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Background Suicide is a serious public health problem, ranked amongst the leading causes of death worldwide. There are no official data on self-harm and suicide in Pakistan; both are illegal acts, and are socially and religiously condemned. This study explored the views of clinicians, including general practitioners (GPs) and hospital physicians (HPs) on self-harm, about their management of people who self-harm and what interventions might be appropriate in Pakistan. Methods This qualitative study, generating data using semi-structured interviews, was nested within a Randomized Controlled Trial (RCT) of a psychosocial intervention for people following self-harm. Clinicians (n = 18) with experience of treating people who self-harm were recruited from public hospitals and general practices. Results Face-to-face interviews were conducted in Urdu and digitally recorded with consent, transcribed and translated into English. Transcripts were checked for cultural and interpretive interpretations by the research team, then analyzed thematically using the principles of constant comparison. The following themes will be presented encountering people with self-harming behaviors; challenges encountered in managing people who self-harm; barriers to accessing care, and what ideal care might look like. Participants identified their lack of training and expertise in the management of people with self-harm behavior. Conclusions This is the first study to explore clinicians' perspectives on self-harm in Pakistan. The study highlighted the need for training for doctors in the identification and management of mental health problems, including the management of people who self-harm.Parents raising children with autism spectrum disorder (ASD) usually carry on their daily life under tremendous stress, but limited empirical research has been devoted to this population. It is known that parents' health status directly impacts therapeutic outcome of ASD children. As an important regulator in cardiovascular, nervous and immune systems, nitric oxide (NO) levels haven't been reported in parents of ASD children yet. In this study, we measured urine nitrite and nitrate from 43 ASD parents (ASD-P), and 43 healthy adults in the same range of age (Control) who didn't have any ASD descendants. Comparison between the ASD-P and Control groups showed that NO 2 - , NO 3 - , and NO 2 - / NO 3 - were all significantly lower in the ASD-P group. Analysis on the interaction effect of sex and group indicated that urine NO 3 - of mothers in ASD-P was lower than that in females of the Control group, but no significant difference was observed between males in both groups. It is for the first time that urine nitric oxide metabolites (nitrite, nitrate) levels were precisely reported to differentiate parents of autistic children from other adults without ASD descendants. This phenomenon suggests that parents (especially mothers) of autistic children might have experienced more mental and physical stressors, which led to decreased NO levels during metabolism. Further investigations are necessary to uncover the etiology of low urine NO among parents of autistic children.Background Scopolamine, a non-selective muscarinic acetylcholine receptor (M1~5-AChR) antagonist, has rapid and robust antidepressant effects in humans and other species. However, which of the five M-AChRs mediates these therapeutic effects has not been fully identified. Several studies implicate M2-AChR as a potential antidepressant target of scopolamine. This study aimed to explore the role of M2-AChR in scopolamine's antidepressant-like effects and determine the underlying mechanisms. Methods We used the classic novelty suppressed feeding test (NSFT), open field test (OFT) and forced swim test (FST) to observe antidepressant-related behaviors of normal rats, medial prefrontal cortex (mPFC) neuron silenced rats and M2-AChR knockdown rats treated with scopolamine. In a further experiment, the M2 cholinergic receptor antagonist methoctramine (MCT) was injected intracerebroventricularly into normal rats. Levels of mTORC1 and brain-derived neurotrophic factor (BDNF) in the mPFC of animals were analyzed by Western blotting. Results Consistent with previous studies, mPFC was required for the antidepressant-like effects of scopolamine, and intracerebroventricular injection of MCT into rats could produce similar antidepressant-like effects. Use of AAV-shRNA to knock down M2-AChR in the mPFC resulted in the antidepressant-like effects of scopolamine being blunted. Furthermore, Western blotting demonstrated increased expression of mTORC1 signaling and BDNF in MCT-treated rats. Conclusion Our results indicate that M2-AChR in the mPFC mediates the antidepressant-like effects of scopolamine by increasing the expression of BDNF and activating the mTORC1 signaling pathway.Background Patients with major depressive disorder (MDD) often present with co-occurring anxiety symptoms. The network method provides a novel view on understanding the co-occurrence of depressive and anxiety symptoms. Thus, the purpose of our study was to explore it by applying network analysis methods. Methods We used electronic medical records from West China Hospital in China. In total, 3,424 patients who met the criteria for MDD were included. R-studio 3.6 was used to estimate the network structure. First, we estimated the network structure of depression and anxiety symptoms using the graphic LASSO algorithm. Then, we estimated the centrality indices of nodes to determine which symptoms are more central in the network. BVD-523 concentration We then estimated the bridge centrality indices using the bridge function via the R package networktools. Results Some strong connections were found like "easy to wake up," "wake up early," and "difficulty falling asleep," "suicidal thoughts," and "hopelessness." "Depressed mood," "somatic anxiety," "hopelessness," "anxiety mood," and "tension" have the higher centrality indices. Results revealed eight bridge symptoms (e.g., concentration/memory difficulty, gastrointestinal symptoms) in the co-occurrence network structure. Conclusions This research suggests that the described approach in mapping the presence of anxiety symptoms in individuals with major depression might potentially increase diagnostic precision and help choose more targeted interventions and potentially reduce the occurrence of treatment resistance.

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