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We observed similar MCA CVR and ICA reactivity in males and females. However, kinetic responses of the MCA to hypercapnia suggest that advancing age slows down the rate at which MCA velocity increases in response to hypercapnia. These data indicate distinct regulatory differences, and an impaired vasomotor control of the cerebrovasculature with advancing age, not detected by traditional methods.

Menopause and its associated decline in oestrogen is linked to chronic conditions like cardiovascular disease and osteoporosis, which may be difficult to disentangle from the effects of ageing. Further, post-menopausal women are at increased risk of cerebrovascular disease, linked to declines in cerebral blood flow (CBF) and cerebrovascular reactivity (CVR), yet the direct understanding of the impact of the menopause on cerebrovascular function is unclear. The aim of this systematic review and meta-analysis was to examine the literature investigating CBF and CVR in pre- compared with post-menopausal women METHODS: Five databases were searched for studies assessing CBF or CVR in pre- and post-menopausal women. Meta-analysis examined the effect of menopausal status on middle cerebral artery velocity (MCAv), and GRADE-assessed evidence certainty RESULTS: Nine studies (n=504) included cerebrovascular outcomes. Six studies (n=239) reported negligible differences in MCAv between pre- and post-menopausal women [2.11cm/s (95% CI: -8.94 to 4.73, p=0.54)], but with a "low" certainty of evidence. MCAv was lower in post-menopausal women in two studies, when MCAv was adjusted for blood pressure. CVR was lower in post- compared with pre-menopausal women in two of three studies, but high-quality evidence is lacking. Across outcomes, study methodology and reporting criteria for menopause were inconsistent CONCLUSIONS: MCAv was similar in post- compared with pre-menopausal women. Methodological differences in characterising menopause and inconsistent reporting of cerebrovascular outcomes make comparisons difficult. Comprehensive assessments of cerebrovascular function of the intra- and extracranial arteries to determine the physiological implications of menopause on CBF with healthy ageing is warranted.

Background The COVID-19 pandemic left countries to rapidly implement diverse and stringent public health measures without recourse to mitigate its effect on the sustenance of routine healthcare services. This study described routine health service disruption and restoration strategies at 6 months into the epidemic in Liberia. Methods Liberia, with 15 counties, has 839 health facilities, with one-third in Montserrado County. A cross-sectional study using a mixed approach - quantitative and qualitative research with concurrent triangulation was conducted using a structured guide for group discussions among key health workers at 42 secondary and most patronized health facilities in 14 counties and 7 Montserrado districts. Additionally, routine health data between January and June 2019 and 2020 were extracted from the source documents to the electronic checklist. We performed a descriptive analysis of quantitative data and plotted the line graph of the relative percentage change. Transcribed audio recording notes were synthesized using ATLAS ti for content analysis to identify the themes and subthemes in line with the study objectives and excerpts presented in the results. Results Liberia declared COVID-19 outbreak on March 16, 2020. From conducted interviews at 41 health facilities, 80% reported disruption in routine health services. From January to June 2020, scheduled routine immunization outreaches conducted decreased by 47%. Using a relative percentage change, outpatient attendance decreased by 32% in May, inpatient admission by 30% in April, malaria diagnosis and treatment by 40% in April, and routine antenatal obstetric care by 28% in April. The fear of contacting COVID-19 infection, redeployment of healthcare workers to COVID-19 response, restriction of movement due to lockdown, inadequate or lack of PPE for healthcare workers, lack of drugs and vaccine supplies for clients, and partial closure of routine healthcare services were common perceived reasons for disruptions. Massive community health education and strict compliance with COVID-19 nonpharmacological measures were some of the health facility recovery strategies. Conclusions The COVID-19 outbreak in Liberia caused a disruption in routine healthcare services, and strategies to redirect the restoration of routine healthcare services were implemented. During epidemics or global health emergencies, countries should sustain routine health services and plan for them.

We address two aims: Aim 1 (Fitness Review) compares the effect of higher cardiorespiratory fitness (CRF) (e.g., endurance athletes) with lower CRF (e.g., sedentary adults) on cerebrovascular outcomes, including middle cerebral artery velocity (MCAv), cerebrovascular reactivity and resistance, and global cerebral blood flow, as assessed by transcranial Doppler (TCD) or magnetic resonance imaging (MRI). Aim 2 (Exercise Training Review) determines the effect of exercise training on cerebrovascular outcomes. Systematic review of studies with meta-analyses where appropriate. Certainty of evidence was assessed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Twenty studies (18 using TCD) met the eligibility criteria for Aim 1, and 14 studies (8 by TCD) were included for Aim 2. There was a significant effect of higher CRF compared with lower CRF on cerebrovascular resistance (effect size = -0.54, 95% confidence interval = -0.91 to -0.16) and cerebrovascular reactivity (0.98, 0.41-1.55). Studies including males only demonstrated a greater effect of higher CRF on cerebrovascular resistance than mixed or female studies (male only: -0.69, -1.06 to -0.32; mixed and female studies: 0.10, -0.28 to 0.49). Exercise training did not increase MCAv (0.05, -0.21 to 0.31) but showed a small nonsignificant improvement in cerebrovascular reactivity (0.60, -0.08 to 1.28; P = 0.09). Exercise training showed heterogeneous effects on regional but little effect on global cerebral blood flow as measured by MRI. High CRF positively effects cerebrovascular function, including decreased cerebrovascular resistance and increased cerebrovascular reactivity; however, global cerebral blood flow and MCAv are primarily unchanged following an exercise intervention in healthy and clinical populations.NEW & NOTEWORTHY Higher cardiorespiratory fitness is associated with lower cerebrovascular resistance and elevated cerebrovascular reactivity at rest. Only adults with a true-high fitness based on normative data exhibited elevated middle cerebral artery velocity. The positive effect of higher compared with lower cardiorespiratory fitness on resting cerebrovascular resistance was more evident in male-only studies when compared with mixed or female-only studies. A period of exercise training resulted in negligible changes in middle cerebral artery velocity and global cerebral blood flow, with potential for improvements in cerebrovascular reactivity.

NEW FINDINGS What is the topic of this review? We have conducted a systematic review and meta-analysis on the current evidence for the effect of heat therapy on blood pressure and vascular function. What advances does it highlight? We found that heat therapy reduced mean arterial, systolic and diastolic blood pressure. We also observed that heat therapy improved vascular function, as assessed via brachial artery flow-mediated dilatation. Our results suggest that heat therapy is a promising therapeutic tool that should be optimized further, via mode and dose, for the prevention and treatment of cardiovascular disease risk factors. ABSTRACT Lifelong sauna exposure is associated with reduced cardiovascular disease risk. Recent studies have investigated the effect of heat therapy on markers of cardiovascular health. We aimed to conduct a systematic review with meta-analysis to determine the effects of heat therapy on blood pressure and indices of vascular function in healthy and clinical populations. Four databases were searched up to September 2020 for studies investigating heat therapy on outcomes including blood pressure and vascular function. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was used to assess the certainty of evidence. A total of 4522 titles were screened, and 15 studies were included. Healthy and clinical populations were included. Heat exposure was for 30-90 min, over 10-36 sessions. Compared with control conditions, heat therapy reduced mean arterial pressure [n = 4 studies; mean difference (MD): -5.86 mmHg, 95% confidence interval (CI): -8.63, -3.10; P

This study is the first to assess the reflex control of sweating in tattooed skin. The novel findings are twofold. First, attenuated increases in sweat rate were observed in tattooed skin compared with adjacent healthy non-tattooed skin in response to a moderate increase (1.0°C) in internal temperature during a passive whole body heat stress. Second, reduced sweating in tattooed skin is likely related to functional damage to the secretory mechanisms of eccrine sweat glands, rendering it less responsive to cholinergic stimulation.

We investigated whether small reductions in skin temperature 60 s after the onset of a simulated hemorrhagic challenge would improve tolerance to lower body negative pressure (LBNP) after exercise heat stress. Eleven healthy subjects completed two trials (High and Reduced). Subjects cycled at ~55% maximal oxygen uptake wearing a warm water-perfused suit until core temperatures increased by ~1.2°C before lying supine and undergoing LBNP to presyncope. LBNP tolerance was quantified as cumulative stress index (CSI; product of each LBNP level multiplied by time; mmHg·min). Skin temperature was similarly elevated from baseline before LBNP and remained elevated 60 s after the onset of LBNP in both High (37.72 ± 0.52°C) and Reduced (37.95 ± 0.54°C) trials (both P < 0.0001). At 60%CSI skin temperature remained elevated in the High trial (37.51 ± 0.56°C) but was reduced to 34.97 ± 0.72°C by the water-perfused suit in the Reduced trial ( P < 0.0001 between trials). Cutaneous vascular conductance was not different between trials [High: 1.57 ± 0.43 vs. Reduced: 1.39 ± 0.38 arbitrary units (AU)/mmHg; P = 0.367] before LBNP but decreased to 0.67 ± 0.19 AU/mmHg at 60%CSI in the Reduced trial while remaining unchanged in the High trial ( P = 0.002 between trials). CSI was higher in the Reduced (695 ± 386 mmHg·min) relative to the High (441 ± 290 mmHg·min; P = 0.023) trial. Mean arterial pressure was not different between trials at presyncope (High: 62 ± 10 vs. Reduced: 62 ± 9 mmHg; P = 0.958). Small reductions in skin temperature after the onset of a simulated hemorrhagic challenge improve LBNP tolerance after exercise heat stress. This may have important implications regarding treatment of an exercise heat-stressed individual (e.g., soldier) who has experienced a hemorrhagic injury.

The American Board of Surgery In-Training Examination (ABSITE) is used by programs to evaluate the knowledge and readiness of trainees to sit for the general surgery qualifying examination. It is often used as a tool for resident promotion and may be used by fellowship programs to evaluate candidates. Burnout has been associated with job performance and satisfaction; however, its presence and effects on surgical trainees' performance are not well studied. We sought to understand factors including burnout and study habits that may contribute to performance on the ABSITE examination.Anonymous electronic surveys were distributed to all residents at 10 surgical residency programs (n = 326). Questions included demographics as well as study habits, career interests, residency characteristics, and burnout scores using the Oldenburg Burnout Inventory, which assesses burnout because of both exhaustion and disengagement. These surveys were then linked to the individual's 2016 ABSITE and United States Medical Licensing Examination (USMLE) step 1 and 2 scores provided by the programs to determine factors associated with successful ABSITE performance.In total, 48% (n = 157) of the residents completed the survey. Of those completing the survey, 48 (31%) scored in the highest ABSITE quartile (≥75th percentile) and 109 (69%) scored less than the 75th percentile. In univariate analyses, those in the highest ABSITE quartile had significantly higher USMLE step 1 and step 2 scores (P 0.001), significantly lower burnout scores (disengagement, P 0.01; exhaustion, P 0.04), and held opinions that the ABSITE was important for improving their surgical knowledge (P 0.01). They also read more frequently to prepare for the ABSITE (P 0.001), had more disciplined study habits (P 0.001), were more likely to study at the hospital or other public settings (e.g., library, coffee shop compared with at home; P 0.04), and used active rather than passive study strategies (P 0.04). Gender, marital status, having children, and debt burden had no correlation with examination success. Backward stepwise multiple regression analysis identified the following independent predictors of ABSITE scores: study location (P 0.0001), frequency of reading (P = 0.0001), Oldenburg Burnout Inventory exhaustion (P = 0.02), and USMLE step 1 and 2 scores (P = 0.007 and 0.0001, respectively).Residents who perform higher on the ABSITE have a regular study schedule throughout the year, report less burnout because of exhaustion, study away from home, and have shown success in prior standardized tests. Further study is needed to determine the effects of burnout on clinical duties, career advancement, and satisfaction.

Melanocortin-4 receptor (MC4R) is a G-protein-coupled receptor expressed in the hypothalamus where it controls feeding behavior. MC4R cycles constitutively and is internalized at the same rate in the presence or absence of stimulation by the agonist, melanocyte-stimulating hormone (α-MSH). This is different from other G-protein-coupled receptors, such as β(2)-adrenergic receptor (β(2)AR), which internalizes more rapidly in response to agonist stimulation. Here, it is found that in immortalized neuronal Neuro2A cells expressing exogenous receptors, constitutive endocytosis of MC4R and agonist-dependent internalization of β(2)AR were equally sensitive to clathrin depletion. Inhibition of MC4R endocytosis by clathrin depletion decreased the number of receptors at the cell surface that were responsive to the agonist, α-MSH, by 75%. Mild membrane cholesterol depletion also inhibited constitutive endocytosis of MC4R by ∼5-fold, while not affecting recycling of MC4R or agonist-dependent internalization of β(2)AR. Reduced cholesterol did not change the MC4R dose-response curve to α-MSH, but it decreased the amount of cAMP generated per receptor number indicating that a population of MC4R at the cell surface becomes nonfunctional. The loss of MC4R function increased over time (25-50%) and was partially reversed by mutations at putative phosphorylation sites (T312A and S329A). This was reproduced in hypothalamic GT1-7 cells expressing endogenous MC4R. The data indicate that constitutive endocytosis of MC4R is clathrin- and cholesterol-dependent. MC4R endocytosis is required to maintain MC4R responsiveness to α-MSH by constantly eliminating from the plasma membrane a pool of receptors modified at Thr-312 and Ser-329 that have to be cycled to the endosomal compartment to regain function.

Many young children pass through a stage of gender appearance rigidity; girls insist on wearing dresses, often pink and frilly, whereas boys refuse to wear anything with a hint of femininity. In 2 studies, we investigated the prevalence of this apparent hallmark of early gender development and its relation to children's growing identification with a gender category. Study 1a examined the prevalence of this behavior and whether it would exhibit a developmental pattern of rigidity followed by flexibility, consistent with past research on identity-related cognitions. Interviews with 76 White, middle-class parents and their 3- to 6-year-old children revealed that about two thirds of parents of 3- and 4-year-old girls and almost half (44%) of parents of 5- and 6-year-old boys reported that their children had exhibited a period of rigidity in their gender-related appearance behavior. Appearance rigidity was not related to parents' preferences for their children's gender-typed clothing. Study 1b examined whether cognitive theories of identity development could shed light on gender appearance rigidity. The more important and positive children considered their gender and the more children understood that gender categories remain stable over time (gender stability), the more likely children were to wear gender-typed outfits. In Study 2, we extended this research to a more diverse population and found that gender appearance rigidity was also prevalent in 267 4-year-old children in the United States from African American, Chinese, Dominican, and Mexican immigrant low-income backgrounds. Results suggest that rigid gender-related appearance behavior can be seen among young children from different backgrounds and might reflect early developing cognitions about gender identity.

This paper examines gender socialization processes during childhood that may contribute to a higher incidence of depression or depressive symptoms in females than in males. It is argued that because of the actions of socialization agents and the impact of gender stereotypes on a child's construction of gender identity, girls may exhibit higher levels of self-evaluative concerns that increase vulnerability to depression. Indeed, a review of the literature on sex differences in self-evaluation suggests that girls may be more susceptible than boys to self-evaluative concerns, particularly as reflected in lower expectations for future success, more maladaptive causal attributions for success or failure outcomes, and negative behavioral and evaluative reactions to failure. Moreover, an examination of the literature on sex differences in depressive symptoms leads to questions about previous conclusions that girls do not exhibit higher levels of depressive symptoms prior to adolescence. Finally, we present some recent original data that support the contention that sex differences in vulnerability to depression may be evident prior to adolescence.

Kohlberg’s (1966) hypothesis that the attainment of gender constancy motivates children to attend to gender norms was reevaluated by examining these links in relation to age. Ninety-four 3- to 7-year-old children were interviewed to assess whether and how constancy mediates age-related changes in gender-related beliefs. As expected, results indicated a general pattern of an increase in stereotype knowledge, the importance and positive evaluation of one’s own gender category, and rigidity of beliefs between the ages of 3 and 5. Moreover, the stability phase, rather than full constancy, mediated some of these relations. After age 5, rigidity generally decreased with age, with relations primarily mediated by consistency.

DBC2 is a tumor suppressor gene linked to breast and lung cancers. Although DBC2 belongs to the RHO GTPase family, it has a unique structure that contains a Broad-Complex/Tramtrack/Bric a Brac (BTB) domain at the C terminus instead of a typical CAAX motif. A limited number of functional studies on DBC2 have indicated its participation in diverse cellular activities, such as ubiquitination, cell-cycle control, cytoskeleton organization and protein transport. In this study, the role of DBC2 in protein transport was analyzed using vesicular stomatitis virus glycoprotein (VSVG) fused with green fluorescent protein. We discovered that DBC2 knockdown hinders the VSVG transport system in 293 cells. Previous studies have demonstrated that VSVG is transported via the microtubule motor complex. We demonstrate that DBC2 mobility depends also on an intact microtubule network. We conclude that DBC2 plays an essential role in microtubule-mediated VSVG transport from the endoplasmic reticulum to the Golgi apparatus.

Foreign Service personnel undergo pertinent parasitologic examinations upon return from foreign duty posts. Under this program, 2800 sera have been evaluated for schistosomiasis in this laboratory. The majority of individuals tested were considered to have limited exposure to schistosomiasis, although a few indigenous people from endemic areas also were screened. Nonindigenous populations usually gave stronger serological reactions than did indigenous populations. A comparison was made between those having protozoan and helminthic infections and those that were negative parasitologically. A number of subjects with tissue-phase helminths were evaluated and consistently gave strong reactions in the indirect fluorescent antibody (IFA) tests. On the other hand, there was no characteristic pattern observed in individuals with low serum titers. The IFA test proved to be highly sensitive and sufficiently specific for screening, provided that low background reactions were disregarded (i.e., when +/− and 1+ reactions were ignored at low serum dilutions). Thus, the IFA test was the method of choice for screening. Recourse to the complement fixation (CF) and slide flocculation (SF) tests, however, was necessary for definitive diagnosis. In view of the differences in the antigens and the serodiagnostic technics used in this survey, absolute correlation of test results could not be expected. Nevertheless, the three procedures (IFA, CF, and SF) showed excellent correlation in proven cases of schistosomiasis.

Eight normotensive and eight essential hypertensive humans were studied when on high and low sodium intake. Total 24-hr exchangeable body sodium, blood volume, serum sodium concentration, hematocrit, body weight, and mean arterial pressures, when the subjects were supine and upright, were measured. Plasma and nonplasma sodium fractions, nonplasma weight, and plasma, cell, and whole blood volumes, as referred to body weight and height, were calculated. Changes in these parameters with diet were also calculated. Specific differences between normotensives and hypertensives were found, in absolute values and with changes with diet. The hypertensives fell into two groups with regard to exchangeable sodium: in four the values varied with diet and in the other four, the values remained low regardless of diet. The "variable-sodium" patients had high upright arterial pressures when on high salt intake and normal upright pressures when on low salt intake. "Low-sodium" patients had high arterial pressures on both diets. Changes in upright pressures of hypertensives correlated significantly (r = 0.73) with changes in nonplasma exchangeable sodium.

Venous responses to stabilized orthostasis (45 degrees head-up tilt) were studied in seven normotensive subjects and eight hypertensive patients, when on high and low dietary sodium intake. Exchangeable sodium and blood volumes were determined to permit correlation with any significant changes in venous behavior. The intent of this study was to detect and analyze any diet-induced changes in responses of forearm veins to prolonged orthostasis. The pharmacological effects of sodium depletion by medication and diet on arteries and veins of hypertensives are discussed. The results of this study indicate that dietary sodium depletion did not have adverse effects on the ability to maintain stabilized venous tone during orthostasis. These results support recommendations that moderate dietary sodium restriction be included as part of antihypertensive regimens.

Cardiovascular effects of acute elevations of intracranial pressure were studied, with special reference to three questions: a) whether vasoconstriction or cardiac stimulation is primarily responsible for the pressor response to this stimulus; b) whether the ultimate nature of the stimulus is neurogenic or humoral; and c) whether or not changes in venous tone occur in response to ICP elevation. It is concluded from the experimental findings that vasoconstriction was the dominant factor in the response, that the reflex is primarily neurogenic, and that the venomotor system shows an active constriction which accompanies the arterial pressure rise.