Nutrition in early childhood can significantly impact physical and mental health outcomes for children. However, research on broadly defined pre/postnatal nutrition interventions is sparse. The present study is a process and outcome evaluation of a primary care-based nutrition intervention targeting low-income Hispanic women. Pregnant women enrolled in the program were in their first trimester and received services through their 6-month well child check. The program provided vouchers for fruits and vegetables from the local farmers' market, nutrition classes, cooking classes, and lactation counseling. We conducted a prospective study of program participants (n = 32) and a comparable group of women for whom the program was not available (n = 29). Panel survey data measured maternal diet, exercise, stress, depression, social support, infant feeding practices, and demographics. Outcome measures obtained from medical records included pregnancy weight gain, infant weight at 6 and 12 months, and infant development at 9 months. Findings reveal that the program was not associated with infant weights. However, despite similar profiles at baseline, women in the intervention group were more likely than women in the comparison group to have significant improvements in diet, exercise, and depression (p ≤ .05). In addition, participants were more likely to breastfeed (p = .07) and their infants were more likely to pass the ages and stages developmental screen (p = .06) than women in the comparison group. The study was limited by a lack of random assignment and small samples. However, the breadth and size of the effects suggest pre/postnatal nutrition interventions integrated into primary care warrant additional investigation.

Using exome sequencing, we identified a de novo mutation (c.2971 A>G; T991 A) in SLC12A6, the gene encoding the K+-Cl- cotransporter KCC3, in a patient with an early-onset, progressive, and severe peripheral neuropathy primarily affecting motor neurons. Normally, the WNK kinase—dependent phosphorylation of T991 tonically inhibits KCC3; however, cell swelling triggers Thr991 dephosphorylation to activate the transporter and restore cell volume. KCC3 T991A mutation in patient cells abolished Thr991 phosphorylation, resulted in constitutive KCC3 activity, and compromised cell volume homeostasis. KCC3T991A/T991A mutant mice exhibited constitutive KCC3 activity and recapitulated aspects of the clinical, electrophysiological, and histopathological findings of the patient. These results suggest that the function of the peripheral nervous system depends on finely tuned, kinase-regulated KCC3 activity and implicate abnormal cell volume homeostasis as a previously unreported mechanism of axonal degeneration.

The nationwide epidemic of pediatric obesity is more prevalent among Hispanic children than white children. Recent literature suggests that obesity has early origins, leading scholars to call for interventions in pregnancy and infancy. However, there is little theoretical or empirical research to guide the development of early prevention programs for Hispanics. The present study seeks to identify risk factors for early childhood obesity among a low-income, predominately Hispanic sample. Data were gathered to inform the design of a primary care childhood obesity prevention program targeting pregnancy through age 12 months. Baseline data were gathered on 153 women attending the clinic for prenatal care or for their child's 2, 6 or 12 month well-check. All women completed surveys on diet, exercise, social support, food security, stress, infant feeding practices, health, and demographics. For women with children (n = 66), survey data were matched with medical records data on infant weight. Results reveal that 55 % of women in the sample had an infant profiling in the 85th percentile or higher, confirming the need for an early childhood obesity intervention. While mothers exhibited several potential risk factors for childhood obesity (e.g. fast food consumption), only maternal consumption of sweets and sugar-sweetened beverages, stress, and SNAP (food stamp receipt) were associated with infant overweight. Findings further reveal that stress and SNAP relate to child overweight, in part, through mothers' sugar-sweetened beverage consumption. Results suggest that obesity prevention efforts must address specific individual choices as well as the external environment that shapes these consumption patterns.

This study describes a 13-yr-old girl with orthostatic intolerance, respiratory weakness, multiple endocrine abnormalities, pancreatic insufficiency, and multiorgan failure involving the gut and bladder. Exome sequencing revealed a de novo, loss-of-function allele in SLC12A2, the gene encoding the Na-K-2Cl cotransporter-1. The 11-bp deletion in exon 22 results in frameshift (p.Val1026Phefs*2) and truncation of the carboxy-terminal tail of the cotransporter. Preliminary studies in heterologous expression systems demonstrate that the mutation leads to a nonfunctional transporter, which is expressed and trafficked to the plasma membrane alongside wild-type NKCC1. The truncated protein, visible at higher molecular sizes, indicates either enhanced dimerization or misfolded aggregate. No significant dominant-negative effect was observed. K+ transport experiments performed in fibroblasts from the patient showed reduced total and NKCC1-mediated K+ influx. The absence of a bumetanide effect on K+ influx in patient fibroblasts only under hypertonic conditions suggests a deficit in NKCC1 regulation. We propose that disruption in NKCC1 function might affect sensory afferents and/or smooth muscle cells, as their functions depend on NKCC1 creating a Cl− gradient across the plasma membrane. This Cl− gradient allows the γ-aminobutyric acid (GABA) receptor or other Cl− channels to depolarize the membrane affecting processes such as neurotransmission or cell contraction. Under this hypothesis, disrupted sensory and smooth muscle function in a diverse set of tissues could explain the patient's phenotype.

BackgroundCharcot-Marie-Tooth disease (CMT) is a clinically and genetically heterogeneous disorder of the peripheral nervous system. Biallelic variants in SLC12A6 have been associated with autosomal-recessive hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC). We identified heterozygous de novo variants in SLC12A6 in three unrelated patients with intermediate CMT.MethodsWe evaluated the clinical reports and electrophysiological data of three patients carrying de novo variants in SLC12A6 identified by diagnostic trio exome sequencing. For functional characterisation of the identified variants, potassium influx of mutated KCC3 cotransporters was measured in Xenopus oocytes.ResultsWe identified two different de novo missense changes (p.Arg207His and p.Tyr679Cys) in SLC12A6 in three unrelated individuals with early-onset progressive CMT. All presented with axonal/demyelinating sensorimotor neuropathy accompanied by spasticity in one patient. Cognition and brain MRI were normal. Modelling of the mutant KCC3 cotransporter in Xenopus oocytes showed a significant reduction in potassium influx for both changes.ConclusionOur findings expand the genotypic and phenotypic spectrum associated with SLC12A6 variants from autosomal-recessive HMSN/ACC to dominant-acting de novo variants causing a milder clinical presentation with early-onset neuropathy.