Physical health complications in children and young people with avoidant restrictive food intake disorder (ARFID): a systematic review and meta-analysis.

BACKGROUND: Avoidant restrictive food intake disorder (ARFID) is a feeding and eating disorder with known acute and longstanding physical health complications in children and young people (CYP) and commonly presents to paediatricians. OBJECTIVE: To systematically review the published literature on physical health complications in CYP with ARFID using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. METHODS: A systematic search of PubMed, Embase, Web of Science, PsycINFO and Cochrane Library was performed on 14 February 2024. Studies reporting physical health complications in CYP ≤25 years with ARFID were included. We pooled studies for meta-analysis comparing ARFID with healthy controls or anorexia nervosa (AN). RESULTS: Of 9058 studies found in searches, we included 132 studies. We found evidence for low weight, nutritional deficiencies and low bone mineral density. CYP with ARFID can present across the weight spectrum; however, the majority of CYP with ARFID were within the healthy weight to underweight range. Most studies reported normal range heart rates and blood pressures in ARFID, but some CYP with ARFID do experience bradycardia and hypotension. CYP with ARFID had higher heart rates than AN (weighted mean difference: 12.93 bpm; 95% CI: 8.65 to 17.21; n=685); heterogeneity was high (I2: 81.33%). CONCLUSION: There is a broad range of physical health complications associated with ARFID requiring clinical consideration. Many CYP with ARFID are not underweight yet still have complications. Less cardiovascular complications found in ARFID compared with AN may be related to chronicity. PROSPERO REGISTRATION NUMBER: CRD42022376866.

Knowledge and Attitudes Regarding Depression Among a Sample of Iraqi Non-Psychiatric Nurses: A Cross-Sectional Study.

Introduction: Nurses, comprising the largest profession in healthcare, play a significant role in the identification and management of mental health disorders in hospitals. Objectives: The study assessed the knowledge and attitudes of non-psychiatric nurses and their encounters with depressive patients throughout their careers. Methods: This was a cross-sectional descriptive study with 400 non-psychiatric nurses from different hospitals in the Kurdistan Region of Iraq during October and November 2022. The independent Student's t-test, one-way analysis of variance, and binary logistic regression were used to assess possible factors associated with knowledge and attitude toward depression. Results: In this study, 400 non-psychiatric nurses were examined, revealing a mean age of 31.57 ± 8.59 years. Their mean scores for knowledge and attitude toward depression were 5.41 out of a maximum of 11 (standard deviation 1.15) and 5.15 out of 18 (standard deviation 1.83), respectively. Notably, differences in mean knowledge scores were observed concerning participant marital status (P = .044), while disparities in mean attitude scores are related to participant gender (P = .010). Upon binary logistic regression analysis, none of the independent variables exhibited an association with good knowledge. Nevertheless, gender emerged as a significant factor influencing attitude toward depression (odds ratio: 0.51; 95% confidence interval: 0.30-0.86; P = .012). Subsequently, in the multivariate binary logistic regression analysis, gender sustained significance (adjusted odds ratio: 0.573; 95% confidence interval: 0.348-0.942; P = .028) as the key variable impacting attitudes toward depression among non-psychiatric nurses. Conclusion: Based on the results of this study, nurses have insufficient awareness and management skills for depression. It has been experienced and reported that nurses lack knowledge and an attitude toward depression management. The study highlights a significant gap in nurses' skills for managing depression, urging the immediate improvement of training programs. Customizing these programs to enhance nurses' abilities in identifying and managing depression is crucial.

Altered mitochondrial function in fibroblast cell lines derived from disease carriers of spinal muscular atrophy.

BACKGROUND: Spinal muscular atrophy (SMA) is an autosomal recessive childhood-onset neuromuscular disease with a carrier frequency of ~1:50. Mitochondrial abnormalities are widespread in patients with SMA. Disease carriers for SMA (i.e., the parents of patients with SMA) are viewed as asymptomatic for SMA disease. As far as we are aware, mitochondria have not been previously examined in SMA carriers, yet as they are maternally inherited, mitochondrial function in SMA carriers has putative implications for disease pathogenesis. METHODS: Fibroblast cell lines derived from SMA carriers and controls were obtained from two different sources and cultured under standard conditions. The mitochondrial membrane potential, reactive oxygen species (ROS) production, citrate synthase activity, and bioenergetic analysis were examined as measures of mitochondrial function. The mitochondrial genome was also sequenced in a subset of the fibroblast cell lines to identify any mitochondrial DNA variants. RESULTS: Here, we show a depolarized mitochondrial membrane potential, increased levels of reactive oxygen species, and reduced citrate synthase activity in SMA carriers compared with controls. A likely pathogenic variant in the MT-CO3 gene (which encodes subunit III of cytochrome c oxidase) was also identified in a paternal carrier. CONCLUSIONS: This study was conducted as a preliminary investigation of mitochondrial function in SMA carriers. Our findings suggest that disease carriers of SMA show differences in mitochondrial function, indicative of a subclinical mitochondrial phenotype. Further investigation in a larger sample set is warranted.

Spinal muscular atrophy (SMA) is a disease that mostly affects children in which the muscles become weaker over time, and often leads to death in untreated individuals. It is caused by a defective gene that children often inherit from their parents. The parents of children with SMA are known as disease carriers if they do not show any symptoms of SMA themselves. We studied skin cells from the parents of people with SMA and found changes in a component of the cells called the mitochondria. These changes are not normally present in healthy individuals. Further work is needed to fully understand the implications of our findings for those with SMA and their parents.

Exploring NICU nurses' views of a novel genetic point-of-care test identifying neonates at risk of antibiotic-induced ototoxicity: A qualitative study.

AIM: To explore the views of neonatal intensive care nursing staff on the deliverability of a novel genetic point-of-care test detecting a genetic variant associated with antibiotic-induced ototoxicity. DESIGN: An interpretive, descriptive, qualitative interview study. METHODS: Data were collected using semi-structured interviews undertaken between January and November 2020. Participants were neonatal intensive care nursing staff taking part in the Pharmacogenetics to Avoid Loss of Hearing trial. RESULTS: Thematic analysis resulted in four themes: perceived clinical utility; the golden hour; point-of-care device; training and support. Recommendations were made to streamline the protocol and ongoing training and support were considered key to incorporating the test into routine care. CONCLUSION: Exploring the views of nurses involved in the delivery of the point-of-care test was essential in its implementation. By the study endpoint, all participants could see the value of routine clinical introduction of the point-of care test. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Nurses are in a key position to support the delivery of point-of-care genetic testing into mainstream settings. This study has implications for the successful integration of other genetic point-of-care tests in acute healthcare settings. IMPACT: The study will help to tailor the training and support required for routine deployment of the genetic point-of-care test. The study has relevance for nurses involved in the development and delivery of genetic point-of-care tests in other acute hospital settings. REPORTING METHOD: This qualitative study adheres to the Standards for Reporting Qualitative Research EQUATOR guidelines and utilizes COREQ and SRQR checklists. PATIENT OR PUBLIC CONTRIBUTION: All staff working on the participating neonatal intensive care units were trained to use the genetic point-of-care test. All inpatients on the participating units were eligible to have testing via the point-of-care test. The Pharmacogenetics to Avoid Loss of Hearing Patient and Public Involvement and Engagement group provided valuable feedback. TRIAL AND PROTOCOL REGISTRATION: Registered within the University of Manchester. Ethics approval reference numbers: IRAS: 253102 REC reference: 19/NW/0400. Also registered with the ISRCTN ref: ISRCTN13704894.

Prevalence, severity and risk factors of psychiatric disorders amongst sexual and gender diverse young people during the COVID-19 pandemic: A systematic review.

Before the COVID-19 pandemic, the prevalence and severity of psychiatric disorders among sexual and gender diverse (SGD) young people was greater than in their heterosexual/cisgender peers. We systematically reviewed literature examining the prevalence, severity, and risk factors for psychiatric disorders among SGD young people aged 25 and under during the pandemic. Four databases (MEDLINE, PsycInfo, Scopus and Web of Science) were searched. Eligibility criteria were studies assessing prevalence rates, mean symptomology scores and risk factors of psychiatric disorders using contemporaneous screening measures or diagnosis. Thirteen studies of mixed quality were identified. Most studies indicated SGD young people were at high risk of experiencing several psychiatric disorders including depressive and generalised anxiety disorder compared to the general population. This group also experienced more severe symptomology of various psychiatric disorders compared to their heterosexual/cisgender peers. Risk factors included those specific to the pandemic along with factors that led to greater risk before the pandemic. This systematic review has indicated evidence of heightened risk of psychiatric disorders among SGD young people during the COVID-19 pandemic. It is important for clinicians to acknowledge the needs of SGD young people, working with them to co-develop more inclusive care as they deal with the pandemic's fallout.

Why was the study done?Before the COVID-19 pandemic, the prevalence and severity of psychiatric disorders in sexual and gender diverse (SGD) young people was greater than in their heterosexual/cisgender peers, based on several risk factors. Research using validated screening measures assessed whether this continued during the pandemic. Yet, these studies have not been brought together in an organised fashion to provide a comprehensive summary of this evidence.What did the researchers do?We reviewed literature examining the prevalence, severity, and risk factors for psychiatric disorders among SGD young people aged 25 and under during the pandemic. Eligibility criteria were studies assessing prevalence rates, mean symptomology scores or risk factors of psychiatric disorders using contemporaneous screening measures or diagnosis.What did the researchers find?Thirteen studies of mixed quality were identified. Most studies indicated SGD young people were more likely to report experiencing several psychiatric disorders including depressive and generalised anxiety disorders compared to the general population. SGD young people also experienced more severe symptomology of various psychiatric disorders compared to their heterosexual/cisgender peers. Risk factors included those specific to the pandemic along with factors that existed before the pandemic.What do the findings mean?This review suggests SGD young people were at greater risk of psychiatric disorders during the COVID-19 pandemic. Clinicians should acknowledge the needs of SGD young people, working with them to co-develop more inclusive care as they deal with the pandemic's fallout.

Clinical effectiveness of point of care tests for diagnosing urinary tract infection: a systematic review.

BACKGROUND: Point of care tests (POCTs) have the potential to improve the urinary tract infection (UTI) diagnostic pathway, as they can provide a diagnosis quickly in near-patient settings, and some also identify causative pathogens/antimicrobial sensitivity. OBJECTIVES: To assess the clinical impact, accuracy, and technical characteristics of POCT for diagnosing UTI. METHODS OF DATA SYNTHESIS: Narrative summary and bivariate random effects meta-analyses to estimate summary sensitivity and specificity. DATA SOURCES: Five electronic databases, two clinical trial registries, study reports and review reference lists, and websites. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials/non-randomized studies and diagnostic test accuracy studies published since 2000. PARTICIPANTS: People with suspected UTI. TESTS: Rapid tests (results <40 minutes): Astrego PA-100 system, Lodestar DX, Uriscreen, UTRiPLEX. Culture tests (results <24 hours): Flexicult Human, ID Flexicult, Diaslide, Dipstreak, Chromostreak, Uricult, Uricult Trio, Uricult Plus. REFERENCE STANDARD: Any. ASSESSMENT OF RISK OF BIAS: Risk of Bias-2, Quality Assessment of Diagnostic Accuracy Studies-2, Quality Assessment of Diagnostic Accuracy Studies-C. RESULTS: Two randomized controlled trials evaluated Flexicult Human (one against standard care; one against ID Flexicult). No difference was reported in antibiotic use concordant with culture results (OR 0.84 95% CI 0.58-1.20) or appropriate antibiotic prescribing (OR 1.44 95% CI 1.03-1.99). Initial antibiotic prescribing was lower with Flexicult than standard care (OR 0.56 95% CI 0.35-0.88). No difference for other measures of antibiotic use, symptom duration, patient enablement, or resource use. Fifteen studies reported accuracy data. Limited data were available, with most POCT evaluated in single studies or not evaluated at all. Uriscreen (four studies), Uricult Trio (three studies), Flexicult Human (four studies), and ID Flexicult (two studies) had modest sensitivity and specificity. POCTs were easier to use and interpret than standard culture. CONCLUSIONS: There is currently insufficient evidence to support the use of POCTs in UTI diagnosis. Due to the rapid development of POCT, this review should be updated regularly.

A novel transcriptional signature identifies T-cell infiltration in high-risk paediatric cancer.

BACKGROUND: Molecular profiling of the tumour immune microenvironment (TIME) has enabled the rational choice of immunotherapies in some adult cancers. In contrast, the TIME of paediatric cancers is relatively unexplored. We speculated that a more refined appreciation of the TIME in childhood cancers, rather than a reliance on commonly used biomarkers such as tumour mutation burden (TMB), neoantigen load and PD-L1 expression, is an essential prerequisite for improved immunotherapies in childhood solid cancers. METHODS: We combined immunohistochemistry (IHC) with RNA sequencing and whole-genome sequencing across a diverse spectrum of high-risk paediatric cancers to develop an alternative, expression-based signature associated with CD8+ T-cell infiltration of the TIME. Furthermore, we explored transcriptional features of immune archetypes and T-cell receptor sequencing diversity, assessed the relationship between CD8+ and CD4+ abundance by IHC and deconvolution predictions and assessed the common adult biomarkers such as neoantigen load and TMB. RESULTS: A novel 15-gene immune signature, Immune Paediatric Signature Score (IPASS), was identified. Using this signature, we estimate up to 31% of high-risk cancers harbour infiltrating T-cells. In addition, we showed that PD-L1 protein expression is poorly correlated with PD-L1 RNA expression and TMB and neoantigen load are not predictive of T-cell infiltration in paediatrics. Furthermore, deconvolution algorithms are only weakly correlated with IHC measurements of T-cells. CONCLUSIONS: Our data provides new insights into the variable immune-suppressive mechanisms dampening responses in paediatric solid cancers. Effective immune-based interventions in high-risk paediatric cancer will require individualised analysis of the TIME.

Patient and public involvement in hearing research: opportunities, impact and reflections with case studies from the Manchester Centre for Audiology and Deafness.

OBJECTIVE: Patient and public involvement (PPI) in research improves relevance to end users and improves processes including recruitment participants. PPI in our research has gone from being non-existent to ubiquitous over a few years. We provide critical reflections on the benefits and challenges of PPI. DESIGN: Case studies are reported according to a modified GRIP2 framework; the aims, methodology, impact of PPI and critical reflections on each case and our experiences with PPI in general. STUDY SAMPLE: We report five UK projects that included PPI from teenagers, families, people living with dementia, autistic people, and people from South Asian and d/Deaf communities. RESULTS: Our experience has progressed from understanding the rationale to grappling methodologies and integrating PPI in our research. PPI took place at all stages of research, although commonly involved input to design including recruitment and development of study materials. Methodologies varied between projects, including PPI co-investigators, advisory panels and online surveys. CONCLUSION: On-going challenges include addressing social exclusion from research for people that lack digital access following increasing on-line PPI and involvement from underserved communities. PPI was initially motivated by funders; however the benefits have driven widespread PPI, ensuring our research is relevant to people living with hearing loss.

Five actionable pillars to engage the next generation of leaders in the co-design of transformative ocean solutions.

Solutions to complex and unprecedented global challenges are urgently needed. Overcoming these challenges requires input and innovative solutions from all experts, including Early Career Ocean Professionals (ECOPs). To achieve diverse inclusion from ECOPs, fundamental changes must occur at all levels-from individuals to organizations. Drawing on insights from across the globe, we propose 5 actionable pillars that support the engagement of ECOPs in co-design processes that address ocean sustainability: sharing knowledge through networks and mentorship, providing cross-boundary training and opportunities, incentivizing and celebrating knowledge co-design, creating inclusive and participatory governance structures, and catalyzing culture change for inclusivity. Foundational to all actions are the cross-cutting principles of justice, equity, diversity, and inclusivity. In addition, the pillars are cross-boundary in nature, including collaboration and innovation across sectors, disciplines, regions, generations, and backgrounds. Together, these recommendations provide an actionable and iterative path toward inclusive engagement and intergenerational exchange that can develop ocean solutions for a sustainable future.

Women need to stay alive and protect reproductive choice.

Defense of reproductive choice is an important motivation in women's self-protection psychology for which the "staying alive theory" cannot fully account. Evidence indicates that some elements of women's self-protection psychology function to protect reproductive choice rather than survival, or may be equally well explained by either motivation. Integrating perspectives will result in greater explanatory breadth and precision in theory testing.

Rapid Point-of-Care Genotyping to Avoid Aminoglycoside-Induced Ototoxicity in Neonatal Intensive Care.

Importance: Aminoglycosides are commonly prescribed antibiotics used for the treatment of neonatal sepsis. The MT-RNR1 m.1555A>G variant predisposes to profound aminoglycoside-induced ototoxicity (AIO). Current genotyping approaches take several days, which is unfeasible in acute settings. Objective: To develop a rapid point-of-care test (POCT) for the m.1555A>G variant before implementation of this technology in the acute neonatal setting to guide antibiotic prescribing and avoid AIO. Design, Setting, and Participants: This pragmatic prospective implementation trial recruited neonates admitted to 2 large neonatal intensive care units between January 6, 2020, and November 30, 2020, in the UK. Interventions: Neonates were tested for the m.1555A>G variant via the rapid POCT on admission to the neonatal intensive care unit. Main Outcomes and Measures: The primary outcome assessed the proportion of neonates successfully tested for the variant of all infants prescribed antibiotics. Secondary outcomes measured whether implementation was negatively associated with routine clinical practice and the performance of the system. The study was statistically powered to detect a significant difference between time to antibiotic administration before and after implementation of the MT-RNR1 POCT. Results: A total of 751 neonates were recruited and had a median (range) age of 2.5 (0-198) days. The MT-RNR1 POCT was able to genotype the m.1555A>G variant in 26 minutes. Preclinical validation demonstrated a 100% sensitivity (95% CI, 93.9%-100.0%) and specificity (95% CI, 98.5%-100.0%). Three participants with the m.1555A>G variant were identified, all of whom avoided aminoglycoside antibiotics. Overall, 424 infants (80.6%) receiving antibiotics were successfully tested for the variant, and the mean time to antibiotics was equivalent to previous practice. Conclusions and Relevance: The MT-RNR1 POCT was integrated without disrupting normal clinical practice, and genotype was used to guide antibiotic prescription and avoid AIO. This approach identified the m.1555A>G variant in a practice-changing time frame, and wide adoption could significantly reduce the burden of AIO.

Erectile Dysfunction and Partner-Directed Behaviors in Romantic Relationships: The Mediating Role of Suspicious Jealousy.

Erectile dysfunction (ED) has been shown to have a considerable impact on romantic relationships. The purpose of the present research was to examine whether the associations that ED had with men's mate retention behaviors, partner-directed insults, partner-directed violence, and injuries inflicted on the partner were mediated by suspicious jealousy but not reactive jealousy. These associations were examined using self-reports of men (Study 1) and partner-reports provided by women about their perceptions of their male partner (Study 2). The results of both studies indicated that suspicious jealousy (but not reactive jealousy) mediated the associations that ED had with the partner-directed behaviors of men in their romantic relationships. Specifically, higher levels of ED were associated with men experiencing (or being perceived to experience) more suspicious jealousy which, in turn, predicted their use of mate retention behaviors, partner-directed insults, and partner-directed violence as well as the infliction of injuries on their female partners. In our discussion, we address the evolutionary implications of these associations, as well as limitations and directions for future research on ED.

InterARTIC: an interactive web application for whole-genome nanopore sequencing analysis of SARS-CoV-2 and other viruses.

MOTIVATION: InterARTIC is an interactive web application for the analysis of viral whole-genome sequencing (WGS) data generated on Oxford Nanopore Technologies (ONT) devices. A graphical interface enables users with no bioinformatics expertise to analyze WGS experiments and reconstruct consensus genome sequences from individual isolates of viruses, such as SARS-CoV-2. InterARTIC is intended to facilitate widespread adoption and standardization of ONT sequencing for viral surveillance and molecular epidemiology. RESULTS: We demonstrate the use of InterARTIC for the analysis of ONT viral WGS data from SARS-CoV-2 and Ebola virus, using a laptop computer or the internal computer on an ONT GridION sequencing device. We showcase the intuitive graphical interface, workflow customization capabilities and job-scheduling system that facilitate execution of small- and large-scale WGS projects on any common virus. AVAILABILITY AND IMPLEMENTATION: InterARTIC is a free, open-source web application implemented in Python that executes best-practice command line workflows from the ARTIC network. The application can be downloaded as a set of pre-compiled binaries that are compatible with all common Linux distributions, Windows with Linux subsystems, MacOSX and ARM systems. All code can be found on GitHub at https://github.com/Psy-Fer/interARTIC/ and documentation can be found at https://github.com/Psy-Fer/interARTIC/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The rise of an exciton in solid ammonia.

We trace a polymorphic phase change in solid ammonia films through the emergence of a Frenkel exciton at 194.4 nm, for deposition temperatures of 48 K, 50 K and 52 K. Observations on a timescale of hours give unparalleled access to the individual processes of nucleation and the phase change itself. The excitonic transition is forbidden in the low temperature phase, but greater flexing of the solid state structure in the higher temperature phase makes the transition allowed, as the nano-crystals approach ∼30 unit cells through nucleation. We find activation energies of 21.7 ± 0.6 kJ mol-1 for nucleation and 22.8 ± 0.6 kJ mol-1 for the phase change, corresponding to the breaking of two to three hydrogen bonds.

Could Reducing Body Fatness Reduce the Risk of Aggressive Prostate Cancer via the Insulin Signalling Pathway? A Systematic Review of the Mechanistic Pathway.

Excess body weight is thought to increase the risk of aggressive prostate cancer (PCa), although the biological mechanism is currently unclear. Body fatness is positively associated with a diminished cellular response to insulin and biomarkers of insulin signalling have been positively associated with PCa risk. We carried out a two-pronged systematic review of (a) the effect of reducing body fatness on insulin biomarker levels and (b) the effect of insulin biomarkers on PCa risk, to determine whether a reduction in body fatness could reduce PCa risk via effects on the insulin signalling pathway. We identified seven eligible randomised controlled trials of interventions designed to reduce body fatness which measured insulin biomarkers as an outcome, and six eligible prospective observational studies of insulin biomarkers and PCa risk. We found some evidence that a reduction in body fatness improved insulin sensitivity although our confidence in this evidence was low based on GRADE (Grading of Recommendations, Assessment, Development and Evaluations). We were unable to reach any conclusions on the effect of insulin sensitivity on PCa risk from the few studies included in our systematic review. A reduction in body fatness may reduce PCa risk via insulin signalling, but more high-quality evidence is needed before any conclusions can be reached regarding PCa.

TNF-mediated neuroinflammation is linked to neuronal necroptosis in Alzheimer's disease hippocampus.

The pathogenetic mechanisms underlying neuronal death and dysfunction in Alzheimer's disease (AD) remain unclear. However, chronic neuroinflammation has been implicated in stimulating or exacerbating neuronal damage. The tumor necrosis factor (TNF) superfamily of cytokines are involved in many systemic chronic inflammatory and degenerative conditions and are amongst the key mediators of neuroinflammation. TNF binds to the TNFR1 and TNFR2 receptors to activate diverse cellular responses that can be either neuroprotective or neurodegenerative. In particular, TNF can induce programmed necrosis or necroptosis in an inflammatory environment. Although activation of necroptosis has recently been demonstrated in the AD brain, its significance in AD neuron loss and the role of TNF signaling is unclear. We demonstrate an increase in expression of multiple proteins in the TNF/TNF receptor-1-mediated necroptosis pathway in the AD post-mortem brain, as indicated by the phosphorylation of RIPK3 and MLKL, predominantly observed in the CA1 pyramidal neurons. The density of phosphoRIPK3 + and phosphoMLKL + neurons correlated inversely with total neuron density and showed significant sexual dimorphism within the AD cohort. In addition, apoptotic signaling was not significantly activated in the AD brain compared to the control brain. Exposure of human iPSC-derived glutamatergic neurons to TNF increased necroptotic cell death when apoptosis was inhibited, which was significantly reversed by small molecule inhibitors of RIPK1, RIPK3, and MLKL. In the post-mortem AD brain and in human iPSC neurons, in response to TNF, we show evidence of altered expression of proteins of the ESCRT III complex, which has been recently suggested as an antagonist of necroptosis and a possible mechanism by which cells can survive after necroptosis has been triggered. Taken together, our results suggest that neuronal loss in AD is due to TNF-mediated necroptosis rather than apoptosis, which is amenable to therapeutic intervention at several points in the signaling pathway.

True Crime Consumption as Defensive Vigilance: Psychological Mechanisms of a Rape Avoidance System.

The circumvention of female reproductive choice via rape is a costly and evolutionarily persistent threat to women's reproductive fitness. This is argued to have generated selection pressure for a precautionary threat management system for rape avoidance among women. Such a system would regulate women's fear of rape as a functional emotional response to inputs providing information about the current risk and reproductive cost of rape. Fear of rape is expected to subsequently motivate adaptive behavior to avoid threats to one's reproductive choice. The current research tested key tenets of this proposed system and found that women report greater fear of rape as a function of characteristics that alter the likelihood of being victimized, including being younger, living in a neighborhood perceived as dangerous, living in close proximity to family, and having been the victim of a sexual assault in the past. We also discuss mixed and null results with respect to the role of relationship status and mate value. In turn, fear of rape was associated with behavior expected to reduce one's risk of being victimized. Specifically, women who were more fearful of rape reported consuming true crime media with greater frequency and indicated that this consumption was specifically motivated by the desire to learn strategies to prevent or escape an attack. Overall, results were fairly consistent with a threat management system approach and may help to explain why fear of rape is a powerful feature of women's psychology.

Revisiting the role of mitochondria in spinal muscular atrophy.

Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disease of variable clinical severity that is caused by mutations in the survival motor neuron 1 (SMN1) gene. Despite its name, SMN is a ubiquitous protein that functions within and outside the nervous system and has multiple cellular roles in transcription, translation, and proteostatic mechanisms. Encouragingly, several SMN-directed therapies have recently reached the clinic, albeit this has highlighted the increasing need to develop combinatorial therapies for SMA to achieve full clinical efficacy. As a subcellular site of dysfunction in SMA, mitochondria represents a relevant target for a combinatorial therapy. Accordingly, we will discuss our current understanding of mitochondrial dysfunction in SMA, highlighting mitochondrial-based pathways that offer further mechanistic insights into the involvement of mitochondria in SMA. This may ultimately facilitate translational development of targeted mitochondrial therapies for SMA. Due to clinical and mechanistic overlaps, such strategies may also benefit other motor neuron diseases and related neurodegenerative disorders.

Meningeal inflammation in multiple sclerosis induces phenotypic changes in cortical microglia that differentially associate with neurodegeneration.

Meningeal inflammation strongly associates with demyelination and neuronal loss in the underlying cortex of progressive MS patients, thereby contributing significantly to clinical disability. However, the pathological mechanisms of meningeal inflammation-induced cortical pathology are still largely elusive. By extensive analysis of cortical microglia in post-mortem progressive MS tissue, we identified cortical areas with two MS-specific microglial populations, termed MS1 and MS2 cortex. The microglial population in MS1 cortex was characterized by a higher density and increased expression of the activation markers HLA class II and CD68, whereas microglia in MS2 cortex showed increased morphological complexity and loss of P2Y12 and TMEM119 expression. Interestingly, both populations associated with inflammation of the overlying meninges and were time-dependently replicated in an in vivo rat model for progressive MS-like chronic meningeal inflammation. In this recently developed animal model, cortical microglia at 1-month post-induction of experimental meningeal inflammation resembled microglia in MS1 cortex, and microglia at 2 months post-induction acquired a MS2-like phenotype. Furthermore, we observed that MS1 microglia in both MS cortex and the animal model were found closely apposing neuronal cell bodies and to mediate pre-synaptic displacement and phagocytosis, which coincided with a relative sparing of neurons. In contrast, microglia in MS2 cortex were not involved in these synaptic alterations, but instead associated with substantial neuronal loss. Taken together, our results show that in response to meningeal inflammation, microglia acquire two distinct phenotypes that differentially associate with neurodegeneration in the progressive MS cortex. Furthermore, our in vivo data suggests that microglia initially protect neurons from meningeal inflammation-induced cell death by removing pre-synapses from the neuronal soma, but eventually lose these protective properties contributing to neuronal loss.