Maximum Likelihood Estimation in the Inverse Weibull Distribution with Type II Censored Data

We consider maximum likelihood estimation for the parameters and certain functions of the parameters in the Inverse Weibull (IW) distribution based on type II censored data. The functions under consideration are the Mean Residual Life (MRL), which is very important in reliability studies, and Tail Value at Risk (TVaR), which is an important measure of risk in actuarial studies. We investigated the performance of the MLE of the parameters and derived functions under various experimental conditions using simulation techniques. The performance criteria are the bias and the mean squared error of the estimators. Recommendations on the use of the MLE in this model are given. We found that the parameter estimators are almost unbiased, while the MRL and TVaR estimators are asymptotically unbiased. Moreover, the mean squared error of all estimators decreased for larger sample sizes and it increased when the censoring proportion is increased for a fixed sample size. The conclusion is that the maximum likelihood method of estimation works well for the parameters and the derived functions of the parameter like the MRL and TVaR. Two examples on a real data set are presented to illustrate the application of the methods used in this paper. The first one is on survival time of pigs while the other is on fire losses.The authors would like to thank the referees for their suggestions and thoughtful comments that resulted in a much-improved version of the paper. This research was supported by a grant from the Office of Research Support at Qatar University, Grant no. QUST-1-CAS-2022-318

Effect of Aromatase Inhibitor Letrozole on the Placenta of Adult Albino Rats: A Histopathological, Immunohistochemical, and Biochemical Study

Background: Letrozole, an aromatase inhibitor, has recently been introduced as the preferred treatment option for ectopic pregnancy. To date, no study has investigated the effect of letrozole alone on placental tissue. The present study aimed to evaluate the effect of different doses of letrozole on the placenta of rats and to clarify the underlying mechanism. Methods: Sixty pregnant female rats were equally divided into three groups, namely the control group (GI), low-dose (0.5 mg/Kg/day) letrozole group (GII), which is equivalent to the human daily dose (HED) of 5 mg, and high-dose (1 mg/Kg/day) letrozole group (GIII), equivalent to the HED of 10 mg. Letrozole was administered by oral gavage daily from day 6 to 16 of gestation. Data were analyzed using a one-way analysis of variance followed by Tukey’s post hoc test and Chi square test. P<0.05 was considered statistically significant.Results: Compared to the GI and GII groups, high-dose letrozole significantly increased embryonic mortality with a high post-implantation loss rate (P<0.001) and significantly reduced the number of viable fetuses (P<0.001) and placental weight (P<0.001) of pregnant rats. Moreover, it significantly reduced placental estrogen receptor (ER) and progesterone receptor (PR) (P<0.001) and the expression of vascular endothelial growth factor (P<0.001), while increasing the apoptotic index of cleaved caspase-3 (P<0.001).Conclusion: Letrozole inhibited the expression of ER and PR in rat placenta. It interrupted stimulatory vascular signals causing significant apoptosis and placental vascular dysfunction. Letrozole in an equivalent human daily dose of 10 mg caused a high post-implantation loss rate without imposing severe side effects

Echocardiographic assessment of diastolic function in non-ST elevation acute coronary syndrome patients and its association with in-hospital diagnosis

Objective: This study was conducted to evaluate the association of echocardiographic parameters used in leftventricular (LV) diastology with the early results of non-ST elevation acute coronary syndrome (NSTE-ACS)workup in the hospital.&nbsp;Methods: This cross-sectional study was performed on patients presenting with acute chest pain and a diagnosis of NSTE-ACS including only patients with unstable angina (UA) and non-ST elevation myocardial infarction&nbsp;(NSTEMI). All patients underwent transthoracic echocardiography in the emergency room (ER) within 12 hours&nbsp;of the last episode of chest pain. An invasive approach was not uniformly pursued in all of the patients so&nbsp;analysis was performed in two different settings. First, analysis was performed in the patients that underwent&nbsp;coronary angiography (CAG) and echocardiographic data were compared between those with normal and abnormal CAG results. Finally, echocardiographic data of the patients with normal diagnostic results (i.e., normal&nbsp;exercise tolerance test (ETT), myocardial perfusion imaging (MPI) or coronary angiography (CAG) results) were&nbsp;compared with the data of the patients with abnormal test results.&nbsp;Results: Eighty patients with a mean age of 54.43 ± 12.38 years were included in the study, of whom 57 (71.2%)&nbsp;were male. Fifty-three patients underwent CAG. In these 53 patients, there was significant difference in mitral annular velocity in early diastole (e’), ratio of mitral inflow velocity to e’ (E/e’), left ventricular end-diastolic&nbsp;diameter (LVEDD) and left ventricular end-diastolic pressure (LVEDP) between patients with coronary artery involvement and those with normal coronary artery (P&lt;0.05). The area under the receiver operating characteristic&nbsp;(ROC) curve to predict CAG results for e’, E/ e’, LVEDD and LVEDP was more than 0.65. The sensitivity and specificity of the LV diastolic dysfunction for predicting coronary involvement was 94.4% and 35.29%, respectively.&nbsp;Comparison of echocardiographic data between patients with normal test results (non-invasive and invasive)&nbsp;and those with abnormal diagnostic tests showed a significant difference in e’, E/e’, acceleration time of E, LV&nbsp;end-diastolic diameter index, size of interventricular septum and left atrial volume.&nbsp;Conclusion: The results suggest that diastolic dysfunction data can be used as an adjunctive method to evaluate&nbsp;ACS patients in the ER

Hyperglycemic conditions induce rapid cell dysfunction-promoting transcriptional alterations in human aortic endothelial cells

Abstract Hyperglycemia is a major risk factor in the development of diabetic complications and promotes vascular complications through dysregulation of endothelial cell function. Various mechanisms have been proposed for endothelial cell dysregulation but the early transcriptomic alterations of endothelial cells under hyperglycemic conditions are not well documented. Here we use deep time-series RNA-seq profiling of human aortic endothelial cells (HAECs) following exposure to normal (NG) and high glucose (HG) conditions over a time course from baseline to 24 h to identify the early and transient transcriptomic changes, alteration of molecular networks, and their temporal dynamics. The analysis revealed that the most significant pathway activation/inhibition events take place in the 1- to 4-h transition and identified distinct clusters of genes that underlie a cascade of coordinated transcriptional events unique to HG conditions. Temporal co-expression and causal network analysis implicate the activation of type 2 diabetes (T2D) and growth factor signalling pathways including STAT3 and NF-κB. These results document HAEC transcriptional changes induced by hyperglycemic conditions and provide basic insight into the rapid molecular alterations that promote endothelial cell dysfunction

Preparation, Characterization, Wound Healing, and Cytotoxicity Assay of PEGylated Nanophytosomes Loaded with 6-Gingerol

Background: Nutrients are widely used for treating illnesses in traditional medicine. Ginger has long been used in folk medicine to treat motion sickness and other minor health disorders. Chronic non-healing wounds might elicit an inflammation response and cancerous mutation. Few clinical studies have investigated 6-gingerol’s wound-healing activity due to its poor pharmacokinetic properties. However, nanotechnology can deliver 6-gingerol while possibly enhancing these properties. Our study aimed to develop a nanophytosome system loaded with 6-gingerol molecules to investigate the delivery system’s influence on wound healing and anti-cancer activities. Methods: We adopted the thin-film hydration method to synthesize nanophytosomes. We used lipids in a ratio of 70:25:5 for DOPC(dioleoyl-sn-glycero-3-phosphocholine): cholesterol: DSPE/PEG2000, respectively. We loaded the 6-gingerol molecules in a concentration of 1.67 mg/mL and achieved size reduction via the extrusion technique. We determined cytotoxicity using lung, breast, and pancreatic cancer cell lines. We performed gene expression of inflammation markers and cytokines according to international protocols. Results: The synthesized nanophytosome particle sizes were 150.16 ± 1.65, the total charge was −13.36 ± 1.266, and the polydispersity index was 0.060 ± 0.050. Transmission electron microscopy determined the synthesized particles’ spherical shape and uniform size. The encapsulation efficiency was 34.54% ± 0.035. Our biological tests showed that 6-gingerol nanophytosomes displayed selective antiproliferative activity, considerable downregulation of inflammatory markers and cytokines, and an enhanced wound-healing process. Conclusions: Our results confirm the anti-cancer activity of PEGylated nanophytosome 6-gingerol, with superior activity exhibited in accelerating wound healing

Awareness about folic acid intake amongst Saudi women of child bearing age in the Aseer region in prevention of neural tube defects in fetus

Background: Folic acid deficiency during pregnancy can lead to critical anomalies called neural tube defects (NTDs) in fetus. Though its prevalence is low (0.5 to 2 per 1000 births) yet efforts must be made to prevent its occurrence. Thus, objective of this study was to speculate the level of awareness of folic acid intake amongst Saudi women of child bearing age in the Aseer region in prevention of NTDs and to propose measures to prevent its occurrence. Method: A descriptive cross-sectional study was carried out on 700 women of child bearing age residing in various areas of Aseer Province. A self designed questionnaire form aiming to assess the awareness of folic acid was distributed to the participants and their responses were analysed. Results: Most of the women resided in villages/small town (54.1%) and were married (66.6%), educated up to graduation level (50.9%), non working (55.4%), non smokers (97.3%) and had monthly family income of less than 5000 Saudi Riyals indicating a relatively lower economic status. Only 18% women were aware that folic acid deficiency during pregnancy could lead to NTDs. Hardly 9.1% women were aware that folic acid should be taken 3 months before the pregnancy and during first 3 months of pregnancy. At the time of study although 53.9 % of study subject women were consuming folic acid supplements because of pregnancy, however 51.3 % women expressed their unwillingness to do so in future if they ever conceived. Conclusion: Awareness about folic acid intake amongst Saudi women of child bearing age in the Aseer region in prevention of NTDs in fetus was found to be low. Therefore formulating better health education strategies, support from healthcare staff, strengthening health care programs and frequent health visits/surveys are the proposed measures to ensure a higher level of awareness on the issue

Randomized controlled trial of favipiravir, hydroxychloroquine, and standard care in patients with mild/moderate COVID-19 disease

Favipiravir has antiviral activity against influenza, West Nile virus, and yellow fever virus and against flaviviruses. The objective of this pilot study was to compare three arms: favipiravir; hydroxychloroquine; standard care (no specific SARS-CoV-2 treatment) only, in symptomatic patients infected by SARS-CoV-2 in an open-labelled randomized clinical trial. The trial was registered with Bahrain National Taskforce for Combatting COVID-19 on the 7th of May 2020 (registration code: NCT04387760). 150 symptomatic patients with COVID-19 disease were randomized into one of three arms: favipiravir, hydroxychloroquine, or standard care only. The primary outcome was the clinical scale at the end of study follow up (day 14 or on discharge/death) based on a points scale. The secondary outcomes were viral clearance, biochemical parameter changes and mortality at 30-days. Baseline characteristics did not differ between groups. The proportion of patients who achieved a clinical scale NCT04387760. Registration date: 07/05/2020

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population