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| 1 | Molecular targets in the treatment of alcoholic hepatitis显示文摘Alcohol related costs to health and society are high. One of the most serious complications of alcohol misuse to the individual is the development of alcoholic hepatitis (AH), a clinical syndrome of jaundice and progressive inflammatory liver injury in patients with a history of recent heavy alcohol use. It has a poor outcome and few existing successful therapies. The use of glucocorticoids in patients with severe AH is still controversial and there remains a group of patients with glucocorticoid-resistant disease. However, as our understanding of the pathogenesis of the condition improves there are opportunities to develop new targeted therapies with specific actions to control liver inflammation without having a detrimental effect on the immune system as a whole. In this article we review the molecular mechanisms of AH concentrating on the activation of the innate and adaptive immune response. We consider existing treatments including glucocorticoids, anti-tumor necrosis factor therapy and pentoxifylline and their limitations. Using our knowledge of the disease pathogenesis we discuss possible novel therapeutic approaches. New targets include pro-inflammatory cytokines such as interleukin (IL)-17, chemokines and their receptors (for example IL-8, CXCL9 and CXCR3) and augmentation of anti-inflam- matory molecules such as IL-10 and IL-22. And there is also future potential to consider combination therapy to selectively modulate the immune response and gain control of disease. | Ashwin D Dhanda Richard WL Lee Peter L Collins C Anne McCune | 2012 | World Journal of Gastroenterology2012，18，39： | 9 |
| 2 | Oxidative stress in alcohol-related liver disease显示文摘Alcohol consumption is one of the leading causes of the global burden of disease and results in high healthcare and economic costs.Heavy alcohol misuse leads to alcohol-related liver disease,which is responsible for a significant proportion of alcohol-attributable deaths globally.Other than reducing alcohol consumption,there are currently no effective treatments for alcohol-related liver disease.Oxidative stress refers to an imbalance in the production and elimination of reactive oxygen species and antioxidants.It plays important roles in several aspects of alcohol-related liver disease pathogenesis.Here,we review how chronic alcohol use results in oxidative stress through increased metabolism via the cytochrome P4502E1 system producing reactive oxygen species,acetaldehyde and protein and DNA adducts.These trigger inflammatory signaling pathways within the liver leading to expression of pro-inflammatory mediators causing hepatocyte apoptosis and necrosis.Reactive oxygen species exposure also results in mitochondrial stress within hepatocytes causing structural and functional dysregulation of mitochondria and upregulating apoptotic signaling.There is also evidence that oxidative stress as well as the direct effect of alcohol influences epigenetic regulation.Increased global histone methylation and acetylation and specific histone acetylation inhibits antioxidant responses and promotes expression of key pro-inflammatory genes.This review highlights aspects of the role of oxidative stress in disease pathogenesis that warrant further study including mitochondrial stress and epigenetic regulation.Improved understanding of these processes may identify novel targets for therapy. | Huey K Tan Euan Yates Kristen Lilly Ashwin D Dhanda | 2020 | World Journal of Hepatology2020，12，7： | 6 |
| 3 | Incidental gall bladder cancers:Are they truly incidental?显示文摘AIM: To seek and analyze features suggestive of gallbladder cancer(GBC) on preoperative imaging and intraoperative findings in patients diagnosed as having incidental GBC(IGBC). METHODS: The study was conducted on 79 patients of IGBC managed in our department over a 10-year period(2003-2012). Review of preoperative imaging and operative notes was done to ascertain any suspicion of malignancy-in-retrospect.RESULTS: Of the 79 patients, Ultrasound abdomen showed diffuse thickening, not suspicious of malignancy in 5 patients, and diffuse suspicious thickening was seen in 4 patients. Focal thickening suspicious of malignancy was present in 24 patients. Preoperative computed tomography/magnetic resonance imaging was done in 9 patients for suspicion of malignancy. In 5 patients, dif-ficult Cholecystectomy was encountered due to dense/inflammatory adhesions. Intraoperative findings showed focal thickening of the gallbladder and a gallbladder mass in 9 and 17 patients respectively. On overall analysis, 37 patients had preoperative imaging or intraoperative findings suggestive of malignancy, which was either a missed GBC or an unsuspected/unexpected GBC. In 42(53.2%) patients, there was no evidence suggestive of malignancy and was an unanticipated diagnosis.CONCLUSION: Our study highlights a potential and not-so-rare pitfall of Laparoscopic Cholecystectomy. A greater awareness of this clinical entity along with a high index of suspicion and a low threshold for conversion to open procedure, especially in endemic areas may avert avoidable patient morbidity and mortality. | Ashwin Rammohan Sathya D Cherukuri Jeswanth Sathyanesan Ravichandran Palaniappan Manoharan Govindan | 2014 | World Journal of Gastrointestinal Oncology2014，6，12： | 5 |
| 4 | Is liver biopsy necessary in the management of alcoholic hepatitis?显示文摘Acute alcoholic hepatitis(AAH)is characterised by deep jaundice in patients with a history of heavy alcohol use,which can progress to liver failure.A clinical diagnosis of AAH can be challenging to make in patients without a clear alcohol history or in the presence of risk factors for other causes of acute liver failure.Other causes of acute on chronic liver failure such as sepsis or variceal haemorrhage should be considered.Liver biopsy remains the only reliable method to make an accurate diagnosis.However,there is controversy surrounding the use of liver biopsy in patients with AAH because of the risks of performing a percutaneous biopsy and limitations in access to transjugular biopsy.We review the existing literature and find there are few studies directly comparing clinical and histological diagnosis of AAH.In the small number of studies that have been conducted the correlation between a clinical and histological diagnosis of AAH is poor.Due to this lack of agreement together with difficulties in accessing transjugular liver biopsy outside tertiary referral centres and research institutions,we cannot advocate universal biopsy for AAH but there remains a definite role for liver biopsy where there is clinical diagnostic doubt or dual pathology.Italso adds value in a clinical trial context to ensure a homogeneous trial population and to further our understanding of the disease pathology.Further prospective studies are required to determine whether non-invasive markers can be used to accurately diagnose AAH. | Ashwin D Dhanda Peter L Collins C Anne McCune | 2013 | World Journal of Gastroenterology2013，19，44： | 4 |
| 5 | Tissue distribution of quercetin in rats and pigs 显示文摘 | Vincent C J Ashwin A D Hester W | 2005 | J Nutr2005，135，7： | 1 |
| 6 | Heat extraction from Non- Convective and Lower Convective Zones of the solar pond: A transient study Original显示文摘 | Date A Yusli Y Ashwin D | 2013 | Solar Energy2013，97，： | 1 |
| 7 | Personalised antiplatelet ther- apy in stent thrombosis :observations from the Clopidogrel Resistance in Stent Thrombosis(CREST) registry 显示文摘 | Nalyaka S Ashwin R Hazel D | 2012 | Heart2012，98，9： | 1 |
| 8 | Stain Induced Precipitation of Complex Carbonitrides in Nb-V and Ti-V Microalloyed Steels显示文摘 | Ashwin Pandit Murugaiyan A Saha Podder A Haldar A Bhattacharjee D Chandra S Ray RK | 2005 | Scripta Materialia2005，，53： | 1 |
| 9 | L-diver- sity: privacy beyond k-anonymity显示文摘 | Ashwin Machanavajjhala A Gehrke J Kifer D | 2007 | ACM Transactions on Knowledge Discovery from Data2007，1，1： | 1 |
| 10 | Calculation of the periodic spectral components in a chaotic DC-DC converter显示文摘 | Deane J H B Ashwin P Hamill D C Jefferies D J | 1999 | IEEE Transactions on Circuits and Systems I: Fundamental Theory and Applications1999，46，11： | 1 |
| 11 | Research into the determination of pillar size显示文摘 | WILSON A H ASHWIN D P | 1972 | The Mining Engineer1972，，131： | 1 |
| 12 | Screw and wire fixation for Lisfranc fracture dislocations显示文摘 | Ghate Sushant D Sistla Vidyasagar M Nemade Vijay Vibhute Dinesh Shahane Sunil M Samant Ashwin D | 2012 | EN2012，，2： | 1 |
| 13 | Calculation of the periodic spectral components in a chaotic DC-DC converter 显示文摘 | Deane J H B Ashwin Peter Hamill D C | 1999 | IEEE Transactions on Circuits and Systems-1:Fundamental Theory and Applications1999，46，11： | 1 |
| 14 | Liver injury associated with drug intake during pregnancy显示文摘Drug use during pregnancy is not common.Drug-induced liver injury(DILI)is a potential complication that is rare but can adversely affect both the mother and the fetus.Although many drugs can directly cause hepatotoxicity,idiosyncratic liver injury is common in pregnancy.Underreporting of adverse drug reactions,lack of adequate literature regarding drug safety in pregnancy,and the inherent difficulty in diagnosing DILI during pregnancy make the management of this condition challenging.This review attempts to describe the existing literature regarding DILI in pregnancy,which is mainly in the form of case reports;several studies have looked at the safety of antithyroid drugs,antiretroviral drugs,and paracetamol,which have an indication for use in pregnancy;the relevant data from these studies with regard to DILI has been presented.In addition,the review describes the diagnosis of DILI,grading the disease severity,assessment of causality linking the drug to the adverse event,regulatory guidelines for evaluating the potential of drugs to cause liver injury,efforts to ensure better participation of women in clinical trials and studies in pregnant women population in particular,and the challenges involved in generating adequate research evidence.The establishment of DILI registries in various countries is an encouraging development;however,there is a need for promoting active,spontaneous reporting of adverse events during pregnancy to ensure rapid generation of evidence regarding the safety of a drug in pregnant women. | Priyanka Kamath Ashwin Kamath Sheetal D Ullal | 2021 | World Journal of Hepatology2021，13，7： | 1 |
| 15 | Research into the determination of pil lar size 显示文摘 | Wilson A H Ashwin D P | 1972 | The Mining Engineering1972，131，： | 1 |
| 16 | Infection does not increase long-term mortality in patients with acute severe alcoholic hepatitis treated with corticosteroids显示文摘AIM To determine whether infection in patients with acute severe alcoholic hepatitis(AAH) treated with corticosteroids is associated with increased mortality.METHODS Consecutive patients with AAH were treated with steroids and recruited to the study. Clinically relevant infections(body temperature > 38 ℃ or < 36 ℃ for more than 4 h, ascitic neutrophil count > 0.25 ×109/L, consolidation on chest radiograph or clinically relevant positive microbiological culture of bodily fluid) were recorded prospectively. Clinical and laboratory parameters were recorded and survival at 90 d and 6 mo was determined. Univariate analysis of factors associated with 90-d mortality was performed and significant variables included in a multivariate analysis.RESULTS Seventy-two patients were included in the final analysis(mean age 47.9 years, 26% female, mean discriminant function 53.0). Overall mortality in the group occurred in 15(21%), 23(32%) and 31(43%) at day 28, day 90 and 1 year respectively. 36(50%) had a clinically relevant infection during their hospitalisation(23 after initiation of steroids). The median time to development of incident infection after commencement of steroids was 10 d. The commonest site of infection was ascites(31%) and bacteraemia(31%) followed by urinary tract(19%) and respiratory tract(8%). Forty-one separate organisms were isolated in 33 patients; the most frequent genus was Escherichia(22%) and Enterococcus(20%). Infection was not associated with 90-d or 1 year mortality but was associated with higher creatinine, model for end-stage liver disease and Lille score. Baseline urea was the only independent predictor of 90-d mortality.CONCLUSION Clinically relevant infections are common in patients with AAH but are not associated with increased 90-d or 1 year mortality. | Ashwin D Dhanda Ashish Sinha Vicky Hunt Sarah Saleem Matthew E Cramp Peter L Collins | 2017 | World Journal of Gastroenterology2017，23，11： | 1 |
| 17 | 促进机器人辅助前列腺癌根治术术后早期尿控恢复的手术技巧(“大家泌尿网”观看手术视频)显示文摘机器人辅助前列腺癌根治术(RARP)目前已经成为局限性有临床意义前列腺癌的根治性治疗的新的金标准。本文介绍了既往研究中通过RAND/UCLA改良法确认和研讨的16项促进RARP术后早期尿控恢复的手术技巧,并对各手术技巧进行了介绍。 | 古迪 王铭 吴祥坤 SRIDHAR Ashwin N RAJAN Prabhakar SOORIAKUMARAN Prasanna SHAW Greg NATHAN Senthil KELLY John D BRIGGS Tim P | 2021 | 现代泌尿外科杂志2021，26，8： | 1 |
| 18 | Goal-driven learning: Fundamental issues (A symposium report)显示文摘 | Ashwin R | 1993 | AI Magazine1993，，： | 1 |
| 19 | Effect of zinc treatment on clinical outcomes in patients with liver cirrhosis:A systematic review and meta-analysis显示文摘BACKGROUNDZinc is an essential trace element integral to many cellular and immune functions.Zinc deficiency is highly prevalent in patients with cirrhosis and related to diseaseseverity.AIMTo evaluate whether zinc supplementation improves clinical outcomes (diseaseseverity and mortality) in patients with cirrhosis.METHODSThis prospectively registered systematic review (PROSPERO reference:CRD42018118219) included all studies in Medline, Embase or Cochrane databasewith inclusion criteria of adult human studies, comparing zinc supplementationof at least 28 d with standard care or placebo in patients with cirrhosis. Mortalityand clinical severity score data were extracted. Random effects meta-analysescompared mortality at 6 mo and 2 years. Risk of bias was assessed using theNational Institutes of Health quality assessment tool.RESULTSSeven hundred and twelve articles were identified of which four were eligible.Zinc formulations and doses varied (elemental zinc 3.4-214 mg daily) for different intervention periods in patients with differing etiology and severity of cirrhosis.Two studies were considered to be at high risk of bias. There was no significantdifference in 6-mo mortality between patients treated with zinc versus controls[risk ratio 0.98 (0.90-1.05)]. Changes in severity scores were not reported in anystudy.CONCLUSIONZinc supplementation is not associated with reduced mortality in patients withcirrhosis. Findings are limited by the small number of eligible studies andsignificant heterogeneity in intervention and patient population. | Huey K Tan Adam Streeter Matthew E Cramp Ashwin D Dhanda | 2020 | World Journal of Hepatology2020，12，7： | 1 |
| 20 | Determination of Cusp Number and Occlusal Groove Pattern in Mandibular Molars:A Preliminary Epidemiological Study in an Indian Population显示文摘Teeth are excellent material in living and nonliving populations for anthropological,genetic,odontologic,and forensic investigations.The present study aims to study the number of a number of cusps in the first and second mandibular molar and to assess the frequency and expression of different types of occlusal groove pattern.The cross‑sectional study is carried out.One hundred patients attending the Outpatient Department of the hospital were recruited for the study based on exclusion and inclusion criteria.Clinical examination was done,and the morphological details of the crown(the number of cusps)were recorded.Dental casts of the mandibular teeth were made.The occlusal grooves were highlighted by using Indian ink and observed under the 2×magnification for the groove pattern(+or y type).Descriptive statistics were carried out for the study.In the case of mandibular first molar,the 5 cusp form was the most frequent occlusal configuration(82%)followed by 6 cusp variety(12%)and 4 cusp variety(4%)bilaterally.The predominant occlusal groove pattern seen in mandibular first molar was“y”shape(65%)followed by“+”pattern(28%).Hence,the most frequent occlusal surface configuration in case of first mandibular molar was“y5”form.In the case of mandibular second molar,the 4 cusp form was the most frequent occlusal configuration(86%),followed by 5 cusp type(12%)bilaterally.The predominant occlusal groove pattern seen in mandibular second molar was a“+”shape(85%)followed by“y”pattern(11%).Hence,the most frequent occlusal surface configuration in case of mandibular second molar was“+4”form.The study of dental morphological characteristics is important in forensic and anthropological research as it can provide information on the phylogenetic relationship between species,as well as variation and diversities within a population. | Urvashi Ashwin Shetty Pushparaja Shetty Audrey Madonna D’Cruz | 2016 | Journal of Forensic Science and Medicine2016，2，2： | 0 |
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