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South Asian American (SAA) youth are culturally diverse with respect to migration patterns, language, religion, and social determinants of health. Culturally specific stressors related to family, acculturation, discrimination, and intersectionality converge during developmentally sensitive periods, impacting mental health and identity development. "Model minority" stereotypes and somatic expressions of distress contribute to underdetection and limited perceived need for treatment. SAA families navigate structural barriers, including limited access to culturally tailored services, limited English proficiency, referral bias, and stigma, resulting in underutilization of services. Cultural considerations must be integrated into diagnostic conceptualization and treatment recommendations to effectively engage SAA youth and families in treatment.

Evidence for hypothalamic regulation of energy homeostasis and thermoregulation in brown adipose tissue (BAT) during aging has been well recognized, yet the central molecular mediators involved in this process are poorly understood. The arcuate hypothalamus (ARC), orexigenic agouti-related peptide (AgRP) neurons control nutrient intake, energy homeostasis, and BAT thermogenesis. To determine the roles of growth hormone receptor (GHR) signaling in the AgRP neurons we used mice with the AgRP-specific GHR deletion (AgRPΔGHR). We found that female AgRPΔGHRmice were resistant to temperature adaptation, and their body core temperature remained significantly lower when held at 10°C, 22°C, or 30°C, compared to control mice. Low body core temperature in female AgRPΔGHRmice has been associated with significant reductions inUcp1andPgc1αexpression in the BAT. Further, neuronal activity in AgRP in response to cold exposure was blunted in AgRPΔGHRfemales, while the number of Fos+AgRP neurons was increased in control females exposed to cold. Global transcriptome from BAT identified increased expression of genes related to immune responses and chemokine activity and decreased expression of genes involved in triglycerides synthesis and metabolic pathways in AgRPΔGHRfemales. Importantly, these were the same genes that are downregulated by thermoneutrality in control mice but not in the AgRPΔGHRanimals. Collectively, these data demonstrate a novel circuit of thermal regulation between the hypothalamic AgRP-GHR and BAT and provide insight into the brain systems that are critical for the thermogenic vitality of the elderly.

Little is known about the use of antioxidants in the clinical treatment of vitiligo. To investigate the specific use of antioxidants in the treatment of vitiligo and the possible reasons behind its use in China, we conducted a prospective questionnaire-based study using an online questionnaire comprising 26 questions in 5 areas. A total of 323 clinical frontline dermatologists participated in this study. Differences among groups were compared using Pearson’s chi-square test. Ordinal logistic regression was used to develop knowledge–use multiple regression models. Among the 323 dermatologists, 293 (90.7%) approved the oxidative stress theory of vitiligo, and 182 (56.3%) encouraged the use of antioxidants for treating vitiligo; nonetheless, only 11.8% frequently treated vitiligo with antioxidants. Insufficient knowledge of antioxidants was a significant predictor of lower frequency of antioxidant usage (adjusted odds ratio, 0.401 [95% confidence interval, 0.256-0.629]; P < .001 ). The predictors associated with higher antioxidant efficacy included advanced or rapid progression, moderate or moderate-to-severe vitiligo, age of 0–2 years or 13–18 years, segmental vitiligo, oral and topical combination therapy, and course duration of

The growth hormone receptor (GHR) is expressed in brain regions that are known to participate in the regulation of energy homeostasis and glucose metabolism. We generated a novel transgenic mouse line (GHRcre) to characterize GHR-expressing neurons specifically in the arcuate nucleus of the hypothalamus (ARC). Here, we demonstrate that ARCGHR+ neurons are co-localized with agouti-related peptide (AgRP), growth hormone releasing hormone (GHRH), and somatostatin neurons, which are activated by GH stimulation. Using the designer receptors exclusively activated by designer drugs (DREADD) technique to control the ARCGHR+ neuronal activity, we demonstrate that the activation of ARCGHR+ neurons elevates a respiratory exchange ratio (RER) under both fed and fasted conditions. However, while the activation of ARCGHR+ promotes feeding, under fasting conditions, the activation of ARCGHR+ neurons promotes glucose over fat utilization in the body. This effect was accompanied by significant improvements in glucose tolerance, and was specific to GHR+ versus GHRH+ neurons. The activation of ARCGHR+ neurons increased glucose turnover and whole-body glycolysis, as revealed by hyperinsulinemic-euglycemic clamp studies. Remarkably, the increased insulin sensitivity upon the activation of ARCGHR+ neurons was tissue-specific, as the insulin-stimulated glucose uptake was specifically elevated in the skeletal muscle, in parallel with the increased expression of muscle glycolytic genes. Overall, our results identify the GHR-expressing neuronal population in the ARC as a major regulator of glycolysis and muscle insulin sensitivity in vivo.

Melanogenesis is a complex process in which melanin is synthesized in melanocytes and transported to keratinocytes, which involves multiple genes and signaling pathways. Epigenetics refers to the potential genetic changes that affect gene expression without involving changes in the original sequence of DNA nucleotides. DNA methylation regulates the expression of key genes such as tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1), dopachrome tautomerase (DCT) and microphthalmia-associated transcription factor (MITF), as well as paracrine factors such as stem cell factor (SCF) and endothelin-1 (ET-1) in melanogenesis. Potential DNA methylation sites are present in the genes of melanogenesis-related signaling pathways such as "Wnt", "PI3K/Akt/CREB" and "MAPK". H3K27 acetylation is abundant in melanogenesis-related genes. Both the upstream activation and downstream regulation of MITF depend on histone acetyltransferase CBP/p300, and pH-induced H3K27 acetylation may be the amplifying mechanism of MITF's effect. HDAC1 and HDAC10 catalyze histone deacetylation of melanogenesis-related gene promoters. Chromatin remodelers SWI/SNF complex and ISWI complex use the energy of ATP hydrolysis to rearrange nucleosomes, while their active subunits BRG1, BRM and BPTF, act as activators and cofactors of MITF. MicroRNAs (miRNAs) can directly target a large number of melanogenesis-related genes, while long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) regulate melanogenesis in a variety of ways. Interactions exist among the epigenetic mechanisms of melanogenesis. For example, the methyl CpG binding domain protein 2 (MeCP2) links DNA methylation, histone deacetylation, and histone methylation. Epigenetic-based therapy provides novel opportunities for treating dermatoses that are caused by pigmentation disturbances. This review summarizes the epigenetic regulation mechanisms of melanogenesis, and examines the pathogenesis and treatment of epigenetics in pigmentation disorders.

Background: The prevalence of depression is alarming all over the world afflicting billions of individuals. Depression is a common mental disorder and is one of the major causes of morbidity worldwide. Although, there are known effective treatment for depression, but antidepressant therapy usually causes a wide range of undesirable adverse effects and also increases the risk for suicide in individuals with ongoing treatment. So in order to reduce the risks associated, a study was conducted to evaluate the antidepressant potential of Musa paradisiacal Linn, commonly known as Banana fruit and to assess whether the natural source could be used to treat depression.

GH and the GH receptor (GHR) are present in regions known to participate in the regulation of feeding, energy balance and glucose metabolism, including the hypothalamus. We have previously demonstrated that GHR signals in nutrient-sensing neurons is critical for hepatic glucose production and lipid metabolism. Given the high expression pattern of GHR in the arcuate nucleus (ARC) of the hypothalamus, we aimed to define the specific role of the ARC GHR-expressing neurons in energy homeostasis and glucose metabolism. For this purpose, we have developed a novel GHR cell-specific molecular tool (GHRcre) using CRISPR/Cas9 gene editing technology. We show that GHR+ neurons in the ARC are mostly co-localized with AgRP, GHRH, and SST neurons and rapidly respond to fasting. Specific chemogenetic activation of GHR+ neurons in the ARC (ARCGHR+) by the DREADDs technique impaired glucose metabolism, suggesting the role of these neurons in metabolic homeostasis. Additionally, while activation of ARCGHR+ neurons increased energy homeostasis (RER, VO2) under metabolic resting phase, the responses to fasting were significantly attenuated, demonstrating the inhibitory role of GHR+ neurons in the ARC for fasting responses. Sirtuin 1 (SIRT1) is highly expressed in the ARC and had been associated with hypothalamic responses to fasting. The majority of ARCGHR+ neurons express SIRT1 and respond to fasting by upregulating the SIRT1 expression. Importantly, hypothalamic upregulation of SIRT1 in response to fasting is blunted in mice lacking GHR in AgRP neurons (AgRPEYFP∆GHR mice), suggesting a novel role of SIRT1 within the hypothalamic GH axis and providing evidence for a link between the somatotropic system and SIRT1 function in responses to fasting. Disclosure J. Lima: None. L.K. Debarba: None. I.T. Ayyar: None. C. Ubah: None. M. Khan: None. H. AlRomdhan: None. M. Alysofi: None. M. Sadagurski: None. Funding American Diabetes Association (1-18-JDF-063 to M.S.); Wayne State University

Opioid modulators have been explored as a treatment option for psychiatric disorders, but their use has been limited due to their abuse potential. Samidorphan (SAM), a μ-opioid receptor antagonist, has gained interest due to its favorable pharmacokinetic and pharmacodynamic profile. In this review article, six electronic databases including PubMed, PsycINFO, PsycARTICLES, Scopus, Web of Science, and CINAHL were searched to find relevant human studies with a focus on different clinical aspects of SAM. SAM was used in combination with buprenorphine (BUP) to counteract the abuse potential while still maintaining effectiveness in the treatment of depression. The BUP/SAM 2 mg/2mg combination improved depression in patients with major depressive disorder (MDD). SAM's ability to mitigate the weight gain associated with olanzapine (OLZ) has also been explored. Initial studies have shown promising results in some parameters of alcohol-use disorder, while no significant benefit in the treatment of binge-eating disorder has been reported. Somnolence and gastrointestinal side effects were the most commonly observed side effects of SAM.

Introduction: As the incidence of diabetes continues to rise and increasingly affects individuals of all ages, including young adults and children, women of childbearing age are at increased risk of diabetes during pregnancy. Objectives of the study: The main objective of the study is to analyze the prevalence and risk factors of diabetes in pregnancy among local female population of Pakistan. Material and methods: This cross sectional study was conducted in Islamic International Medical College Rawalpindi (RIU) during June 2018 to December 2018. The data was collected from 100 female patients. We designed a study to associate maternal BMI and GWG with pregnancy outcomes in local women of Pakistan with GDM and examine whether these narrower pregnancy weight gain recommendations are predictive of adverse perinatal outcomes in Pakistani population. Results: According to the pre-pregnancy BMI, 96 women (11.5%) were underweight, 558 (67.1%) were of normal weight, 134 (16.1%) were overweight and 44 (5.3%) were obese. The level of glycated hemoglobin was significantly higher in the overweight and obese groups than in normal weight and underweight groups (P  Conclusion: It is reasoned that high pre-pregnancy BMI and unnecessary GWG are related with higher frequencies of LGA, and in addition other unfavorable results in Chinese ladies with GDM.

Introduction: Extremity soft tissue and bone sarcomas are a rare heterogeneous group of bone and connective tissue tumors. Their growth behavior and the biological grade of malignancy differ markedly between the histological subtypes. Aims and objectives: The main objective of the study is to analyze the effects of attitude towards disease on quality of life in patients with bone tumors in Pakistan. Methodology of the study: This study was conducted in Islamic International Medical College Rawalpindi (RIU) during September 2018. This study was done for the analysis of quality of life of bone tumor patients in Pakistan. The data were collected through a prepared questionnaire. Participants were given a toll-free number for technical support and to ask any questions regarding the study. All participants provided written consent upon arrival for their physician appointments. Results: The data were collected from 100 patients of both genders. To develop the propensity score model, we used a multinomial logistic regression of the nominal three-category quality of life variable. The age, SF-12, education, sex, and race terms were entered into the model using restricted cubic splines for age, SF-12 PCS, and SF-12 MCSand interactions of sex with age and education. Conclusion: It is concluded that patients with less cancer-related distress were more likely to favor quality of life over length of life. The direction of causation in this relationship cannot be inferred from these data.

Functional expression of recombinant Pseudozyma antarctica lipase B (PalB) in Escherichia coli has been technically problematic due to protein misfolding, ineffective disulfide bond formation, and protein instability associated with intracellular proteolysis. To overcome these problems, an alternative approach was explored in this study by extracellular secretion of PalB via two Sec-independent secretion systems, i.e., the alpha-hemolysin (type I) and the modified flagellar (type III) secretion systems, which can export proteins of interest from the cytoplasm directly to the exterior of the cell. Both shaker flask and bioreactor cultivations were performed to characterize the developed PalB expression/secretion systems. Bioactive PalB was expressed and secreted extracellularly either as a HlyA fusion (i.e., PalB-HlyA via type I system) or an intact protein (via type III system). However, the secretion intermediates in the intracellular fraction of culture samples were non-bioactive even though they were soluble, suggesting that the extracellular secretion did mediate the development of PalB activity. Also importantly, the secretion strategy appeared to have a minimum impact on cell physiology. PalB secretion via the type I system was fast with higher specific PalB activities but poor cell growth. On the other hand, the secretion via the type III system was slow with lower specific PalB activities but effective cell growth.

Functional expression of lipase from Burkholderia sp. C20 (Lip) in various cellular compartments of Escherichia coli was explored. The poor expression in the cytoplasm of E. coli was improved by several strategies, including coexpression of the cytoplasmic chaperone GroEL/ES, using a mutant E. coli host strain with an oxidative cytoplasm, and protein fusion technology. Fusing Lip with the N-terminal peptide tags of T7PK, DsbA, and DsbC was effective in enhancing the solubility and biological activity. Non-fused Lip or Lip fusions heterologously expressed in the periplasm of E. coli formed insoluble aggregates with a minimum activity. Biologically active and intact Lip was obtained upon the secretion into the extracellular medium using the native signal peptide and the expression performance was further improved by coexpression of the periplasmic chaperon Skp. The extracellular expression was even more effective when Lip was secreted as a Lip–HlyA fusion via the α-hemolysin transporter. Finally, Lip could be functionally displayed on the E. coli cell surface when fused with the carrier EstA.