A longitudinal investigation of prosodic sensitivity and emergent literacy

Prosodic sensitivity – the rhythmic patterning of speech – is theorized to influence reading and spelling via vocabulary knowledge, phonological, and morphological awareness. Previously this conceptual model has been evidenced with children who can already read, however as orthographic knowledge can be used to complete phonological awareness tasks it cannot be said definitively that it is prosodic sensitivity influencing reading and spelling and not the reverse. Therefore, the present study sought to test the model in a longitudinal study conducted at the outset of reading development. A sample of 4- to 5-year-old English-speaking children (N = 101) were assessed for their prosodic sensitivity, vocabulary knowledge, phonological and morphological awareness, and one year later (N = 93) for their word reading and spelling. A path analysis revealed that the conceptual model provides an adequate fit to our sample data: prosodic sensitivity in pre-reading children predicts reading and spelling indirectly through other emergent literacy skills. The implications of these findings are discussed in relation to models of literacy development and literacy instruction

Baseline and decline in device‐derived activity level predict risk of death and heart failure in patients with an ICD for primary prevention

BackgroundImplanted defibrillators are capable of recording activity data based on company‐specific proprietary algorithms. This study aimed to determine the prognostic significance of baseline and decline in device‐derived activity level across different device companies in the real world.MethodsWe performed a retrospective cohort study of patients (n = 280) who underwent a defibrillator implantation (Boston, Medtronic, St. Jude, and Biotronik) for primary prevention at the University of Michigan from 2014 to 2016. Graphical data obtained from device interrogations were retrospectively converted to numerical data. The activity level averaged over a month from a week postimplantation was used as baseline. Subsequent weekly average activity levels (SALs) were standardized to this baseline. SAL below 59.4% was used as a threshold to group patients. All‐cause mortality and death/heart failure were the primary end‐points of this study.ResultsFifty‐six patients died in this study. On average, they experienced a 50% decline in SAL prior to death. Patients (n = 129) who dropped their SAL below threshold were more likely to be older, male, diabetic, and have more symptomatic heart failure. They also had a significantly increased risk of heart failure/death (hazard ratio [HR] 3.6, 95% confidence interval [95% CI] 2.3‐5.8, P < .0001) or death (HR 4.2, 95% CI 2.2‐7.7, P < .0001) compared to those who had sustained activity levels. Lower baseline activity level was also associated with significantly increased risk of heart failure/death and death.ConclusionSignificant decline in device‐derived activity level and low baseline activity level are associated with increased mortality and heart failure in patients with an ICD for primary prevention.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156452/2/pace13981.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156452/1/pace13981_am.pd

Effects of a Flaxseed-Derived Lignan Supplement in Type 2 Diabetic Patients: A Randomized, Double-Blind, Cross-Over Trial

Flaxseed consumption has been shown to improve blood lipids in humans and flaxseed-derived lignan has been shown to enhance glycemic control in animals. The study aimed to investigate the effect of a flaxseed-derived lignan supplement on glycemic control, lipid profiles and insulin sensitivity in type 2 diabetic patients.This was a randomized, double-blind, placebo-controlled, cross-over trial and it was conducted between April and December 2006 in Shanghai, China. Seventy-three type 2 diabetic patients with mild hypercholesterolemia were enrolled into the study. Patients were randomized to supplementation with flaxseed-derived lignan capsules (360 mg lignan per day) or placebo for 12 weeks, separated by an 8-week wash-out period. HbA1c, lipid profiles, insulin resistance index and inflammatory factors were measured. Sixty-eight completed the study and were included in the analyses. The lignan supplement significantly improved glycemic control as measured by HbA(1c) (-0.10+/-0.65 % vs. 0.09+/-0.52 %, P = 0.001) compared to placebo; however, no significant changes were observed in fasting glucose and insulin concentrations, insulin resistance and blood lipid profiles. Urinary excretion of lignan metabolites (enterodiol and enterolactone) was significantly higher after the lignan supplement intervention compared to baseline (14.2+/-18.1 vs. 1.2+/-2.4 microg/mL, P<0.001). Data also suggested minimal competition between lignan and isoflavones for bioavailability when measured by the excretion concentrations.Daily lignan supplementation resulted in modest, yet statistically significant improvements in glycemic control in type 2 diabetic patients without apparently affecting fasting glucose, lipid profiles and insulin sensitivity. Further studies are needed to validate these findings and explore the efficacy of lignans on type 2 diabetes.ClinicalTrials.gov NCT00363233

Phenylbutyrate Counteracts Shigella Mediated Downregulation of Cathelicidin in Rabbit Lung and Intestinal Epithelia: A Potential Therapeutic Strategy

BACKGROUND: Cathelicidins and defensins are endogenous antimicrobial peptides (AMPs) that are downregulated in the mucosal epithelia of the large intestine in shigellosis. Oral treatment of Shigella infected rabbits with sodium butyrate (NaB) reduces clinical severity and counteracts the downregulation of cathelicidin (CAP-18) in the large intestinal epithelia. AIMS: To develop novel regimen for treating infectious diseases by inducing innate immunity, we selected sodium 4-phenylbutyrate (PB), a registered drug for a metabolic disorder as a potential therapeutic candidate in a rabbit model of shigellosis. Since acute respiratory infections often cause secondary complications during shigellosis, the systemic effect of PB and NaB on CAP-18 expression in respiratory epithelia was also evaluated. METHODS: The readouts were clinical outcomes, CAP-18 expression in mucosa of colon, rectum, lung and trachea (immunohistochemistry and real-time PCR) and release of the CAP-18 peptide/protein in stool (Western blot). PRINCIPAL FINDINGS: Significant downregulation of CAP-18 expression in the epithelia of rectum and colon, the site of Shigella infection was confirmed. Interestingly, reduced expression of CAP-18 was also noticed in the epithelia of lung and trachea, indicating a systemic effect of the infection. This suggests a causative link to acute respiratory infections during shigellosis. Oral treatment with PB resulted in reduced clinical illness and upregulation of CAP-18 in the epithelium of rectum. Both PB and NaB counteracted the downregulation of CAP-18 in lung epithelium. The drug effect is suggested to be systemic as intravenous administration of NaB could also upregulate CAP-18 in the epithelia of lung, rectum and colon. CONCLUSION: Our results suggest that PB has treatment potential in human shigellosis. Enhancement of CAP-18 in the mucosal epithelia of the respiratory tract by PB or NaB is a novel discovery. This could mediate protection from secondary respiratory infections that frequently are the lethal causes in dysentery

Interaction Between Marginal Zinc and High Fat Supply on Lipid Metabolism and Growth of Weanling Rats

The impact of a moderate Zn deficiency on growth and plasma and liver lipids was investigated in two 4-week experiments with male weanling rats fed fat-enriched diets. Semisynthetic, approximately isocaloric diets containing 3% soybean oil were supplemented with either 7 or 100 mg Zn/kg diet and with 22% beef tallow (BT) or sunflower oil (SF). In Experiment 1, which compared the dietary fat level and the fat source in a factorial design of treatments, all diets were fed ad libitum to 6 × 8 animals, whereas intake of the high-Zn BT and SF diets was restricted in Experiment 2 (5 × 6 rats) to the level of intake of the respective low-Zn diets. The low-Zn SF diet consistently depressed food intake and final live weights of the animals to a greater extent than the other low-Zn diets, while intake and growth were comparable among the animals fed the high-Zn diets. The marginal Zn deficit per se did not alter plasma triglyceride and cholesterol concentrations nor hepatic concentrations of triglyceride, cholesterol and phospholipids. The fatty acid pattern of liver phospholipids did not indicate that chain elongation and desaturation of fatty acids was impaired by a lack of zinc. It was concluded that dietary energy and fat intake, and fat source have a greater effect on plasma and liver lipids than a moderate Zn deficiency. Marginally Zn-deficient diets enriched with sunflower oil as a major energy source cause a greater growth retardation than diets rich in carbohydrates or beef tallow

The effects of long-term saturated fat enriched diets on the brain lipidome

The brain is highly enriched in lipids, where they influence neurotransmission, synaptic plasticity and inflammation. Non-pathological modulation of the brain lipidome has not been previously reported and few studies have investigated the interplay between plasma lipid homeostasis relative to cerebral lipids. This study explored whether changes in plasma lipids induced by chronic consumption of a well-tolerated diet enriched in saturated fatty acids (SFA) was associated with parallel changes in cerebral lipid homeostasis. Male C57Bl/6 mice were fed regular chow or the SFA diet for six months. Plasma, hippocampus (HPF) and cerebral cortex (CTX) lipids were analysed by LC-ESI-MS/MS. A total of 348 lipid species were determined, comprising 25 lipid classes. The general abundance of HPF and CTX lipids was comparable in SFA fed mice versus controls, despite substantial differences in plasma lipid-class abundance. However, significant differences in 50 specific lipid species were identified as a consequence of SFA treatment, restricted to phosphatidylcholine (PC), phosphatidylethanolamine (PE), alkyl-PC, alkenyl-PC, alkyl-PE, alkenyl-PE, cholesterol ester (CE), diacylglycerol (DG), phosphatidylinositol (PI) and phosphatidylserine (PS) classes. Partial least squares regression of the HPF/CTX lipidome versus plasma lipidome revealed the plasma lipidome could account for a substantial proportion of variation. The findings demonstrate that cerebral abundance of specific lipid species is strongly associated with plasma lipid homeostasis

Deficient Liver Biosynthesis of Docosahexaenoic Acid Correlates with Cognitive Impairment in Alzheimer's Disease

Reduced brain levels of docosahexaenoic acid (C22:6n-3), a neurotrophic and neuroprotective fatty acid, may contribute to cognitive decline in Alzheimer's disease. Here, we investigated whether the liver enzyme system that provides docosahexaenoic acid to the brain is dysfunctional in this disease. Docosahexaenoic acid levels were reduced in temporal cortex, mid-frontal cortex and cerebellum of subjects with Alzheimer's disease, compared to control subjects (P = 0.007). Mini Mental State Examination (MMSE) scores positively correlated with docosahexaenoic/α-linolenic ratios in temporal cortex (P = 0.005) and mid-frontal cortex (P = 0.018), but not cerebellum. Similarly, liver docosahexaenoic acid content was lower in Alzheimer's disease patients than control subjects (P = 0.011). Liver docosahexaenoic/α-linolenic ratios correlated positively with MMSE scores (r = 0.78; P<0.0001), and negatively with global deterioration scale grades (P = 0.013). Docosahexaenoic acid precursors, including tetracosahexaenoic acid (C24:6n-3), were elevated in liver of Alzheimer's disease patients (P = 0.041), whereas expression of peroxisomal d-bifunctional protein, which catalyzes the conversion of tetracosahexaenoic acid into docosahexaenoic acid, was reduced (P = 0.048). Other genes involved in docosahexaenoic acid metabolism were not affected. The results indicate that a deficit in d-bifunctional protein activity impairs docosahexaenoic acid biosynthesis in liver of Alzheimer's disease patients, lessening the flux of this neuroprotective fatty acid to the brain

Mechanisms Involved in Nicotinic Acetylcholine Receptor-Induced Neurotransmitter Release from Sympathetic Nerve Terminals in the Mouse Vas Deferens

Prejunctional nicotinic acetylcholine receptors (nAChRs) amplify postganglionic sympathetic neurotransmission, and there are indications that intraterminal Ca2+ stores might be involved. However, the mechanisms by which nAChR activation stimulates neurotransmitter release at such junctions is unknown. Rapid local delivery (picospritzing) of the nAChR agonist epibatidine was combined with intracellular sharp microelectrode recording to monitor spontaneous and field-stimulation-evoked neurotransmitter release from sympathetic nerve terminals in the mouse isolated vas deferens. Locally applied epibatidine (1 µM) produced ‘epibatidine-induced depolarisations’ (EIDs) that were similar in shape to spontaneous excitatory junction potentials (SEJPs) and were abolished by nonselective nAChR antagonists and the purinergic desensitizing agonist α,β-methylene ATP. The amplitude distribution of EIDs was only slightly shifted towards lower amplitudes by the selective α7 nAChR antagonists α-bungarotoxin and methyllcaconitine, the voltage-gated Na+ channel blocker tetrodotoxin or by blocking voltage-gated Ca2+ channels with Cd2+. Lowering the extracellular Ca2+ concentration reduced the frequency of EIDs by 69%, but more surprisingly, the Ca2+-induced Ca2+ release blocker ryanodine greatly decreased the amplitude (by 41%) and the frequency of EIDs by 36%. Ryanodine had no effect on electrically-evoked neurotransmitter release, paired-pulse facilitation, SEJP frequency, SEJP amplitude or SEJP amplitude distribution. These results show that activation of non-α7 nAChRs on sympathetic postganglionic nerve terminals induces high-amplitude junctional potentials that are argued to represent multipacketed neurotransmitter release synchronized by intraterminal Ca2+-induced Ca2+ release, triggered by Ca2+ influx directly through the nAChR. This nAChR-induced neurotransmitter release can be targeted pharmacologically without affecting spontaneous or electrically-evoked neurotransmitter release