Mosquito salivary apyrase regulates blood meal hemostasis and facilitates malaria parasite transmission.

The evolution of hematophagy involves a series of adaptations that allow blood-feeding insects to access and consume blood efficiently while managing and circumventing the host's hemostatic and immune responses. Mosquito, and other insects, utilize salivary proteins to regulate these responses at the bite site during and after blood feeding. We investigated the function of Anopheles gambiae salivary apyrase (AgApyrase) in regulating hemostasis in the mosquito blood meal and in Plasmodium transmission. Our results demonstrate that salivary apyrase, a known inhibitor of platelet aggregation, interacts with and activates tissue plasminogen activator, facilitating the conversion of plasminogen to plasmin, a human protease that degrades fibrin and facilitates Plasmodium transmission. We show that mosquitoes ingest a substantial amount of apyrase during blood feeding, which reduces coagulation in the blood meal by enhancing fibrin degradation and inhibiting platelet aggregation. AgApyrase significantly enhanced Plasmodium infection in the mosquito midgut, whereas AgApyrase immunization inhibited Plasmodium mosquito infection and sporozoite transmission. This study highlights a pivotal role for mosquito salivary apyrase for regulation of hemostasis in the mosquito blood meal and for Plasmodium transmission to mosquitoes and to the mammalian host, underscoring the potential for strategies to prevent malaria transmission.

Autonomic dysfunction as manifestation of ICANS: A case report.

RATIONALE: Anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy is a successful treatment for B-cell malignancies associated with cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Cardiovascular toxicities have also been reported in this setting. However, there is scarce data regarding development of autonomic disorders after CAR-T cell therapy. PATIENT CONCERNS: We report a case with a patient with non-Hodgkin B-cell lymphoma, refractory to 2 prior lines of immunochemotherapy, treated with CAR-T therapy. DIAGNOSES: Orthostatic hypotension secondary to autonomic dysfunction was diagnosed as manifestation of ICANS. INTERVENTIONS: The patient received metilprednisolone 1000 mg IV daily for 3 days and anakinra 100 mg IV every 6h. OUTCOMES: The vast majority of autonomic symptoms ceased and 4 months after CAR-T therapy, autonomic dysfunction was resolved. LESSONS: New-onset autonomic dysfunction can occur as manifestation of ICANS in patients who experience persistent neurologic and cardiovascular symptoms after resolution of acute neurotoxicity and should be early recognized. Differences in differential diagnosis, mechanisms and treatment approaches are discussed.

Aedes (Ochlerotatus) scapularis, Aedes japonicus japonicus, and Aedes (Fredwardsius) vittatus (Diptera: Culicidae): Three Neglected Mosquitoes with Potential Global Health Risks.

More than 3550 species of mosquitoes are known worldwide, and only a fraction is involved in the transmission of arboviruses. Mosquitoes in sylvatic and semi-sylvatic habitats may rapidly adapt to urban parks and metropolitan environments, increasing human contact. Many of these mosquitoes have been found naturally infected with arboviruses from the Alphaviridae, Flaviviridae, and Bunyaviridae families, with many being the cause of medically important diseases. However, there is a gap in knowledge about the vector status of newly invasive species and their potential threat to human and domestic animal populations. Due to their rapid distribution, adaptation to urban environments, and anthropophilic habits, some neglected mosquito species may deserve more attention regarding their role as secondary vectors. Taking these factors into account, we focus here on Aedes (Ochlerotatus) scapularis (Rondani), Aedes japonicus japonicus (Theobald), and Aedes (Fredwardsius) vittatus (Bigot) as species that have the potential to become important disease vectors. We further discuss the importance of these neglected mosquitoes and how factors such as urbanization, climate change, and globalization profoundly alter the dynamics of disease transmission and may increase the participation of neglected species in propagating diseases.

Metastatic hormone-naïve prostate cancer: a distinct biological entity.

Metastatic hormone-naïve prostate cancer (mHNPC) is often the initial form of presentation for metastatic prostate cancer and encompasses a heterogeneous patient population with high inter-patient heterogeneity in prognosis and response to therapy. A more precise treatment of mHNPC, guided by evidence-based biomarkers, remains an unmet medical need. In addition, the limited number of representative laboratory models of mHNPC hampers the translation of basic research into clinical applications. We provide a comprehensive overview of the clinical and biological features that characterize mHNPC, highlight molecular data that could explain the unique prognostic characteristics of mHNPC, and identify key open questions.

Spring-mediated distraction enterogenesis may alter the course of adaptation in porcine short bowel syndrome.

Introduction: Severe forms of short bowel syndrome (SBS) resulting in chronic intestinal failure (IF) have limited therapeutic options, all of which are associated with significant morbidities. Spring-mediated distraction enterogenesis (SMDE) uses an intraluminal self-expanding spring to generate mechanical force to induce intestinal stretching and sustained axial growth, providing a promising novel approach for patients with SBS. Previous studies have established this method to be safe and effective in small and large animal models. However, SMDE has previously not been implemented in a large, clinically relevant animal model. Methods: Juvenile mini-Yucatan pigs with 75% of their small intestine resected had intraluminal springs placed after an initial adaptive period. Morphological and histological assessments were performed on SMDE segments compared to the control region of the intestine undergoing normal adaptive responses to resection. Results: While the initial histologic adaptive response observed following resection was attenuated after a month, the SMDE segments instead augmented these adaptive changes. Specifically, intestinal length increased 2-fold in SMDE segments, and the widths of the epithelial, muscularis, and serosal layers were enhanced in SMDE compared with control segments of the same animal. This data suggests that morphologic intestinal adaptation may be enhanced with SMDE in the setting of SBS. Discussion: Here we demonstrate the successful and reproducible implementation of SMDE in a large animal model in the setting of prior intestinal resection, making SMDE a viable and novel approach for SBS to be explored further.

Differences in early life cognitive function explain the association between low education and early dementia risk.

Major initiatives are currently attempting to prevent dementia by targeting modifiable risk factors. Low education is frequently pointed to as a potential key factor, due to its robust relationship with dementia risk. Impact of education is notoriously difficult to assess, however, because of associations with multiple other risk and protective factors, and large population-representative samples are required to tease the relationships apart. Here, we studied 207,814 Norwegian men born between 1950 and 1959 who underwent compulsory cognitive testing during military conscription as young adults, to systematically test associations of education, cognition, and other potentially important factors. While low education was associated with increased risk for dementia diagnosis (Hazard ratio [HR] = 1.37, CI: 1.17-1.60), this association was fully explained by earlier cognitive test scores (HR = 1.08, CI: .91-1.28). In contrast, low cognitive score was associated with double risk of later dementia diagnosis, even when taking education into account (HR = 2.00, CI: 1.65-2.42). This relationship survived controlling for early-life socioeconomic status and was replicated within pairs of brothers. The latter finding suggests that genetic and environmental factors shared within families, such as common genetics, parental education, childhood socioeconomic status, or other shared experiences, cannot account for the association. Rather, independent, non-familial factors are more important. In contrast, within-family factors accounted for the relationship between low education and diagnosis risk. In conclusion, implementing measures to increase cognitive function in childhood and adolescence appears to be a more promising strategy for reducing dementia burden.

Efficacy and safety of bendamustine-containing bridging therapy in R/R LBCL patients receiving CD19 CAR T-cells.

Bridging therapy (BT) after leukapheresis is required in most relapsed/refractory (R/R) large B-cell lymphoma (LBCL) patients receiving chimeric antigen receptor (CAR) T cells. Bendamustine-containing regimens are a potential BT option. We aimed to assess if this agent had a negative impact on CAR-T outcomes when it was administered as BT. We included R/R LBCL patients from six centers who received systemic BT after leukapheresis from February 2019 to September 2022; patients who only received steroids or had pre-apheresis bendamustine exposure were excluded. Patients were divided into two BT groups, with and without bendamustine. Separate safety and efficacy analyses were carried out for axi-cel and tisa-cel. Of 243 patients who received BT, bendamustine (benda) was included in 62 (26%). There was a higher rate of BT progressors in the non-benda group (62% vs. 45%, p = 0.02). Concerning CAR-T efficacy, complete responses were comparable for benda versus non-benda BT cohorts with axi-cel (70% vs. 53%, p = 0.12) and tisa-cel (44% vs. 36%, p = 0.70). Also, 12-month progression-free and overall survival were not significantly different between BT groups with axi-cel (56% vs. 43% and 71% vs. 63%) and tisa-cel (25% vs. 26% and 52% vs. 48%); there were no differences when BT response was considered. CAR T-cell expansion for each construct was similar between BT groups. Regarding safety, CRS G ≥3 (6% vs. 6%, p = 0.79), ICANS G ≥3 (15% vs. 17%, p = 0.68), severe infections, and neutropenia post-infusion were comparable among BT regimens. BT with bendamustine-containing regimens is safe for patients requiring disease control during CAR T-cell manufacturing.

The PP2A regulator IER5L supports prostate cancer progression.

Prostate cancer exhibits high prevalence and accounts for a high number of cancer-related deaths. The discovery and characterization of molecular determinants of aggressive prostate cancer represents an active area of research. The Immediate Early Response (IER) family of genes, which regulate Protein Phosphatase 2A (PP2A) activity, has emerged among the factors that influence cancer biology. Here, we show that the less studied member of this family, Immediate Early Response 5 like (IER5L), is upregulated in aggressive prostate cancer. Interestingly, the upregulation of IER5L expression exhibits a robust association with metastatic disease in prostate and is recapitulated in other cancer types. In line with this observation, IER5L silencing reduces foci formation, migration and invasion ability in a variety of human and murine prostate cancer cell lines. In vivo, using zebrafish and immunocompromised mouse models, we demonstrate that IER5L-silencing reduces prostate cancer tumor growth, dissemination, and metastasis. Mechanistically, we characterize the transcriptomic and proteomic landscapes of IER5L-silenced cells. This approach allowed us to identify DNA replication and monomeric G protein regulators as downstream programs of IER5L through a pathway that is consistent with the regulation of PP2A. In sum, we report the alteration of IER5L in prostate cancer and beyond and provide biological and molecular evidence of its contribution to tumor aggressiveness.

Development of burnout and moral distress in intensive care nurses: An integrative literature review.

AIMS: To describe, through an integrative literature review, the factors contributing to the development of burnout and moral distress in nursing professionals working in intensive care units and to identify the assessment tools used most frequently to assess burnout and moral distress. METHODS: An integrative literature review was carried out. PubMed, CINAHL, PsycINFO, SciELO, Dialnet, Web of Science, Scopus, and Cochrane databases were reviewed from January 2012 to February 2023. Additionally, snowball sampling was used. The results were analysed by using integrative synthesis, as proposed by Whittemore et al., the Critical Appraisal Skills Programme for literature reviews, the Strengthening the Reporting of Observational Studies in Epidemiology guidelines for quantitative observational studies, and the Joanna Briggs Institute checklist for qualitative research were used to evaluate evidence quality. RESULTS: Forty-one articles were selected for review: 36 were cross-sectional descriptive articles, and five were literature reviews. The articles were grouped into five-factor categories: 1) personal factors, 2) organisational factors, 3) labour relations factors, 4) end-of-life care factors, and 5) factors related to coronavirus disease 2019 (COVID-19). The Maslach Burnout Inventory-Human Services Survey and the Moral Distress Survey-Revised instruments were the most commonly used to measure burnout and moral distress. CONCLUSIONS: This review highlights the multiple personal, organisational, relational, situational, and end-of-life factors promoting burnout and moral distress among critical care nurses. Interventions in these areas are necessary to achieve nurses' job satisfaction and retention while improving nurses' quality of care.

Standardization of the definition of the types of oncological colectomy. Delphi method for consensus of experts of the Spanish Association of Surgeons.

There is no international consensus on the definition of the type of oncological resection that corresponds to each of the colectomies existing in the current literature. The objective is to define for each colectomy described in the literature: embryological dissection plane, vascular pedicles in which to perform central ligation, the extent of the colectomy, and the need for resection of the greater momentum. A consensus of experts is carried out through the Delphi methodology through two rounds from the Coloproctology Section of the Spanish Association of Surgeons. Study period: November 2021-January 2023. 120 experts were surveyed. Degrees of consensus: Very strong: >90%, Strong: 80%-90%, Moderate: 50%-80%, No consensus: <50%. The definition for each oncological colectomy was established by very strong, and strong recommendations. Each oncological colectomy was established as Right hemicolectomy (RHC), RHC with D3 lymphadenectomy, Extended-RHC, transverse colon segmental colectomy, splenic flexure segmental colectomy, subtotal colectomy, total colectomy, left hemicolectomy (LHC), extended-LHC, sigmoidectomy.

A clinical practice guideline for the management of the foot and ankle in rheumatoid arthritis.

Rheumatoid arthritis causes progressive joint destruction in the long term, causing a deterioration of the foot and ankle. A clinical practice guideline has been created with the main objective of providing recommendations in the field of podiatry for the conservative management of rheumatoid arthritis. Thus, healthcare professionals involved in foot care of adults with rheumatoid arthritis will be able to follow practical recommendations. A clinical practice guideline was created including a group of experts (podiatrists, rheumatologists, nurses, an orthopaedic surgeon, a physiotherapist, an occupational therapist and patient with rheumatoid arthritis). Methodological experts using GRADE were tasked with systematically reviewing the available scientific evidence and developing the information which serves as a basis for the expert group to make recommendations. Key findings include the efficacy of chiropody in alleviating hyperkeratotic lesions and improving short-term pain and functionality. Notably, custom and standardized foot orthoses demonstrated significant benefits in reducing foot pain, enhancing physical function, and improving life quality. Therapeutic footwear was identified as crucial for pain reduction and mobility improvement, emphasizing the necessity for custom-made options tailored to individual patient needs. Surgical interventions were recommended for cases which were non-responsive to conservative treatments, aimed at preserving foot functionality and reducing pain. Moreover, self-care strategies and education were underscored as essential components for promoting patient independence and health maintenance. A series of recommendations have been created which will help professionals and patients to manage podiatric pathologies derived from rheumatoid arthritis.

Pharmacotherapeutic value of inflammatory and neurotrophic biomarkers in bipolar disorder: A systematic review.

BACKGROUND: The various pharmacological interventions, ranging from mood stabilizers and antipsychotics to antidepressants, reflect the diff/iculty of treating depressive/manic symptomatology of bipolar disorder (BD). Among a broad range of mechanisms implicated, immune dysregulation may contribute to the increased inflammation that influences the course of BD. Inflammatory, neurotrophic and oxidative stress factors may be identified as promising peripheral biomarkers in brain functioning, perhaps serving as predictors of an effective response to treatment for BD. The present systematic review aimed to examine the evidence supporting the pharmacotherapeutic value of inflammatory and neurotrophic biomarkers in BD. METHODS: PubMed, PsychINFO, Scopus and Web of Science were searched from inception to May 2024 by two independent reviewers. A total of 40 studies with 3371 patients with diagnosis and intervention of BD were selected. RESULTS: Inconsistencies in the effects of pharmacological treatments on the connection between the expected anti-inflammatory response and symptomatologic improvement were identified. Mood stabilizers (lithium), antipsychotics (quetiapine), antidepressants (ketamine) or their combination were described to increase both pro-inflammatory (TNFα, IL-6) and anti-inflammatory (IL-4, IL-8) factors. Other medications, such as memantine and dextromethorphan, autoimmune (infliximab) non-steroidal anti-inflammatory (aspirin, celecoxib) drugs, antidiabetics (pioglitazone), and even dietary supplementation (omega-3), or their combination, clearly decrease inflammatory factors (TNFα, IL-6, IL-1ß, C-reactive protein) and/or increase the neurotrophic factor BDNF in BD patients. CONCLUSION: Inflammation in BD requires further investigation to understand the underlying immunologic mechanism, to identify predictors of treatment response, and to make informed decisions about the use and development of more effective pharmacological interventions for BD.

Assessing Predictive Value of SARS-CoV-2 Epitope-Specific CD8+ T-Cell Response in Patients with Severe Symptoms.

Specific T cell responses against SARS-CoV-2 provided an overview of acquired immunity during the pandemic. Anti-SARS-CoV-2 immunity determines the severity of acute illness, but also might be related to the possible persistence of symptoms (long COVID). We retrospectively analyzed ex vivo longitudinal CD8+ T cell responses in 26 COVID-19 patients diagnosed with severe disease, initially (1 month) and long-term (10 months), and in a cohort of 32 vaccinated healthcare workers without previous SARS-CoV-2 infection. We used peptide-human leukocyte antigen (pHLA) dextramers recognizing 26 SARS-CoV-2-derived epitopes of viral and other non-structural proteins. Most patients responded to at least one of the peptides studied, mainly derived from non-structural ORF1ab proteins. After 10 months follow-up, CD8+ T cell responses were maintained at long term and reaction against certain epitopes (A*01:01-ORF1ab1637) was still detected and functional, showing a memory-like phenotype (CD127+ PD-1+). The total number of SARS-CoV-2-specific CD8+ T cells was significantly associated with protection against long COVID in these patients. Compared with vaccination, infected patients showed a less effective immune response to spike protein-derived peptides restricted by HLA. So, the A*01:01-S865 and A*24:02-S1208 dextramers were only recognized in vaccinated individuals. We conclude that initial SARS-CoV-2-specific CD8+ T cell response could be used as a marker to understand the evolution of severe disease and post-acute sequelae after SARS-CoV-2 infection.

Reducing CLABSI through a quality strategy for the implementation of the aseptic non-touch technique in a pediatric ward.

BACKGROUND: Central line-associated bloodstream infections (CLABSIs) are among the most epidemiologically relevant health care-associated infections. The aseptic non-touch technique (ANTT) is a standardized practice used to prevent CLABSIs. In a pediatric hospital, the overall CLABSI rate was 1.92/1000 catheter days (CD). However, in one unit, the rate was 5.7/1000 CD. METHODS: Nurses were trained in ANTT. For the implementation, plan-do-study-act (PDSA) cycles were completed. Adherence monitoring of the ANTT and epidemiological surveillance were performed. RESULTS: ANTT adherence of 95% was achieved after 6 PDSA cycles. Hand hygiene and general cleaning reached 100% adherence. Port disinfection and material collection had the lowest adherence rates, with 76.2% and 84.7%, respectively. The CLABSI rate decreased from 5.7 to 1.26/1000 CD. CONCLUSION: The implementation of ANTT helped reduce the CLABSI rate. Training and continuous monitoring are key to maintaining ANTT adherence.

INTRODUCCIÓN: Las infecciones relacionadas con catéteres venosos centrales son unas de las infecciones asociadas a la atención de salud con mayor relevancia epidemiológica. La técnica aséptica «no tocar¼ es una práctica estandarizada que se utiliza para prevenir estas infecciones. En un hospital pediátrico, la tasa de infecciones relacionadas con catéteres venosos centrales fue de 1.92/1000 días de catéter. Sin embargo, en una de las unidades la tasa fue de 5.7/1000 días de catéter. MÉTODO: Se capacitaron enfermeras en la técnica aséptica «no tocar¼. Para la implementación se cumplieron ciclos de planificar-hacer-estudiar-actuar (PHEA). Se realizaron seguimiento de la adherencia a la técnica y vigilancia epidemiológica. RESULTADOS: Se logró una adherencia a la técnica aséptica «no tocar¼ del 95% después de seis ciclos. La higiene de manos y la limpieza general alcanzaron un 100% de cumplimiento. La desinfección de los puertos y la recolección de material alcanzaron la menor adherencia, con un 76.2% y un 84.7%, respectivamente. La tasa de infecciones relacionadas con catéteres venosos centrales disminuyó de 5.7 a 1.26 por 1000 días de catéter. CONCLUSIONES: La implementación de la técnica aséptica «no tocar¼ ayudó en la reducción de infecciones relacionadas con catéteres venosos centrales. La capacitación y el seguimiento continuo son clave para mantener el cumplimiento de la técnica.

Reducing CLABSI through a quality strategy for the implementation of the aseptic non-touch technique in a pediatric ward / Reducción de infecciones relacionadas con catéteres venosos centrales por medio de una estrategia de calidad para la implementación de la técnica aséptica «no tocar¼ en una sala de pediatría

Abstract Background: Central line-associated bloodstream infections (CLABSIs) are among the most epidemiologically relevant health care-associated infections. The aseptic non-touch technique (ANTT) is a standardized practice used to prevent CLABSIs. In a pediatric hospital, the overall CLABSI rate was 1.92/1000 catheter days (CD). However, in one unit, the rate was 5.7/1000 CD. Methods: Nurses were trained in ANTT. For the implementation, plan-do-study-act (PDSA) cycles were completed. Adherence monitoring of the ANTT and epidemiological surveillance were performed. Results: ANTT adherence of 95% was achieved after 6 PDSA cycles. Hand hygiene and general cleaning reached 100% adherence. Port disinfection and material collection had the lowest adherence rates, with 76.2% and 84.7%, respectively. The CLABSI rate decreased from 5.7 to 1.26/1000 CD. Conclusion: The implementation of ANTT helped reduce the CLABSI rate. Training and continuous monitoring are key to maintaining ANTT adherence.

Resumen Introducción: Las infecciones relacionadas con catéteres venosos centrales son unas de las infecciones asociadas a la atención de salud con mayor relevancia epidemiológica. La técnica aséptica «no tocar¼ es una práctica estandarizada que se utiliza para prevenir estas infecciones. En un hospital pediátrico, la tasa de infecciones relacionadas con catéteres venosos centrales fue de 1.92/1000 días de catéter. Sin embargo, en una de las unidades la tasa fue de 5.7/1000 días de catéter. Método: Se capacitaron enfermeras en la técnica aséptica «no tocar¼. Para la implementación se cumplieron ciclos de planificar-hacer-estudiar-actuar (PHEA). Se realizaron seguimiento de la adherencia a la técnica y vigilancia epidemiológica. Resultados: Se logró una adherencia a la técnica aséptica «no tocar¼ del 95% después de seis ciclos. La higiene de manos y la limpieza general alcanzaron un 100% de cumplimiento. La desinfección de los puertos y la recolección de material alcanzaron la menor adherencia, con un 76.2% y un 84.7%, respectivamente. La tasa de infecciones relacionadas con catéteres venosos centrales disminuyó de 5.7 a 1.26 por 1000 días de catéter. Conclusiones: La implementación de la técnica aséptica «no tocar¼ ayudó en la reducción de infecciones relacionadas con catéteres venosos centrales. La capacitación y el seguimiento continuo son clave para mantener el cumplimiento de la técnica.

Diet management in congenital diarrheas and enteropathies - general concepts and disease-specific approach, a narrative review.

Congenital diarrheas and enteropathies (CODE) are a group of rare, heterogenous, monogenic disorders that lead to chronic diarrhea in infancy. Definitive treatment is rarely available, and supportive treatment is the mainstay. Nutritional management in the form of either specialized formulas, restrictive diet, or parenteral nutrition support in CODE with poor enteral tolerance is the cornerstone of CODE treatment and long-term growth. The evidence to support the use of specific diet regimens and nutritional approaches in most CODE disorders is limited due to the rarity of these diseases and the scant published clinical experience. The goal of this review was to create a comprehensive guide for nutritional management in CODE, based on the currently available literature, disease mechanism, and the PediCODE group experience. Enteral diet management in CODE can be divided into 3 distinct conceptual frameworks: nutrient elimination, nutrient supplementation, and generalized nutrient restriction. Response to nutrient elimination or supplementation can lead to resolution or significant improvement in the chronic diarrhea of CODE and resumption of normal growth. This pattern can be seen in CODE due to carbohydrate malabsorption, defects in fat absorption, and occasionally in electrolyte transport defects. In contrast, general diet restriction is mainly supportive. However, occasionally it allows parenteral nutrition weaning or reduction over time, mainly in enteroendocrine defects and rarely in epithelial trafficking and polarity defects. Further research is required to better elucidate the role of diet in the treatment of CODE and the appropriate diet management for each disease.

Exploring kidney allograft rejection: A proof-of-concept study using spatial transcriptomics.

In this proof-of-concept study, spatial transcriptomics combined with public single-cell ribonucleic acid-sequencing data were used to explore the potential of this technology to study kidney allograft rejection. We aimed to map gene expression patterns within diverse pathologic states by examining biopsies classified across nonrejection, T cell-mediated acute rejection, interstitial fibrosis, and tubular atrophy. Our results revealed distinct immune cell signatures, including those of T and B lymphocytes, monocytes, mast cells, and plasma cells, and their spatial organization within the renal interstitium. We also mapped chemokine receptors and ligands to study immune cell migration and recruitment. Finally, our analysis demonstrated differential spatial enrichment of transcription signatures associated with kidney allograft rejection across various biopsy regions. Interstitium regions displayed higher enrichment scores for rejection-associated gene expression patterns than tubular areas, which had negative scores. This implies that these signatures are primarily driven by processes unfolding in the renal interstitium. Overall, this study highlights the value of spatial transcriptomics for revealing cellular heterogeneity and immune signatures in renal transplant biopsies and demonstrates its potential for studying the molecular and cellular mechanisms associated with rejection. However, certain limitations must be borne in mind regarding the development and future applications of this technology.

Respiratory viral coinfections in pediatric patients in the primary care setting: a multicenter prospective study within the COPEDICAT network.

Acute respiratory viral infections pose a significant healthcare burden on the pediatric population globally, but data on the dissemination pattern in the community due to the COVID-19 pandemic are scarce. We conducted a two-year prospective multicenter study in Catalonia (Spain) that examined the prevalence and coinfection dynamics of respiratory viruses among 1276 pediatric patients from different age groups attending primary care. Coinfection analysis demonstrated complex patterns and revealed a coinfection rate of 23.8% for SARS-CoV-2, often in association with rhinovirus or influenza A. This study provides valuable data to understand post-pandemic viral interactions, which is imperative for public health interventions.

Propionate and butyrate counteract renal damage and progression to chronic kidney disease.

BACKGROUND: Short-chain fatty acids (SCFAs), mainly acetate, propionate and butyrate, are produced by gut microbiota through fermentation of complex carbohydrates that cannot be digested by the human host. They affect gut health and can contribute at the distal level to the pathophysiology of several diseases, including renal pathologies. METHODS: SCFA levels were measured in chronic kidney disease (CKD) patients (n = 54) at different stages of the disease and associations with renal function and inflammation parameters were examined. The impact of propionate and butyrate in pathways triggered in tubular cells under inflammatory conditions was analysed using genome-wide expression assays. Finally, a pre-clinical mouse model of folic acid-induced transition from acute kidney injury to CKD was used to analyse the preventive and therapeutic potential of these microbial metabolites in the development of CKD. RESULTS: Faecal levels of propionate and butyrate in CKD patients gradually reduce as the disease progresses, and do so in close association with established clinical parameters for serum creatinine, blood urea nitrogen and the estimated glomerular filtration rate. Propionate and butyrate jointly downregulated the expression of 103 genes related to inflammatory processes and immune system activation triggered by TNF-α in tubular cells. In vivo, the administration of propionate and butyrate, either before or soon after injury, respectively prevented and slowed the progression of damage. This was indicated by a decrease in renal injury markers, the expression of pro-inflammatory and pro-fibrotic markers, and recovery of renal function over the long term. CONCLUSIONS: Propionate and butyrate levels are associated with a progressive loss of renal function in CKD patients. Early administration of these SCFAs prevents disease advancement in a pre-clinical model of acute renal damage, demonstrating their therapeutic potential independently of the gut microbiota.