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Long-Term Effects of a 5-Year Randomized Controlled Exercise Trial on Brain Volumes and Cognitive Function in Older Adults: A 4-Year Post-Intervention Follow-Up Study

Sports Med. 2026 Apr 18. doi: 10.1007/s40279-026-02434-3. Online ahead of print.

ABSTRACT

BACKGROUND: The lasting effects of exercise on brain health in older adults are poorly documented.

OBJECTIVE: The aim of this study was to assess the long-term, post-intervention effects 4 years after a 5-year exercise intervention on brain volumes and cognitive abilities in older adults.

METHODS: A total of 106 older adults (70-77 years at baseline) from the randomized controlled trial (RCT) Generation 100 study randomized into high-intensity interval training (HIIT), moderate-intensity continuous training (MICT), or a control group following national physical activity guidelines for 5 years were included. Post-intervention assessment was performed 9 years after inclusion. Brain magnetic resonance imaging (MRI) and exercise characteristics were acquired at baseline and after 1, 3, 5, and 9 years. Cognitive abilities were assessed with verbal list learning, pattern separation, and odor identification tests at baseline and 9 years. Linear mixed models were used to examine the interaction between exercise group and time on brain volumes. The analyses were repeated, including self-reported exercise behaviors (intensity and duration) as covariates. To examine the general effect of exercise intensity independent of group, a separate model was run across all participants with self-reported exercise intensity as independent variable. For cognition, linear regressions examined associations between exercise group and self-reported exercise intensity on cognitive scores at 9 years, and hippocampal volume loss over time on cognitive scores at 9 years. Whether baseline peak oxygen uptake (VO2peak) predicted brain volumes and cognitive scores at 9 years was tested with linear regression.

RESULTS: The time × group interaction revealed greater hippocampal volume loss in the HIIT compared with the control group 4 years after the intervention ended, similar to what was found during the intervention. We did not find that self-reported exercise behavior was associated with hippocampal volume over time. Across all participants, greater hippocampal volume loss was associated with poorer verbal memory at 9 years. The test scores on verbal memory and pattern separation did, however, not differ between the groups, but the MICT, and trending for the HIIT group, had higher odor identification scores at 9 years. Higher baseline VO2peak predicted larger cortical volume and better pattern separation score at 9 years across intervention groups, in line with what was observed during the intervention.

CONCLUSIONS: The control group, which followed the national physical activity guidelines, had the lowest hippocampal volume loss over time, even 4 years after the end of a 5-year exercise intervention in fit older adults. Furthermore, higher baseline VO2peak provided protective effects on both cortical volume and pattern separation ability across almost a decade, independent of exercise group.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01666340 (registered 16 August 2012).

PMID:41999477 | DOI:10.1007/s40279-026-02434-3

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The emerging roles of yeasts as plant growth promoters: mechanisms, benefits, and agricultural applications

World J Microbiol Biotechnol. 2026 Apr 18;42(5):224. doi: 10.1007/s11274-026-04810-7.

NO ABSTRACT

PMID:41999466 | DOI:10.1007/s11274-026-04810-7

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Spesolimab for generalized pustular psoriasis: A prospective study with a 6-month-follow-up

Clin Exp Dermatol. 2026 Apr 18:llag169. doi: 10.1093/ced/llag169. Online ahead of print.

ABSTRACT

BACKGROUND: Generalized pustular psoriasis (GPP) is a rare, life-threatening skin disease. Spesolimab, an anti-IL-36R monoclonal antibody, has shown efficacy in clinical trials, yet real-world data remain limited.

OBJECTIVE: To evaluate the real-world effectiveness and safety of spesolimab in patients with GPP, and the influence of IL36RN mutation status on treatment response.

METHODS: A prospective study was conducted including patients with GPP treated with a single 900 mg intravenous infusion of spesolimab, with follow-ups at day 7, 1 month, 3 months, and 6 months. Disease severity was assessed using the GPPASI score. Screening of the IL36RN c.80T>C (p.L27P) mutation was performed using Sanger sequencing.

RESULTS: Fourteen patients (n=14) (9 women, 5 men; mean age 39.1 years) were included. The mean baseline GPPASI score was 3.61, which rapidly decreased to 1.3 at day 7, 0.52 at 1 month and 0.29 at 3 months, yet slightly increased to 0.35 at 6 months. The Wilcoxon signed-rank test confirmed a statistically significant decrease in GPPASI over time (p<0.05) from baseline which persisted till the third month. Three relapses occurred during follow-up, and they all responded to acitretin reintroduction. Among the 12 patients tested, 7 carried the IL36RN c.80T>C (p.L27P) mutation in the homozygous state. Treatment response was slightly faster in these patients but there were no statistically significant differences, and the 2 groups converged by the third month. No adverse events were observed.

CONCLUSION: Spesolimab demonstrated rapid and marked efficacy with excellent tolerability in GPP flares, regardless of IL36RN mutation status. Most cases had sustained remission, yet relapse occurred in a minority of patients. This calls for further research to optimize long-term and maintenance therapy.

PMID:41999186 | DOI:10.1093/ced/llag169

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Health Care-Related Tasks of Informal Dementia Caregivers in the U.S.: A Systematic Review with Narrative Synthesis

Inquiry. 2026 Jan-Dec;63:469580261438330. doi: 10.1177/00469580261438330. Epub 2026 Apr 18.

ABSTRACT

Health care-related tasks (e.g., making appointments, talking to providers) performed by informal caregivers caring for older adults with dementia have become increasingly common, yet the evidence on caregiving task profiles remains fragmented and has not been comprehensively synthesized. This is a systematic review with narrative synthesis of the patterns of health care-related tasks and the characteristics of caregivers who performed them. We searched PubMed, Embase, PsychInfo, Web of Science, and CINAHL databases. The identified tasks were grouped into health and medical care, advocacy and care coordination, and surrogate tasks. We also reported caregiver characteristics. We included 12 studies. Only 5 studies reported on racial and ethnic minority caregivers. Medication management was the most common health and medical care task. Only 1 study reported surrogate tasks, and 2 studies reported caregivers performing advocacy and care coordination tasks. This study is particularly timely given the recent implementation of the Centers for Medicare and Medicaid Services (CMS) Guiding an Improved Dementia Experience (GUIDE) Model, which includes caregiver support and education as core components of dementia care delivery. Systematically characterizing the health care-related tasks performed by dementia caregivers can inform the design, targeting, and evaluation of the GUIDE Model.

PMID:41999183 | DOI:10.1177/00469580261438330

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A meta-analysis of perceived infectability, germ aversion, disgust and outgroup perceptions: Evaluating research on the behavioural immune system

Br J Psychol. 2026 Apr 18. doi: 10.1111/bjop.70076. Online ahead of print.

ABSTRACT

Scholarship on the behavioural immune system suggests that people who perceive themselves as more susceptible to illnesses are more sensitive to disgust, providing an evolutionary advantage to avoid pathogenic stimuli. This sensitivity causes those with greater perceived susceptibility to be biased against outgroup members and avoid those with dissimilar immunological histories. However, the lack of a quantitative review forces researchers to derive arguments from specific empirical observations, rather than holistically drawing from averaged effects across studies. Researchers may over-rely on studies that produced atypical results, causing biases in research on perceived infectability, germ aversion, disgust and outgroup perceptions. To resolve this tension in the literature, we perform a meta-analysis of 74 sources. Our meta-analytic results demonstrate that perceived infectability produces small relations with disgust and non-significant relations with outgroup perceptions, whereas a construct commonly conflated with perceived infectability, germ aversion, produces larger relations with these two outcomes. A meta-analytic structural equation model demonstrates that the indirect effect of perceived infectability on outgroup perceptions via the mediator of disgust is not statistically significant. These findings indicate that, while perceived infectability relates to disgust, the construct does not relate to perceptions of outgroup members, counter to scholarship on the behavioural immune system.

PMID:41999167 | DOI:10.1111/bjop.70076

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Impact of Therapeutic Ultrasound on Metabolic Hormone Release from Thyroid Gland

J Ultrasound Med. 2026 Apr 18. doi: 10.1002/jum.70265. Online ahead of print.

ABSTRACT

OBJECTIVES: This study focused on determining if ultrasound therapy could stimulate and control the function of the thyroid gland, specifically the synthesis and release of metabolic hormones thyroxine (T4) and triiodothyronine (T3) in a physiologically relevant ex vivo model.

METHODS: Excised thyroid glands obtained from healthy adult Sprague-Dawley rats were diced into sections and placed in wells containing 1 mL of Krebs Ringer Buffer with 5 mmol glucose. Continuous, unfocused ultrasound was applied at 1 W/cm2 for 5 minutes at frequencies of 600 kHz, 800 kHz, and 1 MHz using a circular planar transducer positioned at the near field-far field transition distance. Samples were collected at time points 0, 5, and 35 minutes after ultrasound sonication. T3 and T4 concentrations were analyzed using competitive enzyme-linked immunosorbent assays, and histological examination was performed using hematoxylin and eosin staining.

RESULTS: There was no statistically significant difference in T4 or T3 release between the ultrasound treated and sham treated samples at any combination of frequency and time point tested (p > .05 for all comparisons). Histological analysis revealed no structural abnormalities or gross microscopic changes in ultrasound-treated samples.

CONCLUSIONS: Unlike previous studies demonstrating ultrasound-stimulated insulin release from pancreatic beta cells, therapeutic ultrasound at the tested parameters did not stimulate T3 or T4 release from ex vivo thyroid tissue.

PMID:41999146 | DOI:10.1002/jum.70265

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Hypointensity on Carotid Plaque MRI and Its Relationship to Calcification: Histopathologic Validation With Quantitative Susceptibility Mapping

J Magn Reson Imaging. 2026 Apr 18. doi: 10.1002/jmri.70335. Online ahead of print.

ABSTRACT

BACKGROUND: On conventional carotid plaque MRI, calcification is commonly defined as a region that is hypointense across multiple contrast weightings. However, iron-containing components such as hemosiderin may exhibit similar signal characteristics, raising concerns regarding substrate specificity.

PURPOSE: To evaluate whether quantitative susceptibility mapping (QSM) can distinguish hemosiderin from calcification in carotid atherosclerotic plaques using ex vivo MRI with direct histopathologic correlation.

STUDY TYPE: Ex vivo specimen study.

SPECIMEN: Twenty-four carotid endarterectomy specimens obtained between October 2017 and August 2021.

FIELD STRENGTH/SEQUENCE: 3T MRI including spin-echo T1-weighted, spin-echo T2-weighted, time-of-flight-equivalent gradient-echo (FLASH) imaging, and multi-echo FLASH-based QSM reconstruction.

ASSESSMENT: Histologic sections were stained with hematoxylin-eosin, von Kossa (calcification), and Berlin blue (hemosiderin). With histopathologic findings as reference, two radiologists defined corresponding regions of interest on MRI for substrate-level signal characterization. Contrast-to-noise ratios (CNR) were measured on conventional sequences, and relative susceptibility values (rSV) were measured on QSM.

STATISTICAL TEST: Group comparisons were performed using the Wilcoxon rank-sum test. A two-sided p < 0.05 was considered statistically significant.

RESULTS: Seventy-nine matched cross-sections yielded 41 calcifications and 25 hemosiderin deposits, including 16 sections with both components. On T1-, T2-, and FLASH imaging, CNR values did not differ significantly between calcification and hemosiderin (p = 0.12, p = 0.096, and p = 0.67, respectively), with substantial signal overlap. On QSM, hemosiderin exhibited positive rSVs (mean ± SD: 506.8 ± 320.5 ppb), whereas calcification exhibited negative rSVs (-440.5 ± 296.3 ppb), without polarity overlap in this dataset and with a significant group difference. Hemosiderin deposition was identified in 25 of 79 matched sections, and calcification and hemosiderin coexisted in 16 sections.

DATA CONCLUSIONS: Hypointensity on conventional carotid plaque MRI may not reliably indicate calcification at the substrate level. QSM enables robust differentiation between diamagnetic calcium and paramagnetic iron with histopathologic validation.

TECHNICAL EFFICACY: Stage 2.

PMID:41999130 | DOI:10.1002/jmri.70335

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RAMP-UP: Pharmacist-Led Methadone Titration for Hospitalized Patients With Opioid Use Disorder

Subst Use Addctn J. 2026 Apr 17:29767342261433344. doi: 10.1177/29767342261433344. Online ahead of print.

ABSTRACT

BACKGROUND: Hospitals increasingly start methadone treatment for opioid use disorder (OUD). Rapid methadone titration has been described in hospitals with addiction consult teams; however, most hospitals lack these specialty services. We evaluated whether a pharmacist-led rapid methadone titration protocol (“RAMP-UP”) increased the proportion of hospitalizations that reached a minimally therapeutic dose of methadone (≥60 mg) before discharge.

METHODS: We conducted a retrospective, quasi-experimental, pre-post study comparing outcomes 7 months before versus 7 months after the implementation of RAMP-UP. The study included all adults admitted to a large academic medical center between March 2022 and April 2023 who newly initiated methadone for OUD. We used multivariable regression with generalized estimating equations to evaluate the primary outcome of achieving a total daily methadone dose of at least 60 mg by hospital discharge. Secondary outcomes included days to therapeutic dose, total daily methadone dose, and opioid-related safety events.

RESULTS: We identified n = 155 admissions, 55 pre-intervention and 100 post-intervention, among 124 unique patients with OUD. After RAMP-UP, a higher proportion of encounters reached ≥60 mg total daily dose (TDD) of methadone, but this difference was not significant in adjusted analyses (45.5% pre-implementation vs 60.0% post-implementation, P = .06). Post-implementation encounters had higher methadone TDD on discharge (62 vs 55 mg; P = .04) and, among those who reached 60 mg TDD, achieved this dose faster (9.0 vs 4.0 days, P < .001). Safety events were uncommon and similar (11.0% vs 12.7%; P = .80).

CONCLUSIONS: Pharmacist-guided rapid titration accelerated attainment of therapeutic methadone doses and did not increase adverse events. Although the adjusted increase in the proportion achieving ≥60 mg TDD by discharge was not statistically significant, these findings demonstrate how inpatient clinical pharmacists can modernize inpatient OUD care.

PMID:41999110 | DOI:10.1177/29767342261433344

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Differences in Cancer Patient Experience by Race, Ethnicity, and Preferred Language: A Systematic Review

Cancer Med. 2026 Apr;15(4):e71835. doi: 10.1002/cam4.71835.

ABSTRACT

INTRODUCTION: Patient experience ratings are tied to high quality patient-centered care and value-based health system metrics. Existing research has identified disparities in cancer care access and clinical outcomes. This systematic review summarizes findings on how the cancer patient experience differs by race, ethnicity, and preferred language.

METHODS: Using PRISMA guidelines, we searched PubMed, EMBASE, PsycINFO, CINAHL, and Cochrane CENTRAL through August 2023. Studies were included if the population consisted of White and racial and/or ethnic underrepresented patients who were receiving or had received cancer care; a comparison was made across racial, ethnic, and/or preferred language groups; and outcomes included patient experience ratings or related measures. Studies were excluded if they lacked cancer-specific populations, relative comparisons, or outcomes related to patient experience. Study quality was assessed using Joanna Briggs Institute critical appraisal tools, and data were independently extracted by two authors.

RESULTS: Thirty-six studies (n = 292,345 cancer patients) met inclusion criteria. Twenty-three studies demonstrated worse experiential outcomes among racial and ethnic minority groups compared to non-Hispanic White patients. Among studies including language in their analysis, nine studies indicated cancer patients with a non-English language preference tended to report worse experiences compared to those who prefer to communicate in English.

CONCLUSION: Cancer patients belonging to racial, ethnic, or preferred language minority groups are more likely to report worse care experiences than non-Hispanic White patients. Significant variation exists in how patient experience is defined and measured. These disparities must be addressed to optimize clinical outcomes and ensure equity in health system value-based metrics.

TRIAL REGISTRATION: PROSPERO: CRD42018102189.

PMID:41999109 | DOI:10.1002/cam4.71835

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Chip-Based Digital PCR Approach for Improved SARS-CoV-2 Quantification for Endemic Wastewater Surveillance

Water Environ Res. 2026 Apr;98(4):e70372. doi: 10.1002/wer.70372.

ABSTRACT

The COVID-19 pandemic has revealed the importance of wastewater-based epidemiology (WBE) due to its advantages over traditional surveillance systems. However, low viral prevalence poses a significant challenge for reliable detection of SARS-CoV-2 in endemic wastewater settings. This study aimed to improve detection sensitivity of SARS-CoV-2 by applying the chip-based digital PCR (dPCR) approach targeting the CDC N1 and N2 genes to wastewater samples processed with a combined magnetic bead concentration method during a low-prevalence period in South Korea. Here, the evaluation results using dPCR combined with magnetic bead concentration showed higher viral loads and lower variability compared to the commonly used electronegative filtration method. Comparative analysis of the dual-target N1 + N2 and E-Sarbeco assays revealed that the N1 + N2 assay yielded significantly higher concentrations (4.73 ± 0.19 log10 GC/L) than the E gene assay (4.27 ± 0.25 log10 GC/L) in dPCR analysis (p < 0.01). PMMoV normalization increased the Pearson correlation coefficient between SARS-CoV-2 concentrations and clinical case data from R = 0.1 to R = 0.31; however, this was not statistically significant. These findings contribute to enhancing detection sensitivity for SARS-CoV-2 wastewater surveillance in endemic settings.

PMID:41999093 | DOI:10.1002/wer.70372