Abstract
Globally, 10 million incident tuberculosis (TB) cases are reported annually; 95% of TB cases and 80% of tobacco users reside in low- and middle-income countries. Smoking approximately doubles the risk of TB disease and TB mortality. We estimated the proportion of annual incident TB cases and TB mortality attributable to tobacco smoking in 32 high TB burden countries. We obtained country-specific estimates of TB incidence, TB mortality, and smoking prevalence from the World Health Organization Global TB Report (2017), tobacco surveillance reports (2015), and the Tobacco Atlas. Risk ratios for the effect of smoking on TB incidence and TB mortality were obtained from published meta-analyses. An estimated 17.6% (95% confidence interval (CI): 8.4, 21.4) of TB cases and 15.2% (95% CI: 1.8, 31.9) of TB mortality were attributable to smoking. Among high TB burden countries, Russia had the highest proportion of smoking-attributable TB disease (31.6%, 95% CI: 15.9, 37.6) and deaths (28.1%, 95% CI: 3.8, 51.4). Men (30.3%, 95% CI: 14.7, 36.6) had a greater proportion of TB cases attributable to smoking than women (4.3, 95% CI: 1.7, 5.7). Our findings highlight the need for tobacco control in high TB burden countries to combat TB incidence and TB mortality.Σάββατο 7 Απριλίου 2018
Παρασκευή 6 Απριλίου 2018
Idiopathic facial aseptic granuloma—A diagnostic challenge in pediatric dermatology
Pediatric Dermatology, EarlyView.
Better kitchens and toilets: both needed for better health
Abstract
Both poor water, sanitation, hygiene (WaSH) and household air pollution (HAP) adversely affect the health of millions of people each year around the globe and specifically in developing countries. The objective of current work is to highlight the importance of HAP in parallel to WaSH for decision making to achieve better health specially in developing countries. There are examples, where developing countries are strengthening efforts to tackle the issue of poor water and sanitation such as 'Clean India Mission' was recently launched by the Government of India. However, there is lack of actions to address the issue related to HAP—to extend the coverage of clean fuel, efficient stoves and ventilated kitchens to the deprived population under the 'Clean India Mission'. Most of the rural household and urban slums in developing countries have only a single room, where people cook and sleep. This leads them to exposure to toxic HAP, which can be minimized by developing country specific indoor air quality guidelines and action framework. Hence, there should be policies to provide them not only the subsidy for clean fuel but also to build properly ventilated kitchens along with the promotion of clean toilets and water supplies. There is a need to strengthen global efforts, to jointly address the challenges associated with the risks related to WaSH and HAP in order to efficiently reduce the global burden of disease. Further, this will also help to timely attain the sustainable development goals for better health and environment.
Increased associated effects of topography and litter and soil nutrients on soil enzyme activities and microbial biomass along vegetation successions in karst ecosystem, southwestern China
Abstract
Studying the influence of topography and litter and soil nutrients on soil enzymes and microbial biomass is important to the understanding of soil nutrient transformation and cycling, but these relationships in heterogeneous soils of karst ecosystem remains poorly understood. We determined environment factors influencing the urease (URS) and alkaline phosphatase (ALP) activity and microbial biomass C and N (MBC and MBN) with advancing vegetation succession. The results showed that ALP increased but URS decreased with the advancing vegetation succession. The MBC and MBN were highest in shrubland, but both were lowest in grassland. The URS was positively correlated with the surface cover of rock outcrops (SRO) but negatively correlated with litter N, and soil available N and pH. Conversely, ALP was positively correlated with litter N, soil organic carbon (SOC), and soil available N and pH, but negatively correlated with soil total N. The MBC was positively related to litter quantities and SOC but negatively related to soil pH; the MBN was positively related to slope gradient (SLG), SOC, and soil total P and available P. Additionally, the trends of the index URS/MBN were grassland > secondary forest > shrubland > primary forest, but the index ALP/MBN increased with advancing vegetation succession. It indicated that soil microorganism mainly exudate extracellular URS and ALP to soils. We also found the interactions of topography (SLG and SRO), litter (nutrients and quantity), and soil (nutrients and pH) explained 42.00, 87.00, and 66.00% of the variations in URS, ALP, and microbial biomass, respectively. Path analysis showed that the topography had a directly positive effect on litter nutrients and quantities, but not on soil nutrients; the litter nutrients and quantities had direct positive effect on soil nutrients, which had direct effect on soil enzymes and microbial biomass; the relationships (R2) between the independent variable and enzymes activities and microbial biomass increased with advancing successions. Thus, it suggested that high SLG and SRO are good for collecting litters back to soils and then the topography, litter, and soil factors increased its controlling effect on soil enzymes activities and microbial biomass with advancing successions in karst ecosystem.
Techno-economic and environmental assessment of biogas production from banana peel ( Musa paradisiaca ) in a biorefinery concept
Abstract
Two scenarios for the biogas production using Banana Peel as raw material were evaluated. The first scenario involves the stand-alone production of biogas and the second scenario includes the biogas production together with other products under biorefinery concept. In both scenarios, the influence of the production scale on the process economy was assessed and feasibility limits were defined. For this purpose, the mass and energy balances were established using the software Aspen Plus along with kinetic models reported in the literature. The economic and environmental analysis of the process was performed considering Colombian economic conditions. As a result, it was found that different process scales showed great potential for biogas production. Thus, plants with greater capacity have a greater economic benefit than those with lower capacity. However, this benefit leads to high-energy consumption and greater environmental impact.
Assessment of toxicity of heavy metal-contaminated soils toward Collembola in the paddy fields supported by laboratory tests
Abstract
Effects on soil Collembola of Cu, Zn, Pb, and Cd pollution from Cu smelters over 40 years were investigated in paddy fields from an area of Eastern China. We compared the field effects to those observed in single-species laboratory tests employing the hemiedaphic collembolan Folsomia candida and the epedaphic Sinella curviseta obtained from laboratory cultures and exposed to field-collected polluted soil. The results indicated that different collembolan species responded differently to the pollution in the fields and could be divided into sensitive, indifferent, and tolerant types accordingly. The abundance of sensitive species decreased as the pollution increased, but this was not the same for indifferent and tolerant species. The dominant species changed from sensitive to tolerant species as the pollution increased. The reproduction of F. candida and S. curviseta was most sensitive to the contaminated soil compared to growth and survival; the sensitivity of the two species was similar. The growth was more sensitive than the survival for F. candida but not for S. curviseta. The growth and survival of F. candida were much more sensitive than those of S. curviseta. Sensitivity of field populations of F. candida (EC10 31 [15–46]) and hemiedaphic species Folsomia quadrioculata (EC10 52 [0.7–102]) were comparable with sensitivity of the reproduction of F. candida in the single-species tests (EC10 21 [14–27]), suggesting that single-species test based on laboratory cultures and field soil could be used to link laboratory and field data and then reflect the field situation. S. curviseta could be used as an epedaphic species in single-species tests and F. quadrioculata as an indicator species for assessment of field effect.
Vitamin D-Dependent rickets Type II with alopecia: A rare case report
Divya Vupperla, Snehal Balvant Lunge, Praveen Elaprolu
Indian Journal of Dermatology 2018 63(2):176-179
Vitamin D-dependent rickets type II is a rare hereditary disorder. It occurs due to mutations in the gene chr. 12q12-q14, which codes for vitamin D receptor. End-organ resistance to 1,25-(OH)2vitamin D3 and alopecia in severe cases are the characteristic features. We report a case of a 4-year-old boy with loss of hair over the scalp and body – first observed after 1 month of birth. The boy also developed difficulty in walking at the age of 2 year. On analysis, reduced serum calcium level (7.5 mg/dL) and elevated alkaline phosphatase level (625 IU/L) were reported. Initially, the treatment included intramuscularly administered single dose of 600,000 IU vitamin D, followed by 400 IU of vitamin D along with 1 g of supplemental calcium every day. Periodic follow-up was conducted for 2 months. Improvement was observed in the biochemical parameters and X-rays of the distal radial and ulnar metaphyses, although no improvement was observed in alopecia.
Indian Journal of Dermatology 2018 63(2):176-179
Vitamin D-dependent rickets type II is a rare hereditary disorder. It occurs due to mutations in the gene chr. 12q12-q14, which codes for vitamin D receptor. End-organ resistance to 1,25-(OH)2vitamin D3 and alopecia in severe cases are the characteristic features. We report a case of a 4-year-old boy with loss of hair over the scalp and body – first observed after 1 month of birth. The boy also developed difficulty in walking at the age of 2 year. On analysis, reduced serum calcium level (7.5 mg/dL) and elevated alkaline phosphatase level (625 IU/L) were reported. Initially, the treatment included intramuscularly administered single dose of 600,000 IU vitamin D, followed by 400 IU of vitamin D along with 1 g of supplemental calcium every day. Periodic follow-up was conducted for 2 months. Improvement was observed in the biochemical parameters and X-rays of the distal radial and ulnar metaphyses, although no improvement was observed in alopecia.
Common contact allergens in patients with palmoplantar and scalp psoriasis and impact of their avoidance on dermatology life quality index: A hospital-based study
Farhan Rasool, Saniya Akhtar, Iffat Hassan, Sumaya Zeerak, Syed Mubashir, Gousia Sheikh
Indian Journal of Dermatology 2018 63(2):160-164
Background: Scalp psoriasis and psoriasis limited to palms and/or soles have been referred to as difficult to control psoriasis. Contact allergy has long been suspected to aggravate existing lesions and cause resistance to therapy in these psoriasis variants. Objectives: The objective of the study was to assess common contact allergens in patients with palmoplantar and scalp psoriasis and the impact of their avoidance on dermatology life quality index (DLQI). Materials and Methods: A total of 54 patients with palmoplantar and scalp psoriasis were patch tested with Indian Standard Series. The patch test results were read on day 2 and day 4. DLQI was calculated before patch testing and at 1 month and 3 month in patch test positive patients after instructing allergen avoidance. Results: Sixteen out of fifty-four patients (29.62%) showed positive patch test reactions. Metal antigens like nickel and cobalt were the most common sensitizers identified. Statistically significant improvement in DLQI was observed at 1 month and at 3 month of allergen avoidance. Conclusion: Patch testing is a useful test to determine the triggering or aggravating antigens in patients with palmoplantar and scalp psoriasis and subsequent allergen avoidance should be stressed on.
Indian Journal of Dermatology 2018 63(2):160-164
Background: Scalp psoriasis and psoriasis limited to palms and/or soles have been referred to as difficult to control psoriasis. Contact allergy has long been suspected to aggravate existing lesions and cause resistance to therapy in these psoriasis variants. Objectives: The objective of the study was to assess common contact allergens in patients with palmoplantar and scalp psoriasis and the impact of their avoidance on dermatology life quality index (DLQI). Materials and Methods: A total of 54 patients with palmoplantar and scalp psoriasis were patch tested with Indian Standard Series. The patch test results were read on day 2 and day 4. DLQI was calculated before patch testing and at 1 month and 3 month in patch test positive patients after instructing allergen avoidance. Results: Sixteen out of fifty-four patients (29.62%) showed positive patch test reactions. Metal antigens like nickel and cobalt were the most common sensitizers identified. Statistically significant improvement in DLQI was observed at 1 month and at 3 month of allergen avoidance. Conclusion: Patch testing is a useful test to determine the triggering or aggravating antigens in patients with palmoplantar and scalp psoriasis and subsequent allergen avoidance should be stressed on.
Stamping a case of cutaneous adverse drug reaction: Proving beyond causality assessment
Sudip Das, Projna Biswas, Dayamay Pal, Abhishek De
Indian Journal of Dermatology 2018 63(2):99-106
Different types of skin testing with a suspected drug have been reported to be helpful in determining the cause of cutaneous adverse drug reactions (CADRs). It is of utmost importance for practicing dermatologists to have a first hand knowledge of different types of skin tests available in a case of CADR. In each suspected case, a detailed investigation with the suspected agent and correlation of the positive skin reaction with clinical variant of CADR is advocated. Drug skin tests are performed 6 weeks to 6 months after complete healing of the CADR. Drug patch tests are performed similar to the methods used in patch testing in studying contact dermatitis. The commercialized form of the drug used by the patient is tested at 30% dilution. The pure drug is tested at 10% dilution. In severe CADR, drug patch tests should be performed at lower concentrations. It is also of value to test on the most affected site of the initial CADR.
Indian Journal of Dermatology 2018 63(2):99-106
Different types of skin testing with a suspected drug have been reported to be helpful in determining the cause of cutaneous adverse drug reactions (CADRs). It is of utmost importance for practicing dermatologists to have a first hand knowledge of different types of skin tests available in a case of CADR. In each suspected case, a detailed investigation with the suspected agent and correlation of the positive skin reaction with clinical variant of CADR is advocated. Drug skin tests are performed 6 weeks to 6 months after complete healing of the CADR. Drug patch tests are performed similar to the methods used in patch testing in studying contact dermatitis. The commercialized form of the drug used by the patient is tested at 30% dilution. The pure drug is tested at 10% dilution. In severe CADR, drug patch tests should be performed at lower concentrations. It is also of value to test on the most affected site of the initial CADR.
Autoimmune progesterone dermatitis
Astuty Apurwa, Sharmila Patil, Parag Chaudhari, Nitin J Nadkarni
Indian Journal of Dermatology 2018 63(2):188-190
Indian Journal of Dermatology 2018 63(2):188-190
Unusual and interesting adverse cutaneous drug reactions
Vaishali Masatkar, Ashok Nagure, Lalit Kumar Gupta
Indian Journal of Dermatology 2018 63(2):107-116
Any drug can cause any rash! Cutaneous adverse drug reactions (CADRs) are great mimickers and can be included in the differential diagnosis of any inflammatory dermatoses. Several drugs can cause rash of similar morphology and the same drug can cause rash of different morphology. While some common and specific drug reaction patterns are recognized easily by the clinicians, many a times unusual and interesting patterns can be induced by drug(s), thus leading to erroneous diagnosis and mistreatment. This review aims to familiarize clinicians with some rare, yet interesting patterns of CADR.
Indian Journal of Dermatology 2018 63(2):107-116
Any drug can cause any rash! Cutaneous adverse drug reactions (CADRs) are great mimickers and can be included in the differential diagnosis of any inflammatory dermatoses. Several drugs can cause rash of similar morphology and the same drug can cause rash of different morphology. While some common and specific drug reaction patterns are recognized easily by the clinicians, many a times unusual and interesting patterns can be induced by drug(s), thus leading to erroneous diagnosis and mistreatment. This review aims to familiarize clinicians with some rare, yet interesting patterns of CADR.
Peutz-Jeghers syndrome: A circumventable emergency
Sourav Choudhury, Anupam Das, Priyankar Misra, Udipta Ray, Sujata Sarangi
Indian Journal of Dermatology 2018 63(2):168-171
Peutz-Jeghers syndrome (PJS) is characterized by multiple hamartomatous polyps in the gastrointestinal tract and mucocutaneous pigmentation. Here we present, a case of multiple gastrointestinal hamartomatous polyps in a 22-year-old male who had been operated for intestinal obstruction due to ileocolic intussusception. Resection of the affected segment was done with proximal ileostomy and distal mucous fistula formation. Clinicopathological diagnosis of PJS was made. Later, during ileostomy closure, it was found that the patient had a transverse colonic mass which was resected. Histological examination with immunohistochemistry confirmed it to be a Mucosa-Associated Lymphoid Tissue Lymphoma (MALToma). Colonic MALToma in the background of PJS is a unique case for which it has been reported.
Indian Journal of Dermatology 2018 63(2):168-171
Peutz-Jeghers syndrome (PJS) is characterized by multiple hamartomatous polyps in the gastrointestinal tract and mucocutaneous pigmentation. Here we present, a case of multiple gastrointestinal hamartomatous polyps in a 22-year-old male who had been operated for intestinal obstruction due to ileocolic intussusception. Resection of the affected segment was done with proximal ileostomy and distal mucous fistula formation. Clinicopathological diagnosis of PJS was made. Later, during ileostomy closure, it was found that the patient had a transverse colonic mass which was resected. Histological examination with immunohistochemistry confirmed it to be a Mucosa-Associated Lymphoid Tissue Lymphoma (MALToma). Colonic MALToma in the background of PJS is a unique case for which it has been reported.
Management of stevens-johnson syndrome-toxic epidermal necrolysis: Looking beyond guidelines!
Rajesh Kumar, Anupam Das, Sudip Das
Indian Journal of Dermatology 2018 63(2):117-124
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions, which are mainly caused by drugs; and these are usually associated with high degree of morbidity and mortality. Recently, two detailed guidelines were published on the management of SJS/TEN, Indian guidelines and UK guidelines. Still, there is no consensus on the management of SJS/TEN. In this article, our aim is to conceptualize the management aspect of SJS/TEN considering Indian setup. Early discontinuation of all medicines, supportive measures (hydration, electrolytes, and care of denuded skin), corticosteroids and cyclosporine has been found to be useful. Oral provocation test is reserved for patients, who undergo complete remission and this is to be done after hospitalization, under strict vigilance. As there is no consensus, the treatment should be individualized on case to case basis.
Indian Journal of Dermatology 2018 63(2):117-124
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions, which are mainly caused by drugs; and these are usually associated with high degree of morbidity and mortality. Recently, two detailed guidelines were published on the management of SJS/TEN, Indian guidelines and UK guidelines. Still, there is no consensus on the management of SJS/TEN. In this article, our aim is to conceptualize the management aspect of SJS/TEN considering Indian setup. Early discontinuation of all medicines, supportive measures (hydration, electrolytes, and care of denuded skin), corticosteroids and cyclosporine has been found to be useful. Oral provocation test is reserved for patients, who undergo complete remission and this is to be done after hospitalization, under strict vigilance. As there is no consensus, the treatment should be individualized on case to case basis.
Cutaneous metastasis leading to the diagnosis of carcinoma of the prostate: A rare case report and review of literature
Pritam Sureshchandra Kataria, Pradip Piraji Kendre, Apurva Ashok Patel, Sameer Dalsaniya
Indian Journal of Dermatology 2018 63(2):182-185
Prostate adenocarcinoma is a common urologic malignant neoplasm in man. Distant cutaneous metastases (CMs) of prostate carcinoma are extremely rare with a reported incidence of 0.36% and usually they occur late. Clinically, cutaneous metastasis of prostate carcinoma can mimic other skin conditions such as cellulitis, sebaceous cyst, zosteriform lesions, telangectasias, and more, resulting in a poor recognition. Few cases of true cutaneous metastatic prostate carcinoma exist in the literature. We present a case, where the first sign of carcinoma of the prostate was CM over the anterior abdominal wall. Radiological and histopathological confirmation pointed to a diagnosis of carcinoma of the prostate. The patient was treated with orchidectomy and was started on bicalutamide. After 1 month of bicalutamide therapy there was subjective decrease in the size of the metastasis. A high index of suspicion is required while evaluating the different differential diagnoses of this entity particularly in elderly patients.
Indian Journal of Dermatology 2018 63(2):182-185
Prostate adenocarcinoma is a common urologic malignant neoplasm in man. Distant cutaneous metastases (CMs) of prostate carcinoma are extremely rare with a reported incidence of 0.36% and usually they occur late. Clinically, cutaneous metastasis of prostate carcinoma can mimic other skin conditions such as cellulitis, sebaceous cyst, zosteriform lesions, telangectasias, and more, resulting in a poor recognition. Few cases of true cutaneous metastatic prostate carcinoma exist in the literature. We present a case, where the first sign of carcinoma of the prostate was CM over the anterior abdominal wall. Radiological and histopathological confirmation pointed to a diagnosis of carcinoma of the prostate. The patient was treated with orchidectomy and was started on bicalutamide. After 1 month of bicalutamide therapy there was subjective decrease in the size of the metastasis. A high index of suspicion is required while evaluating the different differential diagnoses of this entity particularly in elderly patients.
Controversies in the management of cutaneous adverse drug reactions
Yashpal Manchanda, Sudip Das, Aarti Sarda, Projna Biswas
Indian Journal of Dermatology 2018 63(2):125-130
Some cutaneous adverse drug reactions (CADRs) are severe life-threatening conditions due to multisystem involvements with a high morbidity and mortality rates ranging from 25 - 70% and require immediate medical care. But there are huge controversies regarding the management because large clinical trials are lacking. Most frequent discussion and division occur regarding the use of systemic corticosteroid as early intervention with corticosteroids controls inflammation. Corticosteroids are potent agents that target several intracellular processes to modify almost all components of inflammatory and immune responses but their impact on the long term disease course is not known. Controlled relapses of rash and hepatitis may occur as corticosteroids are tapered. A chronic HHV6 activation promoted by systemic steroids could explain these relapses. Second important issue is the use of antitubercular drugs (ATD) in case of CADR due to multidrug therapy of ATD. As both the tuberculosis and CADR are life threatening conditions and we can not spare treatment of tuberculosis for CADR, we should come to a conclusion which is not yet decided. In the same way the use of antileprotic MDT in CADR due to MDT raises a similar controversy. So, here we focus on those controversies and discuss the issues.
Indian Journal of Dermatology 2018 63(2):125-130
Some cutaneous adverse drug reactions (CADRs) are severe life-threatening conditions due to multisystem involvements with a high morbidity and mortality rates ranging from 25 - 70% and require immediate medical care. But there are huge controversies regarding the management because large clinical trials are lacking. Most frequent discussion and division occur regarding the use of systemic corticosteroid as early intervention with corticosteroids controls inflammation. Corticosteroids are potent agents that target several intracellular processes to modify almost all components of inflammatory and immune responses but their impact on the long term disease course is not known. Controlled relapses of rash and hepatitis may occur as corticosteroids are tapered. A chronic HHV6 activation promoted by systemic steroids could explain these relapses. Second important issue is the use of antitubercular drugs (ATD) in case of CADR due to multidrug therapy of ATD. As both the tuberculosis and CADR are life threatening conditions and we can not spare treatment of tuberculosis for CADR, we should come to a conclusion which is not yet decided. In the same way the use of antileprotic MDT in CADR due to MDT raises a similar controversy. So, here we focus on those controversies and discuss the issues.
Hidradenitis suppurativa: Inside and out
Sharmila Patil, Astuty Apurwa, Nitin Nadkarni, Shweta Agarwal, Parag Chaudhari, Manjyot Gautam
Indian Journal of Dermatology 2018 63(2):91-98
Hidradenitis suppurativa is a chronic, disabling, suppurative disease characterized by deep tender subcutaneous nodules; complicated by fibrosis and extensive sinuses affecting primarily the apocrine gland bearing areas. It affects all races in early 20s with greater prevalence seen in women (3 to 5:1). The estimated disease prevalence is 1 - 4 %. The disease is speculated to be caused by follicular structural abnormalities with associated risk factors as smoking, obesity, positive family history and shaving. Certain co-morbidities can also be seen such as inflammatory bowel disease, spondyloarthropathies, epithelial tumors, pyoderma gangrenosum etc. Treatment modalities include counseling of the patient to lose weight if obese, to wear loose clothes, stop smoking and maintain good hygiene. Topical antibiotics, like 1% clindamycin, have shown to give good results along with benzoyl peroxide wash. Orally cocktail of antibiotics can be given, though biologicals remain the best treatment option. Surgical excision can be done in later stages and in recalcitrant cases.
Indian Journal of Dermatology 2018 63(2):91-98
Hidradenitis suppurativa is a chronic, disabling, suppurative disease characterized by deep tender subcutaneous nodules; complicated by fibrosis and extensive sinuses affecting primarily the apocrine gland bearing areas. It affects all races in early 20s with greater prevalence seen in women (3 to 5:1). The estimated disease prevalence is 1 - 4 %. The disease is speculated to be caused by follicular structural abnormalities with associated risk factors as smoking, obesity, positive family history and shaving. Certain co-morbidities can also be seen such as inflammatory bowel disease, spondyloarthropathies, epithelial tumors, pyoderma gangrenosum etc. Treatment modalities include counseling of the patient to lose weight if obese, to wear loose clothes, stop smoking and maintain good hygiene. Topical antibiotics, like 1% clindamycin, have shown to give good results along with benzoyl peroxide wash. Orally cocktail of antibiotics can be given, though biologicals remain the best treatment option. Surgical excision can be done in later stages and in recalcitrant cases.
Evaluation of adolescents diagnosed with acne vulgaris for quality of life and psychosocial challenges
Murat Eyuboglu, Incilay Kalay, Damla Eyüboglu
Indian Journal of Dermatology 2018 63(2):131-135
Background: Acne vulgaris is a common skin condition which affects most adolescents. It has a major impact on quality of life and psychosocial well-being. Aims: The aims of the study were to examine the psychosocial effects of acne on adolescents and changes in quality of life, and to reveal any difference in the possible effect between genders. In addition, an investigation of the association between acne severity and quality of life as well as psychosocial stress was conducted. Materials and Methods: The present study included 164 adolescents with a mean age of 12–18 years and was diagnosed with acne vulgaris without any previous treatment. The control group consisted of 188 healthy volunteers. Acne severity was evaluated by the global acne grading system. All patients filled in a Children's Dermatology Life Quality Index, Pediatric Quality of Life Questionnaire (PedsQL), and a Strength and Difficulties Questionnaire (SDQ). Results: The scores of SDQ and PedsQL were significantly lower in the case group. There was no significant correlation found between the genders in the control group for acne severity and scale scores. No significant correlation was found between acne severity and psychosocial challenges. Conclusions: The results of the present study show that acne has a significant effect on quality of life for adolescents, and this has an impact on their psychosocial life. Another important finding of the present study is that worsening in quality of life is not affected by some factors such as duration, severity of acne and age.
Indian Journal of Dermatology 2018 63(2):131-135
Background: Acne vulgaris is a common skin condition which affects most adolescents. It has a major impact on quality of life and psychosocial well-being. Aims: The aims of the study were to examine the psychosocial effects of acne on adolescents and changes in quality of life, and to reveal any difference in the possible effect between genders. In addition, an investigation of the association between acne severity and quality of life as well as psychosocial stress was conducted. Materials and Methods: The present study included 164 adolescents with a mean age of 12–18 years and was diagnosed with acne vulgaris without any previous treatment. The control group consisted of 188 healthy volunteers. Acne severity was evaluated by the global acne grading system. All patients filled in a Children's Dermatology Life Quality Index, Pediatric Quality of Life Questionnaire (PedsQL), and a Strength and Difficulties Questionnaire (SDQ). Results: The scores of SDQ and PedsQL were significantly lower in the case group. There was no significant correlation found between the genders in the control group for acne severity and scale scores. No significant correlation was found between acne severity and psychosocial challenges. Conclusions: The results of the present study show that acne has a significant effect on quality of life for adolescents, and this has an impact on their psychosocial life. Another important finding of the present study is that worsening in quality of life is not affected by some factors such as duration, severity of acne and age.
Primary mucinous adenocarcinoma of skin: Myoepithelial cells are a clue to its diagnosis
Radha Sistla, Tameem Afroz, Jithendran Narayanswamy
Indian Journal of Dermatology 2018 63(2):165-167
Primary mucinous adenocarcinoma is a rare adnexal neoplasm of eccrine gland. Fewer than 200 cases are reported in literature. Clinically, it can be mistaken as a benign lesion. The primary challenge in these lesions is to differentiate these rare primary lesions from more frequent mucinous secondary deposits. Morphologically, they are similar to metastatic deposits of mucinous carcinoma from other viscera such as breast, lung, or gastrointestinal tract. Use of ancillary techniques and a thorough metastatic work up are mandatory to differentiate these lesions from metastases. We report a case of primary mucinous carcinoma of nasojugal region in a 51-year-old female. It was diagnosed on fine-needle aspiration cytology, and later, the lesion was excised and diagnosis confirmed on histopathological examination and immunohistochemistry.
Indian Journal of Dermatology 2018 63(2):165-167
Primary mucinous adenocarcinoma is a rare adnexal neoplasm of eccrine gland. Fewer than 200 cases are reported in literature. Clinically, it can be mistaken as a benign lesion. The primary challenge in these lesions is to differentiate these rare primary lesions from more frequent mucinous secondary deposits. Morphologically, they are similar to metastatic deposits of mucinous carcinoma from other viscera such as breast, lung, or gastrointestinal tract. Use of ancillary techniques and a thorough metastatic work up are mandatory to differentiate these lesions from metastases. We report a case of primary mucinous carcinoma of nasojugal region in a 51-year-old female. It was diagnosed on fine-needle aspiration cytology, and later, the lesion was excised and diagnosis confirmed on histopathological examination and immunohistochemistry.
Lipid accumulation product index as visceral obesity indicator in psoriasis: A Case–control Study
Satyaki Ganguly, Lopamudra Ray, Sheela Kuruvila, Sunil Kumar Nanda, Kandasamy Ravichandran
Indian Journal of Dermatology 2018 63(2):136-140
Background: Psoriasis has well-known associations with individual components of metabolic syndrome such as hypertension, dyslipidemia, insulin resistance, and obesity. Traditional anthropometric measurements of obesity such as waist circumference (WC) and body mass index (BMI) do not differentiate between subcutaneous fat and visceral fat, the latter being associated with cardiovascular risk factors. Lipid accumulation product (LAP) index is a measure of visceral fat and has been found to be a better predictor of cardiovascular risk. However, LAP index has not been well-studied in psoriasis patients. Aims and Objectives: Our objective was to find out if LAP index differs significantly between psoriasis patients and controls and whether LAP index shows a correlation with duration and severity of psoriasis. Materials and Methods: A case–control study was undertaken with 40 chronic plaque psoriasis patients and 42 controls. BMI and LAP index were calculated for all the patients and controls. Psoriasis area severity index (PASI) was calculated for all the psoriasis patients. Mann–Whitney U-test was done for comparing the age, BMI, WC, serum triglyceride, and LAP index between the cases and controls and to compare the LAP index between mild psoriasis and moderate-to-severe psoriasis groups. Spearman's correlation coefficient was used to assess the correlation of LAP index with duration of psoriasis and with PASI. Logistic regression models were done to assess the risk factors in psoriasis. Results: A statistically significant difference was observed between the LAP index of controls (23.79 ± 13.02) and that of psoriasis patients (46.42 ± 27.2). LAP index was significantly higher in the moderate-to-severe psoriasis group as compared to the mild psoriasis group. LAP index was a significant risk factor associated with psoriasis (OR = 1.07; 95% CI: 1.03 – 1.11). Conclusion: Calculation of LAP index in psoriasis patients helps in identification of more individuals at high risk of cardiovascular morbidity than traditional anthropometric measurements of obesity.
Indian Journal of Dermatology 2018 63(2):136-140
Background: Psoriasis has well-known associations with individual components of metabolic syndrome such as hypertension, dyslipidemia, insulin resistance, and obesity. Traditional anthropometric measurements of obesity such as waist circumference (WC) and body mass index (BMI) do not differentiate between subcutaneous fat and visceral fat, the latter being associated with cardiovascular risk factors. Lipid accumulation product (LAP) index is a measure of visceral fat and has been found to be a better predictor of cardiovascular risk. However, LAP index has not been well-studied in psoriasis patients. Aims and Objectives: Our objective was to find out if LAP index differs significantly between psoriasis patients and controls and whether LAP index shows a correlation with duration and severity of psoriasis. Materials and Methods: A case–control study was undertaken with 40 chronic plaque psoriasis patients and 42 controls. BMI and LAP index were calculated for all the patients and controls. Psoriasis area severity index (PASI) was calculated for all the psoriasis patients. Mann–Whitney U-test was done for comparing the age, BMI, WC, serum triglyceride, and LAP index between the cases and controls and to compare the LAP index between mild psoriasis and moderate-to-severe psoriasis groups. Spearman's correlation coefficient was used to assess the correlation of LAP index with duration of psoriasis and with PASI. Logistic regression models were done to assess the risk factors in psoriasis. Results: A statistically significant difference was observed between the LAP index of controls (23.79 ± 13.02) and that of psoriasis patients (46.42 ± 27.2). LAP index was significantly higher in the moderate-to-severe psoriasis group as compared to the mild psoriasis group. LAP index was a significant risk factor associated with psoriasis (OR = 1.07; 95% CI: 1.03 – 1.11). Conclusion: Calculation of LAP index in psoriasis patients helps in identification of more individuals at high risk of cardiovascular morbidity than traditional anthropometric measurements of obesity.
A tale of H syndrome with typical radiographic findings
Praneet Pradeep Awake, Lakshmi Chandravathi Penmetcha, Anil Fonseca, Prasad Prabhakar Jawalkar
Indian Journal of Dermatology 2018 63(2):172-175
H syndrome is a recently described autosomal recessive genodermatosis with cutaneous phenotypes of varying severity and multi-system involvement. Patients suffering from this disorder can be easily mistaken for sclerodermoid conditions. The radiological findings of H syndrome are typical but have been described only anecdotally. We present a case of a 29 year old male patient of H syndrome with typical radiological features.
Indian Journal of Dermatology 2018 63(2):172-175
H syndrome is a recently described autosomal recessive genodermatosis with cutaneous phenotypes of varying severity and multi-system involvement. Patients suffering from this disorder can be easily mistaken for sclerodermoid conditions. The radiological findings of H syndrome are typical but have been described only anecdotally. We present a case of a 29 year old male patient of H syndrome with typical radiological features.
A study of onychomycosis at a tertiary care hospital in Eastern Bihar
Anindita Sen, Deblina Bhunia, Pijush Kanti Datta, Atanu Ray, Parthajit Banerjee
Indian Journal of Dermatology 2018 63(2):141-146
Background: Onychomycosis (OM) is a major public health problem which is increasing worldwide. It is associated with high morbidity and causes physical, psychological, and occupational problems in patients. Aims: This study aims to study the pattern of etiological agents, clinical features, and severity assessment of OM in this part of India. Materials and Methods: Sixty eight clinically suspected patients with positive potassium hydroxide and fungal culture were studied. Results: Males were infected more often than females (1.61:1). The most common age group affected was 21–40 years. Finger nails were affected more frequently than toe nails. Distal and lateral subungual OM was the most common (48 cases, 70.59%) clinical pattern. For most of the patients (66.18%), nail involvement was severe. Discoloration was the most common (67 cases, 98.53%) change, followed by subungual hyperkeratosis (51 cases, 75%). Principal causative agents were dermatophytes (55 cases, 80.88%) with Trichophyton rubrum being the most common one (35 cases, 51.47%). In 9 (13.23%) cases, Candida albicans, in 6 (8.82%) Aspergillus niger and in 1 (1.47%) case Acremonium sp. (AC) have been isolated as the sole causative agent. In 2 (2.94%) cases, mixed infection with dermatophyte and Aspergillus and in 1 (1.47%) case dermatophyte and Candida were noted. Conclusion: Although dermatophytes were the most common causative agent of OM, nondermatophytic molds, and yeasts were also encountered. The genus and species identification helps in the proper diagnosis and management. Morphological changes in nail may help in presumptive diagnosis of OM.
Indian Journal of Dermatology 2018 63(2):141-146
Background: Onychomycosis (OM) is a major public health problem which is increasing worldwide. It is associated with high morbidity and causes physical, psychological, and occupational problems in patients. Aims: This study aims to study the pattern of etiological agents, clinical features, and severity assessment of OM in this part of India. Materials and Methods: Sixty eight clinically suspected patients with positive potassium hydroxide and fungal culture were studied. Results: Males were infected more often than females (1.61:1). The most common age group affected was 21–40 years. Finger nails were affected more frequently than toe nails. Distal and lateral subungual OM was the most common (48 cases, 70.59%) clinical pattern. For most of the patients (66.18%), nail involvement was severe. Discoloration was the most common (67 cases, 98.53%) change, followed by subungual hyperkeratosis (51 cases, 75%). Principal causative agents were dermatophytes (55 cases, 80.88%) with Trichophyton rubrum being the most common one (35 cases, 51.47%). In 9 (13.23%) cases, Candida albicans, in 6 (8.82%) Aspergillus niger and in 1 (1.47%) case Acremonium sp. (AC) have been isolated as the sole causative agent. In 2 (2.94%) cases, mixed infection with dermatophyte and Aspergillus and in 1 (1.47%) case dermatophyte and Candida were noted. Conclusion: Although dermatophytes were the most common causative agent of OM, nondermatophytic molds, and yeasts were also encountered. The genus and species identification helps in the proper diagnosis and management. Morphological changes in nail may help in presumptive diagnosis of OM.
Chronic cutaneous lupus erythematosus in a blaschkoid pattern over face
Manju Meena, Manisha Balai, Sharad Mehta, Garima Bharti
Indian Journal of Dermatology 2018 63(2):180-181
Linear lesions following the lines of Blaschko of chronic cutaneous lupus erythematosus is a highly unusual variant of cutaneous lupus, particularly in adult. The lesions are restricted to one anatomical site with facial predilection in most of the reported cases. We herein, report a case of chronic cutaneous lupus erythematosus due to rarity of presentation and later age of onset.
Indian Journal of Dermatology 2018 63(2):180-181
Linear lesions following the lines of Blaschko of chronic cutaneous lupus erythematosus is a highly unusual variant of cutaneous lupus, particularly in adult. The lesions are restricted to one anatomical site with facial predilection in most of the reported cases. We herein, report a case of chronic cutaneous lupus erythematosus due to rarity of presentation and later age of onset.
Conventional versus giant basal cell carcinoma, a review of 57 Cases: Histologic differences contributing to excessive growth
J Chase Purnell, Jerad M Gardner, J Ahmad Brown, Sara C Shalin
Indian Journal of Dermatology 2018 63(2):147-154
Background: Giant basal cell carcinoma (GBCC) is defined as a basal cell carcinoma (BCC) exceeding 5 cm in size. While these tumors impart significant morbidity due to local tissue destruction and have a higher rate of metastatic disease than their conventional (smaller) counterparts, reasons for their large size remain unclear. While theories relating to neglect or faster growth rate are often invoked; to date, there has not been a comprehensive evaluation of the histologic features of these large tumors that may contribute to their size. Methods: Histologic features of GBCCs (n = 29) were evaluated and compared to those of conventional BCC (n = 28). Available clinical demographic data were also reviewed. Results: GBCCs, in addition to overall larger size, more often were thicker, displayed ulceration, and showed a more infiltrative growth pattern than their conventional counterparts. These rare tumors also displayed an insignificant increased propensity for a brisk host immune response, and the infiltrate significantly more often included clusters of plasma cells. Conclusions: Most histologic features seen in GBCCs likely reflect their large size. Histologic features alone are unlikely to explain the size of these rare tumors. The possibility of an altered host immune response contributing to the growth of these tumors requires further investigation.
Indian Journal of Dermatology 2018 63(2):147-154
Background: Giant basal cell carcinoma (GBCC) is defined as a basal cell carcinoma (BCC) exceeding 5 cm in size. While these tumors impart significant morbidity due to local tissue destruction and have a higher rate of metastatic disease than their conventional (smaller) counterparts, reasons for their large size remain unclear. While theories relating to neglect or faster growth rate are often invoked; to date, there has not been a comprehensive evaluation of the histologic features of these large tumors that may contribute to their size. Methods: Histologic features of GBCCs (n = 29) were evaluated and compared to those of conventional BCC (n = 28). Available clinical demographic data were also reviewed. Results: GBCCs, in addition to overall larger size, more often were thicker, displayed ulceration, and showed a more infiltrative growth pattern than their conventional counterparts. These rare tumors also displayed an insignificant increased propensity for a brisk host immune response, and the infiltrate significantly more often included clusters of plasma cells. Conclusions: Most histologic features seen in GBCCs likely reflect their large size. Histologic features alone are unlikely to explain the size of these rare tumors. The possibility of an altered host immune response contributing to the growth of these tumors requires further investigation.
Perforating calcific elastosis: Revisiting a rare entity
Niharika Ranjan Lal, Debabrata Bandyopadhyay, Rachna Verma, Anjani Kumar Shukla
Indian Journal of Dermatology 2018 63(2):186-188
Indian Journal of Dermatology 2018 63(2):186-188
Antimicrobial susceptibility of tinea capitis in children from Egypt
Reham William Doss, Abdel-Aziz El-Rifaie, Nagla Radi, Aya Yehia El-Sherif
Indian Journal of Dermatology 2018 63(2):155-159
Background: Dermatophytic fungi of genera Trichophyton and Microsporum are the most important fungal species causing tinea capitis. Choice of treatment for tinea capitis is determined by the species of fungus. Aim: The aim of the study was to investigate the most prevalent fungal species causing tinea capitis in children from Egypt and the most useful antifungal agent for treatment. Patients and Methods: A total of 100 patients diagnosed clinically with tinea capitis were included in the study. Samples were collected and sent to the microbiology and immunology laboratory for sample processing and fungal identification by routine laboratory techniques. A study of antifungal susceptibility to chosen antifungal medications (fluconazole, ketoconazole, clotrimazole, miconazole, amphotericin, caspofungin, itraconazole, terbinafine, and griseofulvin) was done by minimum inhibitory concentration technique. Results: Our analysis revealed that Microsporum canis is the most commonly isolated strain. Amphotericin was the most effective antifungal agent followed by terbinafine. The most sensitive strain to fluconazole and griseofulvin is Microsporum gypseum, while Microsporum audouinii was mostly responsive to terbinafine. Conclusion: Identification and evaluation of the antifungal susceptibility of the pathogenic species in a certain geographic region is important to achieve a good clinical response.
Indian Journal of Dermatology 2018 63(2):155-159
Background: Dermatophytic fungi of genera Trichophyton and Microsporum are the most important fungal species causing tinea capitis. Choice of treatment for tinea capitis is determined by the species of fungus. Aim: The aim of the study was to investigate the most prevalent fungal species causing tinea capitis in children from Egypt and the most useful antifungal agent for treatment. Patients and Methods: A total of 100 patients diagnosed clinically with tinea capitis were included in the study. Samples were collected and sent to the microbiology and immunology laboratory for sample processing and fungal identification by routine laboratory techniques. A study of antifungal susceptibility to chosen antifungal medications (fluconazole, ketoconazole, clotrimazole, miconazole, amphotericin, caspofungin, itraconazole, terbinafine, and griseofulvin) was done by minimum inhibitory concentration technique. Results: Our analysis revealed that Microsporum canis is the most commonly isolated strain. Amphotericin was the most effective antifungal agent followed by terbinafine. The most sensitive strain to fluconazole and griseofulvin is Microsporum gypseum, while Microsporum audouinii was mostly responsive to terbinafine. Conclusion: Identification and evaluation of the antifungal susceptibility of the pathogenic species in a certain geographic region is important to achieve a good clinical response.
Multiple eruptive clear cell acanthoma
Sha Zhou, Jianjun Qiao, Juan Bai, Yinhua Wu, Xiaoling Jiang, Yunlei Pan, Lina Xu, Hong Fang
Indian Journal of Dermatology 2018 63(2):190-192
Indian Journal of Dermatology 2018 63(2):190-192
Treatment of nevoid hyperkeratosis of the areola and nipple with topical tacalcitol: A case report
Dermatologic Therapy, EarlyView.
Reconstruction of a buttock defect after excision of inflammatory linear verrucous epidermal nevus
Dermatologic Therapy, EarlyView.
Morphological and genetical changes of endothelial progenitor cells after in-vitro conversion into photoreceptors
Publication date: Available online 6 April 2018
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): Shi Qiang, Hiba Amer Alsaeedi, Cheng Yuhong, Hao Yang, Li Tong, Suresh Kumar, Akon Higuchi, Abdullah A. Alarfaj, Rusheni Munisvaradass, Mok Pooi Ling, Pei Cheng
BackgroundRetinal degeneration is a condition ensued by various ocular disorders such as artery occlusion, diabetic retinopathy, retrolental fibroplasia and retinitis pigmentosa which cause abnormal loss of photoreceptor cells and lead to eventual vision impairment. No efficient treatment has yet been found, however, the use of stem cell therapy such as bone marrow and embryonic stem cells has opened a new treatment modality for retinal degenerative diseases. The major goal of this study is to analyze the potential of endothelial progenitor cells derived from bone marrow to differentiate into retinal neural cells for regenerative medicine purposes.MethodsIn this study, endothelial progenitor cells were induced in-vitro with photoreceptor growth factor (taurine) for 21 days. Subsequently, the morphology and gene expression of CRX and RHO of the photoreceptors-induced EPCs were examined through immunostaining assay.FindingsThe results indicated that the induced endothelial progenitor cells demonstrated positive gene expression of CRX and RHO. Our findings suggested that EPC cells may have a high advantage in cell replacement therapy for treating eye disease, in addition to other neural diseases, and may be a suitable cell source in regenerative medicine for eye disorders.
Chemically synthesized butein and butin: Optical, structure and electrochemical redox functionality at electrode interface
Publication date: Available online 6 April 2018
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): Priya Darshani, Manju Bhargavi Gumpu, Prasanth Thumpati, John Bosco Balaguru Rayappan, Velayutham Ravichandiran, Gururaja Perumal Pazhani, Murugan Veerapandian
Progress in the development of phytochemistry has delivered advancement in materials functionality for range of inter/trans-disciplinary application. Here, we investigated the structural functionality of chemically synthesized phytoconstitutent, chalcone (butein) and flavanone (butin). Photoactive and electroactive behavior of butein and butin were comprehensively studied using UV–vis absorbance, photoluminescence and cyclic voltammetric techniques. Surface morphology of the butein and butin powders was characterized from scanning electron microscope at an operating voltage of 10 kV. Significant ultraviolet absorbance property are observed from butein and butin due to the distribution of π → π* and n → π* transitions. Photoluminescence emission spectra of the prepared materials are well resolved at visible region via keto-enol tautomerization and can be influenced by solvent pH. Cyclic voltammetric studies on the prepared materials enabled a direct electron-transfer reaction at gold-screen printed electrode, indicating the feasibility for analytical validation in herbal industries. Existence of multiple electroactive hydroxyl groups makes butein and butin a redox-functional species at electrode interface. Dispersion ability in aqueous and organic solvents makes butein and butin suitable for variety of photochemical applications. This phytochemical material offers new degrees of optical and redox functionality similar to inorganic nanostructures, in addition to inherent bioactivity, that may be advantageous for further biomedical function.
Graphical abstract
MiR-340/iASPP axis affects UVB-mediated retinal pigment epithelium (RPE) cell damage
Publication date: Available online 6 April 2018
Source:Journal of Photochemistry and Photobiology B: Biology
Author(s): Jiazhao Yan, Yuhui Qin, Jingsheng Yu, Qinghua Peng, Xiangdong Chen
Long-term exposure to ultraviolet B (UVB) light increases the risk of UVB damage due to increased UVB absorption by the retina and may further lead to age-related eye diseases. The retinal pigment epithelium (RPE) cell is a main target of UVB reaching the retina; its degeneration is an essential event in UVB-mediated age-related macular degeneration (AMD). Herein, we first evaluated the expression and effect of iASPP, an inhibitory regulator of apoptosis, in UVB-induced RPE cell damage. Through the mechanism of RNA interference at the post-transcriptional level, miRNA affects a variety of cellular processes, including UVB-mediated cell damage. We next screened for upstream candidate miRNAs that may regulate iASPP expression. Among 8 candidate miRNAs, UVB significantly increased miR-340 levels. We also confirmed the direct binding of miR-340 to the 3′UTR of iASPP, and assessed the combined effect of miR-340 and iASPP on UVB-induced RPE cell damage. Taken together, we demonstrated the possible mechanisms involved in UVB-induced retinal damage. In RPE cells, UVB irradiation inhibits iASPP expression through inducing miR-340 expression, thereby promoting RPE cell apoptosis and suppressing cell viability via affecting p53, p21 and caspase-3 protein expression. Targeting miR-340 to rescue iASPP expression in RPE cells may help treat UVB-mediated retinal damage.
Behaviors of active sunbeds users and their knowledge on the potential health risks; results of cross‐sectional study in Poland
Journal of Cosmetic Dermatology, EarlyView.
Automated muscle segmentation from CT images of the hip and thigh using a hierarchical multi-atlas method
Abstract
Purpose
Patient-specific quantitative assessments of muscle mass and biomechanical musculoskeletal simulations require segmentation of the muscles from medical images. The objective of this work is to automate muscle segmentation from CT data of the hip and thigh.
Method
We propose a hierarchical multi-atlas method in which each hierarchy includes spatial normalization using simpler pre-segmented structures in order to reduce the inter-patient variability of more complex target structures.
Results
The proposed hierarchical method was evaluated with 19 muscles from 20 CT images of the hip and thigh using the manual segmentation by expert orthopedic surgeons as ground truth. The average symmetric surface distance was significantly reduced in the proposed method (1.53 mm) in comparison with the conventional method (2.65 mm).
Conclusion
We demonstrated that the proposed hierarchical multi-atlas method improved the accuracy of muscle segmentation from CT images, in which large inter-patient variability and insufficient contrast were involved.
Exposure of Escherichia coli to human hepcidin results in differential expression of genes associated with iron homeostasis and oxidative stress
Abstract
Hepcidin belongs to the antimicrobial peptide family but has weak activity with regards to bacterial killing. The regulatory function of hepcidin in humans serves to maintain an iron-restricted environment that limits the growth of pathogens; this study explored whether hepcidin affected bacterial iron homeostasis and oxidative stress using the model organism Escherichia coli. Using the Miller assay it was determined that under low iron availability exposure to sub-inhibitory doses of hepcidin (4 -12μM) led to 2-fold and 4-fold increases in the expression of ftnA and bfd respectively (p < 0.05), in both a wild type (WT) and Δfur (ferric uptake regulator) background. Quantitative real-time PCR analysis of oxyR and sodA, treated with 4 or 8μM of hepcidin showed that expression of these genes was significantly (p < 0.05) increased, whereas expression of lexA was unchanged, indicating that hepcidin likely mediated oxidative stress but did not induce DNA damage.Expanding Treatment Options for Injectable Agents
Abstract
Loss of facial volume and soft-tissue support are common to types of facial aging. Restoration of a youthful appearance relies upon correction of this loss, and can be achieved in various capacities through use of biostimulatory or hyaluronic acids (HA) injectable fillers. Here, the authors discuss the versatility of calcium hydroxylapatite (CaHA) in volume replacement and the applications and facial regions for which CaHA, poly-L-lactic acid (PLLA), and HA fillers are best suited.Differentiating Nonpermanent Injectable Fillers: Prevention and Treatment of Filler Complications
Abstract
Though the incidence of complications and adverse events with dermatological fillers is inherently low, practitioners should be well versed in both prevention of filler complications and the treatment algorithms for addressing "granulomas," nodules, infection, and vascular compromise. Appropriate preventative measures, coupled with timely and effective treatment, are critically important for patient safety and satisfaction. In addition to the preventive measures and treatment algorithms outlined here, the authors emphasize that the broad classification and treatment of nodules as "granulomas" is likely to lead to ineffective treatment, or worse, unnecessary exposure to incorrect treatment. In practice, nodules are classified and treated based on clinical manifestation (eg, late vs early or noninflammatory vs inflammatory) rather than on histology. Indeed, classification of a nodule as a granuloma requires a histological examination, rarely available (or necessary) in clinical practice to guide treatment. Thus, the apparent inflammatory nature of the nodule and the time of onset should drive treatment approach. The treatment algorithms presented here are based on these clinically meaningful parameters.Physiochemical Characteristics of Poly-L-Lactic Acid (PLLA)
Abstract
Poly-L-lactic acid (PLLA) is a synthetic, biocompatible, biodegradable polymer. For soft-tissue augmentation, the size and chemical attributes of the PLLA microparticles are central to this agent's ability to promote a subclinical inflammatory response that stimulates deposition of collagen in the extracellular matrix. The resultant restoration of facial volume occurs in a controlled, predictable manner and is long lasting. The unique physiochemical and biostimulatory properties of PLLA differentiate it from other available treatments and are the foundation of the unique treatment methodology required for optimal results.Calcium Hydroxyapatite (CaHA) Indication for Hand Rejuvenation
Abstract
The recent approval in 2015 of Radiesse for injection into the hand by the FDA has spurred an increase in interest among patients and clinicians in nonsurgical hand rejuvenation using fillers. Application of the same techniques used to treat the face to the dorsum of the hands does not account for the unique nature of the skin and underlying anatomy, and can lead to suboptimal outcomes and an increased risk of adverse events such as the formation of nodules. Here, the authors discuss dilution strategies and injection techniques for hand rejuvenation using Radiesse for optimal patient safety and aesthetic outcomes.Composite Facial Volumization With Calcium Hydroxylapatite (CaHA) for the Treatment of Aging
Abstract
Paradigms in the treatment of aging have evolved to address volume loss as a central and primary hallmark of the aging face. The concept of "composite volumization" was recently proposed by Dr. Z. Paul Lorenc to describe the effect of Radiesse (Merz Aesthetics, Inc., Raleigh, NC), when placed on bone in the supraperiosteal plane, on all overlying tissues (skin, superficial and deep fat compartments, and muscle). The physiochemical properties of Radiesse make it especially well suited for efficient and effective volumization of areas especially prone to volume loss; the temple, zygomatic arch, anterior cheek, pyriform aperture, and prejowl sulcus. Placement of Radiesse on bone in these areas creates a scaffold upon which additional restoration of fine lines and wrinkles may be accomplished, restoring a youthful appearance.Physiochemical Characteristics of Calcium Hydroxylapatite (CaHA)
Abstract
The clinical performance of fillers in soft tissue augmentation depends upon their physiochemical properties, anatomical areas injected, interaction with the recipient, and the skill and experience of the physician. Scientific measures of filler properties facilitate appropriate selection of treatments for optimal treatment outcomes, and inform adjustments to treatments that improve patient safety and aesthetic outcomes. The rheological properties of calcium hydroxylapatite (CaHA), elastic modulus (G') and viscosity, coupled with its capacity to offer both immediate results and continued stimulation of collagen type I deposition, support its distinction as an ideal treatment for the volume loss characteristic of aging. Furthermore, the comparatively higher G' of CaHA offers a physiochemical basis for the clinical performance observed by the authors, especially in regions such as the temple and chin, where the force exerted by CaHA against bone permits expansion of overlaying tissue, permitting it to behave as a liquid implant.BI1 is associated with microvascular protection in cardiac ischemia reperfusion injury via repressing Syk–Nox2–Drp1-mitochondrial fission pathways
Abstract
Background
Mitochondrial fission has been identified as the pathogenesis underlying the development of cardiac microvascular ischemia reperfusion (IR) injury, although the regulatory signaling upstream from fission is far from clear. Bax inhibitor is a novel anti-apoptotic factor, and, however, its role of cardiac microvascular IR injury and mitochondrial homeostasis remains unclear.
Methods
The cardiac microvascular IR injury was performed in WT mice and BI1 transgenic (BITG ) mice. The alterations of microvascular structure and function were detected via electron microscope, immunohistochemistry and immunofluorescence in vivo. Cardiac microvascular endothelial cells were isolated form WT and BITG mice and underwent hypoxia/reoxygenation injury in vitro. Cellular viability and apoptosis were analyzed via MTT assay and caspase-3 activity. Mitochondrial function, morphology and apoptosis were detected. Signaling pathways were analyzed via inhibitor, siRNA and mutant plasmid.
Results
Herein, we demonstrated that Bax inhibitor 1 (BI1) was downregulated following cardiac microvascular IR injury, and its expression correlated negatively with microvascular collapse, endothelial cell apoptosis and mitochondrial damage. However, compared to wild-type mice, BI1 transgenic mice were actually protected from the acute microvascular injury and mitochondrial dysfunction. Functional studies illustrated that reintroduced BI1 directly interacted with and inhibited the Syk pathway, leading to the inactivation of Nox2. Subsequently, less Nox2 was associated with ROS downregulation, inhibiting Drp1 phosphorylated activation. Through repression of the Syk–Nox2–Drp1 signaling axis, BI1 strongly disrupted mitochondrial fission, abolishing mitochondrial apoptosis and thus sustaining endothelial cell viability.
Conclusions
In summary, our report illustrates that BI1 functions as a novel microvascular guardian in cardiac IR injury that operates via inhibition of the Syk–Nox2–Drp1-mitochondrial fission signaling axis. Thus, novel therapeutic strategies to regulate the balance between BI1 and mitochondrial fission could provide a survival advantage to microvasculature following IR stress.
Community response to a sustainable restoration plan for a superfund site
Abstract
Large-scale copper (Cu) mining activities in Michigan's Upper Peninsula produced millions of metric tons of mining wastes also known as stamp sands. The stamp sands containing high concentrations of Cu were disposed of into several lakes connected to the Lake Superior. Eventually, as aquatic organisms in these lakes started to exhibit toxicity symptoms, the stamp sands were dredged and discarded on the lake shores. Consequently, these areas turned into degraded, marginal lands and were collectively classified as a Torch Lake Superfund site by the US EPA. Due to the lack of vegetative cover, the Cu-rich stamp sands eroded into the lakes, affecting the aquatic life. To alleviate this issue, a sustainable restoration plan (SRP) was developed and tested in a greenhouse environment prior to field implementation. Cold-tolerant oilseed crops, camelina (Camelina sativa) and field pennycress (Thlaspi arvense), were grown on compost-fertilized stamp sands, which reduced soil erosion by acting as a vegetative cap. Oilseed plants produced normal yield, demonstrating their potential utilization as biofuel feedstock. Prior to implementing the SRP in field-scale in the Torch Lake Superfund site, a public opinion survey of the local community was conducted to understand the views of residents. Door-to-door survey was performed in July–August 2015, which yielded a response rate of 68.1%. Results showed that residents were generally concerned with stamp sand erosion into the Torch Lake and were overwhelmingly supportive of the SRP, which would not only provide environmental benefits but could boost the local economy via biofuel production. To gauge the general environmental awareness of the respondents, the survey included questions on climate change. Most of the respondents acknowledged that climate change is real and anthropogenically mediated. Having college education and a relatively high annual household income showed a positive and significant correlation with climate change awareness.
Moving beyond surveys to assess patient preferences
Publication date: Available online 5 April 2018
Source:Journal of the American Academy of Dermatology
Author(s): Clifford S. Perlis
Πέμπτη 5 Απριλίου 2018
Radiation induces age-dependent deficits in cortical synaptic plasticity
Abstract
Background
Radiation-induced cognitive dysfunction is a significant side effect of cranial irradiation for brain tumors. Clinically, pediatric patients are more vulnerable than adults. However, the underlying mechanisms of dysfunction, including reasons for age dependence, are still largely unknown. Previous studies have focused on the loss of hippocampal neuronal precursor cells and deficits in memory. However, survivors may also experience deficits in attention, executive function, or other non-hippocampal–dependent cognitive domains. We hypothesized that brain irradiation induces age-dependent deficits in cortical synaptic plasticity. Methods
In vivo recordings were used to test neuronal plasticity along the direct pathway from the CA1/subicular region to the prefrontal cortex (PFC). Specifically, long-term potentiation (LTP) in the CA1/subicular-PFC pathway was assessed after cranial irradiation of juvenile and adult Sprague Dawley rats. We further assessed a potential role for glutamate toxicity by evaluating the potential neuroprotective effects of memantine. Results
LTP was greatly inhibited in both adult and juvenile animals at 3 days after radiation but returned to near-normal levels by 8 weeks—only in adult rats. Memantine given before, but not after, irradiation partially prevented LTP inhibition in juvenile and adult rats. Conclusion
Cranial radiation impairs neuroplasticity along the hippocampal-PFC pathway; however, its effects vary by age. Pretreatment with memantine offered protection to both juvenile and adult animals. Deficits in cortical plasticity may contribute to radiation-induced cognitive dysfunction, including deficits in attention and age-dependent sensitivity of such pathways, which may underlie differences in clinical outcomes between juveniles and adults after cranial irradiation.Validation of post-operative residual contrast enhancing tumor volume as an independent prognostic factor for overall survival in newly diagnosed glioblastoma
Abstract
Background
In the current study, we pooled imaging data in newly diagnosed GBM patients from international multicenter clinical trials, single institution databases, and multicenter clinical trial consortiums to identify the relationship between post-operative residual enhancing tumor volume and overall survival (OS). Methods
Data from 1,511 newly diagnosed GBM patients from 5 data sources were included in the current study: 1) a single institution database from UCLA (N=398; Discovery); 2) patients from the Ben and Cathy Ivy Foundation for Early Phase Clinical Trials Network Radiogenomics Database (N=262 from 8 centers; Confirmation); 3) the chemoradiation placebo arm from an international phase III trial (AVAglio; N=394 from 120 locations in 23 countries; Validation); 4) the experimental arm from AVAglio examining chemoradiation plus bevacizumab (N=404 from 120 locations in 23 countries; Exploratory Set 1); and 5) an Alliance (N0874) Phase I/II trial of vorinostat plus chemoradiation (N=53; Exploratory Set 2). Post-surgical, residual enhancing disease was quantified using T1 subtraction maps. Multivariate Cox regression models were used to determine influence of clinical variables, MGMT status, and residual tumor volume on OS. Results
A log-linear relationship was observed between post-operative, residual enhancing tumor volume and OS in newly diagnosed GBM treated with standard chemoradiation. Post-operative tumor volume is a prognostic factor for OS (P<0.01), regardless of therapy, age, and MGMT promoter methylation status. Conclusion
Post-surgical, residual contrast-enhancing disease significantly negatively influences survival in patients with newly diagnosed glioblastoma treated with chemoradiation with or without concomitant experimental therapy.Modeling the diffusion of D-2-hydroxyglutarate from IDH1 mutant gliomas in the central nervous system
Abstract
Background
20-30% of diffusely infiltrative gliomas in adults contain a point mutation in isocitrate dehydrogenase 1 (IDH1mut), which increases production of D-2-hydroxyglutarate (D2HG). This is so efficient that D2HG often reaches 30 mM within IDH1mut gliomas. Yet, while up to 100 µM D2HG can be detected in the circulating cerebrospinal fluid of IDH1mut glioma patients, the exposure of nonneoplastic cells within and surrounding an IDH1mut glioma to D2HG is unknown and difficult to measure directly. Methods
Conditioned medium from patient-derived IDH1wt and IDH1mut glioma cells was analyzed for D2HG by liquid chromatography-mass spectrometry (LC-MS). Mathematical models of D2HG release and diffusion around an IDH1mut glioma were independently generated based on fluid dynamics within the brain, and on previously reported intratumoral and cerebrospinal D2HG concentrations. Results
LC-MS analysis indicates that patient-derived IDH1mut glioma cells release 3.7-97.0 pg D2HG per cell per week. Extrapolating this to an average-sized tumor (30 mL glioma volume and 1x108cells/mL tumor), the rate of D2HG release by an IDH1mut glioma (SA) is estimated at 3.2-83.0x10-12 moles/ml/sec. Mathematical models estimate an SA of 2.9-12.9x10-12 moles/ml/sec, within the range of the in vitro LC-MS data. In even the most conservative of these models, the extracellular concentration of D2HG exceeds 3 mM within a 2 cm radius from the center of an IDH1mut glioma. Conclusions
The microenvironment of an IDH1mut glioma is likely being exposed to high concentrations of D2HG, in the low millimolar range. This has implications for understanding how D2HG affects nonneoplastic cells in an IDH1mut glioma.Volumetric response quantified using T1 subtraction predicts long-term survival benefit from cabozantinib monotherapy in recurrent glioblastoma
Abstract
Background
To overcome challenges with traditional response assessment in anti-angiogenc agents, the current study uses T1 subtraction maps to quantify volumetric radiographic response in cabozantinib monotherapy, an orally bioavailable tyrosine kinase inhibitor with activity against VEGFR2, MET, and AXL, in an open-label, phase II trial in patients with recurrent glioblastoma (NCT00704288). Methods
A total of 108 patients with adequate imaging data and confirmed recurrent GBM were included in this retrospective study from a phase II multicenter trial of cabozantinib monotherapy (XL184-201) at either 100mg (N=87) or 140mg (N=21) per day. Contrast enhanced T1-weighted digital subtraction maps were used to define volume of contrast enhancing tumor at baseline and subsequent follow-up time points. Volumetric radiographic response (>65% reduction in contrast enhancing tumor volume from pre-treatment baseline tumor volume sustained for more than 4 weeks) was tested as an independent predictor of overall survival (OS). Results
Volumetric response rate (VRR) for all therapeutic doses was 38.9% (41.4% and 28.6% for 100mg and 140mg doses, respectively). A log-linear association between baseline tumor volume and OS (P=0.0006) and a linear correlation between initial change in tumor volume and OS (P=0.0256) were observed. A significant difference in OS was observed between responders (median OS=20.6 months) and non-responders (median OS=8.0 months) (HR=0.3050, P<0.0001). Multivariable analyses showed continuous measures of baseline tumor volume (HR=1.0233, P<0.0001) and volumetric response (HR=0.2240, P<0.0001) were independent predictors of OS. Conclusions
T1 subtraction maps provide value in determining response in recurrent GBM treated with cabozantinib and correlated with survival benefit.Targeting the human epidermal growth factor receptor 2 (HER2) oncogene in colorectal cancer
Abstract
BACKGROUND
Human epidermal growth factor receptor 2 (HER2) is an oncogenic driver, and a well-established therapeutic target in breast and gastric cancers. Using functional and genomic analyses of patient-derived xenografts, we previously showed that a subset (approximately 5%) of metastatic colorectal cancer (CRC) tumors are driven by amplification or mutation of HER2. MATERIALS AND METHODS
This paper reviews the role of HER2 as an oncogenic driver, a prognostic and predictive biomarker, and a clinically actionable target in CRC, considering the specifics of HER2 testing in this tumor type. RESULTS
While the role of HER2 as a biomarker for prognosis in CRC remains uncertain, its relevance as a therapeutic target has been established. Indeed, independent studies documented substantial clinical benefit in patients treated with biomarker-driven HER2-targeted therapies, with an impact on response rates and duration of response that compared favorably with immunotherapy and other examples of precision oncology. CONCLUSION
HER2-targeted therapeutic strategies have the potential to change the treatment paradigm for a clinically relevant subgroup of metastatic CRC patients.Wu Song’s Killing of His Sister-in-law: An Ethical Analysis
Abstract
The Water Margin is a great Chinese classical novel; Wu Song's 武松 killing of his sister-in-law, Pan Jinlian 潘金蓮, is one of the most popular episodes of the novel. It depicts Wu as the hero and defender of traditional values, and Pan as the adulterous woman. In contemporary discussion, there has been a dearth of ethical analyses regarding Wu's killing of Pan. How should we judge the moral status of his action? Does the killing signify Wu Song's ethical achievement or his ethical failure? What does the killing tell us about Wu's character or his virtues? Does our appraisal of Wu's action square with our modern belief regarding the treatment of women? I will examine these questions in the article.
Characteristic MR Imaging Findings of the Neonatal Brain in RASopathies [PEDIATRICS]
BACKGROUND AND PURPOSE:
Neuroimaging features in neonates with RASopathies are rarely reported, and to date, there are no neuroimaging studies conducted in this population. Our aim was to investigate the occurrence of supratentorial and posterior fossa abnormalities on brain MRIs of neonates with a RASopathy.
MATERIALS AND METHODS:An observational case-control study of neonates with a confirmed RASopathy was conducted. The presence of an intraventricular and/or parenchymal hemorrhage and punctate white matter lesions and assessments of the splenium of the corpus callosum, gyrification of the cortical gray matter, and enlargement of the extracerebral space were noted. The vermis height, transverse cerebellar diameter, cranial base angle, tentorial angle, and infratentorial angle were measured.
RESULTS:We reviewed 48 brain MR studies performed at 3 academic centers in 3 countries between 2009 and 2017. Sixteen of these infants had a genetically confirmed RASopathy (group 1), and 32 healthy infants were enrolled as the control group (group 2). An increased rate of white matter lesions, extracerebral space enlargement, simplification of the cortical gyrification, and white matter abnormalities were seen in group 1 (P < .001, for each). The vermis height of patients was significantly lower, and tentorial and infratentorial angles were significantly higher in group 1 (P = .01, P < .001, and P = .001, respectively).
CONCLUSIONS:Neonates with a RASopathy had characteristic structural and acquired abnormalities in the cortical gray matter, white matter, corpus callosum, cerebellum, and posterior fossa. This study provides novel neuroimaging findings on supratentorial and posterior fossa abnormalities in neonates with a RASopathy.
Cavitary Plaques in Otospongiosis: CT Findings and Clinical Implications [HEAD & NECK]
BACKGROUND AND PURPOSE:
Cavitary plaques have been reported as a manifestation of otospongiosis. They have been related to third window manifestations, complications during cochlear implantation, and sensorineural hearing loss. However, their etiology and clinical implications are not entirely understood. Our purpose was to determine the prevalence, imaging findings, and clinical implications of cavitary plaques in otospongiosis.
MATERIALS AND METHODS:We identified patients with otospongiosis at a tertiary care academic medical center from January 2012 to April 2017. Cross-sectional CT images and clinical records of 47 patients (89 temporal bones) were evaluated for the presence, location, and imaging features of cavitary and noncavitary otospongiotic plaques, as well as clinical symptoms and complications in those who underwent cochlear implantation.
RESULTS:Noncavitary otospongiotic plaques were present in 86 (97%) temporal bones and cavitary plaques in 30 (35%). Cavitary plaques predominated with increasing age (mean age, 59 years; P = .058), mostly involving the anteroinferior wall of the internal auditory canal (P = .003), and their presence was not associated with a higher grade of otospongiosis by imaging (P = .664) or with a specific type of hearing loss (P = .365). No patients with cavitary plaques had third window manifestations, and those with a history of cochlear implantation (n = 6) did not have complications during the procedure.
CONCLUSIONS:Cavitary plaques occurred in one-third of patients with otospongiosis. Typically, they occurred in the anteroinferior wall of the internal auditory canal. There was no correlation with the degree of otospongiosis, type of hearing loss, or surgical complications. Cavitary plaques tended to present in older patients.
Who's Contributing Most to American Neuroscience Journals: American or Foreign Authors? [RESEARCH PERSPECTIVES]
BACKGROUND AND PURPOSE:
With globalization, the contributions of authors from abroad to the American published literature has increased. We sought to determine the changes with time in the proportional contributions of American and non-American authors in the American neurosciences literature. We hypothesized the following: 1) During the past 21 years, manuscript contributions of American institutions have proportionally decreased in neuroradiology, more than in neurosurgery or neurology; 2) contributions of Asian institutions have affected neuroradiology more than neurosurgery and neurology; and 3) American articles garner more citations.
MATERIALS AND METHODS:We reviewed the May issues of 2 of the highest impact American-based neurology, neurosurgery, and neuroradiology journals published from 1997 to 2017. We counted the number of articles published by nation based on the institution of origin. We looked at trends across time and compared neurology, neurosurgery, and neuroradiology journals. We also gathered data on the number of citations of each article by nationality.
RESULTS:We reviewed 3025 articles. There was a significantly lower ratio of American to non-American authorship in neuroradiology versus neurology/neurosurgery journals (odds ratio = 0.70; 95% confidence interval, 0.60–0.82). There was a significantly decreasing trend in American authorship across the 21 years in neuroradiology. Of the countries outside the United States, Japan contributed most for neuroradiology and neurosurgery journals, and the UK, for neurology. American-authored articles were cited, on average, 1.25 times more frequently than non-American-authored articles.
CONCLUSIONS:Non-American contributions have impacted neuroradiology more than other clinical neuroscience fields with Asian authorship showing the greatest impact. That impact is growing, and the causes are manifold. Nonetheless American-authored articles are cited more.
Accuracy of CT Angiography for Differentiating Pseudo-Occlusion from True Occlusion or High-Grade Stenosis of the Extracranial ICA in Acute Ischemic Stroke: A Retrospective MR CLEAN Substudy [INTERVENTIONAL]
BACKGROUND AND PURPOSE:
The absence of opacification on CTA in the extracranial ICA in acute ischemic stroke may be caused by atherosclerotic occlusion, dissection, or pseudo-occlusion. The latter is explained by sluggish or stagnant flow in a patent artery caused by a distal intracranial occlusion. This study aimed to explore the accuracy of CTA for differentiating pseudo-occlusion from true occlusion of the extracranial ICA.
MATERIALS AND METHODS:All patients from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) with an apparent ICA occlusion on CTA and available DSA images were included. Two independent observers classified CTA images as atherosclerotic cause (occlusion/high-grade stenosis), dissection, or suspected pseudo-occlusion. Pseudo-occlusion was suspected if CTA showed a gradual contrast decline located above the level of the carotid bulb, especially in the presence of an occluded intracranial ICA bifurcation (T-occlusion). DSA images, classified into the same 3 categories, were used as the criterion standard.
RESULTS:In 108 of 476 patients (23%), CTA showed an apparent extracranial carotid occlusion. DSA was available in 46 of these, showing an atherosclerotic cause in 13 (28%), dissection in 16 (35%), and pseudo-occlusion in 17 (37%). The sensitivity for detecting pseudo-occlusion on CTA was 82% (95% CI, 57–96) for both observers; specificity was 76% (95% CI, 56–90) and 86% (95% CI, 68–96) for observers 1 and 2, respectively. The value for interobserver agreement was .77, indicating substantial agreement. T-occlusions were more frequent in pseudo- than true occlusions (82% versus 21%, P < .001).
CONCLUSIONS:On CTA, extracranial ICA pseudo-occlusions can be differentiated from true carotid occlusions.
MRI Planimetry and Magnetic Resonance Parkinsonism Index in the Differential Diagnosis of Patients with Parkinsonism [ADULT BRAIN]
BACKGROUND AND PURPOSE:
Differential diagnosis of multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration from Parkinson disease on clinical grounds is often difficult. MR imaging biomarkers could assist in a more accurate diagnosis. We examined the utility of MR imaging surface measurements (MR imaging planimetry) in the differential diagnosis of patients with parkinsonism.
MATERIALS AND METHODS:Fifty-two patients with Parkinson-plus (progressive supranuclear palsy, n = 24; corticobasal degeneration, n = 9; multiple system atrophy, n = 19), 18 patients with Parkinson disease, and 15 healthy controls were included. Corpus callosum, midbrain, and pons surfaces; relevant indices; and the Magnetic Resonance Parkinsonism Index were calculated. Corpus callosum subsection analysis was performed, and the corpus callosum posteroanterior gradient was introduced.
RESULTS:A Magnetic Resonance Parkinsonism Index value of >12.6 discriminated progressive supranuclear palsy from other causes of parkinsonism with a 91% sensitivity and 95% specificity. No planimetry measurement could accurately discriminate those with multiple system atrophy with parkinsonism from patients with Parkinson disease. A corpus callosum posteroanterior gradient value of ≤191 was highly specific (97%) and moderately sensitive (75%) for the diagnosis of corticobasal degeneration versus all other groups. A midbrain-to-corpus callosum posteroanterior gradient ratio of ≤0.45 was highly indicative of progressive supranuclear palsy over corticobasal degeneration (sensitivity 86%, specificity 88%).
CONCLUSIONS:MR imaging planimetry measurements are potent imaging markers of progressive supranuclear palsy and promising markers of corticobasal degeneration but do not seem to assist in the diagnosis of multiple system atrophy with parkinsonism.
Slow Collateral Flow Is Associated with Thrombus Extension in Patients with Acute Large-Artery Occlusion [INTERVENTIONAL]
BACKGROUND AND PURPOSE:
It is still poorly understood about the dynamic changes of the thrombus after intravenous thrombolysis and how the remaining thrombus affects clinical outcome in human stroke. Collateral flow was assumed to help to deliver endo/exogenous tissue-type plasminogen activator to the clot. We aimed to analyze the impact of collateral flow on the dynamic changes of the thrombus in patients with acute large-artery occlusion who received intravenous thrombolysis.
MATERIALS AND METHODS:We reviewed consecutive patients with acute ischemic stroke with M1 segment or distal internal carotid artery occlusion who underwent multimodal MR imaging or CT perfusion before and 24 hours after intravenous thrombolysis without recanalization. Patients were divided into 3 groups (thrombus extension, shortening, and no change) according to thrombus-length change between baseline and 24 hours. Collateral flow was measured with arrival time delay and the collateral scoring system. Poor outcome was defined as a 3-month modified Rankin Scale score of ≥3.
RESULTS:Among 51 patients, 18 (35.3%) had thrombus extension, 14 (27%) had thrombus shortening, and 19 (37.3%) had thrombus without change. Arrival time delay was independently associated with thrombus extension (OR = 1.499; 95% CI, 1.053–2.135; P = .025). Similarly, the collateral score on the peak artery phase was independently associated with thrombus extension (OR = 0.456; 95% CI, 0.211–0.984; P = .045), whereas baseline National Institutes of Health Stroke Scale score (OR = 0.768; 95% CI, 0.614–0.961; P = .021) and baseline thrombus length (OR = 1.193; 95% CI, 1.021–1.394; P = .026) were associated with thrombus shortening. All patients with thrombus extension had poor outcomes.
CONCLUSIONS:Slow collateral flow was related to thrombus extension in patients with large-artery occlusion without recanalization after intravenous thrombolysis.
Edge Contrast of the FLAIR Hyperintense Region Predicts Survival in Patients with High-Grade Gliomas following Treatment with Bevacizumab [ADULT BRAIN]
BACKGROUND AND PURPOSE:
Treatment with bevacizumab is standard of care for recurrent high-grade gliomas; however, monitoring response to treatment following bevacizumab remains a challenge. The purpose of this study was to determine whether quantifying the sharpness of the fluid-attenuated inversion recovery hyperintense border using a measure derived from texture analysis—edge contrast—improves the evaluation of response to bevacizumab in patients with high-grade gliomas.
MATERIALS AND METHODS:MRIs were evaluated in 33 patients with high-grade gliomas before and after the initiation of bevacizumab. Volumes of interest within the FLAIR hyperintense region were segmented. Edge contrast magnitude for each VOI was extracted using gradients of the 3D FLAIR images. Cox proportional hazards models were generated to determine the relationship between edge contrast and progression-free survival/overall survival using age and the extent of surgical resection as covariates.
RESULTS:After bevacizumab, lower edge contrast of the FLAIR hyperintense region was associated with poorer progression-free survival (P = .009) and overall survival (P = .022) among patients with high-grade gliomas. Kaplan-Meier curves revealed that edge contrast cutoff significantly stratified patients for both progression-free survival (log-rank 2 = 8.3, P = .003) and overall survival (log-rank 2 = 5.5, P = .019).
CONCLUSIONS:Texture analysis using edge contrast of the FLAIR hyperintense region may be an important predictive indicator in patients with high-grade gliomas following treatment with bevacizumab. Specifically, low FLAIR edge contrast may partially reflect areas of early tumor infiltration. This study adds to a growing body of literature proposing that quantifying features may be important for determining outcomes in patients with high-grade gliomas.
Clival Malformations in CHARGE Syndrome [PEDIATRICS]
BACKGROUND AND PURPOSE:
CHARGE syndrome is a multisystemic congenital disorder, most commonly including coloboma, heart malformations, choanal atresia, developmental delay, and genital and ear anomalies. The diagnostic criteria for CHARGE syndrome have been refined with time. However, limited reports describe skull base and craniocervical junction abnormalities. Recently, a coronal clival cleft has been identified in association with CHARGE syndrome. The aim of our study was to assess the prevalence of clival pathology in CHARGE syndrome.
MATERIALS AND METHODS:In this retrospective study, the CT/MR imaging data base at a single academic children's hospital was queried for the phrase "CHARGE syndrome" during a 17-year period (2001–2017). Electronic medical records were reviewed to confirm the diagnosis. Images were assessed for skull base anomalies, specifically clival hypoplasia and dysplasia.
RESULTS:The search yielded 42 examinations (21 CTs and 21 MRIs) from 15 distinct patients (mean age, 4.1 ± 5.6 years; range, 2 days to 19 years). CHARGE syndrome diagnosis was confirmed either by clinical and genetic testing (n = 6) or by clinical diagnosis only (n = 9). A coronal clival cleft was identified in 87% of patients (37 examinations, n = 13 patients), either partial (53%) or complete (33%). Clival hypoplasia without clefting was present in all 5 examinations from the remaining 2 patients.
CONCLUSIONS:Clival pathology is universal in CHARGE syndrome. Coronal clival clefts are extremely common, representing a useful additional diagnostic finding. Detection of a clival cleft should alert the radiologist to examine the palate, choana, eyes, ears, and olfactory centers for other signs of CHARGE syndrome.
Different relationships between personal exposure and ambient concentration by particle size
Abstract
Ambient particulate matter (PM) concentrations at monitoring stations were often used as an indicator of population exposure to PM in epidemiological studies. The correlation between personal exposure and ambient concentrations of PM varied because of diverse time-activity patterns. The aim of this study was to determine the relationship between personal exposure and ambient concentrations of PM10 and PM2.5 with minimal impact of time-activity pattern on personal exposure. Performance of the MicroPEM, v3.2 was evaluated by collocation with central ambient air monitors for PM10 and PM2.5. A field technician repeatedly conducted measurement of 24 h personal exposures to PM10 and PM2.5 with a fixed time-activity pattern of office worker over 26 days in Seoul, Korea. The relationship between the MicroPEM and the ambient air monitor showed good linearity. Personal exposure and ambient concentrations of PM2.5 were highly correlated with a fixed time-activity pattern compared with PM10. The finding implied a high infiltration rate of PM2.5 and low infiltration rate of PM10. The relationship between personal exposure and ambient concentrations of PM10 and PM2.5 was different for high level episodes. In the Asian dust episode, staying indoors could reduce personal exposure to PM10. However, personal exposure to PM2.5 could not be reduced by staying indoors during the fine dust advisory episode.
The association between serum copper concentrations and cardiovascular disease risk factors in children and adolescents in NHANES
Abstract
Copper is an essential element in human beings, alterations in serum copper levels could potentially have effect on human health. To date, no data are available regarding how serum copper affects cardiovascular disease (CVD) risk factors in children and adolescents. We examined the association between serum copper levels and CVD risk factors in children and adolescents. We analyzed data consisting of 1427 subjects from a nationally representative sample of the US population in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014. The CVD risk factors included total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, fasting glucose, glycohemoglobin, fasting insulin, and blood pressure. Multivariate and generalized linear regressions were performed to investigate associations adjusted for age, gender, ethnicity, poverty:income ratio (PIR), BMI, energy intake, and physical activity. We found significant associations between serum copper and total cholesterol (coefficient = 0.132; 95% CI 0.081, 0.182; P for trend < 0.001), glycohemoglobin (coefficient = 0.044; 95% CI 0.020, 0.069; P < 0.001), and fasting insulin (coefficient = 0.730; 95% CI 0.410, 1.050; P < 0.001) among the included participants. Moreover, in the generalized linear models, subjects with the highest copper levels demonstrated a 0.83% (95% CI 0.44%, 1.24%) greater increase in serum total cholesterol (p for trend < 0.001) when compared to participants with the lowest copper concentrations. Our results provide the first epidemiological evidence that serum copper concentrations are associated with total cholesterol concentrations in children and adolescents. However, the underlying mechanisms still need further exploration.
Contrasting congener profiles for persistent organic pollutants and PAH monitoring in European storm petrels ( Hydrobates pelagicus ) breeding in Ireland: a preen oil versus feathers approach
Abstract
Persistent organic pollutants (POPs) and polycyclic aromatic hydrocarbons (PAHs) are anthropogenic contaminants of environmental concern due to their persistence in the environment and capacity to accumulate in biota. Many of these contaminants have been found to have ill effects over wildlife and humans. Birds are known to be particularly affected through endocrine disruption and eggshell thinning. POPs have been banned or restricted through the Stockholm Convention (2001), making monitoring essential for tracking effects of regulation. Seabirds have been used as monitoring tools for being top predators and consuming a diverse array of prey in different trophic levels. Non-destructive sampling has become widely popular using feathers and preen oil, as opposed to carcasses and internal organs. This study aimed to set baseline levels of POP and PAH concentration in a highly pelagic and abundant seabird in Ireland and the Atlantic, the European storm petrel, Hydrobates pelagicus, and to investigate the profiles of contaminant congeners in preen oil and feathers, comparatively. Mean concentrations in preen oil followed: PCB (10.1 ng/g ww) > PAH (7.1 ng/g ww) > OCP (5.4 ng/g ww) > PBDE (3.9 ng/g ww), whilst mean concentrations in feathers followed the order: PAH (38.9 ng/g ww) > PCB (27.2 ng/g ww) > OCP (17.9 ng/g ww) > PBDE (4.5 ng/g ww). Congener profiles highly differed between preen oil and feathers, and little correlation was found between the matrices. These results demonstrate that the sampling of a single matrix alone (preen oil or feathers) might produce confounding results on contamination in seabirds and that more than one matrix is recommended to obtain a full picture of contamination by persistent organic pollutants.
Relationship of inhaled corticosteroid adherence to asthma exacerbations in patients with moderate to severe asthma
Publication date: Available online 5 April 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Alberto Papi, Dermot Ryan, Joan B. Soriano, Henry Chrystyn, Leif Bjermer, Roberto Rodríguez-Roisin, Myrna B. Dolovich, Mark Harris, Lucy Wood, Maria Batsiou, Susannah I. Thornhill, David B. Price
BackgroundPatients with asthma and elevated blood eosinophils are at increased risk of severe exacerbations. Management of these patients should consider non-adherence to inhaled corticosteroid (ICS) therapy as a factor for increased exacerbation risk.ObjectiveTo investigate whether poor adherence to ICS therapy explains the occurrence of asthma exacerbations in patients with elevated blood eosinophil levels.MethodsThis historical cohort study identified patients within the Optimum Patient Care Research Database, aged ≥18 years, at Global Initiative for Asthma (GINA) steps 3 or 4, with ≥2 ICS prescriptions during the year prior to clinical review. Patient characteristics and adherence (based on prescription refills and patient self-report) for ICS therapy were analysed for those with elevated (>400 cells/μL) or normal (≤400 cells/μL) blood eosinophils.ResultsWe studied 7,195 patients (66% female, mean age 60 years) with median eosinophil count of 200 cells/μL and found 81% to be non-fully adherent to ICS therapy. 1,031 patients (14%) had elevated blood eosinophil counts (58% female, mean age 60 years), 83% of whom were non-fully adherent to ICS. An increased proportion of adherent patients in the elevated blood eosinophil group had ≥2 exacerbations (14.0% vs 7.2%; p=0.003) and uncontrolled asthma (73% vs 60.8%; p=0.004) as compared to non-fully adherent patients.ConclusionsApproximately one in seven patients had elevated eosinophils. Adherence to ICS therapy was not associated with decreased exacerbations for these patients. Additional therapy should be considered for these patients, such as biologics, which have been previously shown to improve control in severe uncontrolled eosinophilic asthma.
Intranasal instillation of iron oxide nanoparticles induces inflammation and perturbation of trace elements and neurotransmitters, but not behavioral impairment in rats
Abstract
Over the last decades, engineered nanomaterials have been widely used in various applications due to their interesting properties. Among them, iron oxide nanoparticles (IONPs) are used as theranostic agents for cancer, and also as contrast agents in magnetic resonance imaging. With the increasing production and use of these IONPs, there is an evident raise of IONP exposure and subsequently a higher risk of adverse outcome for humans and the environment. In this work, we aimed to investigate the effects of sub-acute IONP exposure on Wistar rat, particularly (i) on the emotional and learning/memory behavior, (ii) on the hematological and biochemical parameters, (iii) on the neurotransmitter content, and (vi) on the trace element homeostasis. Rats were treated during seven consecutive days by intranasal instillations at a dose of 10 mg/kg body weight. The mean body weight increased significantly in IONP-exposed rats. Moreover, several hematological parameters were normal in treated rats except the platelet count which was increased. The biochemical study revealed that phosphatase alkaline level decreased in IONP-exposed rats, but no changes were observed for the other hepatic enzymes (ALT and AST) levels. The trace element homeostasis was slightly modulated by IONP exposure. Sub-acute intranasal exposure to IONPs increased dopamine and norepinephrine levels in rat brain; however, it did not affect the emotional behavior, the anxiety index, and the learning/memory capacities of rats.
Skin Barrier Restoration and Moisturization Using Horse Oil-Loaded Dissolving Microneedle Patches
Background: Horse oil (HO) has skin barrier restoration and skin-moisturizing effects. Although cream formulations have been used widely and safely, their limited penetration through the stratum corneum is a major obstacle to maximizing the cosmetic efficacy of HO. Therefore, we aimed to encapsulate HO in a cosmetic dissolving microneedle (DMN) for efficient transdermal delivery. Methods: To overcome these limitations of skin permeation, HO-loaded DMN (HO-DMN) patches were developed and evaluated for their efficacy and safety using in vitro and clinical studies. Results: Despite the lipophilic nature of HO, the HO-DMN patches had a sharp shape and uniform array, with an average length and tip diameter of 388.36 ± 16.73 and 38.54 ± 5.29 µm, respectively. The mechanical strength of the HO-DMN patches was sufficient (fracture force of 0.29 ± 0.01 N), and they could successfully penetrate pig skin. During the 4-week clinical evaluation, HO-DMN patches caused significant improvements in skin and dermal density, skin elasticity, and moisturization. Additionally, a brief safety assessment showed that the HO-DMN patches induced negligible adverse events. Conclusion: The HO-DMNs are efficient, safe, and convenient for wide use in cosmetic applications for skin barrier restoration and moisturization.
Skin Pharmacol Physiol 2018;31:163–171
Skin Pharmacol Physiol 2018;31:163–171
Outcomes From Lateral Eyelid Coupling for Facial Paralysis Using Modified Tarsoconjunctival Flap
This cohort study assesses whether lateral eyelid coupling in patients with facial paralysis improves quality of life as measured by the Facial Clinimetric Evaluation scale and Moe Ectropion Grading Scale.
Volumizing Hyaluronic Acid Filler for Infraorbital Hollows
This observational study reports safety and patient satisfaction outcomes of Juvéderm Voluma XC hyaluronic acid filler for correction of infraorbital hollows.
Polygenic risk score: use in migraine research
The latest Genome-Wide Association Study identified 38 genetic variants associated with migraine. In this type of studies the significance level is very difficult to achieve (5 × 10− 8) due to multiple testing. T...
Registration of 3D freehand ultrasound to a bone model for orthopedic procedures of the forearm
Abstract
Purpose
For guidance of orthopedic surgery, the registration of preoperative images and corresponding surgical plans with the surgical setting can be of great value. Ultrasound (US) is an ideal modality for surgical guidance, as it is non-ionizing, real time, easy to use, and requires minimal (magnetic/radiation) safety limitations. By extracting bone surfaces from 3D freehand US and registering these to preoperative bone models, complementary information from these modalities can be fused and presented in the surgical realm.
Methods
A partial bone surface is extracted from US using phase symmetry and a factor graph-based approach. This is registered to the detailed 3D bone model, conventionally generated for preoperative planning, based on a proposed multi-initialization and surface-based scheme robust to partial surfaces.
Results
36 forearm US volumes acquired using a tracked US probe were independently registered to a 3D model of the radius, manually extracted from MRI. Given intraoperative time restrictions, a computationally efficient algorithm was determined based on a comparison of different approaches. For all 36 registrations, a mean (± SD) point-to-point surface distance of \(0.57\,(\pm \,0.08)\,\hbox {mm}\) was obtained from manual gold standard US bone annotations (not used during the registration) to the 3D bone model.
Conclusions
A registration framework based on the bone surface extraction from 3D freehand US and a subsequent fast, automatic surface alignment robust to single-sided view and large false-positive rates from US was shown to achieve registration accuracy feasible for practical orthopedic scenarios and a qualitative outcome indicating good visual image alignment.
Patient-specific catheter shaping for the minimally invasive closure of the left atrial appendage
Abstract
Purpose
The minimally invasive closure of the left atrial appendage is a promising alternative to anticoagulation for stroke prevention in patients suffering from atrial fibrillation. One of the challenges of this procedure is the correct positioning and the coaxial alignment of the tip of the catheter sheath to the implant landing zone.
Method
In this paper, a novel preoperative planning system is proposed that allows patient-individual shaping of catheters to facilitate the correct positioning of the catheter sheath by offering a patient-specific catheter shape. Based on preoperative three-dimensional image data, anatomical points and the planned implant position are marked interactively and a patient-specific catheter shape is calculated if the standard catheter is not considered as suitable. An approach to calculate a catheter shape with four bends by maximization of the bending radii is presented. Shaping of the catheter is supported by a bending form that is automatically generated in the planning program and can be directly manufactured by using additive manufacturing methods.
Results
The feasibility of the planning and shaping of the catheter could be successfully shown using six data sets. The patient-specific catheters were tested in comparison with standard catheters by physicians on heart models. In four of the six tested models, the participating physicians rated the patient-individual catheters better than the standard catheter.
Conclusion
The novel approach for preoperatively planned and shaped patient-specific catheters designed for the minimally invasive closure of the left atrial appendage could be successfully implemented and a feasibility test showed promising results in anatomies that are difficult to access with the standard catheter.
Reduction mechanism of hexavalent chromium by functional groups of undissolved humic acid and humin fractions of typical black soil from Northeast China
Abstract
Soil organic matters (SOM) have a great retention effect on Cr(VI) migration in subsurface environment, which act as the main electron donors for Cr(VI) reduction; however, Cr(VI) reduction mechanism by different SOM fractions is still unclear, such as undissolved humic acid (HA) and humin (HM). In this study, HA and HM fractions extracted from typical black soil from Northeast China were used to investigate the reaction mechanism between humus functional groups and Cr(VI). According to the results, phenol and hydroxyl were determined as the main electron donors for Cr(VI) reduction by HA and HM instead of carboxyl and carbonyl, which were more likely involved in Cr complexation. Furthermore, Cr(VI) reduction was more dependent on aromatic carbon, rather than aliphatic carbon, and functional groups on the particle surfaces of HA and HM were much more active for Cr(VI) reduction than their interior part. Additionally, HM was found to have a relatively low Cr(VI) reduction capability compared with HA resulting from its high content of cellulose structures that are quite resistant to Cr(VI) oxidation. These results suggest that in the soil environment, undissolved HA tends to play a much more important role than HM in Cr(VI) reduction and retention in the condition that their mass contents are comparable.
Correction to: The semantic plights of the ante-rem structuralist
Abstract
In the original publication of the article, footnote 17 was incorrectly published. The corrected footnote is given below.
Cathodic microbial community adaptation to the removal of chlorinated herbicide in soil microbial fuel cells
Abstract
The microbial fuel cell (MFC) that uses a solid electrode as the inexhaustible electron acceptor is an innovative remediation technology that simultaneously generates bioelectricity. Chlorinated pollutants are better metabolized by reductive dechlorination in proximity to the cathode. Here, the removal efficiency of the herbicide metolachlor (ML) increased by 262 and 176% in soil MFCs that were spiked with 10 (C10) and 20 mg/kg (C20) of ML, respectively, relative to the non-electrode controls. The bioelectricity output of the C10 and C20 increased by over two- and eightfold, respectively, compared to that of the non-ML control, with maximum current densities of 49.6 ± 2.5 (C10) and 78.9 ± 0.6 mA/m2 (C20). Based on correlations between ML concentrations and species abundances in the MFCs, it was inferred that Azohydromonas sp., Sphingomonas sp., and Pontibacter sp. play a major role in ML removal around the cathode, with peak removal efficiencies of 56 ± 1% (C10) and 58 ± 1% (C20). Moreover, Clostridium sp., Geobacter sp., Bacillus sp., Romboutsia sp., and Terrisporobacter sp. may be electricigens or closely related microbes due to the significant positive correlation between the bioelectricity generation levels and their abundances around the anode. This study suggests that a directional adaptation of the microbial community has taken place to increase both the removal of chlorinated herbicides around the cathode and the generation of bioelectricity around the anode in bioelectrochemical remediation systems.
Mixed strategy to allocate resources with air pollution treatment in China: based on the analytic network process and large-group decision-making method
Abstract
The resource allocation of air pollution treatment in China is a complex problem, since many alternatives are available and many criteria influence mutually. A number of stakeholders participate in this issue holding different opinions because of the benefits they value. So a method is needed, based on the analytic network process (ANP) and large-group decision-making (LGDM), to rank the alternatives considering interdependent criteria and stakeholders' opinions. In this method, the criteria related to air pollution treatment are examined by experts. Then, the network structure of the problem is constructed based on the relationships between the criteria. Further, every participant in each group provide comparison matrices by judging the importance between criteria according to dominance, regarding a certain criteria (or goal), and the geometric average comparison matrix of each group is obtained. The decision weight of each group is derived by combining the subjective weight and the objective weight, in which the subjective weight is provided by organizers, while the objective weight is determined by considering the consensus levels of groups. The final comparison matrices are obtained by the geometric average of comparison matrices and the decision weights. Next, the resource allocation is made according to the priorities of the alternatives using the super decision software. Finally, an example is given to illustrate the use of the proposed method.
CORRECTION
Publication date: Available online 4 April 2018
Source:Journal of the American Academy of Dermatology
Τετάρτη 4 Απριλίου 2018
Methodology of clinical trials evaluating the incorporation of new drugs in the first line treatment of patients with diffuse large B-cell lymphoma (DLBCL): a critical review
Abstract
Purpose
The first line treatment of diffuse large B-cell lymphoma (DLBCL) is the combination of rituximab with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy, curing approximately 60% of patients. Many clinical trials have been performed over the last 10 years trying to improve the results of this treatment, but the appropriateness of their planning strategies could be rediscussed. Patients and Methods
Reports of phase 3 trials evaluating the addition of molecularly targeted agents (MTA) or new monoclonal antibodies to the classic R-CHOP backbone in first-line induction or maintenance treatment were reviewed. The trial design, primary end point, number of patients enrolled, patient selection criteria, treatment schedule and results were registered for each one. In addition, the phase1 and 2 trials which preceded these phase 3 trials were also reviewed. Results
Among six phase 3 trials with results, only one trial evaluating lenalidomide maintenance after response to R-CHOP induction was positive and reached its primary endpoint. The other 5 trials did not show an improved outcome with the addition of the new agent. The preceding phase 1 and 2 trials were very heterogeneous in their endpoints and design. Even though most of these trials were considered positive, thus encouraging further investigation, so far they failed to predict the results of the subsequent phase 3 trials. Conclusion
The standard of care for DLBCL is still R-CHOP. Phase 1/2 trials failed to predict the results of subsequent phase 3 trials evaluating non-chemotherapeutic agents added to R-CHOP. The methodology of phase 2 trials evaluating new agents in DLBCL needs to be better defined in the future.ADI-PEG 20 Plus Best Supportive Care versus Placebo Plus Best Supportive Care in Patients with Advanced Hepatocellular Carcinoma
Abstract
Background
Arginine depletion is a putative target in hepatocellular carcinoma (HCC). HCC often lacks argininosuccinate synthetase, a citrulline to arginine-repleting enzyme. ADI-PEG 20 is a cloned arginine degrading enzyme – arginine deiminase – conjugated with polyethylene glycol. The goal of this study was to evaluate this agent as a potential novel therapeutic for HCC after first line systemic therapy. Methods and Patients
Patients with histologically proven advanced HCC and Child-Pugh up to B7 with prior systemic therapy, were randomized 2:1 to ADI-PEG 20 18 mg/m2 vs. placebo intramuscular (IM) injection weekly. The primary endpoint was overall survival (OS), with 93% power to detect a 4 to 5.6 months increase in median OS (1-sided α = 0.025). Secondary endpoints included progression-free survival (PFS), safety, and arginine correlatives. Results
635 patients were enrolled: median age 61, 82% male, 60% Asian, 52% hepatitis B, 26% hepatitis C, 76% stage IV, 91% Child-Pugh A, 70% progressed on sorafenib and 16% were intolerant. Median OS was 7.8 months for ADI-PEG 20 vs 7.4 for placebo (p = 0.88, HR = 1.02) and median PFS 2.6 months vs. 2.6 (p = 0.07, HR = 1.17). Grade 3 fatigue and decreased appetite occurred in less than 5% of patients. Two patients on ADI-PEG 20 had ≥ grade 3 anaphylactic reaction. Death rate within 30 days of end of treatment was 15.2% on ADI-PEG 20 vs. 10.4% on placebo, none related to therapy. Post-hoc analyses of arginine assessment at 4, 8, 12 and 16 weeks, demonstrated a trend of improved OS for those with more prolonged arginine depletion. Conclusion
ADI-PEG 20 monotherapy did not demonstrate an OS benefit in second line setting for HCC. It was well tolerated. Strategies to enhance prolonged arginine depletion and synergize the effect of ADI-PEG 20 are underway. Clinical Trial number
www.clinicaltrials (NCT 01287585)Sorption of 17β-estradiol to the dissolved organic matter from animal wastes: effects of composting and the role of fulvic acid-like aggregates
Abstract
Steroid estrogens, such as 17β-estradiol (E2), in animal manure pose a potential threat to the aquatic environment. The transport and estrogenicity of estrogens influence the sorption of estrogens to dissolved organic matter (DOM) in animal manure, and composting treatment alters the structure and composition of the manure. The objectives of the present study were to identify the contribution of the molecular composition of DOM of composted manure to the sorption of E2 and then elucidate the dominant mechanisms involved in the interaction of E2 with manure-derived DOM. The excitation–emission matrix (EEM) spectra and atomic force microscopy (AFM) showed that composting significantly altered the chemical composition and structure of DOM. A decrease in the atomic ratios of oxygen (O)/carbon (C) occurred in conjunction with the formation of DOM aggregates in the composted manure, indicating that the hydrophilicity and polarity of the DOM decreased after composting. Composting increased the sorption coefficients (KDOC-E2) for E2 to DOM, and KDOC-E2 was positively correlated with the proportion of the fulvic acid (FA)-like fraction and molecular weight (MW) fractions of the DOM (range of 1.0 × 103–7.0 × 103 Da and 7.0 × 103–1.4 × 104 Da). Specifically, E2 showed a tendency for sorption to medium-sized FA-like molecules of DOM aggregates in composted manure. Hydrophobic forces and π-π binding appeared to be the main mechanisms underlying the aforementioned interaction.
Intraoperative anaphylaxis secondary to systemic cooling in a pediatric patient with cold-induced urticaria
Publication date: Available online 4 April 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Michelle C. Maciag, Charles Nargozian, Ana Dioun Broyles
Occupational exposures and asthma prevalence among US farmworkers: National Agricultural Workers Survey, 2003-2014
Publication date: Available online 4 April 2018
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Anna J. Chen Arroyo, Lacey B. Robinson, N. Lance Downing, Carlos A. Camargo
Risk assessment, spatial distribution, and source apportionment of heavy metals in Chinese surface soils from a typically tobacco cultivated area
Abstract
The heavy metals (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) in the surface soils of tobacco (Nicotiana tabacum L.) fields in Jiangxi Province were analyzed, and the mean heavy metal concentrations were 3.55, 0.19, 25.89, 14.96, 0.25, 10.89, 27.80, and 44.00 mg/kg, respectively. Spatial distribution analysis showed that the highest concentrations were recorded in the north-western, south-western, and mid-eastern parts of the study area. The index of geo-accumulation and pollution index indicated modest enrichment with Cd and Hg, which were the only two metals posing a potentially high ecological risk to the local agricultural environment. The health risk assessment showed no considerable non-carcinogenic or carcinogenic risks for children and adults from these elements. The principal component analysis (PCA) and cluster analysis (CA) found that the variations in the Cr and Ni concentrations were largely on account of the soil parent rocks, but the As, Cd, Cu, and Hg variations in the soil were largely owing to agricultural practices of years. However, the main factor influencing Pb and Zn was atmospheric deposition.
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