The rapid expansion of medical information highlights the importance of physicians being trained in self-directed learning (SDL) so that they can adapt their practice to incorporate current evidence. The Liaison Committee on Medical Education and the Accreditation Council for Graduate Medical Education highlight SDL as a key training outcome, but residency program integration of this training is not clear. We explored perceptions of directors of family medicine residency programs about their programs' readiness to teach and assess SDL skills. In 2024, we surveyed all US family medicine program directors via e-mail. The survey explored aspects of programs' readiness for SDL instruction and the priority it placed on SDL, as well as the program directors' perception of recent graduates' SDL skills. Data analysis used descriptive and inferential techniques. We received responses from 314 of 705 program directors (44.5% response rate). Of the responding program directors, 294 (93.6%) agreed or strongly agreed that their recent graduates modeled lifelong learning necessary for the practice of medicine. Only 177 (56.3%) agreed or strongly agreed that they collected evidence of engagement in SDL, however. Additionally, 139 (44.2%) agreed or strongly agreed that they had written expectations regarding SDL, 167 (53.2%) reported having a programwide common understanding of SDL, and 181 (57.6%) indicated SDL was a high curricular priority. Although program directors overwhelmingly report that their graduating residents model lifelong learning skills, many also report that they are not investing in SDL curricula, nor are they collecting evidence to demonstrate SDL skills. These gaps may be addressed by creating a standardized curriculum for residency programs and by recommending tools for assessment to enhance program readiness for SDL training.Abstracts also available in: عربي (Arabic); Deutsch (German); Español (Spanish); Francais (French); हिन्दी (Hindi); Indonesia (Indonesian); (Chinese); (Japanese); Portugues (Portuguese).
I came to the United States as a refugee at age eleven, fleeing religious persecution in Iran. Decades later, as a family physician, I found myself caring for newly arrived refugees during the Afghan humanitarian crisis of 2021. Launching and leading a refugee clinic forced a convergence of my personal history and professional identity that I had long avoided. Each patient encounter echoed my own experiences of displacement, fear, and hope, transforming clinical care into an act of witnessing, healing, and shared humanity. Through caring for refugees, I confronted unresolved trauma, discovered unexpected healing, and reaffirmed medicine's moral and spiritual dimensions. As refugee arrivals slowed and policy shifts led me to step away from this work, I carried forward its lessons: that family medicine is uniquely positioned to hold vulnerability and resilience together, and that caring for others whose stories mirror our own can deepen both professional purpose and personal healing.Abstract also available in عربي (Arabic); Deutsch (German); Español (Spanish); Francais (French); हिन्दी (Hindi); Indonesia (Indonesian); (Chinese); (Japanese); Portuguese (Portugese).
In Singapore, cervical cancer screening rates remain suboptimal, with only clinician sampling included in the national screening program. Self-sampling human papillomavirus (HPV) DNA testing might overcome barriers to clinician-based screening and improve uptake. We assessed the effect of offering self-sampling alongside clinician sampling on screening uptake and high-risk HPV detection compared with clinician sampling alone. This pragmatic, 2-arm randomized controlled trial with Zelen design was conducted across NHG Polyclinics, NHG Health in Singapore. Women aged 30-69 years due for cervical cancer screening were randomly assigned (1:1) to intervention (offered selection of clinician sampling followed by self-sampling) or usual care (clinician sampling alone). The primary outcome was high-risk HPV DNA detection, and the secondary outcome was screening uptake. We performed subgroup analysis to examine both outcomes by prior screening history. Multivariable analysis identified factors associated with screening choices. From August 2024 to February 2025, 650 women were randomized, and 640 were included in the analysis (320 per arm). Significantly more high-risk HPV was detected in the intervention arm (3.1% vs 0.3%; absolute difference 2.8%; 95% CI, 0.8-4.8;P < .001), driven by greater screening uptake (56.6% vs 42.8%; absolute difference 13.8%; 95% CI, 6.0-21.4; P < .001), particularly among women with regular screening history and those with no prior screening. Among screened participants in the intervention arm, 56.4% chose self-sampling. Lower educational attainment was associated with lower odds of choosing self-sampling over declining screening. Offering self-sampling HPV DNA testing alongside clinician sampling significantly increased screening uptake and high-risk HPV detection rates. However, uptake remained lower among women with less education, highlighting the need for targeted engagement strategies.Abstract also available in: عربي (Arabic); Deutsch (German); Español (Spanish); Francais (French); हिन्दी (Hindi); Indonesia (Indonesian); (Chinese); (Japanese); Portugues (Portuguese).
Ménière's disease, a chronic disorder of the inner ear, has brought one physician a great deal of both suffering and insight. A variety of treatment options, including dietary changes and medications, have failed to help. However, the physician has found relief from a number of unexpected sources, including meditation, his social support network, and even his six-year-old child. The lessons he has learned have made him a more knowledgeable and empathetic physician.Abstract available in عربي (Arabic); Deutsch (German); Español (Spanish); Francais (French); हिन्दी (Hindi) Indonesia (Indonesian); (Chinese); (Japanese), Portugues (Portuguese).
The struggles faced by individuals and families affected by autism can vary tremendously. This, in turn, means that each family's reality is quite different. The extreme differences in the experiences faced can lead to different needs and different perceptions of autism. In this essay, a physician shares her experiences as a pediatric physician and a mother of a child with autism, and describes a dichotomy of experiences noted within the autism community. As medical professionals, we must understand the differences in perceptions and experiences to properly care for patients with autism and their families.Abstract also available in عربي (Arabic); Deutsch (German); Español (Spanish); Francais (French); हिन्दी (Hindi); Indonesia (Indonesian); (Chinese); (Japanese); Portugues (Portuguese).
To investigate the 3-dimensional (3D) topographic remodeling patterns of choroidal thickness (ChT) in the macular region in children, and their associations with age and myopia related ocular growth. Cross-sectional, population-based study. A total of 3508 children (mean age 13.6 ± 3.0 years, range 7-18 years, 47.7% male). Spectral-domain OCT with a 31-horizontal B-scan protocol was performed on right eyes. Choroidal thickness in each B-scan was automatically segmented and quantified using modified open-source deep learning algorithms (Choroidalyzer). For each eye, a 3D ChT map covering 6 × 6 mm macular region and composed of 12 × 12 grids centered on fovea was generated, and both mean thickness and grid-specific thickness values were calculated. ChT of each grid, cluster, and macular region; correlation with age, axial length (AL), and sex. The mean ChT was 271.8 ± 56.1 μm, with significant variations across nonmyopia, low, moderate, and high myopia groups (P < 0.001). Age-related ChT changes showed a distinct temporal-nasal asymmetry pattern, with the nasal region showing the strongest negative correlation with age (r = -0.12), the central region demonstrating a weak correlation (r = -0.07, both P < 0.001), whereas the temporal region remained relatively stable (r = -0.02, P = 0.255), resulting in 4.3- and 2.6-fold (95% confidence interval: -0.4 to 8.9; -0.4 to 5.7) greater thinning in the nasal and central choroid than in the temporal region, respectively. Axial length-related ChT changes showed a concentric thinning pattern, characterized by more pronounced foveal thinning (r = -0.51, B = -35.2 μm/mm, both P < 0.001) compared with parafoveal (r = -0.48, B = -28.7 μm/mm, both P < 0.001) and perifoveal changes (r = -0.42, B = -22.3 μm/mm, both P < 0.001), corresponding to 1.6- and 1.3-fold (95% confidence interval: 1.4-1.7; 1.2-1.4) greater thinning in the fovea and parafovea than in the perifovea. Using 3D topographic mapping, we provide population-based data on ChT in children, and identified 2 major spatial remodeling patterns: temporal-nasal asymmetry with age and concentric thinning with increasing axial length. These spatially and temporally distinct remodeling patterns likely reflect both physiological growth and myopia-related structural change, supporting the potential role of ChT as a biomarker for myopia development and progression. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
The emergence of aztreonam-avibactam resistance among NDM-producing Escherichia coli represents a major therapeutic and infection control concern. Four cases of aztreonam-avibactam-resistant (AZAR) NDM-producing E. coli, recovered from three blood cultures and one rectal surveillance culture in a hospital of Paris, prompted an investigation based on whole-genome sequencing. The three isolates responsible for bloodstream infection, which were clonally related, belonged to the ST405 and produced NDM-5, DHA-1, CTX-M-15, and TEM-1 β-lactamases. They also had a penicillin-binding protein 3 (PBP3) modified by the insertion of four amino acids (YRIK). On the other hand, the isolate recovered from the rectal swab belonged to another sequence type (ST2083). It produced NDM-5, CMY-42, and TEM-1 β-lactamases and had an altered PBP3 by the insertion of four other residues (YRIN). Epidemiological investigation identified endoscopic retrograde cholangiopancreatography as a potential risk factor, leading to the detection of three additional patients infected with the ST405 clone after exposure to the same duodenoscope. The outcome of the bloodstream infections was favorable except for one patient. In total, seven patients infected or colonized by AZAR NDM-5-producing E. coli were identified over a 5-month period in 2025, six with duodenoscope exposure.IMPORTANCEThis study underlines the emergence of aztreonam-avibactam resistance among NDM-producing Escherichia coli isolates in France. To our knowledge, this report describes the first clonal outbreak due to aztreonam-avibactam-resistant NDM-producing E. coli.
The aging Canadian population has led to an increase in Canada's use of home and community care services. In this context, the healthcare system relies heavily on personal support workers who work in various healthcare settings. A significant proportion of these workers are immigrants, and many live in linguistic minorities. Despite their pivotal role, the experiences and working conditions of these personal support workers are underrepresented in the scientific literature, specifically in intersectional analyses. This scoping review aims to examine the work experiences, health conditions, and well-being of immigrant personal support workers in Canada who work in a minority language setting. Studies addressing the work experiences, health conditions, and well-being of immigrant personal support workers in Canada who work in a minority language setting, and those published in English or French. There will have no restrictions on publication date. This review will follow the JBI recommendations for scoping reviews and incorporate the PRISMA-ScR checklist. We will develop an adapted search strategy for five relevant databases (Medline [Ovide], Web of Science, Embase, CINAHL, and Google Scholar). Two independent reviewers will select full-text articles based on pre-established inclusion criteria and extracted relevant data. The results will be presented in accordance with the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews) guidelines. This scoping review contributes to expanding knowledge about the professional, health, and social realities of immigrant PSWs in Canada's linguistic minority communities.
The use of West African gold in medieval times is thought to have enabled the first globalized trade in history: the Trans-Saharan Trade, through the minting of Islamic dinars, which were considered as the equivalent of today's dollar or euro currencies. Yet, the precise origin of this gold remains debated, as archaeological evidence for such trade is scarce. While textual sources are numerous, they provide only indirect accounts, and the large corpus of surviving dinars has so far yielded limited insight as elemental analyses are not discriminating enough to establish geological provenance. To address this, we combined multi-elemental analysis by LA-ICP-MS with multi-isotope (Pb, Cu, and Fe) data measured by MC-ICP-MS after wet purification chemistry on 11 dinars. This revealed two distinct metal stocks, differentiated by PGE concentrations and Cu isotopes. The Cu and Fe isotope signatures are consistent with supergene and oxidized ores, typical of West African gold mineralization. In contrast, the lead isotopes and calculated model ages of the gold coins do not match the signatures expected for West African mineralization, suggesting that a different, exogenous source is involved in the gold chaîne opératoire. These new data then raise two key historical questions: the location of gold processing, whether it occurred North or South of the Sahara, and the hypothetical reuse of older metal stocks.
The five overseas departments and regions (DROMs) are Guadeloupe, French Guiana, Reunion, Martinique and Mayotte. In the DROMs, certain areas show significantly higher incidence rates for certain cancers, particularly gynaecological cancers; overall, the 5-year net standardised survival rates are lower than those observed in mainland France. Here, we present an overview of the management of gynaecological cancers in each DROM.
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Cerebral macrovasculopathy (CV) is a major complication in children with sickle cell anaemia (SCA) and usually requires a long-term transfusion programme (TP) to prevent stroke. This study aimed to identify factors predicting reversal of CV on TP in a single-centre newborn cohort. Among 375 patients, 50 presented CV and received TP. Median age at diagnosis was 4.9 years [3.6-6.1], with median follow-up of 13.3 years (915 patient-years). Transcranial Doppler (TCD) velocities and magnetic resonance angiography (MRA) normalised in 35 patients, that is, they had reversal of CV (RCV group). Fifteen patients had no reversal of CV (No-RCV group). Kaplan-Meier analysis estimated that 48% (95% confidence interval [CI] [33-62]) still had abnormal TCD and/or MRA 5 years after diagnosis. In a multivariate Cox model, three baseline factors independently predicted CV reversal: age at CV onset, initial severity of stenosis and bronchial obstruction. Older age at diagnosis increased the likelihood of CV reversal (hazard ratio [HR] 1.31 per year, 95% CI [1.08-1.59], p = 0.01). In contrast, severe stenosis (HR 0.72 per 10% increase, 95% CI [0.62-0.85], p < 0.0001) and bronchial obstruction (HR 0.14, 95% CI [0.03-0.63], p = 0.001) reduced the likelihood of CV reversal. These results suggest that, beyond TP, managing bronchial obstruction may improve vascular outcomes.
Platelets promote hemostasis and modulate different inflammatory and immunological processes. Recently, it was reported that platelets interact with pancreatic beta cells to increase insulin secretion. Inflammatory conditions and a lack of sufficient insulin secretion drive the pathogenesis of type 2 diabetes (T2D) in the context of obesity. However, the specific role of platelets during the development of obesity-related T2D has not yet been investigated. Thrombopoietin receptor knockout (MPL-/- ) mice displaying constant thrombocytopenia (approx. 90 % reduction in platelet count) or wild type (WT) mice were fed either a high-fat diet (HFD) or a control diet (CD) for 19 weeks, starting at 8 weeks of age. The mice were metabolically characterized at the end of the feeding period (metabolic caging, glucose and insulin tolerance testing, body and organ weight measurements, and gene expression analyses). Pancreatic tissue was histologically assessed via immunofluorescence, and circulating platelets were characterized by flow cytometry. After HFD feeding, obese MPL-/- mice showed a significantly improved glucose tolerance compared to WT mice. At the same time, MPL-/- mice tended to exhibit a more pronounced insulin resistance. The weight gain of MPL-/- and WT mice did not differ significantly after 19 weeks of feeding, but body weight was higher in MPL-/- between weeks 4 and 12. Likewise, the weight of adipose tissue depots was similar between both genotypes at the end of the study. In metabolic cages, obese MPL-/- mice showed less physical activity than WT, while other parameters like O2-consumption and heat dissipation were similar between the two groups. The expression of genes involved in glucose metabolism in muscle, liver, and epididymal adipose tissue did not show relevant differences between MPL-/- and WT mice. At the end of the study, a significantly higher insulin concentration was measured in the circulation of obese MPL-/- mice. This was accompanied by a higher proportion of pancreatic beta cells in the total analyzed tissue area. These results suggests that thrombocytopenia protects pancreatic beta cells in an obesity mouse model of T2D, thereby preserving insulin secretion and improving glucose tolerance.
TBL1XR1 is frequently mutated in diffuse large B-cell lymphoma (DLBCL), yet its functional impact on tumor microenvironment remains poorly defined. In this study, we characterized TBL1XR1 mutations in a cohort of 1842 newly diagnosed DLBCL patients, identifying mutations in 9.4% of cases (n = 173). These mutations correlated with clinically aggressive features, including older age (> 60 years), high-risk International Prognostic Index, enrichment in non-GCB subtypes, as well as inferior progression-free and overall survival. Mechanistically, TBL1XR1 mutations enhanced H3K27ac levels at the MYC promoter, increased MYC expression and subsequently up-regulated its immune-regulatory targets CD47 and PD-L1. This axis impaired natural killer (NK) cytotoxicity, facilitating immune escape and tumor progression. In a murine A20 B-lymphoma model, tumors harboring Tbl1xr1 mutations exhibited up-regulated MYC, CD47, and PD-L1 expression, resulting in NK cell dysfunction and tumor growth acceleration via the MYC-CD47/PD-L1 axis. Dual blockade of CD47 and PD-L1 restored NK cell-mediated tumor immunity, triggering rapid regression of Tbl1xr1-mutated tumors. Taken together, our findings identified TBL1XR1 mutations as a microenvironment-related mechanism of DLBCL progression and provided clinical rationale of co-targeting CD47 and PD-L1 to treat this genetically defined subset.
[This corrects the article DOI: 10.1016/j.rpth.2026.103364.].
BackgroundBrazil has recognized the need to investigate the health context of Indigenous Peoples by (a) collecting data on service coverage, barriers, needs, and gaps in access to health care; (b) developing, funding, and implementing plans and strategies for multilingual service delivery (c) reducing gender, social, and cultural inequalities as well as geographical barriers that hinder equitable access to quality health services; and, (d) incorporating an intercultural-intersectoral approach in the development of policies and inclusive-participatory research.PurposePropose an original conceptual framework for action research on the socio-cultural aspects of pregnancy, childbirth, and the postpartum cycle among Brazilian Indigenous women.ResultsAn online consultation with healthcare professionals was conducted (April-June 2024) using audio recorded narratives to gather information about the health of pregnant and postpartum Indigenous women. The Canadian model of population health promotion guided information analysis. Fourteen healthcare professionals with experience working in four Brazilian states and with 11 ethnic groups were consulted. A total of 23 modifiable situations were identified, and an original conceptual framework was developed that encompasses the following health promotion areas as modifiable situations: structure of the healthcare network; administrative barriers in healthcare management; operationalization of care delivery; and clinical and social contexts.ConclusionThis article conceptualizes areas for innovative and socially responsive solutions to amend vulnerabilities in Brazilian Indigenous maternal health. The conceptual framework proposed offers a useful operational foundation for designing future interventions in Indigenous maternal health and for strengthening action research as a transformative methodological strategy in contexts marked by persistent historical and social inequalities.
Intra-arterial thrombolysis (IAT) following successful mechanical thrombectomy (MT) in patients with anterior circulation large-vessel occlusion (LVO) improves cerebral tissue reperfusion and consequently clinical outcome, but has to be validated in non-Asian populations. We hypothesised that IAT with alteplase versus no IAT leads to a better clinical outcome in patients with anterior circulation LVO stroke who have successful angiographic recanalisation. Intra-Arterial thrombolysis after SUCCESSful angiographic recanalization in acute large-vessel occlusion stroke of the anterior circulation (IA-SUCCESS) trial is a phase 3 investigator-initiated, multicentre, randomised, open-label, blinded-endpoint (PROBE) clinical trial with a health economic evaluation conducted in France. Patients with acute ischaemic stroke due to anterior circulation LVO within 24 h of stroke onset and successful angiographic reperfusion (defined as extended Thrombolysis in Cerebral Infarction score 2b-3) after intravenous thrombolysis alone, MT alone or both will be randomised in two balanced parallel groups (1:1) to receive either IAT with alteplase (0.225 mg kg-1 and a maximum of 20 mg) injected in the ipsilateral internal carotid artery or no IAT. A total of 626 patients will be included. The primary outcome is the functional outcome on the modified Rankin Scale at 90 (±15) days. Standard secondary clinical outcomes are assessed at 24 (±6) h, 5-7 days, 90 (±15) days and 12 (±1) months. Safety outcomes include mortality at 90 (±15) days and intracranial haemorrhage. The IA-SUCCESS trial will provide high-quality randomised data on the clinical efficacy and safety of intra-arterial alteplase following successful angiographic recanalisation in European patients with ischaemic stroke due to anterior circulation LVO intended for MT. ClinicalTrials.gov NCT06768138.
Blood donor screening occasionally identifies individuals with high HBV surface antigen (HBsAg) levels despite undetectable or extremely low HBV DNA. Molecular basis and transfusion risk of this discordant profile remain unclear. Seventy-five blood donors with HBsAg >100 IU/mL and undetectable or very low HBV DNA (<6 IU/mL), including 39 ID-NAT-nonreactive, were investigated. HBV DNA was further assessed using a second ID-NAT assay, confirmatory PCR following virion concentration, and sequencing. Sequences were compared with those from genotype-matched high-viremia controls. Selected basic core promoter (BCP) and core mutations were introduced into 1.18-mer replication-competent Hepatitis B virus (HBV) plasmids to assess effects on extracellular virion-associated DNA production. Four (5%) samples were nonreactive by the two ID-NAT assays. HBV DNA was confirmed in all donors, often at unquantifiable levels, and all were anti-HBc positive. No consistent molecular signature was identified. Heterogeneous, case-specific mutations were detected in BCP, core, and PreS1, including variants predicted to affect pregenomic RNA transcription, encapsidation, or virion assembly, with no evidence of impaired polymerase activity. In vitro, selected BCP mutations significantly reduced extracellular HBV DNA without affecting HBsAg production. Most core mutations had minimal impact, although two strains carrying cN92T/cM93T or cS170F showed reduced virion-associated DNA. Some constructs exhibited impaired virion secretion or increased naked capsid production. HBsAg-positive/low-DNA profile largely reflects chronic inactive infection with minimal viremia. Diverse regulatory and structural mutations may contribute in a multifactorial manner. Persistent viral genomes and residual replication support continued HBsAg screening where NAT sensitivity is suboptimal and anti-HBc testing cannot be implemented.
HLA-C*07:101 differs from HLA-C*07:04:01:01 by a single nucleotide substitution in codon 35 within exon 2.
The transfer of pesticides to Aiguillon Bay, a major coastal ecosystem on the Atlantic coast of France, was investigated in relation to watershed characteristics, agricultural pressure, and hydrological dynamics. The bay receives inputs from three main rivers (Sèvre Niortaise, Lay, and Curé) as well as from the Vieux channel, a downstream branch of the Lay watershed characterized by distinct land-use and drainage features. This study combined spatial land-use analysis with contamination indicators to clarify pesticide transfer pathways and associated ecological risks in intensively cultivated sub-basins. Monthly surface water samples were analyzed using LC-MS/MS and GC-MS/MS. A Proximity Indicator was developed to identify high-pressure agricultural zones adjacent to watercourses. Individual Risk Quotients (RQs) were also calculated by comparing measured environmental concentrations with Predicted No-Effect Concentrations (PNECs) to evaluate the ecological risk associated with selected pesticide compounds, and the Cumulative Toxic Pressure Index (CTPI) was applied to assess mixture toxicity. CTPI analysis revealed recurrent exceedances of the toxicity threshold (CTPI > 1) across all monitored systems, with strong seasonal variability linked to hydrological conditions. The Sèvre Niortaise and Vieux channel exhibited sustained mixture pressure, whereas the Lay showed pronounced event-driven peaks associated with rainfall episodes. Despite its smaller size, the Curé watershed displayed disproportionately high toxic pressure, reflecting strong hydrological connectivity and cereal-dominated land use. Herbicides and their metabolites were the primary contributors to mixture toxicity, including the persistent metabolite chlorothalonil R471811, frequently detected despite its regulatory ban in 2020, suggesting legacy contamination and progressive remobilization. Although individual Risk Quotients indicated negligible ecological risk for the selected compounds, CTPI revealed repeated mixture toxicity exceedances, demonstrating that cumulative effects represent the primary ecological pressure within the watershed. By integrating land-use characterization, hydrological analysis, statistical comparison, mixture toxicity assessment, and ecological risk evaluation, this study provides a comprehensive framework for understanding pesticide transfer to protected coastal ecosystems and supports the development of more effective watershed management and monitoring strategies.