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1.  Are village health sanitation and nutrition committees fulfilling their roles for decentralised health planning and action? A mixed methods study from rural eastern India 
BMC Public Health  2016;16:59.
In India, Village Health Sanitation and Nutrition Committees (VHSNCs) are participatory community health forums, but there is little information about their composition, functioning and effectiveness. Our study examined VHSNCs as enablers of participatory action for community health in two rural districts in two states of eastern India – West Singhbhum in Jharkhand and Kendujhar, in Odisha.
We conducted a cross-sectional survey of 169 VHSNCs and ten qualitative focus group discussions with purposively selected better and poorer performing committees, across the two states. We analysed the quantitative data using descriptive statistics and the qualitative data using a Framework approach.
We found that VHSNCs comprised equitable representation from vulnerable groups when they were formed. More than 75 % members were women. Almost all members belonged to socially disadvantaged classes. Less than 1 % members had received any training. Supervision of committees by district or block officials was rare. Their work focused largely on strengthening village sanitation, conducting health awareness activities, and supporting medical treatment for ill or malnourished children and pregnant mothers. In reality, 62 % committees monitored community health workers, 6.5 % checked sub-centres and 2.4 % monitored drug availability with community health workers. Virtually none monitored data on malnutrition. Community health and nutrition workers acted as conveners and record keepers. Links with the community involved awareness generation and community monitoring of VHSNC activities. Key challenges included irregular meetings, members’ limited understanding of their roles and responsibilities, restrictions on planning and fund utilisation, and weak linkages with the broader health system.
Our study suggests that VHSNCs perform few of their specified functions for decentralized planning and action. If VHSNCs are to be instrumental in improving community health, sanitation and nutrition, they need education, mobilisation and monitoring for formal links with the wider health system.
PMCID: PMC4722712  PMID: 26795942
Village health sanitation and nutrition committee; Community participation; Decentralized governance; Planning; India
2.  Patents for Toll-like receptor ligands as radiation countermeasures for acute radiation syndrome 
Expert Opinion on Therapeutic Patents  2015;25(10):1085-1092.
Acute radiation exposure induces apoptosis of tissues in the hematopoietic, digestive, cutaneous, cardiovascular and nervous systems; extensive apoptosis of these tissues ultimately leads to acute radiation syndrome. A novel strategy for developing radiation countermeasures has been to imitate the genetic mechanisms acquired by radiation-resistant tumors. Two mechanisms that underlie this ability of tumor cells are the p53 and NF-κB pathways. The loss of p53 function results in the inactivation of pro-apoptotic control mechanisms, while constitutive activation of NF-κB results in the up-regulation of anti-apoptotic genes. Various Toll-like receptor ligands are capable of up regulating the NF-κB pathway, which increases radio-resistance and reduces radiation-induced apoptosis in various tissues. Several Toll-like receptor ligands have been patented and are currently under development as radiation countermeasures for acute radiation syndrome. Ongoing studies suggest that a few of these attractive agents are progressing well along the US FDA approval pathway to become radiation countermeasures.
PMCID: PMC4673515  PMID: 26135043
acute radiation syndrome; NF-κB; radiation; Toll-like receptor ligands
3.  Combined immunomodulator and antimicrobial therapy eliminates polymicrobial sepsis and modulates cytokine production in combined injured mice 
Purpose: A combination therapy for combined injury (CI) using a non-specific immunomodulator, synthetic trehalose dicorynomycolate and monophosphoryl lipid A (STDCM-MPL), was evaluated to augment oral antimicrobial agents, levofloxacin (LVX) and amoxicillin (AMX), to eliminate endogenous sepsis and modulate cytokine production.
Materials and methods: Female B6D2F1/J mice received 9.75 Gy cobalt-60 gamma-radiation and wound. Bacteria were isolated and identified in three tissues. Incidence of bacteria and cytokines were compared between treatment groups.
Results: Results demonstrated that the lethal dose for 50% at 30 days (LD50/30) of B6D2F1/J mice was 9.42 Gy. Antimicrobial therapy increased survival in radiation-injured (RI) mice. Combination therapy increased survival after RI and extended survival time but did not increase survival after CI. Sepsis began five days earlier in CI mice than RI mice with Gram-negative species predominating early and Gram-positive species increasing later. LVX plus AMX eliminated sepsis in CI and RI mice. STDCM-MPL eliminated Gram-positive bacteria in CI and most RI mice but not Gram-negative. Treatments significantly modulated 12 cytokines tested, which pertain to wound healing or elimination of infection.
Conclusions: Combination therapy eliminates infection and prolongs survival time but does not assure CI mouse survival, suggesting that additional treatment for proliferative-cell recovery is required.
PMCID: PMC4673550  PMID: 25994812
Anti-microbial therapy; bacterial translocation; cytokines; chemokines; gamma-radiation; immunomodulator; infection; mice; sepsis
4.  Unravelling the distinct strains of Tharu ancestry 
European Journal of Human Genetics  2014;22(12):1404-1412.
The northern region of the Indian subcontinent is a vast landscape interlaced by diverse ecologies, for example, the Gangetic Plain and the Himalayas. A great number of ethnic groups are found there, displaying a multitude of languages and cultures. The Tharu is one of the largest and most linguistically diverse of such groups, scattered across the Tarai region of Nepal and bordering Indian states. Their origins are uncertain. Hypotheses have been advanced postulating shared ancestry with Austroasiatic, or Tibeto-Burman-speaking populations as well as aboriginal roots in the Tarai. Several Tharu groups speak a variety of Indo-Aryan languages, but have traditionally been described by ethnographers as representing East Asian phenotype. Their ancestry and intra-population diversity has previously been tested only for haploid (mitochondrial DNA and Y-chromosome) markers in a small portion of the population. This study presents the first systematic genetic survey of the Tharu from both Nepal and two Indian states of Uttarakhand and Uttar Pradesh, using genome-wide SNPs and haploid markers. We show that the Tharu have dual genetic ancestry as up to one-half of their gene pool is of East Asian origin. Within the South Asian proportion of the Tharu genetic ancestry, we see vestiges of their common origin in the north of the South Asian Subcontinent manifested by mitochondrial DNA haplogroup M43.
PMCID: PMC4231405  PMID: 24667789
5.  Changing picture of renal cortical necrosis in acute kidney injury in developing country 
World Journal of Nephrology  2015;4(5):480-486.
Renal cortical necrosis (RCN) is characterized by patchy or diffuse ischemic destruction of all the elements of renal cortex resulting from significantly diminished renal arterial perfusion due to vascular spasm and microvascular injury. In addition, direct endothelial injury particularly in setting of sepsis, eclampsia, haemolytic uremic syndrome (HUS) and snake bite may lead to endovascular thrombosis with subsequent renal ischemia. Progression to end stage renal disease is a rule in diffuse cortical necrosis. It is a rare cause of acute kidney injury (AKI) in developed countries with frequency of 1.9%-2% of all patients with AKI. In contrast, RCN incidence is higher in developing countries ranging between 6%-7% of all causes of AKI. Obstetric complications (septic abortion, puerperal sepsis, abruptio placentae, postpartum haemorrhage and eclampsia) are the main (60%-70%) causes of RCN in developing countries. The remaining 30%-40% cases of RCN are caused by non-obstetrical causes, mostly due to sepsis and HUS. The incidence of RCN ranges from 10% to 30% of all cases of obstetric AKI compared with only 5% in non-gravid patients. In the developed countries, RCN accounts for 2% of all cases of AKI in adults and more than 20% of AKI during the third trimester of pregnancy. The reported incidence of RCN in obstetrical AKI varies between 18%-42.8% in different Indian studies. However, the overall incidence of RCN in pregnancy related AKI has decreased from 20%-30% to 5% in the past two decades in India. Currently RCN accounts for 3% of all causes of AKI. The incidence of RCN in obstetrical AKI was 1.44% in our recent study. HUS is most common cause of RCN in non-obstetrical group, while puerperal sepsis is leading cause of RCN in obstetric group. Because of the catastrophic sequelae of RCN, its prevention and aggressive management should always be important for the better renal outcome and prognosis of the patients.
PMCID: PMC4635367  PMID: 26558184
Acute kidney injury; Hemolytic uremic syndrome; Renal cortical necrosis; Postpartum hemorrhage; Septic abortion; Puerperal sepsis; Eclampsia
6.  Tocols induce G-CSF and mobilise progenitors that mitigate radiation injury 
Radiation Protection Dosimetry  2014;162(1-2):83-87.
Tocols induce high levels of granulocyte-colony-stimulating factor (G-CSF). G-CSF mobilises progenitors that allow mice that have been severely immunocompromised by exposure to acute, high-dose ionising irradiation to recover and to survive. The neutralisation of G-CSF abrogates the radioprotective efficacy of tocols. This article reviews studies in which CD2F1 mice were irradiated with sufficiently high doses to cause acute radiation syndrome symptoms and then administered (iv) progenitor-enriched whole blood or peripheral blood mononuclear cells from tocol- and AMD3100-injected donor mice (AMD3100 is a chemokine receptor antagonist used to improve the yield of mobilised progenitors). In some experiments, G-CSF was neutralised completely. Irradiated recipient mice were observed for 30 d post-irradiation for survival, a primary endpoint used for determining therapeutic effectiveness. Additionally, potential tocol-induced biomarkers (cytokines, chemokines and growth factors) were quantified. The authors suggest that tocols are highly effective agents for mobilising progenitors with significant therapeutic potential.
PMCID: PMC4434803  PMID: 24993008
7.  Screening Depression Among Elderly in a City of Southeast Asia 
Changing family structure (Joint to Nuclear), increased life expectancy above 60 years of age, generation and communication gap, financial dependency on children leads to conflict among family members. This may sometime lead to old age home settlement of elderly people. All these condition leads to isolation and insecurity among elderly people and this condition affect the mental status of elderly people which may sometime lead to depression among Old Age Homes residents and family living elderly people.
To study the prevalence of depression and diagnosed systemic morbidities among elderly people. To study the predictors of depression among study subjects.
Materials and Methods
A descriptive cross-sectional study was conducted among elderly people (age ≥60 years) residing in old age homes (OAHs) and in community/families in Lucknow, India. Multistage sampling technique was used to include required sample of subjects from the community and for OAHs all the elderly people living in OAHs were included. Geriatric depression scale was used to screen depression.
Depression was 27.7% among elderly people residing in OAHs while it was 15.6% those residing at their own homes. In community most frequent morbidity was hypertension (17.7%) while 41.1% elderly people had no diagnosed morbidity. In OAHs out of total the musculoskeletal morbidity (33.7%) was most frequent and 18.8% had no diagnosed morbidity. On multivariate analysis financial dependency and education were found to be statistically significant.
Depression was more common among elderly living in Old Age Homes as compare to those living in community. Hypertension, musculoskeletal morbidities and eye related morbidities were most frequent diagnosed morbidities. Financial Dependency & Education were found to be primary predictors of depression.
PMCID: PMC4606253  PMID: 26500924
Education; Financial dependency; Old age home
8.  Simulating Crop Evapotranspiration Response under Different Planting Scenarios by Modified SWAT Model in an Irrigation District, Northwest China 
PLoS ONE  2015;10(10):e0139839.
Modelling crop evapotranspiration (ET) response to different planting scenarios in an irrigation district plays a significant role in optimizing crop planting patterns, resolving agricultural water scarcity and facilitating the sustainable use of water resources. In this study, the SWAT model was improved by transforming the evapotranspiration module. Then, the improved model was applied in Qingyuan Irrigation District of northwest China as a case study. Land use, soil, meteorology, irrigation scheduling and crop coefficient were considered as input data, and the irrigation district was divided into subdivisions based on the DEM and local canal systems. On the basis of model calibration and verification, the improved model showed better simulation efficiency than did the original model. Therefore, the improved model was used to simulate the crop evapotranspiration response under different planting scenarios in the irrigation district. Results indicated that crop evapotranspiration decreased by 2.94% and 6.01% under the scenarios of reducing the planting proportion of spring wheat (scenario 1) and summer maize (scenario 2) by keeping the total cultivated area unchanged. However, the total net output values presented an opposite trend under different scenarios. The values decreased by 3.28% under scenario 1, while it increased by 7.79% under scenario 2, compared with the current situation. This study presents a novel method to estimate crop evapotranspiration response under different planting scenarios using the SWAT model, and makes recommendations for strategic agricultural water management planning for the rational utilization of water resources and development of local economy by studying the impact of planting scenario changes on crop evapotranspiration and output values in the irrigation district of northwest China.
PMCID: PMC4595335  PMID: 26439928
9.  Dating Violence among Male and Female Youth seeking Emergency Department Care 
Annals of emergency medicine  2014;64(4):405-412.e1.
To determine prevalence and correlates of dating violence, dating victimization, and dating aggression among males and females age 14–20 seeking emergency department (ED) care.
Systematic sampling of subjects age 14–20 seeking care at a single large academic ED between 9/2010- 3/2013. Participants completed a computerized, self-administered, cross-sectional survey of demographics, dating violence from physical abuse measures of the Conflict in Adolescent Dating Relationships Inventory, associated behaviors, and ED health service use. Separate analyses were conducted for males and females.
4389 youth (86.1% participation rate) were screened, and 4089 (mean age 17.5 years, 58% female) were eligible for analysis. Almost 1 in 5 females (n= 215, 18.4%) and 1 in 8 males (n= 212, 12.5%) reported past year dating violence. Of females, 10.6% reported dating victimization, and 14.6% dating aggression, while of males, 11.7% reported dating victimization, and 4.9% reported dating aggression. Multivariate analyses showed variables associated with any male dating violence were African American race (AOR 2.26, CI 1.54–3.32), alcohol misuse (AOR 1.03, CI 1.00–1.06), illicit drug misuse (AOR 2.38, CI 1.68–3.38), and depression (AOR 2.13, CI 1.46–3.10); any female dating violence was associated with African-American race (AOR 1.68, CI 1.25–2.25), public assistance (AOR 1.64, CI 1.28–2.09), grades D and below (AOR 1.62, CI 1.07–2.43), alcohol misuse (AOR 1.04, CI 1.02–1.07), illicit drug misuse (AOR 2.85, CI 2.22–3.66), depression (AOR 1.86, CI 1.42–2.44), and any past year ED visit for intentional injury (AOR 2.64, CI 1.30–5.40).
Nearly 1 of 6 male and female adolescents seeking ED care report recent dating violence, and health disparities remain among this population. Dating violence was strongly associated with alcohol, illicit drug misuse, and depression, and correlated with prior ED service utilization among female youth. ED interventions should consider addressing these associated health conditions as well as improving screening protocols to address dating violence among male and female youth.
PMCID: PMC4177973  PMID: 24993689
10.  Butanol production from food waste: a novel process for producing sustainable energy and reducing environmental pollution 
Waste is currently a major problem in the world, both in the developing and the developed countries. Efficient utilization of food waste for fuel and chemical production can positively influence both the energy and environmental sustainability. This study investigated using food waste to produce acetone, butanol, and ethanol (ABE) by Clostridium beijerinckii P260.
In control fermentation, 40.5 g/L of glucose (initial glucose 56.7 g/L) was used to produce 14.2 g/L of ABE with a fermentation productivity and a yield of 0.22 g/L/h and 0.35 g/g, respectively. In a similar fermentation 81 g/L of food waste (containing equivalent glucose of 60.1 g/L) was used as substrate, and the culture produced 18.9 g/L ABE with a high ABE productivity of 0.46 g/L/h and a yield of 0.38 g/g. Fermentation of food waste at higher concentrations (129, 181 and 228 g/L) did not remarkably increase ABE production but resulted in high residual glucose due to the culture butanol inhibition. An integrated vacuum stripping system was designed and applied to recover butanol from the fermentation broth simultaneously to relieve the culture butanol inhibition, thereby allowing the fermentation of food waste at high concentrations. ABE fermentation integrated with vacuum stripping successfully recovered the ABE from the fermentation broth and controlled the ABE concentrations below 10 g/L during fermentation when 129 g/L food waste was used. The ABE productivity with vacuum fermentation was 0.49 g/L/h, which was 109 % higher than the control fermentation (glucose based). More importantly, ABE vacuum recovery and fermentation allowed near-complete utilization of the sugars (~98 %) in the broth.
In these studies it was demonstrated that food waste is a superior feedstock for producing butanol using Clostridium beijerinckii. Compared to costly glucose, ABE fermentation of food waste has several advantages including lower feedstock cost, higher productivity, and less residual sugars.
PMCID: PMC4572674  PMID: 26380581
Butanol; Food waste; Fermentation; Vacuum stripping; Process integration; Energy
11.  The Toll-Like Receptor 5 Agonist Entolimod Mitigates Lethal Acute Radiation Syndrome in Non-Human Primates 
PLoS ONE  2015;10(9):e0135388.
There are currently no approved medical radiation countermeasures (MRC) to reduce the lethality of high-dose total body ionizing irradiation expected in nuclear emergencies. An ideal MRC would be effective even when administered well after radiation exposure and would counteract the effects of irradiation on the hematopoietic system and gastrointestinal tract that contribute to its lethality. Entolimod is a Toll-like receptor 5 agonist with demonstrated radioprotective/mitigative activity in rodents and radioprotective activity in non-human primates. Here, we report data from several exploratory studies conducted in lethally irradiated non-human primates (rhesus macaques) treated with a single intramuscular injection of entolimod (in the absence of intensive individualized supportive care) administered in a mitigative regimen, 1–48 hours after irradiation. Following exposure to LD50-70/40 of radiation, injection of efficacious doses of entolimod administered as late as 25 hours thereafter reduced the risk of mortality 2-3-fold, providing a statistically significant (P<0.01) absolute survival advantage of 40–60% compared to vehicle treatment. Similar magnitude of survival improvement was also achieved with drug delivered 48 hours after irradiation. Improved survival was accompanied by predominantly significant (P<0.05) effects of entolimod administration on accelerated morphological recovery of hematopoietic and immune system organs, decreased severity and duration of thrombocytopenia, anemia and neutropenia, and increased clonogenic potential of the bone marrow compared to control irradiated animals. Entolimod treatment also led to reduced apoptosis and accelerated crypt regeneration in the gastrointestinal tract. Together, these data indicate that entolimod is a highly promising potential life-saving treatment for victims of radiation disasters.
PMCID: PMC4569586  PMID: 26367124
The role of obesity in relation to various disease processes is being increasingly studied, with reports over the last several years increasingly mentioning its association with worse outcomes in acute disease. Obesity has also gained recognition as a risk factor for severe acute pancreatitis (SAP) [1–8]. The mortality in SAP may be as high as 30% and is usually attributable to multi system organ failure (MSOF) earlier in the disease, and complications of necrotizing pancreatitis later [9–11]. To date there is no specific treatment for acute pancreatitis (AP) and the management is largely expectant and supportive. Obesity in general has also been associated with poor outcomes in sepsis and other pathological states including trauma and burns [12–14]. With the role of unsaturated fatty acids (UFA) as propagators in SAP having recently come to light [15] and with the recognition of acute lipotoxicity, there is now an opportunity to explore different strategies to reduce the mortality and morbidity in SAP and potentially other disease states associated with such a pathophysiology. In this review we will discuss the role of fat and implications of the consequent acute lipotoxicity on the outcomes of acute pancreatitis in lean and obese states and during acute on chronic pancreatitis.
PMCID: PMC4185152  PMID: 25278311
13.  Scrub Typhus Incidence Modeling with Meteorological Factors in South Korea 
Since its recurrence in 1986, scrub typhus has been occurring annually and it is considered as one of the most prevalent diseases in Korea. Scrub typhus is a 3rd grade nationally notifiable disease that has greatly increased in Korea since 2000. The objective of this study is to construct a disease incidence model for prediction and quantification of the incidences of scrub typhus. Using data from 2001 to 2010, the incidence Artificial Neural Network (ANN) model, which considers the time-lag between scrub typhus and minimum temperature, precipitation and average wind speed based on the Granger causality and spectral analysis, is constructed and tested for 2011 to 2012. Results show reliable simulation of scrub typhus incidences with selected predictors, and indicate that the seasonality in meteorological data should be considered.
PMCID: PMC4515655  PMID: 26132479
scrub typhus; ANN; meteorological variables
15.  Psycho-neuro-endocrine-immune mechanisms of action of yoga in type II diabetes 
Ancient Science of Life  2015;35(1):12-17.
Yoga has been found to benefit all the components of health viz. physical, mental, social and spiritual well being by incorporating a wide variety of practices. Pathophysiology of Type II DM and co-morbidities in Type II DM has been correlated with stress mechanisms. Stress suppresses body's immune system and neuro-humoral actions thereby aff ecting normal psychological state. It would not be wrong to state that correlation of diabetes with stress, anxiety and other psychological factors are bidirectional and lead to difficulty in understanding the interrelated mechanisms. Type II DM cannot be understood in isolation with psychological factors such as stress, anxiety and depression, neuro-endocrine and immunological factors. There is no review which tries to understand these mechanisms exclusively. The present literature review aims to understand interrelated Psycho-Neuro-Endocrine and Immunological mechanisms of action of Yoga in Type II Diabetes Mellitus. Published literature concerning mechanisms of action of Yoga in Type II DM emphasizing psycho-neuro-endocrine or immunological relations was retrieved from Pubmed using key words yoga, Type II diabetes mellitus, psychological, neural, endocrine, immune and mechanism of action. Those studies which explained the psycho-neuroendocrine and immune mechanisms of action of yoga were included and rest were excluded. Although primary aim of this study is to explain these mechanisms in Type II DM, some studies in non-diabetic population which had a similar pathway of stress mechanism was included because many insightful studies were available in that area. Search was conducted using terms yoga OR yogic AND diabetes OR diabetic IN title OR abstract for English articles. Of the 89 articles, we excluded non-English articles (22), editorials (20) and letters to editor (10). 37 studies were considered for this review. The postulated mechanism of action of yoga is through parasympathetic activation and the associated anti stress mechanism. It reduces perceived stress and HPA axis activation thereby improving overall metabolic and psychological profiles, increasing insulin sensitivity, and improving glucose tolerance and lipid metabolism. Yoga has positive effects on immune system of diabetics.– Overall, Type II DM is influenced by psycho-neuro-endocrine and immune mechanisms where Yoga has important positive role in combating stressors and improving these systems to regain health.
PMCID: PMC4623627  PMID: 26600662
Yoga; Type II DM; psycho-neuro-endocrine; mechanisms of action; immune mechanisms; HIP-PNE model
16.  Metabolic Syndrome Is Associated with Increased Oxo-Nitrative Stress and Asthma-Like Changes in Lungs 
PLoS ONE  2015;10(6):e0129850.
Epidemiological studies have shown an increased obesity-related risk of asthma. In support, obese mice develop airway hyperresponsiveness (AHR). However, it remains unclear whether the increased risk is a consequence of obesity, adipogenic diet, or the metabolic syndrome (MetS). Altered L-arginine and nitric oxide (NO) metabolism is a common feature between asthma and metabolic syndrome that appears independent of body mass. Increased asthma risk resulting from such metabolic changes would have important consequences in global health. Since high-sugar diets can induce MetS, without necessarily causing obesity, studies of their effect on arginine/NO metabolism and airway function could clarify this aspect. We investigated whether normal-weight mice with MetS, due to high-fructose diet, had dysfunctional arginine/NO metabolism and features of asthma. Mice were fed chow-diet, high-fat-diet, or high-fructose-diet for 18 weeks. Only the high-fat-diet group developed obesity or adiposity. Hyperinsulinemia, hyperglycaemia, and hyperlipidaemia were common to both high-fat-diet and high-fructose-diet groups and the high-fructose-diet group additionally developed hypertension. At 18 weeks, airway hyperresponsiveness (AHR) could be seen in obese high-fat-diet mice as well as non-obese high-fructose-diet mice, when compared to standard chow-diet mice. No inflammatory cell infiltrate or goblet cell metaplasia was seen in either high-fat-diet or high-fructose-diet mice. Exhaled NO was reduced in both these groups. This reduction in exhaled NO correlated with reduced arginine bioavailability in lungs. In summary, mice with normal weight but metabolic obesity show reduced arginine bioavailability, reduced NO production, and asthma-like features. Reduced NO related bronchodilation and increased oxo-nitrosative stress may contribute to the pathogenesis.
PMCID: PMC4476757  PMID: 26098111
17.  Potential Influence of Intravenous Lipids on the Outcomes of Acute Pancreatitis 
Parenteral nutrition (PN) has been associated with a higher rate of adverse outcomes compared with enteral feeding in patients with acute pancreatitis (AP). However, PN may be necessary when feeding via the enteral route is poorly tolerated or impossible, and PN is recommended as a second-line nutrition therapy in AP. Intravenous (IV) lipids are commonly used as a part of PN in patients with AP. While the adverse outcomes related to the use of PN in AP have commonly been attributed to infectious complications, data suggest that the unsaturated fatty acids in the triglycerides used in IV lipids may contribute to the development of organ failure. We discuss the clinical and experimental data on this issue and the alternative lipid emulsions that are being studied.
PMCID: PMC4040228  PMID: 24687866
pancreatic diseases; pancreatitis; nutritional support; parenteral nutrition; total parenteral nutrition; intravenous fat emulsions
18.  Radiation countermeasure agents: an update (2011 – 2014) 
Expert Opinion on Therapeutic Patents  2014;24(11):1229-1255.
Despite significant scientific advances over the past 60 years towards the development of a safe, nontoxic and effective radiation countermeasure for the acute radiation syndrome (ARS), no drug has been approved by the US FDA. A radiation countermeasure to protect the population at large from the effects of lethal radiation exposure remains a significant unmet medical need of the US citizenry and, thus, has been recognized as a high priority area by the government.
Area covered
This article reviews relevant publications and patents for recent developments and progress for potential ARS treatments in the area of radiation countermeasures. Emphasis is placed on the advanced development of existing agents since 2011 and new agents identified as radiation countermeasure for ARS during this period.
Expert opinion
A number of promising radiation countermeasures are currently under development, seven of which have received US FDA investigational new drug status for clinical investigation. Four of these agents, CBLB502, Ex-RAD, HemaMax and OrbeShield, are progressing with large animal studies and clinical trials. G-CSF has high potential and well-documented therapeutic effects in countering myelosuppression and may receive full licensing approval by the US FDA in the future.
PMCID: PMC4438421  PMID: 25315070
countermeasures; gastrointestinal syndrome; hematopoietic syndrome; mice; nonhuman primates; radiation
19.  Pattern-based Detection of Toxic Metals in Surface Water with DNA Polyfluorophores** 
Heavy metal contamination of water can be toxic to humans and wildlife; thus the development of methods to detect this contamination is of high importance. Here we describe the design and application of DNA-based fluorescent chemosensors on microbeads to differentiate eight toxic metal ions in water. We developed and synthesized four fluorescent 2′-deoxyribosides of metal-binding ligands. A tetramer-length oligodeoxy-fluoroside (ODF) library of 6561 members was constructed and screened for sequences responsive to metal ions, of which seven sequences were selected. Statistical analysis of the response patterns showed successful differentiation of the analytes at concentrations as low as 100 nm. Sensors were able to classify water samples from 13 varied sites and quantify metal contamination in unknown specimens. The results demonstrate the practical potential of bead-based ODF chemosensors to analyze heavy metal contamination in water samples by a simple and inexpensive optical method.
PMCID: PMC4095765  PMID: 24756982
fluorescence; transition metals; oligonucleotides; sensors; combinatorial chemistry
20.  Comparison of the efficacy of saline, local anesthetics, and steroids in epidural and facet joint injections for the management of spinal pain: A systematic review of randomized controlled trials 
Surgical Neurology International  2015;6(Suppl 4):S194-S235.
The efficacy of epidural and facet joint injections has been assessed utilizing multiple solutions including saline, local anesthetic, steroids, and others. The responses to these various solutions have been variable and have not been systematically assessed with long-term follow-ups.
Randomized trials utilizing a true active control design were included. The primary outcome measure was pain relief and the secondary outcome measure was functional improvement. The quality of each individual article was assessed by Cochrane review criteria, as well as the criteria developed by the American Society of Interventional Pain Physicians (ASIPP) for assessing interventional techniques. An evidence analysis was conducted based on the qualitative level of evidence (Level I to IV).
A total of 31 trials met the inclusion criteria. There was Level I evidence that local anesthetic with steroids was effective in managing chronic spinal pain based on multiple high-quality randomized controlled trials. The evidence also showed that local anesthetic with steroids and local anesthetic alone were equally effective except in disc herniation, where the superiority of local anesthetic with steroids was demonstrated over local anesthetic alone.
This systematic review showed equal efficacy for local anesthetic with steroids and local anesthetic alone in multiple spinal conditions except for disc herniation where the superiority of local anesthetic with steroids was seen over local anesthetic alone.
PMCID: PMC4431057  PMID: 26005584
Chronic pain; epidural injections; facet joint injections; local anesthetic; spinal pain; steroids; saline
21.  Crystal Structure of Fad35R from Mycobacterium tuberculosis H37Rv in the Apo-State 
PLoS ONE  2015;10(5):e0124333.
Fad35R from Mycobacterium tuberculosis binds to the promoter site of Fad35 operon and its DNA binding activities are reduced in the presence of tetracycline and palmitoyl-CoA. We resolved the crystal structure of Fad35R using single-wavelength anomalous diffraction method (SAD). Fad35R comprises canonical DNA binding domain (DBD) and ligand binding domain (LBD), but displays several distinct structural features. Two recognition helices of two monomers in the homodimer are separated by ~ 48 Å and two core triangle-shaped ligand binding cavities are well exposed to solvent. Structural comparison with DesT and QacR structures suggests that ligand binding-induced movement of α7, which adopts a straight conformation in the Fad35R, may be crucial to switch the conformational states between repressive and derepressive forms. Two DBDs are packed asymmetrically, creating an alternative dimer interface which coincides with the possible tetramer interface that connects the two canonical dimers. Quaternary state of alternative dimer mimics a closed-state structure in which two recognition helices are distanced at ~ 35 Å and ligand binding pockets are inaccessible. Results of biophysical studies indicate that Fad35R has the propensity to oligomerize in solution in the presence of tetracycline. We present the first structure of a FadR homologue from mycobacterium and the structure reveals DNA and ligand binding features of Fad35R and also provides a view on alternative quaternary states that mimic open and closed forms of the regulator.
PMCID: PMC4418694  PMID: 25938298
22.  Medical Countermeasures for Radiation Exposure and Related Injuries: Characterization of Medicines, FDA-Approval Status and Inclusion into the Strategic National Stockpile 
Health Physics  2015;108(6):607-630.
World events over the past decade have highlighted the threat of nuclear terrorism as well as an urgent need to develop radiation countermeasures for acute radiation exposures and subsequent bodily injuries. An increased probability of radiological or nuclear incidents due to detonation of nuclear weapons by terrorists, sabotage of nuclear facilities, dispersal and exposure to radioactive materials, and accidents provides the basis for such enhanced radiation exposure risks for civilian populations. Although the search for suitable radiation countermeasures for radiation-associated injuries was initiated more than half a century ago, no safe and effective radiation countermeasure for the most severe of these injuries, namely acute radiation syndrome (ARS), has been approved by the United States Food and Drug Administration (FDA). The dearth of FDA-approved radiation countermeasures has prompted intensified research for a new generation of radiation countermeasures. In this communication, the authors have listed and reviewed the status of radiation countermeasures that are currently available for use, or those that might be used for exceptional nuclear/radiological contingencies, plus a limited few medicines that show early promise but still remain experimental in nature and unauthorized for human use by the FDA.
PMCID: PMC4418776  PMID: 25905522
bone marrow; gamma radiation; health effects; radiation effects
23.  Participatory women’s groups and counselling through home visits to improve child growth in rural eastern India: protocol for a cluster randomised controlled trial 
BMC Public Health  2015;15:384.
Child stunting (low height-for-age) is a marker of chronic undernutrition and predicts children’s subsequent physical and cognitive development. Around one third of the world’s stunted children live in India. Our study aims to assess the impact, cost-effectiveness, and scalability of a community intervention with a government-proposed community-based worker to improve growth in children under two in rural India.
The study is a cluster randomised controlled trial in two rural districts of Jharkhand and Odisha (eastern India). The intervention tested involves a community-based worker carrying out two activities: (a) one home visit to all pregnant women in the third trimester, followed by subsequent monthly home visits to all infants aged 0–24 months to support appropriate feeding, infection control, and care-giving; (b) a monthly women’s group meeting using participatory learning and action to catalyse individual and community action for maternal and child health and nutrition. Both intervention and control clusters also receive an intervention to strengthen Village Health Sanitation and Nutrition Committees.
The unit of randomisation is a purposively selected cluster of approximately 1000 population. A total of 120 geographical clusters covering an estimated population of 121,531 were randomised to two trial arms: 60 clusters in the intervention arm receive home visits, group meetings, and support to Village Health Sanitation and Nutrition Committees; 60 clusters in the control arm receive support to Committees only. The study participants are pregnant women identified in the third trimester of pregnancy and their children (n = 2520). Mothers and their children are followed up at seven time points: during pregnancy, within 72 hours of delivery, and at 3, 6, 9, 12 and 18 months after birth. The trial’s primary outcome is children’s mean length-for-age Z scores at 18 months. Secondary outcomes include wasting and underweight at all time points, birth weight, growth velocity, feeding, infection control, and care-giving practices. Additional qualitative and quantitative data are collected for process and economic evaluations.
This trial will contribute to evidence on effective strategies to improve children's growth in India.
Trial registration
ISRCTN register 51505201; Clinical Trials Registry of India number 2014/06/004664.
Electronic supplementary material
The online version of this article (doi:10.1186/s12889-015-1655-z) contains supplementary material, which is available to authorized users.
PMCID: PMC4410595  PMID: 25886587
Stunting; India; Child; Nutrition; Public health
24.  In Vitro Cytotoxic Evaluation of MgO Nanoparticles and Their Effect on the Expression of ROS Genes 
Water-dispersible MgO nanoparticles were tested to investigate their cytotoxic effects on oxidative stress gene expression. In this in vitro study, genes related to reactive oxygen species (ROS), glutathione S-transferase (GST) and catalase, were quantified using real-time polymerase chain reactions (molecular level) and molecular beacon technologies (cellular level). The monodispersed MgO nanoparticles, 20 nm in size, were used to treat human cancer cell lines (liver cancer epithelial cells) at different concentrations (25, 75 and 150 µg/mL) and incubation times (24, 48 and 72 h). Both the genetic and cellular cytotoxic screening methods produced consistent results, showing that GST and catalase ROS gene expression was maximized at 150 µg/mL nanoparticle treatment with 48 h incubation. However, the genotoxic effect of MgO nanoparticles was not significant compared with control experiments, which indicates its significant potential applications in nanomedicine as a diagnostic and therapeutic tool.
PMCID: PMC4425033  PMID: 25854426
catalase; nano-genotoxicity; MgO nanoparticle; glutathione S-transferase; reactive oxygen species
25.  Soft Computing Methods in Civil Engineering 
The Scientific World Journal  2015;2015:605871.
PMCID: PMC4389987  PMID: 25884034

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