To optimize strategies for liver-directed cell therapy prevention of initial transplanted cell losses is particularly important for subsequent liver repopulation. After cell transplantation in hepatic sinusoids, perturbations in hepatic microcirculation along with changes in various liver cell types are among the earliest changes. Therefore, for advancing further concepts in cell engraftment, we studied vascular and related events in the liver after transplanting syngeneic hepatocytes into dipeptidyl peptidase IV-deficient rats. We treated rats with vascular drugs to define whether deleterious cell transplantation-induced events could be controlled followed by improvements in transplanted cell engraftment and proliferation. We found cell transplantation altered liver gene expression related to vessel tone, inflammation, cell adhesion, thrombosis, or tissue damage/remodeling. This was due to hepatic ischemia, endothelial injury and activation of neutrophils, Kupffer cells and hepatic stellate cells. Treatment of rats before cell transplantation with angiotensin converting enzyme blocker, lisinopril, or angiotensin II receptor blocker, losartan, did not improve cell engraftment. By contrast, direct-acting nitroglycerine or prostacyclin improved cell engraftment and also kinetics of liver repopulation. These drugs lowered hepatic ischemia and inflammation. Whereas pretreatment of rats with the dual endothelin-1 receptor blocker, bosentan, improved cell engraftment independently of hepatic ischemia or inflammation, without improving liver repopulation. However, incubation of hepatocytes with bosentan protected cells from cytokine toxicity in vitro and produced superior cell engraftment and proliferation in vivo. We concluded that cell transplantation-induced changes in hepatic microcirculation contributed to transplanted cell clearances from liver. Vascular drugs, such as nitroglycerine, prostacyclin and bosentan, offer opportunities for improving cell therapy results through superior cell engraftment and liver repopulation. Ongoing clinical use of these drugs will permit rapid translation of the findings in people.
Cell therapy; Inflammation; Ischemia; Vascular; Drugs
Dicer, an RNase III-type endonuclease, is the key enzyme involved in RNA interference and microRNA pathways. Aberrant expression of Dicer is reported in several human cancers. Our aim was to assess the prognostic role of Dicer in breast cancer.
The entire series comprised 666 invasive breast cancers (IBCs), 480 DCIS cases (397 associated with IBC and 83 pure DCIS) and 305 lymph node metastases. Cytoplasmic Dicer expression by immunohistochemistry was scored as negative (no staining) and positive (weak, moderate or strong staining).
Dicer staining was assessable in 446 IBC, 128 DCIS and 101 lymph node metastases. Expression of Dicer was observed in 33% (145/446) of IBCs, 34% (44/128) of DCIS and 57% (58/101) of lymph node metastases. Dicer expression was increased in nodal metastases compared to primary tumours (p<0.001); and was associated with ER negativity (p<0.001), HER2 positivity (p<0.001), high Ki67 labeling index (p<0.001) and expression of basal-like biomarkers (p = 0.002). Dicer positivity was more frequent in the HER2 overexpressing (p<0.001) and basal-like (p = 0.002) subtypes compared to luminal A subtype. Dicer expression was associated with reduced overall survival (OS) on univariate analysis (p = 0.058) and remained an independent predictor of OS on multivariate analysis (HR 2.84, 95% CI 1.43–5.62, p = 0.003), with nodal status (HR 2.61, 95% CI 1.18–5.80, p = 0.018) and PR (HR 0.28, 95% CI 0.13–0.59, p = 0.001). Further, moderate or strong expression of Dicer was associated with improved disease-free survival in the HER2-overexpressing subtype compared to negative or weak expression (p = 0.038).
Deregulated Dicer expression is associated with aggressive tumour characteristics and is an independent prognostic factor for OS. Our findings suggest that Dicer is an important prognostic marker in breast cancer and that its prognostic role may be subtype specific.
Necrotizing soft tissue infections (NSTIs) are fulminant infections of any layer of the soft tissue compartment associated with widespread necrosis and systemic toxicity. Delay in diagnosing and treating these infections increases the risk of mortality. Early and aggressive surgical debridement with support for the failing organs significantly improves the survival. Although there are different forms of NSTIs like Fournier's gangrene or clostridial myonecrosis, the most important fact is that they share common pathophysiology and principles of treatment. The current paper summarizes the pathophysiology, clinical features, the diagnostic workup required and the treatment principles to manage these cases.
Hepatocyte transplantation; Injury; Rescue; Stem cells; Tissue engineering
Nanotechnology (nano: One billionth) is a novel arena with promising applications in the field of medicine, especially pharmaceuticals for safe and targeted drug delivery. The skin is a phenomenal tool for investigation of nanocarriers for drug delivery for topical and dermatological application. The physicochemical characteristics of the nanoparticles, such as rigidity, hydrophobicity, size and charge are crucial to the skin permeation mechanism. Many nanocarriers such as polymeric, inorganic and lipid nanoparticles and nanoemulsions have been developed and some like carbon nanotubes and fullerenes still need further exploration for future use in skin care and dermatological treatments. Risks of nanopollution and cytotoxicity also need to be kept in mind while exploring various nanoparticles for medical use.
Nanocarriers; nanodermatology; nanomedicine; nanopollution nanotechnology
Objectives. To compare the outcome of dorsal buccal mucosal graft (BMG) substitution urethroplasty by dorsal urethrotomy approach with ventral urethrotomy approach in management of stricture urethra. Methods and Materials. A total of 40 patients who underwent dorsal BMG substitution urethroplasty were randomized into two groups. 20 patients underwent dorsal onlay BMG urethroplasty as described by Barbagli, and the other 20 patients underwent dorsal BMG urethroplasty by ventral urethrotomy as described by Asopa. Operative time, success rate, satisfaction rate, and complications were compared between the two groups. Mean follow-up was 12 months (6–24 months). Results. Ventral urethrotomy group had considerably lesser operative time although the difference was not statistically significant. Patients in dorsal group had mean maximum flow rate of 19.6 mL/min and mean residual urine of 27 mL, whereas ventral group had a mean maximum flow rate of 18.8 and residual urine of 32 mL. Eighteen out of twenty patients voided well in each group, and postoperative imaging study in these patients showed a good lumen with no evidence of leak or extravasation. Conclusion. Though ventral sagittal urethrotomy preserves the blood supply of urethra and intraoperative time was less than dorsal urethrotomy technique, there was no statistically significant difference in final outcome using either technique.
Leukemia cutis is the term used for cutaneous manifestations of leukemia, which can have varied clinical presentations. A skin biopsy can help in diagnosing such condition and differentiating it from other skin diseases. We present a case where a 45 years old man presented with diffuse papulovesicular skin lesions mimicking dessiminated herpes. Further workup revealed patient having acute myeloid leukemia (AML-M2) and skin biopsy showed infiltration by myeloblasts. With chemotherapy patient went into remission and skin lesions healed.
Acute myeloid leukemia; Leukemia cutis; Myeloperoxidase
Transplanting pancreatic islets is of significant interest for type 1 diabetes mellitus. After intraportal injection of islets, inferior engraftment and eventual loss of transplanted islets constitute major limitations. Therefore, alternative approaches will be helpful. Here, we evaluated in animals whether an isolated venous sac would support survival of transplanted islets, along with correction of hyperglycemia.
Pancreatic islets isolated from adult Lewis rats were transplanted either into an isolated venous sac made from lumbar vein or into the portal vein of syngeneic rats. The integrity and vascular organization of the venous sac was determined by studies of the local microcirculation. The engraftment, survival, and function of transplanted islets were analyzed by histology, including endocrine function in situ and by glycemic control in rats with streptozotocin-induced diabetes.
Transplanted islets showed normal morphology with insulin expression in isolated venous sac during the long term. Transplanted islets received blood supply from vasa vasorum and had access to drainage through venous tributaries in the venous sac. This resulted in restoration of euglycemia in diabetic rats. Removal of islet graft-bearing venous sac in diabetic rats led to recurrence of hyperglycemia. By contrast, euglycemia was not restored in rats treated by intraportal transplantation of islets.
We demonstrated that pancreatic islets successfully engrafted and functioned in the isolated venous sac with ability to restore euglycemia in diabetic rats. Therefore, the isolated venous sac offers a new site for transplantation of pancreatic islets. This would be clinically beneficial as an alternative to intrahepatic islet transplantation.
Islets; Pancreas; Intravascular transplantation
Global downregulation of microRNAs (miRNAs) is a common feature of human tumors and has been shown to enhance cancer progression. Several components of the miRNA biogenesis machinery (XPO5, DICER and TRBP) have been shown to act as haploinsufficient tumor suppressors. How the deregulation of miRNA biogenesis promotes tumor development is not clearly understood. Here we show that loss of miRNA biogenesis increased resistance to endoplasmic reticulum (ER) stress-induced cell death. We observed that HCT116 cells with a DICER hypomorphic mutation (Exn5/Exn5) or where DICER or DROSHA were knocked down were resistant to ER stress-induced cell death. Extensive analysis revealed little difference in the unfolded protein response (UPR) of WT compared to Exn5/Exn5 HCT116 cells upon ER stress treatment. However, analysis of the intrinsic apoptotic pathway showed that resistance occurred upstream of the mitochondria. In particular, BAX activation and dissipation of mitochondrial membrane potential was attenuated, and there was altered expression of BCL-2 family proteins. These observations demonstrate a key role for miRNAs as critical modulators of the ER stress response. In our model, downregulation of miRNA biogenesis delays ER stress-induced apoptosis. This suggests that disrupted miRNA biogenesis may contribute to cancer progression by inhibiting ER stress-induced cell death.
The Toll-Like receptor 4 (TLR4) plays an important role in immunity, tissue repair, and regeneration. The objective of the present work was to evaluate the association of TLR4 single nucleotide polymorphisms (SNPs) rs4986790, rs4986791, rs11536858 (merged into rs10759931), rs1927911, and rs1927914 with increased diabetic foot ulcer (DFU) risk in patients with type 2 diabetes mellitus (T2DM). PCR-RFLP was used for genotyping TLR4 SNPs in 125 T2DM patients with DFU and 130 controls. The haplotypes and linkage disequilibrium between the SNPs were determined using Haploview software. Multivariate linear regression (MLR) and artificial neural network (ANN) modeling was done to observe their predictability for the risk of DFU in T2DM patients. Risk genotypes of all SNPs except rs1927914 were significantly associated with DFU. Haplotype ACATC (P value = 9.3E − 5) showed strong association with DFU risk. Two haplotypes ATATC (P value = 0.0119) and ATGTT (P value = 0.0087) were found to be protective against DFU. In conclusion TLR4 SNPs and their haplotypes may increase the risk of impairment of wound healing in T2DM patients. ANN model (83%) is found to be better than the MLR model (76%) and can be used as a tool for the DFU risk assessment in T2DM patients.
Excretion of copper into bile requires the copper transporter Atp7b, which is deficient in Wilson disease. We hypothesized that a radiocopper–histidine complex would be effective for diagnosing Wilson disease by molecular imaging and tested this hypothesis in the Long–Evans cinnamon (LEC) rat model with Atp7b deficiency.
We complexed 64Cu to l-histidine and analyzed clearance from blood, uptake in tissues, and excretion in bile of healthy Long–Evans agouti (LEA) rats versus LEC rats modeling Wilson disease. Sixty-minute dynamic PET recordings were obtained in LEA and LEC rats. Possible effects of acute and chronic liver injury induced by carbon tetrachloride were studied in LEA rats. Atp7b deficiency in LEC rats was reconstituted by transplantation of healthy cells to establish the specificity of findings.
Examination of blood, tissue, and bile showed that in healthy rats, radiocopper was incorporated in the liver, followed by rapid excretion in bile. Corresponding blood, tissue, and bile studies in LEC rats showed incorporation of radiocopper in the liver but without copper excretion in bile, leading to hepatic retention of the radiotracer. PET showed onset of copper clearance in the liver of LEA rats, whereas liver copper content progressively increased in LEC rats during the 1-h period. Hepatic radiocopper excretion was not altered by either acute or chronic liver injury. In LEC rats with liver repopulation by transplanted healthy hepatocytes, excretion of radiocopper confirmed that Atp7b was responsible for this effect.
Imaging with the radiocopper–histidine complex successfully identified Atp7b-dependent biliary copper excretion. This principle will advance molecular imaging for Wilson disease.
Atb7b; positron emission tomography; radiocopper; Wilson disease
The global incidence of non-melanoma skin cancer is rising. Significant morbidity leading to unacceptable cosmetic outcomes and/or functional impairment is a major concern. Search for non-surgical, non-invasive and tissue-sparing treatment modalities has led to development of new therapeutic agents. Actinic keratoses (AK) are one part of a continuous spectrum of benign sun damage to squamous cell carcinoma (SCC). Although it is not possible to predict which AK might progress to SCC, the presence of AK is a biomarker of risk for patients and must be treated to avoid possible morbidity and mortality. Ingenol mebutate is a novel topical drug from the latex sap of a plant-Euphorbia peplus that acts by chemoablative and immunostimulatory properties. Clinical studies have proven it to be safe and efficacious, leading to FDA approval of this chemotherapeutic agent for field therapy of AK in 2012. Current topical agents for field therapy of AK must be applied for weeks, whereas ingenol needs to be applied for three days. Ingenol offers a new therapeutic option that is convenient, safe, effective, acceptable and well-tolerated.
Actinic keratosis; ingenol mebutate; nonmelanoma skin cancer
Neuropathology centers are expected to offer a prompt and accurate intraoperative diagnosis regarding tumor/lesion type and grade on fresh unfixed tissue. Level of diagnostic accuracy according to type and grade and also, the experience at a new center has not been reported before.
The aim of this study is to review the agreement patterns according to tumor/lesion type and grade between intraoperative and final histopathologic diagnosis in central nervous system (CNS) lesion samples received by a newly established neuropathology center at a tertiary care neuropsychiatric hospital.
Materials and Methods:
Agreement between intraoperative and final histopathologic diagnosis was classified as: (I) Grade in agreement but type not in agreement; (II) grade not in agreement but type in agreement; (III) grade and type both not in agreement; (IV) grade and type both in agreement.
Confidence interval (CI) of agreements was calculated for various categories of neoplastic as well as non-neoplastic lesions. CI was also calculated for groups where n × p and n × (1 − p) were more than 5, i.e., fulfilled the requirement of the central limit theorem.
On retrospective analysis of 333 cases, 284 (85.3%) cases were categorized as neoplastic while 49 (14.7%) cases were categorized as non-neoplastic. Among the neoplastic lesions agreement was seen in 237 (83.5%) cases while 47 (16.5%) cases showed disagreement. Similarly in non-neoplastic category; 46 (93.9%) cases showed agreement while 3 (6.15%) cases showed disagreement. Of the non-neoplastic lesions, one case fell into the agreement category I, 2 in category III and 46 in IV. Among neoplastic lesions, there were 21 cases in agreement category I, 17 in II, 9 in III and 237 in IV. On analyzing the accuracy of intraoperative reporting according to tumor type, the break up was: - Astrocytic: 2 (I), 16 (II), 2 (III), 86 (IV); oligodendroglial: 8 (I), 1 (II); ependymal: 2 (III), 6 (IV); embryonal: 23 (IV); cranial and spinal nerve tumors: 2 (II), 21 (IV); choroid plexus tumors: 4 (IV); meningeal tumors: 3 (I), 1 (III), 49 (IV); metastatic tumors: 3 (I), 17 (IV); cysts (tumor-like conditions): 14 (IV); neuronal and mixed neuronal glial tumors: 1 (III); malignant lymphoma: 1 (III); sellar tumors: 17 (IV); and mixed gliomas: 5 (I).
This study identifies problem areas of CNS intraoperative reporting, in a new center, with reference to tumor typing and grading. It may forewarn upcoming centers of neuropathology about the potential problem areas of intraoperative reporting.
Central nervous system lesions; intraoperative reporting; new center
Myiasis is derived from the Greek word-“Myia”, meaning “fly”. The term was first introduced by Hope in 1840 and refers to the infestation of human beings with dipterous larvae (maggots). Presence of maggots on exposed parts is already known, but on covered parts like external genitalia it is very rare. We hereby describe a case of young unmarried female who presented with multiple sinuses over external genitalia along with maggots coming out of it.
External genitalia; female; maggots; myiasis; sinuses
Studies of natural hepatitis B virus infection must be restricted to humans or primates due to viral species-specificity. Alternative hepadnavirus animal models, e.g., woodchuck hepatitis virus in captive woodchucks, are not convenient, while in transgenic mice hepatitis B virus or viral proteins are expressed permanently through integrated genomes. Availability of small animal models that are easily produced and permit rapid assays will be quite helpful.
We examined whether transplantation of human cells in the peritoneal cavity of mice will generate an appropriate mass of cells with hepatitis B virus replication.
HepG2 2.2.15 cells were transplanted intraperitoneally into NOD/SCID mice. Replication of hepatitis B virus and viral gene expression was determined by analysis of blood and transplanted tissues with viral DNA and hepatitis B core antigen expression. Interruption of viral replication was examined.
After intraperitoneal transplantation with microcarrier scaffolds, 2.2.15 cells engrafted and proliferated in the peritoneal cavity of NOD/SCID mice. Hepatitis B virus replicated in transplanted 2.2.15 cells as shown by hepatitis B core antigen expression. Moreover, viral particles were secreted into the blood. Hepatitis B virus replication was susceptible to conventional antiviral drug therapy, such as lamivudine, as well as experimental antiviral gene therapy with a synthetic mimic of an antiviral cellular microRNA.
Intraperitoneal transplantation of human cells rapidly provided reservoirs of hepatitis B virus in mice. This simple xeno-transplantation approach will be effective and convenient for studies of hepatitis B and other human viruses in vivo.
cell transplantation; hepatitis B virus; liver; replication; treatment
Organs from nonheart-beating donors are attractive for use in cell therapy. Understanding the nature of molecular perturbations following reperfusion/reoxygenation will be highly significant for nonheart-beating donor cells. We studied nonheart-beating donor rats for global gene expression with Affymetrix microarrays, hepatic tissue integrity, viability of isolated hepatocytes, and engraftment and proliferation of transplanted cells in dipeptidyl peptidase IV-deficient rats. In nonheart-beating donors, liver tissue was morphologically intact for >24 hours with differential expression of 1, 95, or 372 genes, 4, 16 or 34 hours after death, respectively, compared with heart-beating donors. These differentially-expressed genes constituted prominent groupings in ontological pathways of oxidative phosphorylation, adherence junctions, glycolysis/gluconeogenesis, as well as other discrete pathways. We successfully isolated viable hepatocytes from nonheart-beating donors, especially up to 4 hours after death, although the hepatocyte yield and viability were inferior to hepatocytes from heart-beating donors, p<0.05. Similarly, although hepatocytes from nonheart-beating donors engrafted and proliferated after transplantation in recipient animals, this was inferior to hepatocytes from heart-beating donors, p<0.05. Gene expression profiling in hepatocytes isolated from nonheart-beating donors showed far greater perturbations compared with corresponding liver tissue, including representation of pathways in focal adhesion, actin cytoskeleton, extracellular matrix-receptor interactions, multiple ligand-receptor interactions, and signaling in insulin, calcium, wnt, Jak-Stat, or other cascades. Conclusion: Liver tissue remained intact over prolonged periods after death in nonheart-beating donors but extensive molecular perturbations following reperfusion/reoxygenation impaired viability of isolated hepatocytes from these donors. Insights into molecular changes in hepatocytes from nonheart-beating donors offers opportunities for improving donor cell viability, which will advance utility of nonheart-beating donor organs for cell therapy or other applications.
Cell therapy; gene expression; hepatocytes; liver; nonheart-beating donor
Air pollution is responsible for many health problems in the urban areas. Of late, the air pollution status in Delhi has undergone many changes in terms of the levels of pollutants and the control measures taken to reduce them. This paper provides an evidence-based insight into the status of air pollution in Delhi and its effects on health and control measures instituted. The urban air database released by the World Health Organization in September 2011 reported that Delhi has exceeded the maximum PM10 limit by almost 10-times at 198 μg/m3. Vehicular emissions and industrial activities were found to be associated with indoor as well as outdoor air pollution in Delhi. Studies on air pollution and mortality from Delhi found that all-natural-cause mortality and morbidity increased with increased air pollution. Delhi has taken several steps to reduce the level of air pollution in the city during the last 10 years. However, more still needs to be done to further reduce the levels of air pollution.
Air pollution Delhi; control measures; health
The Government of India initiated a cash incentive scheme—Janani Suraksha Yojana (JSY)—to promote institutional deliveries with an aim to reduce maternal mortality ratio (MMR). An observational study was conducted in a tertiary-care hospital of Madhya Pradesh, India, before and after implementation of JSY, with a sample of women presenting for institutional delivery. The objectives of this study were to: (i) determine the total number of institutional deliveries before and after implementation of JSY, (ii) determine the MMR, and (iii) compare factors associated with maternal mortality and morbidity. The data were analyzed for two years before implementation of JSY (2003-2005) and compared with two years following implementation of JSY (2005-2007). Overall, institutional deliveries increased by 42.6% after implementation, including those among rural, illiterate and primary-literate persons of lower socioeconomic strata. The main causes of maternal mortality were eclampsia, pre-eclampsia and severe anaemia both before and after implementation of JSY. Anaemia was the most common morbidity factor observed in this study. Among those who had institutional deliveries, there were significant increases in cases of eclampsia, pre-eclampsia, polyhydramnios, oligohydramnios, antepartum haemorrhage (APH), postpartum haemorrhage (PPH), and malaria after implementation of JSY. The scheme appeared to increase institutional delivery by at-risk mothers, which has the potential to reduce maternal morbidity and mortality, improve child survival, and ensure equity in maternal healthcare in India. The lessons from this study and other available sources should be utilized to improve the performance and implementation of JSY scheme in India.
Conditional cash transfer; Institutional deliveries; Maternal mortality; Maternal survival; India
Background & objectives:
The presence of efficient malaria vectors namely Anopeles culicifacies, An. fluviatilis and An. annularis (Diptera: Culicidae), rapid industrialization causing large influx of population and poor health infrastructure are some of the factors that make malaria an important public health problem in Ranchi, the capital of Jharkhand State, India. A geographical information system (GIS) based retrospective study using spatial statistical tools was initiated in 328 subcentres of 14 primary health centres (PHCs) of the district using malaria epidemiological data of three years (2007-2009) to identify spatial distribution pattern of Plasmodium vivax (Pv) and Plasmodium falciparum (Pf) occurrence, delineation of hot spots and to map directional distribution trend of Pf spread to help formulate evidence-based policy and to prioritize control during 2011.
Spatial statistics tools like Global Moran's I index, Getis-Ord Gi* and Standard Deviational Ellipse were used in GIS domain for analysis.
Spatial distribution pattern of Pv occurrence was found random while Pf distribution was significantly clustered. During 2007-2009, the number of subcentres under Pf hot spot category exhibited downward trend while high Pf risk subcentres exhibited upward trend. One consistent Pf hot spot consisting of five subcentres was identified in Silli PHC. During 2009, one Pf hot spot consisting of 20 subcentres and 18 subcentres under high Pf risk category were identified in Angara, Silli, Burmu and Kanke PHCs. A shifting trend in Pf spread was noticed from north-west to western direction from 2008 onwards.
Interpretation & conclusions:
The study recommended priority control in 20 Pf hot spot and 18 high Pf risk reporting subcentres including five consistent Pf hot spot subcentres in Angara, Silli, Burmu and Kanke PHCs during 2011 to address grave malaria situation in the district in a cost-effective manner.
Cold spots; high risk; hot spots; spatial statistics; Standard Deviational Ellipse
The increasing proportion of elderly persons is contributing to an increase in the prevalence of diabetes. The residents of urban slums are more vulnerable due to poverty and lack of access to health care.
To estimate the prevalence of diabetes in elderly persons in an urban slum and to assess their awareness, treatment and control of this condition.
Materials and Methods:
All persons aged 60 years and above, residing in an urban slum of Delhi, were included in this cross-sectional community- based study. Data were collected on sociodemographic variables. The participants’ awareness and treatment of diabetes was recorded. Their fasting blood sugar was estimated using an automated glucometer. Diabetes was diagnosed if fasting blood glucose was ≥126 mg/dL, or if the participant was taking treatment for diabetes. Impaired fasting blood glucose was diagnosed if fasting blood glucose was 110–125 mg/dL.
Among the 474 participants studied, the prevalence of diabetes was estimated to be 18.8% (95% CI 15.3–21.5). It decreased with increasing age, and was higher among women. The prevalence of impaired fasting blood glucose was 19.8% (95% CI 16.3–23.7). It was higher among women. One-third of the diabetic participants were aware of their condition; two-thirds of these were on treatment and three-fourths of those on treatment had controlled fasting blood sugar level. The awareness, treatment and control were better among women.
Diabetes is common among elderly persons in urban slums. Its magnitude and low awareness warrant effective public health interventions for their treatment and control.
Awareness; diabetes; elderly; older persons; slum
The aim of the present study was to estimate the prevalence of cardiovascular risk factors among administrative employees working at a tertiary hospital (All India Institute of Medical Sciences, New Delhi) and their families.
Methods and results
A cross-sectional survey was conducted among a total of 453 individuals aged 30 years and above. The mean age of the study group was 43.3 ± 9.5 years. There was a high prevalence of major cardiovascular risk factors – current smoking 58 (12.8%), tobacco consumption 26 (5.7%), family history of coronary artery disease 79 (17.4%), diabetes mellitus 25 (5.8%), hypertension 94 (20.7%), hypercholesterolemia 110 (25.7%), hypertriglyceridemia 148 (34.5%), physical inactivity 180 (39.7%), body mass index ≥23 kg/m2 350 (77.3%), central obesity 201 (80.1%) of males and 163 (80.7%) of females, inadequate fruit and vegetable consumption 387 (85.4%), heavy drinking 12 (2.6%), and stress 58 (12.7%).
This indicates an urgent need to initiate a comprehensive health promotion and cardiovascular disease prevention programme at workplace and community level.
Cardiovascular risk factors; Coronary artery disease; Prevalence
The nature of host-virus interactions in hepatitis B virus infection is incompletely understood. Since soluble factors, e.g., cytokines and metals, may exacerbate liver injury in chronic hepatitis, we considered that defining the effects of receptor-mediated signaling upon viral replication will be significant. Consequently, we studied effects of iron or TGF-β-induced TGF-β/BMP signaling in the HepG2 2.2.15 cell model of hepatitis B virus replication. We found iron and TGF-β increased hepcidin mRNA expression or TGF-β receptor kinase activity, respectively, which indicated that 2.2.15 cells responded appropriately to these substances. However, iron increased but TGF-β decreased hepatitis B virus mRNA and DNA expression. TGF-β induced expression at the mRNA level of multiple TGF-β/BMP pathway genes. This change was not observed in iron-treated cells. On the other hand, presence of SMAD proteins in iron or TGF-β-treated cells, including of SMAD4, did confirm convergence of TGF-β/BMP signaling pathways under these conditions. Since transcription factors in TGF-β/BMP signaling pathways could not have directly targeted hepatitis B virus itself, we studied whether iron or TGF-β exerted their effects through alternative mechanisms, such as by involvement of antiviral cellular microRNAs. We discovered cellular microRNA expression profiles were significantly different in iron or TGF-β-treated cells compared with untreated control cells. In many cases, exposure to iron or TGF-β changed microRNA expression in opposite directions. Introduction in cells of sequences representing such differentially expressed microRNAs, e.g., hsa-miR-125a-5p and -151-5p, even reproduced effects on virus replication of iron- or TGF-β. We surmised that TGF-β/BMP pathway members, i.e., SMADs, likely governed iron or TGF-β-induced microRNA expression. Iron may have mediated Drosha/DGCR8/heme-mediated processing of microRNAs. In turn, cellular microRNAs regulated replication of hepatitis B virus in iron or TGF-β-treated cells. This knowledge should advance studies of mechanisms in viral-host interactions, hepatic injury, and therapeutic developments for hepatitis B.