Dietary pro-oxidant therapy by a vitamin K precursor targets PI 3-kinase VPS34 function.

Men taking antioxidant vitamin E supplements have increased prostate cancer (PC) risk. However, whether pro-oxidants protect from PC remained unclear. In this work, we show that a pro-oxidant vitamin K precursor [menadione sodium bisulfite (MSB)] suppresses PC progression in mice, killing cells through an oxidative cell death: MSB antagonizes the essential class III phosphatidylinositol (PI) 3-kinase VPS34-the regulator of endosome identity and sorting-through oxidation of key cysteines, pointing to a redox checkpoint in sorting. Testing MSB in a myotubular myopathy model that is driven by loss of MTM1-the phosphatase antagonist of VPS34-we show that dietary MSB improved muscle histology and function and extended life span. These findings enhance our understanding of pro-oxidant selectivity and show how definition of the pathways they impinge on can give rise to unexpected therapeutic opportunities.

Autistic psychiatrists' experiences of recognising themselves and others as autistic: a qualitative study.

BACKGROUND: Diagnosis of autism falls under the remit of psychiatry. Recognition that psychiatrists could be autistic is recent. Psychiatrists are the second largest specialty group in Autistic Doctors International, a peer support group for autistic doctors. AIMS: To explore the experiences of autistic psychiatrists in relation to recognising themselves and others as autistic. METHOD: This was a qualitative study using loosely structured interviews and an interpretive phenomenological analysis. RESULTS: Eight autistic senior psychiatrists based in the UK participated. One had a childhood diagnosis, two had been diagnosed in adulthood and the remainder self-identified as autistic as adults. Recognition of autism followed diagnosis of their children or encounters with autistic patients. Barriers to self-recognition included lack of autism training, the deficit-based diagnostic criteria and stereotypical views of autism. Recognising that they were autistic led to the realisation that many colleagues were also likely to be autistic, particularly in neurodevelopmental psychiatry. All participants reported the ability to quickly recognise autistic patients and to develop a good rapport easily, once they were aware of their own autistic identity. Difficulties recognising patients as autistic occurred before self-recognition when they shared autistic characteristics and experiences. 'If we don't recognise ourselves as autistic how on earth can we diagnose patients accurately?' CONCLUSIONS: Autistic psychiatrists face multiple barriers to recognising that they are autistic. Lack of self-recognition may impede diagnostic accuracy with autistic patients. Self-recognition and disclosure by autistic psychiatrists may be facilitated by reframing the traditional deficit-based view of autism towards a neurodiversity-affirmative approach, with consequent benefits for autistic patients.

Recognising and responding to physical and mental health issues in neurodivergent girls and women.

People experience life and interact with others in many ways. The term 'neurodivergence' refers to variations from what is considered typical. Research and education into conditions that cooccur with neurodivergence are essential in shaping clinicians' approaches to people who may present with a wide range of symptoms. Neurodivergence may influence a person's style of communication, learning, attitudes, and behaviour, and they often experience inequity and rejection. This review highlights the huge burden of cooccurring conditions carried by neurodivergent women and girls whose medical issues have largely gone under the radar. We suggest how clinicians might increase their awareness of diagnosis and management of their problems with mutual benefit.

Utilization and Impact of a Radiation Nursing Clinic to Address Acute Care Needs for Patients with Gynecologic Cancers.

BACKGROUND: The risk factors for acute care utilization in gynecologic oncology patients are poorly understood. This study aimed to evaluate risk factors for the utilization of our centre's acute care radiation nursing clinic (RNC) by gynecologic oncology patients receiving radiotherapy (RT). METHODS: This was a retrospective cohort study of gynecological cancer patients treated with RT at an academic cancer centre between 1 August 2021 and 31 January 2022. Data on socio-demographics, clinical and treatment characteristics, and RNC visits were collected and summarized by descriptive statistics. The Wilcoxon rank sum test and chi-squared test/Fisher's exact test were used for comparisons of continuous and categorical variables, respectively. RESULTS: RT was delivered to 180 patients, of whom 42 (23%) received concurrent chemoradiation (CCR). Compared to those receiving RT alone, patients receiving CCR had higher rates of RNC utilization (55% vs. 19%, p < 0.001). Within the CCR cohort, patients who presented to the RNC were more likely to be unpartnered (43% vs. 11%, p = 0.04), receive a referral to Psychosocial Oncology (39% vs. 5.3%, p = 0.01), and experience treatment interruptions (52% vs. 16%, p = 0.02). There were no associations between RNC visits and age, disease site, or distance from the cancer centre. CONCLUSIONS: The receipt of CCR and specific psychosocial risk factors were associated with increased RNC utilization. Targeted strategies and early intervention to better meet the supportive care and psychosocial needs of this vulnerable population are needed.

Perspectives of autistic adolescent girls and women on the determinants of their mental health and social and emotional well-being: A systematic review and thematic synthesis of lived experience.

LAY ABSTRACT: Difficulties with mental health and low levels of well-being are more common among autistic girls and women than non-autistic people, but we do not fully understand why. Research does not focus enough on what autistic girls and women could tell us about this. This review aims to summarise the studies where autistic girls and women explain things that affect their mental health and well-being to help us understand how to prevent these difficulties from developing. Three research databases were searched to find possibly relevant studies. There were 877 studies found, which two researchers screened according to particular criteria. They found 52 studies that could be included in this review. One researcher evaluated the quality of these studies and extracted the key information from them. This review summarises the views of 973 autistic girls and women aged between 13 and 70+. The findings from the 52 studies were analysed, and we found many factors that affect the mental health and well-being of autistic girls and women. These factors fall into two categories: (1) difficulties living in a world not designed for autistic people and (2) the impact of stigma due to being autistic.

Optimized strategy for real-time qPCR detection of Onchocerca volvulus DNA in pooled Simulium sp. blackfly vectors.

BACKGROUND: Onchocerca volvulus is a filarial parasite that is a major cause of dermatitis and blindness in endemic regions primarily in sub-Saharan Africa. Widespread efforts to control the disease caused by O. volvulus infection (onchocerciasis) began in 1974 and in recent years, following successful elimination of transmission in much of the Americas, the focus of efforts in Africa has moved from control to the more challenging goal of elimination of transmission in all endemic countries. Mass drug administration (MDA) with ivermectin has reached more than 150 million people and elimination of transmission has been confirmed in four South American countries, with at least two African countries having now stopped MDA as they approach verification of elimination. It is essential that accurate data for active transmission are used to assist in making the critical decision to stop MDA, since missing low levels of transmission and infection can lead to continued spread or recrudescence of the disease. METHODOLOGY/PRINCIPAL FINDINGS: Current World Health Organization guidelines for MDA stopping decisions and post-treatment surveillance include screening pools of the Simulium blackfly vector for the presence of O. volvulus larvae using a PCR-ELISA-based molecular technique. In this study, we address the potential of an updated, practical, standardized molecular diagnostic tool with increased sensitivity and species-specificity by comparing several candidate qPCR assays. When paired with heat-stable reagents, a qPCR assay with a mitochondrial DNA target (OvND5) was found to be more sensitive and species-specific than an O150 qPCR, which targets a non-protein coding repetitive DNA sequence. The OvND5 assay detected 19/20 pools of 100 blackfly heads spiked with a single L3, compared to 16/20 for the O150 qPCR assay. CONCLUSIONS/SIGNIFICANCE: Given the improved sensitivity, species-specificity and resistance to PCR inhibitors, we identified OvND5 as the optimal target for field sample detection. All reagents for this assay can be shipped at room temperature with no loss of activity. The qPCR protocol we propose is also simpler, faster, and more cost-effective than the current end-point molecular assays.

Sexual dimorphism in the gonad lipidome of blue mussels (Mytilus sp.): New insights from a global lipidomics approach.

Blue mussels (Mytilus sp.) are an economically important species for European aquaculture. Their importance as a food source is expected to increase in the coming net-zero society due to their low environmental footprint; however, their production is affected by anthropogenic stressors and climate change. During reproduction, lipids are key molecules for mussels as they are the main source of energy on which newly hatched embryos depend in the first days of their development. In this work, blue mussels of different origins are analysed, focusing on the differences in lipid composition between the ovary (BMO) and the testis (BMT). The lipidome of blue mussel gonads (BMG) is studied here by combining traditional lipid profiling methods, such as fatty acid and lipid class analysis, with untargeted liquid chromatography-mass spectrometry (LC-MS) lipidomics. The approach used here enabled the identification of 770 lipid molecules from 23 different lipid classes in BMG. BMT, which consists of billions of spermatocytes, had greater amounts of cell membrane and membrane lipid components such as FA18:0, C20 polyunsaturated fatty acids (PUFA), free sterols (ST), ceramide phosphoethanolamines (CerPE), ceramide aminoethylphosphonates (CAEP), cardiolipins (CL), glycerophosphocholines (PC), glycerophosphoethanolamines (PE) and glycerophosphoserines (PS). In BMO, saturated fatty acids (FA14:0 and FA16:0), monounsaturated fatty acids (MUFA) and other storage components such as C18-PUFA accumulated in triradylglycerolipids (TG) and alkyldiacylglycerols (neutral plasmalogens, TG O-), which, together with terpenes, wax esters and cholesterol esters, make up most of oocytes yolk reserves. BMO also had higher levels of ceramides (Cer) and generally alkyl/alkenyl glycerophospholipids (mainly plasmanyl/plasmenyl PC), suggesting a role for these lipids in vitellogenesis. Non-methylene interrupted dienoic fatty acids (NMID FA), typically found in plasmalogens, were the only membrane-forming PUFA predominantly detected in BMO. The results of this study are of great importance for clarifying the lipid composition of BMG and provide an important basis for future studies on the reproductive physiology of these organisms.

Barriers to healthcare and a 'triple empathy problem' may lead to adverse outcomes for autistic adults: A qualitative study.

LAY ABSTRACT: Autistic people live with more mental and physical health conditions and, on average, die younger than non-autistic people. Despite widespread commitments to tackling these issues, autistic people still report various barriers to accessing healthcare. This article aims to explore the area in depth, from the perspective of autistic people. This research benefits from being led by autistic people, for autistic people - all of the researchers are autistic, and most of us are also medical doctors. Data, in the form of written comments and stories, were collected as part of a large survey. Here, we explored these for common themes and possible deeper meaning within the experiences. People who took part reported a variety of barriers. Here, our article gives voice to their stories, in their own words. Themes included: early barriers; communication mismatch; doubt - in oneself and from doctors; helplessness and fear; and healthcare avoidance and adverse health outcomes. Our findings allowed us to create a model that aimed to understand and explain the reported barriers in the context of the previously known consequences. We also built on wider autism theories to explain our findings in more depth.

Bridge-building between communities: Imagining the future of biomedical autism research.

A paradigm shift in research culture is required to ease perceived tensions between autistic people and the biomedical research community. As a group of autistic and non-autistic scientists and stakeholders, we contend that through participatory research, we can reject a deficit-based conceptualization of autism while building a shared vision for a neurodiversity-affirmative biomedical research paradigm.

The experiences of autistic doctors: a cross-sectional study.

Introduction: Medicine may select for autistic characteristics. As awareness and diagnosis of autism are growing, more medical students and doctors may be discovering they are autistic. No studies have explored the experiences of autistic doctors. This study aimed to fill that gap. Methods: This is a cross-sectional study. A participatory approach was used to identify the need for the project and to modify a pre-existing survey for use exploring the experiences of autistic doctors. Results: We received 225 responses. 64% had a formal diagnosis of autism. The mean age of receiving a formal diagnosis was 36 (range 3-61). Most were currently working as doctors (82%). The most common specialties were general practice / family medicine (31%), psychiatry (18%), and anesthesia (11%). Almost half of those working had completed specialty training (46%) and 40% were current trainees. 29% had not disclosed being autistic to anyone at work. 46% had requested adjustments in the workplace but of these, only half had them implemented.Three quarters had considered suicide (77%), one quarter had attempted suicide (24%) and half had engaged in self-harm (49%). 80% reported having worked with another doctor they suspected was autistic, but only 22% reported having worked with another doctor they knew was autistic. Having never worked with a potentially autistic colleague was associated with having considered suicide.Most preferred to be called "autistic doctors" (64%). Most considered autism to be a difference (83%). Considering autism to be a disorder was associated with preference for the term "doctors with autism," and with having attempted suicide. Conclusion: Autistic doctors reported many challenges in the workplace. This may have contributed to a culture of nondisclosure. Mental health was poor with high rates of suicidal ideation, self-harm, and prior suicide attempts. Despite inhospitable environments, most were persevering and working successfully. Viewing autism as a disorder was associated with prior suicide attempts and a preference for person-first language. A neurodiversity-affirmative approach to autism may lead to a more positive self-identity and improved mental health. Furthermore, providing adequate supports and improving awareness of autistic medical professionals may promote inclusion in the medical workforce.

Ethical challenges in autism genomics: Recommendations for researchers.

Equitable and just genetic research and clinical translation require an examination of the ethical questions pertaining to vulnerable and marginalized communities. Autism research and advocate communities have expressed concerns over current practices of genetics research, urging the field to shift towards paradigms and practices that ensure benefits and avoid harm to research participants and the wider autistic community. Building upon a framework of bioethical principles, we provide the background for the concerns and present recommendations for ethically sustainable and justice-oriented genetic and genomic autism research. With the primary goal of enhancing the health, well-being, and autonomy of autistic persons, we make recommendations to guide priority setting, responsible research conduct, and informed consent practices. Further, we discuss the ethical challenges particularly pertaining to research involving highly vulnerable individuals and groups, such as those with impaired cognitive or communication ability. Finally, we consider the clinical translation of autism genetics studies, including the use of genetic testing. These guidelines, developed by an interdisciplinary working group comprising autistic and non-autistic individuals, will aid in leveraging the potential of genetics research to enhance the quality of life of autistic individuals and are widely applicable across stigmatized traits and vulnerable communities.

The experiences of autistic medical students: A phenomenological study.

BACKGROUND: Increasing recognition of autism is reflected in the growing awareness of autistic health care providers. Regulatory bodies including the UK General Medical Council and the UK Medical Schools Council have published guidance fostering inclusion. Whilst many autistic doctors and students are thriving, many may not disclose their diagnosis unless difficulties arise, which perpetuates stereotypes. No studies have explored the experiences of autistic medical students. We aimed to do this. METHODS: This was an interpretive phenomenological study. Autistic medical students were recruited using Facebook announcements. Participants underwent audio-recorded, loosely structured interviews. Recordings were transcribed verbatim and underwent an interpretive phenomenological analysis. RESULTS: Five participated from five different UK medical schools. Constructed themes included: Autistic profiles and stereotypes-'I'm a lot better with patients than I am with my peers, with staff, which is hard for a lot of people to understand'; sensory processing and the learning environment-'noises really hurt my ears … It actually hurts'; me, myself and masking-'so, medicine's hard. But I'm also studying myself and I'm figuring myself out and that degree is harder'; the social world-'I always feel like I'm watching my back'; and navigating the system-'[they say] "but you're going to be a doctor one day, so you need to get used to it"'. CONCLUSION: Participants longed for understanding and support from their medical schools. They reported experiences of isolation, bullying and anxiety. Most felt themselves to be victims of the system, whereby they were expected to adapt themselves in order to appear non-autistic. When participants reported not coping due to being autistic, most were advised to 'take time out'. None were offered personalised adjustments to their learning environment. All reported strengths associated with being autistic. This supports the assertion that autistic people can be safe, effective and skilled doctors.

Autistic SPACE: a novel framework for meeting the needs of autistic people in healthcare settings.

Autistic people experience significant health disparities and reduced life expectancy. Barriers to accessing healthcare are associated with adverse health outcomes. Autism training and healthcare professionals' knowledge about autism is variable, and heterogeneity among autistic people leads to additional educational and clinical complexities. Autism remains nebulous for many practitioners, who are unclear about communication differences, access needs or life experiences common to autistic people. Healthcare environments can be challenging for all patients but autistic people may require specific accommodations to allow equitable access. The authors have developed a simple framework which may facilitate equitable clinical services at all points of access and care, using the acronym 'SPACE'. This encompasses five core autistic needs: Sensory needs, Predictability, Acceptance, Communication and Empathy. Three additional domains are represented by physical space, processing space and emotional space. This simple yet memorable framework encompasses commonalities shared by autistic people.

Fenretinide inhibits obesity and fatty liver disease but induces Smpd3 to increase serum ceramides and worsen atherosclerosis in LDLR-/- mice.

Fenretinide is a synthetic retinoid that can prevent obesity and improve insulin sensitivity in mice by directly altering retinol/retinoic acid homeostasis and inhibiting excess ceramide biosynthesis. We determined the effects of Fenretinide on LDLR-/- mice fed high-fat/high-cholesterol diet ± Fenretinide, a model of atherosclerosis and non-alcoholic fatty liver disease (NAFLD). Fenretinide prevented obesity, improved insulin sensitivity and completely inhibited hepatic triglyceride accumulation, ballooning and steatosis. Moreover, Fenretinide decreased the expression of hepatic genes driving NAFLD, inflammation and fibrosis e.g. Hsd17b13, Cd68 and Col1a1. The mechanisms of Fenretinide's beneficial effects in association with decreased adiposity were mediated by inhibition of ceramide synthesis, via hepatic DES1 protein, leading to increased dihydroceramide precursors. However, Fenretinide treatment in LDLR-/- mice enhanced circulating triglycerides and worsened aortic plaque formation. Interestingly, Fenretinide led to a fourfold increase in hepatic sphingomyelinase Smpd3 expression, via a retinoic acid-mediated mechanism and a further increase in circulating ceramide levels, linking induction of ceramide generation via sphingomyelin hydrolysis to a novel mechanism of increased atherosclerosis. Thus, despite beneficial metabolic effects, Fenretinide treatment may under certain circumstances enhance the development of atherosclerosis. However, targeting both DES1 and Smpd3 may be a novel, more potent therapeutic approach for the treatment of metabolic syndrome.

CBL/CAP Is Essential for Mitochondria Respiration Complex I Assembly and Bioenergetics Efficiency in Muscle Cells.

CBL is rapidly phosphorylated upon insulin receptor activation. Mice whole body CBL depletion improved insulin sensitivity and glucose clearance; however, the precise mechanisms remain unknown. We depleted either CBL or its associated protein SORBS1/CAP independently in myocytes and assessed mitochondrial function and metabolism compared to control cells. CBL- and CAP-depleted cells showed increased mitochondrial mass with greater proton leak. Mitochondrial respiratory complex I activity and assembly into respirasomes were reduced. Proteome profiling revealed alterations in proteins involved in glycolysis and fatty acid degradation. Our findings demonstrate CBL/CAP pathway couples insulin signaling to efficient mitochondrial respiratory function and metabolism in muscle.

Posttraumatic Growth in Women Who Have Experienced Intimate Partner Abuse.

The purpose of the current qualitative descriptive study was to describe the experiences of women who have endured intimate partner abuse using the theoretical framework of posttraumatic growth (PTG). Women (N = 14) who reported emotional and/or physical abuse by their male partners were interviewed. Five themes were identified: Acknowledging the Abusive Relationship; Fear of Him: Threats, Control, Pain, and Isolation; Accepting Support: Grabbing the Life Preserver; Rediscovering Myself: Digging Deep; and Appreciating Life and Helping Others. Findings have practical implications for nurses who are in pivotal positions to educate and influence others about the possibility of PTG following partner abuse. Nurses can help women find their way through this trauma and teach others about coping, healing, and recovery. [Journal of Psychosocial Nursing and Mental Health Services, 61(8), 34-41.].

Women's Experiences of a Close Brush With Death and Posttraumatic Growth.

OBJECTIVE: To describe the experiences of women who have had a close brush with death and the elements of posttraumatic growth as a result of their experiences. DESIGN: Using a theoretical framework of posttraumatic growth, we conducted a qualitative descriptive study with interviews of women who have had a close brush with death. SETTING: Women were interviewed in the environment of their choosing: in their home, at a coffee shop, or over the telephone. PARTICIPANTS: Twelve women ages 35 to 79 years from the United States participated in the study, all of whom reported having a close brush with death. METHOD: Interviews were conducted using a semistructured interview guide derived from the theoretical framework. RESULTS: Five themes emerged from the data: My Trauma Experience, My Will to Live, SupportWas Important, Putting the Pieces of My Life Back Together, and Near-Death Experiences. Participants reported having experienced various elements of posttraumatic growth. Many attributed their posttraumatic growth to a myriad of factors such as having a supportive network, their belief in God as a source of strength, and the will to live. Others credited health care professionals for quality care and encouragement. CONCLUSION: Knowledge development regarding posttraumatic growth can enhance nursing practice in the care of women as they navigate life after trauma. Nurses and other health care providers are in strategic positions to educate women about the possibility of posttraumatic growth after adversity. They can help women find their path with a strong voice after trauma. Women who have experienced posttraumatic growth can teach others about healing, coping, empathy, compassion, and the importance of human connection.

Sexual dysfunction in female patients with anal cancer treated with curative intent: A systematic review of the literature.

BACKGROUND AND PURPOSE: Patients with anal squamous cell carcinoma (SCC) are treated with sphincter-preserving radiation therapy and concurrent chemotherapy, achieving excellent oncologic outcomes. Patients, however, may experience treatment-related morbidity including sexual dysfunction. The objective of this systematic review was to review the literature on sexual dysfunction in female patients treated for anal cancer and to identify knowledge gaps. MATERIALS AND METHODS: This systematic review was registered in PROSPERO prior to initiation. Databases searched included MEDLINE, Embase, PubMed, Cochrane, and Google Scholar. There were no restrictions on the study time period. Studies were limited to English. All study designs were included except review articles, letters to the editor, and case reports with less than ten patients. RESULTS: In total, 1801 studies were retrieved and 19 met the inclusion criteria, including: 13 cross-sectional surveys, 3 prospective studies, 1 longitudinal intervention study, 1 retrospective chart review, 1 case control study. Sexual function was assessed using the female sexual functioning index (FSFI), EORTC-QLQ-CR30 and -CR38; response rates were low (<50 % in most studies). Sexual dysfunction was reported by up to 85 % of women; the most common symptoms being dyspareunia (17-65 %), vaginal dryness (22-88 %), and loss of libido (38-95 %). Gastrointestinal issues, such as bowel problems, and body image concerns additionally affected sexual function and quality of life. CONCLUSION: Sexual dysfunction is a common issue affecting most female patients treated for anal cancer and there is a paucity of evidence on the management of this important survivorship issue. There is additionally a lack of ethnic, economic, and educational diversity and there are no studies addressing the unique needs of LGBTQ individuals - future studies should make a concerted effort to include a diverse patient population.