Publications by authors named "Arun Shankar"

31 Publications

A new interventional home care model for COVID management: Virtual Covid IP.

Diabetes Metab Syndr 2021 Jul 23;15(5):102228. Epub 2021 Jul 23.

Department of Diabetology, Jothydev's Diabetes Research Centers, Kerala, India.

Aim: Amidst COVID-19 pandemic, the health care delivery in India faces major challenges owing to the overwhelming hospitals, exhausted healthcare workers, and shortage of crucial medical supplies such as ventilators and oxygen. The study aims to propose a novel successful interventional home care model, the Virtual COVID In-Patient (VCIP) care for effective COVID management.

Methods: The Covid-19 positive patients enrolled in VCIP were chosen for the study. A 24/7 active multidisciplinary WhatsApp group was created for each patient, for remote monitoring of temperature, blood pressure, blood glucose, respiratory and pulse rate along with the symptoms. Advice on sleep and exercises were given along with the medication via video-audio consultations. Lab facility was provided at the doorstep. Training on various devices, medications including steroids, delivering subcutaneous injections etc were given via video platforms.

Results: Among the 220 patients who availed the VCIP facility, only two were hospitalized, yielding a 99.5 % success rate in preventing hospitalizations and patients enrolled have been immensely satisfied with their experience.

Conclusions: With similar pandemics anticipated in near future, VCIP model may be considered for successful domiciliary treatment and overcoming the challenges.
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http://dx.doi.org/10.1016/j.dsx.2021.102228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299213PMC
July 2021

The prevalence of burnout, risk factors, and job-related stressors in gastroenterologists: A systematic review.

J Gastroenterol Hepatol 2021 Sep 29;36(9):2338-2348. Epub 2021 Mar 29.

Department of Medicine, National University of Singapore, Singapore, Singapore.

Background And Aims: Burnout is an important occupational hazard, and the scale of the problem within gastroenterology remains poorly understood. The primary objective of this study was to understand the prevalence of burnout in gastroenterology and ascertain if there was a common prevalence within the field. The secondary objective was to identify factors and job-related stressors that commonly contribute to burnout in gastroenterologists.

Methods: Systematic searches were conducted in PubMed, Scopus, Cochrane, and PsycINFO by two reviewers independently for articles published to 1 September 2020. The primary outcome measure was the reported prevalence of burnout in gastroenterologists. The secondary outcome measures were (i) the prevalence of non-somatic burnout symptoms (emotional exhaustion, depersonalization, and low personal accomplishment) and (ii) the frequency of risk factors and stressors reported in studies. Data were presented, and limited meta-analyses discussed.

Results: Data were extracted from 11 studies. 54.5% (6/11) of these studies reported the prevalence of burnout in gastroenterologists; this ranged from 18.3% to 64.4%. Similar to burnout prevalence, burnout symptoms showed geographical variation and were common in gastroenterologists (up to 63.9%). Factors associated with work volume, age, and female gender were the three most frequently reported risk factors for increased levels of stress and burnout in 72.7% (8/11), 54.5% (6/11), and 45.5% (5/11) of studies, respectively. Significant methodological and clinical heterogeneity was observed.

Conclusions: Burnout and its non-somatic symptoms are common in gastroenterologists, but the syndrome is understudied within the field. Further research and good quality data are needed to help address the problem.
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http://dx.doi.org/10.1111/jgh.15488DOI Listing
September 2021

Time-in-range as a target in type 2 diabetes: An urgent need.

Heliyon 2021 Jan 15;7(1):e05967. Epub 2021 Jan 15.

Jothydev's Diabetes Research Centre, Mudavanmugal, Thiruvananthapuram, Kerala, India.

Time-in-range emerged as a valuable blood glucose metric, 'beyond HbA1c' for a deeper insight into glycemic control in people with diabetes. It denotes the proportion of time that a person's glucose level remains within the desired target range (usually 70-180 mg/dL or 3.9-10.0 mmol/L). Though clinical targets in the current recommendations for type 1 and type 2 diabetes are close enough, their clinical profiles and prevalences are quite different. Type 2 diabetes is the commonest form of diabetes. Many clinical trials have challenged the usefulness of HbA1c as a glycemic target for Type 2 diabetes mellitus. On account of the higher prevalence and complications of type 2 diabetes, more outcomes-based studies are needed to associate time-in-range with its ongoing risk. These studies strongly support the dependability of time-in-range to identify patients with elevated risk in type 2 diabetes. We discuss the utility of time-in-range, a new metric of continuous glucose monitoring as an outcome measure to correlate with type 2 diabetes risks and complications and to analyze the effectiveness of type 2 diabetes management. This approach may support the use of time-in-range as a metric for long-term health outcomes in the type 2 diabetes population.
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http://dx.doi.org/10.1016/j.heliyon.2021.e05967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814148PMC
January 2021

Subtrochanteric femoral shortening for hip centre restoration in complex total hip arthroplasty with functional outcome.

Bone Jt Open 2020 May 22;1(5):152-159. Epub 2020 May 22.

Unit 2, Department of Orthopaedics, Christian Medical College Hospital, Vellore, Tamil Nadu, India.

Aims: Complex total hip arthroplasty (THA) with subtrochanteric shortening osteotomy is necessary in conditions other than developmental dysplasia of the hip (DDH) and septic arthritis sequelae with significant proximal femur migration. Our aim was to evaluate the hip centre restoration with THAs in these hips.

Methods: In all, 27 THAs in 25 patients requiring THA with femoral shortening between 2012 and 2019 were assessed. Bilateral shortening was required in two patients. Subtrochanteric shortening was required in 14 out of 27 hips (51.9%) with aetiology other than DDH or septic arthritis. Vertical centre of rotation (VCOR), horizontal centre of rotation, offset, and functional outcome was calculated. The mean followup was 24.4 months (5 to 92 months).

Results: The mean VCOR was 17.43 mm (9.5 to 27 mm) and horizontal centre of rotation (HCOR) was 24.79 mm (17.2 to 37.6 mm). Dislocation at three months following acetabulum reconstruction required femoral shortening for offset correction and hip centre restoration in one hip. Mean horizontal offset was 39.72 (32.7 to 48.2 mm) compared to 42.89 (26.7 to 50.6 mm) on the normal side. Mean Harris Hip Score (HHS) of 22.64 (14 to 35) improved to 79.43 (68 to 92). Mean pre-operative shortening was 3.95 cm (2 to 8 cm). Residual limb length discrepancy was 1.5 cm (0 to 2 cm). Sciatic neuropraxia in two patients recovered by six months, and femoral neuropraxia in one hip recovered by 12 months. Mean Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was 13.92 (9 to 19). Mean 12-item short form survey (SF-12) physical scores of 50.6 and mental of 60.12 were obtained.

Conclusion: THA with subtrochanteric shortening is valuable in complex hips with high dislocation. The restoration of the hip centre of rotation and offset is important in these hips.

Level Of Evidence Iv: Femoral shortening useful in conditions other than DDH and septic sequelae.Restoration of hip centre combined with offset to be planned and ensured.
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http://dx.doi.org/10.1302/2633-1462.15.BJO-2020-0023.R1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7684393PMC
May 2020

Bouveret Syndrome: A Systematic Review of Endoscopic Therapy and a Novel Predictive Tool to Aid in Management.

J Clin Gastroenterol 2020 10;54(9):758-768

Gastroenterology, Bedford Hospital NHS Trust, Bedford.

Background And Goals: Bouveret syndrome is characterized by gastroduodenal obstruction caused by an impacted gallstone. Current literature recommends endoscopic therapy as the first line of intervention despite significantly lower success rates compared with surgery. The lack of treatment efficacy studies and the paucity of clinical guidelines contribute to current practices being arbitrary. The aim of this systematic review was to identify factors that predict outcomes of endoscopic therapy. Subsequently, a predictive tool was devised to predict the success of endoscopic therapy and recommendations were proposed to improve current management strategies of impacted gallstones in the upper gastrointestinal tract.

Methods: A systematic search of PubMed, Medline, Cochrane, and Scopus was performed for articles that contained the terms "Bouveret syndrome," "Bouveret's syndrome," "gallstone" AND "gastric obstruction" and "gallstone" AND "duodenal obstruction" that were published between January 1, 1950 to April 15, 2018. Articles were reviewed by 3 reviewers and raw data collated. χ and Kolmogorov-Smirnov tests were used to test associations between predictors and endoscopic outcomes. A logistic regression model was then used to create a predictive tool which was cross validated.

Results: Failure of endoscopic therapy is associated with increasing gallstone length (P<0.0001) and impaction in the distal duodenum (P<0.05). Using multiple endoscopic modalities is associated with better success rates (P<0.05). The novel predictive tool predicted success of endoscopic therapy with an area under the receiver operating characteristic score of 0.86 (95% confidence interval: 0.79-0.94).

Conclusion: In Bouveret syndrome, a selective approach to endoscopic therapy can expedite definitive treatment and improve current management strategies.
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http://dx.doi.org/10.1097/MCG.0000000000001221DOI Listing
October 2020

Burnout in gastroenterology registrars: a feasibility study conducted in the East of England using a 31-item questionnaire.

BMJ Open Gastroenterol 2020 07;7(1)

Department of Gastroenterology, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK.

Objective: The scale of burnout in UK gastroenterology trainees and the feasibility to determine its prevalence using the validated Maslach Burnout Inventory-Human Services Survey (MBI-HSS) tool are unknown. The primary objective of this region-wide pilot study was to evaluate the response rate to a 31-item questionnaire. The secondary objectives were to estimate the prevalence of burnout in gastroenterology trainees within the East of England deanery (EoE) and identify common stressors that trainees experience.

Design: This was a cross-sectional study involving gastroenterology trainees from 16 hospitals across the EoE using a 31-item questionnaire. The questionnaire consisted of the 22-item MBI-HSS and nine additional free-text questions. All gastroenterology trainees in the EoE were invited to complete the anonymised survey online. Data were analysed quantitatively and qualitatively.

Results: The response rate for the survey was acceptable: 44.0% (40/91). 57.5% (23/40) of gastroenterology trainees reported emotional exhaustion. 23.5% (8/34) had depersonalisation and 63.9% (23/36) experienced low professional accomplishment. Burnout prevalence was 35.3% (12/34). 48.4% (15/31) of gastroenterology trainees were aware of professional support services within EoE. Stressors related to service requirements (eg, workload, staffing levels) and professional relationships with colleagues and patients were commonly reported: 65.6% and 25.0%, respectively.

Conclusions: It is feasible to use a 31-item questionnaire in a national cohort of UK gastroenterology trainees for future burnout studies. Burnout in EoE gastroenterology trainees was high and this may reflect a national prevalence within the specialty. More extensive studies, greater awareness of burnout and improved access to professional support services are required.
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http://dx.doi.org/10.1136/bmjgast-2020-000401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365426PMC
July 2020

Quantification of aortic pulse wave velocity from a population based cohort: a fully automatic method.

J Cardiovasc Magn Reson 2019 05 13;21(1):27. Epub 2019 May 13.

Department of Radiology, Leiden University Medical Center, Albinusdreef 2, Leiden, 2333 ZA, The Netherlands.

Background: Aortic pulse wave velocity (PWV) is an indicator of aortic stiffness and is used as a predictor of adverse cardiovascular events. PWV can be non-invasively assessed using magnetic resonance imaging (MRI). PWV computation requires two components, the length of the aortic arch and the time taken for the systolic pressure wave to travel through the aortic arch. The aortic length is calculated using a multi-slice 3D scan and the transit time is computed using a 2D velocity encoded MRI (VE) scan. In this study we present and evaluate an automatic method to quantify the aortic pulse wave velocity using a large population-based cohort.

Methods: For this study 212 subjects were retrospectively selected from a large multi-center heart-brain connection cohort. For each subject a multi-slice 3D scan of the aorta was acquired in an oblique-sagittal plane and a 2D VE scan acquired in a transverse plane cutting through the proximal ascending and descending aorta. PWV was calculated in three stages: (i) a multi-atlas-based segmentation method was developed to segment the aortic arch from the multi-slice 3D scan and subsequently estimate the length of the proximal aorta, (ii) an algorithm that delineates the proximal ascending and descending aorta from the time-resolved 2D VE scan and subsequently obtains the velocity-time flow curves was also developed, and (iii) automatic methods that can compute the transit time from the velocity-time flow curves were implemented and investigated. Finally the PWV was obtained by combining the aortic length and the transit time.

Results: Quantitative evaluation with respect to the length of the aortic arch as well as the computed PWV were performend by comparing the results of the novel automatic method to those obtained manually. The mean absolute difference in aortic length obtained automatically as compared to those obtained manually was 3.3 ± 2.8 mm (p < 0.05), the manual inter-observer variability on a subset of 45 scans was 3.4 ± 3.4 mm (p = 0.49). Bland-Altman analysis between the automataic method and the manual methods showed a bias of 0.0 (-5.0,5.0) m/s for the foot-to-foot approach, -0.1 (-1.2, 1.1) and -0.2 (-2.6, 2.1) m/s for the half-max and the cross-correlation methods, respectively.

Conclusion: We proposed and evaluated a fully automatic method to calculate the PWV on a large set of multi-center MRI scans. It was observed that the overall results obtained had very good agreement with manual analysis. Our proposed automatic method would be very beneficial for large population based studies, where manual analysis requires a lot of manpower.
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http://dx.doi.org/10.1186/s12968-019-0530-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518670PMC
May 2019

The investigation of chronic diarrhoea: new BSG guidance.

Br J Gen Pract 2019 05;69(682):262-264

Department of Gastroenterology, Norfolk and Norwich University Hospital NHS Trust, Norwich.

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http://dx.doi.org/10.3399/bjgp19X702653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478460PMC
May 2019

Chronic diarrhoea: the indications for lower GI endoscopy when functional bowel disease is suspected.

Gut 2019 11 30;68(11):2100. Epub 2018 Oct 30.

Department of Gastroenterology, Norfolk and Norwich University Hospital NHS Trust, Norwich, Bedfordshire, UK.

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http://dx.doi.org/10.1136/gutjnl-2018-317574DOI Listing
November 2019

The association between mentoring and training outcomes in junior doctors in medicine: an observational study.

BMJ Open 2018 09 21;8(9):e020721. Epub 2018 Sep 21.

Department of Gastroenterology, Norfolk & Norwich University Hospital, Norwich, UK.

Objective: To determine quantitatively if a positive association exists between the mentoring of junior doctors and better training outcomes in postgraduate medical training within the UK.

Design: Observational study.

Participants: 117 trainees from the East of England Deanery (non-mentored group) and the recently established Royal College of Physicians (RCP) Mentoring scheme (mentored group) who were core medical trainees (CMTs) between 2015 and 2017 completed an online survey. Trainees who received mentoring at the start of higher specialty training, incomplete responses and trainees who were a part of both the East of England deanery and RCP Mentoring scheme were excluded leaving 85 trainees in the non-mentored arm and 25 trainees in the mentored arm. Responses from a total of 110 trainees were analysed.

Main Outcome Measures: Pass rates of the various components of the Membership of the Royal College of Physicians (MRCP) (UK) examination (MRCP Part 1, MRCP Part 2 Written and MRCP Part 2 PACES), pass rates at the Annual Review of Competency Progression (ARCP), trainee involvement in significant events, clinical incidents or complaints and trainee feedback on career progression and confidence.

Results: Mentored trainees reported higher pass rates of the MRCP Part 1 exam versus non-mentored trainees (84.0% vs 42.4%, p<0.01). Mentored international medical graduates (IMGs) reported higher pass rates than non-mentored IMGs in the MRCP Part 2 Written exam (71.4% vs 24.0%, p<0.05). ARCP pass rates in mentored trainees were observed to be higher than non-mentored trainees (95.8% vs 69.9%, p<0.05). Rates of involvement in significant events, clinical incidents and complaints in both groups did not show any statistical difference. Mentored trainees reported higher confidence and career progression.

Conclusions: A positive association is observed between the mentoring of CMTs and better training outcomes. Further studies are needed to investigate the causative effects of mentoring in postgraduate medical training within the UK.
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http://dx.doi.org/10.1136/bmjopen-2017-020721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157572PMC
September 2018

imaging of hepatic neutrophil migration in severe alcoholic hepatitis with In-radiolabelled leucocytes.

Biosci Rep 2018 08 31;38(4). Epub 2018 Jul 31.

Division of Clinical and Laboratory Investigation, Brighton and Sussex Medical School, Brighton, U.K.

The study's aim was to image severe alcoholic hepatitis (SAH) using In-labelled leucocytes with two objectives in mind: firstly for non-invasive diagnosis and secondly to provide a platform for experimental therapies aiming to inhibit intrahepatic neutrophil migration. In-leucocyte scintigraphy was performed 30 min and 24 h post-injection in 19 patients with SAH, 14 abstinent patients with alcohol-related cirrhosis and 11 normal controls. Eleven with SAH and seven with cirrhosis also had Tc-nanocolloid scintigraphy. Change in hepatic In radioactivity was expressed as decay-corrected 24 h:30 min count ratio and, in SAH, compared with histological grading of steatohepatitis and expression of granulocyte marker, CD15. Hepatic microautoradiography on biopsy specimens obtained 24 h post-injection of In-leucocytes was performed in one patient. Median 24 h:30 min hepatic In activity ratio was higher in SAH (2.5 (interquartile range (IQR): 1.7-4.0) compared with cirrhotics and normal controls (1.0 (0.8-1.1) and 0.8 (0.7-0.9) respectively, <0.0001). In SAH, it correlated with CD15 expression (r = 0.62, =0.023) and was higher in marked compared with mild/moderate steatohepatitis (4.0 (3.0-4.6) compared with 1.8 (1.5-2.6), =0.006). Hepatic-to-splenic Tc count rate ratio was reduced in SAH (0.5 (0.4-1.4)) compared with cirrhotics (2.3( 0.6-3.0)) and three historic normal controls (4.2 (3.8-5.0); =0.003), consistent with impaired hepatic reticuloendothelial function. Scintigraphic findings in SAH included prominent lung radioactivity at 30 min, likely the result of neutrophil primimg. Microautoradiography demonstrated cell-associated In in areas of parenchymal neutrophil infiltration. In conclusion, In-leucocyte scintigraphy can non-invasively diagnose SAH and could provide a platform for evaluation of novel treatments aiming to inhibit intrahepatic neutrophil migration.
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http://dx.doi.org/10.1042/BSR20180466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6068468PMC
August 2018

Minocycline in Alcohol Withdrawal Induced Anxiety and Alcohol Relapse in Rats.

Curr Clin Pharmacol 2018 ;13(1):65-72

Department of Pharmacology, Seth GS Medical College & KEM Hospital, Maharashtra 400012, Mumbai, India.

Introduction: Anxiety and negative sensations due to alcohol withdrawal are factors leading to alcohol relapse and addiction. Minocycline, an antibiotic, can decrease alcohol consumption in rats, however, its effects on alcohol withdrawal anxiety and relapse have not been studied.

Material And Methods: Part 1: Forced alcohol drinking in gradually increasing concentration was administered till day 22 in rats. Effect of drugs on anxiety was assessed using elevated plus maze (EPM) and two-chambered box apparatus, after removal of alcohol. Part 2: For relapse, an alcohol deprivation effect model was used, rats were continuously offered alcohol and water for 4 consecutive weeks in a two-bottle choice paradigm, followed by 2 weeks of alcohol deprivation. Effect of drugs on alcohol consumption during the first hour of alcohol reintroduction was assessed. Animals were sacrificed and whole brain Tumor Necrosis Factor (TNF) α was estimated.

Results: Part 1: Anxiety at 3 hours was significantly lower following minocycline (20 mg/kg i.p.) or diazepam compared to vehicle control. Part 2: Acute administration of minocycline (5,10 and 20 mg/kg, i.p.) suppressed alcohol consumption significantly (p value<0.05) as compared to vehicle control. A significant decrease in whole brain TNF α was observed in animals treated with minocycline compared to untreated animals.

Conclusion: Minocycline attenuates alcohol withdrawal anxiety and disrupts alcohol relapse.
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http://dx.doi.org/10.2174/1574884713666180228110310DOI Listing
April 2019

Sitagliptin 100 mg vs glimepiride 1-3 mg as an add-on to insulin and metformin in type 2 diabetes (SWIM).

Endocr Connect 2017 Nov 5;6(8):748-757. Epub 2017 Oct 5.

Jothydev's Diabetes Research CentreTrivandrum, Kerala, India.

Objective: To compare the effect of itagliptin (100 mg) vs glimepiride (1-3 mg) as add-on therapy in Indian type 2 diabetes (T2DM) patients on treatment ith nsulin and etformin (SWIM study).

Research Design And Methods: This 24-week, controlled, open-label study randomized T2DM patients ( = 440) receiving a stable dose of metformin and insulin combination therapy to sitagliptin (100 mg) or glimepiride (1-3 mg) as add-on therapy. Baseline HbA1c was ≥7.3% and ≤8.5%. After a 6-week titration period for glimepiride (dose titrated every 2 weeks by 1 mg up to a maximum of 3 mg daily), patients were continued for 18 weeks on their respective tolerable doses of glimepiride (ranging from 1 mg to 3 mg) or sitagliptin (100 mg) along with metformin and insulin.

Results: Greater reductions in HbA1c and TDD of insulin were achieved with sitagliptin compared to glimepiride. HbA1c targets and reductions in TDD were achieved by more patients on sitagliptin than on glimepiride. Reductions in both body weight and BMI were also noted among patients on sitagliptin when compared to those on glimepiride, and more hypoglycemic events occurred with glimepiride treatment than with sitagliptin.

Conclusions: Sitagliptin (100 mg), when compared to glimepiride (1-3 mg), bestowed beneficial effects to T2DM patients in terms of achieving greater glycemic control and also brought significant reductions in total daily dose of insulin required, bodyweight, BMI and hypoglycemic events. Overall, the results suggest that sitagliptin (100 mg) is a superior agent over glimepiride (1-3 mg) as an add-on to insulin-metformin therapy among Asian Indians with T2DM.
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http://dx.doi.org/10.1530/EC-17-0100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5670271PMC
November 2017

Assessing the Therapeutic Utility of Professional Continuous Glucose Monitoring in Type 2 Diabetes Across Various Therapies: A Retrospective Evaluation.

Adv Ther 2017 08 30;34(8):1918-1927. Epub 2017 Jun 30.

Jothydev's Diabetes Research Centre, Konkalam Road, Mudavanmugal, Trivandrum, Kerala, 695032, India.

Background: There have been few large studies that have analyzed the effect of professional (masked) continuous glucose monitoring (P-CGM) on glycemic control in patients with type 2 diabetes (T2DM) who were on a broad spectrum of baseline therapies.

Methods: We performed a retrospective, blinded evaluation of glycemic control in 296 T2DM adults for 6 months following a 6- to 7-day study of their glycemic profile using masked P-CGM. At baseline, 91% of the patients were on some form of insulin treatment with oral hypoglycemic agents (OHA), while 7% were on one or more OHAs without insulin, and the remaining 2% were on GLP-1RAs. On the basis of the masked CGM profile, patients were counselled on diet and exercise change(s) in their baseline diabetes therapy by our professionally trained diabetes team. They also continued to receive regular treatment advice and dose titrations through our Diabetes Tele-Management System (DTMS). The baseline changes in hemoglobin A1C (A1C) observed in these patients after 6 months of undergoing P-CGM was compared to a matched control group.

Results: P-CGM revealed that the predominant pattern of hyperglycemia was postprandial while previously unknown hypoglycemia was found in 38% of the patients; over half of the cases of hypoglycemia were nocturnal. The mean A1C of the P-CGM group dropped from 7.5 ± 1.4% at baseline vs. 7.0 ± 0.9% at 6 months (p < 0.0001). The frequency of performing self-monitoring of blood glucose (SMBG) was also found to be significantly increased in these patients from the baseline. Meanwhile, no significant improvement in A1C was noted in the control group during the same time frame (7.7 ± 1.1% at baseline vs. 7.4 ± 1.1% at 6 months; p = 0.0663) and frequency of SMBG remained almost unchanged.

Conclusions: P-CGM can provide actionable data and motivate patients for diabetes self-care practices, resulting in an improvement in glycemic control over a wide range of baseline therapies.
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http://dx.doi.org/10.1007/s12325-017-0576-xDOI Listing
August 2017

Unproven Therapies for Diabetes and Their Implications.

Adv Ther 2017 01 18;34(1):60-77. Epub 2016 Nov 18.

Department of Endocrinology, Bharati Hospital, Karnal, Haryana, India.

Diabetes is a chronic disease and is one of the leading causes of morbidity and mortality worldwide. Being an ancient disease, many individuals follow complementary and alternative medicinal (CAM) therapies for either the cure or prevention of the disease. The popularity of these practices among the general public is in no way a testimony to their safety and efficacy. Due to the possibility of undesirable interactions with conventional medicines, it is imperative that patients are asked about CAM use during patient assessment. Patient- and physician-targeted awareness programs on various aspects of CAM use must be initiated to create a better understanding of evidence-based use of these practices. In addition, there should be guidelines in place based on clinical trial outcomes, and stricter regulations need to be enforced on CAM practices to ensure their safety and effectiveness.
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http://dx.doi.org/10.1007/s12325-016-0439-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5216071PMC
January 2017

Telemedicine for diabetes care: An Indian perspective - feasibility and efficacy.

Indian J Endocrinol Metab 2015 Nov-Dec;19(6):764-9

Department of Diabetes, Jothydev's Diabetes Research Centre, Trivandrum, Kerala, India.

Diabetes is a chronic and costly disease. In India, the usual practice among patients is to visit the doctor once in every 2-3 months to get advice on changes in the dosages of medications. The Diabetes Tele Management System (DTMS(®)) is a telemedicine based follow-up program originally introduced at Jothydev's Diabetes Research Centre at Trivandrum South India in 1998. It is a chronic disease management system which enables patient to interact lively with a professionally trained multidisciplinary team comprising of diabetes educators, nurses, dieticians, pharmacists, psychologists, physicians, etc., in modifying the dosages of medications, diet, and physical activity either through telephone/email/secure website. The uniquely designed software and the trained multidisciplinary team overcomes the globally recognized major barriers to diabetes management namely fear of hypoglycemia, polypharmacy, discontinuation of stains, and antihypertensives or wrong injection techniques. DTMS is designed to provide individualized therapy advices on glycosylated hemoglobin, blood pressure, and low density lipoprotein customized to multiple patient characteristics which help attain goals of therapy. The system has been tested on various platforms over a decade and was shown to be a patient friendly approach with successful outcomes due to a live "round-the-clock" interactive communication in contrast to text or recorded messages. The major challenge to the widespread use of DTMS(®) is seeking a source of funding this unique telemedicine program.
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http://dx.doi.org/10.4103/2230-8210.167560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673803PMC
December 2015

CSII as an Alternative Therapeutic Strategy for Managing Type 2 Diabetes: Adding the Indian Experience to a Global Perspective.

Curr Diabetes Rev 2016 ;12(4):312-314

Jothydev's Diabetes Research Centre, Trivandrum, Kerala, India.

Background: Alternative insulin therapy with continuous subcutaneous insulin infusion (CSII) is offered with an objective of achieving better glycemic control, minimising glucose variability and thereby, preventing or reducing the risk of microvascular and macrovascular complications in people with type 1 or type 2 diabetes. Trials conducted across the world have demonstrated that CSII is more beneficial in terms of achieving better metabolic control in type 2 diabetes. Unawareness about the multiple benefits of CSII is a major hurdle to its widespread use. In India, insulin pumps are more popular in type 2 diabetes and we have been deploying pumps since 2004. Previously, we have reported reduction in HbA1c, body weight and total daily dose of insulin in patients on insulin pump therapy (IPT).

Objective: The objective of this study was to assess the attitude and behavior of type 2 diabetes patients on IPT.

Methods: A cross sectional survey was conducted among selected type 2 diabetes patients who have been on IPT for more than 3 years. We administered questionnaires to assess level of satisfaction with pump, improvement in quality of life (QoL), use of the advanced functions and average cost incurred by being on pump. Difference in scores between males and females were assessed using chiquare test for proportions and t-test for differences in means.

Results: Improvement in QoL after being on pump was appreciated by 92%. The level of satisfaction was rated as 'fully satisfied' by 52% of respondents while 26% found being on pump, 'satisfactory'. Ninety percent thought that the pump met their expectations.

Conclusion: The attitude and behavior of type 2 diabetes patients on IPT is positive and promising.
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http://dx.doi.org/10.2174/1573399812666151208112607DOI Listing
March 2017

Persistence of Hepatitis C Virus Traces after Spontaneous Resolution of Hepatitis C.

PLoS One 2015 16;10(10):e0140312. Epub 2015 Oct 16.

Molecular Virology and Hepatology Research Group, Faculty of Medicine, Memorial University, St. John's, Newfoundland and Labrador, Canada.

Hepatitis C virus (HCV) frequently causes chronic hepatitis, while spontaneous recovery from infection is infrequent. Persistence of HCV after self-limited (spontaneous) resolution of hepatitis C was rarely investigated. The current study aimed to assess incidence and robustness of HCV persistence after self-resolved hepatitis C in individuals with normal liver enzymes and undetectable virus by conventional tests. Applying high sensitivity HCV RNA detection approaches, we analyzed plasma and peripheral blood mononuclear cells (PBMC) from individuals with previous hepatitis C infection. Parallel plasma and PBMC from 24 such non-viraemic individuals followed for 0.3-14.4 (mean 6.4) years were examined. Additional samples from 9 of them were obtained 4.5-7.2 (mean 5.9) years later. RNA was extracted from 250 μl plasma and, if HCV negative, from ~5 ml after ultracentrifugation, and from ex vivo stimulated PBMC. PBMC with evidence of HCV replication from 4 individuals were treated with HCV protease inhibitor, telaprevir. HCV RNA was detected in 14/24 (58.3%) plasma and 11/23 (47.8%) PBMC obtained during the first collection. HCV RNA replicative strand was evident in 7/11 (63.6%) PBMC. Overall, 17/24 (70.8%) individuals carried HCV RNA at mean follow-up of 5.9 years. Samples collected 4.5-7.2 years later revealed HCV in 4/9 (44.4%) plasma and 5/9 (55.5%) PBMC, while 4 (80%) of these 5 PBMC demonstrated virus replicative strand. Overall, 6/9 (66.7%) individuals remained viraemic for up to 20.7 (mean 12.7) years. Telaprevir entirely eliminated HCV replication in the PBMC examined. In conclusion, our results indicate that HCV can persist long after spontaneous resolution of hepatitis C at levels undetectable by current testing. An apparently effective host immune response curtailing hepatitis appears insufficient to completely eliminate the virus. The long-term morbidity of asymptomatic HCV carriage should be examined even in individuals who achieve undetectable HCV by standard testing and their need for treatment should be assessed.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0140312PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4608821PMC
June 2016

Lockit Plus Catheter Securement Device for Lumbar Subarachnoid Drains.

J Neurosurg Anesthesiol 2016 07;28(3):277

Department of Anaesthesiology, CMC Vellore, Vellore, Tamil Nadu, India.

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http://dx.doi.org/10.1097/ANA.0000000000000237DOI Listing
July 2016

Efficacy and safety of liraglutide therapy in 195 Indian patients with type 2 diabetes in real world setting.

Diabetes Metab Syndr 2015 Jan-Mar;9(1):30-3. Epub 2014 May 22.

Jothydev's Diabetes Research Centre, Trivandrum, Kerala, India(1).

Background: GLP-1 analogues has established role in the management of type 2 diabetes mellitus (T2DM). Liraglutide, a human GLP-1 analogue is used as an adjunct to diet and exercise in adults with T2DM for improvement of glycemic control.

Objective: To assess the efficacy and safety of liraglutide in Indian patients with T2DM in real-world setting.

Methods: A prospective, open label, single arm, single centre, observational study of 24 weeks duration in a real-world setting. Subjects with T2DM with impaired glucose control despite of antidiabetic therapy and clinically suitable for liraglutide therapy were enrolled and managed. All subjects received liraglutide therapy in addition to their existing anti-diabetic therapy. Starting dose of liraglutide (Victoza) was 0.6 mg/day for 7 days followed by 1.2 mg/day for next 7 days and finally 1.8 mg/day for 22 weeks. Subjects were evaluated at baseline and at 24 weeks. Adverse events (AE) noted during course of therapy were recorded. Student t test (two tailed, dependent) was performed for assessment of statistical significance.

Results: Total 195 subjects were studied over 24 weeks. Mean fasting plasma glucose (FPG) was decreased from 163.81 mg/dL to 111.6 (P<0.001); similarly HbA1c was reduced from 8.14% to 6.96% (P=0.006) at 24 weeks. At week 24, 49.23% and 41.03% subjects treated with liraglutide reached an HbA1c<7.0% and ≤6.5%, respectively. Mean weight was reduced from 86.41 kg to 82.37 kg (P<0.001). Additionally mean systolic and diastolic blood pressure was reduced from 129.31 and 76.18 mm of Hg to 119.59 (P=0.90) and 70.88 (P<0.001) mm of Hg, respectively. Serum cholesterol was reduced from 166.68 mg/dL to 124.86 mg/dL (P<0.001). Twenty-two (11.28%) subjects reported adverse events (AE), the most common AEs being vomiting, tiredness, loose motion and nausea. All AEs were mild to moderate in nature without any serious AE.

Conclusion: In 195 Indian patients with T2DM receiving anti-diabetic drugs, addition of liraglutide resulted in significant improvement in glycemic parameters and was well tolerated. Clinically significant reduction in weight, blood pressure and serum cholesterol were also noted.
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http://dx.doi.org/10.1016/j.dsx.2014.04.034DOI Listing
September 2015

Manganese influx and its utilization efficiency in wheat.

Indian J Exp Biol 2014 Jun;52(6):650-7

Manganese deficiency in wheat has become an important nutritional disorder particularly in alkaline calcareous soils where rice-wheat rotation is followed. This experiment was aimed to study the mechanism of Mn efficiency during various developmental stages in six wheat cultivars grown at two Mn levels viz. 0 and 50 mg Mn kg(-1) soil (Mnapplied as MnSO4 x H20) in pots. The Mn vegetative efficiency calculated on the basis of shoot dry weight at anthesis indicated HD 2967 and PBW 550 (bread wheat) as Mn efficient and durums as Mn inefficient. The efficient cultivars recorded highest values for influx, uptake, shoot dry weight, leaf area/plant, SPAD index, F(v)/F(m)ratio and root length that explained their higher efficiencies whereas inefficiency of durum cultivars was attributed to their smaller roots and lower influx. Under Mn deficiency, PDW 314 and PDW 291 retained 68% and 64%, respectively, of total Mn uptake in vegetative parts (stem and leaves) and lowest in grains 7% and 5%, respectively, whereas PBW 550, BW 9178 and HD 2967 retained 29, 37 and 34% in vegetative parts, and 21, 17 and 15 % in grains, respectively at maturity. Higher utilization efficiency of efficient genotypes also indicated that increased Mn uptake with Mn supply produced more efficiently grains in efficient genotypes but vegetative parts in inefficient genotypes. Hence Mn efficiency of a cultivar could be explained by longer roots, higher uptake, influx and efficiency index during vegetative phase and higher grain yield and utilization efficiency during generative phase.
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June 2014

γ-H2AX+CD8+ T lymphocytes cannot respond to IFN-α, IL-2 or IL-6 in chronic hepatitis C virus infection.

J Hepatol 2013 May 17;58(5):868-74. Epub 2012 Dec 17.

Department of Medicine, School of Clinical Medicine, University of Cambridge, Cambridge, UK.

Background & Aims: Age is the dominant prognostic factor influencing the natural history of hepatitis C virus (HCV) infection and treatment response. Accelerated lymphocyte telomere shortening in HCV infection correlates with adverse clinical outcomes. Critical telomere shortening generates double-stranded DNA breaks (DSB) inducing the DNA damage response, leading to replicative senescence. The phenotype and function of CD8+ T lymphocytes and the in vitro response to IFN-α in relation to the DNA damage response were investigated in patients with chronic HCV infection.

Methods: CD8+ T lymphocytes with DSB were identified by expression of γ-H2AX (Ser-139) in 134 HCV-exposed subjects and 27 controls. Telomere length was determined by flow-FISH; cytokine expression by intracellular cytokine staining; in vitro responses to IFN-α, IL-2 or IL-6 by phospho-STAT1 (Y701) or phospho-STAT5 (Y694) expression.

Results: The proportion of circulating CD8+γ-H2AX+ T lymphocytes rose with increasing fibrosis stage (p=0.0023). CD8+γ-H2AX+ T lymphocytes were enriched in liver compared to blood (p=0.03). CD8+γ-H2AX+ T lymphocytes demonstrated increased IFN-γ (p=0.02) and reduced IL-2 expression (p=0.02). CD8+γ-H2AX+ T lymphocytes failed to phosphorylate STAT1 in response to IFN-α compared to unfractionated CD8+ T lymphocytes (p <0.0001). More widespread failure of Jak/Stat signalling in CD8+γ-H2AX+ T lymphocytes was suggested by impaired phosphorylation of STAT1 with IL-6 (p=0.002) and STAT5 with IL-2 (p=0.0039) compared to unfractionated CD8+ T-lymphocytes.

Conclusions: In chronic HCV infection, CD8+γ-H2AX+ T lymphocytes are highly differentiated with shortened telomeres, are more frequent within the liver, are associated with severe fibrosis and fail to activate Jak/Stat pathways in response to IFN-α, IL-2 or IL-6, perhaps explaining treatment failure in those with severe fibrosis.
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http://dx.doi.org/10.1016/j.jhep.2012.12.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3625113PMC
May 2013

Suggested use of vaccines in diabetes.

Indian J Endocrinol Metab 2012 Nov;16(6):886-93

Department of Diabetology, Jothydev's Diabetes and Research Centre (JDC), Trivandrum, Kerala, India.

Diabetes has emerged as a disease of major public health importance in India affecting the rich and the poor alike. Conventionally, comprehensive diabetes management is aimed at preventing micro and macro vascular complications. However, morbidity and mortality due to infections are also significant. In developing countries like India, the concept of adult immunization is far from reality. Recently the H1N1 pandemic has triggered the necessity for considering immunization in all age groups for the prevention of vaccine-preventable fatal infectious diseases. Considering the economics of immunization in a developing country, providing free vaccines to all adults may not be a practical solution, although the free universal immunization program for children is in existence for several decades. There is no consensus on the use of vaccines in diabetes subjects in India. However, there are some clinics offering routine pneumococcal, influenza and other vaccinations. Patients with diabetes have a deranged immune system making them more prone for infections. Hospitalization and death due to pneumococcal disease and influenza are higher in diabetes patients. They, like other healthy individuals, have a normal humoral response to vaccination with clinically significant benefits. The American Diabetes Association, Advisory Committee on Immunization Practices, Centers for Disease Control and Prevention, World Health Organization, United Kingdom Guidelines and a number of other scientific organizations have well defined guidelines for vaccination in diabetes. In this article we make some suggestions for clinicians in India, regarding use of vaccines in subjects with diabetes.
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http://dx.doi.org/10.4103/2230-8210.102982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3510956PMC
November 2012

Cost-effective use of telemedicine and self-monitoring of blood glucose via Diabetes Tele Management System (DTMS) to achieve target glycosylated hemoglobin values without serious symptomatic hypoglycemia in 1,000 subjects with type 2 diabetes mellitus--a retrospective study.

Diabetes Technol Ther 2012 Sep 26;14(9):772-6. Epub 2012 Jun 26.

Jothydev's Diabetes and Research Center, JDC Junction, Mudavanmugal, Trivandrum, Kerala, India.

Objective: This study assessed the effectiveness, safety, and costs of the Diabetes Tele Management System (DTMS(®); Dr. Jothydev Kesavadev, Jothydev's Diabetes and Research Center, Kerala, India)-based health care in type 2 diabetes (T2D) patients in South India.

Research Design And Methods: We conducted a retrospective cohort study using electronic health records in our Center. The study sample comprised T2D patients enrolled in DTMS-based management, 30-75 years old, eligible for a glycosylated hemoglobin (HbA1c) target <6.5% and actively participating in various components of DTMS such as regular reporting of self-monitoring of blood glucose (SMBG) values and dose adjustments via telemedicine. We analyzed HbA1c, lipid profile, and other parameters measured at the first visit and on subsequent physical visits at months 3 and 6 and estimated the incidence of hypoglycemia.

Results: We analyzed records of 1,000 subjects with 6-month follow-up data (mean age, 53.2 ± 9.8 years; 64% male). Patients had an average of 17 ± 2 telemedicine follow-ups and reported 66,745 SMBG values over 6 months. The mean ± SD HbA1c value was 8.5 ± 1.4% at the initial visit and was reduced to 6.3 ± 0.6% at 6 months (P<0.0001). The rate of SMBG values <70 mg/dL was approximately 0.04/patient/month, with 84% patients reporting no hypoglycemia. The recurring extra cost to patient for DTMS, not considering cost of oral drugs and insulin, was equivalent to 9.66 U.S. dollars/month.

Conclusions: DTMS, based on telemedicine follow-up and multidisciplinary care with SMBG-based monitoring, appears to be safe and cost-effective in the intensive treatment of T2D without serious co-morbidities. This system also avoids limitations of a traditional health care such as the need for very frequent physical visits for each and every drug dose adjustment, diet, and exercise advice.
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http://dx.doi.org/10.1089/dia.2012.0088DOI Listing
September 2012

Liraglutide therapy beyond glycemic control: an observational study in Indian patients with type 2 diabetes in real world setting.

Int J Gen Med 2012 13;5:317-22. Epub 2012 Apr 13.

Jothydev's Diabetes Research Center, JDC Junction, Trivandrum, Kerala, India 695032.

Background: Liraglutide is an analog of human glucagon-like peptide-1 (GLP-1) and acts as a GLP-1 receptor agonist. Liraglutide is presently used in the treatment of selected patients with type 2 diabetes mellitus (T2DM).

Objective: To assess efficacy and safety of liraglutide in, overweight and obese Indian patients with T2DM.

Methods: A single center, prospective, open-labeled, single-arm, observational study for 24 weeks in a real-world setting. Fourteen overweight and obese patients with T2DM who were clinically suitable for liraglutide therapy received liraglutide injections. The starting dose of liraglutide (Victoza) injection was 0.6 mg/day for 3 days followed by 1.2 mg for next 10 days and finally 1.8 mg/day for 22 weeks. Patients were evaluated at baseline and after 12 and 24 weeks of therapy. Adverse events (AE) noted during course of therapy were recorded. A repeated measure analysis of variance was performed to assess statistical significance.

Results: Fourteen patients were studied for 24 weeks. After 24 weeks of liraglutide therapy, mean fasting and postprandial plasma glucose decreased by 48.5 mg/dL and 66.71 mg/dL, respectively (P = 0.002 and P = 0004 over 24 weeks, respectively). A mean reduction of 2.26% of glycosylated hemoglobin was noted (P < 0.001 over 24 weeks). Mean decrease in body weight of 8.65 kg and mean decrease in body mass index of 3.26 kg/m(2) was noted (P < 0.001 over 24 weeks for each parameter). Systolic blood pressure was reduced by 15.15 mm of Hg (P = 0.004). Significant improvement in total cholesterol, low-density lipoprotein, triglycerides, and serum creatinine was noted. Nine patients reported AEs. The AEs noticed were nausea (n = 6), feeling of satiety (n = 3), and vomiting (n = 1). No serious AE or hypoglycemic episodes were observed.

Conclusion: Liraglutide once a day improved overall glycemic control and was well tolerated. Clinically significant reduction in body weight, systolic blood pressure and improvement in lipid profile were noticed with liraglutide therapy in addition to glycemic control.
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http://dx.doi.org/10.2147/IJGM.S27886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3333831PMC
October 2012

An Asian Indian woman with Wolfram syndrome on insulin pump: successful pregnancy and beyond.

Diabetes Technol Ther 2011 Jul 25;13(7):781-5. Epub 2011 Apr 25.

Jothydev's Diabetes and Research Center, Mudavanmugal, Trivandrum, Kerala, India.

Wolfram syndrome (WS), or DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness), is a rare autosomal recessive neurodegenerative disorder with a median life expectancy of 30 years and occurs in one in 770,000 live births. To date only five successful pregnancies have been reported among WS subjects worldwide. Here we describe the sixth report of successful pregnancy in a WS patient and the first from India. The subject is still on an insulin pump, now 31 years old and doing well. She developed diabetes at 5 years of age, optic atrophy at 14 years, and diabetes insipidus at 25 years and had a successful delivery in 2007 while on an insulin pump. Sequencing of exonic regions of the WFS1 gene showed five changes, two of which were pathogenic (exon 8). Magnetic resonance imaging of brain showed generalized neurodegenerative changes. The benefits of continuous subcutaneous insulin infusion and that of tight metabolic control in prevention of abortions and fetal malformations in diabetes associated with pregnancy are well documented. The impression of probable pleiotropic action of insulin pumps over and above that of glycemic reduction is gaining momentum. Recent evidence supports use of insulin pumps in alleviating neuropathic pain in diabetes, probably by virtue of its action in minimizing mean amplitude of glycemic excursions not possible with conventional insulin shots. WS is a progressive neurodegenerative disorder, which will probably help us in understanding the positive impact of continuous subcutaneous insulin infusion in prolonging the life span and retarding neuronal damage in WS.
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http://dx.doi.org/10.1089/dia.2010.0242DOI Listing
July 2011

Effect of open air drying, LPG based drier and pretreatments on the quality of Indian gooseberry (aonla).

J Food Sci Technol 2010 Oct 15;47(5):541-8. Epub 2010 Oct 15.

Department of Natural Resource Management, Central Research Institute for Dryland Agriculture (CRIDA) (Indian Council of Agricultural Research), Hyderabad, 500059 India.

The aonla fruits (whole fruit, pricking, splits, segments) were subjected to pretreatments like blanching, osmotic dehydration with salt (2%) and sugar (40%) in different experiments before drying to obtain a product with better keeping quality. An LPG based drier (CRIDA drier) with capacity to dry 50 kg of fresh Indian gooseberry (aonla) was used. Nutritional quality and rehydration characteristics of CRIDA drier dried products were higher and free from contamination. Drying time was shortest for blanched and osmotically dehydrated segments dried in CRIDA drier and the product had better vitamin C retention, rehydration characteristics and sensory acceptability compared to sun or cabinet drier dried product. The additional expenditure spent on gas in CRIDA drier is compensated by reduced labour cost and higher price for the better quality product. Alternate energy sources like biogas and biomass can be used as fuel in the CRIDA drier.
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http://dx.doi.org/10.1007/s13197-010-0093-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551108PMC
October 2010

Features of immune senescence in liver transplant recipients with established grafts.

Liver Transpl 2010 May;16(5):577-87

Department of Medicine, University of Cambridge, Cambridge, UK.

Immune senescence is the normal process whereby the human immune system ages, but becomes less effective. We investigated whether liver transplant recipients have features of immune senescence. Lymphocytes from 97 liver transplant recipients with established grafts and 41 age-matched and sex-matched controls were subjected to an 8-color flow cytometry assay that measured expression of killer cell lectin-like receptor subfamily G member 1, cluster of differentiation 127 (CD127), CD45RO, CD27, CD28, CD4, CD8, and CD57. Lymphocyte telomere length was assessed by flow-fluorescence in situ hybridization. Cases were compared with controls for each marker of immune senescence using a Mann-Whitney U test. For liver transplant recipients, linear regression analyses identified associations between markers of immune senescence and clinical or demographic characteristics. Lymphocytes from liver transplant recipients expressed more phenotypic markers of maturity than did lymphocytes from controls. Lymphocyte telomeres were shorter in liver transplant recipients than in controls. Age, hepatocellular carcinoma at transplantation, and skin malignancy developing after transplantation were associated independently with shortened lymphocyte telomeres. Increasing age and previous cytomegalovirus infection were associated independently with phenotypic markers of lymphocyte maturity. Thus, lymphocytes from liver transplant recipients are older "biologically" than lymphocytes from age-matched and sex-matched controls. Hepatocellular carcinoma at transplantation, subsequent skin malignancy, and previous cytomegalovirus infection are associated with lymphocyte senescence in liver transplant recipients.
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http://dx.doi.org/10.1002/lt.22033DOI Listing
May 2010
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