A Recurrent Nonsense Mutation in NECTIN4 Underlying Ectodermal Dysplasia-Syndactyly Syndrome with a Novel Phenotype in a Consanguineous Kashmiri Family.

EDSS1, a syndrome characterized by ectodermal dysplasia-syndactyly, is inherited in an autosomal recessive manner due to mutations in the NECTIN4/PVRL4 gene. Clinical manifestations of the syndrome include defective nail plate, sparse to absent scalp and body hair, spaced teeth with enamel hypoplasia, and bilateral cutaneous syndactyly in the fingers and toes. Here, we report a consanguineous family of Kashmiri origin presenting features of EDSS1. Using whole exome sequencing, we found a recurrent nonsense mutation (NM_030916: c.181C > T, p.(Gln61 ∗)) in the NECTIN4 gene. The variant segregated perfectly with the disorder within the family. The candidate variant was absent in 50 in-house exomes pertaining to other disorders from the same population. In addition to the previously reported clinical phenotype, an upper lip cleft was found in one of the affected members as a novel phenotype that is not reported by previous studies in EDSS1 patients. Therefore, the study presented here, which was conducted on the Kashmiri population, is the first to document a NECTIN4 mutation associated with the upper lip cleft as a novel phenotype. This finding broadens the molecular and phenotypic spectrum of EDSS1.

Drug resistance pattern in Mycobacterium tuberculosis to the first line drugs of pulmonary tuberculosis patients at Hazara Region, Pakistan.

INTRODUCTION: Multidrug resistant TB (MDR-TB), defined as resistance to at least rifampicin and isoniazid together, has been rapidly spreading in recent years. In new pulmonary tuberculosis patients, rapid spread of MDR-TB and XDR-TB challenging the effectiveness of national TB control programs especially in many low-income countries. This study was aimed to determine the resistance pattern of Mycobacterium tuberculosis among new cases, cured, failure, relapse, defaulted, treatment completed, treatment not evaluated and suspect to be resistant to first line antitubercular drugs of pulmonary tuberculosis (PTB). MATERIALS AND METHODS: The study was conducted during 2013-2016 in which 148 patients were enrolled infected with pulmonary TB. Three sputum samples were consecutively collected and transported for drug analysis to the Provincial Reference Laboratory (PRL) at Hayatabad Medical complex Peshawar (HMCP) TB laboratory, within three days of collection at +4°C in a cold box. Using the standard proportion method, drug susceptibility test was performed on 132 (89.2%) sputum samples for rifampicin (R), isoniazid (H), pyrazinamide (Z), ethambutol (E), and streptomycin (S). RESULT: Prevalence of resistance to one drug was 5 (3.4%). The highest proportion of mono-drug resistance was observed against E, 3 (2%), followed by H, 1 (0.7%), and R, 1 (0.7%). Pattern of resistant to two drugs was 14 (9.5%). The proportion of poly resistant was 3 (2%). 112 (93.33%) diagnose patients were MDR-TB. CONCLUSIONS: To formulate an effective regimen, it is important to know drug resistant pattern because drug resistant pattern varies from different period of time also from one place to another.

Looking for the Edge of the World: How 3D Immersive Audio Produces a Shift from an Internalised Inner Voice to Unsymbolised Affect-Driven Ways of Thinking and Heightened Sensory Awareness.

In this practice-based case study, we investigate the subjective aesthetic and affective responses to a shift from 2D stereo-based modelling to 3D object-based Dolby Atmos in an audio installation artwork. Dolby Atmos is an infinite object-based audio format released in 2012 but only recently incorporated into more public-facing formats. Our analysis focuses on the artist Sadia Sadia's 30-channel audio installation 'Notes to an Unknown Lover', based on her book of free verse poetry of the same title, which was rebuilt and reformatted in a Dolby Atmos specified studio. We examine what effect altered spatiality with an infinite number of 'placements' has on the psychoacoustic and neuroaesthetic response to the text. The effectiveness of three-dimensional (3D) object-based audio is interrogated against more traditional stereo and two-dimensional (2D) formats regarding the expression and communication of emotion and what effect altered spatiality with an infinite number of placements has on the psychoacoustic and neuroaesthetic response to the text. We provide a unique examination of the consequences of a shift from 2D to wholly encompassing object-based audio in a text-based artist's audio installation work. These findings may also have promising applications for health and well-being issues.