Dapagliflozin Ameliorates Ovulation Disorders via Attenuating Activated Microglia-Mediated Hypothalamic Inflammation in HFD-Fed Mice.

INTRODUCTION: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have shown neuroprotective effects in obese mice. However, whether SGLT2i can ameliorate high-fat diet (HFD)-related ovulation disorders remains unknown. The aim of this research was to investigate whether dapagliflozin improves HFD-induced ovulatory dysfunction by attenuating microglia-mediated hypothalamic inflammation. METHODS: C57BL/6J female mice fed HFD were treated with dapagliflozin (1 mg/kg) for 22 weeks. Plasma insulin, leptin, luteinizing hormone (LH), estradiol (E2), and IL-1ß levels were also tested. Microglial morphology, cell numbers, and SGLT2 expression were evaluated using immunofluorescence. The expression of IL-1ß, NLRP3, kisspeptin, gonadotropin-releasing hormone (GnRH), SGLT2, insulin, and leptin receptors in the hypothalamus was determined using immunohistochemical staining. We also examined the effects of dapagliflozin on glucose metabolism and the release of inflammatory factor in palmitic acid (PA)-treated HMC3 cells. RESULTS: As expected, dapagliflozin improved HFD-induced metabolic disturbances, peripheral versus central insulin and leptin resistance and also restored the regular estrous cycle. Furthermore, dapagliflozin blunted microglia activation, NLRP3 inflammasome priming, hypothalamic inflammation, and increased the expression of GnRH and kisspeptin at proestrus in the hypothalamus. Additionally, dapagliflozin markedly reduced IL-6 and NO release and fat accumulation, decreased lactic acid production and glucose consumption, and inhibited mammalian target of rapamycin (mTOR) and hexokinase 2 (HK2) expression in PA-treated HMC3 cells. These effects suggest that dapagliflozin reduced the mTOR/HK2-mediated aerobic glycolysis. CONCLUSIONS: Dapagliflozin improved HFD-related ovulation disorders by regulating glucose metabolism through mTOR/HK2 signaling and attenuating microglia-mediated hypothalamic inflammation. These results validate the novel role for the neuroprotection of SGLT2i in HFD-induced obesity and ovulation disorders.

Predicting Participation Willingness in Ecological Momentary Assessment of General Population Health and Behavior: Machine Learning Study.

BACKGROUND: Ecological momentary assessment (EMA) is widely used in health research to capture individuals' experiences in the flow of daily life. The majority of EMA studies, however, rely on nonprobability sampling approaches, leaving open the possibility of nonrandom participation concerning the individual characteristics of interest in EMA research. Knowledge of the factors that predict participation in EMA research is required to evaluate this possibility and can also inform optimal recruitment strategies. OBJECTIVE: This study aimed to examine the extent to which being willing to participate in EMA research is related to respondent characteristics and to identify the most critical predictors of participation. METHODS: We leveraged the availability of comprehensive data on a general young adult population pool of potential EMA participants and used and compared logistic regression, classification and regression trees, and random forest approaches to evaluate respondents' characteristic predictors of willingness to participate in the Decades-to-Minutes EMA study. RESULTS: In unadjusted logistic regression models, gender, migration background, anxiety, attention deficit hyperactivity disorder symptoms, stress, and prosociality were significant predictors of participation willingness; in logistic regression models, mutually adjusting for all predictors, migration background, tobacco use, and social exclusion were significant predictors. Tree-based approaches also identified migration status, tobacco use, and prosociality as prominent predictors. However, overall, willingness to participate in the Decades-to-Minutes EMA study was only weakly predictable from respondent characteristics. Cross-validation areas under the curve for the best models were only in the range of 0.56 to 0.57. CONCLUSIONS: Results suggest that migration background is the single most promising target for improving EMA participation and sample representativeness; however, more research is needed to improve prediction of participation in EMA studies in health.

Trajectories of Screen Time across Adolescence and Their Associations with Adulthood Mental Health and Behavioral Outcomes.

Excessive screen time among adolescents is discussed as a significant public health concern. Identifying adolescent longitudinal patterns of time spent on regularly-used media screens and understanding their young adulthood mental health and behavioral issue correlates may help inform strategies for improving these outcomes. This study aimed to characterize joint developmental patterns of time spent on videogames, surfing/chatting the Internet, and TV/DVDs during adolescence (at ages 11, 13, 15, 17) and their associations with mental health (i.e., depression, anxiety, suicidal ideation, and self-injury) and behavioral issues (i.e., substance use, delinquency, aggression) in early adulthood (at age 20). A parallel-process latent class growth analysis was used to model data from a diverse community-ascertained sample of youth in Zurich, Switzerland (n = 1521; 51.7% males). Results suggested that a five-class model best fitted the data: (1) low-screen use, 37.6%; (2) increasing chatting/surfing, 24.0%; (3) moderate-screen use, 18.6%; (4) early-adolescence screen use, 9.9%; and (5) increasing videogame and chatting/surfing, 9.9%. After adjusting for baseline levels of outcomes (primarily at age 11), the trajectory groups differed in their associations with adulthood outcomes of mental health and behavioral problems, indicating the importance of problematic screen usage patterns in predicting these outcomes. Future research to test the directionality of these associations will be important. These findings suggest which patterns of screen use may be a marker for later mental health and behavioral issues in different domains.

Sodium-glucose cotransporter 2 inhibitor ameliorates high fat diet-induced hypothalamic-pituitary-ovarian axis disorders.

High-fat diet (HFD) consumption is known to be associated with ovulatory disorders among women of reproductive age. Previous studies in animal models suggest that HFD-induced microglia activation contributes to hypothalamic inflammation. This causes the dysfunction of the hypothalamic-pituitary-ovarian (HPO) axis, leading to subfertility. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of lipid-soluble antidiabetic drugs that target primarily the early proximal tubules in kidney. Recent evidence revealed an additional expression site of SGLT2 in the central nervous system (CNS), indicating a promising role of SGLT2 inhibitors in the CNS. In type 2 diabetes patients and rodent models, SGLT2 inhibitors exhibit neuroprotective properties through reduction of oxidative stress, alleviation of cerebral atherosclerosis and suppression of microglia-induced neuroinflammation. Furthermore, clinical observations in patients with polycystic ovary syndrome (PCOS) demonstrated that SGLT2 inhibitors ameliorated patient anthropometric parameters, body composition and insulin resistance. Therefore, it is of importance to explore the central mechanism of SGLT2 inhibitors in the recovery of reproductive function in patients with PCOS and obesity. Here, we review the hypothalamic inflammatory mechanisms of HFD-induced microglial activation, with a focus on the clinical utility and possible mechanism of SGLT2 inhibitors in promoting reproductive fitness.

Myeloarchitectonic plasticity in elite golf players' brains.

Human neuroimaging studies have demonstrated that exercise influences the cortical structural plasticity as indexed by gray or white matter volume. It remains elusive, however, whether exercise affects cortical changes at the finer-grained myelination structure level. To answer this question, we scanned 28 elite golf players in comparison with control participants, using a novel neuroimaging technique-quantitative magnetic resonance imaging (qMRI). The data showed myeloarchitectonic plasticity in the left temporal pole of the golf players: the microstructure of this brain region of the golf players was better proliferated than that of control participants. In addition, this myeloarchitectonic plasticity was positively related to golfing proficiency. Our study has manifested that myeloarchitectonic plasticity could be induced by exercise, and thus, shed light on the potential benefits of exercise on brain health and cognitive enhancement.

Par3/integrin ß1 regulates embryo adhesion via changing endometrial luminal epithelium polarity†.

The objective is to investigate the pathophysiological significance of Par3 and integrin ß1 with regard to the functionality of the endometrial luminal epithelium (LE). Design: laboratory study; setting: university research laboratory. Analysis involved endometrial aspirates and endometrial adenocarcinoma cells (HEC-1A) and endometrial carcinoma cells (RL95-2). We first examined the expression and localization of Par3 and integrin ß1 in HEC-1A cells and RL95-2 cells. Then we knocked down Par3 and integrin ß1 in HEC-1A cells and RL95-2 cells, respectively, and found that Par3/integrin ß1 affected embryo adhesion by regulating the intercellular tight junctions' (TJs') structure and thus the polarity of the endometrial LE. These findings were also confirmed in the endometrium specimens from human and mice. The main outcome measures were the expression and localization of Par3 and integrin ß1 in the endometrial epithelial cell lines and endometrium specimens and the regulations of Par3 and integrin ß1 on TJs, polarity, and embryo adhesion. Following the knockdown of Par3 in HEC-1A cells, there was a reduction in the complexity of the TJs and cell polarity, and the adhered blastocysts number was significantly increased. However, the reduction of integrin ß1 in RL95-2 cells resulted in effects that directly opposed those following the knockdown of Par3 in HEC-1A cells. Estrogen and progesterone reduced the expression of Par3 and promoted the expression of integrin ß1 in HEC-1A cells. Par3/integrin ß1 regulates embryo adhesion by regulating intercellular TJs' structure and polarity of endometrial LE under the action of ovarian hormones.

mInscuteable regulates meiotic spindle organization during mouse oocyte meiotic maturation.

Establishment of cellular polarity is one of the key events during oocyte maturation. Inscuteable (Insc) has been identified as a key regulator of cell polarity during asymmetric division in Drosophila. However, the function of its evolutionarily conserved mammalian homologue, mInscuteable (mInsc), in mouse meiotic maturation is not clear. In this study, we investigated the roles of mInsc in mouse oocyte maturation. mInsc was detected at all stages of oocyte maturation. The protein level of mInsc was slightly higher at the germinal vesicle breakdown (GVBD) stage and remained constant during mouse oocyte maturation. The subcellular localization of mInsc overlapped with spindle microtubules. Disruption of microtubules and microfilaments caused changes in the localization of mInsc. Depletion or overexpression of mInsc significantly decreased the maturation rates of mouse oocytes. Depletion of mInsc significantly affected asymmetric division, spindle assembly, alignments of chromosomes and actin cap formation. Taken together, our results demonstrated that mInsc regulates meiotic spindle organization during mouse meiotic maturation.

LGN/mInsc and LGN/NuMA complex structures suggest distinct functions in asymmetric cell division for the Par3/mInsc/LGN and Gαi/LGN/NuMA pathways.

Asymmetric cell division requires the establishment of cortical cell polarity and the orientation of the mitotic spindle along the axis of cell polarity. Evidence from invertebrates demonstrates that the Par3/Par6/aPKC and NuMA/LGN/Gαi complexes, which are thought to be physically linked by the adaptor protein mInscuteable (mInsc), play indispensable roles in this process. However, the molecular basis for the binding of LGN to NuMA and mInsc is poorly understood. The high-resolution structures of the LGN/NuMA and LGN/mInsc complexes presented here provide mechanistic insights into the distinct and highly specific interactions of the LGN TPRs with mInsc and NuMA. Structural comparisons, together with biochemical and cell biology studies, demonstrate that the interactions of NuMA and mInsc with LGN are mutually exclusive, with mInsc binding preferentially. Our results suggest that the Par3/mInsc/LGN and NuMA/LGN/Gαi complexes play sequential and partially overlapping roles in asymmetric cell division.

Relations between childhood psychological maltreatment and mental health dimensions within a higher-order model.

Background: Experiences of childhood psychological maltreatment have been found to be associated with various mental health outcomes, and this association persists into adulthood. Objective: This study investigated whether some types of psychological maltreatment are more harmful than others; whether the harms associated with different types of psychological maltreatment are generalized or specific to particular domains of psychopathology; and whether the associations vary by gender. Method: Participants (N = 544, 63.9 % mother as primary caregiver) were Chinese adults from various regions in China. Participants completed measures of childhood psychological maltreatment experiences perpetrated by their primary caregiver and the mental health outcomes of depression, anxiety, anger, physical aggression, and hostility. The data were analyzed in a hierarchical model in which depression and anxiety were defined as indicators of an internalizing factor, while anger, physical aggression, and hostility were defined as indicators of an externalizing factor. Internalizing and externalizing then defined a higher-order general psychopathology factor. The results suggested equivalent harms of psychological abuse and psychological neglect. Further, the associations between psychological maltreatment and mental health were not unique to specific symptom domains but showed broadband associations with general psychopathology. Results: These findings suggest that trans-diagnostic interventions may be the most effective approach for addressing the mental health impacts of psychological maltreatment. Conclusion: Childhood psychological maltreatment may pose a broadband risk for any and all forms of psychopathology.

Loneliness in the Digital World: protocol for a co-produced ecological momentary assessment study in adolescents.

INTRODUCTION: Loneliness has been identified as an important public health issue, peaking during adolescence. Previous research has suggested that social interaction is a key factor in loneliness, and positive social interaction can act as a protective factor against loneliness. However, it is unclear whether there are differing impacts of in-person and online social interaction on adolescents' loneliness and mental health. Ecological Momentary Assessment (EMA) designs are ideally suited for better understanding these associations. METHOD AND ANALYSIS: In the 'Loneliness in the Digital World' study, we will use a co-developed EMA design to capture daily social interactions, loneliness and mental health such as positive and negative emotions, depression and anxiety in approximately 200 adolescents aged 12-15 years. We will combine this with comprehensive information gathered from online surveys. Analysing the data using techniques such as dynamic structural equation modelling, we will examine, among other research questions, the associations between online and in-person social interaction and feelings of loneliness. The results can help inform interventions to support adolescents with high levels of loneliness and poor mental health. ETHICS AND DISSEMINATION: We received the ethics approval for the data collection from The Academic and Clinical Central Office for Research and Development, followed by the College of Medicine and Veterinary Medicine Ethics panel at University of Edinburgh, and finally reviewed by East of Scotland Research Ethics Service. The results will be disseminated through journal publications, conferences and seminar presentations and to relevant stakeholders such as teachers.

Daily life affective dynamics as transdiagnostic predictors of mental health symptoms: An ecological momentary assessment study.

BACKGROUND: Affective dynamics have been identified as a correlate of a broad span of mental health issues, making them key candidate transdiagnostic factors. However, there remains a lack of knowledge about which aspects of affective dynamics - especially as they manifest in the course of daily life - relate to a general risk for mental health issues versus specific symptoms. METHODS: We leverage an ecological momentary assessment (EMA) study design with four measures per day over a two-week period to explore how negative affect levels, inertia, lability, and reactivity to provocation and stress in the course of daily life relate to mental health symptoms in young adults (n = 256) in the domains of anxiety, depression, psychosis-like symptoms, behaviour problems, suicidality, and substance use. RESULTS: Dynamic structural equation modelling (DSEM) suggested that negative affect levels in daily life were associated with depression, anxiety, indirect and proactive aggression, psychosis, anxiety, and self-injury; negative affective lability was associated with depression, physical aggression, reactive aggression, suicidal ideation, and ADHD symptoms; negative affective inertia was associated with depression, anxiety, physical aggression, and cannabis use; and emotional reactivity to provocation was related to physical aggression. LIMITATIONS: The cross-sectional design, the limited span of mental health issues included, and the convenience nature and small size of the sample are limitations. CONCLUSIONS: Findings suggest that a subset of mental health symptoms have shared negative affective dynamics patterns. Longitudinal research is needed to rigorously examine the directionality of the effects underlying the association between affective dynamics and mental health issues.

[Luteal letrozole administration decreases serum estrogen level but not the risk of ovarian hyperstimulation syndrome].

OBJECTIVE: To explore the efficiency of using aromatase inhibitors during luteal phase in in vitro fertilization IVF stimulated cycles for patients at high risk for ovarian hyperstimulation syndrome (OHSS). METHODS: A total of 139 infertile women undergoing assisted reproductive technique with high risk for OHSS were enrolled in this clinical trial. In the treatment group 43 patients received five consecutive doses of aromatase inhibitors (letrozole) and support therapy combined with embryo cryopreservation. In the control group 96 patients received support therapy alone. All the patients were evaluated clinically, echographically, hematologically and tested for their steroid hormone. RESULTS: There was significantly lower estrogen level in the treatment group 2, 5 and 8 days after oocyte retrieval compared with the control group (P<0.001), There was no significant difference in luteinizing hormone and progesterone levels 2, 5 and 8 days after oocyte retrieval in the treatment group and control group (P>0.05). There were 7 cases of severe OHSS in the treatment group and 18 cases of severe OHSS in the control group. The rate of severe OHSS was not significantly different in the treatment group and control group (P=0.12). No side effect was reported in either group. CONCLUSION: Treatment with letrzolein luteal phase decreases serum estrogen levels of patients after oocyte retrieval,but it couldn't reduce the risk of severe OHSS.

Latent profiles of childhood psychological maltreatment and their links to adult mental health in China and the UK.

BACKGROUND: Though links between childhood maltreatment and mental health have been established, little known about how specific types of childhood maltreatment tend to cluster and how the resulting patterns of exposure impact mental health outcomes. METHOD: The current study used latent profile analyses in Chinese (N = 544) and UK (N = 589) samples to identify childhood psychological maltreatment profiles (i.e., profiles of psychological abuse, psychological neglect, and psychological non-support) in different country contexts, and their associations with a range of mental health (i.e., depression, anxiety, anger, physical aggression, verbal aggression, and hostility), and broader well-being (i.e., self-esteem) outcomes. Unadjusted as well as analyses adjusted for adverse childhood experiences (ACEs) were conducted. RESULTS: Four profiles were identified in both samples, but their nature differed between the Chinese sample ("Psychological Non-support", "Low-Maltreated", "High-Maltreated", and "Severe-Maltreated") and the UK sample ("Low-Maltreated", "Moderate-Maltreated", "High-Maltreated", and "Severe-Maltreated"). Individuals in the "Psychological Non-support" in China and "Low-Maltreated" class in the UK displayed better mental health outcomes-lower levels of depression, anxiety, and aggression, and higher self-esteem. In contrast, individuals in the "Severe-Maltreated" profiles in both the Chinese and UK samples displayed poorer mental health outcomes-higher depression, anxiety, and aggression, and lower self-esteem. Interventions and prevention efforts are needed for individuals categorized in profiles affected by psychological maltreatment. CONCLUSION: This study highlights the importance of using targeted intervention or prevention to prevent psychological maltreatment, as well as improve mental health outcomes in individuals who have experienced psychological maltreatment.

Adipocyte-derived exosomal miR-30c-5p promotes ovarian angiogenesis in polycystic ovary syndrome via the SOCS3/STAT3/VEGFA pathway.

Polycystic ovary syndrome (PCOS) is a systemic endocrine disease affecting women's reproductive health. Ovarian angiogenesis in PCOS patients is abnormal, manifested by increased ovarian stromal vascularization and upregulated proangiogenic factors such as vascular endothelial growth factor (VEGF). However, the specific mechanisms underlying these changes in PCOS remain unknown. In this study, we induced the adipogenic differentiation in preadipocyte 3T3-L1 cells and found that adipocyte-derived exosomes promoted proliferation, migration, tube formation, and VEGFA expression in human ovarian microvascular endothelial cells (HOMECs) by delivering miR-30c-5p. Mechanistically, dual luciferase reporter assay demonstrated that miR-30c-5p directly targeted the 3'- untranslated region (UTR) of suppressor of cytokine signaling 3 (SOCS3) mRNA. In addition, adipocyte-derived exosomal miR-30c-5p activated signal transducer and activator of transcription 3 (STAT3)/VEGFA pathway in HOMECs via targeting SOCS3. In vivo experiments indicated that tail vein injection of adipocyte-derived exosomes exacerbated endocrine and metabolic disorders and ovarian angiogenesis in mice with PCOS via miR-30c-5p. Taken together, the study revealed that adipocyte-derived exosomal miR-30c-5p promotes ovarian angiogenesis via the SOCS3/STAT3/VEGFA pathway, thereby participating in the development of PCOS.

The Impact of Childhood Psychological Maltreatment on Mental Health Outcomes in Adulthood: A Systematic Review and Meta-Analysis.

Childhood emotional abuse (CEA) and childhood emotional neglect (CEN) are the least well-studied forms of childhood maltreatment due to challenges in their definition and in detection. However, the available evidence suggests associations with multiple adulthood mental health problems in clinical and non-clinical populations. This systematic review and meta-analysis (PROSPERO registration number CRD42020197833) explored the associations between CEA and CEN and a range of adulthood mental health problems based on systematic searches of eight databases. In total, 79 English and 11 Chinese studies met our inclusion criteria. Results suggested that CEA and CEN had positive associations with various adulthood mental health problems (d = 0.02-1.84), including depression, anxiety, substance abuse, suicidal ideation or attempts, personality disorders, eating disorders, and other psychological symptoms in the general population and across different geographic regions. Furthermore, findings suggested that compared with the non-clinical population, individuals in clinical populations were more likely to have experienced emotional abuse and neglect during childhood. The review highlights the need for more research on emotional abuse and emotional neglect. Furthermore, future research should include more populations from non-western countries and non-college populations. They further underline the importance of addressing issues related to CEA/CEN experiences in the prevention and treatment of mental health issues in adulthood.

Low dosage of prednisone acetate combined with doxycycline in the treatment of chronic endometritis in patients with repeated implantation failure.

OBJECTIVE: To retrospectively investigate whether the oral administration of prednisone acetate with doxycycline increases the cure rate of chronic endometritis (CE) and improves in vitro fertilization (IVF) outcomes in patients with repeated implantation failure (RIF) with CE. METHODS: In total, 352 patients with RIF were investigated, 128 of whom were diagnosed with CE by hysteroscopy and endometrial immunohistochemical analysis. The patients with CE were divided into CD138-positive high-power field (HPF) counts of 1-2 and ≥3. Forty-five patients were orally administered prednisone acetate tablet 5 mg daily and doxycycline 100 mg twice daily for 14 consecutive days (group A), and 55 patients were administered doxycycline 100 mg orally twice daily for 14 days (group B) and underwent repeated endometrial sampling and histological assessment. Twenty-eight patients (group C) did not receive any treatment. The cure rate of CE and final reproductive outcomes of the frozen-thawed embryo transfer cycle were compared. RESULTS: The total cure rate, cure rate of patients with CE(CD138+ HPF counts: 1-2), and cure rate of patients with CE(CD138+ HPF counts: ≥3) showed no significant difference between groups A and B. Logistics regression analysis indicated that the implantation rate, human chorionic gonadotropin (hCG)-positive rate, clinical pregnancy rate, clinical pregnancy rate with fetal heartbeat on day 30 (D30), and ongoing pregnancy rate was significantly higher in group A than in group C. For CE-cured patients after the treatment, the implantation rate, hCG-positive rate, clinical pregnancy rate, clinical pregnancy rate with fetal heartbeat on D30, and ongoing pregnancy rate were significantly higher in group A than in group B. CONCLUSION: CE is closely related to RIF occurrence, and the combined oral administration of prednisone acetate and doxycycline can be a treatment option for patients with RIF with CE and improves reproductive outcomes, although it does not improve the CE cure rate compared with doxycycline treatment alone.

Analysis of pregnancy outcomes in patients with recurrent implantation failure complicated with chronic endometritis.

Chronic endometritis (CE) has been considered to reduce uterine receptivity and negatively affect reproductive outcomes for in vitro fertilization-embryo transfer (IVF-ET) patients, especially for people undergoing recurrent implantation failure (RIF). To investigate the effects of antibiotic and platelet-rich plasma (PRP) therapy on pregnancy outcomes following frozen-thawed embryo transfer (FET) in RIF patients with CE, endometrial specimens of 327 patients with RIF obtained by endometrial scratching during mid-luteal phase were immunostained by multiple myeloma oncogene-1 (Mum-1)/syndecan-1 (CD138). RIF patients with CE were given antibiotics and PRP treatment. According to the Mum-1+/CD138+ plasmacytes after treatment, patients were divided into persistent weak positive CE (+) group, CE (-) group and non-CE group. FET was performed and the basic characteristics and pregnancy outcomes of patients in three groups were compared. Among 327 RIF patients, 117 patients were complicated with CE, the prevalence was 35.78%. The prevalence of strong positive was 27.22% and that of weak positive was 8.56%. 70.94% patients with CE converted to negative after treatment. There was no significant difference in the basic characteristics, including age, BMI, AMH, AFC, infertility years, infertility types, number of previous transplant cycles, endometrial thickness on transplantation day and number of transplanted embryos (p > 0.05); The positive rate of hCG, clinical pregnancy rate and implantation rate in CE (-) group were significantly increased compared with the weak CE (+) group and non-CE group (p < .01), and the live birth rate also improved (p < .05). Whereas, the rate of early abortion in CE (-) group was 12.70%, which was higher than that in weak CE (+) group and non-CE group (p < .05). After multivariate analysis, number of previous failed cycles and CE remained independent factors associated with live birth rate, while only CE remained to be the independent factor of clinical pregnancy rate. It is recommended to perform CE-related examination for patients with RIF. Antibiotic and PRP treatment can significantly improve pregnancy outcomes of patients with CE negative conversion in FET cycle.

Galpha/LGN-mediated asymmetric spindle positioning does not lead to unequal cleavage of the mother cell in 3-D cultured MDCK cells.

The position of the mitotic spindle plays a key role in spatial control of cell division. It is generally believed that when a spindle is positioned asymmetrically in a dividing cell, the resulting daughter cells are usually unequal in size due to eccentric cleavage of the mother cell. Molecular mechanisms underlying the generation of unequal sized daughter cells have been extensively studied in Drosophila neuroblast and Caenorhabditis elegans zygote where the Gα subunit of the heterotrimeric G proteins and its binding partner - Pins in Drosophila and GPR-1/2 in C. elegans - are shown to be critical in governing spindle positioning and asymmetric cleavage of the mother cell. In mammalian system, although Gα and LGN (mammalian Pins homolog) are also required for spindle orientation, whether they can mediate asymmetric spindle positioning or asymmetric cleavage of the mother cell is not known. Here, by artificially targeting Gαi to the apical cortex in 3-D cultured MDCK cells, we established a system where asymmetric spindle positioning can be consistently induced. Interestingly, this asymmetrically positioned spindle does not lead to asymmetric cleavage; instead it results in equal sized daughter cells. Live cell time-lapse analysis revealed that anaphase spindle elongation compensated the original asymmetric spindle positioning. Our findings demonstrate that asymmetric spindle positioning does not necessarily lead to unequal sized daughter cells in mammalian system. We discuss potential mechanisms in generating unequal sized daughter cells.

Hypothalamic mechanisms of obesity-associated disturbance of hypothalamic-pituitary-ovarian axis.

Ovulatory disorders are the most common clinical feature exhibited among obese women. Initiation of ovulation physiologically requires a surge of gonadotropin-releasing hormone (GnRH) released from GnRH neurons located in the hypothalamus. These GnRH neurons receive metabolic signals from circulation and vicinal neurons to regulate GnRH release. Leptin acts indirectly on GnRH via adjacent leptin receptor (LEPR)-expressing neurons such as proopiomelanocortin (POMC), neuropeptide Y (NPY)/agouti-related peptide (AgRP), and neuronal nitric oxide (NO) synthase (nNOS) neurons to affect GnRH neuronal activities. Additionally, hypothalamic inflammation also affects ovulation independent of obesity. Therefore, this review focuses on hypothalamic mechanisms that underlie the disturbance of hypothalamic-pituitary-ovarian (HPO) axis during obesity with an attempt to promote future studies and/or novel therapeutic strategies for ovulatory disorders in obesity.

The impact of childhood psychological maltreatment on mental health outcomes in adulthood: a protocol for a systematic review and meta-analysis.

BACKGROUND: Research suggests that childhood psychological maltreatment (i.e., emotional abuse and emotional neglect) is associated with mental health problems that persist into adulthood, for example anxiety, depression, post-traumatic stress disorder (PTSD), suicidal ideation, and aggression; however, a systematic review and meta-analysis of the existing literature would help clarify the magnitude and moderators of these associations, and the extent to which they may be affected by publication bias, as well as the methodological strengths and weakness of studies in this area. METHOD: The reporting of this protocol follows the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) Statement. Searches will be carried out via several databases, including Web of Science, Medline, PubMed, PsycINFO, Applied Social Science Index and Abstract, ERIC and EMBASE. Empirical peer-reviewed research articles that fit pre-specified eligibility criteria will be included in the review. Studies will be eligible if they include participants age 18 or over at time of mental health assessment, include information on childhood psychological maltreatment (emotional abuse and/or neglect) perpetrated by a primary caregiver or adult in the same household, and provide quantitative information on the association between these factors. Studies using prospective and retrospective designs and written in either English or Chinese will be eligible. Two independent reviewers will screen and assess studies for inclusion in the review as well as extract the data, with consensus reached through discussion in cases of discrepancy. A third reviewer will be consulted to resolve any discrepancies that remain. The relevant Newcastle-Ottawa scales will be used for assessing the quality of studies. If a sufficient number of comparable studies are retrieved, a meta-analysis will be conducted using a random effects model. Study-level moderators (i.e., year of publication, quality of the study and study geographical location) will be examined in the meta-analyses. DISCUSSION: This systematic review will provide an understanding of the long-term effects of childhood psychological maltreatment on adult mental health, which adds to previous reviews focusing primarily on the effects of physical and sexual abuse. The results of the review will help inform clinical practice in approaches to treating those with a history of psychological maltreatment in childhood. The gaps and weaknesses in the evidence identified will also inform recommendations for future research.