Cureus最新文献

{"title":"Preventing Thyroid Eye Disease with Statins: Evidence from a Meta-Analysis.","authors":"Maxim J Barnett, Tara A John, Carlo Casipit, Sarah Eidbo, Justin Lam, Catherine Anastasopoulou","doi":"10.7759/cureus.84388","DOIUrl":"10.7759/cureus.84388","url":null,"abstract":"<p><p>Statins, a class of medications that inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase, are the first-line treatment for cholesterol reduction. Beyond their anti-lipidemic properties, statins have gained recent attention for their anti-inflammatory effects. Recently, it has been shown that when prescribed early in the course of Graves' disease, there appears to be a reduction in the progression toward thyroid eye disease. This study aims to provide an overall estimate of the effect of statin therapy in relation to the development of thyroid eye disease by conducting a meta-analysis. Both CINAHL and MEDLINE databases were used to screen for studies without a time-restricted period. Studies had to include a control (no statin therapy) and treatment group (received statin therapy) with patients at baseline harboring a diagnosis of Graves' disease. Studies had to provide a hazard (or odds) ratio (HR or OR) and 95% confidence intervals, which were subsequently combined using the generic inverse variance method. Six studies were ultimately included in the meta-analysis (from an initial n = 28 studies identified). A pooled meta-analysis demonstrated a significantly reduced hazard ratio of developing thyroid eye disease in patients treated with statin therapy (HR 0.57; 95% CI 0.44-0.74, p < 0.05). Significant heterogeneity was present in our study (I² = 87.8%). This is the first meta-analysis to provide an overall estimate of the beneficial effects of statins toward preventing the development of thyroid eye disease in patients with Graves' disease. The exact mechanism remains unknown but is believed to be an extra-lipidemic manifestation, relating to the anti-inflammatory properties of the statin medications. Further studies are required to confirm our findings and identify optimal candidates for early initiation of statin therapy in Graves' disease.</p>","PeriodicalId":93960,"journal":{"name":"Cureus","volume":"17 5","pages":"e84388"},"PeriodicalIF":1.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12089743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proposal of the Glaucoma Etiology Complex (GEC): A Structured Framework for Understanding the Multifactorial Nature of Glaucoma.","authors":"Masaki Tanito","doi":"10.7759/cureus.84379","DOIUrl":"10.7759/cureus.84379","url":null,"abstract":"<p><p>The Glaucoma Etiology Complex (GEC) is a conceptual framework encompassing all elements involved in the pathophysiology of glaucoma. Glaucoma is no longer understood as a disease driven solely by intraocular pressure; instead, it is increasingly recognized as a complex condition influenced by ocular, systemic, genetic, vascular, and lifestyle-related factors. The nine components of the GEC are: 1. age, 2. genetic factors, 3. intraocular pressure, 4. ocular characteristics, 5. ocular comorbidities, 6. vascular factors, 7. systemic comorbidities, 8. lifestyle factors, and 9. patient treatment attitude. These components interact with each other to dynamically shape the disease process over time. This editorial presents the structure and significance of the GEC, aiming to provide a comprehensive framework for understanding the multifactorial nature of glaucoma. This perspective may serve as a useful reference for both clinicians and researchers in pursuing individualized risk assessment, early diagnosis, and personalized management strategies for glaucoma.</p>","PeriodicalId":93960,"journal":{"name":"Cureus","volume":"17 5","pages":"e84379"},"PeriodicalIF":1.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12086601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Recurrence of Pleomorphic-Type Anaplastic Pancreatic Carcinoma After Distal Pancreatectomy Causing Delayed-Onset Pancreatic Fistula: A Case Report.","authors":"Masahiro Kobayashi, Masaru Matsumura, Yutaka Takazawa, Junichi Shindoh, Masaji Hashimoto","doi":"10.7759/cureus.84316","DOIUrl":"10.7759/cureus.84316","url":null,"abstract":"<p><p>Pleomorphic-type anaplastic carcinoma of the pancreas is a rare and highly aggressive histological subtype of pancreatic ductal carcinoma. It is characterized by rapid progression and a poor prognosis. Preoperative diagnosis is often challenging due to nonspecific imaging findings and the frequent absence of elevated tumor markers. We present a resected case of pleomorphic-type anaplastic carcinoma of the pancreatic tail, which showed early recurrence in the remnant pancreas, potentially associated with a delayed-onset pancreatic fistula. A 63-year-old man presented with upper abdominal pain. Imaging revealed a cystic lesion in the pancreatic tail. Follow-up imaging showed enlargement of the lesion, and a retention cyst with possible underlying pancreatic carcinoma was suspected. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was not performed due to concerns for cyst rupture. The patient underwent distal pancreatectomy with splenectomy. Histopathological examination confirmed pleomorphic-type anaplastic carcinoma. Although the drain was removed on postoperative day (POD) five due to low amylase levels in the drainage tube, a pancreatic fistula developed on POD 14, resulting in an intractable pancreatic fistula requiring persistent drainage. On POD 53, imaging revealed tumor recurrence in the remnant pancreas, along with peritoneal dissemination and right femoral bone metastasis. Retrospective evaluation of CT on POD 14 showed tumor recurrence compressing the main pancreatic duct, which was suspected to be the cause of the fistula. The patient declined further oncological treatment and died on POD 103. This case highlights the diagnostic and therapeutic challenges of pleomorphic-type anaplastic carcinoma of the pancreas. Early postoperative recurrence can lead to pancreatic stump disruption and the development of intractable pancreatic fistula.</p>","PeriodicalId":93960,"journal":{"name":"Cureus","volume":"17 5","pages":"e84316"},"PeriodicalIF":1.0,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144096287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Splenic and Pancreatic Abscess Secondary to Chronic Corticosteroid Use: A Case Report and Literature Review.","authors":"Fernando Sánchez Martínez, Oscar Sebastian Salinas Rosas, Carlos Ronaldo Martínez Mateo, Alejandro Aguilar Sabori, Erik Ponce Graciano, David Alejandro Rodríguez Herrera, María Fernanda Vázquez Páez, Angeles Yasunari Cortes Garcia","doi":"10.7759/cureus.84325","DOIUrl":"10.7759/cureus.84325","url":null,"abstract":"<p><p>Splenic abscess is a rare but potentially life-threatening condition often associated with immunosuppressive states. We present the case of a 62-year-old man with a history of chronic corticosteroid use who developed fever, anorexia, weight loss, and left upper quadrant abdominal pain. Laboratory studies revealed leukocytosis and elevated inflammatory markers. Contrast-enhanced computed tomography identified multiloculated abscesses in the spleen and pancreatic tail. The patient underwent exploratory laparotomy, splenectomy, and distal pancreatectomy, with a favorable postoperative course complicated only by a superficial surgical site infection. Splenic abscess typically results from hematogenous spread, and its diagnosis is often delayed due to nonspecific symptoms. Imaging, particularly contrast-enhanced CT, is critical for early detection. Management strategies include percutaneous drainage or surgical intervention, depending on the patient's clinical status. Although corticosteroid-induced immunosuppression is a rare risk factor, it should be recognized as a potential cause. Early diagnosis, source control, and targeted antibiotic therapy are crucial for optimizing patient outcomes.</p>","PeriodicalId":93960,"journal":{"name":"Cureus","volume":"17 5","pages":"e84325"},"PeriodicalIF":1.0,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12086024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Immersion to Seizure: A Novel Case of Water Intoxication Complicating a Water Birth.","authors":"Sarah Al-Musawi, Rukhsana Iqbal, Greeshma Rajeev","doi":"10.7759/cureus.84349","DOIUrl":"10.7759/cureus.84349","url":null,"abstract":"<p><p>Water immersion birth (WIB) is increasingly used for pain relief during labour, offering high maternal satisfaction and reduced need for epidural analgesia. However, its potential complications, particularly regarding fluid and electrolyte balance, remain underexplored. We report a case of a healthy 33-year-old woman who developed a generalized tonic-clonic seizure two hours after delivering via WIB. Her antenatal course and labour progression were clinically normal; however, she experienced retention of urine and continued fluid intake during her four hours of immersion. Post-seizure investigations revealed serum sodium measured at 124 mmol/L indicated severe hyponatremia and metabolic acidosis. Neurological imaging and EEG were unremarkable. With supportive care and correction of sodium levels, her condition stabilized. This case highlights the possibility of dilutional hyponatremia associated with prolonged WIB, especially when coupled with high fluid intake and delayed urine output. Water immersion may promote vasopressin release, impair free water clearance, and precipitate acute symptomatic hyponatremia. Although WIB is generally safe, prolonged immersion and unmonitored fluid intake may increase the risk of water intoxication. Vigilant monitoring of fluid balance is essential to prevent complications. In selected cases, serum sodium monitoring should be considered, particularly with prolonged immersion or abnormal urinary output.</p>","PeriodicalId":93960,"journal":{"name":"Cureus","volume":"17 5","pages":"e84349"},"PeriodicalIF":1.0,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144096288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Predictive Value of Tumor Necrosis Factor Receptor-Associated Factor-Interacting Protein With Forkhead-Associated Domain (TIFA) and Interleukin-1 Beta in Sepsis-Associated Acute Kidney Injury: Bioinformatics Analysis and Experimental Validation.","authors":"Zuyi Zhao, Wen Guo, Bozhi Zhao, Long Ma","doi":"10.7759/cureus.84333","DOIUrl":"10.7759/cureus.84333","url":null,"abstract":"<p><p>Background and objective Sepsis is a systemic inflammatory response syndrome caused by severe infection. Sepsis-associated acute kidney injury (SA-AKI) is one of the most common complications of sepsis. Early prediction and subsequent treatment of SA-AKI can improve patient outcomes; hence, the accurate prediction of its occurrence is of paramount importance. This study aimed to investigate the predictive value of the potential biomarkers interleukin-1 beta (IL-1β) and tumor necrosis factor receptor‑associated factor (TRAF)‑interacting protein with forkhead‑associated domain (TIFA) related to the development of SA-AKI.  Methods We identified relevant GSE datasets (225192) from the Gene Expression Omnibus (GEO) database and conducted secondary analyses, revealing increased expression of TIFA and IL-1β in renal tissues. Building on our preliminary findings, we performed a prospective observational study (March 2024 to December 2024) among patients with sepsis who were admitted to the Department of Critical Care Medicine at the First Affiliated Hospital of Xinjiang Medical University. Patients were stratified based on the development of AKI. Plasma samples were collected within 24 hours of ICU admission and analyzed using enzyme-linked immunosorbent assay (ELISA) to measure plasma levels of TIFA and IL-1β.  Results The analysis revealed that the length of hospital stay, albumin/globulin ratio, and white blood cell count did not show any significant differences between groups. However, plasma levels of TIFA and IL-1β were significantly higher in patients with AKI compared to those without AKI. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.912, indicating that TIFA and IL-1β possess high discriminatory power and calibration accuracy. These findings suggest that plasma levels of TIFA and IL-1β are closely associated with respect to the prediction of AKI in patients. Conclusions Bioinformatics analysis and experimental validation revealed that the expression levels of TIFA and IL-1β are significantly upregulated in patients with SA-AKI. These findings suggest that TIFA and IL-1β may serve as potential biomarkers for predicting SA-AKI.</p>","PeriodicalId":93960,"journal":{"name":"Cureus","volume":"17 5","pages":"e84333"},"PeriodicalIF":1.0,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144096401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transient Global Amnesia Following Dobutamine Stress Echocardiography.","authors":"Maryam Hanser, Diana Boyrazyan, Charisse N Chih, Antonio K Liu","doi":"10.7759/cureus.84357","DOIUrl":"10.7759/cureus.84357","url":null,"abstract":"<p><p>Transient global amnesia is an uncommon neurological phenomenon characterized by sudden-onset anterograde amnesia, often accompanied by repetitive questioning and transient cognitive dysfunction, which resolves completely within 24 hours. While self-limiting, this can cause significant distress to both patients and their families, particularly when it arises in the context of medical interventions. Dobutamine stress echocardiography, a widely employed non-invasive diagnostic modality for assessing myocardial ischemia, valvular pathology, and left ventricular function, is generally regarded as safe and well-tolerated. There are only a few cases of transient global amnesia after dobutamine stress echocardiography. Our case report may align with the current belief that the adrenergic and hemodynamic stress induced by dobutamine stress echocardiography can occasionally elicit transient global amnesia in predisposed patients, challenging its reputation as a low-risk diagnostic procedure.</p>","PeriodicalId":93960,"journal":{"name":"Cureus","volume":"17 5","pages":"e84357"},"PeriodicalIF":1.0,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12086023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinicopathologic Analysis of Granuloma Annulare With Insights Into Its Incidence and Demographics in the United Arab Emirates From 2016 to 2023.","authors":"Farah Awadhalla, Hamda Alfalasi, Reem Elbahtimi","doi":"10.7759/cureus.84287","DOIUrl":"10.7759/cureus.84287","url":null,"abstract":"<p><p>Granuloma annulare (GA) is a benign, often chronic dermatologic condition with varying clinical presentations and has been associated in the literature with a notable psychosocial burden, particularly in generalized cases. This retrospective cross-sectional study analyzed the epidemiological and clinicopathological features of GA and its variants in the United Arab Emirates (UAE) from 2016 to 2023. A total of 171 histopathologically confirmed GA cases were included, collected from a single dermatopathology center. The incidence of GA diagnoses showed temporal variation, peaking in 2020 at 0.67% (n = 27) and declining significantly to 0.27% (n = 20) by 2023, as confirmed by a two-proportion z-test (z = 3.24, p = 0.001). However, no significant monotonic trend was observed across the full eight-year period (ρ = -0.19, p = 0.65). Localized GA emerged as the predominant subtype (n = 118, 69.0%), with a marked female predominance across the cohort. The mean age of patients was 39.49 ± 13.87 years, and middle-aged adults (36-55 years) constituted the largest age group (n = 82, 48%). A chi-square goodness-of-fit test demonstrated a statistically significant difference in the distribution of GA variants (χ²(3, N = 171) = 186.54, p < 0.001), with interstitial, papular, and deep GA occurring less frequently than expected. Lesions most frequently involved the upper and lower limbs. While age distribution across GA subtypes did not show a statistically significant association (χ²(12, N = 171) = 13.62, p = 0.326), demographic patterns revealed a richly diverse patient population representing over 35 nationalities, with British and Emirati individuals comprising a notable portion. These findings contribute meaningful insight into the epidemiology and clinicopathology of GA in a multicultural setting and offer a foundation for further exploration into immunologic and genetic factors that could drive precision-based treatment strategies.</p>","PeriodicalId":93960,"journal":{"name":"Cureus","volume":"17 5","pages":"e84287"},"PeriodicalIF":1.0,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144096147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shaping Tomorrow's Surgeons: The Need for Orthopaedic Reform at United Kingdom Medical Schools.","authors":"Daniel I Koshy, David Koshy, Kevin Vinod Joseph, Zabrang Ishaku, Kayaththery Varathan","doi":"10.7759/cureus.84298","DOIUrl":"10.7759/cureus.84298","url":null,"abstract":"<p><p>Musculoskeletal disorders account for a significant portion of healthcare consultations in the UK, yet orthopaedics remains markedly underrepresented in medical school curricula. This disparity limits students' clinical exposure, practical experience, and research opportunities, contributing to reduced interest in orthopaedic careers and exacerbating workforce shortages. This article explores the current limitations of orthopaedic education, highlighting the consequences for patient care and future workforce planning. It proposes a multifaceted reform strategy that includes simulation-based learning, structured mentorship, curriculum redesign, and national standardisation. Enhancing orthopaedic training is essential to ensure equitable, high-quality musculoskeletal care and to prepare a capable, innovative surgical workforce for the future.</p>","PeriodicalId":93960,"journal":{"name":"Cureus","volume":"17 5","pages":"e84298"},"PeriodicalIF":1.0,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12092090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comparative Study on Subcutaneous Negative Suction Drain vs. No Drain in Emergency Laparotomy Wounds for Peritonitis.","authors":"Bhaskar Mallaiah, Bhavana Chinmayee K, Ramachandra J","doi":"10.7759/cureus.84247","DOIUrl":"10.7759/cureus.84247","url":null,"abstract":"<p><p>Aim This study aimed to compare the effectiveness of subcutaneous negative suction drainage vs. no drainage in reducing postoperative complications following emergency laparotomy for peritonitis. Objective The primary objective of this study was to evaluate the effect of subcutaneous negative pressure closure on various postoperative outcomes in patients undergoing emergency surgery. Specifically, the study aims to assess its impact on the incidence of surgical site infection (SSI), wound dehiscence, the need for secondary suturing, and the duration of hospital stay. Additionally, the study seeks to determine whether the observed SSIs are primarily attributable to intra-abdominal infections or are a result of hospital-acquired cross infections. Materials and methods A prospective comparative study was conducted on 60 patients diagnosed with peritonitis who underwent emergency laparotomy. They were randomly assigned into two groups of 30 patients each: Group A (with subcutaneous negative suction drain) and Group B (without drain). In Group A, drain fluid was analyzed for infection characteristics, while wound discharge from both groups was assessed microbiologically, where present. Results Group A included 21 males (70%) and nine females (30%), while Group B had 26 males (86%) and four females (13%). Midline vertical incisions were used in 90% of cases, with the remaining 10% receiving right paramedian incisions. Discharge from the incision site was observed in five patients (16%) in Group A and 13 patients (43%) in Group B (p = 0.024). SSIs occurred in five patients (16.67%) in Group A and in eight patients (26%) in Group B. Seroma formation was observed in five patients (16.67%) in Group B, but none in Group A. No significant differences were noted in wound dehiscence, need for secondary suturing, or duration of hospital stay between the groups. Conclusion Subcutaneous negative suction drainage significantly reduced the incidence of SSI, seroma formation, and discharge from the incision site following emergency laparotomy for peritonitis. This may lower the risk of wound complications and postoperative morbidity. Further randomized controlled trials are recommended to validate these findings.</p>","PeriodicalId":93960,"journal":{"name":"Cureus","volume":"17 5","pages":"e84247"},"PeriodicalIF":1.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12092951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144121858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}