Investigation of the cardiac depressant effect of Caralluma tuberculate N.E.Br on isolated rabbit heart

Purpose: To investigate the histopathological and cardiac depressant effect of the aqueous methanol extract of Caralluma tuberculata N.E. Br (AMECT) (family: Asclepiadaceae)’ and to determine if there is a scientific basis for its cardiovascular diseases-related folkloric use. Methods: The effect of AMECT in different concentrations ranging from 0.00001 to 1.0 mg/mL were evaluated in isolated perfused rabbit heart to assess their effect on the force of contraction and heart rate using Langendorff’s apparatus. Atropine and adrenaline were used to identify the underlying mechanism of response produced by AMECT. The extract was studied for its possible mechanism in the absence and presence of atropine and adrenaline. In addition, sub-chronic toxicity and histopathological study of heart tissues in rats were assessed by administering 500 mg/kg of extract. Results: At all concentrations, AMECT produced significant (p < 0.001) negative ionotropic and negative chronotropic effects. The most significant effect was observed at 0.001 mg/mL and higher concentrations hence 0.001 mg/mL was selected for further studies. Pre-incubation with atropine did not significantly inhibit the effects of AMECT. However, AMECT significantly (p < 0.01) blocked the cardiac stimulant effect of adrenaline. In the histopathological studies, AMECT did not produce any significant cellular changes or signs of toxicity in the sub-chronic toxicity study. Conclusion: The cardiac-depressant responses of AMECT may involve the β-adrenergic receptors in the myocardium of isolated rabbit heart thus confirming the rationale for its use in ethnomedicine for cardiac diseases

Modeling and Forecasting of Energy Scenario in Pakistan with Application of Decentralized Energy Planning

The global energy demand has enlarged in recent years as a result of industrial development and population growth. This scenario has even intensified in Pakistan affecting industrial as well as domestic and agriculture sectors, causing 2-3% of GDP loss annually. According to Pakistan Energy Year Book 2012, Pakistan generation capacity being 95365GWh is far greater than the consumption 76,761GWh, indicating that these power-outages are not because of lack of generation capacity but improper energy management. The current pattern of centralized electricity based on costly imported oil, has resulted in inequities, debts and high transmission losses. Therefore, a change in overall energy mix has to be made considering requirements and regional availability of competent resources which can be possible by introducing Decentralized Energy Planning in power policy. In the present research work a comprehensive energy model for Pakistan has been created using LEAP, identifying the loop-holes in system and presenting possible remedies for the current energy crunch

Smokeless tobacco initiation, use and cessation in south Asia: A qualitative assessment

Introduction: Smokeless tobacco (ST) is a significant South Asian public health problem. This paper reports a qualitative study of a sample of South Asian ST users.Methods: Interviews, using a piloted topic guide, with 33 consenting, urban dwelling adult ST users explored their ST initiation, continued use and cessation attempts. Framework data analysis was used to analyse country specific data before a thematic cross-country synthesis was completed.Results: Participants reported long term ST use and high dependency. All reported strong cessation motivation and multiple failed attempts because of ease of purchasing ST, tobacco dependency and lack of institutional support.Conclusions: Interventions to support cessation attempts amongst consumers of South Asian ST products should address the multiple challenges of developing an integrated ST policy, including cessation services.Implications: This study provides detailed understanding of the barriers and drivers to ST initiation, use and cessation for users in Bangladesh, India and Pakistan. It is the first study to directly compare these three countries. The insight was then used to adapt an existing behavioural support intervention for ST cessation for testing in these countries

Association of Serum Ferritin with Risk of Anemia in Non-Diabetic Adolescents with Family History of Type 2 Diabetes Mellitus

Background: Controversy occurs in the relationship between serum ferritin levels, insulin resistance and risk of developing anemia in adolescents with family history of diabetes. Aims & Objectives: This study was designed to find out the association between serum ferritin levels with risk of developing anemia in non-diabetic adolescents with family history of type 2 diabetes mellitus (T2DM). Materials & Methods: A descriptive cross-sectional was conducted in a local medical institute of Lahore. Study included 50 non-diabetic, non-obese male / female adolescent with family history of type 2 diabetes mellitus and 50 healthy male/female non-obese adolescents without family history of T2DM considered as controls. Level of serum ferritin and serum insulin was estimated by Enzyme Linked Immunosorbent Assay. Blood glucose was estimated by auto-analyzer. Insulin resistance was calculated by HOMA-IR index and beta cell function was assessed by HOMA- beta index. Results: Levels of fasting blood sugar, insulin resistance were found to be increased with decreased level of serum ferritin and decrease beta cell function in both male as well as female cases as compared to controls. Negative correlation was found between serum ferritin and insulin resistance while a positive correlation was found between serum ferritin and beta cell function. Conclusions: Low level of serum ferritin is associated with reduced beta cell function and increased insulin resistance. This may increase the risk of developing iron deficiency anemia that can affect both immune system as well as increase susceptibility to infections

Pathophysiology of Dyslipidemia and its Management by PCSK9 Inhibitors: A Literature Review

Dyslipidemia is a disease of abnormal lipid levels in the blood that contributes to the atherosclerotic process. This atherogenic process leads to the formation of plaque and also leads to thromboembolic events and other vascular accidents. It is known that high-density lipoprotein cholesterol serves as a protective effect on the vessel wall and causes the reduction in the progression of atherosclerosis. And multiple interventions are directed in maintaining a higher level of the aforementioned lipoprotein cholesterol. While the low-density lipoprotein stays controversial but lowering its levels through various therapeutic agents is the main goal in the management of dyslipidemia. A newer group of drugs, PCSK9 inhibitors lowers the levels of low-density lipoprotein through modulating PCKS9 gene involved in cholesterol metabolism and affects the levels of the lipoproteins by controlling the receptors. The inhibitors of this gene decrease PCSK9-induced low-density lipoprotein receptor degradation in the lysosomes of hepatocytes increasing its recycling and expression on the cell surface, causing increased clearance of low-density lipoprotein from the circulation. These drugs Alicuromab, Evolocumab and along with other agents can be a novel approach in controlling dyslipidemic state. This review revisits the literature in understanding the pathophysiology of dyslipidemia along with its management by PCKS9 inhibitors, its mechanism of action, its pharmacokinetics, the results of the clinical trials and the limitations in its application

Identification of hematein as a novel inhibitor of protein kinase CK2 from a natural product library

<p>Abstract</p> <p>Background</p> <p>Casein kinase 2 (CK2) is dysregulated in various human cancers and is a promising target for cancer therapy. To date, there is no small molecular CK2 inhibitor in clinical trial yet. With the aim to identify novel CK2 inhibitors, we screened a natural product library.</p> <p>Methods</p> <p>We adopted cell-based proliferation and CK2 kinase assays to screen CK2 inhibitors from a natural compound library. Dose-dependent response of CK2 inhibitors <it>in vitro </it>was determined by a radioisotope kinase assay. Western blot analysis was used to evaluate down stream Akt phosphorylation and apoptosis. Apoptosis was also evaluated by annexin-V/propidium iodide (PI) labeling method using flow cytometry. Inhibition effects of CK2 inhibitors on the growth of cancer and normal cells were evaluated by cell proliferation and viability assays.</p> <p>Results</p> <p>Hematein was identified as a novel CK2 inhibitor that is highly selective among a panel of kinases. It appears to be an ATP non-competitive and partially reversible CK2 inhibitor with an IC₅₀value of 0.55 μM. In addition, hematein inhibited cancer cell growth partially through down-regulation of Akt phosphorylation and induced apoptosis in these cells. Furthermore, hematein exerted stronger inhibition effects on the growth of cancer cells than in normal cells.</p> <p>Conclusion</p> <p>In this study, we showed that hematein is a novel selective and cell permeable small molecule CK2 inhibitor. Hematein showed stronger growth inhibition effects to cancer cells when compared to normal cells. This compound may represent a promising class of CK2 inhibitors.</p

Smokeless tobacco initiation, use and cessation in South Asia : a qualitative assessment

INTRODUCTION: Smokeless tobacco (ST) is a significant South Asian public health problem. This paper reports a qualitative study of a sample of South Asian ST users. METHODS: Interviews, using a piloted topic guide, with 33 consenting, urban dwelling adult ST users explored their ST initiation, continued use, and cessation attempts. Framework data analysis was used to analyze country specific data before a thematic cross-country synthesis was completed. RESULTS: Participants reported long-term ST use and high dependency. All reported strong cessation motivation and multiple failed attempts because of ease of purchasing ST, tobacco dependency, and lack of institutional support. CONCLUSIONS: Interventions to support cessation attempts among consumers of South Asian ST products should address the multiple challenges of developing an integrated ST policy, including cessation services. IMPLICATIONS: This study provides detailed understanding of the barriers and drivers to ST initiation, use, and cessation for users in Bangladesh, India, and Pakistan. It is the first study to directly compare these three countries. The insight was then used to adapt an existing behavioral support intervention for ST cessation for testing in these countries

Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants

Background Hypertension can be detected at the primary health-care level and low-cost treatments can effectively control hypertension. We aimed to measure the prevalence of hypertension and progress in its detection, treatment, and control from 1990 to 2019 for 200 countries and territories. Methods We used data from 1990 to 2019 on people aged 30-79 years from population-representative studies with measurement of blood pressure and data on blood pressure treatment. We defined hypertension as having systolic blood pressure 140 mm Hg or greater, diastolic blood pressure 90 mm Hg or greater, or taking medication for hypertension. We applied a Bayesian hierarchical model to estimate the prevalence of hypertension and the proportion of people with hypertension who had a previous diagnosis (detection), who were taking medication for hypertension (treatment), and whose hypertension was controlled to below 140/90 mm Hg (control). The model allowed for trends over time to be non-linear and to vary by age. Findings The number of people aged 30-79 years with hypertension doubled from 1990 to 2019, from 331 (95% credible interval 306-359) million women and 317 (292-344) million men in 1990 to 626 (584-668) million women and 652 (604-698) million men in 2019, despite stable global age-standardised prevalence. In 2019, age-standardised hypertension prevalence was lowest in Canada and Peru for both men and women; in Taiwan, South Korea, Japan, and some countries in western Europe including Switzerland, Spain, and the UK for women; and in several low-income and middle-income countries such as Eritrea, Bangladesh, Ethiopia, and Solomon Islands for men. Hypertension prevalence surpassed 50% for women in two countries and men in nine countries, in central and eastern Europe, central Asia, Oceania, and Latin America. Globally, 59% (55-62) of women and 49% (46-52) of men with hypertension reported a previous diagnosis of hypertension in 2019, and 47% (43-51) of women and 38% (35-41) of men were treated. Control rates among people with hypertension in 2019 were 23% (20-27) for women and 18% (16-21) for men. In 2019, treatment and control rates were highest in South Korea, Canada, and Iceland (treatment >70%; control >50%), followed by the USA, Costa Rica, Germany, Portugal, and Taiwan. Treatment rates were less than 25% for women and less than 20% for men in Nepal, Indonesia, and some countries in sub-Saharan Africa and Oceania. Control rates were below 10% for women and men in these countries and for men in some countries in north Africa, central and south Asia, and eastern Europe. Treatment and control rates have improved in most countries since 1990, but we found little change in most countries in sub-Saharan Africa and Oceania. Improvements were largest in high-income countries, central Europe, and some upper-middle-income and recently high-income countries including Costa Rica, Taiwan, Kazakhstan, South Africa, Brazil, Chile, Turkey, and Iran. Interpretation Improvements in the detection, treatment, and control of hypertension have varied substantially across countries, with some middle-income countries now outperforming most high-income nations. The dual approach of reducing hypertension prevalence through primary prevention and enhancing its treatment and control is achievable not only in high-income countries but also in low-income and middle-income settings. Copyright (C) 2021 World Health Organization; licensee Elsevier

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity &gt; 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI &lt;18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For school&#x2;aged children and adolescents, we report thinness (BMI &lt;2 SD below the median of the WHO growth reference) and obesity (BMI &gt;2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesit