The role of nitric oxide and neuroendocrine system in pain generation.

Previous studies have indicated a complex interplay between the nitric oxide (NO) pain signaling pathways and hormonal signaling pathways in the body. This article delineates the role of nitric oxide signaling in neuropathic and inflammatory pain generation and subsequently discusses how the neuroendocrine system is involved in pain generation. Hormonal systems including the hypothalamic-pituitary axis (HPA) generation of cortisol, the renin-angiotensin-aldosterone system, calcitonin, melatonin, and sex hormones could potentially contribute to the generation of nitric oxide involved in the sensation of pain. Further research is necessary to clarify this relationship and may reveal therapeutic targets involving NO signaling that alleviate neuropathic and inflammatory pain.

Dermoscopic Correlation of an Eccentric Case of Kindler Syndrome.

Kindler syndrome (KS) is a rare autosomal recessive skin condition. The FERMT1 gene mutates and causes symptoms such as blistering and epidermal atrophy, as well as an increased risk of cancer and poor wound healing. A male in his 20s sought treatment for his hyper-hypopigmentation over the body with poikiloderma of the face with thin wrinkled cigarette paper skin in association with photosensitivity. He gave a history of developing blisters all over the body during his childhood, which formed raw areas and eventually healed forming atrophic scars. The objective is to assess the correlation of clinical findings with dermoscopy in a case of KS. KS is a rare disorder with poikiloderma, photosensitivity, and acral bullae in infancy as predominant features. Dermoscopy proves to be a useful tool in the diagnosis of this rare disorder as it helps in the identification of poikiloderma, adermatoglyphia, and cigarette paper scarring.

Cutaneous Granulomatous Reaction Secondary to Mesotherapy.

The practice of mesotherapy has gained significant popularity due to its convenience and ability top recisely deliver medications to targeted areas within the skin. However, despite its perceived safety, mesotherapy has been associated with various adverse effects, including granulomatous reactions triggered by certain ingredients present in the injected solutions. This case report highlights a woman in her 50s who developed multiple treatment-resistant cutaneous granulomas following mesotherapy treatment for skin rejuvenation. This case underscores the potential severity of adverse reactions associated with mesotherapy, even with ingredients traditionally considered safe. Furthermore, it emphasizes the challenges in diagnosing and managing such reactions, particularly in the absence of clear causative agents. As mesotherapy continues to gain popularity, clinicians must remain vigilant for the possibility of adverse reactions and consider alternative treatment modalities in cases of persistent or severe adverse events.

Chloracne.

This case report describes hyperpigmented, pruritic lesions on the patient's face and chest that worsened over the previous 3 weeks.

Occurrence of Bullous Pemphigoid in a Longstanding Case of Rheumatoid Arthritis in an Indian Patient: A Rare Association.

Bullous pemphigoid is a subepidermal blistering disease that rarely involves the mucous membranes and possesses circulating antibodies against BP antigen II (BP180) and BP antigen I (BP230). Rheumatoid arthritis (RA) is a progressive inflammatory autoimmune disease that is characterized by joint inflammation and systemic involvement. The co-occurrence of RA, which is likewise linked to autoimmunity, with bullous pemphigoid may not be merely coincidental. A 55-year-old female, a known case of RA for 25 years, presented to us with multiple pruritic vesiculobullous lesions. After a thorough clinical and laboratory assessment, she was diagnosed with bullous pemphigoid. This emphasizes the significance of the simultaneous occurrence of autoimmune disorders and the need for vigilant and timely identification.

Impact of COVID-19 outbreak on healthcare workers in a Tertiary Healthcare Center in India: a cross sectional study.

Numerous speculations have continually emerged, trying to explore the association between COVID-19 infection and a varied range of demographic and clinical factors. Frontline healthcare workers have been the primary group exposed to this infection, and there have been limited global research that examine this cohort. However, while there are a few large studies conducted on Indian healthcare professionals to investigate their potential risk and predisposing factors to COVID-19 infection, to our knowledge there are no studies evaluating the development of long COVID in this population. This cross-sectional study systematically utilized the demographic and clinical data of 3329 healthcare workers (HCW) from a tertiary hospital in India to gain significant insights into the associations between disease prevalence, severity of SARS-Cov-2 infection and long COVID. Most of the study population was found to be vaccinated (2,615, 78.5%), while 654 (19.65%) HCWs were found to be SARS-CoV-2 positive at least once. Of the infected HCWs, 75.1% (491) did not require hospitalization, whereas the rest were hospitalized for an average duration of 9 days. A total of 206 (6.19%) individuals were found to be suffering from long COVID. Persistent weakness/tiredness was the most experienced long-COVID symptom, while females (1.79, 1.25-2.57), individuals who consumed alcohol (1.85, 1.3-2.64) or had blood group B (1.9, 1.33-2.7) were at a significantly higher risk for developing long COVID.

Indian Academy of Pediatrics Revised Guidelines on Evaluation, Prevention and Management of Childhood Obesity.

JUSTIFICATION: The last guidelines for pediatric obesity were released in 2004 by Indian Academy of Pediatrics (IAP). Since then, there has been an alarming increase in prevalence and a significant shift in our understanding in the pathogenesis, risk factors, evaluation, and management of pediatric obesity and its complications. Thus, it was decided to revise and update the previous recommendations. OBJECTIVES: To review the existing literature on the burden of childhood obesity and its underlying etiology and risk factors. To recommend evaluation of childhood obesity and suggest optimum prevention and management strategies of childhood obesity. PROCESS: The following IAP chapters (Pediatric and Adolescent Endocrinology, Infant and Young Child feeding, Nutrition, Non-Communicable Disease and Adolescent Health Academy) were invited to nominate members to become part of the writing committee. The Committee held discussions on various aspects of childhood obesity through online meetings between February and August, 2023. Recommendations were then formulated, which were analyzed, revised and approved by all members of the Committee. RECOMMENDATIONS: Exogenous or primary obesity accounts for the majority of cases of childhood obesity. It is important to differentiate it from endogenous or secondary obesity as evaluation and management changes depending on the cause. In Indian, in children under 5 years of age, weight for length/height using WHO charts, and in children 5-18 years, BMI using IAP 2015 charts is used to diagnose overweight and obesity. Waist circumference should be routinely measured in all overweight and obese children and plotted on India specific charts, as it is a key measure of cardio-metabolic risk. Routine evaluation for endocrine causes is not recommended, except in short and obese children with additional diagnostic clues. All obese children more than ten years old should be evaluated for comorbidities like hypertension, dyslipidemia, hyperglycemia and non-alcoholic fatty liver disease/metabolic dysfunction associated steatotic liver disease (NAFLD/ MASLD). Prevention and management of childhood obesity mainly involves healthy diet practices, daily moderate to vigorous physical activity and reduced screen time. Pharmacotherapy may be offered as an addition to lifestyle interventions only in cases of class 3 obesity or if there are any life-threatening comorbidities. Finally, surgical management may be offered in children older than 12 years of age with class 2 obesity and associated comorbidities or class 3 obesity with/without comorbidities, only after failure of a proper trial of intense lifestyle modifications and pharmacotherapy for at least 6 months.

Genome-wide profiling reveals pervasive transcriptional alterations in fibroblasts derived from lesional skin in vitiligo including a reduced potential to proliferate.

Fibroblasts interact with keratinocytes and melanocytes to maintain skin homeostasis. However, the impact of selective melanocyte loss on the transcriptome of fibroblasts is not fully understood. Thus, we sought to understand the genome-wide transcriptome of fibroblasts derived from non-lesional (NL) and lesional (L) dermis in patients with non-segmental vitiligo. Transcriptional profiling of NL and L fibroblasts was performed on three individuals with vitiligo using next-generation-sequencing. Functional protein-protein interaction (PPI) networks were constructed for the significantly upregulated and downregulated genes, as well as for a common set of genes that were downregulated in both fibroblasts and epidermis in L skin (identified previously). Proliferation potential of NL and L fibroblasts was assessed experimentally. Genome-wide transcriptome analysis revealed a total of 414 (282, downregulated; 132, upregulated) differentially expressed (DE)-transcripts in L as compared to NL fibroblasts. Unsupervised hierarchical clustering of DE-transcripts segregated L and NL fibroblasts into two distinct clades, despite the apparent heterogeneity in lesions of different vitiligo patients. Gene Ontology analysis of downregulated genes revealed enrichment of keratinocyte-specific biological processes such as cornification and keratinization. PPI networks constructed for the downregulated and upregulated genes revealed deregulation of several hub genes associated with cell cycle regulation and cAMP metabolism respectively. Similarly, the PPI networks constructed for 67 genes downregulated in both fibroblasts as well as epidermis of L skin revealed downregulation of hub genes including stratifin, PIK3CG and CDH1. Analysis of the in vitro proliferation potential of L fibroblasts revealed a decrease in the expression of proliferation markers Ki67, MCM6, pERK and pCDK2, a decreased S phase population and an increase in alpha-SMA and collagen expression, corroborating the downregulation of hub genes associated with proliferation identified by PPI network analysis. Our study revealed pervasive transcriptional alterations in L compared to NL fibroblasts in vitiligo. The PPI analysis suggested a reduced potential to proliferate in melanocyte-deprived lesional fibroblasts, which was validated experimentally as well.

Secukinumab significantly reduces inflammation but only mildly improves scaling in four cases of autosomal recessive congenital ichthyosis.

Using the psoriasis regimen, administration of secukinumab 150 mg led to a significant reduction in inflammation and some reduction in scaling in four paediatric cases of autosomal recessive congenital ichthyosis.

Artificial intelligence guided conformational mining of intrinsically disordered proteins.

Artificial intelligence recently achieved the breakthrough of predicting the three-dimensional structures of proteins. The next frontier is presented by intrinsically disordered proteins (IDPs), which, representing 30% to 50% of proteomes, readily access vast conformational space. Molecular dynamics (MD) simulations are promising in sampling IDP conformations, but only at extremely high computational cost. Here, we developed generative autoencoders that learn from short MD simulations and generate full conformational ensembles. An encoder represents IDP conformations as vectors in a reduced-dimensional latent space. The mean vector and covariance matrix of the training dataset are calculated to define a multivariate Gaussian distribution, from which vectors are sampled and fed to a decoder to generate new conformations. The ensembles of generated conformations cover those sampled by long MD simulations and are validated by small-angle X-ray scattering profile and NMR chemical shifts. This work illustrates the vast potential of artificial intelligence in conformational mining of IDPs.