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A systematic and bibliometric review, combined with a meta-analysis, was used to adjust an equation for estimating the physiological responses of Santa Inês sheep subjected to different thermal challenges. The systematic review compiled data on physiological responses and the thermal environment, which were then used in the meta-analysis to adjust regression models. The bibliometric analysis mapped the relationships among studies, highlighting their usefulness in interpreting research findings and biases. Addressing prior methodological critiques, the core of this study involves replacing the linear approach with a non-linear segmented regression model to accurately define the Thermal Neutral Zone (TNZ). The Segmented Regression Model was crucial, establishing the upper limit of the Thermal Neutral Zone (TNZ) at an air temperature (tair) of 34.64 °C, where trectal begins to increase abruptly. The model, while identifying a biologically significant breakpoint, exhibited a moderate Multiple R-squared of 0.3529, highlighting the high heterogeneity and methodological variability in the current Santa Inês literature. This non-linear approach offers a biologically superior tool for identifying the onset of thermal distress.
INTRODUCTION: Dengue virus (DENV) and chikungunya virus (CHIKV) are Aedes-borne arboviruses with overlapping clinical manifestations, shared vectors, and substantial diagnostic challenges in co-endemic settings. This systematic review and meta-analysis synthesized published evidence on molecular detection, serological positivity, and DENV-CHIKV dual positivity/co-infection in human clinical, surveillance, and community-based study populations. CONTENT: Following PRISMA 2020 guidance, five bibliographic databases (PubMed/MEDLINE, Scopus, Web of Science, ScienceDirect, and Google Scholar) and supplementary grey-literature/preprint sources were searched for English-language studies published from 1 January 1980 to 31 December 2024. No prospective PROSPERO or OSF protocol registration was available. Eligible records reported extractable numerators and denominators for DENV and/or CHIKV in humans using recognized molecular or serological assays. A total of 196 studies comprising 158,608 tested or suspected participants were included in the extraction table. The pooled CHIKV estimate was 14.0 % (95 % CI: 12.0-16.4; I2=97.5 %), with molecular and serological estimates of 9.8 and 15.7 %, respectively. The pooled DENV estimate was 13.8 % (95 % CI: 10.9-17.3; I2=99.0 %), with molecular and serological estimates of 13.1 % (95 % CI: 7.9-21.0) and 14.3 % (95 % CI: 10.2-19.8), respectively. DENV-CHIKV dual positivity/co-infection was 52.9 % (95 % CI: 48.7-57.1) among studies that tested and reported both outcomes. Country-level estimates varied widely and should be interpreted as summaries of available studies rather than nationally representative burden estimates. Funnel-plot asymmetry was statistically significant in DENV analyses but not in the overall CHIKV analysis. SUMMARY: Available evidence indicates extensive but highly heterogeneous DENV and CHIKV positivity across selected clinical and surveillance populations. The pooled estimates should be interpreted cautiously because of substantial between-study heterogeneity, diagnostic variability, outbreak-period sampling, and uneven geographic representation. OUTLOOK: The findings support integrated arboviral surveillance, multiplex diagnostics, and vector-control preparedness in co-endemic regions.
INTRODUCTION: Acute pancreatitis (AP) is a common inflammatory disorder that is associated with increased risk for diabetes mellitus (DM). It remains unclear whether recurrent acute pancreatitis (RAP) is associated with further increased risk of incident DM. This study aims to investigate the association between RAP and incident DM using real-world data. METHODS: We conducted a retrospective cohort study using the MerativeTM MarketScan® claims database (2016-2023), identifying patients with AP and no prior history of DM at baseline. The primary exposure of interest, RAP, was defined as one or more episodes of AP occurring ≥90 days after the index AP diagnosis, whereas one episode of AP referred to a single episode of AP (SAP) with no subsequent recurrence within 90 days following the index event. A multivariable stratified Cox proportional hazards regression models were used to determine the association between RAP and incident DM, identified using ICD-10 codes. RESULTS: In total, 16,184 individuals with AP (mean [SD] age: 45.8 [12.3]) contributed 40,712 person-years of follow-up, during which 1,477 incident cases of DM were documented. Individuals with RAP had an increased risk of incident DM compared with those with a SAP(adjusted HR, 1.92; 95% CI, 1.61-2.29). The risk increased significantly with the frequency of RAP. In comparing the modifying effect of patient demographics and comorbidities, a stronger association between RAP and incident DM was observed in females (adjusted HR, 2.44; 95% CI, 1.87-3.19) than in males (adjusted HR, 1.64; 95% CI, 1.30-2.07; Pinteraction=0.03). Also, stronger associations were observed among younger patients (18-46 y) (adjusted HR=2.56; 95% CI, 1.97-3.31) and among non-tobacco abuse (adjusted HR=2.19; 95% CI, 1.81-2.65), with significant interactions for all comparisons (Pinteraction<0.05. CONCLUSIONS: In this real-world study, RAP was associated with an increased risk of incident DM. Our findings highlight an opportunity for glycemic monitoring and proactive management of patients with RAP to mitigate their risk of developing DM.
The current work seeks to evaluate the effectiveness of Cataglyphis saviginyi and Tentyrum sp as indicators of pollution in the city's main industrial regions by analyzing their enzymatic activity and primary metabolites. Soil samples were collected at each site under investigation to analyze soil characteristics and heavy metal content. C. saviginyi and Tentyrum sp were collected across four consecutive seasons (2023-2024) to investigate enzymatic (GPT, GOT, ALP, ACP, LDH) and metabolic (lipid, protein, carbohydrate) biomarkers. The physicochemical properties of the soil differed substantially between the industrial areas and the control site. Soil heavy metal buildup was highest at industrial sites (1 and 4) compared to the control site, with the order being Zn > Cr > Cd > Cu. Heavy metal pollution indices were determined. Increased industrial activity from metal industries, ceramics, and chemical painting companies defines this area, as seen by the high Cdeg, mCd, PI, and PLI values derived for industrial sites 1 and 4. While C. saviginyi and Tentyrum sp deconcentrated and released Cr, Cd, and Zn into the soil via the biological accumulation factor (BAF), Cu acted as a macro-concentrator. Compared with the control site, industrial environments were shown to increase levels of GPT, GOT, LDH, ACP, protein, and carbohydrates in C. saviginyi. However, lipid and ALP activity was suppressed. at industrial sites, Tentyrum sp carbohydrate content was higher than at control sites, but GPT, GOT, ALP, ACP, LDH, protein, and lipid activities were all suppressed. Consequently, enzymatic and metabolic biomarkers proved to be sensitive indicators for assessing industrial heavy metal pollution in desert ecosystems.
BACKGROUND: Aging is associated with progressive declines in skeletal muscle mass (SMM) and substantial interindividual variability in adaptations to resistance training (RT). However, whether training load intensity influences hypertrophic responsiveness in older adults remains unclear. OBJECTIVE: To investigate the effects of two commonly prescribed RT loading schemes (15RM and 10RM) on estimated SMM adaptations and responsiveness in older women. METHODS: Twenty-seven older women (67.7 ± 4.9 years; 65.7 ± 10.6 kg; 154.5 ± 5.8 cm) completed two 8-week RT interventions performed at 15RM and 10RM in a randomized crossover design, separated by a 12-week detraining period. Estimated SMM was assessed using dual-energy X-ray absorptiometry. Responsiveness was operationally defined using the standard error of measurement, and participants were classified as responders (RP) or non-responders (N-RP) according to changes in estimated SMM. RESULTS: Both loading schemes promoted significant and comparable increases in estimated SMM (15RM: +0.62 ± 0.4 kg vs. 10RM: +0.43 ± 0.3 kg). Overall, 61.1% of participants were classified as responders in at least one condition, whereas 38.9% were classified as non-responders. Responsiveness status was consistent across conditions for most participants, with 48.1% classified as responders under both loading schemes and 25.9% as non-responders under both conditions. Only seven participants (25.9%) changed responsiveness status between interventions. No clear pattern indicated a greater likelihood of responsiveness with either loading scheme. CONCLUSIONS: Results suggest that both the 10RM and 15RM RT protocols significantly increase estimated SMM in older women, with no significant differences between training conditions. Although substantial interindividual variability in adaptive responses exists, training load intensity does not appear to meaningfully influence responsiveness status in most individuals. These findings suggest that both loading schemes can be effectively prescribed to promote SMM gains in older women.
BACKGROUND: Little is known about whether epigenetic age acceleration (EAA) clocks are capable of predicting exceptional longevity with or without preserved cognitive function. METHODS: We examined 5844 women from the Women's Health Initiative Memory Study. Fifteen epigenetic clocks were measured at baseline (1996-1999). Longevity outcomes were defined as: 1) survival to age 90 with preserved cognition (n = 1726, 29.5%); or 2) survival to age 90 with cognitive impairment (n = 956, 16.4%); vs. 3) death before age 90 (n = 2611, 44.7%). Logistic regression models examined associations between the 15 clocks and survival to age 90 (vs. death before age 90), adjusting for covariates. Multinomial logistic regression models examined associations with survival to age 90 without cognitive impairment and survival to age 90 with cognitive impairment (each vs. death before age 90), also adjusting for covariates. RESULTS: Each standard deviation increase in EAA for the first-generation clocks was associated with 7%-18% reduced odds of survival to age 90 vs. earlier death. Stronger associations were observed for second- and third-generation clocks, including AgeAccelGrim2 (OR = 0.66; 95% CI 0.61-0.71), PCGrimAge (OR = 0.64; 95% CI 0.59-0.69), PCPhenoAge (OR = 0.73; 95% CI 0.68-0.78) and DunedinPACE (OR = 0.77; 95% CI 0.72-0.82). None of the clocks was more strongly associated with survival to age 90 with preserved cognition than with survival to age 90 with cognitive impairment, relative to death before age 90. CONCLUSION: All epigenetic clocks were associated with exceptional longevity, but none were associated with cognitive healthspan. Developing clocks that can differentiate long survival with and without preserved cognitive function is critical.
Alzheimer's disease (AD) and Parkinson's disease (PD) are the most prevalent late-onset neurodegenerative diseases worldwide. Both are influenced in part by genetic factors and are currently incurable. Tobacco and alcohol, the two most common substances used among the general adult population, are potential AD/PD risk factors and are also heritable. Although important progress has been made, most existing research on the genetics of AD and PD has been carried out in individuals of European genetic ancestry. Investigations in a broad range of groups are crucial to understand disease mechanisms. Given the current availability of ancestry-specific tobacco and alcohol use as well as AD and PD genome-wide association study summary statistics, we performed global and local genetic correlation analyses using East Asian datasets. Genes within the correlated genetic regions were subsequently used to identify potentially enriched biological pathways between substance use and neurodegenerative diseases. We identified a global genetic correlation between smoking cessation and PD, which we confirmed in complementary European genetic ancestry data. Gene set enrichment analyses highlighted potentially shared genetic mechanisms between breast cancer and AD, which warrants further exploration. This work aims to promote further analyses across genetic ancestry groups.
BACKGROUND: Anxiety reactivity to acute stress is a transdiagnostic vulnerability factor. We tested whether a single session of alpha-frequency transcranial alternating current stimulation (tACS) targeting the frontoparietal control network reduces stress-evoked state anxiety in healthy adults. METHODS: In a randomized, blinded, sham-controlled study, 42 participants (mean age 58.9 years) completed an acute stress task before and after stimulation. The task was an adapted moving-circles paradigm in which circle collisions triggered a brief aversive event (mild electric shock plus unpleasant noise and a white flash). Active stimulation consisted of 20 min of 10-Hz tACS (2.0 mA/channel; 30-s ramp up/down) delivered via electrodes at F3, P3, Cz, and T7 (0° phase at F3/P3; 180° at Cz/T7). Sham stimulation used the same montage and ramp periods but no sustained current. RESULTS: State anxiety showed a significant Time × Protocol interaction (F(1,35) = 4.22, p = .047): STAI-S decreased after active tACS (Δ = -3.16) but increased slightly after sham (Δ = +1.17). Perceived stress appraisal (SAAS) did not change. Resting-state alpha power at F3/P3 showed no reliable pre-post effects. During the task, left-frontal relative alpha differed by protocol and showed a trend toward larger increases following active tACS. Electrodermal and pupil indices changed across sessions in both groups, with no differential stimulation effects. CONCLUSIONS: A single alpha-tACS session produced a modest, selective reduction in stress-evoked state anxiety, supporting oscillatory neuromodulation as a scalable approach to dampen anxiety reactivity.
BACKGROUND: Loss of dopaminergic neurones and iron deposition in the substantia nigra pars compacta (SNpc) are two major pathological hallmarks of Parkinson's disease (PD). Such changes can be visualised by advanced techniques including neuromelanin-sensitive MRI (NM-MRI) and quantitative susceptibility mapping (QSM). This systematic review investigates the diagnostic performance and methodological development of the integrated use of NM-MRI and QSM in PD. METHODS: The systematic search was performed in four databases (Scopus, PubMed, ScienceDirect, and Web of Science) according to the PRISMA 2020 guidelines until July 2026. Bias was assessed using QUADAS-2 and certainty of evidence was assessed using GRADE. RESULTS: Seventeen studies with 2228 participants were included. Combined NM-MRI and QSM consistently showed reduced neuromelanin volume/contrast and increased iron deposition in the SNpc of PD patients compared to healthy controls. Multimodal integration yielded a significant improvement in diagnostic accuracy (AUC values 0.86-0.99), and was able to successfully differentiate PD. Recent methodological advances included simultaneous acquisition sequences (e.g. MTC-GRE, STAGE, setMag) and AI-driven automated segmentation, which led to significantly reduced scan times and improved reproducibility. CONCLUSION: The combination of NM-MRI and QSM has a synergistic effect and provides powerful complementary biomarkers for the diagnosis and differential diagnosis of PD.
INTRODUCTION: We performed an analysis of incident hypertension in a randomized trial comparing dolutegravir (DTG) + emtricitabine (F)/tenofovir alafenamide (TAF) versus DTG + F/tenofovir disoproxil fumarate (TDF) versus efavirenz (EFV)/F/TDF in pregnant and postpartum women with HIV. METHODS: Women were randomized at 14-28 weeks gestational age (GA) to start DTG + F/TAF, DTG + F/TDF, or EFV/F/TDF and followed through 50 weeks postpartum. The composite incident hypertension outcome was defined as initiation of antihypertensive medication or ≥2 elevated blood pressures categorized as elevated (130-139 and/or 80-89 mmHg), mild (140-159 and/or 90-99 mmHg), moderate (≥160-179 and/or ≥100-109 mmHg), and severe (≥180 and/or ≥110 mmHg). Incident gestational hypertension was defined by initiation of antihypertensive medication or ≥2 blood pressures ≥ 140 and/or ≥90 mmHg at ≥20 weeks GA with resolution by 12 weeks postpartum. Cox proportional hazard models were used for by-arm comparisons of the composite outcome and to look for the effect of weight change within arm. RESULTS: Of 626 women without baseline hypertension (median age 26.6 years), the composite incident outcome occurred in 49% (n = 308), predominantly due to the incident elevated category of elevated blood pressure, with no significant differences by arm, although hypertension was numerically more likely in the DTG arms. Each additional 5 kg of weight was associated with an 8%-17% higher hazard of the composite hypertension outcome. Twenty-seven participants (4.3%) had gestational hypertension with no apparent differences between arms. CONCLUSIONS: Our data contribute information regarding the safety of DTG-based ART and TAF in pregnant and postpartum women and highlight the importance of monitoring weight and performing hypertension screening as part of maternal health care for young women with HIV.
BACKGROUND AIMS: Cell and gene therapy products face unique regulatory challenges due to their biological complexity and the stringent expectations for manufacturing control, analytical testing, and clinical assessment. As the pipeline grows, understanding the drivers of FDA non‑approval is increasingly important for improving first‑cycle success and reducing development delays. In this study, we aimed to characterize the frequency and impact of refuse‑to‑file actions, major amendments, and complete response letters issued for biologics licensing applications; and to identify recurring patterns of deficiencies contributing to delayed approval. METHODS: Publicly available documents were extracted from the FDA website. Data from each approved cell and gene therapy product's regulatory history-including complete responses, major amendments, inspection timing, and cited deficiencies-were compiled and categorized across clinical, quality, and labeling domains. RESULTS: Analysis showed that informational deficiencies were common across modalities. Major amendments occurred in roughly half of applications, and complete responses had the most significant impact. Quality deficiencies appeared in all complete responses and were the predominant barrier, while clinical and labeling issues were less frequent but meaningful when present. CONCLUSION: Overall, these findings highlight the need for proactive FDA engagement, comprehensive readiness, and early inspection preparation to reduce regulatory risk and improve first cycle approval outcomes.
IMPORTANCE: Stimulant-involved deaths continue to increase in the US, and methamphetamine use remains a weighty public health concern. Treating methamphetamine use disorders is complicated. Contingency management has demonstrated the best effectiveness but is not widely implemented. OBJECTIVE: To examine the effectiveness of dedicated care navigation in linking patients to treatment. DESIGN, SETTING, AND PARTICIPANTS: This prospective randomized clinical trial was conducted at an integrated safety-net health system in Denver, Colorado, between April 10, 2023, and December 31, 2024. Eligible participants were 18 years or older who had a methamphetamine-related encounter in an acute care setting; those with involuntary treatment holds, substance treatment in past 90 days or actively seeking treatment, and inability to provide consent were excluded. Participants completed baseline, 30-day, and 90-day study visits. INTERVENTION: Dedicated care navigation, incorporating contingency management principles, with a focus on addressing health-related social needs. MAIN OUTCOMES AND MEASURES: Linkage to treatment within 30 and 90 days of enrollment defined as a composite measure of at least 1 of the following: electronic health record data indicating a visit at the health system's substance treatment clinic, a behavioral health encounter at an outpatient clinic, temporary residential treatment, or self-reported treatment on the 30- and/or 90-day follow-up survey. RESULTS: Of 192 participants enrolled in the Beginning Early and Assertive Treatment for Methamphetamine Use trial, 156 (81.3%) were male, and the median age was 39 (IQR, 31-47) years. Most participants were unstably housed (163 [84.9%]), not currently employed (158 [82.3%]), and without regular access to a working phone (94 [49.0%]). Of the 96 participants randomized to the intervention, 60 (62.5%) engaged in 2 or more navigation sessions, 45 (46.9%) completed the 30-day study visit, and 47 (49.0%) completed the 90-day study visit compared with 44 (46.3%) and 37 (38.5%), respectively, of the 96 randomized to the control arm. No statistically significant differences in treatment linkage were observed at 30 days (24 participants [25.0%] in both arms; risk ratio, 1.00 [95% CI, 0.61-1.63]) or 90 days post enrollment, (32 [33.3%] in intervention vs 24 [25.0%] in control arms; risk ratio, 1.33 [95% CI, 0.85-2.09]). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, integrating principles of contingency management into the intervention may have increased engagement with a dedicated care navigator but did not increase likelihood of linkage to treatment for methamphetamine use disorder. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06033365.
Technology-facilitated gender-based violence presents critical challenges for politically active women, whose professional roles often expose them to elevated levels of online abuse with far-reaching impacts on their emotional well-being, professional engagement, and participation in public life. This systematic review synthesizes findings from 48 studies employing qualitative, quantitative, and mixed-methods research to examine the psychological and political consequences and coping mechanisms associated with online harassment. Eighty-one percent of the included studies (39/48) report psychological distress, anxiety, and fear among targeted women, with 31% of the studies (15/48) identifying online harassment as a trigger for (re-) traumatization. The political consequences are equally significant, with 62% of the studies (30/48) documenting modifications in political messaging, 39% (19/48) noting reduced engagement with online platforms, and 29% (14/48) showing that women abandon their online presence altogether. Additionally, 20% (10/48) of the studies report cases of women withdrawing from their political roles. In terms of coping strategies, 66% (32/48) report women blocking or muting harassers, while 37% (18/48) document women reporting abuse to authorities or platforms. This study highlights the pervasive impact of technology-facilitated violence on women's emotional well-being, and their political participation and underscores its broader implications for democratic discourse and social equity.
Staphylococcus aureus is a leading cause of community-acquired skin and soft-tissue infections worldwide. One major route of exposure is recreating in marine waters, but knowledge is limited regarding the drivers of S. aureus in surface waters that discharge into marine environments. This study explores spatial and temporal distributions of S. aureus, including antimicrobial-resistant and virulence genes, using both culture-dependent and molecular techniques across a tropical Hawaiian watershed with a gradient of human influence. Negative binomial generalized linear mixed models revealed that the interaction between spatial and temporal factors was the strongest predictor of S. aureus and associated genes. Cultured S. aureus was highest at mid-watershed sites in summer, which included a popular swimming hole, suggesting human shedding as a significant source. Molecular detection of S. aureus (femA gene) yielded concentrations two orders of magnitude higher than cultured concentrations and peaked at estuarine sites with the greatest nutrients and water residence times. In the winter at upstream sites with no public access, staphylococci antibiotic-resistant (mecA) and S. aureus virulence gene (etb) were elevated, indicating highly pathogenic S. aureus strains in surface waters may originate from zoonotic sources. Our findings indicate that human and zoonotic sources contribute antibiotic-resistant and virulent S. aureus to watersheds, with streams facilitating environmental transmission to marine waters. This watershed-scale assessment enables the prediction of spatial and temporal conditions associated with elevated S. aureus concentrations, thereby reducing exposure and infections.
BACKGROUND: Recurrent inguinal hernia remains a significant challenge in abdominal wall surgery despite advances in mesh-based repair techniques and minimally invasive approaches. Although pelvic skeletal morphology has been implicated in inguinal hernia development, its association with recurrent disease remains incompletely understood. This study aimed to evaluate computed tomography (CT)-derived pelvic morphometric parameters and investigate their potential value in preoperative recurrence risk assessment. METHODS: This retrospective study included 251 male patients with preoperative abdominal CT examinations and complete clinical records who underwent elective inguinal hernia repair at a tertiary referral center. After applying the predefined eligibility criteria, 188 patients with unilateral inguinal hernias constituted the primary study cohort, including 162 primary and 26 recurrent unilateral hernias. The Radoievitch angle and Ami's line were measured independently by two blinded radiology residents using a standardized CT-based pelvic morphometric measurement protocol, and the mean values were used for analysis. Multivariable logistic regression and receiver operating characteristic (ROC) curve analyses were performed to evaluate the association between pelvic morphometric parameters and recurrent inguinal hernia. RESULTS: Patients with recurrent unilateral inguinal hernias demonstrated significantly greater affected-side Ami's line measurements (8.27 ± 0.63 vs. 7.90 ± 0.71 cm, p = 0.014) and larger Radoievitch angles (40.68 ± 4.02° vs. 38.80 ± 3.68°, p = 0.018) than patients with primary unilateral hernias. Both the Radoievitch angle (OR 1.14, 95% CI 1.01-1.28, p = 0.033) and Ami's line (OR 2.26, 95% CI 1.14-4.49, p = 0.020) remained independently associated with recurrent inguinal hernia after adjustment for age and body mass index. ROC analysis demonstrated modest discriminatory performance (AUC 0.634 for the Radoievitch angle and 0.633 for Ami's line), while the multivariable model incorporating age, body mass index, and Ami's line showed slightly improved discrimination (AUC 0.655). CONCLUSION: CT-derived pelvic morphometric parameters were independently associated with recurrent unilateral inguinal hernia. Although their individual discriminatory performance was modest, standardized CT-based pelvimetry may serve as an objective adjunctive tool for individualized preoperative recurrence risk assessment in patients who already undergo CT imaging for unrelated clinical indications. Prospective multicenter studies are warranted to validate these findings and determine their clinical applicability.
AIMS/HYPOTHESIS: In healthy lean humans, endogenous glucose-dependent insulinotropic polypeptide (GIP) contributes significantly to the postprandial increase in arteria mesenterica superior blood flow. The vascular biology related to activation of the GIP receptor is markedly impaired in individuals with type 2 diabetes and is sometimes absent. In this population, we investigated the role of endogenous GIP on postprandial splanchnic blood flow by using the GIP receptor antagonist, GIP(3-30)NH2. The primary outcome of this study was the changes in blood flow in arteria mesenterica superior during oral glucose with or without GIP receptor antagonist infusion. METHODS: Ten participants with type 2 diabetes (age 20-80 years, BMI 20-35 kg/m2, and HbA1c >48 mmol/mol and <75 mmol/mol) were investigated in a randomised, placebo-controlled, crossover study. On four separate occasions, participants received the following treatment: oral glucose + i.v. GIP(3-30)NH2; oral glucose + i.v. saline (154 mmol/l NaCl); oral water + i.v. GIP(3-30)NH2; oral water + i.v. saline. Participants were randomly assigned to intervention groups using (random.org). Participants were unaware of allocation, while investigators were aware. No additional allocation concealment procedures were used. During all four interventions, splanchnic blood flow was measured using phase-contrast MRI in the arteria mesenterica superior, truncus coeliacus and vena portae during oral glucose (75 g) or water ingestion. The study was conducted at Rigshospitalet, Copenhagen. Liver volume and oxygenation, as well as gallbladder volume, were assessed. Blood samples were collected and analysed for insulin, C-peptide, GIP, glucagon and glucose. RESULTS: Oral glucose alone increased mean blood flow in arteria mesenterica superior by 57% (95% CI 26, 88) and this was 15% (95% CI -2, 32) lower during concomitant GIP receptor antagonist infusion, p=0.012. Infusion of GIP receptor antagonist during oral glucose treatment did also result in lower insulin secretion, C-peptide and C-peptide/glucose ratio compared with saline infusion, whereas glucagon levels and plasma glucose were unaffected. Oral water did not affect any outcomes. CONCLUSIONS/INTERPRETATION: Endogenous GIP contributes to postprandially increased splanchnic blood flow in people with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT06426823 FUNDING: This work was supported by the Novo Nordisk Foundation.
BACKGROUND: Substantial improvements in air quality have been recorded following the implementation of China's Clean Air Act (CCAA) in 2013. However, the association between CCAA implementation and individual-level cardiovascular disease (CVD) risk remains unclear. We aimed to examine the long-term association between CCAA implementation and individual-level predicted CVD risk. METHODS: In this prospective, quasi-experimental study, we used data from the China Kadoorie Biobank, a prospective cohort study that recruited participants from five urban and five rural areas across China between 2004 and 2008, with three resurveys conducted after the baseline survey (in 2008, 2013-14, and 2020-21). We included 34 862 individuals (mean age 51·3 years) who participated in at least one resurvey and had no history of CVD at baseline. Participants were classified into intervention (n=25 497) and control (n=9365) groups based on the local government's targets for particulate matter reduction. We estimated the 10-year risk of incident CVD morbidity or mortality using a validated risk prediction model. We used a difference-in-difference model to assess the long-term association between CCAA implementation and predicted risk, with adjustments made for regional confounders and individual-level characteristics, including demographics, lifestyle factors, medical history, and indoor air pollution exposure. The relationship between changes in long-term exposure to PM2·5, PM10, and O3 and predicted risk after CCAA implementation was analysed using a linear model. The estimated risk differences associated with air pollutant changes were estimated based on the magnitude of changes and their corresponding effect sizes. FINDINGS: After the CCAA was implemented, PM2·5 and PM10 concentrations declined in both groups, but O3 concentrations increased. The intervention group showed a 3·95% (95% CI 3·18-4·72%) lower increase in predicted risk than the control group, with larger estimated differences under stricter enforcement. Between 2013 and 2021, each 10 μg/m3 change in PM2·5 concentration was positively associated with a 1·80 (1·34-2·27) percentage point change in predicted CVD risk, whereas each 10 μg/m3 change in PM10 concentration was associated with a 1·24 (0·84-1·63) percentage point change and each 10 μg/m3 change in O3 concentration with a 0·58 (0·33-0·83) percentage point change. Overall, the observed changes in air pollutants during the study period were associated with an average 6·6 percentage point reduction in predicted CVD risk. INTERPRETATION: The CCAA and improved air quality were associated with a slower increase in predicted CVD risk, supporting the necessity for stricter, multipollutant air quality policies to maximise public health benefits. FUNDING: National Natural Science Foundation of China, Kadoorie Charitable Foundation, Noncommunicable Chronic Diseases-National Science and Technology Major Project, National Key R&D Program of China, Chinese Ministry of Science and Technology, and UK Wellcome Trust.