Sugar is not always sweet: exploring the relationship between hyperglycemia and COVID-19 in a predominantly African American population.

INTRODUCTION: The purpose of this study is to examine the effect of admission glucose in patients hospitalized with COVID-19 with and without diabetes mellitus in a largely African American cohort. DESIGN AND METHODS: This study included 708 adults (89% non-Hispanic Black) admitted with COVID-19 to an urban hospital between 1 March and 15 May 2020. Patients with diabetes were compared with those without and were stratified based on admission glucose of 140 and 180 mg/dL. Adjusted ORs were calculated for outcomes of mortality, intubation, intensive care unit (ICU) admission, acute kidney injury (AKI), and length of stay based on admission glucose levels. RESULTS: Patients with diabetes with admission glucose >140 mg/dL (vs <140 g/dL) had 2.4-fold increased odds of intubation (95% CI 1.2 to 4.6) and 2.1-fold increased odds of ICU admission (95% CI 1.0 to 4.3). Patients with diabetes with admission glucose >180 mg/dL (vs <180 g/dL) had a 1.9-fold increased mortality (95% CI 1.2 to 3.1). Patients without diabetes with admission glucose >140 mg/dL had a 2.3-fold increased mortality (95% CI 1.3 to 4.3), 2.7-fold increased odds of ICU admission (95% CI 1.3 to 5.4), 1.9-fold increased odds of intubation (95% CI 1.0 to 3.7) and 2.2-fold odds of AKI (95% CI 1.1 to 3.8). Patients without diabetes with glucose >180 mg/dL had 4.4-fold increased odds of mortality (95% CI 1.9 to 10.4), 2.7-fold increased odds of intubation (95% CI 1.2 to 5.8) and 3-fold increased odds of ICU admission (95% CI 1.3 to 6.6). CONCLUSION: Our results show hyperglycemia portends worse outcomes in patients with COVID-19 with and without diabetes. While our study was limited by its retrospective design, our findings suggest that patients presenting with hyperglycemia require closer observation and more aggressive therapies.

Characterization of Colorado residents and radon reduction behaviors through latent class analysis and path models.

Radon is a naturally occurring radioactive gas that enters homes through cracks in the foundation where accumulated levels can cause lung cancer. Within the United States (U.S.), state level radon reduction strategies rely on education and outreach to motivate people to test and mitigate their home. Only about 5% of the housing units in Colorado, U.S. have been tested for radon. This study looks at the 2012 Behavioral Risk Factors Surveillance System (BRFSS) in Colorado to identify distinct groups of people using Latent Class Analysis, and compares radon awareness, testing, and mitigation to understand underlying differences of radon reduction behaviors using path models. Five classes were identified: 1) Wealthy Young Families, 2) Older Singles, 3) Empty Nesters, 4) Smokers, and 5) Struggling Young Families. Significant differences in responses to radon survey questions existed across groups in which Struggling Young Families were the least likely to be aware of radon, have tested their home for radon, and have their home mitigated. Average radon awareness, testing, and mitigation appeared to be influenced by financial stress. Results from this study can be used to tailor future radon interventions and policy initiatives to enhance equity of radon reduction behaviors including legal framework to ensure radon mitigation takes place in rental properties.

Body Mass Index and Leptin Are Related to Cognitive Performance Over 10 Years in Women With and Without HIV Infection.

CONTEXT: It is not yet understood whether people living with HIV infection have an increased risk of Alzheimers Disease and Related Dementias due to enhanced survivorship with highly effective antiretroviral therapies and/or increasing adiposity with aging. OBJECTIVE: This work aimed to determine whether body mass index (BMI) and leptin were longitudinally associated over 10 years with neuropsychological performance (NP) among middle-aged women with HIV (WWH) vs without HIV. METHODS: Women's Interagency HIV Study (WIHS) participants (301 WWH, 113 women without HIV from Brooklyn, New York City, and Chicago had baseline and 10-year BMI and fasting plasma leptin levels using commercial enzyme-linked immunosorbent assay (ng/mL); and demographically adjusted NP T scores (attention/working memory, executive function [EF], processing speed, memory, learning, verbal fluency, motor function, global) at 10-year follow-up. Multivariable linear regression analyses, stratified by HIV serostatus, examined associations between BMI, leptin, and NP. RESULTS: Over 10 years, women (baseline age 39.8 ±â€…9.2 years, 73% Black, 73% WWH) transitioned from average overweight (29.1 ±â€…7.9) to obese (30.5 ±â€…7.9) BMI. Leptin increased 11.4 ±â€…26.4 ng/mL (P < .001). Higher baseline BMI and leptin predicted poorer 10-year EF among all women (BMI ß = -6.97, 95% CI (-11.5 to -2.45) P = .003; leptin ß = -1.90, 95% CI (-3.03 to -0.76), P = .001); higher baseline BMI predicted better memory performance (ß = 6.35, 95% CI (1.96-10.7), P = .005). Greater 10-year leptin increase predicted poorer EF (P = .004), speed (P = .03), and verbal (P = .02) and global (P = 0.005) performance among all women, and WWH. Greater 10-year BMI increase predicted slower processing speed (P = .043) among all women; and among WWH, poorer EF (P = .01) and global (P = .04) performance. CONCLUSION: In middle-aged WIHS participants, 10-year increases in BMI and leptin were associated with poorer performance across multiple NP domains among all women and WWH. Trajectories of adiposity measures over time may provide insight into the role of adipose tissue in brain health with aging.

The impact of family physicians in rural maternity care.

BACKGROUND: Reduced access to maternity care in rural areas of the United States presents a significant burden to pregnant persons and infants. The objective of this study was to estimate the impact of family physicians (FPs) on access to maternity care in rural United States hospitals, especially where other providers may not be available. METHODS: We administered a survey to 216 rural hospitals in 10 US states inquiring about the number of babies delivered from 2013 to 2017, the types of delivering physicians, and the maternity services offered. We calculated the percentage of rural hospitals in our sample where FPs performed vaginal deliveries, cesareans, and vaginal births after cesarean (VBACs), and the percentage of all babies delivered by FPs. We estimated the distance patients would have to travel for care if FPs were not providing care locally. RESULTS: The final study population consisted of 185 rural hospitals. FPs delivered babies in 67% of these hospitals and were the only physicians who delivered babies in 27% of these hospitals. FPs provided VBAC at 18% and cesarean birth services at 46% of the rural hospitals, but with wide geographic differences. Many patients would have to drive an average of 86 miles round-trip to access care if those FPs were to stop delivering. CONCLUSIONS: Family physicians are essential providers of maternity care in the rural United States. Family Medicine residency programs should ensure that trainees who intend to practice in rural locations have adequate maternity care training to maintain and expand access to maternity care for rural patients and their families.

Epistasis, aneuploidy, and functional mutations underlie evolution of resistance to induced microtubule depolymerization.

Cells with blocked microtubule polymerization are delayed in mitosis, but eventually manage to proliferate despite substantial chromosome missegregation. While several studies have analyzed the first cell division after microtubule depolymerization, we have asked how cells cope long-term with microtubule impairment. We allowed 24 clonal populations of yeast cells with beta-tubulin mutations preventing proper microtubule polymerization, to evolve for ˜150 generations. At the end of the laboratory evolution experiment, cells had regained the ability to form microtubules and were less sensitive to microtubule-depolymerizing drugs. Whole-genome sequencing identified recurrently mutated genes, in particular for tubulins and kinesins, as well as pervasive duplication of chromosome VIII. Recreating these mutations and chromosome VIII disomy prior to evolution confirmed that they allow cells to compensate for the original mutation in beta-tubulin. Most of the identified mutations did not abolish function, but rather restored microtubule functionality. Analysis of the temporal order of resistance development in independent populations repeatedly revealed the same series of events: disomy of chromosome VIII followed by a single additional adaptive mutation in either tubulins or kinesins. Since tubulins are highly conserved among eukaryotes, our results have implications for understanding resistance to microtubule-targeting drugs widely used in cancer therapy.

The psychosocial work environment, musculoskeletal disorders and their functional consequences among pediatric healthcare providers.

OBJECTIVE: The goal of this study was to examine the association between aspects of the psychosocial work environment and prevalence of musculoskeletal disorders (MSDs) and associated functional consequences among pediatric healthcare providers. BACKGROUND: The psychosocial work demands make pediatric care providers susceptible to MSDs and subsequent functional consequences, but research on this at-risk group is lacking. METHODS: Randomly selected pediatric registered nurses, behavioral health specialists, and patient care assistants (N = 569) completed a survey assessing psychosocial factors, MSDs, and functional consequences (e.g., missing work). Logistic regression was used to assess associations between psychosocial factors and outcomes. RESULTS: The analysis yielded moderate-to-strong, significant associations between psychosocial environment factors and MSDs and their functional consequences. The odds of MSDs increased nearly three-fold in the highest quartile of the psychosocial summary score vs. the lowest (OR: 2.7, 95% CI: 1.6-4.5). The highest quartiles of the psychosocial environment measures were significantly associated with functional consequences of MSDs. CONCLUSION: Results confirm knowledge about the association between the psychosocial environment and MSDs and demonstrates the association also exists among pediatric providers. Our study highlights the importance of studying the functional consequences of MSDs, which characterize the impact of MSD burden at work and elsewhere.

Urine tungsten and chronic kidney disease in rural Colorado.

BACKGROUND: Chronic kidney disease (CKD) is a cause of global morbidity and mortality in agricultural communities. The San Luis Valley (SLV) is a rural agricultural community in southern Colorado with geographic and sociodemographic risk factors for CKD, including a water supply contaminated by heavy metals. METHODS: We obtained pre-existing sociodemographic, clinical, and urine trace metal data for 1659 subjects from the San Luis Valley Diabetes Study, a prospective cohort study. We assessed prospective associations between urine tungsten (W) and time-to-CKD using accelerated failure time models (n = 1659). Additionally, logistic models were used to assess relationships between urine W and renal injury markers (NGAL, KIM1) using Tobit regression (n = 816), as well as epidemiologically-defined CKD of unknown origin (CKDu) using multiple logistic regression (n = 620). RESULTS: Elevated urine W was strongly associated with decreased time-to-CKD, even after controlling for hypertension and diabetes. Depending on how CKD was defined, a doubling of urine W was associated with a 27% (95% CI 11%, 46%) to 31% (14%, 51%) higher odds of developing CKD within 5 years. The relationship between urine W and select renal injury markers was not significant, although urine NGAL was modified by diabetes status. Elevated (>95%ile) urinary W was significantly associated with CKDu (OR 5.93, 1.83, 19.21) while adjusting for known CKD risk factors. CONCLUSIONS: Our data suggest that increased exposure to W is associated with decreased time-to-CKD and may be associated with CKDu. Given persistence of associations after controlling for diabetes and hypertension, W may exert a primary effect on the kidney, although this needs to be evaluated further in future studies.

Contributions of US Medical Schools to Primary Care (2003-2014): Determining and Predicting Who Really Goes Into Primary Care.

BACKGROUND AND OBJECTIVES: Schools of medicine in the United States may overstate the placement of their graduates in primary care. The purpose of this project was to determine the magnitude by which primary care output is overestimated by commonly used metrics and identify a more accurate method for predicting actual primary care output. METHODS: We used a retrospective cohort study with a convenience sample of graduates from US medical schools granting the MD degree. We determined the actual practicing specialty of those graduates considered primary care based on the Residency Match Method by using a variety of online sources. Analyses compared the percentage of graduates actually practicing primary care between the Residency Match Method and the Intent to Practice Primary Care Method. RESULTS: The final study population included 17,509 graduates from 20 campuses across 14 university systems widely distributed across the United States and widely varying in published ranking for producing primary care graduates. The commonly used Residency Match Method predicted a 41.2% primary care output rate. The actual primary care output rate was 22.3%. The proposed new method, the Intent to Practice Primary Care Method, predicted a 17.1% primary care output rate, which was closer to the actual primary care rate. CONCLUSIONS: A valid, reliable method of predicting primary care output is essential for workforce training and planning. Medical schools, administrators, policy makers, and popular press should adopt this new, more reliable primary care reporting method.

Salmonella-based platform for efficient delivery of functional binding proteins to the cytosol.

Protein-based affinity reagents (like antibodies or alternative binding scaffolds) offer wide-ranging applications for basic research and therapeutic approaches. However, whereas small chemical molecules efficiently reach intracellular targets, the delivery of macromolecules into the cytosol of cells remains a major challenge; thus cytosolic applications of protein-based reagents are rather limited. Some pathogenic bacteria have evolved a conserved type III secretion system (T3SS) which allows the delivery of effector proteins into eukaryotic cells. Here, we enhance the T3SS of an avirulent strain of Salmonella typhimurium to reproducibly deliver multiple classes of recombinant proteins into eukaryotic cells. The efficacy of the system is probed with both DARPins and monobodies to functionally inhibit the paradigmatic and largely undruggable RAS signaling pathway. Thus, we develop a bacterial secretion system for potent cytosolic delivery of therapeutic macromolecules.

Convenience and corner store fruit and vegetable access: attitudes and intentions among Colorado adults, 2014.

Aim: The term food desert generally refers to areas where healthy food options, such as fresh fruits and vegetables, are unavailable within a certain number of miles. However, other factors besides distance may affect the ability to purchase healthier foods. The goal of this study was to understand Colorado adults' perceptions of their access to healthy food options and to assess how other structural and socio-demographic factors may affect that access. Subject and methods: Colorado adults were asked questions about self-reported access to healthy food, likelihood of buying fresh fruits and vegetables from convenience/corner stores if available, perceived characteristics of fruits and vegetables available for purchase near respondents' residence, and demographics. Results: A majority of Colorado adults in 2013-14 reported wanting fresh fruits and vegetables to be more available, more varied, higher quality, and/or less expensive. Socioeconomic status, race/ethnicity, and regular shopping habits were significantly associated with reported likelihood of purchasing fruits and vegetables from a convenience/corner store if available. Conclusion: Factors other than proximity to a grocery store affect Colorado adults' perceived access to healthy food options and should be considered in the development and implementation of public health programs and policies geared toward improving healthy food access.

The Nutrition Benefits Participation Gap: Barriers to Uptake of SNAP and WIC Among Latinx American Immigrant Families.

To examine nutrition benefit under-enrollment in Latinx American immigrant families, we administered a survey to 100 adults attending a NY Latinx American community serving organization. We used a logistic regression approach to analyze misinformation impact on enrollment, and examined non-enrollment explanations, among participants in whose families a child or pregnant or breastfeeding woman appeared SNAP- or WIC-eligible. Among households (N = 51) with ≥ 1 SNAP-eligible child, 49% had no child enrolled. Reasons included repercussion fears (e.g. payback obligation, military conscription, college aid ineligibility, child removal, non-citizen family member penalties), and logistical barriers. In multivariable regression models, having heard the rumor that SNAP/WIC participation makes unauthorized status family members vulnerable to being reported to the government was associated with an 85% lower enrollment rate (OR 0.15, CI 0.03, 0.94). Misinformation impedes nutrition benefit participation. A multi-level intervention is necessary to inform potential applicants and providers regarding eligibility criteria and erroneous rumors, along with an informed discussion of the risks versus benefits of using resources, especially as public charge criteria change.

Citron kinase-dependent F-actin maintenance at midbody secondary ingression sites mediates abscission.

Abscission is the final step of cytokinesis whereby the intercellular bridge (ICB) linking the two daughter cells is cut. The ICB contains a structure called the midbody, required for the recruitment and organization of the abscission machinery. Final midbody severing is mediated by formation of secondary midbody ingression sites, where the ESCRT III component CHMP4B is recruited to mediate membrane fusion. It is presently unknown how cytoskeletal elements cooperate with CHMP4B to mediate abscission. Here, we show that F-actin is associated with midbody secondary sites and is necessary for abscission. F-actin localization at secondary sites depends on the activity of RhoA and on the abscission regulator citron kinase (CITK). CITK depletion accelerates loss of F-actin proteins at the midbody and subsequent cytokinesis defects are reversed by restoring actin polymerization. Conversely, midbody hyperstabilization produced by overexpression of CITK and ANLN is reversed by actin depolymerization. CITK is required for localization of F-actin and ANLN at the abscission sites, as well as for CHMP4B recruitment. These results indicate that control of actin dynamics downstream of CITK prepares the abscission site for the final cut.