Molecular Docking Investigation of New Inhibitors of <i>Falciparum vivax</i>

Despite the vigorous research and development, as of 2017, there is currently no widely available antimalarial vaccine. An effective, commercially available vaccine would be a huge game changer;however, it seems like there is still a long way to go until that target is reached. Therefore, the purpose of this study was to use molecular docking technique to identify new inhibitors for a novel antimalarial target with the overall aim of finding hit compounds which could be further optimized to become potential drug candidates. The docking protocol AutoDockVina was used alongside the molecular visualisation software UCSF Chimera to dock 100 naphthoquinones (labelled TM1-100) and 66 aryl diketones (labelled TM101-166) with the chosen target, Plasmodium vivax N-myristoyltransferase (PvNMT). Each docking session yielded the best 9 binding modes between the ligand and target. The hydrogen bond interactions of all binding modes were analysed, and the top six target molecules (TM) were short listed as the possible hit compounds (TM40, TM65, TM66, TM81, TM94 and TM165). These compounds displayed more than six hydrogen bonds under 3 angstroms over the 9 binding modes. Using Lipinski’s rule of 5, the potential hit compounds were further analysed to determine the drug-likeness and all were found to obey the parameters. Following the same method used to dock the ligands, twelve FDA approved antimalarial drugs were also docked with PvNMT for comparison purposes. Apart from proguanil, the other eleven antimalarial drugs displayed fewer hydrogen bonds under 3 angstroms over the 9 binding modes compared to all six of the potential hit compounds. This study discovered six compounds which displayed stronger interactions with the target protein compared to majority of the FDA approved drugs. The results of this investigation gave us new molecules that could be further investigated for the designing of novel drug-like compounds for the treatment of Malaria.

Efficacy of non-pharmacological interventions in controlling type 2 diabetes in patients of African descent: A systematic review

Purpose: The purpose of this review is to systematically assess the potential effectiveness of targeted educational and other non-pharmacological interventions on diabetes control in populations of African descent in developed countries. Such information can inform intervention strategies and highlight evidence-based approaches to deal with this significant problem in this population. Methods: A systematic review and a meta-analysis of random controlled trials and cohort studies evaluating the influence of education and other non-pharmacological interventions on HbA1Cconcentrations in patients of African descent with diabetes. A comprehensive search of PubMed, EMBASE, CINAHL, ZETOC, SIGLE databases was carried out. Results: Although nine studies (8 randomised controlled trials and 1 cohort study) met the inclusion criteria, relevant HbA1Cdata were available for 6 of the studies for the subsequent meta-analysis. Heterogeneity of meta-analysis was high (I2 = 92%), the random effects pooled standard mean difference favoured the intervention -0.66 (-1.15, -0.17), p = 0.009. After sensitivity analysis, I2 remained moderate to high at 69%. The random effects pooled standard mean difference continued to favour the intervention -0.48 (-0.81, -0.16), p = 0.009. Conclusion: There is evidence supporting the efficacy of educational and other non-pharmacological interventions in diabetes control in populations of African descent in English speaking developed countries. This conclusion is tempered by the significant heterogeneity of selected interventions and paucity of high quality research in the target population.

Activin-Directed Differentiation of Human Embryonic Stem Cells Differentially Modulates Alveolar Epithelial Wound Repair via Paracrine Mechanism

Differentiated embryonic stem cells (ESC) can ameliorate lung inflammation and fibrosis in animal lung injury models;therefore, ESC, or their products, could be candidates for regenerative therapy for incurable lung diseases, such as idiopathic pulmonary fibrosis (IPF). In this study, we have investigated the paracrine effect of differentiated and undifferentiated human ESC on alveolar epithelial cell (AEC) wound repair. hESC line, SHEF-2 cells were differentiated with Activin treatment for 22 days in an embryoid body (EB) suspension culture. Conditioned media (CM) which contain cell secretory factors were collected at different time points of differentiation. CM were then tested onin vitro?wound repair model with human type II AEC line, A549 cells (AEC). Our study demonstrated that CM originated from undifferentiated hESC significantly inhibited AEC wound repair when compared to the control. Whereas, CM originated from Activin-directed hESC differentiated cell population demonstrated a differential reparative effect on AEC wound repair model. CM obtained from Day-11 of differentiation significantly enhanced AEC wound repair in comparison to CM collected from pre- and post-Day-11 of differentiation. Day-11 CM enhanced AEC wound repair through significant stimulation of cell migration and cell proliferation. RT-PCR and immunocytochemistry confirmed that Day-11 CM was originated form a mixed population of endodermal/mesodermal differentiated hESC. This report suggests a putative paracrine-mediated epithelial injury healing mechanism by hESC secreted products, which is valuable in the development of novel stem cell-based therapeutic strategies.

European Specialty Examination in Gastroenterology and Hepatology examination-improving education in gastroenterology and hepatology

The Federation of Royal Colleges,the British Society of Gastroenterology(BSG)and the European Section and Board of Gastroenterology and Hepatology developed the European Specialty Examination in Gastroenterology and Hepatology(ESEGH)from the United Kingdom Specialty Certificate Examination,which was the original examination.Since 2018 the Specialty Certificate Examination and the ESEGH were combined into a single exam,identical across Europe and the rest of the world.The ESEGH is mandated in 4 countries(United Kingdom,Switzerland,The Netherlands and Malta)and the number of entries increased from 50 in 2014 to 490 in 2019.Candidates from countries were the ESEGH is not mandated are sitting the Exam,showing us they realize the enormous interest of holding a certificate for knowledge in their Curriculum.We also have an increasing number of candidates from countries outside Europe.

Emotional Distress and Metabolic Control in Diabetic Patients Attending Primary Health Care in the Eastern Province, Saudi Arabia

Background:Recognition and treatment of emotional distress,which affects 20 to 40%of outpatients with type 1 or type 2 diabetes,are important because of its association with worse diabetes self-care,poor glycemic control,increased rates of mortality and diabetes-related complications,and a rise in healthcare expenditure.However,although the symptoms of emotional distress improve in diabetic patients after psychological and pharmacological interventions,evidence of benefits in glycemic control is still uncertain.Objective:The aim of this study was to assess the metabolic control in diabetic patients with emotional distress attending primary mental care clinics(PMCC)in the Eastern Province of Saudi Arabia.Method:This study was a single group pretest-posttest design conducted on adult diabetic patients with emotional distress attending PMCC.Out of 194 attendees,62 patients who fulfilled the selection criteria were studied.Data were collected from the patients’records using a worksheet designed for the study.Metabolic parameters including BMI,BP,FBS,HbA1c and lipid profile were recorded before and after the management of emotional distress.Socio-demographic characteristics,complications related to diabetes and co-morbidities were also recorded.Paired t-test was used appropriately to compare continuous variables.A p-value of less than 0.05 was considered significant in all statistical analysis.Results:The majority of the patients had type 2 DM(98.2%)and the presence of co-morbidities was high(83.9%).A comparison of the metabolic parameters before and after management of emotional distress,showed a significant reduction in HbA1c(p=0.020)and elevation in HDL(p=0.010).No differences in BMI,BP,FBS,TC,TG or LDL were found.Conclusions:Treating emotional distress in diabetic patients is associated with an improvement in HbA1c and HDL.

Neuromuscular Electrical Stimulation in Intensive Care Unit Patients:Integrative Review

Intensive care units’ acquired muscle weakness is present in approximately 50% of the patients. Although active muscle training can attenuate weakness, a large proportion of critical patients cannot participate in any active mobilization. Neuromuscular electrical stimulation may be an alternative strategy to reverse muscle weakness. The objective of the study was to review the scientific publications on the use of neuromuscular electrical stimulation and its parameters and the main results in patients hospitalized in intensive care units. This is an integrative review surveying studies in online databases. The studies were selected from the following descriptors: neuromuscular electrical stimulation AND parameters AND intensive care units AND muscle weakness. The inclusion criteria included articles that addressed the topic of neuromuscular electrical stimulation and the parameters used in patients admitted to intensive care units, aged 18 years or older. Exclusion criteria were studies involving animals, case reports, letters to the editor and book chapters. The search comprised articles in the Portuguese, English and Spanish languages from January 2013 to March 2019. Of the 185 articles identified, nine met the eligibility criteria. The studies were evaluated assessing the level of evidence, and the relevant information was presented in the table and discussed. The parameters of the neuromuscular electrical stimulation employed in the studies showed positive results for the maintenance of strength and muscle mass. There was evidence of benefits in the local and systemic microcirculation, potentially mobilizing endothelial stem cells, to prevent atrophy, to reduce mechanical ventilation time and stay in intensive care unit;and when incorporated into the usual physiotherapy care, proved to be more effective than usual care. Its use is safe and viable in critically ill patients.

ABCD^(2) risk score does not predict the presence of cerebral microemboli in patients with hyper-acute symptomatic critical carotid artery stenosis

Introduction:ABCD^(2) risk score and cerebral microemboli detected by transcranial Doppler(TCD)have been separately shown to the predict risk of recurrent acute stroke.We studied whether ABCD2 risk score predicts cerebral microemboli in patients with hyper-acute symptomatic carotid artery stenosis.Participants and methods:We studied 206 patients presenting within 2 weeks of transient ischaemic attack or minor stroke and found to have critical carotid artery stenosis(≥50% ).86 patients(age 70±1(SEM:years),58 men,83 Caucasian)had evidence of microemboli;72(84% )of these underwent carotid endarterectomy(CEA).120 patients(age 72±1 years,91 men,113 Caucasian)did not have microemboli detected;102(85% )of these underwent CEA.Data were analysed using X2 and Mann–Whitney U tests and receiver operating characteristic(ROC)curves.Results:140/206(68% :95% CI 61.63 to 74.37)patients with hyper-acute symptomatic critical carotid stenosis had an ABCD2 risk score≥4.There was no significant difference in the NICE red flag criterion for early assessment(ABCD^(2) risk score≥4)for patients with cerebral microemboli versus those without microemboli(59/86 vs 81/120 patients:OR 1.05 ABCD2 risk score≥4(95% CI 0.58 to 1.90,p=0.867)).The ABCD2 risk score was<4 in 27 of 86(31% :95% CI 21 to 41)embolising patients and in 39 of 120(31% :95% CI 23 to 39)without cerebral microemboli.After adjusting for pre-neurological event antiplatelet treatment(APT),area under the curve(AUC)of ROC for ABCD2 risk score showed no prediction of cerebral microemboli(no pre-event APT,n=57:AUC 0.45(95% CI 0.29 to 0.60,p=0.531);preevent APT,n=147:AUC 0.51(95% CI 0.42 to 0.60,p=0.804)).Conclusions:The ABCD2 score did not predict the presence of cerebral microemboli or carotid disease in over one-quarter of patients with symptomatic critical carotid artery stenosis.On the basis of NICE guidelines(refer early if ABCD2≥4),assessment of high stroke risk based on ABCD2 scoring may lead to inappropriate delay in urgent treatment in many patients.

Significance of continuous rotavirus and norovirus surveillance in Indonesia

Background Diarrhea significantly contributes to the global burden of diseases, particularly in developing countries. Rota-virus and norovirus are the most dominant viral agents responsible for diarrheal disease globally. The aim of this review was to conduct a comprehensive assessment of rotavirus and norovirus study in Indonesia. Data sources Articles about rotavirus and norovirus surveillance in Indonesia were collected from databases, including PubMed and Google Scholar. Manual searching was performed to identify additional studies. Furthermore, relevant articles about norovirus diseases were included. Results A national surveillance of rotavirus-associated gastroenteritis has been conducted for years, resulting in substantial evidence about the high burden of the diseases in Indonesia. In contrast, norovirus infection received relatively lower attention and very limited data are available about the incidence and circulating genotypes. Norovirus causes sporadic and epidemic gastroenteritis globally. It is also emerging as a health problem in immunocompromised individuals. During post-rotavirus vaccination era, norovirus potentially emerges as the most frequent cause of diarrheal diseases. Conclusions Our review identifies knowledge gaps in Indonesia about the burden of norovirus diseases and the circulating genotypes. Therefore, there is a pressing need to conduct national surveillance to raise awareness of the community and national health authority about the actual burden of norovirus disease in Indonesia. Continuing rotavirus surveillance is also important to assess vaccine effectiveness and to continue tracking any substantial changes of circulating rotavirus genotypes.

Registry report on prediction by Pocock cardiovascular score of cerebral microemboli acutely following carotid endarterectomy

background Cerebral microemboli may lead to ischaemic neurological complications after carotid endarterectomy(CEA).The association between classical cardiovascular risk factors and acute cerebral microemboli following carotid surgery has not been studied.The aim of this study was to explore whether an established cardiovascular risk score(Pocock score)predicts the presence of cerebral microemboli acutely after CEA.subjects and methods Pocock scores were assessed for the 670 patients from the Carotid Surgery Registry(age 71±1(SEM)years,474(71%)male,652(97%)Caucasian)managed from January 2002 to December 2012 in the Regional Vascular Centre at University Hospitals Coventry and Warwickshire NHS Trust,which serves a population of 950000.CEA was undertaken in 474(71%)patients for symptomatic carotid stenosis and in 196(25%)asymptomatic patients during the same period.74% of patients were hypertensive,71%were smokers and 49% had hypercholesterolaemia.results A high Pocock score(≥2.3%)was significantly associated with evidence of cerebral microemboli acutely following CEA(P=0.039,Mann-Whitney(MW)test).A Pocock score(≥2.3%)did not predict patients who required additional antiplatelet therapy(microemboli signal(MES)rate>50 hour-1:P=0.164,MW test).Receiver operating characteristic analysis also showed that the Pocock score predicts acute postoperative microemboli(area under the curve(AUC)0.546,95%CI 0.502 to 0.590,P=0.039)but not a high rate of postoperative microemboli(MES>50 hour−1:AUC 0.546,95% CI 0.482 to 0.610,P=0.164).A Pocock score≥2.3% showed a sensitivity of 74% for the presence of acute postoperative cerebral microemboli.A Pocock score≥2.3% also showed a sensitivity of 77% and a negative predictive value of 90% for patients who developed a high microembolic rate>50 hour−1 after carotid surgery.Conclusion These findings demonstrate that the Pocock score could be used as a clinical tool to identify patients at high risk of developing acute postoperative microemboli.