Efficacy of Low Dose Chemoprophylaxis for Coccidioidomycosis Infection in Liver Transplant Recipients

Background: Coccidioidomycosis (CM) infections among transplant recipients result in significant morbidity and mortality. The goal of our study was to establish the efficacy of low dose (LD) versus standard dose (LD, 50 mg daily) fluconazole in preventing CM infection. Methods: This was a retrospective study utilizing electronic medical records of liver transplant recipients at the University of Arizona. The primary end point was post-transplant CM status, such as infection, complications and survival. Results: We detected a statistically significant correlation between positive pre-transplant status and positive post-transplant status (hazards ratio: 8.25 (95% confidence interval: 1.028 - 66.192)). There was a trend towards improved survival in patients who had a positive post-transplant CM status in the SD group versus LD group (90.9% versus 81.3%), although not statistically significant. Conclusion: The risk of CM infection among transplant recipients in the absence of prophylaxis is associated with high morbidity and mortality. We currently use SD fluconazole as universal prophylaxis in all transplant recipients despite not establishing statistical significance between LD and SD. We believe that the survival trend detected may have not reached statistical significance due to low power impact. Since the standardization of SD prophylaxis at our institution, we have not diagnosed further new post-transplant CM infections.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Fluorinated Benzofuran and Dihydrobenzofuran as Anti-Inflammatory and Potential Anticancer Agents

Benzofuran and 2,3-dihydrobenzofuran scaffolds are heterocycles of high value in medicinal chemistry and drug synthesis. Targeting inflammation in cancer associated with chronic inflammation is a promising therapy. In the present study, we investigated the anti-inflammatory effects of fluorinated benzofuran and dihydrobenzofuran derivatives in macrophages and in the air pouch model of inflammation, as well as their anticancer effects in the human colorectal adenocarcinoma cell line HCT116. Six of the nine compounds suppressed lipopolysaccharide-stimulated inflammation by inhibiting the expression of cyclooxygenase-2 and nitric oxide synthase 2 and decreased the secretion of the tested inflammatory mediators. Their IC50 values ranged from 1.2 to 9.04 µM for interleukin-6; from 1.5 to 19.3 µM for Chemokine (C-C) Ligand 2; from 2.4 to 5.2 µM for nitric oxide; and from 1.1 to 20.5 µM for prostaglandin E2. Three novel synthesized benzofuran compounds significantly inhibited cyclooxygenase activity. Most of these compounds showed anti-inflammatory effects in the zymosan-induced air pouch model. Because inflammation may lead to tumorigenesis, we tested the effects of these compounds on the proliferation and apoptosis of HCT116. Two compounds with difluorine, bromine, and ester or carboxylic acid groups inhibited the proliferation by approximately 70%. Inhibition of the expression of the antiapoptotic protein Bcl-2 and concentration-dependent cleavage of PARP-1, as well as DNA fragmentation by approximately 80%, were described. Analysis of the structure–activity relationship suggested that the biological effects of benzofuran derivatives are enhanced in the presence of fluorine, bromine, hydroxyl, and/or carboxyl groups. In conclusion, the designed fluorinated benzofuran and dihydrobenzofuran derivatives are efficient anti-inflammatory agents, with a promising anticancer effect and a combinatory treatment in inflammation and tumorigenesis in cancer microenvironments

Dental students’ attitudes and perceptions about intraprofessional collaboration/education

الملخص: أهداف البحث: للتحقيق في مواقف وتصورات طلاب طب الأسنان حول التعاون / التعليم المهني الداخلي (التعليم الداخلي) والتعلم المشترك واستكشاف تأثير التعليم الداخلي على التطوير الشخصي والمهني للطلاب المشاركين. طرق البحث: تم استخدام استبانة مصمم خصيصا في هذه الدراسة المقطعية. تتكون الاستبانة من سبعة عشر سؤالا يستهدف معرفة تصورات الطلاب حول: 1- تفضيل / رأي طلاب طب الأسنان حول التعليم الداخلي؛ 2- خبرة طلاب طب الأسنان حول تأثير التعليم الداخلي على نتائج التعلم والتطوير المهني؛ 3- ملاحظات الطلاب حول أهمية التعليم الداخلي في مختبرات المحاكاة السريرية وإعدادات مكان العمل. قام الطلاب بتقييم كل من العبارات السبعة عشر على مقياس ليكرت من 5 نقاط (النطاق: 1 = لا أوافق بشدة، 5 = أوافق بشدة). النتائج: تم تحليل ما مجموعه 259 استبانة (معدل الاستجابة = 65٪). كان جميع الطلاب على دراية بالتعليم الداخلي في مجال طب الأسنان (متوسط الدرجة = 4.22). فضل الطلاب التعلم التعاوني / المشترك مع زملائهم في الفصل. كان هناك إجماع بين الطلاب حول التأثير الإيجابي للتعليم الداخلي على التعلم المعزز، وتعزيز مهارات الاتصال، وإثراء العلاقات المهنية مع الموظفين الداعمين وكذلك مع المرضى، وتحسين المهارات التحليلية والنفسية الحركية، وفهم المشاكل المعقدة في العيادات، وفهم نقاط القوة والقيود التي تؤدي إلى تحسين الذات وزيادة الكفاءة والإنتاجية. الاستنتاجات: كان للتعليم الداخلي تأثير مقنع وقوي وإيجابي وفقا لتجربة طلاب طب الأسنان المشاركين في الدراسة. يوصى بتصميم منهج موحد ووضع مبادئ توجيهية لـلتعليم الداخلي في مؤسسات طب الأسنان من أجل التفاعل الفعال بين المتعلمين في جميع المراحل. Abstract: Objectives: To investigate dental students’ attitudes and perceptions about intraprofessional collaboration/education (IPC/IPE) and shared learning, and to explore the impact of IPC/IPE on the personal and professional development of participating students. Methods: A custom-designed questionnaire was used in this cross-sectional study. The questionnaire comprised 17 questions targeting to capture the student's perceptions about IPC/IPE using three factors: (1) dental students' preference/opinion about the IPC/IPE; (2) dental students' experience about the impact of IPC/IPE on learning outcomes and professional development; and (3) students' feedback about the significance of IPC/IPE in clinical/clinical simulation labs and workplace setting. The students rated each of the 17 statements on the 5-point Likert scale (range: 1 = strongly disagree to 5 = strongly agree). Results: A total of 259 responses were analysed (response rate = 65%). All students were aware of IPC/IPE in the field of dentistry (mean score = 4.22). The students preferred collaborative/shared learning with their own classmates. There was a consensus among students about the positive impact of IPC/IPE on enhanced learning, enhancement of communication skills, and enrichment of professional relationships with supporting staff as well as with the patients. There was also improved analytical and psychomotor skills, understanding of complex problems in the clinic, and understanding of strengths and limitations leading to self-improvement and increased efficiency and productivity. Conclusion: IPC/IPE had a compelling, powerful, and positive impact according to the experience of the participating dental students. It is recommended that a standardized curriculum be designed and guidelines set for IPC/IPE at dental institutions for effective interactions among students of all stages

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population