Characterization of cytomegalovirus lung infection in non-HIV infected children

Cytomegalovirus (CMV) is a prevalent pathogen in the immunocompromised host and invasive pneumonia is a feared complication of the virus in this population. In this pediatric case series we characterized CMV lung infection in 15 non-HIV infected children (median age 3 years; IQR 0.2–4.9 years), using current molecular and imaging diagnostic modalities, in combination with respiratory signs and symptoms. The most prominent clinical and laboratory findings included cough (100%), hypoxemia (100%), diffuse adventitious breath sounds (100%) and increased respiratory effort (93%). All patients had abnormal lung images characterized by ground glass opacity/consolidation in 80% of cases. CMV was detected in the lung either by CMV PCR in bronchoalveolar lavage (82% detection rate) or histology/immunohistochemistry in lung biopsy (100% detection rate). CMV caused respiratory failure in 47% of children infected and the overall mortality rate was 13.3%. Conclusion: CMV pneumonia is a potential lethal disease in non-HIV infected children that requires a high-index of suspicion. Common clinical and radiological patterns such as hypoxemia, diffuse adventitious lung sounds and ground-glass pulmonary opacities may allow early identification of CMV lung infection in the pediatric population, which may lead to prompt initiation of antiviral therapy and better clinical outcomes

Gene expression changes in mononuclear cells from patients with metabolic syndrome after acute intake of phenol-rich virgin olive oil

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Background Previous studies have shown that acute intake of high-phenol virgin olive oil reduces pro-inflammatory, pro-oxidant and pro-thrombotic markers compared with low phenols virgin olive oil, but it still remains unclear whether effects attributed to its phenolic fraction are exerted at transcriptional level in vivo. To achieve this goal, we aimed at identifying expression changes in genes which could be mediated by virgin olive oil phenol compounds in the human. Results Postprandial gene expression microarray analysis was performed on peripheral blood mononuclear cells during postprandial period. Two virgin olive oil-based breakfasts with high (398 ppm) and low (70 ppm) content of phenolic compounds were administered to 20 patients suffering from metabolic syndrome following a double-blinded, randomized, crossover design. To eliminate the potential effect that might exist in their usual dietary habits, all subjects followed a similar low-fat, carbohydrate rich diet during the study period. Microarray analysis identified 98 differentially expressed genes (79 underexpressed and 19 overexpressed) when comparing the intake of phenol-rich olive oil with low-phenol olive oil. Many of these genes seem linked to obesity, dyslipemia and type 2 diabetes mellitus. Among these, several genes seem involved in inflammatory processes mediated by transcription factor NF-κB, activator protein-1 transcription factor complex AP-1, cytokines, mitogen-activated protein kinases MAPKs or arachidonic acid pathways. Conclusion This study shows that intake of virgin olive oil based breakfast, which is rich in phenol compounds is able to repress in vivo expression of several pro-inflammatory genes, thereby switching activity of peripheral blood mononuclear cells to a less deleterious inflammatory profile. These results provide at least a partial molecular basis for reduced risk of cardiovascular disease observed in Mediterranean countries, where virgin olive oil represents a main source of dietary fat. Admittedly, other lifestyle factors are also likely to contribute to lowered risk of cardiovascular disease in this region.Published versio

Evaluation of Safety of a Newly Formulated Pirfenidone in Chronic Kidney Disease: A Non-Randomized Pilot Study in Mexican Patients

The aim of this pilot clinical trial was to evaluate the safety of a new formulation of prolonged-release Pirfenidone (PR-PFD) in chronic kidney disease (CKD), specifically focal and segmental glomerular hyalinization (FSGH). Open-label, pilot, nonrandomized trial. Eighteen patients previously diagnosed with CKD stages 1– 5 according to “Kidney Disease: Improving Global Outcomes” were enrolled in the study. Target dos-age of PFD was 1200 mg twice a day in the form of prolonged-release tablets to reach a full dosage of 2400 mg daily. Clinical trial was carried out for 60 months to evaluate the safety and efficacy of a newly formulated PR-PFD in patients with CKD. After the treatment for 60 months, it was found that PR-PFD kept renal function from declining significantly in CKD patients, as the glomerular filtration rate (GFR) showed only minimal variations throughout the study. Estimated glomerular filtration rate (eGFR) showed no differences at both baseline and the end points. Proteinuria improved, and creatinine, cystatin C, urea, hemoglobin and hepatic transaminases remained constant without any considerable changes across the study. Minor side effects were noticed when compared with those found in previous studies, indicating an increased tolerance to this pharmaceutical formulation of PFD. Prolonged-released PFD could be safely used as an adjuvant therapy in patients with CKD.Registry number was obtained from ClinicalTrials.gov (NCT02408744)

Cardiovascular Risk in Systemic Autoimmune Diseases: Epigenetic Mechanisms of Immune Regulatory Functions

Autoimmune diseases (AIDs) have been associated with accelerated atherosclerosis (AT) leading to increased cardio- and cerebrovascular disease risk. Traditional risk factors, as well as systemic inflammation mediators, including cytokines, chemokines, proteases, autoantibodies, adhesion receptors, and others, have been implicated in the development of these vascular pathologies. Yet, the characteristics of vasculopathies may significantly differ depending on the underlying disease. In recent years, many new genes and signalling pathways involved in autoimmunity with often overlapping patterns between different disease entities have been further detected. Epigenetics, the control of gene packaging and expression independent of alterations in the DNA sequence, is providing new directions linking genetics and environmental factors. Epigenetic regulatory mechanisms comprise DNA methylation, histone modifications, and microRNA activity, all of which act upon gene and protein expression levels. Recent findings have contributed to our understanding of how epigenetic modifications could influence AID development, not only showing differences between AID patients and healthy controls, but also showing how one disease differs from another and even how the expression of key proteins involved in the development of each disease is regulated

A importância do pré-natal odontológico na saúde bucal do bebê / The importance of dental prenatal in baby's oral health

A colaboração multidisciplinar é essencial para a construção da saúde bucal antes do nascimento, e inclui orientações e a eliminação de focos infecciosos na progenitora. Para isso, a realização do pré-natal odontológico pelas gestantes tem reflexo direto na saúde bucal materna, bem como a fetal e a infantil. Objetivo: O objetivo desse trabalho foi realizar uma revisão de literatura sobre a importância do pré-natal odontológico na saúde bucal do bebê. Materiais e Métodos: Foram consultadas as principais bases de artigos científicos das Ciências da Saúde: Pubmed e Biblioteca Virtual em Saúde (BVS), publicados nos últimos 5 anos. Na Pubmed, os descritores utilizados foram: “pregnancy”, “prenatal care”, “preventive dentistry” e “oral health”, e na BVS: “gravidez”, “cuidado pré-natal”, “odontologia preventiva” e “saúde bucal”, associados entre si pelo operador booleano ‘AND’. Resultados: Os trabalhos demonstraram que mulheres grávidas com problemas de saúde bucal apresentam maior risco de problemas perinatais adversos como prematuridade e baixo peso ao nascer, tendo duas vezes mais chances de terem filhos com cárie dentária e maior gravidade da doença. Observou-se, também, uma relação entre a ocorrência de fissuras labiopalatinas e condições comportamentais materno-gestacionais, passíveis de serem evitadas. Conclusão: A presente revisão de literatura mostrou que, o pré-natal odontológico é necessário a fim de proporcionar uma adequada saúde bucal à gestante e consequente melhor qualidade de vida a ela e ao seu filho

Effects of obstructive sleep apnea and its treatment over the erectile function: a systematic review

Erectile dysfunction (ED) is considered a condition with a broad range of etiologies. Obstructive sleep apnea (OSA) syndrome is one of the lesser studied risk factors for ED. We intend to summarize the current evidence on the relationship between OSA and sexual impairment, focusing on the results in terms of erectile function of the different therapies offered to OSA patients. A systematic review was conducted, selecting articles related to the physiology of OSA and ED, and to the treatments of OSA syndrome and their reported outcomes in erectile and sexual function. Higher prevalences of ED in the OSA groups have been published. However, whether this effect on the erectile function occurs in the entire range of OSA severities remains unclear. Several hypotheses were proposed to explain the physiology of this association. Continuous Positive Airway Pressure as a treatment for OSA patients with ED has achieved a significative improvement in the sexual parameters in most of the studies. Phosphodiesterase type 5 inhibitors (iPDE5) on demand are useful as a treatment for ED in this subgroup of patients, with high satisfaction rates. The surgical treatment for the OSA evidenced benefits over the erectile function, and the effect on the sexual satisfaction of the therapy using Mandibular Advancement Devices is still undefined

Spanish cohort of VEXAS syndrome : clinical manifestations, outcome of treatments and novel evidences about UBA1 mosaicism

The vacuoles, E1-enzyme, X linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease (AID) due to postzygotic UBA1 variants. To investigate the presence of VEXAS syndrome among patients with adult-onset undiagnosed AID. Additional studies evaluated the mosaicism distribution and the circulating cytokines. Gene analyses were performed by both Sanger and amplicon-based deep sequencing. Patients' data were collected from their medical charts. Cytokines were quantified by Luminex. Genetic analyses of enrolled patients (n=42) identified 30 patients carrying UBA1 pathogenic variants, with frequencies compatible for postzygotic variants. All patients were male individuals who presented with a late-onset disease (mean 67.5 years; median 67.0 years) characterised by cutaneous lesions (90%), fever (66.7%), pulmonary manifestations (66.7%) and arthritis (53.3%). Macrocytic anaemia and increased erythrocyte sedimentation rate and ferritin were the most relevant analytical abnormalities. Glucocorticoids ameliorated the inflammatory manifestations, but most patients became glucocorticoid-dependent. Positive responses were obtained when targeting the haematopoietic component of the disease with either decitabine or allogeneic haematopoietic stem cell transplantation. Additional analyses detected the UBA1 variants in both haematopoietic and non-haematopoietic tissues. Finally, analysis of circulating cytokines did not identify inflammatory mediators of the disease. Thirty patients with adult-onset AID were definitively diagnosed with VEXAS syndrome through genetic analyses. Despite minor interindividual differences, their main characteristics were in concordance with previous reports. We detected for the first time the UBA1 mosaicism in non-haematopoietic tissue, which questions the previous concept of myeloid-restricted mosaicism and may have conceptual consequences for the disease mechanisms

Recuperación monumental ambiental de la Alameda Central de la Ciudad de México

752 páginas. Especialización en Diseño.El presente trabajo se centra en el estudio, análisis y rescate de la Alameda Central de la Ciudad de México, la cual se sitúa hoy en el corazón de la gran ciudad, siendo ésta el paseo más antiguo de América y lugar que ha visto acontecer los cambios políticos, sociales y culturales de una nación, que es hoy México. El estudio es una recopilación cronológica de los sucesos que dieron origen al primer parque público de México, así como su desarrollo y los cambios morfológicos que ha presentado a lo largo de los años, lo que le otorga un carácter relevante y lo define como el paseo más importante del país

Characterization of the clinical and immunologic phenotype and management of 157 individuals with 56 distinct heterozygous NFKB1 mutations

Background: An increasing number of NFKB1 variants are being identified in patients with heterogeneous immunologic phenotypes. Objective: To characterize the clinical and cellular phenotype as well as the management of patients with heterozygous NFKB1 mutations. Methods: In a worldwide collaborative effort, we evaluated 231 individuals harboring 105 distinct heterozygous NFKB1 variants. To provide evidence for pathogenicity, each variant was assessed in silico; in addition, 32 variants were assessed by functional in vitro testing of nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-kappa B) signaling. Results: We classified 56 of the 105 distinct NFKB1 variants in 157 individuals from 68 unrelated families as pathogenic. Incomplete clinical penetrance (70%) and age-dependent severity of NFKB1-related phenotypes were observed. The phenotype included hypogammaglobulinemia (88.9%), reduced switched memory B cells (60.3%), and respiratory (83%) and gastrointestinal (28.6%) infections, thus characterizing the disorder as primary immunodeficiency. However, the high frequency of autoimmunity (57.4%), lymphoproliferation (52.4%), noninfectious enteropathy (23.1%), opportunistic infections (15.7%), autoinflammation (29.6%), and malignancy (16.8%) identified NF-kappa B1-related disease as an inborn error of immunity with immune dysregulation, rather than a mere primary immunodeficiency. Current treatment includes immunoglobulin replacement and immunosuppressive agents. Conclusions: We present a comprehensive clinical overview of the NF-kappa B1-related phenotype, which includes immunodeficiency, autoimmunity, autoinflammation, and cancer. Because of its multisystem involvement, clinicians from each and every medical discipline need to be made aware of this autosomal-dominant disease. Hematopoietic stem cell transplantation and NF-kappa B1 pathway-targeted therapeutic strategies should be considered in the future.Peer reviewe

Long daytime napping is associated with increased adiposity and type 2 diabetes in an elderly population with metabolic syndrome

Research examining associations between objectively-measured napping time and type 2 diabetes (T2D) is lacking. This study aimed to evaluate daytime napping in relation to T2D and adiposity measures in elderly individuals from the Mediterranean region. A cross-sectional analysis of baseline data from 2190 elderly participants with overweight/obesity and metabolic syndrome, in the PREDIMED-Plus trial, was carried out. Accelerometer-derived napping was measured. Prevalence ratios (PR) and 95% confidence intervals (CI) for T2D were obtained using multivariable-adjusted Cox regression with constant time. Linear regression models were fitted to examine associations of napping with body mass index (BMI) and waist circumference (WC). Participants napping ≥90 min had a higher prevalence of T2D (PR 1.37 (1.06, 1.78)) compared with those napping 5 to <30 min per day. Significant positive associations with BMI and WC were found in those participants napping ≥30 min as compared to those napping 5 to <30 min per day. The findings of this study suggest that longer daytime napping is associated with higher T2D prevalence and greater adiposity measures in an elderly Spanish population at high cardiovascular risk