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Abstract The non-polymorphic HLA-E molecule offers opportunities for new universal immunotherapeutic approaches to chronic infectious diseases. Chronic Hepatitis B virus (HBV) infection is driven in part by T cell dysfunction due to elevated levels of the HBV envelope (Env) protein hepatitis B surface antigen (HBsAg). Here we report the characterization of three genotypic variants of an HLA-E-binding HBsAg peptide, Env371-379, identified through bioinformatic predictions and verified by biochemical and cellular assays. Using a soluble affinity-enhanced T cell receptor (TCR) (a09b08)-anti-CD3 bispecific molecule to probe HLA-E presentation of the Env371-379 peptides, we demonstrate that only the most stable Env371-379 variant, L6I, elicits functional responses to a09b08-anti-CD3-redirected polyclonal T cells co-cultured with targets expressing endogenous HBsAg. Furthermore, HLA-E-Env371-379 L6I-specific CD8+ T cells are detectable in HBV-naïve donors and people with chronic HBV after in vitro priming. In conclusion, we provide evidence for HLA-E-mediated HBV Env peptide presentation, and highlight the effect of viral mutations on the stability and targetability of pHLA-E molecules.

Abstract The abundance of Lp(a) protein holds significant implications for the risk of cardiovascular disease (CVD), which is directly impacted by the copy number (CN) of KIV-2, a 5.5 kbp sub-region. KIV-2 is highly polymorphic in the population and accurate analysis is challenging. In this study, we present the DRAGEN KIV-2 CN caller, which utilizes short reads. Data across 166 WGS show that the caller has high accuracy, compared to optical mapping and can further phase approximately 50% of the samples. We compared KIV-2 CN numbers to 24 previously postulated KIV-2 relevant SNVs, revealing that many are ineffective predictors of KIV-2 copy number. Population studies, including USA-based cohorts, showed distinct KIV-2 CN, distributions for European-, African-, and Hispanic-American populations and further underscored the limitations of SNV predictors. We demonstrate that the CN estimates correlate significantly with the available Lp(a) protein levels and that phasing is highly important.

This study compares the Melbourne Decision-Making Questionnaire (MDMQ) and the General Decision-Making Style questionnaire (GDMS), two of the most widely used decision-making questionnaires in the literature, in a large age- and sex-weighted general population sample of 714 men (45.7%) and 848 women (54.3%) between 18 and 90 years old. The objective was to evaluate the convergent and construct validity between several aspects of these decision-making style questionnaires. The results indicate that the two questionnaires replicate the factorial structure of four and five factors reported in the original studies, respectively, through exploratory and confirmatory procedures in our cross-cultural context. The domains of both questionnaires that represent a strong or large correlation are Vigilance with Rational (0.50), and Hypervigilance, Buck-passing, and Procrastination with Avoidant (0.45, 0.52, and 0.60). A Structural Equations Model (SEM) between both questionnaires indicates that both latent factors formed by the domains of the MDMQ and the GDMS obtain a correlation of 0.96. It is concluded that the two questionnaires measure similar aspects of the decision-making construct.

We present the case of a 23-year-old man who was admitted to the emergency department due to thoracic trauma with a gunshot wound in the right fifth intercostal space with the anterior axillary line, with an outflow tract in the third intercostal space on the left parasternal line. The patient exhibited signs of cardiac tamponade and grade IV hemorrhagic shock. Bilateral tube thoracostomy was performed, yielding a substantial left hemothorax (1500 mL). As the patient presented deterioration of hemodynamic instability despite adequate resuscitation maneuvers, prompted immediate transportation to the operating room to perform a sternotomy. A posterior brachiocephalic trunk injury was identified, consisting of a laceration of 60% of total circumference, with an extension of over 2 cm. The distal portion of the injury was resected and reconstructed using a 6 mm polytetrafluoroethylene graft, with a proximal graft anastomosis employing a lateral anchor technique and a distal graft anastomosis using a parachute technique, secured with 4-0 polypropylene vascular sutures. The patient's postoperative recovery progressed favorably, he remained in the intensive care unit for 5 days and in general hospitalization for an additional 4 days. Further interventions were not required. A control CT angiography was performed 3 months postoperatively, demonstrating complete graft patency. Resumen: Presentamos el caso de un varón de 23 años que ingresó al servicio de urgencias por traumatismo torácico con herida de bala en el quinto espacio intercostal derecho con la línea axilar anterior, y un tracto de salida en el tercer espacio intercostal en la línea paraesternal izquierda. El paciente presentaba signos de taponamiento cardiaco y shock hemorrágico grado IV. Se realizó toracostomía con inserción de tubo de tórax bilateral, identificado un hemotórax izquierdo sustancial (1.500 mL). Como el paciente presentó deterioro de la inestabilidad hemodinámica a pesar de las adecuadas maniobras de reanimación, se motivó su traslado inmediato al quirófano para realizarle una esternotomía. Se identificó una lesión del tronco braquiocefálico posterior, consistente en una laceración del 60% de la circunferencia total, con una extensión superior a 2 cm. La porción distal de la lesión se resecó y reconstruyó mediante un injerto de politetrafluoroetileno de 6 mm, con una anastomosis del injerto proximal mediante técnica de anclaje lateral y una anastomosis del injerto distal mediante técnica de paracaídas, asegurada con suturas vasculares de polipropileno 4-0. La recuperación postoperatoria del paciente evolucionó favorablemente, permaneció cinco días en unidad de cuidado intensivo y en hospitalización general por cuatro días adicionales. No fueron necesarias más intervenciones. Se realizó una angiografía por TC de control a los tres meses del postoperatorio, demostrando permeabilidad completa del injerto.

Abstract Background Risk scores facilitate the assessment of mortality risk in patients with community-acquired pneumonia (CAP). Despite their utilities, there is a scarcity of evidence comparing the various RS simultaneously. This study aims to evaluate and compare multiple risk scores reported in the literature for predicting 30-day mortality in adult patients with CAP. Methods A retrospective cohort study on patients diagnosed with CAP was conducted across two hospitals in Colombia. The areas under receiver operating characteristic curves (ROC-curves) were calculated for the outcome of survival or death at 30 days using the scores obtained for each of the analyzed questionnaires. Results A total of 7454 potentially eligible patients were included, with 4350 in the final analysis, of whom 15.2% (662/4350) died within 30 days. The average age was 65.4 years (SD: 21.31), and 59.5% (2563/4350) were male. Chronic kidney disease was 3.7% (9.2% vs. 5.5%; p

Pleural extension of pseudomyxoma peritonei is rare, and treatment demands multidisciplinary care. Perioperative management during cytoreductive surgery and hyperthermic intrathoracic chemotherapy challenges anesthesiology and surgical teams in unique ways. Hemodynamic, arrhythmogenic, ventilatory, fluid balance, acid-base, and nephroprotection issues are important considerations. The use of cytoreductive surgery and hyperthermic intrathoracic chemotherapy for extraperitoneal pseudomyxoma peritonei is an innovative and potentially curative approach. Here, we describe our approach to managing these patients.

This case report describes a 23-year-old male who was incidentally diagnosed with Caroli disease while investigating symptoms of recurrent upper quadrant pain and fever. Imagining studies, including magnetic resonance cholangiography revealed the “central dot sign,” which is pathognomonic for this condition, along with cystic dilatations of the intrahepatic bile ducts and the presence of biliary stones. The diagnosis was confirmed and treatment with ursodeoxycholic acid led to a notable reduction in symptoms. This case underscores the need for further research and understanding to develop more effective diagnostic and treatment strategies. Regular follow-up remains essential for managing disease progression and preventing complications.

AbstractMarek’s disease virus (MDV) has become an increasingly virulent pathogen in the poultry industry despite vaccination efforts to control it. Brazil has experienced a significant rise of Marek’s disease (MD) outbreaks in recent years. Our study aimed to analyze the complete meq gene sequences to understand the molecular epidemiological basis of MD outbreaks in Brazilian vaccinated layer farms. We detected a high incidence rate of visceral MD (67.74%) and multiple circulating MDV strains. The most prevalent and geographically widespread genotype presented several clinical and molecular characteristics of a highly virulent strain and evolving under positive selective pressure. Phylogenetic and phylogeographic analysis revealed a closer relationship with strains from the USA and Japan. This study sheds light on the circulation of MDV strains capable of infecting vaccinated birds. We emphasize the urgency of adopting preventive measures to manage MDV outbreaks threatening the poultry farming industry.