Modeling Insights into Potential Mechanisms of Opioid-Induced Respiratory Depression within Medullary and Pontine Networks.

The opioid epidemic is a pervasive health issue and continues to have a drastic impact on the United States. This is primarily because opioids cause respiratory suppression and the leading cause of death in opioid overdose is respiratory failure (, opioid-induced respiratory depression, OIRD). Opioid administration can affect the frequency and magnitude of inspiratory motor drive by activating μ-opioid receptors that are located throughout the respiratory control network in the brainstem.

Resilience and charge-dependent fibrillation of functional amyloid: Interactions of Pseudomonas biofilm-associated FapB and FapC amyloids.

FapC and FapB are biofilm-associated amyloids involved in the virulence of Pseudomonas and other bacteria. We herein demonstrate their exceptional thermal and chemical resilience, suggesting that their biofilm structures might withstand standard sterilization, thereby contributing to the persistence of Pseudomonas aeruginosa infections. Our findings also underscore the impact of environmental factors on functional amyloid in Pseudomonas (Fap) proteins, suggesting that orthologs in different Pseudomonas strains adapt to specific environments and roles.

Scp776, A Novel IGF-1 Fusion Protein for Acute Therapy to Promote Escape From Apoptosis in Tissues Affected by Ischemic Injury: 2 Randomized Placebo-Controlled Phase 1 Studies in Healthy Adults.

Apoptosis is a major driver of cell loss and infarct expansion in ischemic injuries such as acute ischemic stroke (AIS) and acute myocardial infarction (AMI). Insulin-like growth factor-1 (IGF-1) can mitigate cell death and potentiate recovery following acute ischemic injury, but short half-life and nonspecificity limit its therapeutic potential. Scp776 is an IGF-1 fusion protein designed to target damaged tissue and promote apoptosis escape and is in clinical development as an acute therapy for AIS and AMI.

Functional Amyloids: The Biomaterials of Tomorrow?

Functional amyloid (FAs), particularly the bacterial proteins CsgA and FapC, have many useful properties as biomaterials: high stability, efficient, and controllable formation of a single type of amyloid, easy availability as extracellular material in bacterial biofilm and flexible engineering to introduce new properties. CsgA in particular has already demonstrated its worth in hydrogels for stable gastrointestinal colonization and regenerative tissue engineering, cell-specific drug release, water-purification filters, and different biosensors. It also holds promise as catalytic amyloid; existing weak and unspecific activity can undoubtedly be improved by targeted engineering and benefit from the repetitive display of active sites on a surface.

A scoping review of health system guidelines for pharmacist responsibilities when dispensing opioids.

Introduction: Prescription opioid use and evidence of the harm caused by these medicines has increased over the past 20-30 years. Despite a number of system level interventions, the opioid crisis has not yet resolved in Australia or globally. Pharmacists are increasingly required to take a proactive, clinical role to fulfil their responsibility for patient outcomes relating to both medication efficacy and safety.

Macrophage-Immunomodulatory Actions of Bovine Whey Protein Isolate, Glycomacropeptide, and Their In Vitro and In Vivo Digests.

Whey protein isolate (WPI) consists of an array of proteins and peptides obtained as a byproduct of the cheesemaking process. Research suggests that WPI, along with its peptides such as glycomacropeptide (GMP), possesses immunomodulatory properties. These properties hold potential for alleviating the adverse effects of inflammatory conditions such as inflammatory bowel disease.

Effects of Whey Protein Supplementation on Inflammatory Marker Concentrations in Older Adults.

Although whey protein isolate (WPI) has been shown to be immunomodulatory, its ability to modulate production of a broad array of inflammatory markers has not previously been investigated in healthy adults. We investigated the effects of daily supplementation with 35 g of WPI for 3 weeks on inflammatory marker concentrations in the blood serum and feces of 14 older adult subjects (mean age: 59). Serum was analyzed using a multiplex assay to quantify the cytokines IFN-γ, IL-1β, IL-1RA, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL-17A and TNF-α.

Alzheimer's Progenitor Amyloid-β Targets and Dissolves Microbial Amyloids and Impairs Biofilm Function.

Alzheimer's disease (AD) is a leading form of dementia where the presence of extra-neuronal plaques of Amyloid-β (Aβ) is a pathological hallmark. However, Aβ peptide is also observed in the intestinal tissues of AD patients and animal models. In this study, it is reported that Aβ monomers can target and disintegrate microbial amyloids of FapC and CsgA formed by opportunistic gut pathogens, Pseudomonas aeruginosa and Escherichia coli, explaining a potential role of Aβ in the gut-brain axis.

Who Gains Mental Health Benefits from Work Autonomy? The Roles of Gender and Occupational Class.

In recent years, improving work autonomy as an important priority in the UK labour market has been shown to enhance employee mental health and well-being. However, previous theories and empirical studies have paid little attention to the intersectional inequalities in the mental health benefits of work autonomy, preventing us from gaining a comprehensive understanding of the mental consequences of work autonomy. By integrating literature from occupational psychology, gender and social class, this study develops theoretical hypotheses regarding whether and how the mental health benefits of work autonomy vary alongside the intersectional axes of gender and occupational class and tests these hypotheses using long-term panel data in the UK (2010-2021).

Sequence-targeted Peptides Divert Functional Bacterial Amyloid Towards Destabilized Aggregates and Reduce Biofilm Formation.

Functional bacterial amyloid provides structural stability in biofilm, making it a promising target for anti-biofilm therapeutics. Fibrils formed by CsgA, the major amyloid component in E. coli are extremely robust and can withstand very harsh conditions.

The economic impact of the COVID-19 pandemic on ethnic minorities in Manchester: lessons from the early stage of the pandemic.

This review summarizes the economic impacts of the pandemic on ethnic minorities, focusing on the city of Manchester. It utilizes multiple reporting sources to explore various dimensions of the economic shock in the UK, linking this to studies of pre-COVID-19 economic and ethnic composition in Manchester and in the combined authority area of Greater Manchester. We then make inferences about the pandemic's short-term impact specific to the city region.

Respiratory therapies for Amyotrophic Lateral Sclerosis: A state of the art review.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition noteworthy for upper and lower motor neuron death. Involvement of respiratory motor neuron pools leads to progressive pathology. These impairments include decreases in neural activation and muscle coordination, progressive airway obstruction, weakened airway defenses, restrictive lung disease, increased risk of pulmonary infections, and weakness and atrophy of respiratory muscles.

Exploring inspiratory occlusion metrics to assess respiratory drive in patients under acute intermittent hypoxia.

Patients living with Amyotrophic Lateral Sclerosis (ALS) experience respiratory weakness and, eventually, failure due to inspiratory motor neuron degeneration. Routine pulmonary function tests (e.g.

Hospital length of stay for COVID-19 patients: Data-driven methods for forward planning.

Background: Predicting hospital length of stay (LoS) for patients with COVID-19 infection is essential to ensure that adequate bed capacity can be provided without unnecessarily restricting care for patients with other conditions. Here, we demonstrate the utility of three complementary methods for predicting LoS using UK national- and hospital-level data.

Method: On a national scale, relevant patients were identified from the COVID-19 Hospitalisation in England Surveillance System (CHESS) reports.

Length of Stay in ICU of Covid-19 patients in England, March - May 2020.

Introduction: Length of Stay (LoS) in Intensive Care Units (ICUs) is an important measure for planning beds capacity during the Covid-19 pandemic. However, as the pandemic progresses and we learn more about the disease, treatment and subsequent LoS in ICU may change.

Objectives: To investigate the LoS in ICUs in England associated with Covid-19, correcting for censoring, and to evaluate the effect of known predictors of Covid-19 outcomes on ICU LoS.

Intra-Arterial, but Not Intrathecal, Baclofen and Codeine Attenuates Cough in the Cat.

Centrally-acting antitussive drugs are thought to act solely in the brainstem. However, the role of the spinal cord in the mechanism of action of these drugs is unknown. The purpose of this study was to determine if antitussive drugs act in the spinal cord to reduce the magnitude of tracheobronchial (TB) cough-related expiratory activity.

Hierarchical Modelling of COVID-19 Death Risk in India in the Early Phase of the Pandemic.

We improve upon the modelling of India's pandemic vulnerability. Our model is multidisciplinary and recognises the nested levels of the epidemic. We create a model of the risk of severe COVID-19 and death, instead of a model of transmission.

The Development Impacts of COVID-19 at Home and Abroad: Politics and Implications of Government Action.

What is COVID-19's impact on development? What lessons can be drawn from development studies regarding the effects of and recovery from COVID-19? The unprecedented scale and scope of government interventions carry implications at all levels: global, national, and local. In this introduction, our team of Editors underline the importance of systematic substantive study to further knowledge acquisition, and rigorous global-, national-, or context-specific evaluation to inform evidence-based policymaking. The 12 articles summarised here capture these values and sense of "high quality".

Feasible Implementation Strategies for Improving Vocabulary Knowledge of High-Risk Preschoolers: Results From a Cluster-Randomized Trial.

Purpose Many children begin school with limited vocabularies, placing them at a high risk of academic difficulties. The goal of this study was to examine the effects of a vocabulary intervention program, , designed to improve vocabulary knowledge of at-risk preschool children. Method Twenty-four early-childhood classrooms were enrolled in a cluster-randomized design to evaluate the effects of a revised curriculum.

Upfront resection versus neoadjuvant therapy for T1/T2 pancreatic cancer.

Background: The role of neoadjuvant therapy remains controversial for resectable pancreatic neoplasms. We evaluated treatment outcomes for T1/T2 tumors.

Methods: Retrospective study of patients with T1/T2 (Stage I-II) pancreatic cancer within the NCDB.

Postantibiotic effect and postantibiotic sub-MIC effect of LTX-109 and mupirocin on Staphylococcus aureus blood isolates.

Unlabelled: The development of new synthetic antimicrobial peptides like LTX-109 provides a new class of drugs for the treatment of Staphylococcus aureus infections. We evaluated LTX-109 and mupirocin for pharmacodynamic parameters against 10 methicillin-resistant S. aureus isolates.

Well-Being During Recession in the UK.

This article explores the impact of the recent recession on the well-being of the UK working age population by comparing two measures of well-being. One is a measure of evaluative subjective well-being, a measure which previous research has shown to be stable in the UK throughout the economic crisis. The second is a different but complementary measure of positive psychological health.

Attention demands of language production in adults who stutter.

Objective: We investigated whether language production is atypically resource-demanding in adults who stutter (AWS) versus typically-fluent adults (TFA).

Methods: Fifteen TFA and 15 AWS named pictures overlaid with printed Semantic, Phonological or Unrelated Distractor words while monitoring frequent low tones versus rare high tones. Tones were presented at a short or long Stimulus Onset Asynchrony (SOA) relative to picture onset.

LTX-109 is a novel agent for nasal decolonization of methicillin-resistant and -sensitive Staphylococcus aureus.

Nasal decolonization has a proven effect on the prevention of severe Staphylococcus aureus infections and the control of methicillin-resistant S. aureus (MRSA). However, rising rates of resistance to antibiotics highlight the need for new substances for nasal decolonization.