Factors Associated with Primary Care Provider's Job Satisfaction and Organizational Commitment in China: A Machine Learning-Based Random Forest Analysis.

The objective of the study is to explore the factors that influence the job satisfaction and organizational commitment of primary care providers in China, with a focus on the impact of the COVID-19 pandemic and the rescission of restriction policies. We utilized the 20-item Minnesota Satisfaction Questionnaire (MSQ) and the 25-item organizational commitment survey to assess job satisfaction and organizational commitment. In total, 435 valid responses were included in our analysis. The average scores for job satisfaction and organizational commitment were 80.6 and 90.8. After a two-step tuning process, we built random forest models by machine learning. The results show income change, working years, working years in the current institute, and age were the four most important features associated with job satisfaction, organizational commitment, and most of their dimensions. The number of professional fields engaged, gender, job status, and types of endowment insurance were least associated. During pandemic time, income-related factors remain a core concern for primary care providers, whereas job security may lose its importance. These findings suggest that financial bonuses may be an effective way to boost morale, and age-specific motivation plans may be necessary.

Rifaximin ameliorates depression-like behaviour in chronic unpredictable mild stress rats by regulating intestinal microbiota and hippocampal tryptophan metabolism.

BACKGROUND: Chronic unpredictable mild stress (CUMS) can induce depressive behaviours and alter the composition of the gut microbiome. Although modulating gut microbiota can improve depression-like behaviour in rats, the mechanism of action is unclear. Additionally, gut microbiota can affect brain function through the neuroendocrine pathway. This pathway may function by regulating the secretion of neurotransmitters such as tryptophan (TRP). Metabolites of TRP, such as 5-hydroxytryptamine (5-HT) and kynurenine (KYN), are related to the pathophysiological process of depression. Indoleamine-2, 3-dioxygenase-1 (IDO1) and Tryptophan hydroxylase 2 (TPH2) are the key rate-limiting enzymes in TRP metabolism and play an important role in KYN and 5-HT metabolism. METHODS: Rats were subjected to four weeks of CUMS and given rifaximin150 mg/kg by oral gavage daily. After modelling, we investigated the rat's behaviours, composition of the faecal microbiome, neurotransmitter metabolism and key metabolic enzymes of the TRP pathway in the hippocampus (HIP). RESULTS: Rifaximin administration improved depressive behaviour in rats, corrected intestinal microbiota disorders and HIP TRP metabolism and regulated the expression of IDO1 and TPH2 in the HIP. CONCLUSIONS: Rifaximin improves depression-like behaviour in CUMS rats by influencing the gut microbiota and tryptophan metabolism.

Involvement of brain-derived neurotrophic factor methylation in the prefrontal cortex and hippocampus induced by chronic unpredictable mild stress in male mice.

Early life stress alters brain-derived neurotrophic factor (BDNF) promoter IV methylation and BDNF expression, which is closely related to the pathophysiological process of depression. However, the role of abnormal methylation of BDNF induced by stress during adolescence due to depression has not yet been clarified. In this study, adolescent mice were exposed to chronic unpredictable mild stress (CUMS). Depression-like behaviors, BDNF promoter IV methylation, expression of DNA methyltransferases (DNMTs), demethylation machinery enzymes, BDNF protein levels, and neuronal development in the prefrontal cortex (PFC) and hippocampus (HIP) were assessed in adolescent and adult mice. The DNMT inhibitor, 5-Aza-2-deoxycytidine (5-AzaD), was used as an intervention. Stress in adolescence induces behavioral dysfunction, elevated methylation levels of BDNF promoter IV, changes in the expression of DNMT, and demethylation machinery enzymes in adolescent and adult mice. Additionally, the stress in adolescence induced lower levels of BDNF and abnormal hippocampal doublecortin (DCX) expression in adolescent and adult mice. However, DNMT inhibitor treatment in adolescent-stressed mice relieved the abnormal behaviors, normalized the methylation level of BDNF promoter IV, BDNF protein expression, expression of DNMTs, and demethylation machinery enzymes, and improved the neuronal development of adult mice. These results suggest that stress in adolescence induces short- and long-term hypermethylation of BDNF promoter IV, which is regulated by DNMTs, and leads to the development of depression.

Primary care provider's job satisfaction and organizational commitment after COVID-19 restrictions ended: A mixed-method study using a mediation model.

Objectives: More and more countries have decided to cancel most or even all COVD-19 restrictions. However, it is unclear how ending of restrictions will affect primary care providers' job satisfaction and organizational commitment. Our objectives are to explore the current status and possible change in primary care providers' job satisfaction and organizational commitment after massive restriction policies ended in China. Methods: This was a mixed-method study that utilized structured questionnaires and semi-structured qualitative individual interviews. The 20-item Minnesota Satisfaction Questionnaire (MSQ) and 25-item organizational commitment survey were adopted to assess job satisfaction and organization commitment. Descriptive statistics and mediation models, as well as inductive thematic analysis, were used to analyze quantitative and qualitative data. Results: A total of 18 interviews and 435 valid survey responses were included in our analysis. The average scores for job satisfaction and organizational commitment were 80.6 and 90.8. The thematic analysis revealed one major theme: ethical and moral responsibility to provide care as primary care providers, on which we established a mediation model. The mediation analysis revealed that normative commitment could positively affect the other four dimensions of organizational commitment and job satisfaction. The direct effect of affective commitment on job satisfaction was significant (LLCI = 0.11, ULCI = 0.31), and the mediators were identified to have a partial mediating effect instead of a total mediating effect. Conclusion: After COVID-19 restrictions end, the job satisfaction and organizational commitment of primary care providers will return to levels before the pandemic and during this estimated process, a brief rise in resignation is predictable. The normative commitment positively affects the other four dimensions of organizational commitment and job satisfaction for primary care providers, which suggests a possible way to motivate primary care providers when restrictions end.

Effects of traumatic stress in adolescence on PTSD-like behaviors, dendrite development, and H3K9me2/BDNF expression in the amygdala of male rats.

Early detrimental experiences increase the risk of psychiatric disorders, including posttraumatic stress disorder (PTSD). In a previous experiment, we demonstrated that traumatic stress in adolescence triggers changes in the expression of the epigenetic marker H3K9me2 in the hippocampus and prefrontal cortex of adolescent and adult rats, which suppresses transcription of the brain-derived neurotrophic factor (Bdnf) gene that promotes dendrite development and synaptic growth. However, corresponding changes in the amygdala in response to traumatic stress in early life have not yet been fully elucidated. In the current study, we used the inescapable foot shock (IFS) procedure to establish a PTSD model. Half an hour after the end of electric shocks, intraperitoneal injection of the G9a enzyme inhibitor Unc0642, a small molecule inhibitor of EHMT2 that can decrease H3K9me2 expression, was applied to reverse the corresponding epigenetic changes. Exploratory behaviors, anxiety-like behavior, social communication ability, spatial exploration and memory were determined using the open field test (OFT), elevated plus maze (EPM) test, three-chamber sociability test (SIT), Morris water maze (MWM) test, and Y maze test (YMZ), respectively. Additionally, the levels of H3K9me2 and BDNF were measured by quantitative reverse transcription-polymerase chain reaction (qPCR) and Western blotting. Furthermore, neuronal development was examined using Golgi staining. The results showed that the IFS procedure induced anxiety-like and depression-like behaviors, social skills dysfunction, and spatial exploration and memory disorders. It also decreased the mRNA expression of BDNF and BDNF and increased the expression of H3K9me2 in the amygdala. More importantly, compared to unstressed animals, traumatic stress during adolescence induced dendrite maldevelopment in adolescent and adult rats. In summary, the present study indicates that early-life stress alters the epigenetic marker expression of H3K9me2 and decreases levels of BDNF in the amygdala, resulting in dendrite maldevelopment and a higher risk of mental disorders.

Rifaximin-mediated gut microbiota regulation modulates the function of microglia and protects against CUMS-induced depression-like behaviors in adolescent rat.

BACKGROUND: Chronic unpredictable mild stress (CUMS) can not only lead to depression-like behavior but also change the composition of the gut microbiome. Regulating the gut microbiome can have an antidepressant effect, but the mechanism by which it improves depressive symptoms is not clear. Short-chain fatty acids (SCFAs) are small molecular compounds produced by the fermentation of non-digestible carbohydrates. SFCAs are ubiquitous in intestinal endocrine and immune cells, making them important mediators of gut microbiome-regulated body functions. The balance between the pro- and anti-inflammatory microglia plays an important role in the occurrence and treatment of depression caused by chronic stress. Non-absorbable antibiotic rifaximin can regulate the structure of the gut microbiome. We hypothesized that rifaximin protects against stress-induced inflammation and depression-like behaviors by regulating the abundance of fecal microbial metabolites and the microglial functions. METHODS: We administered 150 mg/kg rifaximin intragastrically to rats exposed to CUMS for 4 weeks and investigated the composition of the fecal microbiome, the content of short-chain fatty acids in the serum and brain, the functional profiles of microglia and hippocampal neurogenesis. RESULTS: Our results show that rifaximin ameliorated depressive-like behavior induced by CUMS, as reflected by sucrose preference, the open field test and the Morris water maze. Rifaximin increased the relative abundance of Ruminococcaceae and Lachnospiraceae, which were significantly positively correlated with the high level of butyrate in the brain. Rifaximin increased the content of anti-inflammatory factors released by microglia, and prevented the neurogenic abnormalities caused by CUMS. CONCLUSIONS: These results suggest that rifaximin can regulate the inflammatory function of microglia and play a protective role in pubertal neurodevelopment during CUMS by regulating the gut microbiome and short-chain fatty acids.

H3K9me2 regulation of BDNF expression in the hippocampus and medial prefrontal cortex is involved in the depressive-like phenotype induced by maternal separation in male rats.

BACKGROUND: Early life stress (ELS) induces a depressive-like phenotype and increases the risk of depression. Brain-derived neurotrophic factor (BDNF) has been confirmed to be involved in the pathophysiology of depression. However, the mechanism by which ELS alters the epigenetic regulation of BDNF and changes susceptibility to depression has not been fully clarified. METHODS: The present study used maternal separation (MS) and chronic unpredicted mild stress (CUMS) to establish an MS animal model and a depressive animal model. We assessed depressive-like behaviours, including anhedonia, locomotor activity, anxiety-like behaviour, and spatial memory, using the sucrose preference test, the open field test, the elevated plus maze test, and the Morris water maze test. We also investigated BDNF and H3K9me2 expression in the hippocampus and medial prefrontal cortex (mPFC) by immunohistochemistry, western blotting, and qPCR analysis. Additionally, we used Unc0642, a small molecule inhibitor of histone methyltransferase (G9a), as an intervention. RESULTS: The results showed that CUMS induced depressive-like behaviours in rats and resulted in increased H3K9me2 expression and decreased BDNF expression in the hippocampus and mPFC. More importantly, adult MS rats experiencing CUMS had more severe depressive behaviours, had higher expression of H3K9me2 in the hippocampus and mPFC, and had lower expression of BDNF in the hippocampus and mPFC. In addition, administration of the G9a inhibitor reversed most of the changes. CONCLUSIONS: Our study suggests that ELS changed BDNF and H3K9me2 expression in the rat brain, resulting in a depressive-like phenotype.

Inhibiting Brd4 alleviated PTSD-like behaviors and fear memory through regulating immediate early genes expression and neuroinflammation in rats.

Post-traumatic stress disorder (PTSD) is characterized by depression/anxiety and memory failure, primarily fear memory. According to the reports, neuroinflammation and synaptic plasticity can play a role in the neurophysiological mechanisms underlying PTSD. Bromodomain-containing protein 4 (Brd4) intriguingly affects regulating of inflammatory responses and learning and memory. This study aimed to explore the effect of inhibiting Brd4 on depression/anxiety-like behaviors, spatial and fear memory, and underlying mechanisms in a model of PTSD. Inescapable foot shocks (IFS) with a sound reminder in 6 days were used to induce PTSD-like behaviors which were tested using contextual and cue fear tests, sucrose preference test, open-field test, elevated plus maze test, and Y-maze test. Meanwhile, the Brd4 inhibitor JQ1 was used as an intervention. The results found that IFS induced PTSD-like behaviors and indicated obvious Brd4 expression in microglia of the prefrontal cortex (PFC), hippocampus, and amygdala, pro-inflammatory cytokines over-expression, microglial activation, and nuclear factor-kappa B over-expression in PFC and hippocampus but not in amygdala. Meanwhile, the alterations of immediate early genes (IEGs) were found in PFC, hippocampus, and amygdala. Besides, dendritic spine density was reduced in PFC and hippocampus but was elevated in amygdala of rats with IFS. In addition, treatment with JQ1 significantly reduced freezing time in the contextual and cue fear test, reversed the behavioral impairment, decreased the elevated neuroinflammation, and normalized the alteration in IEGs and dendritic spine densities. The results suggested that Brd4 was involved in IFS-induced PTSD-like behaviors through regulating neuroinflammation, dynamics of IEGs, and synaptic plasticity.

Long-Term Effect of Post-traumatic Stress in Adolescence on Dendrite Development and H3K9me2/BDNF Expression in Male Rat Hippocampus and Prefrontal Cortex.

Exposure to a harsh environment in early life increases in the risk of post-traumatic stress disorder (PTSD) of an individual. Brain derived neurotrophic factor (BDNF) plays an important role in neurodevelopment in developmental stages. Both chronic and traumatic stresses induce a decrease in the level of BDNF and reduce neural plasticity, which is linked to the pathogenesis of PTSD. Also, studies have shown that stress alters the epigenetic marker H3K9me2, which can bind to the promoter region of the Bdnf gene and reduce BDNF protein level. However, the long-term effects of traumatic stress during adolescence on H3K9me2, BDNF expression and dendrite development are not well-known. The present study established a model of PTSD in adolescent rats using an inescapable foot shock (IFS) procedure. Anxiety-like behaviors, social interaction behavior and memory function were assessed by the open field test, elevated plus maze test, three-chamber sociability test and Morris water maze test. In addition, neuronal development and H3K9me2/BDNF expression in hippocampus (HIP) and prefrontal cortex (PFC) were evaluated by Golgi staining, western blotting, qRT-PCR analysis and CHIP-qPCR analysis. Additionally, the Unc0642, a small molecule inhibitor of histone methyltransferase (EHMT2) was used for intervention. The results showed that the IFS procedure induced the PTSD-like behaviors in rats, resulted in fewer dendrite branches and shorter dendrite length in CA1 of HIP and PFC, increased H3K9me2 level and decreased BDNF expression in HIP and PFC. Also, although all the changes can persist to adulthood, Unc0642 administration relieved most of alterations. Our study suggests that traumatic stress in adolescence leads to immediate and long-term mental disorders, neuronal morphological changes, lower BDNF level and increased H3K9me2 level in the HIP and PFC, indicating that H3K9me2/BDNF dysfunction plays a key role in pathogenesis of PTSD.