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

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.

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

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.

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

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.

Manganese influx and its utilization efficiency in wheat.

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.

Adverse Drug Reactions and Prescription Patterns of Antiretroviral Drugs: A Longitudinal Observational Study From a Tertiary Care Hospital in Western India.

Background In 2018, the World Health Organisation (WHO) released interim guidelines, advising a change of regimens to dolutegravir-based first- and second-line antiretroviral therapy (ART), based on which, in 2021, the National Aids Control Organisation (NACO) updated its guidelines to include the tenofovir + lamivudine + dolutegravir (TLD) regimen as a first line of therapy for all people living with HIV (PLHIV) and second- and third-line regimens to dolutegravir-based regimens. Considering this change of regimen, the adverse drug reaction (ADR) profiling and longitudinal prescription pattern of antiretroviral and concomitant medications in adult patients at the ART centre of a tertiary care hospital were assessed in this study. Methods Ninety-seven PLHIV out of all the patients who attended the ART centre from September 2021 to July 2022 were enrolled and followed up for six months. The ADRs that occurred during this period were collected along with details of prescription patterns and analyzed by descriptive statistics. Causality assessment for ADR was done using the World Health Organisation-Uppsala Monitoring Centre (WHO-UMC) scale. Results Seventy-eight percent (n=76 out of 97) of patients experienced at least one ADR, and 128 ADRs were seen in 97 patients. The most common ADRs were increased alkaline phosphatase (39.0%, n=128), dyslipidaemia (12.5%, n=128), and nephrotoxicity (10.1%, n=128). The drug most suspected of causing ADRs was dolutegravir (27.5%, n=342). The most common therapeutic regimen was TLD (71.2%, n=97). The most prescribed drug was lamivudine (30.6%, n=1183). The most prescribed concomitant medication was cotrimoxazole (15%, n=312). Conclusions Dolutegravir-based regimens have been implemented for PLHIV in a phased-out manner from previous non-dolutegravir-based ART regimens, which is in line with the recent NACO guidelines. However, it has also led to an increase in dolutegravir-associated ADRs like increased alkaline phosphatase, dyslipidaemia, and nephrotoxicity. Continuous monitoring of prescriptions and ADRs can add to our knowledge regarding their use and ADRs.

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

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.

Real-World User and Clinician Perspective and Experience with MiniMed™ 780G Advanced Hybrid Closed Loop System.

INTRODUCTION: The advanced hybrid closed loop (AHCL) MiniMed™ 780G system changes basal insulin delivery every 5 min and auto bolus in response to sensor glucose values. We assessed the performance of the AHCL system in real-world settings for individuals with type 1 diabetes (T1DM) as well as user and clinician perspectives and satisfaction. METHODS: We held two peer group discussions: one having adults with T1DM/parents of children and adolescents with T1DM to understand their experiences with the AHCL system and another with healthcare providers (HCPs). Responses from the discussions were analyzed and categorized into themes by two independent researchers, with any inconsistencies resolved by consensus. We also analyzed data from the system uploaded to CareLink personal software. Glycemic outcomes, including time in range (TIR), time below range (TBR), time above range (TAR), mean sensor glucose (SG) levels, glucose management indicator (GMI), sensor use, and percentage of time spent in AHCL, were determined. RESULTS: The peer group discussions revealed numerous key themes and issues for each group, such as the significance of setting reasonable expectations, carbohydrate counting and bolus dosing, technical difficulties, and overall user experience. The users (n = 25; T1DM; 17 female; age 13.8 ± 7.49 years; A1C 6.54 ± 0.45%; duration of diabetes 6 ± 6.78 years) were very satisfied with the system. Most users experienced consistent blood glucose values with very few hypoglycemic episodes. However, there were a few limitations reported, such as hyperglycemic episodes caused by inaccuracies in carb counting, issues with sensor connectivity, and cannula blockages or kinking for those using insulin Fiasp. Users achieved a mean GMI of 6.4 ± 0.26%, TIR of 83.0 ± 8.12%, TBR (54-70 mg/dL) of 2.0 ± 0.81%, TBR* (< 54 mg/dL) of 0%. All of the users achieved a TIR of > 70%. CONCLUSION: The use of the AHCL system in T1DM resulted in robust glycemic control, minimizing hypoglycemia. Providing training to both users and HCPs can help them use the system effectively.

S-adenosyl methionine improves motor co-ordination with reduced oxidative stress, dopaminergic neuronal loss, and DNA methylation in the brain striatum of 6-hydroxydopamine-induced neurodegeneration in rats.

PURPOSE: Parkinson's disease (PD) is the most common age-related neurodegenerative disease worldwide. S-adenosyl methionine (SAMe), a methyl donor that plays an important role in DNA methylation, could replenish the cellular antioxidant glutathione (GSH). Herein, we investigated the neuroprotective effects of SAMe in 6-hydroxydopamine (6-OHDA) rat models of PD and elucidated the underlying mechanism. METHODS: PD model rats were developed by injecting 6-OHDA stereotaxically into the striatum. In Phase 1 of the study, we performed the neurobehavioral tests, GSH assay, and histopathology to evaluate the neuroprotective effects of SAMe. The animals were treated with SAMe (150 or 300 mg/kg body weight) orally for 28 days. The positive control group received selegiline (5 mg/kg), whereas the disease control group received normal saline. In Phase 2, we evaluated the striatal dopamine levels and performed DNA methylation assay to uncover the mechanism of action of SAMe. In this phase, a higher dose of SAMe (300 mg/kg) was used. RESULTS: SAMe (300 mg/kg) treatment for 4 weeks significantly attenuated the abnormal circling behavior in PD rats (p < 0.05). Moreover, SAMe at both doses (150 and 300 mg/kg) enhanced the performance of PD rats in the open field test and stepping test (p < 0.05). SAMe treatment significantly increased the GSH levels, and at high dose, SAMe restricted neuronal loss in the striatum of PD-model rats (p < 0.05). Moreover, SAMe treatment led to a significant recovery in the dopamine levels and improved the DNA methylation status in the dopaminergic neurons (p < 0.05) of PD model rats. CONCLUSION: SAMe exhibits antioxidant activity and DNA methylation modulating effects in 6-OHDA model PD rats. Moreover, SAMe prevents neuronal loss in PD rats suggesting that SAMe has therapeutic potential in preventing PD development. The neuroprotective potential of SAMe is greater at high doses.

Empowering Patients with Type 1 Diabetes through a Multidisciplinary Team-assisted, Technology-Enabled Education Program.

BACKGROUND: Carbohydrate counting is a tool that helps patients with type 1 diabetes (T1D) to control their blood glucose. It calculates the bolus insulin dose needed from the total amount of carbohydrates consumed at each meal. However, carbohydrate counting can be quite challenging. The Diabetes Tele Management System® (DTMS®) is a telemedicine-based program that enables the patient to interact directly with a professionally trained, multidisciplinary team (MDT) of experts. This, along with technology-enabled education programs, could allow people with T1D to achieve glycemic control. METHODS: Fifty patients with T1D between 5 and 35 years with a diabetes duration of at least 6 months, baseline HbA1c of 7 or above, using SCII or MDI and willing to take part in the study were invited to participate in an MDT-assisted technology-enabled program and trained trimonthly on carbohydrate counting. The control group went on to perform carbohydrate counting independently and used technologies at their convenience. The test group additionally received continuous individual assistance from the MDT. RESULTS: The MDT-assisted patients had significantly decreased HbA1c, blood glucose levels, decreased episodes of hyperglycemia and hypoglycemia, and reported a more positive outlook on life. CONCLUSION: Carbohydrate counting remains a challenge for youth with T1D, and errors in counting can have a clinical impact. Our data suggested that the assistance from an MDT of experts was associated with improved carbohydrate counting, which led to improved glycemic control and reduced complications.

Comparing the benefits of applying a vacuum assisted lancing device in reducing lancing pain, improving self-monitoring frequency and reducing HbA1c in people with diabetes.

BACKGROUND AND AIMS: For most people with diabetes (PwD), lancing fingertips for obtaining a blood sample is unavoidable during blood glucose monitoring (BGM). This study investigated the potential benefits of applying a vacuum over the penetration site immediately, before, during, and after lancing to determine if a vacuum would allow a less painful lancing process from fingertips and alternate sites, while still drawing sufficient blood, thereby allowing PwD to have a painless lancing experience and improving self-monitoring frequency. The cohort was encouraged to use a commercially available vacuum assisted lancing device. Change in pain perception, testing frequency, HbA1c, and future probability of VALD use were determined. METHODS: In a 24-week randomized open-label, interventional, cross-over trial, 110 PwD were recruited who used VALD and non-vacuum conventional lancing devices, for 12 weeks each. Percentage reduction in HbA1c, percentage BGM adherence, scores of pain perception, and probability of selecting VALD in the future were measured and compared. RESULTS: There was reduction in overall HbA1c values (mean ± SD), (from 9.01 ± 1.68% at baseline to 8.28 ± 1.66%) and individually in T1D (from 8.94 ± 1.77% to 8.25 ± 1.67%) and T2D (from 8.31 ± 1.17% to 8.59 ± 1.30) after using VALD for 12 weeks. Lower pain perception and high probability of using VALD over conventional devices were observed. CONCLUSION: The study highlights the benefits of applying a vacuum to the lance site which enhances the effectiveness in reducing and eliminating pain, improving self-monitoring frequency, and lowering HbA1c over non-vacuum conventional devices.

Paracetamol toxicity in classic homocystinuria: Effect of N-acetylcysteine on total homocysteine.

Classical homocystinuria (HCU) is caused by cystathionine ß-synthase deficiency leading to impaired homocysteine transsulfuration and accumulation of homocysteine and methionine. Patients present with a wide spectrum of manifestations including ocular, skeletal, neuropsychiatric, and vascular manifestations. We report a 48-year-old female with pyridoxine-unresponsive HCU treated with betaine, cyanocobalamin, and folate. Her diet was non-restricted due to intolerance of low-methionine diet. She was admitted to hospital following a fall, with multiple fractures and subsequently developed acute liver failure with encephalopathy. Shock, sepsis, and liver ischaemia/thrombosis were excluded. In the context of glutathione depletion expected in HCU, hepatic dysfunction was presumed to be due to iatrogenic paracetamol toxicity, despite paracetamol intake at conventional therapeutic dose, with role of hypermethioninemia as a contributing factor being uncertain. Betaine was discontinued on hospital admission. N-Acetylcysteine (NAC) infusion was initiated. Plasma total homocysteine (tHcy) was 3.4 µmol/L 9 days following initiation of NAC treatment with a markedly elevated plasma methionine of 1278 µmol/L. tHcy concentration returned to pre-admission baseline after NAC was discontinued. Recovery following this episode was slow with a prolonged cholestatic phase and gradual improvement in jaundice and coagulopathy. We recommend that paracetamol should be administered cautiously in HCU patients due to underlying glutathione depletion and risk of toxicity even at therapeutic doses. NAC is clearly effective in lowering tHcy in classical HCU in the short-term however further research is required to assess clinical efficacy and use as a potential therapy in classical HCU.

Evaluation of Antidepressant Effect of Minocycline in Alcohol Abstinence-Induced Depression Model in Mice.

Introduction Depression is one of the common comorbidities seen in chronic alcohol use disorder. Also, alcohol withdrawal induces depression and anxiety, which is associated with relapse in alcohol consumption. Minocycline, a tetracycline derivative, has shown an antidepressant effect in preclinical models. However, their effect on alcohol withdrawal-induced depression has not been studied. Therefore, the current study has been undertaken to evaluate the effect of minocycline on alcohol abstinence-induced depression models in mice. Method We conducted the study in two models. C57bl/6 mice were given a two-bottle choice (alcohol + water) for 28 days. During alcohol abstinence of 14 days, mice were treated with 10 mg/kg, 30 mg/kg, and 50 mg/kg of minocycline and were evaluated for behavioral changes using the forced swim test (FST) and tail suspension test (TST). A sucrose preference test was carried out where mice were exposed to binge alcohol drinking protocol for 12 days, where a two-bottle choice (alcohol or water) was given. This was followed by exposing the mice to a two-bottle choice paradigm (alcohol + sucrose) and they were divided into groups - no treatment group, vehicle-treated, minocycline 30 mg/kg or minocycline 50 mg/kg treated - and consumption of sucrose was assessed. Result In the forced swim test, a significant decrease in immobility time (p<0.05) was observed in the high-dose minocycline group (82.75±19.09) as compared to the vehicle control group (128.12±35.44). In the tail suspension test also, a significant decrease in immobility time (p<0.05) was seen in the high-dose minocycline group (83.75±18.61) as compared to the vehicle control group (122.25±18.51). The water and alcohol intake were comparable among all groups. In the sucrose preference test, it was found that the minocycline 50 mg/kg group had the highest sucrose preference (55%) followed by the minocycline 30 mg/kg group (50%) as compared to 42% in the vehicle control group. Significant reduction in brain-derived neurotrophic factor (BDNF) levels was seen with minocycline 50 mg/kg (p<0.05) and minocycline 30 mg/kg group (p<0.05) in BDNF levels when compared to the normal control group. Conclusion Minocycline in a higher dose (50 mg/kg) has shown an effect in alcohol withdrawal-induced depression in the abstinence-induced two-bottle choice model in mice. Both doses of minocycline have shown an effect in the sucrose preference test in the alcohol withdrawal-induced depression model.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.