Role of rafts in neurological disorders.

INTRODUCTION: Rafts are protein-lipid structural nanodomains involved in efficient signal transduction and the modulation of physiological processes of the cell plasma membrane. Raft disruption in the nervous system has been associated with a wide range of disorders. DEVELOPMENT: We review the concept of rafts, the nervous system processes in which they are involved, and their role in diseases such as Parkinson's disease, Alzheimer disease, and Huntington disease. CONCLUSIONS: Based on the available evidence, preservation and/or reconstitution of rafts is a promising treatment strategy for a wide range of neurological disorders.

Porous silicon opto-acoustic detector for ternary gas mixture.

The use of porous phoxonic crystals with coupled optical and acoustic response has been proposed as a sensing device. Due to the porous nature of the crystal, each layer of the structure can be connected to the environment. As the optical and acoustic performances of the phoxonic crystal change when a gas permeates the pores due to modifications of the effective refractive index and density of the system, it results that these structures are suitable platforms for the detection of gases. The sensor designed following these premises can detect the composition of ternary gas mixtures through optical measurements, while an acoustic wave induces a structural oscillation. The amplified acoustic wave produces a mechanical deformation of the crystal layers that is maximized in the center a resonant microcavity. Therefore, under such experimental conditions, the sensitivity of the optical response is not only due to the optical property changes caused by the gas mixture in contact with the porous structure but also to changes in the mechanical deformations due to modifications of the acoustic properties. In this work, we discuss the device theoretical behavior as a multiparameter sensor that distinguishes the components and concentrations of a ternary gas mixture through the transfer matrix method. For a prototype combination of CO2-Air-CH4 mixture, the estimated resolution of the proposed device fabricated in porous silicon can be has high as 0.05% (500 ppm) in the concentration of each individual species.

Non-classical Non-covalent σ-Hole Interactions in Protein Structure and Function: Concepts for Potential Protein Engineering Applications.

The structures and associated functions of biological molecules are driven by noncovalent interactions, which have classically been dominated by the hydrogen bond (H-bond). Introduction of the σ-hole concept to describe the anisotropic distribution of electrostatic potential of covalently bonded elements from across the periodic table has opened a broad range of nonclassical noncovalent (ncNC) interactions for applications in chemistry and biochemistry. Here, we review how halogen bonds, chalcogen bonds and tetrel bonds, as they are found naturally or introduced synthetically, affect the structures, assemblies, and potential functions of peptides and proteins. This review intentionally focuses on examples that introduce or support principles of stability, assembly and catalysis that can potentially guide the design of new functional proteins. These three types of ncNC interactions have energies that are comparable to the H-bond and, therefore, are now significant concepts in molecular recognition and design. However, the recently described H-bond enhanced X-bond shows how synergism among ncNC interactions can be exploited as potential means to broaden the range of their applications to affect protein structures and functions.

Moringa oleifera Improves MAFLD by Inducing Epigenetic Modifications.

BACKGROUND AND AIMS: Metabolic Associated Fatty Liver Disease (MAFLD) encompasses a spectrum of diseases from simple steatosis to nonalcoholic steatohepatitis (NASH). Here, we investigated the hepatoprotective role of Moringa oleifera aqueous extract on hepatic miRNAs, genes and protein expression, as well as histological and biochemical parameters in an experimental model of NASH. METHODS: Male C57BL/6J mice were fed with a high fat diet (HFD, 60% lipids, 42 gr/L sugar in water) for 16 weeks. Moringa extract was administered via gavage during the final 8 weeks. Insulin Tolerance Test (ITT) and HOMA-IR were calculated. Serum levels of insulin, resistin, leptin and PAI-1 and hepatic expression of miR-21a-5p, miR-103-3p, miR-122-5p, miR-34a-5p and SIRT1, AMPKα and SREBP1c protein were evaluated. Alpha-SMA immunohistochemistry and hematoxylin-eosin, Masson's trichrome and sirius red staining were made. Hepatic transcriptome was analyzed using microarrays. RESULTS: Animals treated with Moringa extract improved ITT and decreased SREBP1c hepatic protein, while SIRT1 increased. Hepatic expression of miR-21a-5p, miR-103-3p and miR-122-5p, miR34a-5p was downregulated. Hepatic histologic analysis showed in Moringa group (HF + MO) a significant decrease in inflammatory nodules, macro steatosis, fibrosis, collagen and αSMA reactivity. Analysis of hepatic transcriptome showed down expression of mRNAs implicated in DNA response to damage, endoplasmic reticulum stress, lipid biosynthesis and insulin resistance. Moringa reduced insulin resistance, de novo lipogenesis, hepatic inflammation and ER stress. CONCLUSIONS: Moringa prevented progression of liver damage in a model of NASH and improved biochemical, histological and hepatic expression of genes and miRNAs implicated in MAFLD/NASH development.

Assessment of Noninvasive Markers of Steatosis and Liver Fibrosis in Human Immunodeficiency Virus-Monoinfected Patients on Stable Antiretroviral Regimens.

Background: Nonalcoholic fatty liver disease (NAFLD) is a major nonacquired immune deficiency syndrome-defining condition for persons with human immunodeficiency virus (PWH). We aimed to validate noninvasive tests for the diagnosis of NAFLD in PWH. Methods: This is a cross-sectional study of PWH on stable antiretroviral therapy with persistently elevated transaminases and no known liver disease. The area under the receiver operating characteristic curve (AUROC) was calculated to compare the diagnostic accuracy of liver biopsy with abdominal ultrasound, transient elastography (TE) (including controlled attenuation parameter [CAP]), and noninvasive markers of steatosis (triglyceride and glucose index [TyG], hepatic steatosis index [HSI], fatty liver index [FLI]) and fibrosis ([FIB]-4, aminotransferase-to-platelet ratio index [APRI], NAFLD fibrosis score). We developed a diagnostic algorithm with serial combinations of markers. Results: Of 146 patients with increased transaminase levels, 69 underwent liver biopsy (90% steatosis, 61% steatohepatitis, and 4% F ≥3). The AUROC for steatosis was as follows: ultrasound, 0.90 (0.75-1); CAP, 0.94 (0.88-1); FLI, 0.81 (0.58-1); HSI, 0.74 (0.62-0.87); and TyG, 0.75 (0.49-1). For liver fibrosis ≥F3, the AUROC for TE, APRI, FIB-4, and NAFLD fibrosis score was 0.92 (0.82-1), 0.96 (0.90-1), 0.97 (0.93-1), and 0.85 (0.68-1). Optimal diagnostic performance for liver steatosis was for 2 noninvasive combined models of tests with TyG and FLI/HSI as the first tests and ultrasound or CAP as the second tests: AUROC = 0.99 (0.97-1, P < .001) and 0.92 (0.77-1, P < .001). Conclusions: Ultrasound and CAP performed best in diagnosing liver steatosis, and FLI, TyG, and HSI performed well. We propose an easy-to-implement algorithm with TyG or FLI as the first test and ultrasound or CAP as the second test to accurately diagnose or exclude NAFLD.

Comorbidity and prognostic factors on admission in a COVID-19 cohort of a general hospital.

ANTECEDENTS AND OBJECTIVE: To describe clinical features, comorbidity, and prognostic factors associated with in-hospital mortality in a cohort of COVID-19 admitted to a general hospital. MATERIAL AND METHODS: Retrospective cohort study of patients with COVID-19 admitted from 26th February 2020, who had been discharged or died up to 29th April 2020. A descriptive study and an analysis of factors associated with intrahospital mortality were performed. RESULTS: Out of the 101 patients, 96 were analysed. Of these, 79 (82%) recovered and were discharged, and 17 (18%) died in the hospital. Diagnosis of COVID-19 was confirmed by polymerase chain reaction to SARS-CoV2 in 92 (92.5%). The mean age was 63 years, and 66% were male. The most frequent comorbidities were hypertension (40%), diabetes mellitus (16%) y cardiopathy (14%). Patients who died were older (mean 77 vs 60 years), had higher prevalence of hypertension (71% vs 33%), and cardiopathy (47% vs 6%), and higher levels of lactate dehydrogenase (LDH) and reactive C protein (mean 662 vs 335 UI/L, and 193 vs 121mg/L respectively) on admission. In a multivariant analysis the variables significantly associated to mortality were the presence of cardiopathy (CI 95% OR 2,58-67,07), levels of LDH≥345 IU/L (CI 95% OR 1,52-46,00), and age≥65 years (CI 95% OR 1,23-44,62). CONCLUSIONS: The presence of cardiopathy, levels of LDH≥345 IU/L and age≥65 years, are associated with a higher risk of death during hospital stay for COVID-19. This model should be validated in prospective cohorts.

Pirfenidone modifies hepatic miRNAs expression in a model of MAFLD/NASH.

miRNAs are involved in the development of metabolic associated fatty liver disease (MAFLD) and nonalcoholic steatohepatitis (NASH). We aimed to evaluate modifications by prolonged-release pirfenidone (PR-PFD) on key hepatic miRNAs expression in a MAFLD/NASH model. First, male C57BL/6J mice were randomly assigned into groups and fed with conventional diet (CVD) or high fat and carbohydrate diet (HFD) for 16 weeks. At the end of the eighth week, HFD mice were divided in two and only one half was treated with 300 mg/kg/day of PR-PFD mixed with food. Hepatic expression of miRNAs and target genes that participate in inflammation and lipid metabolism was determined by qRT-PCR and transcriptome by microarrays. Increased hepatic expression of miR-21a-5p, miR-34a-5p, miR-122-5p and miR-103-3p in MAFLD/NASH animals was reduced with PR-PFD. Transcriptome analysis showed that 52 genes involved in lipid and collagen biosynthesis and inflammatory response were downregulated in PR-PFD group. The expression of Il1b, Tnfa, Il6, Tgfb1, Col1a1, and Srebf1 were decreased in PR-PFD treated animals. MAFLD/NASH animals compared to CVD group showed modifications in gene metabolic pathways implicated in lipid metabolic process, inflammatory response and insulin resistance; PR-PFD reversed these modifications.

[Acute sialadenitis by iodine contrast medium administration].

Acute iodide sialadenitis is a rare adverse reaction to iodinated contrast that causes self-limited salivary gland swell-ing. Its pathogenesis is still unclear, although kidney failure may be a risk factor. The diagnosis is initially clinical but angioedema, infections and lithiasis should be included in the differential diagnosis. No treatment or prophylaxis was proven to be beneficial. Although its prognosis is benign, associated complications have been reported. We report a case of 68-year-old man with swelling of the submandibular salivary glands after the administration of iodine-based contrast media during an abdominal computed tomography examination. Because of the widespread use of iodinated contrast enhanced imaging and interventional techniques, clinicians should be aware of this issue.

Incidence of electrocardiographic alterations in the preoperative period of non-cardiac surgery.

BACKGROUND: The electrocardiogram is the most widely used test to assess cardiovascular risk during the preoperative period. The objective of the present study is to evaluate the incidence of electrocardiographic alterations in the general population scheduled for non-cardiac surgery and to determine if the age greater than or equal to 65 years or the revised cardiac risk index ≥1 represent a risk factor for presenting these alterations. MATERIAL AND METHODS: Over a period of one month, all preoperative electrocardiograms (ECG) from the anesthesia clinic were analyzed. Various epidemiological data were collected and the revised cardiac risk index was calculated. Major alterations were defined as those requiring Cardiology follow-up. RESULTS: 476 patients were recruited, of whom 40.8% were ≥65 years, 32.6% had HTN, 14.4% DM and 27.9% dyslipidemia. 16.16% of the patients had a Lee Index ≥1. Of the entire sample, 80.5% had a normal ECG, 6.5% minor alterations and 13.0% major alterations. In the multivariate analysis, age ≥65 years and the presence of HTN were shown as independent risk factors for presenting alterations in the total and major ECG. The Lee index ≥1 was not associated with an increased risk of electrocardiographic abnormalities. CONCLUSIONS: Patients ≥65 years old and those with HTN are at greater risk of presenting major electrocardiographic abnormalities, so we recommend including the ECG as a routine diagnostic test in the preoperative period of non-cardiac surgery.

Role of rafts in neurological disorders. / Participación de rafts en enfermedades neurológicas.

INTRODUCTION: Rafts are function-structural cell membrane nano-domains. They contribute to explain the efficiency of signal transduction at the low physiological membrane concentrations of the signaling partners by their clustering inside specialized signaling domains. DEVELOPMENT: In this article, we review the current model of the membrane rafts and their physio-pathological relevance in the nervous system, including their role in Parkinson, Alzheimer, and Huntington diseases. CONCLUSIONS: Rafts disruption/dysfunction has been shown to relate diverse neurological diseases. Therefore, it has been suggested that preservation of membrane rafts may represent a strategy to prevent or delay neuronal dysfunctions in several diseases.

Incidence of electrocardiographic alterations in the preoperative period of non-cardiac surgery. / Incidencia de alteraciones electrocardiográficas en el preoperatorio de cirugía no cardiaca.

BACKGROUND: The electrocardiogram is the most widely used test to assess cardiovascular risk during the preoperative period. The objective of the present study is to evaluate the incidence of electrocardiographic alterations in the general population scheduled for non-cardiac surgery and to determine if the age greater than or equal to 65 years or the revised cardiac risk index ≥ 1 represent a risk factor for presenting these alterations. MATERIAL AND METHODS: Over a period of one month, all preoperative electrocardiograms (ECG) from the anesthesia clinic were analyzed. Various epidemiological data were collected and the revised cardiac risk index was calculated. Major alterations were defined as those requiring Cardiology follow-up. RESULTS: 476 patients were recruited, of whom 40.8% were ≥ 65 years, 32.6% had HTN, 14.4% DM and 27.9% dyslipidemia. 16.16% of the patients had a Lee Index ≥ 1. Of the entire sample, 80.5% had a normal ECG, 6.5% minor alterations and 13.0% major alterations. In the multivariate analysis, age ≥ 65 years and the presence of HTN were shown as independent risk factors for presenting alterations in the total and major ECG. The Lee index ≥ 1 was not associated with an increased risk of electrocardiographic abnormalities. CONCLUSIONS: Patients ≥ 65 years old and those with HTN are at greater risk of presenting major electrocardiographic abnormalities, so we recommend including the ECG as a routine diagnostic test in the preoperative period of non-cardiac surgery.

Contribución del panel de miositis en el estudio de pacientes con enfermedades pulmonares intersticiales y sospecha de enfermedad del tejido conectivo / Contribution of myositis panel in the study of patients with interstitial lung disease and suspicion of connective tissue disease

INTRODUCCIÓN: La manifestación extramuscular de las miopatías inflamatorias idiopáticas (MII) es la enfermedad pulmonar intersticial (EPI) y el diagnóstico se basa en autoanticuerpos séricos. Los nuevos anticuerpos específicos y asociados a MII han ayudado a identificar nuevas entidades clínicas en el espectro de MII. El objetivo de este estudio es evaluar la contribución diagnóstica de un panel de anticuerpos de miositis (PM) en una cohorte de pacientes chilenos con EPI sin una enfermedad del tejido conectivo (ETC) definitiva. MATERIALES Y MÉTODOS: A partir de enero de 2017 se realizó un panel de miositis a 111 pacientes consecutivos con EPI y sospecha de ETC, pero sin un diagnóstico definitivo a través de otra herramienta diagnóstica, en el programa de Pulmón-Reumatológico del Instituto Nacional del Tórax, Santiago, Chile. Se compararon las características basales clínicas y serológicas de los pacientes que se asociaban más frecuentemente a la probabilidad de tener un panel positivo. RESULTADOS: El PM fue positivo en 56 de 111 pacientes. El síndrome antisintetasa (SAS) fue el diagnóstico más frecuente. Los anticuerpos más frecuentes fueron Ro-52, PM / Scl-75 y Ku. Las variables más frecuentes en el grupo PM(+) fueron la presencia del Raynaud, miositis, manos de mecánico, los anticuerpos Ro y La positivos, la presencia de un patrón combinado de neumonía intersticial inespecífica y neumonía organizada en la tomografía computarizada de tórax. CONCLUSIONES: la incorporación del PM nos ha ayudado a mejorar nuestra precisión diagnóstica en pacientes con EPI / ETC. Presentamos elementos clínicos y serológicos que perfeccionan el rendimiento de la prueba.

INTRODUCTION: The most common extramuscular manifestation of the idiopathic inflammatory myopathies (IIM) is interstitial lung disease (ILD) and the diagnosis is based on serum autoantibodies. The new specific and associated antibodies to IIM have helped to identify new clinical entities in the spectrum of IIM. The objective of this study is to evaluate the diagnostic contribution of a myositis antibodies panel (MP) in a cohort of Chilean patients with ILD without a definitive connective tissue disease (CTD). MATERIALS AND METHODS: Starting on January 2017 we performed a MP to 111 consecutive patients with ILD and suspected CTD but without a definitive diagnosis through another diagnostic tools in the Lung-Rheumatological Program at the "Instituto Nacional del Tórax", Santiago, Chile. The clinical and serological baseline characteristics of the patients that were most frequently associated with the probability of having a positive panel were compared. RESULTS: The MP was positive in 56 of 111 patients. Anti synthetase syndrome (ASS) was the most prevalent diagnosis. The most frequent antibodies were Ro-52, PM/Scl-75 and Ku. The most frequent variables in the positive MP group were the presence of Raynaud's phenomenon, myositis, mechanic's hands, positive Ro and La antibodies and the presence of combined pattern of nonspecific interstitial pneumonia and organizing pneumonia in chest computed tomography scan. CONCLUSIONS: The incorporation of the MP has helped us to improve our diagnostic precision of patients with CTD/ILD. We present clinical and serological elements that refine the performance of the test.

Seroepidemiological evidence for Taenia solium taeniasis/cysticercosis in three Venezuelan rural communities.

Taenia solium is the most common parasite infection of the brain, causing neurocysticercosis and typically found in rural communities with free-ranging pigs. Identification of transmission in rural areas is essential for its control. Risk factors and transmission of the parasite were evaluated in three rural Venezuelan communities (Valle del Rio and Potrero Largo, Cojedes state; and Palmarito, Portuguesa state) by a questionnaire (112 households) and coprological (492 samples) and serological (433 human and 230 porcine sera) analysis, respectively. Typical risk factors were found in all three communities: free-foraging pig husbandry, deficient sanitary conditions, high open defecation and ignorance of the parasite life cycle. Coprological examinations revealed a high level of soil-transmitted parasites. Importantly, two T. solium adult worm carriers were identified in each of the three communities. Anti-metacestode antibodies and the HP10 secreted metacestode glycoprotein were detected at significant levels in human and porcine sera in Valle del Rio, Potrero Largo and Palmarito. In conclusion, these communities may be considered to be endemic for taeniasis/cysticercosis, and the instigation of an appropriate control programme is recommended.

Healthcare-associated pneumonia: a prospective study in Spain.

OBJECTIVE: The aim of the study was to describe the epidemiological characteristics and factors related to outcome in Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA) healthcare-associated pneumonia (HCAP). METHODS: A 3-year prospective observational epidemiological case study of HCAP was conducted in seven Spanish hospitals. Microbiological and patient characteristics and outcomes were collected and classified by causative pathogen into 4 categories: "S. pneumoniae", "MRSA", "Others" and "Unknown". Patients were followed up 30 days after discharge. RESULTS: A total of 258 (84.6%) patients were enrolled (170 were men [65.9%]). Mean age was 72.4 years ± 15 years (95% CI [70.54-74.25]). The etiology of pneumonia was identified in 73 cases (28.3%): S. pneumoniae in 35 patients (13.6%), MRSA in 8 (3.1%), and other microorganisms in 30 patients (11.6%). Significant differences in rates of chronic obstructive pulmonary disease (p < 0.05), previous antibiotic treatment (p<0.05), other chronic respiratory diseases, inhaled corticosteroids (p <0.01), and lymphoma (p < 0.05) were observed among the four groups. Patients with MRSA pneumonia had received more previous antibiotic treatment (87.5%). Thirty-three (12.8%) patients died during hospitalisation; death in 27 (81.2%) was related to pneumonia. CONCLUSIONS: The etiology of HCAP was identified in only one quarter of patients, with S. pneumoniae being the most prevalent microorganism. Patients with chronic respiratory diseases more frequently presented HCAP due to MRSA than to S. pneumoniae. Death at hospital discharge was related in most cases to pneumonia.

Comorbidity and prognostic factors on admission in a COVID-19 cohort of a general hospital. / Comorbilidad y factores pronósticos al ingreso en una cohorte COVID-19 de un hospital general.

ANTECEDENTS AND OBJECTIVE: To describe clinical features, comorbidity, and prognostic factors associated with in-hospital mortality in a cohort of COVID-19 admitted to a general hospital. MATERIAL AND METHODS: Retrospective cohort study of patients with COVID-19 admitted from 26th February, who had been discharged or died, up to 29th April, 2020. A descriptive study and an analysis of factors associated with intrahospital mortality were performed. RESULTS: Out of the 101 patients, 96 were analysed. Of these, 79 (82%) recovered and were discharged, and 17 (18%) died in the hospital. Diagnosis of COVID-19 was confirmed by polymerase chain reaction to SARS-CoV-2 in 92 (92.5%). The mean age was 63 years, and 66% were male. The most frequent comorbidities were hypertension (40%), diabetes mellitus (16%) and cardiopathy (14%). Patients who died were older (mean 77 vs 60 years), had higher prevalence of hypertension (71% vs 33%), and cardiopathy (47% vs 6%), and higher levels of lactate dehydrogenase (LDH) and reactive C protein (mean 662 vs 335UI/L, and 193 vs 121mg/L respectively) on admission. In a multivariant analysis the variables significantly associated to mortality were the presence of cardiopathy (CI 95% OR 2,58-67,07), levels of LDH≥345IU/L (CI 95% OR 1,52-46,00), and age≥65 years (CI 95% OR 1,23-44,62). CONCLUSIONS: The presence of cardiopathy, levels of LDH≥345IU/L and age ≥65 years are associated with a higher risk of death during hospital stay for COVID-19. This model should be validated in prospective cohorts.

Evaluation of a workshop to teach a new surgical technique in abdominal wall reconstruction.

PURPOSE: Assess the utility of a hands-on workshop on abdominal wall reconstruction for teaching the posterior components separation (PCS) with transversus abdominis release. METHODS: Our department has been organizing a training course on abdominal wall reconstruction for the last 6 years. It is a 2-day-long course and 10-12 surgeons with experience in abdominal wall surgery attend to every course. The first day is dedicated to theoretical lectures and two simultaneous live surgeries, and the second day there is a cadaver dissection. Feedback from the trainees was collected at the end of the workshop. A survey was sent to all the surgeons who had completed the course at least a year ago, to inquire how the course had improved their surgical practice. RESULTS: From 2013 to April 2017, we have made 15 editions of the course. A total of 192 surgeons from Europe, South Africa and Middle East attended. All the surgeons answered the survey that was carried out at the end of the course. It showed a very high level of satisfaction in more than 98% of the cases. The second survey was answered by 79 surgeons (41.15%). 96% of the surgeons had modified, after attending the course, their way of dealing with complex abdominal wall problems. Only 29% of the surgeons had made a TAR before attending the course, while 86% are performing it after attending the course and 60% do it on a regular basis. In fact, 43% of surgeons have performed more than five posterior component separations in the last year. CONCLUSIONS: A workshop of abdominal wall surgery that combines live surgery, theoretical content and a cadaver lab can be a very useful tool to expand the use of new surgical techniques.

The microstructure of laminin-111 compensates for dystroglycan loss in mammary epithelial cells in downstream expression of milk proteins.

Laminin-111 (Ln-1), an extracellular matrix (ECM) glycoprotein found in the basement membrane of mammary gland epithelia, is essential for lactation. In mammary epithelial cells (MECs), dystroglycan (Dg) is believed to be necessary for polymerization of laminin-111 into networks., thus we asked whether correct polymerization could compensate for Dg loss. Artificially polymerized laminin-111 and the laminin-glycoprotein mix Matrigel, both formed branching, spread networks with fractal dimensions from 1.7 to 1.8, whereas laminin-111 in neutral buffers formed small aggregates without fractal properties (a fractal dimension of 2). In Dg knockout cells, either polymerized laminin-111 or Matrigel readily attached to the cell surface, whereas aggregated laminin-111 did not. In contrast, polymerized and aggregated laminin-111 bound similarly to Dg knock-ins. Both polymerized laminin-111 and Matrigel promoted cell rounding, clustering, formation of tight junctions, and expression of milk proteins, whereas aggregated Ln-1 did not attach to cells or promote functional differentiation. These findings support that the microstructure of Ln-1 networks in the basement membrane regulates mammary epithelial cell function.