Mutational Analysis of the Nitrogenase Carbon Monoxide Protective Protein CowN Reveals That a Conserved C-Terminal Glutamic Acid Residue Is Necessary for Its Activity.

Nitrogenase is the only enzyme that catalyzes the reduction of nitrogen gas into ammonia. Nitrogenase is tightly inhibited by the environmental gas carbon monoxide (CO). Many nitrogen fixing bacteria protect nitrogenase from CO inhibition using the protective protein CowN. This work demonstrates that a conserved glutamic acid residue near the C-terminus of Gluconacetobacter diazotrophicus CowN is necessary for its function. Mutation of the glutamic acid residue abolishes both CowN's protection against CO inhibition and the ability of CowN to bind to nitrogenase. In contrast, a conserved C-terminal cysteine residue is not important for CO protection by CowN. Overall, this work uncovers structural features in CowN that are required for its function and provides new insights into its nitrogenase binding and CO protection mechanism.

Use patterns of flavored non-cigarette tobacco products among US adults, 2010-2019.

OBJECTIVE: Flavored non-cigarette tobacco product (NCTP) use is common among US adult tobacco users. To update the estimates of use patterns of flavored NCTPs, this study assessed current NCTP use among adults by flavor use and flavor categories from 2010 to 2019. METHODS: We analyzed data from the 2010-2019 Tobacco Use Supplement to the Current Population Survey to estimate the weighted proportion of adult NCTP users by flavor use across survey waves. Flavor use was defined as past 30-day use of any menthol/mint or fruit/other flavors. We used the 2018-2019 data to examine the differences in demographic characteristics and tobacco use patterns among users of menthol/mint or fruit/other flavors compared to exclusive users of tobacco flavor, by product type. RESULTS: Compared to 2014-2015, electronic nicotine delivery system (ENDS) users were more likely (79.0% vs. 66.6%, p < 0.001) to report flavor use in 2018-2019, whereas cigar (26.9% vs. 31.2%, p = 0.030) and pipe (56.3% vs. 65.5%, p = 0.015) smokers were less likely to report flavor use in 2018-2019. In 2018-2019, the most prevalent flavor categories were exclusive use of tobacco flavor among cigar (73.1%) and smokeless tobacco (48.3%) users, and use of fruit/other flavors among ENDS (64.9%) and pipe (48.4%) users. Flavored users were more likely to be young adults aged 18-24 years (cigars, ENDS, smokeless tobacco) and Non-Hispanic Black or Hispanic persons (cigars, ENDS, pipes) compared to tobacco-flavored users. CONCLUSIONS: Flavored product use increased among adult ENDS users but decreased among cigar and pipe smokers. These findings could inform tobacco regulatory efforts concerning flavored NCTPs.

Cigar Cessation Prevalence and Trends by Demographic Characteristics Among US Adults, TUS-CPS, 2010-2019.

INTRODUCTION: Disproportionate rates of cigar smoking across demographic groups can contribute to tobacco-related health disparities in the United States. We assessed overall and demographic-specific cigar cessation rates from 2010 to 2019. AIMS AND METHODS: To characterize cessation prevalence among selected demographic groups over time, we analyzed data from the 2010-2011, 2014-2015, and 2018-2019 Tobacco Use Supplement to the Current Population Survey (TUS-CPS). Individuals who reported either (1) current cigar smoking for at least 2 years or (2) quitting cigar smoking within the past 12 months were included in the study (n = 5262 in 2010-2011; n = 4741 in 2014-2015; n = 3741 in 2018-2019). Among this group, individuals who reported not smoking a cigar within the past 6 months were considered cigar quitters. Chi-square tests were used to test differences in cessation prevalence between the two survey waves within demographic groups as well as between different groups within survey waves. RESULTS: The prevalence of cigar cessation decreased from 2010-2011 to 2018-2019 for non-Hispanic (NH) White individuals, Hispanic individuals, and both males and females. (p < .05 for all groups). NH White individuals had significantly higher cessation prevalence than individuals who identified as NH Black (33.8% vs. 25.0%, respectively, in 2010-2011; 33.4% vs. 20.4% in 2014-2015; 31.1% vs. 22.3% in 2018-2019; p < .05 for all differences). CONCLUSIONS: Overall cigar cessation prevalence significantly decreased from 2010-2011 to 2018-2019. Findings from the study could provide an opportunity to implement strategies that promote cessation strategies targeting certain subpopulations. IMPLICATIONS: Cigar cessation patterns are starkly different across different demographic groups, which leads to a disproportionate burden of health-related effects of continued use of these products. These results can inform policy actions around cigar cessation efforts. Future research to close this disparity should be focused on populations that have lower cessation prevalence.

Characteristics and Patterns of Cigarette Smoking and Vaping By Past-Year Smokers Who Reported Using Electronic Nicotine Delivery System to Help Quit Smoking in the Past Year: Findings From the 2018-2019 Tobacco Use Supplement to the Current Population Survey.

INTRODUCTION: Cigarette smoking has declined, while electronic nicotine delivery system (ENDS) use has increased in the United States. Understanding the role of ENDS in adult smoking quit attempts and cessation is important for estimating their population health impact. AIMS AND METHODS: We used data from 2018 to 2019 tobacco use supplement to the current population survey to examine demographic characteristics and ENDS use patterns among adult ENDS users who reported quitting smoking in the past year by trying to switch to ENDS ("switchers") and smokers who did or did not make a quit attempt in the past year. χ2 tests of proportions and t-tests were used to compare characteristics between groups. RESULTS: In 2018-2019, about three-quarters of switchers reported daily use of ENDS compared to only one-third of dual users with a recent quit attempt by trying to switch to ENDS. Compared to dual users who made a quit attempt by trying to switch to ENDS, switchers were more likely to use menthol/mint-flavored ENDS exclusively (5.6% vs. 13.1%; p = .004) but less likely to use tobacco-flavored ENDS exclusively (21.2% vs. 13.7%; p = .01). CONCLUSIONS: ENDS users who quit smoking in the past year and reported trying to quit by switching to ENDS were more likely to use menthol/mint flavors exclusively and use ENDS daily compared to dual users who made a quit attempt by trying to switch to ENDS. Longer-term prospective data may better clarify the role of ENDS in smoking quit attempts and cessation. IMPLICATIONS: This study provides information on patterns of ENDS use in former smokers and current smokers who tried to quit smoking by switching to ENDS in a national sample of U.S. adults. These results can inform policy actions concerning ENDS products.

CowN sustains nitrogenase turnover in the presence of the inhibitor carbon monoxide.

Nitrogenase is the only enzyme capable of catalyzing nitrogen fixation, the reduction of dinitrogen gas (N2) to ammonia (NH3). Nitrogenase is tightly inhibited by the environmental gas carbon monoxide (CO). Nitrogen-fixing bacteria rely on the protein CowN to grow in the presence of CO. However, the mechanism by which CowN operates is unknown. Here, we present the biochemical characterization of CowN and examine how CowN protects nitrogenase from CO. We determine that CowN interacts directly with nitrogenase and that CowN protection observes hyperbolic kinetics with respect to CowN concentration. At a CO concentration of 0.001 atm, CowN restores nearly full nitrogenase activity. Our results further indicate that CowN's protection mechanism involves decreasing the binding affinity of CO to nitrogenase's active site approximately tenfold without interrupting substrate turnover. Taken together, our work suggests CowN is an important auxiliary protein in nitrogen fixation that engenders CO tolerance to nitrogenase.

Valproate selectively suppresses adolescent anabolic/androgenic steroid-induced aggressive behavior: implications for a role of hypothalamic γ-aminobutyric acid neural signaling.

Pubertal male Syrian hamsters (Mesocricetus auratus) treated with anabolic/androgenic steroids (AASs) during adolescence (P27-P56) display a highly intense aggressive phenotype that shares many behavioral similarities with pathological aggression in youth. Anticonvulsant drugs like valproate that enhance the activity of the γ-aminobutyric acid (GABA) neural system in the brain have recently gained acceptance as a primary treatment for pathological aggression. This study examined whether valproate would selectively suppress adolescent AAS-induced aggressive behavior and whether GABA neural signaling through GABAA subtype receptors in the latero-anterior hypothalamus (LAH; an area of convergence for developmental and neuroplastic changes that underlie aggression in hamsters) modulate the aggression-suppressing effect of this anticonvulsant medication. Valproate (1.0-10.0 mg/kg, intraperitoneal) selectively suppressed the aggressive phenotype in a dose-dependent fashion, with the effective anti-aggressive effects beginning at 5 mg/kg, intraperitoneally. Microinfusion of the GABAA receptor antagonist bicuculline (7.0-700 ng) into the LAH reversed valproate's suppression of AAS-induced aggression in a dose-dependent fashion. At the 70 ng dose of bicuculline, animals expressed the highly aggressive baseline phenotype normally observed in AAS-treated animals. These studies provide preclinical evidence that the anticonvulsant valproate selectively suppresses adolescent, AAS-induced aggression and that this suppression is modulated, in part, by GABA neural signaling within the LAH.

Cumulative solar ultraviolet radiation exposure and basal cell carcinoma of the skin in a nationwide US cohort using satellite and ground-based measures.

BACKGROUND: Basal cell carcinoma of the skin (BCC) is the most common cancer in populations of European ancestry. Although consistently linked with basal cell carcinoma of the skin in case-control studies, few prospective cohort studies have evaluated the shape of the exposure-response of basal cell carcinoma associated with cumulative radiant solar ultraviolet exposure (UVR). METHODS: We followed 63,912 white cancer-free US radiologic technologists from entry (1983-1998) to exit (2003-2005) with known ultraviolet irradiance at up to 5 residential locations. Using generalized-additive and relative risk models we analyzed the exposure-response of basal cell carcinomas associated with ambient cumulative ultraviolet radiant exposure using ground-based National Solar Radiation database Average Daily Total Global data and satellite-based National Aeronautics and Space Administration Total Ozone Mapping Spectrometer data. RESULTS: There were 2151 technologists with an incident primary basal cell carcinoma. Risk of basal cell carcinoma rose with increasing cumulative ultraviolet radiation exposure using both measures, such that 1 MJ cm- 2 increased basal cell carcinoma risk by 8.48 (95% CI 5.22, 11.09, p < 0.001) and by 10.15 (95% CI 6.67, 13.10, p < 0.001) per 10,000 persons per year using the Average Daily Total Global and Total Ozone Mapping Spectrometer ultraviolet data, respectively; relative risk was likewise elevated. There was some evidence of upward curvature in the cumulative ultraviolet exposure response using both exposure measures with a greater increase in risk of basal cell carcinoma at higher levels of ultraviolet radiation exposure, but less evidence for curvature in relative risk. There are indications of substantial variation of relative risk with time after exposure and age at exposure, so that risk is highest for the period 10-14 years after ultraviolet radiation exposure and for those exposed under the age of 25. CONCLUSIONS: We observed increases in risk of basal cell carcinoma and a similar exposure-response for ground-based and satellite ultraviolet radiation measures. Our observations suggest that interventions should concentrate on persons with higher levels of ultraviolet radiation exposure.

Occupational ionising radiation and risk of basal cell carcinoma in US radiologic technologists (1983-2005).

OBJECTIVE: To determine risk for incident basal cell carcinoma from cumulative low-dose ionising radiation in the US radiologic technologist cohort. METHODS: We analysed 65,719 Caucasian technologists who were cancer-free at baseline (1983-1989 or 1994-1998) and answered a follow-up questionnaire (2003-2005). Absorbed radiation dose to the skin in mGy for estimated cumulative occupational radiation exposure was reconstructed for each technologist based on badge dose measurements, questionnaire-derived work history and protection practices, and literature information. Radiation-associated risk was assessed using Poisson regression and included adjustment for several demographic, lifestyle, host and sun exposure factors. RESULTS: Cumulative mean absorbed skin dose (to head/neck/arms) was 55.8 mGy (range 0-1735 mGy). For lifetime cumulative dose, we did not observe an excess radiation-related risk (excess relative risk/Gy=-0.01 (95% CI -0.43 to 0.52). However, we observed that basal cell carcinoma risk was increased for radiation dose received before age 30 (excess relative risk/Gy=0.59, 95% CI -0.11 to 1.42) and before 1960 (excess relative risk/Gy=2.92, 95% CI 1.39 to 4.45). CONCLUSIONS: Basal cell carcinoma risk was unrelated to low-dose radiation exposure among radiologic technologists. Because of uncertainties in dosimetry and sensitivity to model specifications, both our null results and our findings of excess risk for dose received before age 30 and exposure before 1960 should be interpreted with caution.

Work history and mortality risks in 90,268 US radiological technologists.

OBJECTIVES: There have been few studies of work history and mortality risks in medical radiation workers. We expanded by 11 years and more outcomes our previous study of mortality risks and work history, a proxy for radiation exposure. METHODS: Using Cox proportional hazards models, we estimated mortality risks according to questionnaire work history responses from 1983 to 1989 through 2008 by 90,268 US radiological technologists. We controlled for potential confounding by age, birth year, smoking history, body mass index, race and gender. RESULTS: There were 9566 deaths (3329 cancer and 3020 circulatory system diseases). Mortality risks increased significantly with earlier year began working for female breast (p trend=0.01) and stomach cancers (p trend=0.01), ischaemic heart (p trend=0.03) and cerebrovascular diseases (p trend=0.02). The significant trend with earlier year first worked was strongly apparent for breast cancer during baseline through 1997, but not 1998-2008. Risks were similar in the two periods for circulatory diseases. Radiological technologists working ≥5 years before 1950 had elevated mortality from breast cancer (HR=2.05, 95% CI 1.27 to 3.32), leukaemia (HR=2.57, 95% CI 0.96 to 6.68), ischaemic heart disease (HR=1.13, 95% CI 0.96 to 1.33) and cerebrovascular disease (HR=1.28, 95% CI 0.97 to 1.69). No other work history factors were consistently associated with mortality risks from specific cancers or circulatory diseases, or other conditions. CONCLUSIONS: Radiological technologists who began working in early periods and for more years before 1950 had increased mortality from a few cancers and some circulatory system diseases, likely reflecting higher occupational radiation exposures in the earlier years.

Correction: Associations between healthcare utilization and access and diabetic retinopathy complications using All of Us nationwide survey data.

[This corrects the article DOI: 10.1371/journal.pone.0269231.].

Associations between healthcare utilization and access and diabetic retinopathy complications using All of Us nationwide survey data.

PURPOSE: Inadequacies in healthcare access and utilization substantially impact outcomes for diabetic patients. The All of Us database offers extensive survey data pertaining to social determinants that is not routinely available in electronic health records. This study assesses whether social determinants were associated with an increased risk of developing proliferative diabetic retinopathy or related complications (e.g. related diagnoses or procedures). METHODS: We identified 729 adult participants in the National Institutes of Health All of Us Research Program data repository with diabetic retinopathy (DR) who answered survey questions pertaining to healthcare access and utilization. Electronic health record data regarding co-morbidities, laboratory values, and procedures were extracted. Multivariable logistic regression with bi-directional stepwise variable selection was performed from a wide range of predictors. Statistical significance was defined as p<0.05. RESULTS: The mean (standard deviation) age of our cohort was 64.9 (11.4) years. 15.2% identified as Hispanic or Latino, 20.4% identified as Black, 60.6% identified as White, and 19.3% identified as Other. 10-20% of patients endorsed several reasons for avoiding or delaying care, including financial concerns and lack of access to transportation. Additional significant social determinants included race and religion discordance between healthcare provider and patient (odds ratio [OR] 1.20, 95% confidence interval [CI] 1.02-1.41, p = 0.03) and caregiver responsibilities toward others (OR 3.14, 95% CI 1.01-9.50, p = 0.04). CONCLUSIONS: Nationwide data demonstrate substantial barriers to healthcare access among DR patients. In addition to financial and social determinants, race and religion discordance between providers and patients may increase the likelihood of PDR and related complications.

Social Determinants of Health Data Availability for Patients with Eye Conditions.

Purpose: To quantify and characterize social determinants of health (SDoH) data coverage using single-center electronic health records (EHRs) and the National Institutes of Health All of Us research program. Design: Retrospective cohort study from June 2014 through June 2021. Participants: Adults 18 years of age or older with a diagnosis of diabetic retinopathy, glaucoma, cataracts, or age-related macular degeneration. Methods: For All of Us, research participants completed online survey forms as part of a nationwide prospective cohort study. In local EHRs, patients were selected based on diagnosis codes. Main Outcome Measures: Social determinants of health data coverage, characterized by the proportion of each disease cohort with available data regarding demographics and socioeconomic factors. Results: In All of Us, we identified 23 806 unique adult patients, of whom 2246 had a diagnosis of diabetic retinopathy, 13 448 had a diagnosis of glaucoma, 6634 had a diagnosis of cataracts, and 1478 had a diagnosis of age-related macular degeneration. Survey completion rates were high (99.5%-100%) across all cohorts for demographic information, overall health, income, education, and lifestyle. However, health care access (12.7%-29.4%), housing (0.7%-1.1%), social isolation (0.2%-0.3%), and food security (0-0.1%) showed significantly lower response rates. In local EHRs, we identified 80 548 adult patients, of whom 6616 had a diagnosis of diabetic retinopathy, 26 793 had a diagnosis of glaucoma, 40 427 had a diagnosis of cataracts, and 6712 had a diagnosis of age-related macular degeneration. High data coverage was found across all cohorts for variables related to tobacco use (82.84%-89.07%), alcohol use (77.45%-83.66%), and intravenous drug use (84.76%-93.14%). However, low data coverage (< 50% completion) was found for all other variables, including education, finances, social isolation, stress, physical activity, food insecurity, and transportation. We used chi-square testing to assess whether the data coverage varied across different disease cohorts and found that all fields varied significantly (P < 0.001). Conclusions: The limited and highly variable data coverage in both local EHRs and All of Us highlights the need for researchers and providers to develop SDoH data collection strategies and to assemble complete datasets.

Novel Association between Opioid Use and Increased Risk of Retinal Vein Occlusion Using the National Institutes of Health All of Us Research Program.

Purpose: To assess for risk factors for retinal vein occlusion (RVO) among participants in the National Institutes of Health All of Us database, particularly social risk factors that have not been well studied, including substance use. Design: Retrospective, case-control study. Participants: Data were extracted for 380 adult participants with branch retinal vein occlusion (BRVO), 311 adult participants with central retinal vein occlusion (CRVO), and 1520 controls sampled among 311 640 adult participants in the All of Us database. Methods: Data were extracted regarding demographics, comorbidities, income, housing, insurance, and substance use. Opioid use was defined by relevant diagnosis and prescription codes, with prescription use > 30 days. Controls were sampled at a 4:1 control to case ratio from a pool of individuals aged > 18 years without a diagnosis of RVO and proportionally matched to the demographic distribution of the 2019 U.S. census. Multivariable logistic regression identified medical and social determinants significantly associated with BRVO or CRVO. Statistical significance was defined as P < 0.05. Main Outcome Measure: Development of BRVO or CRVO based on diagnosis codes. Results: Among patients with BRVO, the mean (standard deviation) age was 70.1 (10.5) years. The majority (53.7%) were female. Cases were diverse; 23.7% identified as Black, and 18.4% identified as Hispanic or Latino. Medical risk factors including glaucoma (odds ratio [OR], 3.29; 95% confidence interval [CI], 2.22-4.90; P < 0.001), hypertension (OR, 2.15; 95% CI, 1.49-3.11; P < 0.001), and diabetes mellitus (OR, 1.68; 95% CI, 1.18-2.38; P = 0.004) were re-demonstrated to be associated with BRVO. Black race (OR, 2.64; 95% CI, 1.22-6.05; P = 0.017) was found to be associated with increased risk of BRVO. Past marijuana use (OR, 0.68; 95% CI, 0.50-0.92; P = 0.013) was associated with decreased risk of BRVO; however, opioid use (OR, 1.98; 95% CI, 1.41-2.78; P < 0.001) was associated with a significantly increased risk of BRVO. Similar associations were found for CRVO. Conclusions: Understanding RVO risk factors is important for primary prevention and improvement in visual outcomes. This study capitalizes on the diversity and scale of a novel nationwide database to elucidate a previously uncharacterized association between RVO and opioid use.

Acute ischemic stroke & emergency mechanical thrombectomy: The effect of type of anesthesia on early outcome.

BACKGROUND: Endovascular mechanical thrombectomy (EMT) is the standard of care for acute ischemic stroke (AIS) caused by proximal large vessel occlusions. There is conflicting evidence on outcome of patients undergoing EMT under procedural sedation (PS) or general anesthesia (GA). In this retrospective study we analyze the effect of GA and PS on the functional outcome of patients undergoing EMT. METHODS: Patients who have been admitted at our institute AIS and were treated with EMT under GA or PS between January 2015 and September 2018 were included in the study. Primary end point was the proportion of patients with good functional outcome as defined by a modified Rankin score (mRS) 0-2 at discharge. RESULTS: A total of 155 patients were analyzed in this study including 45 (29.03 %) patients who received 97 GA, 110 (70.9 %) PS and 31 of these received Dexmedetomidine/Remifentanil. The median (IQR) 98 mRS at discharge was 4.0 (1.0-4.0) in the GA group Vs 3.00, (1.00-4.00) in the PS group. Among the secondary outcomes the lowest MAP recorded was significantly less in GA group (64.56 100 ± 18.70) compared to PS group (70.86 ± 16.30); p = 0.03. The PS group had a lower odd of mRS 3-5 (after adjustment), however, this finding was statistically not significant (OR 0.52 [0.07-3.5] 102 p = 0.5). CONCLUSIONS: Our retrospective analysis did not find any influence of GA compared to PS whenever this was delivered by target controlled infusion (TCI) of propofol or by remifentanil/dexmedetomidine (REX) on early functional outcome.

Lifetime Ambient UV Radiation Exposure and Risk of Basal Cell Carcinoma by Anatomic Site in a Nationwide U.S. Cohort, 1983-2005.

BACKGROUND: Cutaneous basal cell carcinoma (BCC) has long been associated with UV radiation (UVR) exposure, but data are limited on risks by anatomic site. METHODS: We followed 63,912 cancer-free White U.S. radiologic technologists from cohort entry (1983-1989/1994-1998) to exit (date first BCC via 2003-2005 questionnaire). We estimated associations between cumulative ambient UVR and relative/absolute risks of self-reported BCC by anatomic location via Poisson models. RESULTS: For incident first primary BCC in 2,124 subjects (mean follow-up, 16.9 years) log[excess relative risks] (ERR) of BCC per unit cumulative ambient UVR = 1.27/MJ cm-2 [95% confidence interval (CI): 0.86-1.68; P trend < 0.001] did not vary by anatomic site (P = 0.153). However, excess absolute risks of BCC per unit cumulative ambient UVR were large for the head/neck = 5.46/MJ cm-2/104 person-year (95% CI: 2.92-7.36; P trend < 0.001), smaller for the trunk (2.56; 95% CI: 1.26-3.33; P trend = 0.003), with lesser increases elsewhere. There were lower relative risks, but higher absolute risks, for those with Gaelic ancestry (P < 0.001), also higher absolute risks among those with fair complexion, but relative and absolute risks were not generally modified by other constitutional, lifestyle or medical factors for any anatomic sites. Excess absolute and relative risk was concentrated 5-15 years before time of follow-up. CONCLUSIONS: BCC relative and absolute risk rose with increasing cumulative ambient UVR exposure, with absolute risk highest for the head/neck, to a lesser extent in the trunk. IMPACT: These associations should be evaluated in other White and other racial/ethnic populations along with assessment of possible modification by time outdoors, protective, and behavioral factors.

Clinical Implementation of Predictive Models Embedded within Electronic Health Record Systems: A Systematic Review.

Predictive analytics using electronic health record (EHR) data have rapidly advanced over the last decade. While model performance metrics have improved considerably, best practices for implementing predictive models into clinical settings for point-of-care risk stratification are still evolving. Here, we conducted a systematic review of articles describing predictive models integrated into EHR systems and implemented in clinical practice. We conducted an exhaustive database search and extracted data encompassing multiple facets of implementation. We assessed study quality and level of evidence. We obtained an initial 3393 articles for screening, from which a final set of 44 articles was included for data extraction and analysis. The most common clinical domains of implemented predictive models were related to thrombotic disorders/anticoagulation (25%) and sepsis (16%). The majority of studies were conducted in inpatient academic settings. Implementation challenges included alert fatigue, lack of training, and increased work burden on the care team. Of 32 studies that reported effects on clinical outcomes, 22 (69%) demonstrated improvement after model implementation. Overall, EHR-based predictive models offer promising results for improving clinical outcomes, although several gaps in the literature remain, and most study designs were observational. Future studies using randomized controlled trials may help improve the generalizability of findings.

Is gadolinium necessary for MRI follow-up evaluation of cystic lesions in the pancreas? Preliminary results.

OBJECTIVE: The purpose of our study was to determine whether gadolinium is necessary in the follow-up evaluation of pancreatic cystic lesions. MATERIALS AND METHODS: Fifty-six patients with pancreatic cystic lesions detected on initial MRI and who underwent follow-up MRI were identified. Mean cyst size was 1.9 cm, and mean follow-up was 9.1 months. MRI included multiacquisition T1- and T2-weighted sequences before contrast administration and 3D fat-suppressed T1-weighted images before and after gadolinium administration. Two radiologists independently reviewed the entire initial examination and follow-up MRI using only unenhanced T1- and T2-weighted sequences from the second examination. Each radiologist made one of three recommendations: 1, no follow-up necessary or follow-up imaging in 6-12 months; 2, cyst aspiration; or 3, cyst resection. Four weeks later, imaging studies were reevaluated with the contrast-enhanced images from the second examination. A second recommendation using the same outcomes was made. Interobserver and intraobserver variations for the same patient were summarized in terms of kappa coefficients and the percentage of times the decisions were concordant. A 95% CI for the percentage of times management decisions would change without and with gadolinium was calculated. RESULTS: Concordance between the two different readers for the interpretations (when using the same MRI interpretation technique for follow-up surveillance) was 87.5% with a kappa coefficient to assess interobserver variation of 0.075, suggesting only slight agreement between the two readers. However, treatment recommendations provided by a single reader with and without information from the contrast-enhanced images were discordant only 4.5% of the time. Recommendations were concordant without and with gadolinium 95.5% (107/112; kappa=0.67) of the time, suggesting substantial agreement. A retrospective consensus review of the five cases in which gadolinium effected a change in the observer's recommendation was performed. There was nothing on the gadolinium-enhanced sequences that would specifically alter a change in a management decision, and it is likely that the changes in management decisions in these five cases were simply related to expected variations in categorizing lesions rather than to the use of gadolinium. CONCLUSION: The use of gadolinium has minimal impact in the follow-up MR assessment of pancreatic cystic lesions.

Using causal energy categories to report the distribution of injuries in an active population: An approach used by the U.S. Army.

OBJECTIVES: To describe the etiologic distribution of all injuries among U.S. Army Active Duty soldiers by causal energy categories. DESIGN: Retrospective cohort, descriptive analysis. METHODS: Injury was defined as the interruption of tissue function caused by an external energy transfer (mechanical, thermal, radiant, nuclear, chemical, or electrical energy). A comprehensive injury matrix standardized categories by causal energies, body locations, and injury types. Categories differentiated acute (ACT) from cumulative micro-traumatic (CMT) overuse injuries, and musculoskeletal injuries (MSKI) from those affecting other or multiple body systems (non-MSKI). International Classification of Diseases (ICD) diagnoses codes were organized into established categories. The matrix was applied to electronic health records for U.S. Army soldiers in 2017. RESULTS: Mechanical energy transfers caused most injuries (97%, n = 809,914): 76% were CMT overuse and the remaining were ACT (<21%). The majority (83%) were MSKI (71% CMT, 12% ACT). While almost one-half (47%) were to lower extremities (38% CMT, 9% ACT) the most frequently injured anatomical sites were the knee and lower back (16% each, primarily CMT). CONCLUSIONS: For the first time all soldiers' injuries have been presented in the same context for consistent comparisons. Findings confirm the vast majority of injuries in this physically-active population are MSKI, and most are CMT MSKI. A very small portion are non-MSKI or injuries caused by non-mechanical energy (e.g., heat- or cold-weather). Most Army injuries are to the lower extremities as a grouped body region, but additional matrix specificity indicates the most injured anatomical locations are the knee, lower back, and shoulder.

Acceleration of ß Cell Aging Determines Diabetes and Senolysis Improves Disease Outcomes.

Type 2 diabetes (T2D) is an age-related disease. Although changes in function and proliferation of aged ß cells resemble those preceding the development of diabetes, the contribution of ß cell aging and senescence remains unclear. We generated a ß cell senescence signature and found that insulin resistance accelerates ß cell senescence leading to loss of function and cellular identity and worsening metabolic profile. Senolysis (removal of senescent cells), using either a transgenic INK-ATTAC model or oral ABT263, improved glucose metabolism and ß cell function while decreasing expression of markers of aging, senescence, and senescence-associated secretory profile (SASP). Beneficial effects of senolysis were observed in an aging model as well as with insulin resistance induced both pharmacologically (S961) and physiologically (high-fat diet). Human senescent ß cells also responded to senolysis, establishing the foundation for translation. These novel findings lay the framework to pursue senolysis of ß cells as a preventive and alleviating strategy for T2D.

Application of 3-D Delta check graphs to HbA1c quality control and HbA1c utilization.

Delta checking is a laboratory information system (LIS)-based tool that detects patient and laboratory quality control errors. By using hemoglobin A1c (HbA1c) data, we developed a novel approach to summarizing and presenting patient Delta values to address limitations of current Delta check algorithms. Delta values were calculated from intrapatient pairs of HbA1c (n = 55,327) measured during 2 years in a single referral or a university hospital laboratory. Three-dimensional Delta-time (DeltaT) and percentile limit graphs were constructed. Cumulative distribution function analysis was used to explore clinical utilization. The DeltaT graphs showed that HbA1c Delta values increase asymmetrically over time. Although the 2.5 to 97.5 and 5.0 to 95.0 percentile Delta check limits were similar for both sites, the referral laboratory's 0.5 to 99.5 percentile limits were wider. For acute patient care environments, we recommend limits of -3.5% and 1.8% for measurements between 0 and 60 days and -4.0% and 2.0% for measurements between 60 and 120 days. For the outpatient environment, we recommend limits of -4.2% and 2.1% and 5.0% and 2.5% for measurements between 0 and 60 days and 60 and 120 days, respectively.Delta checking can be significantly improved with customization of limits set by population and interobservation period. Because LIS systems are incapable of these customizations, customers must become advocates for these modifications.