Comparison of Post-Operative Analgesic Effects of Peritonsillar Infiltration of Dexmedetomidine, Lidocaine or Both in Children Following Tonsillectomy

Background: Peritonsillar infiltration of local anesthetics has efficient pain relief in children undergoing tonsillectomy. We hypothesize that lidocaine plus dexmedetomidine will potentiate the analgesic effect of each other rather than. Objectives: This study aimed to compare the analgesic effect of peritonsillar infiltration of lidocaine, dexmedetomidine, or lidocaine/dexmedetomidine on post-tonsillectomy pain. The primary outcome is the time of analgesia. The secondary outcomes are postoperative pain score, the effect of study medications on postoperative hemodynamic, and complications. Patients and Methods: Ninety patients were randomly allocated to three groups, 30 patients each. L group, patients received 2mg/kg lidocaine. D group, patients received 1 μg/kg of dexmedetomidine. LD group, patients received 1 μg/kg of dexmedetomidine plus 2 mg/kg lidocaine. Results: The time of the first analgesia request (h.) was longer in the LD group (13.70 ± 2.91) when compared with the L and D groups. Postoperative pain score was significantly lower in LD and D groups compared with the L group (P <0.05) On the other hand, there was a significantly lower median VAS score in the LD group when compared with the D group (P1 <0.05) Postoperative paracetamol consumption was significantly lower in LD group (0.55 ± 0.51 gm/24h) when compared with D and L groups (0.65 ± 0.59, 2.25 ± 0.44 gm/24h respectively). Conclusion: the use of lidocaine with dexmedetomidine is better than using each drug alone in decreasing posttonsillectomy pain and increasing the time to first request for analgesia with no significant postoperative side effects

Regioselective synthesis of 5-aminopyrazoles from reactions of amidrazones with activated nitriles : NMR investigation and X-ray structural analysis

N-Arylbenzamidrazones and ethyl 2-cyano-3-ethoxybut-2-enoate reacted together in ethanol and catalyzed by triethylamine (Et3N) to give 5-amino-3-methyl-1-(aryl(phenylimino)methyl)-1H-pyrazole derivatives. Reaction of the target amidrazones with bis-(methylthio)methylidene)malononitrile in EtOH/Et3N/DMF mixture proceeded to give the corresponding 5-aminopyrazoles. The structure of the obtained products was proved by IR, mass, and NMR spectra and elemental analyses. Two-dimensional NMR spectroscopy and X-ray structural analyses were used to differentiate the assigned structures from other possible ring systems and regioisomers. The reaction mechanism is discussed.Peer reviewe

Synthesis and Identification of New N,N-Disubstituted Thiourea, and Thiazolidinone Scaffolds Based on Quinolone Moiety as Urease Inhibitor

Synthesis of thiazolidinone based on quinolone moiety was established starting from 4-hydroxyquinol-2-ones. The strategy started with the reaction of ethyl bromoacetate with 4-hydroxyquinoline to give the corresponding ethyl oxoquinolinyl acetates, which reacted with hydrazine hydrate to afford the hydrazide derivatives. Subsequently, hydrazides reacted with isothiocyanate derivatives to give the corresponding N,N-disubstituted thioureas. Finally, on subjecting the N,N-disubstituted thioureas with dialkyl acetylenedicarboxylates, cyclization occurred, and thiazolidinone derivatives were obtained in good yields. The two series based on quinolone moiety, one containing N,N-disubstituted thioureas and the other containing thiazolidinone functionalities, were screened for their in vitro urease inhibition properties using thiourea and acetohydroxamic acid as standard inhibitors. The inhibition values of the synthesized thioureas and thiazolidinones exhibited moderate to good inhibitory effects. The structure−activity relationship revealed that N-methyl quinolonyl moiety exhibited a superior effect, since it was proved to be the most potent inhibitor in the present series achieving (IC50 = 1.83 ± 0.79 µM). The previous compound exhibited relatively much greater activity, being approximately 12-fold more potent than thiourea and acetohydroxamic acid as references. Molecular docking analysis showed a good protein−ligand interaction profile against the urease target (PDBID: 4UBP), emphasizing the electronic and geometric effect of N,N-disubstituted thiourea. View Full-Tex

Regioselective formation of new 3-S-alkylated-1,2,4-triazole-quinolones

Regioselective synthesis of quinolone-1,2,4-triazoles was established starting from 4-hydroxyquinol-2-ones. The strategy started by the reaction of ethyl bromoacetate with 4-hydroxyquinoline to give the corresponding ethyl oxoquinolinyl acetates, which reacted with hydrazine hydrate to afford the hydrazide derivatives. Subsequently, hydrazides reacted with isothiocyanate derivatives to give the corresponding acyl thiosemicarbazides. Finally, subjecting the thiosemicarbazide derivatives with ethyl bromoacetate, the reaction underwent internal cyclization and alkylation processes. Alkylation occurred regioselectivity to the sulfur atom of the thione group and not to the amino group. Thus 3-S-1,2,4-triazole-quinolones were obtained in good yields. The structure of the obtained compounds was proved by different spectroscopic techniques together with elemental analysis and X-ray crystallography.Peer reviewe

Hypoglycaemia Among Insulin-Treated Patients with Diabetes: Evaluation of the United Arab Emirates cohort of the International Operations-Hypoglycaemia Assessment Tool study

Objectives: This study aimed to evaluate the incidence of hypoglycaemia among insulin-treated patients with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) from the United Arab Emirates (UAE) cohort of the non-interventional International Operations-Hypoglycaemia Assessment Tool study. Methods: This cross-sectional observational study took place at 25 patient care centres in the UAE from October 2014 to May 2015. All adult patients with T1DM or T2DM who had been treated with insulin for >12 months were included. Self-assessment questionnaires and patient diaries were used to determine the incidence of documented hypoglycaemia both prospectively (four weeks after baseline) and retrospectively (six months and four weeks before baseline for severe and non-severe hypoglycaemic events, respectively). Results: A total of 325 patients were enrolled in the study, of which 82 (25.2%) had T1DM and 243 (74.8%) had T2DM. Among patients with T1DM, 71.4% reported hypoglycaemic events retrospectively, with an incidence rate (IR) of 102.8 events per patient-year (PY), while 95% reported hypoglycaemic events prospectively, with an IR of 63.1 events per PY. Additionally, 56.3% of patients with T2DM reported hypoglycaemic events retrospectively, with an IR of 42.2 events per PY, while 91.9% reported hypoglycaemic events prospectively, with an IR of 33.3 events per PY. Conclusion: The prevalence and incidence of hypoglycaemia were high among insulin-treated patients with T1DM and T2DM in the UAE. Individualised glycaemic goals, patient education and blood glucose monitoring may help to reduce the incidence of hypoglycaemia in this population. Keywords: Hypoglycemia; Insulin; Type 1 Diabetes Mellitus; Type 2 Diabetes Mellitus; United Arab Emirates

Islet Gene View-a tool to facilitate islet research

Characterization of gene expression in pancreatic islets and its alteration in type 2 diabetes (T2D) are vital in understanding islet function and T2D pathogenesis. We leveraged RNA sequencing and genome-wide genotyping in islets from 188 donors to create the Islet Gene View (IGW) platform to make this information easily accessible to the scientific community. Expression data were related to islet phenotypes, diabetes status, other islet-expressed genes, islet hormone-encoding genes and for expression in insulin target tissues. The IGW web application produces output graphs for a particular gene of interest. In IGW, 284 differentially expressed genes (DEGs) were identified in T2D donor islets compared with controls. Forty percent of DEGs showed cell-type enrichment and a large proportion significantly co-expressed with islet hormone-encoding genes; glucagon (GCG, 56%), amylin (IAPP, 52%), insulin (INS, 44%), and somatostatin (SST, 24%). Inhibition of two DEGs, UNC5D and SERPINE2, impaired glucose-stimulated insulin secretion and impacted cell survival in a human beta-cell model. The exploratory use of IGW could help designing more comprehensive functional follow-up studies and serve to identify therapeutic targets in T2D.Peer reviewe

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed