Publications by authors named "Gursewak Singh"

7 Publications

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Dengue Virus Immunity Increases Zika Virus-Induced Damage during Pregnancy.

Immunity 2019 03 5;50(3):751-762.e5. Epub 2019 Feb 5.

Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address:

Zika virus (ZIKV) has recently been associated with birth defects and pregnancy loss after maternal infection. Because dengue virus (DENV) and ZIKV co-circulate, understanding the role of antibody-dependent enhancement in the context of pregnancy is critical. Here, we showed that the presence of DENV-specific antibodies in ZIKV-infected pregnant mice significantly increased placental damage, fetal growth restriction, and fetal resorption. This was associated with enhanced viral replication in the placenta that coincided with an increased frequency of infected trophoblasts. ZIKV-infected human placental tissues also showed increased replication in the presence of DENV antibodies, which was reversed by FcγR blocking antibodies. Furthermore, ZIKV-mediated fetal pathogenesis was enhanced in mice in the presence of a DENV-reactive monoclonal antibody, but not in the presence of the LALA variant, indicating a dependence on FcγR engagement. Our data suggest a possible mechanism for the recent increase in severe pregnancy outcomes after ZIKV infection in DENV-endemic areas.
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http://dx.doi.org/10.1016/j.immuni.2019.01.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947917PMC
March 2019

Tick-Borne Encephalitis Virus Vaccine-Induced Human Antibodies Mediate Negligible Enhancement of Zika Virus Infection and in a Mouse Model.

mSphere 2018 Jan-Feb;3(1). Epub 2018 Feb 7.

Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Recent reports in the scientific literature have suggested that anti-dengue virus (DENV) and anti-West Nile virus (WNV) immunity exacerbates Zika virus (ZIKV) pathogenesis and in mouse models. Large populations of immune individuals exist for a related flavivirus (tick-borne encephalitis virus [TBEV]), due to large-scale vaccination campaigns and endemic circulation throughout most of northern Europe and the southern Russian Federation. As a result, the question of whether anti-TBEV immunity can affect Zika virus pathogenesis is a pertinent one. For this study, we obtained 50 serum samples from individuals vaccinated with the TBEV vaccine FSME-IMMUN (Central European/Neudörfl strain) and evaluated their enhancement capacity using K562 human myeloid cells expressing CD32 and using a mouse model of ZIKV pathogenesis. Among the 50 TBEV vaccinee samples evaluated, 29 had detectable reactivity against ZIKV envelope (E) protein by enzyme-linked immunosorbent assay (ELISA), and 36 showed enhancement of ZIKV infection . A pool of the most highly reacting and enhanced samples resulted in no significant change in the morbidity/mortality of ZIKV disease in immunocompromised mice. Our results suggest that humoral immunity against TBEV is unlikely to enhance Zika virus pathogenesis in humans. No clinical reports indicating that TBEV vaccinees experiencing enhanced ZIKV disease have been published so far, and though the epidemiological data are sparse, our findings suggest that there is little reason for concern. This study also displays a clear relationship between the phylogenetic distance between two flaviviruses and their capacity for pathogenic enhancement. The relationship between serial infections of two different serotypes of dengue virus and more severe disease courses is well-documented in the literature, driven by so-called antibody-dependent enhancement (ADE). Recently, studies have shown the possibility of ADE in cells exposed to anti-DENV human plasma and then infected with ZIKV and also in mouse models of ZIKV pathogenesis after passive transfer of anti-DENV human plasma. In this study, we evaluated the extent to which this phenomenon occurs using sera from individuals immunized against tick-borne encephalitis virus (TBEV). This is highly relevant, since large proportions of the European population are vaccinated against TBEV or otherwise seropositive.
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http://dx.doi.org/10.1128/mSphereDirect.00011-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806211PMC
February 2018

Treatment of chronic hepatitis C genotype 3 with Sofosbuvir-based therpy: a real-life study.

Hepatol Int 2017 May 31;11(3):277-285. Epub 2017 Mar 31.

Himalayan Institute of Medical Sciences, Dehradun, UttarKhand, India.

Background And Aims: Recently, Sofosbuvir was launched in India at affordable cost. We conducted a real-life study to determine the efficacy and safety of Sofosbuvir plus Ribavirin, with and without peginterferon-alfa 2a, in patients with chronic hepatitis C (CHC) genotype 3, the commonest genotype in South Asia.

Methods: This study included data of CHC patients from 11 sites in northern India between March 2015 and December 2015 (n = 1203). Patients with CHC genotype 3 (n = 931), who were treated with either Sofosbuvir 400 mg plus weight-based Ribavirin, daily ×24 weeks (n = 432) (dual therapy), or Peginterferon-α2a 180 mcg weekly, Sofosbuvir 400 mg plus weight-based Ribavirin, daily ×12 weeks (n = 499) (triple therapy) were included for analysis. Primary outcome was the proportion of patients achieving sustained viral response at 12 weeks post-therapy.

Results: The overall SVR rates were 91 and 92% in the dual and triple therapy arms, respectively. The SVR rates in treatment experienced were 67 and 74% versus 93 and 96% in naïve patients, on the dual and triple therapy arms, respectively. The SVR rates of cirrhotics were 73 and 75% on the dual and triple treatment arms, respectively. The SVR rates were low in the experienced cirrhotic patients: 44% (dual therapy) and 58% (triple therapy). Common adverse events were fatigue, headache, and myalgia.

Conclusion: Both dual and triple therapy regimes resulted in SVR rates of >95% in CHC genotype 3 who were naive non-cirrhotics. However, the SVR rates were low in treatment-experienced cirrhotics.
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http://dx.doi.org/10.1007/s12072-017-9794-1DOI Listing
May 2017

Clinical profile of calcific and noncalcific chronic pancreatitis in north India.

J Clin Gastroenterol 2011 Jul;45(6):546-50

Department of Gastroenterology, Surgery and Radiodiagnosis, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Goals: To compare the clinical profile of calcific and noncalcific chronic pancreatitis (CP) in north India.

Background: The profile of calcific CP has not been adequately studied.

Study: Detailed demographic data were recorded; hematologic, biochemical, and radiologic investigations were carried out on 225 patients with CP. The patients were divided into calcific and noncalcific groups based on the presence of pancreatic calcification, which was detected on computed tomography.

Results: Calcific CP was reported in 46.7% of the patients and noncalcific CP in 53.3%. The mean age, duration of symptoms before presentation, sex ratio, body mass index, and frequency of various symptoms and complications including abdominal pain, ascites, pleural effusion, and segmental portal hypertension was not statistically different between the 2 groups. However, pseudocysts occurred more frequently in noncalcific CP, whereas jaundice because of bile duct stricture, diabetes mellitus, and steatorrhea occurred more frequently in patients with calcific CP (P<0.05). On comparing calcific and noncalcific alcoholic pancreatitis, only steatorrhea was reported more frequently in patients with calcific alcoholic CP. However, pseudocysts and segmental portal hypertension occurred more frequently in noncalcific idiopathic CP, whereas diabetes mellitus occurred more frequently in patients with calcific idiopathic CP (P<0.05). On comparing calcific alcoholic CP with calcific idiopathic CP, we found significantly lower mean age in patients with idiopathic CP and a higher frequency of male patients and pseudocysts in alcoholic CP (P<0.05).

Conclusion: Calcific CP has a higher frequency of bile duct stricture, diabetes mellitus, and steatorrhea, whereas noncalcific CP has higher frequency of pseudocysts and segmental portal hypertension.
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http://dx.doi.org/10.1097/MCG.0b013e3181f8c6bfDOI Listing
July 2011

Effect of mechanical drying air conditions on quality of turmeric powder.

J Food Sci Technol 2010 Jun 29;47(3):347-50. Epub 2010 Jul 29.

Department of Processing and Food Engineering, Punjab Agricultural University, Ludhiana, 141 004 India.

Mother and finger rhizomes 'PCT-8' ('Suvarna') variety of turmeric (Curcuma longa L) were boiled separately in open pan for 45 min at 100°C. The rhizomes were then dried using tray drier at air temperatures of 45, 50, 55, 60 and 65°C and drying air velocities of 1, 2 and 3 m/sec. The rhizomes were dried to ∼10 % (wb) moisture content. The dried rhizomes were polished manually and powdered. The volume of fresh and dried turmeric was determined and shrinkage ratio calculated. The colour of fresh and dried turmeric was determined. Change in colour (ΔE) with drying time was found to be 2.3 and 2.7 for fingers and mothers respectively at 60°C and 2 m/sec air velocity. The oleoresin content was 13.0 and 12.0% for fingers and mothers, respectively. The drying of turmeric took place in the falling rate period and was governed by moisture diffusion. The best quality turmeric was obtained by drying at 60°C air temperature and 2 m/sec air velocity.
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http://dx.doi.org/10.1007/s13197-010-0057-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551030PMC
June 2010

Clinical profile of idiopathic chronic pancreatitis in North India.

Clin Gastroenterol Hepatol 2009 May;7(5):594-9

Department of Gastroenterology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Background & Aims: Tropical pancreatitis, a form of idiopathic chronic pancreatitis (ICP) with unique features, has been described in South and North India. We investigated the clinical profile of ICP patients in North India.

Methods: Detailed demographic data were recorded; hematological and biochemical analyses were performed on samples from 155 patients (mostly from North India) who had been diagnosed with chronic pancreatitis. Ultrasonography and computed tomography were performed on all patients. Magnetic resonance cholangiopancreatography, endoscopic retrograde cholangiopancreatography, glucose tolerance tests, and fecal fat studies were performed on some patients. Patients were divided into groups based on early- or late-onset ICP (before or after 35 years of age).

Results: ICP was reported in 41.3% of patients and alcoholic chronic pancreatitis in 38.1%. The mean age of ICP patients was 33.0 +/- 13.0 years and the mean duration of symptoms at the time of presentation was 40.2 +/- 34.4 months. Pain was the dominant symptom in patients with early- (95.1%) and late-onset (100%) ICP; pseudocyst was the most common local complication. Diabetes was observed in 17.1% of patients with early-onset ICP and 34.8% with late-onset ICP. Pancreatic calcification was noted in 46.3% of patients with early-onset and 47.8% with late-onset ICP. Pseudocyst and segmental portal hypertension occurred more frequently in non-calcific ICP, whereas diabetes mellitus and abnormal fecal fat excretion occurred more frequently in patients with calcific ICP.

Conclusions: In North India, ICP differs from the classical tropical pancreatitis described in the literature. It is associated with a higher prevalence of pain and lower frequencies of diabetes, calcification, and intraductal calculi.
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http://dx.doi.org/10.1016/j.cgh.2009.01.009DOI Listing
May 2009

Endoscopic balloon dilation in caustic-induced chronic gastric outlet obstruction.

Gastrointest Endosc 2009 Apr 10;69(4):800-5. Epub 2009 Jan 10.

Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Background: The standard treatment of caustic-induced gastric outlet obstruction (GOO) is surgery. There are only a few reports in the medical literature on endoscopic balloon dilation (EBD) for caustic-induced GOO.

Objective: To study the short-term and long-term response of EBD in patients with caustic-induced GOO.

Setting: Tertiary-care center in India.

Design: Retrospective analysis of data.

Patients: Of the 49 patients with caustic-induced GOO seen by us between January 1998 and December 2003, 41 were treated by EBD. Thirty-seven patients had consumed an acid and 4 had consumed an alkali a mean (SD) of 19.5 +/- 14.5 weeks earlier. EBD was performed every 3 weeks by using through-the-scope balloons under endoscopic guidance.

Intervention: The balloon was negotiated across the narrowed segment and inflated for 60 seconds by using a pressure gun. Balloons of incremental diameters, up to a maximum of 3 sizes, were used in each sitting. The end point of dilation was 15 mm, after which patients were assessed for recurrence. The patients were observed until August 2007.

Results: All 41 patients (23 men; mean [SD] age 29.6 +/- 8.5 years) could be successfully taken for EBD. Thirty-nine patients underwent successful repeated dilations, which required a mean (SD) of 5.8 +/- 2.6 dilations (range 2-13) to achieve the end point of 15 mm. All 39 patients were followed up for an average (SD) of 35.4 +/- 11.1 months (range 18-58 months). The mean (SD) size of the first dilator was 8.2 +/- 0.6 mm (range 8-10 mm). One patient had a perforation and was subjected to antrectomy; another patient had pain every time he received EBD; he also had surgery. Other complications were minor: self-limiting pain (n = 8) or bleeding (n = 7).

Conclusions: EBD is a safe, effective, and long-lasting alternative to surgery for caustic-induced GOO.
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http://dx.doi.org/10.1016/j.gie.2008.05.056DOI Listing
April 2009