Mexican consensus on cow's milk protein allergy.

BACKGROUND: The aim of this study is to present the current views of a diverse group of experts on the diagnosis and treatment of Cow's Milk Protein Allergy (CMPA) in children under 2 years of age in Mexico. MATERIAL AND METHODS: The study, led by a scientific committee of five experts in CMPA, was divided into six phases, including a modified Delphi process. A total of 20 panelists, all of whom were pediatric specialists, participated in administering a comprehensive 38-item questionnaire. The questionnaire was divided into two blocks: Diagnosis and Treatment (20 items each). RESULTS: Consensus was reached on all the proposed items, with an agreement rate of over 70% for each of them. As a result, a diagnostic and treatment algorithm was developed that emphasized the reduction of unnecessary diagnostic studies and encouraged breastfeeding whenever possible. In cases where breast milk is not available, appropriate use of hypoallergenic formulas was recommended. In addition, recommendations on treatment duration and gradual reintroduction of cow's milk protein were provided. CONCLUSIONS: The recommendations endorsed by 20 Mexican pediatricians through this study are applicable to everyday clinical practice, thereby enhancing the diagnosis and treatment of children under 2 years of age with CMPA. This, in turn, will foster improved health outcomes and optimize the utilization of healthcare resources.

Prevalence of adiposity-based chronic disease and its association with anthropometric and clinical indices: a cross-sectional study.

The present study aimed to determine the prevalence of adiposity-based chronic disease (ABCD) and its association with anthropometric indices in the Mexican population. A cross-sectional study was conducted in 514 adults seen at a clinical research unit. The American Association of Clinical Endocrinology/AACE/ACE criteria were used to diagnose ABCD by first identifying subjects with BMI ≥ 25 kg/m2 and those with BMI of 23-24·9 kg/m2 and waist circumference ≥ 80 cm in women or ≥ 90 cm in men. The presence of metabolic and clinical complications associated with adiposity, such as factors related to metabolic syndrome, prediabetes, type 2 diabetes, dyslipidaemia and arterial hypertension, were subsequently evaluated. Anthropometric indices related to cardiometabolic risk factors were then determined. The results showed the prevalence of ABCD was 87·4 % in total, 91·5 % in men and 86 % in women. The prevalence of ABCD stage 0 was 2·4 %, stage 1 was 33·7 % and stage 2 was 51·3 %. The prevalence of obesity according to BMI was 57·6 %. The waist/hip circumference index (prevalence ratio (PR) = 7·57; 95 % CI 1·52, 37·5) and the conicity index (PR = 3·46; 95 % CI 1·34, 8·93) were better predictors of ABCD, while appendicular skeletal mass % and skeletal muscle mass % decreased the risk of developing ABCD (PR = 0·93; 95 % CI 0·90, 0·96; and PR = 0·95; 95 % CI 0·93, 0·98). In conclusion, the prevalence of ABCD in our study was 87·4 %. This prevalence increased with age. It is important to emphasise that one out of two subjects had severe obesity-related complications (ABCD stage 2).

Low Expression of BRCA1 as a Potential Relapse Predictor in B-Cell Acute Lymphoblastic Leukemia.

B-cell acute lymphoblastic leukemia (B-ALL) is the most common childhood hematological malignancy worldwide. Treatment outcomes have improved dramatically in recent years; despite this, relapse is still a problem, and the potential molecular explanation for this remains an important field of study. We performed microarray and single-cell RNA-Seq data mining, and we selected significant data with a P -value<0.05. We validated BRCA1 gene expression by means of quantitative (reverse transcription-polymerase chain reaction.) We performed statistical analysis and considered a P -value<0.05 significant. We identified the overexpression of breast cancer 1, early onset (BRCA1; P -value=2.52 -134 ), by means of microarray analysis. Moreover, the normal distribution of BRCA1 expression in healthy bone marrow. In addition, we confirmed the increases in BRCA1 expression using real-time (reverse transcription-polymerase chain reaction and determined that it was significantly reduced in patients with relapse ( P -values=0.026). Finally, we identified that the expression of the BRCA1 gene could predict early relapse ( P -values=0.01). We determined that low expression of BRCA1 was associated with B-cell acute lymphoblastic leukemia relapse and could be a potential molecular prognostic marker.

Higher versus lower protein intake in formula-fed term infants.

BACKGROUND: Many infants are fed infant formulas to promote growth. Some formulas have a high protein content (≥ 2.5 g per 100 kcal) to accelerate weight gain during the first year of life. The risk-benefit balance of these formulas is unclear. OBJECTIVES: To evaluate the benefits and harms of higher protein intake versus lower protein intake in healthy, formula-fed term infants. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, LILACS, OpenGrey, clinical trial registries, and conference proceedings in October 2022. SELECTION CRITERIA: We included randomized controlled trials (RCTs) of healthy formula-fed infants (those fed only formula and those given formula as a complementary food). We included infants of any sex or ethnicity who were fed infant formula for at least three consecutive months at any time from birth. We excluded quasi-randomized trials, observational studies, and infants with congenital malformations or serious underlying diseases. We defined high protein content as 2.5 g or more per 100 kcal, and low protein content as less than 1.8 g per 100 kcal (for exclusive formula feeding) or less than 1.7 g per 100 kcal (for complementary formula feeding). DATA COLLECTION AND ANALYSIS: Four review authors independently assessed the risk of bias and extracted data from trials, and a fifth review author resolved discrepancies. We performed random-effects meta-analyses, calculating risk ratios (RRs) or Peto odds ratios (Peto ORs) with 95% confidence intervals (CIs) for dichotomous outcomes, and mean differences (MDs) with 95% CIs for continuous outcomes. We used the GRADE approach to evaluate the certainty of the evidence. MAIN RESULTS: We included 11 RCTs (1185 infants) conducted in high-income countries. Seven trials (1629 infants) compared high-protein formula against standard-protein formula, and four trials (256 infants) compared standard-protein formula against low-protein formula. The longest follow-up was 11 years. High-protein formula versus standard-protein formula We found very low-certainty evidence that feeding healthy term infants high-protein formula compared to standard-protein formula has little or no effect on underweight (MD in weight-for-age z-score 0.05 SDs, 95% CI -0.09 to 0.19; P = 0.51, I2 = 61%; 7 studies, 1629 participants), stunting (MD in height-for-age z-score 0.15 SDs, 95% CI -0.05 to 0.35; P = 0.14, I2 = 73%; 7 studies, 1629 participants), and wasting (MD in weight-for-height z-score -0.12 SDs, 95% CI -0.31 to 0.07; P = 0.20, I2 = 94%; 7 studies, 1629 participants) in the first year of life. We found very low-certainty evidence that feeding healthy infants high-protein formula compared to standard-protein formula has little or no effect on the occurrence of overweight (RR 1.26, 95% CI 0.63 to 2.51; P = 0.51; 1 study, 1090 participants) or obesity (RR 1.96, 95% CI 0.59 to 6.48; P = 0.27; 1 study, 1090 participants) at five years of follow-up. No studies reported all-cause mortality. Feeding healthy infants high-protein formula compared to standard-protein formula may have little or no effect on the occurrence of adverse events such as diarrhea, vomiting, or milk hypersensitivity (RR 0.93, 95% CI 0.76 to 1.13; P = 0.44, I2 = 0%; 4 studies, 445 participants; low-certainty evidence) in the first year of life. Standard-protein formula versus low-protein formula We found very low-certainty evidence that feeding healthy infants standard-protein formula compared to low-protein formula has little or no effect on underweight (MD in weight-for-age z-score 0.0, 95% CI -0.43 to 0.43; P = 0.99, I2 = 81%; 4 studies, 256 participants), stunting (MD in height-for-age z-score -0.01, 95% CI -0.36 to 0.35; P = 0.96, I2 = 73%; 4 studies, 256 participants), and wasting (MD in weight-for-height z-score 0.13, 95% CI -0.29 to 0.56; P = 0.54, I2 = 95%; 4 studies, 256 participants) in the first year of life. No studies reported overweight, obesity, or all-cause mortality. Feeding healthy infants standard-protein formula compared to low-protein formula may have little or no effect on the occurrence of adverse events such as diarrhea, vomiting, or milk hypersensitivity (Peto OR 1.55, 95% CI 0.70 to 3.40; P = 0.28, I2 = 0%; 2 studies, 206 participants; low-certainty evidence) in the first four months of life. AUTHORS' CONCLUSIONS: We are unsure if feeding healthy infants high-protein formula compared to standard-protein formula has an effect on undernutrition, overweight, or obesity. There may be little or no difference in the risk of adverse effects between infants fed with high-protein formula versus those fed with standard-protein formula. We are unsure if feeding healthy infants standard-protein formula compared to low-protein formula has any effect on undernutrition. There may be little or no difference in the risk of adverse effects between infants fed with standard-protein formula versus those fed with low-protein formula. The findings of six ongoing studies and two studies awaiting classification studies may change the conclusions of this review.

Supplementation with antioxidants and phenolic compounds in ruminant feeding and its effect on dairy products: a systematic review.

Milk and dairy products have great importance in human nutrition related to the presence of different nutrients, including protein, fatty acid profile and bioactive compounds. Dietary supplementation with foods containing these types of compounds may influence the chemical composition of milk and dairy products and hence, potentially, the consumer. Our objective was to summarize the evidence of the effect of supplementation with antioxidants and phenolic compounds in the diets of dairy animals and their effects on milk and dairy products. We conducted a systematic search in the MEDLINE/PubMed database for studies published up until July 2022 that reported on supplementation with antioxidants and phenolic compounds in diets that included plants, herbs, seeds, grains and isolated bioactive compounds of dairy animals such as cows, sheep and goats and their effects on milk and dairy products. Of the 94 studies identified in the search, only 15 met the inclusion criteria and were analyzed. The review revealed that supplementation with false flax cake, sweet grass, Acacia farnesiana, mushroom myceliated grains and sweet grass promoted an effect on the milk lipid profile, whereas supplementation with dried grape pomace and tannin extract promoted an effect on the milk and cheese lipid profiles. In six studies, the addition of Acacia farnesiana, hesperidin or naringin, durum wheat bran, mushroom myceliated grains, dried grape pomace and olive leaves increased the antioxidant activity of milk. In conclusion, supplementation with bioactive compounds had a positive impact which ranged from an increase in antioxidant capacity to a decrease in oxidative biomarkers such as malondialdehyde.

Effect of the BCAT2 polymorphism (rs11548193) on plasma branched-chain amino acid concentrations after dietary intervention in subjects with obesity and insulin resistance.

Branched-chain amino acids (BCAA) are considered markers of insulin resistance (IR) in subjects with obesity. In this study, we evaluated whether the presence of the SNP of the branched-chain aminotransferase 2 (BCAT2) gene can modify the effect of a dietary intervention (DI) on the plasma concentration of BCAA in subjects with obesity and IR. A prospective cohort study of adult subjects with obesity, BMI ≥ 30 kg/m2, homeostatic model assessment-insulin resistance (HOMA-IR ≥ 2·5) no diagnosed chronic disease, underwent a DI with an energy restriction of 3140 kJ/d and nutritional education for 1 month. Anthropometric measurements, body composition, blood pressure, resting energy expenditure, oral glucose tolerance test results, serum biochemical parameters and the plasma amino acid profile were evaluated before and after the DI. SNP were assessed by the TaqMan SNP genotyping assay. A total of eighty-two subjects were included, and fifteen subjects with a BCAT2 SNP had a greater reduction in leucine, isoleucine, valine and the sum of BCAA. Those subjects also had a greater reduction in skeletal muscle mass, fat-free mass, total body water, blood pressure, muscle strength and biochemical parameters after 1 month of the DI and adjusting for age and sex. This study demonstrated that the presence of the BCAT2 SNP promotes a greater reduction in plasma BCAA concentration after adjusting for age and sex, in subjects with obesity and IR after a 1-month energy-restricted DI.

Plants Used in Mexican Traditional Medicine for the Management of Urolithiasis: A Review of Preclinical Evidence, Bioactive Compounds, and Molecular Mechanisms.

Urolithiasis (UL) involves the formation of stones in different parts of the urinary tract. UL is a health problem, and its prevalence has increased considerably in developing countries. Several regions use plants in traditional medicine as an alternative in the treatment or prevention of UL. Mexico has known about the role of traditional medicine in the management of urinary stones. Mexican traditional medicine uses plants such as Argemone mexicana L., Berberis trifoliata Hartw. ex Lindl., Costus mexicanus Liebm, Chenopodium album L., Ammi visnaga (L.) Lam., Eysenhardtia polystachya (Ortega) Sarg., Selaginella lepidophylla (Hook. & Grev.) Spring, and Taraxacum officinale L. These plants contain different bioactive compounds, including polyphenols, flavonoids, phytosterols, saponins, furanochromones, alkaloids, and terpenoids, which could be effective in preventing the process of stone formation. Evidence suggests that their beneficial effects might be associated with litholytic, antispasmodic, and diuretic activities, as well as an inhibitory effect on crystallization, nucleation, and aggregation of crystals. The molecular mechanisms involving these effects could be related to antioxidant, anti-inflammatory, and antimicrobial properties. Thus, the review aims to summarize the preclinical evidence, bioactive compounds, and molecular mechanisms of the plants used in Mexican traditional medicine for the management of UL.

Effect of the intake of dietary protein on insulin resistance in subjects with obesity: a randomized controlled clinical trial.

PURPOSE: We compared the effect of diets with different amounts and sources of dietary protein on insulin sensitivity (IS) in subjects with obesity and insulin resistance (IR). METHODS: Eighty subjects with obesity (BMI ≥ 30 kg/m2) and IR (Matsuda index < 4.3 and HOMA-IR ≥ 2.5) over 18 years old were randomized to four groups for a one-month period: a normal protein diet (< 20%) with a predominance of animal protein (Animal NP) or vegetable protein (Vegetable NP) and a high-protein diet (25-30%) with a predominance of animal protein (Animal HP) or vegetable protein (Vegetable HP). Baseline and final measurements of body weight, body composition, biochemical parameters, blood pressure (BP), resting energy expenditure and plasma amino acid profiles were performed. RESULTS: Body weight, BMI and waist circumference decreased in all groups. Interestingly, the IS improved more in the Animal HP (Matsuda index; 1.39 vs 2.58, P = 0.003) and in the Vegetable HP groups (Matsuda index; 1.44 vs 3.14, P < 0.0001) after one month. The fat mass, triglyceride levels, C-reactive protein levels and the leptin/adiponectin index decreased; while, the skeletal muscle mass increased in the Animal and Vegetable HP groups. The BP decreased in all groups except the Animal NP group. CONCLUSION: Our study demonstrates that a high-protein hypocaloric diets improves IS by 60-90% after one month in subjects with obesity and IR, regardless of weight loss and the source of protein, either animal or vegetable. TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov (NCT03627104), August 13, 2018.

Association of BCAT2 and BCKDH polymorphisms with clinical, anthropometric and biochemical parameters in young adults.

BACKGROUND AND AIM: Circulating amino acids are modified by sex, body mass index (BMI) and insulin resistance (IR). However, whether the presence of genetic variants in branched-chain amino acid (BCAA) catabolic enzymes modifies circulating amino acids is still unknown. Thus, we determined the frequency of two genetic variants, one in the branched-chain aminotransferase 2 (BCAT2) gene (rs11548193), and one in the branched-chain ketoacid dehydrogenase (BCKDH) gene (rs45500792), and elucidated their impact on circulating amino acid levels together with clinical, anthropometric and biochemical parameters. METHODS AND RESULTS: We performed a cross-sectional comparative study in which we recruited 1612 young adults (749 women and 863 men) aged 19.7 ± 2.1 years and with a BMI of 24.9 ± 4.7 kg/m2. Participants underwent clinical evaluation and provided blood samples for DNA extraction and biochemical analysis. The single nucleotide polymorphisms (SNPs) were determined by allelic discrimination using real-time polymerase chain reaction (PCR). The frequencies of the less common alleles were 15.2 % for BCAT2 and 9.83 % for BCKDH. The subjects with either the BCAT2 or BCKDH SNPs displayed no differences in the evaluated parameters compared with subjects homozygotes for the most common allele at each SNP. However, subjects with both SNPs had higher body weight, BMI, blood pressure, glucose, and circulating levels of aspartate, isoleucine, methionine, and proline than the subjects homozygotes for the most common allele (P < 0.05, One-way ANOVA). CONCLUSION: Our findings suggest that the joint presence of both the BCAT2 rs11548193 and BCKDH rs45500792 SNPs induces metabolic alterations that are not observed in subjects without either SNP.

Oxalate Content and Antioxidant Activity of Different Ethnic Foods.

OBJECTIVE: There is not enough information on the classification of oxalate content in several foods, particularly in ethnic foods, to recommend their consumption in subjects with urolithiasis (UL). The objective of the present study was to generate reliable information on the oxalate content and antioxidant activity in different foods and classify them by very low, low, medium, high and very high oxalate content and antioxidant activity. METHODS: The oxalate content of 109 foods including ethnic foods was assessed by an enzymatic assay, and the antioxidant activity was measured by the oxygen radical absorbance capacity to determine the oxalate/antioxidant activity ratio. Oxalate consumption was then evaluated in 400 subjects with overweight and obesity using 24-h dietary recalls. RESULTS: The main foods with high oxalate content were raw spinach, huanzontle, purslane, chard, almond, and toasted and sweetened roasted amaranth. The highest antioxidant activity was found in strawberries, all types of chocolates, roselle, morita peppers, and pinolillo. Subjects with overweight or obesity exceed the dietary oxalate daily intake recommendation. CONCLUSIONS: The classification of foods by their oxalate content and antioxidant activity will be very useful to generate nutritional recommendation in different diseases, mainly UL.

Genetic, Immunological, and Clinical Features of the First Mexican Cohort of Patients with Chronic Granulomatous Disease.

PURPOSE: Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by an inability of phagocytes to produce reactive oxygen species, impairing their killing of various bacteria and fungi. We summarize here the 93 cases of CGD diagnosed in Mexico from 2011 to 2019. METHODS: Thirteen Mexican hospitals participated in this study. We describe the genetic, immunological, and clinical features of the 93 CGD patients from 78 unrelated kindreds. RESULTS: Eighty-two of the patients (88%) were male. All patients developed bacterial infections and 30% suffered from some kind of fungal infection. Fifty-four BCG-vaccinated patients (58%) presented infectious complications of BCG vaccine. Tuberculosis occurred in 29%. Granulomas were found in 56% of the patients. Autoimmune and inflammatory diseases were present in 15% of patients. A biological diagnosis of CGD was made in 89/93 patients, on the basis of NBT assay (n = 6), DHR (n = 27), and NBT plus DHR (n = 56). The deficiency was complete in all patients. The median age of biological diagnosis was 17 months (range, 0-186 months). A genetic diagnosis was made in 83/93 patients (when material was available), corresponding to CYBB (n = 64), NCF1 (n = 7), NCF2 (n = 7), and CYBA (n = 5) mutations. CONCLUSIONS: The clinical manifestations in these Mexican CGD patients were similar to those in patients elsewhere. This cohort is the largest in Latin America. Mycobacterial infections are an important cause of morbidity in Mexico, as in other countries in which tuberculosis is endemic and infants are vaccinated with BCG. X-linked CGD accounted for most of the cases in Mexico, as in other Latin American countries. However, a significant number of CYBA and NCF2 mutations were identified, expanding the spectrum of known causal mutations.

Diagnostic concordance between pediatric emergency department physicians and dermatologists in a tertiary hospital in Mexico.

BACKGROUND AND OBJECTIVES: Skin diseases are a common reason for emergency department (ED) consultations; however, few studies have focused on pediatric patients. Diagnostic consistency between ED physicians and dermatologists varies from 43% to 58%, meaning many patients seeking emergency care may receive incorrect diagnoses and treatments. We aimed to determine the diagnostic concordance between ED physicians and pediatric dermatologists. METHODS: We conducted a prospective study including all pediatric patients (<18 years) who were seen for a skin condition at the ED from December 1, 2017, to June 1, 2018, and consented to participate. We classified diagnoses according to their etiology. Patients were diagnosed by ED trainees and attending physicians, followed by blinded pediatric dermatology trainees and attending physicians. We evaluated concordance using Fleiss's kappa coefficient (κ) with a 95% confidence interval. We further stratified the data by level of training. RESULTS: We included 185 patients. Inflammatory conditions were the most common reason for consultation, followed by infections; 10 patients required hospitalization. Concordance between diagnoses given at the ED and at the dermatology clinic was moderate (κ 0.472, 95% CI: 0.389-0.455) with 62.7% agreement. Concordance between different diagnostic categories was lowest for autoimmune disorders and drug reactions (κ 0.392 with 95% CI: 0.248-0.536 and κ 0.258 with 95% CI: 0.114-0.402). CONCLUSIONS: Diagnostic concordance between ED physicians and dermatologists was moderate and differed according to training level and diagnoses. Dermatological education for ED providers, specifically focusing on autoimmune disorders and drug reactions, may improve diagnostic accuracy and patient care.

Development of a Genetic Score to Predict an Increase in HDL Cholesterol Concentration After a Dietary Intervention in Adults with Metabolic Syndrome.

BACKGROUND: Dietary intervention (DI) is a primary strategy to attenuate some of the metabolic abnormalities associated with metabolic syndrome (MetS), including low HDL cholesterol. There is no biomarker that can identify individuals who respond to DI by increasing HDL cholesterol. OBJECTIVE: The aim of this study was to assess the predictive power of a genetic predisposition score (GPS) in Mexican adults with MetS to identify HDL cholesterol responders to DI. METHODS: This study followed a prospective cohort design. Sixty-seven Mexican adults aged 20-60 y (21% men) with BMI ≥25 and ≤39.9 kg/m², who had at least 3 of 5 positive criteria for MetS, were included. Participants consumed a low saturated fat diet for 2.5 mo (<7% energy as saturated fat, <200 mg of cholesterol/d) and reduced their usual diet by ∼440 kcal/d, a reduction in total energy intake of about 25%. Anthropometry and serum biochemical markers, including HDL cholesterol, were measured before and after DI. A multilocus GPS was constructed using previously reported genetic variants associated with response to diet in subjects with MetS. GPS values, designed to predict the response of HDL cholesterol to the DI, were computed for each individual as the sum of the number of effect alleles across 14 SNPs. RESULTS: Individuals were dichotomized as high and low GPS according to median GPS (-2.12) and we observed a difference in HDL cholesterol changes on DI of +3 mg/dL (6.3%) in subjects with low GPS, whereas those with high GPS had HDL cholesterol decreases of -3 mg/dL (-7.9%) (P = 0.04). CONCLUSIONS: Individuals with low GPS showed greater increases in their HDL cholesterol than those with high GPS. Therefore, the GPS can be useful for predicting the HDL cholesterol response to diet.

Effects of Egg Consumption and Choline Supplementation on Plasma Choline and Trimethylamine-N-Oxide in a Young Population.

Background: Plasma trimethylamine-N-oxide (TMAO) concentrations have been associated with cardiovascular disease risk. Eggs are a rich source of choline, which is a precursor of TMAO.Objective: The effects of egg intake versus daily choline supplementation were evaluated on plasma choline and TMAO in a young, healthy population.Methods: Thirty participants (14 males, 16 females; 25.6 ± 2.3 years; body mass index = 24.3 ± 2.9 kg/m2) were enrolled in this 13-week crossover intervention. After a 2-week washout, participants were randomized to consume either 3 eggs/d or a choline bitartrate supplement (∼ 400 mg choline total in eggs or supplement) for 4 weeks. Following a 3-week washout, participants were switched to the alternate treatment. Dietary records were measured at the end of each period. Plasma TMAO and choline were measured at baseline and at the end of each dietary intervention. Gene expression of scavenger receptors associated with plasma TMAO were quantified at the end of each intervention.Results: Compared to the choline supplement, intake of total fat, cholesterol, selenium, and vitamin E were higher (p < 0.05), whereas carbohydrate intake was lower (p < 0.001) with consumption of 3 eggs/d. Fasting plasma choline increased 20% (p = 0.023) with egg intake, while no changes were observed with choline supplementation. Plasma TMAO levels were not different between dietary treatments or compared to baseline.Conclusions: Dietary choline appears to be more bioavailable via egg consumption when compared to a choline supplement. Plasma TMAO concentrations were not affected in healthy participants after 4 weeks of taking ∼400 mg/d choline either via eggs or choline supplementation.

Compared to an Oatmeal Breakfast, Two Eggs/Day Increased Plasma Carotenoids and Choline without Increasing Trimethyl Amine N-Oxide Concentrations.

BACKGROUND: Habitual consumption of eggs has been hypothesized to positively modify biomarkers of cardiovascular disease risk through proposed antioxidant properties. OBJECTIVES: To examine this relationship, 50 young, healthy men and women were enrolled into a randomized crossover clinical intervention. METHODS: Participants consumed either 2 eggs per day or one packet of oatmeal a day for 4 weeks, followed by a 3-week wash-out and crossed over to the alternate breakfast. Fasting blood samples and peripheral blood mononuclear cells (PBMCs) were collected at the end of each intervention period. RESULTS: Increases in plasma large high-density lipoprotein (HDL) and large low-density lipoprotein (LDL) particle concentrations as measured by nuclear magnetic resonance were found following egg consumption (p < 0.001, p < 0.05), respectively, with increases in apolipoprotein concentration as well (p < 0.05). Though there was no difference in the intake of antioxidants lutein and zeaxanthin, a significant increase in plasma concentrations of these carotenoids was observed (p < 0.001) after egg consumption. There was no change in lecithin-cholesterol acyl transferase, cholesteryl ester transfer protein, or paroxanase-1 arylesterase activities between breakfast interventions. Dietary and plasma choline were both higher following egg consumption compared to oatmeal consumption (p < 0.001); however, there was no change in plasma trimethylamine N-oxide (TMAO) concentrations. Two eggs per day had no impact on PBMC gene expression related to cholesterol metabolism, oxidation, or TMAO production. CONCLUSIONS: These results suggest that compared to oatmeal, consumption of 2 eggs for breakfast provided increased plasma carotenoids and improved biomarkers of cardiovascular disease (CVD) risk while not affecting TMAO levels in this population.

Soya protein stimulates bile acid excretion by the liver and intestine through direct and indirect pathways influenced by the presence of dietary cholesterol.

Several studies using different animal models have demonstrated that the consumption of soya protein (SP) reduces serum cholesterol concentrations by increasing the excretion of bile acids (BA). However, the mechanism by which SP enhances BA excretion is not fully understood. Therefore, the aim of the present study was to determine whether the consumption of SP regulates the expression of key enzymes involved in hepatic BA synthesis and the transporters involved in reverse cholesterol transport (RCT) via fibroblast growth factor 15 (FGF15) and/or small heterodimer protein (SHP) in rats. To achieve this aim, four groups of rats were fed experimental diets containing 20 % casein (C) or SP with or without the addition of 0·2 % cholesterol and the expression of hepatic genes involved in BA synthesis and the ileal and hepatic RCT was measured. Rats fed the SP diet had higher concentrations of ileal FGF15 and hepatic FGF15 receptor (FGFR4) and increased expression of SHP and liver receptor homolog 1 (LRH1) than those fed the C diet; as a result, the excretion of faecal BA was greater. The addition of cholesterol to the diet repressed the protein abundance of FGF15 and FGFR4; however, SP increased the expression of SHP and LRH1 to a lesser extent. Nonetheless, the expression of ABCG5/8 was increased in the intestine of rats fed the SP diet, and the effect was enhanced by the addition of cholesterol to the diet. In conclusion, SP in the presence of cholesterol increases BA synthesis via the repressions of FGF15 and SHP and accelerates BA excretion to prevent cholesterol overload in the enterocytes by increasing RCT.

Responsiveness to Change of the Morphea Activity Measure in Pediatric Patients.

Importance: Detecting activity of morphea can be complex but is crucial for adequate treatment and outcome assessment. The Morphea Activity Measure (MAM) was recently validated, but its responsiveness to change in disease activity has not been studied. Objective: To evaluate the internal and external responsiveness of MAM to changes in disease activity in pediatric patients. Design, Setting, and Participants: This multicenter prospective, longitudinal prognostic study was performed from October 2021 to January 2023 at 4 pediatric referral centers in North America. Consecutive pediatric patients with morphea who were available for data collection at baseline and at a follow-up visit at least 3 months later were studied. Exposure: Patient demographics, clinical characteristics, and measurements of disease activity collected at baseline and the subsequent visit. Main Outcome and Measures: Responsiveness of MAM to disease activity according to the modified Localized Scleroderma Severity Index (mLoSSI), the Physician Global Assessment (PGA), and a patient and parent global assessment (PtGA) was analyzed using mean and percentage change, standardized effect size, and standardized response mean (SRM) from baseline to follow-up 3 or more months later. Differences between patients whose activity improved vs did not improve were evaluated using the Mann-Whitney U test. The correlation between percentage change in MAM score and mLoSSI, the PGA, and the PtGA was calculated using Spearman rank correlation. Results: A total of 43 patients (mean [SD] age at onset, 7.11 [3.18] years; 26 [60.5%] female) were included. The mean change and percentage change in MAM score were significantly larger in those whose disease activity improved by the PGA (mean: -18.75 [95% CI, -31.92 to -5.57] vs 2.73 [95% CI, -1.97 to 7.45]; percentage: -108.08% [95% CI, -155.21% to -60.95%] vs -24.11% [95% CI, -81.22% to 32.99%]) and by mLoSSI (mean: -24.15 [95% CI, -41.89 to -6.41] vs -1.30 [95% CI, -8.50 to 5.70]; percentage: -172.06% [95% CI, -263.68% to -80.45%] vs -21.57% [95% CI, -48.13% to 4.97%]) than in those whose activity did not change. The SRM of MAM was significantly different between groups for both measures; the responsiveness was large in those whose activity decreased by the PGA (-0.75 [95% CI, -1.29 to -0.22]) and mLoSSI (-0.97 [95% CI, -1.69 to -0.25]) and none to small in those whose activity did not change by the PGA (0.11 [95% CI, -0.08 to 0.30]) or mLoSSI (-0.05 [95% CI, -0.34 to 0.23]). Percentage change in MAM score correlated strongly and significantly with change in mLoSSI (ρ = 0.69; P < .001) and PGA (ρ = 0.65; P < .001), but there was no correlation with change in the PtGA (ρ = 0.26; P = .09). Conclusions and Relevance: In this prognostic study, MAM was found to be internally and externally responsive to changes in disease activity. Further evaluation in mixed cohorts of all ages and specialties is needed.

Intermittent fasting, calorie restriction, and a ketogenic diet improve mitochondrial function by reducing lipopolysaccharide signaling in monocytes during obesity: A randomized clinical trial.

BACKGROUND: Mitochondrial dysfunction occurs in monocytes during obesity and contributes to a low-grade inflammatory state; therefore, maintaining good mitochondrial conditions is a key aspect of maintaining health. Dietary interventions are primary strategies for treating obesity, but little is known about their impact on monocyte bioenergetics. Thus, the aim of this study was to evaluate the effects of calorie restriction (CR), intermittent fasting (IF), a ketogenic diet (KD), and an ad libitum habitual diet (AL) on mitochondrial function in monocytes and its modulation by the gut microbiota. METHODS AND FINDINGS: A randomized controlled clinical trial was conducted in which individuals with obesity were assigned to one of the 4 groups for 1 month. Subsequently, the subjects received rifaximin and continued with the assigned diet for another month. The oxygen consumption rate (OCR) was evaluated in isolated monocytes, as was the gut microbiota composition in feces and anthropometric and biochemical parameters. Forty-four subjects completed the study, and those who underwent CR, IF and KD interventions had an increase in the maximal respiration OCR (p = 0.025, n2p = 0.159 [0.05, 0.27] 95% confidence interval) in monocytes compared to that in the AL group. The improvement in mitochondrial function was associated with a decrease in monocyte dependence on glycolysis after the IF and KD interventions. Together, diet and rifaximin increased the gut microbiota diversity in the IF and KD groups (p = 0.0001), enriched the abundance of Phascolarctobacterium faecium (p = 0.019) in the CR group and Ruminococcus bromii (p = 0.020) in the CR and KD groups, and reduced the abundance of lipopolysaccharide (LPS)-producing bacteria after CR, IF and KD interventions compared to the AL group at the end of the study according to ANCOVA with covariate adjustment. Spearman's correlation between the variables measured highlighted LPS as a potential modulator of the observed effects. In line with this findings, serum LPS and intracellular signaling in monocytes decreased with the three interventions (CR, p = 0.002; IF, p = 0.001; and KD, p = 0.001) compared to those in the AL group at the end of the study. CONCLUSIONS: We conclude that these dietary interventions positively regulate mitochondrial bioenergetic health and improve the metabolic profile of monocytes in individuals with obesity via modulation of the gut microbiota. Moreover, the evaluation of mitochondrial function in monocytes could be used as an indicator of metabolic and inflammatory status, with potential applications in future clinical trials. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (NCT05200468).

Genetic risk score for insulin resistance based on gene variants associated to amino acid metabolism in young adults.

Circulating concentration of arginine, alanine, aspartate, isoleucine, leucine, phenylalanine, proline, tyrosine, taurine and valine are increased in subjects with insulin resistance, which could in part be attributed to the presence of single nucleotide polymorphisms (SNPs) within genes associated with amino acid metabolism. Thus, the aim of this work was to develop a Genetic Risk Score (GRS) for insulin resistance in young adults based on SNPs present in genes related to amino acid metabolism. We performed a cross-sectional study that included 452 subjects over 18 years of age. Anthropometric, clinical, and biochemical parameters were assessed including measurement of serum amino acids by high performance liquid chromatography. Eighteen SNPs were genotyped by allelic discrimination. Of these, ten were found to be in Hardy-Weinberg equilibrium, and only four were used to construct the GRS through multiple linear regression modeling. The GRS was calculated using the number of risk alleles of the SNPs in HGD, PRODH, DLD and SLC7A9 genes. Subjects with high GRS (≥ 0.836) had higher levels of glucose, insulin, homeostatic model assessment- insulin resistance (HOMA-IR), total cholesterol and triglycerides, and lower levels of arginine than subjects with low GRS (p < 0.05). The application of a GRS based on variants within genes associated to amino acid metabolism may be useful for the early identification of subjects at increased risk of insulin resistance.

Ecthyma gangrenosum in pediatric patients: 10-year experience at the National Institute of Pediatrics.

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.