Deaf individuals’ bilingual abilities: American Sign Language proficiency, reading skills, and family characteristics

The current study investigated the bilingual abilities of 55 Deaf individuals, examining both American Sign Language (ASL) competency and English reading skills. Results revealed a positive relationship between ASL competency and English skills, with highly competent signers scoring higher on a measure of reading comprehension. Additionally, family characteristics (e.g., parental education level, family hearing status) were entered into the analysis to ascertain their effect on Deaf individuals’ bilingual abilities. The findings support the theory that competency in ASL may serve as a bridge to the acquisition of English print. Moreover, the findings provide support for the critical period hypothesis for first language acquisition and its later impact on other cognitive and academic skills

Incidence and Predictors of Seizures in Patients with Alzheimer's Disease

PURPOSE: To determine cumulative incidence and predictors of new-onset seizures in mild Alzheimer's disease (AD) with a cohort followed prospectively. Limited information is available on the incidence of seizures, and no reports exist of seizure predictors in AD patients. METHODS: Mild AD patients were prospectively followed at 6-month intervals to estimate incidence of unprovoked seizures, compare age-specific risk of unprovoked seizures with population norms, and identify characteristics at baseline (demographics, duration and severity of AD, physical and diagnostic test findings, and comorbid medical and psychiatric conditions) influencing unprovoked seizure risk. Review of study charts and medical records supplemented coded end-point data. RESULTS: The cumulative incidence of unprovoked seizures at 7 years was nearly 8%. In all age groups, risk was increased compared with a standard population, with an 87-fold increase in the youngest group (age 50-59 years) and more than a threefold increase in the oldest group (age 85+ years). In multivariate modeling, independent predictors of unprovoked seizures were younger age [relative risk (RR), 0.89 per year increase in age; 95% confidence interval (CI), 0.82-0.97], African-American ethnic background (RR, 7.35; 95% CI, 1.42-37.98), more-severe dementia (RR, 4.15; 95% CI, 1.06-16.27), and focal epileptiform findings on electroencephalogram (EEG) (RR, 73.36; 95% CI, 1.75-3075.25). CONCLUSIONS: Seizure incidence is increased in people starting with mild-to-moderate AD. Younger individuals, African Americans, and those with more-severe disease or focal epileptiform findings on EEG were more likely to have unprovoked seizures

Urinary Bisphenol A Concentrations and Implantation Failure among Women Undergoing in Vitro Fertilization

Background: Bisphenol A (BPA) is a synthetic chemical widely used in the production of polycarbonate plastic and epoxy resins found in numerous consumer products. In experimental animals, BPA increases embryo implantation failure and reduces litter size. Objective: We evaluated the association of urinary BPA concentrations with implantation failure among women undergoing in vitro fertilization (IVF). Methods: We used online solid phase extraction–high performance liquid chromatography–isotope dilution tandem mass spectrometry to measure urinary BPA concentrations in 137 women in a prospective cohort study among women undergoing IVF at the Massachusetts General Hospital Fertility Center in Boston, Massachusetts. We used logistic regression to evaluate the association of cycle-specific urinary BPA concentrations with implantation failure, accounting for correlation among multiple IVF cycles in the same woman using generalized estimating equations. Implantation failure was defined as a negative serum β-human chorionic gonadotropin test (β-hCG < 6 IU/L) 17 days after egg retrieval. Results: Among 137 women undergoing 180 IVF cycles, urinary BPA concentrations had a geometric mean (SD) of 1.53 (2.22) µg/L. Overall, 42% (n = 75) of the IVF cycles resulted in implantation failure. In adjusted models, there was an increased odds of implantation failure with higher quartiles of urinary BPA concentrations {odds ratio (OR) 1.02 [95% confidence interval (CI): 0.35, 2.95}, 1.60 (95% CI: 0.70, 3.78), and 2.11 (95% CI: 0.84, 5.31) for quartiles 2, 3, and 4, respectively, compared with the lowest quartile (p-trend = 0.06). Conclusion: There was a positive linear dose–response association between BPA urinary concentrations and implantation failure

Per- and polyfluoroalkyl substances and kidney function: Follow-up results from the Diabetes Prevention Program trial

Per- and polyfluoroalkyl substances (PFAS) are ubiquitously detected in populations worldwide and may hinder kidney function. The objective of the study was to determine longitudinal associations of plasma PFAS concentrations with estimated glomerular filtration rate (eGFR) and evaluate whether a lifestyle intervention modify the associations. We studied 875 participants initially randomized to the lifestyle or placebo arms in the Diabetes Prevention Program (DPP, 1996–2002) trial and Outcomes Study (DPPOS, 2002–2014). We ran generalized linear mixed models accounting a priori covariates to evaluate the associations between baseline PFAS concentrations and repeated measures of eGFR, separately, for six PFAS (PFOS, PFOA, PFHxS, EtFOSAA, MeFOSAA, PFNA); then used quantile-based g-computation to evaluate the effects of the six PFAS chemicals as a mixture. The cohort was 64.9% female; 73.4% 40–64 years-old; 29.4% with hypertension; 50.5% randomized to lifestyle intervention and 49.5% to placebo and had similar plasma PFAS concentrations as the general U.S. population in 1999–2000. Most participants had normal kidney function (eGFR \u3e 90 mL/min/1.73 m2) over the approximately 14 years of follow-up. We found that plasma PFAS concentrations during DPP were inversely associated with eGFR during DPPOS follow-up. Each quartile increase in baseline plasma concentration of the 6 PFAS as a mixture was associated with 2.26 mL/min/1.73 m2 lower eGFR (95% CI: −4.12, −0.39) at DPPOS Year 5, approximately 9 years since DPP randomization and PFAS measurements. The lifestyle intervention did not modify associations, but inverse associations were stronger among participants with hypertension at baseline. Among prediabetic adults, we found inverse associations between baseline plasma PFAS concentrations and measures of eGFR throughout 14 years of follow-up. The lifestyle intervention of diet, exercise and behavioral changes did not modify the associations, but persons with hypertension may have heightened susceptibility

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24&nbsp;months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500&nbsp;steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30&nbsp;minutes spent performing activities ≥500&nbsp;counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24&nbsp;months), both the number of steps per day (per 500&nbsp;steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500&nbsp;counts per minute (per 30&nbsp;minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score &gt;10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

T-Lymphocytes Enable Osteoblast Maturation via IL-17F during the Early Phase of Fracture Repair

While it is well known that the presence of lymphocytes and cytokines are important for fracture healing, the exact role of the various cytokines expressed by cells of the immune system on osteoblast biology remains unclear. To study the role of inflammatory cytokines in fracture repair, we studied tibial bone healing in wild-type and Rag1−/− mice. Histological analysis, µCT stereology, biomechanical testing, calcein staining and quantitative RNA gene expression studies were performed on healing tibial fractures. These data provide support for Rag1−/− mice as a model of impaired fracture healing compared to wild-type. Moreover, the pro-inflammatory cytokine, IL-17F, was found to be a key mediator in the cellular response of the immune system in osteogenesis. In vitro studies showed that IL-17F alone stimulated osteoblast maturation. We propose a model in which the Th17 subset of T-lymphocytes produces IL-17F to stimulate bone healing. This is a pivotal link in advancing our current understanding of the molecular and cellular basis of fracture healing, which in turn may aid in optimizing fracture management and in the treatment of impaired bone healing

The Evolution of Host Specialization in the Vertebrate Gut Symbiont Lactobacillus reuteri

Recent research has provided mechanistic insight into the important contributions of the gut microbiota to vertebrate biology, but questions remain about the evolutionary processes that have shaped this symbiosis. In the present study, we showed in experiments with gnotobiotic mice that the evolution of Lactobacillus reuteri with rodents resulted in the emergence of host specialization. To identify genomic events marking adaptations to the murine host, we compared the genome of the rodent isolate L. reuteri 100-23 with that of the human isolate L. reuteri F275, and we identified hundreds of genes that were specific to each strain. In order to differentiate true host-specific genome content from strain-level differences, comparative genome hybridizations were performed to query 57 L. reuteri strains originating from six different vertebrate hosts in combination with genome sequence comparisons of nine strains encompassing five phylogenetic lineages of the species. This approach revealed that rodent strains, although showing a high degree of genomic plasticity, possessed a specific genome inventory that was rare or absent in strains from other vertebrate hosts. The distinct genome content of L. reuteri lineages reflected the niche characteristics in the gastrointestinal tracts of their respective hosts, and inactivation of seven out of eight representative rodent-specific genes in L. reuteri 100-23 resulted in impaired ecological performance in the gut of mice. The comparative genomic analyses suggested fundamentally different trends of genome evolution in rodent and human L. reuteri populations, with the former possessing a large and adaptable pan-genome while the latter being subjected to a process of reductive evolution. In conclusion, this study provided experimental evidence and a molecular basis for the evolution of host specificity in a vertebrate gut symbiont, and it identified genomic events that have shaped this process

Pharmacological Fingerprints of Contextual Uncertainty

Successful interaction with the environment requires flexible updating of our beliefs about the world. By estimating the likelihood of future events, it is possible to prepare appropriate actions in advance and execute fast, accurate motor responses. According to theoretical proposals, agents track the variability arising from changing environments by computing various forms of uncertainty. Several neuromodulators have been linked to uncertainty signalling, but comprehensive empirical characterisation of their relative contributions to perceptual belief updating, and to the selection of motor responses, is lacking. Here we assess the roles of noradrenaline, acetylcholine, and dopamine within a single, unified computational framework of uncertainty. Using pharmacological interventions in a sample of 128 healthy human volunteers and a hierarchical Bayesian learning model, we characterise the influences of noradrenergic, cholinergic, and dopaminergic receptor antagonism on individual computations of uncertainty during a probabilistic serial reaction time task. We propose that noradrenaline influences learning of uncertain events arising from unexpected changes in the environment. In contrast, acetylcholine balances attribution of uncertainty to chance fluctuations within an environmental context, defined by a stable set of probabilistic associations, or to gross environmental violations following a contextual switch. Dopamine supports the use of uncertainty representations to engender fast, adaptive responses. \ua9 2016 Marshall et al

Mechanism of KMT5B haploinsufficiency in neurodevelopment in humans and mice.

Pathogenic variants in KMT5B, a lysine methyltransferase, are associated with global developmental delay, macrocephaly, autism, and congenital anomalies (OMIM# 617788). Given the relatively recent discovery of this disorder, it has not been fully characterized. Deep phenotyping of the largest (n = 43) patient cohort to date identified that hypotonia and congenital heart defects are prominent features that were previously not associated with this syndrome. Both missense variants and putative loss-of-function variants resulted in slow growth in patient-derived cell lines. KMT5B homozygous knockout mice were smaller in size than their wild-type littermates but did not have significantly smaller brains, suggesting relative macrocephaly, also noted as a prominent clinical feature. RNA sequencing of patient lymphoblasts and Kmt5b haploinsufficient mouse brains identified differentially expressed pathways associated with nervous system development and function including axon guidance signaling. Overall, we identified additional pathogenic variants and clinical features in KMT5B-related neurodevelopmental disorder and provide insights into the molecular mechanisms of the disorder using multiple model systems