Pathogenicity assessment of genetic variants identified in patients with severe hypertriglyceridemia: novel cases of Familial Chylomicronemia Syndrome from the Dyslipidemia Registry of the Spanish Atherosclerosis Society.

Purpose: Genetic testing is required to confirm a diagnosis of familial chylomicronemia syndrome (FCS). We assessed the pathogenicity of variants identified in the FCS canonical genes to diagnose FCS cases.

Methods: 245 patients with severe hypertriglyceridemia underwent next-generation sequencing.

Spatially explicit estimation of recent migration rates in plants using genotypic data.

We present a new hierarchical Bayesian method using multilocus genotypes to estimate recent seed and pollen migration rates in a spatially explicit framework that incorporates distance effects separately for each type of dispersal. The method additionally estimates population allelic frequencies, population divergence values, individual inbreeding coefficients, individual maternal and paternal ancestries, and allelic dropout rates. We conduct a numerical simulation analysis that indicates that the method can provide reliable estimates of seed and pollen migration rates and allow accurate inference of spatial effects on migration, at affordable sample sizes (25-50 individuals/population) when population genetic divergence is not low (FST≥0.

Upadacitinib: the JAK inhibitor that achieved what other drugs could not.

We present an interesting case of severe ulcerative colitis flare, of challenging management because of a cytomegalovirus co-infection, in which upadacitinib achieved clinical and biochemical remission after poor responses to ganciclovir and tofacitinib.

Periacetabular metastases: Proposed extension of the Harrington classification.

Objectives: To describe the functional outcomes, complications, and reconstruction types in patients with periacetabular metastases and to propose an extension of the Harrington classification.

Methods: Twenty-eight patients (13 males, 15 females) with a mean age of 63.8 ± 15.

Islet-on-a-chip for the study of pancreatic β-cell function.

Diabetes mellitus is a significant public health problem worldwide. It encompasses a group of chronic disorders characterized by hyperglycemia, resulting from pancreatic islet dysfunction or as a consequence of insulin-producing β-cell death. Organ-on-a-chip platforms have emerged as technological systems combining cell biology, engineering, and biomaterial technological advances with microfluidics to recapitulate a specific organ's physiological or pathophysiological environment.

Management of Stent Underexpansion and Aorto-ostial Lesions.

Stent underexpansion (SU) and aorto-ostial lesions (AOL) are challenging conditions commonly faced during clinical practice in the setting of percutaneous coronary interventions. Compared to other interventional settings, both SU and AOL are associated with an increased risk of immediate and late events following percutaneous coronary intervention. Several specific strategies including the systematic use of intracoronary imaging and dedicated techniques for lesions' preparation and calcium debulking have been described.

Prognostication in emergency room patients: comparing ultrasensitive and contemporary quantification of cardiac troponin levels below the 99th percentile.

Introduction: Cardiac troponin levels below the 99th percentile improve the predictive efficacy for cardiovascular events when associated with relevant clinical variables. However, whether ultra-sensitive analytical methods improve this predictive efficacy over less sensitive or contemporary analytical methods remains unknown.

Methods: This retrospective observational study involved consecutive patients who presented to the emergency department for suspected acute coronary syndrome and underwent measurement of ultra-sensitive cardiac troponin I (Singulex) and contemporary cardiac troponin I (Siemens) with levels below the 99th percentile.

Nebulized aminoglycosides for ventilator-associated pneumonia: Methodological considerations and lessons from experimental studies.

Aminoglycosides are concentration-dependent antibiotics exerting a bactericidal effect when concentrations at the site of infection are equal to or greater than 5 times the minimum inhibitory concentrations (MIC). When administered intravenously, they exhibit poor lung penetration and high systemic renal and ototoxicity, imposing to restrict their administration to 5 days. Experimental studies conducted in anesthetized and mechanically ventilated sheep and pigs provide evidence that high doses of nebulized aminoglycosides induce a rapid and potent bacterial killing in the infected lung parenchyma.

Using Anal Cytology and Human Papillomavirus DNA and E6/E7 mRNA Detection to Optimize High-Resolution Anoscopy Referrals in Men Who Have Sex With Men With HIV.

Background: This study was conducted to evaluate screening procedures for anal high-grade squamous intraepithelial lesions (HSILs) with anal liquid-based cytology (aLBC) and biomarkers to identify candidates for high-resolution anoscopy (HRA).

Methods: This cross-sectional study included men who have sex with men with HIV. Participants underwent HRA, aLBC, and biomarker testing.

Pharmaco-Invasive Strategy Vs Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction in Latin America: A Meta-Analysis.

Background: Primary percutaneous coronary intervention (PCI) is the established treatment for ST-segment elevation myocardial infarction (STEMI), but often it is not readily available in low-resource settings. We assessed the safety and efficacy of the pharmaco-invasive strategy compared to primary PCI for STEMI in Latin America.

Methods: MEDLINE, Embase, and Latin American and Caribbean Health Sciences Literature (LILACS) were searched for the period from their inception to September 2023, for studies that compared a pharmaco-invasive strategy vs primary PCI in Latin America.

Community-based model for management and follow-up by non-physician healthcare workers to improve awareness, treatment, and control of hypertension: The COTRACO study protocol.

Introduction: Cardiovascular diseases are the leading cause of death and morbidity worldwide, with a significantly higher burden in low- and middle-income countries. Hypertension, a major risk factor for cardiovascular morbidity and mortality, remains under-diagnosed and poorly controlled, especially in regions such as Latin America. The HOPE-4 study demonstrated that the involvement of non-physician health workers (NPHWs), the use of standardized treatment algorithms, the provision of free antihypertensive drugs and home follow-up can significantly improve hypertension control and reduce cardiovascular risk, as demonstrated in Colombia and Malaysia.

Blood levels of cytokines highlight the role of inflammation in Alzheimer's disease.

Inflammation and angiogenesis have been defined as potential mechanisms associated with clinical progression from a cognitively normal state to Alzheimer's disease (AD). In this observational case-control study, we aimed to determine plasma levels of cytokines as indicators of inflammation involved in cognitive decline. We measured 30 plasma proteins in 49 controls (CTL), 36 individuals with mild cognitive impairment (MCI) and 52 patients diagnosed with probable AD.

Identifying silver ore sources for the earliest coins of Athens.

Unlabelled: This study addresses longstanding questions concerning the ore sources used in the first series of coins of ancient Athens known as the (c.540-c.500 BCE) by combining comprehensive numismatic data on 22 coins (16 new and 6 legacy analyses) with lead isotope and surface elemental measurements (MC-ICP-MS and XRF).

Occluding mucous airway plugs in patients with obstructive lung diseases: a new treatable trait?

https://bit.ly/4gyJHFW.

Long-term outcomes in five patients with autoimmune pulmonary alveolar proteinosis treated with molgramostim inhalation solution.

Autoimmune pulmonary alveolar proteinosis (aPAP), which accounts for >90% of all cases of PAP, is a rare lung disease mediated by granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies that block GM-CSF signalling, leading to reduced surfactant clearance causing abnormal accumulation of alveolar surfactant and impaired gas exchange [1-3]. The current standard of care for aPAP is whole-lung lavage (WLL), which is invasive, resource intensive, carries procedural risk, does not address the underlying cause of disease and often must be repeated regularly [4]. Hence, there is a therapeutical need to address the underlying pathophysiology of the disease.

Developing a Prototype Machine Learning Model to Predict Quality of Life Measures in People Living With HIV.

Background: In the realm of Evidence-Based Medicine, introduced by Gordon Guyatt in the early 1990s, the integration of machine learning technologies marks a significant advancement towards more objective, evidence-driven healthcare. Evidence-Based Medicine principles focus on using the best available scientific evidence for clinical decision-making, enhancing healthcare quality and consistency by integrating this evidence with clinician expertise and patient values. Patient-Reported Outcome Measures (PROMs) and Patient-Reported Experience Measures (PREMs) have become essential in evaluating the broader impacts of treatments, especially for chronic conditions like HIV, reflecting patient health and well-being comprehensively.

Refractive Accuracy of a Novel Swept-Source OCT in Patients With Short and Long Eyes.

To analyze the refractive accuracy of a novel swept-source optical coherence biometer (SS-OCT), that uses individual refractive indices to measure axial length, in short and long eyes implanted with monofocal intraocular lenses (IOLs). This retrospective comparative study considered eyes with short axial length (AL) (< 22.5 mm) or long AL (> 26 mm) bilaterally implanted with the Acrysof IQ monofocal IOL.

Longitudinally aligned inner-patterned silk fibroin conduits for peripheral nerve regeneration.

Unlabelled: Peripheral nerve injuries represent a major clinical challenge, if nerve ends retract, there is no spontaneous regeneration, and grafts are required to proximate the nerve ends and give continuity to the nerve. The nerve guidance conduits (NGCs) presented in this work are silk fibroin (SF)-based, which is biocompatible and very versatile. The formation of conduits is obtained by forming a covalently cross-linked hydrogel in two concentric moulds, and the inner longitudinally aligned pattern of the SF NGCs is obtained through the use of a patterned inner mould.

A multi-country cohort database study to assess pregnancy and infant outcomes after potential maternal or paternal exposure to cladribine tablets in the treatment of multiple sclerosis: the CLEAR study methods and status update.

Background: Cladribine tablets are contraindicated during pregnancy; therefore, safety data on pregnancies exposed to this treatment are limited. CLEAR collects and describes pregnancy outcomes in this understudied population.

Objectives: To describe the main features of the CLEAR study design, including the data sources and the methodological approach, and provide a status update.

A gut instinct for childhood leukemia prevention: microbiome-targeting recommendations aimed at parents and caregivers.

Childhood leukemia accounts for 30% of all pediatric cancer cases with acute lymphoblastic leukemia (ALL) being the most common subtype. Involvement of the gut microbiome in ALL development has recently garnered interest due to an increasing recognition of the key contribution the microbiome plays in maintaining the immune system's homeostatic balance. Commensal gut microbiota provide a first line of defense against different pathogens and gut microbiome immaturity has been implicated in ALL pathogenesis.

Microfluidic model of the alternative vasculature in neuroblastoma.

Unlabelled: Neuroblastoma (NB) is a highly vascularized pediatric tumor arising from undifferentiated neural crest cells early in life, exhibiting both traditional endothelial-cell-driven vasculature and an intriguing alternative vasculature. The alternative vasculature can arise from cancer cells undergoing transdifferentiation into tumor-derived endothelial cells (TEC), a trait associated with drug resistance and tumor relapse. The lack of effective treatments targeting NB vasculature primarily arises from the challenge of establishing predictive in vitro models that faithfully replicate the alternative vasculature phenomenon.