The Effect of Shift Timing on Cesarean Delivery Outcomes and Operative Noise Levels.

OBJECTIVE: Intraoperative noise exposure has been associated with an increased risk of complications, communication errors, and stress among surgical team members. This study evaluates intraoperative noise levels in cesarean deliveries during different shift times, for example, night shifts, day shifts, and hand-off times between shifts. STUDY DESIGN: This is a secondary analysis of a prospective observational study which measured volume in decibels, percentage of time above safe levels (>60 dB), startle noise events (events with rapid increase of decibel level above baseline noise), and peak levels (>75 dB) for cesarean deliveries during a 3-month preintervention and postintervention study. This secondary analysis of noise data evaluated whether there were differences in noise for cases occurring during day shifts (6:31 a.m.-4:59 p.m.), night shifts (6:01 p.m.-5:29 a.m.), and hand-off times (5:30 a.m.-6:30 a.m. and 5:00 p.m.-6:00 p.m.). Correlates and postoperative complications during the respective shifts were additionally analyzed. RESULTS: Noise data were collected for a total of 312 cesarean deliveries; 203 occurred during the day shift, 94 during the night shift, and 15 during hand-off times. Median noise in decibels, median noise at various key intraoperative points, number of startle events, percentage of time above 60 dB, and above 75 dB had no significant differences throughout the various shift times. Significantly larger numbers of postpartum hemorrhages, unscheduled, urgent, and STAT cesarean deliveries occurred at hand-off times and on night shifts. CONCLUSION: Noise levels during cesarean deliveries did not significantly vary when comparing night shifts, day shifts, and hand-off times, despite significantly higher numbers of urgent and STAT cases occurring overnight and during hand-off times. However, more than 60% of case time had noise levels exceeding those considered safe. This suggests that ambient background noise may be contributing more to overall noise levels rather than the specific clinical scenario at hand. KEY POINTS: · Noise in cesarean delivery operating rooms frequently exceeded recommended levels.. · Noise in cesarean delivery operating rooms did not vary with shift type.. · Hand-off times had higher rates of urgent and STAT cesareans.. · Night shifts had higher rates of urgent and STAT cesareans..

Patterns and Correlates of Cervical Cancer Prevention Among Black Immigrant and African American Women in the USA: the Role of Ethnicity and Culture.

Cervical cancer prevention disparities between Black and White women have been researched extensively, but less is known about disparities among Black subpopulations, despite increased risk, distinct cultures, and rapidly increasing numbers of Black immigrant women to the USA. A 74-item survey was used to conduct a cross-sectional descriptive study. Independent sample t tests, logistic multiple regressions, and chi-square tests were used to carry out all comparative analyses. The survey was administered via Psychdata from January 2020 to February 2020. The final sample included 450 eligible participants (African American women [AAW] = 335; Black immigrant women [BIW] from either West, Central, East Africa, or the Caribbean = 115). Compared to AAW, BIW demonstrated much lower knowledge of cervical cancer, AAW were more likely to visit a gynecologist, and to have had a well-woman exam every 3 years or less. A greater percentage of BIW reported not getting Pap smear test because they had no symptoms or because they feared bad results while AAW reported not receiving a Pap smear because it was not convenient, they did not trust any doctor/gynecologist, and lacked access to a gynecologist. Doctor and family advising had a much larger effect on cervical screening among BIW compared to AAW. This study provides evidence of crucial differences in CC knowledge, attitudes, and screening behaviors among BIW and AAW. Funding agencies, program planners and evaluators, and health policymakers are encouraged to require disaggregation of Black women in healthcare research to tease out specific ways interventions can be most effective.

Health Disparities and the Heterogeneity of Blacks/African Americans in the United States: Why Should We Care?

Each year, millions of dollars are spent on research and public health interventions targeted toward reducing health disparities primarily among the "Black/African Americans" community, yet the progress made lags far behind the amount of money and effort spent. We hypothesize that part of the problem is that sociocultural factors play a significant role in disease prevention. Most studies and programs aggregate "Black immigrants" (BIs) and "African Americans" (AAs) as "Black/African American." This categorization assumes that the sociocultural determinants that influence BIs are the same as for AAs. BIs have health and mortality profiles that vary from AAs. This commentary aims to (1) introduce this idea in more depth and provide a brief scope of the problem, (2) provide scientific evidence of noteworthy differences between AAs and BIs in areas of sociodemographics, health behaviors, and health outcomes, (3) discuss implications of considering the Black/AA group as homogeneous and provide recommendations for disaggregation.

A mixed-methods case study exploring the impact of participation in community activity groups for older adults on physical activity, health and wellbeing.

BACKGROUND: Regular physical activity (PA) has many health benefits but declines with age. Community multi-activity groups offering volunteer-led socially-oriented activity programs could provide an opportunity for older people to maintain or increase PA levels and promote their health. The aim of this study was to examine the potential effect of becoming a member of an existing community activity group on PA levels, physical and mental health-related quality of life (HR QoL), comparing any impacts associated with participation in physical activity or social activity programs. METHODS: This mixed-methods case study, combining a longitudinal quantitative-survey with qualitative focus groups to contextualise the survey results, focused on an Australian community organisation called Life Activities Clubs (LACs). LACs provide various physical activities (e.g. walking, cycling, dancing) and social activities (e.g. book groups, dine-outs, craft). Data were collected using a self-report survey administered at baseline, six and twelve-months after joining and group differences between participants of PA programs (PA group) and social programs (social group) were analysed using linear mixed-models. Two focus groups with LAC members were held, one representing each activity type and analysed using content and thematic analysis. RESULTS: 35 people (mean age 67) completed the surveys and 11 people participated in the focus groups. PA levels and physical health-related QoL were maintained over 1 year in the PA group, and declined between baseline and 12-months in the social group. Focus groups suggested social aspects of PA programs increased motivation to maintain regular attendance and do more PA than participants would on their own and that physical activities provided health benefits. Mental HR QoL did not change in either group, focus groups suggested this was because the social aspects of both types of program provide benefits relating to mental health including stress relief, enjoyment and adapting to major life events, to prevent a decline in QoL. CONCLUSIONS: Community PA programs appear to maintain PA levels and physical HR QoL in older adults, and both social and PA programs may maintain mental HR QoL. Incorporating both types of program into one organisation may also encourage less physically active members to try physical activities.

Effect of texturised soy protein and yeast on the instrumental and sensory quality of hybrid beef meatballs.

The study aimed to investigate the effect of introducing texturized soy protein (TSP) at different levels (15% and 30%) with and without nutritional yeast as flavour enhancer on the sensory and instrumental quality of beef meatballs, compared to a soy and yeast-free control. Proximate analysis, colour, instrumental texture, cook loss, and sensory quality were investigated. Sixty participants assessed the samples using Check-all-that-apply (CATA) questions and hedonic scales. Overall, the texture of all TSP-containing samples received significantly higher acceptability scores than control, while 15% TSP with yeast received the highest flavour and overall acceptability scores. Penalty-lift analysis of CATA terms identified the main drivers for liking as "moist looking", "juicy", "soft" and "crumbly and easy to cut". Control samples were significantly more often associated than the other recipes to the term "hard", a key driver for dislike and the least associated to "soft" and "crumbly and easy to cut". Adding 15-30% TSP with or without yeast inclusion could be beneficial for the development of future meat hybrids with acceptable sensory quality.

Correction to: Effect of texturised soy protein and yeast on the instrumental and sensory quality of hybrid beef meatballs.

[This corrects the article DOI: 10.1007/s13197-018-3552-9.].

A mixed methods case study exploring the impact of membership of a multi-activity, multicentre community group on social wellbeing of older adults.

BACKGROUND: Social wellbeing factors such as loneliness and social support have a major impact on the health of older adults and can contribute to physical and mental wellbeing. However, with increasing age, social contacts and social support typically decrease and levels of loneliness increase. Group social engagement appears to have additional benefits for the health of older adults compared to socialising individually with friends and family, but further research is required to confirm whether group activities can be beneficial for the social wellbeing of older adults. METHODS: This one-year longitudinal mixed methods study investigated the effect of joining a community group, offering a range of social and physical activities, on social wellbeing of adults with a mean age of 70. The study combined a quantitative survey assessing loneliness and social support (n = 28; three time-points, analysed using linear mixed models) and a qualitative focus group study (n = 11, analysed using thematic analysis) of members from Life Activities Clubs Victoria, Australia. RESULTS: There was a significant reduction in loneliness (p = 0.023) and a trend toward an increase in social support (p = 0.056) in the first year after joining. The focus group confirmed these observations and suggested that social support may take longer than 1 year to develop. Focus groups also identified that group membership provided important opportunities for developing new and diverse social connections through shared interest and experience. These connections were key in improving the social wellbeing of members, especially in their sense of feeling supported or connected and less lonely. Participants agreed that increasing connections was especially beneficial following significant life events such as retirement, moving to a new house or partners becoming unwell. CONCLUSIONS: Becoming a member of a community group offering social and physical activities may improve social wellbeing in older adults, especially following significant life events such as retirement or moving-house, where social network changes. These results indicate that ageing policy and strategies would benefit from encouraging long-term participation in social groups to assist in adapting to changes that occur in later life and optimise healthy ageing.

The association between social support and physical activity in older adults: a systematic review.

BACKGROUND: The promotion of active and healthy ageing is becoming increasingly important as the population ages. Physical activity (PA) significantly reduces all-cause mortality and contributes to the prevention of many chronic illnesses. However, the proportion of people globally who are active enough to gain these health benefits is low and decreases with age. Social support (SS) is a social determinant of health that may improve PA in older adults, but the association has not been systematically reviewed. This review had three aims: 1) Systematically review and summarise studies examining the association between SS, or loneliness, and PA in older adults; 2) clarify if specific types of SS are positively associated with PA; and 3) investigate whether the association between SS and PA differs between PA domains. METHODS: Quantitative studies examining a relationship between SS, or loneliness, and PA levels in healthy, older adults over 60 were identified using MEDLINE, PSYCInfo, SportDiscus, CINAHL and PubMed, and through reference lists of included studies. Quality of these studies was rated. RESULTS: This review included 27 papers, of which 22 were cross sectional studies, three were prospective/longitudinal and two were intervention studies. Overall, the study quality was moderate. Four articles examined the relation of PA with general SS, 17 with SS specific to PA (SSPA), and six with loneliness. The results suggest that there is a positive association between SSPA and PA levels in older adults, especially when it comes from family members. No clear associations were identified between general SS, SSPA from friends, or loneliness and PA levels. When measured separately, leisure time PA (LTPA) was associated with SS in a greater percentage of studies than when a number of PA domains were measured together. CONCLUSIONS: The evidence surrounding the relationship between SS, or loneliness, and PA in older adults suggests that people with greater SS for PA are more likely to do LTPA, especially when the SS comes from family members. However, high variability in measurement methods used to assess both SS and PA in included studies made it difficult to compare studies.

Influence of Obesity on the Relationship of Cardiometabolic Risks Factors With Cardiovascular Disease in Older African and European Americans.

PURPOSE: This study evaluated the impact of obesity on cardiometabolic risk factors (CRF) interrelationships and predictive efficiency of CVD development in older African (AA) and European Americans (EA). DESIGN: A comparative research design evaluated CRF risk profile differences between participant groups. SETTING: Seven neighborhoods in a southern US city. SUBJECTS: A sample of 179 older AA (n = 128) and EA (n = 51) adults. MEASURES: Non-fasting blood samples were evaluated for lipids and lipoproteins, glycosylated hemoglobin, systolic -(SBP) and diastolic blood pressure (DBP), body mass index (BMI), body fat percentage (BF%) and physical function. ANALYSIS: Data were analysis with descriptive statistics, t-tests, and correlations. RESULTS: AA were heavier than EA although all had above average age-appropriate fitness. Means and relationships between CRF and other variables were different (P < .05) based on race. Both AA (41.3 + 5.8) and EA (38.6 + 6.4) BF% were CRF risks. Holding BMI constant, CRF were generally not related, and the relationships were different for AA and EA. AA had a range of 13.0 to 27.2% more favorable values for cholesterol, HDL-C, and triglyceride. EA had favorable A1c (EA 5.8 vs AA 6.2%) values. CONCLUSIONS: A limitation of this report is the small sample size. Although further research is warranted, these findings suggest population specific CRF selections would improve CVD prediction in AA.

Circulating cell-free DNA-based biomarkers for prognostication and disease monitoring in adrenocortical carcinoma.

OBJECTIVE: Adrenocortical carcinoma (ACC) is a rare aggressive cancer with heterogeneous behaviour. Disease surveillance relies on frequent imaging, which comes with significant radiation exposure. The aim of the study was to investigate the role of circulating cell-free DNA (ccfDNA)-related biomarkers (BMs) for prognostication and monitoring of ACC. DESIGN AND METHODS: We investigated 34 patients with ACC and 23 healthy subjects (HSs) as controls. Circulating cell-free DNA was extracted by commercial kits and ccfDNA concentrations were quantified by fluorimeter (BM1). Targeted sequencing was performed using a customized panel of 27 ACC-specific genes. Leucocyte DNA was used to discriminate somatic variants (BM2), while tumour DNA was sequenced in 22/34 cases for comparison. Serial ccfDNA samples were collected during follow-up in 19 ACC patients (median period 9 months) and analysed in relationship with standard radiological imaging. RESULTS: Circulating cell-free DNA concentrations were higher in ACC than HS (mean ± SD, 1.15 ± 1.56 vs 0.05 ± 0.05 ng/µL, P < .0001), 96% of them being above the cut-off of 0.146 ng/µL (mean HS + 2 SD, positive BM1). At ccfDNA sequencing, 47% of ACC showed at least 1 somatic mutation (positive BM2). A combined ccfDNA-BM score was strongly associated with both progression-free and overall survival (hazard ratio [HR] = 2.63; 95% CI, 1.13-6.13; P = .010, and HR = 5.98; 95% CI, 2.29-15.6; P = .0001, respectively). During disease monitoring, positive BM2 showed the best specificity (100%) and sensitivity (67%) to detect ACC recurrence or progress compared with BM1. CONCLUSION: ccfDNA-related BMs are frequently detected in ACC patients and represent a promising, minimally invasive tool to predict clinical outcome and complement surveillance imaging. Our findings will be validated in a larger cohort of ACCs with long-term follow-up.

Use of computed tomography to identify muscle quality subgroups, spatial mapping, and preliminary relationships to function in those with diabetic peripheral neuropathy.

BACKGROUND: Decreased muscle volume and increased muscle-associated adipose tissue (MAAT, sum of intra and inter-muscular adipose tissue) of the foot intrinsic muscle compartment are associated with deformity, decreased function, and increased risk of ulceration and amputation in those with diabetic peripheral neuropathy (DPN). RESEARCH QUESTION: What is the muscle quality (normal, abnormal muscle, and adipose volumes) of the DPN foot intrinsic compartment, how does it change over time, and is muscle quality related to gait and foot function? METHODS: Computed tomography was performed on the intrinsic foot muscle compartment of 45 subjects with DPN (mean age: 67.2 ± 6.4 years) at baseline and 3.6 years. Images were processed to obtain volumes of MAAT, highly abnormal, mildly abnormal, and normal muscle. For each category, annual rates of change were calculated. Paired t-tests compared baseline and follow-up. Foot function during gait was assessed using 3D motion analysis and the Foot and Ankle Ability Measure. Correlations between muscle compartment and foot function during gait were analyzed using Pearson's correlations. RESULTS: Total muscle volume decreased, driven by a loss of normal muscle and mildly abnormal muscle (p<0.05). MAAT and the adipose-muscle ratio increased. At baseline, 51.5% of the compartment was abnormal muscle or MAAT, increasing to 55.0% at follow-up. Decreased total muscle volume correlated with greater midfoot collapse during gait (r = -0.40, p = 0.02). Greater volumes of highly abnormal muscle correlated with a lower FAAM score (r = -0.33, p = 0.03). SIGNIFICANCE: Muscle volume loss may progress in parallel with MAAT accumulation, impacting contractile performance in individuals with DPN. Only 48.5% of the DPN intrinsic foot muscle compartment consists of normal muscle and greater abnormal muscle is associated with worse foot function. These changes identify an important target for rehabilitative intervention to slow or prevent muscle deterioration and poor foot outcomes.

PLK1 inhibitors as a new targeted treatment for adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is an aggressive malignancy with limited treatment options. Polo-like kinase 1 (PLK1) is a promising drug target; PLK1 inhibitors (PLK1i) have been investigated in solid cancers and are more effective in TP53-mutated cases. We evaluated PLK1 expression in ACC samples and the efficacy of two PLK1i in ACC cell lines with different genetic backgrounds. PLK1 protein expression was investigated by immunohistochemistry in tissue samples and correlated with clinical data. The efficacy of rigosertib (RGS), targeting RAS/PI3K, CDKs and PLKs, and poloxin (Pol), specifically targeting the PLK1 polo-box domain, was tested in TP53-mutated NCI-H295R, MUC-1, and CU-ACC2 cells and in TP53 wild-type CU-ACC1. Effects on proliferation, apoptosis, and viability were determined. PLK1 immunostaining was stronger in TP53-mutated ACC samples vs wild-type (P = 0.0017). High PLK1 expression together with TP53 mutations correlated with shorter progression-free survival (P= 0.041). NCI-H295R showed a time- and dose-dependent reduction in proliferation with both PLK1i (P< 0.05at 100 nM RGS and 30 µM Pol). In MUC-1, a less pronounced decrease was observed (P< 0.05at 1000 nM RGS and 100 µM Pol). 100 nM RGS increased apoptosis in NCI-H295R (P< 0.001), with no effect on MUC-1. CU-ACC2 apoptosis was induced only at high concentrations (P < 0.05 at 3000 nM RGS and 100 µM Pol), while proliferation decreased at 1000 nM RGS and 30 µM Pol. CU-ACC1 proliferation reduced, and apoptosis increased, only at 100 µM Pol. TP53-mutated ACC cell lines demonstrated better response to PLK1i than wild-type CU-ACC1. These data suggest PLK1i may be a promising targeted treatment of a subset of ACC patients, pre-selected according to tumour genetic signature.

The role of social support in students' perceived abilities and attitudes toward math and science.

Social cognitive models examining academic and career outcomes emphasize constructs such as attitude, interest, and self-efficacy as key factors affecting students' pursuit of STEM (science, technology, engineering and math) courses and careers. The current research examines another under-researched component of social cognitive models: social support, and the relationship between this component and attitude and self-efficacy in math and science. A large cross-sectional design was used gathering data from 1,552 participants in four adolescent school settings from 5th grade to early college (41 % female, 80 % white). Students completed measures of perceived social support from parents, teachers and friends as well as their perceived ability and attitudes toward math and science. Fifth grade and college students reported higher levels of support from teachers and friends when compared to students at other grade levels. In addition, students who perceived greater social support for math and science from parents, teachers, and friends reported better attitudes and had higher perceptions of their abilities in math and science. Lastly, structural equation modeling revealed that social support had both a direct effect on math and science perceived abilities and an indirect effect mediated through math and science attitudes. Findings suggest that students who perceive greater social support for math and science from parents, teachers, and friends have more positive attitudes toward math and science and a higher sense of their own competence in these subjects.

Decoding enhancer complexity with machine learning and high-throughput discovery.

Enhancers are genomic DNA elements controlling spatiotemporal gene expression. Their flexible organization and functional redundancies make deciphering their sequence-function relationships challenging. This article provides an overview of the current understanding of enhancer organization and evolution, with an emphasis on factors that influence these relationships. Technological advancements, particularly in machine learning and synthetic biology, are discussed in light of how they provide new ways to understand this complexity. Exciting opportunities lie ahead as we continue to unravel the intricacies of enhancer function.

Noise in cesarean deliveries: a comprehensive analysis of noise environments in the Labor and Delivery operating room and evaluation of a visual alarm noise abatement program.

BACKGROUND: Cesarean delivery is the most common major surgery worldwide. Noise in healthcare settings leads to impaired communication and concentration, and stress among healthcare providers. Limited information is available about noise at cesarean delivery. OBJECTIVE: This study aimed to achieve a comprehensive analysis of noise that occurs during cesarean deliveries. Sound level meters are used to determine baseline noise levels and to describe the frequency of acute noise generated during a cesarean delivery that will cause a human startle response. Secondarily, we aimed to evaluate the effectiveness of a visual alarm system in mitigating excessive noise. STUDY DESIGN: We completed a preintervention/postintervention observational study of noise levels during cesarean deliveries before and after introduction of a visual alarm system for noise mitigation between February 15, 2021 and August 26, 2021. There were 156 cases included from each study period. Sound pressure levels were analyzed by overall case median decibel levels and by time epoch for relevant phases of the operation. Rapid increases in noise events capable of causing a human startle response, "startle events," were detected by retrospective analysis, with quantification for baselines and analysis of frequency by case type. Median noise levels with interquartile ranges are presented. Data are compared between epochs and case characteristics with nonparametric 2-tailed testing. RESULTS: The median acoustic pressure for all cesarean deliveries was 61.8 (58.8-65.9) (median [interquartile range]) dBA (A-weighted decibels). The median dBA for the full case time period was significantly higher in cases with neonatal intensive care unit team presence (62.1 [60.5-63.9]), admission to the neonatal intensive care unit (62.0 [60.4-63.9]), 5-minute Apgar score <7 (62.2 [61.1-64.3]), multiple gestations (62.6 [62.0-64.2]), and intraoperative tubal sterilization (62.8 [61.5-65.1]). The use of visual alarms was associated with a statistically significant reduction of median noise level by 0.7 dBA, from 61.8 (60.6-63.5) to 61.1 (59.8-63.7) dBA (P<.001). CONCLUSION: The noise intensities recorded during cesarean deliveries were commonly at levels that affect communication and concentration, and above the safe levels recommended by the World Health Organization. Although noise was reduced by 0.7 dBA, the reduction was not clinically significant in reaching a discernible amount (a 3-dB change) or in reducing "startle events." Isolated use of visual alarms during cesarean deliveries is unlikely to be a satisfactory noise mitigation strategy.

Prognostic Role of Targeted Methylation Analysis in Paraffin-embedded Samples of Adrenocortical Carcinoma.

CONTEXT: Adrenocortical carcinoma (ACC) is a rare aggressive disease with heterogeneous prognoses. Previous studies identified hypermethylation in the promoter region of specific genes to be associated with poor clinical outcome. OBJECTIVE: Comparative analysis of promising hypermethylated genes as prognostic markers and evaluation of their added value to established clinical prognostic tools. DESIGN: We included 237 patients with ACCs. Tumor DNA was isolated from formalin-fixed paraffin-embedded (FFPE) samples. Targeted pyrosequencing was used to detect promoter region methylation in 5 preselected genes (PAX5, GSTP1, PYCARD, PAX6, G0S2). The prognostic role of hypermethylation pattern was compared with the Stage, Grade, Resection status, Age, Symptoms (S-GRAS) score. Primary endpoints were progression-free (PFS) and overall survival (OS), with disease-free (DFS) as secondary endpoint. RESULTS: A total of 27.9%, 13.9%, 49%, 49%, and 25.3% of cases showed hypermethylation in PAX5, GSTP1, PYCARD, PAX6, and G0S2, respectively. Hypermethylation in all individual genes-except GSTP1-was significantly associated with both PFS and OS-with hazard ratios (HR) between 1.4 and 2.3. However, only hypermethylation of PAX5 remained significantly associated with OS (P = 0.013; HR = 1.95, 95% CI, 1.2-3.3) in multivariable analysis. A model for risk stratification was developed, combining PAX5 methylation status and S-GRAS groups, showing improved prognostic performance compared to S-GRAS alone (Harrell's C index: OS = 0.751, PFS = 0.711, DFS = 0.688). CONCLUSIONS: This study demonstrated that hypermethylation in PAX5 is associated with worst clinical outcome in ACC, even after accounting for S-GRAS score. Assessing methylation in FFPE material is straightforward in the clinical setting and could be used to improve accuracy of prognostic classification, enabling the direction of personalized management.

Tourism operator mental health and its relationship with SME organisational resilience during disasters.

Crises have a negative, and often long-lasting impact on mental health. The stress of dealing with the ongoing and unpredictable aspects of the COVID-19 pandemic has led to an unprecedented rise in mental health problems including low mood, depression and anxiety. Tourism businesses have faced ongoing challenges, with repeated lockdowns and drastically reduced tourist numbers and mental health challenges faced by operators may impact the resilience of tourism organisations and vice versa. Few studies have examined this. Our study in Victoria, Australia documents the mental health impacts of the COVID-19 crisis on owners and managers (operators) of small to medium tourism businesses and explores organisational factors that may impact or protect operator mental health during the crisis. Our findings show that the mental health of the cohort reached critically low levels over the course of the pandemic. We also identify positive associations between tourism organisational resilience and operator mental health.

Systemic and adipocyte transcriptional and metabolic dysregulation in idiopathic intracranial hypertension.

BACKGROUNDIdiopathic intracranial hypertension (IIH) is a condition predominantly affecting obese women of reproductive age. Recent evidence suggests that IIH is a disease of metabolic dysregulation, androgen excess, and an increased risk of cardiovascular morbidity. Here we evaluate systemic and adipose specific metabolic determinants of the IIH phenotype.METHODSIn fasted, matched IIH (n = 97) and control (n = 43) patients, we assessed glucose and insulin homeostasis and leptin levels. Body composition was assessed along with an interrogation of adipose tissue function via nuclear magnetic resonance metabolomics and RNA sequencing in paired omental and subcutaneous biopsies in a case-control study.RESULTSWe demonstrate an insulin- and leptin-resistant phenotype in IIH in excess of that driven by obesity. Adiposity in IIH is preferentially centripetal and is associated with increased disease activity and insulin resistance. IIH adipocytes appear transcriptionally and metabolically primed toward depot-specific lipogenesis.CONCLUSIONThese data show that IIH is a metabolic disorder in which adipose tissue dysfunction is a feature of the disease. Managing IIH as a metabolic disease could reduce disease morbidity and improve cardiovascular outcomes.FUNDINGThis study was supported by the UK NIHR (NIHR-CS-011-028), the UK Medical Research Council (MR/K015184/1), Diabetes UK, Wellcome Trust (104612/Z/14/Z), the Sir Jules Thorn Award, and the Midlands Neuroscience Teaching and Research Fund.

PDX1LOW MAFALOW ß-cells contribute to islet function and insulin release.

Transcriptionally mature and immature ß-cells co-exist within the adult islet. How such diversity contributes to insulin release remains poorly understood. Here we show that subtle differences in ß-cell maturity, defined using PDX1 and MAFA expression, contribute to islet operation. Functional mapping of rodent and human islets containing proportionally more PDX1HIGH and MAFAHIGH ß-cells reveals defects in metabolism, ionic fluxes and insulin secretion. At the transcriptomic level, the presence of increased numbers of PDX1HIGH and MAFAHIGH ß-cells leads to dysregulation of gene pathways involved in metabolic processes. Using a chemogenetic disruption strategy, differences in PDX1 and MAFA expression are shown to depend on islet Ca2+ signaling patterns. During metabolic stress, islet function can be restored by redressing the balance between PDX1 and MAFA levels across the ß-cell population. Thus, preserving heterogeneity in PDX1 and MAFA expression, and more widely in ß-cell maturity, might be important for the maintenance of islet function.

Leaf trait co-ordination in relation to construction cost, carbon gain and resource-use efficiency in exotic invasive and native woody vine species.

BACKGROUND AND AIMS: Success of invasive plant species is thought to be linked with their higher leaf carbon fixation strategy, enabling them to capture and utilize resources better than native species, and thus pre-empt and maintain space. However, these traits are not well-defined for invasive woody vines. METHODS: In a glass house setting, experiments were conducted to examine how leaf carbon gain strategies differ between non-indigenous invasive and native woody vines of south-eastern Australia, by investigating their biomass gain, leaf structural, nutrient and physiological traits under changing light and moisture regimes. KEY RESULTS: Leaf construction cost (CC), calorific value and carbon : nitrogen (C : N) ratio were lower in the invasive group, while ash content, N, maximum photosynthesis, light-use efficiency, photosynthetic energy-use efficiency (PEUE) and specific leaf area (SLA) were higher in this group relative to the native group. Trait plasticity, relative growth rate (RGR), photosynthetic nitrogen-use efficiency and water-use efficiency did not differ significantly between the groups. However, across light resource, regression analyses indicated that at a common (same) leaf CC and PEUE, a higher biomass RGR resulted for the invasive group; also at a common SLA, a lower CC but higher N resulted for the invasive group. Overall, trait co-ordination (using pair-wise correlation analyses) was better in the invasive group. Ordination using 16 leaf traits indicated that the major axis of invasive-native dichotomy is primarily driven by SLA and CC (including its components and/or derivative of PEUE) and was significantly linked with RGR. CONCLUSIONS: These results demonstrated that while not all measures of leaf resource traits may differ between the two groups, the higher level of trait correlation and higher revenue returned (RGR) per unit of major resource need (CC) and use (PEUE) in the invasive group is in line with their rapid spread where introduced.