Plant-based proteins: clinical and technological importance.

Healthy and sustainable diets have seen a surge in popularity in recent years, driven by a desire to consume foods that not only help health but also have a favorable influence on the environment, such as plant-based proteins. This has created controversy because plant-based proteins may not always contain all the amino acids required by the organism. However, protein extraction methods have been developed due to technological advancements to boost their nutritional worth. Furthermore, certain chemicals, such as bioactive peptides, have been identified and linked to favorable health effects. As a result, the current analysis focuses on the primary plant-based protein sources, their chemical composition, and the molecular mechanism activated by the amino acid types of present. It also discusses plant protein extraction techniques, bioactive substances derived from these sources, product development using plant protein, and the therapeutic benefits of these plant-based proteins in clinical research.

Acute Effects of Dietary Protein Consumption on the Postprandial Metabolic Response, Amino Acid Levels and Circulating MicroRNAs in Patients with Obesity and Insulin Resistance.

The post-nutritional intervention modulation of miRNA expression has been previously investigated; however, post-acute dietary-ingestion-related miRNA expression dynamics in individuals with obesity and insulin resistance (IR) are unknown. We aimed to determine the acute effects of protein ingestion from different dietary sources on the postprandial metabolic response, amino acid levels, and circulating miRNA expression in adults with obesity and IR. This clinical trial included adults with obesity and IR who consumed (1) animal-source protein (AP; calcium caseinate) or (2) vegetable-source protein (VP; soy protein isolate). Glycaemic, insulinaemic, and glucagon responses, amino acid levels, and exosomal microRNAs isolated from plasma were analysed. Post-AP ingestion, the area under the curve (AUC) of insulin (p = 0.04) and the plasma concentrations of branched-chain (p = 0.007) and gluconeogenic (p = 0.01) amino acids increased. The effects of different types of proteins on the concentration of miRNAs were evaluated by measuring their plasma circulating levels. Compared with the baseline, the AP group presented increased circulating levels of miR-27a-3p, miR-29b-3p, and miR-122-5p (p < 0.05). Subsequent analysis over time at 0, 30, and 60 min revealed the same pattern and differences between treatments. We demonstrated that a single dose of dietary protein has acute effects on hormonal and metabolic regulation and increases exosomal miRNA expression in individuals with obesity and IR.

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).

Influence of familial forms of inflammatory bowel disease on the use of immunosuppressants, biological agents, and surgery in the era of biological therapies. Results from the ENEIDA project.

BACKGROUND AND AIMS: Familial inflammatory bowel disease (IBD) history is a controversial prognostic factor in IBD. We aimed to evaluate the impact of a familial history of IBD on the use of medical and surgical treatments in the biological era. METHODS: Patients included in the prospectively maintained ENEIDA database and diagnosed with IBD after 2005 were included. Familial forms were defined as those cases with at least one first-degree relative diagnosed with IBD. Disease phenotype, the use of biological agents, or surgical treatments were the main outcomes. RESULTS: A total of 5263 patients [2627 Crohn's disease (CD); 2636 ulcerative colitis (UC)] were included, with a median follow-up of 31 months. Of these, 507 (10%) corresponded to familial forms. No clinical differences were observed between familial and sporadic IBD forms except a lower age at IBD diagnosis and a higher rate of males in familial forms of UC. In CD, the proportions of patients treated with thiopurines (54.4% vs 46.7%; P = .015) and survival time free of thiopurines (P = .009) were lower in familial forms. No differences were found regarding the use of biological agents. Concerning surgery, a higher rate of intestinal resections was observed in sporadic CD (14.8% vs 9.9%, P = .027). No differences were observed in UC. CONCLUSIONS: In the era of biological therapies, familial and sporadic forms of IBD show similar phenotypes and are managed medically in a similar way; whether these is due to lack of phenotypical differences or an effect of biological therapies is uncertain. What is already known on this topic: IBD's etiopathogenesis points to an interaction between environmental and genetic factors, being familial history a controversial prognostic factor. Biological agents use and need for surgery regarding familial or sporadic forms of IBDs present conflicting results. What this study adds: Familial and sporadic forms of IBD have similar phenotypes and are managed medically and surgically in a similar way. How this study might affect research, practice or policy: Familial aggregation should not be considered a factor associated with more aggressive disease.

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.

Need for therapeutic escalation in patients with refractory ulcerative proctitis: Results from the PROCU study of the ENEIDA registry.

BACKGROUND: Ulcerative proctitis (UP) can have a milder, less aggressive course than left-sided colitis or extensive colitis. Therefore, immunosuppressants tend to be used less in patients with this condition. Evidence, however, is scarce because these patients are excluded from randomised controlled clinical trials. Our aim was to describe the characteristics of patients with refractory UP and their disease-related complications, and to identify the need for immunosuppressive therapies. METHODS: We identified patients with UP from the prospective ENEIDA registry sponsored by the GETECCU. We evaluated socio-demographic data and complications associated with immunosuppression. We defined immunosuppression as the use of immunomodulators, biologics and/or small molecules. We used logistic regression to identify factors associated with immunosuppressive therapy. RESULTS: From a total of 34,716 patients with ulcerative colitis, we identified 6281 (18.1%) with UP; mean ± SD age 53 ± 15 years, average disease duration of 12 ± 9 years. Immunosuppression was prescribed in 11% of patients, 4.2% needed one biologic agent and 1% needed two; 2% of patients required hospitalisation, and 0.5% underwent panproctocolectomy or subtotal colectomy. We identified 0.2% colorectal tumours and 5% extracolonic tumours. Patients with polyarthritis (OR 3.56, 95% CI 1.86-6.69; p < 0.001) required immunosuppressants. CONCLUSIONS: Among patients with refractory UP, 11% required immunosuppressant therapy, and 4.2% required at least one biologic agent.

MRI features indicative of permanent colon damage in ulcerative colitis: an exploratory study.

BACKGROUND AND AIMS: It is uncertain whether ulcerative colitis leads to accumulated bowel damage on cross sectional image. We aimed to characterize bowel damage in patients with ulcerative colitis using magnetic resonance imaging and determine its relation with duration of disease and the impact on patients' quality of life. METHODS: In this prospective study, subjects with ulcerative colitis in endoscopic remission underwent MRI without bowel cleansing and completed quality-of-life questionnaires. Subjects' magnetic resonance findings were analyzed considering normal values and thresholds determined in controls with no history of inflammatory bowel disease (n=40) and in patients with Crohn's disease with no history of colonic involvement (n=12). Subjects with UC were stratified according to disease duration (<7 years vs. 7‒14 years vs. >14 years). RESULTS: We analyzed 41 subjects with ulcerative colitis [20 women; Mayo endoscopic subscore 0 in 38 (92.7%) and 1 in 3 (7.3%)]. Paired segment-by-segment comparison of magnetic resonance findings in colonic segments documented of being affected by ulcerative colitis versus controls showed subjects with ulcerative colitis had decreased cross-sectional area (p≤0.0034) and perimeter (p≤0.0005), and increased wall thickness (p=0.026) in all segments. Colon damage, defined as wall thickness ≥3 mm, was seen in 22 (53.7%) subjects. Colon damage was not associated with disease duration or quality of life. CONCLUSIONS: Morphologic abnormalities in the colon were highly prevalent in patients with ulcerative colitis in the absence of inflammation. Structural bowel damage was not associated with disease duration or quality of life.

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.

A Smartphone App for Real-Time Assessment of Malaria Prophylaxis Adverse Events.

Background: Growth of international travel to malarial areas over the last decades has contributed to more travelers taking malaria prophylaxis. Travel-related symptoms may be wrongly attributed to malaria prophylaxis and hinder compliance. Here, we aimed to assess the frequency of real-time reporting of symptoms by travelers following malaria prophylaxis using a smartphone app. Method: Adult international travelers included in this single-center study (Barcelona, Spain) used the smartphone Trip Doctor® app developed by our group for real-time tracking of symptoms and adherence to prophylaxis. Results: Six hundred four (n = 604) international travelers were included in the study; 74.3% (449) used the app daily, and for one-quarter of travelers, malaria prophylaxis was prescribed. Participants from the prophylaxis group traveled more to Africa (86.7% vs. 4.3%; p < 0.01) and to high travel medical risk countries (60.8% vs. 18%; p < 0.01) and reported more immunosuppression (30.8% vs. 23.1% p < 0.01). Regarding symptoms, no significant intergroup differences were observed, and no relationship was found between the total number of malarial pills taken and reported symptoms. Conclusions: In our cohort, the number of symptoms due to malaria prophylaxis was not significantly higher than in participants for whom prophylaxis was not prescribed, and the overall proportion of symptoms is higher compared with other studies.

Clinical and treatment outcomes of a second subcutaneous or intravenous anti-TNF in patients with ulcerative colitis treated with two consecutive anti-TNF agents: data from the ENEIDA registry.

Background: Infliximab seems to be the most efficacious of the three available anti-TNF agents for ulcerative colitis (UC) but little is known when it is used as the second anti-TNF. Objectives: To compare the clinical and treatment outcomes of a second subcutaneous or intravenous anti-TNF in UC patients. Design: Retrospective observational study. Methods: Patients from the ENEIDA registry treated consecutively with infliximab and a subcutaneous anti-TNF (or vice versa), naïve to other biological agents, were identified and grouped according to the administration route of the first anti-TNF into IVi (intravenous initially) or SCi (subcutaneous initially). Results: Overall, 473 UC patients were included (330 IVi and 143 SCi). Clinical response at week 14 was 42.7% and 48.3% in the IVi and SCi groups (non-statistically significant), respectively. Clinical remission rates at week 52 were 32.8% and 31.4% in the IVi and SCi groups (nonsignificant differences), respectively. A propensity-matched score analysis showed a higher clinical response rate at week 14 in the SCi group and higher treatment persistence in the IVi group. Regarding long-term outcomes, dose escalation and discontinuation due to the primary failure of the first anti-TNF and more severe disease activity at the beginning of the second anti-TNF were inversely associated with clinical remission. Conclusion: The use of a second anti-TNF for UC seems to be reasonable in terms of efficacy, although it is particularly reduced in the case of the primary failure of the first anti-TNF. Whether the second anti-TNF is infliximab or subcutaneous does not seem to affect efficacy.

OBJECTIVES: To compare the clinical and treatment outcomes of a second subcutaneous or intravenous anti-TNF in UC patients. DESIGN: Retrospective observational study. METHODS: Patients from the ENEIDA registry treated consecutively with infliximab and a subcutaneous anti-TNF (or vice versa), naïve to other biological agents, were identified and grouped according to the administration route of the first anti-TNF into IVi (intravenous initially) or SCi (subcutaneous initially). RESULTS: Overall, 473 UC patients were included (330 IVi, 143 SCi). Clinical response at week 14 was 42.7% and 48.3% in the IVi and SCi groups (non-statistically significant), respectively. Clinical remission rates at week 52 were 32.8% and 31.4%, in the IVi and SCi groups (nonsignificant differences), respectively. A propensity-matched score analysis showed a higher clinical response rate at week 14 in the SCi group and higher treatment persistence in the IVi group. Regarding long-term outcomes, dose escalation and discontinuation due to the primary failure of the first anti-TNF and more severe disease activity at the beginning of the second anti-TNF were inversely associated with clinical remission. CONCLUSION: The use of a second anti-TNF for UC seems to be reasonable in terms of efficacy, although it is particularly reduced in the case of the primary failure of the first anti-TNF. Whether the second anti-TNF is infliximab or subcutaneous does not seem to affect efficacy.

Clinical and treatment outcomes of a second subcutaneous or intravenous anti-TNF in patients with ulcerative colitis treated with two consecutive anti-TNF agents. Data from the ENEIDA registry Background: Infliximab seems to be the most efficacious of the three available anti-TNF agents for ulcerative colitis (UC), but little is known when it is used as the second anti-TNF.

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.

Modulation of MicroRNAs and Exosomal MicroRNAs after Dietary Interventions for Obesity and Insulin Resistance: A Narrative Review.

MicroRNAs (miRNAs) are small noncoding RNAs approximately 22 nucleotides in length. Their main function is to regulate gene expression at the posttranscriptional level by inhibiting the translation of messenger RNAs (mRNAs). miRNAs originate in the cell nucleus from specific genes, where they can perform their function. However, they can also be found in serum, plasma, or other body fluids travelling within vesicles called exosomes and/or bound to proteins or other particles such as lipoproteins. miRNAs can form complexes outside the cell where they are synthesized, mediating paracrine and endocrine communication between different tissues. In this way, they can modulate the gene expression and function of distal cells. It is known that the expression of miRNAs can be affected by multiple factors, such as the nutritional or pathological state of the individual, or even in conditions such as obesity, insulin resistance, or after any dietary intervention. In this review, we will analyse miRNAs whose expression and circulation are affected in conditions of obesity and insulin resistance, as well as the changes generated after a dietary intervention, with the purpose of identifying new possible biomarkers of early response to nutritional treatment in these conditions.

Embarazo en la adolescencia y su relación con el recién nacido bajo peso / Pregnancy in adolescence and its relationship with low birth weight newborn

Se realizó una investigación retrospectiva en el área del Policlínico Comunitario "Ernesto Guevara de la Serna", de Mir, en el municipio Calixto García, durante el quinquenio de 1994-1998. Nuestro universo estuvo representado por 95 embarazadas adolescentes y sus recién nacidos, y la muestra quedó conformada por 90 embarazadas adolescentes y 16 recién nacidos bajo peso. Este trabajo se realizó por la incidencia de bajo peso al nacer en nuestra área, con el propósito de identificar la relación existente entre el bajo peso al nacer y el embarazo en la adolescencia. Después de una explicación detallada al personal de Estadísticas sobre la necesidad de realizar este trabajo, obtuvimos su consentimiento para recolectar la información; se revisaron los carnés obstétricos y el libro de registros de nacimiento. Los datos obtenidos fueron procesados de forma manual y se observó que las adolescentes presentaron el 18 (por ciento) de recién nacidos con bajo peso. Todas las variables estudiadas estuvieron asociadas significativamente con el bajo peso al nacer y fueron identificadas como factores de riesgo con influencia marcada: en relación con la paridad de las gestantes adolescentes encontramos que las pacientes con un solo parto fueron las que aportaron más bajo peso al nacer y que el grado de escolaridad primaria terminada fue el nivel que más recién nacidos bajo peso aportó; la sepsis vaginal, seguida de las modificaciones cervicales, fueron las complicaciones que más predominaron en el resultado del bajo peso al nacer(AU)

A retrospective research study was carried out from 1994 to 1998 in "Ernesto Guevara de la Serna" community polyclinics located in Mir, Calixto García municipality. Our universe of study was represented by 95 pregnant adolescents and their infants and the sample taken was made up of 90 pregnant adolescents and 16 low birth weight newborns. Due to the incidence of low birth weight in our health area, this paper was conducted to find out the relation between low birth weight and pregnancy in adolescence. After having thoroughly explained the need for this study to the Statistics Department staff, we obtained their consent to gather information; obstetric cards and birth records were reviewed for this end. Data were manually processed. It was observed that adolescents presented 18 percent of low birth newborn. All the studied variables were significantly associated with the low birth weight and the following were identified as marked influential risk factors: as to parity of pregnant adolescents, we found that patients with only one pregnancy were the ones that had infants with the lowest birth weight and that adolescents who had only finished their elementary school were the ones that showed the highest number of low birth weight infants; also, vaginal sepsis and cervical changes were the predominant complications as a result of low birth weight(AU)