Objective
To test whether enhancing the capability of adipose tissue to store lipids using antioxidant supplementation may prevent the lipotoxic effects and improve the metabolic profile of long‐term ...obesity.
Methods
C57BL/6J mice were randomized into three experimental groups for 28 weeks: control group (n = 10) fed chow diet (10% kcal from fat), obese group (O, n = 12) fed high‐fat (HF) diet (45% kcal from fat), and obese group fed HF diet and supplemented twice a week with 150 mg of α‐tocopherol (vitamin E) by oral gavage (OE, n = 12).
Results
HF diet resulted in an obese phenotype with a marked insulin resistance, hypertriglyceridemia, and hepatic steatosis in O mice. Histological analysis of obese visceral adipose tissue (VAT) revealed smaller adipocytes surrounded by a fibrotic extracellular matrix and an increased macrophage infiltration, with the consequent release of proinflammatory cytokines. Vitamin E supplementation decreased oxidative stress and reduced collagen deposition in the VAT of OE mice, allowing a further expansion of the adipocytes and increasing the storage capability. As a result, circulating cytokines were reduced and hepatic steasosis, hypertriglyceridemia, and insulin sensitivity were improved.
Conclusions
Our results suggest that oxidative stress is implicated in extracellular matrix remodeling and may play an important role in metabolic regulation.
Background Metabolic syndrome (MetS) is a serious health problem over the world; thus, the aim of the present work was to develop a lifestyle intervention to decrease the dysbiosis of gut microbiota ...and reduce the biochemical abnormalities of MetS. Methods and Results The prevalence of MetS was evaluated in 1065 subjects of Mexico City, Mexico, and the gut microbiota in a subsample. Subjects with MetS were selected for a pragmatic study based on a lifestyle intervention with a low-saturated-fat diet, reduced-energy intake, with functional foods and physical activity, and a second group was selected for a randomized control-placebo study to assess the gut microbiota after the dietary intervention. Prevalence of MetS was 53%, and the higher the body mass index, the higher the gut microbiota dysbiosis. The higher the Homeostatic Model Assessment for Insulin Resistance, the lower the high-density lipoprotein cholesterol concentration. The pragmatic study revealed that after 15 days on a low-saturated-fat diet, there was a 24% reduction in serum triglycerides; and after a 75-day lifestyle intervention, MetS was reduced by 44.8%, with a reduction in low-density lipoprotein cholesterol, small low-density lipoprotein particles, glucose intolerance, lipopolysaccharide, and branched-chain amino acid. The randomized control-placebo study showed that after the lifestyle intervention, there was a decrease in the dysbiosis of the gut microbiota associated with a reduction in the Prevotella/ Bacteroides ratio and an increase in the abundance of Akkermansia muciniphila and Faecalibacterium prausnitzii. Conclusions A lifestyle intervention significantly decreased MetS components, small low-density lipoprotein particle concentration, gut microbiota dysbiosis, and metabolic endotoxemia, reducing the risk of atherosclerosis. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT03611140.
Antibodies to lipids are part of the first line of defense against microorganisms and regulate the pro/anti-inflammatory balance. Viruses modulate cellular lipid metabolism to enhance their ...replication, and some of these metabolites are proinflammatory. We hypothesized that antibodies to lipids would play a main role of in the defense against SARS-CoV-2 and thus, they would also avoid the hyperinflammation, a main problem in severe condition patients.
Serum samples from COVID-19 patients with mild and severe course, and control group were included. IgG and IgM to different glycerophospholipids and sphingolipids were analyzed using a high-sensitive ELISA developed in our laboratory. A lipidomic approach for studying lipid metabolism was performed using ultra-high performance liquid chromatography coupled to electrospray ionization and quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS).
Mild and severe COVID-19 patients had higher levels of IgM to glycerophosphocholines than control group. Mild COVID-19 patients showed higher levels of IgM to glycerophosphoinositol, glycerophosphoserine and sulfatides than control group and mild cases. 82.5% of mild COVID-19 patients showed IgM to glycerophosphoinositol or glycerophosphocholines plus sulfatides or glycerophosphoserines. Only 35% of severe cases and 27.5% of control group were positive for IgM to these lipids. Lipidomic analysis identify a total of 196 lipids, including 172 glycerophospholipids and 24 sphingomyelins. Increased levels of lipid subclasses belonging to lysoglycerophospholipids, ether and/or vinyl-ether-linked glycerophospholipids, and sphingomyelins were observed in severe COVID-19 patients, when compared with those of mild cases and control group.
Antibodies to lipids are essential for defense against SARS-CoV-2. Patients with low levels of anti-lipid antibodies have an elevated inflammatory response mediated by lysoglycerophospholipids. These findings provide novel prognostic biomarkers and therapeutic targets.
Abstract
Background
Ecthyma gangrenosum (EG) usually results from the hematogenous seeding of the skin in the setting of bacteremia, mostly by
Pseudomonas aeruginosa
, especially in immunocompromised ...patients. It presents as erythematous‐violaceous macules, or plaques with surrounding erythema before rapidly progressing to bullae and necrotic‐ulcerative eschars.
Methods
We performed a retrospective chart review of EG patients diagnosed at the National Institute of Pediatrics. Data included demographics, underlying disease, cutaneous lesions, location, evolution, microbiologic, histopathologic findings, and treatment. Data were analyzed by descriptive statistics; Mann–Whitney
U
test and Fisher's exact test were used to evaluate differences between groups.
Results
Seventeen patients with a mean age of 12.5 (6–16) years were included. The most common underlying disease was acute lymphoblastic leukemia (59%), three patients were not immunocompromised (17%). A total of 18 episodes of EG were recorded, 10 (55%) were disseminated at presentation. Systemic manifestations included fever (100%), pain (88.9%), asthenia and adynamia (22.2%).
P. aeruginosa
was isolated in 10 (55%) cases, followed by
Staphylococcus aureus
in four. Three patients had sepsis at onset (17%). A comparison between localized versus disseminated, pseudomonal versus nonpseudomonal, and bacteremic versus nonbacteremic EG was performed with no statistical difference between any of the groups, except for longer treatment time for pseudomonal EG, and longer hospitalization days for both pseudomonal EG and bacteremia.
Conclusions
Fever and pain in the setting of rapidly evolving necrotic lesions should prompt the clinical suspicion of EG and the installment of empiric treatment pending culture results.
Este libro es una compilación de varios textos producidos por mujeres académicas provenientes, en su mayoría, de países de Latinoamérica como Colombia, Ecuador y México. Es el resultado de un ...encuentro dado en el marco del I Simposio Internacional sobre Estudios Feministas del Desarrollo, llevado a cabo en Granada-España en el año 2021. Me parece necesario resaltar que, el momento en el que se genera el espacio académico que tendrá como resultado este libro, es cuando aún estaban vigentes restricciones por motivo de la pandemia Covid19. En ese contexto, la apuesta de llevar a cabo espacios presenciales y colectivos para el debate y la co-construcción de conocimiento feminista, en este caso entre Europa y Latinoamérica, tiene mayor relevancia, partiendo de comprensiones donde el conocimiento es una elaboración colectiva, que requiere pensar en conversación con otrxs, algo que las autoras dejarán sentado en los diferentes capítulos.
Despite the wide-ranging studies on Corporate Social Responsibility (CSR), firm performance, and Organizational Leadership (OL), there have been only a few studies examining the inter-relationship ...between them. Accordingly, this investigation has tried to investigate how OL contributes to the firm's performance through the CSR strategies. It has an internal orientation to CSR motivations compared to the existing studies that mostly considered the external factors in implementing of CSR in firms; also, it has a comprehensive view toward the firm's performance by considering both financial and non-financial aspects of performance. It could be said that this study has tried to answer the question of whether or not CSR can be as a mediator between the OL and firm performance. Data collection was performed from 285 manufacturing and consumer products firms located in Malaysia during the four-month period of June–September of 2020. AMOS Structural Equation Modeling (AMOS-SEM) method was applied to analyze the model. Following the Baron and Kenny approach in testing the hypotheses, it was found that the relationships of OL and financial performance, as well as OL and non-financial performance were partially mediated by CSR. In addition, the non-financial performance was found as a full mediator between the OL and financial performance. Further, the results revealed two full mediated relationships in this way that non-financial performance was a full mediator variable between CSR and financial performance, as well as CSR and non-financial performance which were found as two multiple full mediators between OL and financial performance. The results help Malaysian managers to understand their current status, capabilities, strong points and weaknesses in leadership regarding to CSR. Moreover, due to the positive effects of CSR on both firm's financial and non-financial performance, CSR is recommended to be integrated in leadership style and the organizational strategies in order to having better performance.
Organizational leadership; Corporate social responsibility; Financial performance; Non-financial performance; Malaysia.
Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease of the central nervous system. It affects young people, and a considerable percentage of patients need the help of a ...wheelchair in 15 years of evolution. Currently, there is not a specific technique for the diagnosis of MS. The detection of oligoclonal IgG bands (OIgGBs) is the most sensitive assay for it, but it is not standardizable, only reference laboratories develop it, and uses cerebrospinal fluid. To obtain this sample, a lumbar puncture is necessary, an invasive proceeding with important side effects. It is important to develop and implement standard assays to obtain a rapid diagnosis because the earlier the treatment, the better the evolution of the disease. There are numerous modifying disease therapies, which delay the progression of the disease, but they have important side effects, and a considerable percentage of patients give up the treatment. In addition, around 40% of MS patients do not respond to the therapy and the disease progresses. Numerous researches have been focused on the characterization of predictive biomarkers of response to treatment, in order to help physicians to decide when to change to a second-line treatment, and then the best therapeutic option. Here, we review the new biomarkers for the diagnosis and response to treatment in MS. We draw attention in a new assay, the detection of serum IgM to phosphatidylcholine, that showed a similar sensitivity as OIgGBs and predicts the response to disease modifying treatments.
Background European cross-sectional studies have suggested that prenatal and postnatal farm exposure decreases the risk of allergic diseases in childhood. Underlying immunologic mechanisms are still ...not understood but might be modulated by immune-regulatory cells early in life, such as regulatory T (Treg) cells. Objective We sought to assess whether Treg cells from 4.5-year-old children from the Protection against Allergy: Study in Rural Environments birth cohort study are critical in the atopy and asthma-protective effect of farm exposure and which specific exposures might be relevant. Methods From 1133 children, 298 children were included in this study (149 farm and 149 reference children). Detailed questionnaires until 4 years of age assessed farming exposures over time. Treg cells were characterized as upper 20% CD4+ CD25+ forkhead box protein 3 (FOXP3)+ (intracellular) in PBMCs before and after stimulation (with phorbol 12-myristate 13-acetate/ionomycin or LPS), and FOXP3 demethylation was assessed. Atopic sensitization was defined by specific IgE measurements; asthma was defined by a doctor's diagnosis. Results Treg cells were significantly increased in farm-exposed children after phorbol 12-myristate 13-acetate/ionomycin and LPS stimulation. Exposure to farm milk was defined as a relevant independent farm-related exposure supported by higher FOXP3 demethylation. Treg cell (upper 20% CD4+ CD25+ , FOXP3+ T cells) numbers were significantly negatively associated with doctor-diagnosed asthma (LPS stimulated: adjusted odds ratio, 0.26; 95% CI, 0.08-0.88) and perennial IgE (unstimulated: adjusted odds ratio, 0.21; 95% CI, 0.08-0.59). Protection against asthma by farm milk exposure was partially mediated by Treg cells. Conclusions Farm milk exposure was associated with increased Treg cell numbers on stimulation in 4.5-year-old children and might induce a regulatory phenotype early in life, potentially contributing to a protective effect for the development of childhood allergic diseases.
Medical education should promote the development of skills and abilities that can be applied to real-world work performance. The aim of this study is to evaluate technical and methodological ...knowledge, as well as physician-patient communication skills, as one of the most important transversal competencies that a good physician should acquire; all this in a reliable, accurate and objective way.
We present a rubric specifically designed and implemented for the evaluation of specific and transversal competencies in the physiology practical sessions, during the second year of the medical degree. The assessment consists in two evaluation tests: 1) a theoretical test that consists of multiple-choice questions. Students must demonstrate that they have acquired adequate theoretical knowledge (specific competency "to know"); 2) a practical test, in which students are evaluated by the rubric through the simulation of a medical consultation. Thus, demonstrating their ability to execute/apply what they have learned in class (specific competency "to know how to do"). They are also evaluated on the transversal competencies that we call "communication with the patient" (transversal competency "to know how to be there") and "dealing with the patient" (transversal competency "to know how to be").
We evaluated whether there were differences in the grades obtained by students when the transversal competencies were not assessed (academic years 2017-2018 and 2018-2019; n = 289), and when the transversal competencies were assessed by applying the rubric in the academic years 2019-2020, 2021-2022, and 2022-2023 (n = 526). Furthermore, we present a student perception that supports the use of clinical simulation and our rubric as a good method within the competency learning process.
The acquisition of these competencies, starting from the first courses of undergraduate education, helps to raise the students' awareness in the development of a more humanized medicine, allowing a better response to the patients' needs. Our rubric, which clearly indicate the performance criteria, have become an excellent method to carry out the assessment of competencies, both for students and teachers, since they allow to obtain clear evidence of the level of acquisition and application of knowledge.
The purpose of the study was to determine the role of fecal calprotectin and lactoferrin in the prediction of inflammatory bowel disease relapses, both in patients with ulcerative colitis (UC) and ...Crohn's disease (CD), in a large, long-term, follow-up study.
The prospective multicenter study included CD and UC patients who had been in clinical remission for 6 months. At baseline, patients provided a single stool sample for calprotectin and lactoferrin determination. Follow-up was 12 months in patients showing no relapse and until activity flare in relapsing patients.
In all, 163 patients (89 CD, 74 UC) were included. Twenty-six patients (16%) relapsed during follow-up. Calprotectin concentrations in patients who suffered a relapse were higher than in nonrelapsing patients (239 +/- 150 versus 136 +/- 158 microg/g; P < 0.001). Relapse risk was higher in patients having high (>150 microg/g) calprotectin concentrations (30% versus 7.8%; P < 0.001) or positive lactoferrin (25% versus 10%; P < 0.05). Fecal calprotectin (>150 microg/g) sensitivity and specificity to predict relapse were 69% and 69%, respectively. Corresponding values for lactoferrin were 62% and 65%, respectively. The area under the receiver operating characteristic curve to predict relapse using calprotectin determination was 0.73 (0.69 for UC and 0.77 for CD). Better results were obtained when only colonic CD disease or only relapses during the first 3 months were considered (100% sensitivity). High fecal calprotectin levels or lactoferrin positivity was associated with clinical relapse in Kaplan-Meier survival analysis, and both fecal tests were associated with relapse in the multivariate analysis.
Fecal calprotectin and lactoferrin determination may be useful in predicting impending clinical relapse-especially during the following 3 months-in both CD and UC patients.