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Πέμπτη 30 Νοεμβρίου 2017

Mitteilungen der GÄCD



Sambandha Versus Sambaddhasambandha: The Semantics of Sixth-Triplet Endings

Abstract

According to the poetician Vāmana, a genitive ending can denote not only a direct relation but also an indirect relation. For example, in kamalasya kandaḥ 'the bulb of the lotus flower' the genitive ending Ṅas introduced after the word kamala denotes the indirect relation between the lotus flower and the bulb, the relation established through the intermediary of the lotus plant (kamalinī) that has a direct relation with both of them. Is such a view acceptable to Pāṇinian grammarians? Careful scrutiny of Patañjali's discussions in the Mahābhāṣya concerning what the affix matUP signifies reveals that he does not accept that a genitive ending occurs to denote an indirect relation: he considers that Aṣṭādhyāyī 2.3.50: ṣaṣṭhī śeṣe, which provides for introducing a genitive ending, has for its domain a direct relation alone. For Vāmana, on the other hand, the poetic expression kamalasya kandaḥ and the like serve to testify to the fact that a genitive ending can be used to signify an indirect relation. What is important is that Aṣṭādhyāyī 2.3.50 as it stands does not exclude this. Just as Patañjali accepts a direct relation as the domain of Aṣṭādhyāyī 2.3.50 on the basis of the usage of model speakers (śiṣṭaprayoga), so does Vāmana accept an indirect relation as its further domain on the basis of the usage of great poets (śiṣṭaprayoga).



Some Remarks on the Genesis of Central Yogācāra-Vijñānavāda Concepts

Abstract

The present paper is a kind of selective summary of my book The Genesis of Yogācāra-Vijñānavāda (2014). [1.–2.] It deals with questions of origin and early development of three basic concepts of this school, viz., the 'idealist' thesis that the whole world is mind only (cittamātra) or manifestation only (vijñaptimātra), the assumption of a subliminal layer of the mind (ālayavijñāna), and the analysis of phenomena in terms of the "Three Natures" (svabhāvatraya). [3.] It has been asserted (H. Buescher) that these three basic concepts are logically inseparable and therefore must have been introduced conjointly. [4.] Still, from Vasubandhu onward treatises have been written in which only one of the three concepts is advocated or demonstrated to be indispensable, without any reference to the other two being made. Likewise, in most of the earlier Yogācāra treatises, the three concepts occur in different sections or contexts, or are even entirely absent, as vijñaptimātra in the Yogācārabhūmi (except for the Saṁdhinirmocanasūtra quotation) and ālayavijñāna in the Mahāyānasūtrālaṁkāra and Madhyāntavibhāga. [5.] It is therefore probable that the three concepts were introduced separately and for different reasons. [5.1.] As regards the concept of the "Three Natures", I very hypothetically suggest that it was stimulated by the Tattvārthapaṭala of the Bodhisatvabhūmi. [5.2.1.] In the case of ālayavijñāna, I still think that my hypothesis that the concept (term + idea) originated from a problem emerging in connection with the "attainment of cessation" (nirodhasamāpatti) holds good and has not been conclusively refuted, but I admit that Prof. Yamabe's hypothesis is a serious alternative. [5.2.2.] An important point is that in the Yogācārabhūmi we come across two fundamentally different concepts of ālayavijñāna, the starting point for the change being, probably, the fifth chapter of the Saṁdhinirmocanasūtra. [5.3.] As for 'idealism', we may have to distinguish two strands, which, however, tend to merge. [5.3.1.] The earlier one uses the concept cittamātra and emerges as early as in the Pratyutpanna-buddha-saṁmukhāvasthita-samādhi-sūtra in connection with an interpretation of visions of the Buddha Amitāyus. [5.3.2.] The later strand introduces the concept vijñaptimātra and seems to have originated in the eighth chapter of the Saṁdhinirmocanasūtra in connection with a reflection on the images perceived in insight meditation. [5.3.3.] In texts like the Mahāyānasūtrālaṁkāra, concepts from other Mahāyānasūtra strands (like abhūtaparikalpa) become prominent in this connection, and it is only in the Mahāyānasaṁgraha that the use of vijñaptimātra is finally established.



Report on the 2nd European Tissue Repair Society summer school, Brussels, Sept 11–12th, 2017



Correction to: Adaptation in toxic environments: comparative genomics of loci carrying antibiotic resistance genes derived from acid mine drainage waters

Abstract

The original version of this article unfortunately contains a mistake.



The seasonal incidence of symptomatic influenza in the United States

Abstract
Background
The seasonal incidence of influenza is often approximated as "5% to 20%".
Methods
We used two methods to estimate the seasonal incidence of symptomatic influenza in the United States. First, we made a statistical estimate extrapolated from influenza-associated hospitalization rates for 2010–11 to 2015–16, collected as part of national surveillance, covering approximately 9% of the United States, and including the existing mix of vaccinated and unvaccinated persons. Second, we performed a literature search and meta-analysis of published manuscripts that followed cohorts of subjects during 1996–2016 to detect laboratory-confirmed symptomatic influenza among unvaccinated persons; we adjusted this result to the United States median vaccination coverage and effectiveness during 2010–2016.
Results
The statistical estimate of influenza incidence among all ages ranged from 3.0–11.3% among seasons, with median values of 8.3 (95% confidence interval [CI] 7.3%, 9.7%) for all ages, 9.3% (CI 8.2%, 11.1%) for children <18 years and 8.9% (CI 8.2%, 9.9%) for adults 18–64 years. Corresponding values for the meta-analysis were 7.1% (CI 6.1, 8.1) for all ages, 8.7% (6.6, 10.5) for children, and 5.1% (3.6, 6.6) for adults.
Conclusions
The two approaches produced comparable results for children and persons of all ages. The statistical estimates are more versatile and permit estimation of season-to-season variation. During 2010–2016, the incidence of symptomatic influenza among vaccinated and unvaccinated United States residents, including both medically attended and non-attended infections, was approximately 8% and varied from 3% to 11% among seasons.

Paradoxic eczema in infants after heart transplantation

Abstract

New-onset psoriasis in patients receiving tumor necrosis factor inhibitors is well recognized in children and adults. We describe three children who underwent cardiac transplantation and developed an analogous form of paradoxic eczema occurring 2-48 months after starting systemic tacrolimus, a drug widely used topically to treat eczema. Anecdotal reports and our experience suggest that tacrolimus taper with alternative systemic antirejection immunosuppressant may lead to skin clearance. Pending additional insight, treatment should include optimizing skin barrier function, minimizing microbial and allergic triggers, and coordinating care to choose the best-tolerated systemic immunosuppressant regimen at the lowest effective dose.



Dermpath & clinic: Multiple clear cell acanthomas



Foreign body reaction three years after injection with polycaprolactone (Ellanse®)



A case of Netherton syndrome with mutation in SPINK5 and FLG



A case of a focal oedematous reaction induced by rituximab overlying lupus erythematosus tumidus



Green pigmentation on the sole with hyperbilirubinaemia



Rapid regression of metastatic brain tumours in a melanoma patient after dabrafenib/trametinib therapy



Clues in skin surgery: The intralabial rotation flap



sQUIZ your knowledge: Brown macules over spinous processes of the back



Narrow-band UVB for pretibial (necrobiosis lipoidica-like) involvement of cutaneous sarcoidosis: a promising therapeutic option



Segmental zoster abdominal paresis (zoster pseudohernia) preceding a skin rash



Pirfenidone-induced phototoxic reaction in a patient with idiopathic pulmonary fibrosis



Fibroblastic connective tissue nevus: the role of histopathological and molecular techniques in differential diagnosis



Indeterminate cell histiocytosis: a case series and review of the literature



Efficacy of biologics in psoriasis patients under hemodialysis



Angiokeratomas on the nipple associated with enlargement of the ipsilateral breast: a rare lesion in an adolescent boy



A case of cutaneous polyarteritis nodosa with PR3-ANCA



A case of non-episodic angioedema with eosinophilia induced by influenza vaccine



Sensitivity of cutaneous chronic myelomonocytic leukaemia lesions to hypomethylating treatment



Pyoderma gangrenosum of the lip involving the oral cavity: a case report and literature review



A mild phenotype of hand, foot and mouth disease caused by Coxsackievirus A6



Lymphographic-Like Technique for the Treatment of Microcystic Lymphatic Malformation Components of <3 mm [HEAD & NECK]

BACKGROUND AND PURPOSE:

The treatment of microcystic lymphatic malformations remains challenging. Our aim was to describe the lymphographic-like technique, a new technique of slow bleomycin infusion for the treatment of microcyst components of <3 mm, performed at our institution.

MATERIALS AND METHODS:

A retrospective analysis of a prospectively collected lymphatic malformation data base was performed. Patients with at least 1 microcystic lymphatic malformation component demonstrated on MR imaging treated by lymphographic-like technique bleomycin infusion were included in the study. Patient interviews and MR imaging were performed to assess subjective and objective (microcystic lymphatic malformation size decrease of >30%) clinical improvement, respectively. Patients were reviewed 3 months after each sclerotherapy session. Lymphographic-like technique safety and efficacy were assessed.

RESULTS:

Between January 2012 and July 2016, sixteen patients (5 males, 11 females; mean age, 15 years; range, 1–47 years) underwent the bleomycin lymphographic-like technique for microcystic lymphatic malformations. Sixty sclerotherapy sessions were performed, with a mean of 4 sessions per patient (range, 1–8 sessions) and a mean follow-up of 26 months (range, 5–58 months). We observed no major and 3 minor complications: 1 eyelid infection, 1 case of severe postprocedural nausea and vomiting, and 1 case of skin discoloration. One patient was lost to follow-up. Overall MR imaging objective improvement was observed in 5/16 (31%) patients; overall improvement of clinical symptoms was obtained in 93% of treated patients.

CONCLUSIONS:

The bleomycin lymphographic-like technique for microcystic lymphatic malformations is safe and feasible with objective improvement in about one-third of patients. MR signal intensity changes after the lymphographic-like technique are associated with subjective improvement of the patient's symptoms.



CT Attenuation Analysis of Carotid Intraplaque Hemorrhage [EXTRACRANIAL VASCULAR]

BACKGROUND AND PURPOSE:

Intraplaque hemorrhage is considered a leading parameter of carotid plaque vulnerability. Our purpose was to assess the CT characteristics of intraplaque hemorrhage with histopathologic correlation to identify features that allow for confirming or ruling out the intraplaque hemorrhage.

MATERIALS AND METHODS:

This retrospective study included 91 patients (67 men; median age, 65 ± 7 years; age range, 41–83 years) who underwent CT angiography and carotid endarterectomy from March 2010 to May 2013. Histopathologic analysis was performed for the tissue characterization and identification of intraplaque hemorrhage. Two observers assessed the plaque's attenuation values by using an ROI (≥ 1 and ≤2 mm2). Receiver operating characteristic curve, Mann-Whitney, and Wilcoxon analyses were performed.

RESULTS:

A total of 169 slices were assessed (59 intraplaque hemorrhage, 63 lipid-rich necrotic core, and 47 fibrous); the average values of the intraplaque hemorrhage, lipid-rich necrotic core, and fibrous tissue were 17.475 Hounsfield units (HU) and 18.407 HU, 39.476 HU and 48.048 HU, and 91.66 HU and 93.128 HU, respectively, before and after the administration of contrast medium. The Mann-Whitney test showed a statistically significant difference of HU values both in basal and after the administration of contrast material phase. Receiver operating characteristic analysis showed a statistical association between intraplaque hemorrhage and low HU values, and a threshold of 25 HU demonstrated the presence of intraplaque hemorrhage with a sensitivity and specificity of 93.22% and 92.73%, respectively. The Wilcoxon test showed that the attenuation of the plaque before and after administration of contrast material is different (intraplaque hemorrhage, lipid-rich necrotic core, and fibrous tissue had P values of .006, .0001, and .018, respectively).

CONCLUSIONS:

The results of this preliminary study suggest that CT can be used to identify the presence of intraplaque hemorrhage according to the attenuation. A threshold of 25 HU in the volume acquired after the administration of contrast medium is associated with an optimal sensitivity and specificity. Special care should be given to the correct identification of the ROI.



John Nash and the Organization of Stroke Care [PRACTICE PERSPECTIVES]

SUMMARY:

The concept of Nash equilibrium, developed by John Forbes Nash Jr, states that an equilibrium in noncooperative games is reached when each player takes the best action for himself or herself, taking into account the actions of the other players. We apply this concept to the provision of endovascular thrombectomy in the treatment of acute ischemic stroke and suggest that collaboration among hospitals in a health care jurisdiction could result in practices such as shared call pools for neurointervention teams, leading to better patient care through streamlined systems.



Influences for Gender Disparity in Academic Neuroradiology [ACADEMIC PERSPECTIVES]

BACKGROUND AND PURPOSE:

There has been extensive interest in promoting gender equality within radiology, a predominately male field. In this study, our aim was to quantify gender representation in neuroradiology faculty rankings and determine any related factors that may contribute to any such disparity.

MATERIALS AND METHODS:

We evaluated the academic and administrative faculty members of neuroradiology divisions for all on-line listed programs in the US and Canada. After excluding programs that did not fulfill our selection criteria, we generated a short list of 85 US and 8 Canadian programs. We found 465 faculty members who met the inclusion criteria for our study. We used Elsevier's SCOPUS for gathering the data pertaining to the publications, H-index, citations, and tenure of the productivity of each faculty member.

RESULTS:

Gender disparity was insignificant when analyzing academic ranks. There are more men working in neuroimaging relative to women (2 = 0.46; P = .79). However, gender disparity was highly significant for leadership positions in neuroradiology (2 = 6.76; P = .009). The median H-index was higher among male faculty members (17.5) versus female faculty members (9). Female faculty members have odds of 0.84 compared with male faculty members of having a higher H-index, adjusting for publications, citations, academic ranks, leadership ranks, and interaction between gender and publications and gender and citations (9).

CONCLUSIONS:

Neuroradiology faculty members follow the same male predominance seen in many other specialties of medicine. In this study, issues such as mentoring, role models, opportunities to engage in leadership/research activities, funding opportunities, and mindfulness regarding research productivity are explored.



Reproducibility of Deep Gray Matter Atrophy Rate Measurement in a Large Multicenter Dataset [ADULT BRAIN]

BACKGROUND AND PURPOSE:

Precise in vivo measurement of deep GM volume change is a highly demanded prerequisite for an adequate evaluation of disease progression and new treatments. However, quantitative data on the reproducibility of deep GM structure volumetry are not yet available. In this paper we aim to investigate this reproducibility using a large multicenter dataset.

MATERIALS AND METHODS:

We have assessed the reproducibility of 2 automated segmentation software packages (FreeSurfer and the FMRIB Integrated Registration and Segmentation Tool) by quantifying the volume changes of deep GM structures by using back-to-back MR imaging scans from the Alzheimer Disease Neuroimaging Initiative's multicenter dataset. Five hundred sixty-two subjects with scans at baseline and 1 year were included. Reproducibility was investigated in the bilateral caudate nucleus, putamen, amygdala, globus pallidus, and thalamus by carrying out descriptives as well as multilevel and variance component analysis.

RESULTS:

Median absolute back-to-back differences varied between GM structures, ranging from 59.6–156.4 μL for volume change, and 1.26%–8.63% for percentage volume change. FreeSurfer had a better performance for the outcome of longitudinal volume change for the bilateral amygdala, putamen, left caudate nucleus (P < .005), and right thalamus (P < .001). For longitudinal percentage volume change, Freesurfer performed better for the left amygdala, bilateral caudate nucleus, and left putamen (P < .001). Smaller limits of agreement were found for FreeSurfer for both outcomes for all GM structures except the globus pallidus. Our results showed that back-to-back differences in 1-year percentage volume change were approximately 1.5–3.5 times larger than the mean measured 1-year volume change of those structures.

CONCLUSIONS:

Longitudinal deep GM atrophy measures should be interpreted with caution. Furthermore, deep GM atrophy measurement techniques require substantially improved reproducibility, specifically when aiming for personalized medicine.



Alphabet Soup: Sagittal Balance Correction Osteotomies of the Spine--What Radiologists Should Know [REVIEW ARTICLE]

SUMMARY:

Global sagittal malalignment has been demonstrated to have correlation with clinical symptoms and is a key component to be restored in adult spinal deformity. In this article, various types of sagittal balance-correction osteotomies are reviewed primarily on the basis of the 3 most commonly used procedures: Smith-Petersen osteotomy, pedicle subtraction osteotomy, and vertebral column resection. Familiarity with the expected imaging appearance and commonly encountered complications seen on postoperative imaging studies following correction osteotomies is crucial for accurate image interpretation.



Time for a Time Window Extension: Insights from Late Presenters in the ESCAPE Trial [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

The safety and efficacy of endovascular therapy for large-artery stroke in the extended time window is not yet well-established. We performed a subgroup analysis on subjects enrolled within an extended time window in the Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE) trial.

MATERIALS AND METHODS:

Fifty-nine of 315 subjects (33 in the intervention group and 26 in the control group) were randomized in the ESCAPE trial between 5.5 and 12 hours after last seen healthy (likely to have groin puncture administered 6 hours after that). Treatment effect sizes for all relevant outcomes (90-day mRS shift, mRS 0–2, mRS 0–1, and 24-hour NIHSS scores and intracerebral hemorrhage) were reported using unadjusted and adjusted analyses.

RESULTS:

There was no evidence of treatment heterogeneity between subjects in the early and late windows. Treatment effect favoring intervention was seen across all clinical outcomes in the extended time window (absolute risk difference of 19.3% for mRS 0–2 at 90 days). There were more asymptomatic intracerebral hemorrhage events within the intervention arm (48.5% versus 11.5%, P = .004) but no difference in symptomatic intracerebral hemorrhage.

CONCLUSIONS:

Patients with an extended time window could potentially benefit from endovascular treatment. Ongoing randomized controlled trials using imaging to identify late presenters with favorable brain physiology will help cement the paradigm of using time windows to select the population for acute imaging and imaging to select individual patients for therapy.



MR Imaging Characteristics Associate with Tumor-Associated Macrophages in Glioblastoma and Provide an Improved Signature for Survival Prognostication [ADULT BRAIN]

BACKGROUND AND PURPOSE:

In glioblastoma, tumor-associated macrophages have tumor-promoting properties. This study determined whether routine MR imaging features could predict molecular subtypes of glioblastoma that differ in the content of tumor-associated macrophages.

MATERIALS AND METHODS:

Seven internally derived MR imaging features were assessed in 180 patients, and 25 features from the Visually AcceSAble Rembrandt Images feature set were assessed in 164 patients. Glioblastomas were divided into subtypes based on the telomere maintenance mechanism: alternative lengthening of telomeres positive (ALT+) and negative (ALT–) and the content of tumor-associated macrophages (with [M+] or without [M–] a high content of macrophages). The 3 most frequent subtypes (ALT+/M–, ALT–/M+, and ALT–/M–) were correlated with MR imaging features and clinical parameters. The fourth group (ALT+/M+) did not have enough cases for correlation with MR imaging features.

RESULTS:

Tumors with a regular margin and those lacking a fungating margin, an expansive T1/FLAIR ratio, and reduced ependymal extension were more frequent in the subgroup of ALT+/M– (P < .05). Radiologic necrosis, lack of cystic component (by both criteria), and extensive peritumoral edema were more frequent in ALT–/M+ tumors (P < .05). Multivariate testing with a Cox regression analysis found the cystic imaging feature was additive to tumor subtype, and O6-methylguanine methyltransferase (MGMT) status to predict improved patient survival (P < .05).

CONCLUSIONS:

Glioblastomas with tumor-associated macrophages are associated with routine MR imaging features consistent with these tumors being more aggressive. Inclusion of cystic change with molecular subtypes and MGMT status provided a better estimate of survival.



Reviewers' list November 2017

JAAD Case Reports (JDCR) is indebted to its reviewers, on whose efforts we rely to maintain the exceptional quality of the journal. We thank the following individuals who volunteered their time and knowledge to review articles (July 2016 - June 2017):

Radiation-induced inflammatory dermatosis: Another facet of the immunocompromised cutaneous district

To the Editor: We read with great interest the letter by De Vita et al1 published in this issue of the Journal that discusses the putative mechanisms underlying our case of radiation-induced hidradenitis suppurativa.2 The authors suggested this clinical presentation to be a typical example of "isoradiotopic response," where the onset of a new skin disease is strikingly limited to a skin area previously exposed to ionizing radiation,3 and of an "immunocompromised cutaneous district" (ICD) where the mechanisms involved in any secondary disorder occurring on irradiated skin areas are connected to local dysfunction of lymph drainage or neuroimmune signaling resulting in immune dysregulation.

Hidradenitis suppurativa after radiotherapy for uterine adenocarcinoma: A typical example of an isoradiotopic response

To the Editor: We read with great interest the case report by Haber et al1 in the May 2017 issue of JAAD Case Reports which described a 57-year-old woman who developed radiation-induced hidradenitis suppurativa (HS) after radiotherapy (RT) for uterine adenocarcinoma. In this patient, HS appeared 1 year after the last cycle of RT and, interestingly, the lesions were strikingly contained within the distinct margins of the radiation treatment, clearly indicating induction by ionizing radiation.

Hair repigmentation associated with the use of brentuximab

Brentuximab vedotin is an antibody-drug conjugate that is approved by the US Food and Drug Administration to treat refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma. Numerous clinical trials are currently evaluating the efficacy of brentuximab for other conditions, including T-cell lymphoma and steroid refractory graft-versus-host disease. Although brentuximab has been associated with various adverse effects, such as neutropenia, peripheral sensory neuropathy, fatigue, nausea, anemia, upper respiratory tract infection, diarrhea, pyrexia, rash, thrombocytopenia, cough, and vomiting, no reports exist to date of changes in hair pigmentation related to brentuximab.

Visual impairment reversal with oral acitretin therapy in keratitis-ichthyosis-deafness (KID) syndrome

Keratitis-ichthyosis-deafness (KID) syndrome is a rare genodermatosis with approximately 100 published cases. Although it is classified as an autosomal dominant disorder, more than 90% of cases are caused by sporadic mutations predominantly in gap junction protein β2 (GJB2) on chromosome 13q11-q12 (OMIM 148210). GJB2 encodes connexin 26, a gap junction protein, which plays a role in epithelial differentiation.1 The characteristic clinical triad includes bilateral sensorineural hearing loss, vascularizing keratitis, and erythrokeratoderma.

Secretory carcinoma of the skin: Case report and review of the literature

Mammary analogue secretory carcinoma is a primary salivary gland tumor that was first described in 2010, with histologic, immunophenotypic, and genetic features reminiscent of secretory carcinoma of the breast.1 Both tumors harbor the same defining ETV6–NTRK3 fusion gene, resulting from the t(12;15) (p13;q25) translocation. Of interest to dermatopathologists, primary cutaneous tumors resembling secretory carcinoma of salivary gland and breast have been recently described in several case reports and a case series.

Granulomatous hepatitis in a healthy adult after bacillus Calmette–Guérin injection into a plantar wart

Viral warts are a common skin disease that occurs in 7% to 10% of the entire population. In most cases, the warts disappear spontaneously within 2 years of their onset, but in about one-third of the cases, the warts recur despite repeated treatment.1 Treatment for warts includes salicylic acid,2 podophyllin,3 bleomycin,4 5-fluorouracil, laser therapy,5 interferons, cauterization, cryosurgery,6 and other surgical methods that usually cause pain and scarring.

Massive perianal ulceration: Entamoeba histolytica and Candida albicans co-infection

Although Entamoeba histolytica, named for its notorious tissue-lysing facility, is a major cause of morbidity and mortality worldwide, cutaneous involvement is rare. Presentation in nonendemic countries is exceptionally rare.1 We present a case of amebiasis cutis presenting as a deeply invasive perianal ulceration. Delayed diagnosis, empiric use of broad-spectrum antibiotics, and systemic corticosteroids provided fertile ground for Candida albicans co-infection. This case highlights the tissue destructive nature of E histolytica and the potential for candidiasis to potentiate this tissue destruction.

Infliximab therapy for Netherton syndrome: A case report

Netherton syndrome (NS), also known as Comèl-Netherton syndrome, was clinically described in 1964 by Wilkinson et al1 and is characterized by the triad of ichthyosis linearis circumflexa, trichorrhexis invaginata, and atopic diathesis.1 The single entities, ichthyosis linearis circumflexa and the "bamboo hair" were previously described by Comèl2 in 1949 and Netherton3 in 1958, respectively.

Intravascular large B-cell lymphoma presenting as panniculitis

Intravascular large B-cell lymphoma (IVLBCL) is a rare disease with an incidence of less than 1 person per 1 million. It is a subtype of diffuse large B-cell lymphoma in which the lymphoma cells reside predominantly within the lumina of blood vessels (particularly capillaries) with circulating neoplastic cells detectable in the peripheral blood in less than 10%.1 Presenting clinical features are extremely variable. We describe a case of IVLBCL presenting as panniculitis. This case emphasizes the importance of collaboration between dermatology and pathology in considering rare but serious diagnoses when clinical features and histologic findings are discordant.

Identification of novel targetable mutations in metastatic anorectal melanoma by next-generation sequencing

The molecular classification of melanomas, which can have diverse clinical and histopathologic features, is defined by the acquisition of somatic mutations. Mutations such as BRAF V600E result in constitutive activation of critical signaling pathways that promote formation of melanocytic nevi.1 Acquisition of subsequent mutations induces the progression to melanomagenesis, and further accumulation of tertiary mutations might promote metastasis. These molecular pathways remain largely undiscovered.

p16+ Squamous cell carcinoma in situ masquerading as genital psoriasis

Cutaneous neoplasms of the male genitalia are an important consideration in older men and immunocompromised patients. They are derived from the squamous epithelium and have an association with human papilloma virus (HPV).1 HPV types 16, 18, and 57b have been isolated, and their DNA is present in approximately 40% to 45% of all penile carcinomas.2,3 Squamous cell neoplasia includes both squamous cell carcinoma in situ (SCCIS) and invasive carcinoma. Risk factors include increasing age, immunosuppression, smoking, exposure to ultraviolet light, benzene, and arsenic.

Combination of imiquimod with cryotherapy in the treatment of penile intraepithelial neoplasia

Penile intraepithelial neoplasia (PIN) is a rare disease that can be associated with great morbidity and mortality. Historically, the term PIN has been used to refer to 3 premalignant penile lesions: Bowen disease (BD), erythroplasia of Queyrat (EQ), and Bowenoid papulosis (BP). Although these clinical variants share similar histopathologic features of squamous cell carcinoma in situ—namely, transepidermal keratinocyte atypia, numerous mitotic figures, and nuclear crowding—they vary in their clinical presentation.

Oral dehydroepiandrosterone might prevent frequent tears in atrophic skin: A case report

Large superficial tears frequently develop during minor trauma to the fragile skin of older men and women. These tears are more common in chronically ill or malnourished patients,1,2 can develop during attempted assisted transfer of weak patients, and were recently reported to have been treated annually in 1.5 × 106 MediCare patients during their care in an acute or long-term medical care facility. They also develop frequently in elderly out-patients and those using inhaled or systemic corticosteroids for extensively lengths of time.

Bullous drug eruption with leukemic cell infiltrate in the setting of new-onset acute myeloid leukemia

Bullous drug eruptions are cutaneous dermal hypersensitivity reactions to systemically administered medications. Classically, these eruptions appear 5 to 14 days after the initiation of the offending agent.1 On histopathologic examination, dermal hypersensitivity reactions are characterized by a superficial perivascular lymphocytic infiltrate, often with admixed eosinophils.2 We report an unusual case of a bullous drug reaction, histologically characterized by leukemic cells in a patient with new-onset acute myeloid leukemia (AML).

Complete spontaneous regression of a metastatic acral melanoma with associated leukoderma

Cutaneous melanoma (CM) is the leading cause of skin cancer mortality worldwide despite constituting only 4% of skin cancers.1 Acral melanoma (AM) is a distinct variant of CM and is generally associated with a poor prognosis. Complete spontaneous regression of CM is a rare but well described phenomenon. We present an unusual case of a complete spontaneously regressed metastatic AM with melanoma-associated leukoderma.

Successful use of dabrafenib after the occurrence of drug rash with eosinophilia and systemic symptoms (DRESS) induced by vemurafenib

Vemurafenib and dabrafenib are 2 BRAF inhibitors that are approved by the US Food and Drug Administration for the treatment of metastatic malignant melanoma with BRAF mutation. These drugs improve overall- and progression-free survival. Some severe vemurafenib-induced reactions have been reported, which commonly require treatment withdrawal. We report the case of a patient with metastatic malignant melanoma in whom DRESS developed likely from vemurafenib. Because the patient did not respond to many previous treatments, dabrafenib, another BRAF inhibitor, was started without reoccurrence of DRESS.

Stewart–Treves syndrome in a spinal cord injury patient with MYC amplification

Angiosarcoma is a rare, aggressive vascular malignancy with a poor prognosis. Primary cutaneous angiosarcoma arises de novo on the head and neck of the elderly, whereas secondary angiosarcoma arises in the setting of known risk factors, including chronic lymphedema or previous irradiation. When associated with chronic lymphedema, it is eponymously referred to as Stewart–Treves syndrome. The pathophysiology of tumorigenesis in these cases is not fully understood, but may be related to ongoing angiogenesis and impaired cellular immunity induced by lymphedema.

Quantification of granuloma volume and response to treatment in cutaneous sarcoidosis using 3-dimensional high-frequency ultrasound scan

Cutaneous involvement occurs in 25% to 30% of patients with sarcoidosis.1 Effective treatment of the disease has historically been challenging given a lack of an objective, reproducible marker of disease activity. Here we present a case using 3-dimensional high-frequency ultrasound (3D HFU) to quantify cutaneous granuloma volume as a measure of disease activity.

Sacral zoster with a primary complaint of difficulty voiding

Motor paresis is a known but rare complication of herpes zoster, estimated to occur between 0% and 6% of all cases.1 The pathogenesis of motor involvement is poorly understood but has been reported occurring with virus reactivation in nerves of the head, trunk, and extremities.1 In addition, visceral motor paresis manifesting as urinary or bowel dysfunction has also been described.1 Here we report a case of a 27-year-old man who presented with a primary complaint of difficulty voiding, which was eventually found to be caused by sacral herpes zoster.

Body Aesthetics

Body Aesthetics

Drastic decrease of the HIV reservoir in a patient treated with nivolumab for lung cancer



Transformation of sulfaquinoxaline by chlorine and UV light in water: kinetics and by-product identification

Abstract

Sulfaquinoxaline (SQX) is an antimicrobial of the sulfonamide class, frequently detected at low levels in drinking and surface water as organic micropollutant. The main goal of the present study is the evaluation of SQX reactivity during chlorination and UV irradiations which are two processes mainly used in water treatment plants. The SQX transformation by chlorination and UV lights (254 nm) was investigated in purified water at common conditions used for water disinfection (pH = 7.2, temperature = 25 °C, [chlorine] = 3 mg L−1). The result shows a slow degradation of SQX during photolysis compared with chlorination process. Kinetic studies that fitted a fluence-based first-order kinetic model were used to determine the kinetic constants of SQX degradation; they were equal to 0.7 × 10−4 and 0.7 × 10−2 s−1corresponding to the half time lives of 162 and 1.64 min during photolysis and chlorination, respectively. In the second step, seven by-products were generated during a chlorination and photo-transformation of SQX and identified using liquid chromatography with electrospray ionization and tandem mass spectrometry (MS-MS). SO2 extrusion and direct decomposition were the common degradation pathway during photolysis and chlorination. Hydroxylation and isomerization were observed during photodegradation only while electrophilic substitution was observed during chlorination process.



Comparative studies on the performance and emissions of a direct injection diesel engine fueled with neem oil and pumpkin seed oil biodiesel with and without fuel preheater

Abstract

In the present experimental analysis, two non-edible oils namely neem oil and pumpkin seed oil were considered. They are converted into respective biodiesels namely neem oil methyl ester (B1) and pumpkin seed oil methyl ester (B2) through transesterification process and their physical and chemical properties were examined using ASTM standards. Diesel was used as a baseline fuel in Kirloskar TV1 model direct injection four stroke diesel engine. A fuel preheater was designed and fabricated to operate at various temperatures (60, 70, and 80 °C). Diesel showed higher brake thermal efficiency (BTE) than biodiesel samples. Lower brake specific fuel consumption (BSFC) was obtained with diesel than B1 sample. B1 exhibited lower BSFC than B2 sample without preheating process. High preheating temperature (80 °C) results in lower fuel consumption for B1 sample. The engine emission characteristics like carbon monoxide (CO), hydrocarbon (HC), and smoke were found lower with B1 sample than diesel and B2 except oxides of nitrogen (NOx) emission. In preheating of fuel, B1 sample with high preheating temperature showed lower CO, HC, and smoke emission (except NOx) than B2 sample.



Effects of lead, cadmium, chromium, and arsenic on the sorption of lindane and norfloxacin by river biofilms, particles, and sediments

Abstract

The sorption of both classic and emerging organic contaminants onto aquatic solids is a critical process that controls their fate in natural waters. Sorption is affected by numerous factors, including coexisting heavy metals. The mechanisms of the influence of heavy metals, especially those occurring in acid radical anions, are still unclear. Here, the effects of Pb, Cd, Cr, and As on the sorption of lindane and norfloxacin (NOR) onto natural biofilms, suspended particles, and sediments from one river were investigated following batch equilibration methods. In addition, changes in representative components that have important roles in sorption from these solids in the presence and absence of metals were characterized by spectrum analyses. The results indicated that sorption of lindane and NOR on the three solids in the absence of heavy metals was highly linear and nonlinear, respectively. Pb and Cd promoted and Cr and As suppressed hydrophobic lindane sorption on the three solids. This was because Pb and Cd enhanced but Cr and As weakened the hydrophobicity of these solids. Pb, Cd, Cr, and As decreased NOR sorption on sediments and suspended particles at pH 5.7~6.3. This was due to electrostatic competition between cationic Pb/Cd and NORH2+, and the combination of Cr/As acid radicals with NORH2+, which suppressed its ion-exchange adsorption. Pb, Cd, Cr, and As generally increased the sorption of NOR onto the biofilms at pH 5.7~6.3. Pb and Cd strengthened the flocculation of dissolved organic matter combined with NORH2+ onto the biofilms. Cr and As enhanced the hydrophilicity of biofilms, and then increased their sorption of NOR with active hydrophilic groups. The mechanisms of how different heavy metals affect NOR sorption by biofilms were more complicated than the mechanisms affecting lindane sorption, as well as by sediments and particles.



Pregnancy and Lifetime Exposure to Fine Particulate Matter and Infant Mortality in Massachusetts, 2001–2007

Abstract
Many studies have found associations between particulate matter having an aerodynamic diameter of ≤2.5 μm (PM2.5) and adult mortality. Comparatively few studies evaluated particles and infant mortality, although infants and children are particularly vulnerable to pollution. Moreover, existing studies mostly focused on short-term exposure to larger particles. We investigated PM2.5 exposure during pregnancy and lifetime and postneonatal infant mortality. The study included 465,682 births with 385 deaths in Massachusetts (2001–2007). Exposures were estimated from PM2.5-prediction models based on satellite imagery. We applied extended Cox proportional hazards modeling with time-dependent covariates to total, respiratory, and sudden infant death syndrome mortality. Exposure was calculated from birth to death (or end of eligibility for outcome, at age 1 year) and pregnancy (gestation and each trimester). Models adjusted for sex, birth weight, gestational length, season of birth, temperature, relative humidity, and maternal characteristics. Hazard ratios for total, respiratory, and sudden infant death syndrome mortality per-interquartile-range increase (1.3 μg/m3) in lifetime PM2.5 exposure were 2.66 (95% confidence interval (CI): 2.11, 3.36), 3.14 (95% CI: 2.39, 4.13), and 2.50 (95% CI: 1.56, 4.00), respectively. We did not observe a statistically significant relationship between gestational exposure and mortality. Our findings provide supportive evidence that lifetime exposure to PM2.5 increases risk of infant mortality.

RE: “TIME SPENT COMMUTING TO WORK AND MENTAL HEALTH: EVIDENCE FROM 13 WAVES OF AN AUSTRALIAN COHORT STUDY”



THE AUTHORS REPLY



Infections in Early Life and Development of Celiac Disease

Abstract
It has been suggested that early infections are associated with increased risk for later celiac disease (CD). We analyzed prospective claims data of infants from Bavaria, Germany, born between 2005 and 2007 (n = 295,420), containing information on medically attended infectious diseases according to International Classification of Diseases, Tenth Revision, codes in quarterly intervals. We calculated hazard ratios and 95% confidence intervals for time to CD diagnosis by infection exposure, adjusting for sex, calendar month of birth, and number of previous healthcare visits. CD risk was higher among children who had had a gastrointestinal infection during the first year of life (hazard ratio = 1.32, 95% confidence interval: 1.12, 1.55) and, to a lesser extent, among children who had had a respiratory infection during the first year of life (hazard ratio = 1.22, 95% confidence interval: 1.04, 1.43). Repeated gastrointestinal infections during the first year of life were associated with particularly increased risk of CD in later life. These findings indicate that early gastrointestinal infections may be relevant for CD development.

Maternal Lifetime Stress and Prenatal Psychological Functioning and Decreased Placental Mitochondrial DNA Copy Number in the PRISM Study

Abstract
Psychosocial stress contributes to placental oxidative stress. Mitochondria are vulnerable to oxidative stress, which can lead to changes in mitochondrial DNA copy number (mtDNAcn). We examined associations of maternal lifetime stress, current negative life events, and depressive and posttraumatic-stress-disorder symptom scores with placental mtDNAcn in a racially/ethnically diverse sample (n = 147) from the Programming of Intergenerational Stress Mechanisms (PRISM) study (Massachusetts, March 2011 to August 2012). In linear regression analyses adjusted for maternal age, race/ethnicity, education, prenatal fine particulate matter exposure, prenatal smoking exposure, and the sex of the child, all measures of stress were associated with decreased placental mtDNAcn (all P values < 0.05). Weighted-quantile-sum (WQS) regression showed that higher lifetime stress and depressive symptoms accounted for most of the effect on mtDNAcn (WQS weights: 0.25 and 0.39, respectively). However, among white individuals, increased lifetime stress and posttraumatic stress disorder symptoms explained the majority of the effect (WQS weights: 0.20 and 0.62, respectively) while among nonwhite individuals, lifetime stress and depressive symptoms accounted for most of the effect (WQS weights: 0.27 and 0.55, respectively). These analyses are first to link increased maternal psychosocial stress with reduced placental mtDNAcn and add to literature documenting racial/ethnic differences in the psychological sequelae of chronic stress that may contribute to maternal-fetal health.

Measuring the Impact of Disasters Using Publicly Available Data: Application to Hurricane Sandy (2012)

Abstract
The unexpected nature of disasters leaves little time or resources for organized health surveillance of the affected population, and even less for those who are unaffected. An ideal epidemiologic study would monitor both groups equally well, but would typically be decided against as infeasible or costly. Exposure and health outcome data at the level of the individual can be difficult to obtain. Despite these challenges, the health effects of a disaster can be approximated. Approaches include 1) the use of publicly available exposure data in geographic detail, 2) health outcomes data—collected before, during, and after the event, and 3) statistical modeling designed to compare the observed frequency of health outcomes with the counterfactual frequency hidden by the disaster itself. We applied these strategies to Hurricane Sandy, which struck the northeastern United States in October 2012. Hospital admissions data from the state of New York with information on primary payer as well as patient demographic characteristics were analyzed. To illustrate the method, we present multivariate logistic regression results for the first 2 months after the hurricane. Inferential implications of admissions data on nearly the entire target population in the wake of a disaster are discussed.

Work-Related Biomechanical Exposure and Job Strain as Separate and Joint Predictors of Musculoskeletal Diseases: A 28-Year Prospective Follow-up Study

Abstract
We investigated how work-related biomechanical exposure and job strain in midlife separately and jointly predicted back and degenerative musculoskeletal diseases (MSDs). A total of 6,257 employees participated in the Finnish Longitudinal Study on Aging Municipal Employees (FLAME) in 1981 and were followed up for 28 years. Risk ratios and the relative excessive risk due to interaction and 95% confidence intervals were modeled for separate and joint prediction estimates, respectively. After adjustment for confounders, job strain predicted degenerative MSDs among women after 4 and 11 years of follow-up. After 11 years, both exposures predicted both types of MSDs among men. Joint exposure predicted both types of MSDs after 4 years among women (for back MSDs, risk ratio (RR) = 1.58, 95% confidence interval (CI): 1.15, 2.18; for degenerative MSDs, RR = 1.59, 95% CI: 1.21, 2.07) and men (for back MSDs, RR = 1.50, 95% CI: 1.05, 2.15; for degenerative MSDs, RR = 1.61, 95% CI: 1.16, 2.22) and both types of MSDs after 11 years (for back MSDs, RR = 1.72, 95% CI: 1.21, 2.43; for degenerative MSDs, RR = 1.68, 95% CI: 1.25, 2.46) among men only, but the relative excessive risk due to interaction was not significant throughout. However, after 28 years, the separate and joint exposures did not predict MSDs. Workplace interventions should be focused on reducing job strain along with biomechanical exposure for possible prevention of MSDs in working life and around the time of retirement, but there may be other pathways of onset of MSDs in old age.

Group-Based Trajectory of Body Shape From Ages 5 to 55 Years and Cardiometabolic Disease Risk in 2 US Cohorts

Abstract
The association of adiposity across the life span with cardiometabolic risk is not completely delineated. We used a group-based modeling approach to identify distinct trajectories of body shape from ages 5 years to 55 years among 84,792 women from the Nurses' Health Study (1976–2010) and 37,706 men from the Health Professionals Follow-up Study (1986–2010) and assessed the associations between these trajectories and incidence of type 2 diabetes and cardiovascular disease (CVD) during a 17-year follow-up period. Compared with those who maintained leanness throughout the life span ("lean-stable" trajectory), participants who maintained a medium body shape ("medium-stable" trajectory) had somewhat increased risk. Those who started lean but had a moderate or marked increase in adiposity ("lean-moderate increase" and "lean-marked increase" trajectories) had even higher risk (e.g., for a "lean-marked increase" trajectory, the hazard ratio for diabetes was 8.11 (95% confidence interval (95% CI): 7.10, 9.27) in women and 2.36 (95% CI: 2.04, 2.74) in men; for CVD, it was 1.38 (95% CI: 1.25, 1.52) in women and 1.28 (95% CI: 1.16, 1.41) in men). Participants who started heavy and became heavier (a "heavy-increase" trajectory) had substantially elevated risk (for diabetes, the hazard ratio was 7.34 (95% CI: 6.40, 8.42) in women and 2.80 (95% CI: 2.37, 3.31) in men; for CVD, it was 1.55 (95% CI: 1.40, 1.71) in women and 1.35 (95% CI: 1.20, 1.53) in men). Our data showed that trajectories of body shape from ages 5 to 55 years were associated with subsequent risk of developing type 2 diabetes and CVD.

Advanced Maternal Age and the Risk of Low Birth Weight and Preterm Delivery: a Within-Family Analysis Using Finnish Population Registers

Abstract
Advanced maternal age at birth is considered a major risk factor for birth outcomes. It is unclear to what extent this association is confounded by maternal characteristics. To test whether advanced maternal age at birth independently increases the risk of low birth weight (<2,500 g) and preterm birth (<37 weeks' gestation), we compared between-family models (children born to different mothers at different ages) with within-family models (children born to the same mother at different ages). The latter procedure reduces confounding by unobserved parental characteristics that are shared by siblings. We used Finnish population registers, including 124,098 children born during 1987–2000. When compared with maternal ages 25–29 years in between-family models, maternal ages of 35–39 years and ≥40 years were associated with percentage increases of 1.1 points (95% confidence intervals: 0.8, 1.4) and 2.2 points (95% confidence intervals: 1.4, 2.9), respectively, in the probability of low birth weight. The associations are similar for the risk of preterm delivery. In within-family models, the relationship between advanced maternal age and low birth weight or preterm birth is statistically and substantively negligible. In Finland, advanced maternal age is not independently associated with the risk of low birth weight or preterm delivery among mothers who have had at least 2 live births.

Neighborhood Physical Environment and Changes in Body Mass Index: Results From the Multi-Ethnic Study of Atherosclerosis

Abstract
Longitudinal associations between neighborhood characteristics and body mass index (BMI; weight (kg)/height (m)2) were assessed from 2000 to 2011 among 5,919 participants in the Multi-Ethnic Study of Atherosclerosis. The perceived availability of healthy food and walking environment were assessed via surveys, and 1-mile (1.6-km) densities of supermarkets, fruit-and-vegetable stores, and recreational facilities were obtained through a commercial database. Econometric fixed-effects models were used to estimate the association between within-person changes in neighborhood characteristics and within-person change in BMI. In fully adjusted models, a 1-standard-deviation increase in the healthy food environment index was associated with a 0.16-kg/m2 decrease in BMI (95% confidence interval (CI): −0.27, −0.06) among participants with obesity at baseline. A 1-standard-deviation increase in the physical activity environment index was associated with 0.13-kg/m2 (95% CI: −0.24, −0.02) and 0.14-kg/m2 (95% CI: −0.27, −0.01) decreases in BMI for participants who were overweight and obese at baseline, respectively. Paradoxically, increases in the physical activity index were associated with BMI increases in persons who were normal-weight at baseline. This study provides preliminary longitudinal evidence that favorable changes in neighborhood physical environments are related to BMI reductions in obese persons, who comprise a substantial proportion of the US population.

Potential for Bias When Estimating Critical Windows for Air Pollution in Children’s Health

Abstract
Evidence supports an association between maternal exposure to air pollution during pregnancy and children's health outcomes. Recent interest has focused on identifying critical windows of vulnerability. An analysis based on a distributed lag model (DLM) can yield estimates of a critical window that are different from those from an analysis that regresses the outcome on each of the 3 trimester-average exposures (TAEs). Using a simulation study, we assessed bias in estimates of critical windows obtained using 3 regression approaches: 1) 3 separate models to estimate the association with each of the 3 TAEs; 2) a single model to jointly estimate the association between the outcome and all 3 TAEs; and 3) a DLM. We used weekly fine-particulate-matter exposure data for 238 births in a birth cohort in and around Boston, Massachusetts, and a simulated outcome and time-varying exposure effect. Estimates using separate models for each TAE were biased and identified incorrect windows. This bias arose from seasonal trends in particulate matter that induced correlation between TAEs. Including all TAEs in a single model reduced bias. DLM produced unbiased estimates and added flexibility to identify windows. Analysis of body mass index z score and fat mass in the same cohort highlighted inconsistent estimates from the 3 methods.

Establishment of integration-free induced pluripotent stem cells from human recessive dystrophic epidermolysis bullosa keratinocytes

Induced pluripotent stem cells (iPSCs) have a pluripotency that is biologically homologous to that of embryoid stem cells, which are generated from various somatic cells by the induction of reprogramming factors such as Nanog, Klf4, Oct3/4 (Pou5f1), Sox2, and c-Myc [1]. Since iPSCs have an unlimited proliferative capacity, they are regarded as a potential source of regenerative therapies for human diseases including Parkinson's disease, spinal cord injury, osteoarthritis, heart failure due to ischemic heart disease or genetic disorders, and diabetes mellitus [2–6].

Reconstructed human epidermis for in vitro studies on atopic dermatitis: A review

Atopic dermatitis (AD) is a chronic inflammatory skin disease causing a strong impact on quality of life. Its pathophysiology is the result of complex interactions involving immunological, genetic and environmental factors. Although there are several published in vitro three-dimensional models mimicking AD, none of them have taken all these pathophysiological features into account; thus, finding the right model may be complicated. This paper reviews the literature on the different reconstructed epidermis models of AD as well as their relevance.

Substance P restores normal skin architecture and reduces epidermal infiltration of sensory nerve fiber in TNCB-induced atopic dermatitis-like lesions in NC/Nga mice

Atopic dermatitis (AD) is a chronic, relapsing, highly pruritic inflammatory skin disease whose onset is often preceded by continuous allergic inflammation [1–3]. Itching is an uncomfortable symptom experienced by patients with AD and also a characteristic feature of chronic dermatitis [4]. Scratching can induce the release of proinflammatory cytokines and chemokines, causing chronic dermatitis. Scratching begins a vicious scratching-itching cycle that further weakens the skin barrier. The impaired skin barrier function in AD leads to increased transepidermal water loss (TEWL) and antigen absorption, which contributes to cutaneous hyper-reactivity to environmental triggers.

Historical anthropogenic mercury in two lakes of Central Chile: comparison between an urban and rural lake

Abstract

Mercury concentrations in the environment tend to decrease in recent years due to environmental restrictions. Lakes store mercury in their sediments, making them potential secondary contamination sources. In South America, the occurrence of mercury in lake systems has been associated mainly with volcanic emissions and only few records anthropogenic contamination in the pre-Hispanic period. The objective of this research was to study historical anthropogenic mercury concentration in two lakes in Central Chile (La Señoraza and Pillo), in order to establish background mercury levels and their variations from preindustrial to modern periods. Different background levels and mercury concentrations were found in each lake, with significantly higher concentrations in Lake La Señoraza during the last 150 years. Mining-related activities during the nineteenth century could have a negligible influence on mercury concentrations. Later on, the use of coal railroads and subsequent employment of mercury in the cellulose industry were associated with three- and fourfold increases in mercury concentration over the nineteenth century background levels, which decrease once these activities ceased. However, in the case of Lake Pillo, an important increase in mercury concentration can be observed between 1990 and the early twenty-first century, which could be related to a higher watershed/lake area ratio, extensive agriculture, and volcanic emission, being the latter that could have contributed with mercury to both systems. Nevertheless, sedimentological characteristics in Lake Pillo can be favorable to retain mercury in this aquatic system up to the present day.



Spatio-temporal evaluation of emerging contaminants and their partitioning along a Brazilian watershed

Abstract

The occurrence, partitioning, and spatio-temporal distribution of seven pharmaceuticals for human use, three steroid hormones and one personal care product were determined in surface water, suspended particulate matter (SPM), and sediment of Piraí Creek and Jundiaí River (Jundiaí River Basin, São Paulo, Brazil). The maximum average detected concentrations of the compounds in the Piraí River samples were < 30 ng L−1, except for caffeine (222 ng L−1). In Jundiaí River samples, most of the compounds were frequently detected, wherein caffeine had the highest concentration, with maximum average concentrations of 14,050 ng L−1, followed by atenolol (431 ng L−1), ibuprofen (268 ng L−1) and diclofenac (214 ng L−1). Atenolol, propranolol, estrone, and triclosan were the contaminants most frequently detected in sediment and SPM samples. Triclosan had the highest average proportion of SPM as opposed to in the aqueous phase (> 75%). Contaminants with acid functional groups showed, in general, a lower tendency to bind to particulate matter and sediments. In addition, hydrophobicity had an important effect on their environmental partitioning. The spatial distribution of contaminants along the Jundiaí River was mainly affected by the higher concentration of contaminants in water samples collected downstream from a sewage treatment plant (STP). The results obtained here clearly showed the importance of the analysis of some contaminants in the whole water, meaning both dissolved and particulate compartments in the water, and that the partitioning is ruled by a set of parameters associated to the physicochemical characteristics of contaminants and the matrix properties of the studied, which need be considered in an integrated approach to understand the fate of emerging chemical contaminants in aquatic environments.



Surgical pearl: strip split-thickness skin graft obtained with DermaBlade to cover large surgical defects on the scalp



Effectiveness Of Low-Level Laser Therapy In Lichen Planopilaris



Pemphigus and hematologic malignancies: A population-based study of 11,859 patients

Hematologic malignancies have been reported sporadically in patients with pemphigus.In the current study, significant associations were observed between pemphigus and chronic leukemia, multiple myeloma, and non-Hodgkin lymphoma.Further research is needed to confirm these findings in other cohorts.

Mitotic Rate is Associated with Positive Lymph Nodes in Thin Melanomas

Mitotic rate will be removed from melanoma staging guidelines in 2018 Mitotic rate is strongly associated with lymph node status in patients with thin cutaneous melanoma Pathology reports should continue to report mitotic rate for cutaneous melanoma

Replacing Epiphenomenalism: a Pluralistic Enactive Take on the Metaplasticity of Early Body Ornamentation

Abstract

In the domain of evolutionary cognitive archaeology, the early body ornaments from the Middle Stone Age/Palaeolithic are generally treated as mere by-products of an evolved brain-bound cognitive architecture selected to cope with looming social problems. Such adaptive artefacts are therefore taken to have been but passive means of broadcasting a priori envisaged meanings, essentially playing a neutral role for the human mind. In contrast to this epiphenomenalist view of material culture, postphenomenology and the Material Engagement Theory (MET) have been making a case for the active role of artefacts on the count that they can actually shape and restructure the human mind. By bringing these dissenting voices together, the paper at hand employs an enactive way of thinking in order to challenge the epiphenomenalist take on early body ornaments. In fact, two variants of enactivism are presented, each advancing a unique explanation of how the engagement of early humans with body ornaments transformed their minds along the two postphenomenological categories of embodied and hermeneutic cognition. Our theoretical frameworks specifically seek to explore how early beadworks could have scaffolded the creation of semiotic categories and the development of cognitive processes. Despite relying on inherently different premises, both theories suggest that beads fostered the emergence of an epistemic apparatus which thoroughly transformed the way humans engaged with the world. Having concurred on the ornaments' transformative effects, we ultimately conclude that the epiphenomenalist paradigm best be replaced with an enactive approach grounded on the dictates of postphenomenology and the MET.



Peak Nasal Inspiratory Flow as an Objective Measure

This study assesses the utility of peak nasal inspiratory flow as an objective diagnostic and outcome measure for functional septorhinoplasty in combination with the Nasal Obstruction Symptom Evaluation scale.

Length of Stay for Free Tissue Transfer to Head and Neck Defects

This database review evaluates patient and surgical factors associated with length of stay and reoperation following surgical procedures for malignant neoplasm of the head and neck involving microvascular free tissue transfer reconstruction.

Indoor air quality of everyday use spaces dedicated to specific purposes—a review

Abstract

According to literature data, some of the main factors which significantly affect the quality of the indoor environment in residential households or apartments are human activities such as cooking, smoking, cleaning, and indoor exercising. The paper presents a literature overview related to air quality in everyday use spaces dedicated to specific purposes which are integral parts of residential buildings, such as kitchens, basements, and individual garages. Some aspects of air quality in large-scale car parks, as a specific type of indoor environment, are also discussed. All those areas are characterized by relatively short time use. On the other hand, high and very high concentration levels of xenobiotics can be observed, resulting in higher exposure risk. The main compounds or group of chemical compounds are presented and discussed. The main factors influencing the type and amount of chemical pollutants present in the air of such areas are indicated.



Water quality in simulated eutrophic shallow lakes in the presence of periphyton under different flow conditions

Abstract

Although the effects of periphyton on water quality and its relationship with flow conditions have been studied by researchers, our understanding about their combined action in eutrophic shallow lakes is poor. In this research, four aquatic model ecosystems with different water circulation rates and hydraulic conditions were constructed to investigate the effect of periphyton and flow condition on water quality. The concentrations of NH4+, TP, and chlorophyll–a and flow conditions were determined. The results show that, as a result of the rising nutrient level at the early stage and the decline in the lower limit, the presence of periphyton can make the ecosystem adaptable to a wider range of nutrients concentration. In terms of the flow condition, the circulation rate and hydraulic condition are influential factors for aquatic ecosystem. Higher circulation rate in the ecosystem, on one hand, facilitates the metabolism by accelerating nutrient cycling which is beneficial to water quality; on the other hand, high circulation rate leads to the nutrient lower limit rising which is harmful to water quality improvement. At low velocities, slight differences in hydraulic conditions, vertical velocity gradient and turbulence intensity gradient could affect the quantity of phytoplankton. Our study suggests that, considering environmental effect of periphyton, flow conditions and their combined action is essential for water quality improvement and ecological restoration in eutrophic shallow lakes.



Volumentherapie mit Eigenfett und Filler

Zusammenfassung

Hintergrund

Sowohl die Injektion synthetischer Filler als auch der autologe Fetttransfer sind in der plastischen und ästhetischen Chirurgie angewandte Techniken zur Behandlung von Konturdeformitäten und Volumendefiziten des gesamten Körpers.

Fragestellung/Ziel der Arbeit

Beschrieben werden Indikation und Anwendung von synthetischen Fillern und autologem Fetttransfer zur Volumentherapie beim Mann.

Material und Methode

Es erfolgten Durchsicht und Auswertung klinischer Berichte und Fallstudien von plastisch und ästhetisch-chirurgischen Eingriffen beim Mann.

Ergebnisse

Obwohl die grundsätzlichen Techniken der Fillerinjektion und autologen Fetttransplantation zwischen Mann und Frau ähnlich sind, existieren verschiedene physiologisch und anatomisch bedingte Unterschiede, z. B. bei der kosmetischen Behandlung des Gesichtes und der Brust. Zusätzlich stellen die Therapie des männlichen Genitales sowie der muskuläre Aufbau mit synthetischen Fillern und Eigenfett ein für das männliche Geschlecht spezifisches Indikationsfeld dar.

Schlussfolgerung

Volumentherapie beim Mann ist ein noch vergleichsweise junges Gebiet in der modernen ästhetisch-plastischen Chirurgie. Die gängigen synthetischen Filler sowie Eigenfett werden gleichermaßen zum Aufbau von Weichgewebe verwendet, wobei deren Potenzial längst noch nicht erschöpft scheint.



The Flipped Curriculum: Dewey’s Pragmatic University

Abstract

Recently Graham Badley (Stud High Educ 41(4):631–641, 2016) made the case that the "pragmatic university" represents a viable future for the post-modern institution. In his construction of the pragmatic university, Badley largely draws upon the vision laid out by Richard Rorty (Philosophy and social hope. Penguin Books, London, 1999). While Rorty's neopragmatism offers an important perspective on the pragmatic institution, I believe that John Dewey's classical pragmatism offers a richer and more capable vision of the university. The aim of this paper is to develop a view of the pragmatic university drawn from Dewey's philosophy. His writings on the university offer a unique and viable path forward because he directly engages a reconstruction of the relationship between knowledge and experience in the context of post-secondary education.



Impact assessment of projected climate change on diffuse phosphorous loss in Xin’anjiang catchment, China

Abstract

Diffuse nutrient loss is a serious threat to water security and has severely deteriorated water quality throughout the world. Xin'anjiang catchment, as a main drinking water source for Hangzhou City, has been a national concern for water environment protection with payment for watershed services construction. Detection of diffuse phosphorous (DP) pollution dynamics under climate change is significant for sustainable water quality management. In this study, the impact of projected climate change on DP load was analyzed using SWAT to simulate the future changes of diffuse components (carriers: water discharge and sediment; nutrient: DP) at both station and sub-catchment scales under three climate change scenarios (RCP2.6, RCP4.5, and RCP8.5). Results showed that wetting and warming years were expected with increasing tendencies of both precipitation and temperature in the two future periods (2020s: 2021~2030, 2030s: 2031~2040) except in the 2020s in the RCP2.6 scenario, and the annual average increasing ratios of precipitation and temperature reached − 1.79~3.79% and 0.48~1.27 °C, respectively, comparing with those in the baseline (2000s: 2001~2010). Climate change evidently altered annual and monthly average water discharge and sediment load, while it has a remarkable impact on the timing and monthly value of DP load at station scale. DP load tended to increase in the non-flood season at Yuliang due to strengthened nutrient flushing from rice land into rivers with increasing precipitation and enhanced phosphorous cycle in soil layers with increasing temperature, while it tended to decrease in the flood season at Yuliang and in most months at Tunxi due to restricted phosphorous reaction with reduced dissolved oxygen content and enhanced dilution effect. Spatial variability existed in the changes of sediment load and DP load at sub-catchment scale due to climate change. DP load tended to decrease in most sub-catchments and was the most remarkable in the RCP8.5 scenario (2020s, − 9.00~2.63%; 2030s, − 11.16~7.89%), followed by RCP2.6 (2020s, − 10.00~2.90%; 2030s, − 9.00~6.63%) and RCP4.5 (2020s, − 6.81~5.49%, 2030s, − 10.00~9.09%) scenarios. Decreasing of DP load mainly aggregated in the western and eastern mountainous regions, while it tended to increase in the northern and middle regions. This study was expected to provide insights into diffuse nutrient loss control and management in Xin'anjiang catchment, and scientific references for the implementation of water environmental protection in China.



The IgG response against Staphylococcus aureus is associated with severe atopic dermatitis in children

Abstract

Background

An altered immune response against Staphylococcus (S.) aureus might contribute to inflammation and barrier damage in atopic dermatitis (AD).

Objectives

We profiled IgG antibodies against 55 S. aureus antigens in sera of children with mild to severe AD using a Luminex assay. Additionally, we evaluated the association between IgG levels and disease severity.

Methods

In this cross-sectional study, we included children with AD of two interventional study cohorts, namely SMA (n= 131) and the older DAVOS cohort (n= 76). AD severity was assessed using the Self Administrated-Eczema Area and Severity Index (SA-EASI) and levels of thymus and activation-regulated chemokine (TARC) in serum. IgG antibody levels against 55 S. aureus antigens were quantified simultaneously using a Luminex assay. Pair-wise correlations were calculated between the 55 IgG levels using the Spearman rank correlation test. A linear regression analysis was performed to test for associations between 55 IgG levels and SA-EASI and TARC adjusting for age, sex and S. aureus colonisation.

Results

In the SMA cohort 16 antigens were associated with SA-EASI and 12 antigens were associated with TARC (10 overlapping antigens; P-values from 0.001 to 0.044). The associated IgG antibodies targeted mainly secreted proteins with immune-modulatory functions. In the DAVOS study, IgG levels against only four and one S. aureus antigen(s) were associated with SA-EASI and TARC, respectively (no overlap).

Conclusions

In young children, severity of AD is associated with an IgG response directed against S. aureus antigens with mainly immune-modulatory functions. These findings encourage further evaluation of the role of S. aureus in AD pathogenesis.

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Individualized Treatment Approaches for Langerhans Cell Histiocytosis

Langerhans cell histiocytosis (LCH) belongs to the rare histiocytic disorders, and has an estimated incidence of 1-2 cases per million adults [1]. Myeloid dendritic cells that express the same antigens (CD1a, CD207) as epidermal Langerhans cell seem to be the precursor cells for LCH [2]. Clinical presentation of patients with LCH may vary in site and extent of involvement. In 45% of patients LCH manifests as a multisystem disease including 77% bone, 39% skin, 19% lymph node, 16% liver, 13% spleen, 13% oral mucosa, 10% lung, and 6% CNS involvement [3].

This article is protected by copyright. All rights reserved.



The Role of Ultrasound in Diagnosis of Temporomandibular Joint Disc Displacement: A Case–Control Study

Abstract

Purpose

Ultrasound is extensively being used for imaging of temporomandibular joint as it is non-invasive and relatively inexpensive. The purpose of this study was to evaluate the use of ultrasound in identifying TMJ with internal derangement and to access its usefulness as a diagnostic tool in patients with TMJ clicking.

Methods

A case–control study was done: 25 patients with a complaint of clicking sound while opening the jaw were randomly selected as the study group and 25 patients who were asymptomatic on TMJ examination were selected as the control group. Both the groups were subjected to bilateral ultrasound scanning of the TMJ. The lateral part of capsule to condyle distance (LCCD) and the anterior part of capsule to condyle distance (ACCD) were measured.

Results

The mean LCCD of all the 50 joints in the control group was 1.3630 mm, and the mean ACCD of the 50 joints was 1.4850 mm. These values were compared with each of the 50 symptomatic joints scanned in the study group. It was noted that 56% of the subjects showed deviation towards right side and 44% showed deviation towards right side. Clicking was heard in all the subjects while opening the mouth on auscultation. The frequency and percentage distribution of negative and non-negative deviations of LCCD from that of control group were noted. In total, 40% showed negative deviation and 60% showed non-negative deviation. In total, 24% of the subjects showed negative deviation and 76% showed non-negative 190 deviation of ACCD when compared with the control group. T test shows that with respect to LCCD measurement there is no significant difference between symptomatic and asymptomatic subjects, whereas ACCD measurements are significantly different between the symptomatic and asymptomatic subjects.

Conclusions

Hence, it can be concluded that auscultation is mandatory in the examination of temporomandibular joint for clicking sound. Ultrasonography, which has shown high specificity, can supplement clinical evaluation in patients with TMJ disorders and can be used as a potential diagnostic tool for identifying internal derangement of the temporomandibular joint with reduction.



IMMUNOGLOBULIN FREE LIGHT CHAINS IN SALIVA: A potential marker for disease activity in multiple sclerosis

SUMMARY

A new procedure was developed and applied to study immunoglobulin free light chains (FLC) in saliva of healthy subjects and patients with multiple sclerosis (MS). The procedure was based on a Western blot analysis for detection and semiquantitative evaluation of monomeric and dimeric FLCs. The FLC indices accounting for the total FLC levels and for the monomer/dimer ratios of κ and λ FLC were calculated, and the cut-off values of the FLC indices were determined to distinguish healthy state from MS disease. The obtained FLC index values were statistically different in the saliva of three groups: active MS patients, MS patients in remission and healthy subjects groups. Our FLC monomer-dimer analysis allowed differentiation between healthy state and active MS with specificity of 100% and a sensitivity of 88.5%. The developed technique may serve as a new non-invasive complimentary tool to evaluate the disease state by differentiating active MS from remission with sensitivity of 89% and specificity of 80%. This article is protected by copyright. All rights reserved.



A Systems Medicine Approach Reveals Disordered Immune System and Lipid Metabolism in Multiple Sclerosis Patients

Summary

Identification of autoimmune processes and introduction of new autoantigens involved in the pathogenesis of multiple sclerosis (MS) can be helpful in the design of new drugs to prevent unresponsiveness and side effects in patients. To find significant changes, we evaluated the autoantibody repertoires in newly diagnosed relapsing-remitting MS patients (NDP) and those receiving disease modifying therapy (RP). Through a random peptide phage library, a panel of NDP- and RP-specific peptides was identified, producing two protein datasets visualized using Gephi, based on protein-protein interactions in the STRING database. The top modules of NDP and RP networks were assessed using Enrichr. Based on the findings, a set of proteins, including ABCC1, NOTCH1, MET, RAF1, and VAV1 was found in NDP and was involved in overrepresented terms correlated with cell-mediated immunity and cancer. In contrast, RELB, EP300, ACACB, ADIPOQ, and PCK2 had major contributions to viral infections and lipid metabolism, as significant events in RP. According to these findings, further research is required to demonstrate the pathogenic roles of such proteins and autoantibodies targeting them in MS and to develop therapeutic agents which can ameliorate disease severity. This article is protected by copyright. All rights reserved.



Introduction to the Special Issue on Healthy Start



Boron neutron capture therapy using reactor epithermal neutron beams could effectively control in-transit and lymph node metastases originating from a cutaneous malignant melanoma



Long-term clinical efficacy and safety of secukinumab for Japanese patients with psoriasis: A single-center experience

Abstract

Secukinumab is a fully human monoclonal antibody that can selectively neutralize interleukin-17A, and its excellent efficacy has been demonstrated in clinical trials for psoriasis. The aim of our study is to assess long-term efficacy and safety of secukinumab for 52 weeks in real-world clinical practise in our facility. A total of 83 patients (71 with psoriasis vulgaris and 12 with psoriatic arthritis) were included, and 49 of them were bio-switched patients. Psoriasis Area and Severity Index (PASI) 75 and PASI-90 responses were 80% and 64% at week 12, 77% and 65% at week 24, and 76% and 58% at week 52, respectively. No significant differences were observed in efficacy between bio-naive and bio-switched patients. Arthralgia showed improvement by week 12 in all patients with psoriatic arthritis with a reduction of serum C-reactive protein level. Treatment was discontinued in 22% (18/83), including eight patients with no improvement or exacerbation of cutaneous manifestations, one patient with new onset of arthritis and two patients with transient infection. Overall, secukinumab showed a sustained clinical response with an acceptable safety profile through week 52 in Japanese psoriatic patients.



Highly variable clinical feature and course of aggressive digital papillary adenocarcinoma

Abstract

Aggressive digital papillary adenocarcinoma (ADPA) is a rare cutaneous tumor with sweat gland differentiation. Due to the high risk of local recurrence and delayed metastasis, the wide local resection of the primary lesion and long-term follow up are recommended for ADPA. Here, we report two cases of ADPA. Case 1 had a blue-gray nodule on the tip of the right middle finger. Case 2 had had a papule on the dorsal side of the left ring finger for 13 years. In both cases, papillary proliferations of the tumor cells showed multilobular adenomatous structures with back-to-back patterns characteristic of ADPA. We amputated the finger at the proximal interphalangeal joint and performed a wide resection of the primary tumor in Case 1 and 2, respectively. Sentinel lymph node biopsy in the axilla was performed, and no sentinel lymph node metastasis was found in either case. Among the previously reported ADPA cases, clinically, most lesions were skin-colored or tan-brown to gray. The blue-gray color in Case 1 is thought to be extraordinary for ADPA. In Case 2, the patient had had the small lesion for more than 13 years and the tumor size had been stable during that long period. The present two cases suggest that ADPA shows a prominent variety of both clinical features and disease courses, and that we cannot exclude the possibility of ADPA even in cases of blue-gray nodules or small, stable, non-progressive papules.



Where did language come from? Connecting sign, song, and speech in hominin evolution

Abstract

Recently theorists have developed competing accounts of the origins and nature of protolanguage and the subsequent evolution of language. Debate over these accounts is lively. Participants ask: Is music a direct precursor of language? Were the first languages gestural? Or is language continuous with primate vocalizations, such as the alarm calls of vervets? In this article I survey the leading hypotheses and lines of evidence, favouring a largely gestural conception of protolanguage. However, the "sticking point" of gestural accounts, to use Robbins Burling's phrase, is the need to explain how language shifted to a largely vocal medium. So with a critical eye I consider Michael Corballis's most recent expression of his ideas about this transition (2017's The Truth About Language: What It Is And Where It Came From). Corballis's view is an excellent foil to mine and I present it as such. Contrary to Corballis's account, and developing Burling's conjecture that musicality played some role, I argue that the foundations of an evolving musicality (i.e., evolving largely independently of language) provided the means and medium for the shift from gestural to vocal dominance in language. In other words, I suggest that an independently evolving musicality prepared ancient hominins, morphologically and cognitively, for intentional articulate vocal production, enabling the evolution of speech.



Clarification of methodology and further results from the pivotal phase 3 study of crisaborole for mild-moderate atopic dermatitis



The Development of the Healthy Pregnancy Stress Scale, and Validation in a Sample of Low-Income African American Women

Abstract

Objectives The association of stress with pregnancy health is well-known. However, few studies take a mixed methods approach to understand the stressors contributing to a woman's pregnancy-related stress. Among African American women, exposure to stressors during pregnancy likely contributes to disparities in pregnancy health outcomes. This work aimed to understand the types and magnitude of stressors African American women are exposed to during pregnancy. Methods Using a mixed methods research design, we developed and administered the Healthy Pregnancy Stress Scale to measure stressors within the stress environment of African American women living in poverty. Results Exploratory factor analysis with one random split-half sample (N = 85) identified a two-factor model. Factor 1, defined as general pregnancy stressors, had significant loadings for ten items that ranged in magnitude from 0.319 to 0.724. Factor 2, defined as relationship strain, had significant loadings for three items ranging in magnitude from 0.613 to 0.856. Confirmatory factor analysis in the second random split-half sample (N = 88) showed a strong fit for the two factor model with factor loadings similar in magnitude. Standard fit statistics and those that adjust for item non-normality suggested an adequate fit to the data (RMSEA = 0.057, CFI = 0.947, TLI = 0.932; Satorra-Bentler RMSEA = 0.037, CFI = 0.972, TLI = 0.965). Conclusions for Practice Our measurement tool may provide a way to determine differences in pregnancy stress experiences across diverse populations of women. Future research should include a test for construct validity by correlating the scale with other measures that should have a specific directional relationship in diverse populations.



Body Satisfaction During Pregnancy: The Role of Health-Related Habit Strength

Abstract

Objectives Body satisfaction during pregnancy is an important determinant of maternal and fetal health outcomes. It is therefore critical to investigate factors related to changes in body satisfaction and to elucidate how body satisfaction changes over time in pregnant women. The purpose of this study was to examine the relation between two novel factors (i.e., healthy eating habit strength and physical activity habit strength) and body satisfaction during pregnancy. Methods Participants (n = 67 pregnant North American women) completed online questionnaires at the beginning of their second trimester (Time 1) and at the end of pregnancy. Maternal characteristics, relationship satisfaction, self-esteem, and psychological distress were assessed at Time 1 and habit strength, body satisfaction, and weight were assessed at both time points. Results Strength of healthy eating and physical activity habits remained stable over time and body satisfaction decreased over time. Healthy eating habit strength at Time 1 predicted increases in body satisfaction from the second trimester to the end of pregnancy, even when controlling for gestational weight gain. Conclusions This study suggests that health-related habit strength in women of reproductive age may offer protection against low levels of body satisfaction during pregnancy.



Des cellules de Sézary : clonales mais versatiles

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Publication date: December 2017
Source:Annales de Dermatologie et de Vénéréologie, Volume 144, Issue 12, Supplement
Author(s): M. Roelens, C. Ram-Wolff, M. Delord, A. Marie-Cardine, A. Alberdi, A. Bensussan, M. Bagot, A. Toubert, H. Moins-Teisserenc
IntroductionNous avons précédemment montré la fiabilité du marqueur CD158k/KIR3DL2 pour l'identification et la caractérisation des cellules de Sézary (CS), et avons ainsi mis en évidence une hétérogénéité inattendue de ces cellules.Matériel et méthodesQuarante-sept échantillons sanguins de patients atteints de syndrome de Sézary (SS), ainsi que 16 biopsies cutanées prélevées le même jour ont été analysés en cytométrie en flux pour l'expression de marqueurs de maturation (CD45RA, CCR7, CD27, CD95) et de lymphocytes T résidents mémoires (TRM : CD69, CD103). La concordance entre les lymphocytes T CD158k+ et le clone Vβ connu du TCR a été vérifiée lorsque l'anticorps était disponible. Le transcriptome de 3 patients a été réalisé sur CS sanguines triées de divers phénotypes, en parallèle de populations T CD4+ de 3 donneurs sains (DS), sur puces Affymetrix HTA 2.0.RésultatsQuarante-trois pour cent des échantillons sanguins présentaient une hétérogénéité des types naïfs/mémoires de CS, avec 15 % de phénotypes TSCM (stem cell memory), précédemment décrits chez le sujet sain comme doués de fortes capacités d'auto-renouvellement et de différenciation, et impliqués comme réservoir tumoral dans le lymphome T de l'adulte (ATL). Dans la peau, les CS présentaient des profils de maturation plus avancés, exclusivement mémoires, avec des marqueurs de TRM. Afin de relier ces phénotypes à un réel profil de T naïf/mémoire, une étude transcriptomique a été réalisée après tri de différents types de CS circulants naïf/TSCM/mémoire, en parallèle des sous-populations correspondantes chez des DS. Les résultats de 3 patients, après élimination des gènes impliqués dans les voies d'activation oncogénique, ont mis en évidence une signature transcriptomique naïve/mémoire proche des sous-types T CD4+ connus : un patient présentait des CS comparables aux TSCM de DS ; un deuxième proche de centrales mémoires (TCM) ; un troisième présentait une hétérogénéité intra-clonale, avec des CS CD45RA+CD95 proches de TSCM, et CD45RACD95 proches de TCM. En revanche, ces CS différaient de leurs homologues naïfs/mémoires des DS par des expressions anormales de transcrits impliqués dans la réponse aux cytokines et dans la différenciation lymphocytaire T.DiscussionNos résultats confirment l'hétérogénéité intra- et inter-individuelle des CS en termes de phénotypes et de profils de maturation. Chez un même patient les phénotypes des CS cutanées présentaient des caractéristiques plus matures que les CS circulantes. Ces phénotypes ont pu être reliés dans le sang chez 3 patients, aux profils transcriptomiques naïfs/mémoires établis chez les sujets sains, notamment TSCM, remettant en cause le dogme selon lequel les CS seraient exclusivement de type TCM.ConclusionCes données contribuent à une meilleure compréhension de l'origine et de l'évolution des CS au cours du SS, ainsi que des interactions entre les compartiments sanguins et cutanés, et pourraient permettre de définir des cibles cellulaires pertinentes pour les immunothérapies du futur.



Editorial board

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Publication date: December 2017
Source:Annales de Dermatologie et de Vénéréologie, Volume 144, Issue 12, Supplement





Sources d’information et parcours de soins des Français avec un problème de peau : quelle place pour les dermatologues ?

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Publication date: December 2017
Source:Annales de Dermatologie et de Vénéréologie, Volume 144, Issue 12, Supplement
Author(s): M.-A. Richard, F. Corgibet, N. Dupin, M. Beylot-Barry, L. Misery, V. Chaussade, S. Abadie, J.-F. Sei, C. Taieb, P. Joly, K. Ezzedine
IntroductionLes patients souhaitent disposer d'une information fiable et immédiate sur leurs problèmes de santé. Cela est possible par un accès à de nombreux outils d'information, notamment Internet. La consultation reste néanmoins un moyen de personnaliser et d'adapter cette information en permettant le « dialogue singulier ». Les demandes d'information et de soin pour les problèmes de peau sont fréquentes. Un Français sur 5, d'après les données de l'étude Objectifs Peau, a consulté dans l'année précédente un dermatologue. Cependant, le parcours de soins coordonné impose le recours au médecin traitant avant de consulter un spécialiste. L'objectif de ce travail était d'étudier les sources d'information des Français et les choix d'accès direct vers les dermatologues selon les problèmes cutanés.Matériel et méthodesUn échantillon de 20 012 sujets représentatifs de la population française >15 ans, a été spécifiquement créé selon la méthode des quotas (sexe, âge, localisation géographique et catégorie socioprofessionnelle) pour répondre à un questionnaire sur Internet, abordant des items concernant les problèmes de santé cutanés, et le parcours de soins. Les croisements entre variables ont été analysés avec le test de Chi2 pour les variables quantitatives, avec le logiciel SAS.RésultatsUn Français sur trois (31,1%) déclare consulter en 1er un dermatologue en cas de problème ou de maladie de peau vs 56,7 % un MG. 36,3% des sujets déjà concernés par un problème de peau solliciteraient encore le dermatologue en 1re intention en cas de nouveau problème cutané, alors que 28,7% des sujets n'ayant jamais eu de dermatose consulteraient le dermatologue en 1re intention (p<0,0001). Les sujets résidant en Île-de-France et dans le sud-est privilégient le dermatologue en 1re intention pour la prise en charge des problèmes cutanés et l'obtention d'une information fiable (respectivement 39,9% et 32,1%) que ceux résidant dans le sud-ouest (30,9%), dans le nord-est (27,7%) et dans le nord-ouest (25,9%) (p<0,0001). En Île-de-France, le recours direct au dermatologue est encore plus marqué dans l'agglomération parisienne (40,7%). Les femmes sont plus nombreuses à avoir recours au dermatologue en 1er (33,7% vs 28,3% des hommes, p<0,0001). Les sujets plus jeunes s'orientent aussi plus souvent vers le dermatologue en 1re intention au (de 36,1% chez les 15–24 ans à 28,9% chez les 65 ans et plus, p<0,0001). À l'inverse, nos aînés s'orientent davantage en 1er vers leur MG en cas de problèmes cutanés (64,9% des 65 ans et plus) que les classes d'âge plus jeunes (p<0,0001). 4,6% des Français déclarent consulter un site Internet lorsqu'ils cherchent une information fiable sur un problème cutané ; cette source d'information est plus consultée par les plus jeunes (de 8,1% chez les 15/24 ans à 2,1% chez les 65 ans et plus, p<0,0001). Globalement, l'entourage est peu sollicité pour aider à résoudre les problèmes de peau (3,3%). Les patients souffrant d'acné sont les plus nombreux (46,4%) ainsi que ceux atteints de rosacée (41,6%) à s'orienter en 1er vers un dermatologue vs 38,5% des patients atopiques et 37,2% des patients avec un psoriasis. Seuls 28,8% des sujets avec une IST, et 29,6 % de ceux ayant des poux ont recours en 1er au dermatologue (Tableau 1).DiscussionConsulter, en première intention, un dermatologue afin d'avoir une prise en charge et une information fiable reste une intention fréquente des Français, notamment pour les dermatoses chroniques (psoriasis) ou identifiées comme relevant de la compétence des dermatologues (acné) malgré le parcours de soins. L'accès plus facile aux consultations dans les zones les mieux « pourvues » en dermatologues explique aussi ces résultats. C'est en Île-de-France, où la densité des dermatologues exerçant est importante (7,4 pour 100 000h vs moyenne nationale 5,2), que l'on observe aussi le plus de recours directs aux dermatologues. Selon les Français interrogés, la prise en charge des poux et des IST se fait via les MG ou directement par les pharmaciens, car cela relève de leurs compétences et ou du fait des délais de rendez-vous chez le dermatologue.ConclusionLe recours aux dermatologues reste une priorité pour la population française.



Syndrome de Stevens-Johnson-radiation recall secondaire au nivolumab

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Publication date: December 2017
Source:Annales de Dermatologie et de Vénéréologie, Volume 144, Issue 12, Supplement
Author(s): L. Rouyer, S. Moawad, L. Charbit, E. Freling, A.C. Bursztejn, J.-L. Schmutz
IntroductionLe nivolumab est une immunothérapie utilisée dans le traitement du mélanome métastatique et plus récemment dans celui du cancer bronchique non à petites cellules. Plusieurs cas de syndromes de Stevens-Johnson (SSJ) secondaires à ce traitement ont déjà été rapportés, mais jamais sous la forme de phénomène radiation recall dermatitis (RRD). Nous rapportons le cas d'un patient ayant présenté un SSJ strictement localisé aux zones antérieurement irradiées.ObservationsUn homme de 63 ans était traité pour un carcinome épidermoïde pulmonaire découvert en 2015 par successivement 3 cures de carboplatine-paclitaxel, puis radiothérapie thoracique (176Gy, début 2016). En raison de la découverte de métastases osseuses du genou gauche fin 2016 puis lombaires en janvier 2017, deux nouvelles irradiations localisées étaient réalisées de 30 et 20Gy respectivement. Puis, une immunothérapie par nivolumab était débutée. Cinq jours après la seconde injection, apparaissaient des lésions érosives de la muqueuse buccale, oculaire et génitale, puis des lésions cutanées à type d'érythème et décollement cutané strictement localisées sur les zones irradiées. La biopsie mettait en évidence une dermite de l'interface avec nécroses en faveur d'un SSJ. En raison de l'imputabilité forte du nivolumab, ce traitement était arrêté. L'évolution cutanée était favorable sous soins locaux. Une prise en charge palliative était décidée dans le contexte de progression métastatique et le patient décédait 3 mois plus tard.DiscussionLe phénomène RRD est une réaction cutanée inflammatoire rare localisée sur une zone cutanée préalablement irradiée en réponse à l'administration d'un médicament. Il survient au moins 8jours après l'irradiation et quelques heures à quelques jours après l'exposition au médicament précipitant. Sa physiopathologie est inconnue. Cliniquement, il s'agit d'une éruption maculo-papuleuse avec érythème, œdème, vésicules, desquamation voire ulcérations et nécrose de sévérité variable. L'analyse histologique est aspécifique. L'actinomycine D était le premier médicament inducteur décrit. Depuis, d'autres chimiothérapies sont souvent incriminées. Un cas de RRD a été décrit quelques heures après l'administration de nivolumab dans le cadre d'un mélanome dans le territoire d'une irradiation lombaire réalisée une semaine auparavant. Ici, le diagnostic de phénomène recall repose sur la localisation des lésions cutanées sur les zones irradiées. Cependant, l'aspect clinique, histologique et les lésions muqueuses associées nous ont fait porter le diagnostic de SSJ-radiation recall, inédit à ce jour (Fig. 1) (Fig. 2).ConclusionNous rapportons le premier cas de SSJ-radiation recall. La radiothérapie, même réalisée un an plus tôt, a certainement fragilisé les tissus pour expliquer l'atteinte aussi localisée.



Impact de l’exposition aux colorations capillaires sur la sensibilité cutanée du visage et du cuir chevelu

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Publication date: December 2017
Source:Annales de Dermatologie et de Vénéréologie, Volume 144, Issue 12, Supplement
Author(s): A. Bernard, A.-S. Ficheux, N. Hornez, A.-S. Nedelec, A. Batardière, A.-C. Roudot, L. Misery
IntroductionEn France, 64 % des femmes se colorent les cheveux dans les 12 derniers mois. L'effet indésirable majeur lié aux colorations capillaires est la dermatite allergique de contact, cependant, d'autres effets peuvent survenir. Le but de cette étude était d'analyser l'impact de l'exposition aux colorations capillaires sur la sensibilité cutanée.Matériel et méthodesLes données provenaient d'une enquête Internet réalisée sur un échantillon de 1257 Françaises de plus de 15 ans, incluant 939 utilisatrices de colorations capillaires. Les participantes devaient remplir un questionnaire sur leur usage des colorations : lieu de réalisation, type de produit, fréquence et quantité d'utilisation. Ce questionnaire regroupait aussi les questions nécessaires à l'évaluation de la sensibilité du cuir chevelu par le Sensitive Scalp Score (3S) et du visage par le Sensitive Scale 10-item (SS-10).RésultatsChez les femmes de 15–24 ans, les utilisatrices de colorations capillaires présentaient des scores de sensibilité du cuir chevelu plus élevés que les non-utilisatrices, avec un score moyen respectif de 3,34 et 2,31 (p=0,026). Les scores de sensibilité différaient entre les utilisatrices chez le coiffeur et les utilisatrices de produits professionnels à domicile, avec respectivement des scores 3S de 1,65 et 2,78 (p<0,0001) et SS-10 de 7,43 et 12,96 (p<0,0001). Le type de coloration capillaire pour lequel les scores étaient les plus forts est la décoloration suivie d'une coloration, avec un score 3S de 3,39 et SS-10 de 24,34. Les scores 3S et SS-10 des utilisatrices ayant une maladie dermatologique étaient supérieurs à ceux des femmes sans maladie (p<0,0001). Les utilisatrices de produits professionnels à domicile étaient les plus exposées aux colorations capillaires avec des 95epercentiles allant de 8,01 à 11,27mg/kg pc/j. Par type de produit, l'exposition la plus forte était retrouvée chez les utilisatrices de décoloration suivie d'une coloration : 10,79mg/kg pc/j.DiscussionL'utilisation de produits cosmétiques peut causer des réactions cutanées correspondant au tableau clinique de peau sensible. Certains ingrédients des colorations capillaires sont propices à provoquer ce type d'effet, notamment chez les utilisatrices présentant déjà une sensibilité.ConclusionNotre étude évalue l'impact des colorations capillaires sur la sensibilité cutanée. Elle met en évidence une sensibilité plus importante chez les utilisatrices de produits professionnels à domicile, les utilisatrices de décoloration et les utilisatrices ayant une maladie dermatologique. Il est important d'évaluer l'effet des colorations capillaires sur la sensibilité car hormis les allergies, les effets néfastes de ces produits sont peu renseignés, bien que pouvant altérer la qualité de vie des utilisatrices.



Editorial board

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Publication date: December 2017
Source:Annales de Dermatologie et de Vénéréologie, Volume 144, Issue 12





Efficacité d’un programme de prise en charge standardisée dans l’eczéma chronique des mains

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Publication date: December 2017
Source:Annales de Dermatologie et de Vénéréologie, Volume 144, Issue 12, Supplement
Author(s): M. Tauber, S. Lourari, E. Bérard, E. Questel, F. Giordano-Labadie, D. Redoules, M. Simon, C. Paul
IntroductionL'eczéma chronique des mains (ECM) altère profondément la qualité de vie (QdV) et peut être responsable d'une morbidité importante. Nous avons mené une étude prospective ouverte dans le but d'évaluer l'intérêt d'une prise en charge standardisée avec éducation thérapeutique (ETP) sur la sévérité clinique, la QdV, la productivité au travail et les pratiques négatives des patients classés en deux groupes : à prédominance atopique/allergique (AA) ou à prédominance irritative (IR).Matériel et méthodesUne étude prospective monocentrique incluait tous les nouveaux patients présentant un ECM ayant signé un consentement éclairé. Les patients avec patch-tests positifs et/ou prick-tests pneumallergènes positifs et/ou antécédent personnel de dermatite atopique étaient classés dans le groupe AA, les autres dans le groupe IR. Une évaluation clinique standardisée était réalisée à m0 et m3 comportant une description clinique, une évaluation de la sévérité clinique par le score modified Total Lesion Symptom Score (mTLSS), de la QdV par le score Dermatology Life Quality Index (DLQI), de la productivité au travail par le questionnaire Work Productivity and Activity Impairment (WPAI), ainsi qu'un questionnaire standardisé de recueil des pratiques (environ 40 items portant en particulier sur les habitudes d'hygiène des mains, le port de gants à la maison, au travail et dans les loisirs). Les patients participaient à une première séance d'ETP à m0, réalisée par une infirmière spécialisée avec définition des objectifs thérapeutiques, abord de la maladie, de ses facteurs aggravants et de ses traitements. Un dermocorticoïde d'activité forte ou très forte ainsi qu'un syndet et une crème émolliente pour les mains étaient prescrits. Une séance d'ETP était renouvelée à m3.RésultatsSoixante et onze patients ont été inclus, dont 42 % d'hommes (n=30). L'âge moyen était de 39 ans (écart-type : 16), 53 patients étaient classés dans le groupe AA et 18 dans le groupe IR. Le score mTLSS à m0 était significativement supérieur dans le groupe AA versus IR (moyenne : 7,6 (3,2) versus 5,7 (2,3), p=0,02), de même que le DLQI (moyenne : 9,2 (5,3) versus 6,2 (4,2), p=0,04). Le recueil des pratiques était comparable entre les 2 groupes en dehors d'une utilisation plus fréquente de solution hydro-alcoolique dans le groupe IR (50 % vs 23 %, p= 0,03). À m3, les scores mTLSS, DLQI et WPAI s'amélioraient de manière significative (p<0,001) pour l'ensemble des patients (moyennes respectives : 3,1 versus 7,1 ; 3,2 versus 8,7 ; 7,6 versus 23,6). Les pratiques négatives diminuaient de manière significative dans les 2 groupes entre m0 et m3 (p<0,01).ConclusionNotre étude souligne l'intérêt d'une prise en charge de l'ECM associant traitement topique et éducation thérapeutique quelle que soit la forme étiologique.



Télédermatologie en établissement d’hébergement pour personnes âgées dépendantes (EHPAD)

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Publication date: December 2017
Source:Annales de Dermatologie et de Vénéréologie, Volume 144, Issue 12, Supplement
Author(s): M.-S. Doutre, N. Salles, K. Libert
IntroductionLe parcours de soins des patients âgés est souvent complexe en pratique. Le programme aquitain de télémédecine (TM) en EHPAD permet la réalisation de téléconsultations (TC) dont nous rapportons le bilan d'activité en dermatologie.Matériel et méthodesUn dispositif de TC est actuellement mis en place dans 50 EHPAD d'Aquitaine. La demande de TC est adressée avec une fiche de renseignements et parfois des photos au secrétariat du centre expert qui donne un rendez-vous dans un délai maximum de 15jours. La consultation se fait par un système de télétransmission type vidéoconférence par réseau Internet sécurisé installé dans le pôle de gérontologie clinique. Dans l'EHPAD, sont présents le patient et parfois un membre de sa famille, 1 ou 2 infirmières et/ou aides-soignantes, le médecin coordinateur ou traitant. Un compte-rendu comportant le diagnostic, le traitement proposé, parfois des examens complémentaires à réaliser et éventuellement un nouveau rendez-vous est adressé à l'EHPAD dans les 2heures suivant la TC.RésultatsCent TC de dermatologie ont été réalisées entre avril 2016 et juin 2017 pour 78 patients, 59 ayant eu une consultation, 16, 2 et 3, 3. Les 78 patients, 23 hommes et 55 femmes étaient âgés de 88 ans en moyenne ; 60 d'entre eux avaient un GIR (groupe iso-ressources) de 1 à 3. Les motifs de demande les plus fréquents étaient le prurit, une dermite d'incontinence, une ou plusieurs tumeurs cutanées et une éruption eczématiforme, les plaies étant prises en charge dans une consultation dédiée. Dans 90 % des cas, la TC a permis de porter un diagnostic et de proposer un traitement adapté. Dans 10 cas, des examens complémentaires ont été demandés (prélèvements bactériologique et mycologique, biopsie cutanée, dosage des anticorps anti-membrane basale). Au vu du résultat de la biopsie, 4 dossiers ont été discutés en RCP d'onco-dermatologie (2 mélanomes et 2 carcinomes épidermoïdes). Deux patients ont été hospitalisés pour un eczéma diffus nécessitant des soins locaux adaptés.DiscussionLa TM est inscrite comme une priorité dans la loi HPST. Les soins dans les structures médico-sociales, en particulier les EHPAD, sont un des 5 axes dans lesquels elle doit se déployer. La TC de dermatologie est appréciée par les patients, les médecins et le personnel paramédical pour la rapidité d'accès à un avis spécialisé, en évitant dans la majorité des cas, un déplacement souvent difficile pour des sujets âgés, peu ou pas autonomes. Bien sûr, elle ne peut répondre à tous les problèmes dermatologiques, comme par exemple, les tumeurs cutanées nécessitant souvent une biopsie.ConclusionCette étude montre que la TD est un outil adapté aux patients vivant en EHPAD. Elle participe aussi à la formation des médecins demandeurs et du personnel paramédical.