Rethinking the physiological cross-sectional area of skeletal muscle reveals the mechanical advantage of pennation.

The shape of skeletal muscle varies remarkably-with important implications for locomotor performance. In many muscles, the fibres are arranged at an angle relative to the tendons' line of action, termed the pennation angle. These pennate muscles allow more sarcomeres to be packed side by side, enabling the muscle to generate higher maximum forces for a given muscle size.

Durlobactam to boost the clinical utility of standard of care β-lactams against lung disease.

β-Lactams present several desirable pharmacodynamic features leading to the rapid eradication of many bacterial pathogens. Imipenem (IPM) and cefoxitin (FOX) are injectable β-lactams recommended during the intensive treatment phase of pulmonary infections caused by (Mab). However, their potency against Mab is many-fold lower than against Gram-positive and Gram-negative pathogens for which they were optimized, putting into question their clinical utility.

PRDX6 contributes to selenocysteine metabolism and ferroptosis resistance.

Selenocysteine (Sec) metabolism is crucial for cellular function and ferroptosis prevention and begins with the uptake of the Sec carrier, selenoprotein P (SELENOP). Following uptake, Sec released from SELENOP is metabolized via selenocysteine lyase (SCLY), producing selenide, a substrate for selenophosphate synthetase 2 (SEPHS2), which provides the essential selenium donor, selenophosphate (HSePO), for the biosynthesis of the Sec-tRNA. Here, we discovered an alternative pathway in Sec metabolism mediated by peroxiredoxin 6 (PRDX6), independent of SCLY.

Multidrug tolerance conferred by loss-of-function mutations in anti-sigma factor RshA of .

Low-level drug resistance in noncanonical pathways can constitute steppingstones toward acquisition of high-level on-target resistance mutations in the clinic. To capture these intermediate steps in (Mab), we performed classic mutant selection experiments with moxifloxacin at twofold its minimum inhibitory concentration (MIC) on solid medium. We found that low-level resistance emerged reproducibly as loss-of-function mutations in RshA (MAB_3542c), an anti-sigma factor that negatively regulates activity of SigH, which orchestrates a response to oxidative stress in mycobacteria.

Effects of altered contractile environment on muscle shape change in the human triceps surae.

Skeletal muscles change shape when they contract. Current insights into the effects of shape change on muscle function have primarily come from experiments on isolated muscles operating at maximal activation levels. However, when muscles contract and change shape, the forces they apply onto surrounding muscles will also change.

Predictive musculoskeletal simulations reveal the mechanistic link between speed, posture and energetics among extant mammals.

An unusual pattern among the scaling laws in nature is that the fastest animals are neither the largest, nor the smallest, but rather intermediately sized. Because of the enormous diversity in animal shape, the mechanisms underlying this have long been difficult to determine. To address this, we challenge predictive human musculoskeletal simulations, scaled in mass from the size of a mouse (0.

Implementing a Care-Based Nursing Workforce Model: Implications for Missed Care, Teamwork, and Satisfaction.

Background: Nursing care delivery models may serve as a significant factor contributing to nurse satisfaction, frequency of missed care, and patient outcomes.

Local Problem: The nursing leadership team at our institution sought to determine if an adaptation of our primary registered nurse (RN) nursing model would enhance satisfaction of bedside nurses and care of patients.

Methods: An improvement study introducing a care-based delivery model was implemented between January 2023 and January 2024 on a medical-surgical neurology/spinal unit at our organization.

Toward better cures for lung disease.

SUMMARYThe opportunistic pathogen (Mab) causes fatal lung infections that bear similarities-and notable differences-with tuberculosis (TB) pulmonary disease. In contrast to TB, no antibiotic is formally approved to treat Mab disease, there is no reliable cure, and the discovery and development pipeline is incredibly thin. Here, we discuss the factors behind the unsatisfactory cure rates of Mab disease, namely intrinsic resistance and persistence of the pathogen, and the use of underperforming, often parenteral and toxic, repurposed drugs.

Using Brainstorming and Affinity Diagramming for Recommending a Care-Based Nursing Workforce Model.

Background: Nursing care delivery models influence nursing workload.

Problem: Poorly designed nursing workforce models may lead to lack of satisfaction in practice, inability to recruit staff, and nursing turnover.

Approach: This paper describes a process that our team undertook to evaluate one nursing unit's nursing care delivery model and provides a recommendation for a nursing workforce model that ensures practice to top of scope while maintaining a balanced workload.

HIV PrEP Coverage Among Black Adults: A Concept Analysis of the Inequities, Disparities, and Implications.

Background: Significant racial disparities exist in HIV pre-exposure prophylaxis (PrEP) coverage in the United States (U.S), with Black individuals experiencing seven times higher new HIV infection rates compared to their White counterparts. Despite being the highest priority population at risk for HIV, Black adults have the lowest PrEP coverage, impacting the overall progress toward meeting the ending the HIV epidemic (EHE) goals in the U.

Splenic marginal zone B cells restrict Mycobacterium tuberculosis infection by shaping the cytokine pattern and cell-mediated immunity.

Understanding the role of B cells in tuberculosis (TB) is crucial for developing new TB vaccines. However, the changes in B cell immune landscapes during TB and their functional implications remain incompletely explored. Using high-dimensional flow cytometry to map the immune landscape in response to Mycobacterium tuberculosis (Mtb) infection, our results show an accumulation of marginal zone B (MZB) cells and other unconventional B cell subsets in the lungs and spleen, shaping an unconventional B cell landscape.

Broad-Spectrum In Vitro Activity of α-Aroyl--Aryl-Phenylalanine Amides against Non-Tuberculous Mycobacteria and Comparative Analysis of RNA Polymerases.

This study investigates the in vitro activity of α-aroyl--aryl-phenylalanine amides (AAPs), previously identified as antimycobacterial RNA polymerase (RNAP) inhibitors, against a panel of 25 non-tuberculous mycobacteria (NTM). The compounds, including the hit compound MMV688845, were selected based on their structural diversity and previously described activity against mycobacteria. Bacterial strains, including the complex, complex, and other clinically relevant NTM, were cultured and subjected to growth inhibition assays.

Persistent glossopharyngeal nerve respiratory discharge patterns after ponto-medullary transection.

Shape and size of the nasopharyngeal airway is controlled by muscles innervated facial, glossopharyngeal, vagal, and hypoglossal cranial nerves. Contrary to brainstem networks that drive facial, vagal and hypoglossal nerve activities (FNA, VNA, HNA) the discharge patterns and origins of glossopharyngeal nerve activity (GPNA) remain poorly investigated. Here, an in situ perfused brainstem preparation (n=19) was used for recordings of GPNA in relation to phrenic (PNA), FNA, VNA and HNA.

Preclinical murine models for the testing of antimicrobials against Mycobacterium abscessus pulmonary infections: Current practices and recommendations.

Mycobacterium abscessus, a rapidly growing nontuberculous mycobacterium, is increasingly recognized as an important pathogen of the human lung, disproportionally affecting people with cystic fibrosis (CF) and other susceptible individuals with non-CF bronchiectasis and compromised immune functions. M. abscessus infections are extremely difficult to treat due to intrinsic resistance to many antibiotics, including most anti-tuberculous drugs.

Effects of passive ankle exoskeletons on neuromuscular function during exaggerated standing sway.

Wearable robotic exoskeletons designed to assist human movement should integrate with the neuromusculoskeletal system. This means assisting movement while not perturbing motor control. We sought to test if passive ankle exoskeletons, which have been shown to successfully assist human gait, affect neuromuscular control of an exaggerated anterior-posterior standing sway task.

Rifampicin has no role in treatment of complex pulmonary disease and bactericidal sterilising drugs are needed: a viewpoint.

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A pairwise approach to revitalize β-lactams for the treatment of TB.

The dual β-lactam approach has been successfully applied to overcome target redundancy in nontuberculous mycobacteria. Surprisingly, this approach has not been leveraged for despite the high conservation of peptidoglycan synthesis. Through a comprehensive screen of oral β-lactam pairs, we have discovered that cefuroxime strongly potentiates the bactericidal activity of tebipenem and sulopenem-advanced clinical candidates-and amoxicillin, at concentrations achieved clinically.

Comparison of Alabama Nurse Experiences Between Practice Areas During the Early COVID-19 Pandemic.

Background: According to the Total Worker Health framework, safety culture including a reasonable workload among healthcare workers is essential to the security and well-being of patients, staff, and healthcare organizations. Evaluating the impact of the pandemic on the nursing workforce in different practice areas is critical for addressing workforce health and sustainability. The purpose of this study was to compare work and selfcare experiences among Alabama nurses between practice areas and the early pandemic years (2020 vs.

Mild untreated hypercholesterolaemia affects mechanical properties of the Achilles tendon but not gastrocnemius muscle.

Tendon xanthoma and altered mechanical properties have been demonstrated in people with familial hypercholesterolaemia. However, it is unclear whether mild, untreated hypercholesterolaemia alters musculotendinous mechanical properties and muscle architecture. We conducted a case-control study of adults aged 50 years and over, without lower limb injury or history of statin medication.

Therapeutic developments for tuberculosis and nontuberculous mycobacterial lung disease.

Tuberculosis (TB) drug discovery and development has undergone nothing short of a revolution over the past 20 years. Successful public-private partnerships and sustained funding have delivered a much-improved understanding of mycobacterial disease biology and pharmacology and a healthy pipeline that can tolerate inevitable attrition. Preclinical and clinical development has evolved from decade-old concepts to adaptive designs that permit rapid evaluation of regimens that might greatly shorten treatment duration over the next decade.