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Abstract Objective To examine the association of long-term weight change with RA risk in a large prospective cohort study. Methods The Nurses’ Health Study II started in 1989 (baseline); after exclusions, we studied 108 505 women 25–42 years old without RA. Incident RA was reported by participants and confirmed by medical record review. Body weight was reported biennially through 2015. We investigated two time-varying exposures: weight changes from baseline and from age 18; change was divided into five categories. We used a marginal structural model approach to account for time-varying weight change and covariates. Results Over 2 583 266 person-years, with a median follow-up time of 25.3 years, 541 women developed RA. Compared with women with stable weight from baseline, weight change was significantly associated with increased RA risk [weight gain 2–<10 kg: RR = 1.98 (95% CI 1.38, 2.85); 10–<20 kg: RR = 3.28 (95% CI 2.20, 4.89); ≥20 kg: RR = 3.81 (95% CI 2.39, 6.07); and weight loss >2 kg: RR = 2.05 (95% CI 1.28, 3.28)]. Weight gain of 10 kg or more from age 18 compared with stable weight was also associated with increased RA risk [10–< 20 kg: RR = 2.12 (95% CI 1.37, 3.27), ≥20 kg: RR = 2.31 (95% CI 1.50, 3.56)]. Consistent findings were observed for seropositive and seronegative RA. Conclusion Long-term weight gain was strongly associated with increased RA risk in women, with weight gain of ≥20 kg associated with more than a three-fold increased RA risk. Maintenance of healthy weight may be a strategy to prevent or delay RA.

( BMJ. 2022;378:e070312) About 8% of US pregnancies are complicated by gestational diabetes mellitus (GDM). Type 2 diabetes is caused by a combination of genetic and lifestyle factors, and undiagnosed diabetes can cause potentially irreversible cardiovascular, renal, or neurological damage. Those affected by GDM are at a heightened risk for type 2 diabetes. This study aimed to evaluate the associations between modifiable risk factors [body mass index (BMI), high-quality diet, regular physical activity, moderate alcohol consumption, and not smoking] and risk of progression to type 2 diabetes in patients who have experienced GDM. A secondary aim was to evaluate whether these associations varied by BMI or genetic susceptibility to type 2 diabetes.

In developed nations, monitoring for drug-induced liver injury through serial measurements of serum transaminases [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] in at-risk individuals is the standard of care. Despite the need, monitoring for drug-related hepatotoxicity in resource-limited settings is often limited by expense and logistics, even for patients at highest risk. This article describes the development and clinical testing of a paper-based, multiplexed microfluidic assay designed for rapid, semiquantitative measurement of AST and ALT in a fingerstick specimen. Using 223 clinical specimens obtained by venipuncture and 10 fingerstick specimens from healthy volunteers, we have shown that our assay can, in 15 min, provide visual measurements of AST and ALT in whole blood or serum, which allow the user to place those values into one of three readout "bins" [<3× upper limit of normal (ULN), 3 to 5× ULN, and >5× ULN, corresponding to tuberculosis/HIV treatment guidelines] with >90% accuracy. These data suggest that the ultimate point-of-care fingerstick device will have high impact on patient care in low-resource settings.

Silicon nanowires (NWs) could enable low-cost and efficient photovoltaics, though their performance has been limited by nonideal electrical characteristics and an inability to tune absorption properties. We overcome these limitations through controlled synthesis of a series of polymorphic core/multishell NWs with highly crystalline, hexagonally-faceted shells, and well-defined coaxial ( p / n ) and p / intrinsic / n ( p / i / n ) diode junctions. Designed 200–300 nm diameter p / i / n NW diodes exhibit ultralow leakage currents of approximately 1 fA, and open-circuit voltages and fill-factors up to 0.5 V and 73%, respectively, under one-sun illumination. Single-NW wavelength-dependent photocurrent measurements reveal size-tunable optical resonances, external quantum efficiencies greater than unity, and current densities double those for silicon films of comparable thickness. In addition, finite-difference-time-domain simulations for the measured NW structures agree quantitatively with the photocurrent measurements, and demonstrate that the optical resonances are due to Fabry-Perot and whispering-gallery cavity modes supported in the high-quality faceted nanostructures. Synthetically optimized NW devices achieve current densities of 17 mA/cm 2 and power-conversion efficiencies of 6%. Horizontal integration of multiple NWs demonstrates linear scaling of the absolute photocurrent with number of NWs, as well as retention of the high open-circuit voltages and short-circuit current densities measured for single NW devices. Notably, assembly of 2 NW elements into vertical stacks yields short-circuit current densities of 25 mA/cm 2 with a backside reflector, and simulations further show that such stacking represents an attractive approach for further enhancing performance with projected efficiencies of &gt; 15% for 1.2 μm thick 5 NW stacks.

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTCovalently-Functionalized Single-Walled Carbon Nanotube Probe Tips for Chemical Force MicroscopyStanislaus S. Wong, Adam T. Woolley, Ernesto Joselevich, Chin Li Cheung, and Charles M. LieberView Author Information Department of Chemistry and Chemical Biology Harvard University, 12 Oxford Street Cambridge, Massachusetts 02138 Cite this: J. Am. Chem. Soc. 1998, 120, 33, 8557–8558Publication Date (Web):August 5, 1998Publication History Received22 May 1998Published online5 August 1998Published inissue 1 August 1998https://pubs.acs.org/doi/10.1021/ja9817803https://doi.org/10.1021/ja9817803rapid-communicationACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views1694Altmetric-Citations218LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (2)»Supporting Information Supporting Information SUBJECTS:Carbon nanotubes,Functionalization,Probes,Surface interactions,Titration Get e-Alerts

&lt;b&gt;Objective:&lt;/b&gt; Coffee may protect against multiple chronic diseases, particularly type 2 diabetes, but the mechanisms remain unclear. &lt;p&gt;&lt;b&gt;Research Design and Methods: &lt;/b&gt;Leveraging dietary and metabolomic data in two large cohorts of women (the Nurses’ Health Study I and II), we identified and validated plasma metabolites associated with coffee intake in 1595 women. We then evaluated the prospective association of coffee-related metabolites with diabetes risk and the added predictivity of these metabolites for diabetes in two nested case-control studies (n=457 cases and 1371 controls). &lt;/p&gt; &lt;p&gt;&lt;b&gt;Results: &lt;/b&gt;Of 461 metabolites, 34 were identified and validated to be associated with total coffee intake, including 13 positive associations (primarily trigonelline, polyphenol metabolites, and caffeine metabolites) and 21 inverse associations (primarily triacylglycerols and diacylglycerols). These associations were generally consistent for caffeinated and decaffeinated coffee, except for caffeine and its metabolites that were only associated with caffeinated coffee intake. The three cholesteryl esters positively associated with coffee intake showed inverse associations with diabetes risk, whereas the 12 metabolites negatively associated with coffee (five diacylglycerols and seven triacylglycerols) showed positive associations with diabetes. Adding the 15 diabetes-associated metabolites to classical risk factors-based prediction model increased the C-statistic from 0.79 (95% CI: 0.76, 0.83) to 0.83 (95% CI: 0.80, 0.86) (&lt;i&gt;P&lt;/i&gt;&lt;0.001). Similar improvement was observed in the validation set.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusion: &lt;/b&gt;Coffee consumption is associated with widespread metabolic changes, among which lipid metabolites may be critical for the anti- diabetes benefit of coffee. Coffee-related metabolites might help improve prediction of diabetes, but further validation studies &lt;a&gt;are &lt;/a&gt;needed.&lt;/p&gt;

Treatment with common household bleach containing hypochlorite destroys dust mites and denatures protein allergens. The purpose of this study was to determine if home use of hypochlorite products results in lowered exposure to bacteria, fungi, and protein allergens and improved quality of life (QOL) for asthmatic persons in the home. Asthmatic and nonasthmatic households containing at least three persons (between 2 and 17 years of age) were recruited. Households were supplied one of three sets of cleaning products (regular products, some containing hypochlorite; regular products plus three additional products with dilute hypochlorite; control, no products). Participants were supplied with cleaning instructions and asthma education. The control group was instructed to clean as usual. Participants completed general health and QOL questionnaires. Asthmatic participants completed an additional asthma QOL questionnaire. Families participated in the study for 8 weeks and completed the full set of questions every 2 weeks. Homes were visited at the beginning of the study and twice thereafter at monthly intervals. Samples evaluated were surface bacteria, viable and nonviable airborne spores, and dust antigen content. Reductions in surface bacteria, airborne fungal spores, and dust antigen levels were achieved. Significant improvement in general health parameters was seen for the asthmatic product groups over the control group. Significant improvement in general QOL and asthma-specific QOL was seen in the asthmatic group. Emphasis on cleaning and cleaning education combined with hypochlorite-based cleaning supplies resulted in significantly improved QOL for families with asthmatic children.

Background: The latest 2015 Dietary Guidelines Advisory Committee Report has recommended healthy dietary patterns as an easier way for the public to understand and act upon. Despite the latest evidence supporting the association of the adherence to diet quality and lower mortality risk, few studies have evaluated changes in diet quality over time in relation to mortality risk. Therefore, we examined changes in diet quality and subsequent risk of total and cause-specific mortality in two large cohort studies. Objective: To evaluate the association between 12-y changes (1986-1998) in three diet quality indices assessed by the Alternative Healthy Eating Index (AHEI), the Alternate Mediterranean Diet (AMED), and the Dietary Approach to Stop Hypertension (DASH)) with total and cause-specific mortality in the Nurses’ Health Study (NHS) and Health Professionals Follow-up Study (HPFS) from 1998-2010. Methods: We followed 44,501 women in the NHS and 23,100 men in the HPFS, both from 1986 to 2010. The AHEI, AMED and DASH were defined from validated food frequency questionnaires and updated every 4 years. Cox proportional hazards models were used to calculate hazard ratios (HR) with adjustment for potential confounders (both at baseline and changes over time). Results across cohorts were pooled by an inverse variance-weighted, random-effect meta-analysis. Results: During 758,683 person-years of follow-up, we documented 9,772 deaths, including 2,292 CVD deaths and 3,314 cancer deaths. The pooled HR comparing participants with the greatest improvement in diet quality (14%-33%) vs. participants whose diet quality remained relatively stable (no change, 0-3%) in the 12-year period was 0.89 (95% confidence interval [CI], 0.83 to 0.95) for AHEI; 0.83 (95 CI%, 0.65 to 1.05) for AMED; and 0.88 (95% CI 0.83 to 0.94) for DASH. In contrast, a decrease in diet quality was significantly associated with increased total mortality. In continuous analyses, a 20th-percentile increase in the three diet quality scores was associated with a 9%-20% lower total mortality (AHEI, 20% [15% to 24%]; AMED, 9% [6% to 12%]; DASH, 13% [9% to17%]). The results were largely similar when evaluated risk of death from CVD and cancer as outcomes. Notably, maintaining a higher vs lower adherence to any of the three dietary patterns during the 12 years was significantly associated with a 23-24% lower total mortality, a 19-27% lower risk of CVD deaths, and a 13-20% lower risk of cancer death. Conclusions: In two large, independent cohorts of U.S. women and men we found consistent associations between increasing diet quality over 12 years and decreased total, CVD, and cancer mortality. These results underscore the importance of the strategies to promote and sustain a healthy diet in improving longevity among middle-aged and older adults.

Altered maternal haemoglobin levels during pregnancy are associated with pre-clinical and clinical conditions affecting the fetus. Evidence from animal models suggests that these associations may be partially explained by differential DNA methylation in the newborn with possible long-term consequences. To test this in humans, we meta-analyzed the epigenome-wide associations of maternal haemoglobin levels during pregnancy with offspring DNA methylation in 3,967 newborn cord blood and 1,534 children and 1,962 adolescent whole-blood samples derived from 10 cohorts. DNA methylation was measured using Illumina Infinium Methylation 450K or MethylationEPIC arrays covering 450,000 and 850,000 methylation sites, respectively. There was no statistical support for the association of maternal haemoglobin levels with offspring DNA methylation either at individual methylation sites or clustered in regions. For most participants, maternal haemoglobin levels were within the normal range in the current study, whereas adverse perinatal outcomes often arise at the extremes. Thus, this study does not rule out the possibility that associations with offspring DNA methylation might be seen in studies with more extreme maternal haemoglobin levels.