Mutations in PNKD causing paroxysmal dyskinesia alters protein cleavage and stability.

Paroxysmal non-kinesigenic dyskinesia (PNKD) is a rare autosomal dominant movement disorder triggered by stress, fatigue or consumption of either alcohol or caffeine. Attacks last 1-4 h and consist of dramatic dystonia and choreoathetosis in the limbs, trunk and face. The disease is associated with single amino acid changes (A7V or A9V) in PNKD, a protein of unknown function. Here we studied the stability, cellular localization and enzymatic activity of the PNKD protein in cultured cells and transgenic animals. The N-terminus of the wild-type (WT) long PNKD isoform (PNKD-L) undergoes a cleavage event in vitro, resistance to which is conferred by disease-associated mutations. Mutant PNKD-L protein is degraded faster than the WT protein. These results suggest that the disease mutations underlying PNKD may disrupt protein processing in vivo, a hypothesis supported by our observation of decreased cortical Pnkd-L levels in mutant transgenic mice. Pnkd is homologous to a superfamily of enzymes with conserved β-lactamase domains. It shares highest homology with glyoxalase II but does not catalyze the same reaction. Lower glutathione levels were found in cortex lysates from Pnkd knockout mice versus WT littermates. Taken together, our results suggest an important role for the Pnkd protein in maintaining cellular redox status

Evolution of Function in the “Two Dinucleotide Binding Domains” Flavoproteins

Structural and biochemical constraints force some segments of proteins to evolve more slowly than others, often allowing identification of conserved structural or sequence motifs that can be associated with substrate binding properties, chemical mechanisms, and molecular functions. We have assessed the functional and structural constraints imposed by cofactors on the evolution of new functions in a superfamily of flavoproteins characterized by two-dinucleotide binding domains, the “two dinucleotide binding domains” flavoproteins (tDBDF) superfamily. Although these enzymes catalyze many different types of oxidation/reduction reactions, each is initiated by a stereospecific hydride transfer reaction between two cofactors, a pyridine nucleotide and flavin adenine dinucleotide (FAD). Sequence and structural analysis of more than 1,600 members of the superfamily reveals new members and identifies details of the evolutionary connections among them. Our analysis shows that in all of the highly divergent families within the superfamily, these cofactors adopt a conserved configuration optimal for stereospecific hydride transfer that is stabilized by specific interactions with amino acids from several motifs distributed among both dinucleotide binding domains. The conservation of cofactor configuration in the active site restricts the pyridine nucleotide to interact with FAD from the re-side, limiting the flow of electrons from the re-side to the si-side. This directionality of electron flow constrains interactions with the different partner proteins of different families to occur on the same face of the cofactor binding domains. As a result, superimposing the structures of tDBDFs aligns not only these interacting proteins, but also their constituent electron acceptors, including heme and iron-sulfur clusters. Thus, not only are specific aspects of the cofactor-directed chemical mechanism conserved across the superfamily, the constraints they impose are manifested in the mode of protein–protein interactions. Overlaid on this foundation of conserved interactions, nature has conscripted different protein partners to serve as electron acceptors, thereby generating diversification of function across the superfamily

Feasibility and pilot study of the effects of microfinance on mortality and nutrition in children under five amongst the very poor in India: study protocol for a cluster randomized controlled trial

Background: The United Nations Millennium Development Goals include targets for the health of children under five years old. Poor health is linked to poverty and microfinance initiatives are economic interventions that may improve health by breaking the cycle of poverty. However, there is a lack of reliable evidence to support this. In addition, microfinance schemes may have adverse effects on health, for example due to increased indebtedness. Rojiroti UK and the Centre for Promoting Sustainable Livelihood run an innovative microfinance scheme that provides microcredit via women’s self-help groups (SHGs). This pilot study, conducted in rural Bihar (India), will establish whether it is feasible to collect anthropometric and mortality data on children under five years old and to conduct a limited cluster randomized trial of the Rojiroti intervention. Methods/Design: We have designed a cluster randomized trial in which participating tolas (small communities within villages) will be randomized to either receive early (SHGs and microfinance at baseline) or late intervention (SHGs and microfinance after 18 months). Using predesigned questionnaires, demographic, and mortality data for the last year and information about participating mothers and their children will be collected and the weight, height, and mid upper arm circumference (MUAC) of children will be measured at baseline and at 18 months. The late intervention group will establish SHGs and microfinance support at this point and data collection will be repeated at 36 months. The primary outcome measure will be the mean weight for height z-score of children under five years old in the early and late intervention tolas at 18 months. Secondary outcome measures will be the mortality rate, mean weight for age, height for age, prevalence of underweight, stunting, and wasting among children under five years of age. Discussion: Despite economic progress, marked inequalities in child health persist in India and Bihar is one of the worst affected states. There is a need to evaluate programs that may alleviate poverty and improve health. This study will help to inform the design of a definitive trial to determine if the Rojiroti scheme can improve the nutrition and survival of children under five years of age in deprived rural communities

Material Study of Co2CrAl Heusler Alloy Magnetic Thin Film and Co2CrAl/n-Si Schottky Junction Device

The structural, optical, magnetic, and electrical properties of Co2CrAl Heusler alloy magnetic thin films grown on n-type silicon (100) substrate (n-Si) and glass substrate were studied. The films were deposited using DC magnetron sputtering. X-ray diffraction (XRD) analysis confirmed the polycrystalline nature of the films. The effect of grain size on transmittance was investigated. Magnetic measurements revealed the presence of magnetic ordering in the films. Partial densities of states (PDOS) of the Co2CrAl were calculated by density functional theory (DFT) methods using the Vienna Ab initio Simulation Package (VASP). Co2CrAl thin film deposited over a silicon substrate was investigated for I-V characteristics. The electrical behaviour confirmed the existence of a Co2CrAl/n-Si Schottky contact, which suggests a spin injection phenomenon from Co2CrAl to n-Si by tunnelling through the lowered Schottky barrier

Transdural herniated lumbar disc disease with muscle patch for closure of durotomy – A Brief review of literature

Purpose Intradural migration of disc (IDMD) is a rare clinical entity accounting for 0.27–0.33% of all herniated disc diseases. Flimsy or dense adhesion between the ventral dural surface and the opposing posterior longitudinal ligament (PLL) is the principal pathology for intradural migrated disc. The most commonly affected lumbar segments are L4-5 (55%), L3-4 (16%), L5-S1 (10%) and less commonly L2L3 and L1L2. No imaging feature is characteristic and the management protocol of durotomy via an endoscopic method is unclear. Methods An L5S1 disc disease was operated by endoscopic method. Difficulty in separating the dural sac from PLL, dense adhesions prompting sharp dissection at this location and a calcified disc are the earliest evidence of intradural migration. MRI features of an intradural location are loss of continuity of posterior longitudinal ligament, beak-like appearance also known as “Hawk-beak sign”, peripheral enhancement around an intradural disc, fluid-filled intradural cyst. Magnification either by Microscope or Endoscope is of importance when dissecting the intradural disc so as to avoid the nerve root injury. Liberal use of fibrin glue and augmentation with muscle patch was performed. Results Ambulated by 48h and discharged by 5th day. Two and 9 months follow up showed no evidence of pseudomeningocoele. Conclusion Autologous muscle patch with fibrin glue for dural rent closure is a simple and effective method which can be performed by endoscopic or minimally invasive approaches. Suturing the dura, being a tedious and cumbersome procedure can be avoided

Analysis of Traumatic brain injury related to Kite flying festival: An institutional study

Introduction: Makar Sankranti or Uttarayan is the kite flying festival in India. The festival marks the end of winter and the beginning of summer as the sun moves to the Tropic of Cancer bringing with it longer and warmer days. But it turns into a difficult day for those who are hospitalised after suffering from kite flying related injuries. Aims & Objectives: The objective of this cross sectional study was to review the demographics, causes injury, severity, treatment and outcome of traumatic brain injuries in victims of this kite flying festival who were admitted in department of Neurosurgery on the occasion this year in January. Patients & Methods: A total of 46 traumatic brain injured patients was admitted under Neurosurgery Services that day, out of which 18 cases were related to kite flying related injury. Data of these 18 patients were analysed and outcome were measured at discharge. Result: kite flying festival related neurotrauma increase 39% more emergency admission burden as compared to routine days in neuro-emergency ward. Most common cause of head injury among them was fall from roof. Majority of them had mild head injury. Associated injuries to other part of body were present in 46% patients. Conclusion: Children were most affected due to unsupervised kite flying on roof and road side catching of kites. Depressed fracture was commonest type of traumatic brain injury. Strict attention to safety measures and parental supervision while flying kites can avoid many preventable injuries to life

Cerebellar pilomyxoid astrocytoma

Pilomyxoid astrocytomas (P.M.A) are new class of Pilocytic Astrocytoma (P.A.) which typically have their origin in hypothalamus and chiasmatic region. There are very few case reports of PMAs arising from cerebellum. Their imaging features are similar to PA but they behave more aggressively than PA. The authors report a case of 10 year old male child who presented with right cerebellar tumour diagnosed as PMA on histopathology

Daily Bread: Women’s Self-Help Microfinance and the Social Meanings of Money

In this article we explore the impacts and implications of ‘Rojiroti’, a women’s self-help group (SHG) microfinance scheme operating in poor communities in Bihar, India. We focus particularly on how improvements found in women’s circumstances and in children’s health might result from Rojiroti SHG membership. Through data from five focus groups and 19 individual interviews with women in communities where Rojiroti operates, we discover how the scheme is regarded and how it affects women’s management of household budgets. Moreover, we explore the relational aspects of SHG microfinance and the ways that it can alter family and social dynamics. Drawing on notions of ‘earmarked’ money (Zelizer, 1997) and ‘safeguarded’ money (Wilkis, 2017), we argue that the money itself has meaning and non-pecuniary value in the form of other currencies including power and agency, which can lead to improved wellbeing and health of families

Rojiroti microfinance and child nutrition: a cluster randomised trial.

OBJECTIVE To determine whether Rojiroti microfinance, for poor Indian women, improves child nutrition. DESIGN Cluster randomised trial. SETTING Tolas (village communities) in Bihar State. PARTICIPANTS Women and children under 5 years. INTERVENTIONS With Rojiroti microfinance, women form self-help groups and save their money to provide loans to group members. After 6 months, they receive larger external loans. Tolas were randomised to receive Rojiroti immediately or after 18 months. OUTCOME MEASURES The primary analysis compared the mean weight for height Z score (WHZ) of children under 5 years in the intervention versus control tolas who attended for weight and height measurement 18 months after randomisation. Secondary outcomes were weight for age Z score (WAZ), height for age Z score, mid-upper arm circumference (MUAC), wasting, underweight and stunting. RESULTS We randomised 28 tolas to each arm and collected data from 2469 children (1560 mothers) at baseline and 2064 children (1326 mothers) at follow-up. WHZ was calculated for 1718 children at baseline and 1377 (674 intervention and 703 control) at follow-up. At 18 months, mean WHZ was significantly higher for intervention (-1.02) versus controls (-1.37; regression coefficient adjusted for clustering β0.38, 95% CI 0.16 to 0.61, p=0.001). Significantly fewer children were wasted in the intervention group (122, 18%) versus control (200, 29%; OR=0.46, 95% CI 0.28 to 0.74, p=0.002). Mean WAZ was better in the intervention group (-2.13 vs -2.37; β0.27, 95% CI 0.11 to 0.43, p=0.001) as was MUAC (13.6 cm vs 13.4 cm; β0.22, 95% CI 0.03 to 0.40, p=0.02). In an analysis adjusting for baseline nutritional measures (259 intervention children and 300 control), only WAZ and % underweight showed significant differences in favour of the intervention. CONCLUSION In marginalised communities in rural India, child nutrition was better in those who received Rojiroti microfinance, compared with controls. TRIAL REGISTRATION NUMBER NCT01845545