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Τετάρτη 20 Ιουνίου 2018

Hsp90/Sec22b promotes unconventional secretion of mature-IL-1β through an autophagosomal carrier in porcine alveolar macrophages during Mycoplasma hyopneumoniae infection

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Publication date: September 2018
Source:Molecular Immunology, Volume 101
Author(s): Zhenzhen Zhang, Yanna Wei, Beibei Liu, Yuzi Wu, Haiyan Wang, Xing Xie, Zhixin Feng, Guoqing Shao, Qiyan Xiong
Interleukin-1β (IL-1β) is a critical inflammatory regulator in response to Mycoplasma hyopneumoniae infection. However, the mechanism involved in the secretion of IL-1β during Mycoplasma hyopneumoniae infection is unclear. In this study, we demonstrated that Mycoplasma hyopneumoniae infection increased the secretion of mature-IL-1β (m-IL-1β), but not pro-IL-1β, in porcine alveolar macrophages. Moreover, Mycoplasma hyopneumoniae infection promoted the generation of autophagosomes, which attributed to the unconventional secretion of m-IL-1β. Further results revealed that Hsp90 was required for the entry of m-IL-1β into autophagosomes during Mycoplasma hyopneumoniae infection. The fusion of m-IL-1β-containing autophagosome and plasma membranes was regulated by Sec22b and independent of lysosomal dysfunction. In conclusion, we provide evidence that Hsp90/Sec22b promotes the unconventional secretion of IL-1β through an autophagosomal carrier during Mycoplasma hyopneumoniae infection. The elucidation of the molecular and cellular machinery in Mycoplasma hyopneumoniae infected mammalian cells in this study suggests avenues for further study and applications and paves the way for novel therapeutic strategies to prevent tissue damage in mycoplasma-associated diseases.



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Complement analysis in the era of targeted therapeutics

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Publication date: Available online 20 June 2018
Source:Molecular Immunology
Author(s): Zoltán Prohászka, Michael Kirschfink, Ashley Frazer-Abel
Complement immunobiology, and with it complement analysis, has undergone a renaissance in the past decade. Classically, complement analysis was limited number of testing C3, C4 in a routine laboratory with the possible addition of CH50 with all other analysis being performed at only few highly esoteric laboratories. This diagnostics expanding beyond specialized laboratories is the result of the growing recognition of the role played by complement dysfunction in many more diseases and disorders and the concomitant increase in interest in complement targeting therapeutics. In response, laboratories specializing in complement analysis have joined with the International Complement Society and the IUIS to coordinate efforts to standardize and improve complement testing, ongoing efforts that have already borne fruit. A recognition of the power of complement analysis has brought forward new testing but also realization of the importance of post-draw specimen handling to limit ex vivo activation, as well as the sometimes large difference between testing laboratory results. The increased usefulness of complement analysis and efforts to standardize and expand it means the future is strong for complement analysis.



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Treatment strategies and outcomes in diffuse large B-cell lymphoma among 1011 patients aged 75 years or older: A Danish population-based cohort study

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Publication date: August 2018
Source:European Journal of Cancer, Volume 99
Author(s): Maja Bech Juul, Pernille Hammershoej Jensen, Henriette Engberg, Sonja Wehberg, Andriette Dessau-Arp, Donika Haziri, Helene Bjoerg Kristensen, Joachim Baech, Lene Schurmann, Michael Roost Clausen, Rebecca Valentin, Lene Meldgaard Knudsen, Lars Munksgaard, Tarec Christoffer El-Galaly, Henrik Frederiksen, Thomas Stauffer Larsen
BackgroundOptimal treatment strategy for the oldest patients with diffuse large B-cell lymphoma (DLBCL) remains controversial, as this group often is precluded from clinical trials, and population-based studies are limited.MethodsAll Danish DLBCL-patients ≥75 years diagnosed from 2003 to 2012 were identified, using the Danish National Lymphoma Registry (LYFO). Information regarding baseline characteristics, treatment, comorbidities and outcomes was retrieved from LYFO, the Danish National health registries and medical records. Patients were stratified by age (75–79; 80–84 and 85 + years), comorbidity score and treatment modality (standard treatment [R-CHOP/CHOP-like], less intensive regimens or palliative treatment).FindingsA total of 1011 patients were included. Standard treatment was initiated in 64%, ranging from 83% among patients aged 75–79 years to 32% among patient aged 85 + years. With standard treatment, median overall survival (OS) estimates were 4·6, 2·6, and 1·9 years for the age groups 75–79, 80–84 and 85+ years. Among patient aged 75–79 and 80–84 years, OS was superior with standard treatment, although high comorbidity scores attenuated this association. Among patients aged 85+ years, survival was not influenced by treatment intensity. Patients ≥80 years had similar OS regardless of intended (R-)CHOP dosing, whereas patients of 75–79 years scheduled for full dose had higher OS. Standard treatment was not associated with increased hospitalisation.InterpretationStandard treatment is feasible with good outcomes in a large proportion of elderly DLBCL-patients. Planned dose reduction in patients aged ≥80 years had no negative impact on OS.



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Watershed microinfarct pathology and cognition in older persons

Publication date: October 2018
Source:Neurobiology of Aging, Volume 70
Author(s): Alifiya Kapasi, Sue E. Leurgans, Bryan D. James, Patricia A. Boyle, Zoe Arvanitakis, Sukriti Nag, David A. Bennett, Aron S. Buchman, Julie A. Schneider
Brain microinfarcts are common in aging and are associated with cognitive impairment. Anterior and posterior watershed border zones lie at the territories of the anterior, middle, and posterior cerebral arteries, and are more vulnerable to hypoperfusion than brain regions outside the watershed areas. However, little is known about microinfarcts in these regions and how they relate to cognition in aging. Participants from the Rush Memory and Aging Project, a community-based clinical-pathologic study of aging, underwent detailed annual cognitive evaluations. We examined 356 consecutive autopsy cases (mean age-at-death, 91 years [SD = 6.16]; 28% men) for microinfarcts from 3 watershed brain regions (2 anterior and 1 posterior) and 8 brain regions outside the watershed regions. Linear regression models were used to examine the association of cortical watershed microinfarcts with cognition, including global cognition and 5 cognitive domains. Microinfarcts in any region were present in 133 (37%) participants, of which 50 had microinfarcts in watershed regions. Persons with multiple microinfarcts in cortical watershed regions had lower global cognition (estimate = −0.56, standard error (SE) = 0.26, p = 0.03) and lower cognitive function in the specific domains of working memory (estimate = −0.58, SE = 0.27, p = 0.03) and visuospatial abilities (estimate = −0.57, SE = 0.27, p = 0.03), even after controlling for microinfarcts in other brain regions, demographics, and age-related pathologies. Neither the presence nor multiplicity of microinfarcts in brain regions outside the cortical watershed regions were related to global cognition or any of the 5 cognitive domains. These findings suggest that multiple microinfarcts in watershed regions contribute to age-related cognitive impairment.



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The contribution of small vessel disease to subtypes of Alzheimer's disease: a study on cerebrospinal fluid and imaging biomarkers

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Publication date: October 2018
Source:Neurobiology of Aging, Volume 70
Author(s): Daniel Ferreira, Sara Shams, Lena Cavallin, Matti Viitanen, Juha Martola, Tobias Granberg, Mana Shams, Peter Aspelin, Maria Kristoffersen-Wiberg, Agneta Nordberg, Lars-Olof Wahlund, Eric Westman
We investigated whether subtypes of Alzheimer's disease (AD), that is, typical, limbic-predominant, hippocampal-sparing, and minimal atrophy AD, had a specific signature of small vessel disease and neurodegeneration. Four hundred twenty-three clinically diagnosed AD patients were included (161 typical, 121 limbic-predominant, 70 hippocampal-sparing, 71 minimal atrophy). One hundred fifty-six fulfilled a biomarkers-based AD diagnosis. White matter hyperintensities and cerebral microbleeds (CMB) had the highest prevalence in limbic-predominant AD, and the lowest prevalence in minimal atrophy AD. CMB existed evenly in lobar and deep brain areas in limbic-predominant, typical, and hippocampal-sparing AD. In minimal atrophy AD, CMB were mainly located in brain lobar areas. Perivascular spaces in the centrum semiovale were more prevalent in typical AD. Small vessel disease contributed to the prediction of Mini-Mental State Examination. Minimal atrophy AD showed highly pathological levels of cerebrospinal fluid Aß1-42, total tau, and phosphorylated tau, in the absence of overt brain atrophy. Cerebral amyloid angiopathy seems to have a stronger contribution to hippocampal-sparing and minimal atrophy AD, whereas hypertensive arteriopathy may have a stronger contribution to typical and limbic-predominant AD.



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The hippocampal longitudinal axis—relevance for underlying tau and TDP-43 pathology

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Publication date: October 2018
Source:Neurobiology of Aging, Volume 70
Author(s): Albert Lladó, Adrià Tort-Merino, Raquel Sánchez-Valle, Neus Falgàs, Mircea Balasa, Beatriz Bosch, Magda Castellví, Jaume Olives, Anna Antonell, Michael Hornberger
Recent studies suggest that hippocampus has different cortical connectivity and functionality along its longitudinal axis. We sought to elucidate the possible different pattern of atrophy in longitudinal axis of hippocampus between Amyloid/Tau pathology and TDP-43-pathies. Seventy-three presenile subjects were included: Amyloid/Tau group (33 Alzheimer's disease with confirmed cerebrospinal fluid [CSF] biomarkers), probable TDP-43 group (7 semantic variant progressive primary aphasia, 5 GRN and 2 C9orf72 mutation carriers) and 26 healthy controls. We conducted a region-of-interest voxel-based morphometry analysis on the hippocampal longitudinal axis, by contrasting the groups, covarying with CSF biomarkers (Aβ42, total tau, p-tau) and covarying with episodic memory scores. Amyloid/Tau pathology affected mainly posterior hippocampus while anterior left hippocampus was more atrophied in probable TDP-43-pathies. We also observed a significant correlation of posterior hippocampal atrophy with Alzheimer's disease CSF biomarkers and visual memory scores. Taken together, these data suggest that there is a potential differentiation along the hippocampal longitudinal axis based on the underlying pathology, which could be used as a potential biomarker to identify the underlying pathology in different neurodegenerative diseases.



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MicroRNA alterations in iPSC-derived dopaminergic neurons from Parkinson disease patients

Publication date: September 2018
Source:Neurobiology of Aging, Volume 69
Author(s): Eduard Tolosa, Teresa Botta-Orfila, Xavier Morató, Carles Calatayud, Raquel Ferrer-Lorente, María-José Martí, Manel Fernández, Carles Gaig, Ángel Raya, Antonella Consiglio, Mario Ezquerra, Rubén Fernández-Santiago
MicroRNA (miRNA) misregulation in peripheral blood has been linked to Parkinson disease (PD) but its role in the disease progression remains elusive. We performed an explorative genome-wide study of miRNA expression levels in dopaminergic neurons (DAn) from PD patients generated by somatic cell reprogramming and induced pluripotent stem cells differentiation. We quantified expression levels of 377 miRNAs in DAn from 3 sporadic PD patients (sPD), 3 leucine-rich repeat kinase 2–associated PD patients (L2PD) (total 6 PD), and 4 healthy controls. We identified differential expression of 10 miRNA of which 5 were upregulated in PD (miR-9-5p, miR-135a-5p, miR-135b-5p, miR-449a, and miR-449b-5p) and 5 downregulated (miR-141–3p, miR-199a-5p, miR-299–5p, miR-518e-3p, and miR-519a-3p). Changes were similar in sPD and L2PD. Integrative analysis revealed significant correlations between miRNA/mRNA expression. Moreover, upregulation of miR-9-5p and miR-135b-5p was associated with downregulation of transcription factors related to the DNA hypermethylation of enhancer elements in PD DAn (FOXA1 and NR3C1). In summary, miRNA changes are associated with monogenic L2PD and sPD and co-occur with epigenetic changes in DAn from PD patients.



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Hematopoietic stem cell therapy for autoimmune diseases – Clinical experience and mechanisms

Publication date: Available online 20 June 2018
Source:Journal of Autoimmunity
Author(s): Tobias Alexander, Dominique Farge, Manuela Badoglio, James O. Lindsay, Paolo A. Muraro, John A. Snowden
With accumulating evidence and improved outcomes along with recognition that modern biological therapies are not universally effective, require chronic administration and have high acquisition costs, hematopoietic stem cell transplantation (HSCT) has become an emerging direction for cell therapy in autoimmune diseases (ADs). The goal of this therapy is to induce medication-free remissions by resetting the immune system into a naïve and self-tolerant state through eradication of the autoreactive immunologic memory and profound re-configuration of the immune system induced by the transplant procedure. Safety of HSCT has generally improved by implementing internal quality management and external accreditation. Inter-disciplinary guidelines for patient selection, transplant technique and supportive care along with greater center experience should optimize safe and appropriate delivery of HSCT in specific ADs. In this review, we discuss the current role and future perspectives of HSCT in AD, focusing on recent published clinical and scientific studies and recommendations in the field.

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Protective role of commensal bacteria in Sjögren Syndrome

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Publication date: Available online 20 June 2018
Source:Journal of Autoimmunity
Author(s): Mahira Zaheer, Changjun Wang, Fang Bian, Zhiyuan Yu, Humberto Hernandez, Rodrigo G. de Souza, Ken T. Simmons, Deborah Schady, Alton G. Swennes, Stephen C. Pflugfelder, Robert A. Britton, Cintia S. de Paiva
CD25 knock-out (CD25KO) mice spontaneously develop Sjögren Syndrome (SS)-like inflammation. We investigated the role of commensal bacteria by comparing CD25KO mice housed in conventional or germ-free conditions. Germ-free CD25KO mice have greater corneal barrier dysfunction, lower goblet cell density, increased total lymphocytic infiltration score, increased expression of IFN-γ, IL-12 and higher a frequency of CD4+IFN-γ+ cells than conventional mice. CD4+ T cells isolated from female germ-free CD25KO mice adoptively transferred to naive immunodeficient RAG1KO recipients caused more severe Sjögren-like disease than CD4+ T cells transferred from conventional CD25KO mice. Fecal transplant in germ-free CD25KO mice reversed the spontaneous dry eye phenotype and decreased the generation of pathogenic CD4+IFN-γ+ cells. Our studies indicate that lack of commensal bacteria accelerates the onset and severity of dacryoadenitis and generates autoreactive CD4+T cells with greater pathogenicity in the CD25KO model, suggesting that the commensal bacteria or their metabolites products have immunoregulatory properties that protect exocrine glands in the CD25KO SS model.



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A Midterm Assessment of Implementation of the Decadal Survey on Life and Physical Sciences Research at NASA.

The 2011 National Research Council decadal survey on biological and physical sciences in space, Recapturing a Future for Space Exploration: Life and Physical Sciences Research for a New Era, was written during a critical period in the evolution of science in support of space exploration. The research agenda in space life and physical sciences had been significantly descoped during the programmatic adjustments of the Vision for Space Exploration in 2005, and this occurred in the same era as the International Space Station (ISS) assembly was nearing completion in 2011. Out of that period of change, Recapturing a Future for Space Exploration presented a cogent argument for the critical need for space life and physical sciences, both for enabling and expanding the exploration capabilities of NASA as well as for contributing unique science in many fields that can be enabled by access to the spaceflight environment.

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Magnesium in the Central Nervous System [Internet].

Our understanding of the physiology and biochemistry of the brain has improved dramatically in the last two decades. In particular, the critical role of cations, including magnesium, has become evident, even if incompletely understood at a mechanistic level.

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Linear IgA bullous dermatosis induced by diclofenac sodium

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Sarita Sanke, Abhinav Kumar, Ram Chander

Indian Journal of Dermatology, Venereology, and Leprology 2018 84(4):496-497



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Paradigm shift in antinuclear antibody negative lupus: Current evidence

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Anup Kumar Tiwary, Piyush Kumar

Indian Journal of Dermatology, Venereology, and Leprology 2018 84(4):384-387



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Generalized multinucleate cell angiohistiocytoma with involvement of palms and soles: An unusual manifestation

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Kulsupa Nimmannitya, Suthep Jerasutus, Suthinee Rutnin

Indian Journal of Dermatology, Venereology, and Leprology 2018 84(4):468-470



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Updates on the use of vaccines in dermatological conditions

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Edith Hanna, Mohammed Dany, Ossama Abbas, Firas Kreidieh, Mazen Kurban

Indian Journal of Dermatology, Venereology, and Leprology 2018 84(4):388-402

Numerous vaccines are being actively developed for use in dermatologic diseases. Advances in the fields of immunotherapy, genetics and molecular medicine have allowed for the design of prophylactic and therapeutic vaccines with immense potential in managing infections and malignancies of the skin. This review addresses the different vaccines available for use in dermatological diseases and those under development for future potential use. The major limitation of our review is its complete reliance on published data. Our review is strictly limited to the availability of published research online through available databases. We do not cite any of the authors' previous publications nor have we conducted previous original research studies regarding vaccines in dermatology. Strength would have been added to our paper had we conducted original studies by our research team regarding the candidate vaccines delineated in the paper.

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Giant eccrine porocarcinoma in an unusual location

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Aylin Türel Ermertcan, M Kürşat Evrenos, Ferdi Öztürk, Peyker Temiz

Indian Journal of Dermatology, Venereology, and Leprology 2018 84(4):521-521



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Incidence of leprosy in Firozabad district (Uttar Pradesh)

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Anil Kumar, Anita Girdhar, Joy Kumar Chakma

Indian Journal of Dermatology, Venereology, and Leprology 2018 84(4):403-407

Objective: To assess incidence of leprosy in Firozabad District (U.P.). Materials and Methods: A random sample of 148,061 population was covered by this second survey, spread over 259 units (230 rural/29 urban). The survey was conducted between March 2011 and November 2012. Clinically confirmed cases detected in known disease-free population were labeled as incident cases and treated. Results: The overall incidence rate of leprosy was found to be 3.4 per 10,000 person years; In healthy contacts it was 3.1, in paucibacillary contacts 29.7 while it was 89.3 in multibacillary contacts. The differences in incidence rate of these three groups were significant (P < 0.001). Incidence rate was significantly higher by age; 1.1 in persons <15 years to 8.0 in those >44 years of age, and in high endemicity areas with three or more cases. In terms of incidence rate ratio (95% confidence interval), the incidence for ages 15–24 years was 3.2 times significantly higher than for those under 15 years, 5.3 times (4.3–6.5) in ages 30–44 years and 7.0 times (5.6–8.7) for age ≥45 years. Incidence rate ratio was also significantly higher in paucibacillary contacts, by 9.5 times (7.0–13.0) and 27.7 times (18.8–40.6) in multibacillary contacts, as compared to healthy controls. Incidence rate ratio (95% confidence interval) was significantly higher by 2.9 times (2.4–3.5) in areas with endemicity status of 3 to 5 cases and by 2.0 times (1.6–2.5) in areas with >5 cases as compared to areas with no endemicity. It was 2.4 times more (1.6–3.5) in Narkhi, 2.4 times higher (1.7–3.5) in Tundla and 3.0 times higher (2.1–4.5) in Aravon blocks than in Aeka block of the district. Incidence rate was also found to be significantly higher (3.7) among females, 1.3 times higher (1.1–1.5) than in males (2.9). Incidence rate ratio (95% confidence interval) was also 2.5 times higher (1.2–5.1) among persons having reported disease of greater than 4 years in comparison to 1.5 in persons having disease for 2 to 3 years. Limitations of Study: None to the best of our knowledge. Conclusion: The present study suggests that incidence rate of leprosy is significantly higher among persons of above 15 years, in females, among contacts of paucibacillary/multibacillary disease, in areas where >3 leprosy cases were found and in Tundla, Narkhi and Aravon blocks in Firozabad district.

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Ulcerated necrobiosis lipoidica: A cutaneous granulomatous reaction associated with systemic B-cell lymphoma

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Hamidreza Mahmoudi, Maryam Daneshpazhooh, Kambiz Kamyab, Negar Bahrololoumi Bafruee, Amin Kiani, Ifa Etesami

Indian Journal of Dermatology, Venereology, and Leprology 2018 84(4):481-484



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Clinical, immunological profile and follow up of patients with pemphigus: A study from India

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Sivaranjini Ramassamy, Poonam Agrawal, Dharshini Sathishkumar, Lydia Mathew, John Victor Peter, Thenmozhi Mani, Renu George

Indian Journal of Dermatology, Venereology, and Leprology 2018 84(4):408-413

Background: Pemphigus has a protracted course and multiple factors influence its prognosis. The objective of this study was to describe the epidemiology and clinical profile of pemphigus patients and to study its influence on treatment end points. Methods: This was a retrospective chart review done in an Indian tertiary care hospital from December 1991 to December 2013. Patients with less than 3 months' follow up and those who had paraneoplastic pemphigus were excluded. Results: There were 132 patients with pemphigus, of which 118 (89.4%) had pemphigus vulgaris and 14 (10.6%) had pemphigus foliaceous. The time to disease control (TDC) was available for 100 patients (n = 100, 75.7%); patients with a minimum follow up of 3 months (n = 80) were included for studying the end points like time to first disease remission (TDR) and time to first disease relapse (TDRe). The median period of follow up was 23 months (range 3–245). Out of the 100 patients, 61.9% were on oral steroids with adjuvant therapy. The steroid dose required for disease control for n = 100, ranged from 0.2 to 1.5 mg/kg body weight. Of these, 60% were treated with steroid dose of 1 mg/kg, 22% with >1 mg/kg, and 18% with <1 mg/kg. The mean time to disease control (in months) in the group which received <1 mg/kg steroid was 1.02 ± 0.68, 1 mg/kg was 0.72 ± 0.51, and >1 mg/kg was 1.02 ± 0.62 (P = 0.017); with a significant difference between the groups 2 and 3 (P = 0.007), implying a faster disease control in those who received 1 mg/kg dose. This difference was significant after adjusting for the steroid sparing drugs taken at baseline (P = 0.009, C.I. - 1.44-13.59). The mean time to first disease remission (TDR) was 11.46 ± 2.06 months. Out of the 80 patients with a minimum follow up of 3 months, 75% had achieved either partial or complete remission. None of the other epidemiological, clinical or immunological parameters had an impact on the TDC or TDR. Conclusions: The epidemiological, clinical or immunological parameters had no impact on the treatment end points like time to disease control and time to first disease remission. The dose of steroids required for disease control higher than 1 mg/kg offered no advantage in the time to disease control as compared to 1 mg/kg. Limitations: The study was retrospective and disease severity scores were not applied. In view of the shorter follow up period, long term prognostic end points and mortality could not be well represented. The median period of follow up was 23 months. The serum anti- desmoglein antibody titres were not available at various treatment end points for correlation at different time intervals.

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Plica polonica: from national plague to death of the disease in the nineteenth-century Vilnius

Eglė Sakalauskaitė-Juodeikienė, Dalius Jatužis, Saulius Kaubrys

Indian Journal of Dermatology, Venereology, and Leprology 2018 84(4):510-514



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Is there a correlation of serum and tissue T helper-1 and -2 cytokine profiles with psoriasis activity and severity? A cross-sectional study

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Sujay Khandpur, Vishal Gupta, Dayasagar Das, Alpana Sharma

Indian Journal of Dermatology, Venereology, and Leprology 2018 84(4):414-418

Background: Previous studies correlating Th1 and Th2 cytokine profiles with psoriasis activity provided inconsistent results. Correlation of tissue cytokine levels with psoriasis severity has not been studied till now. Objective: To compare serum and tissue Th1 and Th2 cytokine profiles of patients with active and stable psoriasis as well as healthy controls, and to correlate them with psoriasis severity. Methodology: This was a cross-sectional study involving adult patients with 'active' psoriasis (untreated progressive chronic plaque psoriasis, guttate psoriasis, and erythrodermic psoriasis), 'stable' psoriasis (stable plaque psoriasis or those with completely resolved lesions) and healthy subjects with non-inflammatory skin lesions as controls. Mean levels of Th1 and Th2 cytokines in serum [interleukin 2 (IL-2), interferon-gamma (IFN-γ), IL-4, IL-10] and tissue mRNA expression (IFN-γ, IL-4) were compared among these three groups. Results: There were 30 patients each in active and stable psoriasis groups, and 15 in the control group. Mean serum IL-2, IFN-γ, and IL-10 levels of patients with psoriasis patients were significantly higher than the controls (P < 0.001 for both active and stable psoriasis), whereas mean serum IL-4 level of patients was significantly lower than the controls (P < 0.001). However, there was no statistically significant difference of serum cytokine levels between active and stable psoriasis groups. Mean quantitative tissue mRNA expression of IFN-γ and IL-4 of patients with active and stable psoriasis were significantly lower than the controls (P < 0.001 and <0.01, respectively), but were not significantly different between active and stable psoriasis groups. Serum and tissue cytokines showed weak correlation with psoriasis area and severity index. Limitations: Small sample size and heterogenous nature of patients with psoriasis in terms of disease activity, morphology and treatment are limitations of this study. Conclusions: There is no significant change in the serum or tissue levels of Th1 and Th2 cytokines with activity or severity of psoriasis.

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Rational use of laboratory tests in dermatology

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Saumya Panda

Indian Journal of Dermatology, Venereology, and Leprology 2018 84(4):377-383



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Intramatricial injections for nail psoriasis: An open-label comparative study of triamcinolone, methotrexate, and cyclosporine

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Jyotisterna Mittal, Bharat Bhushan Mahajan

Indian Journal of Dermatology, Venereology, and Leprology 2018 84(4):419-423

Background: One of the most effective options available for treating psoriatic fingernails is intramatricial injection of triamcinolone acetonide. Efficacies of intramatricial methotrexate and cyclosporine have not been comparatively evaluated to date. Methods: Ninety fingernails in 17 patients were assigned to three groups of thirty nails each, and treated with intramatricial injections of triamcinolone acetonide (10 mg/ml), methotrexate (25 mg/ml) and cyclosporine (50 mg/ml) respectively. Each nail was given two injections with a 6-week interval, and graded at 24 weeks using the Nail Psoriasis Severity Index. Results: In both triamcinolone acetonide and methotrexate groups, 15 (50%) nails out of 30 showed >75% improvement. In the cyclosporine group, only ten (33%) nails showed >75% improvement. Side effects were most in the nails treated with cyclosporine. Limitations: The limited follow-up period of 24 weeks may have been insufficient for detecting delayed remissions. The number of patients was small and there was no randomization or blinding. The lack of a placebo/ no- treatment arm can be considered a limitation. Conclusions: Amongst the three drugs studied, intramatricial methotrexate injection yielded the most improvement with minimum side effects, results being comparable to intramatricial triamcinolone acetonide injection. Cyclosporine was the least effective drug, with the most side effects. Intramatricial injection therapy is a safe, economical, simple and effective therapeutic modality in the management of nail psoriasis.

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Mongolian spots combined with halo-like disappearance surrounding café au lait spots

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Aslı Bilgiç Temel, Cumhur Ibrahim Bassorgun, Banu Nur, Erkan Alpsoy

Indian Journal of Dermatology, Venereology, and Leprology 2018 84(4):474-477



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Eruptive pseudoangiomatosis - cherry angiomas with perilesional halo

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Dimple Chopra, Aastha Sharma, Satwinder Kaur, Ravinder Singh

Indian Journal of Dermatology, Venereology, and Leprology 2018 84(4):424-430

Eruptive pseudoangiomatosis is a rare viral exanthem characterized by acute onset of hemangiomata-like lesions, however, histological findings are distinct from that of true angiomas. This entity has been reported from Europe, North America, Japan, and Korea till date. Here, we report 12 cases of eruptive pseudoangiomatosis from a tertiary care hospital in Punjab.

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Topical timolol in PHACES syndrome: Is it safe?

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Deepika Pandhi, Deepak Jakhar, Anupama Tandon, Archana Singal

Indian Journal of Dermatology, Venereology, and Leprology 2018 84(4):488-491



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Chinese version of the treatment of autoimmune bullous disease quality of life questionnaire: Reliability and validity

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Guo Chen, Baoqi Yang, Zhaoxia Zhang, Qing Yang, Xiaoxiao Yan, Dédée F Murrell, Furen Zhang

Indian Journal of Dermatology, Venereology, and Leprology 2018 84(4):431-436

Background: Treatments for autoimmune blistering disease carry significant risks of medical complications and can affect the patient's quality of life. Recently, the Treatment of Autoimmune Bullous Disease Quality of Life questionnaire was developed in Australia. Objective: The objective of this study was to evaluate the reliability and validity of the Chinese version of the Treatment of Autoimmune Bullous Disease Quality of Life questionnaire in Chinese patients with autoimmune blistering diseases. Methods: The Chinese version of the Treatment of Autoimmune Bullous Disease Quality of Life questionnaire was produced by forward-backward translation and cross-cultural adaptation of the original English version. Autoimmune blistering disease patients recruited in the study self-administered the Chinese Treatment of Autoimmune Bullous Disease Quality of Life questionnaire, the Dermatology Life Quality Index and the 36-item Short-Form Health Survey. Reliability of the Chinese Treatment of Autoimmune Bullous Disease Quality of Life was evaluated using internal consistency and test-retest (days 0 and 7) methods. Validity was analyzed by face, content, construct, convergent and discriminant validity measures. Results: A total of 86 autoimmune blistering disease patients were recruited for the study. Cronbach's alpha coefficient was 0.883 and the intraclass correlation coefficient was 0.871. Face and content validities were satisfactory. Convergent validity testing revealed correlation coefficients of 0.664 for the Treatment of Autoimmune Bullous Disease Quality of Life and Dermatology Life Quality Index and –0.577 for the Treatment of Autoimmune Bullous Disease Quality of Life and 36-item Short-Form Health Survey. With respect to discriminant validity, no significant differences were observed in the Treatment of Autoimmune Bullous Disease Quality of Life scores of men and women (t = 0.251, P = 0.802), inpatients and outpatients (t = 0.447, P = 0.656), patients on steroids and steroid-sparing medications (t = 0.672, P = 0.503) and patients with different autoimmune blistering disease subtypes (F = 0.030, P = 0.971). Limitations: Illiterate patients were excluded from the study. The patients were from a single hospital and most of their conditions were in a relatively stable status. Conclusion: The Chinese version of the Treatment of Autoimmune Bullous Disease Quality of Life questionnaire is a reliable and valid instrument to measure treatment burden and to serve as an end point in clinical trials in Chinese autoimmune blistering disease patients.

https://ift.tt/2toyTDu

The strawberry tongue: What, how and where?

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Keshavmurthy A Adya, Arun C Inamadar, Aparna Palit

Indian Journal of Dermatology, Venereology, and Leprology 2018 84(4):500-505



https://ift.tt/2MKKbLp

Solitary dome-shaped erythematous lump of long duration on the palm

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Deepashree Daulatabad, Deepika Pandhi, Nadeem Tanveer, Sonal Sharma, Ishmeet Kaur

Indian Journal of Dermatology, Venereology, and Leprology 2018 84(4):437-439



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Multiple inflamed cutaneous nodules in an elderly female

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Kiran Preet Malhotra, Azfar Neyaz, Arsh Gupta, Monjyoti Das, Nuzhat Husain

Indian Journal of Dermatology, Venereology, and Leprology 2018 84(4):518-520



https://ift.tt/2MJZzYg

A creeping eruption of the buttocks

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Roger Haber, Julien Bachour

Indian Journal of Dermatology, Venereology, and Leprology 2018 84(4):440-440



https://ift.tt/2ttUv1w

German dative case marking in monolingual and simultaneous bilingual children with and without SLI

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Publication date: Available online 20 June 2018
Source:Journal of Communication Disorders
Author(s): Scherger Anna-Lena
This study explores the role of German dative case marking in disentangling effects of specific language impairment (SLI) and bilingualism. Longitudinal data of German-Italian bilingual children with SLI (N = 3) is compared to cross-sectional data (N = 42) of monolingual and bilingual typically developing (TD) children and monolingual children with SLI (ages four and seven). Spontaneous and elicited speech data is analysed in terms of target-like dative case marking in German. Results show differences between the acquisition of case marking of pronouns and of full Determiner Phrases (DPs). Regarding the target-like dative case marking in total, there were no differences found between bilingual TD, monolingual and bilingual children with SLI by the age of four. They demonstrated a similar delay when compared to monolingual TD children. By the age of seven, however, bilingual TD children 'catch up' with their monolingual peers. Children with SLI do not master the acquisition of dative case marking by this age. Cumulative effects of bilingualism and SLI were not found neither in younger nor in older bilingual children. These findings underline the importance of further research on linguistic markers and of distinguishing between effects of SLI and bilingualism.



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Psychopathological consequences of maltreatment among children and adolescents: A systematic review of the GxE literature

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Publication date: Available online 20 June 2018
Source:Research in Developmental Disabilities
Author(s): Dario Maglione, Marcella Caputi, Benedetta Moretti, Simona Scaini
BackgroundIn the last years, several studies focused on the role of Gene-Environment interactions (GxE) in influencing psychopathological outcomes among maltreated children and adolescents. These studies analysed the effect of different genetic variations.AimsThe aim of the present review is to provide an overview of studies investigating GxE effects among maltreated children and adolescents.Methods and ProceduresA systematic literature review was performed by using the following keywords: "Child maltreatment" and "GxE", "Child maltreatment" and "Psychopathology", "Gene-Environment interaction", "Gene-environment correlation", "GxE and psychopathology", "Childhood trauma" and "Psychiatric symptoms", "Early adverse life events", "Early life stress", "Antisocial behaviour", "Depression", "Internalizing symptoms", through the following electronic databases: PubMed, Scopus and PsycINFO, from 2006 to 2017, finding a total of 31 papers.Outcomes and ResultsThe present review confirm that maltreatment produces worse psychopathological outcomes (antisocial behaviour, depression, and other psychiatric traits) in subjects with a specific genetic vulnerability.Conclusions and ImplicationsComprehending the pathways from child maltreatment to psychopathology in their full complexity will be essential to build efficacious preventive and therapeutic protocols.



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Developmental trajectories of executive functions in young males with fragile X syndrome

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Publication date: Available online 20 June 2018
Source:Research in Developmental Disabilities
Author(s): Stephen R. Hooper, Deborah Hatton, John Sideris, Kelly Sullivan, Peter A. Ornstein, Donald B. Bailey
BackgroundExecutive functions (EF) have been identified as impaired in FXS, but few studies have examined their developmental trajectories.AimsThe primary aim of this longitudinal study was to examine the development of EF in young males with FXS compared to Mental Age (MA)-matched controls.Methods and ProceduresThe sample comprised 56 boys with FXS (ages 7–13 years), and 48 MA-matched typical boys (ages 4–8 years). EF tasks included measures of inhibitory control, working memory, cognitive flexibility/set-shifting, problem solving/planning, and processing speed. Tasks were administered at three time points over five-years.Outcomes and ResultsThe MA-Matched Typical boys significantly outperformed the FXS boys on all EF tasks, with the FXS Group showing a pattern of slow, but positive growth on most EF tasks. For working memory tasks, significant interactions were noted between MA and autism symptom severity, and MA and medication status. The probability of task completion increased with higher MA.Conclusions and ImplicationsThese findings contribute to our understanding of the development of EF in this population. They also lay the foundation for use of EF tasks in treatment efforts, particularly with respect to documenting improvements and practice effects, and in understanding associations with targeted developmental outcomes.



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Corrigendum

Journal of Cutaneous Pathology, Volume 45, Issue 7, Page 555-555, July 2018.


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A case of adult onset folliculocentric Langerhans cell histiocytosis

Journal of Cutaneous Pathology, Volume 45, Issue 7, Page 469-472, July 2018.


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Issue Information

Journal of Cutaneous Pathology, Volume 45, Issue 7, July 2018.


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Secretome analysis of alkaliphilic bacterium Bacillus lehensis G1 in response to pH changes

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Publication date: October 2018
Source:Microbiological Research, Volume 215
Author(s): How Lie Ling, Zaidah Rahmat, Farah Diba Abu Bakar, Abdul Munir Abdul Murad, Rosli Md. Illias
Bacillus lehensis G1 is an alkaliphilic bacterium that is capable of surviving in environments up to pH 11. Secretome related to bacterial acclimation in alkaline environment has been less studied compared to cytoplasmic and membrane proteome. The aim of this study was to gain better understanding of bacterial acclimation to alkaline media through analyzing extracellular proteins of B. lehensis. The pH range for B. lehensis growth was conducted, and two-dimensional electrophoresis and MALDI-TOF/TOF MS analysis were conducted to characterize changes in protein profiling in B. lehensis cultured at pH 8 and pH 11 when compared with those cultured at pH 10 (optimal growth pH). B. lehensis could grow well at pH ranging from 8 to 11 in which the bacteria showed to posses thinner flagella at pH 11. Proteomic analyses demonstrated that five proteins were up-regulated and 13 proteins were down-regulated at pH 8, whereas at pH 11, 14 proteins were up-regulated and 8 were down-regulated. Majority of the differentially expressed proteins were involved in the cell wall, main glycolytic pathways, the metabolism of amino acids and related molecules and some proteins of unknown function. A total of 40 differentially expressed protein spots corresponding to 33 proteins were identified; including GlcNAc-binding protein A, chitinase, endopeptidase lytE, flagellar hook-associated proteins and enolase. These proteins may play important roles in acclimation to alkaline media via reallocation of cell wall structure and changes to cell surface glycolytic enzymes, amino acid metabolism, flagellar hook-associated proteins and chaperones to sustain life under pH-stressed conditions.



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Brevibacterium linens RS16 confers salt tolerance to Oryza sativa genotypes by regulating antioxidant defense and H+ ATPase activity

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Publication date: Available online 19 June 2018
Source:Microbiological Research
Author(s): Poulami Chatterjee, Sandipan Samaddar, Ülo Niinemets, Tong-Min Sa
Soil salinity is one of the major limitations that affects both plant and its soil environment, leading to reduced agricultural production. Evaluation of stress severity by plant physical and biochemical characteristics is an established way to study plant-salt stress interaction, but the halotolerant properties of plant growth promoting bacteria (PGPB) along with plant growth promotion is less studied till date. The aim of the present study was to elucidate the strategy, used by ACC deaminase-containing halotolerant Brevibacterium linens RS16 to confer salt stress tolerance in moderately salt-tolerant (FL478) and salt-sensitive (IR29) rice (Oryza sativa L.) cultivars. The plants were exposed to salt stress using 0, 50, and 100 mM of NaCl with and without bacteria. Plant physiological and biochemical characteristics were estimated after 1, 5, 10 days of stress application. H+ ATPase activity and the presence of hydroxyectoine gene (ectD) that is responsible for compatible solute accumulation were also analyzed in bacteria. The height and dry mass of bacteria inoculated plants significantly increased compared to salt-stressed plants, and the differences increased in time dependent manner. Bacteria priming reduced the plant antioxidant enzyme activity, lipid peroxidation and it also regulated the salt accumulation by modulating vacuolar H+ ATPase activity. ATPase activity and presence of hydroxyectoine gene in RS16 might have played a vital role in providing salt tolerance in bacteria inoculated rice cultivars. We conclude that dual benefits provided by the halotolerant plant growth promoting bacteria (PGPB) can provide a major way to improve rice yields in saline soil.



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Restoring NAD(+) Levels with NAD(+) Intermediates, the Second Law of Thermodynamics, and Aging Delay

Rejuvenation Research, Ahead of Print.


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Direct Immunofluorescence as a Helpful Tool for the Differential Diagnosis of Oral Lichen Planus and Oral Lichenoid Lesions

imageAbstract: A great number of lichenoid lesions have overlapping clinicopathological features, so the use of adjunct tests to establish definitive diagnosis is recommended for correct management and prognosis of the lesions. In this context, direct immunofluorescence (DIF) can be a useful tool. Thus, this study aimed to characterize the clinical, histopathological, and DIF pattern in patients with oral lichen planus (OLP) and patients with oral lichenoid lesions (OLLs). Patients with OLP and patients with OLL were characterized and compared with patients with mucous membrane pemphigoid, pemphigus vulgaris, and fibrous hyperplasia through a cross-sectional study. Patients with OLP (n = 30) and patients with OLL (n = 26) were mostly white women in the fifth decade of age, with reticular lesions mainly on the buccal mucosa. All patients with OLP and half of the patients with OLL showed liquefaction degeneration at the basal cell layer and a band-like lymphocytic infiltrate in the subepithelial tissue. Twenty-two patients with OLP (73.3%), 10 with OLL (38.4%), 25 with mucous membrane pemphigoid (96.1%), and all with pemphigus vulgaris (100%) had positive DIF. There was no positive DIF in patients with fibrous hyperplasia. The most frequent DIF pattern in patients with OLP and patients with OLL was linear fibrinogen at the basement membrane zone, and a logistic regression model for positive DIF found statistically significant difference in OLP versus OLL (odds ratio, 3.73; confidence interval, 1.23–11.38). Although clinical and histopathological features are sufficient for diagnosing most of the patients with OLP and OLL, DIF is a key tool in differentiating some lichenoid lesions and could improve the diagnosis of OLP and OLL, especially in lesions showing typical clinical and histological features of OLP.

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Nonhealing Ulcerations of the Breast: Answer

No abstract available

https://ift.tt/2JZYg5E

Cutaneous Metaplastic Carcinoma: Report of a Case With Sebaceous Differentiation

imageAbstract: In this study, a case of a 56-year-old woman with cutaneous metaplastic carcinoma in the neck is reported. It harbored basal cell carcinoma, squamous cell carcinoma, and sebaceous carcinoma, as well as osteosarcoma (with fibroblastic, osteoblastic, aneurysmal bone cyst-like, and chondroblastic patterns). To our knowledge, the literature does not mention sebaceous carcinoma in cutaneous metaplastic carcinoma. Epidemiology and intact mismatch repair proteins of this case support sporadic pathogenesis for this neoplasm. The patient has been followed up for 3 years after surgery with free margins, and no local recurrence or distant metastases have been observed.

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Sebaceous Neoplasms With Rippled, Labyrinthine/Sinusoidal, Petaloid, and Carcinoid-Like Patterns: A Study of 57 Cases Validating Their Occurrence as a Morphological Spectrum and Showing No Significant Association With Muir–Torre Syndrome or DNA Mismatch Repair Protein Deficiency

imageAbstract: Sebaceous neoplasms with an organoid pattern (rippled, labyrinthine/sinusoidal, carcinoid-like, and petaloid) are rare. Previous studies suggested that the above patterns likely represent variations along a morphological continuum. The objectives of this study were to (1) validate this proposition by studying a large number of cases, (2) determine whether there are specific associations with clinical features, (3) establish their frequency, and (4) determine whether they have any association with Muir–Torre syndrome. Fifty-seven sebaceous neoplasms (54 sebaceomas and 3 sebaceous carcinomas) with organoid growth patterns were studied. These occurred in 36 men and 18 women (sex unknown in 3), with ages at diagnosis ranging from 22 to 89 years (mean, 63 years). All patients presented with a solitary nodule (mean size, 11 mm) on the head and neck area. Of the 57 tumors, 24 manifested a single growth pattern, 23 had a combination of 2 patterns, and 10 a combination of 3 patterns, indicating that these patterns are part of a morphological continuum of changes. The carcinoid-like pattern was the most frequent in the "monopatterned" neoplasms (13 cases), whereas the labyrinthine/sinusoidal pattern comprised most of the "polypatterned" lesions, in which various combinations occurred. Immunohistochemically, mismatch repair protein deficiency was detected in 3 of the 22 cases studied, whereas 5 of the 33 patients with available follow-up had an internal malignancy/premalignancy. In conclusion, sebaceous neoplasms with organoid growth patterns are predominantly sebaceomas having a predilection for the scalp, occurring as solitary lesions in elderly patients (male to female ratio of 2:1). Such patterns are expected to be found in a quarter of sebaceomas. In most cases, more than one of the organoid patterns is present. These lesions do not appear to be associated with internal malignancy or mismatch repair deficiency in most cases. However, confirmation of the absence of any significant association with Muir–Torre syndrome syndrome will require genetic studies.

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Immunophenotype Expression Change From CD52+ to CD52− on Erythrodermic Peripheral T-cell Lymphoma, Not Otherwise Specified After Treatment With Alemtuzumab

imageNo abstract available

https://ift.tt/2JXnfuF

Human Papillomavirus–Driven Squamous Lesions: High-Risk Genotype Found in Conjunctival Papillomas, Dysplasia, and Carcinoma

imageBackground: Human papillomavirus (HPV) is a causative agent for intraepithelial squamous neoplasms, particularly on mucosal surfaces. HPV has a well-established association with squamous cell carcinoma (SCC) of the oropharynx and genital tract, and recent studies suggest a potential role in ocular and periocular squamous neoplasms. Multiple high-risk HPV genotypes are associated with histologically similar squamous neoplasms, and some HPV genotypes have been differentially associated with high- or low-grade lesions. Methods: Squamous lesions were screened with immunohistochemical markers p16 and Ki-67 to compare expression in conjunctival papillomas (n = 21) to papillomas with high-grade dysplasia, SCC in situ, and invasive SCC (n = 40). Polymerase chain reaction was performed using the Roche COBAS HPV assay to identify the 14 most common high-risk HPV genotypes. Results: Compared with squamous papillomas, the lesions showing high-grade dysplasia or worse expressed p16 with greater intensity and in a greater percentage of the lesion. A trend toward mild Ki-67 expression in papillomas versus marked Ki-67 expression in high-grade squamous lesions was also observed. HPV-16 was present in 7 of the SCC in situ and invasive SCC lesions but none of the papillomas. Conclusions: HPV may have an important role in squamous lesions of the conjunctiva. In addition to positive polymerase chain reaction results, strong and diffuse p16 expression with marked Ki-67 is strongly suggestive of an HPV-driven lesion.

https://ift.tt/2M5Hra2

Mammary Analog Secretory Carcinoma With ETV6 Rearrangement Arising in the Conjunctiva and Eyelid

imageAbstract: Mammary analog secretory carcinoma (MASC) of salivary gland is a recently described neoplasm that morphologically and immunohistochemically resembles secretory carcinoma of the breast. Genetically, both of them harbor ETV-6-NTRK-3 fusion rearrangement. One case of primary MASCs arising from the eyelid is reported. The patient was a 52-year-old man. Microscopically, the tumor exhibited nodular aggregation of solid, tubular, and microcystic/macrocystic structures. Characteristic "colloid-like" eosinophilic secretory material was present within intraluminal spaces. Immunohistochemically, the tumor cells were positive for mammaglobin, S-100, STAT5a, vimentin, GCDFP-15, AE1/AE3, EMA, and CK7 and were negative for DOG-1, CK5/6, and SMA. A dual color break-apart fluorescence in situ hybridization probe identified rearrangement of the ETV6 gene locus on chromosome 12. The patient had no history of breast or salivary gland tumor. The tumor was completely excised, and the patient has no evidence of recurrent disease or metastasis after 1-year follow-up. A diagnosis of primary MASC was rendered. MASC has never been reported occurring in ocular region. This type of secretory carcinoma probably originates from sweat glands or accessory lacrimal glands, Wolfring and Krause. This unique case expands the clinicopathologic landscape of MASCs for better characterization of this rare entity.

https://ift.tt/2MHVSlR

Reappraisal of the Confusing Concept “Trichogerminoma” and the Ill-Defined Finding “Cell Balls”: Clinicopathologic Analysis of 6 Cases of Trichogerminoma and Comparison With 2 Cases of Basal Cell Carcinoma With Cell Ball–Like Features

imageNo abstract available

https://ift.tt/2JXn0zL

Naked Hair Shafts as a Marker of Cicatricial Alopecia

imageAbstract: Naked hair shafts (NHS) are free-floating hair shafts devoid of surrounding epithelium, supporting structures, and/or embedded in inflammation that may result from destruction of hair follicles by scarring processes such as inflammation and fibroplasia. Extensive examination of NHS has not been performed in scalp biopsies of alopecia. We retrospectively evaluated 622 scalp biopsies of alopecia [345 cicatricial alopecias (central centrifugal cicatricial alopecia, lichen planopilaris, discoid lupus erythematosus, acne keloidalis nuchae, and folliculitis decalvans] and 277 non–cicatricial alopecias [alopecia areata, androgenic alopecia, telogen effluvium, and psoriatic alopecia)] for the presence of NHS. NHS occurred in 0.72% (2/277) of non–cicatricial alopecias (1/102 of alopecia areata, 1/150 of androgenic alopecia, 0/17 of telogen effluvium, and 0/8 of psoriatic alopecia) and 20% (72/345) of cicatricial alopecias (27/118 of central centrifugal cicatricial alopecia, 29/109 of lichen planopilaris, 2/75 of discoid lupus erythematosus, 11/16 of acne keloidalis nuchae, and 3/27 of folliculitis decalvans). The presence of NHS was significantly increased in cicatricial alopecias in comparison with non–cicatricial alopecias; P value

https://ift.tt/2M8c6n3

Nonhealing Ulcerations of the Breast: Challenge

imageNo abstract available

https://ift.tt/2JVfaq7

Langerhans Cell Histiocytosis With Clinical and Histologic Features of Hidradenitis Suppurativa: Brief Report and Review

imageAbstract: Langerhans cell histiocytosis (LCH) is an uncommon histiocytic disorder in adults. Clinically, this rare entity can mimic other dermatologic conditions, including hidradenitis suppurativa. A case of LCH is reported with clinical and histologic features of hidradenitis suppurativa, along with a review of these unusual findings. Clinical dermatologists and dermatopathologists benefit from awareness of this unique presentation, which may prompt earlier identification and diagnosis of adult patients with LCH.

https://ift.tt/2K3TIv5

ALK Rearrangements Are Infrequent in Cellular Blue Nevus and Deep Penetrating Nevus

imageAbstract: Recent studies have identified kinase fusions in Spitzoid melanocytic neoplasms, and approximately 10% of Spitzoid neoplasms harbor anaplastic lymphoma kinase (ALK) rearrangements and corresponding ALK immunoreactivity. Deep penetrating nevi (DPN), a subset of melanocytic neoplasms, have histologic and immunohistochemical overlap that have historically supported classification of DPN with blue/cellular blue nevi (CBN). However, HRAS mutations have rarely been detected in DPN, thereby also linking them to Spitz nevi. The purpose of this study was to see if DPN or CBN possess ALK rearrangements, thereby providing more evidence that these melanocytic lesions may be pathogenetically related to Spitzoid neoplasms. Using ALK immunohistochemistry as a surrogate for ALK rearrangement, the authors examined 26 DPN, 30 CBN, and 4 conventional blue nevi. ALK immunoreactive cases underwent fluorescent in situ hybridization to investigate for the presence of ALK gene rearrangement. Patchy and focal ALK immunostaining was found in only 1 case of DPN (1/26, 3.8%). Seven cases of CBN (7/30; 23%) showed ALK immunostaining (6 focal/patchy, 1 strong and diffuse). Fluorescent in situ hybridization using ALK break-apart probes showed various degrees of gain of 2p23 and rare ALK break-apart signals. Four CBN showed ALK rearrangement in 2%–4% of cells. Two cases of CBN showed gain of 2p23 in 10%–20% of cells. In our study, ALK rearrangements are uncommon in both CBN and DPN, making ALK an unlikely driver in tumorigenesis and classification of these melanocytic variants. However, our study did identify ALK molecular changes and immunohistochemical staining patterns that have not been previously described in CBN or DPN.

https://ift.tt/2JUHWqL

Acquisition of Somatic NRAS Mutations in Central Nervous System Melanocytes: A Predisposing Risk Factor to Primary Melanoma of the Central Nervous System, a Frequently Forgotten Pitfall in Congenital Nevi

imageAbstract: Congenital melanocytic nevi (CMN) are benign melanocytic proliferations that are usually present at birth. A somatic mosaicism for an NRAS point mutation is responsible for the several phenotypic abnormalities that may be associated with congenital nevi. We report the case of a 7-year-old boy with a proliferative nodule (PN) arising in a Giant CMN completely excised and with several visceral and intraspinal melanoma metastases with no evidence of primary cutaneous melanoma. The careful analysis of the clinical, morphologic, and molecular features allowed the distinction of between the benign PN (BPN) and the melanoma. The BPN showed a characteristic comparative genomic hybridization pattern with gains or losses of whole chromosomes, whereas the melanoma displayed gains or losses involving complex partial chromosomal copy number gains or losses. Leptomeningeal melanocytes are more susceptible to transformation by oncogenic NRAS than cutaneous melanocytes, and central nervous system melanomas are more common than cutaneous melanomas in the setting of CMN. Thus, it has been recommended to characterize the congenital disease in patients with 2 CMN at birth, independently of size and site, with a single magnetic resonance imaging screening younger than the age of 1 year.

https://ift.tt/2K4EQN9

Volar Papulonodules in a Patient With Seronegative Rheumatoid Arthritis: Answer

No abstract available

https://ift.tt/2JXmkdp

Psoriasiform Graft-Versus-Host Disease: Report and Brief Review of the Literature

imageAbstract: Graft-versus-host disease (GVHD) is the primary cause of morbidity and non–relapse-related mortality after hematopoietic stem cell transplantation. GVHD is classically divided into acute and chronic forms; acute cutaneous GVHD presents as a morbilliform eruption, whereas chronic cutaneous GVHD presents with lichen planus–like or sclerodermoid morphology. Psoriasiform GVHD is a rarely described subtype that is challenging to distinguish clinically from psoriasis. In addition to classic psoriasiform histologic findings, demonstration of an often subtle vacuolar interface dermatitis and lymphocyte satellitosis are helpful for discrimination. Herein, the authors describe psoriasiform GVHD and review the clinicopathologic findings of this unusual variant. With the appropriate clinical findings, psoriasiform GVHD should be considered in the histologic differential diagnosis of a mixed tissue reaction pattern with both psoriasiform and interface changes.

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An Indurated Plaque in a Toddler: Answer

imageNo abstract available

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Unusual Case of Combined Gliomeningeal Heterotopia on the Nose of an Infant

imageAbstract: Nasal glial heterotopia ("nasal glioma") and cutaneous heterotopic meningeal nodules ("primary cutaneous meningioma") are rare congenital lesions characterized by the presence of heterotopic mature cerebral tissues. Nasal glial heterotopia occurs predominantly in the nasal area and typically does not contain meningothelial elements, whereas heterotopic meningeal nodules occur predominantly on the scalp and do not contain glial elements. In this article, we report an unusual case of cutaneous heterotopia on the nose of an infant composed of both glial and meningothelial elements. The glial component was characterized by irregular islands of predominantly astrocytic cells, on a fibrillary background. The meningothelial component was characterized by bland ovoid cells with focal intranuclear inclusions forming whorled arrangements, with associated psammomatous calcification. To our knowledge, this is the first time such a lesion has been documented. It has also provided us with an opportunity to review the literature regarding heterotopic deposits of both glial and meningothelial tissues.

https://ift.tt/2K7gIt1

Utility of Examining Deeper Levels and/or Special Stains

No abstract available

https://ift.tt/2JV5NqA

A Case of ALK+ Anaplastic Large-Cell Lymphoma With Aberrant Myeloperoxidase Expression and Initial Cutaneous Presentation

imageAbstract: Anaplastic large-cell lymphoma (ALCL) was first described in 1985 by Stein et al and is a clinically, morphologically, and immunophenotypically heterogeneous neoplasm characterized by ALK expression, rearrangement of the ALK gene, and most characteristically its occurrence in children. Clinically, cutaneous ALK+ ALCL can be divided into primary (cutaneous forms) and the much more common, secondary dissemination by a systemic lymphoma. Systemic ALK+ ALCL represents 10%–15% of childhood non-Hodgkin lymphoma and generally presents with advanced systemic disease. Here, we describe a case of a 9-year-old girl who presented with a solitary ulcerated nodule on the elbow that clinically resembled a pyogenic granuloma yet showed ALK, CD30, and myeloperoxidase expression. Fluorescent in situ hybridization with a break-apart probe for ALK revealed the presence of an ALK gene rearrangement. The initial workup showed no evidence of extracutaneous malignancy, and a diagnosis of primary cutaneous ALK+ ALCL was favored. Subsequent imaging studies revealed mediastinal lymphadenopathy, compatible with a systemic form of T-cell lymphoma, treated subsequently with chemotherapy. This report highlights the importance of an adequate systemic evaluation on the presentation of a cutaneous form of ALK+ ALCL.

https://ift.tt/2JZXO7s

Volar Papulonodules in a Patient With Seronegative Rheumatoid Arthritis: Challenge

imageNo abstract available

https://ift.tt/2MJVpQa

T-pattern detection and analysis for the discovery of hidden features of behaviour

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Publication date: Available online 20 June 2018
Source:Journal of Neuroscience Methods
Author(s): M. Casarrubea, M.S. Magnusson, M.T. Anguera, G.K. Jonsson, M. Castañer, A. Santangelo, M. Palacino, S. Aiello, F. Faulisi, G. Raso, S. Puigarnau, O. Camerino, G. Di Giovanni, G. Crescimanno
BackgroundThe behaviour of all living beings consists of hidden patterns in time; consequently, its nature and its underlying dynamics are intrinsically difficult to be perceived and detected by the unaided observer.MethodSuch a scientific challenge calls for improved means of detection, data handling and analysis. By using a powerful and versatile technique known as T-pattern detection and analysis (TPA) it is possible to unveil hidden relationships among the behavioural events in time.ResultsTPA is demonstrated to be a solid and versatile tool to study the deep structure of behaviour in different experimental contexts, both in human and non human subjects.ConclusionThis review deepens and extends contents recently published by adding new concepts and examples concerning the applications of TPA in the study of behaviour both in human and non-human subjects



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Refinement of embolic stroke model in rats: effect of post-embolization anesthesia duration on arterial blood pressure, cerebral edema and mortality

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Publication date: Available online 20 June 2018
Source:Journal of Neuroscience Methods
Author(s): Bryan T.C. Chuang, Xiaoguang Liu, Alexander J. Lundberg, Tommy J.K. Toung, John A. Ulatowski, Raymond C. Koehler
BackgroundInjection of a clot into the internal carotid artery is an experimental model of ischemic stroke that is considered to closely mimic embolic stroke in humans. In this model, the common carotid artery typically remains temporarily occluded to permit time for stabilization of the clot in the middle cerebral artery. However, the associated lengthening of the anesthesia duration could affect arterial blood pressure and stroke outcome.New methodWe refined the model by examining how increasing isoflurane anesthesia duration from 30 to 60 min after clot embolization affects mortality, infarct volume, edema, blood-brain barrier permeability, and the 8-h post-ischemic time course of blood pressure, which has not been reported previously in this model.ResultsWe found that arterial pressure increased after discontinuing anesthesia in both embolized groups and that the increase was greater than in the corresponding non-embolized sham-operated rats. At 24 h, the group with 60-min post-ischemia anesthesia exhibited greater brain water content and a greater ipsilateral-to-contralateral ratio of extravasated Evans blue dye. Mortality was greater in the 60-min group, but infarct volume among survivors was not different from that in the 30-min anesthesia group.Comparison with existing methodsThis study refines the embolic stroke model by demonstrating the importance of minimizing the duration of anesthesia after embolization.ConclusionsThese data indicate that early discontinuation of isoflurane anesthesia after clot embolization permits an earlier hypertensive response that limits edema formation and mortality without significantly affecting infarct volume in survivors, thereby decreasing the required number of animals.



https://ift.tt/2JSU9MW

Central neuropathic pain in paraplegia alters movement related potentials

Publication date: August 2018
Source:Clinical Neurophysiology, Volume 129, Issue 8
Author(s): Aleksandra Vučković, Mohammed Jarjees, Muhammad Abul Hasan, Makoto Miyakoshi, Matthew Fraser
ObjectivesSpinal Cord Injured (SCI) persons with and without Central Neuropathic Pain (CNP) show different oscillatory brain activities during imagination of movement. This study investigates whether they also show differences in movement related cortical potentials (MRCP).MethodsSCI paraplegic patients with no CNP (n = 8), with CNP in their lower limbs (n = 8), and healthy control subjects (n = 10) took part in the study. EEG clustering involved independent component analysis, equivalent current dipole fitting, and Measure Projection to define cortical domains that have functional modularity during the motor imagery task.ResultsThree domains were identified: limbic system, sensory-motor cortex and visual cortex. The MRCP difference between the groups of SCI with and without CNP was reflected in a domain located in the limbic system, while the difference between SCI patients and control subjects was in the sensorimotor domain. Differences in MRCP morphology between patients and healthy controls were visible for both paralysed and non paralysed limbs.ConclusionSCI but not CNP affects the movement preparation, and both SCI and CNP affect sensory processes.SignificanceRehabilitation strategies of SCI patients based on MRCP should take into account the presence of CNP.



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