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BackgroundPsychological distress is a common occurrence among women during the perinatal period. Maternal psychological distress (MPS) can also have a negative influence on neonatal outcomes such as infant health, child development or mother-child interaction. Hence, interventions to improve mental wellbeing during this period are vital. Mindfulness based intervention (MBI) has been found to be effective in reducing psychological distress. Delivery of MBI via the internet, making it accessible and inexpensive, is showing a promising positive effect in reducing psychological distress. A randomized control trial with sufficient power is required to confirm its positive effect among pregnant women. The positive effects of MBI have been found to be associated with heart rate variability (HRV) biofeedback; however, the efficacy of MBI on HRV has been rarely studied among pregnant women. Also, the potential association of HRV with MBI and psychological wellbeing needs further examination. This research aims to test the effectiveness of guided mobile-based perinatal mindfulness intervention (GMBPMI) among pregnant women experiencing psychological distress during the pre- and post-natal period, as well as examining the efficacy of GMBPMI on HRV.MethodThis study is a randomized controlled trial that follows a parallel design. Consenting pregnant women in their second trimester (between 12th and 20th week gestation) will be randomly assigned to an intervention group (GMBPMI) or a control group (psychoeducation). The intended sample size is 198, with 99 participants in each group. Three levels of outcomes will be measured at baseline, post intervention in both the intervention and control groups, and at 36-week gestation and five-week postpartum. The primary outcomes include maternal psychological stress, mindfulness and positive appraisal HRV. Secondary outcomes are psychological and physical wellbeing. Tertiary outcomes include obstetric and neonatal outcomes, and social support. Analyses will follow an intention-to-treat method and repeated measures MANOVA will be conducted to compare changes in primary and secondary outcomes. A series of mixed-effects models will be fitted to assess the mediation effects.DiscussionThis trial expects to increase understanding of GMBPMI on HRV and psychological wellbeing for pregnant women, with extended support in both pre-and post-natal periods. The study could also potentially provide evidence for delivery of cost-effective and accessible services to pregnant women.Trial registrationClinicalTrials.gov: NCT04876014, registered on 30 March 2021. Protocol Version 1.0., 10 May 2021.

There are limited data regarding bone health in older people living with HIV (PWH), especially those of Asian ethnicity. We aimed to determine whether BMD in well-suppressed HIV-infected men and women aged ≥ 50 years are different from HIV-uninfected controls. In a cross-sectional study, BMD by dual-energy X-ray absorptiometry and calciotropic hormones were measured. A total of 481 participants were consecutively enrolled (209 HIV+ men, 88 HIV- men, 126 HIV+ women and 58 HIV- women). PWH were on average 2.5 years younger [men: 55.0 vs. 57.5 yr; women: 54.0 vs. 58.0 yr] and had lower body mass index (BMI) [men: 23.2 vs. 25.1 kg/m2; women: 23.1 vs. 24.7 kg/m2] compared to the controls. The median duration since HIV diagnosis was 19 (IQR 15–21) years in men and 18 (IQR 15–21) years in women. Three-quarters of PWH had been treated with tenofovir disoproxil fumarate-containing antiretroviral therapy for a median time of 7.4 (IQR 4.5–8.9) years in men and 8.2 (IQR 6.1–10) years in women. In an unadjusted model, HIV+men had significantly lower BMD (g/cm2) at the total hip and femoral neck whereas there was a tend toward lower BMD in HIV+women. After adjusting for age, BMI, and other traditional osteoporotic risk factors, BMD of virologically suppressed older PWH did not differ from participants without HIV (P>0.1). PWH had lower serum 25(OH)D levels but this was not correlated with BMD. In conclusion, BMD in well-suppressed PWH is not different from non-HIV people, therefore, effective control of HIV infection and minimization of other traditional osteoporosis risk factors may help maintain good skeletal health and prevent premature bone loss in Asian PWH. Clinical trial registration: Clinicaltrials.gov # NCT00411983.

Background The prevalence of coeliac disease (CD) is around 1%, but diagnosis is challenged by varied presentation and non-specific symptoms and signs. This study aimed to identify diagnostic indicators that may help identify patients at a higher risk of CD in whom further testing is warranted. Methods International guidance for systematic review methods were followed and the review was registered at PROSPERO (CRD42020170766). Six databases were searched until April 2021. Studies investigating diagnostic indicators, such as symptoms or risk conditions, in people with and without CD were eligible for inclusion. Risk of bias was assessed using the QUADAS-2 tool. Summary sensitivity, specificity, and positive predictive values were estimated for each diagnostic indicator by fitting bivariate random effects meta-analyses. Findings 191 studies reporting on 26 diagnostic indicators were included in the meta-analyses. We found large variation in diagnostic accuracy estimates between studies and most studies were at high risk of bias. We found strong evidence that people with dermatitis herpetiformis, migraine, family history of CD, HLA DQ2/8 risk genotype, anaemia, type 1 diabetes, osteoporosis, or chronic liver disease are more likely than the general population to have CD. Symptoms, psoriasis, epilepsy, inflammatory bowel disease, systemic lupus erythematosus, fractures, type 2 diabetes, and multiple sclerosis showed poor diagnostic ability. A sensitivity analysis revealed a 3-fold higher risk of CD in first-degree relatives of CD patients. Conclusions Targeted testing of individuals with dermatitis herpetiformis, migraine, family history of CD, HLA DQ2/8 risk genotype, anaemia, type 1 diabetes, osteoporosis, or chronic liver disease could improve case-finding for CD, therefore expediting appropriate treatment and reducing adverse consequences. Migraine and chronic liver disease are not yet included as a risk factor in all CD guidelines, but it may be appropriate for these to be added. Future research should establish the diagnostic value of combining indicators.

Most non-Māori-speaking New Zealanders are regularly exposed to Māori throughout their lives without seeming to build any extensive Māori lexicon; at best, they know a small number of words which are frequently used and sometimes borrowed into English. Here, we ask how many Māori words non-Māori-speaking New Zealanders know, in two ways: how many can they identify as real Māori words, and how many can they actively define? We show that non-Māori-speaking New Zealanders can readily identify many more Māori words than they can define, and that the number of words they can reliably define is quite small. This result adds crucial support to the idea presented in earlier work that non-Māori-speaking New Zealanders have implicit form-based (proto-lexical) knowledge of many Māori words, but explicit semantic (lexical) knowledge of few. Building on this distinction, we further ask how different levels of word knowledge modulate effects of phonotactic probability on the accessing of that knowledge, across both tasks and participants. We show that participants’ implicit word knowledge leads to effects of phonotactic probability–and related effects of neighbourhood density–in a word/non-word discrimination task, but not in a more explicit task that requires the active definition of words. Similarly, we show that the effects of phonotactic probability on word/non-word discrimination are strong among participants who appear to lack explicit word knowledge, as indicated by their weak discrimination performance, but absent among participants who appear to have explicit word knowledge, as indicated by their strong discrimination performance. Together, these results suggest that phonotactic probability plays its strongest roles in the absence of explicit semantic knowledge.

[This corrects the article DOI: 10.1371/journal.pone.0265254.].

Focused ultrasound (FUS) exposure with the presence of microbubbles has been shown to transiently open the blood-brain barrier (BBB), and thus has potential to enhance the delivery of various kinds of therapeutic agents into brain tumors. The purpose of this study was to assess the preclinical therapeutic efficacy of FUS-BBB opening for enhanced temozolomide (TMZ) delivery in glioma treatment. FUS exposure with microbubbles was delivered to open the BBB of nude mice that were either normal or implanted with U87 human glioma cells. Different TMZ dose regimens were tested, ranging from 2.5 to 25 mg/kg. Plasma and brain samples were obtained at different time-points ranging from 0.5 to 4 hours, and the TMZ concentration within samples was quantitated via a developed LC-MS/MS procedure. Tumor progression was followed with T2-MRI, and animal survival and brain tissue histology were conducted. Results demonstrated that FUS-BBB opening caused the local TMZ accumulation in the brain to increase from 6.98 to 19 ng/mg. TMZ degradation time in the tumor core was found to increase from 1.02 to 1.56 hours. Improved tumor progression and animal survival were found at different TMZ doses (up to 15% and 30%, respectively). In conclusion, this study provides preclinical evidence that FUS-BBB opening increases the local concentration of TMZ to improve the control of tumor progression and animal survival, suggesting the potential for clinical application to improve current brain tumor treatment.

The purpose of this study is to assess the preclinical therapeutic efficacy of magnetic resonance imaging (MRI)-monitored focused ultrasound (FUS)-induced blood-brain barrier (BBB) disruption to enhance Temozolomide (TMZ) delivery for improving Glioblastoma Multiforme (GBM) treatment. MRI-monitored FUS with microbubbles was used to transcranially disrupt the BBB in brains of Fisher rats implanted with 9L glioma cells. FUS-BBB opening was spectrophotometrically determined by leakage of dyes into the brain, and TMZ was quantitated in cerebrospinal fluid (CSF) and plasma by LC-MS\MS. The effects of treatment on tumor progression (by MRI), animal survival and brain tissue histology were investigated. Results demonstrated that FUS-BBB opening increased the local accumulation of dyes in brain parenchyma by 3.8-/2.1-fold in normal/tumor tissues. Compared to TMZ alone, combined FUS treatment increased the TMZ CSF/plasma ratio from 22.7% to 38.6%, reduced the 7-day tumor progression ratio from 24.03 to 5.06, and extended the median survival from 20 to 23 days. In conclusion, this study provided preclinical evidence that FUS BBB-opening increased the local concentration of TMZ to improve the control of tumor progression and animal survival, suggesting its clinical potential for improving current brain tumor treatment.

Cell polarization occurs along a single axis that is generally determined by a spatial cue. Cells of the budding yeast exhibit a characteristic pattern of budding, which depends on cell-type-specific cortical markers, reflecting a genetic programming for the site of cell polarization. The Cdc42 GTPase plays a key role in cell polarization in various cell types. Although previous studies in budding yeast suggested positive feedback loops whereby Cdc42 becomes polarized, these mechanisms do not include spatial cues, neglecting the normal patterns of budding. Here we combine live-cell imaging and mathematical modeling to understand how diploid daughter cells establish polarity preferentially at the pole distal to the previous division site. Live-cell imaging shows that daughter cells of diploids exhibit dynamic polarization of Cdc42-GTP, which localizes to the bud tip until the M phase, to the division site at cytokinesis, and then to the distal pole in the next G1 phase. The strong bias toward distal budding of daughter cells requires the distal-pole tag Bud8 and Rga1, a GTPase activating protein for Cdc42, which inhibits budding at the cytokinesis site. Unexpectedly, we also find that over 50% of daughter cells lacking Rga1 exhibit persistent Cdc42-GTP polarization at the bud tip and the distal pole, revealing an additional role of Rga1 in spatiotemporal regulation of Cdc42 and thus in the pattern of polarized growth. Mathematical modeling indeed reveals robust Cdc42-GTP clustering at the distal pole in diploid daughter cells despite random perturbation of the landmark cues. Moreover, modeling predicts different dynamics of Cdc42-GTP polarization when the landmark level and the initial level of Cdc42-GTP at the division site are perturbed by noise added in the model.

Retention of substances from systemic circulation in the brain and testes are limited due to high levels of P-glycoprotein (P-gp) in the luminal membranes of brain and testes capillary endothelial cells. From a clinical perspective, P-gp rapidly extrudes lipophilic therapeutic agents, which then fail to reach efficacious levels. Recent studies have demonstrated that acute administration of selective serotonin reuptake inhibitors (SSRI) can affect P-gp function, in vitro and in vivo. However, little is known concerning the time-course of these effects or the effects of different SSRI in vivo.The P-gp substrate, tritiated digoxin ([(3)H] digoxin), was co-administered with fluoxetine or sertraline to determine if either compound increased drug accumulation within the brains and testes of mice due to inhibition of P-gp activity. We undertook parallel studies in endothelial cells derived from brain microvessels to determine the dose-response and time-course of effects.In vitro, sertraline resulted in rapid and potent inhibition of P-gp function in brain endothelial cells, as determined by cellular calcein accumulation. In vivo, a biphasic effect was demonstrated. Brain accumulation of [(3)H] digoxin was increased 5 minutes after treatment with sertraline, but by 60 minutes after sertraline treatment, brain accumulation of digoxin was reduced compared to control. By 240 minutes after sertraline treatment brain digoxin accumulation was elevated compared to control. A similar pattern of results was obtained in the testes. There was no significant effect of fluoxetine on P-gp function, in vitro or in vivo.Acute sertraline administration can modulate P-gp activity in the blood-brain barrier and blood-testes barrier. This clearly has implications for the ability of therapeutic agents that are P-gp substrates, to enter the brain when co-administered with SSRI.

Placental P-glycoprotein (P-gp) acts to protect the developing fetus from exogenous compounds. This protection declines with advancing gestation leaving the fetus and fetal brain vulnerable to these compounds and potential teratogens in maternal circulation. This vulnerability may be more pronounced in pregnancies complicated by infection, which is common during pregnancy. Pro-inflammatory cytokines (released during infection) have been shown to be potent inhibitors of P-gp, but nothing is known regarding their effects at the developing blood-brain barrier (BBB). We hypothesized that P-gp function and expression in endothelial cells of the developing BBB will be inhibited by pro-inflammatory cytokines. We have derived brain endothelial cell (BEC) cultures from various stages of development of the guinea pig: gestational day (GD) 50, 65 (term ~68 days) and postnatal day (PND) 14. Once these cultures reached confluence, BECs were treated with various doses (10(0)-10(4 )pg/mL) of pro-inflammatory cytokines: interleukin-1β (IL-1β), interleukin-6 (IL-6) or tumor necrosis factor- α (TNF-α). P-gp function or abcb1 mRNA (encodes P-gp) expression was assessed following treatment. Incubation of GD50 BECs with IL-1β, IL-6 or TNF-α resulted in no change in P-gp function. GD65 BECs displayed a dose-dependent decrease in function with all cytokines tested; maximal effects at 42%, 65% and 34% with IL-1β, IL-6 and TNF-α treatment, respectively (P

The spindle position checkpoint (SPC) ensures correct mitotic spindle position before allowing mitotic exit in the budding yeast Saccharomyces cerevisiae. In a candidate screen for checkpoint genes, we identified bud2Δ as deficient for the SPC. Bud2 is a GTPase activating protein (GAP), and the only known substrate of Bud2 was Rsr1/Bud1, a Ras-like GTPase and a central component of the bud-site-selection pathway. Mutants lacking Rsr1/Bud1 had no checkpoint defect, as did strains lacking and overexpressing Bud5, a guanine-nucleotide exchange factor (GEF) for Rsr1/Bud1. Thus, the checkpoint function of Bud2 is distinct from its role in bud site selection. The catalytic activity of the Bud2 GAP domain was required for the checkpoint, based on the failure of the known catalytic point mutant Bud2(R682A) to function in the checkpoint. Based on assays of heterozygous diploids, bud2(R682A), was dominant for loss of checkpoint but recessive for bud-site-selection failure, further indicating a separation of function. Tem1 is a Ras-like protein and is the critical regulator of mitotic exit, sitting atop the mitotic exit network (MEN). Tem1 is a likely target for Bud2, supported by genetic analyses that exclude other Ras-like proteins.

Artificial intelligence and machine learning (AI/ML) is becoming increasingly more accessible to biomedical researchers with significant potential to transform biomedicine through optimization of highly-accurate predictive models and enabling better understanding of disease biology. Automated machine learning (AutoML) in particular is positioned to democratize artificial intelligence (AI) by reducing the amount of human input and ML expertise needed. However, successful translation of AI/ML in biomedicine requires moving beyond optimizing only for prediction accuracy and towards establishing reproducible clinical and biological inferences. This is especially challenging for clinical studies on rare disorders where the smaller patient cohorts and corresponding sample size is an obstacle for reproducible modeling results. Here, we present a model-agnostic framework to reinforce AutoML using strategies and tools of explainable and reproducible AI, including novel metrics to assess model reproducibility. The framework enables clinicians to interpret AutoML-generated models for clinical and biological verifiability and consequently integrate domain expertise during model development. We applied the framework towards spinal cord injury prognostication to optimize the intraoperative hemodynamic range during injury-related surgery and additionally identified a strong detrimental relationship between intraoperative hypertension and patient outcome. Furthermore, our analysis captured how evolving clinical practices such as faster time-to-surgery and blood pressure management affect clinical model development. Altogether, we illustrate how expert-augmented AutoML improves inferential reproducibility for biomedical discovery and can ultimately build trust in AI processes towards effective clinical integration.

Background: Understanding variations in women's work participation at lower administrative levels, such as districts, is a missing link in identifying trends, patterns and variation that can offer insights into this long-term stagnation. We link data from the 2019–21 Indian National Family Health Survey and the 2011 Indian Population and Housing Census to generate estimates of women's work within 640 districts of India, and to examine the spatial clustering of women's work across these districts. We examine women's work through three outcome variables, namely, district-level estimates of 1) percentage of women who worked in the past 12 months, 2) percentage of women who were self-employed in the past 12 months, and 3) percentage of women who earned cash in the past 12 months. Results: Diagnostic measures confirm that our model-based estimates are robust enough to provide reliable district-level estimates of women's work in India. Women's work and cash earnings were lowest in the districts of the central, eastern, and northern regions, and highest in the southern region. Self-employment rates for women were generally low in Indian districts, except for districts in Himachal Pradesh and the north-eastern region. Conclusions: Considerable spatial heterogeneity in women's work has been found across 640 districts of India. Our study demonstrates that estimated percentage of women who worked in the past 12 months, estimated percentage of women who earned cash in the past 12 months and estimated percentage of women who were self-employed in the past 12 months all vary substantially at the district level. Having only state-level estimates may thus be inadequate to inform efforts to remediate low levels of women's work in India. The insights from our current study may help in the formulation and implementation of targeted policies that increase opportunities for women to expand their paid work in India. [ABSTRACT FROM AUTHOR]

Objective: Patient reported measures of hospital care are known predictors of readmission, even after accounting for risk related to age and comorbidities. This study aimed to determine the association between patient experience of diabetes-related foot disease (DFD) hospital care and unplanned hospital readmission, with a primary focus on DFD-related readmissions and a secondary focus on all-cause readmissions. Methods: A retrospective longitudinal cohort study was conducted by linking NSW Adult Admitted Patient Survey data with administrative hospital data for persons hospitalised with DFD identified through diagnostic and/or procedure codes. Univariable and multivariable shared-frailty Cox regression models were used to examine the association between key aspects of patient experiences and 90-days unplanned hospital readmission over the period 2019–2022. Results: Overall, 3,173 DFD patients were included. Ninety-day readmission rates for respondents with DFD were 9% for DFD-related readmissions and 16% for all-cause readmissions. Adults with DFD who could not understand explanations offered by health professionals were at increased risk of DFD-related readmission compared to those who could always understand (Hazard ratio (HR) 2.43, CI: 1.47–4.00), as well as patients who did not feel well enough to leave hospital at discharge (HR 1.93, CI: 1.41–2.64) or reported the care received was not well organised (HR 2.24, 1.45–3.47). Patients reporting that they did not receive enough information regarding their condition, treatment, or how to manage care at home were found to have a DFD-related readmission risk that was 1.5 to 1.8-times greater than those who did. Similar patterns were observed for all-cause readmissions, albeit with generally smaller effect sizes. Conclusions: The findings highlight that elements of care related to communication, coordination, and involvement in decision making may influence unplanned readmission rates for patients with chronic conditions, such as DFD. The impact appears to be more pronounced for DFD-related readmissions compared to all-cause readmissions. [ABSTRACT FROM AUTHOR]

Background: Respiratory tract infections are readily transmitted in care homes. Airborne transmission of pathogens causing respiratory tract illness is largely unmitigated. Portable high-efficiency-particulate-air (HEPA) filtration units capture microbial particles from the air, but it is unclear whether this is sufficient to reduce infections in care home residents. The Air Filtration to prevent symptomatic winter Respiratory Infections (including COVID-19) in care homes (AFRI-c) randomized controlled trial will determine whether using HEPA filtration units reduces respiratory infection episodes in care home residents. Methods: AFRI-c is a cluster randomized controlled trial that will be delivered in residential care homes for older people in England. Ninety-one care homes will be randomised to take part for one winter period. The intervention care homes will receive HEPA filtration units for use in communal areas and private bedrooms. Normal infection control measures will continue in all care homes. Anonymised daily data on symptoms will be collected for up to 30 residents. Ten to 12 of these residents will be invited to consent to a primary care medical notes review and (in intervention homes) to having an air filter switched on in their private room. The primary outcome will be number of symptomatic winter respiratory infection episodes. Secondary outcomes include specific clinical measures of infection, number of falls / near falls, number of laboratory confirmed infections, hospitalisations, staff sickness and cost-effectiveness. A mixed methods process evaluation will assess intervention acceptability and implementation. Discussion: The results of AFRI-c will provide vital information about whether portable HEPA filtration units reduce symptomatic winter respiratory infections in older care home residents. Findings about effectiveness, fidelity, acceptability and cost-effectiveness will support stakeholders to determine the use of HEPA filtration units as part of infection control policies. [ABSTRACT FROM AUTHOR]

Gene drive systems provide novel opportunities for insect population suppression by driving genes that confer a fitness cost into pest or disease vector populations; however regulatory issues arise when genes are capable of spreading across international borders. Gene drive systems displaying threshold properties provide a solution since they can be confined to local populations and eliminated through dilution with wild-types. We propose a novel, threshold-dependent gene drive system, Medusa, capable of inducing a local and reversible population crash. Medusa consists of four components--two on the X chromosome, and two on the Y chromosome. A maternally-expressed, X-linked toxin and a zygotically-expressed, Y-linked antidote results in suppression of the female population and selection for the presence of the transgene-bearing Y because only male offspring of Medusa-bearing females are protected from the effects of the toxin. At the same time, the combination of a zygotically-expressed, Y-linked toxin and a zygotically-expressed, X-linked antidote selects for the transgene-bearing X in the presence of the transgene-bearing Y. Together these chromosomes create a balanced lethal system that spreads while selecting against females when present above a certain threshold frequency. Simple population dynamic models show that an all-male release of Medusa males, carried out over six generations, is expected to induce a population crash within 12 generations for modest release sizes on the order of the wild population size. Re-invasion of non-transgenic insects into a suppressed population can result in a population rebound; however this can be prevented through regular releases of modest numbers of Medusa males. Finally, we outline how Medusa could be engineered with currently available molecular tools.

Background: Antibiotics are prescribed for over 50% of respiratory tract infections in primary care, despite good evidence of there being no benefit to the patient, and evidence of over prescribing driving microbial resistance. The high treatment rates are attributed to uncertainty regarding microbiological cause and clinical prognosis. Point-of-care-tests have been proposed as potential antibiotic stewardship tools, with some providing microbiological results in 15 minutes. However, there is little research on their impact on antibiotic use and clinical outcomes in primary care. Methods: This is a multi-centre, individually randomised controlled trial with mixed-methods investigation of microbial, behavioural and antibiotic mechanisms on outcomes in patients aged 12 months and over presenting to primary care in the UK with a suspected respiratory tract infection, where the clinician and/or patient thinks antibiotic treatment may be, or is, necessary. Once consented, all participants are asked to provide a combined nose and throat swab sample and randomised to have a rapid microbiological point-of-care-test or no point-of-care-test. For intervention patients, clinicians review the result of the test, before contacting the patient to finalise treatment. Treatment decisions are made as per usual care in control group patients. The primary outcome is whether an antibiotic is prescribed at this point. All swab samples are sent to the central laboratory for further testing. Patients are asked to complete a diary to record the severity and duration of symptoms until resolution or day 28, and questionnaires at 2 months about their beliefs and intention to consult for similar future illnesses. Primary care medical records are also reviewed at 6-months to collect further infection consultations, antibiotic prescribing and hospital admissions. The trial aims to recruit 514 patients to achieve 90% power with 5% significance to detect a 15% absolute reduction in antibiotic prescribing. Qualitative interviews are being conducted with approximately 20 clinicians and 30 participants to understand any changes in beliefs and behaviour resulting from the point-of-care-test and generate attributes for clinician and patient discrete choice experiments. Discussion: This trial will provide evidence of efficacy, acceptability and mechanisms of action of a rapid microbiological point-of-care test on antibiotic prescribing and patient symptoms in primary care. Trial registration: ISRCTN16039192, prospectively registered on 08/11/2022. [ABSTRACT FROM AUTHOR]

BackgroundVision impairment is a common disability that poses significant challenges to individuals' ability to perform activities essential for independent living, including activities of daily living (ADL) and instrumental activities of daily living (IADL). Despite extensive research, the extent and nature of these associations remain unclear, particularly across varying levels and types of vision impairment.ObjectivesThis meta-analysis aims to estimate associations between vision impairment and difficulties with ADL and IADL.MethodsWe conducted a systematic review of relevant literature from the inception of the databases to February 2024, using electronic database searches, including PubMed, MEDLINE (Ovid), EMBASE, Cochrane CENTRAL, and CDSR. The articles were screened for title and abstract and then for the full-text reports by two independent reviewers and study quality was appraised. Meta-analyses were performed using random effects models to calculate the pooled effect size, expressed as odds ratio (OR) with corresponding 95% confidence interval (CI) of each outcome.ResultsForty-six studies involving 210,960 participants were included. A positive large correlation between vision impairment and difficulties with ADL (Correlation coefficient [r] = 0.55, 95% CI 0.37-0.68, p = 0.001) and IADL (r = 0.60, 95% CI 0.49-0.69, p = 0.001) was shown. We also found that vision impairment was associated with difficulties in ADL (OR = 1.77, 95% CI 1.56-2.01, p < 0.0001) and IADL (OR = 1.96, 95% CI 1.68-2.30, p < 0.0001). Subgroup analysis revealed that moderate to severe impairment resulted in difficulties in ADL (OR = 1.78, 95% CI 1.43-2.21, p = 0.02) and IADL (OR = 1.86, 95% CI 1.57-2.20, p = 0.0003). Further, there was a significant association between mild to moderate vision impairment and difficulties in IADL (OR = 1.38, 95% CI 1.23-1.55, p < 0.0001). Greater impact was observed in individuals with near vision impairment compared to those with distance vision impairment. Near vision impairment was significantly associated with higher difficulties in ADL (OR = 1.77, 95% CI 1.57-2.01, p < 0.0001) and IADL (OR = 1.79, 95% CI 1.32-2.42, p < 0.0001). In contrast, distance vision impairment showed lower but still significant associations with IADL (OR = 1.19, 95% CI 1.05-1.34, p = 0.005) and a nonsignificant association with ADL (OR = 1.12, 95% CI 0.90-1.40, p = 0.30). Meta-regression analysis indicated that for every one-year increase in age, ADL performance decreased by an average of 0.0147 units (p < 0.001), while IADL performance declined at a slower rate of 0.0047 units/year (p = 0.031).ConclusionThe present systematic review and meta-analysis using several statistical methods indicates that vision impairment including near vision impairment, is associated with difficulties in ADL and IADL. Thus, vision impairment remains an urgent and increasingly important public health priority. These findings highlight the need for targeted measures to raise public health awareness to provide rehabilitation and eye care examination strategies to reduce the risk of developing disabilities in adults and the elderly who have vision impairment.

ObjectiveThis study aimed to introduce and evaluate a novel software-based system, BioTrace, designed for real-time monitoring of thermal ablation tissue damage during image-guided radiofrequency ablation for hepatocellular carcinoma (HCC).MethodsBioTrace utilizes a proprietary algorithm to analyze the temporo-spatial behavior of thermal gas bubble activity during ablation, as seen in conventional B-mode ultrasound imaging. Its predictive accuracy was assessed by comparing the ablation zones it predicted with those annotated by radiologists using contrast-enhanced computed tomography (CECT) 24 hours post-treatment, considered the gold standard. The study included 20 liver tumors.ResultsThe median tumor measurement along the major axis was 1.2 cm. The median Dice coefficient, Sensitivity, and Precision between BioTrace and CECT were 0.90, 0.91, and 0.91, respectively. The intraclass correlation showed excellent agreement in volume size between BioTrace and CECT findings (0.98).ConclusionBioTrace effectively generates an ablation damage prediction map based on real-time ultrasound imaging, accurately predicting the ablation zone as confirmed by 24-hour post-procedural CECT. This system has the potential to enhance the safety and efficacy of ablation procedures in clinical settings.

IntroductionTackling the inertia of growing threat of antimicrobial resistance (AMR) requires changes in how antibiotics are prescribed and utilized. The monitoring of antimicrobial prescribing in hospitals is a critical component in optimizing antibiotic use. Point prevalence surveys (PPSs) enable the surveillance of antibiotic prescribing at the patient level in small hospitals that lack the resources to establish antimicrobial stewardship programs (ASP). In this study, we analyzed antibiotic use at two public secondary care hospitals in Mexico using PPSs.MethodsFollowing WHO methodology, we conducted four cross-sectional PPSs on antibiotic use in two public secondary care facilities in Mexico: two surveys in a women's specialty hospital (H1) and two in a general referral hospital (H2). We collected data from clinical records of all patients with active antibiotic prescriptions (APs) across the medical, surgical, and mixed (MIX) wards, and intensive care units (ICUs). Descriptive statistics were computed to analyze the PPSs data using Stata.ResultsThe PPSs collected data on 127 patients, and 283 active APs. The prevalence of antibiotic use was 60.4% (H1, n = 29/48) and 70.5% (H2, n = 98/139). Antibiotics were more frequently used among patients in the MIX wards (H1: 87.5%, n = 14/16) and ICUs (H2: 90%, n = 9/10). The most frequent patient indications for antibiotic use were medical prophylaxis (H1: 51.7%, n = 15/29), community-acquired infections (H2: 42.9%, n = 42/98), and preoperative prophylaxis (H1: 27.6%, n = 8/29; H2: 23.5%, n = 23/98). The APs were mostly empirical (H1: 97%, n = 64/66; H2: 98.2%, n = 213/217), and parenterally administered (H1: 90.9%, n = 60/66; H2: 96.8%, n = 210/217). Most clinical records lacked documented post-prescription reviews (H1: 82.8%, n = 24/29; H2: 98%, n = 96/98). Preoperative prophylaxis was predominantly administered as multiple doses for more than one day. Penicillins with extended-spectrum (24.2%, n = 16/66), aminoglycosides (22.7%, n = 15/66), and first-generation cephalosporins (16.7%, n = 11/66) were the most prescribed antibiotic classes in H1, while third-generation cephalosporins (35%, n = 76/217), fluoroquinolones (14.3%, n = 31/217), and carbapenems (13.4%, n = 29/217) were the most prescribed in H2. No hospital had formally established ASP.ConclusionsThis study shows high prevalence rates of antibiotic use and variations in commonly prescribed antibiotic classes in public Mexican secondary care hospitals, along with shared practices in broad-spectrum antibiotic prescription. PPS-based surveillance enables the identification of specific targets to optimize antibiotic use according to the healthcare needs of patients in each hospital and facilitates comparative evaluations across hospitals.

There are limited data regarding bone health in older people living with HIV (PWH), especially those of Asian ethnicity. We aimed to determine whether BMD in well-suppressed HIV-infected men and women aged ≥ 50 years are different from HIV-uninfected controls. In a cross-sectional study, BMD by dual-energy X-ray absorptiometry and calciotropic hormones were measured. A total of 481 participants were consecutively enrolled (209 HIV+ men, 88 HIV- men, 126 HIV+ women and 58 HIV- women). PWH were on average 2.5 years younger [men: 55.0 vs. 57.5 yr; women: 54.0 vs. 58.0 yr] and had lower body mass index (BMI) [men: 23.2 vs. 25.1 kg/m2; women: 23.1 vs. 24.7 kg/m2] compared to the controls. The median duration since HIV diagnosis was 19 (IQR 15–21) years in men and 18 (IQR 15–21) years in women. Three-quarters of PWH had been treated with tenofovir disoproxil fumarate-containing antiretroviral therapy for a median time of 7.4 (IQR 4.5–8.9) years in men and 8.2 (IQR 6.1–10) years in women. In an unadjusted model, HIV+men had significantly lower BMD (g/cm2) at the total hip and femoral neck whereas there was a tend toward lower BMD in HIV+women. After adjusting for age, BMI, and other traditional osteoporotic risk factors, BMD of virologically suppressed older PWH did not differ from participants without HIV (P>0.1). PWH had lower serum 25(OH)D levels but this was not correlated with BMD. In conclusion, BMD in well-suppressed PWH is not different from non-HIV people, therefore, effective control of HIV infection and minimization of other traditional osteoporosis risk factors may help maintain good skeletal health and prevent premature bone loss in Asian PWH. Clinical trial registration: Clinicaltrials.gov # NCT00411983. [ABSTRACT FROM AUTHOR]