Increase In Death Rate Research Articles

Lower Extremity Burns, Complications, and Outcome

We have encountered many burn cases with lower extremity burn with adverse outcome. The study was a retrospective cohort study in 2 years, mean (SD) of follow up was 12(7) months. All demographic data, cause burn, time, total burn surface area (TBSA), presence lower extremity burn and its burn surface area (BSA), foot burn, delay in treatment, smoking, infection, morbidity, co-morbid diseases, length of stay (LOS), amputation, mortality, and outcome were gathered from patients' files. Statistical analysis was done with SPSS 21software. We had 14,215 burn patients, of them 995 were admitted according to criteria of ABA. Six hundred and ten (61.3%) were male and 358 (37%) female. Male to female ratio was 1.58:1. The mean age ± SD was 33.64 ±23.45. Mean (SD) of lower extremity BSA was 12.09 ± 9.18%. The patients who had 10 to 19% burn, had 3 times more risk of mortality than patients with 0 to 9% burn (P < .018). And those with 20 to 29% burn had 35 times more risk of mortality comparing to patients with 0 to 9% burn. The difference was significant too. (P < .000). Delay in treatment, presence of co-morbid diseases and diabetes would not do any increase in mortality. The sex, weight, cause of burn, diabetes, and delay in treatment have not any influence on the death risk. But age and lower extremity BSA have influence on the risk of death. According to statistical study: with every 1-year increase in age, death rate increased by 4% (P < .0001). With every 1% increase in lower extremity BSA, death rate increase by 9% (P < .0005) and with every 1 day increase in LOS, the death rate increase by 4%. Statistical study shows lower extremity burn, TBSA, age, and LOS have great influence on the outcome of these patients. Sex, weight, cause of burn, and delay in treatment have not affected the risk of mortality.

Contrasting the impact of cytotoxic and cytostatic drug therapies on tumour progression.

A tumour grows when the total division (birth) rate of its cells exceeds their total mortality (death) rate. The capability for uncontrolled growth within the host tissue is acquired via the accumulation of driver mutations which enable the tumour to progress through various hallmarks of cancer. We present a mathematical model of the penultimate stage in such a progression. We assume the tumour has reached the limit of its present growth potential due to cell competition that either results in total birth rate reduction or death rate increase. The tumour can then progress to the final stage by either seeding a metastasis or acquiring a driver mutation. We influence the ensuing evolutionary dynamics by cytotoxic (increasing death rate) or cytostatic (decreasing birth rate) therapy while keeping the effect of the therapy on net growth reduction constant. Comparing the treatments head to head we derive conditions for choosing optimal therapy. We quantify how the choice and the related gain of optimal therapy depends on driver mutation, metastasis, intrinsic cell birth and death rates, and the details of cell competition. We show that detailed understanding of the cell population dynamics could be exploited in choosing the right mode of treatment with substantial therapy gains.

Delaware's 1999-2017 Leading Causes of Death Information Illustrates Its Obesity and Obesity-Related Life-Limiting Disease Burdens.

Using commercially available but powerful big data analytics, this non-clinical obesity and underlying causes of death observational study, analyzed the very large US Centers for Disease Control and Prevention's (CDC) State of Obesity records, the CDC WONDER data, and the US census records. Compared to the 1999-to-2017 US obesity rate increase of 29.8%, an uncontrolled increase in Delaware's obesity rate (81.7%) was observed. During the same time period, CDC WONDER death certificate archives disclosed that there was a 60.53% surge in crude Delawarean mortality rate when obesity was listed as a single underlying cause of death. When any mention of obesity was documented on the death certificate, Delaware's 1999-2017 crude mortality rate advanced by 75.69% and its age-adjusted rate rose by 53.18%. Likewise, except for one year, Delaware's African American/Black population experienced higher crude mortality rate averages but however, between the years of 1997 and 2017, its Caucasian/White inhabitants had an enormous 87.34% death rate increase. With additional available CDC mortality data, Delaware males saw substantially larger age-adjusted death rate increases (79.87%) than their female counterparts (28.92%). Diabetes, circulatory system diseases, and neoplasms (cancer), are three common obesity comorbidities. For these three conditions, Delaware's 1999-2017 mortality rate figures mimic the falling national patterns of mortality rate averages, when each disease is listed as the single underlying cause of death, including observations where there are disproportionate numbers of cases that affect the African American/Black race.

Stagnating National Declines in Stroke Mortality Mask Widespread County-Level Increases, 2010-2016.

Background and Purpose- Recent national and state-level trends show a stalling or reversal of previously declining stroke death rates. These national trends may mask local geographic variation and changes in stroke mortality. We assessed county-level trends in stroke mortality among adults aged 35 to 64 and ≥65 years. Methods- We used data from National Vital Statistics Systems and a Bayesian multivariate space-time conditional autoregressive model to estimate age-standardized annual stroke death rates for 2010 through 2016 among middle-aged adults (35-64 years) and older adults (≥65 years) in US counties. We used log-linear regression models to estimate average annual and total percent change in stroke mortality during the period. Results- Nationally, the annual percent change in stroke mortality from 2010 to 2016 was -0.7% (95% CI, -4.2% to 3.0%) among middle-aged adults and -3.5% (95% CI, -10.7% to 4.3%) among older adults, resulting in 2016 rates of 15.0 per 100 000 and 259.8 per 100 000, respectively. Increasing county-level stroke mortality was more prevalent among middle-aged adults (56.6% of counties) compared with among older adults (26.1% of counties). About half (48.3%) of middle-aged adults, representing 60.2 million individuals, lived in counties in which stroke mortality increased. Conclusions- County-level increases in stroke mortality clarify previously reported national and state-level trends, particularly among middle-aged adults. Roughly 3×as many counties experienced increases in stroke death rates for middle-aged adults compared with older adults. This highlights a need to address stroke prevention and treatment for middle-aged adults while continuing efforts to reduce stroke mortality among the more highly burdened older adults. Efforts to reverse these troubling local trends will likely require joint public health and clinical efforts to develop innovative and integrated approaches for stroke prevention and care, with a focus on community-level characteristics that support stroke-free living for all.

Prey–predator–scavenger model with Monod–Haldane type functional response

In this paper, we have developed a prey, predator and scavenger interaction dynamical model. The positivity, boundedness and stability conditions of our proposed system have been derived. Hopf bifurcation analysis has been done theoretically with respect to half saturation constant in the absence of direct measure of inhibitory effects $$(\phi _1)$$ . Also, we have numerically studied Hopf bifurcation with respect to direct effects of inhibitory effects $$(\phi _2)$$ related to Monod–Haldane type functional response, carrying capacity of prey $$(\gamma )$$ , death rate of scavenger $$(\mu )$$ , conservation rate of prey $$(\alpha )$$ and harvesting rate of predator $$(\eta )$$ . It is observed that the intra-species competition can lead our proposed system towards stability. It is also found that the harvesting of predator can control the chaotic dynamics of our proposed system. The increase of death rate of scavenger species can be stabilized our proposed system. Finally, some numerical simulation results have been presented for better understanding the dynamics of our proposed model.

Racial/Ethnic and Age Group Differences in Opioid and Synthetic Opioid-Involved Overdose Deaths Among Adults Aged ≥18 Years in Metropolitan Areas - United States, 2015-2017.

Among the 47,600 opioid-involved overdose deaths in the United States in 2017, 59.8% (28,466) involved synthetic opioids (1). Since 2013, synthetic opioids, particularly illicitly manufactured fentanyl (IMF), including fentanyl analogs, have been fueling the U.S. overdose epidemic (1,2). Although initially mixed with heroin, IMF is increasingly being found in supplies of cocaine, methamphetamine, and counterfeit prescription pills, which increases the number of populations at risk for an opioid-involved overdose (3,4). With the proliferation of IMF, opioid-involved overdose deaths have increased among minority populations including non-Hispanic blacks (blacks) and Hispanics, groups that have historically had low opioid-involved overdose death rates (5). In addition, metropolitan areas have experienced sharp increases in drug and opioid-involved overdose deaths since 2013 (6,7). This study analyzed changes in overdose death rates involving any opioid and synthetic opioids among persons aged ≥18 years during 2015-2017, by age and race/ethnicity across metropolitan areas. Nearly all racial/ethnic groups and age groups experienced increases in opioid-involved and synthetic opioid-involved overdose death rates, particularly blacks aged 45-54 years (from 19.3 to 41.9 per 100,000) and 55-64 years (from 21.8 to 42.7) in large central metro areas and non-Hispanic whites (whites) aged 25-34 years (from 36.9 to 58.3) in large fringe metro areas. Comprehensive and culturally tailored interventions are needed to address the rise in drug overdose deaths in all populations, including prevention strategies that address the risk factors for substance use across each racial/ethnic group, public health messaging to increase awareness about synthetic opioids in the drug supply, expansion of naloxone distribution for overdose reversal, and increased access to medication-assisted treatment.

55Identification of celastramycin as a novel therapeutic agent for pulmonary arterial hypertension - high-throughput screening of 5,562 compounds

Abstract Background Pulmonary arterial hypertension (PAH) is characterized by enhanced proliferation of pulmonary artery smooth muscle cells (PASMCs) accompanying increased production of inflammatory factors and adaptation of mitochondrial metabolism to a hyperproliferative state. However, at present, since all the drugs in clinical use target pulmonary vascular dilatation, they may not be so effective for patients with advanced PAH. Purposes We aimed to discover a novel drug for PAH that inhibits PASMC proliferation. Methods In the first screening, we examined 5,562 compounds from our original library using high-throughput screening system to discover a compound that inhibits proliferation of PASMCs from PAH patients (PAH-PASMCs). In the second screening, we performed concentration-dependent assays and counter assays with PAH-PASMCs and PASMCs from healthy donors. We also performed apoptosis assays and mechanistic analysis for inflammation, reactive oxygen species (ROS), and mitochondrial function. Results We found that celastramycin, a benzoyl pyrrole-type compound originally found in a bacteria extract, inhibited the proliferation of PAH-PASMCs in a dose-dependent manner with minimal effects on PASMCs from healthy donors. Moreover, celastramycin inhibited proliferation with minimal increase in apoptosis and low rate of cell death. Then, we synthesized 25 analogues of celastramycin, and finally selected the lead compound that significantly inhibited proliferation of PAH-PASMCs and reduced cytosolic ROS levels. Mechanistic analysis demonstrated that celastramycin reduced the protein levels of hypoxia-inducible factor-1α, which was abnormally activated in PAH-PASMCs and impaired aerobic metabolism, and nuclear factor-κB, which induces pro-inflammatory signals, in PAH-PASMCs compared with vehicle controls, leading to reduced secretion of inflammatory cytokines. Importantly, celastramycin treatment reduced the ROS levels in PAH-PASMCs with increased protein levels of NF-E2-related factor 2 (Nrf2), a master regulator of cellular response against oxidative stress. Furthermore, celastramycin treatment improved mitochondrial energy metabolism with recovered mitochondrial network formation in PAH-PASMCs. We also discovered that celastramycin-mediated effects on these transcriptional modulators could be regulated by zinc finger C3H1 domain-containing protein, which is a binding partner of celastramycin. Finally, celastramycin treatment ameliorated pulmonary hypertension in three experimental animal models of PH in mice and rats, accompanied by reduced inflammatory changes in the lungs. Conclusions These results indicate that celastramycin ameliorates pulmonary hypertension through inhibition of excessive proliferation of PAH-PASMCs, for which its anti-inflammatory and beneficial effects on mitochondrial energy metabolism may be involved. Thus, celastramycin could be a novel drug for PAH as it exerts anti-proliferative effects on PAH-PASMCs.

Integrating complex systems science into road safety research and practice, part 1: review of formative concepts

Many of our most persistent public health problems are complex problems. They arise from a web of factors that interact and change over time and may exhibit resistance to intervention...

Increases in Online Posts About Synthetic Opioids Preceding Increases in Synthetic Opioid Death Rates: a Retrospective Observational Study.

Increases in Online Posts About Synthetic Opioids Preceding Increases in Synthetic Opioid Death Rates: a Retrospective Observational Study.

Twin consequences of rising U.S. death rates among young adults: Lower life expectancy and greater lifespan variability

The current study is an original investigation of the U.S. mortality pattern from 2000 to 2017. Previous research has shown that the unusual post-2014 decline in life expectancy is related to the increase in death rates for ages 25–44, mostly due to rising prevalence in drug poisoning and suicide deaths. Our investigation reveals that such increase in younger-age mortality has had an impact not only on life expectancy (or mean age at death), but also, and to a larger extent, on lifespan variability (the dispersion around the mean age at death). Even though lifespan variability is a key component of mortality change, as well as a measure of human well-being, with social, economic, and psychological implications, it has received much less attention than life expectancy has.

Roles for VEGF-C/NRP-2 axis in regulating renal tubular epithelial cell survival and autophagy during serum deprivation.

Vascular endothelial growth factor C (VEGF‐C) is an angiogenic and lymphangiogenic growth factor. Recent research has revealed the role for VEGF‐C in regulating autophagy by interacting with a nontyrosine kinase receptor, neuropilin‐2 (NRP–2). However, whether VEGF‐C participates in regulating cell survival and autophagy in renal proximal tubular cells is unknown. To address this question, we employed a cell modal of serum deprivation to verify the role of VEGF‐C and its receptor NRP–2 in regulating cell survival and autophagy in NRK52E cell lines. The results show that VEGF‐C rescued the loss of cell viability induced by serum deprivation in a concentration‐dependent manner. Furthermore, endogenous VEGF‐C was knocked down in NRK52E cells by using specific small‐interfering RNAs (siRNA), cells were more sensitive to serum deprivation–induced cell death. A similar increase in cell death rate was observed following NRP–2 depletion in serum‐starved NRK52E cells. Autophagy activity in serum‐starved NRK52E cells was confirmed by western blot analysis of microtubule‐associated protein‐1 chain 3 (LC3), immunofluorescence staining of endogenous LC3, and the formation of autophagosomes by electron microscopy. VEGF‐C or NRP–2 depletion further increased LC3 expression induced by serum deprivation, suggesting that VEGF‐C and NRP–2 were involved in controlling autophagy in NRK52E cells. We further performed autophagic flux experiments to identify that VEGF‐C promotes the activation of autophagy in serum‐starved NRK52E cells. Together, these results suggest for the first time that VEGF‐C/NRP–2 axis promotes survival and autophagy in NRK52E cells under serum deprivation condition.Significance of the studyMore researchers had focused on the regulation of autophagy in kidney disease. The effect of VEGF‐C on cell death and autophagy in renal epithelial cells has not been examined. We first identified the VEGF‐C as a regulator of cell survival and autophagy in NRK52E cell lines. And VEGF‐C/NRP–2 may mediate autophagy by regulating the phosphorylation of 4EBP1 and P70S6K. VEGF‐C treatment may be identified as a therapeutic target in renal injury repair due to its capacity to promote tubular cell survival in the future.

China's dusty lung crisis: Rural-urban health inequity as social and spatial injustice

This paper examines rural-urban inequities in dusty lung (pneumoconiosis) deaths in China from 2002 to 2016 and possible causes for such inequities in the framework of social and spatial justice. The research reveals alarming results that have not been reported before. Dusty lung death rates for rural men increased twice as fast as those among urban men. The rural rates were particularly higher among middle-aged men, but lower in older age groups, as compared to urban rates. There were dramatic increases in death rates from 2011 to 2016 particularly among rural men aged 40–49 years old, who were many times more likely to die from dusty lung than urban men of a similar age. Chinese rural male victims also die at a younger age, compared to men in any of the seven countries or regions included in the study. For example, rural Chinese men aged 35–59 years old were many times more likely to die from dusty lung than their American, German, Polish, and Spanish counterparts. A possible explanation for the high death rates among middle-aged rural Chinese men is the tendency for rural migrant workers to be employed in unhealthy and unsafe working conditions in decent decades. Other explanations for the severe spatial injustice include the Hukou (household registration) system and the development policies that prioritize economic growth and urban development over occupational health and safety. The paper demonstrates the usefulness and weakness of the social and spatial justice concepts in understanding health inequity. Therefore, it proposes new definitions and models of social justice and spatial justice that combine the competing distribution and capabilities approaches and highlight interactions among multiple attributes.

Temporal trends in liver cancer mortality by educational attainment in the United States, 2000-2015.

Liver cancer is the most rapidly rising cause of cancer death in the United States. However, it is unclear whether the mortality trend differs by socioeconomic and/or hepatitis C virus (HCV) infection status. Joinpoint analyses and Poisson regression modeling were performed to examine trends in death rates from liver cancer by education and HCV infection status among persons aged 25 to 74years from 2000 to 2015. Disparities in liver cancer mortality were measured as a relative index of inequality by education. From 2000 to 2015, the overall liver cancer death rate (per 100,000persons) increased from 7.5 to 11.2 in men and from 2.8 to 3.8 in women. The increase was generally steeper in less educated groups for women and was confined to persons with ≤15years of education for men. Consequently, the relative disparity increased until 2006 and then levelled off in women, whereas it continued to increase from 3.49 (95% CI, 3.08-3.97) to 7.74 (95% CI, 7.13-8.40) in men, with the increase more pronounced for HCV-related liver cancer than HCV-unrelated liver cancer. The increases in liver cancer death rates in the United States have largely been confined to less educated persons, especially among men. Enhanced and targeted efforts are needed to halt and reverse the undue growing burden of liver cancer in lower socioeconomic groups.

Challenges Related to Three Cases of Fatal Intoxication to Multiple Novel Synthetic Opioids.

In the last two decades, a large increase in opioid overdose death rates has been recorded in North America. This phenomenon, related to the misuse of prescription opioids, has been dubbed an "opioids crisis". Recent years have seen the entrance of novel synthetic opioids (NSO) on the market, compounding the fatal intoxications issue. This brings several challenges for forensic toxicology laboratories: an increased number of cases, a large number of novel structurally similar compounds to include in screening analytical methods, the low concentration of drugs in biological fluids, and the challenging interpretation in the absence of sufficient literature. Three cases of fatal intoxication highlighting those challenges are presented, complete with post-mortem concentrations in cardiac blood, femoral blood and urine. Toxicological screening and quantitative analyses were performed on the biological specimens. In the first and second cases, furanylfentanyl, U-47700 and 4-anilino-N-phenethylpiperidine (4-ANPP) were detected at similar concentrations in cardiac blood. In the third case, a total of seventeen different NSO were detected. All intoxications showed a combination of NSO and other drugs. These three cases appear to be the harbinger of an increased NSO prevalence in the province of Québec, Canada.

Modelling Deaths Associated with Road Traffic Accidents and other Factors on Great North Road in Zambia between the Years 2010 and 2016 Using Poisson Models

Background: According to the World Health Organization (WHO), 1.24 million people die annually on the world’s roads, with 20-50 million sustaining non-fatal injuries. More than 85% (1.05 million) of the global deaths due to injuries occur in the developing world. Road traffic deaths and injuries are a major but neglected public health challenge that requires concerted efforts for effective and sustainable prevention. The objectives of the study were to estimate the incidence rate of death from RTAs, to determine factors associated with serious and fatal Road Traffic Accidents (RTAs) and to determine which of the poisson models fit the count data better. Methods: Data was collected from Zambia Police (ZP), Traffic Division on accidents that occurred on the Great North Road (GNR) highway between Lusaka and Kapiri-Mposhi in Zambia from January 1, 2010 to December 31, 2016. Results from standard Poisson regression were compared to those obtained using the Negative Binomial (NB), Zero-Truncated Negative Binomial (ZTNB) and the Zero-Truncated Poisson (ZTP) regression models. Diagnostic tests were used to determine the best fit model. The data was analysed using STATA software, version 14.0 SE (Stata Corporation, College Station, TX, USA). Results: A total of 1, 023 RTAs were analysed in which 1, 212 people died. Of these deaths, 82 (7%) were Juveniles and 1, 130 (93%) were adults. Cause of accident such as pedestrians crossing the road accounted for 30% (310/1,023) while 29% (295/1,023) were as a result of driver’s excessive speed. The study revealed that driving in the early hours of the day (1AM-6AM) as compared to driving in the night (7PM-12AM) had a significant increase in the incidence rate of death from RTAs, Incidence Rate Ratio (IRR) of 2.1, (95% CI={1.01-4.41}), p-value=0.048. Results further showed that public transport as compared to private transport had an increased incidence rate of death from RTAs (IRR=5.65, 95% CI={2.97-10.73}), p-value&lt;0.0001. The two competing models were the ZTP and the ZTNB. The ZTP had AIC=1304.55, BIC= 1336.55, whereas the ZTNB had AIC=742.25 and BIC=819.69. This indicated that the ZTNB with smaller AIC and BIC was the best fit model for the data. Conclusion: There is a reduced incidence of dying if one is using a private vehicle as compared to a public vehicle. Driving in the early hours of the day (1AM and 6AM) had an increased incidence of death from RTAs. This study suggests that when dealing with counts in which there are a few zeros observed such as in serious and fatal RTAs, ZTNB fits the data well as compared to other models.

Poor Left Ventricular Unloading is Associated with Increased Mortality after Continuous Flow Left Ventricular Assist Device Implantation

Purpose The role of routine right heart catheterization (RHC) to evaluate for left ventricular (LV) unloading remains unclear in patients with continuous flow left ventricular assist devices (CF-LVAD). We hypothesized that persistently elevated pulmonary capillary wedge pressure (PCWP) would be associated with increased mortality on CF-LVAD support. Methods A single center continuous flow LVAD cohort (n=451) was queried for patients with follow-up RHC data at 6 months +/- 3 months (n=179). To determine the relationship between follow-up PCWP and mortality, a multivariable cox regression analysis was performed. Results The mean age of the study cohort was 57±13 years. 79% (141/179) were males, 56% (101/179) had ischemic cardiomyopathy and 74% (133/179) were designated bridge to transplant (BTT). The median follow-up time on LVAD support after RHC was 4.4 years. The only pre-implant variables that were associated with elevated PCWP in the multivariate analysis were renal function and BMI (each 2.5 unit increase in BMI was associated with an adjusted 0.6 mmHg increase in follow-up PCWP, 95% CI 0.2-0.9 mmHg, p=0.004; each 0.5 mg/dL increase in creatinine was associated with a 1.2 mmHg increase in follow-up PCWP, 95% CI 0.4-2.1, p=0.003). In the final multivariate models, each 5 mmHg increase in PCWP at the time of RHC was associated with a 22% increase in the hazards rate of death during follow-up (adjusted HR 1.2, 95% CI 1.01-1.47, p=0.039). All models were adjusted for age, sex, INTERMACS profile, body mass index, bridge to transplant status and renal function. Conclusion Incomplete LV unloading following CF-LVAD implantation is associated with increased all-cause mortality. Our results emphasize the importance of invasive hemodynamic optimization in this patient population. Further studies are warranted to determine the optimal filling pressures in patients with CF-LVAD.

Historical Analysis of U.S. Tornado Fatalities (1808–2017): Population, Science, and Technology

AbstractThe record of tornado fatalities in the United States for over two centuries (1808–2017) and decadal census records have been examined to search for historical trends. Particular attention has been given to the response to population growth and expansion into the tornado-prone regions of the country. The region selected includes the Tornado Alley of the central Great Plains, the Dixie Alley in the southeastern states, and the adjoining states in the Midwest that collectively encompass a 21-state rectangular region. The data record has been divided into two subintervals, Era A (1808–1915) and Era B (1916–2017), each of which consists of three equal-length periods. Era A is characterized by a growing and westward expanding population along with a basic absence of scientific knowledge, technology, and communications (for prediction, detection, and warning). This is followed by a renaissance of discovery and advancement in Era B that contributes to saving lives. The aforementioned periods are defined by a set of notable events that help to define the respective periods. A death per population index (DPI) is used to evaluate the 21 states in each era; there is a rise of mean DPI values to a maximum of 1.50 at the end of Era A and a subsequent fall to 0.21 at the end of Era B. It is also shown for all three periods in Era B that the deadliest tornado states, in ranked order, are Arkansas, Mississippi, Alabama, and Oklahoma. Suggestions are presented for ways to continue the decreasing trend in DPI, which would imply that the death rate increase is not as fast as the rate of population increase (or would even imply a decreasing death rate).

Induction of cell-cycle arrest and apoptosis in human cholangiocarcinoma cells by pristimerin.

Pristimerin, a triterpenoid isolated from Celastraceae and Hippocrateaceae, is known to induce cytotoxicity in several cancer cell lines. However, whether pristimerin can induce apoptosis in cholangiocarcinoma cells and the underlying mechanism remain unexplored. We assessed the function of human cholangiocarcinoma QBC and RBE cell lines using various experimental methods such as the cell viability assay to elucidate the viability of cells, flow cytometry to detect the death rate of cells, and Western blot analysis to evaluate the expression of cell cycle-related proteins and autophagy-related proteins. Human cholangiocarcinoma QBC cells were transplanted to nude mice to establish an animal model, and the effect of pristimerin on tumor growth in this model was observed. QBC and RBE cell lines treated with pristimerin (0, 5, 10, and 20 μmol/L) demonstrated the induction of apoptosis in a dose-dependent manner. The cell viability assay revealed a reduction in the cell viability with an increase in the pristimerin concentration. Similarly, flow cytometry revealed a gradual increase in the cell death rate with an increase in the pristimerin concentration. In addition, pristimerin significantly lowered the expression of apoptosis-related proteins (Bcl-2, Bcl-xL, and procaspase-3), but increased the Bax expression. Furthermore, pristimerin resulted in the G0/G1 cell-cycle arrest, reducing the expression of cell cycle-related proteins (cyclin E, CDK2, and CDK4), and increased the expression of autophagy-related proteins (LC3) in QBC cell line. Treatment with pristimerin could inhibit tumor growth in the nude mouse model. Overall, this study suggests the potential effect of pristimerin on the cell-cycle arrest and apoptosis in human cholangiocarcinoma cells.

Potential application of waste fruit peels (orange, yellow lemon and banana) as wide range natural antimicrobial agent

The antimicrobial potential of three abundantly available fruits peel waste, (orange, yellow lemon and banana) was evaluated on wide range of microorganisms. Three solvents methanol, ethyl acetate, ethanol and distilled water were used for extraction. The resultant extracts were used to test a six gram positive and six gram negative pathogenic bacteria in addition to two microscopic filamentous fungi (MFF) and two yeast species. Presence of trace metals were determined by Atomic Absorption Spectrophotometer and GC-MS Analysis was carried out to find out the total phenolic compounds, which may be responsible for the antimicrobial activity. The antibacterial activity was assessed by the well-bore method, reflected by the diameter of the zones of growth inhibition. Minimum Inhibitory Concentration (MIC) was also determined to confirm the antimicrobial potential of extracts and get quantitative results. Results shows that among the used solvents the extracts exhibited better performance in the order of Distilled water > Methanol > Ethanol > Ethyl acetate which reflects the suitability of solvent for fruit peel extraction. Effectiveness of fruit peel extracts was evaluated and found Yellow lemon > Orange > Banana peel. It was found that gram negative bacteria are more sensitive to the extracts and among them Klebsiella pneumoniae show the highest sensitivity against extract of yellow lemon peel and show the highest zone of inhibition (28 ± 1.4 mm to 3.5 ± 1.3 mm). Similarly, the MIC value was found to be 130 µg/mL which is the least value among other tested microorganisms. This may be attributed to the presence of high concentrations of zinc, magnesium and total phenolic content in the extract of yellow lemon peel. As multidrug resistant strains of microorganisms are emerging and treatment of their infection is becoming difficult with time, infectious diseases are a global cause of increase in death rate. Present study confirms the potential of studied fruit peel waste to be used for therapeutic purpose to combat the multidrug resistant microorganism infection. This will also result in reduction of waste material, reusing it for beneficial purpose in an economical and environmental friendly manner.

Abstract TP198: Urban Versus Rural Stroke Death Rates From 2005-2015 in the United States

Introduction: After 4 decades of decline in the stroke death rate in the United States, from 2013-2015 the rate increased 2.5% per year. Hypothesis: Given that the stroke death rate has historically been higher in rural than urban populations, we propose that the increase in the stroke death rate will be more prominent in rural than urban populations. Methods: This is an analysis of CDC surveillance data. We examined stroke death rates for US residents aged 0-84 years, divided into “urban” (metropolitan) versus “rural” (nonmetropolitan). The stroke death rate was defined as: 1) incidence (# of stroke deaths/total population) and 2) potentially excessive stroke death, which is the percentage of stroke deaths in excess of expected, which is defined yearly by the CDC. Results: There were 853,892 stroke deaths from 2005-15, of which 682,318 were urban and 171,574 were rural. Comparing 2005-12 to 2013-15, while there was not a statistical difference in the increase in urban versus rural stroke death, there were 3 states with an increase in the urban incidence of stroke death versus 11 states with a rural increase (Figure 1); and 30 states with an increase in urban excess stroke death versus 34 states with a rural increase (Figure 2). Conclusion: The increase in the United States stroke death rate may be happening in more states’ rural than urban populations, which is concerning given the existing higher stroke death rate in rural populations and the implications for future trends.