搜索结果：Journal of clinical and translational science

Utilization of the clinical pharmacist practitioner (CPP) providing comprehensive medication management (CMM) has been shown to improve the quadruple aim of healthcare. Unfortunately, rural Veterans often lack access to the expertise of CPP, leading to differences in the quality of care provided as compared to non-rural Veterans. We explored the integration of CPP providing CMM as part of a partnership with the Office of Rural Health funded enterprise-wide initiative. Facilities trained, integrated, and measured CPP regarding quality of care and access to care in a rural Veteran initiative-the Chronic Obstructive Pulmonary Disease Coordinated Access to Reduce Exacerbations (COPD CARE). Twenty-two primary care CPP at 17 facilities were trained focusing on COPD management in addition to CMM. All data and reports were extracted and derived from the VA Corporate Data Warehouse (CDW). For measurement of access, we evaluated the number of Veterans served as well as the number of total encounters performed, and the modality of care provided by the CPP. The overall percentage of Veterans noted as "rural" was also tracked. The percentage of patients that were seen by a primary care provider or CPP within 30, 60, and 90 days of ED or inpatient discharge were compared for those referred to and not referred to the COPD CARE program. Evaluation of quality adherence metrics, based on guideline directed therapy, compared the CPP COPD managed population to all Veterans with COPD. From October 2022 through September 2024, COPD CARE CPP performed 71,520 encounters in 21,168 Veterans with a total program rurality of 70.8%. The percentage of patients that were seen by a primary care provider or CPP within 30, 60, and 90 days of ED or inpatient discharge were consistently higher for those referred to the COPD CARE program versus those who were not. By 90 days, 81.7% of those referred were seen versus 53.2% of those not referred. In the 2 years following hiring of primary care CPPs, 7 of the 10 best practices were delivered on over 90% of visits, where 5 of those best practices were delivered on over 99% of visits. This study demonstrated improved access and improved guideline directed therapy outcomes for rural Veterans seen by a CPP. Integration of the CPP with a focus on the management of COPD can increase access to CMM and increase overall quality.

Team science is central to clinical and translational research; however, systematic evaluation of collaborative efforts remains inconsistent and underdeveloped. To better understand current team science evaluation practices within clinical and translational science programs, we conducted a structured cross-sectional survey of team science and evaluation professionals. We analyzed quantitative data using descriptive statistics and qualitative responses through thematic analysis. Among participating organizations, the majority have implemented team science evaluations, predominantly using mixed-methods approaches combining quantitative metrics and qualitative assessments. Evaluation findings were primarily used to inform programing, improve team functioning, and secure funding. Reported challenges fell into four key areas: methodology; implementation; data analysis; and organization. Facilitators included: methodological enhancements, organizational support, collaborative approaches, and infrastructure elements. Participants emphasized using interim measures (e.g., team dynamics and satisfaction) that move beyond traditional outcome measures so that evaluations better reflect how teams interact, adapt, and progress as they develop. While team science evaluation adoption is substantial among leading translational research institutions, significant methodological gaps persist. Future directions focus on developing standardized frameworks with local flexibility, creating validated instruments, utilizing interim process measures, and demonstrating return on investment (ROI) to advance both evaluation science and translational outcomes.

Cervical cancer is still a significant issue, especially in low- and middle-income countries. Adding HPV self-sampling to cervical cancer screening programs could make the process simpler for people to receive essential health care and support universal health coverage. Therefore, this study is aimed at mapping research output, global trends, and collaboration networks related to the implementation of HPV self-sampling in cervical cancer screening programs. A bibliometric, descriptive, and retrospective study was performed, covering the period from 2006 to October 2025. A search was conducted in Scopus, confined to the TITLE-ABS-KEY fields, without language limitations, and restricted to documents in their final publication stage and original research articles. The search syntax used Boolean operators (AND, OR) to combine four thematic blocks: self-sampling/self-collection, etiological agent, cervical screening, and implementation and programmatic delivery. The study examined a number of indicators, such as the volume of research output, the amount of authorship credit per article, the number of normalized citations, the number of citations, the h-index, the g-index, and the m-index. R (RStudio) Version 4.3.1 was used to analyze the data. There were 824 articles published in 268 journals. The number of research papers published each year went up by 14.90%, and each paper received an average of 21.16 citations per year. Each paper had 8.38 coauthors, and 39.56% of the time, the coauthors were from other countries. The United States and Australia became major contributors, working together in dense networks that crossed continents. Editorial dissemination was primarily found in oncology and public health journals, with cocitation patterns connecting clinical and public health areas. The authorship distribution mirrored Lotka's pattern, with 71.90% of authors contributing a single article and 4.10% producing five or more. The focus shifted from cytology and acceptability to molecular testing and self-sampling from 2006 to 2011. From 2012 to 2016, the focus was more on equity and digital support tools along the screening pathway. The focus on sociocultural issues got stronger between 2017 and 2019. From 2020 to 2025, the literature began to emphasize clinical outcomes, HPV-16, populations living with HIV, and programmatic implementation, including the collection of urine samples. Research on HPV self-sampling is expanding, although it remains geographically concentrated. International collaboration is substantial, and the thematic focus has shifted toward programmatic implementation in higher-risk populations, with increasing emphasis on equity and digital support. These patterns underscore the need for stronger translational partnerships led by stakeholders in high-burden settings and supported by open science practices to reduce geographic disparities and inform context-sensitive public policies.

Spinal cord injury (SCI) triggers persistent neuroinflammation, gliosis, neuronal loss, and demyelination, leading to motor deficits and neuropathic pain (NeP). Botulinum neurotoxin type A (BoNT/A) has shown anti-inflammatory and neuroprotective effects in acute SCI, but its potential in the chronic phase remains unclear. This study investigates whether combining BoNT/A with electrical muscle stimulation (EMS) enhances recovery in chronic SCI. Adult mice with severe thoracic SCI (paraplegic) underwent EMS (30 min/d for 10 non-consecutive days starting 3 d post-injury) or no stimulation. Fifteen days after SCI, animals received a single intrathecal injection of BoNT/A (15 pg/5 μl) or saline. Functional recovery was assessed up to 60 d as well as in moderate and mild SCI mice. NeP onset and maintenance were evaluated. Spinal cord tissue was analysed for astrocytic and microglial morphology, neuronal and oligodendroglial survival, myelin protein expression, and in vitro effects on oligodendrocyte precursor cells (OPCs). The phenotype of hindlimb muscles was evaluated through morphological and gene expression analyses. EMS was able to counteract muscle atrophy and fibrosis, and when combined with BoNT/A, also denervation. Moreover, the combination restored hindlimb motor function in chronic SCI, whereas BoNT/A or EMS alone were ineffective. NeP, a common comorbidity associated with SCI, was mitigated by BoNT/A treatment even when administered in the chronic phase. BoNT/A reduced astrocytic hypertrophy and excitatory synapse association and was associated with a morphology-based redistribution of microglial profiles toward a resting-like classification, decreased apoptosis, and increased neuronal and oligodendroglial survival. Myelin basic protein (MBP) expression was significantly elevated in vivo. In vitro, BoNT/A promoted OPC differentiation into myelinating oligodendrocytes, increased process complexity, and upregulated MBP, galactocerebroside C, proteolipid protein, and myelin oligodendrocyte glycoprotein under both proliferative and differentiating conditions. Cleaved synaptosomal-associated protein 25 colocalization with OPC confirmed direct BoNT/A internalization and activity. BoNT/A exerts neuroprotective effects in chronic SCI by reducing neuroinflammation and supporting neuronal and oligodendroglial preservation. When combined with EMS, it also promotes remyelination and improves muscle homeostasis, suggesting that early stimulation creates a permissive environment for recovery. These findings support the clinical evaluation of BoNT/A as a therapeutic strategy for chronic SCI.

In preparing for our Clinical and Translational Science Award (CTSA) UM1 application, we recognized the need to develop a shared understanding of the distinctions between translational science (TS) and translational research (TR). We describe our efforts to develop and evaluate the reliability of a concise instrument that investigators and reviewers could use to distinguish between TS and TR. Groups of faculty and staff individually reviewed published translational studies to determine whether the project involved TS and, separately, TR. One group (n = 10) first reviewed 14 publications with limited guidance; the same group and a second group (n = 9) then reviewed another set of 14 publications guided by a detailed algorithm. We used kappa statistics to measure agreement in the determinations of TS and TR for each publication. The overall kappa coefficients in the three sets of TS determinations (two by the first group and one by the second group) were 0.61, 0.33, and 0.18, respectively. The overall kappa coefficients in the three sets of TR determinations were 0.26, 0.11, and 0.40, respectively. The median kappa coefficients for all 42 determinations were 0.39 for TS and 0.22 for TR, both indicating only fair agreement. We found no evidence that the algorithm helped to improve agreement rates. Our results show gaps in understanding the distinction between TS and TR among CTSA hub faculty and staff. We discuss some reasons for this gap and propose ways that could improve the recognition of TS and TR.

Obesity is considered a risk factor for pain, and comorbid obesity and pain have a cumulatively worse impact on function and quality of life than either condition alone. The aim of this study was to estimate the prevalence of pain and describe the multidimensional biopsychosocial pain profiles of people with obesity (PwO). This pre-specified cross-sectional study reports the baseline data from a longitudinal cohort study. We recruited 519 PwO from three specialist obesity clinics in Ireland. Participants completed pain-, obesity- and health-related questionnaires to capture the multidimensional biopsychosocial characteristics of their pain experience. Data were analysed using descriptive and inferential statistics. Pain prevalence was 77% (95% CI: 73.1%-80.6%) (70.7% female; mean age 46.6 ± 12.7 years). Participants' pain characteristics reflected heterogeneity in the pain experiences of PwO, including (mean; SD): pain intensity (0-10 numerical rating scale) (3.97 ± 2.9), number of pain locations (0-35) (5.06 ± 5.3), levels of pain-related disability and self-efficacy. The prevalence of nociplastic pain was 54% (95% CI: 49.3%-58.6%) and neuropathic pain was 30% (95% CI: 25.6%-34.8%). Clinically significant levels of pain-related worrying and kinesiophobia were reported by 20.9% (95% CI: 17.3%-24.8%) and 49.9% (95% CI: 45%-54.7%) of participants. The majority (77%) of PwO attending specialist obesity treatment services report experiencing pain. The intensity, nature, and impact of their pain vary. Over half reported nociplastic pain, one-third neuropathic pain, one-fifth significant pain-related worrying, and half kinesiophobia. These findings have implications for pain management in PwO. This is the first multicentre prospective cohort study to investigate the multidimensional pain profiles of PwO. Pain prevalence was 77%. This is the first study to estimate (i) baseline prevalence of nociplastic-dominant pain in PwO (54%); (ii) baseline prevalence of neuropathic pain in PwO (30%); (iii) clinically significant levels of pain-related fear (20.9%); and (iv) clinically significant levels of kinesiophobia (49.9%), in PwO attending specialist obesity treatment services. These findings have clinical implications for the treatment of pain in PwO.

Low-field MRI has recently gained interest due to its potential for increased accessibility, reduced cost, and improved safety. However, high-quality anatomical imaging and robust tissue characterization remains an active area of research, particularly when aiming for a simple, one-click scan that captures all relevant information in a single acquisition. Bright-blood imaging is widely used for visualizing cardiac structures and coronary arteries, whereas black-blood is optimal for delineating the myocardium, atrial and vessel walls. High-resolution imaging is required for the accurate detection and segmentation of small anatomical structures, such as the coronary arteries, to enable assessment of narrowing or blockages. Co-registered T 1 / T 2 $$ {T}_1/{T}_2 $$ mapping enables quantitative myocardial tissue characterization, offering valuable clinical information for the detection of myocardial abnormalities. In this study, we sought to develop a novel free-breathing, motion-compensated 3D multi-contrast high-resolution cardiac MR sequence for simultaneous assessment of whole-heart cardiovascular anatomy via bright- and black-blood imaging and myocardial tissue quantification by joint T 1 $$ {T}_1 $$ and T 2 $$ {T}_2 $$ mapping at 0.55 T in a single scan. Data were acquired over six interleaved contrasts with various preparation modules using a variable flip angle bSSFP spiral-like readout with 2D image-based navigation for translational motion correction, resulting in a predictable acquisition time of ≈ 12 $$ \approx 12 $$ min. Images were reconstructed using non-rigid motion corrected iterative sensitivity encoding followed by high-dimensional patch-based low-rank denoising, resulting in the acquisition, reconstruction and quantitative mapping time of ≈ 31 $$ \approx 31 $$ min. In the phantom study, sequence performance was evaluated using correlation and Bland-Altman analysis against reference gold-standard and clinical mapping methods. In vivo, 3D bright- and black-blood volumes were assessed in multiple views, and vessel sharpness was quantified from multiplanar images. For joint T 1 / T 2 $$ {T}_1/{T}_2 $$ mapping, bull's-eye plots were generated to evaluate the mean, standard deviation, and coefficient of variation for apical, mid-cavity, and basal segments, and results were summarized using violin plots. Differences between the proposed 3D sequence and established 2D methods were analyzed with a two-tailed t $$ t $$ -test. In the phantom study, a small positive bias in T 1 $$ {T}_1 $$ of 6 . 3 ms $$ 6.3\kern0.3em \mathrm{ms} $$ was observed compared with inversion recovery spin-echo and 23 . 5 ms $$ 23.5\kern0.3em \mathrm{ms} $$ with MOLLI, while for T 2 $$ {T}_2 $$ biases of 7 . 3 ms $$ 7.3\kern0.3em \mathrm{ms} $$ compared with spin-echo and 0 . 8 ms $$ 0.8\kern0.3em \mathrm{ms} $$ with T 2 $$ {T}_2 $$ prep bSSFP were found. In vivo, statistically similar T 1 $$ {T}_1 $$ values of ( 648 ± 26 ) ms $$ \left(648\pm 26\right)\kern0.3em \mathrm{ms} $$ and T 2 $$ {T}_2 $$ values of ( 56 . 9 ± 3 . 2 ) ms $$ \left(56.9\pm 3.2\right)\kern0.3em \mathrm{ms} $$ were obtained, with differences versus MOLLI of - 3 ms ± 15 ms $$ -3\kern0.3em \mathrm{ms}\pm 15\kern0.3em \mathrm{ms} $$ ( p = 0 . 75 $$ p=0.75 $$ ) and versus T 2 $$ {T}_2 $$ prep bSSFP of - 0 . 5 ms ± 2 . 1 ms $$ -0.5\kern0.3em \mathrm{ms}\pm 2.1\kern0.3em \mathrm{ms} $$ ( p = 0 . 63 $$ p=0.63 $$ ). The proposed sequence demonstrated high image quality and accurate mapping despite the inherent limitations of low-field strength, suggesting its feasibility for comprehensive cardiac assessment in resource-limited environments.

Artificial intelligence (AI)-enabled digital pathology has advanced rapidly in head and neck squamous cell carcinoma (HNSCC), but its readiness for clinical implementation remains uncertain. This review evaluates the translational maturity of AI-based digital pathology applications in HNSCC and their proximity to routine clinical use. A structured literature search of PubMed and Scopus identified studies published between January 2020 and March 2026. Studies were included if they applied AI or machine learning to histopathologic or whole-slide images in HNSCC or related oral malignancies and reported diagnostic, prognostic, biomarker, or treatment-response outcomes. Given the narrative scope of this review, representative studies aligned with key clinical domains were selected for qualitative synthesis. A six-stage translational maturity framework was used to categorize applications based on development stage, validation, and clinical integration. Of 444 identified records, 358 unique studies were screened, from which representative HNSCC-specific AI digital pathology studies were selected for detailed analysis. Most applications-including diagnostic classification, dysplasia grading, prognostic modeling, and therapy-response prediction-remain at early translational stages (Stage 0-1), typically limited to retrospective, single-center cohorts with minimal external validation. Biomarker quantification and HPV prediction show relatively greater maturity, with some studies approaching Stage 2, reflecting external validation and early prospective evaluation. However, calibration, decision-curve analysis, and outcome-linked endpoints are rarely reported. No HNSCC-specific AI pathology tools have demonstrated outcome-linked deployment or achieved regulatory-grade implementation, and evidence for workflow integration, clinical decision impact, and patient-centered outcomes remains limited. AI-enabled digital pathology in HNSCC remains an early-stage field. Despite promising technical performance, most applications lack the prospective validation, workflow integration, and outcome-based evidence required for clinical adoption. Progress will depend on multi-institutional prospective studies, standardized reporting of clinical utility, and demonstration that AI-assisted decisions improve patient management and outcomes.

Ischemic stroke comprises about 87% of all stroke cases in the US. 20% of these have a cardioembolic (CE) etiology, and 25% are still considered embolic strokes of undetermined sources (ESUS). ESUS strokes are associated with worse functional outcomes and survival rates, underscoring the need for understanding the clinical differences in stroke etiology. We analyzed the Investigation of Clot in Ischemic Stroke and Hematoma Evacuation (INSIGHT) registry (NCT04693767, https://clinicaltrials.gov/study/NCT04693767), which includes n=388 patients total (n=208 CE, n=142 AFIB, n=180 non-CE). We analyzed 123 data features, spanning across domains including demographics, past medical history, baseline blood lab values, intraoperative data, and thrombus characteristics. We found correlations, univariate analyses, and LASSO machine learning models to predict etiology. We found several associations between clinical variables and stroke etiology. Higher baseline prothrombin time and INR (only among patients not on anticoagulants), baseline use of antiarrhythmics and antihypertensives, and a higher baseline mRS were associated with an increased risk of both overall CE and AFIB-specific etiologies. A higher baseline platelet and RBC count was associated with a decreased risk of AFIB stroke etiology. All of these results were significant (p<0.05) across multiple analysis methods. Lastly, our LASSO models predicted CE and AFIB-specific etiologies with an AUC of 0.71 and 0.73, respectively. Several clinical features are strongly correlated with stroke etiology, and these can be combined in a machine learning model to predict stroke etiology.

Despite substantial investment in clinical and translational research, only a small proportion of evidence-based interventions are adopted and sustained in routine practice, contributing to persistent delays between discovery and population benefit. Dissemination and implementation (D&I) science is a critical discipline for addressing this gap, and the NIH Clinical and Translational Science Award (CTSA) program (established 2006) has been strategically positioned as a national infrastructure to advance D&I capacity. We conducted a national environmental scan of publicly available websites and documents from all 66 CTSA hubs (May-July 2025), using a structured extraction tool to capture D&I-specific activities across seven domains: institution and community partnerships, formal D&I organizational structures within the CTSA, consultation services, collaborative programming, training opportunities, educational offerings, and pilot funding mechanisms. Findings reveal substantial heterogeneity in D&I science activities across CTSA hubs; 45% had a formal D&I unit, 54% offered D&I consultation services, and 37% provided collaborative programming. Structured workforce development was limited: 12% offered D&I-focused training grants, 15% offered structured educational programs, and 15% provided D&I-specific pilot funding. Consultation models varied widely in scope, access, and evaluation practices. These findings demonstrate uneven development of D&I science infrastructure across CTSAs and highlight opportunities to strengthen capacity nationally.

Early-stage clinical and translational researchers require not only technical expertise but also leadership and communication skills for long-term success. Many training programs lack structured approaches to building these essential "soft skills." To evaluate the impact and perceived value of a structured coaching and leadership program for trainees in KL2 and T32 programs. This qualitative evaluation assessed a Coaching and Leadership Program (CLP) that include individualized coaching and group workshops incorporating leadership development and the DISC behavioral communication model (Dominance, Influence, Steadiness, and Conscientiousness). Semi-structured interviews were conducted with twelve KL2 and postdoctoral T32 trainees between July and August 2025. Transcripts were analyzed using descriptive content analysis and inductive coding by two analysts in MAXQDA. Five key themes emerged: 1) Both T and K trainees consistently described the CLP as a broadly positive and beneficial experience; 2) Coaching helped trainees build concrete organizational strategies, particularly around time management and logistical processes; 3) The CLP helped build trainees' confidence and professional identity, especially around communication with mentors, bosses, or their team; 4) The CLP was perceived as complementary and well integrated within KL2 and T32 training, particularly by addressing "soft skills" missing elsewhere; and 5) Participants recommended stronger orientation, more opportunities for practical skill-building during sessions, and offering greater variety and choice in coaches. The CLP complements scientific training for early-career translational researchers. Trainees gained practical tools for team management, conflict resolution, and strategic planning, while benefiting from a confidential space for professional growth. Findings suggest coaching is a valuable enhancement to training programs for developing translational research leaders.

Successful completion of industry-sponsored clinical trials requires effective collaboration between sponsors and clinical research sites recruiting patients. As pharmaceutical companies specialize in more therapy areas, complexity and volume of clinical trials increases, with study sites facing growing operational and logistical challenges. These may be administrative, financial, technological, or workforce-related and can prevent sites from meeting trial obligations, inhibiting long-term site sustainability. Here we outline a suggested framework (with metrics) designed to address three key pillars: site infrastructure, workforce, and the establishment of a 'trial funnel' to maintain sufficient trial volume. We review key site-level challenges and barriers to success in clinical trial conduct and argue that issues could be mitigated by sponsors investing programmatically in their site partnerships, including investing in research-na&#xef;ve sites. Long-term programmatic planning and investment has the potential to deliver greater efficiency and sustainability in trial delivery; site investment upfront would increase working capital for the site, maximizing commitment and security on both sides. This, however, requires safeguarding through the implementation of targets and metrics of success. Many of the challenges faced in modern clinical research can be mitigated by new and longer-term thinking, concerning the working relationship and methods adopted between sponsors and research sites.

Human parvovirus B19 (HB19V) infection poses significant clinical challenges in resource-limited settings, particularly regarding blood safety surveillance and diagnosis of associated syndromes. Limited access to validated diagnostic assays restricts clinical management and transfusion safety protocols. The objective is to develop and validate an in-house duplex real-time PCR assay for HB19V detection and evaluate its clinical utility in a resource-limited setting. A duplex real-time PCR assay targeting the conserved NS1 gene of HB19V with RNase P as endogenous control was developed. Analytical validation assessed amplification efficiency, limit of detection (LOD), precision (intra- and inter-assay coefficients of variation), and cross-reactivity. Clinical validation compared qualitative agreement with a CE-certified commercial kit using Cohen's kappa statistic. Positive samples underwent Sanger sequencing for genotype characterization. Clinical specimens from suspected HB19V infections were tested and results correlated with patient presentations. The assay demonstrated 98.82% amplification efficiency with LOD of 6 copies/&#xb5;L. Precision metrics showed excellent reproducibility (CoV&#x2009;<&#x2009;1% intra-assay, <&#x2009;5% inter-assay) with no cross-reactivity. Qualitative agreement with the commercial reference was 100% (Cohen's kappa&#x2009;>&#x2009;0.95). Clinical application identified three significant cases: post-transfusion HB19V in neonatal bilirubin encephalopathy, HB19V consideration in severe anaemia with ventriculitis, and active infection in paediatric Ewing sarcoma with chemotherapy-induced cytopenias requiring IVIG therapy. Genotyping revealed genotypes 1a and 3, confirming regional viral diversity. This validated in-house duplex real-time PCR assay provides a cost-effective, locally sustainable diagnostic tool for HB19V detection. It addresses critical gaps in blood safety surveillance and expands diagnostic capacity for HB19V-associated syndromes in resource-limited settings, while highlighting the necessity of contextual clinical interpretation for optimal patient management.

Dopaminergic medication used in disorders like Parkinson's disease (PD) and restless legs syndrome can cause impulsive-compulsive behaviour (ICB), often with strong negative effects on patients' quality of life. This narrative review presents translational evidence on iatrogenic ICB, taking findings from epidemiological, clinical, neuroimaging and preclinical studies into consideration. Epidemiological and clinical studies find dopamine agonists with high D2/3-selectivity to be most strongly linked to ICB. Their effect on ICB has often been shown to be dose-dependent, but the impact of combining different dopaminergic drugs or applying extended-release formulations is less clear. Intervention studies support tapering or replacing dopamine agonists for ICB reduction, whereas no efficacious pharmacotherapy has been identified for ICB treatment specifically. Adequate animal models for mimicking different types of ICB are available, and point, in line with human neuroimaging studies, towards an involvement of striatum and prefrontal cortex in iatrogenic ICB. Overall, complementary research designs have led to profound evidence regarding the occurrence of ICB in PD and establishing methods transferable to other, less-studied patient populations. A combined approach integrating insights from human studies and animal models could contribute to developing dopaminergic drugs with lower ICB risk but also specific pharmacotherapies for impulsivity or compulsivity in the future. Diseases like Parkinson's disease and restless legs syndrome are treated with drugs that affect dopamine activity in the brain. As a side effect, these drugs can lead to a lower impulse control, manifested, for example, as gambling disorder or hypersexuality. This article summarises research on these side effects, collected through a variety of scientific methods. The drug type with the highest risk for behavioural side effects has been identified, but many details remain unclear, especially in patients with other disorders than Parkinson's disease. Results from both human brain imaging and animal models start to reveal brain pathways involved.

Maternal obesity is a major public health challenge that elevates pregnancy risks and predisposes offspring to lifelong metabolic disorders. Nutrition, as a modifiable determinant of the intrauterine environment, offers opportunities to interrupt this intergenerational cycle. This review synthesizes evidence on polyphenols, vitamins, omega-3 fatty acids, dietary fiber, probiotics, prebiotics, whole grains, and iron, highlighting underlying mechanisms and translational implications for maternal and offspring health. Preclinical studies demonstrate that these interventions improve maternal metabolism, modulate placental function, regulate gut microbiota, alter breast milk composition, and influence epigenetic programming. Clinical evidence is relatively strong for folic acid and vitamin D, whereas evidence for dietary fiber is emerging, with long-term offspring outcomes still insufficiently investigated. Polyphenols and omega-3 fatty acids exert antioxidant and anti-inflammatory effects, but translation is constrained by low bioavailability and limited safety data. Probiotics and prebiotics show potential in modulating maternal-infant gut health, yet trial outcomes are inconsistent and strain-specific. Whole grains and fortified foods may represent feasible options for population-level implementation, although robust longitudinal studies in obese pregnancies are still lacking. Dietary interventions hold promise for mitigating maternal obesity by improving metabolism, reducing inflammation, supporting placental function, and modulating gut microbiota, breast milk composition, and epigenetic programming. However, evidence is largely preclinical and long-term human data are limited. Future research should prioritize well-designed clinical trials and personalized approaches tailored to maternal phenotype and nutritional status to enable effective, scalable strategies for breaking the intergenerational cycle of obesity.

Obesity during pregnancy is at pandemic proportions and predisposes women to pre- and postnatal cardiovascular dysfunction. The mechanisms underlying this maternal cardiovascular vulnerability remain unclear, partly due to a lack of translatable models capable of longitudinal in vivo cardiovascular monitoring. Here, we characterize a novel ovine model of maternal diet-induced obesity during pregnancy. Ewes were fed a control (CON) or obesogenic (OB; ad libitum concentrates) diet for 60&#xa0;days pre-pregnancy and throughout gestation. Pregnant ewes were surgically instrumented with vascular catheters and Transonic flow probes using the wireless CamDAS system, which measured maternal cardiovascular function near term in free-moving ewes. Uterine artery vasoreactivity was assessed ex vivo by in vitro wire myography. OB ewes entered pregnancy 30% heavier than controls (P&#xa0;<&#xa0;0.003) and were hyperglycaemic, hyperinsulinaemic and hyperlipidaemic during pregnancy, relative to CON ewes (all P&#xa0;<&#xa0;0.05). OB ewes had elevated haematocrit and haemoglobin across pregnancy, and were hypertensive near term, with an increase in basal femoral artery blood flow, and elevated peripheral oxygen and glucose delivery (all P&#xa0;<&#xa0;0.05). OB mothers carrying a female fetus showed increased uterine artery vascular resistance in vivo (P&#xa0;<&#xa0;0.005) and reduced smooth muscle-dependent vasorelaxation ex vivo (P&#xa0;<&#xa0;0.05) relative to CON. Conversely, OB mothers carrying a male fetus showed greater NO-independent mechanisms mediating the uterine vasodilator response to methacholine ex vivo (P&#xa0;<&#xa0;0.001). Collectively, this study characterizes a robust model of maternal obesity during pregnancy that offers clinical translational potential and highlights fetal sex-specific changes to uterine artery function. KEY POINTS: Obesity during pregnancy is increasingly common and predisposes women to cardiovascular dysfunction during pregnancy and long after birth, but the specific mechanisms underlying this remain unclear. We developed a novel ovine model of diet-induced obesity during pregnancy that displays maternal hypertension, elevated haemoglobin, metabolic dysfunction, and alterations in uterine and peripheral blood flow and nutrient delivery near term. Mothers with obesity carrying a female fetus had elevated uterine vascular resistance in vivo and reduced uterine artery smooth muscle-dependent vasodilator reactivity ex vivo. Mothers with obesity carrying a male fetus showed no effect on uterine vascular resistance in vivo, but greater NO-independent mechanisms mediating the uterine vasodilator response to methacholine ex vivo. These findings highlight that fetal sex may influence maternal cardiovascular function during obese pregnancy.

Atopic dermatitis (AD), a chronic, immune-mediated inflammatory disease, is characterized by intense itch, eczematous rash, and skin pain, which can have negative impacts to quality-of-life (QoL), sleep, and mental health (especially anxiety and depression). Evaluation of the impacts of AD on the patient's lived experience are most accurately assessed by the patient, making measures of patient-reported outcomes (PROs) indispensable. The objective of the current study was to assess the long-term impact of upadacitinib, a once-daily oral selective Janus kinase inhibitor approved for the treatment of moderate-to-severe AD, on patient-reported outcomes, providing a comprehensive in-depth evaluation of results of patient experience across multiple domains. Using integrated data from the Measure Up 1 & 2 trials, the current study characterizes the efficacy of upadacitinib on several measures that assess the impact of AD on patients' lives, including patient-reported disease and symptom severity, sleep, emotional well-being, daily activities, QoL, and treatment satisfaction. Results demonstrated that rapid improvements in PRO measures of itch, sleep, daily activities, QoL, and emotional well-being reported at week 16 and week 52 were sustained or further improved at week 140 for patients with moderate-to-severe AD continuing upadacitinib 15&#x2009;mg or 30&#x2009;mg therapy, with no new safety signals observed. These findings support upadacitinib as a long-term treatment option to improve patient-reported burdensome symptoms of AD across 140&#x2009;weeks of exposure.

Food and nutrition insecurity are linked to poor health outcomes and disparities, yet how health care systems implement screening and referrals remains poorly understood. We searched for studies evaluating screening and referral processes for food and nutrition insecurity for patients of all ages in US health care settings. Searches were performed through May 2025 in MEDLINE (via PubMed), Cochrane (via Ovid), Cumulative Index of Nursing and Allied Health (EBSCO), and Social Interventions Research and Evaluation Network Evidence and Resource Library. Studies were included if they reported both a screening process and referral mechanism. Findings were synthesized narratively. Of 11&#x2009;406 records identified, 136 studies met the inclusion criteria; all screened for food insecurity, and none screened for nutrition insecurity. Most studies screened general populations across age, sex, race, and ethnicity, with few restricting by socioeconomic status or clinical conditions. Screening primarily used tools embedded within broader social determinants of health screenings (46%) and integrated into electronic health records (48%), typically in outpatient settings (49%). Screening methods varied, most commonly self-administered by patients (21%) or by clinic staff (20%) and were unspecified in one fifth of studies (21%). A total of 129 studies described 39 unique referral strategies across 4 categories: community-based resources (46%), health care-embedded services (35%), federal nutrition programs (12%), and Food Is Medicine interventions (7%), with 46% spanning multiple categories. While about half of studies (46%) reported referral rates, only about one third (37%) reported referral completion. These findings highlight current practices and evidence gaps, informing priorities to strengthen screening and referral systems that advance food security, nutrition, health, and health equity.

A multi-perspective evaluation of a Biostatistics, Epidemiology, and Research Design (BERD) program was conducted within an NIH Clinical and Translational Science Awards hub. The program provides individual and group consultations, an educational forum event, and pilot and conference grants. Surveys from consultants and consultees following 62 BERD consultations spanning one year across four institutions assessed satisfaction, effectiveness, and expectations. Respondents expressed strong satisfaction, intent to recommend consultations, and many noted that the support strengthened their study design and grant preparation. Consultants highlighted the need for additional BERD resources to strengthen pre-consultations guidance, sustained follow-up, and mentoring for early-career investigators.