Modeling the effect of entrained sand particles on pressure transverse in a flowing gas well

Purpose The production of natural gas from the reservoir is always associated with entrained solid particle of different sizes mainly sand particles and crystalline salts. Entrained solid transport along the gas phase has been a great concern for gas production engineer, as the detrimental consequences are often associated to a desirable high operational parameters such rate and pressure transverse in producing well. Design/methodology/approach A variety of models for predicting pressure transverse in flowing gas wells have been reported in the literatures. Most of the models were based on steady state fluid flow equation that did not consider time factor which results in inaccurate at early production time. Some of the early investigators overlooked the effect of the entrained solid on the pressure transverse phenomena in a gas well. Hence, there is a need for developing a more realistic model for estimating pressure transverse at all times in flowing solid-gas vertical well. Findings This study presents equation for pressure drop in flowing vertical well without neglecting any term in the momentum equation by the inclusion of accumulation and kinetic term. The solution of the resulting differential equation gives functional relationship between solid-gas flow rates and pressure at any point in flowing well at any given production time

INFLUENCE OF BOTANICALS ON SOIL FERTILITY POTENTIALS, SEED GERMINATION AND PERFORMANCE OF MAIZE (ZEA MAYS) VARIETIES UNDER LOW FERTILE CONTINUOUSLY-CROPPED SOIL CONDITIONS

It is not unreasonable to state that, even before the introduction of organic agriculture, African local farmers have numerous of undocumented environment-friendly, nature-inclined indigenous techniques for boosting soil fertility and enhancing crop yield. However, despite the versatility of indigenous knowledge, setback is always experienced from western science, which tags such knowledge as being non-scientific and not worthy of scholarly engagements. A field experiment was carried out in the year 2013, at the Teaching and Research Farms, Ladoke Akintola University of Technology, Ogbomoso, to assess the soil fertility and yield promoting potentials of some indigenous plant species’ botanicals used as pre-planting treatments on different maize varieties. It was a 3 by 5 factorial experiment. The treatments introduced were: Three (3) maize varieties (V1 = ACR-DMR-SR-Y, V2 = Local EM-W and V3 = Suwan Solo Yellow and five (5) other treatments (comprising pre-sowing botanical treatments of: Kigelia africana only, Glyphea brevis only, combination of Kigelia africana and Glyphea brevis only, NPK fertilizer application (as a reference) and the control (treated with ordinary water only). The trial was laid out in Split Plot in Randomized Complete Block Design (RCBD), replicated three times. Data were collected on growth and yield parameters, and the data collected were analysed using analysis of variance (ANOVA). Means were compared using Duncan Multiple Range Test (DMRT). All the botanical treatments significantly influenced germination, growth, yield and nutrient uptakes of maize, compared to the control. Either of the botanicals tested (with ordinary basal manure application of the pre-existing plant residues on the field), competed effectively with NPK fertilized plants. Hence, since maize responded better to sole treatments of either Kigelia africana or Glyphea brevis extracts, irrespective of varieties than the combined treatment of the two botanicals, any of the maize varieties is therefore recommended as being suitably compatible with either of the sole botanical treatments, in the study area. Thus, this research is reasonable, particularly in the aspects of fertilizer economy, environment-friendliness, organic farming and more profitable crop production in the tropics, where soils are continuously cropped and marginal

Developing a Mobile App (LYNX) to Support Linkage to HIV/Sexually Transmitted Infection Testing and Pre-Exposure Prophylaxis for Young Men Who Have Sex With Men: Protocol for a Randomized Controlled Trial

BACKGROUND: Young men who have sex with men (YMSM) in the United States have among the highest incidence of HIV and sexually transmitted infection (STI) and the lowest uptake of HIV and STI testing and pre-exposure prophylaxis (PrEP). Nearly universal mobile phone ownership among youth provides an opportunity to leverage mobile health apps to increase HIV/STI testing and PrEP uptake among YMSM. OBJECTIVE: The goals of this project are to develop and refine LYNX, a novel mobile app to support linkage to HIV/STIs testing and PrEP services among YMSM in the United States, and to evaluate the acceptability and feasibility of LYNX in a pilot randomized controlled trial (RCT). METHODS: This research protocol will be conducted in 3 phases: an iterative development phase with a series of 3 focus groups among 20 YMSM to refine the LYNX app; an open technical pilot among 15 YMSM to optimize usability of the app; and then a 6-month pilot RCT among 60 HIV-uninfected YMSM at risk for HIV acquisition. Developed using the Information, Motivation, and Behavioral skills theoretical model, the LYNX app includes an electronic diary to track sexual behaviors (information), a personalized risk score to promote accurate risk perception (information/motivation), testing reminders (motivation/behavioral skills), and access to home-based HIV/STI testing options and geospatial-based HIV/STI testing care sites (behavioral skills). Feasibility and acceptability will be assessed through app analytics of usage patterns and acceptability scales administered via computer-assisted self-interview at 3 and 6 months. We will also evaluate preliminary efficacy by comparing the proportion of YMSM who test at least once during the 6-month pilot and the proportion who successfully link to a PrEP provider in the intervention versus control groups. RESULTS: Formative work is currently underway. The LYNX pilot RCT will begin enrollment in October 2018, with study results available in 2019. CONCLUSIONS: The LYNX app is one of the first mobile apps designed to increase HIV/STI testing and PrEP uptake among YMSM. As low-perceived risk is a barrier to HIV/STI testing and PrEP use among youth, the personalized risk assessment and interactive sexual diary in LYNX could assist YMSM in better understanding their HIV risk and providing motivation to test for HIV/STIs and initiate PrEP. Coupled with community-based recruitment, this novel mobile app has great potential to reach and engage YMSM not currently involved in care and increase rates of HIV/STI testing and PrEP uptake in this vulnerable population

Phase 3 Safety and Efficacy of AZD1222 (ChAdOx1 nCoV-19) Covid-19 Vaccine

BACKGROUND: The safety and efficacy of the AZD1222 (ChAdOx1 nCoV-19) vaccine in a large, diverse population at increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United States, Chile, and Peru has not been known. METHODS: In this ongoing, double-blind, randomized, placebo-controlled, phase 3 clinical trial, we investigated the safety, vaccine efficacy, and immunogenicity of two doses of AZD1222 as compared with placebo in preventing the onset of symptomatic and severe coronavirus disease 2019 (Covid-19) 15 days or more after the second dose in adults, including older adults, in the United States, Chile, and Peru. RESULTS: A total of 32,451 participants underwent randomization, in a 2:1 ratio, to receive AZD1222 (21,635 participants) or placebo (10,816 participants). AZD1222 was safe, with low incidences of serious and medically attended adverse events and adverse events of special interest; the incidences were similar to those observed in the placebo group. Solicited local and systemic reactions were generally mild or moderate in both groups. Overall estimated vaccine efficacy was 74.0% (95% confidence interval [CI], 65.3 to 80.5; P CONCLUSIONS: AZD1222 was safe and efficacious in preventing symptomatic and severe Covid-19 across diverse populations that included older adults. (Funded by AstraZeneca and others; ClinicalTrials.gov number, NCT04516746.)

Molecular dynamics, quantum mechanics and docking studies of some Keap1 inhibitors – An insight into the atomistic mechanisms of their antioxidant potential

Inhibitors of Keap1 would disrupt the covalent interaction between Keap1 and Nrf2 to unleash Nrf2 transcriptional machinery that orchestrates its cellular antioxidant, cytoprotective and detoxification processes thereby, protecting the cells against oxidative stress mediated diseases. In this in silico research, we investigated the Keap1 inhibiting potential of fifty (50) antioxidants using pharmacokinetic ADMET profiling, bioactivity assessment, physicochemical studies, molecular docking investigation, molecular dynamics and Quantum mechanical-based Density Functional Theory (DFT) studies using Keap1 as the apoprotein control. Out of these 50 antioxidants, Maslinic acid (MASA), 18-alpha-glycyrrhetinic acid (18-AGA) and resveratrol stand out by passing the RO5 (Lipinski rule of 5) for the physicochemical properties and ADMET studies. These three compounds also show high binding affinity of -10.6 kJ/mol, -10.4 kJ/mol and -7.8 kJ/mol at the kelch pocket of Keap1 respectively. Analysis of the 20ns trajectories using RMSD, RMSF, ROG and h-bond parameters revealed the stability of these compounds after comparing them with Keap1 apoprotein. Furthermore, the electron donating and accepting potentials of these compounds was used to investigate their reactivity using Density Functional Theory (HOMO and LUMO) and it was revealed that resveratrol had the highest stability based on its low energy gap. Our results predict that the three compounds are potential drug candidates with domiciled therapeutic functions against oxidative stress-mediated diseases. However, resveratrol stands out as the compound with the best stability and therefore, could be the best candidate with the best therapeutic efficacy

Inhibitors of α-glucosidase and Angiotensin-converting Enzyme in the Treatment of Type 2 Diabetes and its Complications: A Review on in Silico Approach

Background: The use of pharmacological agents to synergistically target key enzymes associated with carbohydrate digestion (α-glucosidase) and the hypertension-related angiotensin-converting enzyme (ACE) are critical strategies for the management of type 2 diabetes (T2D) and its end-stage complications. Furthermore, aside from their blood pressure-lowering effect, ACE inhibitors (ACEIs) are important therapeutic agents for preventing diabetic complications, highlighting their synergistic renoprotective and antihypertensive effects in diabetic patients who are normotensive and hypertensive. Objectives: We reviewed the safety and potent activity of phytochemicals discovered based on molecular docking and dynamics in recent years that could be used to treat T2D. Methods: We surveyed recently in silico drug discovery findings on α-glucosidase and ACE retrieved from the PubMed database. Computational in silico ADMET meta-analysis was performed on 57 compounds that could potentially inhibit α-glucosidase or ACE. Results: The review highlighted the fact that most hit compounds of α-glucosidase and ACE involving the use of molecular docking and molecular dynamics techniques are competitive and peptide inhibitors, respectively. Moreover, we found that most authors do not consider absorption distribution metabolism excretion toxicity (ADMET) studies on drug candidates, which is important in determining the safety profile of potent leads. Hence, we performed in silico ADMET meta-analysis of the reported compounds and found some inhibitors with an excellent pharmacological profile. Conclusion: We propose that further studies be conducted on these promising leads to demonstrate their efficacy and safety in the treatment of T2D

GCMS fingerprints and phenolic extracts of Allium sativum inhibit key enzymes associated with type 2 diabetes

المخلص: أهداف البحث: تم الإبلاغ عن تثبيط إنزيمات هضم الكربوهيدرات (ألفا أميلاز وألفا غلوكوزيداز) في الدراسات كنهج علاجي تجاه التحكم أو علاج السكري من النمط ٢ بسبب قدرته على خفض ارتفاع السكر في الدم بعد الأكل. أثبتت الدراسات السابقة احتمالية مكافحة السكري باستخدام الثوم ضد السكري. لذلك، في هذه الدراسة، قمنا بتقييم الإمكانات المضادة لمرض السكر للثوم عند مقرن فحص الإنزيم في المختبر واكتشاف الأدوية الحاسوبية. طرق البحث: استخدمنا في المختبر اختبار تثبيط ألفا أميلاز وألفا غلوكوزيداز لتقييم احتمالية مكافحة السكري وبعد ذلك تم استخدام التحليل الطيفي الكتلي للغاز، لتحديد وقياس المركبات المنشطة حيويا للمستخلص النباتي. بالإضافة إلى ذلك، تم توجيه المركبات المنشطة حيويا المحددة إلى الالتحام وتقييم الحرائك الدوائية. النتائج: تظهر نتائجنا أن المستخلص الفينولي للثوم له إمكانات مثبطة عالية لألفا أميلاز وألفا غلوكوزيداز ذات دلالة إحصائية معتبرة وبطريقة تعتمد على الجرعة. ومن المثير للاهتمام، أن المستخلص ثبط ألفا غلوكوزيداز إلى نصف التركيز المثبط الأقصى من ٥٣.٧٥ ميكروغرام/مل وهو أعلى مما تم الحصول عليه للأكاربوز القياسي. كشفت محاكاة الالتحام عن موريلينول (قيم تقارب متوسطة تبلغ −٧.٣ كيلو كالوري/مول) وفينتولامين (قيم تقارب متوسطة تبلغ −٧.١ كيلو كالوري/مول) كأفضل روابط ألفا غلوكوزيداز. لم يكن لهذه المركبات تقارب جيد مع بقايا الموقع النشط للإنزيم فحسب، بل لها أيضا خصائص ممتازة تشبه الأدوية والحرائك الدوائية التي يمكن أن تستخدم في العيادة. الاستنتاجات: يؤكد بحثنا على احتمالية الثوم كغذاء وظيفي للتحكم بالسكري من النمط الثاني ويحث على النظر في موريلينول وفينتولامين لتطوير الأدوية. Abstract: Objectives: Inhibition of carbohydrate digestion enzymes (α-amylase and α-glucosidase) has been reported in studies as a therapeutic approach for the management or treatment of type 2 diabetes mellitus, owing to its potential to decrease postprandial hyperglycemia. The anti-diabetic potential of Allium sativum (also known as garlic) against diabetes mellitus has been established. Therefore, in this study, we assessed the antidiabetic potential of A. sativum using in vitro enzyme assays after which we explored computational modelling approach using the quantified GC-MS identities to unravel the key bioactive compounds responsible for the anti-diabetic potential. Methods: We used in vitro enzyme inhibition assays (α-amylase and α-glucosidase) to evaluate antidiabetic potential and subsequently performed gas chromatography–mass spectroscopy (GC-MS) to identify and quantify the bioactive compounds of the plant extract. The identified bioactive compounds were subjected to in silico docking and pharmacokinetic assessment. Results: A. sativum phenolic extract showed high dose-dependent inhibition of α-amylase and α-glucosidase (p < 0.05). Interestingly, the extract inhibited α-glucosidase with a half maximal inhibitory concentration of 53.75 μg/mL, a value higher than that obtained for the standard acarbose. Docking simulation revealed that morellinol and phentolamine were the best binders of α-glucosidase, with mean affinity values of −7.3 and −7.1 kcal/mol, respectively. These compounds had good affinity toward active site residues of the enzyme, and excellent drug-like and pharmacokinetic properties supporting clinical applications. Conclusions: Our research reveals the potential of A. sativum as a functional food for the management of type 2 diabetes, and suggests that morellinol and phentolamine may be the most active compounds responsible for this anti-diabetic prowess. Therefore these compounds require further clinical asessment to demonstrate their potential for drug development

HPTN 083-02: factors influencing adherence to injectable PrEP and retention in an injectable PrEP study

INTRODUCTION: HPTN 083 demonstrated the superiority of long-acting cabotegravir (CAB-LA) versus daily oral emtricitabine/tenofovir disoproxil fumarate (TDF/FTC) as pre-exposure prophylaxis (PrEP) among cisgender men and transgender women who have sex with men (MSM/TGW). HPTN 083 provided the first opportunity to understand experiences with injectable PrEP in a clinical trial. METHODS: Participants from two US sites (Chicago, IL and Atlanta, GA) and one international site (Rio de Janeiro, Brazil) were purposively sampled for individual qualitative interviews (N = 40), between November 2019 and March 2020, to explore trial experiences, barriers to adherence and other factors that may have impacted study implementation or outcomes. The blinded phase ended early due to efficacy; this analysis includes interviews conducted prior to unblinding with three groups defined by adherence (i.e. injection visit attendance): adherent (n = 27), non-adherent (n = 12) and early discontinuers (n = 1). Data were organized using NVivo software and analysed using content analysis. RESULTS: Participants (mean age: 27) were primarily cisgender MSM (90%) and Black/African American (60%). Reasons for trial enrolment and PrEP use included a preference for using HIV prevention medication versus treatment in the event of HIV acquisition; the ability to enhance health via study-related education and services; access to a novel, convenient HIV prevention product at no cost; and contributing to MSM/TGW communities through research. Participants contrasted positive experiences with study staff with their routine clinical care, and emphasized increased scheduling flexibility, thorough communication, non-judgemental counselling and open, affirming environments (e.g. compassion, less stigma) as adherence facilitators. Injection experiences were positive overall; some described early injection-related anxiety, which abated with time and when given some measure of control (e.g. pre-injection countdown), and minimal injection site discomfort. Some concerns and misperceptions about injectable PrEP were reported. Barriers to adherence, across all adherence categories, included structural factors (e.g. financial constraints, travel) and competing demands (e.g. work schedules). CONCLUSIONS: Respondents viewed injectable PrEP trial participation as a positive experience and a means of enhancing wellbeing. Study site flexibility and affirming clinic environments, inclusive of non-judgemental counselling, were key facilitators of adherence. To support injection persistence, interventions that address structural barriers and promote flexible means of injection delivery may be most effective