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Abstract Background Sleep disturbance and insomnia are commonly reported by postmenopausal women. However, the relationship between hormone therapy (HT) and sleep disturbances in postmenopausal community-dwelling adults is understudied. Using data from the multicenter Study of Osteoporotic Fractures (SOF), we tested the relationship between HT and sleep-wake estimated from actigraphy. Methods Sleep-wake was ascertained by wrist actigraphy in 3,123 women aged 84 ± 4 years (range 77-99) from the Study of Osteoporotic Fractures (SOF). This sample represents 30% of the original SOF study and 64% of participants seen at this visit. Data were collected for a mean of 4 consecutive 24-hour periods. Sleep parameters measured objectively included total sleep time, sleep efficiency (SE), sleep latency, wake after sleep onset (WASO), and nap time. All analyses were adjusted for potential confounders (age, clinic site, race, BMI, cognitive function, physical activity, depression, anxiety, education, marital status, age at menopause, alcohol use, prior hysterectomy, and medical conditions). Results Actigraphy measurements were available for 424 current, 1,289 past, and 1,410 never users of HT. Women currently using HT had a shorter WASO time (76 vs. 82 minutes, P = 0.03) and fewer long-wake (≥ 5 minutes) episodes (6.5 vs. 7.1, P = 0.004) than never users. Past HT users had longer total sleep time than never users (413 vs. 403 minutes, P = 0.002). Women who never used HT had elevated odds of SE Conclusions Postmenopausal women currently using HT had improved sleep quality for two out of five objective measures: shorter WASO and fewer long-wake episodes. The mechanism behind these associations is not clear. For postmenopausal women, starting HT use should be considered carefully in balance with other risks since the vascular side-effects of hormone replacement may exceed its beneficial effects on sleep.

Abstract Background In recent years there has been an increasing problem with Staphylococcus aureus strains that are resistant to treatment with existing antibiotics. An important starting point for the development of new antimicrobial drugs is the identification of "essential" genes that are important for bacterial survival and growth. Results We have developed a robust microarray and PCR-based method, Transposon-Mediated Differential Hybridisation (TMDH), that uses novel bioinformatics to identify transposon inserts in genome-wide libraries. Following a microarray-based screen, genes lacking transposon inserts are re-tested using a PCR and sequencing-based approach. We carried out a TMDH analysis of the S. aureus genome using a large random mariner transposon library of around a million mutants, and identified a total of 351 S. aureus genes important for survival and growth in culture. A comparison with the essential gene list experimentally derived for Bacillus subtilis highlighted interesting differences in both pathways and individual genes. Conclusion We have determined the first comprehensive list of S. aureus essential genes. This should act as a useful starting point for the identification of potential targets for novel antimicrobial compounds. The TMDH methodology we have developed is generic and could be applied to identify essential genes in other bacterial pathogens.

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Objective: Identify contributors to differences in the muscle size and strength of sedentary and active young and middle-aged adults., Methods: This cross-sectional study included 98 participants aged 20-65 years. Participants were categorized based on age and self-reported physical activity (PA) habits. Participants completed a strength assessment of knee extensors (KEPT), knee flexors (KFPT), plantar flexors (PFPT), and dorsiflexors (DFPT), a 3-day dietary intake log, 7-day accelerometry, and a magnetic resonance imaging (MRI) scan for muscle cross-sectional area analysis of the right quadriceps (CSAq)., Results: There were significant age and activity-related group effects for relative protein intake (p<0.001), relative energy intake (p=0.04), KEPT (p=0.01), CSAq (p=0.002), PFPT (p=0.004) and DFPT (p=0.003). Moderate, moderate-to-vigorous, and vigorous PA were positively associated with CSAq (R 2 =0.69- 0.71; p<0.05), KEPT (R 2 =0.61-0.63; p<0.05), and PFPT (R 2 =0.31-0.36; p<0.05). Relative protein intake and daily leucine intake were significantly and positively associated with CSAq (R 2 =0.70 and 0.67 respectively; p<0.05), KEPT (R 2 =0.62 and 0.65 respectively; p<0.05), and PFPT (R 2 =0.29 and 0.28 respectively; p<0.05)., Conclusion: Muscle size and strength were lower in middle age relative to younger age, but increased PA, protein intake, and leucine intake was associated with the preservation of muscle size and strength in larger muscle groups of the lower body., (Copyright: © 2022 Hylonome Publications.)

Background: Metabolic syndrome (MetS) increases risk for morbidity and premature mortality. Blood pressure, waist circumference, and fasting triglycerides (TG), blood glucose (BG), and high-density lipoprotein cholesterol (HDL) are factors for determining MetS. The Simple Method for Quantifying Metabolic Syndrome (siMS) score and risk score estimate risk of MetS. The purpose for this study was to exam the relationship of animal-based (ABP) and plant-based protein (PLP) with MetS as estimated by siMS score and risk score. Physical activty is another important consideration in MetS as it can reduce blood pressure, waist circumference and blood glucose, and affect blood lipid and lipoprotein concentrations., Methods: A cross-sectional study examined whether physical activity (PA) level and dietary protein source (i.e., animal- or plant-based) among young (18-24 years) and middle-aged (45-60 years) females were associated with siMS score and siMS risk score. Average time spent in sedentary, light, and moderate-to-vigorous PA (MVPA; min/wk), steps (steps/day), energy intake (kcal/day), percent dietary protein to total energy intake, ABP and PLP dietary intake, and ABP:PLP ratio (g/day) were included in the analysis. Volunteers were recruited from North Dakota and Minnesota from 2017 to 2019., Results: Eighty-one female participants (mean ± SD; young, n = 38, 20.4 ± 1.7 years, middle-aged, 52.5 ± 4.8 years) were included in the independent t -tests used to examine group differences in age, body mass index, HDL, BG, TG, systolic blood pressure, waist circumference, energy intake, energy intake percentage of total carbohydrates, fat, protein, ABP, and PLP, ABP:PLP, siMS score, and siMS risk score. Stepwise linear regressions were used to evaluate whether PA level and dietary protein source were predictors of siMS score and siMS risk score among young and middle-aged adult females. There was an inverse relationship between PLP intake and siMS score. The model explained 6.9% of the variance in siMS risk score (F 1, 80  = 5.93). Plant-based protein intake was inversely related to siMS risk score while light PA was positively associated with siMS risk score. The model explained 16% of the variance in siMS risk score (F 1, 80  = 7.53). Animal-based dietary protein intake did not impact siMS score ( p  = 0.180) and siMS risk score ( p  = 0.283)., Conclusions: Plant-based protein intake was associated with a lower risk of MetS via siMS scores, while ABP was not associated. Given the nature of the cross-sectional design of this study, no causal relationship can be determined, but longitudinal studies or randomized control trials to confirm the results from this study are needed in the future., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: Evenness of protein intake is associated with increased lean mass, but its relationship with muscle strength and performance is uncertain., Objectives: We determined the association of evenness of protein intake with lean mass, muscle strength and endurance, and functional ability., Design: This was a cross-sectional study., Setting: Data were collected at a research university in the upper midwestern United States., Participants: One hundred ninety-two healthy women, aged 18 to 79 years, mean ± SEM 41.9 ± 1.3, completed the study., Measurements: Dietary intake was assessed using 3-day food diaries verified with food frequency questionnaires. To assess evenness of protein intake, the day was divided into 3 periods: waking to 11:30, 11:31 to 16:30, and after 16:30. Lean mass was measured with dual energy X-ray absorptiometry. Lower-body muscle strength and endurance were determined using isokinetic dynamometry. Upper-body muscle strength was maximal handgrip strength. Functional ability was assessed using 6-m gait speed and 30-second chair stand tests. Accelerometry measured physical activity., Results: Intakes of 25 g or more of protein at 1 or more of the 3 periods was positively associated with lean mass (β ± S.E.; 1.067 ± 0.273 kg, P  < .001) and upper-body (3.274 ± 0.737 kg, P  < .001) and lower-body strength (22.858 ± 7.918 Nm, P  = .004) when controlling for age, body mass index, physical activity, and energy and protein intakes. Consuming at least 0.24 g/kg/period for those under 60 years and 0.4 g/kg/period for those 60 years and older was related to lean mass (0.754 ± 0.244 kg, P  = .002), upper-body strength (2.451 ± 0.658 kg, P  < .001), and lower-body endurance (184.852 ± 77.185 J, P  = .018), controlling for the same variables., Conclusions: Evenness of protein intake is related to lean mass, muscle strength, and muscular endurance in women. Spreading protein intake throughout the day maximizes the anabolic response to dietary protein, benefiting muscle mass and performance., Competing Interests: Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: This project was funded by Beef Checkoff; this funder was not involved in data collection or analysis and did not affect, or in any way determine the contents of this manuscript., (© The Author(s) 2022.)

The 2015 and 2020 ozone holes set record sizes in October-December. We show that these years, as well as other recent large ozone holes, still adhere to a fundamental recovery metric: the later onset of early spring ozone depletion as chlorine and bromine diminishes. This behavior is also captured in the Whole Atmosphere Chemistry Climate Model. We quantify observed recovery trends of the onset of the ozone hole and in the size of the September ozone hole, with good model agreement. A substantial reduction in ozone hole depth during September over the past decade is also seen. Our results indicate that, due to dynamical phenomena, it is likely that large ozone holes will continue to occur intermittently in October-December, but ozone recovery will still be detectable through the later onset, smaller, and less deep September ozone holes: metrics that are governed more by chemical processes., (© 2021 The Authors.)

Bioconversion processes offer many economic, environmental, and societal advantages for production of fuels and chemicals. Successful commercialization of any biotechnology usually requires accurate characterization of cell growth dynamics, substrate conversion and production excretion rates. Despite recent advancements in analytical equipment, obtaining accurate measurement of gas component uptake or production rates remains challenging due to their high sensitivity to system pressure or volume changes. Specifically, the consumption and production of various gases will result in changes in system pressure (for batch operations) or off-gas flow rate (for continuous operations). These changes would cause significant errors in the estimated gas component uptake and production rates if they were not accounted for. In this work, we propose two easy-to-implement experimental protocols and associated calculation procedures to obtain accurate measurements of gas component consumption and production rates; one is for batch operation and one is for continuous operation. For depressurized (i.e., system pressure below 1 atm) batch cultures, nitrogen (or other inert gases) is used to repressurize the system to 1 atm before taking sample; while for continuous cultures, He (or other inert gases) is used as an internal tracer to accurately measure off-gas flow rate. The effectiveness and accuracy of the two protocols and associated calculation procedures are demonstrated using several case studies with both abiotic and biotic systems.

Climate models consistently predict an acceleration of the Brewer-Dobson circulation (BDC) due to climate change in the 21st century. However, the strength of this acceleration varies considerably among individual models, which constitutes a notable source of uncertainty for future climate projections. To shed more light upon the magnitude of this uncertainty and on its causes, we analyze the stratospheric mean age of air (AoA) of 10 climate projection simulations from the Chemistry Climate Model Initiative phase 1 (CCMI-I), covering the period between 1960 and 2100. In agreement with previous multi-model studies, we find a large model spread in the magnitude of the AoA trend over the simulation period. Differences between future and past AoA are found to be predominantly due to differences in mixing (reduced aging by mixing and recirculation) rather than differences in residual mean transport. We furthermore analyze the mixing efficiency, a measure of the relative strength of mixing for given residual mean transport, which was previously hypothesized to be a model constant. Here, the mixing efficiency is found to vary not only across models, but also over time in all models. Changes in mixing efficiency are shown to be closely related to changes in AoA and quantified to roughly contribute 10% to the long-term AoA decrease over the 21st century. Additionally, mixing efficiency variations are shown to considerably enhance model spread in AoA changes. To understand these mixing efficiency variations, we also present a consistent dynamical framework based on diffusive closure, which highlights the role of basic state potential vorticity gradients in controlling mixing efficiency and therefore aging by mixing., Competing Interests: Competing interests. The authors declare that they have no conflict of interest.

Background: There is an estimate of three to five million people who inject drugs living in Asia. Unsafe injecting drug use is a major driver of both the HIV and hepatitis C (HCV) epidemic in this region, and an increase in incidence among people who inject drugs continues. Although harm reduction is becoming increasingly accepted, a largely punitive policy remains firmly in place, undermining access to life-saving programmes. The aim of this study is to present an overview of key findings on harm reduction in Asia based on data collected for the Global State of Harm Reduction 2014., Methods: A review of international scientific and grey literature was undertaken between May and September 2014, including reports from multilateral agencies and international non-governmental organisations. A qualitative survey comprising open-ended questions was also administered to civil society, harm reduction networks, and organisations of people who use drugs to obtain national and regional information on key developments in harm reduction. Expert consultation from academics and key thinkers on HIV, drug use, and harm reduction was used to verify findings., Results: In 2014, 17 countries in Asia provide needle and syringe programmes (NSP) provision and 15 opioid substitution therapy (OST). It is estimated that between 60 and 90 % of people who use drugs in Asia have HCV; however, treatment still remains out of reach due to cost barriers. TB testing and treatment services are yet to be established for key populations, yet nearly 15 % of the global burden of new cases of HIV-TB co-infection are attributed to southeast Asia. Eighteen percent of the total number of people living with HIV eligible for antiretroviral treatment (ART) accessed treatment. Only Malaysia and Indonesia provide OST in prison, with no NSP provision in prisons in the region., Conclusion: To reduce HIV and viral hepatitis risk among people who inject drugs, there is a necessity to significantly increase harm reduction service provision in Asia. Although there has been progress, work still needs to be done to ensure an appropriate and enabling environment. At present, people who inject drugs are extremely difficult to reach; structural and legal barriers to services must be reduced, integrated holistic services introduced, and further research undertaken.

We investigate the combined effects of transmembrane proteins and the subjacent cytoskeleton on the dynamics of phase separation in multicomponent lipid bilayers using computer simulations of a particle-based implicit solvent model for lipid membranes with soft-core interactions. We find that microphase separation can be achieved by the protein confinement by the cytoskeleton. Our results have relevance to the finite size of lipid rafts in the plasma membrane of mammalian cells.

Background: New technology has made universal newborn hearing screening possible. Our goal was to investigate the feasibility of universal newborn screening using distortion product otoacoustic emissions (DPOAE) on infants in a community hospital in a normal newborn nursery., Methods: We used DPOAE to screen newborn infants from February 1997 to March 1999., Results: Of 1002 infants, 111 failed the initial screen (11.1%). When screening was repeated, only 2 infants failed. One infant failed the second screen and a tympanogram. He was treated and he passed a third use of DPOAE. An additional infant failed the repeat screen but passed the tympanogram. That infant was referred on for auditory brain response testing., Conclusions: DPOAE testing can be accomplished easily in a normal newborn nursery with an acceptable false-positive rate when a two-stage approach is used. The cost for each test was $19.88. The cost to find the 1 infant with sensory neural hearing loss was $22,114.

Background: Lithium can cause nephrogenic diabetes insipidus in up to 20 to 40 percent of patients currently taking the medication, and a subset of these patients will have a persistent concentrating defect long after lithium is discontinued. They are at risk for serious hypernatremia when fluid intake is restricted for any reason., Methods: MEDLINE as used to search the key words "nephrogenic diabetes insipidus" and "lithium" from 1990 to the present. A case report describes a patient who had been off lithium for 8 years and who developed hypernatremia after she was transferred to a new long-term facility and the staff attempted to control the patient's polydipsia. The diagnosis and treatment of nephrogenic diabetes insipidus are also discussed., Results: This case of persistent nephrogenic diabetes insipidus 8 years after discontinuing lithium is the longest ever reported. Certainly, a number of patients have varying degrees of persistent lithium-related nephrogenic diabetes insipidus. Although pathologic changes are associated with persistent nephrogenic diabetes insipidus, the exact mechanism of the persistent defect is unknown. The mechanism of acute lithium-induced nephrogenic diabetes insipidus while the patient is on lithium is related to changes in intracellular cyclic adenosine monophosphate., Conclusions: Patients currently taking lithium and patients with a remote history of lithium treatment need to be monitored for signs and symptoms of nephrogenic diabetes insipidus. Physicians need to be aware of the potential for nephrogenic diabetes insipidus in these patients and care for them appropriately.

A functional neuromuscular stimulation system has been developed to provide grasp-release function in quadriplegic individuals. A single command input from the subject controls the stimulus levels to a number of electrodes, thus simultaneously activating several muscles. A method for synthesizing the command input to stimulus output relationship has been developed. The first step involves electrode profiling, which is a method for characterizing the output of an individual electrode/muscle combination. The electrodes are then grouped according to function and a set of rule based procedures is used to synthesize the basic grasp parameters. Results are presented demonstrating the output from lateral and palmar grasps developed by this method. The method has successfully resulted in grasping patterns that can be utilized functionally. Limitations of the method and future improvements are discussed.