Deficient membrane integration of the novel p.N14D-GJB2 mutant associated with non-syndromic hearing impairment

Mutations in GJB2, the gene encoding for the Gap Junction protein Connexin 26 (Cx26), have been established as the major cause of hereditary, non-syndromic hearing impairment (HI). We report here the identification of a novel point mutation in GJB2, c.40A>G [p.N14D], detected in compound heterozygosity with the c.35delG mutation in two brothers with moderate non-syndromic sensorineural HI. The mother who carried one wildtype and a p.N14D allele displayed normal hearing. The mutation leads to substitution of the neutral amino acid asparagine (N) by the negatively charged aspartic acid (D) at amino acid number 14, a position that is conserved among Cx26 of different organisms and among many other connexin isoforms. To investigate the impact of this mutation on protein function, Cx26 activity was measured by depolarization activated hemichannel conductance in non-coupled Xenopus laevis oocytes. Oocytes injected with the p.N14D mutant cRNA showed strongly reduced currents compared to wildtype. Coinjection of wildtype and mutant cRNA at equimolar levels restored the conductive properties supporting the recessive character of this mutation. Total Cx26 protein expression and cell surface abundance examined by western blotting and by quantitative immunoassays revealed that the hemichannel was properly synthesized but not integrated into the plasma membrane. In this study we have shown that the GJB2 mutation p.N14D is associated with recessively inherited HI and exhibits a defective phenotype due to diminished expression at the cell surface.     

Lower switch rate in depressed patients with bipolar II than bipolar I disorder treated adjunctively with second-generation antidepressants

OBJECTIVES: The authors compared the switch rate into hypomania/mania in depressed patients treated with second-generation antidepressants who had either bipolar I or bipolar II disorder. METHOD: In a 10-week trial, 184 outpatients with bipolar depression (134 with bipolar I disorder, 48 with bipolar II disorder, two with bipolar disorder not otherwise specified) were treated with one of three antidepressants as an adjunct to mood stabilizers. The patients' switch rates were assessed. Switch was defined as a Young Mania Rating Scale (YMRS) score >13 or a Clinical Global Impression (CGI) mania score > or =3 (mildly ill). RESULTS: Depressed subjects with bipolar II disorder had a significantly lower acute switch rate into hypomania/mania when either YMRS or CGI criteria were used to define switch. CONCLUSIONS: These data suggest that depressed patients with bipolar II disorder are less vulnerable than those with bipolar I disorder to switch into hypomania/mania when treated with an antidepressant adjunctive to a mood stabilizer.     

Psychometric Evaluation of the Brunei-Malay SF-36 version 2 Health Survey

Objectives: To culturally adapt the Short Form Health-36 version 2 (SF-36v2) into the Brunei-Malay context anddetermine its reliability and validity for measuring health-related quality of life (HRQOL) in healthy individuals andpatients with chronic kidney disease in Brunei Darussalam. Methods: An iterative multistep strategy involving setting upa bilingual expert panel, pretesting, text revision and back translation was used to prepare the Brunei-Malay SF-36v2 asan adaptation from the Malaysian-Malay SF-36v2. The Brunei-Malay SF-36v2 was then self-administered to a sample ofhealthy individuals (n=95) and predialysis chronic kidney disease outpatients (n=95) resident in Brunei. The mean(SD) age of the participants was 46.6 (17.8) years. Results: Data completion rate was 100% with minimal floor effects(≤0.21) in all the 8 domains and >15% ceiling effects in 3 of the 8 domain scales. Cronbach’s alpha was >0.70 for allthe 8 domain scales. Scaling success was 100% for convergent validity, with 100% item discriminant validity for alldomain scales except Social Functioning (94%), Mental Health (85%) and General Health (85%). Principal componentanalysis of the two-factor dimension explained 68% overall variance and accounted for 81% reliable variance, but theexact SF-36 two-factor summary constructs in the standard algorithm were not replicated in the Bruneian population.Conclusions: The Brunei-Malay SF-36v2 is a valid and reliable instrument for measuring HRQOL in healthy individualsand patients with chronic kidney disease in Brunei. The summary scales should, however, be interpreted with caution.Further studies should be carried out to assess additional psychometric properties of the Brunei-Malay SF-36v2.     

Eating practices and behavior in the urban environment: a study in downtown São Paulo

This study focuses on the implications of urban life style on eating habits and the related symbolic representations. Theoretical references used to approach the food experience are the concepts of social representation and habitus. The methodology consisted of a qualitative analysis of interviews with 21 administrative employees and field observations made at commercial establishments in downtown S?o Paulo, such as snack bars and restaurants. Study of eating behavior and practices was developed along two planes: food actually eaten and food desired. Results were classified into three segments: "ingesting and digesting affection", "determinants of social representations of eating practices", and "rituals in eating practices". Due to their origin in a domestic universe, symbolic aspects associated with food have a strong affective matrix. Concrete conditions of the urban environment associated with the subject's financial limits establish a structure of values and feelings compatible with the subject's possibilities. The study addresses both the abbreviation of food rituals and its implications on food behavior as well as features of the present urban food pattern.     

Does a single control mechanism exist for both forward and backward walking?

It has been proposed that the highly reproducible forward walking (FW) locomotor pattern is generated by a central neuronal program or central pattern generator (CPG) which provides the underlying mechanism which produces the coordinated walking movement. The purpose of this study was to quantify the differences in the muscular activation patterns during FW and backward walking (BW) at a constant step frequency and to determine if common features exist across both locomotor conditions. The hypothesis was that FW and BW are both mediated by the same CPG; therefore, only small modifications in the CPG are required in order to produce the different characteristics of each walking mode. The results noted kinematically reversed patterns at the hip and ankle joints between FW and BW. The knee joint movement pattern was similar between conditions, however, a phase shift of 14.3% of the gait cycle occurred. An approximately 25% phase shift in the muscle activation patterns existed between FW and BW in four of the six muscles studied. Additionally, a pattern recognition technique was applied to the combined EMG signals to determine the minimum number of features required to generate the measured muscular output. Only two main features were necessary to produce the EMG patterns for both the FW and BW condition. The main features in FW were more consistent than noted in BW. The results support the notion that a single spinal mechanism such as a CPG with two main features appears to be in control during both FW and BW.     

The effect of daily zinc and/or multivitamin supplements on early childhood development in Tanzania: results from a randomized controlled trial

Impaired childhood development has lifelong consequences for educational attainment and wage‐earning potential. Micronutrient supplements have the potential to improve development. The objective of this study was to determine the effect of daily zinc and/or multivitamin (vitamins C, E and B‐complex) supplements on development among Tanzanian infants. In this randomized, 2 × 2 factorial, double‐blind trial, 2400 infants were randomized to zinc (Zn), multivitamins (MV), zinc and multivitamins (Zn + MV) or placebo at 6 weeks of age. At approximately 15 months, a sub‐sample of 247 children underwent developmental assessment using the cognitive, language (receptive and expressive) and motor (fine and gross) scales of the Bayley Scales of Infant and Toddler Development Third Edition (BSID‐III). Mean BSID‐III scores were compared using univariate and multivariate linear regression models adjusted for child's sex, post‐conceptual age and test administrator. Logistic regressions were used to assess odds of low developmental scores. We did not detect a significant difference in mean BSID‐III scores in any of the five domains in univariate or multivariate models comparing each of the four treatment groups. We also did not detect a significant difference in mean BSID‐III scores when comparing children who received zinc supplements versus those who did not, or in comparisons of children who received multivitamin supplements versus those who did not. There was no significant difference in odds of a low BSID‐III score in any of the five domains in treatment arms either. Because neither daily zinc nor multivitamin (vitamins B‐complex, C and E) supplementation led to improvements in any of the developmental domains assessed using the BSID‐III, we recommend pursuing alternative interventions to promote early childhood development in vulnerable populations. © 2016 John Wiley & Sons Ltd