cGAS phase separation inhibits TREX1-mediated DNA degradation and enhances cytosolic DNA sensing.

Cyclic GMP-AMP synthase (cGAS) recognition of cytosolic DNA is critical for the immune response to cancer and pathogen infection. Here, we discover that cGAS-DNA phase separation is required to resist negative regulation and allow efficient sensing of immunostimulatory DNA. We map the molecular determinants of cGAS condensate formation and demonstrate that phase separation functions to limit activity of the cytosolic exonuclease TREX1. Mechanistically, phase separation forms a selective environment that suppresses TREX1 catalytic function and restricts DNA degradation to an outer shell at the droplet periphery. We identify a TREX1 mutation associated with the severe autoimmune disease Aicardi-Goutières syndrome that increases penetration of TREX1 into the repressive droplet interior and specifically impairs degradation of phase-separated DNA. Our results define a critical function of cGAS-DNA phase separation and reveal a molecular mechanism that balances cytosolic DNA degradation and innate immune activation.

ER-directed TREX1 limits cGAS activation at micronuclei.

Micronuclei are aberrant nuclear compartments that can form as a result of chromosome mis-segregation. Frequent loss of micronuclear envelope integrity exposes DNA to the cytoplasm, leading to chromosome fragmentation and immune activation. Here, we use micronuclei purification to show that the endoplasmic reticulum (ER)-associated nuclease TREX1 inhibits cGAS activation at micronuclei by degrading micronuclear DNA upon micronuclear envelope rupture. We demonstrate that the ER accesses ruptured micronuclei and plays a critical role in enabling TREX1 nucleolytic attack. TREX1 mutations, previously implicated in immune disease, untether TREX1 from the ER, disrupt TREX1 localization to micronuclei, diminish micronuclear DNA damage, and enhance cGAS activation. These results establish ER-directed resection of micronuclear DNA by TREX1 as a critical regulator of cytosolic DNA sensing in chromosomally unstable cells and provide a mechanistic basis for the importance of TREX1 ER tethering in preventing autoimmunity.

Train at home, but not alone: a randomised controlled multicentre trial assessing the effects of live-streamed tele-exercise during COVID-19-related lockdowns.

OBJECTIVE: Public life restrictions associated with the COVID-19 pandemic caused reductions in physical activity (PA) and decreases in mental and somatic health. Considering the interplay between these factors, we investigated the effects of digital home exercise (DHE) during government-enforced lockdowns. METHODS: A multicentre randomised controlled trial was performed allocating healthy individuals from nine countries (N=763; 523 female) to a DHE or an inactive control group. During the 4-week main intervention, DHE members engaged in live-streamed multicomponent home exercise. Subsequently, both groups had access to prerecorded workouts for an additional 4 weeks. Outcomes, assessed weekly, included PA level (Nordic Physical Activity Questionnaire-Short), anxiety (Generalized Anxiety Disorder Scale-7), mental well-being (WHO-5 Questionnaire), sleep quality (Medical Outcome Study Sleep Scale), pain/disability (Chronic Pain Grade Scale) and exercise motivation (Self-Concordance Scale). Mixed models were used for analysis. RESULTS: Live-streamed DHE consistently increased moderate PA (eg, week 1: 1.65 times more minutes per week, 95% CI 1.40 to 1.94) and vigorous PA (eg, week 1: 1.31 times more minutes per week, 95% CI 1.08 to 1.61), although the effects decreased over time. In addition, exercise motivation, sleep quality and anxiety were slightly improved for DHE in the 4-week live streaming period. The same applied to mental well-being (mean difference at week 4: +0.99, 95% CI 0.13 to 1.86), but an inverted trend was observed after live streaming was substituted by prerecorded exercise. CONCLUSIONS: Live-streamed DHE represents an efficacious method to enhance PA and selected markers of health during pandemic-related public life restrictions. However, research on implementation is warranted to reduce dropout rates. TRIAL REGISTRATION NUMBER: DRKS00021273.

Investigation of the Organocatalytic Chlorination of 2-Phenylpropanal.

Results of an examination of the organocatalytic enantioselective α-chlorination of 2-phenylpropanal are described. Synthetic investigation including the screening of primary and secondary aminocatalysts, many different reaction conditions, and other α-branched aldehydes show that especially primary aminocatalysts can catalyze the formation of the α-chloro branched aldehydes in good yields, but only with moderate enantioselectivities. In order to try to understand the challenge in obtaining high enantioselectivity for the aminocatalytic α-chlorination of α-branched aldehydes a series of experimental investigations were performed employing 2-phenylpropanal as a model system. These investigations have been coupled with computational investigations, which provided important insight into the moderate enantioselectivity of this chlorination reaction. Analysis of the reaction showed, that the lack of control over the selectivity of formation of the (E)- and (Z)-enamine intermediate, and the clustering of reaction barriers of possible reaction pathways help to rationalize difficulties in producing high enantioselectivity.

Organocatalytic Enantioselective 1,3-Dipolar [6+4] Cycloadditions of Tropone.

A highly stereoselective 1,3-dipolar [6+4] cycloaddition towards bridged azabicyclo[4.3.1]decane scaffolds has been developed, reacting aldehydes, 2-aminomalonates and tropone under mild conditions in the presence of a chiral phosphoric acid catalyst. The scope is demonstrated for a series of aldehydes and 2-aminomalonates, and the reaction proceeds in high yields, >95:5 d.r. and up to 99 % ee. A series of transformations, as well as a mechanistic proposal, are presented.

Visible light-mediated intermolecular [2 + 2] photocycloaddition of 1-aryl-2-nitroethenes and olefins.

Despite the importance of cyclobutanes there are not many direct [2 + 2] photocycloaddition reactions which can be performed with visible light in the absence of a catalyst. A notable exception is the reaction of 1-aryl-2-nitroethenes and olefins which can be performed at a wavelength of λ = 419 nm or λ = 424 nm in CH2Cl2 as the solvent. In the present study, a total of 15 1-aryl-2-nitroethenes were found to undergo a [2 + 2] photocycloaddition with 2,3-dimethyl-2-butene (28-86% yield) and a set of 12 olefins was studied in their photocycloaddition to 1-phenyl-2-nitroethene (37-88% yield). All mechanistic results are in agreement with a triplet reaction pathway and with the intermediacy of a 1,4-diradical.

Describing the continuum of collaboration among local health departments with hospitals around the community health assessments.

BACKGROUND: Hospitals and local health departments (LHDs) are under policy requirements from the Affordable Care Act and accreditation standards through the Public Health Accreditation Board. Tax exempt hospitals must perform a community health needs assessment (CHNA), similar to the community health assessment (CHA) required for LHDs. These efforts have led to a renewed interest in hospitals and LHDs working together to achieve common goals. PURPOSE: The purpose of this study is to gain a better understanding of levels of joint action leading toward collaboration between LHDs and hospitals and describe collaboration around CHAs. METHODS: Local health departments were selected on the basis of reporting collaboration (n = 26) or unsure about collaboration (n = 29) with local hospitals. Local health departments were surveyed regarding their relationship with local hospitals. For LHDs currently collaborating with a hospital, a collaboration continuum scale was calculated. Appropriate nonparametric tests, chi-squares, and Spearman's rank correlations were conducted to determine differences between groups. RESULTS: A total of 44 LHDs responded to the survey (80.0%). Currently collaborating LHDs were more likely to be interested in accreditation and to refer to their CHA 5 or more times a year compared to the unsure LHDs. In the analysis, a collaboration continuum was created and is positively correlated with aspects of the CHA and CHA process. CONCLUSIONS: This study is the first attempt to quantify the level of collaboration between LHDs and hospitals around CHAs. Better understanding of the levels of joint action required may assist LHDs in making informed decisions regarding deployment of resources on the path to accreditation.

Intratumoral TREX1 Induction Promotes Immune Evasion by Limiting Type I IFN.

Chromosomal instability is a hallmark of human cancer that is associated with aggressive disease characteristics. Chromosome mis-segregations help fuel natural selection, but they risk provoking a cGAS-STING immune response through the accumulation of cytosolic DNA. The mechanisms of how tumors benefit from chromosomal instability while mitigating associated risks, such as enhanced immune surveillance, are poorly understood. Here, we identify cGAS-STING-dependent upregulation of the nuclease TREX1 as an adaptive, negative feedback mechanism that promotes immune evasion through digestion of cytosolic DNA. TREX1 loss diminishes tumor growth, prolongs survival of host animals, increases tumor immune infiltration, and potentiates response to immune checkpoint blockade selectively in tumors capable of mounting a type I IFN response downstream of STING. Together, these data demonstrate that TREX1 induction shields chromosomally unstable tumors from immune surveillance by dampening type I IFN production and suggest that TREX1 inhibitors might be used to selectively target tumors that have retained the inherent ability to mount an IFN response downstream of STING. See related article by Lim et al., p. 663.

Predictive value of a novel digital risk calculator to determine early patient outcomes after major surgery: a proof-of-concept pilot study.

BACKGROUND: A structured risk assessment of patients with validated and evidence-based tools can help to identify modifiable factors before major surgeries. The Protego Maxima trial investigated the value of a new digitized risk assessment tool that combines tools which can be easily used and implemented in the clinical workflow by doctors and qualified medical staff. The hypothesis was that the structured assessment and risk-grouping is predictive of short-term surgical quality reflected by complications and overall survival. METHODS: The Protego Maxima Trial was a prospective cohort analysis of patients undergoing major surgery (visceral, thoracic, urology, vascular and gynecologic surgeries) as key inclusion criterion and the absence of an acute or acute on chronically decompensated pulmo-cardiovascular decompensation. Patients were risk-scored with the software (The Prehab App) that includes a battery of evidence-based risk assessment tools that allow a structured risk assessment. The data were grouped to predefined high and low risk groups and aggregate and individual scores. The primary outcome was to validate the predictive value of the RAI score and the TUG for overall survival in the high and low risk groups. Secondary outcomes were surgical outcomes at 90-days after surgery (overall survival, Clavien-Dindo (CD) 1-5 (all complications), and CD 3-5 (major complications)). The study was carried out in accordance with the DIN ISO 14,155, and the medical device regulation (MDR) at Frankfurt University Hospital between March 2022 and January 2023. RESULTS: In total 267 patients were included in the intention to treat analysis. The mean age was 62.1 ± 12.4 years. Patients with a RAI score > 25 and/or a timed up and go (TUG) > 8 s had a higher risk for mortality at 90 days after surgery. The low-risk group predicted beneficial outcome and the high-risk group predicted adverse outcome in the ROC analysis (Area Under the Curve Receiver Operator Characteristics: AUROC > 0.800; p = 0.01). Risk groups (high vs. low) showed significant differences for 90-day survival (99.4% vs. 95.5%; p = 0.04) and major complications (16.4% vs. 32.4%; p < 0.001). CONCLUSION: The proof-of-concept trial showed that a risk assessment with 'The Prehab App' may be viable to estimate the preoperative risk for mortality and major complications before major surgeries. The overall performance in this initial set of data indicated a certain reliability of the scoring and risk grouping, especially of the RAI score and the TUG. A larger data set will be required to proof the generalizability of the risk scoring to every subgroup and may be fostered by artificial intelligence approaches. TRIAL REGISTRATION: Ethics number: 2021-483-MDR/MPDG-zuständig monocentric; The Federal Institute for Pharmaceuticals and Medical Devices/BfArM, reference number: 94.1.04-5660-13655; Eudamed: CIV-21-07-0307311; German Clinical Trial Registry: DRKS 00026985.

Myofascial force transmission between the calf and the dorsal thigh is dependent on knee angle: an ultrasound study.

A recent in-vivo experiment has shown that force can be transmitted between the gastrocnemius and the hamstring muscles due to a direct tissue continuity. However, it remains unclear if this mechanical interaction is affected by the stiffness of the structural connection. This study therefore aimed to investigate the impact of the knee angle on myofascial force transmission across the dorsal knee. A randomized, cross-over study was performed, including n = 56 healthy participants (25.36 ± 3.9 years, 25 females). On two separate days, they adopted a prone position on an isokinetic dynamometer (knee extended or 60° flexed). In each condition, the device moved the ankle three times from maximal plantarflexion to maximal dorsal extension. Muscle inactivity was ensured using EMG. High-resolution ultrasound videos of the semimembranosus (SM) and the gastrocnemius medialis (GM) soft tissue were recorded. Maximal horizontal tissue displacement, obtained using cross-correlation, was examined as a surrogate of force transmission. SM tissue displacement was higher at extended (4.83 ± 2.04 mm) than at flexed knees (3.81 ± 2.36 mm). Linear regression demonstrated significant associations between (1) SM and GM soft tissue displacement (extended: R2 = 0.18, p = 0.001; flexed: R2 = 0.17, p = 0.002) as well as (2) SM soft tissue displacement and ankle range of motion (extended: R2 = 0.103, p = 0.017; flexed: R2 = 0.095, p = 0.022). Our results further strengthen the evidence that local stretching induces a force transmission to neighboring muscles. Resulting remote exercise effects such as increased range of motion, seem to depend on the stiffness of the continuity.Trial registration: DRKS (Deutsches Register Klinischer Studien), registration number DRKS00024420, first registered 08/02/2021, https://drks.de/search/de/trial/DRKS00024420 .

Study protocol for a pilot trial analysing the usability, validity and safety of an interventional health app programme for the structured prehabilitation of patients before major surgical interventions: the PROTEGO MAXIMA trial.

INTRODUCTION: Major surgery is associated with a high risk for postoperative complications, leading to an increase in mortality and morbidity, particularly in frail patients with a reduced cardiopulmonary reserve. Prehabilitation, including aerobic exercise training, aims to improve patients' physical fitness before major surgery and reduce postoperative complications, length of hospital stay and costs. The purpose of the study is to assess the usability, validity and safety of an app-based endurance exercise software in accordance with the Medical Device Regulation using wrist-worn wearables to measure heart rate (HR) and distance. METHODS AND ANALYSIS: The PROTEGO MAXIMA trial is a prospective, interventional study with patients undergoing major elective surgery, comprising three tasks. Tasks I and II aim to assess the usability of the app, using evaluation questionnaires and usability scenarios. In Task IIIa, patients will undergo a structured risk assessment by the Patronus App, which will be correlated with the occurrence of postoperative complications after 90 days (non-interventional). In Task IIIb, healthy students and patients will perform a supervised 6 min walking test and a 37 min interval training on a treadmill based on HR reserve, wearing standard ECG limb leads and two smartwatches, which will be driven by the test software. The aim of this task is to assess the accuracy of HR measurement by the wearables and the safety, using specific alarm settings of the devices and lab testing of the participants (interventional). ETHICS AND DISSEMINATION: Ethical approval was granted by the Institutional Review Board of the University Hospital of Frankfurt and by the Federal Institute for Pharmaceuticals and Medical Products (BfArM, reference number 94.1.04-5660-13655) on 7 February 2022. The results from this study will be submitted to peer-reviewed journals and reported at suitable national and international meetings. TRIAL REGISTRATION NUMBERS: European Database on Medical Devices (CIV-21-07-037311) and German Clinical Trial Registry (DRKS00026985).

A toolbox for a structured risk-based prehabilitation program in major surgical oncology.

Prehabilitation is a multimodal concept to improve functional capability prior to surgery, so that the patients' resilience is strengthened to withstand any peri- and postoperative comorbidity. It covers physical activities, nutrition, and psychosocial wellbeing. The literature is heterogeneous in outcomes and definitions. In this scoping review, class 1 and 2 evidence was included to identify seven main aspects of prehabilitation for the treatment pathway: (i) risk assessment, (ii) FITT (frequency, interventions, time, type of exercise) principles of prehabilitation exercise, (iii) outcome measures, (iv) nutrition, (v) patient blood management, (vi) mental wellbeing, and (vii) economic potential. Recommendations include the risk of tumor progression due to delay of surgery. Patients undergoing prehabilitation should perceive risk assessment by structured, quantifiable, and validated tools like Risk Analysis Index, Charlson Comorbidity Index (CCI), American Society of Anesthesiology Score, or Eastern Co-operative Oncology Group scoring. Assessments should be repeated to quantify its effects. The most common types of exercise include breathing exercises and moderate- to high-intensity interval protocols. The program should have a duration of 3-6 weeks with 3-4 exercises per week that take 30-60 min. The 6-Minute Walking Testing is a valid and resource-saving tool to assess changes in aerobic capacity. Long-term assessment should include standardized outcome measurements (overall survival, 90-day survival, Dindo-Clavien/CCI®) to monitor the potential of up to 50% less morbidity. Finally, individual cost-revenue assessment can help assess health economics, confirming the hypothetic saving of $8 for treatment for $1 spent for prehabilitation. These recommendations should serve as a toolbox to generate hypotheses, discussion, and systematic approaches to develop clinical prehabilitation standards.

Myofascial force transmission between the ankle and the dorsal knee: A study protocol.

BACKGROUND: Connective tissue links the skeletal muscles, creating a body-wide network of continuity. A recent in-vivo experiment demonstrated that passive elongation of the calf caused a caudal displacement of the semimembranosus muscle, indicating force transmission across the dorsal knee joint. However, it remains unclear as to whether this observation is dependent on the joint angle. If force would not be transmitted at flexed knees, this would reduce the number of postures and movements where force transmission is of relevance. Our trial, therefore, aims to investigate the influence of passive calf stretching with the knee in extended and flexed position on dorsal thigh soft tissue displacement. METHODS: Participants are positioned prone on an isokinetic dynamometer. The device performs three repetitions of moving the ankle passively (5°/s) between plantar flexion and maximum dorsiflexion. With a washout-period of 24 hours, this procedure is performed twice in randomised order, once with the knee extended (0°) and once with the knee flexed (60°). Two high-resolution ultrasound devices will be used to visualize the soft tissue of the calf and dorsal thigh during the manoeuvre. Maximal horizontal displacement of the soft tissue [mm] during ankle movement will be quantified as a surrogate of force transmission, using a frame-by-frame cross-correlation analysis of the obtained US videos. DISCUSSION: Understanding myofascial force transmission under in-vivo conditions is a pre-requisite for the development of exercise interventions specifically targeting the fascial connective tissue. Our study may thus provide health and fitness professional with the anatomical and functional basis for program design. TRIAL REGISTRATION: The study is registered at the German Clinical Trials Register (TRN: DRKS00024420), registered 8 Februar 2021, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00024420.

Association between physical activity and musculoskeletal pain: an analysis of international data from the ASAP survey.

OBJECTIVE: To explore the association of physical activity (PA) with musculoskeletal pain (MSK pain). DESIGN: Cross-sectional study SETTING: 14 countries (Argentina, Australia, Austria, Brazil, Chile, France, Germany, Italy, the Netherlands, Singapore, South Africa, Spain, Switzerland and the USA). PARTICIPANTS: Individuals aged 18 or older. PRIMARY AND SECONDARY OUTCOME MEASURES: PA volumes were assessed with an adapted version of the Nordic Physical Activity Questionnaire-short. Prevalence of MSK pain was captured by means of a 20-item checklist of body locations. Based on the WHO recommendation on PA, participants were classified as non-compliers (0-150 min/week), compliers (150-300 min/week), double compliers (300-450 min/week), triple compliers (450-600 min/week), quadruple compliers (600-750 min/week), quintuple compliers (750-900 min/week) and top compliers (more than 900 min/week). Multivariate logistic regression was used to obtain adjusted ORs of the association between PA and MSK pain for each body location, correcting for age, sex, employment status and depression risk. RESULTS: A total of 13 741 participants completed the survey. Compared with non-compliers, compliers had smaller odds of MSK pain in one location (thoracic pain, OR 0.77, 95% CI 0.64 to 0.93). Double compliance was associated with reduced pain occurrence in six locations (elbow, OR 0.70, 95% CI 0.50 to 0.98; forearm, OR 0.63, 95% CI 0.40 to 0.99; wrist, OR 0.74, 95% CI 0.57 to 0.98; hand, OR 0.57, 95% CI 0.40 to 0.79; fingers, OR 0.72, 95% CI 0.52 to 0.99; abdomen, OR 0.61, 95% CI 0.41 to 0.91). Triple to top compliance was also linked with lower odds of MSK pain (five locations in triple compliance, three in quadruple compliance, two in quintuple compliance, three in top compliance), but, at the same time, presented increased odds of MSK pain in some of the other locations. CONCLUSION: A dose of 300-450 min WHO-equivalent PA/week was associated with lower odds of MSK pain in six body locations. On the other hand, excessive doses of PA were associated with higher odds of pain in certain body locations.

Intermolecular [2 + 2] Photocycloaddition of α,ß-Unsaturated Sulfones: Catalyst-Free Reaction and Catalytic Variants.

2-Aryl-1-sulfonyl-substituted cyclobutanes were prepared in an intermolecular [2 + 2] photocycloaddition from various α,ß-unsaturated sulfones and olefins upon irradiation at λ = 300 nm (26 examples, 60-99% yield). Lewis acids catalyzed the [2 + 2] photocycloaddition of 2-benzimidazolyl styryl sulfones. At short wavelengths, the latter substrates underwent C-S bond cleavage but AlBr3 (5 mol %) allowed for an intermolecular reaction with 2,3-dimethyl-2-butene at longer wavelengths. A chiral-at-metal Lewis acid (2 mol %) facilitated an enantioselective reaction (up to 77% ee).

Use of Reflective Tape to Detect Ultrasound Transducer Movement: A Validation Study.

During dynamic ultrasound assessments, unintended transducer movement over the skin needs to be prevented as it may bias the results. The present study investigated the validity of two methods quantifying transducer motion. An ultrasound transducer was moved on a pre-specified 3 cm distance over the semitendinosus muscle of eleven adults (35.8 ± 9.8 years), stopping briefly at intervals of 0.5 cm. Transducer motion was quantified (1) measuring the 2-D displacement of the shadow produced by reflective tape (RT) attached to the skin and (2) using a marker-based, three-dimensional movement analysis system (MAS). Differences between methods were detected with Wilcoxon tests; associations were checked by means of intraclass correlation coefficients (ICC 3.1) and Bland-Altman plots. Values for RT (r = 0.57, p < 0.001) and MAS (r = 0.19, p = 0.002) were significantly higher than true distances (TD). Strong correlations were found between RT and TD (ICC: 0.98, p < 0.001), MAS and TD (ICC: 0.95, p < 0.001), and MAS and RT (ICC: 0.97, p < 0.001). Bland-Altman plots showed narrow limits of agreement for both RT (-0.49 to 0.13 cm) and MAS (-0.49 to 0.34 cm) versus TD. RT and MAS are valid methods to quantify US transducer movement. In view of its low costs and complexity, RT can particularly be recommended for application in research and clinical practice.

Drastic Reductions in Mental Well-Being Observed Globally During the COVID-19 Pandemic: Results From the ASAP Survey.

Most countries affected by the COVID-19 pandemic have repeatedly restricted public life to control the contagion. However, the health impact of confinement measures is hitherto unclear. We performed a multinational survey investigating changes in mental and physical well-being (MWB/PWB) during the first wave of the pandemic. A total of 14,975 individuals from 14 countries provided valid responses. Compared to pre-restrictions, MWB, as measured by the WHO-5 questionnaire, decreased considerably during restrictions (68.1 ± 16.9 to 51.9 ± 21.0 points). Whereas 14.2% of the participants met the cutoff for depression screening pre-restrictions, this share tripled to 45.2% during restrictions. Factors associated with clinically relevant decreases in MWB were female sex (odds ratio/OR = 1.20, 95% CI: 1.11-1.29), high physical activity levels pre-restrictions (OR = 1.29, 95% CI 1.16-1.42), decreased vigorous physical activity during restrictions (OR = 1.14, 95% CI: 1.05-1.23), and working (partially) outside the home vs. working remotely (OR = 1.29, 95% CI: 1.16-1.44/OR = 1.35, 95% CI: 1.23-1.47). Reductions, although smaller, were also seen for PWB. Scores in the SF-36 bodily pain subscale decreased from 85.8 ± 18.7% pre-restrictions to 81.3 ± 21.9% during restrictions. Clinically relevant decrements of PWB were associated with female sex (OR = 1.62, 95% CI: 1.50-1.75), high levels of public life restrictions (OR = 1.26, 95% CI: 1.18-1.36), and young age (OR = 1.10, 95% CI: 1.03-1.19). Study findings suggest lockdowns instituted during the COVID-19 pandemic may have had substantial adverse public health effects. The development of interventions mitigating losses in MWB and PWB is, thus, paramount when preparing for forthcoming waves of COVID-19 or future public life restrictions.

A Pandemic within the Pandemic? Physical Activity Levels Substantially Decreased in Countries Affected by COVID-19.

Governments have restricted public life during the COVID-19 pandemic, inter alia closing sports facilities and gyms. As regular exercise is essential for health, this study examined the effect of pandemic-related confinements on physical activity (PA) levels. A multinational survey was performed in 14 countries. Times spent in moderate-to-vigorous physical activity (MVPA) as well as in vigorous physical activity only (VPA) were assessed using the Nordic Physical Activity Questionnaire (short form). Data were obtained for leisure and occupational PA pre- and during restrictions. Compliance with PA guidelines was calculated based on the recommendations of the World Health Organization (WHO). In total, n = 13,503 respondents (39 ± 15 years, 59% females) were surveyed. Compared to pre-restrictions, overall self-reported PA declined by 41% (MVPA) and 42.2% (VPA). Reductions were higher for occupational vs. leisure time, young and old vs. middle-aged persons, previously more active vs. less active individuals, but similar between men and women. Compared to pre-pandemic, compliance with WHO guidelines decreased from 80.9% (95% CI: 80.3-81.7) to 62.5% (95% CI: 61.6-63.3). Results suggest PA levels have substantially decreased globally during the COVID-19 pandemic. Key stakeholders should consider strategies to mitigate loss in PA in order to preserve health during the pandemic.

Bioterrorism knowledge and educational participation of nurses in Missouri.

BACKGROUND: Nurses are integral to bioterrorism preparedness, but nurses' bioterrorism preparedness knowledge has not been evaluated well. METHODS: Missouri Nurses Association members (1,528) were studied in the summer of 2006 to assess their bioterrorism knowledge and the perceived benefits of education as well as barriers to education. RESULTS: The response rate was 31%. Most respondents (60%, n = 284) received no bioterrorism education. Nurses who were nurse practitioners (t = -2.42, p < .05), were male (t = -2.99, p < .01), or were on a planning committee (t = -1.96, p = .05) had received more education than other nurses. The most commonly cited barrier to education (46.6%, n = 221) was not knowing where to obtain training. One third of respondents (31.2%) reported no interest in receiving bioterrorism education in the future. Nurses' average score on the knowledge test was 73%. The most commonly missed questions pertained to infection control and decontamination procedures. CONCLUSION: Bioterrorism preparedness training should be offered through continuing education and nursing school curricula.

Chronic effects of high-intensity functional training on motor function: a systematic review with multilevel meta-analysis.

High-intensity functional training (HIFT) has become a popular method in the sports and fitness sector. In contrast to unimodal approaches such as strength or endurance training, it has been hypothesized to induce concurrent adaptations in multiple markers of motor function. However, to date, the effectiveness of HIFT in this regard has not been studied. The present systematic review quantified the chronic effects of HIFT on motor function in healthy individuals. A multilevel meta-analysis with a robust random effects meta-regession model was used to pool the standardized mean differences (SMD) between (a) HIFT and (b) no-exercise (NEX) as well as conventional endurance, resistance and balance training for outcomes of muscle strength, endurance capacity and balance. The influence of possible effect modifiers such as program duration, session duration, age or sex was examined in a moderator analysis. Seventeen papers with moderate to high methodological quality (PEDro scale) were identified. Compared to NEX, HIFT had small to moderate positive effects on endurance capacity (SMD: 0.42, 95% CI 0.07-0.78, p = 0.03) and strength (0.60, 95% CI 0.02-1.18, p = 0.04) but no effect on balance (SMD: - 0.10, 95% CI - 1.13 to 0.92, p = 0.42). Regarding endurance, HIFT showed similar effectiveness as moderate-intensity endurance training (SMD: - 0.11, 95% CI - 1.17 to 0.95, p = 0.75) and high-intensity interval endurance training (SMD: - 0.15, 95% CI - 1.4 to 1.1, p = 0.66). No comparisons of HIFT vs. classical resistance or balance training were found. Moderator analyses revealed no influence of most effect modifiers. However, regarding endurance, females seemed to respond more strongly to HIFT in the comparison to NEX (p < .05). HIFT appears to represent an appropriate method to induce chronic improvements in motor function. While being superior to NEX and non-inferior to endurance training, current evidence does not allow a comparison against resistance and balance training. The impact of possible effect moderators should be further elucidated in future research.