ASSOCIATION OF VITAMIN D DEFICIENCY WITH PRETERM BIRTH

Background; Every year, 15 million neonates worldwide are born preterm.  Of these, 1.1 million die as a result of complications of being born too soon and even more suffer from serious prematurity-related complications including learning disabilities. Several studies point to the fact that vitamin D is involved in the regulation of acquired and innate immune responses at the fetal-maternal interface across gestation. Vitamin D reduces the risk of spontaneous preterm birth also by maintaining myometrial quiescence. This study was conducted to determine the role of Vitamin D deficiency with preterm labor in our population. Objective; To determine the frequency of vitamin D deficiency in preterm labour. Setting; Department of Obstetrics and Gynaecology, Fatima Memorial Hospital Lahore. Results; A total of 167 pregnant women were registered mean age of our study cases was 28.48 ± 3.58 years. Mean parity was 3.95 ± 1.15. Mean gestational age of our study cases was 30.29 ± 3.02 weeks. Majority of our study cases i.e. 105 (62.9%) had poor socioeconomic status, while 62 (37.1%) were from middle class while none of them were from rich class. Mean vitamin D level was 40.86 ± 8.51 ng/dl (with minimum vitamin D level was 22 ng/dl and maximum vitamin D level was 56 ng/dl). Vitamin D deficiency was seen in 27 (16.2%) of our study cases. Conclusion; High frequency of Vitamin D deficiency was noted in our study population. Pregnant women should be screened routinely for Vitamin D levels, particularly those with previous history of preterm births to avoid them in subsequent pregnancies. Vitamin D deficiency was significantly associated with poor socio-economic status, increasing age and gestational age less than 30 weeks. Keywords; Vitamin D deficiency, preterm labor, gestational age

Correlates of mental health among Pakistani adolescents: an exploration of the interrelationship between attachment, parental bonding, social support, emotion regulation and cultural orientation using Structural Equation Modelling

Background Mental health of the adolescents is an important global public health concern as a leading cause of illness and disability not only for the adolescents, but also their family, and the community. In recent years the broader definition of mental health suggests an overall improved well-being as well as absence of illness. Despite the global recognition of the significance of adolescents’ mental health it remains a seriously neglected area in research and policy in Pakistan. This thesis attempts to understand the epidemiology of mental health among Pakistani adolescents by drawing from developmentally informed framework. This thesis proposes that perceptions of relationship with parents and attachment underlie the adolescents’ successful ability to regulate emotions and perceive social support. It also attempts to understand the role of cultural orientation in the pathway of associations between the factors mentioned above. Objectives A quantitative cross sectional design was applied to investigate the state of mental health among Pakistani adolescents. The study also aimed at investigating the validity of constructs of attachment, parental bonding, emotion regulation, social support and cultural orientation in Pakistan and how these factors interrelate in relation to adolescents’ mental health. Methods A sample of eleven hundred and twenty four was recruited from eight secondary schools from the district of Rawalpindi, Pakistan after formal approval from concerned authorities. A battery of self-report measures was administered in class-room setting. Confirmatory factor analysis (CFA) and Structural equation modelling (SEM) were used to analyse the data. Results Prevalence of depression and anxiety among this sample was 17.2% and 21.4% respectively. Results from the CFA of the Urdu versions of the instruments used in the current study replicated the original factor structures in case of well-being, depression, anxiety, parental bonding, emotion regulation, and social support with minor modifications. However, a two factor model of cultural orientation is supported in the current study. In case of parental bonding, a second order factor was found for mother and father bonding showing that both form common factors of parental warmth, protectiveness and authoritarianism. Present study found support for the hypothesized structural equation model examining pathway of association between attachment, parental bonding, social support, emotion regulation and cultural orientation in understanding depression, anxiety and well-being among Pakistani adolescents. Discussion Findings of this study suggest that parental bonding, attachment, emotion regulation, social support and cultural orientation play a crucial role to further our understanding of adolescents’ depression, anxiety and well-being in Pakistani cultural context. Therefore, these are central constructs within a developmental framework and are important when considering long-term psychosocial functioning of individuals. Further implications are discussed regarding the recommendation of promoting and utilizing a developmentally informed approach when working with adolescent population. These findings may be used as base line information in making policy level decisions regarding evaluation, prevention and intervention and of mental health problems among Pakistani adolescents

Fiscal Decentralization and Human Development in Selected Developing Countries in Asia: Role of Institutionali

The paper aims to investigate the impact of fiscal decentralization on human development and moderating role of political institutions in selected Asian countries for the time period 1990-2019, applying panel data Fixed and Random Effects models. The empirical findings show that fiscal decentralization at both the provincial and local levels significantly affects human development. The optimal level of fiscal decentralization is computed at 1.143 and 0.229, respectively, suggesting that fiscal decentralization above this level may revert the results for human development. The non-linear specification of the model also portrays a rising human development in the wake of fiscal decentralization but at a decreasing rate. Moreover, the role of institutionalization is proved effective in the case of the countries where provincial-level decentralization is controlled in the model. The results imply that a lack of proper coordination and mismanagement due to many governance tiers can subside human development. However, fiscal decentralization is an essential factor for Asian countries to increase the efficiency of the public sector if supported with a controlled decentralization at the sub-national level. JEL Classification: H50, H70, O1

Atomic force microscopy studies of DNA binding properties of the archaeal MCM complex

The MCM (mini-chromosome mainteinance) protein complex has a key role in the replication machinery of Eukaryotes and Archaea. Beside the main unwiding role, this helicase is also supposed to act as one of the essential element licensing replication to ensure that each segment of the genome is replicated only once per cycle. Six homologous MCM proteins belonging to the AAA+ ATPase superfamily, known as MCM2-7, are forming in Eukaryotes a hexameric hetero-complex that is supposed to "load" onto a single DNA strand and to use energy from ATP (Adenosine triphosphate) hydrolysis to unzip the DNA double helix. In Archaea, there is a single MCM gene, coding for a single MCM protein. Therefore the protein complex is made by a homohexamer with six equivalent subunits. The DNA loading mechanism for double-strand unzipping is similar to the Eukaryotes case. The scope of this thesis work is to investigate the structural details of the interaction between DNA and the MCM complex in near physiological condition, by means of Atomic Force Microscopy (AFM) single molecule imaging. For that, we used archaeal MCM from Methanothermobacter Thermautotrophicus as a model system. There are structural and biochemical evidences that MCM interacts with DNA in two ways: the canonical \u201cloaded\u201d mode where the MCM protein complex is encircling the DNA for unwinding, and an \u201cassociated\u201d mode where the DNA is supposed to be wrapped around the external part of the proper ring structure. In this second configuration, less studied than the loaded one, the binding interaction between MCM and DNA might play a role in licencing/initiating the replication process. By means of AFM, we studied the conformational changes induced by the protein complex on blunt-ends, double-stranded (ds) DNA filaments of different lenghts. AFM experiments were carried out in two different conditions: in air to understand the static conformations of DNA-protein complexes; in liquid to follow the interaction dynamics. We first optimized the protocol (surface treatment, buffer condition) for AFM imaging in air to obtain high resolution images of surface-equilibrated DNA molecules before and after the interaction with the protein complex. From statistical analysis of AFM images, we localized the protein complexes along the isolated dsDNA sequences and calculated DNA contour lenght and bending angle before and after the interaction with the protein complex. We discriminated between proteins with DNA wrapped around, calling them \u201cassociated\u201d, and the ones interacting with DNA without inducing any bending, calling them \u201cloaded\u201d. To confirm this topographical assignment, we tested two mutants: N\u3b2H complex, which presents a mutation in the central hole of the hexamer, inhibiting DNA loading; 06sA complex, which presents a mutation in the external part, preventing DNA association. In the case of N\u3b2H, only associated DNA was observed; in the case of 06sA, only loaded complexes were found, to prove the soundness of our assumptions. Moreover, the total number of DNA bound complexes decreased from 84% to 20% from MCM to 06sA, proving that association is involved in favouring the replicative helicase loading, and initiating the double-helix unwinding. Finally, we found a DNA compaction of about 13 nm for wild type MCM and 06sA mutant. In the case of N\u3b2H mutant, the compaction is of about 18nm, and comes together with a bending angle increase of about 16\ub0, strongly supporting the \u201cassociation\u201d model. Finally, we studied the dynamics of DNA-MCM complex interaction, in the presence of ATP, via moderately fast (few seconds/images) AFM imaging in liquid. After ATP loading, we observed a change of topographic height of the DNA strands, consistent with the formation of ssDNA, as a sign of DNA unwinding by the MCM complex. This effect was unexpected, since there are no biochemical evidences in literature of efficient unwinding of MCM complex on blunt-ended DNA

Megalencephalic Leukoencephalopathy with Subcortical Cysts

N

Guided self-help Urdu version of the living life to the full intervention for secondary school adolescents with low mood and anxiety in Pakistan: a feasibility study

There is limited evidence on the efficacy of Cognitive Behavioral Therapy (CBT) based guided self-help programs to improve low mood and anxiety in Pakistani adolescents. The aims of the current study were to assess the effectiveness of an eight week low intensity CBT-based guided self-help program, Living Life to the Full (LLTTF) on depression, anxiety and social functioning among secondary school adolescents in Pakistan. Fifty-six participants were randomly allocated to immediate (n = 28) and delayed access (n = 28) groups. Measures of depression, anxiety and social functioning were collected at baseline, post intervention and three months follow-up. There were significant improvements in measures of depression (t = -3.47, p < 0.01; d = 1.0), anxiety (t = -6.55, p < 0.001; d = 1.91) and social functioning (t = -4.28, p < 0.001) between immediate access and delayed access groups. These differences remained significant at three months follow-up. The study suggests that the Urdu LLTTF book course delivered in classes is effective for reducing depression and anxiety as well as improving social function among adolescents in Pakistan