Target Fisher: a Consensus Structure-Based Target Prediction Tool, and its Application in the Discovery of Selective MAO-B Inhibitors.

In this work we introduce Target Fisher, a consensus structure-based target prediction tool that integrates molecular docking and machine learning with the aim to aid in the identification of potential biological targets and the optimization of the use of bioassays. Target Fisher uses per-residue energy decomposition profiles extracted from docking poses as fingerprints to train target-specific machine learning models. It provides predictions for a curated set of 37 protein targets, covering a diverse range of biological entities, and offers a user-friendly interface accessible via a web server (https://gqc.quimica.unlp.edu.ar/targetfisher/). In this sense, Target Fisher is a valuable tool to aid organic and medicinal chemistry groups in target identification, drug discovery and drug repurposing. As a case study, we demonstrate the efficacy of Target Fisher by screening a small library of assorted natural products for targets relevant to neurodegenerative diseases, which resulted in the identification and experimental validation of selective inhibitors of monoamine oxidase B (MAO-B).

The epidemiological profile of incidence and mortality from epidemics in complex humanitarian emergencies from 1990 to 2022 - A scoping review.

AIM: This study aimed to investigate the impact of communicable diseases with epidemic potential in complex emergency (CE) situations, focusing on the epidemiological profile of incidence and mortality and exploring underlying factors contributing to increased epidemic risks. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Review (PRISMA-ScR) guidelines, we conducted a scoping review of articles published between 1990 and 2022. The search included terms related to complex emergencies, communicable diseases, outbreaks, and epidemics. We identified 92 epidemics related to CE occurring in 32 different countries. RESULTS: Communicable diseases like Shigellosis, Cholera, Measles, Meningococcal meningitis, Yellow Fever, and Malaria caused significant morbidity and mortality. Diarrhoeal diseases, particularly Cholera and Shigellosis, had the highest incidence rates. Shigella specifically had an incidence of 241.0 per 1000 (people at risk), with a mortality rate of 11.7 per 1000, while Cholera's incidence was 13.0 per 1000, with a mortality rate of 0.22 per 1000. Measles followed, with an incidence of 25.0 per 1000 and a mortality rate of 0.76 per 1000. Meningococcal Meningitis had an incidence rate of 1.3 per 1000 and a mortality rate of 0.13 per 1000. Despite their lower incidences, yellow fever at 0.8 per 1000 and malaria at 0.4 per 1000, their high case fatality rates of 20.1% and 0.4% remained concerning in CE. The qualitative synthesis reveals that factors such as water, sanitation, and hygiene, shelter and settlements, food and nutrition, and public health and healthcare in complex emergencies affect the risk of epidemics. CONCLUSION: Epidemics during complex emergencies could potentially lead to a public health crisis. Between 1990 and 2022, there have been no statistically significant changes in the trend of incidence, mortality, or fatality rates of epidemic diseases in CE. It is crucial to understand that all epidemics identified in CE are fundamentally preventable.

Skeletal muscle fiber hypercontraction induced by Bothrops asper myotoxic phospholipases A2 ex vivo does not involve a direct action on the contractile apparatus.

Myonecrosis is a frequent clinical manifestation of envenomings by Viperidae snakes, mainly caused by the toxic actions of secreted phospholipase A2 (sPLA2) enzymes and sPLA2-like homologs on skeletal muscle fibers. A hallmark of the necrotic process induced by these myotoxins is the rapid appearance of hypercontracted muscle fibers, attributed to the massive influx of Ca2+ resulting from cell membrane damage. However, the possibility of myotoxins having, in addition, a direct effect on the contractile machinery of skeletal muscle fibers when internalized has not been investigated. This question is here addressed by using an ex vivo model of single-skinned muscle fibers, which lack membranes but retain an intact contractile apparatus. Rabbit psoas skinned fibers were exposed to two types of myotoxins of Bothrops asper venom: Mt-I, a catalytically active Asp49 sPLA2 enzyme, and Mt-II, a Lys49 sPLA2-like protein devoid of phospholipolytic activity. Neither of these myotoxins affected the main parameters of force development in striated muscle sarcomeres of the skinned fibers. Moreover, no microscopical alterations were evidenced after their exposure to Mt-I or Mt-II. In contrast to the lack of effects on skinned muscle fibers, both myotoxins induced a strong hypercontraction in myotubes differentiated from murine C2C12 myoblasts, with drastic morphological alterations that reproduce those described in myonecrotic tissue in vivo. As neither Mt-I nor Mt-II showed direct effects upon the contractile apparatus of skinned fibers, it is concluded that the mechanism of hypercontraction triggered by both myotoxins in patients involves indirect effects, i.e., the large cytosolic Ca2+ increase after sarcolemma permeabilization.

miR-124 as a Liquid Biopsy Prognostic Biomarker in Small Extracellular Vesicles from NSCLC Patients.

Despite advances in non-small cell lung cancer (NSCLC) research, this is still the most common cancer type that has been diagnosed up to date. microRNAs have emerged as useful clinical biomarkers in both tissue and liquid biopsy. However, there are no reliable predictive biomarkers for clinical use. We evaluated the preclinical use of seven candidate miRNAs previously identified by our group. We collected a total of 120 prospective samples from 88 NSCLC patients. miRNA levels were analyzed via qRT-PCR from tissue and blood samples. miR-124 gene target prediction was performed using RNA sequencing data from our group and interrogating data from 2952 NSCLC patients from two public databases. We found higher levels of all seven miRNAs in tissue compared to plasma samples, except for miR-124. Our findings indicate that levels of miR-124, both free-circulating and within exosomes, are increased throughout the progression of the disease, suggesting its potential as a marker of disease progression in both advanced and early stages. Our bioinformatics approach identified KPNA4 and SPOCK1 as potential miR-124 targets in NSCLC. miR-124 levels can be used to identify early-stage NSCLC patients at higher risk of relapse.

[Trichophyton benhamiae, an emergent zoonotic pathogen in Argentina associated with Guinea pigs: Description of 7cases in Buenos Aires]. / Trichophyton benhamiae, un dermatofito zoofílico emergente en Argentina con reservorio en cobayos: descripción de 7 casos en un hospital de la Ciudad Autónoma de Buenos Aires.

Trichophyton benhamiae is a zoonotic dermatophyte that can cause tinea corporis, tinea faciei and tinea capitis, producing inflammatory lesions, especially in children. In this publication, we describe 7clinical cases of pediatric patients that occurred in our institution between July 2019 and January 2020. All patients underwent a conventional mycological study. The identification of fungi isolates was confirmed by MALDI-TOF MS and sequencing of the ribosomal DNA. T. benhamiae was identified as the etiological agent, whose epidemiological link in all cases was the contact with Guinea pigs. This is the first description of infections caused by T. benhamiae in Argentina. This dermatophyte can be misidentified as other more frequent dermatophytes when performing conventional studies. Molecular technology should be used to reach a definitive diagnosis. It is important to have epidemiological data from patients such as contact with non-traditional pets, especially Guinea pigs, for an adequate presumptive diagnosis of this dermatophytosis.

Clinical characteristics of admission for mental illness in a Regional Psychiatric Hospitalization Unit. Descriptive study 2008-2018 / Características clínicas del ingreso por enfermedad mental en una Unidad de Hospitalización Psiquiátrica Comarcal. Estudio descriptivo 2008-2018.

Objective: To describe the admissions of patients diagnosed with severe mental illness (SMI) and anxiety disorder in a regional hospital; to explore factors related to the patient's referrer upon admission and prolonged stay. Materials and methods: Cross-sectional study of episodes of admission to the regional Psychiatric Hospitalization Unit over a period of 11 years with ICD-10 diagnostic codesF20-29, F30-39, F60-69 and F40-48. The data was extracted through the Admissions Unit and the information from the electronic medical record. For the statistical treatment, descriptive or inferential tests were used with a confidence level of 95%. Results: 961 patients were included (2,324 total discharges), aged 40.8±14.0 years. The most frequent reasons for admission were: positive symptoms (agitation, delusions and hallucinations), followed by suicidal ideation and attempt. The main remitting agent of the patients was the family itself. Approximately 1/5 of the cases were referred by the health system itself, and » of those admitted had self-excluded themselves from specialized supervision for more than a year. Conclusions: The problems that caused the admission and its origin, as well as its lack of follow-up, can be considered as a clear opportunity for improvement in the follow-up of patients with severe mental illness. An orientation towards proactivity, acting before the decompensation, would contribute to improving the care and quality of life of patients with severe mental illness and their environment.

Objetivo: Describir los ingresos de pacientes diagnosticados de enfermedad mental grave y trastorno de ansiedad en un hospital comarcal; explorar los factores relacionados con la derivación del paciente al ingreso y con estancia prolongada. Materiales y métodos: Estudio de corte transversal de los episodios de ingreso en la Unidad de Hospitalización Psiquiátrica comarcal en un periodo de 11 años con los códigos diagnósticos CIE-10 F20-29, F30-39, F60-69 y F40-48. Se extrajeron los datos a través de la Unidad de Admisión y la información de la historia clínica electrónica. Para el tratamiento estadístico se usaron pruebas descriptivas o inferenciales con nivel de confianza del 95%. Resultados: Se incluyeron 961 pacientes (2.324 altas totales), con edad de 40,8±14,0 años. Los motivos más frecuentes de ingreso fueron: síntomas positivos (agitación, delirios y alucinaciones), seguidos de ideación e intento de suicidio. El principal agente remisor de los pacientes fue la propia familia. Aproximadamente 1/5 de casos fue derivado por el propio sistema sanitario, y » de los ingresados se había autoexcluido de la supervisión especializada durante más de un año. Conclusiones: Los problemas causantes del ingreso y su procedencia, así como su falta de seguimiento, pueden considerarse como una oportunidad clara de mejora en el seguimiento del paciente con enfermedad mental grave. Una orientación hacia la proactividad, actuando antes de la descompensación, contribuiría a mejorar la asistencia y calidad de vida de los pacientes con enfermedad mental grave y su entorno.

The Effects of Anesthetics and Perioperative Medications on Immune Function: A Narrative Review.

Preclinical and clinical studies have sought to better understand the effect of anesthetic agents, both volatile and intravenous, and perioperative adjuvant medications on immune function. The immune system has evolved to incorporate both innate and adaptive components, which are delicately interwoven and essential for host defense from pathogens and malignancy. This review summarizes the complex and nuanced relationship that exists between each anesthetic agent or perioperative adjuvant medication studied and innate and adaptive immune function with resultant clinical implications. The most commonly used anesthetic agents were chosen for review including volatile agents (sevoflurane, isoflurane, desflurane, and halothane), intravenous agents (propofol, ketamine, etomidate, and dexmedetomidine), and perioperative adjuvant medications (benzodiazepines, opioids, nonsteroidal anti-inflammatory drugs [NSAIDs], and local anesthetic agents). Patients who undergo surgery experience varying combinations of the aforementioned anesthetic agents and adjuncts, depending on the type of surgery and their comorbidities. Each has unique effects on immunity, which may be more or less ideal depending on the clinical situation. Further study is needed to better understand the clinical effects of these relationships so that patient-specific strategies can be developed to improve surgical outcomes.

Dimensional analysis of the upper airway in obstructive sleep apnoea syndrome patients treated with mandibular advancement device: A bi- and three-dimensional evaluation.

BACKGROUND: The efficiency of the mandibular advancement device (MAD) in patients with obstructive sleep apnoea syndrome (OSAS) has been demonstrated. Nevertheless, the behaviour of the upper airway once MAD is placed and titrated, and its correlation with the apnoea-hypopnoea index (AHI) is still under discussion. OBJECTIVES: To analyse the morphological changes of the upper airway through a bi- and three-dimensional study and correlate it with the polysomnographic variable, AHI. METHODS: Patients were recruited from two different hospitals for the treatment of OSAS with a custom-made MAD. A cone-beam computer tomography and a polysomnography were performed at baseline and once the MAD was titrated. RESULTS: A total of 41 patients completed the study. Treatment with MAD reduced the AHI from 22.5 ± 16.8 to 9.2 ± 11.6 (p ≤ .05). There was a significant increase of the total airway volume with MAD from 21.83 ± 7.05 cm3 to 24.19 ± 8.19 cm3 , at the expense of the oropharynx. Moreover, the correlation between the improvement of the AHI and the augmentation of the volume of the upper airway was not statistically significant. CONCLUSIONS: The oral device used in this prospective study increased the mean upper pharyngeal airway volume and significantly reduced the AHI. Future studies that measure the muscular tone are needed to completely understand the association between the AHI and the physiological and anatomical response of the upper airway.

Mycosis Due to Tropicoporus tropicalis (= Inonotus tropicalis) in a Domestic Dog.

Mycelial basidiomycetes rarely produce mycoses in animals including humans. We report a case of a 9-year-old female mongrel dog with lesions in the prescapular lymph nodes. The histopathology of a lymph node sample showed flexuous septate hyphae, and a sterile mold grew in culture from that specimen. DNA sequencing of the ITS region allowed us to identify the fungus as Tropicoporus tropicalis. The dog was treated with itraconazole, but it was euthanized six months later due to an unfavorable clinical outcome. Tropicoporus tropicalis is an infrequent pathogen of pets, and the use of molecular tools is needed for its identification. Animal infections due to T. tropicalis were not previously been reported in Argentina.

Hepatic Tumor Microenvironments and Effects on NK Cell Phenotype and Function.

The liver is a complex organ with critical physiological functions including metabolism, glucose storage, and drug detoxification. Its unique immune profile with large numbers of cytotoxic CD8+ T cells and significant innate lymphoid population, including natural killer cells, γ δ T cells, MAIT cells, and iNKTcells, suggests an important anti-tumor surveillance role. Despite significant immune surveillance in the liver, in particular large NK cell populations, hepatic cell carcinoma (HCC) is a relatively common outcome of chronic liver infection or inflammation. The liver is also the second most common site of metastatic disease. This discordance suggests immune suppression by the environments of primary and secondary liver cancers. Classic tumor microenvironments (TME) are poorly perfused, leading to accumulation of tumor cell metabolites, diminished O2, and decreased nutrient levels, all of which impact immune cell phenotype and function. Here, we focus on changes in the liver microenvironment associated with tumor presence and how they affect NK function and phenotype.

National production of certified reference fungal cultures.

Reference fungal cultures (RFCs) are essential for the internal quality control of laboratories. The production of these cultures requires standardized procedures (IRAM 14950:2016 and ISO 17034:2016 standards) carried out by a recognized and accredited laboratory. The aim of this work was to produce RFC in paper disks of autochthonous strains, characterized by two, homogeneous and stable reference methods traceable at species level. RFC were produced using 14 regional species (7 yeasts and 7 filamentous fungi) from the fungal culture collection (DMic). Paper disks were impregnated with a culture suspension, dried and packed. Homogeneity, viability, identity and purity were verified. Short- and long-term stability at different temperatures and storage times were studied. Characterization of each strain allowed to confirm its identity and to ensure its traceability at international level. Produced batches were homogeneous and stable at -20±5°C for 30 months. This method of production was adequate to produce homogeneous and stable RFC with phenotypic and genotypic characteristics correctly defined and internationally traceable. Standardized procedures were developed for the production of certified RFC that could be transferred to other microorganisms. Providing RFC that represent regional strains allows laboratories to produce more reliable results with a favorable impact on medical diagnosis, the environment or the food industry.

Effectiveness of a mandibular advancement device in obstructive sleep apnea patients: a prospective clinical trial.

PURPOSE: This study aimed to determine the effectiveness of a mandibular advancement device in a sample of obstructive sleep apnea syndrome patients by the evaluation of respiratory and neurophysiologic parameters and clinical symptoms. Second, the influence of certain predictor factors related with the patient and the intraoral device, were considered in the final response with this treatment option. METHODS: Forty-one patients constituted the final sample. Outcomes were measured using polysomnography, Epworth sleepiness scale and an analogue visual snoring scale, before treatment and once the device was properly titrated. RESULTS: Mean apnea-hypopnea index decreased from 22.5 ± 16.8 to 9.1 ± 11.6 (p ≤ 0.05), influencing only gender and Fujita index as predictor factors. The oxygen saturation, arousal index, percentages of sleep stages and sleep efficiency significantly improved with the mandibular advancement device (MAD) placement. The snoring index improved in absolute terms in 6.1 units and the excessive daytime sleepiness was reduced from 12.2 ± 4.7 to 8.5 ± 3.8 (p ≤ 0.00). CONCLUSIONS: The successful treatment rate with the MAD was 65.8%. The placement and posterior regulation of the intraoral appliance efficiently reduced the apnea-hypopnea index, improved the sleep quality and the clinical symptomatology associated. Obstructive sleep apnea syndrome is a highly prevalent disease. and dentists should be aware of the benefits enhanced by this prosthetic device, considered the first treatment option by certain physicians.

Healthy and Osteoarthritic Synovial Fibroblasts Produce a Disintegrin and Metalloproteinase with Thrombospondin Motifs 4, 5, 7, and 12: Induction by IL-1ß and Fibronectin and Contribution to Cartilage Damage.

Current description of osteoarthritis includes the involvement of synovial inflammation. Studies contributing to understanding the mechanisms of cross-talk and feedback among the joint tissues could be relevant to the development of therapies that block disease progression. During osteoarthritis, synovial fibroblasts exposed to anomalous mechanical forces and an inflammatory microenvironment release factors such as a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) metalloproteinases that mediate tissue damage and perpetuate inflammation. We therefore studied the production of ADAMTS by synovial fibroblasts and their contribution to cartilage degradation. Moreover, we analyzed the implication of two mediators present in the osteoarthritis joint, IL-1ß as proinflammatory cytokine, and 45-kDa fibronectin fragments as products of matrix degradation. We reported that synovial fibroblasts constitutively express and release ADAMTS 4, 5, 7, and 12. Despite the contribution of both mediators to the stimulation of Runx2 and Wnt/ß-catenin signaling pathways, as well as to ADAMTS expression, promoting the degradation of aggrecan and cartilage oligomeric matrix protein from cartilage, fibronectin fragments rather than IL-1ß played the major pathological role in osteoarthritis, contributing to the maintenance of the disease. Moreover, higher levels of ADAMTS 4 and 7 and a specific regulation of ADAMTS-12 were observed in osteoarthritis, suggesting them as new potential therapeutic targets. Therefore, synovial fibroblasts provide the biochemical tools to the chronicity and destruction of the osteoarthritic joints.

Venomics of Scorpion Ananteris platnicki (Lourenço, 1993), a New World Buthid That Inhabits Costa Rica and Panama.

Ananteris is a scorpion genus that inhabits dry and seasonal areas of South and Central America. It is located in a distinctive morpho-group of Buthids, the 'Ananteris group', which also includes species distributed in the Old World. Because of the lack of information on venom composition, the study of Ananteris species could have biological and medical relevance. We conducted a venomics analysis of Ananteris platnicki, a tiny scorpion that inhabits Panama and Costa Rica, which shows the presence of putative toxins targeting ion channels, as well as proteins with similarity to hyaluronidases, proteinases, phospholipases A2, members of the CAP-domain family, and hemocyanins, among others. Venom proteolytic and hyaluronidase activities were corroborated. The determination of the primary sequences carried out by mass spectrometry evidences that several peptides are similar to the toxins present in venoms from Old World scorpion genera such as Mesobuthus, Lychas, and Isometrus, but others present in Tityus and Centruroides toxins. Even when this venom displays the characteristic protein families found in all Buthids, with a predominance of putative Na+-channel toxins and proteinases, some identified partial sequences are not common in venoms of the New World species, suggesting its differentiation into a distinctive group separated from other Buthids.

A murine experimental model of the pulmonary thrombotic effect induced by the venom of the snake Bothrops lanceolatus.

BACKGROUND: The venom of Bothrops lanceolatus, a viperid species endemic to the Lesser Antillean Island of Martinique, induces thrombosis in a number of patients. Previous clinical observations indicate that thrombotic events are more common in patients bitten by juvenile specimens. There is a need to develop an experimental model of this effect in order to study the mechanisms involved. METHODOLOGY/PRINCIPAL FINDINGS: The venoms of juvenile and adult specimens of B. lanceolatus were compared by (a) describing their proteome, (b) assessing their ability to induce thrombosis in a mouse model, and (c) evaluating their in vitro procoagulant activity and in vivo hemostasis alterations. Venom proteomes of juvenile and adult specimens were highly similar, albeit showing some differences. When injected by the intraperitoneal (i.p.) route, the venom of juvenile specimens induced the formation of abundant thrombi in the pulmonary vasculature, whereas this effect was less frequent in the case of adult venom. Thrombosis was not abrogated by the metalloproteinase inhibitor Batimastat. Both venoms showed a weak in vitro procoagulant effect on citrated mouse plasma and bovine fibrinogen. When administered intravenously (i.v.) venoms did not affect classical clotting tests (prothrombin time and activated partial thromboplastin time) but caused a partial drop in fibrinogen concentration. The venom of juvenile specimens induced partial alterations in some rotational thromboelastometry parameters after i.v. injection. When venoms were administered i.p., only minor alterations in classical clotting tests were observed with juvenile venom, and no changes occurred for either venom in rotational thromboelastometry parameters. Both juvenile and adult venoms induced a marked thrombocytopenia after i.p. injection. CONCLUSIONS/SIGNIFICANCE: An experimental model of the thrombotic effect induced by B. lanceolatus venom was developed. This effect is more pronounced in the case of venom of juvenile specimens, despite the observation that juvenile and adult venom proteomes are similar. Adult and juvenile venoms do not induce a consumption coagulopathy characteristic of other Bothrops sp venoms. Both venoms induce a conspicuous thrombocytopenia. This experimental model reproduces the main clinical findings described in these envenomings and should be useful to understand the mechanisms of the thrombotic effect.

Antibody-dependent enhancement of toxicity of myotoxin II from Bothrops asper.

Improved therapies are needed against snakebite envenoming, which kills and permanently disables thousands of people each year. Recently developed neutralizing monoclonal antibodies against several snake toxins have shown promise in preclinical rodent models. Here, we use phage display technology to discover a human monoclonal antibody and show that this antibody causes antibody-dependent enhancement of toxicity (ADET) of myotoxin II from the venomous pit viper, Bothrops asper, in a mouse model of envenoming that mimics a snakebite. While clinical ADET related to snake venom has not yet been reported in humans, this report of ADET of a toxin from the animal kingdom highlights the necessity of assessing even well-known antibody formats in representative preclinical models to evaluate their therapeutic utility against toxins or venoms. This is essential to avoid potential deleterious effects as exemplified in the present study.

Evaluation of the clinical use of MGMT methylation in extracellular vesicle-based liquid biopsy as a tool for glioblastoma patient management.

Glioblastoma (GB) is a devastating tumor of the central nervous system characterized by a poor prognosis. One of the best-established predictive biomarker in IDH-wildtype GB is O6-methylguanine-DNA methyltransferase (MGMT) methylation (mMGMT), which is associated with improved treatment response and survival. However, current efforts to monitor GB patients through mMGMT detection have proven unsuccessful. Small extracellular vesicles (sEVs) hold potential as a key element that could revolutionize clinical practice by offering new possibilities for liquid biopsy. This study aimed to determine the utility of sEV-based liquid biopsy as a predictive biomarker and disease monitoring tool in patients with IDH-wildtype GB. Our findings show consistent results with tissue-based analysis, achieving a remarkable sensitivity of 85.7% for detecting mMGMT in liquid biopsy, the highest reported to date. Moreover, we suggested that liquid biopsy assessment of sEV-DNA could be a powerful tool for monitoring disease progression in IDH-wildtype GB patients. This study highlights the critical significance of overcoming molecular underdetection, which can lead to missed treatment opportunities and misdiagnoses, possibly resulting in ineffective therapies. The outcomes of our research significantly contribute to the field of sEV-DNA-based liquid biopsy, providing valuable insights into tumor tissue heterogeneity and establishing it as a promising tool for detecting GB biomarkers. These results have substantial implications for advancing predictive and therapeutic approaches in the context of GB and warrant further exploration and validation in clinical settings.

Predictors of outcomes after internal fixation of periprosthetic femoral hip fractures Subgroup analysis of the peri-implant and peri-prosthetic fractures Spanish registry (PIPPAS).

PURPOSE: To identify risk factors predisposing patients to poor outcomes after fixation of periprosthetic hip fractures around femoral stems. METHODS: Prospective multicentre cohort study of fractures around a hip replacement stem managed by internal fixation. The primary outcome was one-year mortality, while secondary outcomes were local complications and healthcare burden-related outcomes (nursing facility utilization and hospital length of stay). RESULTS: One-year mortality was 16.2%. Age-adjusted Charlson Comorbidity Index score (OR=1.17; 95%CI=1.03-1.33)), Pfeiffer Short Portable Mental Status Questionnaire (SPMSQ) score (OR=1.16; 1.06-1.28), prosthetic dysfunction (OR=1.90; 1.00-3.61), and postoperative medical complications (OR=1.97; 1.06-3.68) were predictors of mortality. Patients with prior prosthetic dysfunction, lower Pfeiffer SPMSQ scores, Vancouver A fractures, and fractures fixed only using cerclages were at higher risk of local complications, which occurred in 9.3% of cases. Medical (OR=1.81; 1.05-3.13) and local complications (OR=5.56; 2.42-3.13) emerged as consistent risk factors for new institutionalization. Average hospitalization time was 13.9±9.2 days. Each day of fixation delay led to an average 1.4-day increase in total hospitalization. CONCLUSION: Frail periprosthetic hip-fracture patients with poorer functional status, dysfunctional replacements, and postoperative complications are at increased risk of mortality. Postoperative complications are more common in patients with dysfunctional arthroplasties, Vancouver A fractures, and fixation using cerclages alone. Postoperative complications were the most consistent predictor of higher healthcare resource utilization.

Why myotoxin-containing snake venoms possess powerful nucleotidases?

The venom of the snake Bothrops asper causes muscle necrosis, pain and inflammation. This venom contains myotoxins which cause an increase in intracellular Ca(2+) concentration and release of K(+) and ATP from myotubes. ATP is a key danger molecule that triggers a variety of reactions, including activation of the innate immune response. Here, using ATP-luciferase bioluminescence imaging technique, we show for the first time in vivo, that the purified myotoxins induce rapid release of ATP, whilst the complete venom of B. asper does at a very small extent. This apparent contradiction is explained by the finding that the venom contains powerful nucleotidases that in vivo convert ATP into ADP, AMP and Adenosine. These findings indicate that high concentrations of adenosine are generated by the double action of the venom and provide the experimental basis to the suggestion that in situ generated adenosine plays an important role in envenomation via its hypotensive, paralyzing and anti-coagulant activities.

[Behavioral types in relation to burnout, mobbing, personality, and adaptation of self-conduct in health care workers]. / Tipologías comportamentales en relación con el burnout, mobbing, personalidad, autoconcepto y adaptación de conducta en trabajadores sanitarios.

OBJECTIVE: To define the different patterns of behavior among workers in health care in Ceuta. DESIGN: Cross-sectional and descriptive. SITES AND PARTICIPANTS: 200 randomly selected workers in the Ceuta Health Care Area using a stratified sampling of workplace, job and sex. MEASUREMENTS: The instruments used were the MBI, the LIPT by Leymann, a reduced version of the Pinillos CEP, Musitu self concept and adaptation behavior, all adapted in the context of occupational health examinations. RESULTS: Principal components analysis allowed us to define 5 components, one strictly related to the scale of mobbing with 85% of weight; another for burnout with 70% weight; a third to adaptation and family satisfaction with a weight of 64%; a fourth with adaptation, control, emotional self, professional achievement and occupational self-weight of 52%; and a fifth component defined by social evaluations in the levels of extraversion and social adjustment with 73%. CONCLUSIONS: Highlights five different behavioral characteristics peculiar interest for clinical work are highlighted: burnout, mobbing, family work satisfaction; individual occupational and sociable satisfaction.