The Structure of the NPC1L1 N-Terminal Domain in a Closed Conformation

NPC1L1 is the molecular target of the cholesterol lowering drug Ezetimibe and mediates the intestinal absorption of cholesterol. Inhibition or deletion of NPC1L1 reduces intestinal cholesterol absorption, resulting in reduction of plasma cholesterol levels.Here we present the 2.8 Å crystal structure of the N-terminal domain (NTD) of NPC1L1 in the absence of cholesterol. The structure, combined with biochemical data, reveals the mechanism of cholesterol selectivity of NPC1L1. Comparison to the cholesterol free and bound structures of NPC1(NTD) reveals that NPC1L1(NTD) is in a closed conformation and the sterol binding pocket is occluded from solvent.The structure of NPC1L1(NTD) reveals a degree of flexibility surrounding the entrance to the sterol binding pocket, suggesting a gating mechanism that relies on multiple movements around the entrance to the sterol binding pocket

Obesity is associated with insulin resistance and components of the metabolic syndrome in Lebanese adolescents

adolescents has been reported to range between 18–42%, depending on country of origin, thus suggesting an ethnicbased association between obesity and MS. Aim: This study aims to investigate the magnitude of the association between obesity, insulin resistance and components of MS among adolescents in Lebanon. Subjects and methods: The sample included 263 adolescents at 4 th and 5 th Tanner stages of puberty (104 obese; 78 overweight; 81 normal weight). Anthropometric, biochemical and blood pressure measurements were performed. Body fat was assessed using dual-energy X-ray absorptiometry. Results: According to International Diabetes Federation criteria, MS was identified in 21.2 % of obese, 3.8 % of overweight and 1.2 % of normal weight subjects. The most common metabolic abnormalities among subjects having MS were elevated waist circumference (96.2%), low HDL (96.2%) and hypertriglyceridemia (73.1%). Insulin resistance was identified in all subjects having MS. Regression analyses showed that percentage body fat, waist circumference and BMI were similar in their ability to predict the MS in this age group. Conclusions: MSwas identified in asubstantial proportion of Lebanese obese adolescents, thus highlighting the importance of early screening for obesity-associated metabolic abnormalities and of developing successful multi-component interventions addressing adolescent obesity

Coexistence of Standard Modifiable, Other Classical, and Novel and Classical Atherosclerotic Cardiovascular Disease Risk Factors in Middle Eastern Young Women

Abdel-Ellah Al-Shudifat,1 Ayman J Hammoudeh,2 Wesam Al Saud,3 Rashid Ibdah,4 Mohammad Araydah,5 Ayah Zaqqa,6 Zainab Raed Fakhri,7 Lubna Haikal Fawaz Haikal,8 Lina Jamal Abuhalimeh,8 Zahraa Alghabban,8 Daria Ja’arah,9 Abdalluh Nabil Al-Mashayikh,10 Imad Alhaddad11 1Department of Internal and Family Medicine, Faculty of Medicine The Hashemite University, Zarqa, Jordan; 2Department of Cardiology, Istishari Hospital, Amman, Jordan; 3Department of Clinical Pharmacy, Princess Salma Hospital, Ministry of Health, Amman, Jordan; 4Department of Internal Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 5Department of Internal Medicine, Istishari Hospital, Amman, Jordan; 6Department of Clinical Research, Istishari Hospital, Amman, Jordan; 7Medical Education department, King Abdullah University Hospital, Irbid, Jordan; 8Medical Education department, Jordan University Hospital, Amman, Jordan; 9Medical education, Istishari Hospital, Amman, Jordan; 10Internal Medicine Department, Jordan Hospital, Amman, Jordan; 11Director of Cardiovascular Department, Jordan Hospital, Amman, JordanCorrespondence: Wesam Al Saud, Department of Clinical Pharmacy, Princess Salma Hospital, Ministry of Health, P.O.Box 86, Amman, 11118, Jordan, Tel +962780817273, Email [email protected]: The coexistence of multiple standard modifiable risk factors (SMuRFs),classical and novel risk factors (RFs) for atherosclerotic cardiovascular disease (ASCVD) is common in the Middle East (ME). There is a paucity of data on the coexistence of these RFs in ME young women.Aim: Comparing the prevalence and the statistical patterns of the SMuRFs, classical and novel RFs in target population.Methods: In this case-control (1:2) study, consecutive young women aged 18– 50 years were enrolled in 12 centers (July 2021 to October 2023). Prevalence and coexistence of 19 RFs were compared between cases with ASCVD and their controls. The RFs included SMuRFs (hypertension, type 2 diabetes, dyslipidemia, and cigarette smoking), other classical RF (obesity, family history of premature ASCVD, and physical inactivity), novel RFs and social determinants of health (health insurance, place of residence, depression, and level of education).Results: The study included 627 subjects; 209 had ASCVD (median age 46 years, IQR 49– 42 years) and 418 controls (median age 45 years, IQR 48– 41 years). The presence of 1– 2 RFs; (ASCVD: 63.2%, Control: 54.1%, p=0.037) and 3– 4 RFs; (ASCVD: 27.8%, Control: 3.3%, p < 0.001) SMuRFs was more prevalent in women with ASCVD. Similarly, the presence of 4– 5 RFs; (ASCVD: 40.7%, Control: 14.6%, p< 0.001), and 6– 7 (ASCVD: 10.5%, Control: 1%, p < 0.001). The classical RF were also significantly common in these women. The distribution of multiple novel RF was not statistically significant across both groups. Finally, regarding the socioeconomic RFs in women with ASCVDs, the presence of 1– 2 RFs (ASCVD: 59.8%, Control: 76.1%, p < 0.001) was significantly less common while the presence of 3– 4 RFs (ASCVD: 39.2%, Control: 21.8%, p < 0.001) was vastly more common.Conclusion: An elevated rate of coexistence of classical RF in the case group, mainly socioeconomic and SMuRFs. By managing them primary and secondary ASCVDs prevention attained.Keywords: atherosclerotic cardiovascular disease, multiple standard modifiable risk factors, classical cardiovascular disease, novel risk factor

Book Chapter Pengantar Pasar Modal Kelompok Studi Pasar Modal Kabinet Radiant Universitas Siliwangi

Buku ini tidak lain adalah untuk membantu mengedukasikan pasar modal kepada generasi muda khususnya para mahasiswa baik di lingkungan kampus Universitas Siliwinagi maupun dari berbagai kalangan. Buku ini juga akan memberikan informasi secara lengkap mengenai perngertian dan tekhnik dasar di dalam pasar modal. Dengan buku ini juga diharapkan dapat menjadi regenerasi ilmu khususnya dari Kabinet Radiant KSPM UNSIL 2021 kepada generasi selanjutnya, dimana buku ini merupakan kolaborasi beberapa penulis dari Kabinet Radiant KSPM UNSIL 2021