The Relationship between the Source of Protein Intake and Obesity Risk in Children

Background: Previous research has reported a relationship between high protein intake (\u3e15% of energy) during early childhood and an increased risk of obesity later in life. However, few studies have investigated this relationship during middle childhood to early adolescence or examined the effects of different sources of protein. Objective: The aim of this study was to investigate the relationship between the source of protein intake (animal vs. plant) and body mass index (BMI) in children between the ages 6-14 years. Participants/setting: 285 healthy 6-14 year old (male n=154) Caucasian and African American (n=171) children from Pittsburgh, Pennsylvania completed a food frequency questionnaire. Main outcome measures: Median protein intake (grams) by total, animal, and plant protein and BMI-for-age classification. Statistical analysis: The Kruskal-Wallis test was used to evaluate differences in median protein intake (grams) by weight classification (normal weight [BMI 5th%ile to \u3c85th%ile], overweight [BMI 85th%tile to \u3c95th%tile], obese [BMI \u3e95th%tile]). Correlation statistics were also conducted to examine the relationship between protein intake and BMI. Results: The population used in the data analysis included 285 children/early adolescents (median age 9.8 ± 2.1 years; 53% boys; 40% Caucasian). Data from 11 children were excluded due to outliers or missing data. Girls had a significantly higher BMI than boys (20.1 vs. 18.2 kg/m2, respectively; P=P=P= Conclusions: We observed a significant curvilinear versus linear trend in total protein and animal and plant protein intake by weight classification in middle-aged children that may be due to under-reporting in overweight and obese children. Total percent protein intake was significantly higher in children of normal weight. Future longitudinal studies using multiple measures of body fatness should be conducted to determine the relationship between protein intake and BMI during middle childhood to early adolescence

The Effect of Intact Protein from Foods and Phenylalanine Free Medical Foods on Large Neutral Amino Acids in Patients with Phenylketonuria.

Objective: The primary aim of this retrospective cohort study was to determine the association between the source of dietary protein intake and the sum of plasma concentration of large neutral amino acids (LNAA) in patients with Phenylketonuria (PKU). A secondary aim of the study was to examine the effect of dietary compliance on plasma concentration of LNAA. Methods: The analysis included combined participant data from two previous studies conducted at the Emory University School of Medicine. Subjects are males (n=34) and females (n=43) with PKU ages 4-50 years. A Student t-test was used to compare total combined plasma LNAA (excluding tryptophan and phenylalanine) by dietary compliance status (alpha=0.05). Correlation statistics were used to determine the association between the ratio of reported intact food protein to medical food protein on plasma levels of LNAA. Multiple regression analysis was used to examine the contribution of intact protein to medical food protein ratio and other variables to plasma LNAA. Results: The median ratio of intact protein to medical food protein reported was 0.354 (IQR: 0.188, 0.914). Median percent of PHE intake over the PHE intake recommendation was 31.64 (Interquartile range [IQR]; 7.44, 104.98). Plasma concentration of LNAA did not differ significantly between those with plasma PHE levels within the therapeutic range μmol/L (compliant; 611.7 μmol/L [n=19]) vs levels above the therapeutic range (non-compliant; 595.3 μmol/L [n=47]); p=0.613). There was an inverse marginal correlation between the ratio of intact protein to medical food protein and plasma concentration of LNAA for those who were compliant (r = -0.436, r = 0.1) although the association was not statistically significant (p=0.08). No correlation was found for patients who were non-compliant. Regression analysis revealed that plasma concentration of LNAA was not significantly affected by the ratio of intact protein to medical food protein ratio, age, or gender. Conclusions: Although not statistically significant, a negative trend was observed between plasma LNAA concentration and the intact protein to medical food protein ratio in patients compliant with the PHE prescription. This suggests that the ratio of intact dietary protein to protein coming from medical food, as reported by patient diet records, may promote increased plasma LNAA levels in the effective treatment of PKU. The majority of the sample (74%) were non-compliant with diet based on plasma PHE levels. Future studies are needed to determine the consequences of non-compliance by decreased intake of medical food protein or increased intake of intact protein on plasma LNAA concentration and downstream health effects

Practical recommendations for fertility preservation in women by the FertiPROTEKT network. Part I: Indications for fertility preservation.

PURPOSE Most guidelines about fertility preservation are predominantly focused on scientific evidence, but are less practically orientated. Therefore, practically oriented recommendations are needed to support the clinician in daily practice. METHODS A selective literature search was performed based on the clinical and scientific experience of the authors, focussing on the most relevant diseases and gynaecological cancers. This article (Part I) provides information on topics that are essential for the fertility preservation indication, such as disease prognosis, disease therapy and its associated risks to fertility, recommending disease-specific fertility preservation measures. Part II specifically focusses on fertility preservation techniques. RESULTS In breast cancer patients, fertility preservation such as ovarian tissue and oocyte cryopreservation is especially recommended in low-stage cancer and in women < 35 years of age. In Hodgkin's lymphoma, the indication is mainly based on the chemotherapy regime as some therapies have very low, others very high gonadotoxicity. In borderline ovarian tumours, preservation of fertility usually is achieved through fertility sparing surgery, ovarian stimulation may also be considered. In cervical cancer, endometrial cancer, rheumatic diseases and other malignancies such as Ewing sarcoma, colorectal carcinoma, non-Hodgkin lymphoma, leukaemia etc., several other factors must be considered to enable an individual, stage-dependent decision. CONCLUSION The decision for or against fertility preservation depends on the prognosis, the risks to fertility and individual factors such as prospective family planning

“Take Off 4-Health�: Nutrition Education Curriculum for a Healthy Lifestyle Camp for Overweight Youth

There is evidence that residential summer weight loss camps can be effective to initiate or support the small change approach to address childhood obesity. This report describes the development and evaluation of nutrition education for overweight adolescents attending a three week healthy lifestyle camp. Campers were given a diet prescription based on MyPryamid and self-selected their meals and snacks that were served family style. The curriculum included eating strategies known to contribute to healthy weight in youth. Campers demonstrated improved ability to estimate portion sizes. Thirty-four campers completed the three week experience with a weight loss considered to be safe. Note: the deposited item is not the final published version, but rather is the last revised manuscript sent to the publisher

Whole Exome Sequencing Identifies Rare Protein-Coding Variants in Behçet's Disease

Behçet's disease (BD) is a systemic inflammatory disease with an incompletely understood etiology. Despite the identification of multiple common genetic variants associated with BD, rare genetic variants have been less explored. We undertook this study to investigate the role of rare variants in BD by performing whole exome sequencing in BD patients of European descent. METHODS: Whole exome sequencing was performed in a discovery set comprising 14 German BD patients of European descent. For replication and validation, Sanger sequencing and Sequenom genotyping were performed in the discovery set and in 2 additional independent sets of 49 German BD patients and 129 Italian BD patients of European descent. Genetic association analysis was then performed in BD patients and 503 controls of European descent. Functional effects of associated genetic variants were assessed using bioinformatic approaches. RESULTS: Using whole exome sequencing, we identified 77 rare variants (in 74 genes) with predicted protein-damaging effects in BD. These variants were genotyped in 2 additional patient sets and then analyzed to reveal significant associations with BD at 2 genetic variants detected in all 3 patient sets that remained significant after Bonferroni correction. We detected genetic association between BD and LIMK2 (rs149034313), involved in regulating cytoskeletal reorganization, and between BD and NEIL1 (rs5745908), involved in base excision DNA repair (P = 3.22 × 10(-4) and P = 5.16 × 10(-4) , respectively). The LIMK2 association is a missense variant with predicted protein damage that may influence functional interactions with proteins involved in cytoskeletal regulation by Rho GTPase, inflammation mediated by chemokine and cytokine signaling pathways, T cell activation, and angiogenesis (Bonferroni-corrected P = 5.63 × 10(-14) , P = 7.29 × 10(-6) , P = 1.15 × 10(-5) , and P = 6.40 × 10(-3) , respectively). The genetic association in NEIL1 is a predicted splice donor variant that may introduce a deleterious intron retention and result in a noncoding transcript variant. CONCLUSION: We used whole exome sequencing in BD for the first time and identified 2 rare putative protein-damaging genetic variants associated with this disease. These genetic variants might influence cytoskeletal regulation and DNA repair mechanisms in BD and might provide further insight into increased leukocyte tissue infiltration and the role of oxidative stress in BD

HIV-1 Protease Inhibitors Incorporating Stereochemically Defined P2′ Ligands to Optimize Hydrogen Bonding in the Substrate Envelope

A structure-guided design strategy was used to improve the resistance profile of HIV-1 protease inhibitors by optimizing hydrogen bonding and van der Waals interactions with the protease while staying within the substrate envelope. Stereoisomers of 4-(1-hydroxyethyl)benzene and 4-(1,2-dihydroxyethyl)benzene moieties were explored as P2′ ligands providing pairs of diastereoisomers epimeric at P2′, which exhibited distinct potency profiles depending on the configuration of the hydroxyl group and size of the P1′ group. While compounds with the 4-(1-hydroxyethyl)benzene P2′ moiety maintained excellent antiviral potency against a panel of multidrug-resistant HIV-1 strains, analogues with the polar 4-(1,2-dihydroxyethyl)benzene moiety were less potent, and only the (R)-epimer incorporating a larger 2-ethylbutyl P1′ group showed improved potency. Crystal structures of protease-inhibitor complexes revealed strong hydrogen bonding interactions of both (R)- and (S)-stereoisomers of the hydroxyethyl group with Asp30′. Notably, the (R)-dihydroxyethyl group was involved in a unique pattern of direct hydrogen bonding interactions with the backbone amides of Asp29′ and Asp30′. The SAR data and analysis of crystal structures provide insights for optimizing these promising HIV-1 protease inhibitors. © 2019 American Chemical Society