Update on the pathogenesis of atopic dermatitis.

Atopic dermatitis is a chronic, recurrent, and multifactorial skin-mucosal manifestation resulting from the interaction between elements mainly associated with the skin barrier deficit, the homeostasis of the immune response, neurological aspects, and patterns of reactivity to environmental antigens, which are established in genetically predisposed individuals. In addition to the skin, atopic diathesis involves other organs such as the airways (upper and lower), eyes, digestive tract, and neuropsychiatric aspects, which inflict additional morbidity on the dermatological patient. The different phenotypes of the disease fundamentally depend on the participation of each of these factors, in different life circumstances, such as age groups, occupational exposure patterns, physical activity, pollution, genetic load, and climatic factors. A better understanding of the complexity of its pathogenesis allows not only the understanding of therapeutic targets but also how to identify preponderant elements that mediate disease activity in each circumstance, for selecting the best treatment strategies and mitigation of triggering factors. This narrative review presents an update on the pathogenesis of atopic dermatitis, especially aimed at understanding the clinical manifestations, the main disease phenotypes and the context of available therapeutic strategies.

Obesity-related cancer and bariatric surgery: A comprehensive systematic review and meta-analysis protocol.

INTRODUCTION: Obesity is a silent pandemic affecting all ages and is a component of metabolic syndrome. Its treatment is conducted by lifestyle and behavioral changes, pharmacological therapy, and when correctly indicated, bariatric surgery. In recent years, the procedures for weight loss have been investigated due to their relationship with the development of many types of cancer. Although many studies have shown that bariatric surgery decreases cancer risk, other researchers observed an increase in this association. Carcinogenesis is affected by many factors, such as age, sex, type of cancer, and the bariatric surgery performed on each patient. This systematic review and meta-analysis protocol aims to clarify the association between the different modalities of bariatric surgery and the risk of cancer development in adult patients with metabolic syndrome. METHOD AND ANALYSIS: The proposed systematic review and meta-analysis will be reported conforming to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-P) guidelines. This research will include observational studies (case-control and cohort studies) about patients who undergo bariatric surgery due to metabolic syndrome. Will be accepted in any language and any year. Publications without peer review will be excluded from this review. Data will be entered into the Review Manager software (RevMan5.2.3). We extracted or calculated the OR and 95% CI for dichotomous outcomes for each study. In case of heterogeneity (I2>50%), the random-effects model will combine the studies to calculate the OR and 95% CI. ETHICS AND DISSEMINATION: This study will review the published data; Thus, obtaining ethical approval is unnecessary. The findings of this systematic review will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023432079.

EGFR-Tyrosine Kinase Inhibitor Retreatment in Non-Small-Cell Lung Cancer Patients Previously Exposed to EGFR-TKI: A Systematic Review and Meta-Analysis.

We performed a systematic review and meta-analysis to assess the efficacy of EGFR-tyrosine kinase inhibitors (TKI) retreatment in advanced/metastatic non-small-cell lung cancer (NSCLC) patients. We systematically searched PubMed, Embase, Cochrane databases, ASCO, and ESMO websites for studies evaluating EGFR-TKI retreatment in advanced/metastatic NSCLC patients. All analyses were performed using R software (v.4.2.2). We included 19 studies (9 CTs and 10 retrospective cohorts) with a total of 886 patients. In a pooled analysis of all patients during retreatment with TKI, median OS was 11.7 months (95% confidence interval [CI] 10.2-13.4 months) and PFS was 3.2 months (95% CI 2.5-3.9 months). ORR was 15% (95% CI 10-21%) and DCR was 61% (95% CI 53-67%). The subanalysis by generation of TKI in the rechallenge period revealed a slightly better ORR for patients on 3rd generation TKI (p = 0.05). Some limitations include the high heterogeneity of some of the analyses and inability to perform certain subanalyses. Our results unequivocally support the benefit of EGFR-TKI rechallenge in EGFR-mutated NSCLC patients progressing on TKI treatment after a TKI-free interval. These findings may be especially valuable in areas where access to novel therapeutic drugs and clinical trials is limited.

Aquatic therapy in congenital malformation during the use of external fixator for bone lengthening: It is possible?

OBJECTIVES: The objective of this study is to describe the rehabilitation of individuals with Congenital Malformations (CMF) during the use of an External Fixator (EF) in Aquatic Therapy (AT) and to analyze the association between diagnosis, EF type and location with rehabilitation process outcomes, surgical intervention, and adverse effects. METHODS: This retrospective study included 29 medical records from which the personal and rehabilitation data of the patient were collected. The AT used was described and the outcome variables were associated. The medical records were selected by screening the database of the CMF clinic at the AACD. The inclusion criteria were participants with CMF who used EF treated between 2011 and 2019 of both genders and without age restriction. The exclusion criteria were incomplete medical record data or not undergoing AT while using EF. The extracted data included diagnosis, gender, age, EF type and location, objective of the surgery, adverse events, surgical interventions, time of rehabilitation in AT, physiotherapeutic objectives, and rehabilitation process outcomes in AT. RESULTS: The mean age of the participants was 12.1 ± 3.99 years, with male predominance (55 %) and hemimelia cases (37 %). The most used EF was circular (51 %), located in the femur (37 %), and the main objective of surgery was bone lengthening (52 %). The most recurrent adverse effect was infection (62 %) and 76 % completed AT. There was no association between the variables analyzed. CONCLUSIONS: It was possible to describe CMF rehabilitation with EF in AT. There was no association between the variables analyzed.

Comparison of energy expenditure of individuals with Duchenne muscular dystrophy in the sitting posture on the ground and in water.

Duchenne Muscular Dystrophy (DMD) is one of the most frequent childhood dystrophies, affecting cardiopulmonary functions and walking ability. One of the main symptoms is fatigue, which is caused by altered muscle metabolism related to energy expenditure (EE). Aquatic physiotherapy is a therapeutic modality that facilitates the maintenance of this posture because of immersion on the body. This cross-sectional observational study aimed to compare the EE on the ground and water of individuals with DMD through oxygen consumption in the maintenance of sitting posture. The individuals were in a sitting position on the ground and in the water for 20 min for the assessments. The variables peripheral oxygen saturation, heart rate, maximum expiratory pressure, maximum inspiratory pressure, forced vital capacity, respiratory quotient (RQ), and oxygen consumption per kilogram of body weight (VO2 /kg) were compared, adopting a significance of 5 %. No difference was found between medians and quartiles of RQ when comparing the two environments. The same was observed for VO2 /Kg values on the ground and in water. The data from this study demonstrate that the EE of individuals with DMD did not change when maintaining a sitting posture on the ground and in water.

Prevalence and burden of vitiligo in Africa, the Middle East and Latin America.

Vitiligo is a common chronic autoimmune disorder characterized by skin and hair depigmentation that affects 0.5%-2.0% of the global population. Vitiligo is associated with diminished quality of life (QoL) and psychosocial burden. The burden of vitiligo may vary based on skin tone and cultural differences as well as geographical variations in disease awareness, societal stigma, healthcare systems and treatment options. Data on the burden and management of vitiligo in Africa, the Middle East and Latin America are scarce. Literature searches using terms covering vitiligo in Africa, the Middle East and Latin America were conducted using PubMed to identify relevant publications that focused on disease prevalence and burden, QoL and psychosocial impact and disease management between 2011 and 2021. Most of the reviewed studies were conducted in the Middle East, and most Latin American studies were from Brazil. Most studies involved small patient numbers and may not be generalizable. Reported prevalence of vitiligo ranged from 0.18% to 5.3% in Africa and the Middle East, and from 0.04% to 0.57% in Latin America. In several studies, prevalence was higher among female participants. Generally, non-segmental vitiligo was the dominant clinical variant identified and the age at onset varied widely across studies. Common comorbidities include autoimmune diseases such as Hashimoto's thyroiditis, alopecia areata and diabetes. Few treatment guidelines exist in these regions, with the exceptions of guidelines published by the Brazilian and Argentinian Societies of Dermatology. There is a clear unmet need for large epidemiological studies with uniform methodology to accurately ascertain the true prevalence of vitiligo in Africa, the Middle East and Latin America. Additional data on vitiligo burden and management in Africa and Latin America are also needed, along with local disease management guidelines that consider genetic variation, psychosocial burden and socioeconomic diversity in all 3 regions.

BDNF-dependent signaling in the olfactory bulb modulates social recognition memory in mice.

An operative olfactory bulb (OB) is critical to social recognition memory (SRM) in rodents, which involves identifying conspecifics. Furthermore, OB also allocates synaptic plasticity events related to olfactory memories in their intricate neural circuit. Here, we asked whether the OB is a target for brain-derived neurotrophic factor (BDNF), a well-known mediator of plasticity and memory. Adult ICR-CD1 male mice had their SRM evaluated under the inhibition of BDNF-dependent signaling directly in the OB. We also quantified the expression of BDNF in the OB, after SRM acquisition. Our results presented an amnesic effect of anti-BDNF administered 12 h post-training. Although the western blot showed no statistical difference in pro-BDNF and BDNF expression, the analysis of fluorescence intensity in slices suggests SRM acquisition decreases BDNF in the granular cell layer of the OB. Next, to test the ability of BDNF to rescue SRM deficit, we administered the human recombinant BDNF (rBDNF) directly in the OB of socially isolated (SI) mice. Unexpectedly, rBDNF did not rescue SRM in SI mice. Furthermore, BDNF and pro-BDNF expression in the OB was unchanged by SI. Our study reinforces the OB as a plasticity locus in memory-related events. It also adds SRM as another type of memory sensitive to BDNF-dependent signaling.

Bibliometric evaluation of Anais Brasileiros de Dermatologia (2013-2022)

Abstract The Anais Brasileiros de Dermatologia, published since 1925, is the most influential dermatological journal in Latin America, indexed in the main international bibliographic databases, and occupies the 50th position among the 70 dermatological journals indexed in the Journal of Citations Reports, in 2022. In this article, the authors present a critical analysis of its trajectory in the last decade and compare its main bibliometric indices with Brazilian medical and international dermatological journals. The journal showed consistent growth in different bibliometric indices, which indicates a successful editorial policy and greater visibility in the international scientific community, attracting foreign authors. The increases in citations received (4.1 ×) and in the Article Influence Score (2.9×) were more prominent than those of the main Brazilian medical and international dermatological journals. The success of Anais Brasileiros de Dermatologia in the international scientific scenario depends on an assertive editorial policy, on promptly publication of high-quality articles, and on institutional stimulus to encourage clinical research in dermatology.

Bibliometric evaluation of Anais Brasileiros de Dermatologia (2013-2022).

The Anais Brasileiros de Dermatologia, published since 1925, is the most influential dermatological journal in Latin America, indexed in the main international bibliographic databases, and occupies the 50th position among the 70 dermatological journals indexed in the Journal of Citations Reports, in 2022. In this article, the authors present a critical analysis of its trajectory in the last decade and compare its main bibliometric indices with Brazilian medical and international dermatological journals. The journal showed consistent growth in different bibliometric indices, which indicates a successful editorial policy and greater visibility in the international scientific community, attracting foreign authors. The increases in citations received (4.1×) and in the Article Influence Score (2.9×) were more prominent than those of the main Brazilian medical and international dermatological journals. The success of Anais Brasileiros de Dermatologia in the international scientific scenario depends on an assertive editorial policy, on promptly publication of high-quality articles, and on institutional stimulus to encourage clinical research in dermatology.

Aquatic therapy in congenital malformation during the use of external fixator for bone lengthening: It is possible?

Abstract Objectives: The objective of this study is to describe the rehabilitation of individuals with Congenital Malformations (CMF) during the use of an External Fixator (EF) in Aquatic Therapy (AT) and to analyze the association between diagnosis, EF type and location with rehabilitation process outcomes, surgical intervention, and adverse effects. Methods: This retrospective study included 29 medical records from which the personal and rehabilitation data of the patient were collected. The AT used was described and the outcome variables were associated. The medical records were selected by screening the database of the CMF clinic at the AACD. The inclusion criteria were participants with CMF who used EF treated between 2011 and 2019 of both genders and without age restriction. The exclusion criteria were incomplete medical record data or not undergoing AT while using EF. The extracted data included diagnosis, gender, age, EF type and location, objective of the surgery, adverse events, surgical interventions, time of rehabilitation in AT, physiotherapeutic objectives, and rehabilitation process outcomes in AT. Results: The mean age of the participants was 12.1 ± 3.99 years, with male predominance (55 %) and hemimelia cases (37 %). The most used EF was circular (51 %), located in the femur (37 %), and the main objective of surgery was bone lengthening (52 %). The most recurrent adverse effect was infection (62 %) and 76 % completed AT. There was no association between the variables analyzed. Conclusions: It was possible to describe CMF rehabilitation with EF in AT. There was no association between the variables analyzed.

A scaling investigation of urban form features in Latin America cities.

This paper examines scaling behaviors of urban landscape and street design metrics with respect to city population in Latin America. We used data from the SALURBAL project, which has compiled and harmonized data on health, social, and built environment for 371 Latin American cities above 100,000 inhabitants. These metrics included total urbanized area, effective mesh size, area in km2 and number of streets. We obtained scaling relations by regressing log(metric) on log (city population). The results show an overall sub-linear scaling behavior of most variables, indicating a relatively lower value of each variable in larger cities. We also explored the potential influence of colonization on the current built environment, by analyzing cities colonized by Portuguese (Brazilian cities) or Spaniards (Other cities in Latin America) separately. We found that the scaling behaviors are similar for both sets of cities.

Biomimetic catalysis of nitrite reductase enzyme using copper complexes in chemical and electrochemical reduction of nitrite.

Copper nitrite reductase mimetics were synthesized using three new tridentate ligands sharing the same N,N,N motif of coordination. The ligands were based on L-proline modifications, attaching a pyridine and a triazole to the pyrrolidine ring, and differ by a pendant group (R = phenyl, n-butyl and n-propan-1-ol). All complexes coordinate nitrite, as evidenced by cyclic voltammetry, UV-Vis, FTIR and electron paramagnetic resonance (EPR) spectroscopies. The coordination mode of nitrite was assigned by FTIR and EPR as κ2O chelate mode. Upon acidification, EPR experiments indicated a shift from chelate to monodentate κO mode, and 15N NMR experiments of a Zn2+ analogue, suggested that the related Cu(II) nitrous acid complex may be reasonably stable in solution, but in equilibrium with free HONO under non catalytic conditions. Reduction of nitrite to NO was performed both chemically and electrocatalytically, observing the highest catalytic activities for the complex with n-propan-1-ol as pendant group. These results support the hypothesis that a hydrogen bond moiety in the secondary coordination sphere may aid the protonation step.

JAK-STAT pathway inhibitors in dermatology.

The JAK-STAT signaling pathway mediates important cellular processes such as immune response, carcinogenesis, cell differentiation, division and death. Therefore, drugs that interfere with different JAK-STAT signaling patterns have potential indications for various medical conditions. The main dermatological targets of JAK-STAT pathway inhibitors are inflammatory or autoimmune diseases such as psoriasis, vitiligo, atopic dermatitis and alopecia areata; however, several dermatoses are under investigation to expand this list of indications. As JAK-STAT pathway inhibitors should gradually occupy a relevant space in dermatological prescriptions, this review presents the main available drugs, their immunological effects, and their pharmacological characteristics, related to clinical efficacy and safety, aiming to validate the best dermatological practice.

Prevalence of immune-mediated inner ear disease in non-segmental vitiligo: A cross-sectional study.

BACKGROUND: Sensorineural hearing loss (SNHL) is associated with non-segmental vitiligo (NSV); however, the aetiology of SNHL has not been explored. The concomitance of autoimmune disease in vitiligo patients demands the investigation of immune-mediated inner ear disease (IMIED) as a cause of SNHL in NSV. The anti-Hsp70 antibody is a serological marker of IMIED, which may help in the early diagnosis of this disease. OBJECTIVE: To evaluate the prevalence of IMIED in NSV patients. METHODS: Cross-sectional study involving NSV adult patients and a control group, evaluated through audiometry and serological dosage of the anti-Hsp70 antibody. RESULTS: In total, 112 cases and 23 controls were evaluated. Bilateral SNHL was found in 28 (25.0%; 95%CI 17.9%-32.1%) patients and in 1 (4.3%) control (p = 0.019). Six cases (5.4%; 95%CI 2.7%-8.0%) presented bilateral SNHL of unexplained aetiology, and anti-Hsp70 antibody positivity, fulfilling the diagnostic criteria for IMIED. No controls met the diagnostic criteria for IMIED. Serum anti-Hsp70 antibodies were higher in cases with IMIED: median 220.9 vs. 85.1 ng/ml (p = 0.001). CONCLUSION: The prevalence of IMIED is remarkable in NSV adult patients.

Experimental approaches to assess melanocytes mosaicism in segmental vitiligo

Abstract Vitiligo is an autoimmune disease of the skin that results in localized or disseminated white macules. One common feature of several existing classification protocols is the distribution of the disease into two main subtypes, non-segmental vitiligo (NSV) and segmental vitiligo (SV). SV is characterized by depigmentation spreading within one or more skin segments while NSV is widespread. Several clinical-epidemiological observations suggest that SV has distinct autoimmune pathophysiology compared to NSV. Furthermore, the clinical distribution pattern of SV lesions closely resembles other melanocyte mosaicism diseases. These observations led us to hypothesize that SV is caused by a localized autoimmune reaction targeting epidermal mosaicism melanocytes. Here, we proposed examples of experimental approaches to assess mosaicism in SV patients.

Expert opinion about laser and intense pulsed light (IPL)-induced leukoderma or vitiligo: a cross-sectional survey study.

Vitiligo patients may desire laser hair removal, skin rejuvenation, vascular treatments, and other laser or intense pulsed light (IPL) assisted treatments. However, there is a risk of inducing new depigmented patches (Koebner phenomenon). In absence of guidelines on the safe use of laser or IPL in vitiligo patients, dermatologists tend to be reluctant to administer these treatments. The aim of this survey study was to provide an estimation of the occurrence and related risk factors of laser/IPL-induced leukoderma or vitiligo. A cross-sectional survey study was performed among 15 vitiligo experts from 11 countries, with 14 questions about affected patients, involved laser/IPL treatments and the physicians' approach. In a total of 11,300 vitiligo patients, laser/IPL-induced leukoderma or vitiligo was reported in 30 patients (0.27%). Of these, 12 (40%) patients had a medical history of vitiligo and seven (58%) of these patients had stable (> 12 months) vitiligo before the treatment. Most frequently reported were hair removal procedures and localization of the face and legs. Side effects like blistering, crusting, and erosions occurred in 56.7% of the cases. These vitiligo experts based their advice on the risk of the laser treatment on stability of the vitiligo (43%) and activity signs (50%), and 50% discuss the risks before starting a laser treatment. Relevant activity signs are the Koebner phenomenon (57.1%), confetti-like lesions (57.1%) and hypochromic borders (50%). Laser-induced leukoderma or vitiligo is an uncommon phenomenon. Remarkably, a minority had a medical history of vitiligo of which 58% were stable. Consequently, most cases could not have been prevented by not treating vitiligo patients. However, a majority had laser/IPL-induced skin damage. Therefore, caution is advised with aggressive settings and test-spots prior to the treatment are recommended. This study showed significant variation in the current recommendations and approach of vitiligo experts regarding laser/IPL-induced leukoderma or vitiligo.