Neurotrophic factor-α1 prevents stress-induced depression through enhancement of neurogenesis and is activated by rosiglitazone.

Major depressive disorder is often linked to stress. Although short-term stress is without effect in mice, prolonged stress leads to depressive-like behavior, indicating that an allostatic mechanism exists in this difference. Here we demonstrate that mice after short-term (1 h per day for 7 days) chronic restraint stress (CRS), do not display depressive-like behavior. Analysis of the hippocampus of these mice showed increased levels of neurotrophic factor-α1 (NF-α1; also known as carboxypeptidase E, CPE), concomitant with enhanced fibroblast growth factor 2 (FGF2) expression, and an increase in neurogenesis in the dentate gyrus. In contrast, after prolonged (6 h per day for 21 days) CRS, mice show decreased hippocampal NF-α1 and FGF2 levels and depressive-like responses. In NF-α1-knockout mice, hippocampal FGF2 levels and neurogenesis are reduced. These mice exhibit depressive-like behavior that is reversed by FGF2 administration. Indeed, studies in cultured hippocampal neurons reveal that NF-α1 treatment directly upregulates FGF2 expression through extracellular signal-regulated kinase-Sp1 signaling. Thus, during short-term CRS, hippocampal NF-α1 expression is upregulated and has a key role in preventing the onset of depressive-like behavior through enhanced FGF2-mediated neurogenesis. To evaluate the therapeutic potential of this pathway, we examined, rosiglitazone (Rosi), a PPARγ agonist, which has been shown to have antidepressant activity in rodents and humans. Rosi upregulates FGF2 expression in a NF-α1-dependent manner in hippocampal neurons. Mice fed Rosi show increased hippocampal NF-α1 levels and neurogenesis compared with controls, thereby indicating the antidepressant action of this drug. Development of drugs that activate the NF-α1/FGF2/neurogenesis pathway can offer a new approach to depression therapy.

Water dynamics in rigid ionomer networks.

The dynamics of water within ionic polymer networks formed by sulfonated poly(phenylene) (SPP), as revealed by quasi-elastic neutron scattering (QENS), is presented. These polymers are distinguished from other ionic macromolecules by their rigidity and therefore in their network structure. QENS measurements as a function of temperature as the fraction of ionic groups and humidity were varied have shown that the polymer molecules are immobile while absorbed water molecules remain dynamic. The water molecules occupy multiple sites, either bound or loosely constrained, and bounce between the two. With increasing temperature and hydration levels, the system becomes more dynamic. Water molecules remain mobile even at subzero temperatures, illustrating the applicability of the SPP membrane for selective transport over a broad temperature range.

Anaesthetic management of a patient with dermatomyositis and valvular heart disease.

Dermatomyositis is an idiopathic inflammatory myopathy with involvement of muscle, skin and other organs. Valvular heart disease increases the risk of perioperative adverse cardiac events. Only a little information is available about the anaesthetic management of a patient with dermatomyositis and valvular heart disease. Here we considered combined spinal-epidural technique for total abdominal hysterectomy, minimizing the risk of delayed recovery from muscle relaxants, aspiration pneumonitis, arrhythmias and cardiac failure.

Targeted deletion of GD3 synthase protects against MPTP-induced neurodegeneration.

Parkinson's disease is a debilitating neurodegenerative condition for which there is no cure. Converging evidence implicates gangliosides in the pathogenesis of several neurodegenerative diseases, suggesting a potential new class of therapeutic targets. We have shown that interventions that simultaneously increase the neuroprotective GM1 ganglioside and decrease the pro-apoptotic GD3 ganglioside - such as inhibition of GD3 synthase (GD3S) or administration of sialidase - are neuroprotective in vitro and in a number of preclinical models. In this study, we investigated the effects of GD3S deletion on parkinsonism induced by 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP was administered to GD3S-/- mice or controls using a subchronic regimen consisting of three series of low-dose injections (11 mg/kg/day × 5 days each, 3 weeks apart), and motor function was assessed after each. The typical battery of tests used to assess parkinsonism failed to detect deficits in MPTP-treated mice. More sensitive measures - such as the force-plate actimeter and treadmill gait parameters - detected subtle effects of MPTP, some of which were absent in mice lacking GD3S. In wild-type mice, MPTP destroyed 53% of the tyrosine-hydroxylase (TH)-positive neurons in the substantia nigra pars compacta (SNc) and reduced striatal dopamine 60.7%. In contrast, lesion size was only 22.5% in GD3S-/- mice and striatal dopamine was reduced by 37.2%. Stereological counts of Nissl-positive SNc neurons that did not express TH suggest that neuroprotection was complete but TH expression was suppressed in some cells. These results show that inhibition of GD3S has neuroprotective properties in the MPTP model and may warrant further investigation as a therapeutic target.

Intrauterine growth curves for singleton live babies in Paropakar Maternity and Women's Hospital in Nepal.

BACKGROUND: To construct birth weight, crown heel length and head circumference centile chart referenced to gestational age for Nepalese infants. METHODS: The study was conducted over a period of six months. It included consecutive live births from 28 to 42 weeks of gestation. Their birth weight, crown-heel length and head circumference were recorded. Smoothed percentile values along with curves were created using the Lambda Mu Sigma (LMS) method. The curves were compared with one of the Indian study. RESULTS: A total of 9710 newborns were measured. The mean birth weight, crown-heel length, head circumference at 40 weeks were 3023g, 49.22cm and 33.61cm respectively. Smoothed percentile values calculated gave the cutoffs for defining small and large gestational age for Nepalese newborns. Comparison with Indian study showed significant difference (p<0.01) in weight. The Indian babies weighed less than Nepalese babies. CONCLUSIONS: The referenced growth standards help in clinical assessment, defining and identifying high risk newborns, thus, leading to improved care and management of neonates. It should help public health policy makers to track population difference due to several factors, intervene and find response over time.

State of maternal, newborn and child health programmes in Nepal: what may a continuum of care model mean for more effective and efficient service delivery?

The cost-effective interventions exist across the continuum of maternal to child survival at each level of the health system that can contribute to achieve the Millennium Development Goals 4 and 5. However, implementation inefficiency, low coverage and equity gaps along this continuum remain a serious challenge to Nepal's efforts to achieve these goals. This paper proposes a continuum of care model; discusses the readiness of policy and programs to provide high impact interventions across the continuum; identifies existing gaps in MNCHN programs; and recommends policy and program actions to improve coverage, equity, effectiveness and efficiency along the continuum of MNCHN service delivery in Nepal. The literature review includes systematic desk review, followed by discussions and deliberations amongst a group of professionals and MNCH experts in Nepal. Within the government health system in Nepal, a continuum of care approach is feasible, as policies and plans exist to ensure an integrated approach across the maternal to child care continuum. However, health programs largely remain vertically oriented. Achieving integration across the maternal to child continuum of care remains a challenge at each level of health system. An integrated system of program management for maternal, newborn and child health would be a feasible solution to enable an efficient and effective delivery of intervention packages. A collaborative and partnership approach to strengthen health systems, building managerial capacity, improving governance and engaging the private and civil sectors remains vital to achieve effective coverage and improve equity across the continuum of care.

Developing community-based intervention strategies and package to save newborns in Nepal.

In Nepal, the proportion of under 5 deaths that are neonatal (0-28 days) has been increasing in the last decade, due to faster declines in infant and child mortality than in neonatal mortality. This trend is likely due to a focus on maternal and child survival programs that did not adequately address newborn health needs. Policy and actions to save newborn lives resulted from increased attention to newborn deaths in 2001, culminating in the endorsement of the National Neonatal Health Strategy in 2004, a milestone that established newborn health and survival as a national priority. Operationalization of the National Neonatal Health Strategy took place in 2007 with the development of the Community-Based Newborn Care Package (CB-NCP). This paper describes how national stakeholders used global, regional and in-country research and policies to develop the CB-NCP, thus outlining key ingredients to make newborn health programming a reality in Nepal. A technical working group was constituted to review existing evidence on interventions to improve newborn survival, develop a tool to prioritize neonatal interventions, and conduct program learning visits to identify key components appropriate to the Nepal context that should be included in the Community Based Integrated Newborn Care Package. The group identified interventions based on the evidence of impact on newborn survival, potential mechanisms within the existing health system to deliver the interventions, and linkages with existing programs and different tiers of the health system. Not only was Nepal one of the first countries in south-east Asia where government adopted a national strategy to reduce neonatal deaths, but it was also one of the first to endorse a package of neonatal interventions for pilot testing and scaling up through existing community-based health systems that provide basic health services throughout the country. CB-NCP was designed to be gradually scaled up throughout the country by integration with Safe Motherhood and Child survival programs that are currently operating at scale. Under Ministry of health and Population leadership, a network of academia, professional bodies and partners developed a common vision for improving newborn health and survival, and launched district-level pilot programs to demonstrate and learn how newborn health interventions could be effectively and efficiently delivered and scaled up in Nepal.

Fitting Community Based Newborn Care Package into the health systems of Nepal.

Community-based strategies for delivering effective newborn interventions are an essential step to avert newborn death, in settings where the health facilities are unable to effectively deliver the interventions and reach their population. Effective implementation of community-based interventions as a large scale program and within the existing health system depends on the appropriate design and planning, monitoring and support systems. This article provides an overview of implementation design of Community-Based Newborn Care Package (CB-NCP) program, its setup within the health system, and early results of the implementation from one of the pilot districts. The evaluation of CB-NCP in one of the pilot districts shows significant improvement in antenatal, intrapartum and post natal care. The implementation design of the CB-NCP has six different health system management functions: i) district planning and orientation, ii) training/human resource development, iii) monitoring and evaluation, iv) logistics and supply chain management, v) communication strategy, and vi) pay for performance. The CB-NCP program embraced the existing system of monitoring with some additional components for the pilot phase to test implementation feasibility, and aligns with existing safe motherhood and child health programs. Though CB-NCP interventions are proven independently in different local and global contexts, they are piloted in 10 districts as a "package" within the national health system settings of Nepal.