Adapting Reach Up and Learn in Crisis and Conflict Settings: An Exploratory Multiple Case Study.

Objectives: In 2019, >71 million children aged <5 had spent their entire lives in conflict-affected settings. Compounding adversities including violence, poverty, and displacement have immediate and long-term effects on early childhood development, health, behavior, and well-being. In response, adaptations of Reach Up have been implemented in conflict and crisis settings.

Vaccination in pregnancy: The role of the midwife.

Midwives are the front-line workers providing maternity care for women in many countries. The role of the midwife includes providing information about, and recommendations for, maternal vaccination in pregnancy and for the baby in the postnatal period. Vaccinations recommended in pregnancy include those to prevent influenza, pertussis, tetanus and now COVID-19.

The National COVID-19 Clinical Evidence Taskforce: pregnancy and perinatal guidelines.

Introduction: Pregnant women are at higher risk of severe illness from coronavirus disease 2019 (COVID-19) than non-pregnant women of a similar age. Early in the COVID-19 pandemic, it was clear that evidenced-based guidance was needed, and that it would need to be updated rapidly. The National COVID-19 Clinical Evidence Taskforce provided a resource to guide care for people with COVID-19, including during pregnancy.

Identifying and dismantling racism in Australian perinatal settings: Reframing the narrative from a risk lens to intentionally prioritise connectedness and strengths in providing care to First Nations families.

Introduction: The perinatal period is a time when provision of responsive care offers a life course opportunity for positive change to improve health outcomes for mothers, infants and families. Australian perinatal systems carry the legacy of settler-colonialism, manifesting in racist events and interactions that First Nations parents encounter daily.

Objective: The dominance of a western risk lens, and conscious and unconscious bias in the child protection workforce, sustains disproportionately high numbers of First Nations infants being removed from their parents' care.

Erectile Dysfunction and Cardiovascular Risk in Men With Rheumatoid Arthritis: A Population-based Cohort Study.

Objective: Both erectile dysfunction (ED) and rheumatoid arthritis (RA) are associated with increased cardiovascular (CV) risk. It is unknown if these diagnoses are associated or if their combination confers additional CV risk. We aimed to define the incidence of ED in RA, and to determine if ED correlates with increased CV risk in RA.

The septin cytoskeleton regulates natural killer cell lytic granule release.

Natural killer (NK) cell-mediated killing involves the membrane fusion of preformed lytic granules. While the roles of actin and microtubules are well accepted during this process, the function of septins, another cytoskeletal component that associates with actin and microtubules, has not been investigated. Here we show that genetic depletion or pharmacologic stabilization of the septin cytoskeleton significantly inhibited NK cell cytotoxicity.

Developmental brain abnormalities and acute encephalopathy in a patient with myopathy with extrapyramidal signs secondary to pathogenic variants in MICU1.

Mitochondria play a variety of roles in the cell, far beyond their widely recognized role in ATP generation. One such role is the regulation and sequestration of calcium, which is done with the help of the mitochondrial calcium uniporter (MCU) and its regulators, MICU1 and MICU2. Genetic variations in MICU1 and MICU2 have been reported to cause myopathy, developmental disability and neurological symptoms typical of mitochondrial disorders.

Profound intellectual disability caused by homozygous TRAPPC9 pathogenic variant in a man from Malta.

Background: Intellectual disability is a complex multi-faceted condition with diverse underlying etiologies. One rare form of intellectual disability is secondary to the loss of TRAPPC9, an activator of NF-κB and a mediator of intracellular protein processing and trafficking. TRAPPC9 deficiency has been described in 48 patients with more than 15 pathologic variants.

NK cell defects in X-linked pigmentary reticulate disorder.

X-linked reticulate pigmentary disorder (XLPDR, Mendelian Inheritance in Man #301220) is a rare syndrome characterized by recurrent infections and sterile multiorgan inflammation. The syndrome is caused by an intronic mutation in POLA1, the gene encoding the catalytic subunit of DNA polymerase-α (Pol-α), which is responsible for Okazaki fragment synthesis during DNA replication. Reduced POLA1 expression in this condition triggers spontaneous type I interferon expression, which can be linked to the autoinflammatory manifestations of the disease.

NKG2D-DAP10 signaling recruits EVL to the cytotoxic synapse to generate F-actin and promote NK cell cytotoxicity.

Natural killer (NK) cells eliminate abnormal cells through the release of cytolytic granule contents. In this process, NK cells must adhere to target cells through integrin-mediated adhesion, which is highly dependent on the generation of F-actin. Ena/VASP-like (EVL) is an actin regulatory protein previously shown to regulate integrin-mediated adhesion in other cell types, but its role in NK cell biology is not known.

Short- and long-term continuous positive airway pressure usage in the post-stroke population with obstructive sleep apnea.

Purpose: Obstructive sleep apnea (OSA) is highly prevalent in post-stroke patients and observational evidence suggests that untreated it is a harbinger of poorer outcomes in this population. Clinical trials on the impact of treatment of OSA with continuous positive airway pressure (CPAP) have countered difficulties with patient engagement and adherence to CPAP therapy. Real-world data on continuous positive airway pressure initiation and usage in the post-stroke population with obstructive sleep apnea is limited.

The early proximal αβ TCR signalosome specifies thymic selection outcome through a quantitative protein interaction network.

During αβ T cell development, T cell antigen receptor (TCR) engagement transduces biochemical signals through a protein-protein interaction (PPI) network that dictates dichotomous cell fate decisions. It remains unclear how signal specificity is communicated, instructing either positive selection to advance cell differentiation or death by negative selection. Early signal discrimination might occur by PPI signatures differing qualitatively (customized, unique PPI combinations for each signal), quantitatively (graded amounts of a single PPI series), or kinetically (speed of PPI pathway progression).

VASP Regulates NK Cell Lytic Granule Convergence.

NK cells eliminate viral-infected and malignant cells through a highly orchestrated series of cytoskeletal rearrangements, resulting in the release of cytolytic granule contents toward the target cell. Central to this process is the convergence of cytolytic granules to a common point, the microtubule-organizing center (MTOC), before delivery to the synapse. In this study, we show that vasodialator-stimulated phosphoprotein (VASP), an actin regulatory protein, localizes to the cytolytic synapse, but surprisingly, shows no impact on conjugate formation or synaptic actin accumulation despite being required for human NK cell-mediated killing.

Risk of Obstructive Sleep Apnea and Its Association with Cardiovascular and Noncardiac Vascular Risk in Patients with Rheumatoid Arthritis: A Population-based Study.

Objective: To define the incidence of obstructive sleep apnea (OSA) in patients with rheumatoid arthritis (RA) and determine whether OSA diagnosis predicts future cardiovascular disease (CVD) and noncardiac vascular events.

Methods: Medical information pertaining to RA, OSA, CVD, and vascular diagnoses was extracted from a comprehensive medical record system for a geographically defined population of 813 patients previously diagnosed with RA and 813 age- and sex-matched comparator subjects.

Results: The risk for OSA in persons with RA versus comparators was elevated, although not reaching statistical significance (HR 1.

Novel Assessment of Interstitial Lung Disease Using the "Computer-Aided Lung Informatics for Pathology Evaluation and Rating" (CALIPER) Software System in Idiopathic Inflammatory Myopathies.

Purpose: To evaluate the correlation between measurements from quantitative thoracic high-resolution CT (HRCT) analysis with "Computer-Aided Lung Informatics for Pathology Evaluation and Rating" (CALIPER) software and measurements from pulmonary function tests (PFTs) in patients with idiopathic inflammatory myopathies (IIM)-associated interstitial lung disease (ILD).

Methods: A cohort of patients with IIM-associated ILD seen at Mayo Clinic was identified from medical record review. Retrospective analysis of HRCT data and PFTs at baseline and 1 year was performed.

Malignancy Incidence, Management, and Prevention in Patients with Rheumatoid Arthritis.

Traditional and biologic disease-modifying antirheumatic drugs (DMARDs) are effective medications for the management of rheumatoid arthritis (RA). However, the effects of these medications on immune function raises concern that they may increase long-term cancer risk. The baseline risk for some cancers appears to differ in patients with RA compared to the general population, with the former having an increased risk of lymphoma, lung cancer and renal cancer, but a decreased risk of colorectal and breast cancer.

In-hospital diagnosis of sleep apnea in stroke patients using a portable acoustic device.

Purpose: Sleep apnea (SA) is highly prevalent in post-stroke patients. Due to physical disability and relative inaccessibility of polysomnography (PSG) to test for SA, patients with stroke frequently remain undiagnosed and untreated. Portable SA monitoring can facilitate at-home or in-hospital testing for SA.

Malignancy incidence in patients with psoriatic arthritis: a comparison cohort-based incidence study.

Malignancy is a major cause of death in patients with inflammatory disease. The risk of individual malignancies is altered in some inflammatory diseases, such as rheumatoid arthritis and psoriasis. This study aimed to examine malignancy incidence in patients with psoriatic arthritis (PsA), a related inflammatory disease.

Cardiovascular risk profile at the onset of psoriatic arthritis: a population-based cohort study.

Objective: The role of cardiovascular disease (CVD) risk factors in psoriatic arthritis (PsA) is poorly understood. We examined the prevalence of CVD risk factors at initial onset of PsA and compared the observed incidence of CVD events with that predicted by the Framingham Risk Score (FRS) to determine its applicability in this patient population.

Methods: A population-based incidence cohort of 158 patients with PsA who fulfilled Classification of Psoriatic Arthritis criteria for PsA in 1989-2008 was assembled.

Slow angled-descent forepaw grasping (SLAG): an innate behavioral task for identification of individual experimental mice possessing functional vision.

Background: There is significant interest in the generation of improved assays to clearly identify experimental mice possessing functional vision, a property that could qualify mice for inclusion in behavioral and neuroscience studies. Widely employed current methods rely on mouse responses to visual cues in assays of reflexes, depth perception, or cognitive memory. However, commonly assessed mouse reflexes can sometimes be ambiguous in their expression, while depth perception assays are sometimes confounded by variation in anxiety responses and exploratory conduct.