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Abstract Tick-borne encephalitis virus (TBEV) vaccine breakthrough (VBT) infections are not uncommon in endemic areas. The clinical and immunological outcomes have been poorly investigated. We assessed the magnitude and specificity of virus-specific antibody and T cell responses after TBE in previously vaccinated subjects and compared the results with those of unvaccinated TBE patients and study subjects that received vaccination without VBT infection. Symptomatic TBEV infection of unvaccinated study subjects induced virus-specific antibody responses to the E protein and non-structural protein 1 (NS1) as well as T cell responses to structural and other non-structural (NS) proteins. After VBT infections, significantly impaired NS1-specific antibody responses were observed, while the virus-specific T cell responses to the NS proteins were relatively strong. VBT infection caused predominantly moderate to severe disease during hospitalization. The level of TBEV EDIII- and NS1-specific antibodies in unvaccinated convalescent patients inversely correlated with TBE severity and neurological symptoms early after infection.

ObjectiveWe used the lateral fluid percussion injury (LFPI) model of moderate-to-severe traumatic brain injury (TBI) to identify early plasma biomarkers predicting injury, early post-traumatic seizures or neuromotor functional recovery (neuroscores), considering the effect of levetiracetam, which is commonly given after severe TBI.MethodsAdult male Sprague-Dawley rats underwent left parietal LFPI, received levetiracetam (200 mg/kg bolus, 200 mg/kg/day subcutaneously for 7 days [7d]) or vehicle post-LFPI, and were continuously video-EEG recorded (n = 14/group). Sham (craniotomy only, n = 6), and naïve controls (n = 10) were also used. Neuroscores and plasma collection were done at 2d or 7d post-LFPI or equivalent timepoints in sham/naïve. Plasma protein biomarker levels were determined by reverse phase protein microarray and classified according to injury severity (LFPI vs. sham/control), levetiracetam treatment, early seizures, and 2d-to-7d neuroscore recovery, using machine learning.ResultsLow 2d plasma levels of Thr231 -phosphorylated tau protein (pTAU-Thr231 ) and S100B combined (ROC AUC = 0.7790) predicted prior craniotomy surgery (diagnostic biomarker). Levetiracetam-treated LFPI rats were differentiated from vehicle treated by the 2d-HMGB1, 2d-pTAU-Thr231 , and 2d-UCHL1 plasma levels combined (ROC AUC = 0.9394) (pharmacodynamic biomarker). Levetiracetam prevented the seizure effects on two biomarkers that predicted early seizures only among vehicle-treated LFPI rats: pTAU-Thr231 (ROC AUC = 1) and UCHL1 (ROC AUC = 0.8333) (prognostic biomarker of early seizures among vehicle-treated LFPI rats). Levetiracetam-resistant early seizures were predicted by high 2d-IFNγ plasma levels (ROC AUC = 0.8750) (response biomarker). 2d-to-7d neuroscore recovery was best predicted by higher 2d-S100B, lower 2d-HMGB1, and 2d-to-7d increase in HMGB1 or decrease in TNF (P

Antecedentes: el consumo de drogas ilícitas en el Perú es preocupante, siendo la marihuana la más utilizada en la población escolar. Objetivo: este estudio se propuso identificar los factores de riesgo predictores del consumo de marihuana en estudiantes de secundaria entre 13 y 18 años en Lima Metropolitana, así como describir la presencia de estos factores en los estudiantes y determinar las diferencias entre consumidores y no consumidores respecto de los factores. Método: la muestra incluyó 975 estudiantes de colegios públicos y se midieron variables relacionadas al consumo de drogas, expectativas, autoeficacia, búsqueda de sensaciones y monitoreo parental. Resultados: la prevalencia de vida de consumo de marihuana fue del 6.2%, con una edad promedio de 14.18 años. Se destacan la disponibilidad y el consumo de marihuana en el entorno estudiantil como factores de riesgo. Además, se encontraron diferencias significativas entre consumidores y no consumidores en la búsqueda de sensaciones, expectativas, autoeficacia, control y comunicación parental, y percepción de riesgo. La regresión logística mostró que las variablesdicotómicas, como consumo de tabaco, la curiosidad de probar marihuana, la disponibilidad de la droga y la búsqueda de sensaciones, tenían una mayor capacidad predictiva. Conclusión: se encuentran como principales factores de riesgo el consumo previo de alcohol y tabaco, la curiosidad de probar marihuana y la percepción de riesgo del consumo. Asimismo, se encuentran diferencias significativas entre consumidores y no consumidores en expectativas de consumo, búsqueda de sensaciones, autoeficacia para el rechazo de consumo, así como la comunicación y control parental.

Rift Valley fever (RVF) is a mosquito-borne zoonotic disease caused by RVF virus (RVFV). RVFV infections in humans are usually asymptomatic or associated with mild febrile illness, although more severe cases of haemorrhagic disease and encephalitis with high mortality also occur. Currently, there are no licensed human vaccines available. The safety and efficacy of a genetically engineered four-segmented RVFV variant (hRVFV-4s) as a potential live-attenuated human vaccine has been tested successfully in mice, ruminants, and marmosets though the correlates of protection of this vaccine are still largely unknown. In the present study, we have assessed hRVFV-4s-induced humoral and cellular immunity in a mouse model of RVFV infection. Our results confirm that a single dose of hRVFV-4s is highly efficient in protecting naïve mice from developing severe disease following intraperitoneal challenge with a highly virulent RVFV strain and data show that virus neutralizing (VN) serum antibody titres in a prime-boost regimen are significantly higher compared to the single dose. Subsequently, VN antibodies from prime-boost-vaccinated recipients were shown to be protective when transferred to naïve mice. In addition, hRVFV-4s vaccination induced a significant virus-specific T cell response as shown by IFN-γ ELISpot assay, though these T cells did not provide significant protection upon passive transfer to naïve recipient mice. Collectively, this study highlights hRVFV-4s-induced VN antibodies as a major correlate of protection against lethal RVFV infection.

ABSTRACTTick-borne encephalitis virus (TBEV) infection may cause acute central nervous system inflammation varying in clinical manifestations and severity. A possible correlation of TBEV-specific antibody and cell-mediated immune responses, shortly after infection, with clinical manifestations, severity and long-term outcome has been poorly investigated. In a cohort of thirty early tick-borne encephalitis (TBE) patients, we assessed the magnitude, specificity and functional properties of TBEV-specific T-cell and antibody responses. These responses early during disease were assessed in view of clinical manifestations, severity and long-term outcome. TBEV-specific T-cell responses to C, E, NS1, and NS5 proteins were significantly lower in patients with severe acute illness than in patients with mild TBE. Lower T-cell responses to E, NS1, and NS5 proteins also correlated with the development of meningoencephalomyelitis. Virus-specific antibody titres early after infection did not correlate with disease severity, clinical manifestations, or long-term outcome in this study, possibly due to the small number of patients of which matching serum and peripheral blood mononuclear cells were available. The findings suggest that virus-specific T cells afford a certain degree of protection against the development of severe TBEV-induced disease.

Introducción: la violencia contra las mujeres es una problemática social y de salud pública vigente en todo el mundo. A pesar de la diversidad de estudios de prevalencia realizados en los servicios de salud de Iberoamérica, hasta la fecha no se han efectuado revisiones en dicha región. Este trabajo tiene el objetivo de revisar la literatura para conocer cómo se detecta esa violencia y cómo se mide su prevalencia en los servicios de atención primaria de la salud de los países iberoamericanos. Metodología: se llevó a cabo una revisión bibliográfica narrativa de artículos académicos publicados entre 2001 y 2021 orientados a detectar y a medir la prevalencia de la violencia contra las mujeres en el sector salud. Se seleccionaron 42 artículos originales y se sintetizaron los resultados de forma integrativa. Resultados: la detección y/o la medición de la violencia contra las mujeres en los centros de salud se ha concretado mediante variados instrumentos, en su mayoría, de tipo diagnóstico. Se identificaron tres perspectivas teóricas; cada una construye una imagen sobre el problema de la violencia. Conclusión: es necesario formular datos válidos y confiables sobre esta temática, con posibilidad de ser comparados entre regiones y a lo largo del tiempo. Es de importancia anclar los diseños de investigación en las teorías sociales, para lograr una comprensión contextualizada y multidimensional del fenómeno. Se debe indagar sobre el modo más apropiado para detectar y atender la violencia contra las mujeres en el ámbito de la salud.

Lithium-ion Batteries are widely used in several applications but require complex management systems to ensure their safe and effective usage. Algorithm development and functional testing are among the most complex and time-consuming phases of lithium-ion battery management system design. Furthermore, the use of real batteries in those phases introduces safety hazards. The hardware-in-the-loop approach allows the designers to overcome these limitations by replacing real batteries with hardware emulators. This article presents a low-cost battery emulator platform to reproduce the main electrical and thermal behaviors of elementary battery cells. The platform allows the user to manually control the emulator outputs or automatically reproduce specific voltage, temperature, and current profiles. In addition, the platform can independently reproduce the battery cell behaviors by using a customizable 2-RC equivalent electrical model. The functional testing and the balancing algorithm assessment of a custom battery management system are used as a case study to evaluate the developed battery emulator platform. Results demonstrate the effective advantages of the developed platform to assess the battery management system safety functionalities and algorithms. Finally, the platform is made freely available to accelerate research and innovation in the field of energy storage technology.

Buildings are complex assets, characterized by environments and uses that change over time, variable occupancies, and long life cycles. They have high operational costs, mostly due to their energy requirements, and account for 30% to 40% of global greenhouse gas emissions. Consequently, substantial effort has been made to forecast their energy needs, with the scope of optimizing their economic and environmental impact. In this regard, the available literature focuses mainly on short-term modeling through the implementation of sets of physics-based equations (i.e., white-box), functional relationships between input and output variables (i.e., black-box), or a combination of both (i.e., grey-box). On the other hand, more research is required on long-term forecast models with the aim of reducing the energy needs. Within this context, this article presents an original automatic procedure for forecasting the energy needs of buildings in short- and long-term time horizons. This is accomplished by scaling an unknown facility from a similar facility that is already known and by executing a black-box approach based on machine learning algorithms. The proposed method is implemented in real case studies in Italy, predicting the energy needs (i.e., heating, cooling, and electricity) of Sant’Anna Hospital in Ferrara using the historical data of Ca’ Foncello Hospital in Treviso. The results show an adjusted coefficient of determination above 0.7 and an average error below 10% for all the energy vectors, demonstrating a feasible forecast performance with a low training set-to-test set ratio.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition with a strong genetic basis. We accurately assessed 209 ASD subjects, categorized in complex (47) and essential (162), and performed array comparative genomic hybridization to identify pathogenic and recurrent Copy Number Variants (CNVs). We found 117 CNVs in 75 patients, 11 classified as pathogenic. The complex ASD subjects have higher frequency of pathogenic CNVs with a diagnostic yield of 12.8%. Familiality, cognitive and verbal abilities, severity of autistic symptoms, neuroimaging and neurophysiological findings are not related to genetic data. This study identifies loci of interest for ASD and highlights the importance of a careful phenotypic characterization, as complex ASD is related to higher rate of pathogenic CNVs.

Influenza viruses are notorious for their capacity to evade host immunity. Not only can they evade recognition by virus-neutralizing antibodies, there is also evidence that they accumulate mutations in epitopes recognized by virus-specific CD8+ T cells. In addition, we have shown previously that human influenza A viruses were less well recognized than avian influenza viruses by CD8+ T cells directed to the highly conserved, HLA-A*02:01 restricted M158–66 epitope located in the Matrix 1 (M1) protein. Amino acid differences at residues outside the epitope were responsible for the differential recognition, and it was hypothesized that this reflected immune adaptation of human influenza viruses to selective pressure exerted by M158–66-specific CD8+ T cells in the human population. In the present study, we tested this hypothesis and investigated if selective pressure exerted by M158–66 epitope-specific CD8+ T cells could drive mutations at the extra-epitopic residues in vitro. To this end, isogenic influenza A viruses with the M1 gene of a human or an avian influenza virus were serially passaged in human lung epithelial A549 cells that transgenically express the HLA-A*02:01 molecule or not, in the presence or absence of M158–66 epitope-specific CD8+ T cells. Especially in the virus with the M1 gene of an avian influenza virus, variants emerged with mutations at the extra-epitopic residues associated with reduced recognition by M158–66-specific T cells as detected by Next Generation Sequencing. Although the emergence of these variants was observed in the absence of selective pressure exerted by M158–66 epitope-specific CD8+ T cells, their proportion was much larger in the presence of this selective pressure.

Introduction Remote monitoring technologies (RMTs) can measure cognitive and functional decline objectively at-home, and offer opportunities to measure passively and continuously, possibly improving sensitivity and reducing participant burden in clinical trials. However, there is skepticism that age and cognitive or functional impairment may render participants unable or unwilling to comply with complex RMT protocols. We therefore assessed the feasibility and usability of a complex RMT protocol in all syndromic stages of Alzheimer's disease and in healthy control participants. Methods For 8 weeks, participants (N = 229) used two activity trackers, two interactive apps with either daily or weekly cognitive tasks, and optionally a wearable camera. A subset of participants participated in a 4-week sub-study (N = 45) using fixed at-home sensors, a wearable EEG sleep headband and a driving performance device. Feasibility was assessed by evaluating compliance and drop-out rates. Usability was assessed by problem rates (e.g., understanding instructions, discomfort, forgetting to use the RMT or technical problems) as discussed during bi-weekly semi-structured interviews. Results Most problems were found for the active apps and EEG sleep headband. Problem rates increased and compliance rates decreased with disease severity, but the study remained feasible. Conclusions This study shows that a highly complex RMT protocol is feasible, even in a mild-to-moderate AD population, encouraging other researchers to use RMTs in their study designs. We recommend evaluating the design of individual devices carefully before finalizing study protocols, considering RMTs which allow for real-time compliance monitoring, and engaging the partners of study participants in the research.

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a betacoronavirus that is of special interest for public health. Dromedary camels have been identified as natural animal reservoirs, with >90% MERS-CoV [...]

Streptococcus equi subspecies zooepidemicus is a P-hemolytic streptococcus expressing Lancefield group C antigen and is 1 of 3 S. equi subspecies. S. equi subsp. zooepidemicus is an opportunistic pathogen that [...]

Pollen food allergy syndrome (PFAS) is an allergic reaction to specific foods in persons previously sensitised to pollen. The diagnosis of PFAS is made after taking a patient’s medical history and, in some cases, conducting skin tests and oral food tests with raw fruit or vegetables. The aim of the present study was to evaluate the role of Pru p 7 in patients suspected of having PFAS, who show clinical symptoms, positivity for Cup a 1 and negativity for Pru p 1 and Pru p 3. A total of 51 patients (mean age ± standard deviation, 33 ± 15 years; 20 men and 31 women), referred to the respiratory diseases and allergology units of Siena University Hospital, were enrolled retrospectively. All of them underwent allergy consultation and IgE evaluation for Cup a 1, Pru p 1 and Pru p 3 by immuno solid-phase allergen chip (ISAC). Pru p 7 assay was performed by the ImmunoCAP Phadia method in patients who tested positive for Cup a 1 and simultaneously negative for Pru p 1 and Pru p 3 by ISAC. The serum of 51 patients was tested for sensitisation to Pru p 7 by the ImmunoCAP Phadia method, and nine patients (17.65%) were found positive. An area under the receiver operating characteristic (AUROC) curve of 99.51% made it possible to distinguish PFAS and non-PFAS patients on the basis of Pru p 7 values. The best cut-off value was 0.16 kUA/l, which gave a 85.7% sensitivity and 97.73% specificity. This study helps define the role of Pru p 7 in PFAS patients sensitised to cypress pollen and testing negative to Pru p 1 and Pru p 3. A fast, easy and non-invasive diagnostic method is proposed to detect IgE specific for Pru p 7. Inclusion of Pru p 7 in the ISAC assay panel would facilitate the diagnosis of PFAS.

Resumen Este estudio explora el impacto de las leyes de paridad de género vigentes en la provincia de Córdoba en los últimos veinte años. Desde su implementación, tales normativas han contemplado un criterio de paridad vertical por el cual las listas electorales deben conformarse con un porcentaje equivalente de mujeres y varones, organizado con una alternancia secuencial aplicada tanto a titulares como a suplentes. Sin embargo, el efecto de estas normativas se debilita al aplicarse en Cámaras Legislativas como la de Córdoba, organizada bajo un sistema mixto que combina bancas correspondientes a distritos plurinominales y uninominales. Este estudio analiza la composición de la Unicameral Cordobesa, evidenciando los obstáculos que imposibilitan alcanzar una composición paritaria en la Cámara. Los resultados dan cuenta también de la subrepresentación de mujeres en otros roles jerárquicos dentro de la Cámara y en los Ministerios. En base a los hallazgos se realizan una serie de recomendaciones.

Abstract Objective We used the lateral fluid percussion injury (LFPI) model of moderate‐to‐severe traumatic brain injury (TBI) to identify early plasma biomarkers predicting injury, early post‐traumatic seizures or neuromotor functional recovery (neuroscores), considering the effect of levetiracetam, which is commonly given after severe TBI. Methods Adult male Sprague–Dawley rats underwent left parietal LFPI, received levetiracetam (200 mg/kg bolus, 200 mg/kg/day subcutaneously for 7 days [7d]) or vehicle post‐LFPI, and were continuously video‐EEG recorded (n = 14/group). Sham (craniotomy only, n = 6), and naïve controls (n = 10) were also used. Neuroscores and plasma collection were done at 2d or 7d post‐LFPI or equivalent timepoints in sham/naïve. Plasma protein biomarker levels were determined by reverse phase protein microarray and classified according to injury severity (LFPI vs. sham/control), levetiracetam treatment, early seizures, and 2d‐to‐7d neuroscore recovery, using machine learning. Results Low 2d plasma levels of Thr231‐phosphorylated tau protein (pTAU‐Thr231) and S100B combined (ROC AUC = 0.7790) predicted prior craniotomy surgery (diagnostic biomarker). Levetiracetam‐treated LFPI rats were differentiated from vehicle treated by the 2d‐HMGB1, 2d‐pTAU‐Thr231, and 2d‐UCHL1 plasma levels combined (ROC AUC = 0.9394) (pharmacodynamic biomarker). Levetiracetam prevented the seizure effects on two biomarkers that predicted early seizures only among vehicle‐treated LFPI rats: pTAU‐Thr231 (ROC AUC = 1) and UCHL1 (ROC AUC = 0.8333) (prognostic biomarker of early seizures among vehicle‐treated LFPI rats). Levetiracetam‐resistant early seizures were predicted by high 2d‐IFNγ plasma levels (ROC AUC = 0.8750) (response biomarker). 2d‐to‐7d neuroscore recovery was best predicted by higher 2d‐S100B, lower 2d‐HMGB1, and 2d‐to‐7d increase in HMGB1 or decrease in TNF (P

We developed an ELISPOT assay for evaluating Middle East respiratory syndrome coronavirus (MERS-CoV)‒specific T-cell responses in dromedary camels. After single modified vaccinia virus Ankara-MERS-S vaccination, seropositive camels showed increased levels of MERS-CoV‒specific T cells and antibodies, indicating suitability of camel vaccinations in disease-endemic areas as a promising approach to control infection.

Problematic Internet use (PIU) can lead to dysfunction and undesired consequences, especially in adolescents and youths. Preventive interventions can reduce them, but should be built on sound evidence. This review synthesizes the available evidence on the effectiveness of primary prevention programs for PIU in adolescents and youths. It adds to previous reviews by broadening the search to general and specific problematic behavior. Two independent reviewers performed a systematic search for published studies on PIU and internet addiction in English, French and Spanish using PubMed, PsycINFO, Cochrane Register of Controlled Trials, and Scopus. Published experimental and quasi-experimental studies that assessed the effectiveness of primary prevention programs targeting PIU behaviors were considered for inclusion. Full texts for eligible studies were retrieved and assessed for quality. Five studies were retained for narrative synthesis. Three of them based the intervention strategy on an underlying theory, one on media literacy, and one used an educational-based approach. A meta-analysis showed that all five interventions were effective in preventing internet addiction separately. However, when using the Hartung-Knapp-Sidik-Jonkman (HKSJ) estimator and removing one of the studies because of a disproportionate Hedges’ g, combined effects were no longer significant. Although PIU is a popular topic, little is known about ways to prevent it. This review demonstrates that prevention programs can be based on different theoretical approaches, but that the available evidence is too heterogeneous to derive generalizable conclusions concerning their effectiveness.

During November 2021–May 2022, we identified 37 clinical cases of Streptococcus equi subspecies zooepidemicus infections in central Italy. Epidemiologic investigations and whole-genome sequencing showed unpasteurized fresh dairy products were the outbreak source. Early diagnosis by using sequencing technology prevented the spread of life-threatening S. equi subsp. zooepidemicus infections.