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The numerous health benefits of physical activity include reduced risk for chronic disease and improved mental health and quality of life (1). Physical activity can improve physical function and reduce pain and fall risk among adults with arthritis, a group of approximately 100 conditions affecting joints and surrounding tissues (most commonly osteoarthritis, fibromyalgia, gout, rheumatoid arthritis, and lupus) (1). Despite these benefits, the 54.6 million U.S. adults currently living with arthritis are generally less active than adults without arthritis, and only 36.2% of adults with arthritis are aerobically active (i.e., meet aerobic physical activity guidelines*) (2). Little is known about which physical activities adults with arthritis engage in. CDC analyzed 2019 Behavioral Risk Factor Surveillance System (BRFSS) data to examine the most common nonwork-related physical activities among adults with arthritis who reported any physical activity during the past month, nationally and by state. In 2019, 67.2% of adults with arthritis reported engaging in physical activity in the past month; among these persons, the most commonly reported activities were walking (70.8%), gardening (13.3%), and weightlifting (7.3%). In 45 U.S. states, at least two thirds of adults with arthritis who engaged in physical activity reported walking. Health care providers can help inactive adults with arthritis become active and, by encouraging physical activity and referring these persons to evidence-based physical activity programs, improve their health and quality of life.

J.R. and G.A.B. thank GlaxoSmithKline (GSK) and the Engineering and Physical Sciences Research Council (EPSRC) for an industrial CASE studentship. MMA is supported by a studentship from the government of Libya, and MAU by a studentship from the Petroleum Technology Development Fund (PTDF), Abuja, Nigeria. A selective mono-N-arylation strategy of amidines under Chan-Lam conditions is described. During the reaction optimization phase, the isolation of a mononuclear Cu(II) complex provided unique mechanistic insight into the operation of Chan-Lam mono-N-arylation. The scope of the process is demonstrated, and then applied to access the first mono-N-arylated analogues of pentamidine. Sub-micromolar activity against kinetoplastid parasites was observed for several analogues with no cross-resistance in pentamidine and diminazene-resistant trypanosome strains and against Leishmania mexicana. A fluorescent mono-N-arylated pentamidine analogue revealed rapid cellular uptake, accumulating in parasite nuclei and the kinetoplasts. The DNA binding capability of the mono-N-arylated pentamidine series was confirmed by UV-melt measurements using AT-rich DNA. This work highlights the potential to use Chan-Lam mono-N-arylation to develop therapeutic leads against diamidine-resistant trypanosomiasis and leishmaniasis. Publisher PDF

Background: Surveillance is a core function of public health, and approaches to national surveillance of physical activity and sedentary behavior have evolved over the past 2 decades. The purpose of this paper is to provide an overview of surveillance of physical activity and sedentary behavior in the United States over the past 2 decades, along with related challenges and emerging opportunities. Methods: The authors reviewed key national surveillance systems for the assessment of physical activity and sedentary behavior among youth and adults in the United States between 2000 and 2019. Results: Over the past 20 years, 8 surveillance systems have assessed physical activity, and 5 of those have assessed sedentary behavior. Three of the 8 originated in nonpublic health agencies. Most systems have assessed physical activity and sedentary behavior via surveys. However, survey questions varied over time within and also across systems, resulting in a wide array of available data. Conclusion: The evolving nature of physical activity surveillance in the United States has resulted in both broad challenges (eg, balancing content with survey space; providing data at the national, state, and local level; adapting traditional physical activity measures and survey designs; and addressing variation across surveillance systems) and related opportunities.

Background: Healthy People 2030 includes objectives to increase meeting the aerobic physical activity guideline for ages 6–13 years (of ages 6–17 y, monitored by National Survey of Children’s Health [NSCH]) and grades 9 to 12 (mostly aged 14–18+ y, monitored by Youth Risk Behavior Survey [YRBS]). This study compares methodologies, prevalence, and patterns of meeting the guideline, particularly for overlapping ages 14–17 years. Methods: Nationally representative surveys, 2016–2017 NSCH (adult proxy report, 6–17 y) and 2015 and 2017 YRBS (self-report, grades 9–12), assess meeting the guideline of ≥60 minutes of daily moderate to vigorous physical activity. Prevalence and odds ratios were estimated by age group and demographics. Results: For youth aged 14–17 years, 17.4% (95% confidence interval [CI], 16.1–18.7; NSCH) and 27.0% (95% CI, 25.6–28.5; YRBS) met the guideline. 25.9% (95% CI, 24.8–27.2) aged 6–13 years (NSCH) and 26.6% (95% CI, 25.3–28.0) in grades 9 to 12 (YRBS) met the guideline. Across surveys, fewer females (P P Conclusions: Neither methodology nor estimates for meeting the aerobic guideline are similar across surveys, so age continuity between juxtaposed estimates should not be assumed by magnitude nor age for separate Healthy People 2030 youth physical activity objectives.

Background: Although disparities in leisure-time physical activity (LTPA) participation by race/ethnicity and income are known, the combined association of these characteristics with LTPA participation is less understood. This study aims to describe trends and determine whether racial/ethnic differences in adult physical activity by income level have changed over the past 2 decades. Methods: The authors estimated LTPA participation (outcomes: any aerobic activity, meeting the aerobic activity guideline, meeting the muscle-strengthening guideline, and meeting the combined aerobic and muscle-strengthening guidelines) among adults ≥18 years by race/ethnicity across income levels using 1998–2018 National Health Interview Survey data in 3-year aggregates. They also tested for trends, prevalence differences, and difference in differences using logistic regression. Results: LTPA participation increased from 1998–2000 to 2016–2018 for all outcomes for non-Hispanic white, non-Hispanic black, and Hispanic adults at all income levels. Disparities narrowed for some groups but persisted between white and racial/ethnic minority groups across income levels for engaging in any aerobic activity and meeting the aerobic guideline (0.2–8.8 percentage point difference in differences). Disparities in meeting the muscle-strengthening and combined guidelines were less common. Conclusions: Opportunities exist to ensure that adults, particularly members of lower income racial/ethnic minority groups, have support to help them participate in LTPA.

Background Physical activity (PA) provides numerous health benefits relevant to the COVID-19 pandemic. However, concerns exist that PA levels may have decreased during the pandemic thus exacerbating health disparities. This study aims to determine changes in and locations for PA and reasons for decreased PA during the pandemic. Methods Reported percentage of changes in and locations for PA and reasons for decreased PA were examined in 3829 US adults who completed the 2020 SummerStyles survey. Results Overall, 30% reported less PA, and 50% reported no change or no activity during the pandemic; percentages varied across subgroups. Adults who were non-Hispanic Black (Black) or Hispanic (vs. non-Hispanic White, (White)) reported less PA. Fewer Black adults (vs. White) reported doing most PA in their neighborhood. Concern about exposure to the virus (39%) was the most common reason adults were less active. Conclusions In June 2020, nearly one-third of US adults reported decreased PA; 20% reported increased PA. Decreased activity was higher among Black and Hispanic compared to White adults; these two groups have experienced disproportionate COVID-19 impacts. Continued efforts are needed to ensure everyone has access to supports that allow them to participate in PA while still following guidance to prevent COVID-19 transmission.

Hyperthermia, or extreme elevations in body temperature, can be life-threatening and may be caused by prescription drugs or illegal substances acting at a number of different levels of the neuraxis. Several psychotropic drug classes and combinations have been associated with a classic clinical syndrome of hyperthermia, skeletal muscle hyper-metabolism, rigidity or rhabdomyolysis, autonomic dysfunction and altered mental status ranging from catatonic stupor to coma. It is critical for clinicians to have a high index of suspicion for these relatively uncommon drug-induced adverse effects and to become familiar with their management to prevent serious morbidity and mortality. Although these syndromes look alike, they are triggered by quite different mechanisms, and apart from the need to withdraw or restore potential triggering drugs and provide intensive medical care, specific treatments may vary. Clinical similarities have led to theoretical speculations about common mechanisms and shared genetic predispositions underlying these syndromes, suggesting that there may be a common "thermic stress syndrome" triggered in humans and animal models by a variety of pharmacological or environmental challenges.

Reducing the required frequence of drug dosing can improve the adherence of patients to chronic treatments. Hence, drugs with longer in vivo half-lives are highly desirable. One of the most promising approaches to extend the in vivo half-life of drugs is conjugation to human serum albumin (HSA). In this work, we describe the use of AlbuBinder 1, a small-molecule noncovalent HSA binder, to extend the in vivo half-life and pharmacology of small-molecule BMP1/TLL inhibitors in humanized mice (HSA KI/KI). A series of conjugates of AlbuBinder 1 with BMP1/TLL inhibitors were prepared. In particular, conjugate c showed good solubility and a half-life extension of >20-fold versus the parent molecule in the HSA KI/KI mice, reaching half-lives of >48 h with maintained maximal inhibition of plasma BMP1/TLL. The same conjugate showed a half-life of only 3 h in the wild-type mice, suggesting that the half-life extension was principally due to specific interactions with HSA. It is envisioned that conjugation to AlbuBinder 1 should be applicable to a wide range of small molecule or peptide drugs with short half-lives. In this context, AlbuBinders represent a viable alternative to existing half-life extension technologies.

We report the application of Bronsted acid–activated N-acyl imidazoliums as versatile intermediates in carbonyl transformations. The efficient and scalable procedure was validated on a diverse set ...

In Huntington's disease (HD), the output of striatal indirect pathway medium-sized spiny neurons (MSNs) is altered in its target region, the external globus pallidus (GPe). In a previous study we demonstrated that selective optogenetic stimulation of indirect pathway MSNs induced prolonged decay time of γ-aminobutyric acid (GABA) responses in GPe neurons. Here we identified the mechanism underlying this alteration. Electrophysiological recordings in slices from symptomatic R6/2 and wildtype (WT) mice were used to evaluate, primarily, the effects of GABA transporter (GAT) antagonists on responses evoked by optogenetic activation of indirect pathway MSNs. In addition, immunohistochemistry (IHC) and Western blots (WBs) were used to examine GAT-3 expression in HD and WT mice. A GAT-3 blocker (SNAP5114) increased decay time of GABA responses in WT and HD GPe neurons, but the effect was significantly greater in WT neurons. In contrast, a GAT-1 antagonist (NO-711) or a GABAB receptor antagonist (CGP 54626) produced small increases in decay time but no differential effects between genotypes. IHC and WBs showed reduction of GAT-3 expression in the GPe of HD mice. Thus, reduced expression or dysfunction of GAT-3 could underlie alterations of GPe responses to GABA inputs from striatum and could be a target for therapeutic intervention.

Migraña; Fracaso del tratamiento; Productividad laboral Migraine; Treatment failure; Work productivity Migranya; Fracàs del tractament; Productivitat laboral Introduction Migraine is consistently ranked as one of the most disabling neurological conditions in the world, often causing a substantial impairment of daily activities and quality of life. It also carries a high economic burden of direct and indirect healthcare costs. Patients with difficult-to-treat migraine often cycle through different preventive therapies, but real-world prospective evidence describing the burden of migraine in patients with prior preventive treatment failure (PPTF) in Europe is limited. In BECOME, we aimed to characterize and assess the prevalence and burden of migraine in patients with PPTF attending specialist headache centers in Europe and Israel. Furthermore, we assessed this burden in pre-specified subgroups based on the frequency of monthly migraine days (MMD) and number of PPTFs. Methods BECOME was a prospective, non-interventional study conducted in two concurrent parts across 17 countries in Europe and Israel. In part 1, patients visiting the centers over a 3-month period were screened for frequency of PPTF, MMD, and other characteristics. In part 2, patients from part 1 with ≥ 1 PPTF and ≥ 4 MMD were enrolled, and impact of migraine on patient-reported outcomes, and healthcare resource utilization (HRU) were examined. Results In part 1 (n = 20,837), 62.2% of patients reported ≥ 1 PPTF. In part 2 (n = 2419), 15.3% of patients reported ≥ 4 PPTF. In part 2, the migraine burden measured by the EuroQoL 5 dimensions 5 level (EQ-5D-5L) questionnaire indicated an impact of at least moderate severity in performing usual activities in 26.5% of patients, pain/discomfort in 51.2%, and 26.1% reported being at least moderately anxious/depressed. Most patients reported a severe impact on daily activities and disability due to migraine. Abnormal Hospital Anxiety and Depression subscale scores of ≥ 11 were observed in 29% (anxiety) and 19.8% (depression) of the population. In part 2, analysis of HRU showed 21.2% patients visited an emergency department and 8.4% were hospitalized for headache/migraine in the past year. Conclusions This study provides real-world evidence of the high personal, social, and HRU burden of migraine in Europe and Israel. This study was funded by Novartis Pharma AG, Basel, Switzerland. The study sponsor participated in the study design, data collection, data review, data analysis and writing of the report. The Rapid Service Fee was funded by Novartis Pharma AG, Basel, Switzerland.

PURPOSE The US youth physical activity guideline recommends participation in four types of physical activity: moderate-to-vigorous intensity aerobic (MVPA), vigorous-intensity aerobic (VPA), muscle-strengthening, and bone-strengthening physical activity. Current national prevalence estimates of meeting the youth physical activity guideline are typically based on measures of the MVPA and muscle-strengthening components. This study sought to examine differences in prevalence estimates using this current approach and then including measures of all four components. METHODS Data from US high school student respondents to the 2010 National Youth Physical Activity and Nutrition Survey were analyzed (n = 10,596). Prevalence of students meeting the youth physical activity guideline were assessed and compared using 1) measures of MVPA and muscle-strengthening components only and 2) also including measures of the VPA and bone-strengthening components. RESULTS Overall, 15.2% students met the MVPA, 50.7% met the muscle-strengthening, 70.6% met the VPA, and 80.7% met the bone-strengthening components. In total, 12.1% (95% confidence interval: 10.9, 13.3) of students met both the MVPA and muscle-strengthening components, and 11.2% (95% confidence interval: 10.0, 12.4) met all four components. CONCLUSIONS Incorporating additional measures of VPA and bone-strengthening activity into current surveillance systems may not meaningfully impact national estimates of meeting the youth physical activity guideline.

Background: During the past decade, guidelines for youth aerobic and muscle-strengthening physical activity remained unchanged. Active People, Healthy NationSM highlighted school and youth strategies (eg, sports and physical education [PE]) to increase physical activity. Sex, grade, and race/ethnicity disparities exist. This study examines sex-specific trends and differences by grade and race/ethnicity for the prevalence of 5 youth physical activity behaviors from 2009 to 2019. Methods: The national Youth Risk Behavior Survey assesses adolescents (grades 9–12) meeting the aerobic, muscle-strengthening, and both guidelines (2011–2019) and sports participation and daily PE (2009–2019). Sex-stratified logistic regression assessed trends and 2009 or 2011–2019 differences by grade and racial/ethnic subgroups. Results: Decreases in meeting the aerobic, muscle-strengthening, and both guidelines were observed for nearly all male subgroups by grade and race/ethnicity, whereas female subgroups exhibited declines or no change to low prevalence. Sports and PE participation remained mostly constant; select subgroups showed decreases (ie, Hispanic males [sports]; Black males and ninth-grade females [PE]). Conclusions: Past decade prevalence and patterns suggest that school-based and other strategies for all adolescents and tailored interventions for sex-specific subgroups may be needed to supplement sports and PE in promoting high school youth physical activity.

Primary care providers (PCPs) are uniquely positioned to promote physical activity for cardiovascular health. We sought to determine the types of physical activity that PCPs most often recommend to patients at risk for cardiovascular disease (CVD) and how these recommendations vary by PCPs' physical activity counseling practices. We examined the types of physical activity (walking, supervised exercise sessions, or other) PCPs most often suggested for CVD prevention among respondents to the 2018 DocStyles survey (N = 1,088). Most PCPs (80.0%) suggested walking to their patients at risk for CVD; however, PCPs who infrequently discussed physical activity with their patients at risk for CVD suggested walking less often than those who more frequently discussed physical activity. Walking is an easy and low-cost form of physical activity, and opportunities exist for certain PCPs to promote walking as part of their physical activity counseling practices for CVD prevention.

Several barriers separate the central nervous system (CNS) from the rest of the body. These barriers are essential for regulating the movement of fluid, ions, molecules, and immune cells into and out of the brain parenchyma. Each CNS barrier is unique and highly dynamic. Endothelial cells, epithelial cells, pericytes, astrocytes, and other cellular constituents each have intricate functions that are essential to sustain the brain’s health. Along with damaging neurons, a traumatic brain injury (TBI) also directly insults the CNS barrier-forming cells. Disruption to the barriers first occurs by physical damage to the cells, called the primary injury. Subsequently, during the secondary injury cascade, a further array of molecular and biochemical changes occurs at the barriers. These changes are focused on rebuilding and remodeling, as well as movement of immune cells and waste into and out of the brain. Secondary injury cascades further damage the CNS barriers. Inflammation is central to healthy remodeling of CNS barriers. However, inflammation, as a secondary pathology, also plays a role in the chronic disruption of the barriers’ functions after TBI. The goal of this paper is to review the different barriers of the brain, including (1) the blood-brain barrier, (2) the blood-cerebrospinal fluid barrier, (3) the meningeal barrier, (4) the blood-retina barrier, and (5) the brain-lesion border. We then detail the changes at these barriers due to both primary and secondary injury following TBI and indicate areas open for future research and discoveries. Finally, we describe the unique function of the pro-inflammatory cytokine interleukin-1 as a central actor in the inflammatory regulation of CNS barrier function and dysfunction after a TBI.

Background: To estimate the proportion of adults’ and parents’ knowledge of the adult aerobic and youth physical activity guidelines, respectively, in the United States. Methods: Data were analyzed from a national sample of adults in the 2017 ConsumerStyles survey. Prevalence of knowledge of the adult aerobic guideline (ie, 150 min/wk of moderate-intensity activity) was estimated among all respondents (n = 3910) and of the youth guideline (ie, 60 min/d of physical activity on 7 d/wk) among parents (n = 1288). Odds ratios were estimated using logistic regression models adjusting for demographic characteristics. Results: Overall, 2.5% (95% confidence interval, 2.0–3.1) of adults and 23.0% (95% confidence interval, 20.5–25.7) of parents were knowledgeable of the adult aerobic and youth guidelines, respectively. After adjustment, odds of knowledge of the adult guideline differed significantly by sex and physical activity level, whereas knowledge of the youth guideline differed by parental education level. Conclusions: Despite the release of the 2008 Physical Activity Guidelines for Americans nearly a decade ago, most US adults and parents lack knowledge of the adult aerobic and youth physical activity guidelines. Effective communication strategies may help raise awareness of current and future editions of national guidelines for physical activity.

The occurrence of drug hypersensitivity reactions (DHRs) following administration of low molecular weight (LMW) drugs is an important health concern. However, in vivo animal models which could be used as tools for the prediction of DHRs are lacking. As a result, research has focused on development of in vitro tools for predicting DHRs. In this study a novel human in vitro pre-clinical skin explant test was used to predict T cell-mediated hypersensitivity responses induced by LMW drugs. Responses in the skin explant test for 12 LMW drugs associated with T cell-mediated hypersensitivity in the clinic (abacavir, amoxicillin, carbamazepine, diclofenac, lamotrigine, lapatinib, lumiracoxib, nevirapine, ofloxacin, phenytoin, propranolol, sulfamethoxazole) were compared with responses for 5 drugs with few/no reports of T cell-mediated hypersensitivity reactions (acetaminophen, cimetidine, flecainide, metformin, verapamil). Changes in skin histology following in vitro exposure to the drugs as well as T cell proliferation and interferon gamma (IFNγ) production were studied. The results of the skin explant assays showed a good positive correlation (r = 0.77, p .001) between the test outcome (prediction of positive or negative) and the clinical classification of the tested drugs. The T cell proliferation assay showed a correlation of r = 0.60 (p .01) and the IFNγ assay r = 0.51 (p .04). The data suggest that the skin explant model could be a useful tool to predict the potential of LMW drugs to induce DHRs.

Promotion of walking is a promising strategy for increasing physical activity levels in the U.S. The proportion of adults who report walking for either transportation or leisure has increased in recent years, but evidence on trends in walking for specific purposes is limited.The 2005, 2010, and 2015 National Health Interview Survey assessed self-reported participation in and volume (minutes/week) of walking for transportation and leisure in the past week among adults aged ≥18 years. Linear and quadratic trends in the prevalence and mean volume of walking for each purpose were evaluated using logistic and linear regression. Analyses were performed in 2017.The prevalence of transportation walking increased from 28.4% (2005) to 31.7% (2015) (linear trend: p0.05). Leisure walking prevalence increased from 42.1% (2005) to 52.1% (2015), but the increased stalled from 2010 to 2015 with only a 2.3 percentage point increase (linear and quadratic trends: p0.05). Across purposes, the mean walking volume decreased from 2005 to 2015, with no significant changes between 2010 and 2015 (linear and quadratic trends: p0.05). The proportion of adults who walked for both transportation and leisure in the past week increased steadily (linear trend: p0.05), and this group reported the greatest total volume of walking.Although the prevalence of self-reported transportation and leisure walking increased during the last decade, the time spent walking decreased. Strategies that encourage walking for multiple purposes may present an opportunity for increasing both participation in walking and the amount of time spent walking.

Background: Physical activity is central to the management and control of many chronic health conditions. The authors examined trends during the past 2 decades in the prevalence of US adults with and without select chronic health conditions who met the minimal aerobic physical activity guideline. Methods: The 1998–2018 National Health Interview Survey data were analyzed. Prevalence of meeting the minimal aerobic physical activity guideline among adults with and without 6 chronic health conditions was estimated across 3-year intervals. Linear and higher-order trends were assessed overall and by age group. Results: During the past 2 decades, prevalence of meeting the aerobic guideline increased among adults with diabetes, hypertension, coronary heart disease, stroke, cancer, and arthritis. However, the absolute increase in prevalence was lower among adults with hypertension, coronary heart disease, and arthritis compared to counterparts without each condition, respectively. Prevalence was persistently lower among those with most chronic health conditions, except cancer, and among older adults compared to their counterparts. Conclusions: Although rising trends in physical activity levels among adults with chronic health conditions are encouraging for improving chronic disease management, current prevalence remains low, particularly among older adults. Increasing physical activity should remain a priority for chronic disease management and control.

Background: Surveillance of domain-specific physical activity in the United States is lacking. Thus, the authors describe domain-specific moderate to vigorous physical activity (MVPA) in a nationwide sample of US adults. Methods: Participants from the AmeriSpeak panel (n = 2649; 20–75 y; 50% female) completed the Activities Completed Over Time in 24-Hours previous-day recall. The authors estimated average MVPA duration (in hours per day) overall and in major life domains by sex, age, race/ethnicity, and education. They also described the most commonly reported MVPAs and timing of MVPA during the day. Results: Across all life domains, participants reported an average of 2.5 hours per day in MVPA. Most MVPA was accumulated during work (50% of total, 1.2 h/d) and household activities (28%, 0.7 h/d) with less MVPA reported in leisure time (15%, 0.4 h/d). Time reported in MVPA varied by sex, and race/ethnicity (P Conclusions: Work and household activities accounted for 78% of overall MVPA reported, while leisure-time MVPA accounted for only 15% of the total. Encouraging MVPA during leisure time and transportation remain important targets for promoting MVPA in US adults.

Our objective was to identify the percentage of marijuana-using caregivers who have been asked about their marijuana use by their child’s pediatrician. Data was collected from a cross-sectional, convenience sample survey study of 1500 caregivers presenting with their children to the Children’s Hospital Colorado Pediatric Emergency Department between December 2015 and July 2017. Of the 1500 caregivers surveyed, 167 (11%) reported using marijuana. When asked if their child’s pediatrician had ever inquired/counseled about caregiver marijuana use, 165 marijuana-using caregivers responded; 149 caregivers (90.3%) reported “no,” 9 caregivers (5.4%) reported “yes,” and 7 caregivers (4.2%) reported “unsure.” We concluded that of marijuana-using caregivers, only a small percentage indicated their child’s pediatrician had inquired about caregiver marijuana use. This suggests pediatricians are not engaging caregivers about marijuana use and the subsequent secondhand marijuana smoke exposure for children. The continued rise of marijuana use among parents makes this research of public health importance.

The noninvasive vascular laboratory plays a critical role in screening patients at risk for development of abdominal aortic aneurysm (AAA). One-time duplex ultrasound screening reduces aneurysm-related mortality due to rupture and is cost-effective. Population screening based on AAA risk factors is recommended, as it allows for proactive, elective repair of aneurysms at risk for rupture, and surveillance of smaller aneurysms for enlargement. Utilization of societal screening guidelines, such as those published by the Society for Vascular Surgery, can be employed by vascular laboratories to justify individual patient screening, aid primary care physicians to refer patients for testing, and encourage integrated medical health care systems to build prompts in patient electronic health records to ensure compliance with a AAA screening program. Risk factors for developing AAA, that is, age older than 65 years, male sex, family history, and a smoking history of >100 cigarettes, should be used to recommend patient screening, including for women and other elderly (older than 75 years) patients who fall outside of professional societal guidelines.

The importance of physical activity and community-level promotion strategies are well established, but little is known about adult perception of the importance of physical activity. In a nationwide sample of US adults, we examined self-reported importance of regular physical activity and the importance of living in walkable neighborhoods. About 55% of adults strongly agreed that regular physical activity is important, 40% strongly agreed that living in a walkable neighborhood is important, and 31% strongly agreed that both are important. Separately for each measure, estimates were lower among adults with lower education levels and who did not meet the aerobic physical activity guideline. Opportunities exist to improve the perception of the importance of physical activity and the importance of walkable neighborhoods.

Objective This study aims to determine the cost effectiveness of rapid frozen section (RFS) for indeterminate thyroid nodules. Materials and methods A retrospective chart review was conducted between January 2009 and June 2013 at a tertiary care institution. Main outcomes were number needed to treat, RFS efficacy, and cost-savings of avoiding second completion thyroidectomy. Cost-effectiveness was estimated using 2015 Medicare reimbursement rate. Results Out of 1,114 patients undergoing thyroid surgery, 314 had preoperative AUS/FLUS cytopathology and subsequent thyroid lobectomy with RFS. RFS identified 13 of the 32 patients with malignancy resulting in a total thyroidectomy. 19 of the 29 malignancies not detected by RFS were papillary microcarcinomas. Conclusions Completion thyroidectomy was avoided in 1 out of every 24 patients resulting in cost-savings of $ 80.04 per patient. In the era of outpatient thyroid surgery, intraoperative RFS for indeterminate thyroid nodules is cost-effective.

Background A mild traumatic brain injury (TBI) occurs to millions of people each year. Translational approaches to understanding the pathogenesis of neurological diseases and the testing of the effectiveness of interventions typically require cognitive function assays in rodents. New methods Our goal was to validate the active avoidance task using the GEMINI avoidance system in a mouse model of mild closed head injury (CHI). Results We found that shock intensity had only a marginal effect on the test. We found that sex was an important biological variable, as female mice learned the task better than male mice. We demonstrate that a single mild CHI in mice caused deficits in the task at four weeks post-injury. Comparison with existing methods Active avoidance is a classical conditioning test in which mice must pair the presence of a conditioned stimulus with moving between two chambers to avoid an electric shock. External conditions (i.e., apparatus), as well as inherent differences in the mice, which may not be directly linked to the model of the disease (i.e., sensory differences), can affect the reproducibility of a behavioral assay. Before our study, there was a lack of standard operating procedures and validated methods for the active avoidance behavior for phenotyping mouse models of injury and disease. Conclusion We offer a method for validating the active avoidance test, and a standard operating procedure, which will be useful in other models of neurological injury and disease.

The Environmental Protection Agency created the National Walkability Index (Index) to compare and analyze walkability among US communities. Index elements include design, distance to transit, and diversity of land uses. Associations between the Index and walking behavior have not been examined. This study describes associations between the Index and transportation and leisure walking among US adults. Past week self-reported participation in transportation and leisure walking among adults (n = 33,672) was obtained from the 2015 Cancer Control Supplement of the National Health Interview Survey (NHIS) and analysis completed in 2019. Index scores were linked to NHIS data based on the respondent's residence and classified into least, below average, above average, and most walkable communities. Associations between Index categories and walking were examined with regression models. Overall, the Index was associated with a higher likelihood of walking, especially for transportation. Transportation walking was more common in areas with higher walkability (21.6%–51.6%, least to most walkable). Leisure walking was also more common with greater walkability (48.4%–56.5%, least to most walkable). Transportation and leisure walking by Index categories in urban areas were similar to the overall population; however, it was not associated with walking in rural areas. US adults living in more walkable areas report more transportation and leisure walking, especially among urban areas. Consistent with elements in the Index, associations were stronger for transportation than leisure walking. Findings support the use of the Walkability Index by researchers, professionals, and other relevant stakeholders as a viable indicator of walkability.

Background: The US Preventive Services Task Force recommends adults with certain cardiovascular disease (CVD) risk factors be offered or referred to intensive behavioral counseling to promote a healthful diet and physical activity for CVD prevention. However, only 1 in 12 primary care providers (PCPs) currently follow this recommendation. This study assessed system and programmatic features PCPs reported would increase their likelihood of referring patients at risk for CVD to intensive behavioral counseling and whether this varied by the percentage of at-risk patients with whom they discuss physical activity. Methods: DocStyles 2018, a web-based panel survey of PCPs, assessed the percentage of at-risk patients with whom PCPs discuss physical activity and the degree to which select features would increase their likelihood of referring to intensive behavioral counseling. Results: Overall, 60.8% of PCPs discussed physical activity with most of their at-risk patients; 21.8% did so with many and 17.4% with few or some. The proportion of PCPs identifying features as increasing their likelihood of referring to intensive behavioral counseling by a great extent ranged from 24.1% for an automated referral in electronic health records, 35.3% for patient progress reports, 41.5% for the program being accredited or evidence-based, to 67.2% for the program having no cost to the patient (Table). These proportions increased for each feature as the percentage of at-risk patients with whom they discuss physical activity increased. Conclusion: PCPs identified programmatic features (i.e. being accredited and of no cost) as having the greatest influence on their likelihood of referring patients at risk for CVD to intensive behavioral counseling, although this varied by the percentage of at-risk patients with whom they discuss physical activity. Findings suggest that the effectiveness of strategies to improve behavioral counseling referrals by PCPs may depend on their current physical activity counseling practices.

The updated Physical Activity Guidelines for Americans (2nd edition) removes the requirement that physical activity should occur in bouts lasting 10 minutes or more to count toward the minimum aerobic guideline. Using self-reported data from the 2017 Behavioral Risk Factor Surveillance System (N = 386,960), we examined differences in national physical activity estimates with and without this requirement. Overall, 1.9% of adults reported activities in short bouts (

The rapid decrease in Arctic sea ice is motivating development and increasing oil and gas extraction activities. However, few observations of these local Arctic emissions exist, limiting the understanding of impacts on atmospheric composition and climate. To address this knowledge gap, the chemical composition of atmospheric aerosols was measured within the North Slope of Alaska oil fields during August and September 2016 using an aerosol time-of-flight mass spectrometer (ATOFMS) and a time-of-flight aerosol chemical speciation monitor (ToF-ACSM). Plumes from oil and gas extraction activities were characterized by soot internally mixed with sulfate (matching diesel soot) and organic carbon particles containing aminium sulfate salts. Sea spray aerosol at the coastal site was frequently internally mixed with sulfate and nitrate, from multiphase chemical processing from elevated NOx and SO2 within the oil field. Background (nonplume) air masses were characterized by aged combustion aerosol. No periods of "clean" (nonpolluted) Arctic air were observed. The composition of the nonrefractory aerosol measured with the ACSM was similar during plume and background periods and was consistent with the mass concentrations of nonrefractory particles measured by ATOFMS. Two ultrafine aerosol growth events were observed during oil field background periods and were correlated with fine mode amine-containing particles.

Purpose: The US Preventive Services Task Force recommends that adults at risk for cardiovascular disease (CVD) be offered or referred to intensive behavioral counseling interventions to promote a healthful diet and physical activity for CVD prevention. We assessed primary care providers’ (PCPs) awareness of local physical activity-related behavioral counseling services, whether this awareness was associated with referring eligible patients, and the types and locations of services to which they referred. Design: Cross-sectional survey. Setting: Primary care providers practicing in the United States. Subjects: 1256 respondents. Measures: DocStyles 2016 survey assessing PCPs’ awareness of and referral to physical activity-related behavioral counseling services. Analysis: Calculated prevalence and adjusted odds ratios (aORs). Results: Overall, 49.9% of PCPs were aware of local services. Only 12.6% referred many or most of their at-risk patients and referral was associated with awareness of local services (aOR = 2.81, [95% confidence interval: 1.85-4.25]). Among those referring patients, services ranged from a health-care worker within their practice or group (25.4%) to an organized program in a medical facility (41.2%). Primary care providers most often referred to services located outside their practice or group (58.1%). Conclusion: About half of PCPs were aware of local behavioral counseling services, and referral was associated with awareness. Establishing local resources and improving PCPs’ awareness of them, especially using community–clinical linkages, may help promote physical activity among adults at risk for CVD.

The understanding of deep chlorophyll layers (DCLs) in the Great Lakes—largely reported as a mix of picoplankton and mixotrophic nanoflagellates—is predominantly based on studies of deep (&gt, 30 m), offshore locations. Here, we document and characterize nearshore DCLs from two meso-oligotrophic embayments, Twelve Mile Bay (TMB) and South Bay (SB), along eastern Georgian Bay, Lake Huron (Ontario, Canada) in 2014, 2015, and 2018. Both embayments showed the annual formation of DCLs, present as dense, thin, metalimnetic plates dominated by the large, potentially toxic, and bloom-forming cyanobacteria Planktothrix cf. isothrix. The contribution of P. cf. isothrix to the deep-living total biomass (TB) increased as thermal stratification progressed over the ice-free season, reaching 40% in TMB (0.6 mg/L at 9.5 m) and 65% in South Bay (3.5 mg/L at 7.5 m) in 2015. The euphotic zone in each embayment extended down past the mixed layer, into the nutrient-enriched hypoxic hypolimnia, consistent with other studies of similar systems with DCLs. The co-occurrence of the metal-oxidizing bacteria Leptothrix spp. and bactivorous flagellates within the metalimnetic DCLs suggests that the microbial loop plays an important role in recycling nutrients within these layers, particularly phosphate (PO4) and iron (Fe). Samples taken through the water column in both embayments showed measurable concentrations of the cyanobacterial toxins microcystins (max. 0.4 µg/L) and the other bioactive metabolites anabaenopeptins (max. ~7 µg/L) and cyanopeptolins (max. 1 ng/L), along with the corresponding genes (max. in 2018). These oligopeptides are known to act as metabolic inhibitors (e.g., in chemical defence against grazers, parasites) and allow a competitive advantage. In TMB, the 2018 peaks in these oligopeptides and genes coincided with the P. cf. isothrix DCLs, suggesting this species as the main source. Our data indicate that intersecting physicochemical gradients of light and nutrient-enriched hypoxic hypolimnia are key factors in supporting DCLs in TMB and SB. Microbial activity and allelopathy may also influence DCL community structure and function, and require further investigation, particularly related to the dominance of potentially toxigenic species such as P. cf. isothrix.

The RGD integrins are recognized therapeutic targets for thrombosis, fibrosis, and cancer, among others. Current inhibitors are designed to mimic the tripeptide sequence (arginine–glycine–aspartic acid) of the natural ligands; however, the RGD-mimetic antagonists for αIIbβ3 have been shown to cause partial agonism, leading to the opposite pharmacological effect. The challenge of obtaining oral activity and synthetic tractability with RGD-mimetic molecules, along with the issues relating to pharmacology, has left integrin therapeutics in need of a new strategy. Recently, a new generation of inhibitor has emerged that lacks the RGD-mimetic. This review will discuss the discovery of these non-RGD-mimetic inhibitors and the progress that has been made in this promising new chemotype.

The α-synuclein protein exists in vivo in a variety of covalently modified and aggregated forms associated with Parkinson's disease (PD) pathology. However, the specific proteoform structures involved with neuropathological disease mechanisms are not clearly defined. Since α-synuclein plays a role in presynaptic neurotransmitter release, an in vitro enzyme-based assay was developed to measure glutamate release from mouse forebrain synaptoneurosomes (SNs) enriched in synaptic endings. Glutamate measurements utilizing SNs from various mouse genotypes (WT, over-expressers, knock-outs) suggested a concentration dependence of α-synuclein on calcium/depolarization-dependent presynaptic glutamate release from forebrain terminals. In vitro reconstitution experiments with recombinant human α-synuclein proteoforms including monomers and aggregated forms (fibrils, oligomers) produced further evidence of this functional impact. Notably, brief exogenous applications of fibrillated forms of α-synuclein enhanced SN glutamate release but monomeric forms did not, suggesting preferential membrane penetration and toxicity by the aggregated forms. However, when applied to brain tissue sections just prior to homogenization, both monomeric and fibrillated forms stimulated glutamate release. Immuno-gold and transmission electron microscopy (TEM) detected exogenous fibrillated α-synuclein associated with numerous SN membranous structures including synaptic terminals. Western blots and immuno-gold TEM were consistent with SN internalization of α-synuclein. Additional studies revealed no evidence of gross disruption of SN membrane integrity or glutamate transporter function by exogenous α-synuclein. Overall excitotoxicity, due to enhanced glutamate release in the face of either overexpressed monomeric α-synuclein or extrasynaptic exposure to fibrillated α-synuclein, should be considered as a potential neuropathological pathway during the progression of PD and other synucleinopathies. © 2017 Wiley Periodicals, Inc.

Assess the impact of ostomy formation on quality of life for U.S. Service Members.U.S. personnel sustaining colorectal trauma from 2003 to 2011 were identified using the Department of Defense Trauma Registry. A cross-sectional observational study was conducted utilizing prospective interviews with standard survey instruments. Primary outcome measures were the Stoma Quality of Life Scale and Veterans RAND 36 scores and subjective responses. Patients with colorectal trauma not requiring ostomy served as controls.Of 177 available patients, 90 (50.8%) male veterans consented to participate (55 ostomy, 35 control). No significant differences were observed between ostomy and control groups for Injury Severity Score (25.6 ± 9.9 vs. 22.9 ± 11.8, p = 0.26) or mechanism of injury (blast: 55 vs. 52%, p = 0.75); nonostomates had fewer anorectal injuries (3.2 vs. 47.9%, p0.01). Median follow-up was 6.7 years. Veterans RAND-36 Physical and Mental Component Scores were similar between groups. About 45.8% of ostomates were willing-to-trade a median of 10 years (interquartile range = 5-15) of their remaining life for gastrointestinal continuity. At last follow-up, 95.9% of respondents' combat-related ostomies were reversed with a median duration of 6 (range = 3-19) months diverted.Ostomy creation in a combat environment remains safe and does not have a quantifiable impact on long-term quality of life.

The purpose of this study was to explore the link between bisexual women’s experiences of anti-bisexual discrimination and disordered eating, while examining potential mediating variables underlyin...

Neighborhood supports have been associated with walking, but this association may be modified by reports about the usefulness of these supports for promoting walking. This study examined the association between reported presence of neighborhood supports and walking and whether usefulness modified this association in a nationwide sample of U.S. adults. Measures of reported presence and use or potential use (i.e., usefulness) of neighborhood supports (shops within walking distance, transit stops, sidewalks, parks, interesting things to look at, well-lit at night, low crime rate, and cars following speed limit) were examined in 3,973 adults who completed the 2014 SummerStyles survey. Multinomial regression models were used to examine the association between presence of supports with walking frequency (frequently, sometimes, rarely (referent)) and the role usefulness had on this association. The interaction term between reported presence and usefulness was significant for all supports (p < 0.05). For adults who reported a support as useful, a positive association between presence of the support and walking frequency was observed for all supports. For adults who did not report a support as useful, the association between presence of the support and walking frequency was null for most supports and negative for sidewalks, well-lit at night, and low crime rate. The association between presence of neighborhood supports and walking is modified by reported usefulness of the support. Tailoring initiatives to meet a community’s supply of and affinity for neighborhood supports may help initiatives designed to promote walking and walkable communities succeed.

Background In the setting of vascular injury, vein interposition graft is the preferred conduit, but may have limited availability. This study seeks to develop a large animal model assessing the graft performance of polytetrafluoroethylene (PTFE) and Dacron in the setting of a polymicrobial infection. Methods Thirty-seven animals were placed into 4 groups for a 21-day survival period. Six-millimeter PTFE or Dacron interposition grafts were placed in the right iliac artery with a standardized bacterial inoculation. Native vessel with and without contamination served as control groups. The inoculant was 1 × 10 7 of genetically labeled Pseudomonas aeruginosa and Staphylococcus aureus . The primary end points were graft patency (determined by duplex ultrasound and necropsy) and graft infection (culture with molecular analysis). Secondary end points included physiological measurements, blood cultures, laboratory data, and histopathology. Results PTFE and Dacron had similar infection rates of 85.7% and 75%, respectively. There was no significant difference in infectious organisms between graft materials. PTFE and Dacron exhibited bacterial ingrowth and transmigration to the intraluminal portion of the conduit. Forty-five percent of the Dacron group and 40% of the PTFE group remained patent at postoperative day 21 ( P = 0.98). Clinical data, including white blood cell count, percent neutrophils, and lactate, did not vary significantly between groups. Conclusions PTFE and Dacron perform similarly in terms of infection rates and graft failure as both have a propensity toward bacterial ingrowth and occlusion when compared with controls. This is a valid animal model to assess graft performance in the setting of polymicrobial infection and provides an avenue for studying novel prosthetic conduits.