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"Drozd, Christopher"
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Fitness, straight-up : how to be a better athlete, or at least look like one
\"Whether you aim to be a better athlete, just look like one, or desire some fitness results altogether different, this book gives you real-world conditioning strategies you can use, now and always. As you read through this text, you'll discover: Thirty-four key exercises to increase your athletic strength & flexibility; exactly the right exercise zones to get you burning the most bodyfat; a seasonal planning framework that lets you turn ordinary workouts into consistent, progressive training successes; simple eating & sleeping patterns that ensure you recover faster from exercise, feel more rested, and remain lean, focused, and confident; potent self-hypnosis guidelines that allow you to harness and direct your vast, underlying reserves of mental power; and much more!\"--p. [4] of cover.
Book
An autism-causing calcium channel variant functions with selective autophagy to alter axon targeting and behavior
Common and rare variants of the CACNA1C voltage-gated calcium channel gene have been associated with autism and other neurodevelopmental disorders including schizophrenia, bipolar disorder and ADHD. However, little is known about how CACNA1C variants affect cellular processes to alter neurodevelopment. The Timothy syndrome mutation is a rare de novo gain-of-function variant in CACNA1C that causes autism with high penetrance, providing a powerful avenue into investigating the role of CACNA1C variants in neurodevelopmental disorders. Here, we use egl-19, the C. elegans homolog of CACNA1C, to investigate the role of voltage-gated calcium channels in autism. We show that an egl-19(gof) mutation that is equivalent to the Timothy syndrome mutation can alter axon targeting and affect behavior in C. elegans. We find that wildtype egl-19 negatively regulates axon termination. The egl-19(gof) mutation represses axon termination to cause axon targeting defects that lead to the misplacement of electrical synapses and alterations in habituation to light touch. Moreover, genetic interactions indicate that the egl-19(gof) mutation functions with genes that promote selective autophagy to cause defects in axon termination and behavior. These results reveal a novel genetic mechanism whereby a de novo mutation in CACNA1C can drive alterations in circuit formation and behavior.
Journal Article
Prevalence and Factors Associated with Hazardous Alcohol Use Among Persons Living with HIV Across the US in the Current Era of Antiretroviral Treatment
Hazardous alcohol use is associated with detrimental health outcomes among persons living with HIV (PLWH). We examined the prevalence and factors associated with hazardous alcohol use in the current era using several hazardous drinking definitions and binge drinking defined as ≥5 drinks for men versus ≥4 for women. We included 8567 PLWH from 7 U.S. sites from 2013 to 2015. Current hazardous alcohol use was reported by 27% and 34% reported binge drinking. In adjusted analyses, current and past cocaine/crack (odd ratio [OR] 4.1:3.3–5.1, p < 0.001 and OR 1.3:1.1–1.5, p < 0.001 respectively), marijuana (OR 2.5:2.2–2.9, p < 0.001 and OR 1.4:1.2–1.6, p < 0.001), and cigarette use (OR 1.4:1.2–1.6, p < 0.001 and OR 1.3:1.2–1.5, p < 0.001) were associated with increased hazardous alcohol use. The prevalence of hazardous alcohol use remains high in the current era, particularly among younger men. Routine screening and targeted interventions for hazardous alcohol use, potentially bundled with interventions for other drugs, remain a key aspect of HIV care.
Journal Article
Frailty and the risk of all‐cause mortality and hospitalization in chronic heart failure: a meta‐analysis
To estimate the risk of all‐cause mortality and hospitalization in frail patients with chronic heart failure (HF), a systematic search and meta‐analysis was carried out to identify all prospective cohort studies conducted among adults with HF where frailty was quantified and related to the primary endpoints of all‐cause mortality and/or hospitalization. Twenty‐nine studies reporting the link between frailty and all‐cause mortality in 18 757 patients were available for the meta‐analysis, along with 11 studies, with 13 525 patients, reporting the association between frailty and hospitalization. Frailty was a predictor of all‐cause mortality and hospitalization with summary hazard ratios (HRs) of 1.48 [95% confidence interval (CI): 1.31–1.65, P < 0.001] and 1.40 (95% CI: 1.27–1.54, P < 0.001), respectively. Summary HRs for all‐cause mortality among frail inpatients undergoing ventricular assist device implantation, inpatients hospitalized for HF, and outpatients were 1.46 (95% CI: 1.18–1.73, P < 0.001), 1.58 (95% CI: 0.94–2.22, P = not significant), and 1.53 (95% CI: 1.28–1.78, P < 0.001), respectively. Summary HRs for all‐cause mortality and frailty based on Fried's phenotype were 1.48 (95% CI: 1.03–1.93, P < 0.001) and 1.42 (95% CI: 1.05–1.79, P < 0.001) for inpatients and outpatients, respectively, and based on other frailty measures were 1.42 (95% CI: 1.12–1.72, P < 0.001) and 1.60 (95% CI: 1.43–1.77, P < 0.001) for inpatients and outpatients, respectively. Across clinical contexts, frailty in chronic HF is associated with an average of 48% and 40% increase in the hazard of all‐cause mortality and hospitalization, respectively. The relationship between frailty and all‐cause mortality is similar across clinical settings and comparing measurement using Fried's phenotype or other measures.
Journal Article
Ten-year Survival by Race/Ethnicity and Sex Among Treated, HIV-infected Adults in the United States
Background. Ensuring equal access to antiretroviral therapy (henceforth therapy) should alleviate disparities in health outcomes among persons infected with human immunodeficiency virus (HIV). However, evidence supporting the persistence of disparities in survival following therapy initiation is mixed. Methods. Patients initiating therapy in eight academic medical centers in the Centers for AIDS Research Network of Integrated Clinical Systems between 1 January 1998 and 30 December 2011. Patients (n = 10 017) were followed from therapy initiation until death from any cause, administrative censoring at 10 years after therapy initiation or the end of follow-up on 31 December 2011. The 10-year risk of all-cause mortality was calculated from standardized Kaplan–Meier survival curves. Results. Patients were followed for a median of 4.7 years (interquartile range: 2.2, 8.2). During 51 121 personyears of follow-up, 1224 of the 10 017 patients died. The overall 10-year mortality risk was 20.2% (95% confidence interval [CI], 19.2%, 21.3%). Black men and women experienced standardized 10-year all-cause mortality risks that were 7.2% (95% CI, 4.3%, 10.1%) and 7.9% (95% CI, 3.9%, 12.0%) larger (absolute difference) than white men. White women, Hispanic men, and Hispanic women all had lower 10-year mortality than white men. Conclusions. These data serve as a call to action to identify modifiable mechanisms leading to these observed mortality disparities among HIV-infected black patients. Effective interventions are needed to ensure that the goal of the National HIV/AIDS Strategy to overcome health disparities becomes a reality.
Journal Article
COVID-19 and the Vulnerabilities of Community-Dwelling Older Adults: Findings From a Statewide Survey of Home-Delivered Meals Recipients
COVID-19’s impact on community-dwelling older adults, especially those in rural and underserved areas, as well as those who are homebound, is of interest to policy makers and clinicians, now and in the future. This study aims to examine the consequences of the COVID-19 pandemic on community-dwelling older adults with the greatest social and economic needs residing in a mostly rural state. Using a self-administered survey, we collected data from 1852 home-delivered meal recipients, age 60 years and older, served by Nebraska’s eight Area Agencies on Aging. Results highlight three areas of importance: social connections, healthcare access and utilization, and technology. We found that while most older adults maintained social interaction, despite the restrictions imposed by the pandemic, feelings of loneliness persisted or even increased, with 35% of respondents feeling lonelier because of the pandemic. Our findings further reveal that 42% of older adults skipped or postponed healthcare visits during the pandemic, although the majority expressed interest in using telehealth. Finally, the rural‐urban divide was evident in our data, with less than one-half of respondents (45%) having access to reliable internet. Suggestions on how to prepare the most vulnerable people for similar crises are included.
Journal Article
UNC-16 interacts with LRK-1 and WDFY-3 to regulate the termination of axon growth
MAPK8IP3 (unc-16/JIP3) is a neurodevelopmental-disorder associated gene that can regulate the termination of axon growth. However, its role in this process is not well understood. Here, we report that UNC-16 promotes axon termination through a process that includes the LRK-1(LRRK-1/LRRK-2) kinase and the WDFY-3 (WDFY3/Alfy) selective autophagy protein. Genetic analysis suggests that UNC-16 promotes axon termination through an interaction between its RH1 domain and the dynein complex. Loss of unc-16 function causes accumulation of late endosomes specifically in the distal axon. Moreover, we observe synergistic interactions between loss of unc-16 function and disruptors of endolysosomal function, indicating that the endolysosomal system promotes axon termination. We also find that the axon termination defects caused by loss of UNC-16 function require the function of a genetic pathway that includes lrk-1 and wdfy-3, two genes that have been implicated in autophagy. These observations suggest a model where UNC-16 promotes axon termination by interacting with the endolysosomal system to regulate a pathway that includes LRK-1 and WDFY-3.Competing Interest StatementThe authors have declared no competing interest.
Paper
Perspectives on Negation and Polarity Items
This study hypothesises that neg-raising is a cognitive phenomenon which arises while the human mind is processing the content of the sentence under the normal assumption of closed world. A 'neg-raised sentence' conveys an epistemic attitude towards the proposition expressed by the subordinate clause. The hedge consists in making it clear that a certain conclusion is compatible with the current information state, but cannot be proven.
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