Cause Of Morbimortality Worldwide Research Articles

Role of LCN2 in a murine model of hindlimb ischemia and in peripheral artery disease patients, and its potential regulation by miR-138-5P

Background and aimsPeripheral arterial disease (PAD) is a leading cause of morbimortality worldwide. Lipocalin-2 (LCN2) has been associated with higher risk of amputation or mortality in PAD and might be involved in muscle regeneration. Our aim is to unravel the role of LCN2 in skeletal muscle repair and PAD. Methods and resultsWT and Lcn2−/− mice underwent hindlimb ischemia. Blood and crural muscles were analyzed at the inflammatory and regenerative phases. At day 2, Lcn2−/− male mice, but not females, showed increased blood and soleus muscle neutrophils, and elevated circulating pro-inflammatory monocytes (p < 0.05), while locally, total infiltrating macrophages were reduced (p < 0.05). Moreover, Lcn2−/− soleus displayed an elevation of Cxcl1 (p < 0.001), and Cxcr2 (p < 0.01 in males), and a decrease in Ccl5 (p < 0.05). At day 15, Lcn2 deficiency delayed muscle recovery, with higher density of regenerating myocytes (p < 0.04) and arterioles (αSMA+, p < 0.025). Reverse target prediction analysis identified miR-138-5p as a potential regulator of LCN2, showing an inverse correlation with Lcn2 mRNA in skeletal muscles (rho = -0.58, p < 0.01). In vitro, miR-138-5p mimic reduced Lcn2 expression and luciferase activity in murine macrophages (p < 0.05). Finally, in human serum miR-138-5p was inversely correlated with LCN2 (p ≤ 0.001 adjusted, n = 318), and associated with PAD (Odds ratio 0.634, p = 0.02, adjusted, PAD n = 264, control n = 54). ConclusionsThis study suggests a possible dual role of LCN2 in acute and chronic conditions, with a probable role in restraining inflammation early after skeletal muscle ischemia, while being associated with vascular damage in PAD, and identifies miR-138-5p as one potential post-transcriptional regulator of LCN2.

Apnea of prematurity induces short and long-term development-related transcriptional changes in the murine cerebellum

Apnea of prematurity (AOP) affects more than 50% of preterm infants and leads to perinatal intermittent hypoxia (IH) which is a major cause of morbimortality worldwide. At birth, the human cerebellar cortex is still immature, making it vulnerable to perinatal events. Additionally, studies have shown a correlation between cerebellar functions and the deficits observed in children who have experienced AOP. Yet, the cerebellar alterations underpinning this link remain poorly understood. To gain insight into the involvement of the cerebellum in perinatal hypoxia-related consequences, we developed a mouse model of AOP. Our previous research has revealed that IH induces oxidative stress in the developing cerebellum, as evidenced by the over-expression of genes involved in reactive oxygen species production and the under-expression of genes encoding antioxidant enzymes. These changes suggest a failure of the defense system against oxidative stress and could be responsible for neuronal death in the cerebellum.Building upon these findings, we conducted a transcriptomic study of the genes involved in the processes that occur during cerebellar development. Using real-time PCR, we analyzed the expression of these genes at different developmental stages and in various cell types. This enabled us to pinpoint a timeframe of vulnerability at P8, which represents the age with the highest number of downregulated genes in the cerebellum. Furthermore, we discovered that our IH protocol affects several molecular pathways, including proliferation, migration, and differentiation. This indicates that IH can impact the development of different cell types, potentially contributing to the histological and behavioral deficits observed in this model. Overall, our data strongly suggest that the cerebellum is highly sensitive to IH, and provide valuable insights into the cellular and molecular mechanisms underlying AOP. In the long term, these findings may contribute to the identification of novel therapeutic targets for improving the clinical management of this prevalent pathology.

Performance of a Real Time PCR for Pneumocystis jirovecii Identification in Induced Sputum of AIDS Patients: Differentiation between Pneumonia and Colonization.

Pneumocystis jirovecii pneumonia (PcP) remains an important cause of morbimortality worldwide and a diagnostic challenge. Conventional methods have low accuracy, hardly discriminating colonization from infection, while some new high-cost or broncho-alveolar lavage-based methods have limited usefulness in developing countries. Quantitative PCR (qPCR) tests may overcome these limitations due to their high accuracy, possibility of automation, and decreasing cost. We evaluated an in-house qPCR targeting the fungus mtSSU gene using induced sputum. Sensitivity of the assay (ten target gene copies/assay) was determined using recombinant plasmids. We prospectively studied 86 AIDS patients with subacute respiratory symptoms in whom PcP was suspected. qPCR results were determined as quantification cycles (Cq) and compared with a qualitative PCR performed in the same IS, serum 1,3-β-D-Glucan assay, and a clinical/laboratory/radiology index for PcP. The qPCR clustered the patients in three groups: 32 with Cq ≤ 31 (qPCR+), 45 with Cq ≥ 33 (qPCR-), and nine with Cq between 31-33 (intermediary), which, combined with the other three analyses, enabled us to classify the groups as having PcP, not P. jirovecii-infected, and P. jirovecii-colonized, respectively. This molecular assay may contribute to improve PcP management, avoiding unnecessary treatments, and our knowledge of the natural history of this infection.

PostCOVID effect on endothelial function in hypertensive patients: A new research opportunity.

SARS‐CoV‐2 is causing devastation both in human lives and economic resources. When the world seems to start overcoming the pandemics scourge, the threat of long‐term complications of COVID‐19 is rising. Reports show that some of these long‐term effects may contribute to the main cause of morbimortality worldwide: the vascular diseases. Given the evidence of damage in the endothelial cells due to SARS‐CoV‐2 and that endothelial dysfunction precedes the development of arteriosclerosis, the authors propose to measure endothelial function around 6–12 months after acute disease in hypertensive patients, especially if they have other cardiovascular risk factors or overt vascular disease. The methods the authors propose are cost‐effective and can be made available to any hypertension unit. These methods could be the “in vivo” assessment of endothelial function by flow mediated vasodilatation after ischemia by Laser‐Doppler flowmetry and the measurement of plasma free circulating DNA and microparticles of endothelial origin.

Macrolides: a novel risk factor for carbapenemase-producing Enterobacterales in intensive care units.

Carbapenemase-producing Enterobacterales (CPE) have emerged as a substantial cause of morbi-mortality worldwide, with a prevalence of approximately 5% in areas with high endemicity. However, available data may not be representative of developing countries, such as Ecuador. In this study, the incidence of CPE in Ecuador and risk factors for infection/colonisation were evaluated. A prospective cohort study was performed from February to April 2016 in seven intensive-care units of Guayaquil, Ecuador. Samples were processed according to the Centers for Disease Control and Prevention laboratory protocol and the CHROMagar mSuper CARBA agar method. Resistance to carbapenems was defined according to Clinical and Laboratory Standards Institute breakpoints. A modified carbapenemase inactivation method was used to identify carbapenamase production phenotypically with molecular confirmation by multiplex polymerase chain reaction. In total, 640 patients were enrolled. The incidence of CPE was 36.4% (N = 233). A multivariate analysis indicated that several factors were associated with CPE acquisition, included a long intensive care unit stay (OR 1.05; 95% CI 1.03-1.08; p < 0.01), tracheostomy (OR 3.52; 95% CI 1.90-6.75; p < 0.01), hospitalisation 3 months prior to admission (OR 2.07; 95% CI 1.17-3.71; p < 0.01), vancomycin use (OR 3.31; 95% CI 2.02-5.18; p < 0.01), and macrolide use (OR 3.31; 95% CI 1.43-7.76; p < 0.01). Macrolide use was a risk factor for CPE acquisition. This association should be evaluated further, especially in developing countries.

HbA1c as a Predictor of Postoperative Infection in Type 2 Diabetic Patients after Coronary Artery Bypass Grafting

Coronary artery disease (CAD) is one of the leading causes of morbimortality worldwide. In patients with diabetes mellitus type 2 (DM2), CAD is more likely to be a complex disease and often requires cardiac surgery. Furthermore, perioperative blood glucoselevels control is associated with the following outcomes: surgery success, mortality, and infection postoperative. This is a retrospective study, we have collected data form, 43 patients, between 2015 and 2017, with diabetes type 2 and who had passed through a Coronary Artery Bypass Grafting. Those with infection postoperative had a glycohemoglobin 7,9 (SD ±1,4), and those without infection had an HbA1c 7,25 (SD ±0,94) and a p-value from 0,039. Adding this was identified that the average of creatinine clearance in patients with the infectious disease was 59 (SD ±21,3) and 67(SD ±26)in those without infection, calculated a p-value from 0,039. High levels of Hb1Ac are a predictor of infection disease postoperative.

Influenza A and B in a cohort of outpatient children and adolescent with influenza like-illness during two consecutive influenza seasons

IntroductionInfluenza is an important cause of morbimortality worldwide. Although people at the extremes of age have a greater risk of complications, influenza has been more frequently investigated in the elderly than in children, and inpatients than outpatients. Yearly vaccination with trivalent or quadrivalent vaccines is the main strategy to control influenza. ObjectivesDetermine the clinical and molecular characteristics of influenza A and B infections in children and adolescents with influenza-like illness (ILI). MethodsA cohort of outpatient children and adolescents with ILI was followed for 20 months. Influenza was diagnosed with commercial multiplex PCR platforms. Results179 patients had 277 episodes of ILI, being 79 episodes of influenza A and 20 episodes of influenza B. Influenza A and B cases were mild and had similar presentation. Phylogenetic tree of influenza B viruses showed that 91.6% belonged to the B/Yamagata lineage, which is not included in trivalent vaccines. ConclusionsInfluenza A and B are often detected in children and adolescents with ILI episodes, with similar and mild presentation in outpatients. The mismatch between the circulating influenza viruses and the trivalent vaccine offered in Brazil may have contributed to the high frequency of influenza A and B in this population.

Pharmacologic potential of new nitro-compounds as antimicrobial agents against nosocomial pathogens: design, synthesis, and in vitro effectiveness.

Nosocomial infections are an important cause of morbi-mortality worldwide. The increase in the rate of resistance to conventional drugs in these microorganisms has stimulated the search for new therapeutic options. The nitro moiety (NO2) is an important pharmacophore of molecules with high anti-infective activity. We aimed to synthesize new nitro-derivates and to evaluate their antibacterial and anti-Candida potential in vitro. Five compounds [3-nitro-2-phenylchroman-4-ol (3); 3-nitro-2-phenyl-2H-chromene (4a); 3-nitro-2-(4-chlorophenyl)-2H-chromene (4b); 3-nitro-2-(4-fluorophenyl)-2H-chromene (4c), and 3-Nitro-2-(2,3-dichlorophenyl)-2H-chromene (4d)] were efficiently synthesized by Michael-aldol reaction of 2-hydroxybenzaldehyde with nitrostyrene, resulting in one β-nitro-alcohol (3) and four nitro-olefins (4a-4d). The antibacterial and anti-Candida potentials were evaluated by assaying minimal inhibitory concentration (MIC), minimum fungicidal concentration (MFC), and minimum bactericidal concentration (MBC). Mono-halogenated nitro-compounds (4b and 4c) showed anti-staphylococcal activity with MIC values of 15.6-62.5μg/mL and MBC of 62.5μg/mL. However, the activity against Gram-negative strains was showed to be considerably lower and our data suggests that this effect was associated with the outer membrane. Furthermore, nitro-compounds 4c and 4d presented activity against Candida spp. with MIC values ranging from 7.8-31.25μg/mL and MFC of 15.6-500μg/mL. In addition, these compounds were able to induce damage in fungal cells increasing the release of intracellular material, which was associated with actions on the cell wall independent of quantitative changes in chitin and β-glucan. Together, these findings show that nitro-compounds can be exploited as anti-staphylococcal and anti-Candida prototypes.

Systems biology identifies cytosolic PLA2 as a target in vascular calcification treatment.

Although cardiovascular disease (CVD) is the leading cause of morbimortality worldwide, promising new drug candidates are lacking. We compared the arterial high-resolution proteome of patients with advanced versus early-stage CVD to predict, from a library of small bioactive molecules, drug candidates able to reverse this disease signature. Of the approximately 4000 identified proteins, 100 proteins were upregulated and 52 were downregulated in advanced-stage CVD. Arachidonyl trifluoromethyl ketone (AACOCF3), a cytosolic phospholipase A2 (cPLA2) inhibitor was predicted as the top drug able to reverse the advanced-stage CVD signature. Vascular cPLA2 expression was increased in patients with advanced-stage CVD. Treatment with AACOCF3 significantly reduced vascular calcification in a cholecalciferol-overload mouse model and inhibited osteoinductive signaling in vivo and in vitro in human aortic smooth muscle cells. In conclusion, using a systems biology approach, we have identified a potentially new compound that prevented typical vascular calcification in CVD in vivo. Apart from the clear effect of this approach in CVD, such strategy should also be able to generate novel drug candidates in other complex diseases.

Modelos de predicción de riesgo cardiovascular

Cardiovascular disease is the leading cause of morbi-mortality worldwide. This disease is caused by the presence of multiple risk factors in the population. Its prevention is based on the identification and control of these risk factors, thus, seeking to impact the clinical course or the natural history of the disease, depending on the presence of the manifestation in a specific individual. The prediction models are an approach to assess the prognosis; they mathematically combine multiple risk predictors for the development of cardiovascular disease. The estimation values of these predictors vary from one model to another and depend on the population where the model was developed. Therefore, the assessment of the cardiovascular risk in a different population requires external validation, which prevents overestimation and underestimation of the cardiovascular risk.

Associated metabolic and nutritional side effects to biological cancer therapy

The different types of cancer represent one of the main causes of morbimortality worldwide. Classical anti-tumor therapy (surgery, chemotherapy, radiotherapy) has notably increased the survival rate. Biological therapies, with selective and frequently specific mechanisms of action, are a relatively recent acquisition in oncologic therapy; among the most commonly used ones are: cytokines, monoclonal antibodies, tyrosine kinase inhibitors, and mTOR inhibitors. The nutritional and metabolic adverse effects of classical therapy are well documented in the literature and the clinical guidelines, which is not the case for biological therapy. To review the literature in this field and to detail in an organized manner the results obtained. Indexed literature and the technical data sheets of the drugs included in the different families were revised through the Spanish Agency of Medicines and Health Care Products until July of 2013. The symptoms and clinical signs of a theoretical action on the nutritional and metabolic status were recorded. The specific action of each family is described. The possible adverse effects of each one of them on the nutritional and metabolic status are grouped, detailing and differentiating them in tables for easier and more friendly-user consultation. The most prevalent possible side effects observed are those related with the appetite, the gastrointestinal tract, and electrolytic impairments. the possible side effects associated to biological therapies are plenty and occur with different frequency and severity. It is important to know the nutritional and metabolic impact when using these therapies for preventing and managing them.

Multiprofissionalidade em Saúde Cardiovascular: Atuação Integrada em Clínica Cirúrgica

Introduction: Cardiovascular diseases are leading causes of morbi-mortality in the world. In 2006, represented more than 30.0000 deaths in Brazil, and 20.000 in Paraiba. Thus, Introduction: Cardiovascular diseases are the leading causes of morbi-mortality worldwide. In 2006, they represented more than 30.0000 deaths in Brazil and 20.000 in the state of Paraiba. Thus, the Multi-professional Integrated Residence in Hospital Care provides care for cardiopath patients to have a better quality of life. Objective: This study aimed to characterize single- and multi-professional actions directed to the users of the wards of Cardiology in Surgical Clinics of a public hospital in Joao Pessoa, Paraiba. Material and Methods: This was an exploratory cross-sectional study with quantitative approach using the records of treatments performed from April to September 2010. Results: We analyzed 75 cases, of which 51% corresponded to female patients and 39% had age ranging from 61 to 80 years. With regard to the procedures, it was mostly performed coronary artery bypass grafting (48%) and valve surgery (41%). Conclusion: The uni and multidisciplinary actions were characterized by user embracement, qualified hearing and comprehensive care, encouraging users’ active participation and practices of health education towards their rehabilitation. DESCRIPTORS Cardiovascular Diseases. Patient Care Team. Comprehensive Health Care.

Enfermedad meningocócica en España (1940-2012). Tendencias de la incidencia y evolución de los serogrupos antes y después de las campañas de vacunación

IntroductionMeningococcal disease (MD) remains a major cause of morbimortality worldwide, affecting children and adolescents. It is more common in overcrowded and poor areas. In Spain, since the mid-twentieth century there have been some changes in incidence and temporal variations in the proportion of the serogroups causing disease. ObjectivesTo determine the levels and trends of MD from 1940 to 2012 in Spain, and the evolution of serogroups, before and after the introduction of vaccination campaigns against serogroup C. MethodsDescriptive study was conducted in Spain since 1940 using official data published by the Ministry of Health and other institutions. ResultsIn Spain, since 1940 there have been 5 epidemic waves, the 2 largest in 1971 and 1979. This has been the highest in the period. From 1986 gradually increased serogroup C, and in 1996-1997 was the largest forcing it to use the polysaccharide vaccine against serogroups A+C. In the autumn of 2000 is introduced serogroup C conjugate vaccine. During the 2006-2012 period decreases the incidence of serogroup C, but with high case fatality especially in women. MD rates down, also decreasing the incidence of serogroups B and C. ConclusionsMD is an important public health problem in Spain. The serogroup C conjugate vaccine has succeeded in controlling meningococcal disease caused by serogroup C. The new vaccines against serogroup B offer the possibility of minimizing the incidence of MD. All this creates a scenario of caution and moderate optimism for this disease, keeping vaccines available for their control.

A promoção da saúde e a prevenção integrada dos fatores de risco para doenças cardiovasculares

Cardiovascular diseases are currently the most common causes of morbimortality worldwide. In the context of disease prevention, actions creating favorable health environments and promoting healthy choices prove fundamental. Intervention programs with a community basis have been introduced in different countries since the beginning of the 1970s, aiming to modify cardiovascular risk factors and decrease morbidity and mortality due to cardiovascular diseases. In such experiences, the importance of public policies and cardiovascular risk vigilance systems needs to be stressed, permitting a more accurate assessment of the magnitude of the problem and the development of more cost-effective actions. The scope of this bibliographical study was to describe community-geared experiences in many countries in the campaign against cardiovascular diseases through health promotion and primary prevention of risk factors, as well as to identify in Brazil the vigilance actions of the risk factors of non-transmissible chronic diseases, stressing the strategic challenges facing the Family Health Program in tackling cardiovascular diseases.