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PubMed2026

Dietary approaches for glycemic management in type 1 diabetes: A systematic review of Mediterranean and low-carbohydrate diets.

BACKGROUND/OBJECTIVES: Specific dietary approaches for better management of type 1 diabetes (T1D) have not been thoroughly investigated. We conducted a systematic review to evaluate the Mediterranean and low-carbohydrate diets for glycemic management in people with T1D. METHODS: We examined longitudinal studies (cohort studies and clinical trials) including individuals with T1D who followed low-carbohydrate diets (<26% calories from carbohydrates and/or <130 g of carbohydrates per day) and/or a Mediterranean diet, while hemoglobin A1c (HbA1c) and/or time in range (TIR) were measured. Additional eligibility criteria included publication in English and availability of a full-text primary research article. Non-longitudinal studies, abstracts, and studies published in languages other than English were excluded. Results were synthesized narratively, and the GRADEpro Guideline Development Tool was used to assess article quality. RESULTS: A total of 565 studies were identified from PubMed, the Web of Science, and citation chasing. After removal of duplicates and further evaluation, 22 studies (6 cohort studies and 16 clinical trials; total n = 3284) were included in this review. The search was initially completed in May 2024, and updated February 2026. Low-carbohydrate diets were associated with better glycemic management when compared to usual diets or baseline glycemic parameters. Studies using CGM were overall underpowered. The impact of Mediterranean diets was less clear, but generally appeared to be less effective at improving glycemic management than low-carbohydrate diets. DISCUSSION: Although structured dietary interventions for T1D hold promise for improving glycemic outcomes, further research is needed to determine exactly which dietary intervention is most beneficial for this population. The evidence provided by included studies is limited by small sample sizes and short durations; better powered, longer-term studies are required to inform clinical recommendations.

Humans↗

PubMed2026

Improving Sleep and PTSD Outcomes in Service Members: A Randomized Controlled Trial Examining the Long-Term Effects of an Integrated Treatment.

Trauma-induced sleep disturbances often persist after successful posttraumatic stress disorder (PTSD) treatment. While integrated protocols combining sleep and exposure-based treatments may maximize outcomes, prior studies are limited and have largely relied on subjective sleep measures or failed to include long-term follow up assessments. Active-duty service members with PTSD (n = 82) were randomly assigned to Compressed Prolonged Exposure (CPE) treatment or Trauma Management Therapy (TMT), which integrates exposure therapy with sleep hygiene training and other skills-based interventions. PTSD symptoms and actigraphy-based sleep were measured at baseline, posttreatment, 3- and 6-month follow-up and data were compared between groups and across time. Posttreatment, both groups showed negligible to small changes in sleep compared to baseline. However, the TMT group evidenced improvements in most sleep parameters by the 3- and 6-month follow-ups, while sleep health generally worsened in the CPE group over time. Between groups, those randomized to TMT exhibited better sleep efficiency (g = 0.24) and onset latency (g = -0.34) at 3-month follow-up, and better sleep quality (g = 0.70), efficiency (g = 0.51), and wake after sleep onset (g = -0.52) at 6-month follow-up. Within both treatment groups, poorer sleep at the 6-month follow-up was correlated with greater PTSD symptom severity measured at the same time point. Integrated treatment for sleep and PTSD produced superior objective sleep outcomes compared to exposure alone, with the most meaningful improvements in sleep observed 6 months after treatment completion. Several critical directions for future studies are discussed.

Humans↗

PubMed2026

Form and function of actin impacts actin health and aging.

The actin cytoskeleton is a fundamental and highly conserved structure that functions in diverse cellular processes, yet its direct contribution to organismal aging remains unclear. Here, we systematically interrogated how genetic and pharmacologic perturbations of actin structure and function influence lifespan and various hallmarks of aging in Caenorhabditis elegans. Whole-animal and tissue-specific knockdown of actin and key actin-binding proteins (ABPs)-arx-2 (Arp2/3), unc-60 (cofilin), and lev-11 (tropomyosin)-led to premature disruption of filament organization, reduced lifespan, and tissue-specific physiological defects. Actin dysfunction also displayed a more "aged" transcriptome using previously validated transcriptomics clocks, and broadly exacerbated many age-associated phenotypes, including mitochondrial dysfunction, lipid dysregulation, loss of proteostasis, impaired autophagy, and intestinal barrier failure. Pharmacological destabilization with Latrunculin A mirrored genetic knockdowns, while mild stabilization with Jasplakinolide modestly extended lifespan, emphasizing that optimal and finely tuned actin function is critical for healthy aging. Finally, analysis of human genome-wide association data revealed that common ACTB polymorphisms correlate with differences in age-related decline in gait speed, suggesting some links between aging and actin across organisms. Taken together, our results provide a comprehensive and publicly accessible resource that maps, for the first time, how changes in actin integrity correlate with diverse aging phenotypes across tissues. This descriptive framework is intended to enable future mechanistic discovery by offering a deep, unbiased dataset that can be integrated with emerging studies to define how actin dynamics can potentially influence aging.

actin↗

PubMed2026

Perioperative Depression and Anxiety Care in Older Patients: A Randomized Clinical Trial.

IMPORTANCE: Depression and anxiety are common among older adults undergoing surgery and are associated with adverse postoperative outcomes. However, effective tailored perioperative mental health interventions are lacking. OBJECTIVE: To evaluate a perioperative intervention to optimize mental health. DESIGN, SETTING, AND PARTICIPANTS: A single-blind, hybrid, type 1, effectiveness-implementation randomized clinical trial was conducted (November 1, 2022, to March 31, 2025), with 3-month postoperative follow-up, at a US academic and community practice hospital network. Participants were 60 years or older; scheduled for cardiac, oncologic, or orthopedic surgery; and had clinically meaningful symptoms of depression and/or anxiety based on the Patient Health Questionnaire-Anxiety and Depressive Symptom (PHQ-ADS) scale. A total of 3159 patients were screened for eligibility, with 1518 ineligible, 1079 declining participation, and 236 excluded for other reasons. A total of 326 patients were enrolled and randomized (1:1), with 20 excluded after surgery cancelation. INTERVENTION: Participants were assigned to receive a perioperative intervention combining psychological management and pharmacologic optimization or enhanced usual care (materials for self-managing symptoms). MAIN OUTCOMES AND MEASURES: The primary outcome was change in PHQ-ADS score from baseline to 3 months after surgery. Other outcomes included persistent postsurgical pain, delirium, falls, quality of life, patient satisfaction, length of stay, and rehospitalizations. Implementability was evaluated through semistructured interviews and reach, acceptability, feasibility, appropriateness, and fidelity measures. RESULTS: A total of 306 older adults were included in analysis (mean [SD] age, 68.5 [6.1] years; 209 [68.3%] female; 153 randomized to intervention and 153 randomized to enhanced usual care): 102 cardiac, 100 oncologic, and 104 orthopedic patients. Participants' mean (SD) baseline PHQ-ADS score was 18.5 (7.4). At 3 months, there was a significant decrease in PHQ-ADS scores in the intervention group compared with the enhanced usual care group (mean difference, 2.20; 95% CI, 0.16-4.24; P = .03). Effects varied by surgical subgroups (oncologic patients: mean difference, 4.93; 95% CI, 1.51-8.36; P = .005; cardiac patients: mean difference, 2.68; 95% CI, -0.98 to 6.35; P = .15; and orthopedic patients: mean difference, -1.11; 95% CI, -4.62 to 2.40; P = .54). Patients and interventionists perceived the intervention as appropriate, with high-fidelity delivery and broad reach across the target population. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, psychological management and pharmacologic optimization reduced anxiety and depression in older adults undergoing surgery. Future studies should assess reproducibility and determine which patients benefit most. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT05575128, NCT05685511, and NCT05697835.

Humans↗

PubMed2026

Proteomic characterization of the acquired enamel pellicle under acidic challenges at early and mature formation stages.

OBJECTIVES: This study aimed to characterize acquired enamel pellicle (AEP) proteomic changes after exposure to citric acid (CA) and hydrochloric acid (HCl) under different pellicle formation times (3 and 120 min) in the same volunteers. DESIGN: Nine healthy volunteers participated in this randomized crossover in vivo study. The AEP was allowed to form for 3 or 120 min and subsequently exposed for 10 s to deionized water (control), 1% CA (pH 2.5), or 0.01 M HCl (pH 2.0). Pellicle samples were collected, followed by protein extraction, tryptic digestion, and analysis by nanoliquid chromatography (nanoLC) coupled to mass spectrometry (MS) with MSE (data-independent acquisition; nanoLC-MSᴱ). Label-free quantitative proteomics were performed for relative quantification using t-test (p < 0.05). RESULTS: At 120 min, CA exposure markedly reduced several typical AEP proteins, especially acidic proline-rich proteins (PRPs). Conversely, basic PRPs were upregulated, suggesting acid-resistance protein signature. At 3 min, basal-layer proteins (PRPs, cystatins, histatins and mucins) were more abundant. Hemoglobins increased 6-8-fold (up to 150-fold in 3 min control), suggesting association with early pellicle formation and an acid-resistant protein signature. CA exposures for 120 min also upregulated typical AEP proteins (PRPs, mucins, cystatins, immunoglobulins), while HCl exposure depleted albumins and lactotransferrin. CONCLUSION: Intrinsic and extrinsic acids induce distinct proteomic signatures in the AEP. Hemoglobin and PRPs appear consistently enriched in the early pellicle layer, reflecting an initial acid-resistant protein signature. These findings provide new insights into the molecular remodeling of the AEP following intrinsic and extrinsic acid exposure, highlighting proteins potentially involved in early-stage pellicle formation.

Humans↗

PubMed2026

Discrimination, chronic stress, and multimorbidity in cohort of Black and Latina transgender women with HIV: Longitudinal findings from the LITE Plus study.

Black and Latina transgender women with HIV (BLTWH) are exposed to repeated, intersecting discrimination based on race, gender, and serostatus. Minority stress theory conceptualizes discrimination as minority-specific stressors that drive health inequities. Allostatic load theory posits a pathway between discrimination and chronic disease through multisystem physiological dysregulation caused by chronic stress. To test this pathway, a longitudinal cohort of 108 BLTWH, enrolled December 2020 - June 2022 in Boston, New York City, and Washington, DC, were followed for 24 months, with biomarkers measured at baseline, 12, and 24 months. Questionnaires administered every 6 months assessed anticipated discrimination, everyday discrimination, perceived stress, and other psychosocial factors. Multimorbidity was measured via self-reported non-HIV chronic conditions. In mixed-effects mediation models, allostatic load did not mediate relationships between multimorbidity outcomes and anticipated discrimination (β: -0.0004 [95% CI: -0.004, 0.003]) nor everyday discrimination (β: -0.002 [95%CI: -0.009, 0.003]). Perceived stress demonstrated indirect effects on multimorbidity in unadjusted models of anticipated discrimination (β: 0.024, [95% CI: 0.015, 0.081]) and everyday discrimination (β: 0.021 [95%CI: 0.016, 0.077]). Indirect effects remained significant, with attenuated effects (β: 0.020 for anticipated discrimination; β: 0.017 for everyday discrimination) after adjusting for social support, community connection, and resilient coping. Total effects were only significant for the adjusted model of everyday discrimination (β: 0.056 [0.014, 0.099]). Findings suggest discrimination impacted health through specific psychosocial pathways. Alongside efforts to eliminate intersectional discrimination, stress-lowering interventions and increased access to social support and community connection may be effective approaches to reducing multimorbidity in this highly marginalized group.

Humans↗

PubMed2026

Prevention of postpartum methamphetamine use with micronized progesterone trial (PROMPT): A pilot randomized controlled trial.

OBJECTIVES: Methamphetamine use disorder (MUD) contributes to postpartum morbidity and mortality. Postpartum progesterone decline may destabilize γ-aminobutyric acid pathways, increasing craving and return to use. We assessed the feasibility and safety of micronized progesterone, generating efficacy estimates for preventing postpartum methamphetamine use. METHODS: We conducted a double-blind, randomized, placebo-controlled feasibility trial (November 2021-January 2024) at an academic center with a perinatal addiction clinic. Participants ≤ 12 weeks postpartum with ≥ 4 weeks of abstinence were randomized 1:1, stratified by opioid use disorder (OUD), to micronized progesterone 400mg (200mg twice daily) or identical placebo for 12 weeks. The primary outcome was feasibility, defined as achieving ≥ 80% of planned enrollment. Safety outcomes included adverse events (AEs) and serious adverse events (SAEs). Efficacy outcomes were return to methamphetamine use (weekly self-report and every two weeks urine toxicology) and methamphetamine craving. Analyses included intent-to-treat and per-protocol approaches, with loss to follow-up imputed as return to use. Craving trajectories were modeled using adjusted regression with interaction terms for medication for OUD (MOUD). RESULTS: Of 253 screened individuals, 43 were eligible and 34 were enrolled (91.8%; 18 progesterone, 16 placebo). Retention at 12 weeks was 88%. AE frequency was similar between groups (78% vs 81%; p > 0.05), and no maternal SAEs occurred. Four infant SAEs were deemed unrelated to treatment. Return to methamphetamine use did not differ between groups. Craving trajectories differed by MOUD type. CONCLUSIONS: Micronized progesterone was feasible and safe for postpartum individuals with MUD. MOUD-specific craving effects support evaluation in larger, multicenter efficacy trials. GOV REGISTRATION NUMBER: NCT05128071 NCT REGISTRATION: Prevention of postpartum methamphetamine use with micronized progesterone trial https://clinicaltrials.gov/study/NCT05128071.

Humans↗

PubMed2026

Predictors of transition readiness in adolescents with neurogenic lower urinary tract dysfunction.

PURPOSE: Adolescents with Neurogenic Lower Urinary Tract Dysfunction (NLUTD) face significant challenges in their quality of life and readiness to transition to adult healthcare services. This study examines the impact of various demographic and clinical factors on transition readiness. METHODS: We performed a retrospective review of prospectively collected data from 75 adolescents with NLUTD managed at a specialized tertiary referral pediatric facility. We employed multivariate linear regression analysis to explore the relationship between transition readiness scores collected from the Good2Go questionnaire, including the total transition readiness score and its sub-domains (self-advocacy, knowledge, self-care, and social support), and predictors such as age, sex, reconstructive surgery status, and clean intermittent catheter (CIC) usage. RESULTS: The mean age of participants was 16.74 years (SD 2.44). Reconstructive surgery had been performed in 32 % of patients, and 77.3 % were on CIC. Multivariate regression analysis indicated that age significantly predicted transition readiness across several domains. Each additional year of age was associated with a 4.40-point increase in the total transition readiness score, a 3.66-point increase in knowledge, a 4.26-point increase in self-advocacy and a 5.41-point increase in self-care. Conversely, CIC significantly negatively impacted the social support domain, with scores decreasing by 9.69 points. Reconstructive surgery was significantly associated with lower self-care scores, with an average decrease of 12.12 points among those who had undergone surgery. CONCLUSION: Age significantly improves transition readiness in adolescents with NLUTD, reflecting cognitive and developmental growth. However, the negative effects of CIC on social support and reconstructive surgery on self-care underscore the need for personalized interventions to optimize health outcomes during the transition to adult care.

Humans↗

PubMed2026

Yoga MAT: A factorial randomized study using the Multiphase Optimization Strategy to develop a multicomponent yoga intervention for people with chronic pain taking medications for opioid use disorder.

BACKGROUND: People taking medications for opioid use disorder (MOUD) commonly experience chronic pain. Yoga interventions show promise for decreasing pain-related disability in other populations. More time spent in yoga practice may improve pain-related outcomes. METHODS: The Multiphase Optimization Strategy (MOST) provided the framework for developing an optimized yoga intervention package. In a 2x2x2x2 factorial experiment, we evaluated four candidate intervention components which, when added to a weekly yoga class, might increase yoga engagement. The primary outcome was minutes per week of yoga practice (classes and other yoga practice) over the 12-week intervention period. We sought to determine which combination of intervention components was associated with the most yoga practice for people with chronic pain taking buprenorphine or methadone as MOUD. RESULTS: We enrolled 192 adults. There was a significant main effect for Component "B" (having two private sessions with a yoga teachers; IRR = 1.10, 90%CI 1.02; 1.18), and a synergistic interaction between Components "B" and "D" (D was financial incentives for attending class; IRR = 1.11, 90%CI 1.02; 1.19). This combination of these two components (without other potential components) was associated with the second highest model-predicted mean minutes of yoga per week (157.1min; 90% CI = 120.1-194.0) which was only 4min less than the combination including all four components. CONCLUSIONS: We identified a combination of intervention components as the optimized intervention. A next step will be to test the effect of this optimized intervention on pain and substance use outcomes in a randomized controlled clinical trial.

Humans↗

PubMed2026

Targeting SIRT6: the design and therapeutic implications of activators and inhibitors.

Sirtuin 6 (SIRT6) is an NAD+-dependent deacylase that maintains genomic stability, regulates metabolism, and influences aging, making it an attractive but challenging therapeutic target. Pharmacological modulation of SIRT6 holds promise for cancer and metabolic disorders, yet its context-dependent functions demand precise intervention strategies. Potent, selective, and drug-like chemical probes are therefore essential to dissect SIRT6 biology and to validate its therapeutic potential. This review critically evaluates recent medicinal chemistry advances in SIRT6 modulation. We focus on structure-guided design strategies and structure-activity relationships (SAR) that have transformed initial hits into optimized leads for both activators and inhibitors, highlighting the remaining challenges in achieving isoform selectivity and drug-like properties.

Sirtuins↗

PubMed2026

RNA dysregulation as a determinant of aging and neurodegenerative vulnerability.

In the nervous system, aging causes deterioration of cellular and molecular processes that are associated with declines in cognition, sensory perception, and motor coordination. Aging is also the strongest risk factor for neurodegenerative disease, yet the mechanisms by which aging predisposes neurons to dysfunction remain incompletely understood. While genomic instability, proteostasis decline, mitochondrial dysfunction, and chronic inflammation have dominated prevailing models, recent evidence highlights RNA dysregulation as a central component of age-associated decline. In this review, we summarize recent findings suggesting that aging progressively erodes RNA regulatory fidelity through alterations in RNA-binding protein abundance, localization, biophysical behavior, and RNA interactions. We argue that age-dependent RNA dysregulation represents an important mechanism that converges with genetic risk to drive neuronal vulnerability and neurodegeneration.

RNA dysregulation↗

PubMed2026

Nourishing collaboration: interdisciplinary nutrition education for health care professionals.

Nutrition education remains insufficient in many health care professional training programs despite the central role of diet in the prevention and management of chronic disease. Contemporary nutrition science increasingly recognizes that dietary behaviors and health outcomes are shaped by complex interactions among biological, behavioral, environmental, and food system factors. This perspective proposes an interdisciplinary framework for nutrition education that integrates the complementary expertise of physicians, dietitians, chefs, and farmers. By bridging clinical care, nutrition science, culinary practice, and agricultural systems, such an approach may strengthen the translation of evidence into practice, improve nutrition-related competencies among health care professionals, and ultimately enhance population health outcomes.

Humans↗

PubMed2026

Complete genome sequence of the Anaplasma phagocytophilum clinical isolate NCH-1.

Anaplasma phagocytophilum is an obligate intracellular gram-negative bacterium and etiologic agent of human granulocytic anaplasmosis. A. phagocytophilum genomic sequencing has historically been performed via short-read platforms. Our optimized bacterial isolation protocol combined with Nanopore sequencing produced a single, closed 1,481,805 bp circular A. phagocytophilum strain NCH-1 chromosome.

Anaplasma phagocytophilum↗

PubMed2026

The effect of zalunfiban on high sensitivity cardiac troponin and the association with clinical outcomes in patients with STEMI.

BACKGROUND: Among individuals with ST-segment elevation myocardial infarction (STEMI), a single subcutaneous injection of the short-acting glycoprotein IIb/IIIa receptor blocker antagonist zalunfiban at first medical contact significantly improved the primary outcome including clinical endpoints. The impact of zalunfiban on Myocardial Infarction (MI) size and association with downstream outcomes remains unclear. METHODS: In a prespecified analysis, we studied results among study participants treated with 2 doses of zalunfiban who had core laboratory measurements concentrations of hs-cTnT. RESULTS: More elevated hs-cTnT concentrations at presentation were associated with less resolution of ST deviation (P = .006) and more frequent Q wave development (P < .001). At coronary angiography more elevated hs-cTnT at presentation was associated with higher thrombus grade and worse epicardial and myocardial perfusion (all P < .05). In multivariable analyses, higher hs-cTnT concentrations at 24 hours were associated with greater adjusted risk for all-cause death (odds ratio [OR] 1.83 per log unit increase; P = .03), cardiovascular death (OR 1.83 per log unit increase; P = .03), heart failure (OR 2.74 per log unit increase; P < .001) or the composite of death and heart failure (P < .001) by 30 days. At 24 hours, those treated with zalunfiban had lower hs-cTnT compared to placebo (P = .04) and across multiples ≥ 10 to ≥ 1,000 times elevation, treatment with zalunfiban resulted in smaller hs-cTnT determined MI size. CONCLUSIONS: Among patients with STEMI, more elevated concentrations of hs-cTnT are associated with worse measures of reperfusion and higher-risk for short-term death or heart failure. A single dose of zalunfiban at first medical contact reduced MI size. TRIAL REGISTRATION: A phase 3 study of zalunfiban in subjects with ST-elevation MI (CELEBRATE); NCT04825743.

Humans↗

PubMed2026

Triazole resistance in clinical Aspergillus fumigatus isolates in India, a multicenter surveillance study.

BACKGROUND: Triazole resistance in Aspergillus fumigatus is a global public health concern associated with treatment failure, notably in invasive aspergillosis. However, population-level data on triazole resistance from India remain limited, with most reports originating from single-center studies. METHODS: We conducted a multicenter surveillance study to assess the prevalence of triazole resistance among clinical A. fumigatus isolates across India. Antifungal susceptibility testing was performed using the CLSI broth microdilution method (M38-Ed3), and molecular characterization was conducted on resistant isolates. A total of 518 isolates were analyzed: 115 prospectively collected from 13 tertiary-care hospitals from 2015-2020, and 403 archived isolates obtained from the National Culture Collection of Pathogenic Fungi (1994-2020). RESULTS: The overall pooled prevalence of non-wildtype isolates was 4.1% for itraconazole (95% CI: 2.54-6.17%), 3.9% for posaconazole (95% CI: 2.39-5.94%), while 1.4% were resistant to voriconazole (95% CI: 0.55-2.77%). One multi-azole-resistant isolate from an immunocompromised, mold-active triazole-naïve patient carried the TR34/L98H mutation, suggesting environmental acquisition. Prevalence of resistance did not differ significantly across geographic regions or between public and private sector hospitals. Linear regression analysis revealed a significant temporal increase in median MICs of all three licensed triazoles between 1994 and 2020. Approximately 29% of isolates exhibited amphotericin B MICs exceeding the epidemiological cutoff value; however, the clinical significance of this finding remains uncertain. CONCLUSIONS: Azole resistance among clinical A. fumigatus isolates in India remains uncommon (<5%), supporting the continued use of triazoles as first-line therapy. However, the observed temporal increase in triazole MICs underscores the need for sustained national surveillance to detect emerging resistance trends.

Aspergillus fumigatus↗

PubMed2026

Implementation factors shaping British Columbia's drug decriminalization pilot: A systematic review with narrative synthesis.

BACKGROUND: In January 2023, British Columbia (BC) became the first Canadian province to implement a legally sanctioned drug decriminalization policy, removing criminal penalties for adults possessing 2.5 g or less of opioids, cocaine, methamphetamine, and MDMA. Introduced as a three-year pilot, it aimed to reframe substance use as a public health issue, reduce stigma, and improve health and social service engagement. Criminal penalties were reintroduced for drug possession in most public spaces in May 2024, and the pilot ended in January 2026. Its termination has been interpreted as policy failure; this review aimed to examine how the pilot was implemented in practice and to identify factors that shaped its operationalization and early implementation-relevant outcomes. METHODS: We conducted a systematic review with narrative synthesis of peer-reviewed literature examining implementation-relevant aspects of BC's decriminalization pilot. Six databases were searched (January-February 2026) for studies published May 31, 2022-February 1, 2026. The protocol was registered in PROSPERO (CRD420251271694). RESULTS: Twenty-seven studies were included. Four cross-cutting implementation barriers were identified: pilot design features, public and cross-sector communication gaps, limited frontline training, and insufficient funding and infrastructure. Design features included the 2.5 g possession threshold, misalignment with real-world drug use patterns; the three-year timeframe, which constrained system-level effects; and the May 2024 amendment, which introduced additional instability. The pilot was implemented without commensurate investment in harm reduction, treatment, or housing infrastructure, within already constrained systems. CONCLUSION: BC's decriminalization pilot suggests the effects of legal reform are shaped by implementation context. Early outcomes may reflect design features, institutional readiness, and system capacity rather than legal change alone; longer-term impacts remain uncertain. Future reforms should align legal change with coordinated implementation, operational guidance, public communication, and adequate service infrastructure.

British Columbia↗

PubMed2026

Metabolomic Signatures of Inflammation in Chronic Kidney Disease.

RATIONALE & OBJECTIVE: Inflammation is associated with adverse kidney, cardiovascular, and mortality outcomes. Investigation of the metabolic milieu as it relates to inflammation may provide important insights into these disease processes. STUDY DESIGN: Prospective cohort. SETTING & PARTICIPANTS: African American Study of Kidney Disease and Hypertension (AASK), Atherosclerosis Risk in Communities (ARIC) study, and Boston Kidney Biopsy Cohort (BKBC) participants with available metabolomics and inflammatory protein data. PREDICTORS: Baseline blood levels of 718 metabolites. OUTCOMES: Baseline and longitudinal changes in blood levels of tumor necrosis factor receptors 1 and 2 (TNFR1, TNFR2), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukins 6, 8, and 10 (IL-6, IL-8, IL-10), uromodulin (UMOD), and epidermal growth factor (EGF). ANALYTICAL APPROACH: Multivariable linear regression and linear mixed-effects models. RESULTS: Among 491 AASK participants (mean age 54 years; 37% women; mean glomerular filtration rate, 45 mL/min/1.73 m2), 367 cross-sectional associations between metabolites and inflammatory proteins were significant after correction for multiple comparisons. The direction of association was mostly positive for TNFR1 (97%), TNFR2 (97%), IL-8 (77%), and IL-10 (100%); negative for UMOD (80%) and EGF (97%); and variable for TNF-⍺, IFN-γ, and IL-6. Pathways were distinct for several inflammatory proteins (eg, tryptophan metabolism for TNFR2). Forty-five associations between metabolites and longitudinal change in inflammatory proteins were identified. Notable metabolites included tigylcarnitine and N 2,N 5-diacetylornithine, which were associated with 2-year increases in TNFR1 and/or TNFR2, and 1,5-anhydroglucitol, where lower levels were associated with decreases in UMOD. In ARIC (n = 3,773) and BKBC (n = 413), replication of cross-sectional associations was excellent for TNFR1 (ARIC 83%; BKBC 85%) and TNFR2 (ARIC 64%; BKBC 79%) but poor for IL-8 (ARIC 3%; BKBC 3%). LIMITATIONS: Metabolite data limited to baseline visit; potential for residual confounding. CONCLUSIONS: Using an untargeted approach, multiple metabolites were cross-sectionally and longitudinally associated with inflammatory proteins in persons with chronic kidney disease.

Chronic kidney disease↗

PubMed2026

Cost-Effectiveness and the Economics of Genomic Testing and Molecularly Matched Therapies.

Cost-effectiveness analysis of precision oncology can help guide value-driven care. Next-generation sequencing is increasingly cost-efficient over single gene testing because diagnostic algorithms require multiple individual gene tests to determine biomarker status. Matched targeted therapy is often not cost-effective due to the high cost associated with drug treatment. However, genomic profiling can promote cost-effective care by identifying patients who are unlikely to benefit from therapy. Additional applications of genomic profiling such as universal testing for hereditary cancer syndromes and germline testing in patients with cancer may represent cost-effective approaches compared with traditional history-based diagnostic methods.

Humans↗