Characterization and Functional Rescue of Congenital Muscular Dystrophy with Megaconial Myopathy in a Mouse Model of the Disease

Congenital muscular dystrophy with megaconial myopathy (MDCMC) is an autosomal recessive disorder characterized by progressive muscle weakness and wasting. Megamitochondria in skeletal muscle biopsies and cognitive impairments in MDCMC patients are observations exclusive to this type of muscular dystrophy. The disease is caused by loss of function mutations in the choline kinase beta (CHKB) gene which results in dysfunction of the Kennedy pathway for the synthesis of phosphatidylcholine (PC). A rostro-caudal muscular dystrophy (rmd) mouse with a deletion in the Chkb gene resulting in MDCMC-like symptoms has been reported by our lab. In order to test if the rmd mice show signs of cognitive impairments as observed in MDCMC patients, I engineered a transgenic rmd mouse model (Tgrmd) which I used for MS/MSALL mass spectrometry analysis of brain tissue and to test for working memory and learning impairments. These tests show us that even though Tg-rmd mice showed significantly different lipid profiles in brain, these changes were not translated in the behavioral assays conducted. I have worked on the development of and tested gene therapy strategies for the rescue and alleviation of dystrophy symptoms using the rmd mouse model. I have observed that introduction of a muscle-specific Chkb transgene completely rescues motor and behavioral function in the rmd mouse model, confirming the cell-autonomous nature of the disease. Intramuscular gene therapy, post-disease onset, using an AAV6 vector carrying a functional copy of Chkb gene is capable of rescuing the dystrophy phenotype in rmd mice. In addition, upregulating choline kinase alpha (Chka), a gene paralog of Chkb, via a similar AAV6 viral vector showed increased muscle regeneration and alleviation of muscular dystrophy symptoms as was observed with Chkb AAV injections. Together, my results suggest rmd mice do not model the cognitive impairments observed in MDCMC patients and that replacement of the Chkb gene or upregulation of endogenous Chka could serve as potential lines of therapy for MDCMC patients

Person Organization Fit, Organizational Commitment and Knowledge Sharing Attitude–An Analytical Study

The purpose of this study is to analyze the relationship among Person Organization Fit (POF), Organizational Commitment (OC) and Knowledge Sharing Attitude (KSA). The paper develops a conceptual frame based on a theory and literature review. A quantitative approach has been used to measure the level of POF and OC as well as to explore the relationship of these variables with KSA & with each other by using a sample of 315 academic managers of public sector institutions of higher education. POF has a positive relationship with OC and KSA. A positive relationship also exists between OC and KSA. It would be an effective contribution in the existing body of knowledge. Managers and other stakeholders may be helped to recognize the significance of POF, OC and KSA as well as their relationship with each other for ensuring selection of employee’s best fitted in the organization and for creating and maintaining a conducive environment for improving organizational commitment and knowledge sharing of the employees which will ultimately result in enhanced efficacy and effectiveness of the organization

Time taken to reach undetectable viral loads in therapy-naïve HIV patients commencing ART

Peer reviewedPublisher PD

Linguistic Human Rights of Minorities and Language Policy: A Case Study of Balochi Language in Education in Lyari, Karachi, Pakistan

Most of the neo-colonial nation-states in South America, Africa and Asia have historically remained multilingual. Particularly, subcontinent, being the part of Indus Civilization, successfully maintained the legacy of religious and cultural diversity. Pre-colonial lingo-cultural diversity in subcontinent was discouraged and displaced by new linguistic hierarchy during colonial times. In the milieu of WW-II and national liberation movements throughout the world, classical colonial structure was largely weakened at global level and paved the way for internal colonialism. Political leadership of newly formed multiethnic states principally preferred to govern their people as colonial subjects rather than free citizens. European model of ‘one language, one culture and one state’ has hitherto resulted in many ethno-linguistic movements in different neo-colonial states. Neo-colonial forms of knowledge, categories and instruments of oppression; particularly language policy; is still prevailing in such (in)dependent states where Pakistan is not an exception. Since 1947, language policy in Pakistan has been mainly shaped by and still continues to be overshadowed by its colonial past. This article critically investigates promise(s) and practice(s) of national language policy and the status of linguistic human rights of minorities in education in Lyari, Karachi, Pakistan. The data was collected from various (inter)national public policy documents/declarations along with semi-structured interviews from four different groups of participants i.e. academics, cultural activists, teachers and parents. Findings reveal two diametrically opposed orientations in terms of the use of mother tongue in classroom. School teachers stridently advocated assimilationist language ideology and viewed multilingualism in classroom as a problem to be solved, whereas, cultural activists and academics consider the same as a cultural resource to be properly utilized and the right of the child to be respected. Parents’ views are also considered in order to explore the tension between the language of schooling and the language of early socialization of children at home. Moreover, Language Rights model is applied in order to explore (re)production of linguistic injustice through language policy in education. Keywords: language policy, language rights, internal linguistic colonialism, Linguistic justice, Multilingualism Indigenous/minoritised languages in early education DOI: 10.7176/JLLL/83-06 Publication date: November 30th 202

Unsteady three dimensional flow of couple stress fluid over a stretching surface with chemical reaction

The unsteady three-dimensional flow of couple stress fluid over a stretched surface is investigated. Analysis has been performed in the presence of mass transfer and chemical reaction. Nonlinear flow analysis is computed by a homotopic approach. Plots are presented and analyzed for the various parameters of interest. A comparative study with existing solutions in a limiting sense is made

Sleep Fainting: A Neurocardiogenic Entity

Fainting is a common clinical presentation, with vagally mediated (neurocardiogenic) causes being the most common for syncope presentation to the emergency room, and for hospital admissions. Classic teaching is that upright posture is a prerequisite for vagally mediated syncope (VMS) and that syncope in the supine position has more sinister causes. We present five patients, three males and two females, with a mean age of 44.4 (range 29-67) years, who presented with VMS in the supine position (sleep fainting). Four patients also had a history of classic upright syncope. Based on their clinical features and thorough investigations, we excluded other causes of loss of consciousness and diagnosed these patients to be having VMS in the supine position (sleep fainting). We further describe the management and follow-up of these patients. Sleep fainting/syncope is a new entity and has to be recognized for appropriate management. A diagnosis can be established if there is clinical suspicion, preserved left ventricular function without evidence of coronary artery disease, no high-risk electrocardiographic evidence of pre-excitation, long or short QT syndrome, Brugada syndrome or arrhythmogenic right ventricular dysplasia, and normal neurological work-up

Development of a stress scale for pregnant women in the South Asian context: the A-Z Stress Scale.

Stress in pregnancy can lead to low-birth-weight and preterm babies and to psychological consequences such as anxiety and depression during pregnancy and the puerperium. Previous scales to measure stress contain items that overlap with the symptoms of pregnancy. A stress scale was developed based on in-depth interviews with pregnant women in Pakistan. Construct validity, test-retest reliability and inter-rater reliability were carried out. Cronbach alpha was 0.82 for the 30 short-listed items, with item-total correlations of 0.2-0.8. Multidimensional scaling determined 2 dimensions: socioenvironmental hassles and chronic illnesses. This was the first scale developed for pregnant women based on stressors in a developing country in South Asia

Effect of Job Design on Employee Satisfaction (A Study of Fertilizer Companies Listed in Lahore Stock Exchange)

Human is declared as “Better” in all living creation. That is the reason behind the importance of the Human Resource whether in Business Organizations or Non-Business Organization. It is the asset which can neither be copied nor be created. In the past two decades, the importance of Human Resource becomes shinier for the organizations especially for the business sectors. Human Resource Management, now a day, is the most important area for Business Organizations and Vital Topic for the Researchers as well. Achieving target and goals, capturing new markets and niches, acquiring and selling are one dimension of success for the organization, but now organizations are putting a valuable consideration to Human Resource Management and its issues. Job Design, Job Enrichment, Job Enlargement, Employee Satisfaction and Motivation, Brain Drain, Performance and Reward are some factors which captured the attention of the organizations. This Research exist in the orbit of the topic “Effect of job design on Employee Satisfaction” and declare 6 Variables of job design which is Independent Variable and find the relation of these variables with employee satisfaction through correlation and linear regression technique. Through Questionnaire, Primary data is collected and by the use of SPSS and Excel 2007, the results are concluded that there is a strong positive correlation between Job Design and Employee Satisfaction and both of these variables move in the same direction. Keyword: Job Design, Employee Satisfaction, Fertilizer Companies, Lahore Stock Exchang

Distribution of lower urinary tract symptoms (LUTS) in adult women

OBJECTIVE: To determine the distribution of lower urinary tract symptoms in adult women and the frequency with which the women consulted a health care provider for their symptoms. DESIGN: Cross-sectional analytical study. PLACE AND DURATION OF STUDY: Community Health Center of Aga Khan University Hospital from November 1st to 30th, 2002. SUBJECTS AND METHODS: A trained interviewer administered a structured questionnaire to women patients or attendants aged 18 years and older coming to the center. RESULTS: Fifty-two percent of the study subjects reported having at least one or more urinary complaints in the past. Stress incontinence was the highest reported complaint (38.4%) followed by burning (34.4%), frequency (26%), painful micturition (20.4%), urge incontinence (18.8 %), incomplete emptying of bladder (14.4%), dribbling (12.4%) and poor stream (8.4%). Forty-three percent of the women with LUTS never consulted a health care provider for their problem.CONCLUSION: Although the distribution of LUTS among females was found to be high, the patients did not consider it important enough to consult a health care provider. There is a need to create awareness among females regarding LUTS and the need to consult a health care provider for their problems

Urdu version of the neck disability index: a reliability and validity study

Abstract Background Despite the wide use of the neck disability index (NDI) for assessing disability in patients with neck pain, the NDI has not yet been translated and validated in Urdu. The first purpose of the present study was to translate and cross-culturally adapt the NDI into the Urdu language (NDI-U). The second purpose was to investigate the reliability, validity and responsiveness of the NDI-U in Urdu-speaking patients experiencing chronic mechanical neck pain (CMNP). Methods Translation and cross-cultural adaptation of the original version of the NDI were carried out using previously described procedures. Seventy-six patients with CMNP and thirty healthy participants were recruited for the study. NDI-U and visual analogue scales for pain intensity (VASpain) and disability (VASdisability) were administered to all the participants at baseline and to the patients 3 weeks after receiving physiotherapy intervention. The global rating of change scale (GROC) was also administered at this time. Test-retest reliability and internal consistency were carried out on forty-six randomly selected patients two days after they completed the NDI-U. The NDI-U was evaluated for factor analysis, content validity, construct validity (discriminative and convergent validity) and responsiveness. Results An intra-class correlation coefficient (ICC2,1) revealed excellent test-retest reliability for all items (ICC2,1 = 0.86–0.98) and total scores (ICC2,1 = 0.99) of the NDI-U. The NDI-U was found internally consistent with a Cronbach’s alpha of 0.90 and a fair to good correlation between single items and the NDI-U total scores (r = 0.34 to 0.89). Factor analysis of the NDI-U produced two factors explaining 66.71% of the variance. Content validity was good, as no floor or ceiling effects were detected for the NDI-U total score. To determine discriminative validity, an independent t-test revealed a significant difference in the NDI-U total scores between the patients and healthy controls (P < 0.001). For convergent validity, Pearson’s correlation coefficient showed a strong correlation between NDI-U and VASdisability (r = 0.83, P < 0.001) and a moderate correlation between NDI-U and VASpain (r = 0.62, P < 0.001). To measure responsiveness, an independent t-test showed a significant difference in the NDI-U change scores between the stable and the improved groups (P < 0.001). Furthermore, moderate correlations were found between the NDI-U change scores and the GROC (r = 0.50, P < 0.001), VASdisability change scores (r = 0.58, P < 0.001) and VASpain change scores (r = 0.55, P < 0.001). Conclusion The results showed that the NDI-U is a reliable, valid and responsive questionnaire to measure disability in Urdu-speaking patients with CMNP