated proteins. Coexpression with Kv2.1 or its paralog Kv2.2 was sufficient to recruit VAPs to ER-PM junctions. Multiplex immunolabeling revealed colocalization of Kv2.1 and Kv2.2 with endogenous VAPs at ER-PM junctions in brain neurons from male and female mice in situ and in cultured rat hippocampal neurons, and KO of VAPA in mammalian cells reduces Kv2.1 clustering. The association of VAPA with Kv2.1 relies on a "two phenylalanines in an acidic tract" (FFAT) binding domain on VAPA and a noncanonical phosphorylation-dependent FFAT motif comprising the Kv2-specific clustering or PRC motif. These results suggest that Kv2.1 localizes to and organizes neuronal ER-PM junctions through an interaction with VAPs.
SIGNIFICANCE STATEMENT Our study identified the endoplasmic reticulum (ER) proteins vesicle-associated membrane protein-associated proteins isoforms A and B (VAPA and VAPB) as proteins copurifying with the plasma membrane (PM) Kv2.1 ion channel. We found that expression of Kv2.1 recruits VAPs to ER-PM junctions, specialized membrane contact sites crucial to distinct aspects of cell function. We found endogenous VAPs at Kv2.1-mediated ER-PM junctions in brain neurons and other mammalian cells and that knocking out VAPA expression disrupts Kv2.1 clustering. We identified domains of VAPs and Kv2.1 necessary and sufficient for their association at ER-PM junctions. Our study suggests that Kv2.1 expression in the PM can affect ER-PM junctions via its phosphorylation-dependent association to ER-localized VAPA and VAPB.
In Spoken Word Recognition, the Future Predicts the Past
Speech is an inherently noisy and ambiguous signal. To fluently derive meaning, a listener must integrate contextual information to guide interpretations of the sensory input. Although many studies have demonstrated the influence of prior context on speech perception, the neural mechanisms supporting the integration of subsequent context remain unknown. Using MEG to record from human auditory cortex, we analyzed responses to spoken words with a varyingly ambiguous onset phoneme, the identity of which is later disambiguated at the lexical uniqueness point. Fifty participants (both male and female) were recruited across two MEG experiments. Our findings suggest that primary auditory cortex is sensitive to phonological ambiguity very early during processing at just 50 ms after onset. Subphonemic detail is preserved in auditory cortex over long timescales and re-evoked at subsequent phoneme positions. Commitments to phonological categories occur in parallel, resolving on the shorter timescale of ~450 ms. These findings provide evidence that future input determines the perception of earlier speech sounds by maintaining sensory features until they can be integrated with top-down lexical information.
SIGNIFICANCE STATEMENT The perception of a speech sound is determined by its surrounding context in the form of words, sentences, and other speech sounds. Often, such contextual information becomes available later than the sensory input. The present study is the first to unveil how the brain uses this subsequent information to aid speech comprehension. Concretely, we found that the auditory system actively maintains the acoustic signal in auditory cortex while concurrently making guesses about the identity of the words being said. Such a processing strategy allows the content of the message to be accessed quickly while also permitting reanalysis of the acoustic signal to minimize parsing mistakes.
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Publication date: Available online 25 July 2018 Source: Journal of Photochemistry and Photobiology B: Biology Author(s): Marco Ballestr...
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Editorial AJR Reviewers: Heartfelt Thanks From the Editors and Staff Thomas H. Berquist 1 Share + Affiliation: Citation: American Journal...
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https://www.youtube.com/watch?v=DFOhpBjLqN4&t=1s , Η ΘΕΡΑΠΕΙΑ ΓΙΑ ΟΛΕΣ ΤΙΣ ΑΣΘΕΝΕΙΕΣ 1 Περιεχόμενα Σύντομο βιογραφικό Πρόλογος μεταφραστ...
