Current Progress of Phytomedicine in Glioblastoma Therapy.

Glioblastoma multiforme, an intrusive brain cancer, has the lowest survival rate of all brain cancers. The chemotherapy utilized to prevent their proliferation and propagation is limited due to modulation of complex cancer signalling pathways. These complex pathways provide infiltrative and drug evading properties leading to the development of chemotherapy resistance. Therefore, the development and discovery of such interventions or therapies that can bypass all these resistive barriers to ameliorate glioma prognosis and survival is of profound importance. Medicinal plants are comprised of an exorbitant range of phytochemicals that have the broad-spectrum capability to target intrusive brain cancers, modulate anti-cancer pathways and immunological responses to facilitate their eradication, and induce apoptosis. These phytocompounds also interfere with several oncogenic proteins that promote cancer invasiveness and metastasis, chemotherapy resistance and angiogenesis. These plants are extremely vital for promising anti-glioma therapy to avert glioma proliferation and recurrence. In this review, we acquired recent literature on medicinal plants whose extracts/bioactive ingredients are newly exploited in glioma therapeutics, and also highlighted their mode of action and pharmacological profile.

Intestinal permeability and inflammation mediate the association between nutrient density of complementary foods and biochemical measures of micronutrient status in young children: results from the MAL-ED study.

BACKGROUND: Environmental enteric dysfunction (EED) is thought to increase the risk of micronutrient deficiencies, but few studies adjust for dietary intakes and systemic inflammation. OBJECTIVE: We tested whether EED is associated with micronutrient deficiency risk independent of diet and systemic inflammation, and whether it mediates the relation between intake and micronutrient status. METHODS: Using data from 1283 children in the MAL-ED (Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health) birth cohort we evaluated the risk of anemia, low retinol, zinc, and ferritin, and high transferrin receptor (TfR) at 15 mo. We characterized gut inflammation and permeability by myeloperoxidase (MPO), neopterin (NEO), and α-1-antitrypsin (AAT) concentrations from asymptomatic fecal samples averaged from 9 to 15 mo, and averaged the lactulose:mannitol ratio z-score (LMZ) at 9 and 15 mo. Nutrient intakes from complementary foods were quantified monthly from 9 to 15 mo and densities were averaged for analyses. α-1-Acid glycoprotein at 15 mo characterized systemic inflammation. Relations between variables were modeled using a Bayesian network. RESULTS: A greater risk of anemia was associated with LMZ [1.15 (95% CI: 1.01, 1.31)] and MPO [1.16 (1.01, 1.34)]. A greater risk of low ferritin was associated with AAT [1.19 (1.03, 1.37)] and NEO [1.22 (1.04, 1.44)]. A greater risk of low retinol was associated with LMZ [1.24 (1.08, 1.45)]. However, MPO was associated with a lower risk of high transferrin receptor [0.86 (0.74, 0.98)], NEO with a lower risk of low retinol [0.75 (0.62, 0.89)], and AAT with a lower risk of low plasma zinc [0.83 (0.70, 0.99)]. Greater nutrient intake densities (vitamins A and B6, calcium, protein, and zinc) were negatively associated with EED. Inverse associations between nutrient densities and micronutrient deficiency largely disappeared after adjustment for EED, suggesting that EED mediates these associations. CONCLUSIONS: EED is independently associated with an increased risk of low ferritin, low retinol, and anemia. Greater nutrient density from complementary foods may reduce EED, and the control of micronutrient deficiencies may require control of EED.

Effect of provision of home-based curative health services by public sector health-care providers on neonatal survival: a community-based cluster-randomised trial in rural Pakistan.

BACKGROUND: Although the effectiveness of community mobilisation and promotive care delivered by community health workers in reducing perinatal and neonatal mortality is well established, evidence in support of home-based neonatal resuscitation and infection management is mixed. We assessed the effectiveness of adding training in neonatal bag and mask resuscitation and oral antibiotic therapy for suspected neonatal infections to a basic preventive and promotive interventions package delivered by public sector community-based lady health workers (LHWs) in rural Pakistan. METHODS: We did a cluster-randomised controlled trial in two subdistricts of Naushahro Feroze in rural Sindh, Pakistan, between April 15, 2009, and Dec 10, 2012. LHWs, trained in basic newborn resuscitation and in recognition and treatment (with oral amoxicillin) of suspected neonatal respiratory infections, were linked with traditional birth attendants and encouraged to attend home births. Control clusters received routine care through the existing national programme. The primary outcome was all-cause neonatal mortality. Independent data collection teams recorded data for all pregnancies and their outcomes, morbidity, mortality, and household practices related to maternal and newborn care. FINDINGS: Of the 27 randomised clusters with functional LHW programmes, 13 were allocated to the intervention group (n=242 749) and 14 to the control group (n=256 985). In the intervention group, LHWs did 80% of the planned community mobilisation sessions, but were able to attend only 1184 (14%) of 8425 deliveries and 4318 (25%) of 17 288 neonatal visits within 72 h of birth (p<0·0001 for both variables compared with the control group). The neonatal mortality rate was 42 deaths per 1000 livebirths in intervention clusters compared with 55 per 1000 in the control group (risk ratio 0·80, 95% CI 0·68-0·93; p=0·005). INTERPRETATION: The reduction in neonatal mortality in intervention clusters occurred against a background of improvements in domiciliary practices for maternal and newborn care. However, the poor reach of LHWs in accessing newborn infants at birth and in the early postnatal period underscores the limitations of tasking community health workers in public sector programmes working in similar circumstances with such complex interventions. Such community-based interventions in health systems should be accompanied by concerted efforts to improve quality of care in facilities and referral systems. FUNDING: Saving Newborn Lives, Save the Children USA.

A mixed methods study to assess the effectiveness of food-based interventions to prevent stunting among children under-five years in Districts Thatta and Sujawal, Sindh Province, Pakistan: study protocol.

BACKGROUND: Maternal and child malnutrition is widely prevalent in low and middle income countries. In Pakistan, widespread food insecurity and malnutrition are the main contributors to poor health, low survival rates and the loss of human capital development. The nutritional status trends among children exhibit a continuous deteriorating with rates of malnutrition exceeding the WHO critical threshold. With the high prevalence of maternal and child malnutrition, it is important to identify effective preventative approaches, especially for reducing stunting in children under-five years of age. The primary aim of this study is to assess the effectiveness of food-based interventions to prevent stunting in children under-five years. METHODS: A mixed methods study design will be conducted to evaluate the effectiveness of food-based interventions to prevent stunting among children under-five years in districts Thatta and Sujawal, Sindh Province, Pakistan. The study will include cross sectional surveys, a community-based cluster randomized controlled trial and a process evaluation. The study participants will be pregnant women, lactating mothers and children under-five years. The cross-sectional surveys will be conducted with 7360 study participants at baseline and endline. For the randomized control trial, 5000 participants will be recruited and followed monthly for compliance of food-based supplements, dietary diversity, pregnancy outcomes, and maternal and child morbidity and mortality. Anthropometric measurements and hemoglobin levels will be measured at baseline, quarterly and at endline. The interventions will consist of locally produced lipid-based nutrient supplement (Wawamum) for children 6-23 months, micronutrient powders for children 24-59 months, and wheat soya blends for pregnant and lactating mothers. Government lady health workers will deliver interventions to participants. The effectiveness of the project will be measured in terms of the impact of the proposed interventions on stunting, nutritional status, micronutrient deficiencies, and other key indicators of the participants. The process evaluation will assess the acceptability, feasibility and potential barriers of project implementation through focus group discussions, key informant interviews and household surveys. Data analysis will be conducted using STATA version 12. DISCUSSION: There is considerable evidence on the effectiveness of food-based interventions in managing stunting in developing countries. However, these studies do not account for the local environmental factors and widespread nutrient deficiencies in Pakistan. These studies are often conducted in controlled environments, where the results cannot be generalized to programs operating under field conditions. The findings of this study will provide sufficient evidence to develop policies and programs aimed to prevent stunting in children 6-59 months and to improve maternal and child health and growth outcomes in poor resource settings. TRIAL REGISTRATION: NCT02422953 . Registered on April 15, 2015.

Improved accessibility of emergency obstetrics and newborn care (EmONC) services for maternal and newborn health: a community based project.

BACKGROUND: Every year an estimated three million neonates die globally and two hundred thousand of these deaths occur in Pakistan. Majority of these neonates die in rural areas of underdeveloped countries from preventable causes (infections, complications related to low birth weight and prematurity). Similarly about three hundred thousand mother died in 2010 and Pakistan is among ten countries where sixty percent burden of these deaths is concentrated. Maternal and neonatal mortality remain to be unacceptably high in Pakistan especially in rural areas where more than half of births occur. METHOD/DESIGN: This community based cluster randomized controlled trial will evaluate the impact of an Emergency Obstetric and Newborn Care (EmONC) package in the intervention arm compared to standard of care in control arm. Perinatal and neonatal mortality are primary outcome measure for this trial. The trial will be implemented in 20 clusters (Union councils) of District Rahimyar Khan, Pakistan. The EmONC package consists of provision of maternal and neonatal health pack (clean delivery kit, emollient, chlorhexidine) for safe motherhood and newborn wellbeing and training of community level and facility based health care providers with emphasis on referral of complicated cases to nearest public health facilities and community mobilization. DISCUSSION: Even though there is substantial evidence in support of effectiveness of various health interventions for improving maternal, neonatal and child health. Reduction in perinatal and neonatal mortality remains a big challenge in resource constrained and diverse countries like Pakistan and achieving MDG 4 and 5 appears to be a distant reality. A comprehensive package of community based low cost interventions along the continuum of care tailored according to the socio cultural environment coupled with existing health force capacity building may result in improving the maternal and neonatal outcomes. The findings of this proposed community based trial will provide sufficient evidence on feasibility, acceptability and effectiveness to the policy makers for replicating and scaling up the interventions within the health system.