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author:("Kumar, away")
1.  Tuberculosis Management Practices of Private Practitioners in Pune Municipal Corporation, India 
PLoS ONE  2014;9(6):e97993.
Background
Private Practitioners (PP) are the primary source of health care for patients in India. Limited representative information is available on TB management practices of Indian PP or on the efficacy of India’s Revised National Tuberculosis Control Programme (RNTCP) to improve the quality of TB management through training of PP.
Methods
We conducted a cross-sectional survey of a systematic random sample of PP in one urban area in Western India (Pune, Maharashtra). We presented sample clinical vignettes and determined the proportions of PPs who reported practices consistent with International Standards of TB Care (ISTC). We examined the association between RNTCP training and adherence to ISTC by calculating odds ratios and 95% confidence intervals.
Results
Of 3,391 PP practicing allopathic medicine, 249 were interviewed. Of these, 55% had been exposed to RNTCP. For new pulmonary TB patients, 63% (158/249) of provider responses were consistent with ISTC diagnostic practices, and 34% (84/249) of responses were consistent with ISTC treatment practices. However, 48% (120/249) PP also reported use of serological tests for TB diagnosis. In the new TB case vignette, 38% (94/249) PP reported use of at least one second line anti-TB drug in the treatment regimen. RNTCP training was not associated with diagnostic or treatment practices.
Conclusion
In Pune, India, despite a decade of training activities by the RNTCP, high proportions of providers resorted to TB serology for diagnosis and second-line anti-TB drug use in new TB patients. Efforts to achieve universal access to quality TB management must account for the low quality of care by PP and the lack of demonstrated effect of current training efforts.
doi:10.1371/journal.pone.0097993
PMCID: PMC4045673  PMID: 24897374
2.  Whole-Genome Sequence of a Classical Swine Fever Virus Isolated from the Uttarakhand State of India 
Genome Announcements  2014;2(3):e00371-14.
We report the first complete genome sequence of a classical swine fever (CSF) virus of subgenotype 2.2. The virus (CSFV/IND/UK/LAL-290) was isolated from the Uttarakhand state of India from a backyard pig suspected of having CSF. This genome sequence will give useful insight for future molecular epidemiological studies and the development of an effective vaccine in India.
doi:10.1128/genomeA.00371-14
PMCID: PMC4014687  PMID: 24812219
3.  Burden of Invasive Pneumococcal Disease in Children Aged 1 Month to 12 Years Living in South Asia: A Systematic Review 
PLoS ONE  2014;9(5):e96282.
Objective
The primary objective was to estimate the burden of invasive pneumococcal disease (IPD) in children aged 1 month to 12 years in South Asian countries.
Methods
We searched three electronic databases (PubMed, Embase and the Cochrane Library) using a comprehensive search strategy, we manually searched published databases (Index Medicus and Current Contents) and we also searched the bibliographies of the included studies and retrieved reviews. The searches were current through June 2013. Eligible studies (community-based and hospital-based) were pooled and a separate analysis for India was also completed. A meta-regression analysis and heterogeneity analysis were performed. The protocol was registered with PROSPERO registration number CRD42013004483.
Results
A total of 22 studies surveying 36,714 children were included in the systematic review. Hospital-based prospective studies from South Asia showed that 3.57% of children had IPD, and 15% of all bacterial pneumonia cases were due to Streptococcus pneumoniae. Indian studies showed that the incidence of IPD was 10.58% in children admitted to hospitals with suspected invasive bacterial diseases, and 24% of all bacterial pneumonia cases were due to S. pneumonia. Population-based studies from South Asian countries showed that 12.8% of confirmed invasive bacterial diseases were caused by S. pneumonia whereas retrospective hospital-based studies showed that 28% of invasive bacterial diseases were due to S. pneumoniae. Meta-regression showed that there was a significant influence of the antigen testing method for diagnosing IPD on IPD prevalence.
Conclusion
S. pneumoniae is responsible for a substantial bacterial disease burden in children of South Asian countries including India despite the presence of high heterogeneity in this meta-analysis. Treatment guidelines must be formulated, and preventive measures like vaccines must also be considered.
doi:10.1371/journal.pone.0096282
PMCID: PMC4010478  PMID: 24798424
4.  Current status of management, control, complications and psychosocial aspects of patients with diabetes in India: Results from the DiabCare India 2011 Study 
Objectives:
DiabCare India 2011 was a cross-sectional study in patients with diabetes mellitus, undertaken to investigate the relationship between diabetes control, management and complications in a subset of urban Indian diabetes patients treated at referral diabetes care centres in India.
Materials and Methods:
This was a cross-sectional, multicentre (330 centres) survey in 6168 diabetes patients treated at general hospitals, diabetes clinics and referral clinics across India. Patient data, including medical and clinical examination reports during the past year were collected during their routine visit. The patients’ and physicians’ perceptions about diabetes management were recorded using a questionnaire.
Results:
A total of 6168 subjects with diabetes (95.8% type 2), mean age 51.9 ± 12.4 years and mean duration of diabetes, 6.9 ± 6.4 years were included. Mean HbA1c was 8.9 ± 2.1% and the mean fasting (FPG), post prandial (PPG) and random (RBG) plasma glucose levels were 148 ± 50 mg/dl 205 ± 66 mg/dl and 193 ± 68mg/dl respectively. Neuropathy was the most common complication (41.4%); other complications were: Foot (32.7%), eye (19.7%), cardiovascular (6.8%) and nephropathy (6.2%). The number of diabetic complications increased with mean duration of diabetes. Most (93.2%) of the patients were on oral anti-diabetic drugs (OADs) and 35.2% were on insulin (±OADs). More than 15% physicians felt that the greatest barrier to insulin therapy from patient's perspective were pain and fear of using injectable modality; 5.2% felt that the greatest barrier to insulin therapy from physician's perspective was the treatment cost; 4.8% felt that the major barriers to achieve optimum diabetic care in practice was loss to follow-up followed by lack of counselling (3.9%) and treatment compliance (3.6%).
Conclusion:
DiabCare India 2011 has shown that type 2 diabetes sets in early in Indians and glycaemic control is often sub-optimal in these patients. These results indicate a need for more structured intervention at an early stage of the disease and need for increased awareness on benefits of good glycaemic control. It cannot be overemphasized that the status of diabetes care in India needs to be further improved. (ClinTrials.gov identifier: NCT01351922)
doi:10.4103/2230-8210.129715
PMCID: PMC4056138  PMID: 24944934
Control and complications; current status of diabetes care; DiabCare India
5.  Intensive-Phase Treatment Outcomes among Hospitalized Multidrug-Resistant Tuberculosis Patients: Results from a Nationwide Cohort in Nigeria 
PLoS ONE  2014;9(4):e94393.
Background
Nigeria is faced with a high burden of Human Immunodeficiency Virus (HIV) infection and multidrug-resistant tuberculosis (MDR-TB). Treatment outcomes among MDR-TB patients registered across the globe have been poor, partly due to high loss-to-follow-up. To address this challenge, MDR-TB patients in Nigeria are hospitalized during the intensive-phase(IP) of treatment (first 6–8 months) and are provided with a package of care including standardized MDR-TB treatment regimen, antiretroviral therapy (ART) and cotrimoxazole prophylaxis (CPT) for HIV-infected patients, nutritional and psychosocial support. In this study, we report the end-IP treatment outcomes among them.
Methods
In this retrospective cohort study, we reviewed the patient records of all bacteriologically-confirmed MDR-TB patients admitted for treatment between July 2010 and October 2012.
Results
Of 162 patients, 105(65%) were male, median age was 34 years and 28(17%) were HIV-infected; all 28 received ART and CPT. Overall, 138(85%) were alive and culture negative at the end of IP, 24(15%) died and there was no loss-to-follow-up. Mortality was related to low CD4-counts at baseline among HIV-positive patients. The median increase in body mass index among those documented to be underweight was 2.6 kg/m2 (p<0.01) and CD4-counts improved by a median of 52 cells/microL among the HIV-infected patients (p<0.01).
Conclusions
End-IP treatment outcomes were exceptional compared to previously published data from international cohorts, thus confirming the usefulness of a hospitalized model of care. However, less than five percent of all estimated 3600 MDR-TB patients in Nigeria were initiated on treatment during the study period. Given the expected scale-up of MDR-TB care, the hospitalized model is challenging to sustain and the national TB programme is contemplating to move to ambulatory care. Hence, we recommend using both ambulatory and hospitalized approaches, with the latter being reserved for selected high-risk groups.
doi:10.1371/journal.pone.0094393
PMCID: PMC3983205  PMID: 24722139
6.  High attrition among HIV-infected patients with advanced disease treated in an intermediary referral center in Maputo, Mozambique 
Global Health Action  2014;7:10.3402/gha.v7.23758.
Background
In Mozambique, antiretroviral therapy (ART) scale-up has been successfully implemented. However, attrition in care remains a major programmatic challenge. In 2009, an intermediary-level HIV referral center was created in Maputo to ensure access to specialized care for HIV-infected patients with complications (advanced clinical-immunological stage, Kaposi sarcoma, or suspected ART failure).
Objective
To determine the attrition from care and to identify risk factors that lead to high attrition among patients referred to an intermediary-level HIV referral center.
Design
This was a retrospective cohort study from 2009 to 2011.
Results
A total of 1,657 patients were enrolled, 847 (51%) were men, the mean age was 36 years (standard deviation: 11), the mean CD4 count was 27 cells/µl (interquartile range: 11–44), and one-third were severely malnourished. The main reasons for referral were advanced clinical stages (WHO stages 3 and 4, and CD4 count <50 cells/µl) in 70% of the cases, and 19% had Kaposi sarcoma. The overall attrition rate was 28.7 per 100 person-years (PYs) – the mortality rate was 5.0 (95% confidence interval [CI]: 4.2–5.9) per 100 PYs, and the loss-to-follow-up rate was 23.7 (95% CI: 21.9–25.6) per 100 PYs. There were 793 attritions – 137 deaths and 656 lost to follow-up (LTFU); 77% of all attrition happened within the first year. The factors independently associated with attrition were male sex (adjusted hazard ratio [aHR]: 1.15, 95% CI: 1.0–1.3), low body mass index (aHR: 1.51, 95% CI: 1.2–1.8), WHO clinical stage 3 or 4 (aHR: 1.30, 95% CI: 1.0–1.6; and aHR: 1.91, 95% CI: 1.4–2.5), later year of enrollment (aHR 1.61, 95% CI 1.3–1.9), and ‘being already on ART’ at enrollment (aHR 13.71, 95% CI 11.4–16.4).
Conclusions
Attrition rates among HIV-infected patients enrolled in an intermediary referral center were high, mainly related to advanced stage of clinical disease. Measures are required to address this, including innovative strategies for HIV-testing uptake, earlier ART initiation and nutritional supplementation, and special attention to men and those who are already on ART at enrolment. Qualitative research is required to understand the reasons for being LTFU and design informed evidence-based interventions.
doi:10.3402/gha.v7.23758
PMCID: PMC3982117  PMID: 24717189
operational research; retention in care; resource-limited settings; attrition; HIV referral center
7.  Indirect targeting of IGF receptor signaling in vivo by substrate-selective inhibition of PAPP-A proteolytic activity 
Oncotarget  2014;5(4):1014-1025.
The insulin-like growth factor (IGF) signaling pathway is involved in certain human cancers, and the feasibility of directly targeting the IGF receptor has been actively investigated. However, recent evidence from clinical trials suggests that this approach can be problematic. We have developed an alternative strategy to indirectly inhibit the IGF signaling by targeting the metalloproteinase, pregnancy-associated plasma protein-A (PAPP-A). PAPP-A associated with the cell surface cleaves IGF binding protein-4 (IGFBP-4), when IGF is bound to IGFBP-4, and thereby increases IGF bioavailability for receptor activation in an autocrine/paracrine manner. We hypothesized that inhibition of PAPP-A would suppress excessive local IGF signaling in tissues where this is caused by increased PAPP-A proteolytic activity. To test this hypothesis, we developed an inhibitory monoclonal antibody, mAb 1/41, which targets a unique substrate-binding exosite of PAPP-A. This inhibitor selectively and specifically inhibits proteolytic cleavage of IGFBP-4 with an inhibitory constant (Ki) of 135 pM. In addition, it inhibited intracellular signaling of the IGF receptor (AKT phosphorylation) in monolayers of A549 cells, an IGF-responsive lung cancer-derived cell line found to express high levels of PAPP-A. We further showed that mAb 1/41 is effective towards PAPP-A bound to cell surfaces, and that it is capable of inhibiting PAPP-A activity in vivo. Using a murine xenograft model of A549 cells, we demonstrated that mAb 1/41 administered intraperitoneally significantly inhibited tumor growth. Analysis of xenograft tumor tissue recovered from treated mice showed penetration of mAb 1/41, reduced IGFBP-4 proteolysis, and reduced AKT phosphorylation. Our study provides proof of concept that IGF signaling can be selectively reduced by targeting a regulatory proteinase that functions extracellularly, upstream of the IGF receptor. PAPP-A targeting thus represents an alternative therapeutic strategy for inhibiting IGF receptor signaling.
PMCID: PMC4011579  PMID: 24572990
insulin-like growth factor receptor; pregnancy-associated plasma protein-A; proteolytic inhibition; therapeutic antibody; xenograft mouse model
8.  Microstructural Abnormalities in Language and Limbic Pathways in Orphanage-reared Children: A Diffusion Tensor Imaging Study 
Journal of child neurology  2013;29(3):318-325.
This study utilized diffusion tensor imaging fiber tractography to examine the miscrostructural integrity of limbic and paralimbic white matter tracts in thirty-six children (Mean age=124 months) with histories of early deprivation, raised from birth in orphanages and subsequently adopted into the United States, compared to 16 age-matched typically developing children. We found increased mean diffusivity bilaterally in the arcuate fasciculus, and increased mean diffusivity and reduced fractional anisotropy bilaterally in the uncinate fasciculus and cingulum in children with early deprivation. Microstructural integrity of the left arcuate fasciculus and right cingulum was related to language and behavioral functioning, respectively. White matter abnormalities were also associated with length of deprivation and time in the adoptive home. Our findings suggest that white matter pathways, connecting limbic and paralimbic brain regions is abnormal in children with histories of early deprivation; with some pathways appearing more susceptible to early deprivation than others.
doi:10.1177/0883073812474098
PMCID: PMC3659189  PMID: 23358628
Orphans; Diffusion tensor imaging; Fiber tractography; Neuroimaging; White-matter
9.  Synthesis of embedded Au nanostructures by ion irradiation: influence of ion induced viscous flow and sputtering 
Summary
The ion-irradiation induced synthesis of embedded Au nanoparticles (NPs) into glass from islands of Au on a glass substrate is studied in the context of recoiling atoms, sputtering and viscous flow. Cross sectional transmission electron microscopy studies revealed the formation of Au NPs embedded in the glass substrates by the 50 keV Si− ion irradiation of irregularly shaped Au nanostructures on the glass surfaces at a fluence of 3 × 1016 ions/cm2. The depth profiles of Au in the samples were obtained from high-resolution Rutherford backscattering spectrometry studies. The results from TRIDYN simulation reveal the role of various ion-induced processes during the synthesis of the embedded Au NPs, viz. sputtering and recoiling atoms. Simulation and experimental results suggest that the viscous flow is one of the major factors that are responsible for the embedding of Au nanoparticles into the glass substrate.
doi:10.3762/bjnano.5.10
PMCID: PMC3944145  PMID: 24605276
embedded nanoparticles; ion beam irradiation; recoil implantation
10.  Ruptured venous aneurysm of cervicomedullary junction 
Background:
Ruptured venous aneurysm is often seen with arterio-venous malformation (AVM) or developmental venous anomaly (DVA). However, isolated venous aneurysm is unusual.
Case Description:
We present a case of ruptured venous aneurysm that presented with subarachnoid hemorrhage (SAH) and intraventricular hemorrhage (IVH). Digital substraction angiography (DSA) revealed a saccular contrast filling pouch in the left lateral aspect of cervicomedullary junction (CMJ). Endovascular intervention was not a viable option. During surgery, a saccular pliable structure approx. 1.5 × 1 cm was found in the subarachnoid space that was clipped and excised. There were no arterial feeders, no evidence of surrounding AVM, and no dilated perimedullary vein.
Conclusion:
This is perhaps the first reported case of ruptured venous aneurysm (without associated AVM) of CMJ, which was successfully managed surgically. The possible etiologies remain an unnoticed head trauma or a congenital vessel wall abnormality. Surgically clipping and excision remains the treatment of choice for such lesion.
doi:10.4103/2152-7806.124977
PMCID: PMC3927081  PMID: 24575317
Arterio-venous malformation; cervico medullary junction; venous aneurysm
11.  15O PET Measurement of Blood Flow and Oxygen Consumption in Cold-Activated Human Brown Fat 
Although it has been believed that brown adipose tissue (BAT) depots disappear shortly after the perinatal period in humans, PET imaging using the glucose analog 18F-FDG has shown unequivocally the existence of functional BAT in adult humans, suggesting that many humans retain some functional BAT past infancy. The objective of this study was to determine to what extent BAT thermogenesis is activated in adults during cold stress and to establish the relationship between BAT oxidative metabolism and 18F-FDG tracer uptake.
Methods
Twenty-five healthy adults (15 women and 10 men; mean age ± SD, 30 ± 7 y) underwent triple-oxygen scans (H215O, C15O, and 15O2) as well as measurements of daily energy expenditure (DEE; kcal/d) both at rest and after exposure to mild cold (15.5°C [60°F]) using indirect calorimetry. The subjects were divided into 2 groups (high BAT and low BAT) based on the presence or absence of 18F-FDG tracer uptake (standardized uptake value [SUV] > 2) in cervical–supraclavicular BAT. Blood flow and oxygen extraction fraction (OEF) were calculated from dynamic PET scans at the location of BAT, muscle, and white adipose tissue. Regional blood oxygen saturation was determined by near-infrared spectroscopy. The total energy expenditure during rest and mild cold stress was measured by indirect calorimetry. Tissue-level metabolic rate of oxygen (MRO2) in BAT was determined and used to calculate the contribution of activated BAT to DEE.
Results
The mass of activated BAT was 59.1 ± 17.5 g (range, 32–85 g) in the high-BAT group (8 women and 1 man; mean age, 29.6 ± 5.5 y) and 2.2 ± 3.6 g (range, 0–9.3 g) in the low-BAT group (9 men and 7 women; mean age, 31.4 ± 10 y). Corresponding maximal SUVs were significantly higher in the high-BAT group than in the low-BAT group (10.7 ± 3.9 vs. 2.1 ± 0.7, P = 0.01). Blood flow values were significantly higher in the high-BAT group than in the low-BAT group for BAT (12.9 ± 4.1 vs. 5.9 ± 2.2 mL/100 g/min, P = 0.03) and white adipose tissue (7.2 ± 3.4 vs. 5.7 ± 2.3 mL/100 g/min, P = 0.03) but were similar for muscle (4.4 ± 1.9 vs. 3.9 ± 1.7 mL/100 g/min). Moreover, OEF in BAT was similar in the 2 groups (0.51 ± 0.17 in high-BAT group vs. 0.47 ± 0.18 in low-BAT group, P = 0.39). During mild cold stress, calculated MRO2 values in BAT increased from 0.97 ± 0.53 to 1.42 ± 0.68 mL/100 g/min (P = 0.04) in the high-BAT group and were significantly higher than those determined in the low-BAT group (0.40 ± 0.28 vs. 0.51 ± 0.23, P = 0.67). The increase in DEE associated with BAT oxidative metabolism was highly variable in the high-BAT group, with an average of 3.2 ± 2.4 kcal/d (range, 1.9–4.6 kcal/d) at rest, and increased to 6.3 ± 3.5 kcal/d (range, 4.0–9.9 kcal/d) during exposure to mild cold. Although BAT accounted for only a small fraction of the cold-induced increase in DEE, such increases were not observed in subjects lacking BAT.
Conclusion
Mild cold-induced thermogenesis in BAT accounts for 15–25 kcal/d in subjects with relatively large BAT depots. Thus, although the presence of active BAT is correlated with cold-induced energy expenditure, direct measurement of MRO2 indicates that BAT is a minor source of thermogenesis in humans.
doi:10.2967/jnumed.112.111336
PMCID: PMC3883579  PMID: 23362317
brown fat thermogenesis; BAT oxidative metabolism; 15O PET imaging
12.  Anterior Roux-en-Y Pancreatico-jejunostomy for Pancreatic Trauma 
Isolated pancreatic laceration is a rare injury. The typical mechanism by which it occurs is overstretching of the pancreas across the vertebral column during blunt abdominal trauma. The management depends on the location and extent of the injury. Disruption of the pancreatic duct usually requires operative treatment. Operative options for pancreatic laceration at the neck include distal pancreatectomy or suturing of the cephalic remnant and Roux-en-Y pancreatico-jejunostomy on the left remnant. We are reporting two cases of isolated pancreatic injury with disruption of the pancreatic duct but preserved posterior surface of the pancreas. These patients were managed by performing anterior Roux-en-Y pancreatico-jejunostomy at the lacerated area. Both the patients had successful outcome with removal of drains by 6th postoperative day. Anterior Roux-en-Y pancreatico-jejunostomy in this particular scenario is easy, less time consuming, and has the advantage of preserving the pancreas and the spleen.
doi:10.4103/2006-8808.135147
PMCID: PMC4090977
Pancreatic trauma; Roux-en-Y pancreatico-jejunostomy; anterior pancreatico-jejunostomy
13.  Sharp Curvature of Frontal Lobe White Matter Pathways in Children with Autism Spectrum Disorder: Tract-Based Morphometry Analysis 
AJNR. American journal of neuroradiology  2011;32(9):10.3174/ajnr.A2557.
Background and Purpose
As we had previously observed geometrical changes of frontal lobe association pathways in children with autism spectrum disorder (ASD), in the present study we analyzed the curvature of these white matter pathways using an objective tract based morphometry (TBM) analysis.
Materials and Methods
Diffusion tensor imaging (DTI) was performed in 32 children with ASD and 14 children with typical development. Curvature, fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) of bilateral arcuate fasciculus (AF), uncinate fasciculus (UF), and genu of corpus callosum (gCC) were investigated using the TBM group analysis assessed by False Discovery Rate p-value (PFDR) for multiple comparisons.
Results
Significantly higher curvatures were found in children with ASD especially at the parieto-temporal junction for AF (left: PFDR < 0.001; right: PFDR < 0.01), at the fronto-temporal junction for UF (left: PFDR < 0.005; right: PFDR < 0.03), and at the midline of the gCC (PFDR < 0.0001). RD was significantly higher in children with ASD at the same bending regions of AF (left: PFDR < 0.03, right: PFDR < 0.02), UF (left: PFDR < 0.04), and gCC (PFDR < 0.01).
Conclusion
Higher curvature and curvature dependent RD changes in children with ASD may be the result of higher density of thinner axons in these frontal lobe tracts.
doi:10.3174/ajnr.A2557
PMCID: PMC3868442  PMID: 21757519
Autisim spectrum disorders; Diffusion tensor MRI; Frontal lobe white matter pathways; Curvature; Diffusivity
14.  Intensified Tuberculosis Case Finding among Malnourished Children in Nutritional Rehabilitation Centres of Karnataka, India: Missed Opportunities 
PLoS ONE  2013;8(12):e84255.
Background
Severe acute malnutrition (SAM) is the most serious form of malnutrition affecting children under-five and is associated with many infectious diseases including Tuberculosis (TB). In India, nutritional rehabilitation centres (NRCs) have been recently established for the management of SAM including TB. The National TB Programme (NTP) in India has introduced a revised algorithm for diagnosing paediatric TB. We aimed to examine whether NRCs adhered to these guidelines in diagnosing TB among SAM children.
Methods
A cross-sectional study involving review of records of all SAM children identified by health workers during 2012 in six tehsils (sub-districts) with NRCs (population: 1.8 million) of Karnataka, India.
Results
Of 1927 identified SAM children, 1632 (85%) reached NRCs. Of them, 1173 (72%) were evaluated for TB and 19(2%) were diagnosed as TB. Of 1173, diagnostic algorithm was followed in 460 (37%). Among remaining 763 not evaluated as per algorithm, tuberculin skin test alone was conducted in 307 (41%), chest radiography alone in 99 (13%) and no investigations in 337 (45%). The yield of TB was higher among children evaluated as per algorithm (4%) as compared to those who were not (0.3%) (OR: 15.3 [95%CI: 3.5-66.3]). Several operational challenges including non-availability of a full-time paediatrician, non-functioning X-ray machine due to frequent power cuts, use of tuberculin with suboptimal strength and difficulties in adhering to a complex diagnostic algorithm were observed.
Conclusion
This study showed that TB screening in NRCs was sub-optimal in Karnataka. Some children did not reach the NRC, while many of those who did were either not or sub-optimally evaluated for TB. This study pointed to a number of operational issues that need to be addressed if this collaborative strategy is to identify more TB cases amongst malnourished children in India.
doi:10.1371/journal.pone.0084255
PMCID: PMC3865256  PMID: 24358350
15.  Myelopoietic Efficacy of Orlistat in Murine Hosts Bearing T Cell Lymphoma: Implication in Macrophage Differentiation and Activation 
PLoS ONE  2013;8(12):e82396.
Orlistat, an inhibitor of fatty acid synthase (FASN), acts as an antitumor agent by blocking de novo fatty acid synthesis of tumor cells. Although, myelopoiesis also depends on de novo fatty acid synthesis, the effect of orlistat on differentiation of macrophages, which play a central role in host’s antitumor defence, remains unexplored in a tumor-bearing host. Therefore, the present investigation was undertaken to examine the effect of orlistat administration on macrophage differentiation in a T cell lymphoma bearing host. Administration of orlistat (240 mg/kg/day/mice) to tumor-bearing mice resulted in a decline of tumor load accompanied by an augmentation of bone marrow cellularity and survival of bone marrow cells (BMC). The expression of apoptosis regulatory caspase-3, Bax and Bcl2 was modulated in the BMC of orlistat-administered tumor-bearing mice. Orlistat administration also resulted in an increase in serum level of IFN-γ along with decreased TGF-β and IL-10. BMC of orlistat-administered tumor-bearing mice showed augmented differentiation into macrophages accompanied by enhanced expression of macrophage colony stimulating factor (M-CSF) and its receptor (M-CSFR). The macrophages differentiated from BMC of orlistat-administered mice showed characteristic features of M1 macrophage phenotype confirmed by expression of CD11c, TLR-2, generation of reactive oxygen species, phagocytosis, tumor cell cytotoxicity, production of IL-1,TNF-α and nitric oxide. These novel findings indicate that orlistat could be useful to support myelopoesis in a tumor-bearing host.
doi:10.1371/journal.pone.0082396
PMCID: PMC3857782  PMID: 24349275
16.  Thermodynamic parameters of U (VI) sorption onto soils in aquatic systems 
SpringerPlus  2013;2:530.
The thermodynamic parameters viz. the standard free energy (∆Gº), Standard enthalpy change (∆Hº) and standard entropy change (∆Sº) were determined using the obtained values of distribution coefficient (kd) of U (VI) in two different types of soils (agricultural and undisturbed) by conducting a batch equilibrium experiment with aqueous media (groundwater and deionised water) at two different temperatures 25°C and 50°C. The obtained distribution coefficients (kd) values of U for undisturbed soil in groundwater showed about 75% higher than in agricultural soil at 25°C while in deionised water, these values were highly insignificant for both soils indicating that groundwater was observed to be more favorable for high surface sorption. At 50°C, the increased kd values in both soils revealed that solubility of U decreased with increasing temperature. Batch adsorption results indicated that U sorption onto soils was promoted at higher temperature and an endothermic and spontaneous interfacial process. The high positive values of ∆Sº for agricultural soil suggested a decrease in sorption capacity of U in that soil due to increased randomness at solid-solution interface. The low sorption onto agricultural soil may be due to presence of high amount of coarse particles in the form of sand (56%). Geochemical modeling predicted that mixed hydroxo-carbonato complexes of uranium were the most stable and abundant complexes in equilibrium solution during experimental.
doi:10.1186/2193-1801-2-530
PMCID: PMC3824716  PMID: 24255833
Soil; Groundwater; Deionised water; Distribution coefficients; Uranium
17.  The Impact of Isoniazid Resistance on the Treatment Outcomes of Smear Positive Re-Treatment Tuberculosis Patients in the State of Andhra Pradesh, India 
PLoS ONE  2013;8(10):e76189.
Background
Multi drug resistant and rifampicin resistant TB patients in India are treated with the World Health Organization (WHO) recommended standardized treatment regimens but no guidelines are available for the management of isoniazid (INH) resistant TB patients. There have been concerns that the standard eight-month retreatment regimen being used in India (2H3R3Z3E3S3/1H3R3Z3E3/5H3R3E3; H-Isoniazid; R-Rifampicin; Z-Pyrazinamide; E-Ethambutol; S-Streptomycin) may be inadequate to treat INH resistant TB cases and leads to poor treatment outcomes. We aimed to assess if INH resistance is associated with unfavorable treatment outcomes (death, default, failure and transferred out) among a cohort of smear positive retreatment TB patients registered in three districts of Andhra Pradesh, India.
Methods
We conducted a retrospective record review of all smear positive retreatment TB patients without rifampicin resistance registered during April–December 2011.
Results
Of 1,947 TB patients, 1,127 (58%) were tested with LPA—50 (4%) were rifampicin resistant, 933 (84%) were sensitive to INH and rifampicin and 144 (12%) were INH resistant. Of 144 INH resistant cases, 64 (44%) had poor treatment outcomes (25 (17%) default, 22 (15%) death, 12 (8%) failure and 5 (3%) transfer out) as compared to 287 (31%) among INH sensitive cases [aRR 1.46; 95%CI (1.19–1.78)].
Conclusion
Our study confirms that INH resistance is independently associated with unfavorable treatment outcomes among smear positive retreatment TB patients, indicating that the current treatment regimen may be inadequate. These findings call for an urgent need for randomized controlled trials to discover the most effective treatment regimen for managing INH resistant TB.
doi:10.1371/journal.pone.0076189
PMCID: PMC3795751  PMID: 24146839
18.  LED-Fluorescence Microscopy for Diagnosis of Pulmonary Tuberculosis under Programmatic Conditions in India 
PLoS ONE  2013;8(10):e75566.
Background
Light-emitting diode fluorescence microscopy (LED-FM) has been shown to be more sensitive than conventional bright field microscopy using Ziehl-Neelsen (ZN) stain in detecting sputum smear positive tuberculosis in controlled laboratory conditions. In 2012, Auramine O staining based LED-FM replaced conventional ZN microscopy in 200 designated microscopy centres (DMC) of medical colleges operating in collaboration with India’s Revised National Tuberculosis Control Programme. We aimed to assess the impact of introduction of LED-FM services on sputum smear positive case detection under program conditions.
Methods
This was a before and after comparison study. In 15 randomly selected medical college DMCs, all presumptive TB patients who underwent sputum smear examination in the years 2011 (before LED-FM) and 2012 (after LED-FM) were compared. An additional 15 comparable DMCs that implemented conventional ZN sputum smear microscopy were also selected for comparison between 2011 and 2012.
Results
The proportion of presumptive TB patients (PTP)found sputum smear positive increased by 30%- from 13.6% (3432/25159) in 2011 to 17.8% (4706/26426) in 2012 (P value <0.01) in the sites that implemented LED-FM microscopy, whereas in DMCs where the ZN staining procedure is followed the proportion of sputum smear positive had remained unchanged (13.0%versus 12.6%;P value0.31).
Conclusion
Use of LED-FM significantly increased the proportion of smear positive cases among presumptive TB patients under routine program conditions in high workload laboratories. The study provides operational evidence needed to scale-up the use of LED-FM in similar settings in India and beyond.
doi:10.1371/journal.pone.0075566
PMCID: PMC3794029  PMID: 24130719
19.  Waxing and waning tracheal tube obstruction: A diagnostic dilemma! 
doi:10.4103/0970-9185.119132
PMCID: PMC3819861  PMID: 24250004
20.  All Madelung deformities are not endocrine 
Madelung deformity is a rare inherited disorder associated with endocrine disorders like Turner's syndrome, pseudohypoparathyroidism, but can be seen with short stature homeobox deficiency conditions such as Leri-Weill dyschondrosteosis (LWD) and Langers mesomelic dysplasia. It has also been reported following trauma to the distal radius epiphysis neoplasia mucopolysaccharidosis (MPS) and achondroplasia. Madelung deformity is an abnormality of distal radial epiphysis where in progressive ulnar and volar tilt of the articular surface occurring in association with distal subluxation of ulna. A 13-year-old girl was referred to us for evaluation of bilateral deformity of wrist and short stature. There was ulnar deviation and dorsal tilt of bilateral hands without history of pain to the joint trauma and family history of similar illness. On X-ray, wrist showed malformed distal radial epiphysis with dorsal and ulnar shift and with increased length of phalanges suggestive of Madelung deformity. X-ray spine was normal. Ultrasound abdomen showed normal uterus and ovary and her follicle stimulating hormone. Luteinizing hormone was normal and so was urine MPS screening. Based on the above points the diagnosis of LWD was made.
doi:10.4103/2230-8210.119581
PMCID: PMC3830315  PMID: 24251169
Achondroplasia; dyschondrosteosis; Madelung
21.  Comparing Same Day Sputum Microscopy with Conventional Sputum Microscopy for the Diagnosis of Tuberculosis – Chhattisgarh, India 
PLoS ONE  2013;8(9):e74964.
Background
The World Health Organization (WHO) recommends same day sputum microscopy (spot-spot) in preference to conventional strategy (spot-morning) for the diagnosis of smear positive tuberculosis with the view that completing diagnosis on a single day may be more convenient to the patients and reduce pre-treatment losses to follow-up.
Methods
We conducted a cross-sectional study in seven selected district level hospitals of Chhattisgarh State, India. During October 2012 – March 2013, two sputum specimens (spot-early morning) were collected from consecutively enrolled adult (≥18 years) presumptive TB patients as per current national guidelines. In addition, a second sample was collected (one hour after the collection of first spot sample) from the same patients. All the samples were examined by ziehl-Neelsen (ZN) microscopy. McNemar’s test was used to compare statistical differences in the proportion smear positive between the two approaches (spot-spot versus spot-morning).
Results
Of 2551 presumptive TB patients, 69% were male. All patients provided the first spot specimen, 2361 (93%) provided the second spot specimen, and 2435 (96%) provided an early morning specimen. 72% of specimens were mucopurulent in conventional strategy as compared to 60% in same day strategy. The proportion of smear-positive patients diagnosed by same day microscopy was 14%, as compared to 17% by the conventional method (p<0.001). A total of 73 (16.9%) potential cases were missed by the same day method compared to only 2 (0.5%) by the conventional method.
Conclusion
Same-day microscopy method missed 17% of smear-positive cases and contrary to prior perception, did not increase the proportion of suspects providing the second sample. These findings call for an urgent need to revisit the WHO recommendation of switching to same-day diagnosis over the current policy.
doi:10.1371/journal.pone.0074964
PMCID: PMC3781139  PMID: 24086412
22.  Chemopreventive Properties of Dietary Rice Bran: Current Status and Future Prospects12 
Advances in Nutrition  2012;3(5):643-653.
Emerging evidence suggests that dietary rice bran may exert beneficial effects against several types of cancer, such as breast, lung, liver, and colorectal cancer. The chemopreventive potential has been related to the bioactive phytochemicals present in the bran portion of the rice such as ferulic acid, tricin, β-sitosterol, γ-oryzanol, tocotrienols/tocopherols, and phytic acid. Studies have shown that the anticancer effects of the rice bran–derived bioactive components are mediated through their ability to induce apoptosis, inhibit cell proliferation, and alter cell cycle progression in malignant cells. Rice bran bioactive components protect against tissue damage through the scavenging of free radicals and the blocking of chronic inflammatory responses. Rice bran phytochemicals have also been shown to activate anticancer immune responses as well as affecting the colonic tumor microenvironment in favor of enhanced colorectal cancer chemoprevention. This is accomplished through the modulation of gut microflora communities and the regulation of carcinogen-metabolizing enzymes. In addition, the low cost of rice production and the accessibility of rice bran make it an appealing candidate for global dietary chemoprevention. Therefore, the establishment of dietary rice bran as a practical food-derived chemopreventive agent has the potential to have a significant impact on cancer prevention for the global population.
doi:10.3945/an.112.002303
PMCID: PMC3648746  PMID: 22983843
23.  The journey to antiretroviral therapy in Karnataka, India: who was lost on the road? 
Introduction
One important operational challenge facing antiretroviral treatment (ART) programmes in low- and middle-income countries is the loss to follow-up between diagnosis of human immunodeficiency virus (HIV) and initiation of ART. This is a major obstacle to achieving universal access to ART. This study from Karnataka, India, tried to measure such losses by determining the number of HIV-positive individuals diagnosed, the number of them reaching ART centres, the number initiated on ART and the reasons for non-initiation of ART.
Methods
A review of records routinely maintained under the National AIDS Control Programme (NACP) was carried out in six districts of Karnataka. HIV-positive persons diagnosed during the months from January to June 2011 in 233 public HIV-testing sites were followed up until December 2011 based on the pre-ART registers. A chi-square test was used to assess statistical significance.
Results
Of 2291 HIV-positive persons diagnosed (52% male; mean age of 35 years), 1829 (80%) reached ART centres. Of the latter, 1166 (64%) were eligible for ART, and 959 (82%) were initiated on treatment. Overall losses (attrition) on the road between HIV diagnosis and ART initiation were 669 (29%). Deaths, migration and not willing to go to the ART centres were cited as the main known reasons for not reaching ART centres. For ART-eligible individuals who did not initiate ART, the most common known reasons for non-initiation included dying before initiation of ART and not being willing to start ART.
Conclusions
In a large state of India, eight in ten HIV-positive persons reached ART centres, and of those found ART eligible, 82% start treatment. Although this is an encouraging achievement, the programme needs to take further steps to improve the current performance by further reducing pre-ART attrition. We recommend online registering of diagnosed HIV-positive patients to track the patients more efficiently.
doi:10.7448/IAS.16.1.18502
PMCID: PMC3756231  PMID: 23985346
operational research; ART centres; loss to follow-up; India
24.  Tuberculosis Management Practices by Private Practitioners in Andhra Pradesh, India 
PLoS ONE  2013;8(8):e71119.
Setting
Private medical practitioners in Visakhapatnam district, Andhra Pradesh, India.
Objectives
To evaluate self-reported TB diagnostic and treatment practices amongst private medical practitioners against benchmark practices articulated in the International Standards of Tuberculosis Care (ISTC), and factors associated with compliance with ISTC.
Design
Cross- sectional survey using semi-structured interviews.
Results
Of 296 randomly selected private practitioners, 201 (68%) were assessed for compliance to ISTC diagnostic and treatment standards in TB management. Only 11 (6%) followed a combination of 6 diagnostic standards together and only 1 followed a combination of all seven treatment standards together. There were 28 (14%) private practitioners who complied with a combination of three core ISTC (cough for tuberculosis suspects, sputum smear examination and use of standardized treatment). Higher ISTC compliance was associated with caring for more than 20 TB patients annually, prior sensitization to TB control guidelines, and practice of alternate systems of medicine.
Conclusion
Few private practitioners in Visakhapatnam, India reported TB diagnostic and treatment practices that met ISTC. Better engagement of the private sector is urgently required to improve TB management practices and to prevent diagnostic delay and drug resistance.
doi:10.1371/journal.pone.0071119
PMCID: PMC3742777  PMID: 23967158
25.  Scaling Up Antiretroviral Treatment Services in Karnataka, India: Impact on CD4 Counts of HIV-Infected People 
PLoS ONE  2013;8(8):e72188.
Setting
Twelve antiretroviral treatment centres under National AIDS Control Programme (NACP), Karnataka State, India.
Objective
For the period 2004-2011, to describe the trends in the numbers of people living with HIV (PLHIV) registered for care and their median baseline CD4 counts, disaggregated by age and sex.
Design
Descriptive study involving analysis of routinely captured data (year of registration, age, sex, baseline CD4 count) under NACP.
Results
34,882 (97% of total eligible) PLHIV were included in analysis. The number registered for care has increased by over 12 times during 2004-11; with increasing numbers among females. The median baseline CD4 cell count rose from 125 in 2004 to 235 in 2011 – the increase was greater among females as compared to males. However, about two-thirds still presented at CD4 cell counts less than 350.
Conclusion
We found an increasing trend of median CD4 counts among PLHIV presenting to ART centres in Karnataka, an indicator of enhanced and early access to HIV care. Equal proportion of females and higher baseline CD4 counts among them allays any fear of differential access by gender. Despite this relative success, a substantial proportion still presented at low CD4 cell counts indicating possibly delayed HIV diagnosis and delayed linkage to HIV care. Universal HIV testing at health care facilities and strengthening early access to care are required to bridge the gap.
doi:10.1371/journal.pone.0072188
PMCID: PMC3738558  PMID: 23951294

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