Explore the vast range of titles available.

The major pathophysiological symptom of the menopause affecting daily life is hot flushes, which are also associated with elevated cardiovascular disease risk. A hot flush is a sudden and intense heat sensation causing skin flushing and profuse sweating. Menopause-induced oestrogen deficiency could increase the sensitivity of skin blood vessels and sweat glands in postmenopausal women, which could result in more frequent and larger increases in skin blood flow in postmenopausal women consistent with hot flushes. Furthermore, oestrogen withdrawal could also alter the structure of the skin blood vessels and/or sweat glands which may also contribute to hot flushes. This trial aims to examine the function and structure of skin blood vessels and sweat glands in premenopausal and postmenopausal women. This is a single-centre multi-cohort observational study. Participants will attend the laboratory at Liverpool John Moores University (LJMU) on two separate occasions, ∼7 days apart. Visit 1 will consist of anthropometry, a blood sample and assessment of post-ganglionic skin blood vessel and sweat gland responsiveness via cutaneous microdialysis. At visit 2, participants will return for a skin punch biopsy. A between groups statistical analysis of the pre- and postmenopausal cohorts will be conducted in a blinded manner. The trial was approved by the North West - Greater Manchester South Research Ethics Committee (22/NW/0300) in the UK. The study adheres to The Declaration of Helsinki and is being conducted in accordance with the UK Policy Framework for Health and Social Care Research. Identifying functional and/or structural changes in skin blood vessels or sweat glands in women with hot flushes would increase our understanding of their cause(s) and side effects, and help to design effective treatments, including interventions that can manipulate the activity of the skin blood vessels and/or sweat glands via pharmacological or non-pharmacological methods. NCT06222073.

Purpose The aim of this study was to examine if catechin‐rich green tea abrogates the negative effects of 7‐days of physical inactivity and excessive calorie‐intake on insulin homeostasis and peripheral vascular function. Methods Using a randomized, double‐blind, crossover design, twelve healthy men (29 ± 6 yrs) underwent 7‐days unhealthy lifestyle (UL), including physical inactivity (−50% steps/day) and overfeeding (+50% kcal/day). This was combined with green tea consumption (UL‐tea; 3 doses/day) or placebo (UL‐placebo). Before and after each intervention, we examined postprandial blood glucose and insulin (3‐h after a 1,202 kcal meal) and upper and lower limb vascular function (flow‐mediated dilation (FMD%)) and carotid artery reactivity (CAR%). Results UL‐placebo increased postprandial glucose and insulin, while UL‐tea decreased postprandial glucose and insulin (Time*Intervention interaction effects: both p < 0.05). UL‐placebo decreased CAR% and femoral FMD%, while UL‐tea prevented these effects (Time*Intervention interaction effects of p < 0.04 and p < 0.001, respectively). There was no main effect of Time or Time*Intervention interaction (both p > 0.05) for brachial FMD%. Conclusion Seven days of physical inactivity and overfeeding impair insulin homeostasis and vascular function. These effects were mitigated by a daily intake of catechin‐rich green tea. The aim of this study was to examine if catechin‐rich green tea abrogates the negative effects of short‐term physical inactivity and excessive calorie‐intake on insulin homeostasis and peripheral vascular function. Twelve healthy men (29 ± 6 yrs) underwent 7‐days unhealthy lifestyle (UL), including physical inactivity (−50% steps/day) and overfeeding (+50% kcal/day) combined with green tea consumption (UL‐tea; 3 doses/day) or placebo (UL‐placebo). UL‐placebo increased post‐prandial glucose and insulin, while UL‐tea decreased post‐prandial glucose and insulin. UL‐placebo decreased carotid artery reactivity and lower limb vascular function, while UL‐tea prevented these effects. Seven days of physical inactivity‐ and overfeeding‐induced impairments in insulin homeostasis and vascular function were mitigated by daily intake of catechin‐rich green tea.

Background Although dual antiplatelet therapy (DAPT) improves the outcomes of patients undergoing percutaneous coronary intervention (PCI), sex-specific differences in efficacy and safety of DAPT remain unresolved. We compared sex differences for DAPT outcomes and DAPT durations (1–3 months [short-term], 6 months [mid-term], and >12 months [extended] vs. 12 months). Methods We searched databases through 31 December 2023 for trials reporting DAPT after PCI. The endpoints were major adverse cardiovascular and cerebrovascular events (MACCE), net adverse clinical and cerebrovascular events (NACCE), and any bleeding. Extracted data were pooled in a frequentist network and pairwise, random-effects meta-analysis. Results Twenty-two trials (99,591 participants, 25.2% female) were included. Female sex was significantly associated with a higher 1-year MACCE risk (hazard ratio 1.14 [95% confidence interval 1.02–1.28]) and bleeding (1.13 [1.00–1.28]), but not NACCE (1.12 [0.96–1.31]). In sub-analyses, the association between female sex and MACCE was related to use of clopidogrel as the second antiplatelet agent (1.11 [1.03–1.20]), whereas higher bleeding events were related to newer P2Y12 inhibitors (P2Y12i) (1.58 [1.01–2.46]). For DAPT duration, short-term DAPT followed by P2Y12i monotherapy was non-inferior for MACCE in females and males (0.95 [95% CI 0.83–1.10; and 0.96 [0.80–1.16]) but tended to be superior in males for NACCE versus 12-month DAPT (0.96 [0.91–1.01]); mid-term DAPT tended to be associated with a lower bleeding risk in males (0.43 [0.17–1.09]). Conclusions Female sex is associated with higher MACCE and bleeding when newer P2Y12i agents are used. Short-term DAPT followed by P2Y12i monotherapy is safe and effective in both sexes undergoing PCI. Clinical Trials Registration PROSPERO ID: CRD42021278663. Graphical Abstract Sex differences in outcomes of clinical trials of dual antiplatelet therapy (DAPT) after percutaneous coronary interventions (PCI).

BackgroundHumans display an age-related decline in cerebral blood flow and increase in blood pressure (BP), but changes in the underlying control mechanisms across the lifespan are less well understood. We aimed to; (1) examine the impact of age, sex, cardiovascular disease (CVD) risk, and cardio-respiratory fitness on dynamic cerebral autoregulation and cardiac baroreflex sensitivity, and (2) explore the relationships between dynamic cerebral autoregulation (dCA) and cardiac baroreflex sensitivity (cBRS).Methods206 participants aged 18–70 years were stratified into age categories. Cerebral blood flow velocity was measured using transcranial Doppler ultrasound. Repeated squat-stand manoeuvres were performed (0.10 Hz), and transfer function analysis was used to assess dCA and cBRS. Multivariable linear regression was used to examine the influence of age, sex, CVD risk, and cardio-respiratory fitness on dCA and cBRS. Linear models determined the relationship between dCA and cBRS.ResultsAge, sex, CVD risk, and cardio-respiratory fitness did not impact dCA normalised gain, phase, or coherence with minimal change in all models (P > 0.05). cBRS gain was attenuated with age when adjusted for sex and CVD risk (young–older; β = − 2.86 P < 0.001) along with cBRS phase (young–older; β = − 0.44, P < 0.001). There was no correlation between dCA normalised gain and phase with either parameter of cBRS.ConclusionAgeing was associated with a decreased cBRS, but dCA appears to remain unchanged. Additionally, our data suggest that sex, CVD risk, and cardio-respiratory fitness have little effect.

Ultra-endurance has been defined as any exercise bout that exceeds 6 h. A number of exceptional, record-breaking performances by female athletes in ultra-endurance sport have roused speculation that they might be predisposed to success in such events. Indeed, while the male-to-female performance gap in traditional endurance sport (e.g., marathon) remains at ~ 10%, the disparity in ultra-endurance competition has been reported as low as 4% despite the markedly lower number of female participants. Moreover, females generally outperform males in extreme-distance swimming. The issue is complex, however, with many sports-specific considerations and caveats. This review summarizes the sex-based differences in physiological functions and draws attention to those which likely determine success in extreme exercise endeavors. The aim is to provide a balanced discussion of the female versus male predisposition to ultra-endurance sport. Herein, we discuss sex-based differences in muscle morphology and fatigability, respiratory-neuromechanical function, substrate utilization, oxygen utilization, gastrointestinal structure and function, and hormonal control. The literature indicates that while females exhibit numerous phenotypes that would be expected to confer an advantage in ultra-endurance competition (e.g., greater fatigue resistance, greater substrate efficiency, and lower energetic demands), they also exhibit several characteristics that unequivocally impinge on performance (e.g., lower O 2 -carrying capacity, increased prevalence of GI distress, and sex-hormone effects on cellular function/injury risk). Crucially, the advantageous traits may only manifest as ergogenic in the extreme endurance events which, paradoxically, are those that females less often contest. The title question should be revisited in the coming years, when/if the number of female participants increases.

Despite the vast array of different geochronological tools available, dating the Paleolithic remains one of the discipline’s greatest challenges. This review focuses on two different dating approaches: trapped charge and amino acid geochronology. While differing in their fundamental principles, both exploit time-dependent changes in signals found within crystals to generate a chronology for the material dated and hence, the associated deposits. Within each method, there is a diverse range of signals that can be analyzed, each covering different time ranges, applicable to different materials and suitable for different paleoenvironmental and archaeological contexts. This multiplicity of signals can at first sight appear confusing, but it is a fundamental strength of the techniques, allowing internal checks for consistency and providing more information than simply a chronology. For each technique, we present an overview of the basis for the time-dependent signals and the types of material that can be analyzed, with examples of their archaeological application, as well as their future potential.

Background Medical student wellbeing – a consensus statement from Australia and New Zealand outlines recommendations for optimising medical student wellbeing within medical schools in our region. Worldwide, medical schools have responsibilities to respond to concerns about student psychological, social and physical wellbeing, but guidance for medical schools is limited. To address this gap, this statement clarifies key concepts and issues related to wellbeing and provides recommendations for educational program design to promote both learning and student wellbeing. The recommendations focus on student selection; learning, teaching and assessment; learning environment; and staff development. Examples of educational initiatives from the evidence-base are provided, emphasising proactive and preventive approaches to student wellbeing. Main recommendations The consensus statement provides specific recommendations for medical schools to consider at all stages of program design and implementation. These are: Design curricula that promote peer support and progressive levels of challenge to students. Employ strategies to promote positive outcomes from stress and to help others in need. Design assessment tasks to foster wellbeing as well as learning. Provide mental health promotion and suicide prevention initiatives. Provide physical health promotion initiatives. Ensure safe and health-promoting cultures for learning in on-campus and clinical settings. Train staff on student wellbeing and how to manage wellbeing concerns. Conclusion A broad integrated approach to improving student wellbeing within medical school programs is recommended. Medical schools should work cooperatively with student and trainee groups, and partner with clinical services and other training bodies to foster safe practices and cultures. Initiatives should aim to assist students to develop adaptive responses to stressful situations so that graduates are prepared for the realities of the workplace. Multi-institutional, longitudinal collaborative research in Australia and New Zealand is needed to close critical gaps in the evidence needed by medical schools in our region.

ACE2 expression is altered in pregnancy disorders and ACE2 gene variants are associated with several major pregnancy complications including small-for-gestational-age, fetal growth restriction and preeclampsia. This study utilised gene-editing to generate both ACE2 knockout and ACE2 rs2074192 placental organoids, facilitating mechanistic studies into the role of ACE2 in placental development, and the effect of fetal carriage of ACE2 rs2074192 CC, CT and TT genotypes. Parameters of cell and organoid growth were measured, together with qPCR, Western Blotting, and ELISA assessments, in all groups from both organoid models. Here, we report that ACE2 knockout results in delayed placental cell growth and increased cell death. ACE2 knockout organoids had lower ACE protein expression, reduced organoid diameters and asymmetrical growth. Placental organoids with the ACE2 rs2074192 TT genotype had significantly higher expression of ACE2 mRNA and ACE2 protein with elevated ACE2:ACE expression ratio and no change in ACE protein. Despite increased expression of ACE2 protein, ACE2 enzyme activity was significantly decreased in ACE2 rs2074192 TT placental organoids. TT organoids also had reduced diameters and asymmetrical growth. Our research provides a new molecular understanding of the role of ACE2 in placental development, with potential implications for pregnancy in the carriage of the ACE2 rs2074192 gene variant.

Background The successful development and sustaining of professional identity is critical to being a successful doctor. This study explores the enduring impact of significant early role models on the professional identity formation of senior doctors. Methods Personal Interview Narratives were derived from the stories told by twelve senior doctors as they recalled accounts of people and events from the past that shaped their notions of being a doctor. Narrative inquiry methodology was used to explore and analyse video recording and transcript data from interviews. Results Role models were frequently characterised as heroic, or villainous depending on whether they were perceived as good or bad influences respectively. The degree of sophistication in participants’ characterisations appeared to correspond with the stage of life of the participant at the time of the encounter. Heroes were characterised as attractive, altruistic, caring and clever, often in exaggerated terms. Conversely, villains were typically characterised as direct or covert bullies. Everyday events were surprisingly powerful, emotionally charged and persisted in participants’ memories much longer than expected. In particular, unresolved emotions dating from encounters where bullying behaviour had been witnessed or experienced were still apparent decades after the event. Conclusion The characterisation of role models is an important part of the professional identity and socialisation of senior doctors. The enduring impact of what role models say and do means that all doctors, need to consistently reflect on how their own behaviour impacts the development of appropriate professional behaviours in both students and training doctors. This is especially important where problematic behaviours occur as, if not dealt with, they have the potential for long-lasting undesirable effects. The importance of small acts of caring in building a nurturing and supportive learning atmosphere at all stages of medical education cannot be underestimated.