Animal models for human genetic diseases

The study of human genetic diseases can be greatly aided by animal models because of their similarity to humans in terms of genetics. In addition to understand diverse aspects of basic biology, model organisms are extensively used in applied research in agriculture, industry, and also in medicine, where they are used to model and understand disease and to test new systems of treating disease. The range of model organisms is large, extending from microbes to primates. Mice are widely considered to be the prime model of genetic human disease. In this review, we will mainly focus on the mouse, which is the mammalian species with the best studied genetics.Key words: Animal models, mice, genetic diseases

Hepcidin Antimicrobial Peptide (HAMP) Screening for P.CYS70ARG Variant and Iron Overload in β -Thalassemia Major Patients

Hereditary Hemochromatosis is a rare genetic iron overload disorder characterized by iron accumulation in vital body organs such as the lungs, liver, and pancreas. HAMP mutations are reported as one of the principal sources for the disturbance of iron homeostasis. This study was designed to screen the involvement of p.Cys70Arg HAMP variant in iron overload in the β-thalassemia patients. For the purpose, bioinformatics tools were used for the structural and functional manifestation of mutated protein which revealed 1.93 kcal/mol energy differences between the wild-type and mutated proteins, causing the stability decline. Following that, clinical data was collected for 106 β-thalassemia major (β-TM) patients which showed a higher prevalence of splenectomy, hepatomegaly and ascites. The PCR-RFLPs were performed to screen the HAMP p.Cys70Arg in 27 controls and 106 β-TM patients. Sac ӀӀ restriction enzyme was used to screen genetically affected and ethnically matched control samples but no control was found with HAMP p.Cys70Arg variant. Out of these 106 β-thalassemia patients, eight patients were HCV+ with higher levels of ferritin in blood. HAMP exon 3 Sanger sequencing did not reveal any mutation in these patients conferring iatrogenic hemochromatosis. Future recommendations include sequencing of complete HAMP gene with its three exons in a large sample size

Probiotic potential of encapsulated Lactobacillus species in yogurt formation indigenously isolated from dairy source

Background: Exploration of beneficial bacteria as probiotics inputs are drawing interest in dairy industry but their long-term survival and viability is an important consideration.Methods: The current work focused on the exploration of probiotic potential of indigenously isolated Lactobacillus strains from dairy products and their encapsulation and utilization in yogurt formation.Results: These Lactobacillus strains were identified as Lactobacillus fermentum MGA23-1 and Lactobacillus fermentum LMEM19 and found resistant to inhibitory substances like phenol (0.2%), bile salts (0.3%), pancreatin (0.5%) and pepsin (0.3%). The highest antibacterial activity was observed by Lactobacillus fermentum MGA23-1 against Pseudomonas aeruginosa (13mm). Encapsulation experiment showed that the number of bacterial CFU/g increased significantly (p < 0.05) in beads during storage up to 7 days. Chemical characterization of microcapsules was assessed using FTIR and showed characteristics wavelength major at 1541 – 1716 cm-1 and 3336 cm-1. Yogurt was prepared using a single probiotic strain, in a consortium of Lactobacillus fermentum MGA23-1 and Lactobacillus fermentum LMEM19 and in the form of beads. Best results were observed in the case of microencapsulation.Conclusion: It was concluded that both strains had the potential to be used as a probiotic in the dairy industry.Keywords: Probiotic; Tolerance to inhibitory substances; Antibacterial activity; Adhesion ability; Safety; Microencapsulation; FTIR  

Identification and Characterization of Active Ingredient Eugenol from Syzygium Aromaticum (Clove Oil) through HPLC and its Phytochemical Analysis

Clove, Syzygium aromaticum, is one of the most valuable, ancient and premium essential oil which has been used as source of spice in agro-food industry and therapeutics for centuries. The aim of the present study was to analyze biological activities of clove oil as well as characterization of its active component Eugenol to make it worthwhile for different food and pharmaceutical formulations. Clove oil extraction was performed by Soxhlet method. Its phytochemical analysis showed the presence of carbohydrates, flavonoids, coumarins, steroids, saponnins, and tannins while proteins and leucoanthocyanins were absent in it. DPPH (2, 2-diphenyl-1-picrylhydrazyl) scavenging assay was performed which showed an increase in percentage inhibition with an increase in concentration of clove oil which confirmed its antioxidant property. Antimicrobial activity of clove oil was tested against three gram positive strains Bacillus subtilis, Staphylococcus aureus and Bacillus thuringiensis and one gram negative strain Escherichia coli by well diffusion and disc diffusion methods. E.coli presented largest zone of inhibition. T-test was applied for statistical analysis of antimicrobial activity. P-value obtained was 0.0215 which is ˂0.05. Aqueous clove nanoparticles were made and were found to have antimicrobial activity against E.coli and B.subtilis. Correlation coefficient (R2) through HPLC was found to be 0.973531. Quantitative estimation showed the presence of 740 ppm eugenol. These properties of clove proved it as a valuable spice in pharmaceutical and agro-food sector

Predicting Bankruptcy Using Z-Score and Z Double Prime (Z”): A Study of Pakistan Stock Exchange

Due to the unprecedented happenings and dynamic conditions of international economic system, firms are always at the verge of bankruptcy no matter how sound they are, their sustainability is always in jeopardy. Besides, lenders are continuously raising red flags and giving consistent warnings about possible perils of corporate failure due to fragile economic conditions and increasing debt levels in both corporate and individual businesses these days. Hence there was an exigency to ‘develop indicators for monitoring long term progress and sustainability of companies. Thereof it would contribute in illustrating to business analysts, firm stakeholders about the relevance of embracing these active checks for predicting bankruptcy as a sustainable business practice. This created a bizarre cult to look into the matter seriously. For this there is no mantra, no clever feats, sure-fire quick strategies. Instead there are well-defined, simple, systematic and sophisticated models to assess sustainability of companies. Thus, to avoid the tide of massive/substantial corporate failure and any future catastrophe; there is a dire need to identify the most suitable and preeminent model that can truly forecast the likelihood of default ahead of time in given circumstances. And, mainstay of this study is to provide an answer of question in hand by comparing two most venerable model choices i.e. Altman’s Z-score and Z double prime (Z”)

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Analysis Of Difficulties In The Co-Education System Of Pakistan: A Gender Perspective

Education brings desirable changes in human behaviour. The survival of any nation is not ensured without education as it becomes the cause of prosperity when the individuals of any society become familiar with it. Pakistan is far behind in the competition of education of an individual and especially women's education. Co-education refers to educating males and females in one setting. This type of learning has so many difficulties for the male and female while learning in the. Total population of the study was 145 students. A sample size of 105 students was determined by using the online website www.surveysystem.com.  A well-structured interview schedule was developed to collect data. Gender inequality affects negatively the educational performance of female students. The confidence level of female students is negatively affected in the co-educational system. All the ethical concerns were kept intact throughout the research. The data were analyzed through software (SPSS). Finding and conclusion were reported in the form of a thesis according to the standard format of the University of Agriculture, Faisalabad. The majority 65.7 %  of respondents’ were reported yes to the harassment in the co-educational institutions while around 34.3 % of the respondents answered no about the harassment in the co-educational institution.  Female students feel hesitation and shyness while participating in co-educational classes Around 5.2 % of the respondents were strongly agree that there is hesitation and shyness in co-educational classes. While 33.3% of the respondents were agreed and 11.4 % of the respondents were undecided about the hesitation and shyness while participating in the coeducational classe

Rise Over Thermal Estimation Algorithm Optimization and Implementation

The uplink load for the scheduling of Enhanced-Uplink (E-UL) channels determine the achievable data rate for Wideband Code Division Multiple Access (WCDMA) systems, therefore its accurate measurement carries a prime significance. The uplink load also known as Rise-over-Thermal (RoT), which is the quotient of the Received Total Wideband Power (RTWP) and the Thermal Noise Power floor. It is a major parameter which is calculated at each Transmission Time Interval (TTI) for maintaining cell coverage and stability. The RoT algorithm for evaluation of uplink load is considered as a complex and resource demanding among several Radio Resource Management (RRM) algorithms running in a radio system. The main focus of this thesis is to study RoT algorithm presently deployed in radio units and its possible optimization by reducing complexity of the algorithm in terms of memory usage and processing power. The calculation of RoT comprises three main blocks a Kalman filter, a noise floor estimator and the RoT computation. After analyzing the complexity of each block it has been established that the noise floor estimator block is consuming most of the processing power producing peak processor load since it involves many complex floating point calculations. However, the other blocks do not affect the processing load significantly. It was also observed that some block updates can be reduced in order to decrease the average load on the processor. Three techniques are proposed for reducing the complexity of the RoT algorithm, two for the reduction of peak load and one for the reduction of average load. For reducing the peak load, an interpolation approach is used instead of performing transcendental mathematical calculations. Also, the calculations involving noise floor estimation are extended over several TTIs by keeping in view that the estimation is not time critical. For the reduction of average load, the update rate for the Kalman Filter block is reduced. Based on these optimization steps, a modified algorithm for RoT computation with reduced complexity is proposed. The proposed changes are tested by means of MATLAB simulations demonstrating the improved performance with consistency in the output results. Finally, an arithmetic operation count is done using the hardware manual of Power PC (PPC405) used in Platform 4, which gives a rough estimate of decrease in the percentage of calculations after [email protected]

Rise Over Thermal Estimation Algorithm Optimization and Implementation

The uplink load for the scheduling of Enhanced-Uplink (E-UL) channels determine the achievable data rate for Wideband Code Division Multiple Access (WCDMA) systems, therefore its accurate measurement carries a prime significance. The uplink load also known as Rise-over-Thermal (RoT), which is the quotient of the Received Total Wideband Power (RTWP) and the Thermal Noise Power floor. It is a major parameter which is calculated at each Transmission Time Interval (TTI) for maintaining cell coverage and stability. The RoT algorithm for evaluation of uplink load is considered as a complex and resource demanding among several Radio Resource Management (RRM) algorithms running in a radio system. The main focus of this thesis is to study RoT algorithm presently deployed in radio units and its possible optimization by reducing complexity of the algorithm in terms of memory usage and processing power. The calculation of RoT comprises three main blocks a Kalman filter, a noise floor estimator and the RoT computation. After analyzing the complexity of each block it has been established that the noise floor estimator block is consuming most of the processing power producing peak processor load since it involves many complex floating point calculations. However, the other blocks do not affect the processing load significantly. It was also observed that some block updates can be reduced in order to decrease the average load on the processor. Three techniques are proposed for reducing the complexity of the RoT algorithm, two for the reduction of peak load and one for the reduction of average load. For reducing the peak load, an interpolation approach is used instead of performing transcendental mathematical calculations. Also, the calculations involving noise floor estimation are extended over several TTIs by keeping in view that the estimation is not time critical. For the reduction of average load, the update rate for the Kalman Filter block is reduced. Based on these optimization steps, a modified algorithm for RoT computation with reduced complexity is proposed. The proposed changes are tested by means of MATLAB simulations demonstrating the improved performance with consistency in the output results. Finally, an arithmetic operation count is done using the hardware manual of Power PC (PPC405) used in Platform 4, which gives a rough estimate of decrease in the percentage of calculations after [email protected]