The Utility of a High-intensity Exercise Protocol to Prospectively Assess ACL Injury Risk.

This study investigated the utility of a 5-min high-intensity exercise protocol (SAFT(5)) to include in prospective cohort studies investigating ACL injury risk. 15 active females were tested on 2 occasions during which their non-dominant leg was analysed before SAFT(5) (PRE), immediately after (POST0), 15 min after (POST15), and 30 min after (POST30). On the first occasion, testing included 5 maximum isokinetic contractions for eccentric and concentric hamstring and concentric quadriceps and on the second occasion, 3 trials of 2 landing tasks (i. e., single-leg hop and drop vertical jump) were conducted. Results showed a reduced eccentric hamstring peak torque at POST0, POST15 and POST30 (p<0.05) and a reduced functional HQ ratio (Hecc/Qcon) at POST15 and POST30 (p<0.05). Additionally, a more extended knee angle at POST30 (p<0.05) and increased knee internal rotation angle at POST0 and POST15 (p<0.05) were found in a single-leg hop. SAFT(5) altered landing strategies associated with increased ACL injury risk and similar to observations from match simulations. Our findings therefore support the utility of a high-intensity exercise protocol such as SAFT(5) to strengthen injury screening tests and to include in prospective cohort studies where time constraints apply

Valoración de una Encuesta sobre Servicios de Atención Farmacéutica a Farmacéuticos de Alicante

INTRODUCCIÓN: Hay descritas barreras y facilitadores para implantar la AF. Algunos facilitadores podrían ser proporcionados desde los colegios profesionales. OBJETIVO: Conocer el interés de los farmacéuticos comunitarios alicantinos por los servicios de AF, y sus preferencias para implantar/mejorar éstos. MÉTODO: Estudio transversal realizado marzo-mayo de 2012, mediante un cuestionario anónimo a todos los colegiados ejercientes en OF, consensuado por la comisión de AF del COFA, disponible en la web colegial 70 días. Con preguntas referentes a su implantación, protocolización, registros, evaluación y ayudas sugeridas para su implantación/mejora.   RESULTADOS: Respondieron 19,9% de los colegiados ejercientes en FC, afirmando la mayoría querer mejorar su trabajo. Siguen protocolos para IF el 58%, automedicación un 60% y 33% para dispensación con receta. Realizan SFT un 23% y SPD 15%. La mayoría no registra las actuaciones, siendo 77% en IF, 70% en automedicación, 78% dispensación con receta, excepto SFT con 25%. Como formato de registro, se prefiere papel, excepto en SFT que son aplicaciones informáticas. La mayoría evalúa el resultado en ocasiones, solo un 8% lo hace siempre. En SFT lo evalúan siempre un 29%. Se prefiere un servicio de información frente a dudas, seguido de uno de apoyo a la implantación. CONCLUSIONES: Existe interés entre los farmacéuticos alicantinos por la AF. Sería deseable un mayor grado de implantación de estos servicios, existiendo gran recorrido de mejora en la protocolización, el registro y la evaluación de los resultados. Como herramientas para ello, destaca la solicitud al colegio de un servicio de información frente a dudas

Valoración de una Encuesta sobre Servicios de Atención Farmacéutica a Farmacéuticos de Alicante

INTRODUCCIÓN: Hay descritas barreras y facilitadores para implantar la AF. Algunos facilitadores podrían ser proporcionados desde los colegios profesionales. OBJETIVO: Conocer el interés de los farmacéuticos comunitarios alicantinos por los servicios de AF, y sus preferencias para implantar/mejorar éstos. MÉTODO: Estudio transversal realizado marzo-mayo de 2012, mediante un cuestionario anónimo a todos los colegiados ejercientes en OF, consensuado por la comisión de AF del COFA, disponible en la web colegial 70 días. Con preguntas referentes a su implantación, protocolización, registros, evaluación y ayudas sugeridas para su implantación/mejora.   RESULTADOS: Respondieron 19,9% de los colegiados ejercientes en FC, afirmando la mayoría querer mejorar su trabajo. Siguen protocolos para IF el 58%, automedicación un 60% y 33% para dispensación con receta. Realizan SFT un 23% y SPD 15%. La mayoría no registra las actuaciones, siendo 77% en IF, 70% en automedicación, 78% dispensación con receta, excepto SFT con 25%. Como formato de registro, se prefiere papel, excepto en SFT que son aplicaciones informáticas. La mayoría evalúa el resultado en ocasiones, solo un 8% lo hace siempre. En SFT lo evalúan siempre un 29%. Se prefiere un servicio de información frente a dudas, seguido de uno de apoyo a la implantación. CONCLUSIONES: Existe interés entre los farmacéuticos alicantinos por la AF. Sería deseable un mayor grado de implantación de estos servicios, existiendo gran recorrido de mejora en la protocolización, el registro y la evaluación de los resultados. Como herramientas para ello, destaca la solicitud al colegio de un servicio de información frente a dudas

Improved procedural workflow for catheter ablation of paroxysmal AF with high-density mapping system and advanced technology: Rationale and study design of a multicenter international study

The antral region of pulmonary veins (PV)s seems to play a key role in a strategy aimed at preventing atrial fibrillation (AF) recurrence. Particularly, low-voltage activity in tissue such as the PV antra and residual potential within the antral scar likely represent vulnerabilities in antral lesion sets, and ablation of these targets seems to improve freedom from AF. The aim of this study is to validate a structured application of an approach that includes the complete abolition of any antral potential achieving electrical quiescence in antral regions.The improveD procEdural workfLow for cathETEr ablation of paroxysmal AF with high density mapping system and advanced technology (DELETE AF) study is a prospective, single-arm, international post-market cohort study designed to demonstrate a low rate of clinical atrial arrhythmias recurrence with an improved procedural workflow for catheter ablation of paroxysmal AF, using the most advanced point-by-point RF ablation technology in a multicenter setting. About 300 consecutive patients with standard indications for AF ablation will be enrolled in this study. Post-ablation, all patients will be monitored with ambulatory event monitoring, starting within 30 days post-ablation to proactively detect and manage any recurrences within the 90-day blanking period, as well as Holter monitoring at 3, 6, 9, and 12 months post-ablation. Healthcare resource utilization, clinical data, complications, patients' medical complaints related to the ablation procedure and patient's reported outcome measures will be prospectively traced and evaluated.The DELETE AF trial will provide additional knowledge on long-term outcome following a structured ablation workflow, with high density mapping, advanced algorithms and local impedance technology, in an international multicentric fashion. DELETE AF is registered at ClinicalTrials.gov (NCT05005143).© 2022 The Authors. Clinical Cardiology published by Wiley Periodicals LLC

Localization of a bacterial group II intron-encoded protein in human cells

Group II introns are mobile retroelements that self-splice from precursor RNAs to form ribonucleoparticles (RNP), which can invade new specific genomic DNA sites. This specificity can be reprogrammed, for insertion into any desired DNA site, making these introns useful tools for bacterial genetic engineering. However, previous studies have suggested that these elements may function inefficiently in eukaryotes. We investigated the subcellular distribution, in cultured human cells, of the protein encoded by the group II intron RmInt1 (IEP) and several mutants. We created fusions with yellow fluorescent protein (YFP) and with a FLAG epitope. We found that the IEP was localized in the nucleus and nucleolus of the cells. Remarkably, it also accumulated at the periphery of the nuclear matrix. We were also able to identify spliced lariat intron RNA, which co-immunoprecipitated with the IEP, suggesting that functional RmInt1 RNPs can be assembled in cultured human cells.This work was supported by research grants CSD 2009–0006 from the Consolider-Ingenio, BIO2011-24401 and BIO2014-51953-P from the Spanish Ministerio de Economía y Competitividad all including ERDF (European Regional Development Funds). We thank Dr. Antonio Barrientos Durán for technical advice. MRC was supported by an FPI Ph.D grant. J.L.G.P´s laboratory is supported by CICE-FEDER-P09-CTS-4980, CICE-FEDER-P12-CTS-2256, Plan Nacional de I+D+I 2008–2011 and 2013–2016 (FIS-FEDER-PI11/01489 and FIS-FEDER-PI14/02152), PCIN-2014-115-ERA-NET NEURON II, the European Research Council (ERC-Consolidator ERC-STG-2012-233764) and by an International Early Career Scientist grant from the Howard Hughes Medical Institute (IECS-55007420).Peer Reviewe

Investigating the impact of poverty on colonization and infection with drug-resistant organisms in humans: a systematic review

Background Poverty increases the risk of contracting infectious diseases and therefore exposure to antibiotics. Yet there is lacking evidence on the relationship between income and non-income dimensions of poverty and antimicrobial resistance. Investigating such relationship would strengthen antimicrobial stewardship interventions. Methods A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Ovid, MEDLINE, EMBASE, Scopus, CINAHL, PsychINFO, EBSCO, HMIC, and Web of Science databases were searched in October 2016. Prospective and retrospective studies reporting on income or non-income dimensions of poverty and their influence on colonisation or infection with antimicrobial-resistant organisms were retrieved. Study quality was assessed with the Integrated quality criteria for review of multiple study designs (ICROMS) tool. Results Nineteen articles were reviewed. Crowding and homelessness were associated with antimicrobial resistance in community and hospital patients. In high-income countries, low income was associated with Streptococcus pneumoniae and Acinetobacter baumannii resistance and a seven-fold higher infection rate. In low-income countries the findings on this relation were contradictory. Lack of education was linked to resistant S. pneumoniae and Escherichia coli. Two papers explored the relation between water and sanitation and antimicrobial resistance in low-income settings. Conclusions Despite methodological limitations, the results suggest that addressing social determinants of poverty worldwide remains a crucial yet neglected step towards preventing antimicrobial resistance

Mass spectrometry imaging identifies palmitoylcarnitine as an immunological mediator during Salmonella Typhimurium infection

Salmonella Typhimurium causes a self-limiting gastroenteritis that may lead to systemic disease. Bacteria invade the small intestine, crossing the intestinal epithelium from where they are transported to the mesenteric lymph nodes (MLNs) within migrating immune cells. MLNs are an important site at which the innate and adaptive immune responses converge but their architecture and function is severely disrupted during S. Typhimurium infection. To further understand host-pathogen interactions at this site, we used mass spectrometry imaging (MSI) to analyse MLN tissue from a murine model of S. Typhimurium infection. A molecule, identified as palmitoylcarnitine (PalC), was of particular interest due to its high abundance at loci of S. Typhimurium infection and MLN disruption. High levels of PalC localised to sites within the MLNs where B and T cells were absent and where the perimeter of CD169+ sub capsular sinus macrophages was disrupted. MLN cells cultured ex vivo and treated with PalC had reduced CD4+CD25+ T cells and an increased number of B220+CD19+ B cells. The reduction in CD4+CD25+ T cells was likely due to apoptosis driven by increased caspase-3/7 activity. These data indicate that PalC significantly alters the host response in the MLNs, acting as a decisive factor in infection outcome

Photoswitchable diacylglycerols enable optical control of protein kinase C.

Increased levels of the second messenger lipid diacylglycerol (DAG) induce downstream signaling events including the translocation of C1-domain-containing proteins toward the plasma membrane. Here, we introduce three light-sensitive DAGs, termed PhoDAGs, which feature a photoswitchable acyl chain. The PhoDAGs are inactive in the dark and promote the translocation of proteins that feature C1 domains toward the plasma membrane upon a flash of UV-A light. This effect is quickly reversed after the termination of photostimulation or by irradiation with blue light, permitting the generation of oscillation patterns. Both protein kinase C and Munc13 can thus be put under optical control. PhoDAGs control vesicle release in excitable cells, such as mouse pancreatic islets and hippocampal neurons, and modulate synaptic transmission in Caenorhabditis elegans. As such, the PhoDAGs afford an unprecedented degree of spatiotemporal control and are broadly applicable tools to study DAG signaling

The effect of excess weight on circulating inflammatory cytokines in drug-naïve first-episode psychosis individuals

Background: Low-grade inflammation has been repeatedly associated with both excess weight and psychosis. However, no previous studies have addressed the direct effect of body mass index (BMI) on basal serum cytokines in individuals with first-episode psychosis (FEP). Objectives: The aim of this study is to analyze the effect of BMI on basal serum cytokine levels in FEP patients and control subjects, separating the total sample into two groups: normal-weight and overweight individuals. Methods: This is a prospective and open-label study. We selected 75 FEP patients and 75 healthy controls with similar characteristics to patients according to the following variables: sex, age, and cannabis and tobacco consumption. Both controls and patients were separated into two groups according to their BMI: subjects with a BMI under 25 were considered as normal weight and those with a BMI equal to or more than 25 were considered as overweight. Serum levels of 21 cytokines/chemokines were measured at baseline using the Human High Sensitivity T Cell Magnetic Bead Panel protocol from the Milliplex® Map Kit. We compared the basal serum levels of the 21 cytokines between control and patient groups according to their BMI. Results: In the normal-weight group, IL-8 was the only cytokine that was higher in patients than in the control group (p = 0.001), whereas in the overweight group, serum levels of two pro-inflammatory cytokines (IL-6, p = 0.000; IL-1?, p = 0.003), two chemokines (IL-8, p = 0.001; MIP-1?, p = 0.001), four Th-1 and Th-2 cytokines (IL-13, p = 0.009; IL-2, p = 0.001; IL-7, p = 0.001; IL-12p70, p = 0.010), and one Type-3 cytokine (IL-23, p = 0.010) were higher in patients than in controls. Conclusions: Most differences in the basal serum cytokine levels between patients and healthy volunteers were found in the overweight group. These findings suggest that excess weight can alter the homeostasis of the immune system and therefore may have an additive pro-inflammatory effect on the one produced by psychosis in the central nervous system.Funding: The present study was carried out at the Hospital Marqués de Valdecilla, University of Cantabria, Santander, Spain, under the following grant support from MINECO SAF2013-46292-R, Instituto de Salud Carlos III, and Fundación Marqués de Valdecilla. No pharmaceutical company has participated in the study concept and design, data collection, analysis and interpretation of the results, and drafting of the manuscript. We thank the Valdecilla Biobank for blood sampling handling and storage. We also wish to thank the participants and their families for enrolling in this study. The study, designed and directed by B C-F, conformed to international standards for research ethics and was approved by the local institutional review board