Post-CART-T Cell Infection: Etiology, pathogenesis, and therapeutic approaches.

Chimeric antigen receptor (CAR) T cell therapy targeting CD-19 has revolutionized the treatment of refractory B-cell malignancies. However, patients undergoing this therapy face an increased risk of infections due to compromised immune function, lymphodepleting chemotherapy, hospitalization, and therapy-related complications such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome. Patients with systemic corticosteroid use, low immunoglobulin levels, and severe CRS, are at higher risk of infection. This review article highlights the spectrum of infections encountered in CAR T cell therapy, including bacterial, viral, and fungal infections. Following consensus guidelines for vaccination and immunoglobulin replacement is recommended. Clear criteria for antibiotic usage and vaccinating household members against respiratory viruses are crucial. Understanding the risk factors, spectrum of infections, and implementing appropriate prophylactic measures are essential to optimize outcomes in patients undergoing CAR T cell therapy. By prioritizing infection prevention strategies, healthcare professionals can effectively improve patient care.

Identifying the most important data for research in the field of infectious diseases: thinking on the basis of artificial intelligence.

OBJECTIVE: Clinical data on which artificial intelligence (AI) algorithms are trained and tested provide the basis to improve diagnosis or treatment of infectious diseases (ID). We aimed to identify important data for ID research to prioritise efforts being undertaken in AI programmes. METHODS: We searched for 1,000 articlesfrom high-impact ID journals on PubMed, selecting 288 of the latest articles from 10 top journals. We classified them into structured or unstructured data. Variables were homogenised and grouped into the following categories: epidemiology, admission, demographics, comorbidities, clinical manifestations, laboratory, microbiology, other diagnoses, treatment, outcomes and other non-categorizable variables. RESULTS: 4,488 individual variables were collected, from the 288 articles. 3,670 (81.8%) variables were classified as structured data whilst 818 (18.2%) as unstructured data. From the structured data, 2,319 (63.2%) variables were classified as direct-retrievable from electronic health records-whilst 1,351 (36.8%) were indirect. The most frequent unstructured data were related to clinical manifestations and were repeated across articles. Data on demographics, comorbidities and microbiology constituted the most frequent group of variables. CONCLUSIONS: This article identified that structured variables have comprised the most important data in research to generate knowledge in the field of ID. Extracting these data should be a priority when a medical centre intends to start an AI programme for ID. We also documented that the most important unstructured data in this field are those related to clinical manifestations. Such data could easily undergo some structuring with the use of semi-structured medical records focusing on a few symptoms.

Boar sperm motility is modulated by CCK at a low concentration of bicarbonate under capacitation conditions.

In a previous study, our group detected the cholecystokinin (CCK) protein in the porcine oviduct. This fact, together with the involvement of CCK in the regulation of sperm protein tyrosine phosphorylation by the modulation of HCO3 - uptake (in mice and humans) suggests a role for CCK during sperm capacitation. Therefore, on the one hand, the expression of CCK receptors (CCK1R and CCK2R) on boar testes has been investigated and probed; on the other hand, boar spermatozoa (from seminal doses of 1-day and 5-day storage) were exposed to different concentrations of CCK (0-control, 25 or 50 µM) in a medium supporting capacitation supplemented with 0, 5 or 25 mmol/L of HCO3 - for 1 h at 38.5°C. Sperm motion (total and progressive motility), kinetic parameters, viability, acrosome status, and mitochondrial activity were determined. No differences between groups (0, 25 or 50 µM of CCK) were observed when HCO3 - was absent in the media (p > .05). However, the results showed that when the media was supplemented with 5 mmol/L HCO3 - in 1-day seminal dose storage, the linearity index (LIN, %), straightness index (STR, %) and oscillation index (WOB, %) (sperm kinetics parameters) increased in the presence of CCK regardless the concentration (p < .05). Nevertheless, CCK in sperm from 5-day storage only increased the WOB parameter in comparison to the control (p < .05). Furthermore, the average amplitude of the lateral displacement of the sperm head (ALH, µm) and curvilinear velocity (VCL, µm/s) decreased when CCK was present, depending on its concentration and sperm aging (1-day vs. 5-days) (p < .05). In the case of the media supporting capacitation supplemented with 25 mmol/L HCO3 - , any differences were observed except for sperm viability in the 5-day seminal doses, which increased in the 50 µM-CCK group compared to the control (p < .05). In conclusion, these data suggest an implication of CCK protein during sperm capacitation under low bicarbonate concentration increasing the sperm linear trajectory.

Use of a nanocrystalline silver dressing on lymphatic ulcers in patients with chronic lymphoedema.

OBJECTIVE: A prospective evaluation to explore the effect of treating patients with chronic lower limb lymphoedema and lymphatic ulcers using a nanocrystalline dressing and multilayer bandaging. METHOD: Ulcers were cleansed and dressed with a nanocrystalline silver dressing, an alginate dressing and a hydrocellular dressing, followed by multilayer short-stretch compression bandages. A digital planimetry system was used to calculate the ulcer surface area. In cases of multiple ulcers, the areas were added together. RESULTS: Eight patients with chronic lower limb lymphoedema plus ulcers were included. Median age was 53.7 years (range 39.2-72.3). Mean ulcer size was 10.5cm2 (range: 0.8-33.8). All ulcers completely healed after one to nine weeks of treatment. CONCLUSION: This protocol has been effective in healing lymphatic ulcers and was well accepted by patients. There were no adverse effects or withdrawals. Further studies with larger numbers of patients are required to support these results.

Valoración nutricional de los menús de la guardería de la Universidad Politécnica de Valencia / Nursery Menu assessment from Politechnical University of Valencia

Introducción: la alimentación del niño de 1 a 3 años debe tener como objetivo satisfacer las necesidades nutricionales y potenciar un adecuado crecimiento y desarrollo. El menú del comedor escolar debe aportar entre un 30 y un 35 por ciento de las necesidades energéticas diarias, y debe ajustarse a las necesidades de micronutrientes esenciales. Objetivos: en el presente trabajo de investigación se evaluó el aporte de calorías y nutrientes de los menús ofrecidos por la guardería de la Universidad Politécnica de Valencia, con el fin de corregir deficiencias (por exceso o defecto), y obtener una oferta más saludable y equilibrada. Resultados: los resultados obtenidos ponen de manifiesto que los menús ofrecidos en la guardería presentan aportes inadecuados de energía, proteínas, y grasas. Asimismo, se han detectado déficits de algunos micronutrientes esenciales, como el hierro, ácido fólico, zinc y vitamina B12, nutrientes de gran relevancia en la nutrición de los escolares. Conclusiones y recomendaciones: se considera esencial el rol de los padres en la optimización de la calidad de la alimentación de los niños, y en la importancia del desayuno, como aporte energético elemental en la etapa de crecimiento y desarrollo (AU)

Analysis of chimeric receptors shows that multiple distinct functional activities of scavenger receptor, class B, type I (SR-BI), are localized to the extracellular receptor domain.

Scavenger receptor BI (SR-BI) mediates the selective uptake of high-density lipoprotein (HDL) cholesteryl ester (CE), a process by which HDL CE is taken into the cell without degradation of the HDL particle. In addition, SR-BI stimulates the bi-directional flux of free cholesterol (FC) between cells and lipoproteins, an activity that may be responsible for net cholesterol efflux from peripheral cells as well as the rapid hepatic clearance of FC from plasma HDL. SR-BI also increases cellular cholesterol mass and alters cholesterol distribution in plasma membrane domains as judged by the enhanced sensitivity of membrane cholesterol to extracellular cholesterol oxidase. In contrast, CD36, a closely related class B scavenger receptor, has none of these activities despite binding HDL with high affinity. In the present study, analyses of chimeric SR-BI/CD36 receptors and domain-deleted SR-BI have been used to test the various domains of SR-BI for functional activities related to HDL CE selective uptake, bi-directional FC flux, and the alteration of membrane cholesterol mass and distribution. The results show that each of these activities localizes to the extracellular domain of SR-BI. The N-terminal cytoplasmic tail and transmembrane domains appear to play no role in these activities other than targeting the receptor to the plasma membrane. The C-terminal tail of SR-BI is dispensable for activity as well for targeting to the plasma membrane. Thus, multiple distinct functional activities are localized to the SR-BI extracellular domain.

High density lipoprotein phospholipid composition is a major determinant of the bi-directional flux and net movement of cellular free cholesterol mediated by scavenger receptor BI.

The role of high density lipoprotein (HDL) phospholipid in scavenger receptor BI (SR-BI)-mediated free cholesterol flux was examined by manipulating HDL(3) phosphatidylcholine and sphingomyelin content. Both phosphatidylcholine and sphingomyelin enrichment of HDL enhanced the net efflux of cholesterol from SR-BI-expressing COS-7 cells but by two different mechanisms. Phosphatidylcholine enrichment of HDL increased efflux, whereas sphingomyelin enrichment decreased influx of HDL cholesterol. Although similar trends were observed in control (vector-transfected) COS-7 cells, SR-BI overexpression amplified the effects of phosphatidylcholine and sphingomyelin enrichment of HDL 25- and 2.8-fold, respectively. By using both phosphatidylcholine-enriched and phospholipase A(2)-treated HDL to obtain HDL with a graded phosphatidylcholine content, we showed that SR-BI-mediated cholesterol efflux was highly correlated (r(2) = 0.985) with HDL phosphatidylcholine content. The effects of varying HDL phospholipid composition on SR-BI-mediated free cholesterol flux were not correlated with changes in either the K(d) or B(max) values for high affinity binding to SR-BI. We conclude that SR-BI-mediated free cholesterol flux is highly sensitive to HDL phospholipid composition. Thus, factors that regulate cellular SR-BI expression and the local modification of HDL phospholipid composition will have a large impact on reverse cholesterol transport.