Reviews on recent clinical trials最新文献

{"title":"Impact of a Symbiotic Mixture on Moderate-to-severe Diverticular Disease of the Colon.","authors":"Antonio Tursi, Giammarco Mocci, Paolo Usai Satta, Walter Elisei","doi":"10.2174/0115748871308652240712101604","DOIUrl":"10.2174/0115748871308652240712101604","url":null,"abstract":"<p><strong>Background: </strong>Microbial imbalance is thought to play a role in the pathogenesis of Diverticular Disease (DD).</p><p><strong>Objective: </strong>We aimed to assess the efficacy of a symbiotic mixture (<i>Prolactis GG Plus®</i>) in the treatment of moderate to severe DD, scored according to the Diverticular Inflammation and Complication Assessment (DICA) classification.</p><p><strong>Methods: </strong>A retrospective study was conducted enrolling the following patients: at the first diagnosis of DD; in whom DD was diagnosed with colonoscopy and scored according to DICA classification; treated with <i>Prolactis GG Plus®</i> two times/daily for 2 consecutive months; in whom the severity of the abdominal pain was scored with a 10-points visual-analogue scale (VAS) at baseline and the end of follow-up; in whom fecal calprotectin (FC) was assessed at baseline and the end of follow-up as μg/g.</p><p><strong>Results: </strong>Twenty-four patients were identified (10 males, 14 females; 16 as DICA 2, and 8 as DICA 3). <i>Prolactis GG Plus®</i> decreased the severity of abdominal pain both in DICA 2 (p =0.02) and DICA 3 patients (p =0.01), while FC decreased significantly in DICA 2 (p <0.02) but not in DICA 3 (p =0.123) patients. Acute diverticulitis occurred during the follow-up in two DICA 3 patients but none DICA 2 patients. Add-on therapy was required by eight DICA 2 (50%) and six DICA 3 patients (75%).</p><p><strong>Conclusion: </strong>In newly diagnosed patients with DD, the symbiotic mixture <i>Prolactis GG Plus®</i> can be a potential treatment for moderate (DICA 2) DD as a single treatment.</p>","PeriodicalId":21174,"journal":{"name":"Reviews on recent clinical trials","volume":" ","pages":"27-35"},"PeriodicalIF":1.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141760694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study Rapid, Quantitative, and Simultaneous Detection of Drug Residues and Immunoassay in Chickens.","authors":"Mohamad Hesam Shahrajabian, Wenli Sun","doi":"10.2174/0115748871305331240724104132","DOIUrl":"10.2174/0115748871305331240724104132","url":null,"abstract":"<p><p>Different levels of residual drugs can be monitored within a relatively safe range without causing harm to human health if the appropriate dosing methodology is considered and the drug withdrawal period is controlled during poultry and livestock raising. Antimicrobials are factors that can suppress the growth of microorganisms, and antibiotic residues in livestock farming have been considered as a potential cause of antimicrobial resistance in animals and humans. Antimicrobial drug resistance is associated with the capability of a microorganism to survive the inhibitory effects of the antimicrobial components. Antibiotic residue presence in chicken is a human health concern due to its negative effects on consumer health. Neglected aspects related to the application of veterinary drugs may threaten the safety of both humans and animals, as well as their environment. The detection of chemical contaminants is essential to ensure food quality. The most important antibiotic families used in veterinary medicines are β-lactams (penicillins and cephalosporins), tetracyclines, chloramphenicols, macrolides, spectinomycin, lincosamide, sulphonamides, nitrofuranes, nitroimidazoles, trimethoprim, polymyxins, quinolones, and macrocyclics (glycopeptides, ansamycins, and aminoglycosides). Antibiotic residue presence is the main contributor to the development of antibiotic resistance, which is considered a chief concern for both human and animal health worldwide. The incorrect application and misuse of antibiotics carry the risk of the presence of residues in the edible tissues of the chicken, which can cause allergies and toxicity in hypersensitive consumers. The enforcement of the regulation of food safety depends on efficacious monitoring of antimicrobial residues in the foodstuff. In this review, we have explored the rapid detection of drug residues in broilers.</p>","PeriodicalId":21174,"journal":{"name":"Reviews on recent clinical trials","volume":" ","pages":"2-17"},"PeriodicalIF":1.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Patents to Progress: Unraveling Gout's Journey Through Clinical Trials and Advancements.","authors":"Vikash Singh Bhadouria, Sushma Verma, Chhaya Agarwal, Deep Shikha Sharma","doi":"10.2174/0115748871308473240926044126","DOIUrl":"10.2174/0115748871308473240926044126","url":null,"abstract":"<p><p>Gout, an inflammatory arthritis form, is renowned for its historical association with affluence. This review delves into its pathophysiology, exploring hyperuricemia, urate crystal formation, and the ensuing inflammatory response. The epidemiology of gout is examined, focusing on its rising prevalence and impact on public health. In this study, progress in gout management is discussed, involving pharmacological interventions, dietary changes, and emerging therapies. Genetic predisposition and triggers like alcohol, temperature, and diet are highlighted in this study. Prevention strategies, including serum urate-lowering therapy and lifestyle modifications, aim to reduce recurrent flares and complications. The inflammatory response in acute gout attacks is elucidated, involving immune cells, cytokines, and the NLRP3 inflammasome. Chronic gout manifestations, such as gouty tophus formation, are explored for their destructive impact on surrounding tissues. Recent advancements in gout treatment, including nanotherapies and novel compounds, are discussed, along with promising urate-lowering drugs. Cutting-edge research on zinc ferrite nanoparticles, dimethyl fumarate, and myricetin/nobiletin hybrids addresses oxidative stress and inflammation in gout. Additionally, the potential therapeutic role of methanolic leaf extract of Euphorbia milii and tip-loaded CLC-Soluplus® MAPs is explored as natural and transdermal alternatives for gout management. The review also covers the development status of new urate-lowering drugs, providing insights into promising candidates and their mechanisms. Patents on gout and recent diagnostic advancements using techniques like laser confocal micro Raman spectrometer, FTIR, and THz-TDS offer a more accurate approach for gout stone analysis, enabling early detection and targeted treatment.</p>","PeriodicalId":21174,"journal":{"name":"Reviews on recent clinical trials","volume":" ","pages":"96-112"},"PeriodicalIF":1.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the Mysteries of Alzheimer's Disease Using Artificial Intelligence.","authors":"Siddhant Tripathi, Yashika Sharma, Dileep Kumar","doi":"10.2174/0115748871330861241030143321","DOIUrl":"10.2174/0115748871330861241030143321","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a multidimensional, complex condition that affects individuals all over the world. Despite decades of experimental and clinical research that has revealed various processes, many concerns concerning the origin of Alzheimer's disease remain unresolved. Despite the notion that there isn't a complete set of jigsaw pieces, the growing number of public data-sharing initiatives that collect biological, clinical, and lifestyle data from those suffering from Alzheimer's disease has resulted in virtually endless volumes of knowledge about the disorder, far beyond what humans can comprehend. Furthermore, combining Big Data from multi- -omics research gives a chance to investigate the pathophysiological processes underlying the whole biological spectrum of Alzheimer's disease. To improve knowledge on the subject of Alzheimer's disease, Artificial Intelligence (AI) offers a wide variety of approaches for evaluating complex and significant data. The introduction of next-generation sequencing and microarray technologies has resulted in significant growth in genetic data research. When it comes to assessing such complex projects, AI technology beats conventional statistical techniques of data processing. This review focuses on current research and potential challenges for AI in Alzheimer's disease research. This article, in particular, examines how AI may assist healthcare practitioners with patient stratification, estimating an individual's chance of AD conversion, and diagnosing AD using computer-aided diagnostic methodologies. Ultimately, scientists want to develop individualized, efficient medicines.</p>","PeriodicalId":21174,"journal":{"name":"Reviews on recent clinical trials","volume":" ","pages":"124-141"},"PeriodicalIF":1.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Colchicine for Prevention of Recurrent Stroke in Ischemic Stroke Patients with Atrial Fibrillation: A Randomized Double-blinded Placebo-controlled Trial.","authors":"Zahra Molaeimanesh, Davood Kashipazha, Davood Shalilahmadi, Gholamreza Shamsaei, Shooka Mohammadi","doi":"10.2174/0115748871325292240904060109","DOIUrl":"10.2174/0115748871325292240904060109","url":null,"abstract":"<p><strong>Background: </strong>It has been proposed that colchicine may have the potential to prevent cardiovascular and cerebrovascular dysfunctions.</p><p><strong>Objective: </strong>This study evaluated the impact of colchicine on preventing recurrent stroke in patients with both ischemic stroke (IS) and atrial fibrillation (AF).</p><p><strong>Methods: </strong>A randomized, double-blinded, placebo-controlled trial was conducted at Golestan Hospital (Ahvaz, Iran) over one year, involving IS patients with AF. Demographic and clinical data were collected from the participants, who were then assigned to either the intervention or placebo groups. The experimental group was administered colchicine at a dosage of 0.05 mg twice daily for one year, while the control group received a placebo at a comparable dosage over the same timeframe.</p><p><strong>Results: </strong>In one year, 108 patients completed the study. There were 55 patients in the intervention group and 53 patients in the placebo group. During the second trimester of the trial, three patients in the colchicine group and 10 patients in the placebo group experienced recurrent strokes. Gastrointestinal issues were the most commonly reported complications (33 cases) among the two groups, followed by myalgia (8 patients). There were significant differences in the frequency of recurrent stroke and serum levels of C-reactive protein (CRP) between the colchicine and placebo groups (p < 0.05) after intervention.</p><p><strong>Conclusion: </strong>In this study, colchicine was effective in reducing recurrent stroke and CRP levels in IS patients with AF compared to the control group. Further randomized controlled trials with larger sample sizes and extended durations are recommended to validate the results of this trial.</p>","PeriodicalId":21174,"journal":{"name":"Reviews on recent clinical trials","volume":" ","pages":"59-67"},"PeriodicalIF":1.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Navigating Dry Eye Research: A Comprehensive Review of Etiology, Clinical Trials, Patents, and Recent Advancements.","authors":"Vindhya Pal, Sushma Verma","doi":"10.2174/0115748871310261240929163138","DOIUrl":"https://doi.org/10.2174/0115748871310261240929163138","url":null,"abstract":"<p><strong>Background: </strong>Millions of people worldwide suffer from dry eye disease. Dry eye, a multifunctional condition of the ocular surface, typically occurs in conjunction with an unbalanced tear film. With increasing age, the dry eye problem becomes worse. Aqueous-deficit dry eye and evaporative dry eye are the two traditional classifications for dry eye. Various examination tools are used to diagnose dry eye. Clinical trials are conducted in four phases to check the safety and efficacy of drugs. The quick clearance from the precorneal space is ensured by the eye's advanced defense mechanism. It restricts the integrated medicine's entry into the eyes, resulting in a usually low bioavailability for topical eyedrops. In this study, we focus on recently developed formulations for curing dry eye.</p><p><strong>Objective: </strong>This review's goal was to outline the etiology, clinical discovery and development, patents, and recent advancements for dry eye disease.</p><p><strong>Results: </strong>The current study has described the widespread incidence of dry eye, which was found to be more common as people aged and recently developed formulations are treating dry eyes. According to research, novel formulations are enhancing ocular drug delivery.</p><p><strong>Conclusion: </strong>In this review, etiology, clinical data, dry eye formulation patents, and recent advancements are all included.</p>","PeriodicalId":21174,"journal":{"name":"Reviews on recent clinical trials","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WITHDRAWN: Comparison of the Efficacy of Oral Magnesium with Oral Ketorolac for Postoperative Pain Management in Anorectal Surgery: A Double-blinded Randomized Clinical Trial","authors":"Seyed Jalal Eshagh Hoseini, Farzanesadat Ghazi, Mohsen Eshraghi, Mostafa Vahedian, Mohammad Reza Pashaei, Mohamad Amin Habibi, Sajjad Ahmadpour","doi":"10.2174/0115748871290318240218195517","DOIUrl":"10.2174/0115748871290318240218195517","url":null,"abstract":"<p><p>The article has been withdrawn at the request of the editor of the journal Reviews on Recent Clinical Trials.</p><p><p>Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.</p><p><p>The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php</p><p><strong>Bentham science disclaimer: </strong>It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.</p>","PeriodicalId":21174,"journal":{"name":"Reviews on recent clinical trials","volume":" ","pages":""},"PeriodicalIF":1.4,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140207498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic Review and Meta-analysis of the Impact of Metabolic Surgery on Hepatic Stiffness.","authors":"Tannaz Jamialahamdi, Matthew Kroh, Sorour Ashari, Wael Almahmeed, Ali Jangjoo, Luis E Simental-Mendía, Sepideh Salehabadi, Khalid Al-Rasadi, Amirhossein Sahebkar","doi":"10.2174/0115748871303052240529102003","DOIUrl":"10.2174/0115748871303052240529102003","url":null,"abstract":"<p><strong>Background: </strong>Bariatric surgery is one of the effective therapeutic options for people with obesity and obesity-related co-morbidities. In addition to weight-related co-morbid diseases, including diabetes, hypertension, and hypercholesterolemia, non-alcoholic fatty liver disease (NAFLD) is common in patients with morbid obesity. Bariatric surgery is one of the therapeutic options in the management of NAFLD. Hence, this review focused on the potential role of bariatric surgery on hepatic elasticity measured through shear wave elastography.</p><p><strong>Methods: </strong>A systematic literature search was performed, and the studies regarding heterogeneity were evaluated using the random-effects model.</p><p><strong>Results: </strong>The meta-analysis on 6 trials (3-12 months follow-up) including 350 participants showed a significant reduction of liver elasticity after surgery (WMD: -1.149, 95% CI: -1.767, -0.532, p < 0.001; I2:81.55%).</p><p><strong>Conclusion: </strong>Bariatric surgery is associated with decreased liver elasticity. This improvement could be related to weight loss or other mechanisms of bariatric surgery.</p>","PeriodicalId":21174,"journal":{"name":"Reviews on recent clinical trials","volume":" ","pages":"236-241"},"PeriodicalIF":1.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141311543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Introduction of Various Models of Palliative Oncology Care: A Systematic Review.","authors":"Mahdieh Arian, Fatemeh Hajiabadi, Zakiyeh Amini, Mohammad Bagher Oghazian, Ali Valinejadi, Amirhossein Sahebkar","doi":"10.2174/0115748871272511231215053624","DOIUrl":"10.2174/0115748871272511231215053624","url":null,"abstract":"<p><strong>Background: </strong>The aim of this study is to synthesize the existing evidence on various palliative care (PC) models for cancer patients. This effort seeks to discern which facets of PC models are suitable for various patient cohorts, elucidate their mechanisms, and clarify the circumstances in which these models operate.</p><p><strong>Methods: </strong>A comprehensive search was performed using MeSH terms related to PC and cancer across various databases. The Preferred Reporting Items for Systematic Reviews and a comprehensive evidence map were also applied.</p><p><strong>Results: </strong>Thirty-three reviews were published between 2009 and 2023. The conceptual PC models can be classified broadly into time-based, provider-based, disease-based, nurse-based, issue-based, system-based, team-based, non-hospice-based, hospital-based, community-based, telehealth-based, and setting-based models. The study argues that the outcomes of PC encompass timely symptom management, longitudinal psychosocial support, enhanced communication, and decision-making. Referral methods to specialized PC services include oncologist-initiated referral based on clinical judgment alone, via referral criteria, automatic referral at the diagnosis of advanced cancer, or referral based on symptoms or other triggers.</p><p><strong>Conclusion: </strong>The gold standard for selecting a PC model in the context of oncology is a model that ensures broad availability of early PC for all patients and provides well-timed, scheduled, and specialized care for patients with the greatest requirement.</p>","PeriodicalId":21174,"journal":{"name":"Reviews on recent clinical trials","volume":" ","pages":"109-126"},"PeriodicalIF":1.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139058640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Fecal Calprotectin in Patients Presenting to the Emergency Department with Abdominal Pain with or without Diarrhea or Rectal Bleeding.","authors":"Angela Saviano, Carmine Petruzziello, Christian Zanza, Marcello Candelli, Maurizio Gabrielli, Alessio Migneco, Francesco Franceschi, Veronica Ojetti","doi":"10.2174/0115748871259008231006071656","DOIUrl":"10.2174/0115748871259008231006071656","url":null,"abstract":"<p><strong>Background and objective: </strong>Abdominal pain is a frequent reason for admission to the Emergency Department. It may be a symptom of an underlying \"organic\" disease or a \"functional\" manifestation without an underlying anatomic or physiologic alteration. The evaluation of patients with abdominal pain is a challenge for the emergency physician and the selection of patients for second-level radiological examinations or endoscopic procedures is not always easy to perform. Faecal calprotectin could be a useful diagnostic marker to distinguish between \"organic\" or \"functional\" form and its determination could be helpful to select patients for further examinations in the context of an emergency setting.</p><p><strong>Materials and methods: </strong>This is an observational and retrospective study on 146 patients with abdominal pain and/or diarrhea (with or without rectal bleeding) admitted to the Emergency Department of Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, who collected a fecal sample to evaluate fecal calprotectin. We evaluated and correlated the level of fecal calprotectin with the final diagnosis they received.</p><p><strong>Results: </strong>50/146 patients (34,24%) received a diagnosis of acute diverticulitis, in particular, 14/50 (28%) were complicated and 36/50 (72%) were uncomplicated; 4/146 (2,7%) were cholangitis, 32/146 (21,9%) were colitis, 6/146 (4,1%) gastritis, 42/146 (28,7%), Irritable bowel syndrome and 12/146 (8,2%) Inflammatory bowel disease. For the differential diagnosis between Irriable or inflammatory bowel diseses, our study showed a VPP and a VPN of 100% meanwhile for the differential diagnosis between Acute complicated and uncomplicated diverticulitis, our study showed a VPP of 40% and a VPN of 84%.</p><p><strong>Conclusion: </strong>In the emergency setting, faecal calprotectin could be a helpful marker to select patients with abdominal pain who need second-level radiological examinations or endoscopic procedures, guiding the emergency physician in the evaluation of such a complex and wideranging symptom.</p>","PeriodicalId":21174,"journal":{"name":"Reviews on recent clinical trials","volume":" ","pages":"70-75"},"PeriodicalIF":1.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71426411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}