Nobody's land? The oldest evidence of early Upper Paleolithic settlements in inland Iberia.

The Iberian Peninsula is a key region for unraveling human settlement histories of Eurasia during the period spanning the decline of Neandertals and the emergence of anatomically modern humans (AMH). There is no evidence of human occupation in central Iberia after the disappearance of Neandertals ~42,000 years ago until approximately 26,000 years ago, rendering the region "nobody's land" during the Aurignacian period. The Abrigo de la Malia provides irrefutable evidence of human settlements dating back to 36,200 to 31,760 calibrated years before the present (cal B.P.) This site also records additional levels of occupation around 32,420 to 26,260 cal B.P., suggesting repeated settlement of this territory. Our multiproxy examination identifies a change in climate trending toward colder and more arid conditions. However, this climatic deterioration does not appear to have affected AMH subsistence strategies or their capacity to inhabit this region. These findings reveal the ability of AMH groups to colonize regions hitherto considered uninhabitable, reopening the debate on early Upper Paleolithic population dynamics of southwestern Europe.

Small intestinal bacterial overgrowth in obese patients with biopsy-confirmed metabolic dysfunction-associated steatotic liver disease: a cross-sectional study.

Background/aims: The metabolic dysfunction-associated steatotic liver disease (MASLD) and obesity are frequent comorbidities with a high prevalence worldwide. Their pathogenesis are multifactorial, including intestinal dysbiosis. The role of small intestinal bacterial overgrowth (SIBO) in MASLD progression in obese patients remains unknown. We aimed to determine the association between SIBO and the severity of MASLD in obese patients. Methods: An observational and cross-sectional study was conducted in obese patients, diagnosed with or without MASLD by liver biopsy. Metabolic dysfunction-associated steatotic liver (MASL), metabolic dysfunction-associated steatohepatitis without fibrosis (MASH-NF), MASH with fibrosis (MASH-F), or without MASLD (control subjects, CS) were identified by presence of steatosis, portal and lobular inflammation, and fibrosis. SIBO was determined by standardized lactulose breath tests. Results: A total of 59 patients with MASLD, 16 with MASL, 20 with MASH-NF, 23 with MASH-F, and 14 CS were recruited. Higher percentages of SIBO were observed in MASLD patients (44.2%) compared to CS (14.2%; p = 0.0363). Interestingly, MASH-F showed higher percentages of SIBO (65.2%) in comparison to non-fibrotic MASLD (33.3%; p = 0.0165). The presence of SIBO was not correlated with the level of hepatic steatosis in MASLD patients. Conclusions: A positive correlation between MASLD and SIBO in obese patients was principally explained by the presence of liver fibrosis. Our findings suggest a pathogenic role of intestinal dysbiosis in the progression of MASLD. Future research will elucidate the underlying mechanisms of SIBO in MASLD advancement.

Glycogen synthase kinase 3 activity enhances liver inflammation in MASH.

Background & Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by excessive circulating toxic lipids, hepatic steatosis, and liver inflammation. Monocyte adhesion to liver sinusoidal endothelial cells (LSECs) and transendothelial migration (TEM) are crucial in the inflammatory process. Under lipotoxic stress, LSECs develop a proinflammatory phenotype known as endotheliopathy. However, mediators of endotheliopathy remain unclear. Methods: Primary mouse LSECs isolated from C57BL/6J mice fed chow or MASH-inducing diets rich in fat, fructose, and cholesterol (FFC) were subjected to multi-omics profiling. Mice with established MASH resulting from a choline-deficient high-fat diet (CDHFD) or FFC diet were also treated with two structurally distinct GSK3 inhibitors (LY2090314 and elraglusib [9-ING-41]). Results: Integrated pathway analysis of the mouse LSEC proteome and transcriptome indicated that leukocyte TEM and focal adhesion were the major pathways altered in MASH. Kinome profiling of the LSEC phosphoproteome identified glycogen synthase kinase (GSK)-3ß as the major kinase hub in MASH. GSK3ß-activating phosphorylation was increased in primary human LSECs treated with the toxic lipid palmitate and in human MASH. Palmitate upregulated the expression of C-X-C motif chemokine ligand 2, intracellular adhesion molecule 1, and phosphorylated focal adhesion kinase, via a GSK3-dependent mechanism. Congruently, the adhesive and transendothelial migratory capacities of primary human neutrophils and THP-1 monocytes through the LSEC monolayer under lipotoxic stress were reduced by GSK3 inhibition. Treatment with the GSK3 inhibitors LY2090314 and elraglusib ameliorated liver inflammation, injury, and fibrosis in FFC- and CDHFD-fed mice, respectively. Immunophenotyping using cytometry by mass cytometry by time of flight of intrahepatic leukocytes from CDHFD-fed mice treated with elraglusib showed reduced infiltration of proinflammatory monocyte-derived macrophages and monocyte-derived dendritic cells. Conclusion: GSK3 inhibition attenuates lipotoxicity-induced LSEC endotheliopathy and could serve as a potential therapeutic strategy for treating human MASH. Impact and Implications: LSECs under lipotoxic stress in MASH develop a proinflammatory phenotype known as endotheliopathy, with obscure mediators and functional outcomes. The current study identified GSK3 as the major driver of LSEC endotheliopathy, examined its pathogenic role in myeloid cell-associated liver inflammation, and defined the therapeutic efficacy of pharmacological GSK3 inhibitors in murine MASH. This study provides preclinical data for the future investigation of GSK3 pharmacological inhibitors in human MASH. The results of this study are important to hepatologists, vascular biologists, and investigators studying the mechanisms of inflammatory liver disease and MASH, as well as those interested in drug development.

Childhood-Onset Non-Infectious Uveitis in the "Biologic Era". Results From Spanish Multicenter Multidisciplinary Real-World Clinical Settings.

OBJECTIVE: To characterize and describe clinical experience with childhood-onset non-infectious uveitis. STUDY DESIGN: A multicenter retrospective multidisciplinary national web-based registry of 507 patients from 21 hospitals was analyzed. Cases were grouped as immune disease-associated (IMDu), idiopathic (IDIu) or ophthalmologically distinct. Characteristics of juvenile idiopathic arthritis-associated (non-HLA-B27-related) uveitis (JIAu), IDIu, and pars planitis (PP) were compared. RESULTS: IMDu (62.3%) and JIAu (51.9%) predominated in young females; and IDIu (22.7%) and PP (13.6%) in older children, without sex imbalance. Ocular complications occurred in 45.3% of cases (posterior synechiae [28%], cataracts [16%], band keratopathy [14%], ocular hypertension [11%] and cystoid macular edema [10%]) and were associated with synthetic (86%) and biologic (65%) disease-modifying antirheumatic drug (DMARD) use. Subgroups were significantly associated (p < 0.05) with different characteristics. JIAu was typically anterior (98%), insidious (75%), in ANA-positive (69%), young females (82%) with fewer complications (31%), better visual outcomes, and later use of uveitis-effective biologics. In contrast, IDIu was characteristically anterior (87%) or panuveitic (12.1%), with acute onset (60%) and more complications at onset (59%: synechiae [31%] and cataracts [9.6%]) and less DMARD use, while PP is intermediate, and was mostly bilateral (72.5%), persistent (86.5%) and chronic (86.8%), with more complications (70%; mainly posterior segment and cataracts at last visit), impaired visual acuity at onset, and greater systemic (81.2%), subtenon (29.1%) and intravitreal (10.1%) steroid use. CONCLUSION: Prognosis of childhood uveitis has improved in the "biologic era," particularly in JIAu. Early referral and DMARD therapy may reduce steroid use and improve outcomes, especially in PP and IDIu.

Development of a Six-Degree-of-Freedom Analog 3D Tactile Probe Based on Non-Contact 2D Sensors.

In this paper, a six-degree-of-freedom analog tactile probe with a new, simple, and robust mechanical design is presented. Its design is based on the use of one elastomeric ring that supports the stylus carrier and allows its movement inside a cubic measuring range of ±3 mm. The position of the probe tip is determined by three low-cost, noncontact, 2D PSD (position-sensitive detector) sensors, facilitating a wider application of this probe to different measuring systems compared to commercial ones. However, several software corrections, regarding the size and orientation of the three LED light beams, must be carried out when using these 2D sensors for this application due to the lack of additional focusing or collimating lenses and the very wide measuring range. The development process, simulation results, correction models, experimental tests, and calibration of this probe are presented. The results demonstrate high repeatability along the X-, Y-, and Z-axes (2.0 µm, 2.0 µm, and 2.1 µm, respectively) and overall accuracies of 6.7 µm, 7.0 µm, and 8.0 µm, respectively, which could be minimized by more complex correction models.

Exploring the geometry of the bifurcation sets in parameter space.

By studying a nonlinear model by inspecting a p-dimensional parameter space through ( p - 1 ) -dimensional cuts, one can detect changes that are only determined by the geometry of the manifolds that make up the bifurcation set. We refer to these changes as geometric bifurcations. They can be understood within the framework of the theory of singularities for differentiable mappings and, in particular, of the Morse Theory. Working with a three-dimensional parameter space, geometric bifurcations are illustrated in two models of neuron activity: the Hindmarsh-Rose and the FitzHugh-Nagumo systems. Both are fast-slow systems with a small parameter that controls the time scale of a slow variable. Geometric bifurcations are observed on slices corresponding to fixed values of this distinguished small parameter, but they should be of interest to anyone studying bifurcation diagrams in the context of nonlinear phenomena.

Models Used by Nurse Case Managers in Different Autonomous Communities in Spain: A Scoping Review.

(1) Background: The role of the nurse case manager is unknown to the population. The main objective is to analyze the existing differences within the national territory in order to make known the situation in Spain with a view to the recognition of its functions and the creation of the professional profile in an equal manner. (2) Methods: A scoping review was conducted in order to achieve the main aim. Selected articles were subjected to a critical reading, and the levels of evidence and grades of recommendation of the Joanna Briggs Institute were verified. The search field was limited to the last ten years. (3) Results: Case management models are heterogeneous in different autonomous communities in Spain. Case nurse management is qualified for high-complexity patients, follow up on chronic patients, and coordinate health assistance. (4) Conclusions: It concludes that nursing's role is crucial in the field of case management, being required in the follow-up of chronic patients of high complexity. Despite the proven health benefits, efficacy, and efficiency of case management, there are many heterogeneous models that coexist in Spain. This involves a restriction in the development of a nursing career because of the lack of a definition of its functions and competences.

Alteration of Gut Microbiota Composition in the Progression of Liver Damage in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a complex disorder whose prevalence is rapidly growing in South America. The disturbances in the microbiota-gut-liver axis impact the liver damaging processes toward fibrosis. Gut microbiota status is shaped by dietary and lifestyle factors, depending on geographic location. We aimed to identify microbial signatures in a group of Chilean MASLD patients. Forty subjects were recruited, including healthy controls (HCs), overweight/obese subjects (Ow/Ob), patients with MASLD without fibrosis (MASLD/F-), and MASLD with fibrosis (MASLD/F+). Both MASLD and fibrosis were detected through elastography and/or biopsy, and fecal microbiota were analyzed through deep sequencing. Despite no differences in α- and ß-diversity among all groups, a higher abundance of Bilophila and a lower presence of Defluviitaleaceae, Lachnospiraceae ND3007, and Coprobacter was found in MASLD/F- and MASLD/F+, compared to HC. Ruminococcaceae UCG-013 and Sellimonas were more abundant in MASLD/F+ than in Ow/Ob; both significantly differed between MASLD/F- and MASLD/F+, compared to HC. Significant positive correlations were observed between liver stiffness and Bifidobacterium, Prevotella, Sarcina, and Acidaminococcus abundance. Our results show that MASLD is associated with changes in bacterial taxa that are known to be involved in bile acid metabolism and SCFA production, with some of them being more specifically linked to fibrosis.

Parenting practices and interventions during the COVID-19 pandemic lockdown: an exploratory cross-sectional study of caregivers in Brazil, Mexico, and the United States.

INTRODUCTION: The COVID-19 pandemic led countries' governments to rapidly establish lockdowns and social distancing, which altered family routines and the quality of family relationships worldwide. OBJECTIVES: This exploratory cross-sectional study aimed to identify the impacts of the social distancing and lockdown in parenting practices of caregivers from Brazil, Mexico, and the USA, and to analyze the continuity of parenting intervention support for children and their families at the beginning of the pandemic in these countries. METHODS: The sample consisted of 704 caregivers of children (286 from Brazil, 225 from Mexico, and 193 from the USA) who answered an online survey about parenting practices before/after quarantine, caregiver/child routines, feelings related to quarantine, changes in everyday life since the beginning of the COVID-19 pandemic, contact with health professionals, and sources of parenting information. RESULTS: Data indicate that caregivers from the three countries experienced similar parenting practices during this time, and did not report significant changes before and after the lockdown. They sought information about parenting predominantly via social media. Those receiving previous mental health care perceived the transition from in-person to telehealth services during the pandemic as feasible and acceptable. CONCLUSION: This study will be helpful for clinicians and parents to contextualize their practices amid long-standing effects that the COVID-19 pandemic can have on children and their families during and post-pandemic from multiple cultural backgrounds.

Interleukin 21 Drives a Hypermetabolic State and CD4+ T-Cell-Associated Pathogenicity in Chronic Intestinal Inflammation.

BACKGROUND & AIMS: Incapacitated regulatory T cells (Tregs) contribute to immune-mediated diseases. Inflammatory Tregs are evident during human inflammatory bowel disease; however, mechanisms driving the development of these cells and their function are not well understood. Therefore, we investigated the role of cellular metabolism in Tregs relevant to gut homeostasis. METHODS: Using human Tregs, we performed mitochondrial ultrastructural studies via electron microscopy and confocal imaging, biochemical and protein analyses using proximity ligation assay, immunoblotting, mass cytometry and fluorescence-activated cell sorting, metabolomics, gene expression analysis, and real-time metabolic profiling utilizing the Seahorse XF analyzer. We used a Crohn's disease single-cell RNA sequencing dataset to infer the therapeutic relevance of targeting metabolic pathways in inflammatory Tregs. We examined the superior functionality of genetically modified Tregs in CD4+ T-cell-induced murine colitis models. RESULTS: Mitochondria-endoplasmic reticulum appositions, known to mediate pyruvate entry into mitochondria via voltage-dependent anion channel 1 (VDAC1), are abundant in Tregs. VDAC1 inhibition perturbed pyruvate metabolism, eliciting sensitization to other inflammatory signals reversible by membrane-permeable methyl pyruvate supplementation. Notably, interleukin (IL) 21 diminished mitochondria-endoplasmic reticulum appositions, resulting in enhanced enzymatic function of glycogen synthase kinase 3 ß, a putative negative regulator of VDAC1, and a hypermetabolic state that amplified Treg inflammatory response. Methyl pyruvate and glycogen synthase kinase 3 ß pharmacologic inhibitor (LY2090314) reversed IL21-induced metabolic rewiring and inflammatory state. Moreover, IL21-induced metabolic genes in Tregs in vitro were enriched in human Crohn's disease intestinal Tregs. Adoptively transferred Il21r-/- Tregs efficiently rescued murine colitis in contrast to wild-type Tregs. CONCLUSIONS: IL21 triggers metabolic dysfunction associated with Treg inflammatory response. Inhibiting IL21-induced metabolism in Tregs may mitigate CD4+ T-cell-driven chronic intestinal inflammation.

Persistent Monkeypox-Associated Keratouveitis in a Post-LASIK Cornea: A Case Report With Flap Removal.

PURPOSE: This study aimed to report a case of persistent keratouveitis associated with mpox virus infection in an immunocompetent patient with a history of laser-assisted in situ keratomileusis (LASIK), leading to the need for flap removal. METHODS: A comprehensive literature review was conducted, and a detailed case report was presented. RESULTS: A 44-year-old immunocompetent male patient with a history of LASIK and HIV infection presented with conjunctival and corneal lesions indicative of mpox infection. Despite initial topical treatment, the condition worsened, leading to severe epithelial and stromal keratitis with anterior chamber inflammation. Polymerase chain reaction testing confirmed the presence of mpox virus in conjunctival, corneal, and aqueous humor samples. The patient underwent various treatments, including tecovirimat, oral and topical corticosteroids, and topical trifluridine, and eventually flap removal with amniotic membrane application. Subsequent polymerase chain reaction testing of the aqueous humor yielded negative results, and the cornea gradually reepithelialized without inflammation. After 8 months, the patient's eye remained stable, with a central stromal scar. CONCLUSIONS: This case highlights the rare occurrence of mpox-associated keratouveitis and emphasizes the challenges faced in its management. The successful outcome achieved through a combination of antiviral therapy, antiinflammatories, and surgical intervention underscores the importance of a multidisciplinary approach in managing such cases.

Tesis doctorales españolas de ciencias de la salud en materia de género (1976-2022) / Spanish doctoral thesis in health sci-ences on gender subjects (1976-2022)

Objetivo principal: analizar cuantitativamente la producción de las tesis doctorales en materia sanitaria relacionadas con el género en España. Metodología: síntesis cuantitativa de indicadores de productividad de las tesis doctorales conseguidas en la base de datos española TESEO y defendidas en Universidades españolas entre 1976 y 2022. Los análisis empleados han sido descriptivos y el cálculo de predicción se basó en la metodología del modelo Holt-Winters. Resultados principales: el 18,75% de las tesis defendidas pertenecen a una Universidad de Madrid. El 75% de ellas son defendidas por graduados en Medicina. La temática de las tesis es en el 25% la violencia de género. El 87,5% son doctoras, pero solamente el 44% de las mujeres dirigen tesis. La predicción para los futuros 24 años indica que se generará alrededor de 1 tesis al año. Conclusión principal: la investigación española en tesis doctorales clínicas de género es escasa y masculinizada.(AU)

Main objective: to quantitatively analyze the production of gender-related doctoral theses in health in Spain. Methodology: quantitative synthesis of productivity indicators of the doctoral theses obtained in the Spanish TESEO database and defended in Spanish Universities between 1976 and 2022. The analyzes used have been descriptive and the prediction calculation was based on the methodology of the Holt- Winters. Main results: 18.75% of the theses defended belong to a University of Madrid. 75% of them are defended by graduates in Medicine. The theme of the theses is gender violence in 25%. 87.5% are doctors, but only 44% of women direct theses. The prediction for the future 24 years indicates that around 1 thesis will be generated per year. Main conclusion: Spanish research in gender clinical doctoral theses is scarce and masculinized.(AU)

Testimonio profesional de la psicología de la salud en la región central de Cuba. (1964-2023)

Fundamento: las llamadas provincias de Las Villas y La Habana atesoran las primeras experiencias sobre la psicología en Cuba, después del triunfo de la Revolución; aunque esta historia ha sido insuficientemente divulgada en la región central del país. Objetivo: identificar aspectos distintivos de la psicología de la salud desde 1964 hasta 2023 en la antigua provincia de Las Villas, y posteriormente, en Villa Clara. Métodos: se realizó una investigación de tipo histórico en la Universidad de Ciencias Médicas de Villa Clara, entre enero-marzo 2023. Se emplearon métodos teóricos y empíricos: investigación documental en fuentes históricas de probada veracidad, entrevistas a informantes clave y testimonios de las autoras. Resultados: en el curso 1968-1969 se insertó la Psicología en los programas del Ministerio de Salud Pública, en La Habana y Las Villas. A partir de la fundación de la Sociedad Nacional de Psicología de la Salud y la Filial de Las Villas (1975), la especialidad ha ido en progreso: la graduación de varios especialistas, realización de cuatro maestrías y una línea de investigación doctoral, varios eventos con participación internacional, los intercambios científicos con otras universidades, y la acreditación de la especialidad son algunos de los avances que la distinguen. Conclusiones: la psicología de la salud en la región central de Cuba ha ido en ascenso desde su fundación. Sus logros en los escenarios científicos y académicos se han fortalecido bajo la dirección de un grupo de fundadores que con creatividad y responsabilidad se han convertido en promotores y actores de sus éxitos.

Background: the so-called provinces of Las Villas and Havana treasure the first experiences on health psychology in Cuba; although this story has been insufficiently disseminated in the central region of the country. Objective: to identify distinctive aspects of health psychology from 1964 to 2023 in the former province of Las Villas, and later, in Villa Clara. Methods: a historical research was carried out at Villa Clara University of Medical Sciences, from January to March 2023. Theoretical methods were used: analysis-synthesis, induction-deduction, historical-logical and systemic; empirical: documentary research in historical sources of proven veracity, interviews with key informants and testimonies of the authors. Results: in the 1968-1969 academic year, Psychology was inserted into the programs of the Ministry of Public Health, in Havana and Las Villas. Since the founding of the National Society of Health Psychology and the Las Villas Branch in 1975, the specialty has been in progress: the graduation of several specialists, completion of four master's degrees and a line of doctoral research, several events with participation International exchange, scientific exchanges with other universities, and the accreditation of the specialty are some of the advances that distinguish it. Conclusions: health psychology in the central region of Cuba has been on the rise since its foundation. Its achievements in the scientific and academic scenarios have been strengthened under the direction of a group of founders who, with creativity and responsibility, have become promoters and actors of its successes.

Trajetória das políticas de saúde mental na Argentina e no Brasil: por que diferentes padrões de reforma? / The trajectory of Mental Health Policies in Argentina and Brazil: why different reform patterns?

Resumo As reformas psiquiátricas nos países da América Latina são heterogêneas, apesar de ideais e com objetivos comuns. O artigo analisa a trajetória das políticas de saúde mental no Brasil e na Argentina entre 1990 e 2020. Sob um desenho histórico-comparativo, explora fatores político-institucionais que podem explicar diferenças nas políticas estabelecidas nestes países. Os resultados apontam para a importância do papel desenvolvido por empreendedores de mudanças, com movimentos sociais mais coesos no Brasil. A expansão de regras e serviços comunitários ocorreu principalmente no contexto político de governos progressistas, embora este não seja um fator suficiente para explicá-la. O federalismo não se mostrou um obstáculo a tais políticas, porém na Argentina, a produção legislativa nacional tem sofrido mais constrangimentos do que no caso brasileiro. A reforma psiquiátrica ainda é um processo em disputa nos dois países.

Abstract Psychiatric reforms in Latin American countries are heterogeneous, although common ideals and objectives. The article analyzes the trajectory of mental health policies in Brazil and Argentina between 1990 and 2020. Under a historical-comparative design, explores political-institutional factors that may explain differences in policies established in these countries. The results point to the importance of the role developed by entrepreneurs of change, with social movements more cohesive in Brazil. The expansion of community rules and services took place especially in the political context of progressive governments, although this is not a sufficient factor to explain it. Federalism has not proved to be an obstacle to this. policies, but in Argentina, national legislative production has suffered more constraints than in the Brazilian case. Psychiatric reform is still a process in dispute in both countries.

Parenting practices and interventions during the COVID-19 pandemic lockdown: an exploratory cross-sectional study of caregivers in Brazil, Mexico, and the United States

Abstract Introduction The COVID-19 pandemic led countries' governments to rapidly establish lockdowns and social distancing, which altered family routines and the quality of family relationships worldwide. Objectives This exploratory cross-sectional study aimed to identify the impacts of the social distancing and lockdown in parenting practices of caregivers from Brazil, Mexico, and the USA, and to analyze the continuity of parenting intervention support for children and their families at the beginning of the pandemic in these countries. Methods The sample consisted of 704 caregivers of children (286 from Brazil, 225 from Mexico, and 193 from the USA) who answered an online survey about parenting practices before/after quarantine, caregiver/child routines, feelings related to quarantine, changes in everyday life since the beginning of the COVID-19 pandemic, contact with health professionals, and sources of parenting information. Results Data indicate that caregivers from the three countries experienced similar parenting practices during this time, and did not report significant changes before and after the lockdown. They sought information about parenting predominantly via social media. Those receiving previous mental health care perceived the transition from in-person to telehealth services during the pandemic as feasible and acceptable. Conclusion This study will be helpful for clinicians and parents to contextualize their practices amid long-standing effects that the COVID-19 pandemic can have on children and their families during and post-pandemic from multiple cultural backgrounds.

Hematoma subcapsular esplénico espontáneo y mononucleosis infecciosa: una asociación de interés para el cirujano

La rotura espontánea de bazo es una complicación infrecuente pero muy grave de la mononucleosis infecciosa. Dada la urgencia con la que suele presentarse tal situación, la esplenectomía suele ser la opción quirúrgica más utilizada. Presentamos el caso de un paciente en el que con el diagnóstico de rotura esplénica espontánea se somete a laparoscopia diagnóstica en la que se consigue la preservación del bazo con buena evolución clínica. A la luz de este paciente, consideramos que, en caso de estabilidad clínica y hematomas subcapsulares de bazo, la laparoscopia con preservación esplénica es una opción viable y con buenos resultados. (provisto por Infomedic International)

Spontaneous rupture of the spleen is a rare but very serious complication of infectious mononucleosis. Given the urgency with which such a situation usually presents, splenectomy is usually the most used surgical option. We present the case of a patient diagnosed with spontaneous splenic rupture who underwent diagnostic laparoscopy in which spleen preservation was achieved with good clinical evolution. In the light of this patient, we consider that, in the case of clinical stability and subcapsular haematomas of the spleen, laparoscopy with splenic preservation is a viable option with good results. (provided by Infomedic International)

"Direct and indirect impacts of the COVID-19 pandemic on operational conduct of pediatric vaccine clinical trials".

The coronavirus 2019 (COVID-19) pandemic, as well as the resulting public health measures, impacted many aspects of society. The conduct of important pediatric vaccine trials was among these. Analyzing data from six ongoing non-COVID-19 pediatric vaccine trials we aimed to assess the operational impact of the COVID-19 pandemic using descriptive analyses. We identified multiple operational disruptions in trial conduct. Additionally, we identified higher percentages of missed routine vaccinations than investigational vaccines throughout the observation period. Overall, the impact of the COVID-19 pandemic was most apparent early in the pandemic period while adaptations to the pandemic were developed; however, some disruptions persisted throughout the observation period. Pediatric vaccine clinical trials are critical to developing new and/or improved vaccines for the pediatric population. Continued evaluation of the impacts of COVID-19 on pediatric vaccine clinical trials is warranted.

Long-term antibody titers variation in unvaccinated patients receiving convalescent plasma or placebo for severe SARS-CoV-2 pulmonary infection.

BACKGROUND: Convalescent plasma (CP) became a prominent treatment in the early stages of the SARS-CoV-2 pandemic. In Argentina, a randomized clinical trial was executed to compare the use of CP in inpatients with severe COVID-19 pneumonia versus placebo. No differences in clinical outcomes or overall mortality between groups were observed. We conducted a cohort study in outpatients enrolled in the trial to describe long-term antibody titer variations between CP and placebo recipients. METHODS: Patients' total SARS-CoV-2 IgG antibodies against spike protein were collected 3, 6 and 12 months after hospital discharge from August 2020 to December 2021. In addition, reinfections, deaths and vaccination status were retrieved. Statistical analysis was performed using antibody geometric mean titers (GMT). All estimations were made considering the date of the trial infusion (placebo or CP) as time 0. RESULTS: From the 93 patients included in the follow-up, 64 had received CP and 29 placebo. We excluded all 12-month measurements because they were collected after the patients' vaccination date. At 90 days post-infusion, patients had an antibody GMT of 8.1 (IQR 7.4-8.1) in the CP group and 8.8 (IQR 8.1-9.1) in the placebo group. At 180 days, both groups had a GMT of 8.1 (IQR 7.4-8.1). No statistical differences in GMT were found between CP and placebo groups at 90 days (p = 0.12) and 180 days (p = 0.25). No patients registered a new COVID-19 infection; one died in the CP group from an ischemic stroke. CONCLUSIONS: No differences were observed in long-term antibody titers in unvaccinated patients that received CP or placebo after severe COVID-19 pneumonia.

The Chlamydia effector CpoS modulates the inclusion microenvironment and restricts the interferon response by acting on Rab35.

The obligate intracellular bacterium Chlamydia trachomatis inserts a family of inclusion membrane (Inc) proteins into the membrane of its vacuole (the inclusion). The Inc CpoS is a critical suppressor of host cellular immune surveillance, but the underlying mechanism remained elusive. By complementing a cpoS mutant with various natural orthologs and variants of CpoS, we linked distinct molecular interactions of CpoS to distinct functions. Unexpectedly, we found CpoS to be essential for the formation of inclusion membrane microdomains that control the spatial organization of multiple Incs involved in signaling and modulation of the host cellular cytoskeleton. While the function of CpoS in microdomains was uncoupled from its role in the suppression of host cellular defenses, we found the ability of CpoS to interact with Rab GTPases to be required not only for the manipulation of membrane trafficking, such as to mediate transport of ceramide-derived lipids (sphingolipids) to the inclusion, but also for the inhibition of Stimulator of interferon genes (STING)-dependent type I interferon responses. Indeed, depletion of Rab35 phenocopied the exacerbated interferon responses observed during infection with CpoS-deficient mutants. Overall, our findings highlight the role of Inc-Inc interactions in shaping the inclusion microenvironment and the modulation of membrane trafficking as a pathogenic immune evasion strategy. IMPORTANCE Chlamydia trachomatis is a prevalent bacterial pathogen that causes blinding ocular scarring and urogenital infections that can lead to infertility and pregnancy complications. Because Chlamydia can only grow within its host cell, boosting the intrinsic defenses of human cells may represent a novel strategy to fight pathogen replication and survival. Hence, CpoS, a Chlamydia protein known to block host cellular defenses, or processes regulated by CpoS, could provide new opportunities for therapeutic intervention. By revealing CpoS as a multifunctional virulence factor and by linking its ability to block host cellular immune signaling to the modulation of membrane trafficking, the present work may provide a foundation for such rationale targeting and advances our understanding of how intracellular bacteria can shape and protect their growth niche.