[Cardiovascular manifestations in pediatric multisystem inflammatory syndrome associated with COVID-19 in a tertiary care pediatric center in Mexico City]. / Alteraciones cardiovasculares en el síndrome inflamatorio multisistémico pediátrico asociado a COVID-19 en un hospital pediátrico de tercer nivel de la Ciudad de México.

Objective: The objective is to expose the cardiovascular alterations in patients diagnosed with pediatric inflammatory multisystem syndrome (PIMS) associated with COVID-19 during the SARS-CoV-2 pandemic, in order to understand the disease, its evolution, and optimal management upon diagnosis. Method: Retrospective, observational, cross-sectional analytical study of patients diagnosed with PIMS according to the criteria of the World Health Organization at the National Institute of Pediatrics, from March 2020 to December 2021. Results: During the study period, 77 patients with PIMS were diagnosed. The results showed correlation between the shock state and alteration of laboratory markers (platelets 144217.29 ± 139321.6 µL [p < 0.001], procalcitonin 27.37 ± 38.37 ng/ml [p = 0.05] and ferritin 1937.87 ± 2562.63 [p < 0.001]). The ventricular function in patients with shock was significantly lower compared to those without shock (49.6 ± 9.1% vs. 58.1 ± 8.4 %; t-Student p < 0.001), as well as injury to the left coronary artery (p = 0.02). There is a correlation between NT-proBNP and ventricular dysfunction (Kruskal-Wallis p = 0.007). Statistical significance was found in the association between death, elevation of inflammatory markers and ventricular dysfunction (p < 0.001). Conclusions: The cardiovascular alterations observed, in order of frequency, were pericardial effusion (25.7%), myocarditis (15%), mild ventricular dysfunction (13.5%) and small coronary aneurysm with predominance of the left coronary artery and the anterior descending one.

Objetivo: Exponer las alteraciones cardiovasculares en los pacientes diagnosticados con síndrome inflamatorio multisistémico pediátrico (PIMS) asociado a COVID-19 durante la pandemia por SARS-CoV-2 con el fin de comprender la enfermedad, su evolución y el manejo óptimo al diagnóstico. Método: Estudio retrospectivo, observacional, transversal y analítico de pacientes con diagnóstico de PIMS de acuerdo con los criterios de la Organización Mundial de la Salud en el Instituto Nacional de Pediatría, de marzo de 2020 a diciembre de 2021. Resultados: Durante el periodo de estudio se diagnosticaron 77 pacientes con PIMS. Los resultados demostraron una correlación entre el estado de choque y la alteración de los marcadores de laboratorio (plaquetas 144217.29 ± 139321.6 µl [p < 0.001], procalcitonina 27.37 ± 38.37 ng/ml [p = 0.05] y ferritina 1937.87 ± 2562.63 [p < 0.001]). La función ventricular en los pacientes con choque se registró significativamente menor en comparación con aquellos sin choque (49.6 ± 9.1 % vs. 58.1 ± 8.4 %; t de Student p < 0.001), así como lesión en la arteria coronaria izquierda (p = 0.02). Existe una correlación entre el NT-proBNP y la disfunción ventricular (Kruskal-Wallis p = 0.007). Se encontró significancia estadística en la asociación entre fallecimiento, elevación de los marcadores inflamatorios y disfunción ventricular (p < 0.001). Conclusiones: Las alteraciones cardiovasculares observadas fueron, en orden de frecuencia, derrame pericárdico (25.7%), miocarditis (15%), disfunción ventricular leve (13.5%) y aneurisma pequeño coronario con predominio de la arteria coronaria izquierda y la descendente anterior.

Natural Hydrogels Support Kidney Organoid Generation and Promote In Vitro Angiogenesis.

To date, strategies aiming to modulate cell to extracellular matrix (ECM) interactions during organoid derivation remain largely unexplored. Here renal decellularized ECM (dECM) hydrogels are fabricated from porcine and human renal cortex as biomaterials to enrich cell-to-ECM crosstalk during the onset of kidney organoid differentiation from human pluripotent stem cells (hPSCs). Renal dECM-derived hydrogels are used in combination with hPSC-derived renal progenitor cells to define new approaches for 2D and 3D kidney organoid differentiation, demonstrating that in the presence of these biomaterials the resulting kidney organoids exhibit renal differentiation features and the formation of an endogenous vascular component. Based on these observations, a new method to produce kidney organoids with vascular-like structures is achieved through the assembly of hPSC-derived endothelial-like organoids with kidney organoids in 3D. Major readouts of kidney differentiation and renal cell morphology are assessed exploiting these culture platforms as new models of nephrogenesis. Overall, this work shows that exploiting cell-to-ECM interactions during the onset of kidney differentiation from hPSCs facilitates and optimizes current approaches for kidney organoid derivation thereby increasing the utility of these unique cell culture platforms for personalized medicine.

Saving Hearts in Rural West Texas: The Impact of Critical Care Access on Mortality Rates.

Background The Critical Access Hospital (CAH) designation program was created in 1997 by the US Congress to reduce the financial vulnerability of rural hospitals and improve access to healthcare by keeping fundamental services in rural communities. Methods This is a retrospective observational study. Information on CAHs in West Texas in rural counties was extrapolated from the Flex Monitoring Team between 2010 and 2020. The study population included adults aged ≥25 years with a known heart failure (HF) diagnosis who were identified using ICD-10 codes. Mortality rates were obtained from the CDC Wide-ranging ONline Data for Epidemiologic Research (WONDER) database. The HF population was categorized by age, sex, and ethnicity. Mortality differences among these groups were analyzed using a two-sample t-test. The significance level was considered to be p < 0.05. Results The total study population analyzed was 1,348,001. A statistically significant difference in age-adjusted mortality rate (AAMR) was observed between the study and control groups, with a value of 3.200 (95% CI: 3.1910-3.2090, p < 0.0001) in favor of a lower mortality rate in rural counties with CAHs. When comparing gender-related differences, males and females had lower AAMRs in rural counties with CAHs. Among each gender, statistically significant differences were noted between males (95% CI: 2.181-2.218, p < 0.001) and females (95% CI: 3.382-3.417, p < 0.001). When examining the data by ethnicity, the most significant difference in mortality rate was observed within the Hispanic population, 6.400 (95% CI: 6.3770-6.4230, p < 0.0001). When adjusted to age, the crude mortality rate was calculated, which favored CAH admission in the younger population (10.200 (95% CI: 10.1625-10.2375, p < 0.001) and 11.500 (95% CI: 11.4168-11.5832, p < 0.001) in the 55-64 and 65-74 age groups, respectively). Conclusion The data clearly showed that West Texas rural county hospitals that received CAH designation performed better in terms of mortality rates in the HF population compared to non-CAH.

Educational interventions in pharmacovigilance to improve the knowledge, attitude and the report of adverse drug reactions in healthcare professionals: Systematic Review and Meta-analysis.

OBJECTIVES: Underreporting of adverse drug reactions (ADRs) limits and delays the detection of signs. The aim of this systematic review with meta-analyses was to synthesize the evidence of educational interventions (EIs) efficacy in health professionals to increase ADR reporting, attitudes, and knowledge of pharmacovigilance. EVIDENCE ACQUISITION: A systematic literature review was carried out to identify randomized clinical trials evaluating the efficacy of EI in pharmacovigilance in health professionals to improve ADR reports, knowledge, and attitude toward pharmacovigilance. ADR reports were pooled by calculating Odds Ratio (OR) with a 95% confidence interval (95%CI), while pharmacovigilance knowledge and attitude were pooled by calculating a mean difference (MD) with 95%CI. In addition, the subanalysis was performed by EI type. Meta-analysis was performed with RevMan 5.4 software. PROSPERO registry CRD42021254270. RESULTS: Eight hundred seventy-five articles were identified as potentially relevant, and 11 were included in the systematic review. Metanalysis showed that EI increased ADR reporting in comparison with control group (OR = 4.74, [95%CI, 2.46 to 9.12], I2 = 93%, 5 studies). In subgroup analysis, the workshops (OR = 6.26, [95%CI, 4.03 to 9.73], I2 = 57%, 3 studies) increased ADR reporting more than telephone-based interventions (OR = 2.59, [95%CI, 0.77 to 8.73], I2 = 29%, 2 studies) or combined interventions (OR = 5.14, [95%CI, 0.97 to 27.26], I2 = 93%, 3 studies). No difference was observed in pharmacovigilance knowledge. However, the subanalysis revealed that workshops increase pharmacovigilance knowledge (SMD = 1.85 [95%CI, 1.44 to 2.27], 1 study). Only one study evaluated ADR reporting attitude among participants and showed a positive effect after the intervention. CONCLUSION: EI improves ADR reports and increases pharmacovigilance knowledge. Workshops are the most effective EI to increase ADR reporting.

ANCUT1, a novel thermoalkaline cutinase from Aspergillus nidulans and its application on hydroxycinnamic acids lipophilization.

One of the four cutinases encoded in the Aspergillus nidulans genome, ANCUT1, is described here. Culture conditions were evaluated, and it was found that this enzyme is produced only when cutin is present in the culture medium, unlike the previously described ANCUT2, with which it shares 62% amino acid identity. The differences between them include the fact that ANCUT1 is a smaller enzyme, with experimental molecular weight and pI values of 22 kDa and 6, respectively. It shows maximum activity at pH 9 and 60 °C under assayed conditions and retains more than 60% of activity after incubation for 1 h at 60 °C in a wide range of pH values (6-10) after incubations of 1 or 3 h. It has a higher activity towards medium-chain esters and can modify long-chain length hydroxylated fatty acids constituting cutin. Its substrate specificity properties allow the lipophilization of alkyl coumarates, valuable antioxidants and its thermoalkaline behavior, which competes favorably with other fungal cutinases, suggests it may be useful in many more applications.

Transition of care: lessons from the Standardizing Care to Improve Outcomes in Pediatric End Stage Renal Disease (SCOPE) dialysis collaborative.

BACKGROUND: Acknowledging the importance of preparing the pediatric dialysis patient for successful transfer to adult providers, centers from the Standardizing Care to Improve Outcomes in Pediatric End Stage Renal Disease (SCOPE) Dialysis Collaborative developed transition tools and performed iterative implementation of a transition of care (TOC) program to gain real-life insight into drivers and barriers towards implementation of a transition program for patients receiving dialysis. METHODS: A TOC innovation workgroup was developed in 2019 from within SCOPE Collaborative that developed nine educational modules, along with introductory letter and assessment tool to be utilized by SCOPE centers. A 4-month pilot implementation study among six centers of varying patient population (age ≥ 11 years) was performed. TOC tools were further refined, and broader implementation within the collaborative was performed. Interim assessment of TOC tool utilization and implementation success was performed among 11 centers, as a foundation towards broader discussion regarding process, barriers, and success towards TOC implementation among 26 centers. RESULTS: Transition champion was a key driver of successful implementation, and lack of institutional support and collaboration with adult dialysis centers were important barriers towards sustainability. COVID pandemic and increased staff turnover affected longer term implementation of TOC program. CONCLUSIONS: Successful transition and transfer of adolescents/young adults with kidney failure on dialysis remains a challenge. This study represents the experience of the largest cohort of pediatric dialysis centers, with diversity in population size and geography, towards development and implementation of a TOC program. This adds to the resources available to assist centers towards transition and transfer, with particular focus on transitioning patients on dialysis.

Reclassification of Adolescent Ambulatory Prehypertension and Unclassified Blood Pressures by 2022 American Heart Association Pediatric Ambulatory Blood Pressure Monitoring Guidelines.

OBJECTIVE: To describe the epidemiology of reclassification of prehypertensive and unclassified adolescents by 2022 American Heart Association pediatric ambulatory blood pressure monitoring (ABPM) guidelines, and to evaluate the association of the new diagnostic categories with left ventricular hypertrophy (LVH). STUDY DESIGN: A single-center, retrospective review of ABPM reports from adolescents 13-21 years old, from 2015 through 2022, was performed. Adolescents with prehypertension or unclassified by 2014 guidelines were reclassified by 2022 definitions. Logistic regression models evaluated the association of reclassification phenotypes with LVH. RESULTS: A majority of prehypertensive adolescents reclassified to hypertension (70%, n = 49/70). More than one-half (57%, n = 28/49) of the hypertension was isolated nocturnal hypertension, and 80% was systolic hypertension. Reclassification to hypertension was more common in males. The majority (55.6%) of unclassified adolescents were reclassified to normotension. No demographic or clinical variables were associated with reclassification categories. LVH was not associated with hypertension in the reclassified prehypertensive or unclassified groups. CONCLUSIONS: The 2022 ABPM guidelines clearly define blood pressure phenotypes. However, reclassification to hypertension was not associated with an increased odds of LVH. Because most prehypertensive adolescents reclassified as hypertensive by nighttime BPs alone, this study highlights the lowered threshold for nocturnal hypertension. Prospective studies in larger, well-defined cohorts are needed to describe better the predictive value of 2022 BP phenotypes for target organ damage.

Type A acute aortic dissection presenting as a stroke in a young male patient.

A male patient in his 40s with a history of nephrolithiasis and found in the desert after 10 days without oral intake was admitted to the hospital for severe dehydration, acute kidney injury and rhabdomyolysis. He had acute-onset loss of consciousness during hospitalisation with new left-sided hemiparesis and hemineglect. After haemorrhage was excluded, prompt thrombolysis was given. He later had chest pain and became hypotensive. An echocardiogram revealed pericardial effusion and dilation of the ascending aorta with suspected dissection. Magnetic resonance angiography of the brain and neck reported bilateral parieto-occipital areas of stroke in a watershed distribution and dissection of the right internal carotid artery. CT angiography showed type A aortic dissection from the ascending aorta extending into the bilateral common iliac arteries. Thrombolysis was reversed and the patient underwent ascending aorta replacement, resuspension of the aortic valve and aortic arch debranching at outside facility with complete recovery.

Molecular Imaging of Monoamine Oxidase A Expression in Highly Aggressive Prostate Cancer: Synthesis and Preclinical Evaluation of Positron Emission Tomography Tracers.

The role of monoamine oxidase A (MAO-A) in the aggressiveness of prostate cancer (PCa) has been established in recent years. The molecular imaging of MAO-A expression could offer a noninvasive tool for the visualization and quantification of highly aggressive PCa. This study reports the synthesis and preclinical evaluation of 11C- and 18F-labeled MAO-A inhibitors as positron emission tomography (PET) tracers for proof-of-concept studies in animal models of PCa. Good manufacturing practice production and quality control of these radiotracers using an automated platform was achieved. PET imaging was performed in an LNCaP tumor model with high MAO-A expression. The tumor-to-muscle (T/M) uptake ratio of [11C]harmine (4.5 ± 0.5) was significantly higher than that for 2-[18F]fluoroethyl-harmol (2.3 ± 0.7) and [11C]clorgyline (2.0 ± 0.1). A comparable ex vivo biodistribution pattern in all radiotracers was observed. Furthermore, the tumor uptake of [11C]harmine showed a dramatic reduction (T/M = 1) in a PC3 tumor model with limited MAO-A expression, and radioactivity uptake in LNCaP tumors was blocked in the presence of nonradioactive harmine. Our findings suggest that [11C]harmine may serve as an attractive PET probe for the visualization of MAO-A expression in highly aggressive PCa. These radiotracers have the potential for clinical translation and may aid in the development of personalized therapeutic strategies for PCa patients.

CD300f immune receptor contributes to healthy aging by regulating inflammaging, metabolism, and cognitive decline.

Emerging evidence suggests that immune receptors may participate in many aging-related processes such as energy metabolism, inflammation, and cognitive decline. CD300f, a TREM2-like lipid-sensing immune receptor, is an exceptional receptor as it integrates activating and inhibitory cell-signaling pathways that modulate inflammation, efferocytosis, and microglial metabolic fitness. We hypothesize that CD300f can regulate systemic aging-related processes and ultimately healthy lifespan. We closely followed several cohorts of two strains of CD300f-/- and WT mice of both sexes for 30 months and observed an important reduction in lifespan and healthspan in knockout mice. This was associated with systemic inflammaging, increased cognitive decline, reduced brain glucose uptake observed by 18FDG PET scans, enrichment in microglial aging/neurodegeneration phenotypes, proteostasis alterations, senescence, increased frailty, and sex-dependent systemic metabolic changes. Moreover, the absence of CD300f altered macrophage immunometabolic phenotype. Taken together, we provide strong evidence suggesting that myeloid cell CD300f immune receptor contributes to healthy aging.

The prevalence and outcomes of hyponatremia in children with COVID-19 and multisystem inflammatory syndrome in children (MIS-C).

Introduction: To assess the prevalence of hyponatremia among pediatric patients with coronavirus disease 2019 (COVID-19) and Multisystem Inflammatory Syndrome in Children (MIS-C) and determine if pediatric hyponatremia was associated with an increased length of stay, higher rates of mechanical ventilation, and/or elevated inflammatory markers on admission as compared to eunatremic patients. Methods: Electronic health records were retrospectively analyzed for 168 children less than 18 years old with COVID-19 or MIS-C who were admitted to pediatric units within the Northwell Health system. The primary exposure was hyponatremic status (serum sodium <135 mEq/L) and the primary outcomes were length of stay, mechanical ventilation usage and increased inflammatory markers. Results: Of the 168 children in the study cohort, 95 (56%) were admitted for COVID-19 and 73 (43.5%) for MIS-C. Overall, 60 (35.7%) patients presented with hyponatremia on admission. Patients with hyponatremia had higher rates of intensive care unit admission when compared to eunatremic patients (32/60 [53.3%] vs. 39/108 [36.1%], p = 0.030). In regression models, hyponatremia was not significantly associated with increased length of stay or mechanical ventilation rates. After adjustment for relevant confounders, hyponatremia remained associated with an increased square root CRP (ß = 1.79: 95% CI: 0.22-3.36) and lower albumin levels (ß = -0.22: 95% CI: -0.42--0.01). Conclusion: Hyponatremia is common in pediatric COVID-19 and MIS-C. Hyponatremia was associated with a lower albumin and higher square root CRP levels. This may suggest an association of inflammation with lower serum sodium levels.

Assessment of photo electro-Fenton and solar photo electro-Fenton processes for the efficient degradation of asulam herbicide.

The degradation of asulam herbicide by photo electro-Fenton (PEF) and solar photo electro-Fenton (SPEF) processes was studied using an undivided electrochemical BDD/carbon-felt cell to generate H2O2 continuously. A central composite design combined with response surface methodology was applied to determine the optimal operating conditions of current intensity = 0.30 A, [Fe2+] = 0.3 mM, and [Na2SO4] = 0.11 M at pH 3 to achieve the complete degradation of asulam by electro-Fenton. Subsequently, the SPEF process was more efficient treatment compared to PEF, achieving a complete degradation of asulam and 98% of mineralization in 180 min. Moreover, 4-aminobenzenesulfonamide, 4-aminophenol, and 4-benzoquinone were detected as aromatic intermediates, whereas acetic acid, oxalic acid, and NO3- ions were identified as final degradation by-products. Thus, the SPEF process is an efficient alternative for the complete degradation and mineralization of herbicide asulam in an aqueous solution under natural sunlight.

Reclassification of Adolescent Ambulatory Prehypertension and Unclassified Blood Pressures by 2022 American Heart Association Pediatric Ambulatory Blood Pressure Monitoring Guidelines.

Background: The 2022 American Heart Association (AHA) pediatric ambulatory blood pressure monitoring (ABPM) guidelines eliminated the prehypertension phenotype and blood pressure loads in ABPM interpretation criteria. Adolescents who were prehypertensive or unclassified according to the 2014 AHA pediatric ABPM guidelines will be reclassified as having hypertension or normotension. The epidemiology and association of reclassification phenotype with target organ damage (TOD) is not yet known. Methods: A single center retrospective review of adolescents ages 13-21 years old between 2015-2022 was performed. Adolescents diagnosed with prehypertension or unclassified by the 2014 AHA pediatric ABPM guidelines were reclassified by the 2022 definitions. Logistic regression models adjusted for body mass index z-score evaluated the association of reclassification phenotype with left ventricular hypertrophy (LVH). Results: Among 88 adolescents with prehypertension, 68% (N = 60) were reclassified as hypertensive. The majority (58%, N = 35) of hypertensive reclassification was based on isolated nocturnal blood pressures ≥ 110/65 mmHg. Taller males were more likely to reclassify as hypertensive. Adolescents reclassified as hypertensive had a greater-than-six-fold increased odds of LVH in adjusted models [OR 6.4 95%CI 1.2-33.0, p = 0.027]. Of 40 adolescents with unclassified blood pressures, 37.5% (N = 15) reclassified to normotension. There were no significant clinical or demographic variables associated with reclassification category nor was there an association with LVH. Conclusions: The new ABPM guidelines effectively reclassify adolescents who were previously prehypertensive as normotensive or hypertensive based on risk of TOD. Further studies are needed to describe the long-term outcomes of ABPM phenotypes with the implementation of these guidelines.

An adenoviral-vectored vaccine confers seroprotection against capsular group B meningococcal disease.

Adenoviral-vectored vaccines are licensed for prevention of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Ebola virus, but, for bacterial proteins, expression in a eukaryotic cell may affect the antigen's localization and conformation or lead to unwanted glycosylation. Here, we investigated the potential use of an adenoviral-vectored vaccine platform for capsular group B meningococcus (MenB). Vector-based candidate vaccines expressing MenB antigen factor H binding protein (fHbp) were generated, and immunogenicity was assessed in mouse models, including the functional antibody response by serum bactericidal assay (SBA) using human complement. All adenovirus-based vaccine candidates induced high antigen-specific antibody and T cell responses. A single dose induced functional serum bactericidal responses with titers superior or equal to those induced by two doses of protein-based comparators, as well as longer persistence and a similar breadth. The fHbp transgene was further optimized for human use by incorporating a mutation abrogating binding to the human complement inhibitor factor H. The resulting vaccine candidate induced high and persistent SBA responses in transgenic mice expressing human factor H. The optimized transgene was inserted into the clinically relevant ChAdOx1 backbone, and this vaccine has now progressed to clinical development. The results of this preclinical vaccine development study underline the potential of vaccines based on genetic material to induce functional antibody responses against bacterial outer membrane proteins.

Efficient removal of veterinary drugs from aqueous solutions using magnetically separable carbonaceous materials derived from cobalt and iron metal-organic frameworks.

Rapid synthesis of carbon-based magnetic materials derived from cobalt and iron metal-organic frameworks (MOFs), ZIF-67, and MIL-100(Fe), by microwave-assisted method, followed by carbonization under a N2 atmosphere is described in this study. The carbon-derived MOFs (CDMs) were evaluated for the removal of the emerging pollutants sulfadiazine (SDZ) and flumequine (FLU) used as veterinary drugs. The study aimed to link the adsorption behavior with their surface properties and elemental composition. C-ZIF-67 and C-MIL-100(Fe) showed hierarchical porous structures with specific surface areas of 295.6 and 163.4 m2 g-1, respectively. The Raman spectra of the CDMs show the characteristic D and G bands associated with defect-rich carbon and sp2 graphitic carbon, respectively. The CDMs exhibit cobalt species (Co3O4, CoO, and Co) in C-ZIF-67 and iron species (Fe2O3, Fe3O4, and Fe) in C-MIL-100 (Fe) which are related to the magnetic behavior of CDMs. C-ZIF-67 and C-MIL-100 (Fe) had saturation magnetization values of 22.9 and 53.7 emu g-1, respectively, allowing easy solid-liquid separation using a magnet. SDZ and FLU removal rates on CDMs follow pseudo-second-order kinetics, and adsorption isotherms fit the Langmuir model based on regression coefficient values. Adsorption thermodynamics calculations showed that the adsorption of SDZ and FLU by CDMs was a thermodynamically favorable process. Therefore, these properties of C-ZIF-67 and C-MIL-100 (Fe) and their regeneration ability facilitate their use as adsorbents for emerging pollutants.

[Dental occlusal disruptor as a strategy to moderate caloric intake: two case report]. / Disruptor oclusal dental como estrategia para moderar ingesta calórica: reporte de dos casos.

Background: Obesity is a global public health challenge, closely related with the progression of other diseases. In recent years, odontology has intervened against obesity through the implementation of intraoral devices that contribute with weight control treatments. Objective: To study the use of a dental occlusal disruptor as a strategy to moderate caloric intake. Material and methods: Pilot study which included 2 patients. It was used a dental occlusal disruptor that has an impact on the smaller amount of food at each bite. Patients attended five appointments in which a stomatological evaluation was carried out and anthropometric measurements were taken. All adverse effects were reported in each patient's clinical history. Results: Patients presented weight and body fat loss, increased muscle mass and decreased both body mass index and waist and hip measurements. Conclusions: The use of the disruptor does not alter the stomatological assessment, it promotes masticatory regulation and the decrease in body weight. It is necessary to analyze its use in a larger number of patients.

Introducción: la obesidad es un reto para la salud pública mundial y está relacionada con la aparición y progresión de diversas enfermedades. En los últimos años, la odontología ha intervenido en el combate a la obesidad mediante la implementación de aditamentos intraorales que coadyuvan en el tratamiento del control de peso. Objetivo: estudiar el uso de un disruptor oclusal dental como estrategia para moderar la ingesta calórica. Material y métodos: estudio piloto que incluyó 2 pacientes. Se empleó un disruptor oclusal dental que incide en que la cantidad de alimento en cada bocado sea menor. Los pacientes acudieron a 5 citas para valoración estomatológica y toma de medidas antropométricas. Se reportaron todos los efectos adversos en la historia clínica de cada paciente. Resultados: ambos pacientes presentaron pérdida de peso y de grasa corporal, aumento de masa muscular y disminución tanto del índice de masa corporal como de mediciones de cintura y cadera. Conclusiones: el uso del disruptor no altera la valoración estomatológica, propicia la regulación masticatoria y promueve la disminución del peso corporal. Es necesario analizar su uso en mayor número de pacientes.

Immunisation with purified Coxiella burnetii phase I lipopolysaccharide confers partial protection in mice independently of co-administered adenovirus vectored vaccines.

Q fever is a highly infectious zoonosis caused by the Gram-negative bacterium Coxiella burnetii. The worldwide distribution of Q fever suggests a need for vaccines that are more efficacious, affordable, and does not induce severe adverse reactions in vaccine recipients with pre-existing immunity against Q fever. Potential Q fever vaccine antigens include lipopolysaccharide (LPS) and several C. burnetii surface proteins. Antibodies elicited by purified C. burnetii lipopolysaccharide (LPS) correlate with protection against Q fever, while antigens encoded by adenoviral vectored vaccines can induce cellular immune responses which aid clearing of intracellular pathogens. In the present study, the immunogenicity and the protection induced by adenoviral vectored constructs formulated with the addition of LPS were assessed. Multiple vaccine constructs encoding single or fusion antigens from C. burnetii were synthesised. The adenoviral vectored vaccine constructs alone elicited strong cellular immunity, but this response was not correlative with protection in mice. However, vaccination with LPS was significantly associated with lower weight loss post-bacterial challenge independent of co-administration with adenoviral vaccine constructs, supporting further vaccine development based on LPS.

Evolution of long-term vaccine-induced and hybrid immunity in healthcare workers after different COVID-19 vaccine regimens.

BACKGROUND: Both infection and vaccination, alone or in combination, generate antibody and T cell responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the maintenance of such responses-and hence protection from disease-requires careful characterization. In a large prospective study of UK healthcare workers (HCWs) (Protective Immunity from T Cells in Healthcare Workers [PITCH], within the larger SARS-CoV-2 Immunity and Reinfection Evaluation [SIREN] study), we previously observed that prior infection strongly affected subsequent cellular and humoral immunity induced after long and short dosing intervals of BNT162b2 (Pfizer/BioNTech) vaccination. METHODS: Here, we report longer follow-up of 684 HCWs in this cohort over 6-9 months following two doses of BNT162b2 or AZD1222 (Oxford/AstraZeneca) vaccination and up to 6 months following a subsequent mRNA booster vaccination. FINDINGS: We make three observations: first, the dynamics of humoral and cellular responses differ; binding and neutralizing antibodies declined, whereas T and memory B cell responses were maintained after the second vaccine dose. Second, vaccine boosting restored immunoglobulin (Ig) G levels; broadened neutralizing activity against variants of concern, including Omicron BA.1, BA.2, and BA.5; and boosted T cell responses above the 6-month level after dose 2. Third, prior infection maintained its impact driving larger and broader T cell responses compared with never-infected people, a feature maintained until 6 months after the third dose. CONCLUSIONS: Broadly cross-reactive T cell responses are well maintained over time-especially in those with combined vaccine and infection-induced immunity ("hybrid" immunity)-and may contribute to continued protection against severe disease. FUNDING: Department for Health and Social Care, Medical Research Council.

Coevolution of language and tools in the human brain: An ALE meta-analysis of neural activation during syntactic processing and tool use.

Language and complex tool use are often cited as behaviors unique to humans and may be evolutionarily linked owing to the underlying cognitive processes they have in common. We executed a quantitative activation likelihood estimation (ALE) meta-analysis (GingerALE 2.3) on published, whole-brain neuroimaging studies to identify areas associated with syntactic processing and/or tool use in humans. Significant clusters related to syntactic processing were identified in areas known to be related to language production and comprehension, including bilateral Broca's area in the inferior frontal gyrus. Tool use activation clusters were all in the left hemisphere and included the primary motor cortex and premotor cortex, in addition to other areas involved with sensorimotor transformation. Activation shared by syntactic processing and tool use was only significant at one cluster, located in the pars opercularis of the left inferior frontal gyrus. This minimal overlap between syntactic processing and tool use activation from our meta-analysis of neuroimaging studies indicates that there is not a widespread common neural network between the two. Broca's area may serve as an important hub that was initially recruited in early human evolution in the context of simple tool use, but was eventually co-opted for linguistic purposes, including the sequential and hierarchical ordering processes that characterize syntax. In the future, meta-analyses of additional components of language may allow for a more comprehensive examination of the functional networks that underlie the coevolution of human language and complex tool use.