Tollip coordinates Parkin-dependent trafficking of mitochondrial-derived vesicles.

Multiple mitochondrial quality control pathways exist to maintain the health of mitochondria and ensure cell homeostasis. Here, we investigate the role of the endosomal adaptor Tollip during the mitochondrial stress response and identify its interaction and colocalisation with the Parkinson's disease-associated E3 ubiquitin ligase Parkin. The interaction between Tollip and Parkin is dependent on the ubiquitin-binding CUE domain of Tollip, but independent of Tom1 and mitophagy. Interestingly, this interaction is independent of Parkin mitochondrial recruitment and ligase activity but requires an intact ubiquitin-like (UBL) domain. Importantly, Tollip regulates Parkin-dependent endosomal trafficking of a discrete subset of mitochondrial-derived vesicles (MDVs) to facilitate delivery to lysosomes. Retromer function and an interaction with Tom1 allow Tollip to facilitate late endosome/lysosome trafficking in response to mitochondrial stress. We find that upregulation of TOM20-positive MDVs upon mitochondrial stress requires Tollip interaction with ubiquitin, endosomal membranes and Tom1 to ensure their trafficking to the lysosomes. Thus, we conclude that Tollip, via an association with Parkin, is an essential coordinator to sort damaged mitochondrial-derived cargo to the lysosomes.

Sleep and Diet: Mounting Evidence of a Cyclical Relationship.

Two factors intrinsic to health are diet and sleep. These two behaviors may well influence one another. Indeed, that insufficient sleep adversely impacts dietary intakes is well documented. On the other hand, diet may influence sleep via melatonin and its biosynthesis from tryptophan. Experimental data exist indicating that provision of specific foods rich in tryptophan or melatonin can improve sleep quality. Whole diets rich in fruits, vegetables, legumes, and other sources of dietary tryptophan and melatonin have been shown to predict favorable sleep outcomes. Although clinical trials are needed to confirm a causal impact of dietary patterns on sleep and elucidate underlying mechanisms, available data illustrate a cyclical relation between these lifestyle factors. We recommend adopting a healthful diet to improve sleep, which may further promote sustained favorable dietary practices.

The impact of cultural beliefs and practices on parents' experiences of bereavement following stillbirth: a qualitative study in Uganda and Kenya.

BACKGROUND: Stillbirth is an extremely traumatic and distressing experience for parents, with profound and long-lasting negative impacts. Cultural beliefs and practices surrounding death vary considerably across different contexts and groups, and are a key influence on individual experiences, impacting grief, adjustment, and support needs. Few studies have explored cultural influences surrounding stillbirth in an African context. This study explored the influence of cultural beliefs and practices on the experiences of bereaved parents and health workers after stillbirth in urban and rural settings in Kenya and Uganda. METHODS: A qualitative descriptive study design was employed. Face to face interviews were conducted with parents (N = 134) who experienced a stillbirth (≤ 1 year) and health workers (N = 61) at five facilities in Uganda and Kenya. Interviews were conducted in English or the participants' local language, audio-recorded and transcribed verbatim. Analysis was conducted using descriptive thematic analysis. RESULTS: Commonalities in cultural beliefs and practices existed across the two countries. Three main themes were identified: 1) Gathering round, describes the collective support parents received from family and friends after stillbirth. 2)'It is against our custom' addresses cultural constraints and prohibitions impacting parents' behaviour and coping in the immediate aftermath of the baby's death. 3) 'Maybe it's God's plan or witchcraft' summarises spiritual, supernatural, and social beliefs surrounding the causes of stillbirth. CONCLUSIONS: Kinship and social support helped parents to cope with the loss and grief. However, other practices and beliefs surrounding stillbirth were sometimes a source of stress, fear, stigma and anxiety especially to the women. Conforming to cultural practices meant that parents were prevented from: holding and seeing their baby, openly discussing the death, memory-making and attending the burial. The conflict between addressing their own needs and complying with community norms hindered parents' grief and adjustment. There is an urgent need to develop culturally sensitive community programmes geared towards demystifying stillbirths and providing an avenue for parents to grieve in their own way.

Effects of maternal mental health on prenatal movement profiles in twins and singletons.

AIM: Prenatal experiences, including maternal stress, depression and anxiety, form crucial building blocks affecting the maturation of the foetal central nervous system. Previous research has examined foetal movements without considering effects of maternal mental health factors critical for healthy foetal development. The aim of this research is to assess the effects of maternal mental health factors on foetal twin compared with singleton movement profiles. METHOD: We coded foetal touch and head movements in 56 ultrasound scans, from a prospective opportunity sample of 30 mothers with a healthy pregnancy (mean gestational age 27.8 weeks for singleton and 27.2 for twins). At the ultrasound scan appointment, participants completed questionnaires assessing their stress, depression and anxiety. RESULTS: Maternal depression increased foetal self-touch significantly. In foetal twins, maternal stress significantly decreased and maternal depression significantly increased other twin touch. Maternal mental health factors affected the head movements of twins significantly more than singletons, with maternal depression decreasing head movement frequency for twins significantly. CONCLUSION: These results indicate that maternal mental health might have an impact on types of body schemata formed in utero, in twin compared with singleton pregnancies. Future research needs to examine whether these prenatal effects affect postnatal differences in body awareness.

Heterogeneity in helminth infections: factors influencing aggregation in a simple host-parasite system.

The almost universally-occurring aggregated distributions of helminth burdens in host populations have major significance for parasite population ecology and evolutionary biology, but the mechanisms generating heterogeneity remain poorly understood. For the direct life cycle monogenean Discocotyle sagittata infecting rainbow trout, Oncorhynchus mykiss, variables potentially influencing aggregation can be analysed individually. This study was based at a fish farm where every host individual becomes infected by D. sagittata during each annual transmission period. Worm burdens were examined in one trout population maintained in isolation for 9 years, exposed to self-contained transmission. After this year-on-year recruitment, prevalence was 100% with intensities 10-2628, mean 576, worms per host. Parasite distribution, amongst hosts with the same age and environmental experience, was highly aggregated with variance to mean ratio 834 and negative binomial parameter, k, 0.64. The most heavily infected 20% of fish carried around 80% of the total adult parasite population. Aggregation develops within the first weeks post-infection; hosts typically carried intensities of successive age-specific cohorts that were consistent for that individual, such that heavily-infected individuals carried high numbers of all parasite age classes. Results suggest that host factors alone, operating post-infection, are sufficient to generate strongly overdispersed parasite distributions, rather than heterogeneity in exposure and initial invasion.

A qualitative study of partner engagement in HIV testing in Malawi and Kenya.

In low-income settings, partner engagement in HIV testing during pregnancy is well recognised, but uptake remains low. To understand why men fail to engage, 76 in-depth, individual interviews were conducted with women (n = 23), men (n = 36) and community stakeholders (n = 17) in Malawi and Kenya. Transcribed data were analysed thematically. Male engagement was verbally supported. However, definitions of 'engagement' varied; women wanted a shared experience, whereas men wanted to offer practical and financial support. Women and stakeholders supported couples-testing, but some men thought separate testing was preferable. Barriers to couples-testing were strongly linked to barriers to antenatal engagement, with some direct fear of HIV-testing itself. The major themes identified included diverse definitions of male engagement, cultural norms, poor communication and environmental discomfort - all of which were underpinned by hegemonic masculinity. Couples-testing will only increase when strategies to improve reproductive health care are implemented and men's health is given proper consideration within the process. As social norms constitute a barrier, community-based interventions are likely to be most effective. A multi-pronged approach could include advocacy through social media and community forums, the provision of tailored information, the presence of positive role models and a welcoming environment.

Legionella longbeachae Is Immunologically Silent and Highly Virulent In Vivo.

BACKGROUND: Legionella longbeachae (Llo) and Legionella pneumophila (Lpn) are the most common pneumonia-causing agents of the genus. Although both species can be lethal to humans and are highly prevalent, little is known about the molecular pathogenesis of Llo infections. In murine models of infection, Lpn infection is self-limited, whereas Llo infection is lethal. METHODS: We used mouse macrophages, human macrophages, human epithelial cells, and mouse infections in vivo to evaluate multiple parameters of the infection. RESULTS: We determined that the Llo Dot/Icm secretion system is critical for virulence. Different than Lpn, Llo disseminates and the animals develop a severe pulmonary failure, as demonstrated by lung mechanics and blood oxygenation assays. As compared to Lpn, Llo is immunologically silent and fails to trigger the production of cytokines in human pulmonary epithelial cells and in mouse and human macrophages. Infections in Tnfr1-/-, Ifng-/-, and Il12p40-/- mice supported the participation of cytokines for the resistance phenotype. CONCLUSIONS: Both Lpn and Llo require the Dot/Icm system for pathogenesis, but the infection outcome is strikingly different. Llo is immunologically silent, highly virulent, and lethal. The differences reported herein may reflect unappreciated clinical differences in patients infected with Lpn or Llo.

When proteostasis goes bad: Protein aggregation in the cell.

Protein aggregation is a hallmark of the major neurodegenerative diseases including Alzheimer's, Parkinson's, Huntington's and motor neuron and is a symptom of a breakdown in the management of proteome foldedness. Indeed, it is remarkable that under normal conditions cells can keep their proteome in a highly crowded and confined space without uncontrollable aggregation. Proteins pose a particular challenge relative to other classes of biomolecules because upon synthesis they must typically follow a complex folding pathway to reach their functional conformation (native state). Non-native conformations, including the unfolded nascent chain, are highly prone to aberrant interactions, leading to aggregation. Here we review recent advances in knowledge of proteostasis, approaches to monitor proteostasis and the impact that protein aggregation has on biology. We also include discussion of the outstanding challenges. © 2017 IUBMB Life, 69(2):49-54, 2017.

No. 245-Alcohol Use and Pregnancy Consensus Clinical Guidelines.

OBJECTIVE: To establish national standards of care for the screening and recording of alcohol use and counselling on alcohol use of women of child-bearing age and pregnant women based on the most up-to-date evidence. EVIDENCE: Published literature was retrieved through searches of PubMed, CINAHL, and the Cochrane Library in May 2009 using appropriate controlled vocabulary (e.g., pregnancy complications, alcohol drinking, prenatal care) and key words (e.g., pregnancy, alcohol consumption, risk reduction). Results were restricted to literature published in the last five years with the following research designs: systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no language restrictions. Searches were updated on a regular basis and incorporated in the guideline to May 2010. Grey (unpublished) literature was identified through searching the websites of health technology assessment (HTA) and HTA-related agencies, national and international medical specialty societies, clinical practice guideline collections, and clinical trial registries. Each article was screened for relevance and the full text acquired if determined to be relevant. The evidence obtained was reviewed and evaluated by the members of the Expert Workgroup established by the Society of Obstetricians and Gynaecologists of Canada. The quality of evidence was evaluated and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care. VALUES: The quality of evidence was rated using the criteria described by the Canadian Task Force on Preventive Health Care (Table 1). SPONSOR: The Public Health Agency of Canada and the Society of Obstetricians and Gynaecologists of Canada. ENDORSEMENT: These consensus guidelines have been endorsed by the Association of Obstetricians and Gynecologists of Quebec; the Canadian Association of Midwives; the Canadian Association of Perinatal, Women's Health and Neonatal Nurses (CAPWHN); the College of Family Physicians of Canada; the Federation of Medical Women of Canada; the Society of Rural Physicians of Canada; and Motherisk. SUMMARY STATEMENTS: RECOMMENDATIONS.

Dot/Icm Effector Translocation by Legionella longbeachae Creates a Replicative Vacuole Similar to That of Legionella pneumophila despite Translocation of Distinct Effector Repertoires.

Legionella organisms are environmental bacteria and accidental human pathogens that can cause severe pneumonia, termed Legionnaires' disease. These bacteria replicate within a pathogen-derived vacuole termed the Legionella-containing vacuole (LCV). Our understanding of the development and dynamics of this vacuole is based on extensive analysis of Legionella pneumophila. Here, we have characterized the Legionella longbeachae replicative vacuole (longbeachae-LCV) and demonstrated that, despite important genomic differences, key features of the replicative LCV are comparable to those of the LCV of L. pneumophila (pneumophila-LCV). We constructed a Dot/Icm-deficient strain by deleting dotB and demonstrated the inability of this mutant to replicate inside THP-1 cells. L. longbeachae does not enter THP-1 cells as efficiently as L. pneumophila, and this is reflected in the observation that translocation of BlaM-RalFLLO (where RalFLLO is the L. longbeachae homologue of RalF) into THP-1 cells by the L. longbeachae Dot/Icm system is less efficient than that by L. pneumophila. This difference is negated in A549 cells where L. longbeachae and L. pneumophila infect with similar entry dynamics. A ß-lactamase assay was employed to demonstrate the translocation of a novel family of proteins, the Rab-like effector (Rle) proteins. Immunofluorescence analysis confirmed that these proteins enter the host cell during infection and display distinct subcellular localizations, with RleA and RleC present on the longbeachae-LCV. We observed that the host Rab GTPase, Rab1, and the v-SNARE Sec22b are also recruited to the longbeachae-LCV during the early stages of infection, coinciding with the LCV avoiding endocytic maturation. These studies further our understanding of the L. longbeachae replicative vacuole, highlighting phenotypic similarities to the vacuole of L. pneumophila as well as unique aspects of LCV biology.

Self-inflicted burn injuries in the Australian context.

OBJECTIVE: The primary objective was to calculate the number of self-inflicted burn injuries of all admissions in an Australian hospital burns unit. The secondary objectives included examining the demographic profile, length of stay and co-morbidity of mental illness in these cases compared with the total admissions to the burns unit. METHODS: A retrospective study of medical records was conducted at a tertiary burns unit over a 5-year period. RESULTS: A total of 33 self-inflicted burn injury cases were identified which represented 2.2% of all burns unit admissions. These patients were 70% male, the average age was 36.1 years and 11 were born overseas, which was similar to the profile of all admissions. Twenty-four (73%) patients were diagnosed with a mental illness, compared with 14% for all admissions. The average length of stay was 52 days, compared with the burns unit average of 12 days. CONCLUSIONS: While the percentage of self-inflicted burn cases of all burns unit admissions was low, these cases have a greater burden of care due to their longer admission time and higher frequency of co-morbid mental illness. This finding supports the need for close involvement of consultation liaison psychiatry teams within a burns unit.

Quality indicators for a consultation-liaison psychiatry service.

PURPOSE: Consultation-liaison psychiatry (CLP) researchers have not yet developed accepted quality indicators to measure efficiency or effectiveness. The purpose of this paper is to combine objective and subjective quality indicators to assess hospital-based CLP service utilisation, efficiency and effectiveness. DESIGN/METHODOLOGY/APPROACH: Service utilisation rate was calculated over the service's first four years. Patient characteristics and objective quality indicators relating to response timeliness in 2012 were examined. Totally, 41 staff and 52 consecutive patients completed evaluation surveys to subjectively evaluate effectiveness. FINDINGS: The utilisation rate increased initially and then slightly declined to 1.03 per cent of all hospital admissions. In 2012, 91.5 per cent were seen on the same referral day and 99.4 per cent by the next day. The benchmark for urgent referrals was not met (77.4 per cent). Patients rated involvement with the CLP service a positive experience (90 per cent), but were less clear about follow-up plans (68 per cent). Staff believed that the service improved the patients' hospital course (98 per cent) and was communicated well (93-95 per cent). Only 63 per cent agreed that relevant CLP education was provided and 76 per cent rated follow-up plans as clear. ORIGINALITY/VALUE: This CLP service was evaluated by measuring utilisation rates, referral response timeliness and consumer feedback. Referral to contact time is a useful objective quality indicator but should be combined with subjective yet standardised measures surveying service recipients (patients and referring staff) to be comprehensive and meaningful.

Rehabilitation Techniques for Adults Undergoing External Fixation Treatment for Lower Limb Reconstruction: A Systematic Review.

Introduction: External fixation devices are commonly used in orthopaedic surgery to manage a range of pathologies. In this patient population, there is currently no consensus on optimal rehabilitation techniques. There exists a large variation in practice, with a limited understanding of how these affect treatment outcomes. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, a systematic review was conducted of Allied and Complementary Medicine Database (AMED), Cumulative Index to Nursing and Allied Health Literature (CINAHL), MEDLINE, PEDro, and COCHRANE databases, grey literature sources and forward and backward searching of included articles. Studies were selected following rigorous screening with predefined inclusion criteria. Data quality was assessed using validated appraisal tools. Articles were synthesised by rehabilitation type and descriptive analysis was subsequently performed. Results: From 1,156 articles identified, 18 were eligible for inclusion. The overall quality was low, with clinical commentaries and case studies being the most common study type. Studies were synthesised by rehabilitation type, the most common themes being gait re-education, strengthening, therapy-assisted, active exercises and weight-bearing exercises. Conclusion: There is a lack of high-quality evidence to support meaningful recommendations and guide rehabilitation practices for this patient cohort. Further research for patients being treated in external fixation, especially related to the potential effects of physical rehabilitation on bone healing, return of strength, mobility and independent function is likely to have transferability within wider orthopaedic populations. Clinical significance: This systematic review is unable to provide clinical recommendations due to the poor quality of the available literature. However, it is hoped this paper will provide a foundation for further research to improve rehabilitation for patients being treated with external fixation. How to cite this article: Pawson JR, Church D, Fletcher J, et al. Rehabilitation Techniques for Adults Undergoing External Fixation Treatment for Lower Limb Reconstruction: A Systematic Review. Strategies Trauma Limb Reconstr 2024;19(1):45-55.

Mitochondrial Dysfunction and Fatigue in Sjögren's Disease.

Objectives: Sjögren's disease (SjD) is a common exocrine disorder typified by chronic inflammation and dryness, but also profound fatigue, suggesting a pathological basis in cellular bioenergetics. In healthy states, damaged or dysfunctional mitochondrial components are broken down and recycled by mitophagy, a specialized form of autophagy. In many autoimmune disorders, however, evidence suggests that dysfunctional mitophagy allows poorly functioning mitochondria to persist and contribute to a cellular milieu with elevated reactive oxygen species. We hypothesized that mitophagic processes are dysregulated in SjD and that dysfunctional mitochondria contribute to overall fatigue. We sought to link fatigue with mitochondrial dysfunction directly in SjD, heretofore unexamined, and further sought to assess the pathogenic extent and implications of dysregulated mitophagy in SjD. Methods: We isolated pan T cells via negative selection from the peripheral blood mononuclear cells of 17 SjD and 8 age-matched healthy subjects, all of whom completed fatigue questionnaires prior to phlebotomy. Isolated T cells were analyzed for mitochondrial oxygen consumption rate (OCR) and glycolysis using Seahorse, and linear correlations with fatigue measures were assessed. A mitophagy transcriptional signature in SjD was identified by reanalysis of whole-blood microarray data from 190 SjD and 32 healthy subjects. Differential expression analyses were performed by case/control and subgroup analyses comparing SjD patients by mitophagy transcriptional cluster against healthy subjects followed by bioinformatic interpretation using gene set enrichment analysis. Results: Basal OCR, ATP-linked respiration, maximal respiration, and reserve capacity were significantly lower in SjD compared to healthy subjects with no observed differences in non-mitochondrial respiration, basal glycolysis, or glycolytic stress. SjD lymphocytic mitochondria show structural alterations compared to healthy subjects. Fatigue scores related to pain/discomfort in SjD correlated with the altered OCR. Results from subgroup analyses by mitophagic SjD clusters revealed highly variable inter-cluster differentially expressed genes (DEGs) and expanded the number of SjD-associated gene targets by tenfold within the same dataset. Conclusion: Mitochondrial dysfunction, associated with fatigue, is a significant problem in SjD and warrants further investigation.

Toward enhancement of antibody thermostability and affinity by computational design in the absence of antigen.

Over the past two decades, therapeutic antibodies have emerged as a rapidly expanding domain within the field of biologics. In silico tools that can streamline the process of antibody discovery and optimization are critical to support a pipeline that is growing more numerous and complex every year. High-quality structural information remains critical for the antibody optimization process, but antibody-antigen complex structures are often unavailable and in silico antibody docking methods are still unreliable. In this study, DeepAb, a deep learning model for predicting antibody Fv structure directly from sequence, was used in conjunction with single-point experimental deep mutational scanning (DMS) enrichment data to design 200 potentially optimized variants of an anti-hen egg lysozyme (HEL) antibody. We sought to determine whether DeepAb-designed variants containing combinations of beneficial mutations from the DMS exhibit enhanced thermostability and whether this optimization affected their developability profile. The 200 variants were produced through a robust high-throughput method and tested for thermal and colloidal stability (Tonset, Tm, Tagg), affinity (KD) relative to the parental antibody, and for developability parameters (nonspecific binding, aggregation propensity, self-association). Of the designed clones, 91% and 94% exhibited increased thermal and colloidal stability and affinity, respectively. Of these, 10% showed a significantly increased affinity for HEL (5- to 21-fold increase) and thermostability (>2.5C increase in Tm1), with most clones retaining the favorable developability profile of the parental antibody. Additional in silico tests suggest that these methods would enrich for binding affinity even without first collecting experimental DMS measurements. These data open the possibility of in silico antibody optimization without the need to predict the antibody-antigen interface, which is notoriously difficult in the absence of crystal structures.

Influence of alcohol use and family history of alcoholism on neural response to alcohol cues in college drinkers.

BACKGROUND: Heavy drinkers show altered functional magnetic resonance imaging (fMRI) response to alcohol cues. Little is known about alcohol cue reactivity among college age drinkers, who show the greatest rates of alcohol use disorders. Family history of alcoholism (family history positive [FHP]) is a risk factor for problematic drinking, but the impact on alcohol cue reactivity is unclear. We investigated the influence of heavy drinking and family history of alcoholism on alcohol cue-related fMRI response among college students. METHODS: Participants were 19 family history negative (FHN) light drinkers, 11 FHP light drinkers, 25 FHN heavy drinkers, and 10 FHP heavy drinkers, aged 18 to 21. During fMRI scanning, participants viewed alcohol images, nonalcohol beverage images, and degraded control images, with each beverage image presented twice. We characterized blood oxygen level-dependent (BOLD) contrast for alcohol versus nonalcohol images and examined BOLD response to repeated alcohol images to understand exposure effects. RESULTS: Heavy drinkers exhibited greater BOLD response than light drinkers in posterior visual association regions, anterior cingulate, medial frontal cortex, hippocampus, amygdala, and dorsal striatum, and hyperactivation to repeated alcohol images in temporo-parietal, frontal, and insular regions (clusters > 8,127 µl, p < 0.05). FHP individuals showed increased activation to repeated alcohol images in temporo-parietal regions, fusiform, and hippocampus. There were no interactions between family history and drinking group. CONCLUSIONS: Our results parallel findings of hyperactivation to alcohol cues among heavy drinkers in regions subserving visual attention, memory, motivation, and habit. Heavy drinkers demonstrated heightened activation to repeated alcohol images, which could influence continued drinking. Family history of alcoholism was associated with greater response to repeated alcohol images in regions underlying visual attention, recognition, and encoding, which could suggest aspects of alcohol cue reactivity that are independent of personal drinking. Heavy drinking and family history of alcoholism may have differential impacts on neural circuitry involved in cue reactivity.

Perspectives of occupational therapists working in primary health promotion.

BACKGROUND/AIM: Given a global reorientation of health services towards upstream, or primary health promotion, there is a need to explore the role of occupational therapy in this area of practice. This study aimed to explore and describe the primary health promotion practice of community health workers with an occupational therapy background. The study highlights their practice working at a community or population (macro) level, rather than at the client service (micro) level, and explores related enablers and barriers to this practice. METHODS: The study utilised the qualitative methodology of narrative enquiry. Five workers with an occupational therapy background were recruited from community health services within Victoria. Data were gathered via in-depth interviews. Individual participant interview data were ordered to form a narrative detailing each participant's experience. These narratives were then analysed to generate themes representing important aspects of participant's experiences. RESULTS: Although some practitioners with an occupational therapy background perform primary health promotion, the findings indicate that a number of barriers deter occupational therapists from engaging in this type of practice, including lack of funding, preparation and limited understanding of the role of occupational therapy in health promotion. Enablers to engagement included undertaking further education, gaining clinical experience and establishing a professional identity. CONCLUSION: This study provides insights into the experiences of occupational therapists who work at a macro rather than micro-level of practice, and emphasises some of the barriers and enablers to embracing the sorts of roles that are emerging as part of a changing health system.

A mutant allele of glycoprotein M6-B (Gpm6b) facilitates behavioral flexibility but increases delay discounting.

The neuronal membrane glycoprotein M6B (Gpm6b) gene encodes a membrane glycoprotein that belongs to the proteolipid protein family, and is enriched in neurons, oligodendrocytes, and subset of astrocytes in the central nervous system. GPM6B is thought to play a role in neuronal differentiation, myelination, and inactivation of the serotonin transporter via internalization. Recent human genome-wide association studies (GWAS) have implicated membrane glycoproteins (both GPM6B and GPM6A) in the regulation of traits relevant to psychiatric disorders, including neuroticism, depressed affect, and delay discounting. Mouse studies have implicated Gpm6b in sensorimotor gating and regulation of serotonergic signaling. We used CRISPR to create a mutant Glycoprotein M6B (Gpm6b) allele on a C57BL/6J mouse background. Because Gpm6b is located on the X chromosome, we focused on male Gpm6b mutant mice and their wild-type littermates (WT) in two behavioral tests that measured aspects of impulsive or flexible decision-making. We found that Gpm6b deletion caused deficits in a delay discounting task. In contrast, reward sensitivity was enhanced thereby facilitating behavioral flexibility and improving performance in the probabilistic reversal learning task. Taken together these data further delineate the role of Gpm6b in decision making behaviors that are relevant to multiple psychiatric disorders.

The experiences and psychological outcomes for pregnant women who have had FGM: A systematic review.

Female genital mutilation (FGM) is a global issue, with 200 million women and girls thought to be affected. FGM is defined as removal of female external genitalia, either partial or total, for non-medical purposes. FGM is embedded in tradition, including cultural beliefs about sexual behaviour. Associated risks include haemorrhage, infection, death, dyspareunia, childbirth complications and psychological issues. Although FGM negatively impacts on women's psychological wellbeing, little is known about the impact on pregnancy experiences. Psychological consequences of FGM are likely to be intensified during pregnancy when women have concerns about their own and their baby's wellbeing. This mixed-method systematic review aimed to provide insight into the psychological impact of FGM on women who subsequently become pregnant. Nine electronic databases were searched, using a search strategy to identify relevant studies. Studies were considered for inclusion if they were primary studies (qualitative, quantitative or mixed-method) involving pregnant women of any age who have previously undergone FGM. Relevant studies were evaluated using the MMAT appraisal tool. Analysis was guided by the review questions and the evidence identified. One quantitative and 9 qualitative papers were included. Qualitative data were analysed using meta-ethnography. Narrative analysis of the quantitative study was conducted. Findings relate to power of choice linked to reinfibulation, deinfibulation, birth procedures and pain management; importance of knowledgeable and sensitive health care professionals; and relived trauma experienced during childbirth. These findings could inform the development of supportive interventions for women with FGM within maternity services.