miR-449a Mediated Repression of the Cell Cycle Machinery Prevents Neuronal Apoptosis.

Aberrant activation of the cell cycle of terminally-differentiated neurons results in their apoptosis and is known to contribute to neuronal loss in various neurodegenerative disorders like Alzheimer's Disease. However, the mechanisms that regulate Cell Cycle Related Neuronal Apoptosis (CRNA) are poorly understood. We identified several miRNA that are dysregulated in neurons from a transgenic APP/PS1 mouse model for AD (TgAD). Several of these miRNA are known to and/or are predicted to target cell cycle-related genes. Detailed investigation on miR-449a revealed: a. it promotes neuronal differentiation by suppressing the neuronal cell cycle; b. its expression in cortical neurons was impaired in response to amyloid peptide Aß42; c. loss of its expression resulted in aberrant activation of the cell cycle leading to apoptosis. miR-449a may prevent CRNA by targeting cyclin D1 and protein phosphatase CDC25A, which are important for G1-S transition. Importantly, the lentiviral mediated delivery of miR-449a in TgAD mouse brain significantly reverted the defects in learning and memory, which are associated with AD.

Protective effect of Indole-3-carbinol, an NF-κB inhibitor in experimental paradigm of Parkinson's disease: In silico and in vivo studies.

Parkinson's disease (PD) is a progressive neurodegenerative disorder, majorly with symptoms of motor dysfunction. Study was performed to explore the effect of nuclear factor κB (NF-κB) inhibitors against neurobehavioral abnormalities and neuroinflammation in PD. Cost effective in silico approaches of docking-based ligand -target complex predictions and optimal physicochemical properties were utilised to identify lead NF-κB inhibitor using database. Our studies revealed the potential hit Indole-3-carbinol (I3C) which was considered for the next phase, pharmacological validations. Intranigral administration of lipopolysaccharide (LPS) in rats is utilized as a neuroinflmmation model of PD. In the present study it caused an impairment in motor functions, its coordination, learning and memory as demonstrated in rotarod apparatus, beam balance test, open field test and Morris water maze test. Chronic administration of I3C for 21 days in intranigral LPS treated rats led to a significant improvement in motor functions, coordination, learning and memory which were associated with a decrease in the activity of inflammatory cytokines such as TNF-α and IL-6. Further, it was found to inhibit NF-κB whose levels increased after LPS administration. Moreover, decreased levels of malondialdehyde and increased levels of reduced glutathione, superoxide dismutase and catalase were observed in cortex and striatum after I3C administration in LPS rats. These results suggest a possible neuroprotective effect of I3C via amelioration of LPS-induced behavioural alterations, oxidative damage and neuroinflammation which in turn is attributed to its potent antioxidant and anti-inflammatory (NF-κB inhibition) property. The effect produced by I3C (50 mg/kg) was found to be comparable with levodopa-carbidopa combination (LD:CD) while, I3C (50 mg/kg) in combination with LD:CD exhibited a potentiating effect in improving motor impairments and cognitive deficit. The results thus depict I3C as a promising agent to delay neurodegeneration of the neurons in PD with improvement in motor functions and cognitive function.

Similar functional outcome using single anterior portal and standard two portals technique in recurrent dislocation of shoulder.

PURPOSE: Recurrent dislocation of shoulder (RDS) is a common injury in high demand professionals, like athletes and military personnel. The treatment for the patients with Bankart lesion is the arthroscopic repair. This present study compares the outcomes of two different techniques of arthroscopic Bankart repair i.e. a standard two anterior portals technique and a single anterior portal technique in patients with RDS. METHODS: Patients with traumatic RDS met the inclusion criteria were managed with Bankart repair using either two anterior portals (Group A) or a single anterior portal (Group B) technique. Patients were evaluated before the intervention and at the mean follow-up of approximately two years using Rowe score, Oxford shoulder score and Tegner activity scale. RESULTS: The mean age of the patients in Groups A (n = 34) and B (n = 37) was 29.64 years and 29.05 years respectively (p = 0.66). The dominant shoulder was involved in 27 patients in Group A and 22 patients in Group B (p = 0.069). The operative time in Group A and B was 68.52 min and 46.35 min, respectively (p < 0.001). The complications at follow-up, the mean Rowe score and Oxford score improved significantly in both groups compared with the pre-operative values. However, the final outcome scores were not significantly different between the both groups. The median Tegner's score preoperatively and at follow-up was 7 and 6, respectively in Groups A and B. CONCLUSIONS: Single anterior portal technique is an effective treatment modality, yielding a similar outcome as two anterior portals technique in the management of RDS.

Risk factors for stillbirths: how much can a responsive health system prevent?

BACKGROUND: The stillbirth rate is an indicator of quality of care during pregnancy and delivery. Good quality care is supported by a functional heath system. The objective of this study was to explore the risk factors for stillbirths, particularly those related to a health system. METHODS: This case-control study was conducted in two districts of Bihar, India. Information on cases (stillbirths) were obtained from facilities as reported by Health Management Information System; controls were consecutive live births from the same population as cases. Data were collected from 400 cases and 800 controls. The risk factors were compared using a hierarchical approach and expressed as odds ratio, attributable fractions and population attributable fractions. RESULTS: Of all the factors studied, 22 risk factors were independently associated with stillbirths. Health system-related factors were: administration of two or more doses of oxytocics to augment labour before reaching the facilities (OR 1.6; 95% CI 1.2-2.1), any complications during labour (OR 2.3;1.7-3.1), >30 min to reach a facility from home (OR 1.4;1.05-1.8), >10 min to attend to the pregnant woman after reaching the facility (OR 2.8;1.7-4.5). In the final regression model, modifiable health system-related risk factors included: >10 min taken to attend to women after they reach the facilities (AOR 3.6; 95% CI 2.5-5.1), untreated hypertension during pregnancy (AOR 2.9; 95% CI 1.5-5.6) and presence of any complication during labour, warranting treatment (AOR 1.7; 95% CI 1.2-2.4). Among mothers who reported complications during labour, time taken to reach the facility was significantly different between stillbirths and live births (2nd delay; 33.5 min v/s 25 min; p < 0.001). Attributable fraction for any complication during labour was 0.56 (95% CI 0.42-0.67), >30 min to reach the facility 0.48 (95% CI 0.31-0.60) and institution of management 10 min after reaching the facility 0.68 (95% CI 0.58-0.75). Reaching a facility within 30 min, initiation of management within 10 min of reaching the facility and timely management of complications during labour could have prevented 17%, 37% and 20% of stillbirths respectively. CONCLUSION: A pro-active health system with accessible, timely and quality obstetric services can prevent a considerable proportion of stillbirths in low and middle income countries.

Pulmonary hypertension and right heart failure due to severe hypernatremic dehydration.

INTRODUCTION: Neonates are at risk of developing hypernatremic dehydration and its associated complications, such as stroke, dural sinus thrombosis and renal vein thrombosis. Pulmonary hypertension has not been described as a complication of hypernatremia. CASE REPORT: We report a case of a seven-day-old neonate with severe hypernatremic dehydration who went on to develop pulmonary hypertension and right heart failure needing extracorporeal membrane oxygenation (ECMO). DISCUSSION: Normal or high anion gap metabolic acidosis commonly accompanies hypernatremic dehydration. The presence of acidosis and/or hypoxia can delay the normal drop in pulmonary vascular resistance (PVR) after birth, causing pulmonary hypertension and right ventricular failure. CONCLUSION: A high index of suspicion is paramount to diagnose pulmonary hypertension and aggressive correction of the acidosis and hypoxia is needed. In the presence of severe right ventricular failure, ECMO can be used as a bridge to recovery while underlying metabolic derangements are being corrected.

Toxicophore exploration as a screening technology for drug design and discovery: techniques, scope and limitations.

Toxicity is a common drawback of newly designed chemotherapeutic agents. With the exception of pharmacophore-induced toxicity (lack of selectivity at higher concentrations of a drug), the toxicity due to chemotherapeutic agents is based on the toxicophore moiety present in the drug. To date, methodologies implemented to determine toxicophores may be broadly classified into biological, bioanalytical and computational approaches. The biological approach involves analysis of bioactivated metabolites, whereas the computational approach involves a QSAR-based method, mapping techniques, an inverse docking technique and a few toxicophore identification/estimation tools. Being one of the major steps in drug discovery process, toxicophore identification has proven to be an essential screening step in drug design and development. The paper is first of its kind, attempting to cover and compare different methodologies employed in predicting and determining toxicophores with an emphasis on their scope and limitations. Such information may prove vital in the appropriate selection of methodology and can be used as screening technology by researchers to discover the toxicophoric potentials of their designed and synthesized moieties. Additionally, it can be utilized in the manipulation of molecules containing toxicophores in such a manner that their toxicities might be eliminated or removed.

An assessment of bicycle intervention to improve service delivery by accredited social health activists in selected blocks of West Champaran district of Bihar.

BACKGROUND: Several programmatic and logistic issues affect the overall performance of Accredited Social Health Activists (ASHAs). Bihar Government provided bicycles to ASHAs in West Champaran district for increasing coverage of services by improving their mobility. OBJECTIVE: To assess the use of bicycles by ASHAs and it's effect on service delivery. It also captures the perspectives of ASHAs in terms of its utilization for performing tasks. METHODS: A community-based quasi-experimental study was undertaken during March-May 2016. Proportion of newborn babies visited within 24 h of birth was the primary outcome. Data were collected from two intervention blocks (West Champaran district) and a control block from the neighboring East Champaran district. A total of 323 (177 from intervention blocks and 146 from control block) mothers having children <3 years of age and who had delivered at home were interviewed. Besides, 88 ASHAs working in intervention blocks were also interviewed. RESULTS: Significantly higher proportion of mothers and newborn babies (44%) received postnatal care within 24 h of delivery in intervention blocks as compared to the control block (16%, P < 0.001). Nearly 73.1% of ASHAs were using the bicycle themselves. ASHAs were twice more likely to visit a newborn on the day of delivery if she was provided with mobility support. However, the likelihood of continuing visits after the 1st day was not statistically significant. CONCLUSION: The intervention demonstrated the potential of ASHAs to improve their functioning at the grass-root level. The scale-up of bicycle intervention should be supplemented with reforms in financial incentives disbursement and better system support.

Computer tablet-based health technology for strengthening maternal and child tracking in Bihar.

BACKGROUND: UNICEF along with the State Government of Bihar launched a computer tablet-based Mother and Child Tracking System (MCTS) in 2014, to capture real-time data online and to minimize the challenges faced with the conventional MCTS. OBJECTIVE: The article reports the process of implementation of tablet-based MCTS in Bihar. METHODS: In-depth interviews with medical officers, program managers, data managers, auxiliary nurse midwives (ANMs), and a monitoring and evaluation specialist were conducted in October 2015 to understand the process of implementation, challenges and possibility for sustainability, and scale-up of the innovation. RESULTS: MCTS innovation was introduced initially in one Primary Health Centre each in Gaya and Purnia districts. The device, supported with Android MCTS software and connected to a dummy server, was given to ANMs. ANMs were trained in its application. The innovation allows real-time data entry, instant uploading, and generation of day-to-day work plans for easy tracking of beneficiaries for providing in-time health-care services. The nonlinking of the dummy server to the national MCTS portal has not lessened the burden of data entry operators, who continue to enter data into the national portal as before. CONCLUSION: The innovation has been successfully implemented to meet its objective of tracking the beneficiaries. The national database should be linked to the dummy server or visible impact. The model is sustainable if the challenges can be met. Mobile technology offers a tremendous opportunity to strengthen the capacity of frontline workers and clinicians and increase the quality, completeness, and timeliness of delivery of critical health services.

Assessment of newborn care corners in selected public health facilities in Bihar.

BACKGROUND: A functional newborn care corner (NBCC) is critical to provide immediate care to newborns including resuscitation, warmth, and initial care to sick newborns. NBCC provides an acceptable environment for all infants at birth, and it is mandatory for all delivery points at all levels in the health system including operation theaters. OBJECTIVE: The objective of this study was to find the status of availability of NBCCs and service provision in selected public health facilities of Bihar. METHODS: A total of 57 NBCCs, having high delivery load (>100 deliveries/month), across 25 high-priority districts in Bihar, were selected purposively in consultation with the State Health Society, Bihar, for the assessment. These facilities were assessed for the availability and/or functioning of infrastructure, equipment maintenance, human resource, supply of drugs and consumables, adherence to protocols, and record keeping. RESULTS: Only 22.8% of the NBCCs were found to be fully functional, majority (68.4%) were partially functional, and 9% were nonfunctional. Thirty-seven (64.9%) NBCCs were located inside the labor room premises. Approximately, one-third of the neonates delivered were kept in NBCCs. Equipment though available lacked the provision of annual maintenance contract. Essential drugs such as adrenaline (24.6%) and Vitamin K injection (42.1%) were not available in many facilities. Only 6.2% of the newborns had low birth weight, indicating underreporting. Majority of the health-care staff available were trained but possessed poor skills. Data recording and reporting was also suboptimal. CONCLUSION: The network of NBCCs needs to be strengthened across the state and linked with higher facilities to achieve the desired reduction in neonatal morbidity and mortality.

Rollout of quality assurance interventions in labor room in two districts of Bihar, India.

BACKGROUND: Quality of care at the facilities during childbirth remains a major concern. Improved quality could have the greatest dividend in saving maternal and newborn lives. OBJECTIVE: The objective of this study was to implement quality assurance measures in the labor rooms of select public health facilities in two districts of Bihar. METHODS: The labor room quality assurance intervention was implemented in two districts, Gaya and Purnea in Bihar. Health facilities having >200 deliveries/month were assessed using labor room quality assurance checklist developed by the Ministry of Health and Family Welfare. The critical gaps affecting service delivery were identified, and a list of priority actions for quality improvement was developed. An intervention model was rolled out in consultation with the district authorities focusing on the building blocks of the health system. The interventions were implemented from August 2014 to March 2016 in selected facilities after which an assessment was conducted. RESULTS: Initial assessment of labor room was conducted in 24 facilities. After 2 years of intervention, there was a definite improvement in quality assurance scores in most facilities. The infection control scores increased by 20 points in Gaya (from 40 to 59.9) and 10 points in Purnea (from 57.6 to 67.1). The highest gain in scores was observed in quality management component in Gaya (from 6.2 to 58.2). The model attempted to incorporate all the elements of the health system to ensure scalability and sustainability. CONCLUSION: It is possible to have an implementable quality assurance mechanism within public health system with sustained efforts and commitment.

Mobile-based effective vaccine management tool: An m-health initiative implemented by UNICEF in Bihar.

BACKGROUND: UNICEF launched the mobile-based Effective Vaccine Management (EVM) system in Bihar in 2014 along with the state government to electronically capture information and identify gaps in the existing vaccine management system for appropriate action. OBJECTIVE: This study accessed the implementation process of this initiative. METHODS: Quantitative data related to vaccine supply chain management indicators were collected in November-December 2015 using factsheets and dashboards, representing the situation of the vaccine supply and cold chain management system at regular intervals since the launch. In-depth interviews were conducted with the program specialists to understand the initiative's genesis, its challenges and strengths. RESULTS: This initiative resulted in an increased cold chain space from 49% (July 2014) to 87% (September 2015), deployment of sufficient human resource; 38 cold chain technicians for regular maintenance of the machines and equipment, installation of necessary equipment, and upgradation of state and regional vaccine stores. In health facilities, district vaccine stores, and regional vaccine stores, marked improvements were observed in the overall EVM criteria indicators (82%, 84%, and 80% in September 2015, respectively, as against 51%, 46%, and 43% in July 2014, respectively) as well as EVM category indicators (83%, 84%, and 76% in September 2015, respectively, as compared to 54%, 53%, and 54% in July 2014, respectively). CONCLUSION: The EVM mobile initiative was successfully implemented and it complies with its objective of providing experienced guidance to the human resource responsible for vaccine cold chain management. The initiative is scalable and its sustainability depends on its thoughtful merger with the existing immunization ecosystem.

Rolling out of kangaroo mother care in secondary level facilities in Bihar-Some experiences.

BACKGROUND: Preterm birth is one of the leading causes of under-five child deaths worldwide and in India. Kangaroo mother care (KMC) is a powerful and easy-to-use method to promote health and well-being and reduce morbidity and mortality in preterm/low birth weight (LBW) babies. OBJECTIVE: As the part of the roll-out of India Newborn Action Plan interventions, we implemented KMC in select facilities with an objective to assess the responsiveness of public health system to roll out KMC. METHODS: KMC intervention was implemented in two select high priority districts, Gaya and Purnea in Bihar over the duration of 8 months from August 2015 to March 2016. The implementation of intervention was phased out into; situation analysis, implementation of intervention, and interim assessment. KMC model, as envisaged keeping in mind the building blocks of health system, was established in 6 identified health-care facilities. A pretested simple checklist was used to assess the awareness, knowledge, skills, and practice of KMC during baseline situational analysis and interim assessment phases for comparison. RESULTS: The intervention clearly seemed to improve the awareness among auxiliary nurse midwives/nurses about KMC. Improvements were also observed in the availability of infrastructure required for KMC and support logistics like facility for manual expression of breast milk, cups/suitable devices such as paladi cups for feeding small babies and digital weighing scale. Although the recording of information regarding LBW babies and KMC practice improved, still there is scope for much improvement. CONCLUSION: There is a commitment at the national level to promote KMC in every facility. The present experience shows the possibility of rolling out KMC in secondary level facilities with support from government functionaries.

Design, microwave-mediated synthesis and biological evaluation of novel 4-aryl(alkyl)amino-3-nitroquinoline and 2,4-diaryl(dialkyl)amino-3-nitroquinolines as anticancer agents.

Design, microwave-assisted synthesis of novel 4-aryl (alkyl)amino-3-nitroquinoline (1a-1l) and 2,4-diaryl (dialkyl)amino-3-nitroquinolines (2a-2k and 3a) via regioselective and complete nucleophilic substitution of 2,4-dichloro-3-nitroquinoline, respectively in water are presented. The newly synthesized compounds were evaluated for the first time for antiproliferative activity against EGFR overexpressing human lung (A-549 and H-460) and colon (HCT-116-wild type and HCT-116-p53 null) cancer cell lines. Some notions about structure-activity relationships (SAR) are presented. Compounds 2e, 2f, 2j and 3a overall exhibited excellent anticancer activity comparable to erlotinib which was used as a positive control. Molecular modeling studies disclosed the recognition pattern of the compounds and also supported the observed SAR.

Hypoplastic left heart syndrome in the emergency department: an update.

BACKGROUND: Among currently available surgical options for the first stage of surgery for infants with hypoplastic left heart syndrome (HLHS), the hybrid procedure is relatively new and less well known among primary care and emergency physicians. This procedure involves placement of a stent within the ductus arteriosus to maintain systemic blood flow and bands around both pulmonary arteries to prevent pulmonary overcirculation. As the number of infants undergoing this procedure increases, emergency physicians will likely encounter them in their practice and should be familiar with their unique physiology and potential complications. OBJECTIVES: Review various emergency department (ED) presentations and management of a patient after the hybrid procedure. CASE REPORT: A 4-month-old male infant with HLHS who had undergone an uncomplicated hybrid procedure in the neonatal period presented to a community ED with severe metabolic acidosis and poor perfusion. He was intubated and received mechanical ventilation with an inspired oxygen concentration of 60%. Initial capillary blood gas revealed PO2 59 torr, which, in the context of his clinical presentation, was suggestive of pulmonary overcirculation with "systemic steal." Approximately 60 min after presentation to the ED, he experienced a bradycardic arrest. He expired 40 min later. CONCLUSION: This case highlights the potential of infants who undergo the hybrid procedure for HLHS to present to the ED with high acuity and, accordingly, the importance of adding this disease process to the vast burden of knowledge facing ED physicians.

The memory ameliorating effects of novel N-benzyl pyridine-2-one derivatives on scopolamine-induced cognitive deficits in mice.

BACKGROUND: Alzheimer's disease (AD), the most common form of progressive dementia in the elderly, is a chronic neurological disorder that decreases cognitive ability. Although the underlying cause of AD is yet unknown, oxidative stress and brain acetylcholine shortage are the key pathogenic causes. RESULTS: The current study shows that these derivatives have the potential to improve memory in mice by inhibiting scopolamine-induced acetylcholinesterase activity, oxidative and nitrosative stress, and improving locomotor activity and muscle grip strength in the rota rod test. When compared to the illness control, the memory-enhancing potential of novel N-benzyl pyridine-2-one derivatives was highly significant (P < 0.0001). CONCLUSIONS: The observed memory ameliorating effect of novel N-benzyl pyridine-2-one makes them as a a good choice for treatment of individuals with cognitive impairment.

Novel Substituted Pyrimidine Derivatives as Potential Anti-Alzheimer's Agents: Synthesis, Biological, and Molecular Docking Studies.

The most frequent type of age-related dementia is Alzheimer's disease. To discover novel therapeutic agents for Alzheimer's disease, a series of substituted pyrimidine derivatives were synthesized and evaluated for anti-Alzheimer's activity. All the synthesized compounds were validated by 1HNMR, 13CNMR, and HRMS to assess the structural conformance of the newly synthesized compounds. The synthesized compounds were then evaluated for their in vivo acute toxicity study. Evaluation of acute toxicity showed that none of the synthesized compounds showed toxicity up to 1000 mg/kg. After in vivo acute toxicity studies, the compounds were subjected to behavioral and biochemical studies. Compound N4-(4-chlorophenyl)-N2-(2-(piperidin-1-yl)ethyl)pyrimidine-2,4-diamine 5b (SP-2) displayed an excellent anti-Alzheimer's profile, while the rest of the compounds showed satisfactory results in comparison to donepezil. Docking studies confirmed the results obtained through in vivo experiments and showed that 5b (SP-2) showed a similar interaction to that of donepezil. Further, in silico molecular property predictions showed that 5b (SP-2) possesses favorable drug-likeness and ADME properties for CNS activity. These results implied that 5b could serve as an appropriate lead molecule for the development of anti-Alzheimer's agent.

Chemical (Alkali) Burn-Induced Neurotrophic Keratitis Model in New Zealand Rabbit Investigated Using Medical Clinical Readouts and In Vivo Confocal Microscopy (IVCM).

PURPOSE: Chemical eye injury is an acute emergency that can result in vision loss. Neurotrophic keratitis (NK) is the most common long-term manifestation of chemical injury. NK due to alkali burn affects ocular surface health and is one of its most common causes. Here, we established a rabbit model of corneal alkali burns to evaluate the severity of NK-associated changes. MATERIAL METHODS: Alkali burns were induced in NZ rabbits by treating the cornea with (i) a 5 mm circular filter paper soaked in 0.75 N NaOH for 10 s (Mild NK) and (ii) trephination using a guarded trephine (5 mm diameter and 150-micron depth), followed by alkali burn, with a 5 mm circular filter paper soaked in 0.75 N NaOH for 10 s (a severe form of NK). Immediately after, the cornea was rinsed with 10 mL of normal saline to remove traces of NaOH. Clinical features were evaluated on Day 0, Day 1, Day 7, Day 15, and Day 21 post-alkali burn using a slit lamp, Pentacam, and anterior segment optical coherence tomography (AS-OCT). NK-like changes in epithelium, sub-basal nerve plexus, and stroma were observed using in vivo confocal microscopy (IVCM), and corneal sensation were measured using an aesthesiometer post alkali injury. After 21 days, pro-inflammatory cytokines were evaluated for inflammation through ELISA. RESULTS: Trephination followed by alkali burn resulted in the loss of epithelial layers (manifested using fluorescein stain), extensive edema, and increased corneal thickness (550 µm compared to 380 µm thickness of control) evaluated through AS-OCT and increased opacity score in alkali-treated rabbit (80 compared to 16 controls). IVCM images showed complete loss of nerve fibers, which failed to regenerate over 30 days, and loss of corneal sensation-conditions associated with NK. Cytokines evaluation of IL6, VEGF, and MMP9 indicated an increased angiogenic and pro-inflammatory milieu compared to the milder form of NK and the control. DISCUSSION: Using clinical parameters, we demonstrated that the alkali-treated rabbit model depicts features of NK. Using IVCM in the NaOH burn animal model, we demonstrated a complete loss of nerve fibers with poor self-healing capability associated with sub-basal nerve degeneration and compromised corneal sensation. This pre-clinical rabbit model has implications for future pre-clinical research in neurotrophic keratitis.

Medicinal attributes of pyrazolo[3,4-d]pyrimidines: a review.

Pyrazolopyrimidines are the fused heterocyclic ring systems which structurally resemble purines which prompted biological investigations to assess their potential therapeutic significance. They are known to play a crucial role in numerous disease conditions. The advent of their first bioactivity as adenosine antagonistic property divulged their medicinal potential. Radioactivity test on mice cells, morphometric and serological tests on rat hepatocytes, antitumor testing against L1210 and P388 leukemias in mice threw light on their biophysical aspects of significance. Biochemical properties were explored via xanthine oxidase assay, antioxidant enzyme assays, Western blot analysis, mRNA expression of apoptopic genes, receptor binding assays, and tryptan blue exclusion cytotoxicity evaluation. The collective results of biochemical and biophysical properties foregrounded their medicinal significance in central nervous system, cardiovascular system, cancer, inflammation etc. The present manuscript to the best of our knowledge is the first compilation on synthesis and medicinal aspects including structure-activity relationships of pyrazolo[3,4-d]pyrimidines reported to date.

Courses in reproductive and child health in India: an overview.

Defining the human resource needs for providing quality maternal, newborn, and child health services across such a large and diverse population country like India is truly challenging. The effective response to significant challenges and increased requirements of evidence-based effectiveness of the public health projects on maternal and child health is putting pressure on existing program managers to acquire new advanced academic training and information. The data regarding the existing courses on reproductive and child health and related fields in the country were obtained by a predefined search made on the Internet through the Google search engine in December 2011. The collected data were the name and location of the institution offering the respective course, theme, course duration, course structure, eligibility criteria, and mode of learning. In India, around 15 institutes are offering certificate/postgraduate diploma courses on maternal and child health either as a regular program or through distance education program. The admission procedure for each institute is independent of others. The courses vary in terms of duration, eligibility criteria, and fee structure. Conceptualizing an educational initiative in response to national demands for increased workforce capacity to eliminate key medical and nonmedical educational barriers and financial and nonfinancial barriers to advanced academic preparation would enhance the quality of services available in the region.

Neuroprotective effects of novel pyrrolidine-2-one derivatives on scopolamine-induced cognitive impairment in mice: Behavioral and biochemical analysis.

Alzheimer's disease (AD) is a long-term neurodegenerative condition that impairs cognitive abilities. In brain acetylcholine deficit and oxidative stress may be considered the key pathogenic causes for AD, even though the basic etiology is still unknown. The effects of some novel pyrrolidine-2-one derivatives on the learning and memory deficits caused by scopolamine in mice were examined in the current study. The learning and memory parameters were assessed using the morris water maze test, rota rod test the and locomotor activity. A number of biochemical factors were also evaluated, including acetylcholinesterase (AChE), lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CA), and nitrite oxide (NO) assay. The current study shows that these derivatives were more effective and comparable to donepezil at treating the behavioral and biochemical changes brought on by scopolamine. The observed results showed pyrrolidine-2-one derivatives as a promising candidate for diseases associated with cognitive deficits.