An assessment of uncontrolled human interventions on the contemporary sediment budget and morphological alterations of the Vu Gia Thu Bon River basin, central Vietnam.

The Vu Gia Thu Bon (VGTB) River basin is critical for regional development and prosperity in water resources. However, human interventions (e.g., dam construction and sand mining) have significantly affected this basin's sediment budget and morphological alterations over recent decades. Such humane actions drive an imbalance in water resources in the basin from upstream to downstream. Therefore, this study investigated spatiotemporal changes in sediment budget and morphology alterations using long-term data and bathymetric surveys; from these data, dams and sand mining contributions were quantified and differentiated. Based on field survey data and interviews, we estimated the sand-mining volume by incorporating reported and a newly proposed empirical formula. The results show that the total riverbed incision volume from 2010 to 2021 was 63.30 Mm3, with an incision rate of 0.14 m/yr. The officially reported sand-mining rate was 1.12 Mm3/yr, while the newly proposed empirical formula estimated 4.4 Mm3/yr. According to the developed empirical formula, the percentage reductions in the sediment budget due to sand mining and upstream dams were 69.7 % and 30.3 %, respectively, according to reports, and 17.8 % and 82.2 %. The statistical method was thus likely too conservative compared to the developed empirical formula. We found that the natural sediment supplies sourced from upstream were insufficient to compensate for the mined bed material. Therefore, our combination of different datasets permitted the assessment of future geomorphological developments within the VGTB River basin under the ongoing sediment deficits. The results of this study provide valuable insights into the impacts of human interventions, specifically sand mining, on the sediment budget, morphological alterations, and riverbed incision. The developed assessment forms the foundation for developing and expanding the region's water/sediment resource management strategies.

An efficient hybrid deep learning architecture for predicting short antimicrobial peptides.

Short-length antimicrobial peptides (AMPs) have been demonstrated to have intensified antimicrobial activities against a wide spectrum of microbes. Therefore, exploration of novel and promising short AMPs is highly essential in developing various types of antimicrobial drugs or treatments. In addition to experimental approaches, computational methods have been developed to improve screening efficiency. Although existing computational methods have achieved satisfactory performance, there is still much room for model improvement. In this study, we proposed iAMP-DL, an efficient hybrid deep learning architecture, for predicting short AMPs. The model was constructed using two well-known deep learning architectures: the long short-term memory architecture and convolutional neural networks. To fairly assess the performance of the model, we compared our model with existing state-of-the-art methods using the same independent test set. Our comparative analysis shows that iAMP-DL outperformed other methods. Furthermore, to assess the robustness and stability of our model, the experiments were repeated 10 times to observe the variation in prediction efficiency. The results demonstrate that iAMP-DL is an effective, robust, and stable framework for detecting promising short AMPs. Another comparative study of different negative data sampling methods also confirms the effectiveness of our method and demonstrates that it can also be used to develop a robust model for predicting AMPs in general. The proposed framework was also deployed as an online web server with a user-friendly interface to support the research community in identifying short AMPs.

Combining machine learning with high-content imaging to infer ciprofloxacin susceptibility in isolates of Salmonella Typhimurium.

Antimicrobial resistance (AMR) is a growing public health crisis that requires innovative solutions. Current susceptibility testing approaches limit our ability to rapidly distinguish between antimicrobial-susceptible and -resistant organisms. Salmonella Typhimurium (S. Typhimurium) is an enteric pathogen responsible for severe gastrointestinal illness and invasive disease. Despite widespread resistance, ciprofloxacin remains a common treatment for Salmonella infections, particularly in lower-resource settings, where the drug is given empirically. Here, we exploit high-content imaging to generate deep phenotyping of S. Typhimurium isolates longitudinally exposed to increasing concentrations of ciprofloxacin. We apply machine learning algorithms to the imaging data and demonstrate that individual isolates display distinct growth and morphological characteristics that cluster by time point and susceptibility to ciprofloxacin, which occur independently of ciprofloxacin exposure. Using a further set of S. Typhimurium clinical isolates, we find that machine learning classifiers can accurately predict ciprofloxacin susceptibility without exposure to it or any prior knowledge of resistance phenotype. These results demonstrate the principle of using high-content imaging with machine learning algorithms to predict drug susceptibility of clinical bacterial isolates. This technique may be an important tool in understanding the morphological impact of antimicrobials on the bacterial cell to identify drugs with new modes of action.

An Effective Health System Approach to End TB: Implementing the Double X Strategy in Vietnam.

Countries that are high burden for TB must reverse the COVID-19 pandemic's devastating effects to accelerate progress toward ending TB. Vietnam's Double X (2X) strategy uses chest radiography (CXR) and GeneXpert (Xpert) rapid diagnostic testing to improve early detection of TB disease. Household contacts and vulnerable populations (e.g., individuals aged 60 years and older, smokers, diabetics, those with alcohol use disorders, and those previously treated for TB) with and without TB symptoms were screened in community campaigns using CXRs, followed by Xpert for those with a positive screen. In public non-TB district facilities, diabetics, respiratory outpatients, inpatients with lung disease, and other vulnerable populations underwent 2X evaluation. During COVID-19 restrictions in Vietnam, the 2X strategy improved access to TB services by decentralization to commune health stations, the lowest level of the health system, and enabling self-screening using a quick response mobile application. The number needed to screen (NNS) with CXRs to diagnose 1 person with TB disease was calculated for all 2X models and showed the highest yield among self-screeners (11 NNS with CXR), high yield for vulnerable populations in communities (60 NNS) and facilities (19 NNS), and moderately high yield for household contacts in community campaigns (154 NNS). Computer-aided diagnosis for CXRs was incorporated into community and facility implementation and improved physicians' CXR interpretations and Xpert referral decisions. Integration of TB infection and TB disease evaluation increased eligibility for TB preventive treatment among household contacts, a major challenge during implementation. The 2X strategy increased the rational use of Xpert, employing a health system-wide approach that reached vulnerable populations with and without TB symptoms in communities and facilities for early detection of TB disease. This strategy was effectively adapted to different levels of the health system during COVID-19 restrictions and contributed to post-pandemic TB recovery in Vietnam.

The influence of attributes on community preferences regarding antibiotic treatment: evidence from a discrete choice model.

Antibiotic resistance (AR) rates in Vietnam are among the highest in Asia, and recent infections due to multi-drug resistance in the country have caused thousands of deaths each year. This study investigated a Vietnamese community's preferences for antibiotic treatment and its knowledge and attitudes regarding antibiotics. A discrete choice experiment-based survey was developed and administered to the population of interest. The respondents were given sociodemographic-, knowledge- and attitude-related items and 17 pairs of choice tasks. Two hypothetical options were included in each choice task. Latent class analysis was conducted to determine the differences among the respondents' preferences. Among 1,014 respondents, 805 (79.4%) gave valid questionnaires. A three-latent-class model with four covariates (age, healthcare-related education or career, occupation, and attitude classifications) was used in the analysis. All five attributes significantly influenced the respondents' decisions. The majority, including young employed respondents with non-healthcare-related work or education, found treatment failure more important. Older respondents who had healthcare-related education/careers and/or appropriate antibiotic use- and antibiotics resistance-related attitudes, regarded contribution to antibiotic resistance as an important attribute in selecting antibiotic treatments. Unemployed individuals with correct knowledge identified the cost of antibiotic treatment as the most essential decision-making factor. Findings suggest minimal antibiotic impact on resistance; only 7.83% view it as amajor concern. The respondents exhibited substantial preference heterogeneity, and the general Vietnamese public had poor knowledge of and attitudes toward antibiotic use and antibiotic resistance. This study emphasizes the need for individual responsibility for antibiotic resistance and appropriate antibiotic use.

Amyloid fibril polymorphism in the heart of an ATTR amyloidosis patient with polyneuropathy attributed to the V122Δ variant.

ATTR amyloidosis is a phenotypically heterogeneous disease characterized by the pathological deposition of transthyretin in the form of amyloid fibrils into various organs. ATTR amyloidosis may stem from mutations in variant (ATTRv) amyloidosis, or aging in wild-type (ATTRwt) amyloidosis. ATTRwt generally manifests as a cardiomyopathy phenotype, whereas ATTRv may present as polyneuropathy, cardiomyopathy, or mixed, in combination with many other symptoms deriving from secondary organ involvement. Over 130 different mutational variants of transthyretin have been identified, many of them being linked to specific disease symptoms. Yet, the role of these mutations in the differential disease manifestation remains elusive. Using cryo-electron microscopy, here we structurally characterized fibrils from the heart of an ATTRv patient carrying the V122Δ mutation, predominantly associated with polyneuropathy. Our results show that these fibrils are polymorphic, presenting as both single and double filaments. Our study alludes to a structural connection contributing to phenotypic variation in ATTR amyloidosis, as polymorphism in ATTR fibrils may manifest in patients with predominantly polyneuropathic phenotypes.

Spatial and temporal-trend assessment of desertification-sensitive land using the desertification sensitivity index in the provincial Ninh Thuan, Vietnam.

Desertification is a specific land-degrading process, reducing soil productivity and potentially threatening global food security. Therefore, spatially and temporally identifying and mapping desertification-sensitive areas is essential for better management. The current study aimed to (1) assess spatial areas sensitive to desertification and (2) examine the changing tendency of the desertification-sensitive areas over the past 25 years in the provincial Ninh Thuan. The desertification sensitivity index (DSI) was computed based on the Medalus model using 10 quantitative parameters, grouped into the soil, climate, and vegetation quality indexes, computed for the years 1996, 2005, 2010, and 2016. GIS was used to map desertification-sensitive areas associated with five DSI classes. Results showed that classes II and III had the highest area percentage, followed by classes IV and V, and class I. The classes most sensitive to desertification (classes IV and V) covered around 13 to 17%, and classes II and III were 25 to 32% of the total study area, respectively. The coastal areas located in the southeastern parts were more sensitive to desertification than the other parts. Over the four examined periods, the areas of classes IV and V increased while those of classes II and I decreased. These indicated that the study province tended to increase in its desertification sensitivity with a severe increase in the coastal areas over the past 25 years. The key factors involved in these changes could be related the human activities and climate variation, which could be more serious in southeastern areas than in the other areas.

The association of diet quality and physical activity with cardiovascular disease and mortality in 85,545 older Australians: A longitudinal study.

BACKGROUND: A quality diet and an active lifestyle are both important cornerstones of cardiovascular disease (CVD) prevention. However, despite their interlinked effects on metabolic health, the 2 behaviors are rarely considered jointly, particularly within the context of CVD prevention. We examined the independent, interactive, and joint associations of diet and physical activity with CVD hospitalization, CVD mortality, and all-cause mortality. METHODS: CVD-free Australian participants aged 45-74 years (n = 85,545) reported physical activity, diet, and sociodemographic and lifestyle characteristics at baseline (2006-2009) and follow-up (2012-2015), and data were linked to hospitalization and death registries (03/31/2019 for CVD hospitalization and all-cause mortality and 12/08/2017 for CVD mortality). Diet quality was categorized as low, medium, and high based on meeting dietary recommendations. Physical activity was operationalized as (a) total moderate-to-vigorous physical activity (MVPA) as per guidelines, and (b) the composition of MVPA as the ratio of vigorous-intensity physical activity (VPA) to total MVPA. We used a left-truncated cause-specific Cox proportional hazards model using time-varying covariates. RESULTS: During a median of 10.7 years of follow-up, 6576 participants were admitted to the hospital for CVD and 6581 died from all causes (876 from CVD during 9.3 years). A high-quality diet was associated with a 17% lower risk of all-cause mortality than a low-quality diet, and the highest MVPA category (compared with the lowest) was associated with a 44% and 48% lower risk of CVD and all-cause mortality, respectively. Multiplicative interactions between diet and physical activity were non-significant. For all outcomes, the lowest risk combinations involved a high-quality diet and the highest MVPA categories. Accounting for total MVPA, some VPA was associated with further risk reduction of CVD hospitalization and all-cause mortality. CONCLUSION: For CVD prevention and longevity, one should adhere to both a healthy diet and an active lifestyle and incorporate some VPA when possible.

Trajectories of Physical Activity and Chronic Conditions Among Mid-Aged Women.

INTRODUCTION: Women's physical activity levels vary throughout adulthood. However, the associations between trajectories of physical activity and health outcomes have been little studied. The aim of this study was to examine the associations of physical activity trajectories with incident diabetes, hypertension, obesity, depression, and physical disability in mid-aged women. METHODS: Data were from the 1946-51 cohort of the Australian Longitudinal Study on Women's Health (n=11,611). Mailed surveys at 3-year intervals from 1998 (age 47-52) to 2019 (age 68-73) were used to collect data on physical activity and each outcome. The analyses were conducted in 2023/24. Physical activity trajectories from age 47-61 (2-4 time-points) were identified using group-based trajectory modeling. Cox regression models with time-varying covariates were used to examine the associations of physical activity trajectories with adverse health outcomes onset from ages 56-73 (2-5 time-points). RESULTS: Trajectories of physical activity were labeled as Low (59.7% of participants), Declining (5.9%), Increasing (26.3%), and High (8.1%). The median of 9-year overall physical activity (MET.minutes/week) was 450 in the Low, 1324 in the Declining, 1399 in the Increasing, and 2323 in the High group. Compared with the Low group, the risks of diabetes, obesity and physical disability were lower in the Increasing and High groups, and the risk of depression was lower in the High group. Conversely, the risk of obesity was higher in the Declining group. CONCLUSIONS: Targeting mid-aged women with declining physical activity for prevention programs could enhance health in later life.

A prediction model of abnormal acid reflux in gastroesophageal reflux disease.

BACKGROUND AND AIM: The measurement of esophageal acid exposure time (AET) using combined multichannel intraluminal impedance-pH (MII-pH) tests is the gold standard for diagnosing gastroesophageal reflux disease (GERD). However, this catheter-based 24-h test can cause considerable patient discomfort. Our aim is to identify factors affecting AET and to develop a scoring model for predicting AET abnormalities before conducting the MII-pH test. METHODS: Of the 366 patients who underwent MII-pH test at two facilities in Japan and Vietnam, 255 patients who also had esophagogastroduodenoscopy and high-resolution manometry were included in this study. Logistic regression analysis was conducted using risk factors for AET > 6% identified from a derivation cohort (n = 109). A scoring system predicting AET > 6% was then constructed and externally validated with a separate cohort (n = 146). RESULTS: Three variables were derived from the prediction model: male gender, Hill grades III-IV, and weak mean distal contractile integrals. Based on these scores, patients were classified into low (0 point), intermediate (1-3 points), and high (4 points) risk groups. The probabilities of having an AET > 6% were 6%, 34%, and 100% for these groups, respectively. A score of < 1 excluded patients with abnormal AET, with a negative predictive value of 93.8% in the derivation cohort and 80.0% in the validation cohort. CONCLUSIONS: We derived and externally validated a prediction model for abnormal AET. This system could assist in guiding the appropriate treatment strategies for GERD.

Identification of Critical Immune Regulators and Potential Interactions of IL-26 in Riemerella anatipestifer-Infected Ducks by Transcriptome Analysis and Profiling.

Riemerella anatipestifer (RA) is an economically important pathogen in the duck industry worldwide that causes high mortality and morbidity in infected birds. We previously found that upregulated IL-17A expression in ducks infected with RA participates in the pathogenesis of the disease, but this mechanism is not linked to IL-23, which primarily promotes Th17 cell differentiation and proliferation. RNA sequencing analysis was used in this study to investigate other mechanisms of IL-17A upregulation in RA infection. A possible interaction of IL-26 and IL-17 was discovered, highlighting the potential of IL-26 as a novel upstream cytokine that can regulate IL-17A during RA infection. Additionally, this process identified several important pathways and genes related to the complex networks and potential regulation of the host immune response in RA-infected ducks. Collectively, these findings not only serve as a roadmap for our understanding of RA infection and the development of new immunotherapeutic approaches for this disease, but they also provide an opportunity to understand the immune system of ducks.

Digital Interventions to Understand and Mitigate Stress Response: Protocol for Process and Content Evaluation of a Cohort Study.

BACKGROUND: Staffing and resource shortages, especially during the COVID-19 pandemic, have increased stress levels among health care workers. Many health care workers have reported feeling unable to maintain the quality of care expected within their profession, which, at times, may lead to moral distress and moral injury. Currently, interventions for moral distress and moral injury are limited. OBJECTIVE: This study has the following aims: (1) to characterize and reduce stress and moral distress related to decision-making in morally complex situations using a virtual reality (VR) scenario and a didactic intervention; (2) to identify features contributing to mental health outcomes using wearable, physiological, and self-reported questionnaire data; and (3) to create a personal digital phenotype profile that characterizes stress and moral distress at the individual level. METHODS: This will be a single cohort, pre- and posttest study of 100 nursing professionals in Ontario, Canada. Participants will undergo a VR simulation that requires them to make morally complex decisions related to patient care, which will be administered before and after an educational video on techniques to mitigate distress. During the VR session, participants will complete questionnaires measuring their distress and moral distress, and physiological data (electrocardiogram, electrodermal activity, plethysmography, and respiration) will be collected to assess their stress response. In a subsequent 12-week follow-up period, participants will complete regular assessments measuring clinical outcomes, including distress, moral distress, anxiety, depression, and loneliness. A wearable device will also be used to collect continuous data for 2 weeks before, throughout, and for 12 weeks after the VR session. A pre-post comparison will be conducted to analyze the effects of the VR intervention, and machine learning will be used to create a personal digital phenotype profile for each participant using the physiological, wearable, and self-reported data. Finally, thematic analysis of post-VR debriefing sessions and exit interviews will examine reoccurring codes and overarching themes expressed across participants' experiences. RESULTS: The study was funded in 2022 and received research ethics board approval in April 2023. The study is ongoing. CONCLUSIONS: It is expected that the VR scenario will elicit stress and moral distress. Additionally, the didactic intervention is anticipated to improve understanding of and decrease feelings of stress and moral distress. Models of digital phenotypes developed and integrated with wearables could allow for the prediction of risk and the assessment of treatment responses in individuals experiencing moral distress in real-time and naturalistic contexts. This paradigm could also be used in other populations prone to moral distress and injury, such as military and public safety personnel. TRIAL REGISTRATION: ClinicalTrials.gov NCT05923398; https://clinicaltrials.gov/study/NCT05923398. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54180.

ATTRv-V30M Type A amyloid fibrils from heart and nerves exhibit structural homogeneity.

ATTR amyloidosis is a systemic disease characterized by the deposition of amyloid fibrils made of transthyretin, a protein integral to transporting retinol and thyroid hormones. Transthyretin is primarily produced by the liver and circulates in blood as a tetramer. The retinal epithelium also secretes transthyretin, which is secreted to the vitreous humor of the eye. Because of mutations or aging, transthyretin can dissociate into amyloidogenic monomers triggering amyloid fibril formation. The deposition of transthyretin amyloid fibrils in the myocardium and peripheral nerves causes cardiomyopathies and neuropathies, respectively. Using cryo-electron microscopy, here we determined the structures of amyloid fibrils extracted from cardiac and nerve tissues of an ATTRv-V30M patient. We found that fibrils from both tissues share a consistent structural conformation, similar to the previously described structure of cardiac fibrils from an individual with the same genotype, but different from the fibril structure obtained from the vitreous humor. Our study hints to a uniform fibrillar architecture across different tissues within the same individual, only when the source of transthyretin is the liver. Moreover, this study provides the first description of ATTR fibrils from the nerves of a patient and enhances our understanding of the role of deposition site and protein production site in shaping the fibril structure in ATTRv-V30M amyloidosis.

Multi-organ structural homogeneity of amyloid fibrils in ATTRv-T60A amyloidosis patients, revealed by Cryo-EM.

ATTR amyloidosis is a degenerative disorder characterized by the systemic deposition of the protein transthyretin. These amyloid aggregates of transthyretin (ATTR) can deposit in different parts of the body causing diverse clinical manifestations. Our laboratory aims to investigate a potential relationship between the different genotypes, organ of deposition, clinical phenotypes, and the structure of ATTR fibrils. Using cryo-electron microscopy, we have recently described how the neuropathic related mutations ATTRv-I84S and ATTRv-V122∆ can drive structural polymorphism in ex vivo fibrils. Here we question whether the mutation ATTRv-T60A, that commonly triggers cardiac and neuropathic symptoms, has a similar effect. To address this question, we extracted and determined the structure of ATTR-T60A fibrils from multiple organs (heart, thyroid, kidney, and liver) from the same patient and from the heart of two additional patients. We have found a consistent conformation among all the fibril structures, acquiring the "closed-gate morphology" previously found in ATTRwt and others ATTRv related to cardiac or mixed manifestations. The closed-gate morphology is composed by two segments of the protein that interact together forming a polar channel, where the residues glycine 57 to isoleucine 68 act as a gate of the polar cavity. Our study indicates that ATTR-T60A fibrils present in peripheral organs adopt the same structural conformation in all patients, regardless of the organ of deposition.

Low HBV knowledge is associated with low HBV vaccination uptake in general adult population despite incentivization of HBV vaccination.

BACKGROUND: Hepatitis B virus (HBV) vaccination in Vietnamese adults remains low and unequally distributed. We conducted a study on HBV-naïve adults living in Ho Chi Minh City, Viet Nam, to determine barriers associated with HBV vaccination uptake after removing the financial barrier by providing free coupons for HBV vaccination. METHODS: After being screened for HBsAg, anti-HBs, and anti-HBc, 284 HBV-naïve study participants aged 18 and over (i.e., negative for HBsAg, anti-HBs, and anti-HBc total) were provided free 3-dose HBV vaccine coupons. Next, study participants' receipt of 1st, 2nd, and 3rd doses of HBV vaccine was documented at a pre-specified study healthcare facility, where HBV vaccines were distributed at no cost to the participants. Upon study entry, participants answered questionnaires on sociodemographics, knowledge of HBV and HBV vaccination, and related social and behavioral factors. The proportions of three doses of HBV vaccine uptake and their confidence intervals were analyzed. Associations of HBV vaccine initiation with exposures at study entry were evaluated using modified Poisson regression. RESULTS: 98.9% (281 of 284) of study participants had complete data and were included in the analysis. The proportion of participants obtaining the 1st, 2nd, and 3rd doses of HBV vaccine was 11.7% (95% Confidence Interval [95% CI] 8.0-15.5%), 10.7% (95%CI 7.1-14.3%), and 8.9% (95%CI 5.6-12.2%), respectively. On the other hand, participants were more likely to initiate the 1st dose if they had adequate knowledge of transmission (adjusted relative risk [aRR] = 2.58, 95% CI 1.12-5.92), adequate knowledge of severity (aRR = 6.75, 95%CI 3.38-13.48), and annual health-checking seeking behavior (aRR = 2.04, 95%CI 1.07-3.87). CONCLUSION: We documented a low HBV vaccination uptake despite incentivization. However, increased vaccine initiation was associated with better HBV knowledge and annual health check-up adherence. When considering expanding HBV vaccination to the general adult population, we should appreciate that HBV knowledge is an independent predictor of vaccine uptake.

Physical activity across midlife and health-related quality of life in Australian women: A target trial emulation using a longitudinal cohort.

BACKGROUND: There is little long-term causal evidence on the effect of physical activity on health-related quality of life. This study aimed to examine the associations between longitudinal patterns of physical activity over 15 years and health-related quality of life in both the physical and mental health domains, in a cohort of middle-aged Australian women. METHODS AND FINDINGS: We used data collected at 3-year intervals (1998 to 2019) from 11,336 participants in the Australian Longitudinal Study on Women's Health (ALSWH) (1946 to 1951 birth cohort). Primary outcomes were the physical (PCS) and mental health component summary (MCS) scores (range from 0 to 100; higher scores indicate higher perceived physical/mental health) from the SF-36 in 2019 (when women aged 68 to 73 years). Using target trial emulation to imitate a randomized controlled trial (RCT), we tested 2 interventions: (1) meeting the World Health Organization (WHO) physical activity guidelines consistently throughout the 15-year "exposure period" (2001 to 2016; when women aged 50-55 to 65-70 years; physical activity assessed every 3 years); and (2) not meeting the guidelines at the beginning of the exposure period but starting to first meet the guidelines at age 55, 60, or 65; against the control of not meeting the guidelines throughout the exposure period. Analysis controlled for confounding using marginal structural models which were adjusted for sociodemographic and health variables and conditions. Consistent adherence to guidelines during the exposure period (PCS: 46.93 [99.5% confidence interval [CI]: 46.32, 47.54]) and first starting to meet the guidelines at age 55 (PCS: 46.96 [99.5% CI: 45.53, 48.40]) were associated with three-point higher PCS (mean score difference: 3.0 [99.5% CI: 1.8, 4.1] and 3.0 [99.5% CI:1.2, 4.8]) than consistent non-adherence (PCS: 43.90 [99.5% CI: 42.79, 45.01]). We found a similar pattern for most SF-36 subscales but no significant effects of the interventions on MCS. The main limitations of the study were that it may not account for all underlying health conditions and/or other unmeasured or insufficiently measured confounders, the use of self-reported physical activity and that findings may not be generalizable to all mid-age women. CONCLUSIONS: Results from the emulated RCT suggest women should be active throughout mid-age, ideally increasing activity levels to meet the guidelines by age 55, to gain the most benefits for physical health in later life.

Enhanced photoreduction efficiency of Cr(VI) driven by visible light in a new Zr-based metal-organic framework modified by hydroxyl groups.

While metal-organic framework (MOF) photocatalysts have demonstrated a unique Cr(VI) photoreduction capability in recent decades, their performance is still insufficient for practical applications because of their low Cr(VI) uptake and poor visible light response. To cope with these drawbacks, a new OH-modified Zr-based MOF, termed HCMUE-1, was successfully prepared via a solvothermal method in this work. The complete characterization of HCMUE-1 was performed through various techniques, including powder X-ray diffraction (PXRD), Raman spectroscopy, Fourier transform infrared (FT-IR), thermogravimetric analysis and differential scanning calorimetry (TGA-DSC), scanning electron microscopy combined with energy-dispersive X-ray (SEM-EDX), and X-ray photoelectron spectroscopy (XPS). The obtained data exhibited the excellent Cr(VI) photoreduction efficiency of HCMUE-1, reaching up to 98% after 90 min and almost 100% after 120 min under visible light illumination in a low acidic medium. Noteworthily, HCMUE-1 retained the same Cr(VI) removal rate for at least seven cycles without considerable loss. Further experimental investigations demonstrated that the structural stability and surface morphology of HCMUE-1 were retained after photoreduction. Moreover, the photocatalytic reduction mechanism of Cr(VI) to Cr(III) was interpreted through a series of systematic experimental measurements. These results indicate that HCMUE-1 possesses potential as an efficient photocatalyst for reducing toxic Cr(VI) species from wastewater in real-life conditions.

Subunit Communication within Dimeric SF1 DNA Helicases.

Monomers of the Superfamily (SF) 1 helicases, E. coli Rep and UvrD, can translocate directionally along single stranded (ss) DNA, but must be activated to function as helicases. In the absence of accessory factors, helicase activity requires Rep and UvrD homo-dimerization. The ssDNA binding sites of SF1 helicases contain a conserved aromatic amino acid (Trp250 in Rep and Trp256 in UvrD) that stacks with the DNA bases. Here we show that mutation of this Trp to Ala eliminates helicase activity in both Rep and UvrD. Rep(W250A) and UvrD(W256A) can still dimerize, bind DNA, and monomers still retain ATP-dependent ssDNA translocase activity, although with ∼10-fold lower rates and lower processivities than wild type monomers. Although neither wtRep monomers nor Rep(W250A) monomers possess helicase activity by themselves, using both ensemble and single molecule methods, we show that helicase activity is achieved upon formation of a Rep(W250A)/wtRep hetero-dimer. An ATPase deficient Rep monomer is unable to activate a wtRep monomer indicating that ATPase activity is needed in both subunits of the Rep hetero-dimer. We find the same results with E. coli UvrD and its equivalent mutant (UvrD(W256A)). Importantly, Rep(W250A) is unable to activate a wtUvrD monomer and UvrD(W256A) is unable to activate a wtRep monomer indicating that specific dimer interactions are required for helicase activity. We also demonstrate subunit communication within the dimer by virtue of Trp fluorescence signals that only are present within the Rep dimer, but not the monomers. These results bear on proposed subunit switching mechanisms for dimeric helicase activity.

Comparative Analysis of Antibiotic Resistance and Biofilm Characteristics of Two Major Enterococcus Species from Poultry Slaughterhouses in South Korea.

The spread of antibiotic-resistant Enterococcus in the poultry industry poses significant public health challenges due to multidrug resistance and biofilm formation. We investigated the antibiotic resistance profiles and biofilm characteristics of E. faecalis and E. faecium isolates from chicken meat in poultry slaughterhouses in South Korea. Ninety-six isolates (forty-eight each of E. faecalis and E. faecium) were collected between March and September 2022. Both species were analyzed using MALDI-TOF, PCR, antibiotic susceptibility testing, and biofilm assays. A high level of multidrug resistance was observed in E. faecalis (95.8%) and E. faecium (93.8%), with E. faecium exhibiting a broader range of resistance, particularly to linezolid (52.1%) and rifampicin (47.9%). All E. faecalis isolates formed biofilm in vitro, showing stronger biofilm formation than E. faecium with a significant difference (p < 0.001) in biofilm strength. Specific genes (cob, ccf, and sprE) were found to be correlated with biofilm strength. In E. faecium isolates, biofilm strength was correlated with resistance to linezolid and rifampicin, while a general correlation between antibiotic resistance and biofilm strength was not established. Through analysis, correlations were noted between antibiotics within the same class, while no general trends were evident in other analyzed factors. This study highlights the public health risks posed by multidrug-resistant enterococci collected from poultry slaughterhouses, emphasizing the complexity of the biofilm-resistance relationship and the need for enhanced control measures.

Cryo-EM confirms a common fibril fold in the heart of four patients with ATTRwt amyloidosis.

ATTR amyloidosis results from the conversion of transthyretin into amyloid fibrils that deposit in tissues causing organ failure and death. This conversion is facilitated by mutations in ATTRv amyloidosis, or aging in ATTRwt amyloidosis. ATTRv amyloidosis exhibits extreme phenotypic variability, whereas ATTRwt amyloidosis presentation is consistent and predictable. Previously, we found an unprecedented structural variability in cardiac amyloid fibrils from polyneuropathic ATTRv-I84S patients. In contrast, cardiac fibrils from five genotypically-different patients with cardiomyopathy or mixed phenotypes are structurally homogeneous. To understand fibril structure's impact on phenotype, it is necessary to study the fibrils from multiple patients sharing genotype and phenotype. Here we show the cryo-electron microscopy structures of fibrils extracted from four cardiomyopathic ATTRwt amyloidosis patients. Our study confirms that they share identical conformations with minimal structural variability, consistent with their homogenous clinical presentation. Our study contributes to the understanding of ATTR amyloidosis biopathology and calls for further studies.