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To find out the association of polymorphism of the TLL1 gene in hepatocellular carcinoma. A cross-sectional study was conducted from January 2020 to September 2020. Subjects were enrolled from Mayo Hospital, Lahore, Jinnah Hospital Lahore and the Liver Transplant Unit of Sheikh Zayed Hospital, Lahore. A total of 200 individuals were registered and segregated into the Control group (n=100) and hepatocellular carcinoma (HCC) group (n=100). DNA was extracted from obtained blood samples and Restriction Fragments Length Polymorphism (RFLP) was carried out at the laboratories of LCWU by using specific primers and restriction endonuclease enzymes. The data were analyzed statistically. The high proportion of smoking, hepatitis B, hepatitis C, cirrhosis and Body Mass Index (BMI) were established risk factors in the HCC group. Subjects with hepatocellular carcinoma had low socioeconomic status. Heterozygous bands in the HCC group were observed after RFLP. TLL1 genotype was AA (72 %) and AT/TT (28 %). The patient’s clinical aspects were similar across TLL1 genotypes. It was concluded that RFLP on the exon region by using their specific enzymes HpyCH4III showed heterozygous bands in the HCC group that indicated a mutation in the TLL1 gene though this mutation does have a significant association with HCC.

Education is a systemic framework for building the cornerstone of civilization. It is animportant factor in any country's success worldwide. Early Childhood Education (ECE) is a branch ofeducational philosophy that refers to education for young children up to the age of eight years. The mainobjective of this study was to find out teachers’ perceptions of this ECE setup. A teacher is a part andparcel of our education system and any policy can’t succeed without satisfaction. The population of thisstudy was teachers involved in early childhood education set up in the district Nankana Sahib. Whereas,308 teachers were selected as a sample using a stratified sampling technique. The data was collectedthrough instruments by survey method. On the whole, it was found that most of the statements on thequestionnaire had a mean score higher than 3 which shows teachers’ positive perception of the ECEsetup. There was a significant difference in the perception of teachers based on gender. This study isbeneficial for the development of early childhood education.

In the present study, a novel application of integrated evolutionary computing paradigm is presented for the analysis of nonlinear systems of differential equations representing the dynamics of virus propagation model in computer networks by exploiting the discretization strength of finite difference procedure, global search efficacy of genetic algorithms (GAs) aided with interior-point method (IPM) as efficient local search mechanism. Residual error based cost function is constructed by utilizing the effectiveness of approximation in mean square error sense and combined strength of GA-IPM is used as a viable optimization mechanism to find the solution of the problem. The proposed scheme is implemented for dynamical analysis of the model in terms of susceptible-infected and protected computer nodes by varying the probabilities of infections, countermeasures, curing and immunity while keeping connected and disconnected rates fixed. The statistical performance evaluated by means of deviations from reference Adams numerical results are practiced viably through performance metrics of accuracy and computational complexity to demonstrate the worth of integrated stochastic solver.

Laccases are blue multicopper oxidases that oxidize a wide range of phenolic as well as non-phenolic substrates in the presence or absence of mediators. They occur in various species of bacteria, fungi, insects, and plants; bacterial laccases show high substrate specificity. Bacteria produce these enzymes either extracellularly or intracellularly and exhibit stability to a wide range of pH and temperature. Therefore, they are suitable for various industrial processes such as food, textile, and paper and pulp industry. They are also valuable for producing biofuels, pharmaceuticals, biosensors, and degradation of various environmental pollutants and xenobiotics compounds. Since bacterial laccases are more versatile in the sense of nutritional needs and ecological factors, their use can provide a promising solution to various problems related to industry and the field of biotechnology. However, there is a need for a thorough understanding of the chemistry and activity of bacterial laccases to enable their full potential use in bioremediation and biofuel production.

Transcription factors play a fundamental role in cardiovascular adaptation to stress. Nuclear receptor subfamily 4 group A member 2 (NR4A2; NURR1) is an immediate-early gene and transcription factor with a versatile role throughout many organs. In the adult mammalian heart and particularly in cardiac myocytes, NR4A2 is strongly up-regulated in response to beta-adrenergic stimulation. The physiological implications of this increase remain unknown. In this study, we aimed to interrogate the consequences of cardiac NR4A2 up-regulation under normal conditions and in response to pressure overload. In mice, tamoxifen-dependent, cardiomyocyte-restricted overexpression of NR4A2 led to left ventricular hypertrophy and dilation, heart failure, and death within 40 days. Chronic NR4A2 induction also precipitated cardiac decompensation during transverse aortic constriction (TAC)-induced pressure overload. Mechanistically, NR4A2 caused adult cardiac myocytes to return to a fetal-like phenotype, with a switch to glycolytic metabolism and disassembly of sarcomeric structures. NR4A2 also re-activated cell cycle progression and stimulated DNA replication and karyokinesis but failed to induce cytokinesis, thereby promoting polyploidization and multinucleation of cardiac myocytes. Activation of cell cycle checkpoints led to induction of an apoptotic response which ultimately resulted in excessive loss of cardiac myocytes and impaired left ventricular contractile function. In summary, myocyte-specific overexpression of NR4A2 in the postnatal mammalian heart results in increased cell cycle re-entry and DNA replication but does not result in cardiac myocyte division. Our findings expose a novel function for the nuclear receptor as a critical regulator in the self-renewal of the cardiac myocyte and heart regeneration.

Educational theories play a key role in attaining e-learning success. This contribution of theories is even more important for primary education which requires special attention since children possess childish behaviors.However, research shows that most e-learning systems lack theoretical foundations. We argue that these systems can be more effectively utilized by integrating educational theories. Therefore, we offer an e-learning system design framework based on learning and e-learning theories for primary education. The paper first discusses educational theories from different domains. Next, we provide an overview of how each theory can contribute toa successful e-learning system. Ethnographic Content Analysis (ECA) was conductedof the most renowned theories to construct this framework. Shortlisted theories belonged to domains of constructivism, early education, and e-learning. Design principles from each theory were extracted with the help of grounded theory methodology. These principles were mapped to e-learning system components including tasks, tools, and interfaces by performing thematic analysis.A comprehensive framework based on theoretical design principles was constructed. Lastly, the framework was validated by developing an e-learning system based on design principles. We evaluated students academic performance after they used the developed system for three weeks. Findings revealed that an e-learning system has great potential in primary education and can assist practitioners in achieving desired learning outcomes by integrating educational theories. It was also found that the sequence in which learning activities are performed can overshadow a systems performance and hence needs to be addressed for e-learning success. &nbsp

Visual Abstract, Highlights • Leptin protects against progression to heart failure after myocardial infarction. • This beneficial effect requires activation of the brain melanocortin system. • Stimulation of brain MC4R recapitulates the cardiac protective effects of leptin. • Leptin-MC4R activation improves cardiac substrate oxidation and mitochondrial function. • It also improves Ca2+ coupling and contractile function in viable cardiomyocytes after MI., Summary Heart failure has a high mortality rate, and current therapies offer limited benefits. The authors demonstrate that activation of the central nervous system leptin-melanocortin pathway confers remarkable protection against progressive heart failure following severe myocardial infarction. The beneficial cardiac-protective actions of leptin require activation of brain melanocortin-4 receptors and elicit improvements in cardiac substrate oxidation, cardiomyocyte contractility, Ca2+ coupling, and mitochondrial efficiency. These findings highlight a potentially novel therapeutic approach for myocardial infarction and heart failure.

BACKGROUND: High dietary fat and sugar promote cardiac hypertrophy independently from an increase in blood pressure. The respective contribution that each macronutrient exerts on cardiac growth signaling pathways remains unclear. OBJECTIVE: The goal of this study was to investigate the mechanisms by which high amounts of dietary fat and sugar affect cardiac growth regulatory pathways. METHODS: Male C57BL/6 mice (9 wk old; n = 20/group) were fed a standard rodent diet (STD; kcal% protein-fat-carbohydrate, 29-17-54), a high-fat diet (HFD; 20-60-20), a high-fat and high-sugar Western diet (WD; 20-45-35), a high-sugar diet with mixed carbohydrates (HCD; 20-10-70), or a high-sucrose diet (HSD; 20-10-70). Body composition was assessed weekly by EchoMRI. Whole-body glucose utilization was assessed with an intraperitoneal glucose tolerance test. After 6 wk on diets, mice were treated with saline or 20 mg/kg isoproterenol (ISO), and the activity of cardiac growth regulatory pathways was analyzed by immunoblotting. Data were analyzed by ANOVA with data from the STD group included for references only. RESULTS: Compared with HCD and HSD, WD and HFD increased body fat mass 2.7- to 3.8-fold (P 1.5-fold (P 47%; P 34%; P 64%; P

Protein scarcity is the most vital cause of long-lasting diseases and even untimely deaths in some developing nations. The application of protein in food is advantageous from the point of view of non-toxicity, biocompatibility, and dietary benefits. This study aimed to determine the protein contents of the sprouts of

Nearly one million Rohingya refugees of Myanmar have fled to neighboring Bangladesh for seeking shelter from systematic oppression since 25 August 2017. The speed and scale of the influx has led to...

Background Left ventricular diastolic dysfunction, an early stage in the pathogenesis of heart failure with preserved ejection fraction, is exacerbated by joint exposure to hypertension and obesity; however, the molecular mechanisms involved remain uncertain. The mitochondrial UCP3 (uncoupling protein 3) is downregulated in the heart with obesity. Here, we used a rat model of UCP3 haploinsufficiency (ucp3 +/‐ ) to test the hypothesis that decreased UCP3 promotes left ventricular diastolic dysfunction during hypertension. Methods and Results Ucp3 +/‐ rats and ucp3 +/+ littermates fed a high‐salt diet (HS; 2% NaCl) and treated with angiotensin II (190 ng/kg per min for 28 days) experienced a similar rise in blood pressure (158±4 versus 155±7 mm Hg). However, UCP3 insufficiency worsened diastolic dysfunction according to echocardiographic assessment of left ventricular filling pressures (E/e’; 18.8±1.0 versus 14.9±0.6; P P P +/‐ rats. Histological and molecular analyses further revealed that UCP3 insufficiency accelerated left ventricular concentric remodeling, detrimental interstitial matrix remodeling, and fetal gene reprogramming during hypertension. Moreover, UCP3 insufficiency increased oxidative stress and led to greater impairment of protein kinase G signaling. Conclusions Our findings identified UCP3 insufficiency as a cause for increased incidence of left ventricular diastolic dysfunction during hypertension. The results add further support to the use of antioxidants targeting mitochondrial reactive oxygen species as an adjuvant therapy for preventing heart failure with preserved ejection fraction in individuals with obesity.

BackgroundPre-exposure prophylaxis (PrEP) is a promising strategy to break the chain of transmission of novel coronavirus (2019-nCoV).AimsThis trial aimed to evaluate the safety and efficacy of PrEP with various doses of HCQ against a placebo among high-risk healthcare providers (HCPs).MethodsA phase II, randomized, placebo-controlled trial was conducted at a tertiary care hospital. A total of 228 HCPs were screened, we included 200 subjects with no active or past SARS-CoV-2 infection. Subjects of experimental groups 1-3 received HCQ in various doses and those in the control group received placebo. The study outcomes in terms of safety and efficacy were monitored. Participants exhibiting COVID-19 symptoms were tested for SARS-CoV-2 during the study and also by the end of the 12th week, with PCR or IgM and IgG serology.ResultsOverall, 146 of 200 participants reported exposure to a confirmed COVID-19 case in the first month, 189 in the 2nd month and 192 were exposed by the 12th week of the study. Moreover, the precautionary practices, i.e. use of personal protective equipment (PPE), significantly varied; initially more than 80% of the exposed HCPs weren’t ensuring the PPE used by the patients treated by them. However, it gradually developed with the increasing knowledge of the virus. As far as safety is concerned, mild treatment-related side effects were observed among the interventional and placebo arm patients. While none of the participants were critical, and a few had mild illness by the end of the 12th week, requiring only outpatient observation with no hospitalization. There was no significant clinical benefit of PrEP with HCQ as compared to placebo (p>0.05).ConclusionIt is concluded from the study findings that the PrEP HCQ does not significantly prevent illness compatible with COVID-19 or confirmed infection among high-risk HCPs.

Sustained elevation of sympathetic activity is an important contributor to pathological cardiac hypertrophy, ventricular arrhythmias, and left ventricular contractile dysfunction in chronic heart failure. The orphan nuclear receptor NR4A2 is an immediate early-response gene activated in the heart under β-adrenergic stimulation. The goal of this study was to identify the transcriptional remodeling events induced by increased NR4A2 expression in cardiomyocytes and their impact on the physiological response of those cells to sustained β-adrenergic stimulation. Treatment of adult rat ventricular myocytes with isoproterenol induced a rapid (

This article deals with the determinants of Pakistan relations with Afghanistan with reference to past present and future. There are numerous writings on the topic under consideration mainly in terrorism perspective but this study deals with the socio-cultural, political, economic and diplomatic relations between Pakistan and Afghanistan. Unique relationship of two Muslim and neighboring countries as peace and security of both countries is inter-linked. Although Pakistan and Afghanistan are facing many challenges but both of them are doing their best to handle the issues of terrorism, Pakhtunstan and Durand line. Present study will fill this gap. Since independence Pakistan has endeavored to maintain good relations with Afghanistan in pursuance of its policy to have good relations with Muslim Countries. By focusing on the need to improve socio-economic and cultural ties of both countries is very important for the peaceful co- existence of both the countries which will ensure peace and prosperity in the region. Pakistan, has its plus points and can be useful for the development of the Afghanistan while Afghanistan has colossal untapped mineral and labour assets which can help Pakistan to build its economy. Also, Afghans might have the ability to get coordinate access to Pakistan's ports of Arabian Sea, while Pakistanis can get steer access to Central Asian markets.

The rapid growth of urbanization has altered the urban surfaces posing serious threats to natural ecosystems in the urban area worldwide. Landscape changes have a negative impact on urban ecosystem services. In this paper, we estimated the changes in ecosystem services value (ESV) in terms of land use land cover (LULC) for the 2014-2019 period in the Khulna City of Bangladesh. Landsat-8 images were used to estimate land use land cover changes over the study periods. The changes of ESV were calculated by following the previously published global value coefficient. The results show that the water body and vegetation significantly decreased in the study area. The net decline of ESV from 2014-2019 was US$ 2.4 million. The highest contribution of change in total ESV was the loss to the water body. We suggest formulating a sustainable land use policy to ensure ecological balance with urban growth.

Objective Uncoupling protein 3 (UCP3) is a mitochondrial carrier related to fatty acid metabolism. Although gene variants of UCP3 are associated with human obesity, their contribution to increased adiposity remains unclear. This study investigated the impact that loss of UCP3 has on diet-induced obesity in rats. Methods Male UCP3 knockout rats (ucp3-/- ) and wild-type littermates (ucp3+/+ ) were fed a high-fat, high-carbohydrate Western diet for 21 weeks. Body composition was analyzed by EchoMRI. Whole-body insulin sensitivity and rates of tissue glucose uptake were determined by using hyperinsulinemic-euglycemic clamp. Changes in tissue physiology were interrogated by microscopy and RNA sequencing. Results Loss of UCP3 decreased fat mass gain, white adipocytes size, and systemic inflammation. The ucp3-/- rats also exhibited preserved insulin sensitivity and increased glucose uptake in interscapular brown adipose tissue (iBAT). Brown adipocytes from ucp3-/- rats were protected from cellular degeneration caused by lipid accumulation and from reactive oxygen species-induced protein sulfonation. Increased glutathione levels in iBAT from ucp3-/- rats were linked to upregulation of genes encoding enzymes from the transsulfuration pathway in that tissue. Conclusions Loss of UCP3 partially protects rats from diet-induced obesity. This phenotype is related to induction of a compensatory antioxidant mechanism and prevention of iBAT whitening.

This research was conducted through analysing existing agricultural information services through ICT and traditional platforms and their usefulness in farming practices, and to explore farmers’ needs of a virtual platform (using ICT) for weather and climate information for sustainable agricultural in peri-urban Khulna. The result shows that local farmers cannot use available weather information for agricultural decision-making as it lacks location and time specific information service. Besides, majority of the farmers do not know about availability of the existing information services. In total 44% of farmers strongly agreed for an ICT based information service. Besides, 43% of farmers were agreed, and 10% of farmers were undecided for ICT based information service for agricultural decision-making. Very few farmers (only 3%) were disagreed for ICT based platform. For crop related decision-making, 27% of farmers were interested in rainfall forecast, 21% of farmers were interested in cyclone and storm surge forecast, 18% of farmers were interested in hailstorm forecast, 16% of farmers interested in temperature forecast, 14% of farmers were interested in fog forecast and 4% of farmers were interested in humidity forecast. Among 200 interviewed farmers, 34% of them told that one-week lead-time forecast is enough to prepare, while 32% of them claimed a minimum one-month led-time forecast is necessary for extra preparation according to the weather situation. This study shows that farmers preferred ICT tools are mobile apps, where 60% of them demanded information service with text, audio, and video format. This study concludes that at present situation an information service tool may have potential for sustainable agricultural practices by local farmers in the study area. In addition, to enhancing uptake and use of the existing weather information, farmers’ capacity building would bring the maximum output for informed agricultural decision-making.

Farmers in the lower Bengal Delta around the city of Khulna, Bangladesh, are particularly vulnerable to hydro-climatic variability. Phenomena such as heavy rain, drought and salt intrusion increasingly affect their crop production, with far-reaching socio-economic and environmental impacts. Reliable hydro-climatic information service received in a timely manner could help farmers improve their responses to hydro-climatic variability, thus improving their agricultural decision-making. However, significant challenges persist regarding information uptake and the role of information from the available sources. We designed an explorative research framework combining different participatory methods and analysis of climate data. Our aim was to examine three key research questions: (i) what information is currently available to farmers for agricultural practices and decision-making?, (ii) what is the perceived quality of the available hydro-climatic information in response to water and weather related stresses?, (iii) how does the available information influence farmers&rsquo, decision-making? We found that farmers had access to information from five main sources: informal contacts, formal contacts, education and training programs, traditional media (like television) and modern ICT tools/social media. However, informal contacts, particularly with peer farmers and private input suppliers, were the farmers&rsquo, main source, in addition to their own previous experiences. Farmers perceived hydro-climatic variability as high and the quality of available hydro-climatic information as poor. They indicated a need for more accurate, time-specific, trusted and actionable information for improving agricultural decision-making. We conclude that there is high potential and need for hydro-climatic information services tailored for farmers in the study area.

Objective: Hypothalamic obesity (HO) is an intractable form of obesity syndrome occurring in patients following hypothalamic insults. It is characterized by significant polyphagia, lack of satiety, and rapid weight gain not usually responsive to caloric restriction or lifestyle modification. There are no established treatment modalities for HO. Liraglutide, a glucagon-like peptide-1 analog, has been approved for long-term treatment of obesity. We present a case of successful treatment with liraglutide of HO following resection of craniopharyngioma. Methods: We present a case report and review of the literature. Results: A 23-year-old female had developed panhypopituitarism and HO immediately following resection of a craniopharyngioma at age 8. She complained of poor quality of life due to weight gain from excessive hunger and lack of satiety. A trial of triiodothyronine at age 9, and dextroamphetamine starting at age 13, in addition to lifestyle modification had had limited efficacy. She began treatment with liraglutide at age 21 with a starting body mass index of 35.3 kg/m2, and noted marked improvement in polyphagia, began to recognize satiety after meals, and was able to lose 20 pounds over 6 months. She felt remarkably well both physically and emotionally, and no adverse effects of the medication were noted. Weight reduction has been maintained over 27 months with liraglutide use. Conclusion: Significant reduction in weight and recognition of satiety without adverse effects is noted in a young woman with HO with extended use of liraglutide. The use of glucagon-like peptide-1 analogs may represent attractive treatment options for treatment of HO.

Purpose The purpose of this paper is to analyse the impact of ownership structure on firm valuation and performance across different geographical regions within mainland China. Design/methodology/approach The authors classify China in six geographical regions and use cross-sectional data of companies with A-shares listed on domestic stock exchanges in China for the year-end 2015. Using data from CSMAR and Wind database, they use multivariate regression technique and analytically compare the consistency of relationship between operational variables of ownership structure with corporate performance and evaluation. Findings The authors find that institutional ownership and state ownership negatively affect market valuation throughout various geographical regions of China. Further, in East, Northwest, South Central and Southwestern parts of China, managerial ownership and concentration of shareholding among top ten shareholders positively influence return on equity (ROE). Interestingly, institutional shareholding negatively affects return on assets (ROA), while institutional ownership has a neutral effect on profitability margin in Northeast China. Although in northern part of China, this relationship is slightly positive. In East China region, state ownership and ownership concentration are directly proportional to profitability margin. Practical implications As some of the findings exhibit weak state of market efficiency in some regions, the study may also be useful in identifying arbitrage opportunities across different regions. Moreover, this study suggests that regions with the same business environment and conditions anywhere around the globe invite same or similar ownership structure for better firm performance and valuation. Originality/value The study provides unique understanding of relationship between ownership structure, market valuation and firm performance in various parts of China and will be an addition to the relevant literature. Given a change in company’s ownership structure and considering its region of incorporation, this study will help investment analysts in assessing performance and market valuation of the firm. It will also assist several classes of investors, financial institutions and international businesses in making their investment decisions.

Automobile workshops can be found in many places in Pakistan and most of them are located near the residential areas. Some activities in automobile workshops can release heavy metals, having the adverse impacts for human health. Islamabad and Rawalpindi are twin cities in northern Pakistan where automobile workshops have been operated almost forty years and have never been studied their impact on the surroundings. Therefore, there is a need to identify heavy metal contaminants in the groundwater to avoid the health hazards. This research aimed to evaluate the heavy metal contaminants in the groundwater samples from thirty selected locations points near automobile workshops. The physicochemical properties including pH, electrical conductance (EC), total suspended solids (TSS), total dissolved solids (TDS), and the concentrations of anionic (F− and Cl−) and several heavy metal ions were assessed. The pH and TDS values of almost all samples were within the permissible limits. The EC values were ranging from 0.79 to 1.80 μS/cm with an average value of 1.12 μS/cm while the TSS values were ranging from 210 to 620 mg/L with an average value of 431.3 mg/L. Several samples had higher level of F− ions and several others had free of F− ions. The concentrations of Cl− ions were below the permissible limits. Almost all heavy metal ions such as Ni2+, Co2+, Zn2+, Pb2+, Cr3+, Cd2+, Fe2+ and Mn2+ were obtained in higher concentration than the permissible limits, except for As3+ ions. Besides, the existing of one metal has correlation with other metals. In future, the rapid, green, facile, and new method to remove or adsorb the heavy metal ions from groundwater or other environmental water samples can be investigated for large scale production.

The thyroglossal duct cyst (TGDC) is a well-known developmental abnormality encountered in the neck. It represents over 75% of childhood midline neck masses and 7% of the adult population.

Patients with insulin resistance and type 2 diabetes have poor cardiac outcomes following myocardial infarction (MI). The mitochondrial uncoupling protein 3 (UCP3) is down-regulated in the heart with insulin resistance. We hypothesized that decreased UCP3 levels contribute to poor cardiac recovery following ischemia/reperfusion (I/R). After confirming that myocardial UCP3 levels were systematically decreased by 20–49% in animal models of insulin resistance and type 2 diabetes, we genetically engineered Sprague–Dawley rats with partial loss of UCP3 (ucp3+/−). Wild-type littermates (ucp3+/+) were used as controls. Isolated working hearts from ucp3+/− rats were characterized by impaired recovery of cardiac power and decreased long-chain fatty acid (LCFA) oxidation following I/R. Mitochondria isolated from ucp3+/− hearts subjected to I/R in vivo displayed increased reactive oxygen species (ROS) generation and decreased respiratory complex I activity. Supplying ucp3+/− cardiac mitochondria with the medium-chain fatty acid (MCFA) octanoate slowed electron transport through the respiratory chain and reduced ROS generation. This was accompanied by improvement of cardiac LCFA oxidation and recovery of contractile function post ischemia. In conclusion, we demonstrated that normal cardiac UCP3 levels are essential to recovery of LCFA oxidation, mitochondrial respiratory capacity, and contractile function following I/R. These results reveal a potential mechanism for the poor prognosis of type 2 diabetic patients following MI and expose MCFA supplementation as a feasible metabolic intervention to improve recovery of these patients at reperfusion. Electronic supplementary material The online version of this article (10.1007/s00395-018-0707-9) contains supplementary material, which is available to authorized users.