Drug Development for Alzheimer's and Parkinson's Disease: Where Do We Go Now?

Neurodegenerative diseases (NDs) are a set of progressive, chronic, and incurable diseases characterized by the gradual loss of neurons, culminating in the decline of cognitive and/or motor functions. Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common NDs and represent an enormous burden both in terms of human suffering and economic cost. The available therapies for AD and PD only provide symptomatic and palliative relief for a limited period and are unable to modify the diseases' progression. Over the last decades, research efforts have been focused on developing new pharmacological treatments for these NDs. However, to date, no breakthrough treatment has been discovered. Hence, the development of disease-modifying drugs able to halt or reverse the progression of NDs remains an unmet clinical need. This review summarizes the major hallmarks of AD and PD and the drugs available for pharmacological treatment. It also sheds light on potential directions that can be pursued to develop new, disease-modifying drugs to treat AD and PD, describing as representative examples some advances in the development of drug candidates targeting oxidative stress and adenosine A2A receptors.

Proteomic Profiling of Plasma- and Gut-Derived Extracellular Vesicles in Obesity.

Obesity entails metabolic alterations across multiple organs, highlighting the role of inter-organ communication in its pathogenesis. Extracellular vesicles (EVs) are communication agents in physiological and pathological conditions, and although they have been associated with obesity comorbidities, their protein cargo in this context remains largely unknown. To decipher the messages encapsulated in EVs, we isolated plasma-derived EVs from a diet-induced obese murine model. Obese plasma EVs exhibited a decline in protein diversity while control EVs revealed significant enrichment in protein-folding functions, highlighting the importance of proper folding in maintaining metabolic homeostasis. Previously, we revealed that gut-derived EVs' proteome holds particular significance in obesity. Here, we compared plasma and gut EVs and identified four proteins exclusively present in the control state of both EVs, revealing the potential for a non-invasive assessment of gut health by analyzing blood-derived EVs. Given the relevance of post-translational modifications (PTMs), we observed a shift in chromatin-related proteins from glycation to acetylation in obese gut EVs, suggesting a regulatory mechanism targeting DNA transcription during obesity. This study provides valuable insights into novel roles of EVs and protein PTMs in the intricate mechanisms underlying obesity, shedding light on potential biomarkers and pathways for future research.

Competências auto percebidas pelos enfermeiros de família: Controlo e prevenção da infeção por Vírus Imunodeficiência Humana / Family nurses' self-perceived competencies: Control and prevention of Human Immunodeficiency Virus infection / Competencias autopercibidas por los enfermeros de familia: Control y prevención de la infección por el virus de la inmunodeficiencia humana

Resumo Enquadramento: A infeção pelo Vírus da Imunodeficiência Humana (VIH) constitui um problema de saúde pública. O Enfermeiro de Família desempenha um papel significativo na Prevenção e Controlo da Infeção (PCI). Objetivo: Analisar a auto perceção dos enfermeiros face às competências que detêm na PCI por VIH e a sua relação com a formação na área. Metodologia: Estudo quantitativo e descritivo-correlacional. Amostra selecionada a partir dos enfermeiros de família da Administração Regional de Saúde do Norte que aceitaram participar no estudo. Utilizou-se um formulário que integrou a ECAPC-VIH_CSP. Recorreu-se à estatística descritiva e inferencial através do IBM SPSS Statistics, versão 25.0. Resultados: Os enfermeiros apresentaram um nível medio (M = 4,44 ± 1,24) de auto perceção de competências na PCI por VIH. Os enfermeiros com formação específica apresentam maior perceção da competência. Conclusão: Os resultados evidenciam um nível medio de competências na PCI por VIH auto percebidas pelos enfermeiros. Conclui-se da necessidade da formação dos enfermeiros para o desenvolvimento das competências para a qualidade e segurança na PCI por VIH.

Abstract Background: Human Immunodeficiency Virus (HIV) infection is a public health issue. Family nurses play a significant role in HIV Infection Prevention and Control (IPC). Objective: To analyze nurses' self-perceived competencies in HIV IPC and determine their association with training in the area. Methodology: Quantitative and descriptive-correlational study. The sample was selected from family nurses from the Northern Regional Health Administration who agreed to participate. A form that included the ECAPC-VIH_CSP scale was applied. Data were analyzed through descriptive and inferential statistics in IBM SPSS Statistics, version 25.0. Results: Nurses had an average level (M = 4.44 ± 1.24) of self-perceived competencies in HIV IPC. Nurses with specific training had higher self-perceived competence. Conclusion: The results show that nurses had an average level of self-perceived competencies in HIV IPC. Nurses require training to develop competencies in HIV IPC, improving the quality and safety of care.

Resumen Marco contextual: La infección por el virus de la inmunodeficiencia humana (VIH) es un problema de salud pública. El enfermero de familia desempeña un papel importante en la prevención y el control de las infecciones (PCI). Objetivo: Analizar la autopercepción de los enfermeros sobre sus competencias en PCI del VIH y su relación con la formación en este ámbito. Metodología: Estudio cuantitativo y descriptivo-correlacional. Muestra seleccionada entre los enfermeros de familia de la Administración Sanitaria Regional del Norte que aceptaron participar en el estudio. Se utilizó un formulario que integró el ECAPC-VIH_CSP. Se utilizó la estadística descriptiva e inferencial a través del IBM SPSS Statistics, versión 25.0. Resultados: Los enfermeros presentaron un nivel medio (M = 4,44 ± 1,24) de autopercepción de competencias en la PCI del VIH. Los enfermeros con formación específica mostraron una mayor percepción de la competencia. Conclusión: Los resultados mostraron un nivel medio de competencias autopercibidas en la PCI del VIH entre el personal de enfermería. Se concluye que es necesario formar al personal de enfermería para que desarrolle competencias de calidad y seguridad en la PCI del VIH.

COVID-19 or threat of a nuclear war in Europe? A cross-sectional study of anxiety levels in adults living in Portugal.

Background: Since 2019, Europe has experienced ongoing stressors with the emergence of the COVID-19 pandemic and the Russian-Ukrainian War, which have had social, financial, physical, and psychological impacts. Studies suggest that anxiety, fear, post-traumatic stress disorder, depression, and other psychological disorders are common in such situations, and there is a need for more research on the impact of the war on mental health in Portugal. The main goal of the present study was to assess the impact of the fear of COVID-19 and anxiety related to nuclear war on the general anxiety levels of adult individuals living in Portugal. Methods: A cross-sectional study was conducted from May to July 2022 using an online questionnaire built on the Google Forms platform. Portuguese-speaking male and female individuals aged 18 years or older, who provided informed consent and agreed to participate, were included. The outcome variable was defined using the Portuguese version of the GAD-7 scale, while the main predictors were the FCV-19S and the NWA Scale in Portuguese. Linear and logistic regression models were used to test associations between predictors and outcome variable. Results: The study included 1,182 participants, with a mean age of 46.5 (±11.7) years, mostly women (80.6%). The global mean GAD-7 score was 5.8 (±4.5) points, and 17.9% of the participants scored above the 10-point cutoff. Higher scores were found in both the FCV-19S and the NWA scale among participants with anxiety, as measured by both a 10-point cutoff (p < 0.001), and GAD-7 scale mean scores (p < 0.001). The study showed that fear of COVID-19 [OR of 1.133 (95%CI: 1.097-1.170)] and, at a lesser extent, nuclear war anxiety [OR of 1.020 (95%CI, 1.009-1.031)] contribute to anxiety in the general population. This is also true for those with a personal history of anxiety, revealed by multiple regression. Discussion: This study contributes to the research on COVID-19's impact on anxiety and provides the first comprehensive assessment of nuclear war anxiety in Portugal. Results highlight the need for long-term care for anxiety, as prevalence is expected to increase due to the pandemic and war, even in non-conflict areas like Portugal.

Big data and machine learning to tackle diabetes management.

BACKGROUND: Type 2 Diabetes (T2D) diagnosis is based solely on glycaemia, even though it is an endpoint of numerous dysmetabolic pathways. Type 2 Diabetes complexity is challenging in a real-world scenario; thus, dissecting T2D heterogeneity is a priority. Cluster analysis, which identifies natural clusters within multidimensional data based on similarity measures, poses a promising tool to unravel Diabetes complexity. METHODS: In this review, we scrutinize and integrate the results obtained in most of the works up to date on cluster analysis and T2D. RESULTS: To correctly stratify subjects and to differentiate and individualize a preventive or therapeutic approach to Diabetes management, cluster analysis should be informed with more parameters than the traditional ones, such as etiological factors, pathophysiological mechanisms, other dysmetabolic co-morbidities, and biochemical factors, that is the millieu. Ultimately, the above-mentioned factors may impact on Diabetes and its complications. Lastly, we propose another theoretical model, which we named the Integrative Model. We differentiate three types of components: etiological factors, mechanisms and millieu. Each component encompasses several factors to be projected in separate 2D planes allowing an holistic interpretation of the individual pathology. CONCLUSION: Fully profiling the individuals, considering genomic and environmental factors, and exposure time, will allow the drive to precision medicine and prevention of complications.

Distinct impacts of fat and fructose on the liver, muscle, and adipose tissue metabolome: An integrated view.

Objective: In the last years, changes in dietary habits have contributed to the increasing prevalence of metabolic disorders, such as non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). The differential burden of lipids and fructose on distinct organs needs to be unveiled. Herein, we hypothesized that high-fat and high-fructose diets differentially affect the metabolome of insulin-sensitive organs such as the liver, muscle, and different adipose tissue depots. Methods: We have studied the impact of 12 weeks of a control (11.50% calories from fat, 26.93% from protein, and 61.57% from carbohydrates), high-fat/sucrose (HFat), or high-fructose (HFruct) feeding on C57Bl/6J male mice. Besides glucose homeostasis, we analyzed the hepatic levels of glucose and lipid-metabolism-related genes and the metabolome of the liver, the muscle, and white (WAT) and brown adipose tissue (BAT) depots. Results: HFat diet led to a more profound impact on hepatic glucose and lipid metabolism than HFruct, with mice presenting glucose intolerance, increased saturated fatty acids, and no glycogen pool, yet both HFat and HFruct presented hepatic insulin resistance. HFat diet promoted a decrease in glucose and lactate pools in the muscle and an increase in glutamate levels. While HFat had alterations in BAT metabolites that indicate increased thermogenesis, HFruct led to an increase in betaine, a protective metabolite against fructose-induced inflammation. Conclusions: Our data illustrate that HFat and HFruct have a negative but distinct impact on the metabolome of the liver, muscle, WAT, and BAT.

Increased Intake of Both Caffeine and Non-Caffeine Coffee Components Is Associated with Reduced NAFLD Severity in Subjects with Type 2 Diabetes.

Coffee may protect against non-alcoholic fatty liver disease (NAFLD), but the roles of the caffeine and non-caffeine components are unclear. Coffee intake by 156 overweight subjects (87% with Type-2-Diabetes, T2D) was assessed via a questionnaire, with 98 subjects (all T2D) also providing a 24 h urine sample for quantification of coffee metabolites by LC-MS/MS. NAFLD was characterized by the fatty liver index (FLI) and by Fibroscan® assessment of fibrosis. No associations were found between self-reported coffee intake and NAFLD parameters; however, total urine caffeine metabolites, defined as Σcaffeine (caffeine + paraxanthine + theophylline), and adjusted for fat-free body mass, were significantly higher for subjects with no liver fibrosis than for those with fibrosis. Total non-caffeine metabolites, defined as Σncm (trigonelline + caffeic acid + p-coumaric acid), showed a significant negative association with the FLI. Multiple regression analyses for overweight/obese T2D subjects (n = 89) showed that both Σcaffeine and Σncm were negatively associated with the FLI, after adjusting for age, sex, HbA1c, ethanol intake and glomerular filtration rate. The theophylline fraction of Σcaffeine was significantly increased with both fibrosis and the FLI, possibly reflecting elevated CYP2E1 activity-a hallmark of NAFLD worsening. Thus, for overweight/obese T2D patients, higher intake of both caffeine and non-caffeine coffee components is associated with less severe NAFLD. Caffeine metabolites represent novel markers of NAFLD progression.

Rho-Kinase as a Therapeutic Target for Nonalcoholic Fatty Liver Diseases.

Nonalcoholic fatty liver disease (NAFLD) is a major public health problem and the most common form of chronic liver disease, affecting 25% of the global population. Although NAFLD is closely linked with obesity, insulin resistance, and type 2 diabetes mellitus, knowledge on its pathogenesis remains incomplete. Emerging data have underscored the importance of Rho-kinase (Rho-associated coiled-coil-containing kinase [ROCK]) action in the maintenance of normal hepatic lipid homeostasis. In particular, pharmacological blockade of ROCK in hepatocytes or hepatic stellate cells prevents the progression of liver diseases such as NAFLD and fibrosis. Moreover, mice lacking hepatic ROCK1 are protected against obesity-induced fatty liver diseases by suppressing hepatic de novo lipogenesis. Here we review the roles of ROCK as an indispensable regulator of obesity-induced fatty liver disease and highlight the key cellular pathway governing hepatic lipid accumulation, with focus on de novo lipogenesis and its impact on therapeutic potential. Consequently, a comprehensive understanding of the metabolic milieu linking to liver dysfunction triggered by ROCK activation may help identify new targets for treating fatty liver diseases such as NAFLD.

Optimizing a Multi-Component Intranasal Entamoeba Histolytica Vaccine Formulation Using a Design of Experiments Strategy.

Amebiasis is a neglected tropical disease caused by Entamoeba histolytica. Although the disease burden varies geographically, amebiasis is estimated to account for some 55,000 deaths and millions of infections globally per year. Children and travelers are among the groups with the greatest risk of infection. There are currently no licensed vaccines for prevention of amebiasis, although key immune correlates for protection have been proposed from observational studies in humans. We previously described the development of a liposomal adjuvant formulation containing two synthetic TLR ligands (GLA and 3M-052) that enhanced antigen-specific fecal IgA, serum IgG2a, a mixed IFNγ and IL-17A cytokine profile from splenocytes, and protective efficacy following intranasal administration with the LecA antigen. By applying a statistical design of experiments (DOE) and desirability function approach, we now describe the optimization of the dose of each vaccine formulation component (LecA, GLA, 3M-052, and liposome) as well as the excipient composition (acyl chain length and saturation; PEGylated lipid:phospholipid ratio; and presence of antioxidant, tonicity, or viscosity agents) to maximize desired immunogenicity characteristics while maintaining physicochemical stability. This DOE/desirability index approach led to the identification of a lead candidate composition that demonstrated immune response durability and protective efficacy in the mouse model, as well as an assessment of the impact of each active vaccine formulation component on protection. Thus, we demonstrate that both GLA and 3M-052 are required for statistically significant protective efficacy. We also show that immunogenicity and efficacy results differ in female vs male mice, and the differences appear to be at least partly associated with adjuvant formulation composition.

S-Nitrosoglutathione Reverts Dietary Sucrose-Induced Insulin Resistance.

The liver is a fundamental organ to ensure whole-body homeostasis, allowing for a proper increase in insulin sensitivity from the fast to the postprandial status. Hepatic regulation of glucose metabolism is crucial and has been shown to be modulated by glutathione (GSH) and nitric oxide (NO). However, knowledge of the metabolic action of GSH and NO in glucose homeostasis remains incomplete. The current study was designed to test the hypothesis that treatment with S-nitrosoglutathione is sufficient to revert insulin resistance induced by a high-sucrose diet. Male Wistar rats were divided in a control or high-sucrose group. Insulin sensitivity was determined: (i) in the fast state; (ii) after a standardized test meal; (iii) after GSH + NO; and after (iv) S-nitrosoglutathione (GSNO) administration. The fasting glucose level was not different between the control and high-sucrose group. In the liver, the high-sucrose model shows increased NO and unchanged GSH levels. In control animals, insulin sensitivity increased after a meal or administration of GSH+NO/GSNO, but this was abrogated by sucrose feeding. GSNO was able to revert insulin resistance induced by sucrose feeding, in a dose-dependent manner, suggesting that they have an insulin-sensitizing effect in vivo. These effects are associated with an increased insulin receptor and Akt phosphorylation in muscle cells. Our findings demonstrate that GSNO promotes insulin sensitivity in a sucrose-induced insulin-resistant animal model and further implicates that this antioxidant molecule may act as a potential pharmacological tool for the treatment of insulin resistance in obesity and type 2 diabetes.

Neurobehavioural signatures in race car driving: a case study.

Recent technological developments in mobile brain and body imaging are enabling new frontiers of real-world neuroscience. Simultaneous recordings of body movement and brain activity from highly skilled individuals as they demonstrate their exceptional skills in real-world settings, can shed new light on the neurobehavioural structure of human expertise. Driving is a real-world skill which many of us acquire to different levels of expertise. Here we ran a case-study on a subject with the highest level of driving expertise-a Formula E Champion. We studied the driver's neural and motor patterns while he drove a sports car on the "Top Gear" race track under extreme conditions (high speed, low visibility, low temperature, wet track). His brain activity, eye movements and hand/foot movements were recorded. Brain activity in the delta, alpha, and beta frequency bands showed causal relation to hand movements. We herein demonstrate the feasibility of using mobile brain and body imaging even in very extreme conditions (race car driving) to study the sensory inputs, motor outputs, and brain states which characterise complex human skills.

Author Correction: Apolipoprotein J is a hepatokine regulating muscle glucose metabolism and insulin sensitivity.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Apolipoprotein J is a hepatokine regulating muscle glucose metabolism and insulin sensitivity.

Crosstalk between liver and skeletal muscle is vital for glucose homeostasis. Hepatokines, liver-derived proteins that play an important role in regulating muscle metabolism, are important to this communication. Here we identify apolipoprotein J (ApoJ) as a novel hepatokine targeting muscle glucose metabolism and insulin sensitivity through a low-density lipoprotein receptor-related protein-2 (LRP2)-dependent mechanism, coupled with the insulin receptor (IR) signaling cascade. In muscle, LRP2 is necessary for insulin-dependent IR internalization, an initial trigger for insulin signaling, that is crucial in regulating downstream signaling and glucose uptake. Of physiologic significance, deletion of hepatic ApoJ or muscle LRP2 causes insulin resistance and glucose intolerance. In patients with polycystic ovary syndrome and insulin resistance, pioglitazone-induced improvement of insulin action is associated with an increase in muscle ApoJ and LRP2 expression. Thus, the ApoJ-LRP2 axis is a novel endocrine circuit that is central to the maintenance of normal glucose homeostasis and insulin sensitivity.

Paraoxonase-1 as a Regulator of Glucose and Lipid Homeostasis: Impact on the Onset and Progression of Metabolic Disorders.

Metabolic disorders are characterized by an overall state of inflammation and oxidative stress, which highlight the importance of a functional antioxidant system and normal activity of some endogenous enzymes, namely paraoxonase-1 (PON1). PON1 is an antioxidant and anti-inflammatory glycoprotein from the paraoxonases family. It is mainly expressed in the liver and secreted to the bloodstream, where it binds to HDL. Although it was first discovered due to its ability to hydrolyze paraoxon, it is now known to have an antiatherogenic role. Recent studies have shown that PON1 plays a protective role in other diseases that are associated with inflammation and oxidative stress, such as Type 1 and Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease. The aim of this review is to elucidate the physiological role of PON1, as well as the impact of altered PON1 levels in metabolic disorders.

Psychometric properties of a medium version of the Copenhagen Psychosocial Questionnaire (COPSOQ II) for southern Brazil.

BACKGROUND: The emerging frequency of Behavioural Mental Health Disorders among Brazilian workers and the recent legal demand for analysis of psychosocial risks in the workplace highlight the importance of standardizing measures to assess these risks as a way to allow identification and proper comparison among different populations. OBJECTIVE: To assess the psychometric properties of the COPSOQ II questionnaire medium version for southern Brazil, based on the Spanish medium-length version of COPSOQ-ISTAS21 II. METHODS: A sample of 426 workers from a university in southern Brazil answered the model under study online. Content validity and internal consistency were analyzed through Confirmatory Factor Analysis (AFC) and Exploratory Factor Analysis (AFE) and Cronbach's α coefficient. RESULTS: The study model presented a response rate of 48.46%. The analyses indicated the possibility of the instrument to present reliability and validity of content. From the AFE, the final model consisted of 13 dimensions and 70 items, and presented a Cronbach's alpha of 0.82, which is considered a good internal consistency. CONCLUSIONS: The results showed that the final model of this study presents acceptable levels of reliability and internal validity for the application in Brazil, along with the groups of workers that resemble the participants of the research, to assess psychosocial risks in the workplace.

Rho-kinase/AMPK axis regulates hepatic lipogenesis during overnutrition.

Obesity is a major risk factor for developing nonalcoholic fatty liver disease (NAFLD). NAFLD is the most common form of chronic liver disease and is closely associated with insulin resistance, ultimately leading to cirrhosis and hepatocellular carcinoma. However, knowledge of the intracellular regulators of obesity-linked fatty liver disease remains incomplete. Here we showed that hepatic Rho-kinase 1 (ROCK1) drives obesity-induced steatosis in mice through stimulation of de novo lipogenesis. Mice lacking ROCK1 in the liver were resistant to diet-induced obesity owing to increased energy expenditure and thermogenic gene expression. Constitutive expression of hepatic ROCK1 was sufficient to promote adiposity, insulin resistance, and hepatic lipid accumulation in mice fed a high-fat diet. Correspondingly, liver-specific ROCK1 deletion prevented the development of severe hepatic steatosis and reduced hyperglycemia in obese diabetic (ob/ob) mice. Of pathophysiological significance, hepatic ROCK1 was markedly upregulated in humans with fatty liver disease and correlated with risk factors clustering around NAFLD and insulin resistance. Mechanistically, we found that hepatic ROCK1 suppresses AMPK activity and a ROCK1/AMPK pathway is necessary to mediate cannabinoid-induced lipogenesis in the liver. Furthermore, treatment with metformin, the most widely used antidiabetes drug, reduced hepatic lipid accumulation by inactivating ROCK1, resulting in activation of AMPK downstream signaling. Taken together, our findings establish a ROCK1/AMPK signaling axis that regulates de novo lipogenesis, providing a unique target for treating obesity-related metabolic disorders such as NAFLD.

Mutant A53T α-Synuclein Improves Rotarod Performance Before Motor Deficits and Affects Metabolic Pathways.

The protein α-synuclein (α-Syn) interferes with glucose and lipid uptake and also activates innate immune cells. However, it remains unclear whether α-Syn or its familial mutant forms contribute to metabolic alterations and inflammation in synucleinopathies, such as Parkinson's disease (PD). Here, we address this issue in transgenic mice for the mutant A53T human α-Syn (α-SynA53T), a mouse model of synucleinopathies. At 9.5 months of age, mice overexpressing α-SynA53T (homozygous) had a significant reduction in weight, exhibited improved locomotion and did not show major motor deficits compared with control transgenic mice (heterozygous). At 17 months of age, α-SynA53T overexpression promoted general reduction in grip strength and deficient hindlimb reflex and resulted in severe disease and mortality in 50 % of the mice. Analysis of serum metabolites further revealed decreased levels of cholesterol, triglycerides and non-esterified fatty acids (NEFA) in α-SynA53T-overexpressing mice. In fed conditions, these mice also showed a significant decrease in serum insulin without alterations in blood glucose. In addition, assessment of inflammatory gene expression in the brain showed a significant increase in TNF-α mRNA but not of IL-1ß induced by α-SynA53T overexpression. Interestingly, the brain mRNA levels of Sirtuin 2 (Sirt2), a deacetylase involved in both metabolic and inflammatory pathways, were significantly reduced. Our findings highlight the relevance of the mechanisms underlying initial weight loss and hyperactivity as early markers of synucleinopathies. Moreover, we found that changes in blood metabolites and decreased brain Sirt2 gene expression are associated with motor deficits.

Incomodidad corporal, carga física y nivel de flexibilidad en trabajadores del sector administrativo de una institución de enseñanza superior en Florianópolis, del sur de Brasil / Body discomfort, cargo physical and flexibility in level workers in the administrative sector a higher education institution in southern Brazil

RESUMEN El objetivo de este estudio fue identificar el perfil de los funcionarios de una oficina de una institución de enseñanza superior con relación a las tareas desarrolladas y a sus manifestaciones de dolor, incomodidad corporal. Hicieron parte de este estudio 41 funcionarios que desempeñan sus actividades laborales en posición sentada. Los instrumentos utilizados en la colecta de datos fueron: la escala de Dolor o incomodidad corporal, o método RULA y el banco de Wells. Los datos fueron analizados por medio de estadística descriptiva (media, desviación estándar, frecuencia relativa) y estadística inferencial. En cuanto al análisis de las posiciones de los diferentes segmentos se observó que ninguna posición fue considerada aceptable; en pocas palabras, todas las posturas generan un riesgo a la salud del trabajador. Consideramos de esta manera un perfil negativo de los funcionarios del presente estudio con relación a la presencia de manifestación de dolor, incomodidad corporal, posiciones y sobrecarga biomecánica durante la realización de tareas y nivel de flexibilidad corporal. Que separadamente o en conjunto causan riesgo a la salud del trabajador afectando posiblemente su desempeño y calidad de vida.

ABSTRACT The aim of this study was to identify the profile of the employees of a Secretary of an Education Institution with regard to the complaint of pain and discomfort body. Participants were 41 employees who perform their work activities in sitting on computerized terminals. The instruments used in data collection were: Scale of Pain and/or Discomfort Body, RULA method, Wells's seat. The data were processed using descriptive statistics (mean, standard deviation, relative frequency) and inferential. The analysis of the attitudes of different segments was observed that no position was considered acceptable, it means, all postures generate risk on health of the worker. It is thus a negative profile of employees of this study with regard to the complaint of pain and discomfort body postures and biomechanical overload during task performance and level of body flexibility, which separately or together may cause risks to health worker possibly affecting their performance and quality of life.

Methylsulfonylmethane (MSM), an organosulfur compound, is effective against obesity-induced metabolic disorders in mice.

Methylsulfonylmethane (MSM), an organosulfur compound, has been used as a dietary supplement that can improve various metabolic diseases. However, the effect of MSM on obesity-linked metabolic disorders remains unclear. The goal of the current study is to determine whether MSM has beneficial effects on glucose and lipid homeostasis in obesity-associated pathophysiologic states. High-fat diet-induced obese (DIO) and genetically obese diabetic db/db mice treated with MSM (1%-5% v/v, by drinking water) were studied. Metabolic parameters involved in glucose and lipid metabolism were determined. Treatment of DIO mice with MSM leads to a significant decrease in blood glucose levels. DIO mice treated with MSM are hypersensitive to insulin, as evidenced by decreased serum insulin and an increase in the area above the curve during an ITT. Concurrently, MSM reduces hepatic triglyceride and cholesterol contents in DIO mice. These effects are accompanied by reductions in gene expression of key molecules involved in lipogenesis and inflammation. FACS analysis reveals that MSM markedly increases the frequency of B cells and decreases the frequency of myeloid cells in peripheral blood and in bone marrow. Moreover, overnutrition-induced changes of femur microarchitecture are restored by MSM. In db/db mice, a marked impairment in glucose and lipid metabolic profiles is notably ameliorated when MSM is supplemented. These data suggest that MSM has beneficial effects on multiple metabolic dysfunctions, including hyperglycemia, hyperinsulinemia, insulin resistance, and inflammation. Thus, MSM could be the therapeutic option for the treatment of obesity-related metabolic disorders such as type 2 diabetes and fatty liver diseases.