Fatty Acid Transfer from Blood to Milk Is Disrupted in Mothers with Low Milk Production, Obesity, and Inflammation.

BACKGROUND: Obesity is associated with chronic inflammation and is a risk factor for insufficient milk production. Inflammation-mediated suppression of LPL could inhibit mammary uptake of long-chain fatty acids (LCFAs; >16 carbons). OBJECTIVES: In an ancillary case-control analysis, we investigated whether women with low milk production despite regular breast emptying have elevated inflammation and disrupted transfer of LCFAs from plasma into milk. METHODS: Data and specimens from a low milk supply study and an exclusively breastfeeding control group were analyzed, with milk production measured by 24-h test-weighing at 2-10 wk postpartum. Low milk supply groups were defined as very low (VL; <300 mL/d; n = 23) or moderate (MOD; ≥300 mL/d; n = 20) milk production, and compared with controls (≥699 mL/d; n = 18). Serum and milk fatty acids (weight% of total) were measured by GC, serum and milk TNF-α by ELISA, and serum high-sensitivity C-reactive protein (hsCRP) by clinical analyzer. Group differences were assessed by linear regression models, chi-square exact tests, and Kruskal-Wallis nonparametric tests. RESULTS: VL cases, as compared with MOD cases and controls, had higher prevalence of elevated serum hsCRP (>5 mg/L; 57%, 15%, and 22%, respectively; P = 0.004), detectable milk TNF-α (67%, 32%, and 33%, respectively; P = 0.04), and obesity (78%, 40%, and 22%, respectively; P = 0.003). VL cases had lower mean ± SD LCFAs in milk (60% ± 3%) than MOD cases (65% ± 4%) and controls (66% ± 5%) (P < 0.001). Milk and serum LCFAs were strongly correlated in controls (r = 0.82, P < 0.001), but not in the MOD (r = 0.25, P = 0.30) or VL (r = 0.20, P = 0.41) groups (Pint < 0.001). CONCLUSIONS: Mothers with very low milk production have significantly higher obesity and inflammatory biomarkers, lower LCFAs in milk, and disrupted association between plasma and milk LCFAs. These data support the hypothesis that inflammation disrupts normal mammary gland fatty acid uptake. Further research should address impacts of inflammation and obesity on mammary fatty acid uptake for milk production.

Phase I Study of Ramucirumab Plus Merestinib in Previously Treated Metastatic Colorectal Cancer: Safety, Preliminary Efficacy, and Pharmacokinetic Findings.

LESSONS LEARNED: The combination of the antivascular endothelial growth factor receptor 2 monoclonal antibody, ramucirumab, and the type II MET kinase inhibitor, merestinib, is tolerable. Preliminary efficacy data suggest that the combination may provide clinical benefit to patients with metastatic colorectal cancer (mCRC). Further development of this combination would likely necessitate the identification of subsets of patients with mCRC where the clinical benefit is of clinical relevance. BACKGROUND: This study evaluated safety, preliminary efficacy, and pharmacokinetics of ramucirumab plus merestinib in patients with MCR previously treated with oxaliplatin and/or irinotecan. METHODS: Open-label phase Ia/b study comprising 3+3 dose-limiting toxicity (DLT) observation and expansion parts. Treatment was ramucirumab 8 mg/kg on days 1 and 15 and merestinib 80 mg once daily (QD; 28-day cycle). Primary objective was safety and tolerability. Secondary objectives were pharmacokinetics and preliminary antitumor activity. Exploratory objective was biomarker associations. RESULTS: Safety findings: DLT (proteinuria) of 7 phase Ia patients (the expansion part started at the initial recommended dose level); 16 patients (70%) with grade ≥3 treatment-emergent adverse events (TEAEs); 10 patients (43%) with grade ≥3 treatment-related TEAEs. The most common grade ≥3 treatment-related TEAEs were fatigue (4 patients [17%]) and increased blood alkaline phosphatase, diarrhea, and hypertension (2 patients each [9%]). One patient discontinued treatment because of cholestatic hepatitis. Geometric mean trough concentrations at cycle 1, day 15, were ramucirumab, 24.8 µg/mL; merestinib, 130 ng/mL. No complete or partial response was seen; 12 patients (52%) achieved stable disease. Median progression-free survival was 3.3 months (95% confidence interval [CI]: 1.6-4.4). Median overall survival was 8.9 months (95% CI: 3.5-12.7). There were no associations between genetic alterations and efficacy. CONCLUSION: Ramucirumab plus merestinib is tolerable and may have clinical benefit in biomarker-unselected, heavily pretreated patients with mCRC.

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.

Open science: The open clinical trials data journey.

Open data sharing and access has the potential to promote transparency and reproducibility in research, contribute to education and training, and prompt innovative secondary research. Yet, there are many reasons why researchers don't share their data. These include, among others, time and resource constraints, patient data privacy issues, lack of access to appropriate funding, insufficient recognition of the data originators' contribution, and the concern that commercial or academic competitors may benefit from analyses based on shared data. Nevertheless, there is a positive interest within and across the research and patient communities to create shared data resources. In this perspective, we will try to highlight the spectrum of "openness" and "data access" that exists at present and highlight the strengths and weakness of current data access platforms, present current examples of data sharing platforms, and propose guidelines to revise current data sharing practices going forward.

Protective coding variants in CFH and PELI3 and a variant near CTRB1 are associated with age-related macular degeneration†.

Although numerous common age-related macular degeneration (AMD) alleles have been discovered using genome-wide association studies, substantial disease heritability remains unexplained. We sought to identify additional common and rare variants associated with advanced AMD. A total of 4,332 cases and 25,268 controls of European ancestry from three different populations were genotyped using the Illumina Infinium HumanExome BeadChip. We performed meta-analyses to identify associations with common variants, and single variant and gene-based burden tests to identify rare variants. Two protective, low-frequency, non-synonymous variants were significantly associated with a decrease in AMD risk: A307V in PELI3 (odds ratio [OR] = 0.14, P = 4.3 × 10-10) and N1050Y in CFH (OR = 0.76, P = 6.2 × 10-12). The new variants have a large effect size, similar to some rare mutations we reported previously in a targeted sequencing study, which remain significant in this analysis: CFH R1210C (OR = 18.82, P = 3.5 × 10-07), C3 K155Q (OR = 3.27, P = 1.5 × 10-10) and C9 P167S (OR = 2.04, P = 2.8 × 10-07). We also identified a strong protective signal for a common variant (rs8056814) near CTRB1 associated with a decrease in AMD risk (logistic regression: OR = 0.71, P = 1.8 × 10-07). Suggestive protective loci were identified in the COL4A3 and APOH genes. Our results support the involvement of common and low-frequency protective variants in this vision-threatening condition. This study expands the roles of the innate immune pathway as well as the extracellular matrix and high-density lipoprotein pathways in the aetiology of AMD.

Rare genetic variants in the CFI gene are associated with advanced age-related macular degeneration and commonly result in reduced serum factor I levels.

To assess a potential diagnostic and therapeutic biomarker for age-related macular degeneration (AMD), we sequenced the complement factor I gene (CFI) in 2266 individuals with AMD and 1400 without, identifying 231 individuals with rare genetic variants. We evaluated the functional impact by measuring circulating serum factor I (FI) protein levels in individuals with and without rare CFI variants. The burden of very rare (frequency <1/1000) variants in CFI was strongly associated with disease (P = 1.1 × 10(-8)). In addition, we examined eight coding variants with counts ≥5 and saw evidence for association with AMD in three variants. Individuals with advanced AMD carrying a rare CFI variant had lower mean FI compared with non-AMD subjects carrying a variant (P < 0.001). Further new evidence that FI levels drive AMD risk comes from analyses showing individuals with a CFI rare variant and low FI were more likely to have advanced AMD (P = 5.6 × 10(-5)). Controlling for covariates, low FI increased the risk of advanced AMD among those with a variant compared with individuals without advanced AMD with a rare CFI variant (OR 13.6, P = 1.6 × 10(-4)), and also compared with control individuals without a rare CFI variant (OR 19.0, P = 1.1 × 10(-5)). Thus, low FI levels are strongly associated with rare CFI variants and AMD. Enhancing FI activity may be therapeutic and measuring FI provides a screening tool for identifying patients who are most likely to benefit from complement inhibitory therapy.

The Relation between Breast Milk Sodium to Potassium Ratio and Maternal Report of a Milk Supply Concern.

We report that, among exclusively breastfeeding mothers at day 7 postpartum, those with milk supply concerns were significantly more likely to exhibit biochemical evidence of less progress toward mature lactation (elevated ratio of breast milk sodium to potassium concentration). Furthermore, an elevated ratio of breast milk sodium to potassium concentration was predictive of early weaning.

Expression profile based gene clusters for ischemic stroke detection.

In microarray studies alterations in gene expression in circulating leukocytes have shown utility for ischemic stroke diagnosis. We studied forty candidate markers identified in three gene expression profiles to (1) quantitate individual transcript expression, (2) identify transcript clusters and (3) assess the clinical diagnostic utility of the clusters identified for ischemic stroke detection. Using high throughput next generation qPCR 16 of the 40 transcripts were significantly up-regulated in stroke patients relative to control subjects (p<0.05). Six clusters of between 5 and 7 transcripts were identified that discriminated between stroke and control (p values between 1.01e-9 and 0.03). A 7 transcript cluster containing PLBD1, PYGL, BST1, DUSP1, FOS, VCAN and FCGR1A showed high accuracy for stroke classification (AUC=0.854). These results validate and improve upon the diagnostic value of transcripts identified in microarray studies for ischemic stroke. The clusters identified show promise for acute ischemic stroke detection.

In-hospital formula use increases early breastfeeding cessation among first-time mothers intending to exclusively breastfeed.

OBJECTIVE: To evaluate in-hospital formula supplementation among first-time mothers who intended to exclusively breastfeed and determined if in-hospital formula supplementation shortens breastfeeding duration after adjusting for breastfeeding intention. STUDY DESIGN: We assessed strength of breastfeeding intentions prenatally in a diverse cohort of expectant primiparae and followed infant feeding practices through day 60. Among mothers planning to exclusively breastfeed their healthy term infants for ≥1 week, we determined predictors, reasons, and characteristics of in-hospital formula supplementation, and calculated the intention-adjusted relative risk (ARR) of not fully breastfeeding days 30-60 and breastfeeding cessation by day 60 with in-hospital formula supplementation (n = 393). RESULTS: Two hundred ten (53%) infants were exclusively breastfed during the maternity stay and 183 (47%) received in-hospital formula supplementation. The most prevalent reasons mothers cited for in-hospital formula supplementation were: perceived insufficient milk supply (18%), signs of inadequate intake (16%), and poor latch or breastfeeding (14%). Prevalence of not fully breastfeeding days 30-60 was 67.8% vs. 36.7%, ARR 1.8 (95% CI, 1.4-2.3), in-hospital formula supplementation vs exclusively breastfed groups, respectively, and breastfeeding cessation by day 60 was 32.8% vs. 10.5%, ARR 2.7 (95% CI, 1.7-4.5). Odds of both adverse outcomes increased with more in-hospital formula supplementation feeds (not fully breastfeeding days 30-60, P = .003 and breastfeeding cessation, P = .011). CONCLUSIONS: Among women intending to exclusively breastfeed, in-hospital formula supplementation was associated with a nearly 2-fold greater risk of not fully breastfeeding days 30-60 and a nearly 3-fold risk of breastfeeding cessation by day 60, even after adjusting for strength of breastfeeding intentions. Strategies should be sought to avoid unnecessary in-hospital formula supplementation and to support breastfeeding when in-hospital formula supplementation is unavoidable.

Youth as partners, participants or passive recipients: a review of children and adolescents in community-based participatory research (CBPR).

Community-based participatory research (CBPR) is an orientation to research that places value on equitable collaborations between community members and academic partners, reflecting shared decision making throughout the research process. Although CBPR has become increasingly popular for research with adults, youth are less likely to be included as partners. In our review of the literature, we identified 399 articles described by author or MeSH keyword as CBPR related to youth. We analyzed each study to determine youth engagement. Not including misclassified articles, 27 % of percent of studies were community-placed but lacked a community partnership and/or participatory component. Only 56 (15 %) partnered with youth in some phase of the research process. Although youth were most commonly involved in identifying research questions/priorities and in designing/conducting research, most youth-partnered projects included children or adolescents in several phases of the research process. We outline content, methodology, phases of youth partnership, and age of participating youth in each CBPR with youth project, provide exemplars of CBPR with youth, and discuss the state of the youth-partnered research literature.

Machine learning within the Parkinson's progression markers initiative: Review of the current state of affairs.

The Parkinson's Progression Markers Initiative (PPMI) has collected more than a decade's worth of longitudinal and multi-modal data from patients, healthy controls, and at-risk individuals, including imaging, clinical, cognitive, and 'omics' biospecimens. Such a rich dataset presents unprecedented opportunities for biomarker discovery, patient subtyping, and prognostic prediction, but it also poses challenges that may require the development of novel methodological approaches to solve. In this review, we provide an overview of the application of machine learning methods to analyzing data from the PPMI cohort. We find that there is significant variability in the types of data, models, and validation procedures used across studies, and that much of what makes the PPMI data set unique (multi-modal and longitudinal observations) remains underutilized in most machine learning studies. We review each of these dimensions in detail and provide recommendations for future machine learning work using data from the PPMI cohort.

Optimal Intensity and Duration of Walking Rehabilitation in Patients With Chronic Stroke: A Randomized Clinical Trial.

Importance: For walking rehabilitation after stroke, training intensity and duration are critical dosing parameters that lack optimization. Objective: To assess the optimal training intensity (vigorous vs moderate) and minimum training duration (4, 8, or 12 weeks) needed to maximize immediate improvement in walking capacity in patients with chronic stroke. Design, Setting, and Participants: This multicenter randomized clinical trial using an intent-to-treat analysis was conducted from January 2019 to April 2022 at rehabilitation and exercise research laboratories. Survivors of a single stroke who were aged 40 to 80 years and had persistent walking limitations 6 months or more after the stroke were enrolled. Interventions: Participants were randomized 1:1 to high-intensity interval training (HIIT) or moderate-intensity aerobic training (MAT), each involving 45 minutes of walking practice 3 times per week for 12 weeks. The HIIT protocol used repeated 30-second bursts of walking at maximum safe speed, alternated with 30- to 60-second rest periods, targeting a mean aerobic intensity above 60% of the heart rate reserve (HRR). The MAT protocol used continuous walking with speed adjusted to maintain an initial target of 40% of the HRR, progressing up to 60% of the HRR as tolerated. Main Outcomes and Measures: The main outcome was 6-minute walk test distance. Outcomes were assessed by blinded raters after 4, 8, and 12 weeks of training. Results: Of 55 participants (mean [SD] age, 63 [10] years; 36 male [65.5%]), 27 were randomized to HIIT and 28 to MAT. The mean (SD) time since stroke was 2.5 (1.3) years, and mean (SD) 6-minute walk test distance at baseline was 239 (132) m. Participants attended 1675 of 1980 planned treatment visits (84.6%) and 197 of 220 planned testing visits (89.5%). No serious adverse events related to study procedures occurred. Groups had similar 6-minute walk test distance changes after 4 weeks (HIIT, 27 m [95% CI, 6-48 m]; MAT, 12 m [95% CI, -9 to 33 m]; mean difference, 15 m [95% CI, -13 to 42 m]; P = .28), but HIIT elicited greater gains after 8 weeks (58 m [95% CI, 39-76 m] vs 29 m [95% CI, 9-48 m]; mean difference, 29 m [95% CI, 5-54 m]; P = .02) and 12 weeks (71 m [95% CI, 49-94 m] vs 27 m [95% CI, 3-50 m]; mean difference, 44 m [95% CI, 14-74 m]; P = .005) of training; HIIT also showed greater improvements than MAT on some secondary measures of gait speed and fatigue. Conclusions and Relevance: These findings show proof of concept that vigorous training intensity is a critical dosing parameter for walking rehabilitation. In patients with chronic stroke, vigorous walking exercise produced significant and meaningful gains in walking capacity with only 4 weeks of training, but at least 12 weeks were needed to maximize immediate gains. Trial Registration: ClinicalTrials.gov Identifier: NCT03760016.

Measures of Maternal Metabolic Health as Predictors of Severely Low Milk Production.

Background: A comprehensive approach to breastfeeding support requires elucidation of how metabolic health influences milk production. Objective: We compared metabolic health indicators in women with severely low milk output versus those with moderate/normal milk output using a case-control study design, with nested and external control groups. Design: Cases and nested controls were derived from women screened for a low milk supply trial, with cases defined as severely low milk output (<300 mL/24 hours), and nested controls defined as moderate/normal milk output (>300 mL/24 hours). In addition, we included an external control group of exclusively breastfeeding women. All were enrolled at 2-10 weeks postdelivery of a healthy term infant. Milk output and breast emptying frequency were recorded through test-weigh. Metabolic health variables included all components of the metabolic syndrome, homeostatic model assessment of insulin resistance (HOMA-IR), and diagnosis of gestational diabetes mellitus (GDM). Results: Maximum milk output, mL/24 hours, ranged as follows: 30-281 in cases (n = 18), 372-801 in nested controls (n = 12), and 661-915 in external controls (n = 12). Mean breast emptying frequency in cases was not significantly different from nested or external controls. All metabolic syndrome components and HOMA-IR were significantly worse in cases as compared with both nested and external control groups (p < 0.05). There was no significant difference between the nested and external control groups for these variables. GDM prevalence was 39%, 0%, and 8%, across cases, nested control, and external control groups, respectively (chi-square p-value = 0.02). Conclusion: Results from this small case-control study identify class 2+ obesity and poor metabolic health as strong risk factors for severely low milk production. These findings should be further validated in larger prospective cohort studies designed to identify individuals at risk for metabolically driven low milk supply. In addition, clinical and qualitative research studies aimed at improving patient-centered approaches to the management of persistent low milk supply are needed.

Moderate-intensity exercise versus high-intensity interval training to recover walking post-stroke: protocol for a randomized controlled trial.

BACKGROUND: Stroke results in neurologic impairments and aerobic deconditioning that contribute to limited walking capacity which is a major barrier post-stroke. Current exercise recommendations and stroke rehabilitation guidelines recommend moderate-intensity aerobic training post-stroke. Locomotor high-intensity interval training is a promising new strategy that has shown significantly greater improvements in aerobic fitness and motor performance than moderate-intensity aerobic training in other populations. However, the relative benefits and risks of high-intensity interval training and moderate-intensity aerobic training remain poorly understood following stroke. In this study, we hypothesize that locomotor high-intensity interval training will result in greater improvements in walking capacity than moderate-intensity aerobic training. METHODS: Using a single-blind, 3-site randomized controlled trial, 50 chronic (> 6 months) stroke survivors are randomly assigned to complete 36 locomotor training sessions of either high-intensity interval training or moderate-intensity aerobic training. Main eligibility criteria are age 40-80 years, single stroke for which the participant received treatment (experienced 6 months to 5 years prior to consent), walking speed ≤ 1.0 m/s, able to walk at least 3 min on the treadmill at ≥ 0.13 m/s (0.3 mph), stable cardiovascular condition (American Heart Association class B), and the ability to walk 10 m overground without continuous physical assistance. The primary outcome (walking capacity) and secondary outcomes (self-selected and fast gait speed, aerobic fitness, and fatigue) are assessed prior to initiating training and after 4 weeks, 8 weeks, and 12 weeks of training. DISCUSSION: This study will provide fundamental new knowledge to inform the selection of intensity and duration dosing parameters for gait recovery and optimization of aerobic training interventions in chronic stroke. Data needed to justify and design a subsequent definitive trial will also be obtained. Thus, the results of this study will inform future stroke rehabilitation guidelines on how to optimally improve walking capacity following stroke. TRIAL REGISTRATION: ClinicalTrials.gov NCT03760016 . Registered on November 30, 2018.

Validity of a 3-Hour Breast Milk Expression Protocol in Estimating Current Maternal Milk Production Capacity and Infant Breast Milk Intake in Exclusively Breastfeeding Dyads.

Objective: An efficient method for measuring maternal milk production is needed. Our objectives were to: (1) validate a milk production rate (MPR) protocol in exclusively breastfeeding mothers; (2) determine MPR change following 48 hours of increased breast emptying; (3) assess agreement between MPR and infant test-weighing; and (4) characterize MPR in early postpartum exclusively breastfeeding mothers. Materials and Methods:N = 23 mothers emptied both breasts hourly over 3 hours (h0, h1, h2, and h3). We estimated steady-state MPR as mean (h2 and h3). Subset A mothers (n = 5) also completed MPR measurements after 48 hours of increased breast emptying. Subset B mothers (n = 16) also test-weighed for 48 hours. We used paired t-test to examine within-participant change in hourly milk yield and MPR; and we used Bland-Altman analysis to compare 24-hour milk production (g/24 hours) measured using test-weight versus MPR. Results are reported as mean ± standard deviation or (±95% limits of agreement). Results: Mothers were 54 ± 14 days postpartum. Paired difference in h3-h2 hourly milk yield was not significantly different (p > 0.05, 3 ± 10 g/hour). In Subset A (n = 5), MPR declined from 50 ± 13 to 43 ± 16 g/hour (p = 0.003) following 48 hours of increased breast emptying. In Study B (n = 16), mean infant test-weighed intake (TW) was 717 ± 119 g/24 hours, and mean MPR was 1,085 ± 300 g/24 hours. Mean difference (MPR-test-weigh) and mean ratio (MPR/test-weigh) significantly increased as MPR increased (p < 0.05). For infants with adequate weight gain (>20 g/24 hours, n = 12), mean MPR = 48 ± 12 g/hour (range, 35-78 g/hour). Conclusion: MPR is a valid measure of current maternal milk production capacity, but is not accurate for evaluating infant intake in exclusively breastfeeding dyads.

Feasibility and Acceptability of Metformin to Augment Low Milk Supply: A Pilot Randomized Controlled Trial.

BACKGROUND: Metformin improves insulin action, but feasibility in treating low milk supply is unknown. RESEARCH AIM: To determine the feasibility of a metformin- versus-placebo definitive randomized clinical trial in women with low milk production and signs of insulin resistance. METHODS: Pilot trial criteria included: Mother 1-8 weeks postpartum (ideally 1-2 weeks), low milk production, and ≥1 insulin resistance sign; and singleton, healthy, term infant. Eligible mothers were randomly assigned 2:1 (metformin:placebo) and instructed in frequent milk removal for 28 days with option to stop at 14 days. RESULTS: From 02/2015 through 06/2016, we screened 114 women, completed baseline assessments on 46, and trialed 15 (median, 36 days postpartum). Comparing metformin-assigned ( n = 10) to placebo ( n = 5), 70% versus 80% continued to day 28; peak median change in milk output was +8 versus -58 mL/24 hr ( p = .31) and 80% peaked at Day 14 for both groups; 0% versus 20% desired to continue assigned drug after study completion; 44% versus 0% reported nausea/vomiting. Post-hoc, median peak change in milk output was +22 (metformin completers, n = 8) versus -58 mL/24 hr (placebo + non-completers, n = 7, p = .07). At baseline assessment, median milk production was significantly lower in those with ( n = 31), versus those without ( n = 15) signs of insulin resistance ( p = .002). CONCLUSIONS: Although results trend toward hypothesized direction, trial feasibility concerns include late enrollment and only 20% of metformin-assigned participants sustaining improved milk output to Day 28, with none perceiving metformin worthwhile. Better tools are needed to identify and treat metabolically-driven low milk production. Registered at ClinicalTrials.gov (NCT02179788) on 02/JUL/2014.

Short-term exposure to a high-protein diet differentially affects glomerular filtration rate but not Acid-base balance in older compared to younger adults.

There is conflicting evidence regarding the effects of high protein intake on kidney health, especially as it relates to age. We investigated the short-term effects of a high-protein diet on kidney function and systemic acid-base homeostasis in older compared to younger adults. The subjects were healthy men and women either between the ages of 25 and 40 years (n=12) or 55 and 70 years (n=10). They underwent a two-period crossover trial with each period consisting of 2 weeks of usual diet followed by a 1-week experimental diet. During the experimental diet period subjects consumed metabolic meals that provided either low protein content (0.5 g protein/kg/day) or high protein content (2.0 g protein/kg/day). Outcome measures included blood and urine markers of renal function and acid-base balance. An analysis of variance was used to assess differences between age groups with respect to experimental diet. The older group, mainly women, showed an increase in glomerular filtration rate after the high-protein compared to low-protein diet; the younger group did not. Urinary pH was significantly lower, and ammonium excretion was significantly higher after the high-protein diet in both age groups, but neither group developed a clinically detectable acidosis after the week of receiving a high-protein diet.

Extending TCGA queries to automatically identify analogous genomic data from dbGaP.

Data sharing is critical to advance genomic research by reducing the demand to collect new data by reusing and combining existing data and by promoting reproducible research. The Cancer Genome Atlas (TCGA) is a popular resource for individual-level genotype-phenotype cancer related data. The Database of Genotypes and Phenotypes (dbGaP) contains many datasets similar to those in TCGA. We have created a software pipeline that will allow researchers to discover relevant genomic data from dbGaP, based on matching TCGA metadata. The resulting research provides an easy to use tool to connect these two data sources.