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Purpose: Insurers often commission psychiatric experts to evaluate the eligibility of workers with mental disorders for disability benefits, by estimating their residual work capacity (RWC). We investigated the validity of a standardized, computer-based battery of established diagnostic instruments, for evaluating the personality, cognition, performance, symptom burden, and symptom validity of claimants., Methods: One hundred and fifty-three claimants for benefits were assessed by the assembled test battery, which was applied in addition to a conventional clinical work disability evaluation., Results: A principal component analysis of the test and questionnaire battery data revealed six factors ( Negative Affectivity, Self-Perceived Work Ability , Behavioral Dysfunction , Working Memory , Cognitive Processing Speed , and Excessive Work Commitment ). Claimants with low, medium, and high RWC exclusively varied in the factor Negative Affectivity . Importantly, this factor also showed a strong association to psychiatric ratings of capacity limitations in psychosocial functioning., Conclusions: The findings demonstrate that the used test battery allows a substantiation of RWC estimates and of psychiatric ratings by objective and standardized data. If routinely incorporated in work disability evaluations, the test battery could increase their transparency for all stakeholders (insurers, claimants, medical experts, expert case-coordinators, and legal practitioners) and would open new avenues for research in the field of insurance medicine.Implications for rehabilitationThe residual work capacity (RWC) estimation by medical experts is internationally good practice, but plagued by a relatively low interrater agreement.The current study shows that psychiatric RWC estimates and capacity limitation ratings can be substantiated by data from objective, standardized psychometric instruments.Systematically using such instruments might help to improve the poor interrater agreement for RWC estimates in work disability evaluations.Such data could also be used for adopting vocational trainings and return-to-work programs to the individual needs of workers with mental health problems.

Medicine has separated the two cultures of biological science and social science in research, even though they are intimately connected in the lives of our patients. To understand the cause, progression, and treatment of long COVID , biology and biography, the patient's lived experience, must be studied together., (Copyright © 2022. Published by Elsevier Inc.)

Objective: To analyze the impact of interview date on the applicant rank for Neurology residencies in the United States., Methods: A multi-institutional retrospective review of interview dates and applicant rank list data for the National Resident Matching Program (NRMP) was conducted for five Neurology programs, totaling 1932 interviewed applicants over a combined total of 31 interview years. For each candidate, the interview date and applicant rank were abstracted along with the total number of interviews for that season. Statistical analyses were completed on the cumulative institution data set as well for each individual institution to assess for a possible relationship between interview date and applicant rank., Results: The cumulative institutional analysis showed that the mean applicant rank decreased as the interview season progressed. Applicants who interviewed on the first day of the interview season were ranked 11.4% higher than those who interviewed on the last interview day. Additionally, applicants interviewed on the first interview day more likely to be ranked higher when compared to all other interview dates. Independent analysis of each program's data identified comparable, statistically significant, differences in mean applicant rank and interview position at three out of the five institutions., Conclusions: This study evaluated the impact of interview order on the ranking of applicants by Neurology residency programs, noting a temporal relationship with applicant rank and interview date. The primacy bias appreciated in our data merits further evaluation in other medical specialties. Strategies to minimize the impact of this bias should be employed by residency programs who use medical matching services., (© 2021 John Wiley & Sons Ltd and The Association for the Study of Medical Education.)

In the postgenome era, biology and medicine are rapidly evolving towards quantitative and systems studies of complex biological systems. Emerging breakthroughs in microfluidic technologies and innovative applications are transforming systems biology by offering new capabilities to address the challenges in many areas, such as single-cell genomics, gene regulation networks, and pathology. In this review, we focus on recent progress in microfluidic technology from the perspective of its applications to promoting quantitative and systems biomolecular analysis in biology and medicine.

Dendritic cells (DCs) orchestrate a repertoire of immune responses that bring about resistance to infection and silencing or tolerance to self. In the settings of infection and cancer, microbes and tumours can exploit DCs to evade immunity, but DCs also can generate resistance, a capacity that is readily enhanced with DC-targeted vaccines. During allergy, autoimmunity and transplant rejection, DCs instigate unwanted responses that cause disease, but, again, DCs can be harnessed to silence these conditions with novel therapies. Here we present some medical implications of DC biology that account for illness and provide opportunities for prevention and therapy.

The development of a robust national clinical research enterprise is needed to improve health care, but faces formidable challenges. To define the impediments and formulate solutions, the Institute of Medicine's Clinical Research Roundtable convened leaders from medical specialty and clinical research societies in 2003. Participants considered how to influence clinical research funding priorities, promote mechanisms to train physicians and other health care professionals to conduct clinical research, and how to encourage health care providers to follow evidence-based medical practice. Consensus emerged on multiple issues, including intersociety collaboration, the need for a core clinical research curriculum for training the new cadre of clinical researchers, joint advocacy for increased funding of clinical research and for the education of policymakers and the public on the benefits of clinical research. Specific recommendations were made on mechanisms for recruitment, training, and retention of clinical research trainees and mentors. Steps were outlined (1) to overcome career disincentives and develop appropriate reward systems for mentors and trainees, (2) to encourage use of web-based and continuing-medical-education-based mechanisms to bring practitioners up to date on issues in and results of clinical research, and (3) to create incentives for individuals, clinics, and hospitals to practice evidence-based medicine (EBM). Collectively, the response and proposed strategies can serve as a roadmap to improve clinical research funding and training, evidence-based medical practice, and health care quality.

Emerging scientific technologies provide rich sources of predictive biomarkers, which could transform health care. Identification of causal biomarkers will enable the development of tools to quantify risk and anticipate disease. Accurate health risk analysis is rapidly becoming feasible, so health care can become rational, preventive and personalized.

Abstract Essential oils (EO) are known for their antibacterial and anti-inflammatory properties and can be used as an alternative to reduce the reliance on antimicrobials in dairy cattle. While many studies have explored the beneficial properties of EO in vitro, their effects on milk quality and milk microbiota, when applied directly to the udder skin, remain relatively unknown. This study aimed to investigate the impact of Thymus capitatus essential oil (TCEO), known for its high antibacterial and antioxidant properties, on milk microbiota using 16S rRNA sequencing, the lipidomic profile via liquid chromatography-quadrupole time-of-flight mass spectrometry, udder skin microbiota, and inflammatory biomarkers of dairy cows at the end of lactation. Sixteen-quarters of 12 Holstein cows were selected, and TCEO was topically applied to the udder skin twice a day for 7 days. Milk was collected aseptically on days 0, 7, 21, and 28 before morning farm milking. The results showed no significant changes in microbiota composition after the EO treatment in alpha and beta diversity or taxonomical composition at the phylum and genus levels. TCEO induced limited changes in the milk lipidome, primarily affecting diacylglycerols at T21. The treatment did not affect inflammatory biomarkers, milk sensory properties, or quality. Our study is the first to demonstrate that a local application of 10% TCEO on cow’s quarters does not significantly alter milk quality or microbiota composition in milk and skin. More studies should be conducted to ensure the safe use of TCEO in dairy cows and explore its potential benefits on antibiotic-resistant bacteria as an alternative or support for antibiotic therapy.

In a longitudinal study in a first-level hospital in Luanda, Angola, we found rifampin-resistant and multidrug-resistant tuberculosis (TB) in 38 (8%, 95% CI 5.7–10.8) of 474 patients with no previous history of TB. Of note, 2 patients (0.4%, 95% CI 0.1–1.5) demonstrated pre–extensively drug-resistant TB.

Abstract The application of upconversion nanoparticles (UCNPs) for cell and tissue analysis requires a comprehensive understanding of their interactions with biological entities to prevent toxicity or harmful effects. Whereas most studies focus on cancer cells, this work addresses non-cancerous cells with their regular in vitro physiology. Since it is generally accepted that surface chemistry largely determines biocompatibility in general and uptake of nanomaterials in particular, two bilayer surface coatings with different surface shielding properties have been studied: (i) a phospholipid bilayer membrane (PLM) and (ii) an amphiphilic polymer (AP). Both surface modifications are applied to (12–33) nm core-shell UCNPs NaYF4(Yb, Er)@NaYF4, ensuring colloidal stability in biological media. The impact of UCNPs@AP and UCNPs@PLM on non-cancerous epithelial-like kidney cells in vitro was found to differ significantly. UCNPs@PLM did not exhibit any measurable effect on cell physiology, even with prolonged exposure. In contrast, UCNPs@AP caused changes in cell morphology and induced cell-death after approximately 30 h. These variations in toxicity are attributed to the distinct chemical stability of these particles, which likely influences their intracellular disintegration.

Abstract Despite decades of improvements in cytotoxic therapy, the current standard of care for locally advanced pancreatic cancer (LAPC) provides, on average, only a few months of survival benefit. Stereotactic Body Radiation Therapy (SBRT), a technique that accurately delivers high doses of radiation to tumors in fewer fractions, has emerged as a promising therapy to improve local control of LAPC; however, its effects on the tumor microenvironment and hypoxia remain poorly understood. To explore how SBRT affects pancreatic tumors, we combined an orthotopic mouse model of pancreatic cancer with an intravital microscopy platform to visualize changes to the in vivo tumor microenvironment in real-time. Mice received SBRT (5 × 8 Gy) or were left untreated, and were imaged before and 1, 4, 7, and 14 days after treatment (n = 7/group). A fluorescent human pancreatic cancer cell line (BxPC3-DsRed) engineered to express GFP under hypoxic conditions (driven by hypoxia-inducible factor, HIF) was used to monitor tumor hypoxia. Immunohistochemical staining was also performed on tissues to validate in vivo data. Our findings demonstrate a persistent decrease in pancreatic tumor hypoxia as early as one day after SBRT. This coincided with a decrease in both tumor cell proliferation and cell density in the SBRT group. Reduced demand for oxygen after SBRT (due to cell death and growth arrest from treatment) significantly contributed to reoxygenation of the pancreatic TME. Understanding how this reoxygenation phenomenon occurs in a dose-dependent manner will help improve dosing and fractionation schemes for clinical SBRT.

Abstract Diabetes is a pandemic disease that causes the loss of control of glucose regulation in the organism, in consequence of dysfunction of insulin production or functionality. In this work, the antidiabetic bioactivity of 182 fractions from 19 cyanobacteria strains derived from the LEGE Culture Collection were analysed using the 2-NBDG assay in zebrafish larvae. From this initial screening, two fractions (57 (06104_D) and 107 (03283_B)) were identified as promising insulin mimetics. These were further characterized by measuring glucose levels in whole larvae, the expression of glucose transporters (GLUT 1–3) using western blot, and the mRNA expression levels of the glut2, pepck, and insa genes using real-time qPCR. Both fractions showed a decrease in free glucose levels. Furthermore, exposure to fraction 06104_D decreased GLUT1 and increased insa mRNA levels. The chemical composition of these fractions was determined using LC-HRESIMS/MS and compared to inactive fractions of the same polarity in order to identify the unique bioactive molecules. The molecular networks constructed using the GNPS platform revealed that fraction 06104_D contained mass clusters primarily composed of chlorins, lipids, and terpenoids, while fraction 03283_B contained xanthophylls, peptides, and terpenoids. To correlate the observed activity with the chemical composition of fraction 06104_D, pheophorbide a was chosen as a representative of chlorophyll derivatives. Exposure to zebrafish larvae at 10 and 20 µM confirmed the increased glucose uptake on the 2-NBDG assay. These findings highlight the bioactivity of chlorophyll derivatives as insulin mimetic compounds, as well as cyanobacteria as a source of potential therapeutic diabetes applications.

Abstract Background The number of known inherited metabolic diseases (IMDs) has been expanding, and the rate of diagnosis is improving with the development of innovative approaches including next generation sequencing (NGS). However, a substantial proportion of IMDs remain undetected by traditional diagnostic approaches. We aim to highlight the spectrum of IMDs diagnosed by the Undiagnosed Diseases Network (UDN) and to learn from the UDN diagnostic processes that were able to detect IMDs. Methods We conducted a retrospective analysis of 757 UDN participants diagnosed from 2015 until 2023 using the cohort database, which were divided into a cohort with IMDs (n = 194; 27%) and a cohort whose phenotypes were not explained by an IMD (n = 563; 73%), based on the International Classification of Inherited Metabolic Disorders (ICIMD). Then, we divided the causes of the metabolic 194 diagnoses into seven groups that included all the ICIMD categories. We inspected which clinical and laboratory approaches contributed to a final UDN diagnosis. We also present a UDN case example from each group to highlight the diagnostic yields that resulted from combining newer diagnostic approaches in the UDN and illustrate potential pitfalls of current NGS methods. Results These 194 cases of IMDs included examples from 21/25 (84%) of the ICIMD categories. Of the UDN subjects 164/194 (85%) were diagnosed with IMDs through NGS. Conclusion The spectrum of IMDs detected in the UDN cohort is large and growing and appropriate use of newer multiple diagnostic approaches should further increase diagnosis of IMDs that are presently missed by the traditional laboratory screening methods.

We used cross-sectional data from 226 patients with monkeypox virus to investigate the association between anatomic exposure site and lesion development. Penile, anorectal, and oral exposures predicted lesion presence at correlating anatomic sites. Exposure site also predicted the first lesion site of the penis and anus.

Abstract Cyclic fluorescence microscopy enables multiple targets to be detected simultaneously. This, in turn, has deepened our understanding of tissue composition, cell-to-cell interactions, and cell signaling. Unfortunately, analysis of these datasets can be time-prohibitive due to the sheer volume of data. In this paper, we present CycloNET, a computational pipeline tailored for analyzing raw fluorescent images obtained through cyclic immunofluorescence. The automated pipeline pre-processes raw image files, quickly corrects for translation errors between imaging cycles, and leverages a pre-trained neural network to segment individual cells and generate single-cell molecular profiles. We applied CycloNET to a dataset of 22 human samples from head and neck squamous cell carcinoma patients and trained a neural network to segment immune cells. CycloNET efficiently processed a large-scale dataset (17 fields of view per cycle and 13 staining cycles per specimen) in 10 min, delivering insights at the single-cell resolution and facilitating the identification of rare immune cell clusters. We expect that this rapid pipeline will serve as a powerful tool to understand complex biological systems at the cellular level, with the potential to facilitate breakthroughs in areas such as developmental biology, disease pathology, and personalized medicine.

Abstract Background Postpartum depression (PPD) constitutes a significant mental health disorder affecting almost one fifth of pregnancies globally. Despite extensive research, the precise etiological mechanisms underlying PPD remain elusive. However, several risk factors like genetic predisposition, hormonal fluctuations, and stress-related environmental and psychosocial triggers have been found to be implicated in its development. Main Recently, an increased risk of PPD has been reported to be associated with gestational diabetes mellitus (GDM), which is characterized by the disruption of glucose metabolism, primarily attributed to the emergence of insulin resistance (IR). While IR during pregnancy seems to be an evolutionary adaptative mechanism to handle the profound metabolic alterations during pregnancy, its subsequent resolution following delivery necessitates a reconfiguration of the metabolic landscape in both peripheral tissues and the central nervous system (CNS). Considering the pivotal roles of energy metabolism, particularly glucose metabolism, in CNS functions, we propose a novel model that such pronounced changes in IR and the associated glucose metabolism seen postpartum might account for PPD development. This concept is based on the profound influences from insulin and glucose metabolism on brain functions, potentially via modulating neurotransmitter actions of dopamine and serotonin. Their sudden postpartum disruption is likely to be linked to mood changes, as observed in PPD. Conclusions The detailed pathogenesis of PPD might be multifactorial and still remains to be fully elucidated. Nevertheless, our hypothesis might account in part for an additional etiological factor to PPD development. If our concept is validated, it can provide guidance for future PPD prevention, diagnosis, and intervention.

Abstract Background Several surgical options for degenerative lumbar spinal stenosis (LSS) are available, but current guidelines do not recommend which one should be prioritized. Although previous network meta-analyses (NMAs) have been performed on this topic, they have major methodological problems and could not provide the convincing evidence and clinical practical information required. Methods Randomized controlled trials (RCTs) comparing at least two surgical interventions were included by searching AMED, CINAHL, EMBASE, the Cochrane Library, and MEDLINE (inception to August 2023). A frequentist random-effects NMA was performed for physical function and adverse events due to any reason. For physical function, three follow-up time points were included: short-term (

Abstract Background BI 836880 is a humanized bispecific nanobody® that binds to and blocks vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2). A comprehensive biomarker and modeling approach is presented here that supported dose finding for BI 836880. Methods Two Phase I dose-escalation studies (1336.1 [NCT02674152], 1336.6 [NCT02689505]) assessed BI 836880 in adults with confirmed locally advanced or metastatic solid tumors, refractory to standard therapy or for which standard therapy was not reliably effective. Two dosing schedules were investigated, 3 weeks (q3w) or once weekly (qw), starting at a dose of 40 mg. In a comprehensive biomarker approach, soluble pharmacodynamic markers (free and total plasma VEGF-A and Ang-2), as well as circulating angiogenic factors (soluble VEGF3, soluble Tie2 and placenta growth factor, amongst others) were analyzed to assess target engagement in peripheral blood for q3w doses. A Population based pharmacokinetics/pharmacodynamics (PopPK/PD) model was built using the limited Phase I dataset to support dose finding by simulations. In order to demonstrate drug activity in the tumor, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was applied. Results DCE-MRI scans supported target engagement in the tumor. Free VEGF-A was depleted at all doses, whereas free Ang-2 decreased dose-dependently, reaching depletion in most patients from 360 mg q3w onwards. While total VEGF-A levels increased in a dose-dependent manner, reaching saturation at 360 mg q3w, total Ang-2 levels increased, but did not plateau. Angiogenic biomarkers showed changes from doses ≥ 360 mg q3w. PopPK/PD modeling showed that doses ≥ 360 mg q3w led to > 90% inhibition of free Ang-2 at steady-state in most patients. By increasing the dose to ≥ 500 mg q3w, > 90% of patients are expected to achieve this level. Conclusions The comprehensive analyses of multiple target engagement markers support BI 836880 720 mg q3w as a biologically relevant monotherapy dose schedule. Trial registration: NCT02674152 and NCT02689505.

Abstract This study investigates the prevalence and evaluates the prognostic implications of acute kidney injury (AKI) in COVID-19 patients, with a novel emphasis on the evaluation of serum uromodulin (sUmod) as a potential kidney-specific biomarker. A cohort of hospitalised COVID-19 patients (n = 378) was examined for AKI using standard criteria. In addition to traditional urinary biomarkers, sUmod levels were analysed. Univariable and multivariable regression models were employed to evaluate the association of sUmod and AKI and in-hospital mortality. Levels of sUmod were significantly lower in patients with CKD (91.8 ± 60.7 ng/ml) compared to patients with normal kidney function (204.7 ± 91.7 ng/ml; p

Abstract Background A heart positioned on the right side of the thorax can be more a complex situation than it seems, also the potentially associated congenital cardiopathies are variable. In this regard, patients with dextrocardia presenting with complete atrioventricular block require a thorough anatomical investigation to map the veno-arterial system and potential cardiovascular defects before proceeding with a permanent pacing procedure. Case presentation A 73-year-old Caucasian woman with no significant medical history presented with syncope. Physical examination showed regular heart sounds with an average heart rate of 35–40 beats per minute and no other relevant physical findings. Chest X-rays revealed a heart positioned in the right hemithorax. A standard electrocardiogram revealed complete atrioventricular block with junctional escape rhythm at nearly 35–40 beats per minute. A transthoracic echocardiogram showed a mirror image dextrocardia without any other remarkable abnormalities. Venogram performed using the left peripheral cephalic vein showed normal venous return into the right atrium positioned on the left side. Surgical intervention consisted of permanent dual chamber pacemaker implantation using the left subclavian vein. Discussion is provided based on the relevant medical literature outlining different potential scenarios with associated cardiac and major vessels abnormalities. Conclusion This case highlights an atypical presentation of atrioventricular block in a patient with dextrocardia and situs inversus, for whom a successful dual-pacemaker implantation procedure was performed.

Abstract Bile acids (BA) are supposed to cause metabolic alterations after bariatric surgery (BS). Here we report the longitudinal dynamics of the human BA metabolome by LC–MS/MS after BS versus low calory diet (LCD) in two obesity cohorts over 12 months. Rapid and persistent oscillations of 23 BA subspecies could be identified with highly specific patterns in BS vs. LCD. TCDCA, GLCA, and TLCA represent most promising candidates for drug development.

Background The 2013-2016 West African Ebola Virus Disease (EVD) outbreak resulted in 28,600 cases and 11,300 deaths officially reported to the World Health Organization. Previous studies investigating factors associated with death had conflicting findings, interventions showing promising outcomes had small sample sizes, studies were often single- or dual-country based and most focused on laboratory-confirmed EVD and not on clinically-suspected EVD. We used the Ebola data platform of the Infectious Disease Data Observatory (IDDO) to review individual patient records to assess factors associated with death, and particularly whether there were differences between laboratory-confirmed and clinically-suspected cases. Methods This was a cohort study involving analysis of secondary data in the IDDO database. The study population included all patients classified as having either clinically-suspected or laboratory-confirmed EVD, admitted to 22 Ebola Treatment Units (ETU) in Guinea, Liberia and Sierra Leone between December 2013 and March 2016. Baseline characteristics and treatments were documented along with ETU exit outcomes. Factors associated with death were investigated by multivariable modified Poisson regression. Results There were 14,163 patients, of whom 6,208 (43.8%) were laboratory-confirmed and 7,955 (56.2%) were clinically-suspected. Outcomes were not recorded in 2,889 (20.4%) patients. Of the 11,274 patients with known outcomes, 4,090 (36.3%) died: 2,956 (43.6%) with laboratory-confirmed EVD and 1,134 (18.8%) with clinically-suspected EVD. The strongest risk factor for death was confirmed disease status. Patients with laboratory-confirmed disease had 2.9 times higher risk of death compared to clinically-suspected patients, after adjusting for other co-variables. Other factors significantly associated with death included a higher risk for patients aged ≥60 years and a lower risk for patients in Sierra Leone. Conclusions Although laboratory-confirmed patients admitted to ETUs fared worse than clinically-suspected patients, the latter still had a substantial risk of death and more attention needs to be paid to this group in future EVD outbreaks.

Introduction Gestational diabetes mellitus (GDM) is increasingly becoming a serious public health challenge. Innovative, effective and scalable lifestyle interventions to support women with GDM to manage their condition and prevent adverse obstetric and neonatal outcomes as well as later morbidity are required. This study aims to evaluate whether a novel, multilingual and scalable mobile health (mHealth) intervention (SPARK; SmartPhone App for gestational diabetes patients suppoRting Key lifestyle behaviours and glucose control) can improve self-management and treatment of GDM and prevent adverse maternal and offspring outcomes.Methods/analyses SPARK is a multicentre two-arm randomised controlled trial recruiting women diagnosed with GDM in south-eastern Sweden. A total of 412 women will be randomised to either standard care (control) or the SPARK intervention. The SPARK online platform (accessed through a mobile app) provides a behaviour change programme for healthy eating, physical activity and glycaemic control. To increase reach, SPARK is available in Swedish, English, Arabic and Somali. SPARK also comes with a clinician portal where healthcare professionals monitor and intervene when glycaemic control is unsatisfactory (above certain cut-offs). Primary outcomes are glycaemic control that is, time in range and HbA1c, while diet, physical activity (ActiGraph), gestational weight gain, metabolic and inflammatory biomarkers in weeks 37–38, adherence to protocol for daily glucose sampling, as well as adverse obstetric and neonatal outcomes are secondary outcomes. Secondary outcomes also include cardiometabolic risk evaluation, physical activity and healthy eating behaviours 1 year postpartum. A health economic evaluation of SPARK vs standard care will also be conducted.Ethics and dissemination This study has been approved by the Swedish Ethical Review Authority (2021-06627-01; 2022-03842-02; 2023-05911-02). Results will be disseminated through scientific papers in peer-reviewed journals, posts in traditional and social media, and presentations at scientific and healthcare professionals’ conferences.Trial registration number This trial was registered at the ClinicalTrials.gov register platform (ID NCT05348863) 27 April 2022.

BackgroundThe lack of osteoporosis treatment initiation after fragility fractures is a significant gap, especially in primary care. It is unclear whether barriers for primary care physicians (PCPs) arise from uncertainty about investigations, treatment initiation, or medication side effects. Key questions remain about whether active learning platforms improve treatment initiation rates better than passive methods and how PCP demographics affect learning outcomes. With PCPs increasingly using web-based platforms for continuing professional development due to time constraints and heavy workloads, an interactive community fracture capture (CFC) tool may serve as an effective alternative to in-person learning. Our CFC pilot study tested this new program’s design and content, showing promising potential. ObjectiveWe aim to evaluate the interactive, case-based, web-based CFC Learning Hub, examining user acceptance and engagement with the platform, focusing on participants’ interactions, satisfaction levels, and overall experience. MethodsParticipating PCPs are recruited through Praxhub, a web-based medical education platform, and provide electronic consent for data use after deidentification. They have been allocated into small groups (12-20 members) and join the CFC Learning Hub, a secure web-based community. This hub includes a web-based discussion forum with participant-contributed case studies and a knowledge repository. Over the 6-week program, participants will receive weekly modules with instructions, resources, discussion threads, and quizzes, along with interactive discussions moderated by experienced PCPs and physicians. The platform also hosts web-based surveys that, in combination with platform analytics, allow assessment of baseline knowledge gaps, level of activity or engagement, and improvements following the course completion. This study protocol demonstrates the creation and proposed evaluation of the CFC Learning Hub, featuring an interactive, case-based, small-group web-based learning platform equipped with flexibly scheduled, tailored modules to address the fracture treatment gap within the community. Both qualitative (via thematic analysis) and quantitative (by using 2-tailed paired t tests, Wilcoxon signed rank tests, and multivariable regression analysis) analyses will be used to assess levels of engagement and acceptance and changes in PCPs’ knowledge and confidence after engagement with the CFC Learning Hub. ResultsRecruitment of participants started in May 2022. Data collection, analysis, and reporting will be completed following the completion of four 6-week cycles of the program. ConclusionsThe study described in this protocol will provide important insights into the function and effectiveness of the CFC Learning Hub. This information will guide the expansion of the program. This initiative offers a simple digital solution for promoting current bone health practices tailored to PCPs’ needs and thereafter to expand the rollout of the e-learning hub and implementation of fracture liaison models at a primary care level in Australia and elsewhere. Future applications may extend to other clinical areas and professions. International Registered Report Identifier (IRRID)DERR1-10.2196/57511

Introduction As a result of improving survival rates, the adverse consequences of rectal cancer surgery are becoming increasingly recognised. Low anterior resection syndrome (LARS) is one such consequence and describes a constellation of bowel symptoms after rectal cancer surgery which includes urgency, faecal incontinence, stool clustering and incomplete evacuation. LARS has a significant adverse impact on quality of life (QoL) and symptoms are present in up to 75% of patients in the first year after surgery. Despite this, little is known about the natural history and there is poor evidence to support current treatment options.Methods and analysis The objectives of POLARiS are to explore the natural history of LARS and to evaluate the clinical and cost-effectiveness of transanal irrigation (TAI) or sacral neuromodulation (SNM) compared with optimised conservative management (OCM) for people with major LARS.POLARiS is a prospective, international, open-label, multi-arm, phase 3 randomised superiority trial within a cohort design, with internal pilot phase, qualitative sub-study, process evaluation and economic evaluation. Approximately 1500 adult participants from UK hospitals and 500 from Australian hospitals who have undergone a high or low anterior resection for colorectal cancer in the last 10 years will be recruited into the cohort. Six-hundred participants from the UK and 200 participants from Australia, with major LARS symptoms, defined as a LARS score of ≥30, will be recruited to the randomised controlled trial (RCT) element. Participants entering the RCT will be randomised between OCM, TAI or SNM, all with equal allocation ratios.Cohort and RCT participants will be followed up for a 24-month period, completing a series of questionnaires measuring LARS symptoms and QoL, as well as clinical review for those in the RCT. A process evaluation, qualitative sub-study and economic evaluation will also be conducted.The primary outcome measure of the POLARiS cohort and RCT is the LARS score up to 24 months post-registration/randomisation. Analyses of the RCT will be conducted on an intention-to-treat basis. Comparative effectiveness analyses for each endpoint will consist of two pairwise treatment comparisons: TAI versus OCM and SNM versus OCM. Secondary outcomes include health-related QoL, adverse events, treatment compliance and cost-effectiveness (up to 24 months post-registration/randomisation).Ethics and dissemination Ethical approval has been granted by Wales REC 4 (reference: 23/WA/0171) in the UK and Sydney Local Health District HREC (reference: 2023/ETH00749) in Australia. The results of this trial will be disseminated to participants on request and published on completion of the trial in a peer-reviewed journal and at international conferences.Trial registration number ISRCTN12834598; ACTRN12623001166662.

ObjectiveTo evaluate the relative strengths of 3 frailty assessment instruments for predicting mortality and prolonged hospitalization in acute coronary syndrome patients.DesignProspective cohort study.SettingAcute cardiac care units in New Zealand.Participants1174 patients >70 years of age hospitalized with an acute coronary syndrome.InterventionsThe Clinical Frailty Scale (CFS), Edmonton Frail Scale (EFS) and Fried Criteria (Fried), were completed during hospital admission following an acute coronary syndrome when the patient was clinically stable.Primary and secondary outcome measuresAll-cause mortality over the next ~5 years and hospitalization for >10 days in the next year determined from national administrative data.ResultsDuring median follow-up of 5.1 years there were 353 deaths. Harrell's C-statistic for mortality for EFS was 0.663, Fried 0.648 and CFS 0.640 (p10 days (n = 267, 22%) were EFS 0.649, Fried 0.628, and CFS 0.584 (pConclusionIn older patients assessed following an acute coronary syndrome the EFS discriminated the risk of all cause mortality and prolonged hospitalization better than the CFS and Fried tests, and improved risk discrimination when added to clinical risk scores.

BackgroundHeart failure (HF) is a chronic, progressive condition where the heart cannot pump enough blood to meet the body’s needs. In addition to the daily challenges that HF poses, acute exacerbations can lead to costly hospitalizations and increased mortality. High health care costs and the burden of HF have led to the emerging application of new technologies to support people living with HF to stay well while living in the community. However, many digital solutions have not involved consumers and health care professionals in their design, leading to poor adoption. The SmartHeart project aimed to codevelop a smart health ecosystem to support the early detection of HF deterioration and encourage self-care, potentially preventing hospitalizations. ObjectiveThis study aims to provide an overview of the SmartHeart project by describing our approach to designing the SmartHeart system, outlining its features, and describing the planned pilot study to determine the feasibility of the system. MethodsWe used the Integrate, Design, Assess, and Share (IDEAS) framework to guide the development of the SmartHeart system, involving users (people with HF and their caregivers) and stakeholders (health care providers involved in the management of HF) in its design. SmartHeart is a complete remote heart health monitoring and automated feedback delivery system. It includes 2 user interfaces for patients: an Amazon Alexa conversational agent and a smartphone app. The system collects physiological, symptom, and behavioral data through wireless sensors and self-reports from users. These data are processed and analyzed to provide personalized health insights, self-care support, and alerts in case of health deterioration. The system also includes a web-based user interface for health care professionals, allowing them to access data, send messages to users, and receive notifications about potential health deterioration. A single-arm, multicenter pilot trial (N=20) is planned to determine the feasibility and acceptability of SmartHeart before evaluation through a randomized controlled trial. The primary outcome will be a description of the study's feasibility (recruitment, attrition, engagement, and changes in self-care). ResultsThe SmartHeart study started in January 2021 on procurement of funding. Recruitment for the pilot trial started in August 2024 and will be completed by March 2025. We have currently enrolled 12 participants. Follow-up of all participants will be completed by the end of May 2025. ConclusionsWe have co-designed and developed a complete remote heart health monitoring and automated feedback delivery system for the early detection of HF deterioration and prevention of HF-related hospitalizations. The next step is a pilot study, which will provide valuable information on feasibility and preliminary effects to inform a larger evaluation trial. SmartHeart has the potential to augment existing health services and help people with HF stay well while living in the community. International Registered Report Identifier (IRRID)DERR1-10.2196/62964

A febrile man in Italy who had traveled to Cuba in July 2024 was diagnosed with Oropouche fever. Reverse transcription PCR detected prolonged shedding of Oropouche virus RNA in whole blood, serum, urine, and semen. Sixteen days after symptom onset, replication-competent virus was detected in semen, suggesting risk for sexual transmission.

Abstract This review seeks to address major gaps and delays between our rapidly evolving body of knowledge on type 2 diabetes and its translation into real-world practice. Through updated and improved best practices informed by recent evidence and described herein, we stand to better attain A1c targets, help preserve beta cell integrity and moderate glycemic variability, minimize treatment-emergent hypoglycemia, circumvent prescribing to “treatment failure,” and prevent long-term complications. The first topic addressed in this review concerns updates in the 2023 and 2024 diabetes treatment guidelines for which further elaboration can help facilitate integration into routine care. The second concerns advances in diabetes research that have not yet found their way into guidelines, though they are endorsed by strong evidence and are ready for real-world use in appropriate patients. The final theme addresses lingering misconceptions about the underpinnings of type 2 diabetes—fundamental fallacies that continue to be asserted in the textbooks and continuing medical education upon which physicians build their approaches. A corrected and up-to-date understanding of the disease state is essential for practitioners to both conceptually and translationally manage initial onset through late-stage type 2 diabetes.

Abstract The suprachiasmatic nucleus (SCN) contains a population of cell-autonomous circadian oscillators essential for entrainment to daily light–dark (LD) cycles. Synchrony among SCN oscillators is modified by photoperiod and determines functional properties of SCN clock cycling, including its amplitude, phase angle of entrainment, and free running periodicity (τ). For many species, encoding of daylength in SCN output is critical for seasonal regulation of metabolism and reproduction. C57BL/6 mice do not show seasonality in these functions, yet do show photoperiodic modulation of SCN clock output. The significance of this for brain systems and functions downstream from the SCN in these species is largely unexplored. C57BL/6 mice housed in a long-day photoperiod have been reported to perform better on tests of object, spatial and fear memory compared to mice in a standard 12 h photoperiod. We previously reported that encoding of photoperiod in SCN output, evident in τ in constant dark (DD), can be blocked by limiting food access to a 4 h mealtime in the light period. To determine whether this might also block the effect of long days on memory, mice entrained to 18 h:6 h (L18) or 6 h:18 h (L6) LD cycles were tested for 24 h object memory (novel object preference, NOP) and spatial working memory (Y-maze spontaneous alternation, SA), at 4 times of day, first with food available ad libitum and then during weeks 5–8 of daytime restricted feeding. Photoperiod modified τ as expected, but did not affect performance on the NOP and SA tests, either before or during restricted feeding. NOP performance did improve in the restricted feeding condition in both photoperiods, eliminating a weak time of day effect evident with food available ad-libitum. These results highlight benefits of restricted feeding on cognitive function, and suggest a dose–response relationship between photoperiod and memory, with no benefits at daylengths up to 18 h.

Abstract During captivity, round stingrays, Urobatis halleri, became infected with the marine leech Branchellion lobata. When adult leeches were deprived of blood meal, they experienced a rapid decrease in body mass and did not survive beyond 25 days. If kept in aquaria with host rays, B. lobata fed frequently and soon produced cocoons, which were discovered adhered to sand grains. A single leech emerged from each cocoon (at ~ 21 days), and was either preserved for histology or molecular analysis, or monitored for development by introduction to new hosts in aquaria. Over a 74-day observation period, leeches grew from ~ 2 to 8 mm without becoming mature. Newly hatched leeches differed from adults in lacking branchiae and apparent pulsatile vesicles. The microbiome of the hatchlings was dominated by a specific, but undescribed, member of the gammaproteobacteria, also recovered previously from the adult leech microbiome. Raising B. lobata in captivity provided an opportunity to examine their reproductive strategy and early developmental process, adding to our limited knowledge of this common group of parasites.

Abstract The combination of cisplatin and pemetrexed remains the gold standard chemotherapy for malignant pleural mesothelioma (MPM), although resistance and poor response pose a significant challenge. Cytidine deaminase (CDA) is a key enzyme in the nucleotide salvage pathway and is involved in the adaptive stress response to chemotherapy. The cytidine analog capecitabine and its metabolite 5′-deoxy-5-fluorocytidine (5’-DFCR) are converted via CDA to 5-fluorouracil, which affects DNA and RNA metabolism. This study investigated a schedule-dependent treatment strategy, proposing that initial chemotherapy induces CDA expression, sensitizing cells to subsequent capecitabine treatment. Basal CDA protein expression was low in different mesothelioma cell lines but increased in the corresponding xenografts. Standard chemotherapy increased CDA protein levels in MPM cells in vitro and in vivo in a schedule-dependent manner. This was associated with epithelial-to-mesenchymal transition and with HIF-1alpha expression at the transcriptional level. In addition, pretreatment with cisplatin and pemetrexed in combination sensitized MPM xenografts to capecitabine. Analysis of a tissue microarray (TMA) consisting of samples from 98 human MPM patients revealed that most human MPM samples had negative CDA expression. While survival curves based on CDA expression in matched samples clearly separated, significance was not reached due to the limited sample size. In non-matched samples, CDA expression before but not after neoadjuvant therapy was significantly associated with worse overall survival. In conclusion, chemotherapy increases CDA expression in xenografts, which is consistent with our in vitro results in MPM and lung cancer. A subset of matched patient samples showed increased CDA expression after therapy, suggesting that a schedule-dependent treatment strategy based on chemotherapy and capecitabine may benefit a selected MPM patient population.

Abstract Glioblastoma is the most common and aggressive primary malignant brain tumor with poor prognosis. Novel immunotherapeutic approaches are currently under investigation. Even though magnetic resonance imaging (MRI) is the most important imaging tool for treatment monitoring, response assessment is often hampered by therapy-related tissue changes. As tumor and therapy-associated tissue reactions differ structurally, we hypothesize that biomechanics could be a pertinent imaging proxy for differentiation. Longitudinal MRI and magnetic resonance elastography (MRE) were performed to monitor response to immunotherapy with a toll-like receptor 7/8 agonist in orthotopic syngeneic experimental glioma. Imaging results were correlated to histology and light sheet microscopy data. Here, we identify MRE as a promising non-invasive imaging method for immunotherapy-monitoring by quantifying changes in response-related tumor mechanics. Specifically, we show that a relative softening of treated compared to untreated tumors is linked to the inflammatory processes following therapy-induced re-education of tumor-associated myeloid cells. Mechanistically, combined effects of myeloid influx and inflammation including extracellular matrix degradation following immunotherapy form the basis of treated tumors being softer than untreated glioma. This is a very early indicator of therapy response outperforming established imaging metrics such as tumor volume. The overall anti-tumor inflammatory processes likely have similar effects on human brain tissue biomechanics, making MRE a promising tool for gauging response to immunotherapy in glioma patients early, thereby strongly impacting patient pathway.

Abstract Chronic Otitis Media (COM) is defined as long term inflammation and colonization with pathogenic bacteria due to a defect or retraction of the tympanic membrane. Surgical interventions are often augmented by antibiotic resistance development and therefore, off-label treatment using the natural drug 1,8-Cineol was carried out. All COM patients underwent antibiotic therapy and middle ear surgery and developed antibiotic resistances. Microbiological investigations from the auditory canal and stool samples were performed in correlation with the clinical course. Therapy of COM patients with 1,8-Cineol revealed a clear reduction of inflammatory microbes P. aeruginosa and Proteus mirabilis in ear samples as well as intestinal Prevotella copri, which was associated with an improved clinical outcome in certain individuals. The present off-label study revealed manifold anti-inflammatory effects of the natural monoterpene 1,8-Cineol in Otitis media patients. A better understanding of the underlying mechanisms will improve the current treatment options and possible forms of application of this natural drug.

Introduction Sciatica is a debilitating condition that often becomes chronic, and for which there are few effective treatment options. Treatments such as the anti-depressant duloxetine have shown promise, but the evidence is inconclusive. We are describing a high quality, definitive trial to investigate the efficacy, safety and cost-effectiveness of duloxetine in chronic sciatica.Methods and analysis The duloxetine for chronic sciatica (DREAM) trial is a randomised, superiority, parallel-group, placebo-controlled, triple-blinded (participant, clinician, assessor) trial with an adaptive group sequential design investigating the efficacy and safety of duloxetine in participants with chronic sciatica of at least 3 months duration. Participants will be randomised at a 1:1 ratio to duloxetine or placebo. 332 participants will be recruited on presentation to general practices, specialist clinics and hospital emergency departments or from hospital in-patient wards and from the community. In the active treatment group, participants will receive duloxetine 60 mg per day for 12 weeks, including 1 week of titration at 30 mg/day. The treatment phase will be followed by a 2-week tapering phase where they will receive duloxetine 30 mg/day. Participants will be followed-up for 1 year, with outcomes being measured 4, 8, 12, 16, 26, and 52 weeks post-randomisation. The primary outcome is leg pain intensity at 12 weeks post-randomisation. Secondary outcomes include back pain intensity, disability, time to recovery, quality of life, depressive and anxiety symptoms, and sleep disturbance. Adverse events will be recorded, and a cost-effectiveness analysis will be conducted.Ethics and dissemination Ethical approval has been granted by the University of Sydney Human Research Ethics Committee. Trial results will be disseminated by publications, conference presentations and via the media.Trial registration number ACTRN12624000919516.

Introduction Exertion-induced desaturation (EID) is a common complication of numerous pulmonary disorders and often treated with supplementary oxygen during exertion. We performed a systematic review and meta-analysis of randomised clinical trials (RCTs) to evaluate the efficacy of supplementary oxygen for EID in pulmonary disorders. Material and methods Medline and Embase were systematically searched from July 2022 to June 2023 following PRISMA guidelines. RCTs that met predefined inclusion criteria were included. Means and standard deviations were extracted and standardised mean differences (SMDs), the difference in means between groups divided by the standard deviation, and 95% confidence intervals were calculated. Exercise capacity was the primary outcome; exercise dyspnoea, baseline dyspnoea and quality of life were secondary objectives. The immediate, post-rehabilitation, short-term and ambulatory effects of oxygen supplementation were evaluated. Results We included 15 studies in our analysis. Oxygen supplementation to treat adult EID had been investigated for COPD and idiopathic pulmonary fibrosis (IPF) only. Oxygen supplementation was superior to placebo for its immediate effect on exercise capacity for COPD (SMD 0.42, 95% CI 0.15–0.69, I2=3%) and IPF (SMD 0.41, 95% CI 0.08–0.75, I2=57%) and exercise dyspnoea for COPD (SMD −0.40, 95% CI −0.76–−0.04, I2=31%). Sensitivity analysis revealed similar results. Conclusions Our study revealed the efficacy of supplemental oxygen for EID and only a positive immediate effect on exercise capacity and dyspnoea, but no improvement in other short-term or long-term measures.

In nature, animal vocalizations can provide crucial information about identity, including kinship and hierarchy. However, lab-based vocal behavior is typically studied during brief interactions between animals with no prior social relationship, and under environmental conditions with limited ethological relevance. Here, we address this gap by establishing long-term acoustic recordings from Mongolian gerbil families, a core social group that uses an array of sonic and ultrasonic vocalizations. Three separate gerbil families were transferred to an enlarged environment and continuous 20-day audio recordings were obtained. Using a variational autoencoder (VAE) to quantify 583,237 vocalizations, we show that gerbils exhibit a more elaborate vocal repertoire than has been previously reported and that vocal repertoire usage differs significantly by family. By performing gaussian mixture model clustering on the VAE latent space, we show that families preferentially use characteristic sets of vocal clusters and that these usage preferences remain stable over weeks. Furthermore, gerbils displayed family-specific transitions between vocal clusters. Since gerbils live naturally as extended families in complex underground burrows that are adjacent to other families, these results suggest the presence of a vocal dialect which could be exploited by animals to represent kinship. These findings position the Mongolian gerbil as a compelling animal model to study the neural basis of vocal communication and demonstrates the potential for using unsupervised machine learning with uninterrupted acoustic recordings to gain insights into naturalistic animal behavior.

BackgroundThe World Health Organization and the Centers for Disease Control and Prevention have set ambitious hepatitis C virus (HCV) elimination targets for 2030. Current estimates show that the United States is not on pace to meet elimination targets due to multiple patient, clinic, institutional, and societal level barriers that contribute to HCV testing and treatment gaps. Among these barriers are unawareness of testing and treatment needs, misinformation concerning adverse treatment reactions, need for substance use sobriety, and treatment efficacy. Strategies to improve viral hepatitis education are needed. ObjectiveWe aim to provide a high-quality HCV educational app for patients and health care workers, particularly nonprescriber staff. The app was vetted by health care providers and designed to guide users through the HCV testing and treatment stages in a self-exploratory way to promote engagement and knowledge retention. The app is comprised of five learning modules: (1) Testing for Hep C (hepatitis C), (2) Tests for Hep C Positive Patients, (3) Treatments Available to You, (4) What to Expect During Treatment, and (5) What to Expect After Treatment. MethodsAn HCV knowledge assessment survey was administered to providers and patients at the Yale School of Medicine and 11 Connecticut HIV clinics as part of a grant-funded activity. The survey findings and pilot testing feedback guided the app’s design and content development. Data on app usage from November 2019 to November 2022 were analyzed, focusing on user demographics, engagement metrics, and module usage patterns. ResultsThere were 561 app users; 216 (38.5%) accessed the training modules of which 151 (69.9%) used the app for up to 60 minutes. Of them, 65 (30.1%) users used it for >60 minutes with a median time spent of 5 (IQR 2-8) minutes; the median time between initial accession and last use was 39 (IQR 18-60) days. Users accessed one or more modules and followed a nonsequential pattern of use: module 1: 163 (75.4%) users; module 4: 82 (38%); module 5: 67 (31%); module 3: 49 (22.7%); module 2: 41 (19%). ConclusionsThis app, created in an academic setting, is one of a few available in English and Spanish that provides content-vetted HCV education for patients and health care supportive staff. It offers the convenience of on-demand education, allowing users to access crucial information about HCV management and treatment in a self-directed fashion that acknowledges and promotes variable preferences in learning approaches. While app uptake was relatively limited, we propose that future efforts should focus on combined promotion efforts with marketing strategies experts aligned with academic experts. Incorporating ongoing user feedback and integrating personalized reminders and quizzes, will further enhance engagement, supporting the broader public health HCV elimination goals.

Summary: Background: Plasma phospho-tau 217 (pTau217) assays can accurately detect Alzheimer's disease (AD) pathology, but clinical application is limited by the need for specialised equipment. This study tests the performance of a plasma pTau217 assay performed on the Lumipulse-G® platform, that is in widespread clinical use, for selecting patients for therapy based on β-amyloid (Aβ) status and tau staging. Methods: Participants included 388 individuals with 18F-NAV4694 Aβ-PET and 18F-MK6240 tau-PET. Association of pTau217 with PET was examined using Spearman's correlation. Discriminative performance for Aβ and tau PET status as well as tau staging was assessed using Receiver Operating Characteristic analysis. Findings: Plasma pTau217 had a high correlation with both Aβ Centiloid (r = 0.76) and tau SUVRmeta-temporal (r = 0.78). Area under curve (AUC) was 0.93 for Aβ− vs Aβ+ and 0.94 for tau− vs tau+. Applying one threshold (Youden's index), pTau217 was 87% accurate in classification of participants to Aβ− vs Aβ+. Applying two thresholds to classify participants into Low, Indeterminate, and High zones, 17.8% had Indeterminate results and among Low/High zone participants, 92% were correctly classified as Aβ− or Aβ+. The assay accurately discriminated moderate/high neocortical tau from no tau or tau limited to mesial-temporal lobe (AUC 0.97) and high neocortical tau from all others (AUC 0.94). Interpretation: Plasma pTau217, measured by the widely-available, fully-automated Lumipulse®, was a strong predictor of both Aβ and tau PET status and demonstrated strong predictive power in identifying individuals likely to benefit the most from anti-Aβ treatments. Funding: NHMRC grants 1132604, 1140853, 1152623 and AbbVie.

Objectives: 주관적 인지 저하(subjective cognitive decline, SCD)는 객관적인 중대한 저하의 증거 없이 자신의 인지 기능에 대한 자기 또는 타인의 우려를 의미하며, 이는 치매 위험의 지표이다. 현재 사용 가능한 SCD 측정 도구의 신뢰도와 타당성에 대한 합의가 부족하다. 따라서 새로운 심리측정학적으로 타당한 SCD 측정 도구를 도입하는 것이 시급하다. 새로운 SCD 측정 도구인 맥커스커 주관적 인지 장애 자가보고서(McCusker Subjective Cognitive Impairment Inventory, McSCI-S)의 심리측정학적 특성을 보고한다. Methods: 기존에 출판된 측정 도구의 검토와 SCD를 가진 사람들에 대한 임상 및 연구 데이터를 바탕으로, 기억력, 언어능력, 지남력, 주의력 및 집중력, 시공간 구성 능력 및 실행 기능의 6가지 인지 영역에 대한 우려를 평가하기 위한 46문항 자가보고 설문지를 개발했다. McSCI-S를 526명의 참가자를 대상으로 요인 분석, 문항 반응 이론(item response theory) 분석 및 의사결정 기준점(receiver operating characteristic) 곡선을 통해 검증하였다. Results: 단일차원 모델(unidimensional model)이 적합한 것으로 나타났다(comparative fit index=0.94, Tucker–Lewis index=0.94, root mean square error of approximation[90% CI]=0.052[0.049, 0.055], weighted root mean square residual=1.45). McSCI-S의 내적 일관성은 우수했다(α=0.96). SCD를 가진 참가자를 식별하기 위해 ≥24의 기준 점수(cut-off value)를 제안한다. McSCI-S 점수가 높을수록 연령, 성별 및 교육 수준을 통제한 후에도 전반적인 인지 기능, 일화적 언어 기억력, 실행 기능의 저하 및 더 큰 기억력 불만 및 우울 점수와 관련이 있었다(P

Background: The Global Burden of Disease (GBD) 2021 study updated methods for attributing burden to physical inactivity, to include all conditions from fasting plasma glucose (FPG) due to physical inactivity. However, physical inactivity influences several additional GBD risk factors that also effect other diseases. This study estimated effects of physical activity on high blood pressure (hypertension), FPG (as diabetes), osteoporosis, and LDL-cholesterol, to enable mediation effects modelling. Methods: MEDLINE, ProQuest Central, Scopus, EMBASE, SPORTDiscus, and Cochrane Library databases were searched from inception to 29 June 2024 for systematic reviews reporting total physical activity levels as an exposure and at least one of the above GBD risk factors or BMI as outcomes. Results: There were 25 systematic reviews that met the inclusion criteria (3 for hypertension, 5 for diabetes, 1 for osteoporosis, and 16 for LDL-cholesterol). Physical activity reduced levels of the risk factors investigated, with dose–response effects observed for blood pressure (6 % for every 600 MET-min/week; 19 % for high versus low activity level) and diabetes (14–28 % if active versus being inactive). Relative to adults not reporting any activity, approximately 600 METs/week reduced levels of LDL-cholesterol by 3.2 % (95 % CI: 1.0 % to 5.4 %) and reduced low bone mineral density by an odds ratio of 0.76 (0.64 to 0.91). No studies of high BMI were identified. Conclusion: Current risk factor models do not comprehensively assess indirect effects of physical activity through all of the relevant biomedical risk factors. Our study estimated input parameters that can be used to assess these indirect pathways.

Cabazitaxel, a second-generation taxane chemotherapy agent, has demonstrated efficacy in treating metastatic castration-resistant prostate cancer (mCRPC) in patients who have previously received docetaxel-based therapy. By targeting microtubule dynamics, cabazitaxel inhibits cancer cell division and induces apoptosis, thereby extending survival and delaying disease progression in this challenging patient population. A systematic review and meta-analysis were done by searching the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, MEDLINE (including MEDLINE InProcess; OvidSP), Web of Science, Embase (OvidSP), and Scopus databases. ROB2 Cochrane tools assessment for RCTs. In the analysis, we used RevMan Cochrane software. Our research reveals significantly improved outcomes in terms of patient survival rates, both progression-free survival (PFS) and overall survival (OS), for cabazitaxel over comparative treatment (PFS HR 0.77 [0.61, 0.97]) (OS HR 0.79 [0.70, 0.88]). The treatment response rates were also favorable for cabazitaxel, reported as PSA Reduction Response of more than 50% (PRR) (odds ratio (OR) = 1.59 [0.56, 4.52]) and tumor response rate (TRR) (OR = 2.34 [1.28, 4.28]). Cabazitaxel was associated with significantly more incidence of adverse events. The risk ratio (RR) for serious adverse events was 1.64 [1.14, 2.35] for cabazitaxel compared to the current regimen. A systematic review and meta-analysis were done by searching in the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, MEDLINE (including MEDLINE InProcess; OvidSP), Web of Science, Embase (OvidSP), and Scopus databases. ROB2 Cochrane tools assessment for RCTs. In the analysis, we used RevMan Cochrane software.

Objective Helping people to change their health behaviours is becoming a greater feature within the role of health professionals, including through whole system initiatives such as Making Every Contact Count. Health services provide an ideal setting to routinely promote health behaviours, including physical activity. Snacktivity is a novel approach that promotes small bouts of physical activity (activity snacks) throughout the day. This study explored health professionals’ initial experiences of delivering a Snacktivity intervention to promote physical activity within routine health consultations. A further aim was to investigate health professionals’ ability/fidelity in delivering the Snacktivity intervention to their patients.Design Semistructured interviews (n=11) and audio recording of consultations (n=46).Setting and participants Healthcare professionals from a variety of specialisms who delivered the Snacktivity intervention within patient consultations.Results Analyses revealed two higher-level themes of interest: (1) health professionals’ conceptualisation of Snacktivity (subthemes: observations/reflections about patients’ understanding, engagement and enthusiasm for delivering the Snacktivity intervention) and (2) health professionals’ understanding of Snacktivity and experience in delivering the intervention (subthemes: delivering Snacktivity; limitations, challenges and possible improvements). Consultation audio recordings demonstrated health professionals delivered the Snacktivity intervention with high levels of fidelity. Health professionals were proficient and supportive of delivering the Snacktivity intervention within consultations although practical barriers to implementation such as time constraints were raised, and confidence in doing so was mixed.Conclusions Health professionals were proficient and supportive of delivering the Snacktivity intervention within consultations. The primary barrier to implementation was the time to deliver it, however, gaining greater experience in the intervention and improving behaviour change counselling skills may reduce this barrier.Trial registration number ISRCTN64851242.