Caffeine has no effect on submaximal running in hypoxia in low caffeine consuming males and females.

BACKGROUND: Exposure to hypoxia immediately challenges a variety of physiologic systems that limit exercise capacity. Under normoxia, caffeine (CAFF) increases ventilation and subsequent oxygenation of hemoglobin (SpO2) and skeletal muscle (SmO2). CAFF improves exercise performance at altitude. However, little attention has been given to submaximal exercise in hypoxia, particularly regarding low CAFF consumers and female participants. The aim of this study was to determine the effect of CAFF on pulmonary, metabolic, and perceptual variables in response to submaximal running in hypoxia in low CAFF consuming males and females. METHODS: In a double blinded, counterbalanced design, 14 (6 females) individuals (24.1±5.1 years; VO2max: 40.6±5.6 mL × kg-1 × min-1; 20.8±8.0% body fat), who habitually consumed ≤150 mg/day of CAFF performed treadmill running at workloads of 25%, 40%, 60%, and 75% of sea level VO2max in normobaric hypoxia (FIO2=0.15) on two separate occasions: 1) 60 minutes after 6 mg/kg of CAFF; or 2) placebo. RESULTS: CAFF had no effect on any variable measured. Specifically, VE (condition: P=0.12; interaction: P=0.19), VT (condition: P=0.16; interaction: P=0.57), and Ve:VO2 (condition: P=0.07; interaction: P=0.69) were similar between groups. Further, CAFF had no effect on relative VO2 (condition: P=0.84; interaction: P=0.95), HR (condition: P=0.28; interaction: P=0.35), SmO2 (condition: P=0.66; interaction: P=0.82), or SpO2 (condition: P=0.16; interaction: P=0.97). Finally, rating of perceived exertion (RPE; P=0.92) and acute mountain sickness scores (P=0.29) were similar across conditions. CONCLUSIONS: These data demonstrate that CAFF provides no physiologic advantage to submaximal exercise in acute, normobaric hypoxia with low CAFF consuming males and females.

Prescribing Practices of Recommended Treatment for Trichomonas vaginalis and Chlamydia trachomatis after 2021 STI Treatment Guideline Update.

ABSTRACT: We evaluated the proportion of patients with trichomoniasis and chlamydial infections who received recommended versus non-recommended antibiotic therapy after the updated 2021 Sexually Transmitted Infections Guideline. Of 712 patients, 473 (66%) received recommended therapy. Receipt of emergency department care was independently associated with recommended therapy (adjOR, 2.1; 95% CI 1.5-2.9).

New technology to address affected vs nonaffected arm contributions to ergometer performance in people poststroke.

BACKGROUND: When pedaling a coupled-crank arm ergometer, individuals with hemiplegia may experience nonparetic arm overcompensation, and paretic arm resistance, due to neuromechanical deficits. Technologies that foster independent limb contributions may increase the effectiveness of exercise for people poststroke. OBJECTIVE: Examine the speed during uncoupled pedaling with the Advanced Virtual Exercise Environment Device among individuals poststroke and non-impaired comparisons. METHODS: We recruited 2 groups:Poststroke and Comparison. Participants attended one lab session and performed peak speed tests and a graded exercise repeated for bilateral pedaling, unilateral (left, right). RESULTS: Thirty-one participants completed the protocol (16 women, 15 men). Poststroke participants pedaled slower during the bilateral speed test (64 ± 39 RPM, p < .001), and graded exercise, (54 ± 28 RPM, p < .001) versus comparisons (141 ± 19, 104 ± 12 RPM). Poststroke individuals had lower peak RPM during the unilateral speed test with their paretic arm (70 ± 46 RPM, p < .001) and graded exercise (58 ± 33 RPM, p < .001) compared to their unilateral speed test (130 ± 37 RPM) and graded exercise (108 ± 25 RPM) with their nonparetic arm. Comparisons did not differ between arms during speed tests and graded exercise. Poststroke participants demonstrated lower peak speed with their affected arm during the bilateral speed test (52 ± 42 RPM, p < .001) and graded exercise (49 ± 28 RPM, p = .008) compared to the same arm during unilateral speed (70 ± 46 RPM) and graded exercise (58 ± 33 RPM). CONCLUSIONS: Poststroke participants pedaled faster with their affected arm unilaterally versus bilateral pedaling, suggesting interhemispheric interference that reduces the ability to recruit the paretic arm during bilateral exercise.

Development and Formative Evaluation of a Virtual Exercise Platform for a Community Fitness Center Serving Individuals With Physical Disabilities: Mixed Methods Study.

BACKGROUND: People with disabilities experience numerous barriers to being physically active, such as transportation issues, a lack of trained exercise professionals who understand disabilities, and facility access. The use of a virtual exercise platform (VEP) may provide an alternative and limit certain barriers. OBJECTIVE: The aim of this mixed method study was to evaluate user interaction (effectiveness, efficiency, and satisfaction), the strengths and weaknesses of the user interface, and the user experience with a VEP. METHODS: Participants were recruited from a community fitness facility that offers programs for people with disabilities. Inclusion criteria were being older than 18 years, fluent in English, and availability of internet access. Features of the VEP included articles, prerecorded videos, live Zoom classes, web-based class registration, weekly progress tracking, incentives, and surveys. A one-on-one Zoom session was scheduled with each participant, during which they completed certain tasks: (1) create an account or login, (2) register for class, (3) join class, (4) add to calendar, and (5) complete surveys. As participants completed tasks, quantitative observations (time on task, task success, rate of task completion, and number of errors by users, which determined task difficulty), qualitative observations were made and interviews were conducted at the end of the session. The "concurrent think-aloud" method was encouraged by the moderator to gauge participants' thoughts as they worked through testing. Participants also completed the System Usability Scale (SUS) and Questionnaire for User Interface Satisfaction (QUIS). RESULTS: A total of 5 people with disabilities (3 male, 2 female), aged 36-78 (mean 54) years, with education levels from high school to PhD, were recruited. Devices used for testing included a laptop (n=3), a Chromebook (n=1), and a desktop (n=1). All participants completed tasks #1 and #2 without errors but could not complete task #4. One participant completed task #5 with difficulty and another completed task #3 with difficulty. The average time to complete each task was: (1) 82 seconds (55-110), (2) 11 seconds (4-21), (3) 9 seconds (5-27), and (4) 921.5 seconds (840-958). The mean SUS score was 86.5/100, and the mean user QUIS score was 8.08 out of 10. Qualitative observations indicated that the system was simple, user-friendly, and accessible. CONCLUSIONS: People with disabilities reported high usability and user satisfaction with the web-based exercise platform, and the system appears to be an efficient and effective physical activity option.

The Usability of a Touchpad Active Video Game Controller for Individuals With Impaired Mobility: Observational Study.

BACKGROUND: Video games are a popular sedentary activity among people with impaired mobility; however, active video game hardware typically lacks accessibility and customization options for individuals with mobility impairments. A touchpad video game system can elicit moderate physical activity in healthy adults; however, it is unclear if this system is usable by adults with impaired mobility. OBJECTIVE: The purpose of this study was to assess the usability of a touchpad video game controller system adapted for adults with impaired mobility. Additional outcomes explored were enjoyment, perceived exertion, self-efficacy, participant feedback, and researcher observations of gameplay. METHODS: Participants played several video game titles for 20 minutes with a touchpad video game controller as they stood or sat in a chair or their wheelchair. Usability was assessed with the System Usability Scale (SUS) and the Health Information Technology Usability Evaluation Scale (Health-ITUES) surveys after gameplay. After each video game, participants reported enjoyment using a visual analog scale (0 to 100 mm) and a rating of perceived exertion using the OMNI 0 to 10 scale. Self-efficacy was measured before and after gameplay. Participants provided feedback at the end of their session. RESULTS: In total, 21 adults (6 females and 15 males) with a mean age of 48.8 (SD 13.8) years with various mobility impairments participated in this study. The touchpads received mean usability scores on the SUS 80.1 (SD 18.5) and Health-ITUES 4.23 (SD 0.67). CONCLUSIONS: The SUS scores reported suggest the touchpad system is "usable"; however, the Health-ITUES scores were slightly below a suggested benchmark. Participants reported moderate to high enjoyment but perceived the exertion as "somewhat easy." Self-efficacy was moderate to high and did not differ pre- to postgame play. The participants regarded the touchpads as novel, fun, and entertaining. The generalizability of our results is limited due to the heterogenous sample; however, our participants identified several areas of improvement for future iteration.

Sequence Similarity among Structural Repeats in the Piezo Family of Mechanosensitive Ion Channels.

Members of the Piezo family of mechanically activated cation channels are involved in multiple physiological processes in higher eukaryotes, including vascular development, cell differentiation, touch perception, hearing, and more, but they are also common in single-celled eukaryotic microorganisms. Mutations in these proteins in humans are associated with a variety of diseases, such as colorectal adenomatous polyposis, dehydrated hereditary stomatocytosis, and hereditary xerocytosis. Available 3D structures for Piezo proteins show nine regions of four transmembrane segments each that have the same fold. Despite the remarkable similarity among the nine characteristic structural repeats in the family, no significant sequence similarity among them has been reported. Using bioinformatics approaches and the Transporter Classification Database (TCDB) as reference, we reliably identified sequence similarity among repeats based on four lines of evidence: (1) hidden Markov model-profile similarities across repeats at the family level, (2) pairwise sequence similarities between different repeats across Piezo homologs, (3) Piezo-specific conserved sequence signatures that consistently identify the same regions across repeats, and (4) conserved residues that maintain the same orientation and location in 3D space.

Respiratory culture nudge improves antibiotic prescribing for Moraxella catarrhalis and Haemophilus influenzae lower respiratory tract infections.

We compared optimal antibiotic prescribing before and after implementing an interpretive ß-lactamase microbiology comment for Haemophilus influenzae and Moraxella catarrhalis in lower respiratory-tract infections. The postintervention group was associated with 5-fold increased odds of optimal de-escalation (adjusted odds ratio, 5.03; 95% confidence interval, 2.57-9.87).

Usability of the GAIMplank Video Game Controller for People With Mobility Impairments: Observational Study.

BACKGROUND: Replacing sedentary behaviors during leisure time with active video gaming has been shown to be an enjoyable option for increasing physical activity. However, most off-the-shelf active video gaming controllers are not accessible or usable for individuals with mobility impairments. To address this requirement, a universal video game controller (called the GAIMplank) was designed and developed. OBJECTIVE: This study aimed to assess the usability of the GAIMplank video game controller for playing PC video games among individuals with mobility impairments. Measures of enjoyment, perceived exertion, and qualitative data on the user experience were also examined. METHODS: Adults (aged 18-75 years) with a mobility impairment were recruited to participate in a single testing session in the laboratory. Before testing began, basic demographic information, along with minutes of weekday and weekend physical activity, minutes of weekday and weekend video game play, and video game play experience were collected. The GAIMplank was mapped to operate as a typical joystick controller. Depending on their comfort and functional ability, participants chose to play seated in a chair, standing, or in their own manual wheelchair. Leaning movements of the trunk created corresponding action in the game (ie, lean right to move right). The participants played a total of 5 preselected video games for approximately 5 minutes each. Data were collected to assess the usability of the GAIMplank, along with self-efficacy regarding execution of game play actions, rating of perceived exertion and enjoyment for each game, and overall qualitative feedback. RESULTS: A total of 21 adults (n=15, 71% men; n=6, 29% women) completed the usability testing, with a mean age of 48.8 (SD 13.8; range 21-73) years. Overall, 38% (8/21) of adults played while standing, 33% (7/21) of adults played while seated in a chair, and 29% (6/21) played in their own manual wheelchair. Scores from the System Usability Scale indicated above average (74.8, SD 14.5) usability, with scores best for those who played seated in a chair, followed by those standing, and then individuals who played seated in their own wheelchairs. Inconsistencies in the responsiveness of the controller and general feedback for minor improvements were documented. Rating of perceived exertion scores ranged from light to moderate intensity, with the highest scores for those who played seated in a chair. Participants rated their experience with playing each game from above average to very enjoyable. CONCLUSIONS: The GAIMplank video game controller was found to be usable and accessible, providing an enjoyable option for light-to-moderate intensity exercise among adults with mobility impairments. Minor issues with inconsistencies in controller responsiveness were also recorded. Following further development and refinement, the next phase will include a pilot exercise intervention using the GAIMplank system.

Filtering and improved Uncertainty Quantification in the dynamic estimation of effective reproduction numbers.

The effective reproduction number Rt measures an infectious disease's transmissibility as the number of secondary infections in one reproduction time in a population having both susceptible and non-susceptible hosts. Current approaches do not quantify the uncertainty correctly in estimating Rt, as expected by the observed variability in contagion patterns. We elaborate on the Bayesian estimation of Rt by improving on the Poisson sampling model of Cori et al. (2013). By adding an autoregressive latent process, we build a Dynamic Linear Model on the log of observed Rts, resulting in a filtering type Bayesian inference. We use a conjugate analysis, and all calculations are explicit. Results show an improved uncertainty quantification on the estimation of Rt's, with a reliable method that could safely be used by non-experts and within other forecasting systems. We illustrate our approach with recent data from the current COVID19 epidemic in Mexico.

Active Videogaming Interventions in Adults with Neuromuscular Conditions: A Scoping Review.

This review synthesized active videogaming (AVG) intervention literature over a 10-year period (2010-2020) for people with neuromuscular conditions (18-64 years of age), examining interventions that aimed to improve health and secondary conditions, physical activity, and outcomes quality of life (QOL). Systematic searches yielded 40 eligible studies. The major groups were multiple sclerosis (40%) and stroke (33%), and the study participants had mostly mild-to-moderate disability who were able to play games in a standing position. Research designs primarily involved randomized controlled trials (65%) and pre/post-trial design without a control group (28%). The majority of interventions used commercial off-the-shelf gaming systems, such as Nintendo Wii and Microsoft Kinect. Studies reported significant improvements in health outcomes, specifically in balance (n = 30/36), mobility (n = 24/27), and cardiorespiratory fitness (n = 6/8). Positive changes were also seen in secondary conditions (n = 8/12), physical activity (n = 3/4), and QOL outcomes (n = 8/16). AVG research for people with neuromuscular conditions has grown in both quantity and quality but several gaps remain. Study findings provide a roadmap for future AVG trials on understudied populations, and highlight technology and targeted outcomes as drivers of future intervention research.

Bayesian sequential data assimilation for COVID-19 forecasting.

We introduce a Bayesian sequential data assimilation and forecasting method for non-autonomous dynamical systems. We applied this method to the current COVID-19 pandemic. It is assumed that suitable transmission, epidemic and observation models are available and previously validated. The transmission and epidemic models are coded into a dynamical system. The observation model depends on the dynamical system state variables and parameters, and is cast as a likelihood function. The forecast is sequentially updated over a sliding window of epidemic records as new data becomes available. Prior distributions for the state variables at the new forecasting time are assembled using the dynamical system, calibrated for the previous forecast. Epidemic outbreaks are non-autonomous dynamical systems depending on human behavior, viral evolution and climate, among other factors, rendering it impossible to make reliable long-term epidemic forecasts. We show our forecasting method's performance using a SEIR type model and COVID-19 data from several Mexican localities. Moreover, we derive further insights into the COVID-19 pandemic from our model predictions. The rationale of our approach is that sequential data assimilation is an adequate compromise between data fitting and dynamical system prediction.

Forecasting hospital demand in metropolitan areas during the current COVID-19 pandemic and estimates of lockdown-induced 2nd waves.

We present a forecasting model aim to predict hospital occupancy in metropolitan areas during the current COVID-19 pandemic. Our SEIRD type model features asymptomatic and symptomatic infections with detailed hospital dynamics. We model explicitly branching probabilities and non-exponential residence times in each latent and infected compartments. Using both hospital admittance confirmed cases and deaths, we infer the contact rate and the initial conditions of the dynamical system, considering breakpoints to model lockdown interventions and the increase in effective population size due to lockdown relaxation. The latter features let us model lockdown-induced 2nd waves. Our Bayesian approach allows us to produce timely probabilistic forecasts of hospital demand. We have applied the model to analyze more than 70 metropolitan areas and 32 states in Mexico.

Human placental mesenchymal stem cells improve stroke outcomes via extracellular vesicles-mediated preservation of cerebral blood flow.

BACKGROUND: Besides long-term trans-differentiation into neural cells, benefits of stem cell therapy (SCT) in ischemic stroke may include secretion of protective factors, which partly reflects extracellular vesicle (EVs) released by stem cell. However, the mechanism(s) by which stem cells/EVs limit stroke injury have yet to be fully defined. METHODS: We evaluated the protection effect of human placenta mesenchymal stem cells (hPMSC) as a potential form of SCT in experimental ischemic stroke 'transient middle cerebral artery occusion (MCAO)/reperfusion' mice model. FINDINGS: We found for the first time that intraperitoneal administration of hPMSCs or intravenous hPMSC-derived EVs, given at the time of reperfusion, significantly protected the ipsilateral hemisphere from ischemic injury. This protection was associated with significant restoration of normal blood flow to the post-MCAO brain. More importantly, EVs derived from hPMSC promote paracrine-based protection of SCT in the MCAO model in a cholesterol/lipid-dependent manner. INTERPRETATION: Together, our results demonstrated beneficial effects of hPMSC/EVs in experimental stroke models which could permit the rapid "translation" of these cells into clinical trials in the near-term.

Optimal surface estimation and thresholding of confocal microscope images of biofilms using Beer's Law.

Beer's Law explains how light attenuates into thick specimens, including thick biofilms. We use a Bayesian optimality criterion, the maximum of the posterior probability distribution, and computationally efficiently fit Beer's Law to the 3D intensity data collected from thick living biofilms by a confocal scanning laser microscope. Using this approach the top surface of the biofilm and an optimal image threshold can be estimated. Biofilm characteristics, such as bio-volumes, can be calculated from this surface. Results from the Bayesian approach are compared to other approaches including the method of maximum likelihood or simply counting bright pixels. Uncertainty quantification (i.e., error bars) can be provided for the parameters of interest. This approach is applied to confocal images of stained biofilms of a common lab strain of Pseudomonas aeruginosa, stained biofilms of Janthinobacterium isolated from the Antarctic, and biofilms of Staphylococcusaureus that have been genetically modified to fluoresce green.

Obstructive sleep apnea intensifies stroke severity following middle cerebral artery occlusion.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a sleep disorder caused by transient obstruction of the upper airway and results in intermittent hypoxia, sleep fragmentation, sympathetic nervous system activation, and arousal which can have an adverse effect on cardiovascular disease. It is theorized that OSA might intensify stroke injury. Our goal here was to develop a new model of experimental OSA and test its ability to aggravate behavioral and morphological outcomes following transient brain ischemia/reperfusion. METHODS: We used a 3D printed OSA device to expose C57BL6 mice to 3 h of OSA (obstructive apnea index of 20 events per hour) for three days. These mice were then subjected to ischemia/reperfusion using the middle cerebral artery occlusion model (MCAO) stroke and examined for overall survival, infarct size and neurological scoring. RESULTS: We found that OSA transiently decreased respiration and reduced oxygen saturation with bradycardia and tachycardia typical of human responses during apneic events. Brain injury from MCAO was significantly increased by OSA as measured by infarct size and location as well as by intensification of neurological deficits; mortality following MCAO was also increased in OSA animals. CONCLUSIONS: Our findings suggest that our new model of OSA alters respiratory and cardiovascular physiological functions and is associated with enhanced ischemia/reperfusion mediated injury in our non-invasive, OSA intensified model of stroke.

Autologous Adipose Tissue-Derived Mesenchymal Stem Cells Introduced by Biliary Stents or Local Immersion in Porcine Bile Duct Anastomoses.

Biliary complications (strictures and leaks) represent major limitations in living donor liver transplantation. Mesenchymal stem cells (MSCs) are a promising modality to prevent biliary complications because of immunosuppressive and angiogenic properties. Our goal was to evaluate the safety of adipose-derived MSC delivery to biliary anastomoses in a porcine model. Secondary objectives were defining the optimal method of delivery (intraluminal versus extraluminal) and to investigate MSC engraftment, angiogenesis, and fibrosis. Pigs were divided into 3 groups. Animals underwent adipose collection, MSC isolation, and expansion. Two weeks later, animals underwent bile duct transection, reanastomosis, and stent insertion. Group 1 received plastic stents wrapped in unseeded Vicryl mesh. Group 2 received stents wrapped in MSC-seeded mesh. Group 3 received unwrapped stents with the anastomosis immersed in an MSC suspension. Animals were killed 1 month after stent insertion when cholangiograms and biliary tissue were obtained. Serum was collected for liver biochemistries. Tissue was used for hematoxylin-eosin and trichrome staining and immunohistochemistry for MSC markers (CD44 and CD34) and for a marker of neoangiogenesis (CD31). There were no intraoperative complications. One pig died on postoperative day 3 due to acute cholangitis. All others recovered without complications. Cholangiography demonstrated no biliary leaks and minimal luminal narrowing. Surviving animals exhibited no symptoms, abnormal liver biochemistries, or clinically significant biliary stricturing. Group 3 showed significantly greater CD44 and CD34 staining, indicating MSC engraftment. Fibrosis was reduced at the anastomotic site in group 3 based on trichrome stain. CD31 staining of group 3 was more pronounced, supporting enhanced neoangiogenesis. In conclusion, adipose-derived MSCs were safely applied to biliary anastomoses. MSCs were locally engrafted within the bile duct and may have beneficial effects in terms of fibrosis and angiogenesis.

Brain Endothelial Cells Release Apical and Basolateral Microparticles in Response to Inflammatory Cytokine Stimulation: Relevance to Neuroinflammatory Stress?

Microparticles (MP) are regarded both as biomarkers and mediators of many forms of pathology, including neurovascular inflammation. Here, we characterized vectorial release of apical and basolateral MPs (AMPs and BMPs) from control and TNF-α/IFN-γ treated human brain endothelial monolayers, studied molecular composition of AMPs and BMPs and characterized molecular pathways regulating AMP and BMP release. The effects of AMPs and BMPs on blood-brain barrier properties and human brain microvascular smooth muscle tonic contractility in vitro were also evaluated. We report that human brain microvascular endothelial cells release MPs both apically and basolaterally with both AMP and BMP release significantly increased following inflammatory cytokine challenge (3.5-fold and 3.9-fold vs. control, respectively). AMPs and BMPs both carry proteins derived from parent cells including those in BBB junctions (Claudin-1, -3, -5, occludin, VE-cadherin). AMPs and BMPs represent distinct populations whose release appears to be regulated by distinctly separate molecular pathways, which depend on signaling from Rho-associated, coiled-coil containing protein kinase (ROCK), calpain as well as cholesterol depletion. AMPs and BMPs modulate functions of neighboring cells including BBB endothelial solute permeability and brain vascular smooth muscle contractility. While control AMPs enhanced brain endothelial barrier, cytokine-induced AMPs impaired BBB. Cytokine-induced but not control BMPs significantly impaired human brain smooth muscle contractility as early as day 1. Taken together these results indicate that AMPs and BMPs may contribute to neurovascular inflammatory disease progression both within the circulation (AMP) and in the brain parenchyma (BMP).

Antibiotics in 3D-printed implants, instruments and materials: benefits, challenges and future directions.

3D printing is an additive manufacturing technology, which permits innovative approaches for incorporating antibiotics into 3D printed constructs. Antibiotic-incorporating applications in medicine have included medical implants, prostheses, along with procedural and surgical instruments. 3D-printed antibiotic-impregnated devices offer the advantages of increased surface area for drug distribution, sequential layers of antibiotics produced through layer-by-layer fabrication, and the ability to rapidly fabricate constructs based on patient-specific anatomies. To date, fused deposition modeling has been the main 3D printing method used to incorporate antibiotics, although inkjet and stereolithography techniques have also been described. This review offers a state-of-the-art summary of studies that incorporate antibiotics into 3D-printed constructs and summarizes the rationale, challenges, and future directions for the potential use of this technology in patient care.