Search

In uncertain environments and with increasing age, humans often walk, slower while taking shorter, quicker, and wider steps, reflective of a cautious gait., Understanding when humans opt to use a cautious gait and the differences in gait, strategies used as people age could be examined with perturbations on a self-paced, treadmill that allows participants to adjust their walking speed. Adding varying degrees, of unpredictability, an inherent element of real-world walking, could also improve, understanding of when specific gait strategies are used We investigated how healthy young and older adults adjust their, gait strategies when responding to perturbations of varying unpredictability. We, hypothesized that more unpredictable perturbations would produce more cautious gait, strategies and be more pronounced in older adults than young adults Ten young and ten older adults walked on a self-paced treadmill with, discrete mediolateral treadmill shift perturbations. We changed the shift magnitude, and/or the timing of the perturbations during the gait cycle to vary perturbation, unpredictability. We analyzed walking speed and step kinematics from treadmill and, motion capture data Surprisingly, participants walked faster, not slower, for the conditions with, perturbations. Even more surprising, older adults walked faster overall than young, adults. As expected, participants took faster and wider steps for the most unpredictable, perturbation but also took longer steps, which was not expected. Step kinematic, variability and average step width also increased as perturbation unpredictability, increased, suggesting that the more unpredictable conditions demanded greater, balance control. Additionally, older adults had greater step kinematic variability, highlighted further using detrended step length variability, compared to young adults Overall, these findings provide new insights about gait strategies and, suggest that perturbations such as discrete mediolateral treadmill shifts can potentially, be designed to encourage participants to walk faster, if it is beneficial. • Discrete mediolateral perturbations were applied during self-paced treadmill walking. • Varying unpredictable perturbations probed gait strategies of young and older adults. • Walking speed increased with the addition of perturbations in young and older adults. • Step width and gait variability increased as perturbation unpredictability increased. • Perturbation features (e.g. timing and size) could be tuned to alter walking speed. [ABSTRACT FROM AUTHOR]

For decades, sarcomeric myosin heavy chain proteins were assumed to be restricted to striated muscle where they function as molecular motors that contract muscle. However, MYH7b, an evolutionarily ancient member of this myosin family, has been detected in mammalian nonmuscle tissues, and mutations in MYH7b are linked to hereditary hearing loss in compound heterozygous patients. These mutations are the first associated with hearing loss rather than a muscle pathology, and because there are no homologous mutations in other myosin isoforms, their functional effects were unknown. We generated recombinant human MYH7b harboring the D515N or R1651Q hearing loss-associated mutation and studied their effects on motor activity and structural and assembly properties, respectively. The D515N mutation had no effect on steady-state actin-activated ATPase rate or load-dependent detachment kinetics but increased actin sliding velocity because of an increased displacement during the myosin working stroke. Furthermore, we found that the D515N mutation caused an increase in the proportion of myosin heads that occupy the disordered-relaxed state, meaning more myosin heads are available to interact with actin. Although we found no impact of the R1651Q mutation on myosin rod secondary structure or solubility, we observed a striking aggregation phenotype when this mutation was introduced into nonmuscle cells. Our results suggest that each mutation independently affects MYH7b function and structure. Together, these results provide the foundation for further study of a role for MYH7b outside the sarcomere. [ABSTRACT FROM AUTHOR]

Myosin heavy chain 7b (MYH7b) is an evolutionarily ancient member of the sarcomeric myosin family, which typically supports striated muscle function. However, in mammals, alternative splicing prevents MYH7b protein production in cardiac and most skeletal muscles and limits expression to a subset of specialized muscles and certain nonmuscle environments. In contrast, MYH7b protein is abundant in python cardiac and skeletal muscles. Although the MYH7b expression pattern diverges in mammals versus reptiles, MYH7b shares high sequence identity across species. So, it remains unclear how mammalian MYH7b function may differ from that of other sarcomeric myosins and whether human and python MYH7b motor functions diverge as their expression patterns suggest. Thus, we generated recombinant human and python MYH7b protein and measured their motor properties to investigate any species-specific differences in activity. Our results reveal that despite having similar working strokes, the MYH7b isoforms have slower actin-activated ATPase cycles and actin sliding velocities than human cardiac β-MyHC. Furthermore, python MYH7b is tuned to have slower motor activity than human MYH7b because of slower kinetics of the chemomechanical cycle. We found that the MYH7b isoforms adopt a higher proportion of myosin heads in the ultraslow, super-relaxed state compared with human cardiac β-MyHC. These findings are supported by molecular dynamics simulations that predict MYH7b preferentially occupies myosin active site conformations similar to those observed in the structurally inactive state. Together, these results suggest that MYH7b is specialized for slow and energy-conserving motor activity and that differential tuning of MYH7b orthologs contributes to species-specific biological roles. [ABSTRACT FROM AUTHOR]

Patients taking warfarin require frequent international normalized ratio (INR) monitoring in healthcare settings, putting them at increased risk of Coronavirus disease 2019 (COVID-19) exposure during the pandemic. Thus, strategies to limit in-person visits to healthcare facilities were recommended by the Anticoagulation Forum. The objective of this study was to describe the number and types of changes made to anticoagulation therapy as a result of pharmacist intervention during the COVID-19 pandemic. A retrospective chart review of patients included in a primary care COVID-19 anticoagulation intervention was conducted. During this intervention, pharmacists provided individualized recommendations for anticoagulation changes in patients taking warfarin to limit their healthcare facility exposure while also maintaining safe anticoagulation management practices. As a result of pharmacist intervention, 83 (55.7 %) of the 149 patients included in the intervention had changes in anticoagulation including: switching to a direct oral anticoagulant (n = 12), extending the INR monitoring interval (n = 48), switching to home INR monitoring (n = 21), or stopping anticoagulation (n = 2). For those patients who were taking warfarin for the entire 6 months pre- and post-intervention, the total number of healthcare facility and laboratory visits with an INR completed decreased from 8.8 to 6.4 (p < 0.001) per patient without a statistically significant decrease in time in therapeutic range (p = 0.76). This study depicts rapid implementation of a population health-based approach to assess all patients taking warfarin for options to minimize healthcare visits and decrease risk for COVID-19 exposure. Methods to reduce healthcare visit burden while maintaining patient safety should be considered as a regular component of anticoagulation management post-pandemic. [ABSTRACT FROM AUTHOR]

This study examines the negative consequences of perceived isolation and its influence on intentions to travel and visit hospitality businesses. Drawing on compensatory control theory, we explore the multi-faceted effects of perceived isolation (e.g., functional, emotional, and social loss) on subsequent within-domain (e.g., functional loss – functional compensation) and cross-domain (e.g., functional loss – social/emotional compensation) compensatory needs, which eventually drive intentions to seek experiential consumptions. We conduct this research via a two-phase design, each of which involves a national consumer panel of U.S. adults (Phase 1 = 840; Phase 2 = 1087) who have participated in "shelter-in-place"/ "stay-at-home" ordinances during the national lockdown. Across two phases, we find that perceived isolation leads to compensatory needs and intentions for travel and hospitality consumption. Our study also reveals the dynamics between two-phase models regarding the within and cross-domain compensation pathways and the effect on experiential consumption intentions. [ABSTRACT FROM AUTHOR]

Sexual harassment is pervasive globally within hospitality organizations. This conceptual study identifies organizational climate characteristics that make the restaurant work environment unique as compared to other industries. The work environment is based upon keeping the customer happy, includes gender gaps in power structures, emphasis on appearances, entrepreneurial in nature, the physical work environment, and alcohol is served. A framework for sexual harassment training must consider organizational factors, pre/post training, design, and evaluation. The study also provides a framework for sexual harassment training given these distinctive esthetics. [ABSTRACT FROM AUTHOR]

Importance: Latent tuberculosis infection (LTBI) can progress to active tuberculosis disease, causing morbidity and mortality. Objective: To review the evidence on benefits and harms of screening for and treatment of LTBI in adults to inform the US Preventive Services Task Force (USPSTF). Data Sources: PubMed/MEDLINE, Cochrane Library, and trial registries through December 3, 2021; references; experts; literature surveillance through January 20, 2023. Study Selection: English-language studies of LTBI screening, LTBI treatment, or accuracy of the tuberculin skin test (TST) or interferon-gamma release assays (IGRAs). Studies of LTBI screening and treatment for public health surveillance or disease management were excluded. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality; qualitative synthesis of findings; meta-analyses conducted when a sufficient number of similar studies were available. Main Outcomes and Measures: Screening test accuracy; development of active tuberculosis disease, transmission, quality of life, mortality, and harms. Results: A total of 113 publications were included (112 studies; N = 69 009). No studies directly evaluated the benefits and harms of screening. Pooled estimates for sensitivity of the TST were 0.80 (95% CI, 0.74-0.87) at the 5-mm induration threshold, 0.81 (95% CI, 0.76-0.87) at the 10-mm threshold, and 0.60 (95% CI, 0.46-0.74) at the 15-mm threshold. Pooled estimates for sensitivity of IGRA tests ranged from 0.81 (95% CI, 0.79-0.84) to 0.90 (95% CI, 0.87-0.92). Pooled estimates for specificity of screening tests ranged from 0.95 to 0.99. For treatment of LTBI, a large (n = 27 830), good-quality randomized clinical trial found a relative risk (RR) for progression to active tuberculosis at 5 years of 0.35 (95% CI, 0.24-0.52) for 24 weeks of isoniazid compared with placebo (number needed to treat, 112) and an increase in hepatotoxicity (RR, 4.59 [95% CI, 2.03-10.39]; number needed to harm, 279). A previously published meta-analysis reported that multiple regimens were efficacious compared with placebo or no treatment. Meta-analysis found greater risk for hepatotoxicity with isoniazid than with rifampin (pooled RR, 4.22 [95% CI, 2.21-8.06]; n = 7339). Conclusions and Relevance: No studies directly evaluated the benefits and harms of screening for LTBI compared with no screening. TST and IGRAs were moderately sensitive and highly specific. Treatment of LTBI with recommended regimens reduced the risk of progression to active tuberculosis. Isoniazid was associated with higher rates of hepatotoxicity than placebo or rifampin. This systematic review to support the 2023 US Preventive Services Task Force Recommendation Statement on screening for latent tuberculosis infection in adults summarizes published evidence on the benefits and harms of screening for, and treatment of, tuberculosis in asymptomatic persons 18 years or older. [ABSTRACT FROM AUTHOR]

The article discusses research into harm implications of employment discrimination. Referencing a similar study by J. K. Swim and colleagues, published in an issue of "Journal of Personality and Social Psychology," it hypothesizes that individuals are more likely to be in favor of the plaintiff with overt racism in an employment discrimination case. It also explores how said type of discrimination contributes to impaired performance and decline in psychological well-being.

Purpose The posterior superior alveolar (PSA) block injection is one of many techniques used to provide profound anesthesia for invasive dental procedures. This technique has a high success rate but is not without complication risks. The purpose of this study was to determine if pulpal anesthesia of the maxillary second molar could be achieved using a reduced needle depth of 10mm or 5mm compared to the traditional needle depth of 16mm. Methods Sixty participants were asked to participate in three sessions. Each session started with a pre neural response test, followed by one randomized needle depth PSA injection, and ending with a post neural response test. The neural response test consisted of two parts, a cold refrigerant and a dental probe, on the buccal and interproximal surface of the maxillary second molar. After receiving a positive neural response, each participant received a posterior superior alveolar block injection using a short (21mm), 27-gauge dental needle with a randomized needle penetration depth of 16mm, 10mm, or 5mm. A post neural response test consisting of the same two parts as the pre-test was conducted on the maxillary second molar to evaluate for profound anesthesia. Results Positive neural responses were obtained from 100% of the participants (n=167) during the pretests. Study results demonstrated an 85% success rate at the traditional 16mm needle depth and a 93% and 92% success rates for the reduced needle depths of 10mm and 5mm, respectively. Pulpal anesthesia of the maxillary second molar had been achieved at all three needle depths with no statistically significant difference in the rate of success. Furthermore, there were no adverse events observed. Conclusion The reduced needle depth technique showed promise in achieving desired results of pulpal anesthesia with a reduced risk for complications associated with the PSA block injection. Additional studies are recommended to achieve evidence-based support for this reduced needle depth technique. [ABSTRACT FROM AUTHOR]

Striated muscles express an array of sarcomeric myosin motors that are tuned to accomplish specific tasks. Each myosin isoform found in muscle fibers confers unique contractile properties to the fiber in order to meet the demands of the muscle. The sarcomeric myosin heavy chain (MYH) genes expressed in the major cardiac and skeletal muscles have been studied for decades. However, three ancient myosins, MYH7b, MYH15, and MYH16, remained uncharacterized due to their unique expression patterns in common mammalian model organisms and due to their relatively recent discovery in these genomes. This article reviews the literature surrounding these three ancient sarcomeric myosins and the specialized muscles in which they are expressed. Further study of these ancient myosins and how they contribute to the functions of the specialized muscles may provide novel insight into the history of striated muscle evolution. [ABSTRACT FROM AUTHOR]

The design of compounds that can discriminate between closely related target proteins remains a central challenge in drug discovery. Specific therapeutics targeting the highly conserved myosin motor family are urgently needed as mutations in at least six of its members cause numerous diseases. Allosteric modulators, like the myosin-II inhibitor blebbistatin, are a promising means to achieve specificity. However, it remains unclear why blebbistatin inhibits myosin-II motors with different potencies given that it binds at a highly conserved pocket that is always closed in blebbistatin-free experimental structures. We hypothesized that the probability of pocket opening is an important determinant of the potency of compounds like blebbistatin. To test this hypothesis, we used Markov state models (MSMs) built from over 2 ms of aggregate molecular dynamics simulations with explicit solvent. We find that blebbistatin's binding pocket readily opens in simulations of blebbistatin-sensitive myosin isoforms. Comparing these conformational ensembles reveals that the probability of pocket opening correctly identifies which isoforms are most sensitive to blebbistatin inhibition and that docking against MSMs quantitatively predicts blebbistatin binding affinities (R²=0.82). In a blind prediction for an isoform (Myh7b) whose blebbistatin sensitivity was unknown, we find good agreement between predicted and measured IC50s (0.67 µM vs. 0.36 µM). Therefore, we expect this framework to be useful for the development of novel specific drugs across numerous protein targets. [ABSTRACT FROM AUTHOR]

Miocene basins of the Lake Mead region (southwestern United States) contain a well-exposed record of rifting and the evolving paleogeography of the eastern central Basin and Range. The middle Miocene Horse Spring Formation and red sandstone unit allow for detailed stratigraphic, chronostratigraphic, and structural analysis for better understanding the geologic history of extension in this region. We present new data from the White Basin and Lovell Wash areas (Nevada) to interpret the evolution of faulting, basin fill, and paleogeography. We conclude that tectonics strongly influenced sedimentation and hypothesize that climate may have played a secondary but important role in creating stratigraphic variations. Deposited from 14.5 to 13.86 Ma, the microbialitic Bitter Ridge Limestone Member of the Horse Spring Formation, the stratigraphically lowest unit in this study, records a widespread shallow and uniform lake which had moderate and steady sedimentation rates, both of which were controlled by a few faults. The persistent lake was broken up by fault reorganization followed by deposition of the highly variable fluviallacustrine facies of the Lovell Wash Member from 13.86 to 12.7 Ma. During this time, faulting shifted from the northeast-trending, oblique normal left-lateral White Basin fault to the northwest-trending, normal Muddy Peak fault and other smaller northwest-trending faults. The lower and middle portions of the red sandstone unit, 12.7-11.4 Ma, record an increase in the sedimentation rate of basin fill near the Muddy Peak fault as well as the return to widespread lacustrine conditions. Sedimentation and faulting slowed during deposition of the uppermost red sandstone unit, but some deformation occurred post--11.4 Ma. This study records basin-fill evolution including variations in depositional environments laterally and vertically, documents changes in the location and magnitude of faulting, supports earlier work that hypothesized faulting proceeded in discrete westward steps across the Lake Mead area, and helps constrain the paleogeographic and tectonic evolution of the region. [ABSTRACT FROM AUTHOR]

Objective: Hydroxychloroquine (HCQ) is commonly used in the treatment of various autoimmune diseases related to its many benefits and favorable safety profile. Although HCQ retinopathy was considered to be uncommon, a prevalence of 7.5% was described in a recent study making early detection critical. The most updated screening guidelines by the American Academy of Ophthalmology were published in 2016; however, it lacked pediatric-specific recommendations and the overall compliance with screening guidelines was poor in previous studies. We developed a quality improvement (QI) initiative aiming to create institutional screening recommendations. Additionally, to increase eye screening in pediatric rheumatology clinic for patients receiving HCQ from 65% to 85% in 12 months and to sustain that rate for at least 6 months. Methods: We formed a multidisciplinary team of pediatric rheumatologists and ophthalmologists, clinical pharmacist, clinic nurses, QI specialist, quality data technician and administrative staff. We included patients receiving HCQ and who were evaluated at Nationwide Children's Hospital rheumatology clinic. A key driver diagram was formulated to identify barriers to compliance and determine possible interventions. Main interventions included summarizing screening guidelines in a step by step algorithm, increasing awareness of these guidelines among patients and providers, improving collaboration and communication with ophthalmologists, and initiating pre-visit planning. Results: Baseline performance data included 164 patients. Fifty-four (33%) of those patients were at high risk for HCQ retinopathy. Of them, 50% were on HCQ dose of >5 mg/kg/day and 31.5% had been taking HCQ for ≥5 years. Two center line shifts were noticed over the course of the project. The target of 85% compliance was reached in February 2019 and was sustained until December 2019. Conclusions: Our study highlights the importance of interdisciplinary communication to increase awareness of screening guidelines among medical providers and patients. Pre-visit planning played a major role in identifying patients and opportunities for optimizing eye screening in patients at risk for HCQ retinopathy. Collaboration between rheumatologists and ophthalmologists is crucial in managing patients on HCQ. The implementation of same-day eye screening allowed this collaboration to be more efficient. Future efforts are being directed at monitoring and improving utilization of the effective interventions. [ABSTRACT FROM AUTHOR]