Dietary Intervention on Overweight and Obesity after Confinement by COVID-19.

BACKGROUND: Obesity has become a public health problem in our society and is associated with many diseases, including type 2 diabetes mellitus, cardiovascular diseases, dyslipidemia, respiratory diseases, and cancer. Several studies relate weight loss in obese patients to improved anthropometric measurements and cardiometabolic risk. The objective of our study was to evaluate anthropometric changes, analytical parameters, insulin resistance, fatty liver, and metabolic scales, after a personalized weight loss program, through dietary advice to increase adherence to the Mediterranean diet and a motivational booster via mobile SMS messaging. METHODS: Intervention study on a sample of 1964 workers, in which different anthropometric parameters were evaluated before and after dietary intervention: the metabolic score of insulin resistance; non-alcoholic fatty liver disease using different scales; metabolic syndrome; atherogenic dyslipidemia; and the cardiometabolic index. A descriptive analysis of the categorical variables was performed, by calculating the frequency and distribution of the responses for each one. For quantitative variables, the mean and standard deviation were calculated, since they followed a normal distribution. Bivariate association analysis was performed by applying the chi-squared test (corrected by Fisher's exact statistic when conditions required it) and Student's t-test for independent samples (for comparison of means). RESULTS: The population subjected to the Mediterranean diet improved in all the variables evaluated at 12 months of follow-up and compliance with the diet. CONCLUSIONS: Dietary advice on a Mediterranean diet and its reinforcement with reminder messages through the use of mobile phones may be useful to improve the parameters evaluated in this study and reduce the cardiometabolic risk of patients.

Waist Circumference Is an Essential Factor in Predicting Insulin Resistance and Early Detection of Metabolic Syndrome in Adults.

BACKGROUND: Metabolic syndrome (Met-S) is considered one of the most important health problems of the 21st century. It includes a group of metabolic disorders that increase the risk of cardiovascular diseases such as overweight and obesity, elevated lipid profile and blood pressure and insulin resistance (IR). Based on the information mentioned above in which there seems to be a relationship between IR and Met-S, the objective of this work was twofold: on the one hand, to assess the relationship between the values of different insulin resistance risk scales and Met-S determined with three different scales, and on the other, to determine whether any of the components of Met-S predispose more to the appearance of IR. METHODS: A descriptive cross-sectional study of 418,343 workers. Waist circumference was measured and evaluated together with six formulas to assess the insulin resistance index. Categorical variables were evaluated by calculating the frequency and distribution of each one. For quantitative variables, mean and standard deviation were determined, and Student's t-test was applied, while for qualitative variables, the chi-square test was performed. The usefulness of the different risk scales for insulin resistance for predicting metabolic syndrome was evaluated using ROC curves, the area under the curve (AUC), as well as their cut-off points for sensitivity, specificity, and the Youden index. RESULTS: People with metabolic syndrome applying any criteria had higher values in the IR risk scales. The different IR scales made it possible to adequately classify people with metabolic syndrome. Of the three definitions of Met-S, the one that showed the greatest relationship with IR was IDF. CONCLUSIONS: Most risk scales for insulin resistance enable the presence of metabolic syndrome to be adequately classified, finding the best ones if the International Diabetes Federation (IDF) criteria are applied. Of the elements included in the Met-S, the one that seems to increase the risk of presenting IR the most is waist circumference; hence, the Met-S definition that is most related to IR is that of the IDF, which is the only one of the three in which a high value of waist circumference is necessary to be able to diagnose Met-S. Waist circumference can be considered the central essential component for detecting insulin resistance and, therefore, the early detection of metabolic syndrome.

Characterization of nontypable Haemophilus influenzae isolates recovered from adult patients with underlying chronic lung disease reveals genotypic and phenotypic traits associated with persistent infection.

Nontypable Haemophilus influenzae (NTHi) has emerged as an important opportunistic pathogen causing infection in adults suffering obstructive lung diseases. Existing evidence associates chronic infection by NTHi to the progression of the chronic respiratory disease, but specific features of NTHi associated with persistence have not been comprehensively addressed. To provide clues about adaptive strategies adopted by NTHi during persistent infection, we compared sequential persistent isolates with newly acquired isolates in sputa from six patients with chronic obstructive lung disease. Pulse field gel electrophoresis (PFGE) identified three patients with consecutive persistent strains and three with new strains. Phenotypic characterisation included infection of respiratory epithelial cells, bacterial self-aggregation, biofilm formation and resistance to antimicrobial peptides (AMP). Persistent isolates differed from new strains in showing low epithelial adhesion and inability to form biofilms when grown under continuous-flow culture conditions in microfermenters. Self-aggregation clustered the strains by patient, not by persistence. Increasing resistance to AMPs was observed for each series of persistent isolates; this was not associated with lipooligosaccharide decoration with phosphorylcholine or with lipid A acylation. Variation was further analyzed for the series of three persistent isolates recovered from patient 1. These isolates displayed comparable growth rate, natural transformation frequency and murine pulmonary infection. Genome sequencing of these three isolates revealed sequential acquisition of single-nucleotide variants in the AMP permease sapC, the heme acquisition systems hgpB, hgpC, hup and hxuC, the 3-deoxy-D-manno-octulosonic acid kinase kdkA, the long-chain fatty acid transporter ompP1, and the phosphoribosylamine glycine ligase purD. Collectively, we frame a range of pathogenic traits and a repertoire of genetic variants in the context of persistent infection by NTHi.

Genotypic and phenotypic diversity of the noncapsulated Haemophilus influenzae: adaptation and pathogenesis in the human airways

The human respiratory tract contains a highly adapted microbiota including commensal and opportunistic pathogens. Noncapsulated or nontypable Haemophilus influenzae (NTHi) is a human-restricted member of the normal airway microbiota in healthy carriers and an opportunistic pathogen in immunocompromised individuals. The duality of NTHi as a colonizer and as a symptomatic infectious agent is closely related to its adaptation to the host, which in turn greatly relies on the genetic plasticity of the bacterium and is facilitated by its condition as a natural competent. The variable genotype of NTHi accounts for its heterogeneous gene expression and variable phenotype, leading to differential host-pathogen interplay among isolates. Here we review our current knowledge of NTHi diversity in terms of genotype, gene expression, antigenic variation, and the phenotypes associated with colonization and pathogenesis. The potential benefits of NTHi diversity studies discussed herein include the unraveling of pathogenicity clues, the generation of tools to predict virulence from genomic data, and the exploitation of a unique natural system for the continuous monitoring of long-term bacterial evolution in human airways exposed to noxious agents. Finally, we highlight the challenge of monitoring both the pathogen and the host in longitudinal studies, and of applying comparative genomics to clarify the meaning of the vast NTHi genetic diversity and its translation to virulence phenotypes (AU)

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Genotypic and phenotypic diversity of the noncapsulated Haemophilus influenzae: adaptation and pathogenesis in the human airways.

The human respiratory tract contains a highly adapted microbiota including commensal and opportunistic pathogens. Noncapsulated or nontypable Haemophilus influenzae (NTHi) is a human-restricted member of the normal airway microbiota in healthy carriers and an opportunistic pathogen in immunocompromised individuals. The duality of NTHi as a colonizer and as a symptomatic infectious agent is closely related to its adaptation to the host, which in turn greatly relies on the genetic plasticity of the bacterium and is facilitated by its condition as a natural competent. The variable genotype of NTHi accounts for its heterogeneous gene expression and variable phenotype, leading to differential host-pathogen interplay among isolates. Here we review our current knowledge of NTHi diversity in terms of genotype, gene expression, antigenic variation, and the phenotypes associated with colonization and pathogenesis. The potential benefits of NTHi diversity studies discussed herein include the unraveling of pathogenicity clues, the generation of tools to predict virulence from genomic data, and the exploitation of a unique natural system for the continuous monitoring of long-term bacterial evolution in human airways exposed to noxious agents. Finally, we highlight the challenge of monitoring both the pathogen and the host in longitudinal studies, and of applying comparative genomics to clarify the meaning of the vast NTHi genetic diversity and its translation to virulence phenotypes.

Nontypable Haemophilus influenzae displays a prevalent surface structure molecular pattern in clinical isolates.

Non-typable Haemophilus influenzae (NTHi) is a gram negative pathogen that causes acute respiratory infections and is associated with the progression of chronic respiratory diseases. Previous studies have established the existence of a remarkable genetic variability among NTHi strains. In this study we show that, in spite of a high level of genetic heterogeneity, NTHi clinical isolates display a prevalent molecular feature, which could confer fitness during infectious processes. A total of 111 non-isogenic NTHi strains from an identical number of patients, isolated in two distinct geographical locations in the same period of time, were used to analyse nine genes encoding bacterial surface molecules, and revealed the existence of one highly prevalent molecular pattern (lgtF+, lic2A+, lic1D+, lic3A+, lic3B+, siaA-, lic2C+, ompP5+, oapA+) displayed by 94.6% of isolates. Such a genetic profile was associated with a higher bacterial resistance to serum mediated killing and enhanced adherence to human respiratory epithelial cells.

Evidence for a non-replicative intracellular stage of nontypable Haemophilus influenzae in epithelial cells.

Nontypable Haemophilus influenzae (NTHi) is a Gram-negative, non-capsulated human bacterial pathogen, a major cause of a repertoire of respiratory infections, and intimately associated with persistent lung bacterial colonization in patients suffering from chronic obstructive pulmonary disease (COPD). Despite its medical relevance, relatively little is known about its mechanisms of pathogenicity. In this study, we found that NTHi invades the airway epithelium by a distinct mechanism, requiring microtubule assembly, lipid rafts integrity, and activation of phosphatidylinositol 3-kinase (PI3K) signalling. We found that the majority of intracellular bacteria are located inside an acidic subcellular compartment, in a metabolically active and non-proliferative state. This NTHi-containing vacuole (NTHi-CV) is endowed with late endosome features, co-localizing with LysoTracker, lamp-1, lamp-2, CD63 and Rab7. The NTHi-CV does not acquire Golgi- or autophagy-related markers. These observations were extended to immortalized and primary human airway epithelial cells. By using NTHi clinical isolates expressing different amounts of phosphocholine (PCho), a major modification of NTHi lipooligosaccharide, on their surfaces, and an isogenic lic1BC mutant strain lacking PCho, we showed that PCho is not responsible for NTHi intracellular location. In sum, this study indicates that NTHi can survive inside airway epithelial cells.

Nontypeable Haemophilus influenzae clearance by alveolar macrophages is impaired by exposure to cigarette smoke.

Nontypeable Haemophilus influenzae (NTHI) is an opportunistic gram-negative pathogen that causes respiratory infections and is associated with progression of respiratory diseases. Cigarette smoke is a main risk factor for development of respiratory infections and chronic respiratory diseases. Glucocorticoids, which are anti-inflammatory drugs, are still the most common therapy for these diseases. Alveolar macrophages are professional phagocytes that reside in the lung and are responsible for clearing infections by the action of their phagolysosomal machinery and promotion of local inflammation. In this study, we dissected the interaction between NTHI and alveolar macrophages and the effect of cigarette smoke on this interaction. We showed that alveolar macrophages clear NTHI infections by adhesion, phagocytosis, and phagolysosomal processing of the pathogen. Bacterial uptake requires host actin polymerization, the integrity of plasma membrane lipid rafts, and activation of the phosphatidylinositol 3-kinase (PI3K) signaling cascade. Parallel to bacterial clearance, macrophages secrete tumor necrosis factor alpha (TNF-alpha) upon NTHI infection. In contrast, exposure to cigarette smoke extract (CSE) impaired alveolar macrophage phagocytosis, although NTHI-induced TNF-alpha secretion was not abrogated. Mechanistically, our data showed that CSE reduced PI3K signaling activation triggered by NTHI. Treatment of CSE-exposed cells with the glucocorticoid dexamethasone reduced the amount of TNF-alpha secreted upon NTHI infection but did not compensate for CSE-dependent phagocytic impairment. The deleterious effect of cigarette smoke was observed in macrophage cell lines and in human alveolar macrophages obtained from smokers and from patients with chronic obstructive pulmonary disease.