Immunogenicity of RV1 and RV5 vaccines administered in standard and interchangeable mixed schedules: a randomized, double-blind, non-inferiority clinical trial in Mexican infants.

Introduction: Rotavirus-associated diarrheal diseases significantly burden healthcare systems, particularly affecting infants under five years. Both Rotarix™ (RV1) and RotaTeq™ (RV5) vaccines have been effective but have distinct application schedules and limited interchangeability data. This study aims to provide evidence on the immunogenicity, reactogenicity, and safety of mixed RV1-RV5 schedules compared to their standard counterparts. Methods: This randomized, double-blind study evaluated the non-inferiority in terms of immunogenicity of mixed rotavirus vaccine schedules compared to standard RV1 and RV5 schedules in a cohort of 1,498 healthy infants aged 6 to 10 weeks. Participants were randomly assigned to one of seven groups receiving various combinations of RV1, and RV5. Standard RV1 and RV5 schedules served as controls of immunogenicity, reactogenicity, and safety analysis. IgA antibody levels were measured from blood samples collected before the first dose and one month after the third dose. Non-inferiority was concluded if the reduction in seroresponse rate in the mixed schemes, compared to the standard highest responding scheme, did not exceed the non-inferiority margin of -0.10. Reactogenicity traits and adverse events were monitored for 30 days after each vaccination and analyzed on the entire cohort. Results: Out of the initial cohort, 1,365 infants completed the study. Immunogenicity analysis included 1,014 infants, considering IgA antibody titers ≥20 U/mL as seropositive. Mixed vaccine schedules demonstrated non-inferiority to standard schedules, with no significant differences in immunogenic response. Safety profiles were comparable across all groups, with no increased incidence of serious adverse events or intussusception. Conclusion: The study confirms that mixed rotavirus vaccine schedules are non-inferior to standard RV1 and RV5 regimens in terms of immunogenicity and safety. This finding supports the flexibility of rotavirus vaccination strategies, particularly in contexts of vaccine shortage or logistic constraints. These results contribute to the global effort to optimize rotavirus vaccination programs for broader and more effective pediatric coverage.Clinical trial registration: ClinicalTrials.gov, NCT02193061.

Precision Enhancement of CAR-NK Cells through Non-Viral Engineering and Highly Multiplexed Base Editing.

Natural killer (NK) cells' unique ability to kill transformed cells expressing stress ligands or lacking major histocompatibility complexes (MHC) has prompted their development for immunotherapy. However, NK cells have demonstrated only moderate responses against cancer in clinical trials and likely require advanced genome engineering to reach their full potential as a cancer therapeutic. Multiplex genome editing with CRISPR/Cas9 base editors (BE) has been used to enhance T cell function and has already entered clinical trials but has not been reported in human NK cells. Here, we report the first application of BE in primary NK cells to achieve both loss-of-function and gain-of-function mutations. We observed highly efficient single and multiplex base editing, resulting in significantly enhanced NK cell function. Next, we combined multiplex BE with non-viral TcBuster transposon-based integration to generate IL-15 armored CD19 CAR-NK cells with significantly improved functionality in a highly suppressive model of Burkitt's lymphoma both in vitro and in vivo. The use of concomitant non-viral transposon engineering with multiplex base editing thus represents a highly versatile and efficient platform to generate CAR-NK products for cell-based immunotherapy and affords the flexibility to tailor multiple gene edits to maximize the effectiveness of the therapy for the cancer type being treated.

Performance Evaluation of a Novel Combination of Four- and Five-Carbon [Butyric and Valeric] Short-Chain Fatty Acid Glyceride Esters in Broilers.

A novel combination of Butyric and Valeric acid glycerol esters with oregano oil in a dry powder form was evaluated for performance improvements in broilers. The dosing regimen (500 g/Ton feed in starter and grower; 250 g/Ton in finisher feed) was considered low compared to conventional practices using non-esterified Butyric and Valeric short-chain fatty acids (SCFA). Six trials were conducted at various trial facilities in Italy, United Kingdom, Spain, and Poland. Supplemented broilers weighed significantly more than the control birds at 28 days of age (+3.4%; 1459 g vs. 1412 g; p = 0.0006) and at 42 days of age (+2.5%; 2834 g vs. 2763 g; p = 0.0030). Supplementation significantly reduced mortality from 1.9% to 0.8% during the finisher phase (from 29 to 42 days of age); however, average mortality was 3.2% for the whole 42-day growth period and was not affected. Further, supplemented broilers grew more (66.4 vs. 64.5 g/day; p = 0.0005), ate more feed (104.7 vs. 103.1 g/day; p = 0.0473), converted feed significantly more efficiently (1.58 vs. 1.60; p = 0.0072), leading to better EPEF value (410 vs. 389; p = 0.0006) than the control broilers. Meta-analysed trial performance data for novel SCFA formulations such as these are not commonly available, and serve to facilitate efficacy determination from an end-user perspective. The use of short- and medium-chain fatty acid esters in optimal low-dose combinations to reliably augment gut health and performance appears promising in commercial broiler production, and may lead to further improvements in industry practices and reduced antibiotic use.

Open-source controller for dynamic cardiovascular models.

Cardiovascular pressure sensors require dedicated, reliable, and customisable performance testing equipment. Devices available on the market, such as pulsatile pumps and pulse multipliers, offer limited adaptability to the needs of pressure sensor testing or are highly complex tools designed for other purposes. Therefore, there is a strong need to provide an adaptable and versatile device for characterisation during prototype development, prior to animal model testing. Early development requires detailed characterisation of a sensor performance in a realistic environmental scenario. To address this need, we adapted an off-the-shelf pressure chamber with a custom Arduino-based controller to achieve a rapid change in pressure that simulates the pulsatile profile of human blood pressure. The system is a highly customisable tool, and we have experimentally shown that it works successfully in a wide range of pressures from 30 mmHg to 400 mmHg with a resolution of 2 mmHg. By adjusting the chamber volume using a water balloon, we achieved a cycle rate of up to 120 beats per minute. The device can be operated directly from the Arduino IDE or with a customised graphical user interface developed by our research group. The proposed system is intended to assist other researchers in the development of industrial and biomedical pressure sensors.

Effect of a Bacillus-Based Probiotic on Performance and Nutrient Digestibility When Substituting Soybean Meal with Rapeseed Meal in Grower-Finisher Diets.

The objective of the present study was to test the hypothesis of B. subtilis and B. licheniformis supplementation to a negative control diet in comparison to a standard control diet, had the potential to improve the performance and nutrient digestibility of growing-finishing pigs. For this purpose, 384 fattening pigs of 85 d of age were allotted to three treatments: a standard diet, a negative control (NC) diet (5% soybean meal replaced by 5% rapeseed meal), or a NC diet + probiotic. After reaching a body weight of approximately 110 kg, all animals going to the slaughterhouse (87% of total pigs) were selected to measure carcass quality. Moreover, the apparent total tract digestibility of protein was evaluated at the end of the grower period. The results of this study indicate that supplementation of the tested Bacillus-based probiotic significantly improved average daily gain (ADG, +14.6%) and Feed:gain ratio (F:G, -9.9%) during the grower phase compared to the NC diet. The improvement observed during the grower phase was maintained for the whole fattening period (ADG, +3.9%). Probiotic supplementation significantly improved the total apparent faecal digestibility of dry matter and crude protein in pigs at the end of the grower period. The improvements observed with the additive tested could indicate that supplementation of the Bacillus-based probiotic was able to counteract the lower level of crude protein and standardised ileal digestible amino acids in the NC diet by means of improved protein digestibility.

Microsurgical and endoscopic-assisted supraorbital keyhole approach for intra-suprasellar cysticercosis.

Background: Treatment for intra/suprasellar cysticercosis can be challenging and may result in visual disturbances if not managed properly. Despite its limited knowledge, an effective surgical option exists to treat this condition. This article presents three cases of sellar cysticercosis, comprising one female and two male patients, managed with microsurgical supraorbital keyhole approach (mSKA) and endoscopic-assisted supraorbital keyhole approach (eaSKA). Case Description: The first patient is a 35-year-old man with no prior medical history who suffered from memory deficits and visual disturbances due to a sellar cyst pushing the orbitofrontal gyrus treated with mSKA. The second case involved a 52-year-old man who experienced visual deficits caused by a rostral sellar cyst with posterior displacement of the pituitary gland treated with eaSKA. The third case was a 46-year-old woman who experienced decreased visual acuity and memory loss due to multifocal neurocysticercosis (NCC) with sellarsuprasellar cyst extension treated with mSKA. All case diagnoses were confirmed by neuropathology department. Conclusion: The authors confidently suggest that the SKA is an effective surgical option and could be considered for removing sellar cystic lesions with suprasellar extension. With endoscopic assistance, it improves adequate neurovascular structure visualization.

Summary-data based Mendelian randomization identifies gene expression regulatory polymorphisms associated with bovine paratuberculosis by modulation of the nuclear factor Kappa ß (NF-κß)-mediated inflammatory response.

Genome-wide association studies (GWAS) have identified host genetic variants associated with paratuberculosis (PTB) susceptibility. Most of the GWAS-identified SNPs are in non-coding regions. Connecting these non-coding variants and downstream affected genes is a challenge and, up to date, only a few functional mutations or expression quantitative loci (cis-eQTLs) associated with PTB susceptibility have been identified. In the current study, the associations between imputed whole-genome sequence genotypes and whole RNA-Sequencing data from peripheral blood (PB) and ileocecal valve (ICV) samples of Spanish Holstein cows (N = 16) were analyzed with TensorQTL. This approach allowed the identification of 88 and 37 cis-eQTLs regulating the expression levels of 90 and 37 genes in PB and ICV samples, respectively (False discorey rate, FDR ≤ 0.05). Next, we applied summary-based data Mendelian randomization (SMR) to integrate the cis-eQTL dataset with GWAS data obtained from a cohort of 813 culled cattle that were classified according to the presence or absence of PTB-associated histopathological lesions in gut tissues. After multiple testing corrections (FDR ≤ 0.05), we identified two novel cis-eQTLs affecting the expression of the early growth response factor 4 (EGR4) and the bovine neuroblastoma breakpoint family member 6-like protein isoform 2 (MGC134040) that showed pleiotropic associations with the presence of multifocal and diffuse lesions in gut tissues; P = 0.002 and P = 0.017, respectively. While EGR4 acts as a brake on T-cell proliferation and cytokine production through interaction with the nuclear factor Kappa ß (NF-κß), MGC134040 is a target gene of NF-κß. Our findings provide a better understanding of the genetic factors influencing PTB outcomes, confirm that the multifocal lesions are localized/confined lesions that have different underlying host genetics than the diffuse lesions, and highlight regulatory SNPs and regulated-gene targets to design future functional studies.

Cell-mediated and Neutralizing Antibody Responses to the SARS-CoV-2 Omicron BA.4/BA.5-adapted Bivalent Vaccine Booster in Kidney and Liver Transplant Recipients.

Background: The immunogenicity elicited by the Omicron BA.4/BA.5-adapted bivalent booster vaccine after solid organ transplantation (SOT) has not been characterized. Methods: We assessed cell-mediated and neutralizing IgG antibody responses against the BA.4/BA.5 spike receptor-binding domain at baseline and 2 wk after the administration of an mRNA-based bivalent (ancestral strain and BA.4/BA.5 subvariants) vaccine among 30 SOT recipients who had received ≥3 monovalent vaccine doses. Previous coronavirus disease 2019 history was present in 46.7% of them. We also recruited a control group of 19 nontransplant healthy individuals. Cell-mediated immunity was measured by fluorescent ELISpot assay for interferon (IFN)-γ secretion, whereas the neutralizing IgG antibody response against the BA.4/BA.5 spike receptor-binding domain was quantified with a competitive ELISA. Results: The median number of BA.4/BA.5 spike-specific IFN-γ-producing spot-forming units (SFUs) increased from baseline to 2 wk postbooster (83.8 versus 133.0 SFUs/106 peripheral blood mononuclear cells; P = 0.0017). Seropositivity rate also increased (46.7%-83.3%; P = 0.001), as well as serum neutralizing activity (4.2%-78.3%; P < 0.0001). Patients with no prior coronavirus disease 2019 history experienced higher improvements in cell-mediated and neutralizing responses after booster vaccination. There was no correlation between BA.4/BA.5 spike-specific IFN-γ-producing SFUs and neutralizing activity. Nontransplant controls showed more robust postbooster cell-mediated immunity than SOT recipients (591.1 versus 133.0 IFN-γ-producing SFUs/106 peripheral blood mononuclear cells; P < 0.0001), although no differences were observed for antibody responses in terms of postbooster seropositivity rates or neutralizing activity. Conclusions: Booster with the BA.4/BA.5-adapted bivalent vaccine generated strong subvariant-specific responses among SOT recipients. Booster-induced cell-mediated immunity, however, remained lower than in immunocompetent individuals.

Sensibilidad y especificidad de la oximetría de pulso para detectarcardiopatías congénitas en recién nacidos / Sensitivity and specificity of pulse oximetry to detect congenital heart disease in newborns

Resumen Objetivo: Determinar la sensibilidad y especificidad de la oximetría de pulso, para detectar cardiopatías congénitas en recién nacidos sanos en alojamiento conjunto. Material y métodos: El estudio es de tipo multicéntrico, prospectivo y transversal, evaluando pacientes del Hospital Regional de Alta Especialidad "Bicentenario 2010" y el Hospital General "Dr. Norberto Treviño Zapata", en ciudad Victoria Tamaulipas, en un periodo que comprendió desde marzo del 2015 a marzo de 2017. Se determinó la oximetría de pulso a recién nacidos sanos antes del egreso hospitalario. Resultados: Se estudiaron 511 recién nacidos. La sensibilidad detectada fue del 88.89 % y una especificidad del 99.80%. Conclusión: Las cardiopatías congénitas en recién nacidos sanos en alojamiento conjunto, se pueden determinar mediante la oximetría de pulso pre y post-ductal.

Abstract Objective: To determine the sensitivity and specificity of pulse oximetry to detect congenital heart disease in healthy newborns in rooming-in. Material and methods: The study is multicenter, prospective and cross-sectional, evaluating patients from the Regional Hospital of High Specialty "Bicentenario 2010" and the General Hospital "Dr. Norberto Treviño Zapata", in the city of Victoria Tamaulipas, in a period from march 2015 to March 2017. Pulse oximetry was determined in healthy newborns before hospital discharge. Results: 511 newborns were studied. The sensitivity detected was 88.89% and a specificity of 99.80%. Conclusion: Congenital heart disease in healthy newborns in rooming-in can be determined by pre- and post-ductal pulse oximetry.

Association between High Interferon-Gamma Production in Avian Tuberculin-Stimulated Blood from Mycobacterium avium subsp. paratuberculosis-Infected Cattle and Candidate Genes Implicated in Necroptosis.

The mechanisms underlying host resistance to Mycobacterium avium subsp. paratuberculosis (MAP) infection are largely unknown. In the current study, we hypothesize that cows with an ability to produce higher levels of interferon-gamma (IFNÉ£) might control MAP infection more successfully. To test this hypothesis, IFNÉ£ production was measured using a specific IFNÉ£ ELISA kit in avian purified protein derivative (aPPD)-stimulated blood samples collected from 152 Holstein cattle. DNA isolated from peripheral blood samples of the animals included in the study was genotyped with the EuroG Medium-Density Bead Chip, and the genotypes were imputed to whole-genome sequencing. A genome-wide association analysis (GWAS) revealed that high levels of IFNÉ£ in response to the aPPD were associated with a specific genetic profile (heritability = 0.64) and allowed the identification of 71 SNPs, 40 quantitative trait loci (QTL), and 104 candidate genes. A functional analysis using the 104 candidate genes revealed a significant enrichment of genes involved in the innate immune response and, more specifically, in necroptosis. Taken together, our results define a heritable and distinct immunogenetic profile associated with the production of high IFNÉ£ levels and with the capacity of the host to lyse MAP-infected macrophages by necroptosis.

Invasive Aedes mosquitoes in an urban-peri-urban gradient in northern Spain: evidence of the wide distribution of Aedes japonicus.

BACKGROUND: The expansion of invasive mosquitoes throughout Europe has increased in recent decades. In northern Spain, Aedes albopictus was detected for the first time in 2014, and Aedes japonicus was detected in the three Basque provinces in 2020. This study aimed to evaluate the distribution of these mosquito species and their association with factors related to urbanization. METHODS: In 2021, a total of 568 ovitraps were deployed in 113 sampling sites from 45 municipalities with > 10,000 inhabitants. Oviposition substrate sticks were replaced each fortnight and examined for Aedes eggs from June to November. Aedes eggs were counted, and the eggs from a selection of positive oviposition sticks, encompassing at least one stick from each positive ovitrap, were hatched following their life cycle until the adult stage. When egg hatching was not successful, PCR targeting the COI gene and sequencing of amplicons were carried out. RESULTS: Eggs were detected in 66.4% of the sampling sites and in 32.4% of the ovitraps distributed in the three provinces of the Basque Country. Aedes albopictus and Ae. japonicus were widespread in the studied area, confirming their presence in 23 and 26 municipalities, respectively. Co-occurrence of both species was observed in 11 municipalities. The analysis of the presence of Aedes invasive mosquitoes and the degree of urbanization (urban, suburban, peri-urban) revealed that Ae. albopictus showed a 4.39 times higher probability of being found in suburban areas than in peri-urban areas, whereas Ae. japonicus had a higher probability of being found in peri-urban areas. Moreover, the presence of Ae. albopictus was significantly associated with municipalities with a higher population density (mean = 2983 inh/km2), whereas Ae. japonicus was associated with lower population density (mean = 1590 inh/km2). CONCLUSIONS: The wide distribution of Ae. albopictus and Ae. japonicus observed confirmed the spread and establishment of these species in northern Spain. A new colonization area of Ae. japonicus in Europe was confirmed. Due to the potential impact of Aedes invasive mosquitoes on public health and according to our results, surveillance programs and control plans should be designed considering different urbanization gradients, types of environments, and population density.

Optimizing Cardiac Wireless Implant Communication: A Feasibility Study on Selecting the Frequency and Matching Medium.

Cardiac wireless implantable medical devices (CWIMD) have brought a paradigm shift in monitoring and treating various cardiac conditions, including heart failure, arrhythmias, and hypertension. One of the key elements in CWIMD is the implant antenna which uses radio frequency (RF) technology to wirelessly communicate and transmit data to external devices. However, wireless communication with a deeply implanted antenna using RF can be challenging due to the significant loss of electromagnetic (EM) signal at the air-skin interface, and second, due to the propagation and reflection of EM waves from different tissue boundaries. The air-skin interface loss of the EM wave is pronounced due to the absence of a matching medium. This paper investigates the EM propagation losses in the human body and presents a choice of optimal frequency for the design of the cardiac implant antenna and the dielectric properties of the matching medium. First, the dielectric properties of all tissues present in the human thorax including skin, fat, muscle, cartilage, and heart are analyzed as a function of frequency to study the EM wave absorption at different frequencies. Second, the penetration of EM waves inside the biological tissues is analyzed as a function of frequency. Third, a transmission line (TL) formalism approach is adopted to examine the optimal frequency band for designing a cardiac implant antenna and the matching medium for the air-skin interface. Finally, experimental validation is performed at two ISM frequencies, 433 MHz and 915 MHz, selected from the optimal frequency band (0.4-1.5 GHz) suggested by our analytical investigation. For experimental validation, two off-the-shelf flexible dipole antennas operating at selected ISM frequencies were used. The numerical and experimental findings suggested that for the specific application of a cardiac implant with a penetration depth of 7-17 cm, the most effective frequency range for operation is within 0.4-1.5 GHz. The findings based on the dielectric properties of thorax tissues, the penetration depth of EM waves, and the optimal frequency band have provided valuable information on developing and optimizing CWIMDs for cardiac care applications.

Inborn Error of STAT2-Dependent IFN-I Immunity in a Patient Presented with Hemophagocytic Lymphohistiocytosis and Multisystem Inflammatory Syndrome in Children.

Human inborn errors of immunity (IEI) affecting the type I interferon (IFN-I) induction pathway have been associated with predisposition to severe viral infections. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening systemic hyperinflammatory syndrome that has been increasingly associated with inborn errors of IFN-I-mediated innate immunity. Here is reported a novel case of complete deficiency of STAT2 in a 3-year-old child that presented with typical features of HLH after mumps, measles, and rubella vaccination at the age of 12 months. Due to the life-threatening risk of viral infection, she received SARS-CoV-2 mRNA vaccination. Unfortunately, she developed multisystem inflammatory syndrome in children (MIS-C) after SARS-CoV-2 infection, 4 months after the last dose. Functional studies showed an impaired IFN-I-induced response and a defective IFNα expression at later stages of STAT2 pathway induction. These results suggest a possible more complex mechanism for hyperinflammatory reactions in this type of patients involving a possible defect in the IFN-I production. Understanding the cellular and molecular links between IFN-I-induced signaling and hyperinflammatory syndromes can be critical for the diagnosis and tailored management of these patients with predisposition to severe viral infection.

Decreased breadth of the antibody response to the spike protein of SARS-CoV-2 after repeated vaccination.

Introduction: The rapid development of vaccines to prevent COVID-19 has raised the need to compare the capacity of different vaccines in terms of developing a protective humoral response. Previous studies have shown inconsistent results in this area, highlighting the importance of further research to evaluate the efficacy of different vaccines. Methods: This study utilized a highly sensitive and reliable flow cytometry method to measure the titers of IgG1 isotype antibodies in the blood of healthy volunteers after receiving one or two doses of various vaccines administered in Spain. The method was also used to simultaneously measure the reactivity of antibodies to the S protein of the original Wuhan strain and variants B.1.1.7 (Alpha), B.1.617.2 (Delta), and B.1.617.1 (Kappa). Results: Significant differences were observed in the titer of anti-S antibodies produced after a first dose of the vaccines ChAdOx1 nCov-19/AstraZeneca, mRNA-1273/Moderna, BNT162b2/Pfizer-BioNTech, and Ad26.COV.S/Janssen. Furthermore, a relative reduction in the reactivity of the sera with the Alpha, Delta, and Kappa variants, compared to the Wuhan strain, was observed after the second boosting immunization. Discussion: The findings of this study provide a comparison of different vaccines in terms of anti-S antibody generation and cast doubts on the convenience of repeated immunization with the same S protein sequence. The multiplexed capacity of the flow cytometry method utilized in this study allowed for a comprehensive evaluation of the efficacy of various vaccines in generating a protective humoral response. Future research could focus on the implications of these findings for the development of effective COVID-19 vaccination strategies.

Prevalencia de infección de herida quirúrgica en pacientes con profilaxis antimicrobiana en cesárea programada / Prevalence of surgical wound infection in patients with antimicrobial prophylaxis in planned cesarean section

Resumen: Objetivo: Determinar la prevalencia de infecciones en la herida quirúrgica en cesáreas programadas del HRAEV. Materiales y método: Estudio retrospectivo, descriptivo, observacional tipo corte transversal para determinar la prevalencia de IHQ en pacientes llevadas a cesárea programada con profilaxis antibiótica en HRAEV. Resultados: Se evaluaron 185 expedientes de pacientes sometidas a cesárea programada, con edad entre 28 a 37 años (48.1%) con un peso promedio 81 kg (DE=10.1) con un índice de masa corporal (IMC) promedio de 30 (DE=4.24) es decir un IMC entre 25.76 a 34.24. De ellas, 4 pacientes (2.16%) presentaron infección de herida quirúrgica durante cesárea programada, las cuales recibieron ceftriaxona como PA mayor a 120 minutos previo a la incisión de la piel, estos pacientes se clasifican como ASA II y tenían un IMC superior a 30 kg/m2 y sin comorbilidades registradas. El tiempo de profilaxis antibiótica más frecuente en las pacientes llevadas a cesárea programada fue >120 minutos (34.08%) y se administró ceftriaxona en el 84.86% de la población que en su mayoría es ASA II (97.83%). El 100% de las heridas fueron superficiales. Conclusiones: En el presente estudio se encontró que la prevalencia de IHQ en cesáreas programadas en HRAEV fue de 2.16%, cifra que se encuentra por debajo de la prevalencia a nivel mundial, dado a que las pacientes seleccionadas no contaban con algunos de los factores de riesgo añadidos que aumentaran el riesgo de IHQ en comparación con otros estudios.

Abstract: Objective: To determine the prevalence of surgical wound infections in scheduled HRAEV cesarean sections. Materials and method: Retrospective, descriptive, observational cross-sectional study to determine the prevalence of IHC in patients undergoing scheduled cesarean section with antibiotic prophylaxis in HRAEV. Results: 185 records of patients undergoing scheduled cesarean section were evaluated, aged between 28 to 37 years (48.1%) with an average weight of 81 kg (SD = 10.1) with an average body mass index (BMI) of 30 (SD = 4.24) that is, a BMI between 25.76 and 34.24. Of these, 4 patients (2.16%) presented surgical wound infection during scheduled cesarean section, who received ceftriaxone as PA greater than 120 minutes prior to skin incision, these patients are classified as ASA II and had a BMI greater than 30 kg/m2 and without recorded comorbidities. The most frequent antibiotic prophylaxis time in patients undergoing scheduled cesarean section was >120 minutes (34.08%) and ceftriaxone was administered in 84.86% of the population, which is mostly ASA II (97.83%). 100% of the wounds were superficial. Conclusions: In the present study, it was found that the prevalence of IHC in cesarean sections scheduled in HRAEV was 2.16%, a figure that is below the worldwide prevalence, given that the selected patients did not have some of the risk factors. added risk that increased the risk of SSI compared to other studies.

Defending against SARS-CoV-2: The T cell perspective.

SARS-CoV-2-specific T cell response has been proven essential for viral clearance, COVID-19 outcome and long-term memory. Impaired early T cell-driven immunity leads to a severe form of the disease associated with lymphopenia, hyperinflammation and imbalanced humoral response. Analyses of acute SARS-CoV-2 infection have revealed that mild COVID-19 course is characterized by an early induction of specific T cells within the first 7 days of symptoms, coordinately followed by antibody production for an effective control of viral infection. In contrast, patients who do not develop an early specific cellular response and initiate a humoral immune response with subsequent production of high levels of antibodies, develop severe symptoms. Yet, delayed and persistent bystander CD8+ T cell activation has been also reported in hospitalized patients and could be a driver of lung pathology. Literature supports that long-term maintenance of T cell response appears more stable than antibody titters. Up to date, virus-specific T cell memory has been detected 22 months post-symptom onset, with a predominant IL-2 memory response compared to IFN-γ. Furthermore, T cell responses are conserved against the emerging variants of concern (VoCs) while these variants are mostly able to evade humoral responses. This could be partly explained by the high HLA polymorphism whereby the viral epitope repertoire recognized could differ among individuals, greatly decreasing the likelihood of immune escape. Current COVID-19-vaccination has been shown to elicit Th1-driven spike-specific T cell response, as does natural infection, which provides substantial protection against severe COVID-19 and death. In addition, mucosal vaccination has been reported to induce strong adaptive responses both locally and systemically and to protect against VoCs in animal models. The optimization of vaccine formulations by including a variety of viral regions, innovative adjuvants or diverse administration routes could result in a desirable enhanced cellular response and memory, and help to prevent breakthrough infections. In summary, the increasing evidence highlights the relevance of monitoring SARS-CoV-2-specific cellular immune response, and not only antibody levels, as a correlate for protection after infection and/or vaccination. Moreover, it may help to better identify target populations that could benefit most from booster doses and to personalize vaccination strategies.

Dietary Protected Sodium Butyrate and/or Olive Leaf and Grape-Based By-Product Supplementation Modifies Productive Performance, Antioxidant Status and Meat Quality in Broilers.

To meet the demand for chicken meat production, new additives that promote growth and health without adverse effects on meat quality are being investigated. This study was conducted to investigate the effect of protected sodium butyrate (PSB) (0 vs. 2 g/kg), an olive leaf and grape-based by-product (OLG-mix), or a combined supplementation of PSB and OLG-mix on productive performance, antioxidant status, carcass, and meat quality in broilers. PSB improved performance parameters with greater effect in the initial phase. Both, PSB and OLG-mix increased the plasma superoxide dismutase (SOD); however, PSB supplementation was more effective to delay the lipid oxidation of meat from the initial day of storage. OLG-mix produced meat with greater color intensity, b* value and lesser drip losses than PSB. The combination of PSB + OLG-mix did not produce more marked effects that the individual administration; except to control the oxidation of meat. Linear and positive correlations between antioxidant enzymes and weight gain were observed. Significant linear and negative relationships were quantified between plasma SOD and meat lipid oxidation according to dietary treatment. Therefore, the present study would be a first approximation to the possibilities for predicting growth range and meat quality through the evaluation of the blood oxidative status.

Development of an Effective Immune Response in Adults With Down Syndrome After Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccination.

BACKGROUND: Immune dysregulation in individuals with Down syndrome (DS) leads to an increased risk for hospitalization and death due to coronavirus disease 2019 (COVID-19) and may impair the generation of protective immunity after vaccine administration. METHODS: The cellular and humoral responses of 55 individuals with DS who received a complete SARS-CoV-2 vaccination regime at 1 to 3 (visit [V 1]) and 6 (V2) months were characterized. RESULTS: SARS-CoV-2-reactive CD4+ and CD8+ T lymphocytes with a predominant Th1 phenotype were observed at V1 and increased at V2. Likewise, an increase in SARS-CoV-2-specific circulating Tfh (cTfh) cells and CD8+ CXCR5+ PD-1hi lymphocytes was already observed at V1 after vaccine administration. Specific immunoglobulin G (IgG) antibodies against SARS-CoV-2 S protein were detected in 96% and 98% of subjects at V1 and V2, respectively, although IgG titers decreased significantly between both time points. CONCLUSIONS: Our findings show that DS individuals develop an effective immune response to usual regimes of SARS-CoV-2 vaccination.

Metabolic Reprogramming in SARS-CoV-2 Infection Impacts the Outcome of COVID-19 Patients.

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection triggers inflammatory clinical stages that affect the outcome of patients with coronavirus disease 2019 (COVID-19). Disease severity may be associated with a metabolic imbalance related to amino acids, lipids, and energy-generating pathways. The aim of this study was to characterize the profile of amino acids and acylcarnitines in COVID-19 patients. A multicenter, cross-sectional study was carried out. A total of 453 individuals were classified by disease severity. Levels of 11 amino acids, 31 acylcarnitines, and succinylacetone in serum samples were analyzed by electrospray ionization-triple quadrupole tandem mass spectrometry. Different clusters were observed in partial least squares discriminant analysis, with phenylalanine, alanine, citrulline, proline, and succinylacetone providing the major contribution to the variability in each cluster (variable importance in the projection >1.5). In logistic models adjusted by age, sex, type 2 diabetes mellitus, hypertension, and nutritional status, phenylalanine was associated with critical outcomes (odds ratio=5.3 (95% CI 3.16-9.2) in the severe vs. critical model, with an area under the curve of 0.84 (95% CI 0.77-0.90). In conclusion the metabolic imbalance in COVID-19 patients might affect disease progression. This work shows an association of phenylalanine with critical outcomes in COVID-19 patients, highlighting phenylalanine as a potential metabolic biomarker of disease severity.

Cellular and humoral immune responses and breakthrough infections after three SARS-CoV-2 mRNA vaccine doses.

Background: SARS-CoV-2 vaccination has proven the most effective measure to control the COVID-19 pandemic. Booster doses are being administered with limited knowledge on their need and effect on immunity. Objective: To determine the duration of specific T cells, antibodies and neutralization after 2-dose vaccination, to assess the effect of a third dose on adaptive immunity and to explore correlates of protection against breakthrough infection. Methods: 12-month longitudinal assessment of SARS-CoV-2-specific T cells, IgG and neutralizing antibodies triggered by 2 BNT162b2 doses followed by a third mRNA-1273 dose in a cohort of 77 healthcare workers: 17 with SARS-CoV-2 infection prior to vaccination (recovered) and 60 naïve. Results: Peak levels of cellular and humoral response were achieved 2 weeks after the second dose. Antibodies declined thereafter while T cells reached a plateau 3 months after vaccination. The decline in neutralization was specially marked in naïve individuals and it was this group who benefited most from the third dose, which resulted in a 20.9-fold increase in neutralization. Overall, recovered individuals maintained higher levels of T cells, antibodies and neutralization 1 to 6 months post-vaccination than naïve. Seventeen asymptomatic or mild SARS-CoV-2 breakthrough infections were reported during follow-up, only in naïve individuals. This viral exposure boosted adaptive immunity. High peak levels of T cells and neutralizing antibodies 15 days post-vaccination associated with protection from breakthrough infections. Conclusion: Booster vaccination in naïve individuals and the inclusion of viral antigens other than spike in future vaccine formulations could be useful strategies to prevent SARS-CoV-2 breakthrough infections.