Role of JAK2/STAT3 Signaling Pathway in the Tumorigenesis, Chemotherapy Resistance, and Treatment of Solid Tumors: A Systemic Review

Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway is a common signaling pathway used to transduce signals from the extracellular to the intracellular (nucleus) upon the binding of cytokines and growth factors to the extracellular domain of specific cell surface receptors. This signaling pathway is tightly regulated and has a multitude of biological functions such as cell proliferation, differentiation, and apoptosis. Besides, the regulated JAK2/STAT3 signaling plays a crucial role in embryonic development, hemopoiesis, and controlling the immune system. Conversely, aberrantly activated JAK2/STAT3 is frequently detected in varieties of tumors and involved in oncogenesis, angiogenesis, and metastasis of many cancer diseases that are usually refractory to the standard chemotherapy. However, the JAK3/STAT3 pathway recently emerged interestingly as a new site for the development of novel anti-tumor agents and becomes a promising therapeutic target in the treatment of many solid malignancies. Herein, this review aimed to provide insight into the JAK2/STAT3 pathway, in the hope to gain an understanding of its potential role in the pathogenesis, progression, chemotherapy resistance, and cancer therapy of solid tumors

Diagnostic performance of lactate dehydrogenase as a potential biomarker in predicting preeclampsia and associated factors

Background: Preeclampsia (PE), a pregnancy specific syndrome, is defined as new-onset hypertension (≥140/90 mmHg) and proteinuria diagnosed after gestational week 20 or new-onset pre-eclampsia associated signs in the absence of proteinuria, and it may tend to present as late as 4–6 weeks’ postpartum period. It is a leading cause of maternal mortality in both developed and developing countries. In order to prevent PE, the disease must be diagnosed at its earliest stage, however, the triads of high blood pressure, edema and albuminuria is neither specific nor sensitive enough for diagnosing the disease. Lactate dehydrogenase (LDH) is useful biochemical marker reflecting the occurrence of complications associated with preeclampsia. Besides, it has been suggested as potential biomarker to predict the severity of preeclampsia and as indicator of multi-organ involvement. The aim of this study was to investigate the diagnostic accuracy of LDH, which is affordable and easy to test, as a potential clinical biomarker to predict onset of preeclampsia. Methods: A hospital based cross-sectional study was conducted as of September 9 to December 24, 2022 at Debre Birhan Comprehensive Specialized Hospital (DBCSH). A total of 132 study subjects (66 preeclamptic and 66 normotensive controls) were enrolled in the study. A receiver operating characteristics (ROC) curve was used to calculate the area under the curve (AUC) and determine diagnostic accuracy of LDH. Youden’s index was used to identify an optimal cut-off point for LDH in detecting preeclampsia associated complications. Result: AUC for LDH was found to be 0.963 (95% CI, 0.91, 1.0; p = 0.000) from ROC curve analysis. An optimal cut-off point for LDH was 376.5 U/L having a sensitivity and specificity of 87.5 and 90.8%, respectively. Conclusion: Serum LDH had an AUC of greater than 0.8 and showed good diagnostic accuracy in predicting development of preeclampsia. Disease duration, gestational age, systolic and diastolic blood pressure among enormous number of predictor variables had association with serum level of LDH

Molecular and cellular mechanisms in diabetic heart failure: potential therapeutic targets

Diabetes Mellitus (DM) is a worldwide health issue that can lead to a variety of complications. DM is a serious metabolic disorder that causes long-term microvascular and macro-vascular complications, as well as the failure of various organ systems. Diabetes-related cardiovascular diseases (CVD) including heart failure cause significant morbidity and mortality worldwide. Concurrent hypertensive heart disease and/or coronary artery disease have been thought to be the causes of diabetic heart failure in DM patients. However, heart failure is extremely common in DM patients even in the absence of other risk factors such as coronary artery disease and hypertension. The occurrence of diabetes-induced heart failure has recently received a lot of attention. Understanding how diabetes increases the risk of heart failure and how it mediates major cellular and molecular alteration will aid in the development of therapeutics to prevent these changes. Hence, this review aimed to summarize the current knowledge and most recent findings in cellular and molecular mechanisms of diabetes-induced heart failure

Incidence, time to occurrence and predictors of peripheral intravenous cannula-related complications among neonates and infants in Northwest Ethiopia: an institutional-based prospective study

Background: Peripheral intravenous cannulas (PIVC) are venous access devices commonly used for the administration of intravenous fluids, drugs, blood products, and parenteral nutrition. Despite its frequent use, it has complications that can seriously threaten patient safety, prolong hospital stays, and increases medical care costs. PIVC complications are associated with increased morbidity and reinsertion attempts are painful and anxiety-provoking for children and their parents. Therefore, this study was aimed to assess the incidence, time to occurrence and identify predictors for PIVC complications among infants admitted to Debre Tabor Comprehensive Specialized Hospital (DTCSH), Northwest Ethiopia. Methods and setting: An institutional-based prospective cohort study was conducted on 358 infants admitted to a neonatal intensive care unit and pediatric ward, DTCSH from January 1 to April 30, 2022. A systematic sampling technique was employed. Results: The incidence rate of PIVC complication was 11.6 per 1000 person-hours observation. PIVC complication was observed in 56.4% (202) of PIVCs, of which infiltration (42.1%) was the most common complication followed by phlebitis (29.7%). The median time to complication was 46 h. Anatomical insertion site (AHR = 2.85, 95%CI: 1.63–6.27), admission unit (AHR = 1.88, 95%CI: 1.07–4.02), sickness (AHR = 0.24, 95% CI: 1.31–4.66), medication type (AHR = 2.04, 95%CI: 1.13–3.66), blood transfusion (AHR = 0.79, 95%CI: 0.02–0.99), clinical experience (AHR = 0.52, CI:0.26–0.84), and flushing (AHR = 0.71, 95%CI: 0.34–0.98) were potential predictors of PIVC complication. Conclusion: Knowing the predictor factors helps clinicians to provide effective care and to detect complications early

Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017

Background Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings From 1950 to 2017, TFRs decreased by 49·4% (95% uncertainty interval [UI] 46·4–52·0). The TFR decreased from 4·7 livebirths (4·5–4·9) to 2·4 livebirths (2·2–2·5), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83·8 million people per year since 1985. The global population increased by 197·2% (193·3–200·8) since 1950, from 2·6 billion (2·5–2·6) to 7·6 billion (7·4–7·9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2·0%; this rate then remained nearly constant until 1970 and then decreased to 1·1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2·5% in 1963 to 0·7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2·7%. The global average age increased from 26·6 years in 1950 to 32·1 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59·9% to 65·3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1·0 livebirths (95% UI 0·9–1·2) in Cyprus to a high of 7·1 livebirths (6·8–7·4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0·08 livebirths (0·07–0·09) in South Korea to 2·4 livebirths (2·2–2·6) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0·3 livebirths (0·3–0·4) in Puerto Rico to a high of 3·1 livebirths (3·0–3·2) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2·0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress

Global, regional, and national disability-adjusted life-years (DALYs) for 359 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.

BACKGROUND: How long one lives, how many years of life are spent in good and poor health, and how the population's state of health and leading causes of disability change over time all have implications for policy, planning, and provision of services. We comparatively assessed the patterns and trends of healthy life expectancy (HALE), which quantifies the number of years of life expected to be lived in good health, and the complementary measure of disability-adjusted life-years (DALYs), a composite measure of disease burden capturing both premature mortality and prevalence and severity of ill health, for 359 diseases and injuries for 195 countries and territories over the past 28 years. METHODS: We used data for age-specific mortality rates, years of life lost (YLLs) due to premature mortality, and years lived with disability (YLDs) from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 to calculate HALE and DALYs from 1990 to 2017. We calculated HALE using age-specific mortality rates and YLDs per capita for each location, age, sex, and year. We calculated DALYs for 359 causes as the sum of YLLs and YLDs. We assessed how observed HALE and DALYs differed by country and sex from expected trends based on Socio-demographic Index (SDI). We also analysed HALE by decomposing years of life gained into years spent in good health and in poor health, between 1990 and 2017, and extra years lived by females compared with males. FINDINGS: Globally, from 1990 to 2017, life expectancy at birth increased by 7·4 years (95% uncertainty interval 7·1-7·8), from 65·6 years (65·3-65·8) in 1990 to 73·0 years (72·7-73·3) in 2017. The increase in years of life varied from 5·1 years (5·0-5·3) in high SDI countries to 12·0 years (11·3-12·8) in low SDI countries. Of the additional years of life expected at birth, 26·3% (20·1-33·1) were expected to be spent in poor health in high SDI countries compared with 11·7% (8·8-15·1) in low-middle SDI countries. HALE at birth increased by 6·3 years (5·9-6·7), from 57·0 years (54·6-59·1) in 1990 to 63·3 years (60·5-65·7) in 2017. The increase varied from 3·8 years (3·4-4·1) in high SDI countries to 10·5 years (9·8-11·2) in low SDI countries. Even larger variations in HALE than these were observed between countries, ranging from 1·0 year (0·4-1·7) in Saint Vincent and the Grenadines (62·4 years [59·9-64·7] in 1990 to 63·5 years [60·9-65·8] in 2017) to 23·7 years (21·9-25·6) in Eritrea (30·7 years [28·9-32·2] in 1990 to 54·4 years [51·5-57·1] in 2017). In most countries, the increase in HALE was smaller than the increase in overall life expectancy, indicating more years lived in poor health. In 180 of 195 countries and territories, females were expected to live longer than males in 2017, with extra years lived varying from 1·4 years (0·6-2·3) in Algeria to 11·9 years (10·9-12·9) in Ukraine. Of the extra years gained, the proportion spent in poor health varied largely across countries, with less than 20% of additional years spent in poor health in Bosnia and Herzegovina, Burundi, and Slovakia, whereas in Bahrain all the extra years were spent in poor health. In 2017, the highest estimate of HALE at birth was in Singapore for both females (75·8 years [72·4-78·7]) and males (72·6 years [69·8-75·0]) and the lowest estimates were in Central African Republic (47·0 years [43·7-50·2] for females and 42·8 years [40·1-45·6] for males). Globally, in 2017, the five leading causes of DALYs were neonatal disorders, ischaemic heart disease, stroke, lower respiratory infections, and chronic obstructive pulmonary disease. Between 1990 and 2017, age-standardised DALY rates decreased by 41·3% (38·8-43·5) for communicable diseases and by 49·8% (47·9-51·6) for neonatal disorders. For non-communicable diseases, global DALYs increased by 40·1% (36·8-43·0), although age-standardised DALY rates decreased by 18·1% (16·0-20·2). INTERPRETATION: With increasing life expectancy in most countries, the question of whether the additional years of life gained are spent in good health or poor health has been increasingly relevant because of the potential policy implications, such as health-care provisions and extending retirement ages. In some locations, a large proportion of those additional years are spent in poor health. Large inequalities in HALE and disease burden exist across countries in different SDI quintiles and between sexes. The burden of disabling conditions has serious implications for health system planning and health-related expenditures. Despite the progress made in reducing the burden of communicable diseases and neonatal disorders in low SDI countries, the speed of this progress could be increased by scaling up proven interventions. The global trends among non-communicable diseases indicate that more effort is needed to maximise HALE, such as risk prevention and attention to upstream determinants of health