Neonatal diabetes mellitus with pancreatic agenesis in an infant with homozygous IPF-1 Pro63fsX60 mutation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75447/1/j.1399-5448.2009.00526.x.pd

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Perlindungan Hukum terhadap Konsumen Atas Penyalahgunaan Data Pribadi pada Aplikasi Financial TECHNOLOGY Peer To Peer Lending Ilegal di Indonesia

Maraknya penggunaan peer-to-peer lending berbasis Fintech Illegal di Indonesia menimbulkan banyak pelanggaran terhadap perlindungan konsumen. Pada Kenyataannya masih banyak masyarakat yang menggunakan peer-to-peer lending berbasis fintech illegal. Fintech illegal memiliki kemampuan dalam mempromosikan nama mereka dengan iming-iming pinjaman suku bunga rendah, pinjaman 1 jam cair, dan lainnya. Di sisi lain, Fintech ilegal seringkali juga melakukan penagihan dengan cara yang kasar hingga penyalahgunaan data pribadi yang dilakukan oleh penyelenggara fintech illegal tersebut. Penyalahgunaan data pribadi acap kali terjadi apabila konsumen tidak mampu membayar tagihan sehingga data konsumen disebarluaskan dengan maksud untuk menimbulkan itikad membayar konsumen serta seringkali mendapatkan ancaman-ancaman melalui whatsapp, sms, dan telepon. Dengan demikian, bagaimana bentuk perlindungan hukum bagi konsumen terhadap data pribadi yang disalahgunakan berbasis fintech illegal di Indonesia? Bagaimana regulasi-regulasi yang mengatur mengenai perlindungan data pribadi. Penelitian ini menggunakan metode yuridis normatif dengan menganalisa latar belakang dan permasalahan tersebut, dihubungkan dengan kerangka pemikiran hukum kualitatif. Berdasarkan penelitian ini, masih ditemukannya ketidakefektifan regulasi dengan masalah tersebut sehingga perlu adanya upaya perlindungan hukum yang jelas bagi konsumen atas penyalahgunaan data pribadi berbasis fintech. Kata Kunci: Perlindungan Data Pribadi, Financial Technology, Peer to Peer Lending, Data Pribadi, Konsume

Antihyperglycemic Potential of Grewia asiatica Fruit Extract against Streptozotocin-Induced Hyperglycemia in Rats: Anti-Inflammatory and Antioxidant Mechanisms

Diabetes mellitus is regarded as a serious chronic disease that carries a high risk for considerable complications. In folk medicine, the edible Grewia asiatica fruit is used in a number of pathological conditions. This study aimed to investigate the possible curative effect of G. asiatica fruit ethanolic extract against streptozotocin- (STZ-) induced hyperglycemia in rats. Furthermore, mechanism of antihyperglycemic action is investigated. Hyperglycemic rats are either treated with 100 or 200 mg/kg/day G. asiatica fruits extract. Serum glucose, liver glycogen, malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), interleukin- (IL-) 1β, and tumor necrosis factor- (TNF-) α are measured. G. asiatica fruits extract reduces blood glucose and pancreatic MDA levels. It increases liver glycogen and pancreatic GSH contents and SOD enzyme activity. Furthermore, Grewia asiatica fruits extract decreases serum IL-1β and TNF-α. The treatment also protects against STZ-induced pathological changes in the pancreas. The results of this study indicated that G. asiatica fruit extract exerts antihyperglycemic activity against STZ-induced hyperglycemia. The improvement in the pancreatic β-cells and antioxidant and anti-inflammatory effects of G. asiatica fruit extract may explain the antihyperglycemic effect

Cisatracurium dose–response relationship in patients with chronic liver disease

Objective: Cisatracurium is approximately 3 times more potent than atracurium, devoid of histamine release and cardiovascular side effects and mainly eliminated by Hofmann degradation. Patients with liver disease exhibit abnormal response to most of muscle relaxants. This study was designed to evaluate the dose–response of cisatracurium in patients with mild–moderate liver impairment in comparison with healthy subjects. Methods: Eighty ASA physical status I–II patients of both sexes, scheduled for elective surgical procedures under general anesthesia, were divided according to their preoperative hepatic status and laboratory investigations into two groups; Group I (control group with normal liver functions, n = 40) and Group II (Liver dysfunction group, Child-Pugh Score A or B, n = 40). The dose–response curve was constructed, ED50 and ED95 were estimated. Results: The preoperative laboratory parameters showed statistically significant differences between the two groups regarding serum albumin, total bilirubin, ALT, AST, PT, PC and INR. The operative data showed statistically insignificant difference between the two groups regarding the 1st dose response (p = 0.152), the estimated ED80 (p = 0.886) and the calculated 2nd dose (p = 0.886) and statistically significant differences between the two groups regarding the 2nd dose response (p = 0.006), the measured ED50 (p = 0.010) and the measured ED95 (p = 0.001). In conclusion, the measured ED50 and ED95 through two-dose dose–response curve technique were clinically insignificant from using the single-dose technique. The dose–response curve of cisatracurium in patients with chronic liver disease was clinically insignificant in comparison with healthy subjects

Biochemical Analysis of Four Missense Mutations in the HSD17B3 Gene Associated With 46,XY Disorders of Sex Development in Egyptian Patients

Mutations in the HSD17B3 gene are associated with a 46,XY disorder of sexual development (46,XY DSD) as a result of low testosterone production during embryogenesis.; To elucidate the molecular basis of the disorder by chemically analyzing four missense mutations in HSD17B3 (T54A, M164T, L194P, G289S) from Egyptian patients with 46,XY DSD.; Expression plasmids for wild-type 17β-hydroxysteroid hydrogenase type 3 (17β-HSD3) and mutant enzymes generated by site-directed mutagenesis were transiently transfected into human HEK-293 cells. Protein expression was verified by western blotting and activity was determined by measuring the conversion of radiolabeled Δ4-androstene-3,17-dione to testosterone. Application of a homology model provided an explanation for the observed effects of the mutations.; Testosterone formation by wild-type and mutant 17β-HSD3 enzymes was compared.; Mutations T54A and L194P, despite normal protein expression, completely abolished 17β-HSD3 activity, explaining their severe 46,XY DSD phenotype. Mutant M164T could still produce testosterone, albeit with significantly lower activity compared with wild-type 17β-HSD3, resulting in ambiguous genitalia or a microphallus at birth. The substitution G289S represented a polymorphism exhibiting comparable activity to wild-type 17β-HSD3. Sequencing of the SRD5A2 gene in three siblings bearing the HSD17B3 G289S polymorphism disclosed the homozygous Y91H mutation in the former gene, thus explaining the 46,XY DSD presentations. Molecular modeling analyses supported the biochemical observations and predicted a disruption of cofactor binding by mutations T54A and M164T and of substrate binding by L196P, resulting in the loss of enzyme activity. In contrast, the G289S substitution was predicted to disturb neither the three-dimensional structure nor enzyme activity.; Biochemical analysis of mutant 17β-HSD3 enzymes is necessary to understand genotype-phenotype relationships.; Biochemical analysis combined with molecular modeling provides insight into disease mechanism. However, the stability of mutant proteins in vivo cannot be predicted by this approach.; The 17β-HSD3 G289S substitution, previously reported in other patients with 46,XY DSD, is a polymorphism that does not cause the disorder; thus, further sequence analysis was required and disclosed a mutation in SRD5A2, explaining the cause of 46,XY DSD in these patients. Engeli RT, Tsachaki M, Hassan HA, et al. Biochemical Analysis of Four Missense Mutations in the HSD17B3 Gene Associated With 46,XY Disorders of Sex Development in Egyptian Patients. J Sex Med 2017;14:1165-1174