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Immunization is a highly cost-effective investment in health, proven to be an effective tool in controlling and eliminating dangerous infectious diseases. Health science students require evidence-based knowledge to tackle challenges in healthcare, particularly in the field of vaccination. The aim of the current study is to asses students' knowledge on vaccinations and further explore their feedback after attending Educating Vaccination Competence web-based course (EDUVAC web-based course). Students from five Higher Educational Institutes voluntarily participated in the EDUVAC web-based course. The course provided various study materials, including PowerPoint presentations, videos, quizzes, texts, and references to reputable websites. It also offered small assignments and self-tests for self-evaluation. An online questionnaire was available to students before and after they completed the EDUVAC web-based course. The mean knowledge score on vaccines increased significantly after the EDUVAC web-based course (p<0.001). The majority of the students (95%) felt that the web-based course has benefitted them for their future career and 96.4% would encourage other students to attend the EDUVAC web-based course. Overall, our findings suggest that EDUVAC is a valuable resource for those seeking to enhance their understanding of vaccination.

Congenital myasthenic syndrome-22 (CMS22, OMIM 616224) is a rare genetic disorder caused by deleterious genetic variation in the prolyl endopeptidase-like (PREPL) gene. Previous reports have described patients with deletions and nonsense variants in PREPL, but nothing is known about the effect of missense variants in the pathology of CMS22. In this study, we have functionally characterized missense variants in PREPL from 3 patients with CMS22, all with hallmark phenotypes. Biochemical evaluation revealed that these missense variants do not impair hydrolase activity, thereby challenging the conventional diagnostic criteria and disease mechanism. Structural analysis showed that the variants affect regions most likely involved in intraprotein or protein-protein interactions. Indeed, binding to a selected group of known interactors was differentially reduced for the 3 variants. The importance of nonhydrolytic functions of PREPL was investigated in catalytically inactive PREPL p.Ser559Ala cell lines, which showed that hydrolytic activity of PREPL is needed for normal mitochondrial function but not for regulating AP1-mediated transport in the transgolgi network. In conclusion, these studies showed that CMS22 can be caused not only by deletion and truncation of PREPL but also by missense variants that do not necessarily result in a loss of hydrolytic activity of PREPL.

ABSTRACT: The evaluation of dairy cow feed efficiency using residual feed intake accounts for known energy sinks. However, behavioral traits may also contribute to the variation in feed efficiency. Our objective was to estimate the heritability and repeatability of behavioral traits and their genetic correlations with feed efficiency and its components in lactating Holstein cows. The first dataset consisted of 36,075 daily rumination and lying time records collected using a SMARTBOW ear-tag accelerometer (Zoetis, Parsippany, NJ) and 6,371 weekly feed efficiency records of 728 cows from the University of Wisconsin–Madison. The second dataset consisted of 59,155 daily activity records, measured as number of steps, recorded by pedometers (AfiAct; SAE Afikim, Kibbutz Afikim, Israel) and 8,626 weekly feed efficiency records of 635 cows from the University of Florida. Feed efficiency and its components included DMI, change in BW, metabolic BW, secreted milk energy, and residual feed intake. The statistical models included the fixed effect of cohort, lactation number, and days in milk, and the random effects of animal and permanent environment. Heritability estimates for behavioral traits using daily records were 0.19 ± 0.06 for rumination and activity, and 0.37 ± 0.07 for lying time. Repeatability estimates for behavioral traits using daily data ranged from 0.56 ± 0.02 for activity to 0.62 ± 0.01 for lying time. Both heritability and repeatability estimates were larger when weekly records instead of daily records were used. Rumination and activity had positive genetic correlations with residual feed intake (0.40 ± 0.19 and 0.31 ± 0.22, respectively) and lying time had a negative genetic correlation with this residual feed intake (−0.27 ± 0.11). These results indicate that more efficient cows tend to spend more time lying and less time active. Additionally, less efficient cows tend to eat more and therefore also tend to ruminate longer. Overall, sensor-based behavioral traits are heritable and genetically correlated with feed efficiency and its components and, therefore, they could be used as indicators to identify feed-efficient cows within the herd.

El desarrollo de la civilización se asocia con un incremento en la edad de la población. Hoy en Argentina el adulto mayor (AM: persona de 65 años o más) varón tiene una expectativa de vida de 76 años y la mujer de 80 años, lo que representa el 15% del porcentaje de la población en los grandes centros urbanos. Se estima que el porcentaje de AM con diabetes mellitus (DM) es entre el 20-30%. Esta patología, sus comorbilidades y complicaciones (en especial cardiovasculares, infecciosas, cognitivas y oncológicas) llaman a un esfuerzo del equipo de salud y, en especial, de las personas dedicadas a este grupo etario. Es importante un enfoque multidisciplinario, adaptado a las circunstancias de la persona y su situación sociocultural y económica, orientando los recursos de prevención primaria, secundaria y terciaria. Frente al cambio constante, actualmente se requiere la participación del equipo de salud para brindar respuestas a soluciones donde el control metabólico, cardiovascular, cognitivo y de la movilidad tiendan a mantener la independencia funcional de la persona a fin de priorizar la seguridad de las técnicas diagnósticas y terapéuticas en un marco de diálogo y acuerdos.

The rising migration and travel from and towards endemic areas has brought renewed concerns about many parasitic infections, including neglected tropical diseases, such as schistosomiasis. Although serology is the most widely used method for the screening of schistosomiasis in non-endemic countries, this technique lacks sensitivity, especially to distinguish between past and ongoing infections. More recently, a molecular test based on the detection of Schistosoma cell-free DNA in the serum has been proposed as a diagnostic procedure for parasitosis. To test the performance of a blood PCR assay, this work investigated 102 serum samples collected from migrants coming from endemic areas by using primers specific to genomic regions of S. mansoni and S. haematobium patients. The results were then compared with the detection of specific IgG Abs with serological tests. Molecular analysis detected Schistosoma DNA in 32 patients. Among them, we characterized nine S. haematobium, 20 S. mansoni, and three coinfections. Compared with molecular assay, serological analysis detected specific antibodies against Schistosoma antigens in 52 out of 102 patients. Concordance between the two tests was found in 76 out of 102 patients (74.51%): in particular, both diagnostic tests were positive in 29 patients (28.43%) and negative in 47 (46.08%). The specificity of the molecular test was 94%. Overall, our data suggest that serological diagnosis could be combined with the molecular approach, providing the clinician with the serotyping of the parasite and useful information about the infection as well as the required further diagnostic procedures.

Abstract This study aims to learn more about the structure of densified silica with focus on the metamict-like silica phase (density = 2.26 g/cm3) by examining the formation of E’ point defects and interstitial molecular oxygen O2 by 2.5 MeV electron irradiation. High-dose (11 GGy) irradiation creates a metamict-like phase and a large amount of interstitial O2, which is destroyed upon subsequent additional lower-dose electron irradiation. The O2 cathodoluminescence (CL) data indicate that the formation of O2 from peroxy linkages Si–O–O–Si in silica network is strongly dependent on the intertetrahedral void sizes. The position and shape of the O2 emission line support the idea that the configuration of these voids in metamict phase is close to that of non-densified silica. Moreover, data support the strong correlation between the formation of 3-membered rings of Si–O bonds and E’-centers when silica density increases from 2.20 to 2.26 g/cm3.

Residual feed intake (RFI) has been used as a measure of feed efficiency in farm animals. In lactating dairy cattle, RFI is typically obtained as the difference between dry matter intake observations and predictions from regression on known energy sinks, and effects of parity, days in milk, and cohort. The impact of parity (lactation number) on the estimation of RFI is not well understood, so the objectives of this study were to (1) evaluate alternative RFI models in which the energy sinks (metabolic body weight, body weight change, and secreted milk energy) were nested or not nested within parity, and (2) estimate variance components and genetic correlations for RFI across parities. Data consisted of 72,474 weekly RFI records of 5,813 lactating Holstein cows collected from 2007 to 2022 in 5 research stations across the United States. Estimates of heritability, repeatability, and genetic correlations between weekly RFI for parities 1, 2, and 3 were obtained using bivariate repeatability animal models. The nested RFI model showed better goodness of fit than the nonnested model, and some partial regression coefficients of dry matter intake on energy sinks were heterogeneous between parities. However, the Spearman's rank correlation between RFI values calculated from nested and nonnested models was equal to 0.99. Similarly, Spearman's rank correlation between the RFI breeding values from these 2 models was equal to 0.98. Heritability estimates for RFI were equal to 0.16 for parity 1, 0.19 for parity 2, and 0.22 for parity 3. Repeatability estimates for RFI across weeks within parities were high, ranging from 0.51 to 0.57. Spearman's rank correlations of sires' breeding values were 0.99 between parities 1 and 2, 0.91 between parities 1 and 3, and 0.92 between parities 2 and 3. We conclude that nesting energy sinks within parity when computing RFI improves model goodness of fit, but the impact on the estimated breading values appears to be minimal.

Abstract Background During the COVID-19 pandemic, migrants arriving in host countries irregularly have not infrequently been perceived as increasing the COVID-19 burden. Italy is a transit and destination country for migrants who cross the Central Mediterranean route and, during the pandemic, all migrants who landed on Italian shores were COVID-19 tested and quarantined. Our study aimed to investigate the impact of the SARS-CoV-2 infection among migrants who landed on the Italian coasts by analyzing both incidence and health outcomes. Methods A retrospective observational study has been designed. The population of interest was represented by 70,512 migrants (91% male, 99%

Wound healing is a dynamic and complex process, characterized by the coordinated activities of multiple cell types, each with distinct roles in the stages of hemostasis, inflammation, proliferation, and remodeling. The cells of the immune system not only act as sentinels to monitor the skin and promote homeostasis, but they also play an important role in the process of skin wound repair. Skin-resident and recruited immune cells release cytokines and growth factors that promote the amplification of the inflammatory process. They also work with non-immune cells to remove invading pathogens and debris, as well as guide the regeneration of damaged host tissues. Dysregulation of the immune system at any stage of the process may lead to a prolongation of the inflammatory phase and the development of a pathological condition, such as a chronic wound. The present review aims to summarize the roles of different immune cells, with special emphasis on the different stages of the wound healing process.

The evident necessity to transition away from a reliance on fossil resources implies the need to produce high-value-added chemicals from non-conventional sources, such as lignocellulosic biomass. The cellulosic fraction of this resource can be converted into 5-hydroxymethylfurfural (HMF), which can be further transformed to 2,5-bis(hydroxymethyl)furan (BHMF), a polymeric precursor, or 2,5-dimethylfuran (DMF), serving as a substitute or additive of conventional gasoline. This work investigates the effect of the synthesis method of the Ni-Cu/ZrO2 catalyst on the conversion of HMF to BHMF or DMF. The preparation process exerts influence on the dispersion of metals, the acidity of the catalyst, and the interaction of Ni-Cu. Consequently, product selectivity varied depending on the catalyst preparation method, with BHMF being the primary product when the catalyst was prepared through wet impregnation and DMF when precipitation was the chosen synthesis method. Concretely, a BHMF yield of 60 % yield was achieved at 150 °C with the impregnated catalyst, while a 65 % yield was obtained for DMF when employing the precipitation-prepared catalyst. Furthermore, a noticeable effect of the temperature on product selectivity was also detected.

Introduction: Vancomycin is widely prescribed to treat or prevent Gram-positive infections in pediatric liver transplant recipients. The objective of this prospective cohort study is to describe vancomycin pharmacokinetics and to evaluate the therapeutic target attainment after initial dose regimen. Materials and methods: Patients with previous renal injury were excluded. Vancomycin therapy started with 40‒60 mg/kg/day. The pharmacokinetic parameters were assessed using two steady-state blood samples and the first-order kinetic equations. Therapeutic target was defined as vancomycin 24-hour Area Under the Curve/Minimum Inhibitory Concentration (AUC/MIC) ≥ 400 and < 600. Results: Sixteen patients were included. The found vancomycin clearance, half-life, and volume of distribution were, respectively: 2.1 (1.3‒2.8) mL/kg/min, 3.3 (2.7‒4.4) hours, and 0.7 (0.5‒0.9) L/kg. With the initial dose, only 6 (37 %) patients reached the therapeutic target against Gram-positive pathogens with MIC 1 mg/L. After individual dose adjustments, all patients reached the target. The correlation between trough levels and AUC was low (R2 = 0.5). Conclusions: Pediatric patients with preserved renal function after liver transplantation have an increased volume of distribution for vancomycin, and most patients present subtherapeutic levels after the standard initial dosing regimen. With the vancomycin AUC-guided monitoring and dosing, it is possible to improve therapeutic target attainment.

El presente artículo es un estudio de caso sobre la configuración del deber de imparcialidad en el desarrollo jurisprudencial de los tribunales de derechos humanos y su influencia en los tribunales domésticos peruanos. En esa línea, se analiza la forma en que se ha construido la distinción entre imparcialidad subjetiva y objetiva —identificada con la «teoría de las apariencias»— y, más adelante, se determina la relación entre imparcialidad y sesgos cognitivos. Ello con la finalidad de realizar una crítica a la teoría de las apariencias y proponer la formulación de un estándar en el que se distinguen tres dimensiones de la garantía de imparcialidad: subjetiva, objetivo-funcional y objetivo-cognitiva. Finalmente, se aborda la distinción entre independencia judicial externa e interna, y se determina su diferencia con la imparcialidad.

Different signal transduction pathways contribute to the differentiation and metabolic activities of osteoblasts, with special regard to the calcium-related pathway of phosphoinositide specific phospholipase C (PLC) enzyme family. PLC enzymes were demonstrated to be involved in the differentiation of osteoblasts and differently localize in the nucleus, cytoplasm or both depending on the isoform. The amino-steroid molecule U-73122 inhibits the enzymes belonging to the PLC family. In addition to the temporary block of the enzymatic activity, U-73122 promotes off-target effects, including modulation of the expression of selected PLC genes and different localization of PLC enzymes, depending on the cell line, in different cell lines. In order to evaluate possible off-target effects of the molecule in human osteoblasts, we investigated the expression of PLC genes and the localization of PLC enzymes in cultured human osteoblasts (hOBs) in the presence of low dose U-73122. Our results confirm that all PLC genes are transcribed in hOBs, that probably splicing variants of selected PLC genes are expressed and that all PLC enzymes are present in hOBs, except for PLC δ3 in quiescent hOBs at seeding. Our results confirm literature data excluding toxicity of U-73122 on cell survival. Our results indicate that U-73122 did not significantly affect the transcription of PLC genes. It acts upon the localization of PLC enzymes, as PLC enzymes are detected in cell protrusions or pseudopodia-like structures, at the nuclear or the plasma membrane, in membrane ruffles and/or in the endoplasmic reticulum.