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This article introduces a new framework for therapists to develop an exercise program to delay mobility disability in people with Parkinson disease (PD). Mobility, or the ability to efficiently navigate and function in a variety of environments, requires balance, agility, and flexibility, all of which are affected by PD. This article summarizes recent research identifying how constraints on mobility specific to PD, such as rigidity, bradykinesia, freezing, poor sensory integration, inflexible program selection, and impaired cognitive processing, limit mobility in people with PD. Based on these constraints, a conceptual framework for exercises to maintain and improve mobility is presented. An example of a constraint-focused agility exercise program, incorporating movement principles from tai chi, kayaking, boxing, lunges, agility training, and Pilates exercises, is presented. This new constraint-focused agility exercise program is based on a strong scientific framework and includes progressive levels of sensorimotor, resistance, and coordination challenges that can be customized for each patient while maintaining fidelity. Principles for improving mobility presented here can be incorporated into an ongoing or long-term exercise program for people with PD. [ABSTRACT FROM AUTHOR]

A clinical practice guideline on Parkinson disease was developed by an American Physical Therapy Association volunteer guideline development group that consisted of physical therapists and a neurologist. The guideline was based on systematic reviews of current scientific and clinical information and accepted approaches for management of Parkinson disease. The Spanish version of this clinical practice guideline is available as a supplement (Suppl. Appendix 1). [ABSTRACT FROM AUTHOR]

Background Incidence of early-onset colorectal cancer (CRC) has increased globally in recent decades. We examined early-onset CRC incidence trends worldwide for potential cohort effects, defined as changes associated with time of birth (eg, early-life exposure to carcinogens), and period effects, defined as changes associated with calendar periods (eg, screening programs). Methods We obtained long-term incidence data for early-onset CRC diagnosed in patients aged 20 to 49 years through the year 2012 for 35 countries in the Cancer Incidence in Five Continents database. We used a smoothing method to help compare cohort and period trends of early-onset CRC and used an age-period-cohort model to estimate cohort and period effects. Results Cohort effects had a more dominant role than period effects in the early-onset CRC incidence in Shanghai (China), the United Kingdom, Australia, New Zealand, Canada, the United States, and Osaka (Japan). The smoothed trends show the specific birth cohorts when early-onset CRC began to increase: the 1940s-1950s birth cohorts in the United States; the 1950s-1960s birth cohorts in other Western countries; the 1960s birth cohorts in Osaka; and the 1970s-1980s birth cohorts in Shanghai. Such increases occurred earlier for early-onset cancers of the rectum than of the colon. For the other countries, the results were less clear. Conclusions Recent birth cohorts may have been exposed to risk factors different from earlier cohorts, contributing to increased early-onset CRC incidence in several developed countries or regions in the West and Asia. Such increases began in earlier birth cohorts in Western countries than in developed regions of Asia. [ABSTRACT FROM AUTHOR]

Objective Parkinson disease (PD) is associated with a predictable decline in motor function and mobility that is commonly managed with exercise. There is a limited understanding of the effects of group exercise compared to individual exercise (IE) and usual care (UC) on motor function and mobility. Our purpose was to investigate the effects of group exercise compared to IE and UC on motor function and mobility for people with PD. Methods A systematic review and meta-analysis was performed with randomized control trials that investigated the effects of group compared with IE and UC on motor function and mobility for people with PD. A systematic search was performed in PubMed, EBSCO, and Science Direct databases. Methodological quality was assessed using the Cochrane Grading of Recommendations Assessment, Development, and Evaluation approach. Results Twenty-three studies assessed at least 1 mobility-related outcome measure, met our inclusion criteria, and were included in quantitative analysis. There was no significant difference on motor function and mobility between group exercise and IE for all standardized outcome assessment meta-analyses. Motor function and mobility were significantly improved with group exercise compared to UC in 9 of 11 standardized outcome assessment meta-analyses. Results were based upon low to moderate quality of evidence. Conclusion Based upon low to moderate quality of evidence, group exercise has a similar to larger effect as IE and UC on improving motor function and mobility for people with PD. When used in combination with skilled physical therapy, group exercise may be an appropriate adjunct to individualized physical therapy to maximize mobility and function. Impact Long-term adherence to exercise is essential to maintain mobility and motor function for people with PD. Our study suggests group exercise is as effective as IE and may be an appropriate option to encourage long-term adherence related to increased access, socialization, and accountability. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to establish the test–retest reliability of metrics obtained from wearable inertial sensors that reflect turning performance during tasks designed to imitate various turns in daily activity. Methods Seventy-one adults who were healthy completed 3 turning tasks: a 1-minute walk along a 6-m walkway, a modified Illinois Agility Test (mIAT), and a complex turning course (CTC). Peak axial turning and rotational velocity (yaw angular velocity) were extracted from wearable inertial sensors on the head, trunk, and lumbar spine. Intraclass correlation coefficients (ICCs) were established to assess the test–retest reliability of average peak turning speed for each task. Lap time was collected for reliability analysis as well. Results Turning speed across all tasks demonstrated good to excellent reliability, with the highest reliability noted for the CTC (45-degree turns: ICC = 0.73–0.81; 90-degree turns: ICC = 0.71–0.83; and 135-degree turns: ICC = 0.72–0.80). The reliability of turning speed during 180-degree turns from the 1-minute walk was consistent across all body segments (ICC = 0.74–0.76). mIAT reliability ranged from fair to excellent (end turns: ICC = 0.52–0.72; mid turns: ICC = 0.50–0.56; and slalom turns: ICC = 0.66–0.84). The CTC average lap time demonstrated good test–retest reliability (ICC = 0.69), and the mIAT average lap time test–retest reliability was excellent (ICC = 0.91). Conclusion Turning speed measured by inertial sensors is a reliable outcome across a variety of ecologically valid turning tasks that can be easily tested in a clinical environment. Impact Turning performance is a reliable and important measure that should be included in clinical assessments and clinical trials. [ABSTRACT FROM AUTHOR]

Objectives Studies have examined floor-to-stand performance in varied adult populations both quantitatively and qualitatively. Despite an elevated risk of falls and inability to independently return to stand after a fall, few have examined the ability to stand from the floor in patients recovering from stroke. There were 2 objectives of the study: to identify the relationships between floor-to-stand performance using a timed supine-to-stand test (TSS) and physical performance measures of gait, balance, and balance confidence among persons in the subacute phase after stroke; and to analyze descriptive strategies used in the completion of the TSS. Methods A cross-sectional design was implemented. Fifty-eight adults (mean age = 59.2 [standard deviation (SD) = 13.9] years; 34 [58.6%] men) who were in the subacute phase after ischemic or hemorrhagic stroke and who could stand from the floor with no more than supervision completed the TSS and physical performance assessments. Results The median time to complete the TSS in our sample was 13.0 (interquartile range = 15.5) seconds. TSS time was significantly correlated with physical performance tests, including the Timed "Up & Go" Test (ρ = 0.70), gait speed (ρ = −0.67), Dynamic Gait Index (ρ = −0.52), and Activities-Specific Balance Confidence Scale (ρ = −0.43). Thirty-two percent of the variance in TSS time was attributed to Timed "Up & Go" Test time and the use of the quadruped position to transition to standing. Participants who used a gait device were more likely to use a chair during rise to stand. Conclusion The TSS demonstrates concurrent validity with physical performance measures. Impact Findings serve to improve functional mobility examination after stroke and to formulate effective treatment interventions to improve floor-to-stand performance. [ABSTRACT FROM AUTHOR]

T cells play key protective but also pathogenic roles in COVID-19. We studied the expression of long non-coding RNAs (lncRNAs) in COVID-19 T-cell transcriptomes by integrating previously published single-cell RNA sequencing datasets. The long intergenic non-coding RNA MALAT1 was the most highly transcribed lncRNA in T cells, with Th1 cells demonstrating the lowest and CD8+ resident memory cells the highest MALAT1 expression, amongst CD4+ and CD8+ T-cells populations, respectively. We then identified gene signatures that covaried with MALAT1 in single T cells. A significantly higher number of transcripts correlated negatively with MALAT1 than those that correlated. Enriched functional annotations of the MALAT1- anti-correlating gene signature included processes associated with T-cell activation such as cell division, oxidative phosphorylation, and response to cytokine. The MALAT1 anti-correlating gene signature shared by both CD4+ and CD8+ T-cells marked dividing T cells in both the lung and blood of COVID-19 patients. Focussing on the tissue, we used an independent patient cohort of post-mortem COVID-19 lung samples and demonstrated that MALAT1 suppression was indeed a marker of MKI67+ proliferating CD8+ T cells. Our results reveal MALAT1 suppression and its associated gene signature are a hallmark of human proliferating T cells. T cells play important roles in the body's response to COVID-19. We found gene signatures anti-correlating to MALAT1 expression as a marker of proliferating CD4+ Th1 and CD8+ exhausted sub-populations. [ABSTRACT FROM AUTHOR]

Background The COVID-19 pandemic is a widespread source of stress with adverse mental health impacts. Meaning in life, both as a trait and as momentary awareness of what is personally meaningful (meaning salience), is associated with positive health outcomes and may buffer against the deleterious effects of stress. Purpose This project examines prospective associations between baseline meaning salience (daily, post-laboratory stressor) and meaning in life with perceived stress during COVID-19. Methods A community sample of healthy adults (n = 147) completed a laboratory stress protocol in 2018–2019, where perceived stress, meaning in life, and meaning salience (daily, post-stressor) were assessed. During April and July 2020 (n = 95, and 97, respectively), participants were re-contacted and reported perceived stress. General linear mixed-effects models accounting for repeated measures of stress during COVID-19 were conducted. Results Partial correlations holding constant baseline perceived stress showed that COVID-19 perceived stress was correlated with daily meaning salience (r = –.28), post-stressor meaning salience (r = –.20), and meaning in life (r = –.22). In mixed-effects models, daily and post-stressor meaning salience and higher meaning in life, respectively, predicted lower perceived stress during COVID-19, controlling for age, gender, and baseline perceived stress. Conclusions Individuals more capable of accessing meaning when exposed to laboratory stress reported lower perceived stress during a global health crisis. Despite study limitations concerning generalizability, results support meaning in life and meaning salience as important aspects of psychological functioning that may promote well-being by affecting stress appraisals and available resources for coping. [ABSTRACT FROM AUTHOR]

Additionally, as MVP expands eligibility to Veterans who may not use the VA for health care services, the importance of self-report data becomes imperative as MVP builds the infrastructure to access external health records. For greater applicability, it is envisioned that the MVP Baseline and MVP Lifestyle Surveys will be validated in future MVP scientific projects to enhance the understanding of Veteran health and wellbeing. Data resource access As described in detail in Gaziano's MVP introduction paper[3] and MVP website [https://www.research.va.gov/mvp/], access to MVP data and/or samples is governed by the scope of MVP informed consent and VA policies and requires scientific review by appropriate VA review committees. Keywords: Health surveys; Veteran health; cohort studies; survey development; Veteran lifestyle EN Health surveys Veteran health cohort studies survey development Veteran lifestyle e1 e17 17 02/16/23 20230201 NES 230201 Key Features The Department of Veterans Affairs (VA) Million Veteran Program (MVP) is a national voluntary research programme designed to examine genetic influences on health with the goal of improving health for Veterans. [Extracted from the article]

Acidic water electrolysis is of great importance for boosting the development of renewable energy. However, it severely suffers from the trade-off between high activity and long lifespan for oxygen evolution catalysts on the anode side. This is because the sluggish kinetics of oxygen evolution reaction necessitates the application of a high overpotential to achieve considerable current, which inevitably drives the catalysts far away from their thermodynamic equilibrium states. Here we demonstrate a new oxygen evolution model catalyst-hierarchical palladium (Pd) whose performance even surpasses the benchmark Ir- and Ru-based materials. The Pd catalyst displays an ultralow overpotential (196 mV), excellent durability and mitigated degradation (66 μV h−1) at 10 mA cm−2 in 1 M HClO4. Tensile strain on Pd (111) facets weakens the binding of oxygen species on electrochemical etching-derived hierarchical Pd and thereby leads to two orders of magnitudes of enhancement of mass activity in comparison to the parent Pd bulk materials. Furthermore, the Pd catalyst displays the bifunctional catalytic properties for both oxygen and hydrogen evolutions and can deliver a current density of 2 A cm–2 at a low cell voltage of 1.771 V when fabricated into polymer electrolyte membrane electrolyser. [ABSTRACT FROM AUTHOR]

Individuals who experience burns are at higher risk of developing posttraumatic stress disorder and chronic pain. A synergistic relationship exists between posttraumatic stress disorder and chronic pain. We sought to evaluate the role of individual posttraumatic stress disorder symptom clusters as predictors of pain interference. We hypothesized that the hyperarousal and emotional numbing symptom clusters would be predictive of pain interference, even when accounting for the other two posttraumatic stress disorder symptom clusters, pain intensity, and other covariates. Multivariate linear regression analyses were completed using data from the Burn Model System National Database. A total of 439 adult participants had complete responses on self-report measures assessing posttraumatic stress disorder symptoms, pain intensity, and pain interference at 6-month after discharge and were included in analyses. Results indicate hyperarousal (B =.10, p =.03) and emotional numbing (B =.13, p =.01) posttraumatic stress disorder symptom clusters were each significantly associated with pain interference, even when accounting for pain intensity (B =.64, p <.001). Results highlight the importance of the emotional numbing and hyperarousal posttraumatic stress disorder symptom clusters in explaining pain interference. Findings suggest that when posttraumatic stress disorder symptoms or chronic pain are present, screening for and treating either condition may be warranted to reduce pain interference. Further, psychological interventions that target emotional numbing and hyperarousal posttraumatic stress disorder symptoms may be fruitful for promoting better coping with chronic pain and reducing pain interference. [ABSTRACT FROM AUTHOR]

Background: The British Antarctic bases offer a semi-closed environment for assessing the transmission and persistence of seasonal respiratory viruses.Methods: Weekly swabbing was performed for respiratory pathogen surveillance (including SARS-CoV-2), at two British Antarctic Survey bases, during 2020: King Edward Point (KEP, 30 June-29 September, 9 participants, 124 swabs) and Rothera (9 May-6 June, 27 participants, 127 swabs). Symptom questionnaires were collected for any newly symptomatic cases that presented during this weekly swabbing period.Results: At KEP, swabs tested positive for non-SARS-CoV-2 seasonal coronavirus (2), adenovirus (1) parainfluenza 3 (1) and respiratory syncytial virus B (1). At Rothera, swabs tested positive for non-SARS-CoV-2 seasonal coronavirus (3), adenovirus (2) parainfluenza 4 (1) and human metapneumovirus (1). All bacterial agents identified were considered to be colonizers and not pathogenic.Conclusions: At KEP, the timeline indicated that the parainfluenza 3 and adenovirus infections could have been linked to some of the symptomatic cases that presented. For the other viruses, the only other possible sources were the visiting ship crew members. At Rothera, the single symptomatic case presented too early for this to be linked to the subsequent viral detections, and the only other possible source could have been a single non-participating staff member. [ABSTRACT FROM AUTHOR]

The suicide phenomenon involves complex interactions between psychological, biological, cultural and socio-environmental factors. This study aimed to assess the epidemiological and toxicological profiles of officially confirmed suicide victims. A retrospective study was performed using autopsy reports, forensic anthropology examinations and police summaries of all suicide cases that underwent toxicological analysis at an Official Forensic Laboratory (Minas Gerais, Brazil) in 1 year. The sample set was composed of 351 suicide victims, predominantly men (70.32%), most of them were adults between 31 and 64 years old (62.11%), with mixed skin colour (48.89%) and low educational level (66.44%). The most common suicide method was hanging (57.79%), followed by intoxication (30.45%). Most victims presented positive toxicological results (56.41%), especially for the presence of medicines (37.6%), illicit drugs (36.3%) and pesticides (26.1%). Our study corroborated previous data that most suicide victims have low educational levels. The most common toxicological findings were medicines, especially prescription drugs, followed by illicit drugs and pesticides. We hope this study contributes to reflections and planning of preventive suicide programmes, considering the described profiles of victims. Suicide is a global phenomenon. Each year, more than 793 000 suicides occur worldwide, which result from interactions between psychological, biological, cultural and socio-environmental factors. The goal of this study was to describe and analyze the epidemio-toxicological profiles of 351 suicide victims in a Forensic Unit in Southwest Brazil. The victims were mainly men (70.32%), most of the adults between 31 and 64 years old (62.11%), with mixed skin colour (48.89%) and low educational level (66.44%). The most common suicide method was hanging (57.79%), followed by intoxication (30.45%). Most victims presented positive toxicological results (56.41%), especially for the presence of medicines (37.6%), illicit drugs (36.3%) and pesticides (26.1%). [ABSTRACT FROM AUTHOR]

Background Reports indicate that the proportion of adults using drugs of abuse has been increasing in recent years in Europe. Although there are various indicators of increased drug use in Sweden over time, few studies could demonstrate an increase in the proportion of adults using drugs. To investigate changes in drug use prevalence over time, drug testing at the workplace has been used for a 25-year period. Methods The urine samples of employees sent by occupational health services from all over Sweden during a 25-year period were analyzed. The analyzing capacity increased over time (from 3411 in 1994 to 60 315 samples analyzed in 2019), and the majority of the samples was analyzed for the following drugs: cannabis (tetrahydrocannabinol), amphetamine, opiates, cocaine, and benzodiazepines. Results There was an overall increase in the proportion of samples that tested positive for illicit drugs over a 25-year period. This increase seemed to take place step-wise, with phases of linear increases and plateaus that over time became shorter. About 1.3% of samples tested positive for drugs in 1994, whereas 5.6% tested positive in 2019. Since 2007, the rate of positive samples has increased for cannabis and decreased for benzodiazepines. Although the rate of samples tested positive for opiates had remained relatively stable over the last 20 years, this rate had increased for amphetamine and cocaine between 2013 and 2019. Conclusion The results indicate that the use of illicit drugs among employees at Swedish workplaces has increased during a 25-year period. [ABSTRACT FROM AUTHOR]

Background falls and fall-related injuries are common in older adults, have negative effects on functional independence and quality of life and are associated with increased morbidity, mortality and health related costs. Current guidelines are inconsistent, with no up-to-date, globally applicable ones present. Objectives to create a set of evidence- and expert consensus-based falls prevention and management recommendations applicable to older adults for use by healthcare and other professionals that consider: (i) a person-centred approach that includes the perspectives of older adults with lived experience, caregivers and other stakeholders; (ii) gaps in previous guidelines; (iii) recent developments in e-health and (iv) implementation across locations with limited access to resources such as low- and middle-income countries. Methods a steering committee and a worldwide multidisciplinary group of experts and stakeholders, including older adults, were assembled. Geriatrics and gerontological societies were represented. Using a modified Delphi process, recommendations from 11 topic-specific working groups (WGs), 10 ad-hoc WGs and a WG dealing with the perspectives of older adults were reviewed and refined. The final recommendations were determined by voting. Recommendations all older adults should be advised on falls prevention and physical activity. Opportunistic case finding for falls risk is recommended for community-dwelling older adults. Those considered at high risk should be offered a comprehensive multifactorial falls risk assessment with a view to co-design and implement personalised multidomain interventions. Other recommendations cover details of assessment and intervention components and combinations, and recommendations for specific settings and populations. Conclusions the core set of recommendations provided will require flexible implementation strategies that consider both local context and resources. [ABSTRACT FROM AUTHOR]

Study Question: What is the genetic basis of female infertility involving abnormal oocyte morphology with the production of a large first polar body (PB1)?Summary Answer: The homozygous missense variant (c.791C>G) and compound missense variants (c.596A>T and c.875C>T) in MOS proto-oncogene, serine/threonine kinase (MOS) (Online Mendelian Inheritance in Man (OMIM) reference: 190060; NM_005372.1) are responsible for abnormal oocyte morphology with the production of a large PB1 to cause infertility in women.What Is Known Already: MOS, an oocyte-specific gene, encodes a serine/threonine-protein kinase that directly phosphorylates mitogen-activated protein kinase (MAPK) kinase (MEK) to activate MAPK (also called extracellular-signal-regulated kinase (ERK)) signal cascade in the oocyte. Female mice lacking Mos remained viable, but infertile because of oocyte symmetric division, spontaneous parthenogenetic activation and early embryonic arrest. Recently, two independent studies demonstrated that female infertility with early embryonic arrest and fragmentation can be caused by biallelic mutations in MOS. However, so far, MOS variants have not been associated with the phenotype of large PB1 extrusion in human oocytes to contribute to female infertility.Study Design, Size, Duration: Two independent infertile families characterized by the presence of large PB1 in oocytes were recruited between December 2020 and February 2022.Participants/materials, Setting, Methods: Genomic DNA was extracted from the peripheral blood samples of the subjects for whole-exome sequencing. Pedigree analysis was validated by Sanger sequencing. Then, the pathogenic effects of the MOS variants on MOS protein properties and ERK1/2 activation were determined in HEK293 cells and mouse oocytes.Main Results and the Role Of Chance: We identified three rare missense variants in MOS, including a homozygous missense variant (c.791C>G) from Patient 1 in Family 1 and two compound missense variants (c.596A>T and c.875C>T) from twin sisters in Family 2. The MOS variants followed a recessive inheritance pattern in infertile patients. All three patients displayed a high percentage of large PB1 extrusion in the oocytes. The three MOS variants could not activate MEK1/2 and ERK1/2 in oocytes and HEK293 cells. In addition, when compared with wild-type MOS, the MOS variants decreased the MOS protein level and attenuated the binding capacity with MEK1. Microinjection of wild-type human MOS complementary RNAs (cRNAs) reversed the symmetric division of oocytes after siMos treatment. In contrast, the three MOS variants demonstrated no rescuing ability.Large Scale Data: N/A.Limitations, Reasons For Caution: Owing to the scarcity of human oocyte samples and the associated ethical restrictions, we could not perform the rescue attempt for the study patients.Wider Implications Of the Findings: Our findings expand the genetic and phenotypic spectrum of MOS variants in causing female infertility. Our study findings facilitate the early genetic diagnosis of abnormal oocyte morphology characterized as large PB1 that eventually causes infertility in women.Study Funding/competing Interest(s): This study was supported by the National Natural Science Foundation of China (82071640 and 82001633), Natural Science Foundation of Zhejiang Province (LD22C060001), the Key Projects Jointly Constructed by the Ministry and the Province of Zhejiang Medical and Health Science and Technology Project (WKJ-ZJ-2005), China Postdoctoral Science Foundation (2020M682575 and 2021T140198), the Changsha Municipal Natural Science Foundation (kq2007022) and Hunan Provincial Grant for Innovative Province Construction (2019SK4012). None of the authors declare any competing interests.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Objective. Concussion can cause deficits in balance and gait. Much of what is known about how concussion affects balance and gait has been derived from studies involving youth, high school, and university athletes. However, investigation into the effects of concussion on balance and gait in community-dwelling young, middle-age, and older aged adults is limited. This study aimed to present descriptive reference values for common balance and gait measures in community-dwelling adults between the ages of 20 and 69 years with concussion. Methods. In this observational study, 318 participants were enrolled from a concussion care clinic at a rehabilitation hospital in an urban center and were assessed within 7 days of injury. Balance measures included the Balance Error Scoring System (BESS), modified BESS, and center-of-pressure root mean square during quiet standing. Gait measures included velocity (absolute and height adjusted), cadence, and step length during self-paced gait. Data were binned by decade-long age range. Results. Mean (SD) per-decade scores for the BESS ranged from 14.8 (5.1) to 21.8 (5.6) errors and 4.0 (3.0) to 9.4 (4.6) errors for the modified BESS. Mean values for center-of-pressure root mean square in the anteroposterior direction ranged from 0.42 (0.18) to 0.52 (0.26) with the eyes open, and from 0.49 (0.19) to 0.62 (0.39) with eyes closed. Mean absolute gait velocity ranged from 98.5 (9.1) to 119.3 (21.3) cm/s. The range of step length values was 58.2 (6.8) to 66.3 (7.3) cm and cadence ranged from 102.1 (9.8) to 108.6 (10.8) steps/min across age groups. Conclusion. These data provide insight into the impact of concussion on balance and mobility in community-dwelling adults across the lifespan. Impact. Community-dwelling adults can experience concussion across the lifespan. Availability of reference values for commonly used balance and gait measures can help to inform clinical strategies and progression of recovery of balance and mobility after injury. [ABSTRACT FROM AUTHOR]

Objective Challenges remain in sports-related concussion (SRC) assessment to better inform return to play. Reliance on self-reported symptoms within the Sports Concussion Assessment Tool means that there are limited data on the effectiveness of novel methods to assess a player's readiness to return to play. Digital methods such as wearable technologies may augment traditional SRC assessment and improve objectivity in making decisions regarding return to play. Methods The participant was a male university athlete who had a recent history of SRC. The single-participant design consisted of baseline laboratory testing immediately after SRC, free-living monitoring, and follow-up supervised testing after 2 months. The primary outcome measures were from traditional assessment (eg, Sports Concussion Assessment Tool and 2-minute instrumented walk/gait test; secondary outcome measures were from remote (free-living) assessment with a single wearable inertial measurement unit (eg, for gait and sleep). Results The university athlete (age = 20 years, height = 175 cm, weight = 77 kg [176.37 lb]) recovered and returned to play 20 days after SRC. Primary measures returned to baseline levels after 12 days. However, supervised (laboratory-based) wearable device assessment showed that gait impairments (increased step time) remained even after the athlete was cleared for return to play (2 months). Similarly, a 24-hour remote gait assessment showed changes in step time, step time variability, and step time asymmetry immediately after SRC and at return to play (1 month after SRC). Remote sleep analysis showed differences in sleep quality and disturbance (increased movement between immediately after SRC and once the athlete had returned to play [1 month after SRC]). Conclusion The concern about missed or delayed SRC diagnosis is growing, but methods to objectively monitor return to play after concussion are still lacking. This report showed that wearable device assessment offers additional objective data for use in monitoring players who have SRC. This work could better inform SRC assessment and return-to-play protocols. Impact Digital technologies such as wearable technologies can yield additional data that traditional self-report approaches cannot. Combining data from nondigital (traditional) and digital (wearable) methods may augment SRC assessment for improved return-to-play decisions. Lay Summary Inertia-based wearable technologies (eg, accelerometers) may be useful to help augment traditional, self-report approaches to sports-related concussion assessment and management by better informing return-to-play protocols. [ABSTRACT FROM AUTHOR]

A clinical practice guideline on Parkinson disease was developed by an American Physical Therapy Association volunteer guideline development group that consisted of physical therapists and a neurologist. The guideline was based on systematic reviews of current scientific and clinical information and accepted approaches for management of Parkinson disease. The Spanish version of this clinical practice guideline is available as a supplement (Suppl. Appendix 1). [ABSTRACT FROM AUTHOR]

Earth is experiencing widespread ecological transformation in terrestrial, freshwater, and marine ecosystems that is attributable to directional environmental changes, especially intensifying climate change. To better steward ecosystems facing unprecedented and lasting change, a new management paradigm is forming, supported by a decision-oriented framework that presents three distinct management choices: resist, accept, or direct the ecological trajectory. To make these choices strategically, managers seek to understand the nature of the transformation that could occur if change is accepted while identifying opportunities to intervene to resist or direct change. In this article, we seek to inspire a research agenda for transformation science that is focused on ecological and social science and based on five central questions that align with the resist–accept–direct (RAD) framework. Development of transformation science is needed to apply the RAD framework and support natural resource management and conservation on our rapidly changing planet. [ABSTRACT FROM AUTHOR]

Objective The purpose of this study was to assess the static balance of children with sensorineural hearing loss (SNHL) according to the degrees of SNHL and the function of the vestibular system. Methods This cross-sectional study was conducted in public schools located in Caruaru, Pernambuco state, Brazil, with 130 children (65 with normal hearing and 65 with SNHL as documented by air and bone conduction audiometry) of both sexes between 7 and 11 years old. Static balance was assessed by a stabilometric analysis using a force platform consisting of the circular area of center-of-pressure displacement of the children evaluated in 3 positions: bipedal support with feet together and parallel (PF), tandem feet (TF), and 1 foot (OF), carried out under 2 sensory conditions each, with eyes open and eyes closed. After balance assessments, the children with SNHL received examinations of auditory and vestibular functions—through audiometry and computerized vectoelectronystagmography, respectively—to compose the groups according to degrees of SNHL and vestibular function. Results The children with severe and profound SNHL demonstrated more static balance instabilities than the children with normal hearing in 5 positions assessed with eyes open (PF, TF, and OF) and eyes closed (PF and TF). The same phenomenon occurred in children with SNHL and associated vestibular dysfunction in all of the positions assessed with eyes open and eyes closed (PF, TF, and OF). Conclusion The larger the degree of SNHL, the greater the balance instability of the children. The children with SNHL and associated vestibular dysfunction showed the highest balance instabilities in this study. Impact Children with larger degrees of SNHL and associated vestibular dysfunction might require prolonged periods to rehabilitate their balance. [ABSTRACT FROM AUTHOR]

Background: Studies comparing the clinical outcomes of second-generation biodegradable polymer drug-eluting stents (BP-DES) and second-generation durable polymer drug-eluting stents (DP-DES) in patients with ST-segment elevation myocardial infarction (STEMI) with follow-up duration of more than 1 year are still limited.Objective: This study aimed to compare the 2-year clinical outcome of BP-DES with second-generation DP-DES in patients undergoing primary percutaneous coronary intervention (PPCI).Methods: This is a retrospective cohort study in patients with STEMI, the primary endpoint was major adverse cardiac events (MACE) defined as recurrent myocardial infarction, total repeat revascularisation and cardiac death. The secondary endpoint was stent thrombosis (ST) defined as definite, probable or possible.Results: A total of 400 patients were analysed (197 BP-DES groups and 203 DP-DES groups). BP-DES were independently associated with lower incidence of MACE (adjusted HR 0.67, 95% CI 0.21 to 0.91, p=0.005) and ST (adjusted HR 0.62, 95% CI 0.19 to 0.73, p<0.016) within 2 years of follow-up. Subgroup analysis of MACE individual components showed that BP-DES were associated with lower cardiac deaths (HR 0.35; 95% CI 0.18 to 0.94; p<0.001) compared to DP-DES, but not recurrent myocardial infarction and total repeat revascularisation.Conclusions: BP-DES were associated with better clinical outcomes compared to second-generation DP-DES in patients with STEMI undergoing PPCI. [ABSTRACT FROM AUTHOR]

N-glycosylation is a ubiquitous posttranslational modification that may influence folding, subcellular localization, secretion, solubility and oligomerization of proteins. In this study, we examined the effects of N-glycans on the activity of human Gb3/CD77 synthase, which catalyzes the synthesis of glycosphingolipids with terminal Galα1→4Gal (Gb3 and the P1 antigen) and Galα1→4GalNAc disaccharides (the NOR antigen). The human Gb3/CD77 synthase contains two occupied N-glycosylation sites at positions N121 and N203. Intriguingly, we found that while the N-glycan at N203 is essential for activity and correct subcellular localization, the N-glycan at N121 is dispensable and its absence did not reduce, but, surprisingly, even increased the activity of the enzyme. The fully N-glycosylated human Gb3/CD77 synthase and its glycoform missing the N121 glycan correctly localized in the Golgi, whereas a glycoform without the N203 site partially mislocalized in the endoplasmic reticulum. A double mutein missing both N-glycans was inactive and accumulated in the endoplasmic reticulum. Our results suggest that the decreased specific activity of human Gb3/CD77 synthase glycovariants resulted from their improper subcellular localization and, to a smaller degree, a decrease in enzyme solubility. Taken together, our findings show that the two N-glycans of human Gb3/CD77 synthase have opposing effects on its properties, revealing a dual nature of N-glycosylation and potentially a novel regulatory mechanism controlling the biological activity of proteins. [ABSTRACT FROM AUTHOR]

Background Pakistan's explosive human immunodeficiency virus (HIV) epidemic among people who inject drugs (PWID) varies widely across cities. We evaluated possible drivers for these variations. Methods Multivariable regression analyses were undertaken using data from 5 national surveys among PWID (n = 18 467; 2005–2017) to determine risk factors associated with variations in city-level HIV prevalence. A dynamic HIV model was used to estimate the population-attributable fraction (PAF; proportion of HIV infections prevented over 10 years when that risk factor is removed) of these risk factors to HIV transmission and impact on HIV incidence of reducing their prevalence. Results Regression analyses suggested that city-level HIV prevalence is strongly associated with the prevalence of using professional injectors at last injection, heroin use in last month, and injecting ≥4 times per day. Through calibrating a model to these associations, we estimate that the 10-year PAFs of using professional injectors, heroin use, and frequent injecting are 45.3% (95% uncertainty interval [UI], 4.3%–79.7%), 45.9% (95% UI, 8.1%–78.4%), and 22.2% (95% UI, 2.0%–58.4%), respectively. Reducing to lowest city-level prevalences of using professional injectors (2.8%; median 89.9% reduction), heroin use (0.9%; median 91.2% reduction), and frequent injecting (0.1%; median 91.8% reduction) in 2020 reduces overall HIV incidence by 52.7% (95% UI, 6.1%–82.0%), 53.0% (95% UI, 11.3%–80.2%), and 28.1% (95% UI, 2.7%–66.6%), respectively, over 10 years. Conclusions Interventions should focus on these risk factors to control Pakistan's explosive HIV epidemic among PWID, including a concomitant expansion of high-coverage needle/syringe provision, opioid substitution therapy, and antiretroviral therapy. [ABSTRACT FROM AUTHOR]

Objectives There is a growing acceptance of the need for routine implementation of patient-reported experience measures (PREMs) in health care. Rheumatology patients, as frequent and long-term users of care, stand to benefit from collection of experience-related data. The aim of this study was to perform a systematic review to identify and critically appraise the development and psychometric validation of PREMs in rheumatology. Methods Six databases were searched systematically from inception to 14 December 2020: MEDLINE, EMBASE, PsycINFO, SCOPUS, Cochrane and Google Scholar. We included articles in English that described the use or development of PREMs, with results of psychometric testing, in an adult outpatient rheumatology context. This study is registered with PROSPERO (CRD42021233819). Articles were appraised using the COnsensus Based Standards for the selection of health status Measurement Instruments (COSMIN) (i) Risk of Bias checklist and (ii) criteria for good measurement properties. Results The search yielded 3809 publications, and six studies met inclusion criteria. All the included studies on PREM development fulfilled COSMIN standards for 'doubtful' or 'inadequate' quality of instrument development. One study fulfilled a 'sufficient' rating for content validity, and the remainder fulfilled 'inconsistent' ratings. During validity testing, studies fulfilled between one and four of the eight COSMIN checklist criteria for good measurement properties. Conclusion Methodological concerns regarding instrument development and validation limit the generalizability of the existing six validated PREMs in use in rheumatology contexts. There is a need for further well-designed studies to validate existing and new PREMs in this area. [ABSTRACT FROM AUTHOR]

Background Information about pain and injury from equipment on a particular deployment is not disaggregated in the literature; thus, the nature of the issue is unclear. Aims To determine the prevalence of pain or injury during a particular deployment that military personnel attributed to equipment they used on this deployment; and to document the types of equipment they identified, the type of pain or injury and how they thought the pain or injury occurred. Methods This paper analyses data from a deployment and health survey of Australian Defence Force personnel. The participants are 8932 personnel who deployed to Iraq and 6534 who deployed to Afghanistan. Participants indicated whether they experienced pain or injury from equipment they used on deployment and detailed their experiences in response to an open-ended question (n = 563). Results Sixteen per cent of Iraq-deployed and 21% of Afghanistan-deployed participants reported pain or injury from equipment they used on deployment. Body armour was the most common equipment identified; however, a wide range of equipment was related to pain or injury. A new finding is that pain or injury related to armour was attributed to its wear in vehicles and during vehicle ingress or egress. Conclusions Knowledge of the nature of pain or injury related to equipment used on deployment may help inform improved designs and practices to reduce or prevent avoidable harm to serving personnel. [ABSTRACT FROM AUTHOR]

Introduction: Reducing cigarette use is a major public health goal in the United States. Questions remain, however, about the potential for the social environment in the adult years-particularly in the 30s and beyond-to influence cigarette use. This study tested pathways hypothesized by the social development model to understand the extent to which social environmental factors at age 33 (eg, involvement with smokers or with physically active people) contribute to changes in cigarette use from age 30 to age 39. Both combustible and electronic cigarette use were investigated.Methods: Data were from the Seattle Social Development Project, a longitudinal study of 808 diverse participants with high retention. Self-reports assessed social developmental constructs, combustible and electronic cigarette use, and demographic measures across survey waves.Results: At age 30, 32% of the sample reported past-month cigarette use. Using structural equation modeling, results showed high stability in cigarette use from age 30 to 39. After accounting for this stability, cigarette-using social environments at age 33 predicted personal beliefs or norms about smoking (eg, acceptability and social costs), which in turn predicted combustible cigarette use at age 39. Cigarette-using environments, however, directly predicted electronic cigarette use at age 39, with no significant role for beliefs about smoking.Conclusions: Cigarette use was highly stable across the 30s, but social environmental factors provided significant partial mediation of this stability. Pathways were different for combustible and electronic cigarette use, however, with personal smoking norms playing an important role for the former but not the latter.Implications: This study addresses the need for longitudinal investigation of social mechanisms and cigarette use in the 30s. Findings reinforce efforts to prevent the uptake of cigarettes prior to the 30s because, once started, smoking is highly stable. But social environmental factors remain viable intervention targets in the 30s to disrupt this stability. Addressing personal norms about smoking's acceptability and social costs is likely a promising approach for combustible cigarette use. Electronic cigarettes, however, present a new challenge in that many perceived social costs of cigarette use do not readily translate to this relatively recent technology. [ABSTRACT FROM AUTHOR]

Aims The effects of alcohol on gamma-aminobutyric acid (GABA) transmission are key for the development and maintenance of alcohol use disorder (AUD). Previous research consistently indicates that GABAB receptor agonists such as baclofen can attenuate addiction-related behaviors in preclinical models of AUD. More importantly, baclofen has also shown promise in clinical studies, particularly in severely alcohol-dependent patients. However, despite this promise, other clinical studies have not confirmed its efficacy and chiefly, larger clinical trials have not been conducted. Therefore, with the exception of France, baclofen is not approved for the treatment of AUD in any other country. Furthermore, it is also important to keep in mind that some patients treated with baclofen may experience important side-effects, including sedation, drowsiness and sleepiness. Methods This short review will first discuss the history of baclofen for AUD treatment. We will then summarize preclinical behavioral results that have investigated the efficacy of GABAB PAMs for addiction treatment, with a special focus on our recent work that investigated the effects of ADX71441, a novel GABAB PAM, on several alcohol-related behaviors in rats that model important aspects of human AUD. Finally, in light of the recent criticism about the translational value of animal models of addiction, the specific translational potential of our work and of other preclinical studies that have unanimously reported the efficacy of GABAB PAMs to attenuate multiple alcohol-related behaviors will be discussed. Results Positive allosteric modulators (PAMs) of the GABAB receptor offer an attractive alternative approach to baclofen and have the potential to achieve mechanistic and therapeutic effects similar to GABAB agonists, while avoiding the tolerance and toxicity issues associated with baclofen. To date, all preclinical behavioral results have invariably shown the efficacy of GABAB PAMs for addiction treatment. Conclusions Preclinical studies indicate that GABAB PAMs have a higher therapeutic index than orthosteric agonists, at least in terms of mitigating the sedative effects of GABAB agonism. This predicts that GABAB PAMs have a high translational potential in humans and merit being tested clinically, in particular in patients with severe AUD. [ABSTRACT FROM AUTHOR]

Aims To demonstrate that early adolescent binge drinking (BD) increases the risk for and/or severity of psychopathology in post-9/11 Veterans and determine if mild traumatic brain injury (mTBI) modifies risk. Methods Post-9/11 Veterans (n = 375) were classified into two groups: 57 Veterans with a history of early adolescent BD (E-BD; age of onset <15) and 318 who did not BD until age 15 or older (late-BD or L-BD; age of onset ≥15). History of military mTBI and mental health disorders were also assessed following military service. Results Logistic regression and analysis of variance (ANOVA) analyses revealed that the E-BD's had significantly higher prevalence of alcohol use disorders (AUDs) and more severe symptoms of AUD, substance use disorder (SUD), depression and stress. Two-way ANOVAs showed that history of military mTBI was differentially associated with posttraumatic stress disorder (PTSD) incidence and severity among Veterans who had engaged in early adolescent BD. Specifically, Veterans with a history of both early adolescent BD and military mTBI were at greater risk for a PTSD diagnosis and had more severe symptoms of PTSD than those with only a history of adolescent BD. The greater PTSD symptom severity in the comorbid group was driven by hyperarousal symptoms. Conclusions A history of BD during early adolescence is prevalent among Veterans and is related to higher risk for AUD and more severe AUD, SUD, mood and stress symptoms later in life. Veterans with early BD and military mTBI showed greater incidence and severity of PTSD, indicating that mTBI, a common comorbidity among post-9/11 Veterans, exacerbates risk. [ABSTRACT FROM AUTHOR]

Aims Consensus is lacking regarding the best treatment for coronary in-stent restenosis (ISR). The two most effective treatments are angioplasty with paclitaxel-coated balloon (PCB) and repeat stenting with drug-eluting stent (DES) but individual trials were not statistically powered for clinical endpoints, results were heterogeneous, and evidence about comparative efficacy and safety in relevant subsets was limited. Methods and results The Difference in Anti-restenotic Effectiveness of Drug-eluting stent and drug-coated balloon AngiopLasty for the occurrence of coronary in-Stent restenosis (DAEDALUS) study was a comprehensive, investigator-initiated, collaborative, individual patient data meta-analysis comparing angioplasty with PCB alone vs. repeat stenting with DES alone for the treatment of coronary ISR. The protocol was registered with PROSPERO (CRD42017075007). All 10 available randomized clinical trials were included with 1976 patients enrolled, 1033 assigned to PCB and 943 to DES. At 3-year follow-up, PCB was associated with a significant increase in the risk of target lesion revascularization (TLR) compared with DES [hazard ratio (HR) 1.32, 95% CI 1.02–1.70, P = 0.035; number-needed-to-harm 28.5]. There was a significant interaction between treatment effect and type of restenosed stent (P = 0.029) with a more marked difference in patients with DES-ISR and comparable effects in patients with bare-metal stent-ISR. At 3-year follow-up, the primary safety endpoint of all-cause death, myocardial infarction, or target lesion thrombosis was comparable between treatments (HR 0.80, 95% CI 0.58–1.09, P = 0.152). A pre-specified subgroup analysis indicated a significant interaction between treatment effect and type of DES used to treat ISR (P = 0.033), with a lower incidence of events associated with PCB compared with first-generation DES and similar effect between PCB and second-generation DES (HR 1.06, 95% CI 0.71–1.60, P = 0.764). Long-term all-cause mortality was similar between PCB and DES (HR 0.81, 95% CI 0.53–1.22, P = 0.310); results were consistent comparing PCB and non-paclitaxel-based DES (HR 1.42, 95% CI 0.80–2.54, P = 0.235). Myocardial infarction and target lesion thrombosis were comparable between treatments. Conclusions In patients with coronary ISR, repeat stenting with DES is moderately more effective than angioplasty with PCB at reducing the need for TLR at 3 years. The incidence of a composite of all-cause death, myocardial infarction, or target lesion thrombosis was similar between groups. The rates of individual endpoints, including all-cause mortality, were not significantly different between groups. [ABSTRACT FROM AUTHOR]

Changing disturbance regimes and climate can overcome forest ecosystem resilience. Following high-severity fire, forest recovery may be compromised by lack of tree seed sources, warmer and drier postfire climate, or short-interval reburning. A potential outcome of the loss of resilience is the conversion of the prefire forest to a different forest type or nonforest vegetation. Conversion implies major, extensive, and enduring changes in dominant species, life forms, or functions, with impacts on ecosystem services. In the present article, we synthesize a growing body of evidence of fire-driven conversion and our understanding of its causes across western North America. We assess our capacity to predict conversion and highlight important uncertainties. Increasing forest vulnerability to changing fire activity and climate compels shifts in management approaches, and we propose key themes for applied research coproduced by scientists and managers to support decision-making in an era when the prefire forest may not return. [ABSTRACT FROM AUTHOR]

Background: Key dimensions of cardiac arrest-induced posttraumatic stress disorder (PTSD) symptoms include reexperiencing, avoidance, numbing, and hyperarousal. It remains unknown which dimensions are most predictive of outcome.Purpose: To determine which dimensions of cardiac arrest-induced PTSD are predictive of clinical outcome within 13 months posthospital discharge.Methods: PTSD symptoms were assessed in survivors of cardiac arrest who were able to complete psychological screening measures at hospital discharge via the PTSD Checklist-Specific scale, which queries for 17 symptoms using five levels of severity. Responses on items for each symptom dimension of the four-factor numbing model (reexperiencing, avoidance, numbing, and hyperarousal) were converted to Z-scores and treated as continuous predictors. The combined primary endpoint was all-cause mortality (ACM) or major adverse cardiovascular events (MACE; hospitalization for myocardial infarction, unstable angina, heart failure, emergency coronary revascularization, or urgent defibrillator/pacemaker placements) within 13 months postdischarge. Four bivariate Cox proportional hazards survival models evaluated associations between individual symptom dimensions and ACM/MACE. A multivariable model then evaluated whether significant bivariate predictors remained independent predictors of the primary outcome after adjusting for age, sex, comorbidities, premorbid psychiatric diagnoses, and initial cardiac rhythm.Results: A total of 114 patients (59.6% men, 52.6% white, mean age: 54.6 ± 13 years) were included. In bivariate analyses, only hyperarousal was significantly associated with ACM/MACE. In a fully adjusted model, 1 standard deviation increase in hyperarousal symptoms corresponded to a two-times increased risk of experiencing ACM/MACE.Conclusions: Greater level of hyperarousal symptoms was associated with a higher risk of ACM/MACE within 13 months postcardiac arrest. This initial evidence should be further investigated in a larger sample. [ABSTRACT FROM AUTHOR]

Rapid shifts in biotic communities due to environmental variability challenge the detection of anthropogenic impacts by current biomonitoring programs. Metacommunity ecology has the potential to inform such programs, because it combines dispersal processes with niche-based approaches and recognizes variability in community composition. Using intermittent rivers—prevalent and highly dynamic ecosystems that sometimes dry—we develop a conceptual model to illustrate how dispersal limitation and flow intermittence influence the performance of biological indices. We produce a methodological framework integrating physical- and organismal-based dispersal measurements into predictive modeling, to inform development of dynamic ecological quality assessments. Such metacommunity-based approaches could be extended to other ecosystems and are required to underpin our capacity to monitor and protect ecosystems threatened under future environmental changes. [ABSTRACT FROM AUTHOR]

Background: Although health goals are recognized as a central feature of health behavior theories, the relational context through which goals are conceptualized is often overlooked. Interdependence theory represents a valuable framework for understanding goals in the adoption of health behaviors, such as pre-exposure prophylaxis (PrEP), among gay and bisexual men in primary relationships.Purpose: We examined the content and focus of men's sexual health goals, as well as whether goal content, goal focus, or perceptions of goal congruence with a primary partner were related to PrEP adoption among gay and bisexual men in primary relationships.Methods: Mixed-methods data were collected from a PrEP demonstration project from 145 HIV-negative gay and bisexual men in primary relationships. Participants reported their sexual health goals and completed measures of perceptions of goal congruence, relationship factors, and sociodemographic factors.Results: Three main goal content categories were identified: prevention, satisfaction, and intimacy. In expressing these goals, participants framed them with either a self-focus or a relationship-focus. Men in serodiscordant relationships reported more intimacy goals and greater perceptions of goal congruence. There were no differences in goal content or focus by sexual agreement. In the multivariable logistic regression model, perceived goal congruence was associated with PrEP adoption, over and above covariates.Conclusions: Intimate relationships play a significant role in the formation of health-related goals. Goal content, focus, and perceived congruence with partners may represent important targets for HIV prevention interventions for gay and bisexual men in primary relationships, especially in the context of PrEP. [ABSTRACT FROM AUTHOR]

Bradykinesia is one of the cardinal motor symptoms of Parkinson's disease and other parkinsonisms. The various clinical aspects related to bradykinesia and the pathophysiological mechanisms underlying bradykinesia are, however, still unclear. In this article, we review clinical and experimental studies on bradykinesia performed in patients with Parkinson's disease and atypical parkinsonism. We also review studies on animal experiments dealing with pathophysiological aspects of the parkinsonian state. In Parkinson's disease, bradykinesia is characterized by slowness, the reduced amplitude of movement, and sequence effect. These features are also present in atypical parkinsonisms, but the sequence effect is not common. Levodopa therapy improves bradykinesia, but treatment variably affects the bradykinesia features and does not significantly modify the sequence effect. Findings from animal and patients demonstrate the role of the basal ganglia and other interconnected structures, such as the primary motor cortex and cerebellum, as well as the contribution of abnormal sensorimotor processing. Bradykinesia should be interpreted as arising from network dysfunction. A better understanding of bradykinesia pathophysiology will serve as the new starting point for clinical and experimental purposes. [ABSTRACT FROM AUTHOR]

Urine drug test (UDT) is an effective tool used in chronic opioid therapy to ensure patient adherence to treatment and detect nonmedical opioid use. The two main types of UDT used in routine clinical practice are the screening tests or immunoassays and the confirmatory tests or laboratory‐based specific drug identification tests such as gas chromatography–mass spectrometry, liquid chromatography–mass spectrometry, or tandem mass spectrometry. UDT produces objective data on some nonmedical opioid use that may otherwise go undetected, such as the use of undisclosed medications, the nonuse of prescribed medications, and the use of illegal drugs. It allows clinicians to initiate an open and effective conversation about nonmedical opioid use with their patients. However, the test has certain limitations that sometimes compromise its use. Its interpretation can be challenging to clinicians because of the complexity of the opioid metabolic pathways. Clear guidelines or recommendations regarding the use of UDT in cancer pain is limited. As a result, UDT appears to be underused among patients with cancer pain receiving opioid therapy. More studies are needed to help standardize the integration and use of UDT in routine cancer pain management. Implications for Practice: Despite its potential benefits, urine drug testing (UDT) appears to be underused among patients with cancer pain receiving opioid therapy. This is partly because its interpretation can be challenging owing to the complexity of the opioid metabolic pathways. Information regarding the use of UDT in opioid therapy among patients with cancer is limited. This review article will improve clinician proficiency in UDT interpretation and assist oncologists in developing appropriate treatment plans during chronic opioid therapy. It is important for oncologists to use effective strategies in managing patients with cancer pain to reduce nonmedical opioid use while protecting those who merit unrestricted access to opioids for their pain. Strategies include initial screening to determine risk and effective monitoring strategies. This article discusses a key element of the universal precautions approach, urine drug testing. [ABSTRACT FROM AUTHOR]

We conducted a systematic review that examined the link between individual drug categories and violent outcomes. We searched for primary case-control and cohort investigations that reported risk of violence against others among individuals diagnosed with drug use disorders using validated clinical criteria, following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We identified 18 studies published during 1990-2019, reporting data from 591,411 individuals with drug use disorders. We reported odds ratios of the violence risk in different categories of drug use disorders compared with those without. We found odds ratios ranging from 0.8 to 25.0 for most individual drug categories, with generally higher odds ratios among individuals with polydrug use disorders. In addition, we explored sources of between-study heterogeneity by subgroup and meta-regression analyses. Cohort investigations reported a lower risk of violence than case-control reports (odds ratio =  2.7 (95% confidence interval (CI): 2.1, 3.5) vs. 6.6 (95% CI: 5.1, 8.6)), and associations were stronger when the outcome was any violence rather than intimate partner violence (odds ratio = 5.7 (95% CI: 3.8, 8.6) vs. 1.7 (95% CI: 1.4, 2.1)), which was consistent with results from the meta-regression. Overall, these findings highlight the potential impact of preventing and treating drug use disorders on reducing violence risk and associated morbidities. [ABSTRACT FROM AUTHOR]

Previous research suggests that judgments about a male speaker's trustworthiness vary due to the speaker's voice pitch (mean F 0) and differ across domains. However, mixed results in terms of the direction and extent of such effects have been reported. Moreover, no study so far has investigated whether men's mean F 0 is, indeed, a valid cue to their self-reported and behavioral trustworthiness, and whether trustworthiness judgments are accurate. We tested the relation between mean F 0 and actual general, economic, and mating-related trustworthiness in 181 men, as well as trustworthiness judgments of 95 perceivers across all three domains. Analyses show that men's mean F 0 is not related to Honesty–Humility (as a trait indicator of general trustworthiness), trustworthy intentions, or trust game behavior, suggesting no relation of mean F 0 to general or economic trustworthiness. In contrast, results suggest that mean F 0 might be related to mating-related trustworthiness (as indicated by self-reported relationship infidelity). However, lower mean F 0 was judged as more trustworthy in economic but less trustworthy in mating-related domains and rather weakly related to judgments of general trustworthiness. Trustworthiness judgments were not accurate for general or economic trustworthiness, but exploratory analyses suggest that women might be able to accurately judge men's relationship infidelity based on their voice pitch. Next to these analyses, we report exploratory analyses involving and controlling for additional voice parameters. [ABSTRACT FROM AUTHOR]

Adult granulosa cell tumor (aGCT) is a rare type of ovarian cancer characterized by estrogen excess. Interestingly, only the single somatic mutation FOXL2 C134W was found across virtually all aGCTs. We previously reported that FOXL2C134W stimulates CYP19 transcription synergistically with SMAD3, leading to elevated estradiol synthesis in a human granulosa cell line (HGrC1). This finding suggested a key role for FOXL2C134W in causing the typical estrogen overload in patients with aGCTs. We have now investigated the effect of FOXO1, a tumor suppressor, on CYP19 activation by FOXL2C134W in the presence of SMAD3. Intriguingly, FOXO1 antagonized the positive, synergistic effect of FOXL2C134W and SMAD3 on CYP19 transcription. Similar to FOXL2C134W, FOXO1 binds SMAD3 but not the proximal FOXL2C134W binding site (−199 bp) of the CYP19 promoter identified in our earlier studies. The results of a competitive binding assay suggested a possible underlying mechanism in which FOXO1 sequesters SMAD3 away from FOXL2C134W, thereby negating the cooperative action of FOXL2C134W and SMAD3 in inducing CYP19 expression. To our knowledge, this study is the first to demonstrate the ability of FOXO1 to restore an altered CYP19 expression by FOXL2C134W and SMAD3 and provides insight as to why FOXO1 deficiency promotes GCT development in mice. [ABSTRACT FROM AUTHOR]

Objective: To investigate the incidence of violent crime conviction among Swedish military veterans after deployment to Afghanistan versus non-deployed comparators. The main outcome was first conviction of a violent crime, retrieved from the Swedish National Council for Crime Prevention Register until December 31, 2013.Methods: This was a cohort study of military veterans identified through personnel registers regarding deployment to Afghanistan between 2002 and 2013 (n = 5894). To each military veteran, up to five non-deployed comparators identified via the Military Service Conscription Register were matched by age, sex, conscription year, cognitive ability, psychological assessment, self-reported mental health, body mass index, antidepressants/anxiolytics prescriptions and self-harm (fully matched comparators; n = 28 895). Multivariable adjustment was made for substance abuse and previous health care visits with psychiatric diagnoses. An additional comparator group matched only for age, sex and conscription year was also used (age-sex-matched comparators; n = 29 410).Results: During 21 898 person-years of follow-up (median = 3.6 years) there were 26 events among deployed military veterans compared with 98 in non-deployed fully matched comparators [12 vs 9 per 10 000 person-years, adjusted hazard ratio (aHR) 1.36; 95% confidence interval (CI) 0.88-2.10]. Among non-deployed age-sex-matched comparators there were 170 violent crime convictions (16 per 10 000 person-years; aHR 0.85; 95% CI 0.56-1.29). Factors associated with greater risk of violent crime convictions were younger age, lower scores on cognitive ability tests and psychological assessment, and convictions preceding deployment.Conclusion: The violent crime conviction rate after returning from military deployment to Afghanistan was not different compared with non-deployed comparators in individuals without history of violent crime convictions. [ABSTRACT FROM AUTHOR]

Ninety per cent of the human population has been right-handed since the Paleolithic, yet the brain signature and genetic basis of handedness remain poorly characterized. Here, we correlated brain imaging phenotypes from ∼9000 UK Biobank participants with handedness, and with loci found significantly associated with handedness after we performed genome-wide association studies (GWAS) in ∼400 000 of these participants. Our imaging-handedness analysis revealed an increase in functional connectivity between left and right language networks in left-handers. GWAS of handedness uncovered four significant loci (rs199512, rs45608532, rs13017199, and rs3094128), three of which are in-or expression quantitative trait loci of-genes encoding proteins involved in brain development and patterning. These included microtubule-related MAP2 and MAPT, as well as WNT3 and MICB, all implicated in the pathogenesis of diseases such as Parkinson's, Alzheimer's and schizophrenia. In particular, with rs199512, we identified a common genetic influence on handedness, psychiatric phenotypes, Parkinson's disease, and the integrity of white matter tracts connecting the same language-related regions identified in the handedness-imaging analysis. This study has identified in the general population genome-wide significant loci for human handedness in, and expression quantitative trait loci of, genes associated with brain development, microtubules and patterning. We suggest that these genetic variants contribute to neurodevelopmental lateralization of brain organization, which in turn influences both the handedness phenotype and the predisposition to develop certain neurological and psychiatric diseases. [ABSTRACT FROM AUTHOR]

Although social marketing principles have been successfully employed in school-based interventions to prevent obesity, use in early care and education (ECE) settings has been limited. This paper describes the use of the social marketing approach to develop an ECE-based intervention that encourages an ECE provider–parent partnership to improve the quality of preschool children's diets and their level of physical activity. A six-step social marketing approach for public health interventions guided the development of this ECE-based intervention. These steps were as follows: (i) initial planning, (ii) formative research, (iii) strategy development, (iv) program development, (v) implementation, and (vi) monitoring and evaluation. During this process, we reviewed current literature, conducted focus groups with ECE providers and parents, developed a detailed conceptual model and content map, created and tested the campaign concept, and developed final campaign materials along with strategies for its implementation. The final intervention resulting from this process was an 8-month campaign known as Healthy Me, Healthy We. The campaign is delivered by the child care center and includes branded materials for use in the classroom and at home. The final campaign is being evaluated in a cluster-randomized trial. Healthy Me, Healthy We offers an innovative approach to promoting healthy eating and physical activity during early childhood, a key developmental period, that leverages partnership between ECE providers and parents to affect behavior change. [ABSTRACT FROM AUTHOR]

Background: Chronic pain directly or indirectly interferes with valued personal goals. Goal adjustment plays a central role in patients' adaptation. Studies on the relationship between optimism and goal regulation have shown that people with high dispositional optimism adjust their goals in a flexible way, and that flexible goal adjustment promotes quality of life.Purpose: The aim of this study was to analyze the relationship among optimism, goal adjustment, and adaptation in patients with chronic pain.Methods: A sample of 258 patients with chronic musculoskeletal pain completed questionnaires on optimism, reengagement, disengagement, flexibility, tenacity, rumination, purpose in life, well-being, pain intensity, daily functioning, and impairment.Results: Structural equation modeling analysis showed that optimism had a positive association with reengagement, flexibility, and tenacity, and a negative association with disengagement. Disengagement was positively associated with rumination, whereas reengagement, flexibility, and tenacity were associated with higher levels of purpose in life, which were strongly associated with adaptation in patients with chronic pain.Conclusions: This study supports the conclusions of previous research on the role of goal adjustment as a mediator variable between optimism and well-being. [ABSTRACT FROM AUTHOR]

View large Download slide View large Download slide OBJECTIVES This study aimed to compare the mid-term results of coronary artery bypass grafting (CABG) with those of percutaneous coronary intervention (PCI) with second-generation drug-eluting stents (DESs) for triple-vessel disease. METHODS Between February 2010 and December 2015, 607 patients underwent primary isolated CABG and 264 patients underwent PCI with second-generation DESs (everolimus-eluting stent, biolimus-eluting stent or zotarolimus-eluting stent) for triple-vessel disease with or without left main disease. We compared the CABG group with the second-generation DES group using propensity score matching analysis. The study end points were major adverse cardiac and cerebrovascular events. RESULTS After propensity score matching, 238 pairs of patients were successfully matched (C-statistic 0.762). The mean number of distal anastomoses in the CABG group was 4.7 and that of implanted stents in the second-generation DES group was 2.8. The 30-day mortality was similar between the groups (0.8% vs 0.4%; P  = 0.564). The median follow-up period was 3.4 years in the CABG group and 3.8 years in the second-generation DES group. Although there was no significant difference in the incidence of all-cause death and cerebrovascular accidents, the incidence of myocardial infarction [hazard ratio (HR) 11.76; 95% confidence interval (CI) 2.32–214.15, P  = 0.003] and repeat revascularization (HR 3.78; 95% CI 2.35–6.38; P  < 0.001) was significantly higher in the second-generation DES group than in the CABG group. This resulted in a higher incidence of major adverse cardiac and cerebrovascular events (HR 2.27; 95% CI 1.61–3.24; P  < 0.001). CONCLUSIONS CABG might be superior to PCI with second-generation DESs for treatment of triple-vessel disease in terms of major adverse cardiac and cerebrovascular events. [ABSTRACT FROM AUTHOR]