Comparative studies of xanthine oxidase inhibitors viz. allopurinol and febuxostat against induced hyperuricaemia in a poultry model.

In this study, an attempt was made to evaluate the relative efficacy of two important anti-gout agents, viz. allopurinol and febuxostat, in the control of hyperuricaemia/gout using a poultry model. A 21-day study was conducted on 48 Vencobb-400 broiler chicks randomly divided into four groups. In one group hyperuricaemia/gout was induced by the oral administration of diclofenac (group D); in two other groups the ameliorative effect of the two drugs under study was investigated by providing both simultaneously, i.e. diclofenac and allopurinol (group DA), diclofenac and febuxostat (group DF); and the fourth group was kept un-induced and untreated as a control (group C). Both allopurinol and febuxostat inhibit xanthine oxidase enzymes, thereby reducing the production of uric acid. The birds kept on diclofenac alone exhibited the highest level of hyperuricaemia, clinical signs of gout, and overt adverse changes in the visceral organs, whereas these changes were lesser in allopurinol- and febuxostat-treated groups. Furthermore, haematological, biochemical, patho-morphological, and ultra-structural studies using transmission electron microscopy were carried out to evaluate the pathology and, thus, the ameliorative effect of allopurinol and febuxostat. The findings proved that allopurinol and febuxostat carry definite ameliorative potential as anti-hyperuricemic and anti-gout agents in poultry, which was better expressed by febuxostat compared to allopurinol.

An Exploratory-Descriptive Analysis of Training Programs for Leadership in Health Research and Services in India.

BACKGROUND: There are several leadership training programs for health researchers in India. However, there is a need to develop context-tailored leadership and mentoring approaches. OBJECTIVE: The objective of the study is to critically analyze the available leadership training programs in India for health researchers and service providers, for the leadership domains incorporated and overall training approaches. MATERIALS AND METHODS: We used an exploratory-descriptive design to identify and review leadership training programs for health researchers and service providers/managers that had been offered by Indian institutions between 2013 and 2018. Our analytic approach was based on "transformational leadership" and "leader-member exchange" theories of leadership, curricula of popular leadership training programs worldwide, and the International Clinical Epidemiology Network model for leadership in health research in India based on a nationwide primary study. RESULTS: We identified and reviewed 20 leadership training programs. These were heterogeneous in aim, scope (broad-based/thematic), course content, design, target participants and class profile, mode of delivery and training method, duration, frequency, and fund arrangements. The programs infrequently included topics on soft skills, mentoring, risk mitigation, collaboration for research, funding dynamics, institutional transformation, self-view and peer perception, and personal well-being. The programs insufficiently addressed contextual challenges of career exploration and risk mitigation, project management, strategic planning, and decision-making, ethics and integrity, negotiations, networking and collaboration, understanding funding dynamics, and mentoring. Only three programs linked to the training to the participants' ecosystem. CONCLUSIONS: There is a need to develop customized course contents and training strategies that address the requirements of the local context vis-à-vis globally connected research ecosystems.

Endothelin-1 acutely increases nitric oxide production via the calcineurin mediated dephosphorylation of Caveolin-1.

Endothelin (ET)-1 is an endothelial-derived peptide that exerts biphasic effects on nitric oxide (NO) levels in endothelial cells such that acute exposure stimulates-while sustained exposure attenuates-NO production. Although the mechanism involved in the decrease in NO generation has been identified but the signaling involved in the acute increase in NO is still unresolved. This was the focus of this study. Our data indicate that exposing pulmonary arterial endothelial cells (PAEC) to ET-1 led to an increase in NO for up to 30min after which levels declined. These effects were attenuated by ET receptor antagonists. The increase in NO correlated with significant increases in pp60Src activity and increases in eNOS phosphorylation at Tyr83 and Ser1177. The ET-1 mediated increase in phosphorylation and NO generation were attenuated by the over-expression of a pp60Src dominant negative mutant. The increase in pp60Src activity correlated with a reduction in the interaction of Caveolin-1 with pp60Src and the calcineurin-mediated dephosphorylation of caveolin-1 at three previously unidentified sites: Thr91, Thr93, and Thr95. The calcineurin inhibitor, Tacrolimus, attenuated the acute increase in pp60Src activity induced by ET-1 and a calcineurin siRNA attenuated the ET-1 mediated increase in eNOS phosphorylation at Tyr83 and Ser1177 as well as the increase in NO. By using a Caveolin-1 celluSpot peptide array, we identified a peptide targeting a sequence located between aa 41-56 as the pp60Src binding region. This peptide fused to the TAT sequence was found to decrease caveolin-pp60Src interaction, increased pp60Src activity, increased eNOS pSer1177 and NO levels in PAEC and induce vasodilation in isolated aortic rings in wildtype but not eNOS knockout mice. Together, our data identify a novel mechanism by which ET-1 acutely increases NO via a calcineurin-mediated dephosphorylation of caveolin-1 and the subsequent stimulation of pp60Src activity, leading to increases in phosphorylation of eNOS at Tyr83 and Ser1177.

Growth studies in commercial broiler birds offered citric acid in formulated feed with low mineral density.

Study of 35 days was conducted to evaluate citric acid (CA) as an additive in poultry broiler feed with lower mineral content of calcium (Ca) and total phosphorus (TP) in commercial broiler poultry birds for its effect on growth, nutrient utilization, carcass characteristics, and economics. Vancobb-400 strain day old broiler chicks were divided into four main treatment groups T0, T1, T2, and T3. Treatment groups were further divided into eight replicates with ten chicks in each. T0 served as control, given standard corn-soy flakes-based ration (Pre-starter %: Crude protein (CP)-23, Ca-1.00, TP-0.70; Starter %: CP-22, Ca-1.10, TP-0.72, and Finisher %: CP-20, Ca-0.99, TP-0.70). Treatment T1 served as positive control with added 0.5% CA (Pre-starter %: CP-23, Ca-1.00, TP-0.70; Starter %: CP-22, Ca-1.10, TP-0.72 and Finisher %: CP-20, Ca-0.99, TP-0.70). Treatment T2 was given feed containing 0.5% CA with low Ca and TP content (Pre-starter %: CP-23, Ca-0.90, TP-0.66; Starter %: CP-22, Ca-0.99, TP-0.71 and Finisher %: CP-20, Ca-0.90, TP-0.69), whereas treatment T3 was given feed containing 0.5% CA with moderately low Ca and TP content (Pre-starter %: CP-23, Ca-0.80, TP-0.65; Starter %: CP-22, Ca-0.88, TP-0.70 and Finisher %: CP-20, Ca-0.79, TP-0.68). Birds offered moderately low Ca and TP with 0.5% CA addition, exhibited higher growth rate (P < 0.05), better nutrient utilization with positive influence on dressing percentage and forequarters weight. Economics of broiler feeding revealed that 0.5% CA supplementation fetched highest gross return above feed cost in broiler birds offered feed with moderately low Ca and TP content whereas lowest profit was recorded in feed with low content of Ca and TP. In conclusion, supplementation of 0.5% CA in feed with low and moderately low Ca and TP content positively influenced overall growth, and carcass characteristics. Economics of broiler feeding with moderately low Ca and TP content revealed highest profit with CA (0.5%) supplementation.

Knowledge and attitude on prevention of COVID-19 among community health workers in Nepal-a cross-sectional study.

BACKGROUND: Emerging and reemerging pathogens are global challenges for public health and the pandemic of Coronavirus disease 2019is a reemerging case of an infectious disease caused by Severe Acute Respiratory Syndrome-Corornavirus-2. Health care worker worldwide are at higher risk worldwide and the situation is the same in Nepal. The knowledge and attitude of health workers will certainly mark the outcome towards this pandemic. So, this study aims to assess the knowledge and attitude of community health workers towards the prevention of COVID-19 virus. METHODS: A descriptive cross-sectional study was carried out among the community health workers of various provinces of Nepal. A semi-structured, self-administered questionnaire was prepared in Google form and circulated to the sampled health workers through various social media platforms like face book, messenger, Instagram and g-mails. A total of 650 invitations were send and among them 420 responded and among them only 399 provided complete response. Responses containing anonymized data was collected analyzed in using SPSS-version-20. The results were interpreted and was checked with various demographic and enabling factors using chi-square test and logistic regression model. Also, ethical approval was taken from NHRC (Nepal Health Research Council (protocol registration number: 360/2020P) prior to the conduction of study. RESULTS: Out the total sample size of 450, we took 399 responses taking into consideration all the inclusion criteria. So, from 399 valid response, 230 (47.6%) were males and 169 (42.4%) were females. 380 (95.2%) employed participants thought that wearing PPE will reduce the chances of getting COVID-19, majority of the participants 80.5% (321) responded that COVID-19 will successfully be controlled and staffs receiving excellent support from palika had high knowledge level. Knowledge level was significantly associated with the enabling factor "support from palika" (P = 0.045).45.9% of the respondents had no availability of COVID-19 response medical items for prevention of COVID-19 at their respective health facilities. Also the logistic regression analysis revealed that the odds of knowledge level was 2 times higher (AOR=1.913 at 95% CI: 1.266-2.891) compared to the female participants (Ref- female). CONCLUSIONS: Proper and adequate knowledge and attitude towards COVID-19 is a paramount in the prevention and control of SARS-COV-2. Health care workers are knowledgeable about COVID-19 and are proactively practicing the preventive measures to minimize the spread of infection but some lack optimistic attitude. Hence, the constantly updated educational programs related to COVID-19 will surely contribute to improving the healthcare workers knowledge and attitude towards COVID-19.

A review on traditional uses, phytochemistry, pharmacology, and clinical research of dietary spice Cuminum cyminum L.

Cuminum cyminum L. is a versatile spice belonging to family Apiaceae. Though the plant has pan-tropical distribution but it is indigenous to Egypt, the Mediterranean, and South Asian countries. It exhibits numerous culinary, traditional, and pharmacological attributes. Its traditional uses also validate its immense pharmacological potential. Cuminum cyminum is the hub of numerous bioactives such as alkaloids, flavonoids, terpenoids, and so forth. Cuminaldehyde is the major bioactive, rendered to most of its pharmacological as well as clinical significance. The present study comprised of current knowledge on its taxonomy, nutritional, traditional, phytochemistry, pharmacology (antimicrobial, antioxidant, anti-inflammation, antidiabetic, wound healing, anticancer, etc.), toxicology, and clinical attributes. Besides, the mechanism of action is also well explained. The present study provides a rationale for further bioprospection of this wonder plant. Future studies are needed to fill the research gaps, particularly on relevant phytocompound isolation, their pre-clinical and clinical characterization, evaluation, and structure-activity relationship. Moreover, well-designed and highly appropriate clinical and placebo trials are still needed to demonstrate the trustworthy role of cumin on human health.

Extracellular adenosine enhances pulmonary artery vasa vasorum endothelial cell barrier function via Gi/ELMO1/Rac1/PKA-dependent signaling mechanisms.

The vasa vasorum (VV), the microvascular network around large vessels, has been recognized as an important contributor to the pathological vascular remodeling in cardiovascular diseases. In bovine and rat models of hypoxic pulmonary hypertension (PH), we have previously shown that chronic hypoxia profoundly increased pulmonary artery (PA) VV permeability, associated with infiltration of inflammatory and progenitor cells in the arterial wall, perivascular inflammation, and structural vascular remodeling. Extracellular adenosine was shown to exhibit a barrier-protective effect on VV endothelial cells (VVEC) via cAMP-independent mechanisms, which involved adenosine A1 receptor-mediated activation of Gi-phosphoinositide 3-kinase-Akt pathway and actin cytoskeleton remodeling. Using VVEC isolated from the adventitia of calf PA, in this study we investigated in more detail the mechanisms linking Gi activation to downstream barrier protection pathways. Using a small-interference RNA (siRNA) technique and transendothelial electrical resistance assay, we found that the adaptor protein, engulfment and cell motility 1 (ELMO1), the tyrosine phosphatase Src homology region 2 domain-containing phosphatase-2, and atypical Gi- and Rac1-mediated protein kinase A activation are implicated in VVEC barrier enhancement. In contrast, the actin-interacting GTP-binding protein, girdin, and the p21-activated kinase 1 downstream target, LIM kinase, are not involved in this response. In addition, adenosine-dependent cytoskeletal rearrangement involves activation of cofilin and inactivation of ezrin-radixin-moesin regulatory cytoskeletal proteins, consistent with a barrier-protective mechanism. Collectively, our data indicate that targeting adenosine receptors and downstream barrier-protective pathways in VVEC may have a potential translational significance in developing pharmacological approach for the VV barrier protection in PH.

Characteristics and potential biomarkers of adult sickle cell patients with chronic pain.

OBJECTIVES: In this study, we investigated the evolution of chronic pain in sickle cell patients (SCD) as an age-dependent phenomenon and studied the frequency of vaso-occlusive episode frequency, opioid use, quantitative sensory testing (QST), and biomarkers of chronic pain (CP). METHODS: We undertook a cross-sectional study of the evolution of CP in SCD. A total of 72 subjects (age 15-66) were enrolled. VOE frequency, presence of CP hydroxyurea (HU) therapy, opioid use, and laboratory parameters were collected. QST was performed, and plasma tryptase, substance P, and NGF (Nerve Growth Factor) levels were assayed. RESULTS: There was an age-dependent increase in frequency of CP, VOEs, opioid use, and Von Frey monofilament values. CP patients had significantly higher opioid use (daily morphine equivalents) (52.8 mg vs 6.94 mg, P = .009), suggesting a correlation between opioid use and hyperalgesia. NGF levels were also significantly higher (P = .051). Our results confirm previous observations of an age-dependent increase in the proportion of patients with CP and support the contributing role of mast cell activation and neurogenic inflammation. CONCLUSIONS: This is the first study of NGF as a possible biomarker of CP in SCD. If confirmed, this could provide a diagnostic marker and therapeutic target for CP in SCD.

Leadership through the eyes of a public health professional: A journey of 43 years.

Leadership skills in a public health professional (PHP) are more important today in view of rapidly changing disease pattern, higher priority to universal health coverage, health in all policies, health being demanded as a human right, and emergence of pandemics from zoonotic diseases. Most of us become accidental leaders as we never receive training in leadership skills. This not only undermines the effectiveness of PHP but also undermines the credibility of public health as a specialty. Jim Collin's five levels of leadership are useful to understand the various levels of leadership for a PHP. Technical excellence which denotes first level of leadership is necessary but not sufficient to become a leader. One needs team work, emotional competencies, prioritization ( first things first), listening skills, advocacy, negotiation, networking skills, along with conviction, commitment, and courage to do what one thinks is right. Leadership is a life-long journey, not a destination. Being engaged in leadership for more than a decade, I developed a three domain leadership capacity development model very useful in designing and conducting leadership development trainings to develop leadership skills among PHPs, academicians, and health researchers.

Addressing health inequity through strategic planning and management.

Substantial progress has been made to improve health in India in terms of availability, accessibility, cost-effectiveness, and quality. However, there are major health inequalities between and within the states. Strategic planning of health programs is required to address inequities in health. Need of the hour is to address this using a simplified strategic approach; who is left out, why are they left out, what causes are responsible for it and what are the determinants of inequality. The basic steps of strategic management, including strategic assessment, objectives, strategy formulation, and implementation, can be used to address the health equity. This article cites the examples of Serbia immunization programme, Government of India programme on Mission Indradhanush, and Thailand's universal health coverage to get better understanding to use strategic management to address health inequity. This approach is crucial in achieving sustainable development goals.

Significance of super spreader events in COVID-19.

The number of secondary cases from each primary case determines how fast an epidemic grows. It is known that all cases do not spread the infection equally; super spreaders play an important role as they contribute disproportionately to a much larger number of cases including in the ongoing COVID-19 pandemic. Super spreaders have been reported for more than a century, but limited information is available in scientific literature. An epidemic containment strategy needs to include early identification of super spreaders to limit an explosive growth. Super spreaders tend to get stigmatized, resulting in late reporting and hiding of cases. It is important for program managers to be sensitive to the manner in which related information is shared with media and general public.

Insights from COVID-19 cluster containment in Bhilwara District, Rajasthan.

BACKGROUND: In March 2020, a healthcare professional from a renowned private hospital, in the textile city of Bhilwara, Rajasthan, reported clustering of cases of pneumonia amongst doctors and paramedical staff suspected to be due to COVID-19. The basis of suspicion was clinico-eco-epidemiologic-radiological findings as, by that time, about 20 COVID19 cases were reported from the state of Rajasthan including a big Italian group of tourists who travelled extensively in Rajasthan, including Udaipur city. OBJECTIVES: The current study presents the field experience of the Central and the State Rapid Response Teams (RRTs) in the cluster containment at Bhilwara. Methods: The information regarding the sociodemographic profile of the cases was provided by the Senior Medical Officer In-charge. The containment strategy was modeled under 6 pillars. Google Maps was used for preparing spot map. RESULTS: Immediate public health actions of cluster containment including contact tracing, quarantine, and isolation were initiated using epidemiological approach of mapping the cluster and taking care of reservoir of infection by the District Public Health Team supported by Multidisciplinary Rapid Response Team. This was supplemented by strict enforcement of lock down in the District taking care of daily need of the community by the leadership of administration with very strong intersectoral co-ordination (locally called "ruthless containment"). CONCLUSION: The forthcoming challenge resides in re-establishment of inter-district and inter-state travel, which can become a risk of re-entry of the new cases, which needs to be taken care of, with the help of stringent administrative measures and screening at all points of entry. The team in Bhilwara needs to remain vigilant to pick up any imported cases early before local transmission establishes.

Differential mechanisms of adenosine- and ATPγS-induced microvascular endothelial barrier strengthening.

Maintenance of the endothelial cell (EC) barrier is critical to vascular homeostasis and a loss of barrier integrity results in increased vascular permeability. While the mechanisms that govern increased EC permeability have been under intense investigation over the past several decades, the processes regulating the preservation/restoration of the EC barrier remain poorly understood. Herein we show that the extracellular purines, adenosine (Ado) and adenosine 5'-[γ-thio]-triphosphate (ATPγS) can strengthen the barrier function of human lung microvascular EC (HLMVEC). This ability involves protein kinase A (PKA) activation and decreases in myosin light chain 20 (MLC20) phosphorylation secondary to the involvement of MLC phosphatase (MLCP). In contrast to Ado, ATPγS-induced PKA activation is accompanied by a modest, but significant decrease in cyclic adenosine monophosphate (cAMP) levels supporting the existence of an unconventional cAMP-independent pathway of PKA activation. Furthermore, ATPγS-induced EC barrier strengthening does not involve the Rap guanine nucleotide exchange factor 3 (EPAC1) which is directly activated by cAMP but is instead dependent upon PKA-anchor protein 2 (AKAP2) expression. We also found that AKAP2 can directly interact with the myosin phosphatase-targeting protein MYPT1 and that depletion of AKAP2 abolished ATPγS-induced increases in transendothelial electrical resistance. Ado-induced strengthening of the HLMVEC barrier required the coordinated activation of PKA and EPAC1 in a cAMP-dependent manner. In summary, ATPγS-induced enhancement of the EC barrier is EPAC1-independent and is instead mediated by activation of PKA which is then guided by AKAP2, in a cAMP-independent mechanism, to activate MLCP which dephosphorylates MLC20 resulting in reduced EC contraction and preservation.

The Treponema pallidum Outer Membrane.

The outer membrane (OM) of Treponema pallidum, the uncultivatable agent of venereal syphilis, has long been the subject of misconceptions and controversy. Decades ago, researchers postulated that T. pallidum's poor surface antigenicity is the basis for its ability to cause persistent infection, but they mistakenly attributed this enigmatic property to the presence of a protective outer coat of serum proteins and mucopolysaccharides. Subsequent studies revealed that the OM is the barrier to antibody binding, that it contains a paucity of integral membrane proteins, and that the preponderance of the spirochete's immunogenic lipoproteins is periplasmic. Since the advent of recombinant DNA technology, the fragility of the OM, its low protein content, and the lack of sequence relatedness between T. pallidum and Gram-negative outer membrane proteins (OMPs) have complicated efforts to characterize molecules residing at the host-pathogen interface. We have overcome these hurdles using the genomic sequence in concert with computational tools to identify proteins predicted to form ß-barrels, the hallmark conformation of OMPs in double-membrane organisms and evolutionarily related eukaryotic organelles. We also have employed diverse methodologies to confirm that some candidate OMPs do, in fact, form amphiphilic ß-barrels and are surface-exposed in T. pallidum. These studies have led to a structural homology model for BamA and established the bipartite topology of the T. pallidum repeat (Tpr) family of proteins. Recent bioinformatics has identified several structural orthologs for well-characterized Gram-negative OMPs, suggesting that the T. pallidum OMP repertoire is more Gram-negative-like than previously supposed. Lipoprotein adhesins and proteases on the spirochete surface also may contribute to disease pathogenesis and protective immunity.

LPS-induced Acute Lung Injury Involves NF-κB-mediated Downregulation of SOX18.

One of the early events in the progression of LPS-mediated acute lung injury in mice is the disruption of the pulmonary endothelial barrier resulting in lung edema. However, the molecular mechanisms by which the endothelial barrier becomes compromised remain unresolved. The SRY (sex-determining region on the Y chromosome)-related high-mobility group box (Sox) group F family member, SOX18, is a barrier-protective protein through its ability to increase the expression of the tight junction protein CLDN5. Thus, the purpose of this study was to determine if downregulation of the SOX18-CLDN5 axis plays a role in the pulmonary endothelial barrier disruption associated with LPS exposure. Our data indicate that both SOX18 and CLDN5 expression is decreased in two models of in vivo LPS exposure (intraperitoneal, intratracheal). A similar downregulation was observed in cultured human lung microvascular endothelial cells (HLMVECs) exposed to LPS. SOX18 overexpression in HLMVECs or in the mouse lung attenuated the LPS-mediated vascular barrier disruption. Conversely, reduced CLDN5 expression (siRNA) reduced the HLMVEC barrier-protective effects of SOX18 overexpression. The mechanism by which LPS decreases SOX18 expression was identified as transcriptional repression through binding of NF-κB (p65) to a SOX18 promoter sequence located between -1,082 and -1,073 bp with peroxynitrite contributing to LPS-mediated NF-κB activation. We conclude that NF-κB-dependent decreases in the SOX18-CLDN5 axis are essentially involved in the disruption of human endothelial cell barrier integrity associated with LPS-mediated acute lung injury.

A single high-fat meal provokes pathological erythrocyte remodeling and increases myeloperoxidase levels: implications for acute coronary syndrome.

High-fat meal (HFM) consumption can produce acute lipemia and trigger myocardial infarction in patients with atherosclerosis, but the mechanisms are poorly understood. Erythrocytes (red blood cells, RBCs) intimately interact with inflammatory cells and blood vessels and play a complex role in regulating vascular function. Chronic high-fat feeding in mice induces pathological RBC remodeling, suggesting a novel link between HFM, RBCs, and vascular dysfunction. However, whether acute HFM can induce RBC remodeling in humans is unknown. Ten healthy individuals were subjected to biochemical testing and assessment of endothelial-dependent flow-mediated dilation (FMD) before and after a single HFM or iso-caloric meal (ICM). Following the HFM, triglyceride, cholesterol, and free fatty acid levels were all significantly increased, in conjunction with impaired post-prandial FMD. Additionally, peripheral blood smears demonstrated microcytes, remodeled RBCs, and fatty monocytes. Increased intracellular ROS and nitration of protein band 3 was detected in RBCs following the HFM. The HFM elevated plasma and RBC-bound myeloperoxidase (MPO), which was associated with impaired FMD and oxidation of HDL. Monocytic cells exposed to lipid in vitro released MPO, while porcine coronary arteries exposed to fatty acids ex vivo took up MPO. We demonstrate in humans that a single HFM induces pathological RBC remodeling and concurrently elevates MPO, which can potentially enter the blood vessel wall to trigger oxidative stress and destabilize vulnerable plaques. These novel findings may have implications for the short-term risk of HFM consumption and alimentary lipemia in patients with atherosclerosis.

Urban health: Needs urgent attention.

Urban population in our country has increased at an annual rate of 2.7% during the last decade and it is estimated that by 2031, there would be about 600 million people living in urban India. The fast pace of urbanization has come to stay with increasing proportion of urban poor and vulnerable with health indicators much worse than their rural counterparts. The need to provide health care to urban poor has been emphasized in the past in various health committees' reports and National 5-year Development Plans, but no significant dent was made to improve the urban health scenario of the country. The National Urban Health Mission launched in May 2013 provides us a concrete mechanism to address special health needs of urban population with focus on urban poor. There is a strong need to set up primary healthcare system in urban areas and systematically deal with urban health challenges in terms of vector-borne diseases, rising incidence of noncommunicable diseases, air pollution and acute respiratory infections, road traffic accidents, trauma, and injuries. The initiatives to address these challenges do not remain confined to health sector alone but also need to be supported by sectors other than health such as social welfare, women and child development, road transport and highways, school education, drinking water, and sanitation. We really need to address wider and social determinants of health to effectively improve the urban health scenario.

Food adulteration: Sources, health risks, and detection methods.

Adulteration in food has been a concern since the beginning of civilization, as it not only decreases the quality of food products but also results in a number of ill effects on health. Authentic testing of food and adulterant detection of various food products is required for value assessment and to assure consumer protection against fraudulent activities. Through this review we intend to compile different types of adulterations made in different food items, the health risks imposed by these adulterants and detection methods available for them. Concerns about food safety and regulation have ensured the development of various techniques like physical, biochemical/immunological and molecular techniques, for adulterant detection in food. Molecular methods are more preferable when it comes to detection of biological adulterants in food, although physical and biochemical techniques are preferable for detection of other adulterants in food.

Altered Carnitine Homeostasis in Children With Increased Pulmonary Blood Flow Due to Ventricular Septal Defects.

OBJECTIVES: Congenital heart disease with increased pulmonary blood flow results in progressive pulmonary vascular endothelial dysfunction and associated increased perioperative morbidity. Using our ovine model of congenital heart disease with increased pulmonary blood flow, we have previously demonstrated progressive endothelial dysfunction associated with disruption in carnitine homeostasis, mitochondrial dysfunction, decreased nitric oxide signaling, and enhanced reactive oxygen species generation. However, potential alterations in these parameters in patients with congenital heart disease have not been investigated. The objective of this study was to test the hypothesis that children with increased pulmonary blood flow will have evidence of altered carnitine homeostasis, mitochondrial dysfunction, decreased nitric oxide levels, and increased reactive oxygen species generation. DESIGN: A prospective single-center cohort study. SETTING: A tertiary care cardiac ICU/PICU. PATIENTS: Arterial blood samples from 18 patients with congenital heart disease associated with increased pulmonary blood flow (ventricular septal defect), 20 with congenital heart disease without increased pulmonary blood flow (tetralogy of Fallot), and 10 without heart disease (controls) were obtained. INTERVENTIONS: Plasma levels of total carnitine, free carnitine, acylcarnitine, and lactate-to-pyruvate ratios, an indicator of mitochondrial function, were determined and compared. In addition, levels of superoxide and hydrogen peroxide were determined and compared in patients with ventricular septal defect and controls. Statistical analysis was performed using an unpaired t test and analysis of variance. MEASUREMENTS AND MAIN RESULTS: Baseline acylcarnitine levels (25.7 ± 13 vs 12.7 ± 8.3; p < 0.05), the acylcarnitine-to-free carnitine ratio (0.8 ± 0.1 vs 0.3 ± 0.05; p < 0.05), and the lactate-to-pyruvate ratio were higher in ventricular septal defect (27.5 ± 3.8 vs 11.1 ± 4.1, p < 0.05) than tetralogy of Fallot; there were no differences between tetralogy of Fallot and control. Superoxide and H2O2 levels were also higher in ventricular septal defect compared with controls, and NOx levels were lower in ventricular septal defect patients compared with tetralogy of Fallot and controls (p < 0.05). CONCLUSIONS: These data suggest that increased pulmonary blood flow from ventricular septal defect results in altered carnitine and mitochondrial homeostasis, decreased nitric oxide signaling, and increased reactive oxygen species production. These data are consistent with our animal data demonstrating that altered carnitine homeostasis results in mitochondrial dysfunction, increased reactive oxygen species production, and decreased bioavailable nitric oxide. Since disruption of carnitine metabolism may contribute to endothelial dysfunction, carnitine supplementation may attenuate endothelial dysfunction associated with increased pulmonary blood flow and warrants further investigation.

Discordance in self-report and observation data on mistreatment of women by providers during childbirth in Uttar Pradesh, India.

BACKGROUND: The study aims to assess the discordance between self-reported and observed measures of mistreatment of women during childbirth in public health facilities in Uttar Pradesh, India, as well as correlates of these measures and their discordance. METHODS: Cross sectional data were collected through direct observation of deliveries and follow-up interviews with women (n = 875) delivering in 81 public health facilities in Uttar Pradesh. Participants were surveyed on demographics, mistreatment during childbirth, and maternal and newborn complications. Provider characteristics (training, age) were obtained through interviews with providers, and observation data were obtained from checklists completed by trained nurse investigators to document quality of care at delivery. Mistreatment was assessed via self-report and observed measures which included 17 and 6 items respectively. Cohen's kappas assessed concordance between the 6 items common in the self-report and observed measures. Regression models assessed associations between characteristics of women and providers for each outcome. RESULTS: Most participants (77.3%) self-reported mistreatment in at least 1 of the 17-item measure. For the 6 items included in both self-report and observations, 9.1% of women self-reported mistreatment, whereas observers reported 22.4% of women being mistreated. Cohen's kappas indicated mostly fair to moderate concordance. Regression analyses found that multiparous birth (AOR = 1.50, 95% CI = 1.06-2.13), post-partum maternal complications (AOR = 2.0, 95% CI = 1.34-3.06); new-born complications (AOR = 2.6, 95% CI = 1. 96-4.03) and not having an Skilled Birth Attendant (SBA) trained provider (AOR = 1.47, 95% CI = 1.05-2.04) were associated with increased risk for mistreatment as measured by self-report. In contrast, only provider characteristics like older provider (AOR = 1.03, 95% CI = 1.02-1.05) and provider not trained in SBA (AOR = 1.44, 95% CI = 1.02-2.02) were associated with mistreatment as measured through observations. Younger age at marriage (AOR = 0.86, 95% CI = 0.78-0.95) and provider characteristics (older provider AOR = 1.05, 95% CI = 1.01-1.09; provider not trained in SBA AOR = 0.96, 95% CI = 0.92-0.99) were associated with discordance (based on mistreatment reported by observer but not by women). CONCLUSION: Provider mistreatment during childbirth is prevalent in Uttar Pradesh and may be under-reported by women, particularly when they are younger or when providers are older or less trained. The findings warrant programmatic action as well as more research to better understand the context and drivers of both behavior and reporting. TRIAL REGISTRATION: CTRI/2015/09/006219. Registered 28 September 2015.