Background: Obesity is a strong risk factor for type 2 diabetes. However, few studies have compared the predictive power of overall obesity with that of central obesity. The cutoffs for waist ...circumference (WC) and waist-to-hip ratio (WHR) as measures of abdominal adiposity remain controversial. Objective: The objective was to compare body mass index (BMI), WC, and WHR in predicting type 2 diabetes. Design: A prospective cohort study (Health Professionals Follow-Up Study) of 27 270 men was conducted. WC, WHR, and BMI were assessed at baseline. Covariates and potential confounders were assessed repeatedly during the follow-up. Results: During 13 y of follow-up, we documented 884 incident type 2 diabetes cases. Age-adjusted relative risks (RRs) across quintiles of WC were 1.0, 2.0, 2.7, 5.0, and 12.0; those of WHR were 1.0, 2.1, 2.7, 3.6, and 6.9; and those of BMI were 1.0, 1.1, 1.8, 2.9, and 7.9 (P for trend < 0.0001 for all). Multivariate adjustment for diabetes risk factors only slightly attenuated these RRs. Adjustment for BMI substantially attenuated RRs for both WC and WHR. The receiver operator characteristic curve analysis indicated that WC and BMI were similar and were better than WHR in predicting type 2 diabetes. The cumulative proportions of type 2 diabetes cases identified according to medians of BMI (greater than or equal to 24.8), WC (greater than or equal to 94 cm), and WHR (greater than or equal to 0.94) were 82.5%, 83.6%, and 74.1%, respectively. The corresponding proportions were 78.9%, 50.5%, and 65.7% according to the recommended cutoffs. Conclusions: Both overall and abdominal adiposity strongly and independently predict risk of type 2 diabetes. WC is a better predictor than is WHR. The currently recommended cutoff for WC of 102 cm for men may need to be reevaluated; a lower cutoff may be more appropriate.
Hypoxia‐inducible factor prolyl 4‐hydroxylases (HIF‐PHDs) are important targets against oxidative stress. We hypothesized that inhibition HIF‐PHD by adaptaquin reduces hypoxic‐ischemic brain injury ...in a neonatal mouse model. The pups were treated intraperitoneally immediately with adaptaquin after hypoxia‐ischemia (HI) and then every 24 h for 3 days. Adaptaquin treatment reduced infarction volume by an average of 26.3% at 72 h after HI compared to vehicle alone, and this reduction was more pronounced in males (34.8%) than in females (11.7%). The protection was also more pronounced in the cortex. The subcortical white matter injury as measured by tissue loss volume was reduced by 24.4% in the adaptaquin treatment group, and this reduction was also more pronounced in males (28.4%) than in females (18.9%). Cell death was decreased in the cortex as indicated by Fluoro‐Jade labeling, but not in other brain regions with adaptaquin treatment. Furthermore, in the brain injury area, adaptaquin did not alter the number of cells positive for caspase‐3 activation or translocation of apoptosis‐inducing factor to the nuclei. Adaptaquin treatment increased glutathione peroxidase 4 mRNA expression in the cortex but had no impact on 3‐nitrotyrosine, 8‐hydroxy‐2 deoxyguanosine, or malondialdehyde production. Hif1α mRNA expression increased after HI, and adaptaquin treatment also stimulated Hif1α mRNA expression, which was also more pronounced in males than in females. However, nuclear translocation of HIF1α protein was decreased after HI, and adaptaquin treatment had no influence on HIF1α expression in the nucleus. These findings demonstrate that adaptaquin treatment is neuroprotective, but the potential mechanisms need further investigation.
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Neonatal hypoxia‐ischemia (HI)–induced neuronal cell death and brain injury is still an important cause of neurological disability. Recent data suggest that hypoxia‐inducible factor (HIF) prolyl‐hydroxylases (PHDs) may serve as potential therapeutic targets in paradigms of regulated cell death. We found, adaptaquin (AQ), a selective PHD inhibitor, reduced non‐apoptotic cell death and brain injury in the neonatal mouse HI model. The potential mechanisms may include both HIF‐dependent and ‐independent signaling pathways (such as up‐regulated glutathione peroxidase 4, GPX4).
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We have investigated the Gd55Ni10Co35 amorphous microwires with a large supercooling temperature range of 132 K in terms of thermally induced microstructural evolution and their magnetocaloric effect ...(MCE). With the emerging and growth of the nanocrystals against the maintained amorphous matrix, there appears a threshold annealing temperature of 513 K where the Curie temperature (Tc) sees an abrupt increase from 192 K to 212 K as a result of competition between amorphous and crystalline phase. Another effect from these two phases is to conspire to a broadening of working temperature range. The scaling factor n as in ΔSM∝Hn is found to follow a Boltzmann type of dependency on the annealing temperature and can hence serve as an indicator for the desirable microstructure in favor of MCE. All these results demonstrate that the MCE performance of Gd-based amorphous microwires can be formulated via the fine control of microstructure.
Purpose: A longer stent is associated with adverse events after percutaneous coronary intervention (PCI). However, little information is available on the relationship between stent length and ...periprocedural prognosis in patients with ST segment elevation myocardial infarction (STEMI). We aimed to assess the target vessel stent length influence on angiographic outcomes and in-hospital major adverse cardiovascular event (MACE) during primary PCI in patients with STEMI. Patients and Methods: This single-center retrospective observational study included 246 patients with STEMI admitted to the Zhejiang Provincial People's Hospital between January 2019 and December 2021, who underwent primary PCI and successful stent implantation. The exclusion criteria included left main lesion, multiple diseased vessel-stenting, bleeding disorders, contrast allergy, and incomplete data. Patients were divided into two groups based on the median stents length: group A (less than or equal to29 mm, n=125) and group B (>29mm, n=121). Periprocedural outcomes were slow fow/no-refow (SF-NR) and in-hospital MACE, which included acute heart failure, malignant arrhythmia, cardiovascular death, non-fatal stroke, non-fatal myocardial infarction, and urgent revascularization. Multivariate logistic analyses were used to explore the correlation between stent length and SF-NR. Results: A total of 246 patients (82.9% males) with a mean age of 59.9+ or -12.6 years were included in the analysis. The incidence of SF-NR was significantly higher in group B than in group A (36.4% vs 23.2%, p=0.024). However, the in-hospital MACE incidence rate was similar between the two groups (7.2% vs 7.4%, p=0.943). Multivariate logistic regression analysis showed that stent length and diameter, and peak troponin I level were independent risk factors for SF-NR. Conclusion: Excessive stent length is an independent risk factor for SF-NR, without any significant influence on the risk of MACE during hospitalization. Keywords: coronary stent, ST segment elevation myocardial infarction, primary percutaneous coronary intervention, slow fow/noreflow, major adverse cardiovascular event
The objective of this study was to aggregate data for the first genomewide association study meta-analysis of cluster headache, to identify genetic risk variants, and gain biological insights.
A ...total of 4,777 cases (3,348 men and 1,429 women) with clinically diagnosed cluster headache were recruited from 10 European and 1 East Asian cohorts. We first performed an inverse-variance genomewide association meta-analysis of 4,043 cases and 21,729 controls of European ancestry. In a secondary trans-ancestry meta-analysis, we included 734 cases and 9,846 controls of East Asian ancestry. Candidate causal genes were prioritized by 5 complementary methods: expression quantitative trait loci, transcriptome-wide association, fine-mapping of causal gene sets, genetically driven DNA methylation, and effects on protein structure. Gene set and tissue enrichment analyses, genetic correlation, genetic risk score analysis, and Mendelian randomization were part of the downstream analyses.
The estimated single nucleotide polymorphism (SNP)-based heritability of cluster headache was 14.5%. We identified 9 independent signals in 7 genomewide significant loci in the primary meta-analysis, and one additional locus in the trans-ethnic meta-analysis. Five of the loci were previously known. The 20 genes prioritized as potentially causal for cluster headache showed enrichment to artery and brain tissue. Cluster headache was genetically correlated with cigarette smoking, risk-taking behavior, attention deficit hyperactivity disorder (ADHD), depression, and musculoskeletal pain. Mendelian randomization analysis indicated a causal effect of cigarette smoking intensity on cluster headache. Three of the identified loci were shared with migraine.
This first genomewide association study meta-analysis gives clues to the biological basis of cluster headache and indicates that smoking is a causal risk factor. ANN NEUROL 2023;94:713-726.
Background. Whether community-associated methicillin-resistant Staphylococcus aureus (MRSA) genotypes (e.g., USA300) are a major cause of bloodstream infections (BSIs) and health care—associated ...infections has been poorly defined. Methods. Consecutive MRSA isolates recovered from patients with BSIs were prospectively collected at an urban public hospital. Molecular typing studies were performed. Prevalence and risk factors for the MRSA USA300 genotype were assessed. Results. One hundred thirty-two cases of MRSA BSI were documented over 7.5 months in 2004 (incidence, 6.79 per 1000 admissions); 116 isolates were available for genotyping. Characteristics of the 116 evaluable cases included: a mean age 47 years; 62% were male, 82% were African American, and 22% were HIV seropositive. The crude in-hospital mortality rate was 22%. In 107 cases (92%), there was contact with a health care facility within the year prior to infection, and a nosocomial infection (defined as positive blood culture results obtained >48 h after admission) occurred in 49 cases (42%). PFGE demonstrated that 39 (34%) of the 116 isolates were the MRSA USA300 genotype; 34 (29%) were USA100; 42 (36%) were USA500; and 1 (1%) was USA800. MRSA USA300 accounted for 28% of health care—associated BSIs and 20% of nosocomial MRSA BSIs. In multivariate analysis, isolation of the USA300 genotype was associated with injectiondrug use (OR, 3.67; 95% CI, 1.10–12.28) and skin and soft tissue infection (OR, 4.26; 95% CI, 1.08–16.84). Patients who resided in long-term care facilities (OR, 0.09; 95% CI, 0.01–0.82) and those who were treated with antimicrobials in the prior year were less likely to have MRSA USA300 genotype recovered (OR, 0.10; 95% CI, 0.02–0.49). Conclusions. MRSA USA300 genotype, the predominant cause of community-associated MRSA infections in our area (Atlanta, GA), has now emerged as a significant cause of health care—associated and nosocomial BSI. MRSA USA300 as a nosocomial pathogen presents new challenges to infection control programs.
The relationship between admission glucose levels and outcomes in older diabetic and nondiabetic patients with acute myocardial infarction is not well defined.
We evaluated a national sample of ...elderly patients (n=141,680) hospitalized with acute myocardial infarction from 1994 to 1996. Admission glucose was analyzed as a categorical (< or =110, >110 to 140, >140 to 170, >170 to 240, >240 mg/dL) and continuous variable for its association with mortality in patients with and without recognized diabetes. A substantial proportion of hyperglycemic patients (eg, 26% of those with glucose >240 mg/dL) did not have recognized diabetes. Fewer hyperglycemic patients without known diabetes received insulin during hospitalization than diabetics with similar glucose levels (eg, glucose >240 mg/dL, 22% versus 73%; P<0.001). Higher glucose levels were associated with greater risk of 30-day mortality in patients without known diabetes (for glucose range from < or =110 to >240 mg/dL, 10% to 39%) compared with diabetics (range, 16% to 24%; P for interaction <0.001). After multivariable adjustment, higher glucose levels continued to be associated with a graded increase in 30-day mortality in patients without known diabetes (referent, glucose < or =110 mg/dL; range from glucose >110 to 140 mg/dL: hazard ratio HR, 1.17; 95% CI, 1.11 to 1.24; to glucose >240 mg/dL: HR, 1.87; 95% CI, 1.75 to 2.00). In contrast, among diabetic patients, greater mortality risk was observed only in those with glucose >240 mg/dL (HR, 1.32; 95% CI, 1.17 to 1.50 versus glucose < or =110 mg/dL; P for interaction <0.001). One-year mortality results were similar.
Elevated glucose is common, rarely treated, and associated with increased mortality risk in elderly acute myocardial infarction patients, particularly those without recognized diabetes.
Genome-wide association studies (GWAS) of chronic lymphocytic leukemia (CLL) have shown that common genetic variation contributes to the heritable risk of CLL. To identify additional CLL ...susceptibility loci, we conducted a GWAS and performed a meta-analysis with a published GWAS totaling 1,739 individuals with CLL (cases) and 5,199 controls with validation in an additional 1,144 cases and 3,151 controls. A combined analysis identified new susceptibility loci mapping to 3q26.2 (rs10936599, P = 1.74 × 10(-9)), 4q26 (rs6858698, P = 3.07 × 10(-9)), 6q25.2 (IPCEF1, rs2236256, P = 1.50 × 10(-10)) and 7q31.33 (POT1, rs17246404, P = 3.40 × 10(-8)). Additionally, we identified a promising association at 5p15.33 (CLPTM1L, rs31490, P = 1.72 × 10(-7)) and validated recently reported putative associations at 5p15.33 (TERT, rs10069690, P = 1.12 × 10(-10)) and 8q22.3 (rs2511714, P = 2.90 × 10(-9)). These findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to CLL.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
To identify common variants influencing colorectal cancer (CRC) risk, we performed a meta-analysis of five genome-wide association studies, comprising 5626 cases and 7817 controls of European ...descent. We conducted replication of top ranked single nucleotide polymorphisms (SNPs) in additional series totalling 14 037 cases and 15 937 controls, identifying a new CRC risk locus at 10q24.2 rs1035209; odds ratio (OR) = 1.13, P = 4.54 × 10(-11). We also performed meta-analysis of our studies, with previously published data, of several recently purported CRC risk loci. We failed to find convincing evidence for a previously reported genome-wide association at rs11903757 (2q32.3). Of the three additional loci for which evidence of an association in Europeans has been previously described we failed to show an association between rs59336 (12q24.21) and CRC risk. However, for the other two SNPs, our analyses demonstrated new, formally significant associations with CRC. These are rs3217810 intronic in CCND2 (12p13.32; OR = 1.19, P = 2.16 × 10(-10)) and rs10911251 near LAMC1 (1q25.3; OR = 1.09, P = 1.75 × 10(-8)). Additionally, we found some evidence to support a relationship between, rs647161, rs2423297 and rs10774214 and CRC risk originally identified in East Asians in our European datasets. Our findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to CRC.
A model using administrative claims data that is suitable for profiling hospital performance for heart failure would be useful in quality assessment and improvement efforts.
We developed a ...hierarchical regression model using Medicare claims data from 1998 that produces hospital risk-standardized 30-day mortality rates. We validated the model by comparing state-level standardized estimates with state-level standardized estimates calculated from a medical record model. To determine the stability of the model over time, we used annual Medicare cohorts discharged in 1999-2001. The final model included 24 variables and had an area under the receiver operating characteristic curve of 0.70. In the derivation set from 1998, the 25th and 75th percentiles of the risk-standardized mortality rates across hospitals were 11.6% and 12.8%, respectively. The 95th percentile was 14.2%, and the 5th percentile was 10.5%. In the validation samples, the 5th and 95th percentiles of risk-standardized mortality rates across states were 9.9% and 13.9%, respectively. Correlation between risk-standardized state mortality rates from claims data and rates derived from medical record data was 0.95 (SE=0.015). The slope of the weighted regression line from the 2 data sources was 0.76 (SE=0.04) with intercept of 0.03 (SE=0.004). The median difference between the claims-based state risk-standardized estimates and the chart-based rates was <0.001 (25th percentile=-0.003; 75th percentile=0.002). The performance of the model was stable over time.
This administrative claims-based model produces estimates of risk-standardized state mortality that are very good surrogates for estimates derived from a medical record model.
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