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1.  Xanthogranulomatous Appendicitis with a Fulminant Course: Report of a Case 
Xanthogranulomatous inflammation is a well-described entity with involvement of various body organs. But the involvement of vermiform appendix in the disease process is quite rare with only few cases are reported in literature. This case report describes a 50-year-old man, who was diagnosed as a case of acute appendicitis with appendicular lump on the basis of clinical history, physical examination, and hematological and radiological investigations. Patient underwent surgical interventions twice. But, he succumbed to the disease. We are reporting this case in view of rarity of the disease and the fulminant course, which has not been described in any other reports.
PMCID: PMC4316294  PMID: 25653988
Appendicectomy; Xanthogranulomatous; Vermiform appendix
2.  Clinical experience of switching from biphasic human insulin to biphasic insulin aspart 30 in Indian patients with type 2 diabetes in the A1chieve study 
The aim of the following study is to evaluate the safety and effectiveness of switching from biphasic human insulin (BHI) to biphasic insulin aspart 30 (BIAsp 30) in Indian patients with type 2 diabetes as a sub-analysis of the 24-week, non-interventional A1chieve study.
Materials and Methods:
Indian patients switching from BHI to BIAsp 30 based on the physicians’ decisions were included. The primary outcome was the incidence of serious adverse drug reactions (SADRs), including major hypoglycemic events; secondary outcomes included changes in hypoglycemia in the 4 weeks preceding baseline and week 24 and changes from baseline to week 24 in glycated hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPPG), body weight and quality of life (QoL).
Overall, 1976 patients (mean ± standard deviation age, 55.1 ± 10.6 years and diabetes duration, 10.1 ± 5.3 years) on a mean pre-study BHI dose of 0.44 ± 0.18 U/kg were included. The mean BIAsp 30 dose was 0.43 ± 0.17 U/kg at baseline and 0.44 ± 0.17 U/kg at week 24. No SADRs were reported. The proportion of patients reporting overall hypoglycemic events reduced significantly from baseline to week 24 (15.0% vs. 2.9%, P < 0.0001). The mean HbA1c level improved significantly from 9.1 ± 1.4% at baseline to 7.5 ± 1.0% at week 24, along with improvements in FPG, post-breakfast PPPG and QoL (P < 0.001). The mean body weight decreased from 69.3 ± 10.8 kg at baseline to 69.1 ± 10.4 kg at week 24 (P = 0.003).
Switching from BHI to BIAsp 30 therapy was well-tolerated and was associated with improved glycemic control.
PMCID: PMC4287754  PMID: 25593837
Biphasic human insulin; biphasic insulin aspart 30; India; type 2 diabetes
4.  Biological Activity of N-Hydroxyethyl-4-aza-2,3-didehydropodophyllotoxin Derivatives upon Colorectal Adenocarcinoma Cells 
Etoposide is a chemotherapy drug derived from the natural lignin podophyllotoxin. Our novel generated Aza-podophyllotoxin compounds (AZP 8a & AZP 9a) are analogues of podophyllotoxin and were previously screened for anti-cancer activity through the NCI 60 cell line screening panel showing activity on various cell types including colon cancer. This study expands the toxicological screening by studying apoptosis and various hallmark events as part of the mechanism of action of these compounds on colon cancer cells. The COLO 205 cell line was selected and exposed to AZP to determine the IC50 doses at 24 hours treatment. Apoptosis hallmark events such as migration of phosphatidylserine (PS) to the cell membrane, DNA fragmentation, cell cycle effects, mitochondrial membrane permeabilization and caspase activation were included. Experiments were performed in triplicates for all tested compounds including AZP 8a, AZP 9a, camptothecin as positive control and vehicle as negative control. Our results present contrasting apoptotic activity between the experimental compounds. Compound 8a presented migration of PS (annexin V assay), DNA fragmentation and cell cycle arrest at S phase. Compound 9a presented PS migration with fragmented DNA, cell cycle arrest at S phase, mitochondrial membrane permeabilization and activation of caspase 3, 8 and 9. Compound 8a without the oxygen atoms in ring A appears to cause effects similarly to autophagy as induced by etoposide, a cancer drug analogue of our heterocyclic compounds. Compound 9a with the oxygen atoms in expanded ring A presented induction of cell death following activation of a classical apoptosis pathway. Our results suggest that minor structural differences among these AZP can account for the difference in biological response and cancer cell toxicity.
PMCID: PMC4279218  PMID: 25554737
Etoposide; Podophyllotoxin; Aza-Podophyllotoxin; Colon Cancer; COLO 205
5.  Exposure to endosulfan influences sperm competition in Drosophila melanogaster 
Scientific Reports  2014;4:7433.
Dwindling male fertility due to xenobiotics is of global concern. Accordingly, male reproductive toxicity assessment of xenobiotics through semen quality analysis in exposed males, and examining progeny production of their mates is critical. These assays, in part, are biased towards monogamy. Females soliciting multiple male partners (polyandry) is the norm in many species. Polyandry incites sperm competition and allows females to bias sperm use. However, consequences of xenobiotic exposure to the sperm in the light of sperm competition remain to be understood. Therefore, we exposed Drosophila melanogaster males to endosulfan, and evaluated their progeny production as well as the ability of their sperm to counter rival control sperm in the storage organs of females sequentially mated to control/exposed males. Endosulfan (2 μg/ml) had no significant effect on progeny production and on the expression of certain genes associated with reproduction. However, exposed males performed worse in sperm competition, both as 1st and 2nd male competitors. These findings indicate that simple non-competitive measures of reproductive ability may fail to demonstrate the harmful effects of low-level exposure to xenobiotics on reproduction and advocate consideration of sperm competition, as a parameter, in the reproductive toxicity assessment of xenobiotics to mimic situations prevailing in the nature.
PMCID: PMC4262826  PMID: 25503806
6.  Operational research capacity building using ‘The Union/MSF’ model: adapting as we go along 
BMC Research Notes  2014;7(1):819.
We have conducted 23 operational research (OR) courses since 2009, based on ‘The Union/ Médecins Sans Frontières (MSF)’ model, now popularly known as SORT-IT (Structured Operational Research and Training Initiative) model - wherein participants are mentored through the whole research process from protocol development (module 1) to data analysis (module 2) to publication (module 3) over a period of 9–12 months. We have faced a number of challenges including shortage of time, especially for data analysis and interpretation, and a heavy mentorship burden on limited numbers of experienced facilitators. To address these challenges, we have made several modifications to the structure of the OR course. In this article, we describe the revised structure and our experience (successes and challenges) of implementing it in Asia in 2013.
The key changes introduced included extending the duration of the course modules (by a day each in module 1 and 2 and by three days in module 3), increasing the numbers of facilitators and standardizing milestones related to data entry and analysis. We successfully implemented this revised structure in the second Asian OR Course held in Nepal in 2013. Eleven of twelve participants successfully completed all the milestones and submitted 13 scientific manuscripts (two participants completed two projects) to international peer-reviewed journals. Though, this posed two challenges – increased costs and increased time away for faculty and participants.
The revised structure of ‘The Union/MSF’ model of OR capacity building addressed previous issues of insufficient time and overburdened mentors and we intend to continue with this model for future courses.
PMCID: PMC4253003  PMID: 25409542
Operational research; Training; Asia; Capacity building; SORT IT
7.  Rice Varietal Differences in Bioactive Bran Components for Inhibition of Colorectal Cancer Cell Growth 
Food chemistry  2013;141(2):1545-1552.
Rice bran chemical profiles differ across rice varieties and have not yet been analyzed for differential chemopreventive bioactivity. A diverse panel of 7 rice bran varieties was analyzed for growth inhibition of human colorectal cancer (CRC) cells. Inhibition varied from 0–99%, depending on the variety of bran used. Across varieties, total lipid content ranged 5–16%, individual fatty acids had 1.4 to 1.9 fold differences, vitamin E isoforms (α-, γ-, δ- tocotrienols and tocopherols) showed 1.3 to 15.2 fold differences, and differences in γ- oryzanol and total phenolics ranged between 100–275 ng/mg and 57–146 ng GAE/mg, respectively. Spearman correlation analysis was used to identify bioactive compounds implicated in CRC cell growth inhibitory activity. Total phenolics and γ- tocotrienol were positively correlated with reduced CRC cell growth (p < 0.05). Stoichiometric variation in rice bran components and differential effects on CRC viability merit further evaluation elucidate their role in dietary CRC chemoprevention.
PMCID: PMC3720235  PMID: 23790950
Chemoprevention; Colorectal Cancer; Bioactive Components; γ-tocotrienol; Phenolics; Rice Bran; Vitamin E
8.  The Synthetic Tryptanthrin Analogue Suppresses STAT3 Signaling and Induces Caspase Dependent Apoptosis via ERK Up Regulation in Human Leukemia HL-60 Cells 
PLoS ONE  2014;9(11):e110411.
Tryptanthrin is a natural product which has been reported to have several medicinal properties. In this study, we tried to investigate the detailed molecular mechanism of its bromo analogue (TBr), a potent cytotoxic agent in the induction of cancer cell death. It was found that TBr primarily targets STAT3 and ERK signaling during the induction of apoptosis in several human leukemia cell lines. In HL-60 cells, TBr treatment caused early down regulation of p-STAT3 with concomitant up regulation of p-ERK which led to the activation of intrinsic and extrinsic pathways of apoptosis. The mechanism of TBr mediated inhibition of p-STAT3 was found to be due to the activation of ubiquitin dependent degradation of tyrosine 705 and serine 727 p-STAT3. As IL-6 is the main driver of the STAT3 pathway, the effect of TBr on cell death was subdued when treated in the combination with IL-6 in HL60 cells. Interestingly, PD98059 significantly reduced the apoptotic effects of TBr, thus showing the direct involvement of p-ERK in TBr mediated cell death. It was further shown that apoptotic protein Bax silencing in HL-60 cells resists TBr mediated ERK dependent apoptosis. In summary, for the first time we report the mechanism of TBr mediated cell death in human leukemia cell lines by targeting STAT3 and ERK pathways.
PMCID: PMC4226462  PMID: 25383546
9.  Alarming Levels of Drug-Resistant Tuberculosis in HIV-Infected Patients in Metropolitan Mumbai, India 
PLoS ONE  2014;9(10):e110461.
Drug-resistant tuberculosis (DR-TB) is a looming threat to tuberculosis control in India. However, no countrywide prevalence data are available. The burden of DR-TB in HIV-co-infected patients is likewise unknown. Undiagnosed and untreated DR-TB among HIV-infected patients is a major cause of mortality and morbidity. We aimed to assess the prevalence of DR-TB (defined as resistance to any anti-TB drug) in patients attending public antiretroviral treatment (ART) centers in greater metropolitan Mumbai, India.
A cross-sectional survey was conducted among adults and children ART-center attendees. Smear microscopy, culture and drug-susceptibility-testing (DST) against all first and second-line TB-drugs using phenotypic liquid culture (MGIT) were conducted on all presumptive tuberculosis patients. Analyses were performed to determine DR-TB prevalence and resistance patterns separately for new and previously treated, culture-positive TB-cases.
Between March 2013 and January 2014, ART-center attendees were screened during 14135 visits, of whom 1724 had presumptive TB. Of 1724 attendees, 72 (4%) were smear-positive and 202 (12%) had a positive culture for Mycobacterium tuberculosis. Overall DR-TB was diagnosed in 68 (34%, 95% CI: 27%–40%) TB-patients. The proportions of DR-TB were 25% (29/114) and 44% (39/88) among new and previously treated cases respectively. The patterns of DR-TB were: 21% mono-resistant, 12% poly-resistant, 38% multidrug-resistant (MDR-TB), 21% pre-extensively-drug-resistant (MDR-TB plus resistance to either a fluoroquinolone or second-line injectable), 6% extensively drug-resistant (XDR-TB) and 2% extremely drug-resistant TB (XDR-TB plus resistance to any group-IV/V drug). Only previous history of TB was significantly associated with the diagnosis of DR-TB in multivariate models.
The burden of DR-TB among HIV-infected patients attending public ART-centers in Mumbai was alarmingly high, likely representing ongoing transmission in the community and health facilities. These data highlight the need to promptly diagnose drug-resistance among all HIV-infected patients by systematically offering access to first and second-line DST to all patients with ‘presumptive TB’ rather than ‘presumptive DR-TB’ and tailor the treatment regimen based on the resistance patterns.
PMCID: PMC4204864  PMID: 25333696
11.  Cause of Death in “John Doe & Jane Doe”: A 5 year review 
Sometimes the opinion regarding the cause of death in “John Doe or Jane Doe” i.e. on unknown dead bodies is a test of ability of the forensic expert and on many occasions it yields little or no results. Here the identification of the body as such poses problems; rest aside the opinion regarding the cause/ manner of death. The present 5yr study was undertaken in the Department of Forensic Medicine & Toxicology, Government Medical College & Hospital, Chandigarh to find the patterns of cause of death in unknown dead bodies, as very little literature is available with regard to John Doe or Jane Doe cases as a group, in India. Unidentified bodies comprised 4 % of the total 3165 cases brought for post-mortem examination to the department. Maximum cases belonged to the age group 41 - 50 years, 30 %. Majority of the opinions regarding the cause of death were given as “no definite opinion” (31%), followed by “cranio-cerebral damage” (30 %) and coronary insufficiency/ Cardiac disease/ aortic aneurysm rupture, (8.9%). Following measures should be undertaken to increase the chances of getting these unknown bodies identified and thereby increasing the chances of arriving at a definite cause of death: drafting of additional legislation for the management of unidentified dead bodies along with streamlining of work on the part of police, use of active investigation and modern investigative techniques, fixing the accountability of the police. Internet based sites of the police like ZIPNET (Zonal Integrated Police Networking) in Northern India, should also be used.
PMCID: PMC4190741  PMID: 25302219
Identification; Postmortem examination; Unidentified bodies
12.  Candida tropicalis brain abscess in a neonate: An emerging nosocomial menace 
Fungi are a relatively uncommon cause of brain abscess in neonates and early infancy. They are usually associated with predisposing factors like prematurity, low birth weight, use of broad-spectrum antibiotics, and prolonged stay in the intensive care unit. Candida tropicalis (C. tropicalis) is rapidly emerging as a nosocomial threat in the neonatal intensive care settings. This case report describes a neonate with C. tropicalis brain abscess who was diagnosed early and managed aggressively with a favorable outcome. Inadvertent use of intravenous antibiotics can have serious complications such as invasive fungal infection. Correct microbiological diagnosis is the key to successful treatment of deep-seated pyogenic infection. Fungal etiology should always be studied in relevant clinical settings.
PMCID: PMC4251023  PMID: 25506171
Brain abscess; Candida tropicalis; fungal; neonate
13.  Distribution of Serotypes, Vaccine Coverage, and Antimicrobial Susceptibility Pattern of Streptococcus Pneumoniae in Children Living in SAARC Countries: A Systematic Review 
PLoS ONE  2014;9(9):e108617.
Each SAARC nation falls in the zone of high incidence of pneumococcal disease but there is a paucity of literature estimating the burden of pneumococcal disease in this region.
To identify the prevalent serotypes causing invasive pneumococcal disease in children of SAARC countries, to determine the coverage of these serotypes by the available vaccines, and to determine the antibiotic resistance pattern of Streptococcus pneumoniae.
We searched major electronic databases using a comprehensive search strategy, and additionally searched the bibliography of the included studies and retrieved articles till July 2014. Both community and hospital based observational studies which included children aged ≤12 years as/or part of the studied population in SAARC countries were included.
A total of 17 studies were included in the final analysis. The period of surveillance varied from 12–96 months (median, 24 months). The most common serotypes country-wise were as follows: serotype 1 in Nepal; serotype 14 in Bangladesh and India; serotype 19F in Sri Lanka and Pakistan. PCV-10 was found to be suitable for countries like India, Nepal, Bangladesh, and Sri Lanka, whereas PCV-13 may be more suitable for Pakistan. An increasing trend of non-susceptibility to antibiotics was noted for co-trimoxazole, erythromycin and chloramphenicol, whereas an increasing trend of susceptibility was noted for penicillin.
Due to paucity of recent data in majority of the SAARC countries, urgent large size prospective studies are needed to formulate recommendations for specific pneumococcal vaccine introduction and usage of antimicrobial agents in these regions.
PMCID: PMC4182530  PMID: 25268974
14.  HIV, multidrug-resistant TB and depressive symptoms: when three conditions collide 
Global Health Action  2014;7:10.3402/gha.v7.24912.
Management of multidrug-resistant TB (MDR-TB) patients co-infected with human immunodeficiency virus (HIV) is highly challenging. Such patients are subject to long and potentially toxic treatments and may develop a number of different psychiatric illnesses such as anxiety and depressive disorders. A mental health assessment before MDR-TB treatment initiation may assist in early diagnosis and better management of psychiatric illnesses in patients already having two stigmatising and debilitating diseases.
To address limited evidence on the baseline psychiatric conditions of HIV-infected MDR-TB patients, we aimed to document the levels of depressive symptoms at baseline, and any alteration following individualized clinical and psychological support during MDR-TB therapy, using the Patient Health Questionnaire-9 (PHQ-9) tool, among HIV-infected patients.
This was a retrospective review of the medical records of an adult (aged >15 years) HIV/MDR-TB cohort registered for care during the period of August 2012 through to March 2014.
A total of 45 HIV/MDR-TB patients underwent baseline assessment using the PHQ-9 tool, and seven (16%) were found to have depressive symptoms. Of these, four patients had moderate to severe depressive symptoms. Individualized psychological and clinical support was administered to these patients. Reassessments were carried out for all patients after 3 months of follow-up, except one, who died during the period. Among these 44 patients, three with baseline depressive symptoms still had depressive symptoms. However, improvements were observed in all but one after 3 months of follow-up.
Psychiatric illnesses, including depressive symptoms, during MDR-TB treatment demand attention. Routine administration of baseline mental health assessments by trained staff has the potential to assist in determining appropriate measures for the management of depressive symptoms during MDR-TB treatment, and help in improving overall treatment outcomes. We recommend regular monitoring of mental health status by trained counsellors or clinical staff, using simple, validated and cost-effective tools.
PMCID: PMC4161725  PMID: 25215909
MDR-TB; HIV; depressive symptoms; depression; PHQ-9; operational research; counselling; psychiatric illnesses; India
15.  How Many People Living with HIV Will Be Additionally Eligible for Antiretroviral Treatment in Karnataka State, India as per the World Health Organization 2013 Guidelines? 
PLoS ONE  2014;9(9):e107136.
The National AIDS control programme (NACP) in India is currently following the World Health Organization (WHO) 2010 antiretroviral therapy (ART) guidelines. In 2013, the WHO revised its recommendations for initiating ART among people living with HIV (PLHIV) by increasing the threshold for ART initiation to a CD4 count ≤500 cells/uL. For certain patient groups, ART is recommended irrespective of CD4 count (PLHIV with active tuberculosis, hepatitis B virus infection, pregnant and breast feeding women, children aged under five years and those living in a sero-discordant relationship). In this operational research, we assess the effect of applying this recommendation on the number of PLHIV additionally eligible for ART.
This was a cross-sectional analysis of routinely collected programme data from all PLHIV registered in Karnataka State (population 60 million), India in 2012.
Of 37,044 PLHIV, 27,074 (73%) were eligible for initiating ART as per WHO-2010 criteria. As per the WHO-2013 criteria (CD4 count ≤500 and all pregnant women and under-five children irrespective of CD4 count), an additional 5104 (14%) HIV-infected people would be eligible for initiating ART. There were no data to inform the additional patient load due to sero-discordance.
Adopting the WHO-2013 guidelines for India has important resource implications. However, given the significant patient and programmatic benefits of adopting the new guidelines, this has been considered favourably by the NACP in India and steps are being planned to integrate ART care into the general health system to cope with the increased numbers of patients.
PMCID: PMC4156435  PMID: 25192338
16.  Treatment of Ruptured Saccular Aneurysms of the Fenestrated Vertebrobasilar Junction with Balloon Remodeling Technique 
Interventional Neuroradiology  2013;19(3):289-298.
Fenestration of the intracranial arteries is a relatively common occurrence. This anatomic variation may predispose to aneurysm formation at certain sites. Treatment of such aneurysms is difficult as it may occlude one of the limbs of fenestration with resultant deficit. Thus, preservation of both the limbs with adequate exclusion of the aneurysm from the circulation should be the aim of any treatment. We describe a series of four cases of ruptured aneurysms arising from a fenestrated vertebrobasilar junction treated with endovascular balloon remodeling technique.
PMCID: PMC3806003  PMID: 24070077
aneurysm, vertebrobasilar junction, fenestration, coiling
17.  Comparative Evaluation of Porous Versus Nonporous Mucoadhesive Films as Buccal Delivery System of Glibenclamide 
AAPS PharmSciTech  2013;14(4):1321-1332.
The present research work focused on the comparative assessment of porous versus nonporous films in order to develop a suitable buccoadhesive device for the delivery of glibenclamide. Both films were prepared by solvent casting technique using the 32 full factorial design, developing nine formulations (F1–F9). The films were evaluated for ex vivo mucoadhesive force, ex vivo mucoadhesion time, in vitro drug release (using a modified flow-through drug release apparatus), and ex vivo drug permeation. The mucoadhesive force, mucoadhesion time, swelling index, and tensile strength were observed to be directly proportional to the content of HPMC K4M. The optimized porous film (F4) showed an in vitro drug release of 84.47 ± 0.98%, ex vivo mucoadhesive force of 0.24 ± 0.04 N, and ex vivo mucoadhesion time of 539.11 ± 3.05 min, while the nonporous film (NF4) with the same polymer composition showed a release of 62.66 ± 0.87%, mucoadhesive force of 0.20 ± 0.05 N, and mucoadhesive time of 510 ± 2.00 min. The porous film showed significant differences for drug release and mucoadhesion time (p < 0.05) versus the nonporous film. The mechanism of drug release was observed to follow non-Fickian diffusion (0.1 < n < 0.5) for both porous and nonporous films. Ex vivo permeation studies through chicken buccal mucosa indicated improved drug permeation in porous films versus nonporous films. The present investigation established porous films to be a cost-effective buccoadhesive delivery system of glibenclamide.
PMCID: PMC3840781  PMID: 23990119
buccoadhesive drug delivery; glibenclamide; in vitro release and ex vivo permeation; porous film
18.  α-[11C]-Methyl-l-tryptophan–PET in 191 patients with tuberous sclerosis complex 
Neurology  2013;81(7):674-680.
This was an observational study done on a large cohort of patients with tuberous sclerosis complex (TSC) to determine whether i) the presence of α-[11C]-methyl-l-tryptophan (AMT) hotspots is related to the duration of seizure intractability, ii) the presence of AMT hotspots is related to specific TSC gene mutations, and iii) there is concordance between areas with an AMT hotspot and seizure lateralization/localization on scalp EEG.
One hundred ninety-one patients (mean age: 6.7 years; median: 5 years; range: 3 months to 37 years) with TSC and intractable epilepsy were included. All patients underwent AMT-PET scan. AMT uptake in each tuber and normal-appearing cortex was measured and correlated with clinical, scalp EEG, and, if available, electrocorticographic data.
The longer the duration of seizure intractability, the greater the number of AMT hotspots (r = 0.2; p = 0.03). AMT hotspots were seen in both TSC1 and TSC2. There was excellent agreement in seizure focus lateralization between ictal scalp EEG and AMT-PET (Cohen κ 0.94) in 68 of 95 patients in whom both ictal video-EEG and AMT-PET showed lateralizing findings; in 28 of 68 patients (41%), AMT was more localizing. Furthermore, AMT-PET was localizing in 10 of 17 patients (58%) with nonlateralized ictal EEG.
AMT-PET, when used together with video-EEG, provides additional lateralization/localization data, regardless of TSC mutation. The duration of seizure intractability may predict the multiplicity of areas with AMT hotspots.
PMCID: PMC3775695  PMID: 23851963
19.  Beneficial Effect of Isoniazid Preventive Therapy and Antiretroviral Therapy on the Incidence of Tuberculosis in People Living with HIV in Ethiopia 
PLoS ONE  2014;9(8):e104557.
IPT with or without concomitant administration of ART is a proven intervention to prevent tuberculosis among PLHIV. However, there are few data on the routine implementation of this intervention and its effectiveness in settings with limited resources.
To measure the level of uptake and effectiveness of IPT in reducing tuberculosis incidence in a cohort of PLHIV enrolled into HIV care between 2007 and 2010 in five hospitals in southern Ethiopia.
A retrospective cohort analysis of electronic patient database was done. The independent effects of no intervention, “IPT-only,” “IPT-before-ART,” “IPT-and-ART started simultaneously,” “ART-only,” and “IPT-after-ART” on TB incidence were measured. Cox-proportional hazards regression was used to assess association of treatment categories with TB incidence.
Of 7,097 patients, 867 were excluded because they were transferred-in; a further 823 (12%) were excluded from the study because they were either identified to have TB through screening (292 patients) or were on TB treatment (531). Among the remaining 5,407 patients observed, IPT had been initiated for 39% of eligible patients. Children, male sex, advanced disease, and those in Pre-ART were less likely to be initiated on IPT. The overall TB incidence was 2.6 per 100 person-years. As compared to those with no intervention, use of “IPT-only” (aHR = 0.36, 95% CI = 0.19–0.66) and “ART-only” (aHR = 0.32, 95% CI = 0.24–0.43) were associated with significant reduction in TB incidence rate. Combining ART and IPT had a more profound effect. Starting IPT-before-ART (aHR = 0.18, 95% CI = 0.08–0.42) or simultaneously with ART (aHR = 0.20, 95% CI = 0.10–0.42) provided further reduction of TB at ∼80%.
IPT was found to be effective in reducing TB incidence, independently and with concomitant ART, under programme conditions in resource-limited settings. The level of IPT provision and effectiveness in reducing TB was encouraging in the study setting. Scaling up and strengthening IPT service in addition to ART can have beneficial effect in reducing TB burden among PLHIV in settings with high TB/HIV burden.
PMCID: PMC4126726  PMID: 25105417
20.  Recognizing Disguised Faces: Human and Machine Evaluation 
PLoS ONE  2014;9(7):e99212.
Face verification, though an easy task for humans, is a long-standing open research area. This is largely due to the challenging covariates, such as disguise and aging, which make it very hard to accurately verify the identity of a person. This paper investigates human and machine performance for recognizing/verifying disguised faces. Performance is also evaluated under familiarity and match/mismatch with the ethnicity of observers. The findings of this study are used to develop an automated algorithm to verify the faces presented under disguise variations. We use automatically localized feature descriptors which can identify disguised face patches and account for this information to achieve improved matching accuracy. The performance of the proposed algorithm is evaluated on the IIIT-Delhi Disguise database that contains images pertaining to 75 subjects with different kinds of disguise variations. The experiments suggest that the proposed algorithm can outperform a popular commercial system and evaluates them against humans in matching disguised face images.
PMCID: PMC4100743  PMID: 25029188
21.  Dysregulation of matricellular proteins is an early signature of pathology in laminin-deficient muscular dystrophy 
Skeletal Muscle  2014;4:14.
MDC1A is a congenital neuromuscular disorder with developmentally complex and progressive pathologies that results from a deficiency in the protein laminin α2. MDC1A is associated with a multitude of pathologies, including increased apoptosis, inflammation and fibrosis. In order to assess and treat a complicated disease such as MDC1A, we must understand the natural history of the disease so that we can identify early disease drivers and pinpoint critical time periods for implementing potential therapies.
We found that DyW mice show significantly impaired myogenesis and high levels of apoptosis as early as postnatal week 1. We also saw a surge of inflammatory response at the first week, marked by high levels of infiltrating macrophages, nuclear factor κB activation, osteopontin expression and overexpression of inflammatory cytokines. Fibrosis markers and related pathways were also observed to be elevated throughout early postnatal development in these mice, including periostin, collagen and fibronectin gene expression, as well as transforming growth factor β signaling. Interestingly, fibronectin was found to be the predominant fibrous protein of the extracellular matrix in early postnatal development. Lastly, we observed upregulation in various genes related to angiotensin signaling.
We sought out to examine the dysregulation of various pathways throughout early development (postnatal weeks 1-4) in the DyW mouse, the most commonly used mouse model of laminin-deficient muscular dystrophy. Muscle function tests (stand-ups and retractions) as well as gene (qRT-PCR) and protein levels (western blot, ELISA), histology (H&E, picrosirius red staining) and immunohistochemistry (fibronectin, TUNEL assay) were used to assess dysregulation of matricelluar protieins.
Our results implicate the involvement of multiple signaling pathways in driving the earliest stages of pathology in DyW mice. As opposed to classical dystrophies, such as Duchenne muscular dystrophy, the dysregulation of various matricellular proteins appears to be a distinct feature of the early progression of DyW pathology. On the basis of our results, we believe that therapies that may reduce apoptosis and stabilize the homeostasis of extracellular matrix proteins may have increased efficacy if started at a very early age.
PMCID: PMC4114446  PMID: 25075272
Apoptosis; CMD; ECM; Fibrosis; Inflammation; Matricellular; MDC1A
22.  Cost-effectiveness analysis of baclofen and chlordiazepoxide in uncomplicated alcohol-withdrawal syndrome 
Indian Journal of Pharmacology  2014;46(4):372-377.
Benzodiazepines (BZDs) are the first-line drugs in alcohol-withdrawal syndrome (AWS). Baclofen, a gamma-aminobutyric acidB (GABAB) agonist, controls withdrawal symptoms without causing significant adverse effects. The objective of this study was to compare the cost-effectiveness of baclofen and chlordiazepoxide in the management of uncomplicated AWS.
Materials and Methods:
This was a randomized, open label, standard controlled, parallel group study of cost-effectiveness analysis (CEA) of baclofen and chlordiazepoxide in 60 participants with uncomplicated AWS. Clinical efficacy was measured by the Clinical Institute Withdrawal Assessment for alcohol (CIWA-Ar) scores. Lorazepam was used as supplement medication if withdrawal symptoms could not be controlled effectively by the study drugs alone. Both direct and indirect medical costs were considered and the CEA was analyzed in both patient's perspective and third-party perspective.
The average cost-effectiveness ratio (ACER) in patient's perspective of baclofen and chlordiazepoxide was Rs. 5,308.61 and Rs. 2,951.95 per symptom-free day, respectively. The ACER in third-party perspective of baclofen and chlordiazepoxide was Rs. 895.01 and Rs. 476.29 per symptom-free day, respectively. Participants on chlordiazepoxide had more number of symptom-free days when compared with the baclofen group on analysis by Mann-Whitney test (U = 253.50, P = 0.03).
Both study drugs provided relief of withdrawal symptoms. Chlordiazepoxide was more cost-effective than baclofen. Baclofen was relatively less effective and more expensive than chlordiazepoxide.
PMCID: PMC4118528  PMID: 25097273
Alcohol-withdrawal syndrome; baclofen; chlordiazepoxide; clinical institute withdrawal assessment for alcohol; cost-effectiveness analysis
23.  Acute transplant renal artery thrombosis due to distal renal artery stenosis: A case report and review of the literature 
Journal of Nephropathology  2014;3(3):105-108.
Background: Acute renal artery thrombosis is a devastating complication of renal transplantation that can result in graft loss if not detected early. Surgical and technical errors are the major cause of renal artery thrombosis. In this article, for the first time, we are reporting a case of acute renal artery thrombosis that developed early post-transplantation due to distal renal artery stenosis.
Case Presentation: A 71-year-old woman presented with nausea, vomiting and decreased urine output 7 days after a deceased donor kidney transplant. Doppler ultrasound showed absent renal and venous flow in the transplanted kidney. Transplant renal artery angiogram showed renal artery thrombosis. Catheterization and thrombectomy were done in the occluded renal artery. After thrombectomy, renal angiogram showed distal renal artery stenosis which was dilated by stenting. Post-stenting angiogram showed good blood flow in the entire renal arterial system. However, the patient,s kidney function did not improve within next 24 hours and the patient eventually lost the kidney. Kidney biopsy showed widespread kidney infarction with no evidence of rejection.
Conclusions: Our case shows that renal artery thrombosis can develop due to distal renal artery stenosis and if not detected early could result in graft loss.
PMCID: PMC4119325  PMID: 25093158
Renal artery thrombosis; Doppler ultrasound; Graft loss; Thrombectomy
24.  Video-Assisted Anal Fistula Treatment 
Background and Objectives:
Fistula in ano is a common disease seen in the surgical outpatient department. Many procedures are advocated for the treatment of fistula in ano. However, none of the procedures is considered the gold standard. The latest addition to the list of treatment options is video-assisted anal fistula treatment (VAAFT). It is a minimally invasive, sphincter-saving procedure with low morbidity. The aim of our study was to compare the results with a premier study done previously.
The procedure involves diagnostic fistuloscopy and visualization of the internal opening, followed by fulguration of the fistulous tract and closure of the internal opening with a stapling device or suture ligation. The video equipment (Karl Storz, Tuttlingen, Germany) was connected to an illuminating source.
The study was conducted from July 2010 to March 2014. Eighty-two patients with fistula in ano were operated on with VAAFT and were followed up according to the study protocol. The recurrence rate was 15.85%, with recurrences developing in 13 cases. Postoperative pain and discomfort were minimal.
VAAFT is a minimally invasive procedure performed under direct visualization. It enables visualization of the internal opening and secondary branches or abscess cavities. It is a sphincter-saving procedure and offers many advantages to patients. Our initial results with the procedure are quite encouraging.
PMCID: PMC4236078  PMID: 25419106
Fistula in ano; Video-assisted anal fistula treatment (VAAFT); Fistuloscopy; Visual analog score (VAS); Sphincter-saving surgery
25.  Molecular diversity and functional variability of environmental isolates of Bacillus species 
SpringerPlus  2014;3:312.
In the present study, out of 264 phosphate (P) solubilizing Bacillus strains isolated from apple rhizosphere, only twelve isolates were found to be efficient (showed most of the plant growth promoting activity) which were further characterized at molecular level using 16S rDNA partial gene sequencing. Out of 12 isolates, MZPSB 207 was found to be most efficient P-solubilizing (864.71 μg/ml) isolate which also showed indole acetic acid production (51.83 μg/ml), siderophore production, ammonia production, antagonistic property (against Rhizoctonia solani and Fusarium oxysporum), hydrolytic enzymes productions (protease, chitinase and cellulase), 1-aminocyclopropane-1-carboxylate (ACC) deaminase production (7.7 μm αKB mg-1 h-1). The in-vitro seed germination assay showed that Bacillus (twelve isolates) inoculated seeds showed more seed germination and seedling vigor rate as compared to uninoculated control treatment.
For the genetic diversity studies of efficient 12 strains, the polyphasic approach using 16S-rDNA, Repetitive element sequence (rep) based PCR (ERIC-PCR and BOX-PCR) were used. Based on 16S rDNA partial gene sequencing the isolated Bacillus genus was divide into four groups. First group (five isolates), second group (two isolates), third group (three isolates) and fourth group (two isolates) which showed close genetic relatedness to the B. subtilis, B. pumulis, B. megaterium and B. amyloliquefaciens, respectively. The rep PCR fingerprinting showed variability between and within the species. The large variability was showed by ERIC-PCR whereas some variability was showed by BOX-PCR. The results clearly showed that 16S rRNA gene sequencing is unable to discriminate the isolates at strain level. But rep-PCR fingerprinting is excellent tool to characterize and discriminate the strains at the genomic level.
PMCID: PMC4169128  PMID: 25279279
ACC deaminase; Bacillus genetic diversity; Plant growth promoting activity; Rep PCR fingerprinting; 16S rDNA; Seed germination

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