Progastrin production transitions from Bmi1+/Prox1+ to Lgr5high cells during early intestinal tumorigenesis.

Progastrin is an unprocessed soluble peptide precursor with a well-described tumor-promoting role in colorectal cancer. It is expressed at small levels in the healthy intestinal mucosa, and its expression is enhanced at early stages of intestinal tumor development, with high levels of this peptide in hyperplastic intestinal polyps being associated with poor neoplasm-free survival in patients. Yet, the precise type of progastrin-producing cells in the healthy intestinal mucosa and in early adenomas remains unclear. Here, we used a combination of immunostaining, RNAscope labelling and retrospective analysis of single cell RNAseq results to demonstrate that progastrin is produced within intestinal crypts by a subset of Bmi1+/Prox1+/LGR5low endocrine cells, previously shown to act as replacement stem cells in case of mucosal injury. In contrast, our findings indicate that intestinal stem cells, specified by expression of the Wnt signaling target LGR5, become the main source of progastrin production in early mouse and human intestinal adenomas. Collectively our results suggest that the previously identified feed-forward mechanisms between progastrin and Wnt signaling is a hallmark of early neoplastic transformation in mouse and human colonic adenomas.

Consensus and development of document for management of stabilized acute decompensated heart failure with reduced ejection fraction in India.

AIM: Ensuring adherence to guideline-directed medical therapy (GDMT) is an effective strategy to reduce mortality and readmission rates for heart failure (HF). Use of a checklist is one of the best tools to ensure GDMT. The aim was to develop a consensus document with a robust checklist for stabilized acute decompensated HF patients with reduced ejection fraction. While there are multiple checklists available, an India-specific checklist that is easy to fill and validated by regional and national subject matter experts (SMEs) is required. METHODOLOGY: A total of 25 Cardiology SMEs who consented to participate from India discussed data from literature, current evidence, international guidelines and practical experiences in two national and four regional meetings. RESULTS: Recommendations included HF management, treatment optimization, and patient education. The checklist should be filled at four time points- (a) transition from intensive care unit to ward, (b) at discharge, (c) 1st follow-up and (d) subsequent follow-up. The checklist is the responsibility of the consultant or the treating physician which can be delegated to a junior resident or a trained HF nurse. CONCLUSION: This checklist will ensure GDMT, simplify transition of care and can be used by all doctors across India. Institutions, associations, and societies should recommend this checklist for adaptability in public and private hospital. Hospital administrations should roll out policy for adoption of checklist by ensuring patient files have the checklist at the time of discharge and encourage practice of filling it diligently during follow-up visits.

Assessment of healthcare measures, healthcare resource use, and cost of care among severe hemophilia A patients in Mumbai region of India.

Background: In India, the low public health priority given to rare disorders such as hemophilia hinders their management and optimal care, leading to relatively poor health outcomes. This study aims to profile the multidimensional health status of patients with severe hemophilia A, and its association with the use of healthcare resources and the cost of care in Mumbai region of India. Subjects and Methods: A cross-sectional, single-center study was conducted during January-May 2011, among 160 patients diagnosed with severe hemophilia A in Mumbai region of India. Their health status was documented using the Hemophilia Utilization Group Study's validated instrument of Functional Health Status Measure (FHS) and a single item of Self-care Measure. Results: Of 160 patients, 55% (n = 88) scored on the lower side on the FHS, with an average score of 6.65 ± 2.85. The use of healthcare resources and cost of treatment were considerable for patients with a lower mean rank score on the FHS and a higher mean rank score on the self-care measure. The consumption of clotting factor concentrates (CFCs), number of visits to a health facility and incidence of inpatient episodes were significantly associated with a relatively low score on the FHS. Similarly, a higher cost of treatment, in terms of the cost of CFCs, direct cost, emergency room cost, and indirect cost, were significantly associated with a lower score on the FHS. Conclusion: The health status of patients with severe hemophilia A is compromised and has a significant impact on the use of healthcare resources and the cost of treatment.

Study of Acidithiobacillus ferrooxidans and enzymatic bio-Fenton process-mediated corrosion of copper-nickel alloy.

This study presents the corrosion behavior of the copper-nickel (Cu-Ni) alloy in the presence of Acidithiobacillus ferrooxidans (A. ferrooxidans) and glucose oxidase (GOx) enzyme. In both the cases ferric ions played an important role in weight loss and thereby to carry out the corrosion of the Cu-Ni alloy. A corrosion rate of 0.6 (±0.008), 2.11 (±0.05), 3.69 (±0.26), 0.7 (±0.006) and 0.08 (±0.002) mm/year was obtained in 72 h using 9K medium with ferrous sulfate, A. ferrooxidans culture supernatant, A. ferrooxidans cells, GOx enzyme and hydrogen peroxide (H2O2) solution respectively. The scanning electron microscopy (SEM) micrographs showed that a variable extent of corrosion was caused by 9K medium with ferrous sulfate, GOx and A. ferrooxidans cells. An arithmetic average surface roughness (Ra) of 174.78 nm was observed for the control work-piece using optical profilometer. The change in Ra was observed with the treatment of the Cu-Ni alloy using various systems. The Ra for 9K medium with ferrous sulfate, GOx and A. ferrooxidans cells was 374.54, 607.32 and 799.48 nm, respectively, after 24 h. These results suggest that A. ferrooxidans cells were responsible for more corrosion of the Cu-Ni alloy than other systems used.

Hydrometallurgical Recovery of Metals from Large Printed Circuit Board Pieces.

The recovery of precious metals from waste printed circuit boards (PCBs) is an effective recycling process. This paper presents a promising hydrometallurgical process to recover precious metals from waste PCBs. To simplify the metal leaching process, large pieces of PCBs were used instead of a pulverized sample. The chemical coating present on the PCBs was removed by sodium hydroxide (NaOH) treatment prior to the hydrometallurgical treatment. Among the leaching reagents examined, hydrochloric acid (HCl) showed great potential for the recovery of metals. The HCl-mediated leaching of waste PCBs was investigated over a range of conditions. Increasing the acid concentration decreased the time required for complete metal recovery. The shaking speed showed a pronounced positive effect on metal recovery, but the temperature showed an insignificant effect. The results showed that 1 M HCl recovered all of the metals from 4 cm × 4 cm PCBs at room temperature and 150 rpm shaking speed in 22 h.

Microbial leaching of waste solder for recovery of metal.

This study proposes an environment-friendly bioleaching process for recovery of metals from solders. Tin-copper (Sn-Cu), tin-copper-silver (Sn-Cu-Ag), and tin-lead (Sn-Pb) solders were used in the current study. The culture supernatant of Aspergillus niger removed metals faster than the culture supernatant of Acidithiobacillus ferrooxidans. Also, the metal removal by A. niger culture supernatant is faster for Sn-Cu-Ag solder as compared to other solder types. The effect of various process parameters such as shaking speed, temperature, volume of culture supernatant, and increased solder weight on bioleaching of metals was studied. About 99 (±1.75) % metal dissolution was achieved in 60 h, at 200-rpm shaking speed, 30 °C temperature, and by using 100-ml A. niger culture supernatant. An optimum solder weight for bioleaching was found to be 5 g/l. Addition of sodium hydroxide (NaOH) and sodium chloride (NaCl) in the bioleached solution from Sn-Cu-Ag precipitated tin (85 ± 0.35 %) and silver (80 ± 0.08 %), respectively. Passing of hydrogen sulfide (H2S) gas at pH 8.1 selectively precipitated lead (57.18 ± 0.13 %) from the Sn-Pb bioleached solution. The proposed innovative bioleaching process provides an alternative technology for recycling waste solders to conserve resources and protect environment.

Pharmacologic reperfusion therapy with indigenous tenecteplase in 15,222 patients with ST elevation myocardial infarction - the Indian Registry.

OBJECTIVE: To study the efficacy and safety of single intravenous bolus administration of indigenously developed tenecteplase (TNK-tPA) in the management of patients with ST-elevation myocardial infarction (STEMI) in clinical practice. METHODS: Observational, prescription-event monitoring study. RESULTS: Data of 15,222 patients who had STEMI and received weight adjusted TNK injection was analyzed. Overall 95.43% patients had clinically successful thrombolysis (CST). In the different subgroups, hypertensives, diabetics, smokers and hyperlipidemic patients had CST rates comparable to the general patient data. CST rates were significantly lower in the elderly patients (>70 years; 92.11%; p < 0.0001), in patients with history of Ischemic Heart Disease (IHD, 93.86%; p = 0.0004) and in patients receiving delayed treatment (>6 h after onset of chest pain; 85.38%; p < 0.0001). CST was significantly higher in patients who received an early thrombolysis (<3 h after onset of chest pain; 96.54%; p = 0.006). Overall mortality was 1.69%, while it was significantly higher in the elderly (4.42%), patients with history of IHD (2.67%), females (2.93%) and in those who received delayed treatment (4.98%). The overall incidences of intracranial hemorrhage (ICH), bleeding excluding ICH, stroke and ventricular tachyarrhythmia were 0.39%, 2.01%, 0.16% and 2.35% respectively. Age >70 years, diabetes, hyperlipidemia and history of IHD were associated with a higher incidence of heart failure, myocardial re-infarction or ventricular tachyarrhythmias. However, incidence of ICH and bleeding other than ICH was comparable amongst all patient subgroups. CONCLUSION: This study confirms the safety and efficacy of indigenous tenecteplase in Indian patients with STEMI, including high risk subgroups. It also highlights the fact that delayed treatment denotes denial of benefits of pharmacologic reperfusion therapy.

Effect of cardiopulmonary bypass on tissue injury markers and endothelial activation during coronary artery bypass graft surgery.

BACKGROUND: Coronary artery bypass grafting (CABG) is done either using cardiopulmonary bypass (CPB) or without using CPB (OPCAB). But, recently, reports have shown that CPB is associated with increased postoperative morbidity because of the involvement of many systems. AIMS: The aim of this prospective study was to evaluate the influence of the technique of surgery on various tissue injury markers and the extent of endothelial activation in patients undergoing CABG and OPCAB coronary revascularization. SETTINGS AND DESIGN: This study was conducted at a tertiary healthcare center during the period May 2008 to December 2009. MATERIALS AND METHODS: This was a prospective nonrandomized blinded study. The activities of Creatine Phosphokinase (CK) and its isoenzyme CK-MB, Lactate dehydrogenase (LDH), levels of cardiac Troponin I, soluble vascular cell adhesion molecule-1 (sVCAM-I) and systemic nitric oxide production were assessed. STATISTICAL ANALYSIS: All the results were expressed as Mean ± SD. P value ≤ 0.05 was considered significant. The statistical analysis was carried out using SPSS Version 11.5-computer software (SPSS Inc., Chicago, IL, USA). RESULTS: The surgical trauma had elevated CK, CK-MB and Troponin I in both the groups and further elevation was seen in the CABG group in comparison to OPCAB (P<0.001). The Troponin I concentrations showed an increase from 0.11 ± 0.02 preoperatively to 6.59 ± 0.59 (ng/ml) at 24 h (P<0.001) compared to the OPCAB group. Mean serum levels of sVCAM-1 increased significantly after surgery in both the groups (P<0.02). To determine serum nitric oxide (NO) production, NO2- and NO3- (stable end products of NO oxidation) were analyzed which also increased significantly at 24 h in both the groups. But the increase was not significant at 48 h in both the groups compared to the preoperative value in our study. CONCLUSION: The present study indicates that, despite comparable surgical trauma, the OPCAB significantly reduces tissue injury. The overall pattern of endothelial activation after OPCAB is significantly lower than that after CABG. This may contribute to improved organ function, and improved postoperative recovery.

Efficacy & safety of tenecteplase in 6000 patients with ST-elevation myocardial infarction from the Elaxim Indian Registry.

OBJECTIVE: To study the efficacy and safety of single intravenous bolus administration of indigenously developed tenecteplase in the management of patients presenting with ST-elevation myocardial infarction in clinical practice. METHODS: Post-licensure, observational, prescription-event monitoring study. RESULTS: Data of 6000 patients who had ST-elevation myocardial infarction and received weight-adjusted tenecteplase injection was analyzed. Overall 90.93% patients had clinically successful thrombolysis, with highest success rate (93.2%) in patients treated within 3 hours. Overall mortality was 3.23%. The elderly (< or = 65 yrs; 24.58%) and diabetics (38.2%) had clinically successful thrombolysis of 87.73% and 90.49% respectively. Female patients (16.38%) had success rates comparable to males but with higher (6.41%) mortality. The overall incidences of intracranial hemorrhage (ICH), severe bleeding, stroke and ventricular tachyarrhythmia were 0.62%, 3.18%, 0.12% and 3.07% respectively and were not significantly different in females, diabetics and elderly patients. Delay in treatment beyond 6 hours was associated with increased incidence of heart failure, ventricular tachyarrhythmia and mortality. CONCLUSION: This study confirms the efficacy and safety of indigenous tenecteplase in the management of patients with ST-elevation myocardial infarction.

Efficacy and safety of tenecteplase in ST elevation myocardial infarction patients from the Elaxim Indian Registry.

OBJECTIVE: to study the efficacy and safety of indigenously developed tenecteplase injection in the management of Indian STEMI patients in clinical practice. METHODS: post-licensure, observational, prescription event monitoring study. RESULTS: 2100 patients received weight-adjusted tenecteplase injection. More than 90% patients received aspirin, clopidogrel, and enoxaparin/heparin. Clinically successful thrombolysis was reported in 86.71%, in-hospital mortality was 3.48%. The adverse events recorded were comparable with previously published data. Any bleeding (excluding intra-cranial hemorrhage) was seen in 4.62% patients which was reported in 0.90% patients of which 47.34% patients had also received GpIIb/IIIa inhibitors. CONCLUSION: This study confirms the efficacy and safety of indigenous tenecteplase in Indian STEMI patients.

Biodegradation of disperse textile dye Brown 3REL by newly isolated Bacillus sp. VUS.

AIMS: To isolate the potential micro-organism for the degradation of textile disperse dye Brown 3 REL and to find out the reaction mechanism. METHODS AND RESULTS: 16S rDNA analysis revealed an isolate from textile effluent contaminated soil as Bacillus sp. VUS and was able to degrade (100%) dye Brown 3REL within 8 h at static anoxic condition. A significant increase in the activities of lignin peroxidase, laccase and NADH-DCIP reductase was observed up to complete decolourization of Brown 3REL. The optimum temperature required for degradation was 40 degrees C and pH 6.5-12.0. Phyto-toxicity and chemical oxygen demand revealed nontoxic products of dye degradation. The biodegradation was monitored by UV-VIS, FTIR spectroscopy and HPLC. The final products 6,8-dichloro-quinazoline-4-ol and cyclopentanone were characterized by gas chromatography-mass spectrometry. This Bacillus sp. VUS also decolourized (80%) textile dye effluent within 12 h. CONCLUSIONS: This study suggests that Bacillus sp. VUS could be a useful tool for textile effluent treatment. SIGNIFICANCE AND IMPACT OF THE STUDY: The newly isolated Bacillus sp. VUS decolourized 16 textile dyes and textile dye effluent also. It achieved complete biodegradation of Brown 3REL. Phytotoxicity study demonstrated no toxicity of the biodegraded products for plants with respect to Triticum aestivum and Sorghum bicolor.

Rheumatic mitral valve surgery in the fifth decade: our experience.

AIM: Rheumatic mitral patients reach their fifth decade of life more often now than in the past. The purpose of this study is to provide insight into improving morbidity and mortality in these patients. METHODS: This retrospective study included 105 patients aged 50 years or more. Seventy-five underwent mechanical valve replacement and 30 received a bioprosthetic valve. Data were collected from medical records and outpatient department (OPD) registers. Follow-up included transthoracic 2D echocardiography, supported by clinical parameters, and X-ray findings. RESULTS: Mean age was 58.52+/-2.4 years. Follow-up period ranged from one to eleven years (mean 6.8+/-0.9 years). Immediate perioperative mortality included five patients (4.76%) and long term mortality included three patients (3%). 35 patients previously underwent closed and open commissurotomy and balloon valvotomy. Multivariate analysis showed age, repeat surgery, atrial fibrillation, tricuspid valve disease, and preoperative functional status to be incremental risk factors. Freedom from repeat operation at 3 and 6 years was 90% and 85% in group I (<60 years), respectively. Actuarial survival at 4 and 6 years of follow up was 94.24% and 88.52%, respectively. CONCLUSION: With improving life expectancy and early interventions, the number of < or = 50-year old rheumatic valvular disease patients is increasing. The present study showed a marked improvement for this subset of patients, although age still remains the main risk factor along with atrial fibrillation, repeat surgery, stroke and tricuspid valve disease.

Thrombocytopenia in malaria--correlation with type and severity of malaria.

AIM OF THE STUDY: Malaria is a major health problem in the tropics with increased morbidity and mortality. Thrombocytopenia is a common finding in malaria. Although a reliable diagnostic marker, prognostic implications could vary in the two types of malaria. This study was undertaken to correlate the presence and severity of thrombocytopenia with the type of malaria. DESIGN: A total of 1565 subjects were included in the study and identified positive for malaria parasites on peripheral smear examination with conventional microscopy. Platelet count was done on a fully automated, quantitative, hematology Coulter analyser. RESULTS: Normal platelet count was noted in 21.6% cases. The mean platelet count in vivax malaria (n=973) was 1,15,390/microl (SD 64,580) with a range of 8000-5,73,000/microl, as against falciparum malaria (n=590) where the mean platelet count was 100,900/microl (SD 75,437) with a range of 2000-497,000/microl (Pearson coefficient 8.825, p < 0.0001). Platelet count < 20,000/microl was noted in only 1.5% cases in vivax malaria as against 8.5% cases of falciparum malaria, and none of the subjects with vivax malaria had a platelet count less than 5000/microl. CONCLUSION: Although absence of thrombocytopenia is uncommon in malaria, its presence is not a distinguishing feature between the two types. Thrombocytopenia less than 20,000/microl can occur in P. vivax malaria although statistically more common with P. falciparum malaria. The above findings can have therapeutic implications in context of avoiding unnecessary platelet infusions with the relatively more benign course in P. vivax malaria.

Apolipoproteins: correlation with carotid intimamedia thickness and coronary artery disease.

BACKGROUND: Lower levels of plasma apolipoprotein AI (Apo A-I) and higher levels of ApoB, and the ratio of ApoB to ApoA-I are considered to be independent risk factors for coronary heart disease, and may assume importance in the definite subset of Indian patients with normal levels of traditional lipid risk factors and an early-onset of coronary artery disease (CAD). Carotid intima-media thickness is considered as a marker of atherosclerosis and in prediction of clinical coronary events and coronary artery disease. With increasing interest in the role of non-traditional lipid risk factors in CAD and few studies reported in Indian subjects, we undertook this study to correlate the apolipoprotein levels with CAD and their impact on arterial thickening utilizing the carotid intima-media thickness as a surrogate marker. METHODS AND RESULTS: Traditional lipid profile, apolipoprotein A-I and B and carotid artery Intima-media thickness (IMT) with a B-mode scan were measured in 309 patients recruited for the study (age group 36-64 years), which included 193 males and 116 females. Mean of maximal IMT exceeding 0.8 mm at the far wall of common carotid artery, excluding plaques, was selected as the higher values for comparison. One hundred and twenty two subjects had evidence for CAD as diagnosed by documented hospitalization with myocardial infarction or acute coronary syndrome, coronary angiography when feasible or noninvasive cardiac evaluation. Prevalence of subjects with increased IMT was higher among subjects with an apolipoprotein B: apolipoprotein A-I ratio exceeding one compared to those with a ratio less than one (30.6% vs 16.5%, p = 0.005). Prevalence of CAD was significantly higher among subjects with apolipoprotein B: apolipoprotein A-I ratio exceeding one as compared to those with a ratio less than one (53.7% vs 30.3%, p = 0.0002). Subjects with apolipoprotein B: apolipoprotein A-I ratio exceeding one and carotid IMT more than 0.8 mm had a 2.7-fold prevalence for CAD as against those with a ratio less than one and IMT less than 0.8 mm. On multivariate logistic regression analysis, apolipoprotein B: apolipoprotein A-I ratio exceeding one was significantly associated with increased IMT (odds ratio 2.27) and CAD (odds ratio 2.50) even after inclusion of sex, smoking, body mass index, total cholesterol, LDL-cholesterol, HDL-cholesterol, total cholesterol:HDL-cholesterol ratio and serum triglycerides into the model. CONCLUSIONS: We conclude that apolipoprotein B to A-I ratio shows a strong association with carotid intimal medial thickening and coronary artery disease in this Western Indian population and may play an important role is assessment of coronary risk in addition to traditional coronary risk factors.

Prognostic implications of white cell differential count and white cell morphology in Malaria.

BACKGROUND: Malaria is of immense importance amongst the tropical diseases in India. There is a need to develop newer diagnostic aids and research is necessary to identify new prognostic markers for prediction of the course and complications. AIMS: To evaluate the white cell differential count and morphology in Plasmodium vivax and Plasmodium falciparum malaria and study their prognostic utility. SUBJECTS AND METHODS: Two hundred and sixty-four adult patients in the age range of 20 to 65 years presenting to the hospital over a period of 4 months with clinical features of malaria and a positive peripheral smear examination were studied. RESULTS: No statistically significant difference was noted in the white blood cell (WBC) count and neutrophil count in P.vivax versus P. falciparum malaria. Band cells were more frequently noted in P. falciparum malaria than in P.vivax malaria (p < 0.0001). Toxic granulation of the neutrophils was noted in 9.5% of the patients and exclusively in P. falciparum malaria. Presence of toxic granulation of the polymorphs in subjects with P. falciparum malaria was significantly associated with anaemia (p=0.019), jaundice, cerebral involvement, adult respiratory distress syndromes, renal dysfunction and death (p < 0.0001 for all these parameters). CONCLUSION: Band cells were seen in P. vivax and P. falciparum malaria, although in higher numbers in P. falciparum malaria. Toxic granulation of the neutrophils was noted only in the presence of P. falciparum malaria in this study and correlated with severity.

Association of microalbuminuria with carotid intima-media thickness and coronary artery disease--a cross-sectional study in Western India.

OBJECTIVE: Microalbuminuria, a slightly elevated albumin excretion in the urine, is considered a novel atherosclerotic risk factor, both in diabetics subjects and in general population. Carotid intima-media thickness assessed non-invasively by a B-mode ultrasound has been recently shown to be an early marker for atherosclerosis. This study aims at determining the role of microalbuminuria as an atherosclerotic risk factor and its association with coronary artery disease. METHODS: We measured the urine microalbumin excretion and carotid intima-media thickness (IMT) in 301 subjects, with or without evidence for coronary artery disease (CAD). Microalbuminuria was diagnosed if urinary excretion of albumin exceeded 20 microgm/ml. RESULTS: Of the 301 subjects (age group--30-80 years) recruited for the study, 194 were males, 107 females. One hundred amd eighteen subjects had evidence of CAD as diagnosed by documented hospitalization with myocardial infarction or acute coronary syndrome, coronary angiography when feasible or non-invasive cardiac evaluation. One hundred and sixty three subjects had diabetes mellitus. Microalbuminuria was detected in 74 subjects (24.6%). Prevalence of subjects with increased IMT was higher among subjects with microalbuminuria compared to normoalbuminuria (42% vs 21.4%, p < 0.003). Prevalence of CAD was significantly higher among diabetic subjects with microalbuminuria compared to those with normoalbuminuria (Diabetic subjects: 58% vs 31.9%, p = 0.002, Non-diabetic subjects: 41.7% vs 37.7%, p = 0.718). Multivariate logistic regression analysis using carotid intimal medial thickness as a dependent variable revealed a statistically significant association with microalbuminuria in diabetic subjects (p = 0.027). CONCLUSION: We conclude that microalbuminuria shows a strong association with increased carotid intimal medial thickening and coronary artery disease in diabetic subjects in this Western Indian population.