Utility of Methicillin-Resistant Staphylococcus aureus Nasal PCR Testing in Pediatric Patients With Suspected Respiratory Infections.

Observational studies in adults suggest nasal methicillin-resistant Staphylococcus aureus (MRSA) swabs have a high negative predictive value (NPV) for ruling out MRSA pneumonia, however, pediatric data are limited. This retrospective study of 505 pediatric patients found a 99.8% NPV among children with suspected respiratory infections.

Cystic fibrosis airway inflammation enables elexacaftor/tezacaftor/ivacaftor-mediated rescue of N1303K CFTR mutation.

Rescue of N1303K CFTR by highly effective modulator therapy (HEMT) is enabled by CF airway inflammation. These findings suggest that evaluation of HEMT for rare CFTR mutations must be performed under inflammatory conditions relevant to CF airways. https://bit.ly/3tTcoJE.

Reimagining From Abroad: Speech-Language Pathologists as Interprofessional Partners Supporting Justice-Involved Youth in America.

PURPOSE: With application to the United States, this tutorial explores barriers in the American juvenile justice system for justice-involved youth (JIY) with cognitive-communication disorders (CCDs). It outlines models from abroad and reimagines the American juvenile justice system to include speech-language pathologists (SLPs) as interprofessional practice partners. METHOD: Interprofessional (i.e., criminal justice, speech-language pathology) literature from the United States and overseas is reviewed and summarized to explain the American juvenile justice system, outline areas of concern for youth with CCDs, and describe potential solutions. RESULTS: The application of speech-language pathology services within the juvenile justice system is explained and visually depicted. This framework was informed by intervention models and approaches from international examples. CONCLUSIONS: There is an opportunity to embed speech-language pathology services from intake into court action and through disposition for JIY with cognitive-communication impairments. This includes interprofessional education and development, SLPs providing direct intervention, and multidisciplinary screening efforts. Speech-language pathologists as interprofessional advocates and practice partners can improve life chances and outcomes for youth with CCDs in the juvenile justice system.

Dietary Intake and Arterial Stiffness in Children and Adolescents: A Systematic Review.

Arterial stiffness is a risk factor for cardiovascular disease that is affected by diet. However, research understanding how these dietary risk factors are related to arterial stiffness during childhood is limited. The purpose of this review was to determine whether various dietary factors were associated with arterial stiffness in the pediatric population. Five databases were systematically searched. Intervention studies, cross-sectional and cohort studies were included that investigated nutrient or food intake and outcomes of arterial stiffness, primarily measured by pulse wave velocity (PWV) and augmentation index (AIx), in the pediatric population (aged 0-18 years). A final 19 studies (six intervention and 13 observational) were included. Only two intervention studies, including a vitamin D and omega-3 supplementation trial, found protective effects on PWV and AIx in adolescents. Findings from observational studies were overall inconsistent and varied. There was limited evidence to indicate a protective effect of a healthy dietary pattern on arterial stiffness and an adverse effect of total fat intake, sodium intake and fast-food consumption. Overall, results indicated that some dietary factors may be associated with arterial stiffness in pediatric populations; however, inconsistencies were observed across all study designs. Further longitudinal and intervention studies are warranted to confirm the potential associations found in this review.

The Dangers of Short-Term Confinement: Indicators of Safety Risks Among Individuals in Jail.

Guided by the premise that an individual's safety may be more at risk when their routines, personal attributes, or lack of guardianship influence their opportunity for exposure to violence, we examined the factors that influenced victimization risks and safety perceptions among a representative sample of respondents incarcerated at a large Midwestern jail. Results showed that vulnerable individuals such as those who were victimized prior to their incarceration, and those who antagonized others such as those who perpetrated assault, were threatened more often, were more at risk of assault victimization, and perceived more dangerous conditions. Conversely, females and individuals with greater self-control were less likely to have experienced victimization and generally felt safer in jail. Our results illustrate the importance of identifying and protecting individuals who might experience greater safety risks during jail incarceration and should be interpreted alongside research and policy aimed at improving safety and welfare within correctional institutions.

Muscle Protein Synthesis Responses Following Aerobic-Based Exercise or High-Intensity Interval Training with or Without Protein Ingestion: A Systematic Review.

BACKGROUND: Systematic investigation of muscle protein synthesis (MPS) responses with or without protein ingestion has been largely limited to resistance training. OBJECTIVE: This systematic review determined the capacity for aerobic-based exercise or high-intensity interval training (HIIT) to stimulate post-exercise rates of MPS and whether protein ingestion further significantly increases MPS compared with placebo. METHODS: Three separate models analysed rates of either mixed, myofibrillar, sarcoplasmic, or mitochondrial protein synthesis (PS) following aerobic-based exercise or HIIT: Model 1 (n = 9 studies), no protein ingestion; Model 2 (n = 7 studies), peri-exercise protein ingestion with no placebo comparison; Model 3 (n = 14 studies), peri-exercise protein ingestion with placebo comparison. RESULTS: Eight of nine studies and all seven studies in Models 1 and 2, respectively, demonstrated significant post-exercise increases in either mixed or a specific muscle protein pool. Model 3 observed significantly greater MPS responses with protein compared with placebo in either mixed or a specific muscle fraction in 7 of 14 studies. Seven studies showed no difference in MPS between protein and placebo, while three studies reported no significant increases in mitochondrial PS with protein compared with placebo. CONCLUSION: Most studies reporting significant increases in MPS were confined to mixed and myofibrillar PS that may facilitate power generating capacity of working skeletal muscle with aerobic-based exercise and HIIT. Only three of eight studies demonstrated significant increases in mitochondrial PS post-exercise, with no further benefits of protein ingestion. This lack of change may be explained by the acute analysis window in most studies and apparent latency in exercise-induced stimulation of mitochondrial PS.

Outcomes of Upper Gastrointestinal Bleeding in Hospitalized Patients With Generalized Anxiety Disorder.

Background Upper gastrointestinal bleeding (UGIB) has a high morbidity and mortality. Social deprivation is a risk factor for UGIB and is associated with anxiety. The primary pharmaceutical therapeutic agents for anxiety are selective serotonin reuptake inhibitors. Anxiety is prevalent in the general population and generalized anxiety disorder (GAD) is a common form of anxiety. This study explores the impact of GAD on the outcomes of adult patients hospitalized with UGIB. Methods Adult UGIB patients were selected utilizing the National (Nationwide) Inpatient Sample database from year 2014 and International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. The outcomes of UGIB patients with and without GAD were investigated. The outcomes explored include inpatient mortality, hypotension/shock, acute renal failure, acute hepatic failure, acute respiratory failure and acute myocardial infarction. A multivariate logistic regression analysis was used to determine if GAD is an independent predictor of the outcomes. Results Among 19,850 UGIB patients studied, 2357 had comorbid GAD. GAD was identified as a risk factor for acute renal failure (adjusted odds ratio [aOR] 1.37, 95% confidence interval [CI] 1.30-1.57, p < 0.05) and inpatient mortality (aOR 1.50, 95% CI 1.01-2.06, p < 0.05). The aORs of hypotension/shock, acute hepatic failure, acute respiratory failure and acute myocardial infarction were not statistically significant. Conclusion UGIB patients with comorbid GAD are at elevated risk of inpatient mortality and acute renal failure. These results may gain increasing relevance as GAD prevalence has increased since the start of the coronavirus disease 2019 (COVID-19) pandemic.

Incorporating Oral Health Considerations for Medication Management in Care Transitions.

Transitions of care involve multifaceted considerations for patients, which can pose significant challenges if factors like oral health are overlooked when evaluating medication management. This article examines how oral health factors should be considered in medication management of patients who may be at risk for hospital readmission. This article also explores successes and challenges of a pharmacy consult service integrated into a dental clinic practice, and the opportunities within that setting to improve overall patient outcomes including those related to care transitions.

The Impact of the 2008 Council of Emergency Residency Directors (CORD) Panel on Emergency Medicine Resident Diversity.

BACKGROUND: In 2008, the Council of Emergency Medicine Residency Directors (CORD) developed a set of recruitment strategies designed to increase the number of under-represented minorities (URMs) in Emergency Medicine (EM) residency. OBJECTIVES: We conducted a survey of United States (US) EM residency program directors to: describe the racial and ethnic composition of residents; ascertain whether each program had instituted CORD recruitment strategies; and identify program characteristics associated with recruitment of a high proportion of URM residents. METHODS: The survey was distributed to accredited, nonmilitary US EM residency programs during 2013. Programs were dichotomized into high URM and low URM by the percentage of URM residents. High- and low-URM programs were compared with respect to size, geography, percentage of URM faculty, importance assigned to common applicant selection criteria, and CORD recruitment strategies utilized. Odds ratios and 95% confidence limits were calculated. RESULTS: Of 154 residency programs, 72% responded. The median percentage of URM residents per program was 9%. Only 46% of EM programs engaged in at least two recruitment strategies. Factors associated with higher resident diversity (high-URM) included: diversity of EM faculty (high-URM) (odds ratio [OR] 5.3; 95% confidence interval [CI] 2.1-13.0); applicant's URM status considered important (OR 4.9; 95% CI 2.1-11.9); engaging in pipeline activities (OR 4.8; 95% CI 1.4-15.7); and extracurricular activities considered important (OR 2.6; 95% CI 1.2-6.0). CONCLUSION: Less than half of EM programs have instituted two or more recruitment strategies from the 2008 CORD diversity panel. EM faculty diversity, active pipeline programs, and attention paid to applicants' URM status and extracurricular activities were associated with higher resident diversity.

Mitochondrial import efficiency of ATFS-1 regulates mitochondrial UPR activation.

To better understand the response to mitochondrial dysfunction, we examined the mechanism by which ATFS-1 (activating transcription factor associated with stress-1) senses mitochondrial stress and communicates with the nucleus during the mitochondrial unfolded protein response (UPR(mt)) in Caenorhabditis elegans. We found that the key point of regulation is the mitochondrial import efficiency of ATFS-1. In addition to a nuclear localization sequence, ATFS-1 has an N-terminal mitochondrial targeting sequence that is essential for UPR(mt) repression. Normally, ATFS-1 is imported into mitochondria and degraded. However, during mitochondrial stress, we found that import efficiency was reduced, allowing a percentage of ATFS-1 to accumulate in the cytosol and traffic to the nucleus. Our results show that cells monitor mitochondrial import efficiency via ATFS-1 to coordinate the level of mitochondrial dysfunction with the protective transcriptional response.

Protective coupling of mitochondrial function and protein synthesis via the eIF2α kinase GCN-2.

Cells respond to defects in mitochondrial function by activating signaling pathways that restore homeostasis. The mitochondrial peptide exporter HAF-1 and the bZip transcription factor ATFS-1 represent one stress response pathway that regulates the transcription of mitochondrial chaperone genes during mitochondrial dysfunction. Here, we report that GCN-2, an eIF2α kinase that modulates cytosolic protein synthesis, functions in a complementary pathway to that of HAF-1 and ATFS-1. During mitochondrial dysfunction, GCN-2-dependent eIF2α phosphorylation is required for development as well as the lifespan extension observed in Caenorhabditis elegans. Reactive oxygen species (ROS) generated from dysfunctional mitochondria are required for GCN-2-dependent eIF2α phosphorylation but not ATFS-1 activation. Simultaneous deletion of ATFS-1 and GCN-2 compounds the developmental defects associated with mitochondrial stress, while stressed animals lacking GCN-2 display a greater dependence on ATFS-1 and stronger induction of mitochondrial chaperone genes. These findings are consistent with translational control and stress-dependent chaperone induction acting in complementary arms of the UPR(mt).

Mitochondrial protein quality control during biogenesis and aging.

Mitochondrial dysfunction has long been associated with the aging process and the onset of numerous diseases. Regulation of the complex protein-folding environment within the organelle is essential for maintaining efficient metabolic output. Over time, dysregulation of protein homeostasis arises through stress induced by the accumulation of reactive oxygen species and mutations in the mitochondrial genome introduced during replication. To preserve organelle function during biogenesis, remodeling and stress, quality control of mitochondrial proteins must be monitored by molecular chaperones and proteases stationed in the four compartments of the organelle. Here, we review mitochondrial protein quality control with a focus on organelle biogenesis and aging.

Dislocation of an endoplasmic reticulum membrane glycoprotein involves the formation of partially dislocated ubiquitinated polypeptides.

Accumulation of improperly folded polypeptides in the endoplasmic reticulum (ER) can trigger a stress response that leads to the export of aberrant proteins into the cytosol and their ultimate proteasomal degradation. Human cytomegalovirus encodes a type I glycoprotein, US11, that binds to nascent MHC class I heavy chain molecules and causes their dislocation from the ER to the cytosol where they are degraded by the proteasome. Examination of US11-mediated class I degradation has identified a host of cellular proteins involved in the dislocation reaction, including the cytosolic AAA ATPase p97, the membrane protein Derlin-1, and the E3 ubiquitin ligase Sel1L. However, the intermediate steps occurring between the initiation of dislocation and full extraction of the misfolded substrate into the cytosol are not known. We demonstrate that US11 itself undergoes ER export and proteasomal degradation and utilize this system to define multiple steps of US11 dislocation. Treatment of US11-expressing cells with proteasome inhibitor resulted in the accumulation of glycosylated and ubiquitinated species as well as a deglycosylated US11 intermediate. Subcellular fractionation of proteasome-inhibited US11 cells demonstrated that deglycosylated intermediates continued to be integrated within the ER membrane, suggesting that the proteasome functions in the latter steps of dislocation. The data supports a model in which US11 is modified with ubiquitin, whereas the transmembrane region is integrated in the ER membrane, and deglycosylation occurs before complete dislocation.