25 research outputs found
Weakness of will and its connection with practical reasons
This thesis pursues two main goals. First, it aspires to develop a plausible account of weakness of will that can make sense of our attribution of weakness of will to a range of cases. My proposal to account for weakness of will is that weakness of will arises when the agent withdraws (abandons, revises or acts against) her practical commitment(s) without a good enough normative reason. The idea that a proper analysis of weakness of will involves, among other things, the claims about good enough normative reasons leads us to the second purpose of this thesis. This is to consider what happens when the proposed account of weakness of will is conjoined with a theory of reasons. The motivation for doing so has twofold. First, I take it to be a completion of my proposed account since I believe that a proper understanding of weakness of will needs to make use of the notion of practical reasons. Second, this will be an attempt to bridge the gap between two relatively independent debates, the dispute over “weakness of will” and “practical reasons”; and I take this to be a distinctive contribution of my thesis. To elaborate my proposal further by adding to it a theory of reasons, I will combine the proposed account of weakness of will with Humeanism and Kantianism in turn, and consider the implications of the resulting conjoint view
The Correlation Between SMG1 Promoter Methylation and Its Expression in Acute Lymphoblastic Leukemia Patient
Background: Acute lymphoblastic leukemia (ALL) comprises a heterogeneous group of disorders which originate from various important genetic lesions in B and T progenitor cells, including mutations that lead to stage-specific developmental arrest and those that impart the capacity for unlimited self-renewal, resulting in clonal expansion of immature progenitor cells. Acute lymphoblastic leukaemia occurs in both children and adults but its incidence peaks between 2 and 5 years of age. Causation is multifactorial and exogenous or endogenous exposures, genetic susceptibility, and chance have roles. Survival in pediatric acute lymphoblastic leukaemia has improved to roughly 90% in trials with risk stratification by biological features of leukaemic cells and response to treatment, treatment modification based on patients' pharmacodynamics and pharmacogenomics, and improved supportive. The promoter methylation pattern of DNA in cancer cells is different with the normal cells. Suppressor with morphogenetic effect on genitalia family member (SMG1) belongs to a family of phosphoinositide 3-kinase-related kinases and is the main kinase involved in nonsense-mediated mRNA decay.Materials and Methods: This study was performed to investigate the correlation between SMG1 promotor methylation and its expression levels in acute lymphoblastic leukemia using methylation specific PCR (MSP). Our patients and control samples were collected from Children's Medical Center of children medical center of Imam Khomeini hospital of Tehran. To confirm the MSP results, we used Quantitative Real time-PCR (qRT-PCR ) to measure the expression level of mRNA to find out if there is any relation between pattern of methylation and expression.Results: After performing MSP, we found that SMG1 promoter was hypermethylated. Hyper methylation of SMG1 was detected in 67/74% (21/31) of ALL samples compared to control group. SMG1 mRNA expression was down- regulated 2.74 fold compared to control group.Conclusion: The aim of this study was to investigate the effect of methylation pattern on gene expression. Our findings suggest that SMG1 acts as a functional tumor suppressor gene which was down-regulated by CpG islands hypermethylation in ALL patients. It was shown that the methylation of SMG1 was occurred in the 67/74% of samples
In vitro cytotoxic effect of urtica dioica extracts on acute myelogenous leukemia cell line (kg-1)
Background: Urtica dioica is one of the medicinal herbs with many uses in treating various diseases. In some studies, its antiproliferative and apoptotic effects on cancer cell lines have been shown. Therefore, the evaluation of U. dioica effect was performed on KG-1 cell line for acute myelogenous leukemia (AML) for the first time in this study.Materials and Methods: KG-1 cell line was treated by various extracts (aqueous, hydroalcoholic, chloroform and ethyl acetate) of U. dioica aerial parts and roots in different concentrations. Metabolic activity of extracts on cell line was assessed by MTT assay. To evaluate the percentage of apoptotic cells, the flow cytometry was performed by FITC Annexin V-PI apoptosis detection kit in KG-1 cell line treated with root chloroform (UDC-R) and ethyl acetate (UDE-R) extracts. The results have been reported as percentage of cell viability and IC50.Results: Based on MTT results, the strongest IC50 in KG-1 cell line (219.361μg/ml) was related to UDC-R. The flow cytometric analysis showed that UDC-R and UDE-R in IC50 concentration induced early (53.6% and 57.4%, respectively) and late (27% and 33.2%, respectively) apoptosis in KG-1 cells after 24 hrs. The inhibition of cell proliferation by various extracts of U. dioica was dependent on concentration (p=0.000).Conclusion: Flow cytometric analysis confirmed that UDC-R and UDE-R extracts affect on proliferation reduction of KG-1 cells by activating the apoptotic pathway
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Total Sitting Time and Sitting Pattern in Postmenopausal Women Differ by Hispanic Ethnicity and are Associated With Cardiometabolic Risk Biomarkers.
Background Sedentary behavior is pervasive, especially in older adults, and is associated with cardiometabolic disease and mortality. Relationships between cardiometabolic biomarkers and sitting time are unexplored in older women, as are possible ethnic differences. Methods and Results Ethnic differences in sitting behavior and associations with cardiometabolic risk were explored in overweight/obese postmenopausal women (n=518; mean±SD age 63±6 years; mean body mass index 31.4±4.8 kg/m2). Accelerometer data were processed using validated machine-learned algorithms to measure total daily sitting time and mean sitting bout duration (an indicator of sitting behavior pattern). Multivariable linear regression was used to compare sitting among Hispanic women (n=102) and non-Hispanic women (n=416) and tested associations with cardiometabolic risk biomarkers. Hispanic women sat, on average, 50.3 minutes less/day than non-Hispanic women (P<0.001) and had shorter (3.6 minutes less, P=0.02) mean sitting bout duration. Among all women, longer total sitting time was deleteriously associated with fasting insulin and triglyceride concentrations, insulin resistance, body mass index and waist circumference; longer mean sitting bout duration was deleteriously associated with fasting glucose and insulin concentrations, insulin resistance, body mass index and waist circumference. Exploratory interaction analysis showed that the association between mean sitting bout duration and fasting glucose concentration was significantly stronger among Hispanic women than non-Hispanic women (P-interaction=0.03). Conclusions Ethnic differences in 2 objectively measured parameters of sitting behavior, as well as detrimental associations between parameters and cardiometabolic biomarkers were observed in overweight/obese older women. The detrimental association between mean sitting bout duration and fasting glucose may be greater in Hispanic women than in non-Hispanic women. Corroboration in larger studies is warranted
The Relationship between the Results of Coagulation Profile and Severity of Pulmonary Involvement in COVID-19 Patients
Introduction: COVID-19 is currently a global pandemic, and coagulation-related mortality has been widely reported in patients suffering from it. Objective: this article aimed to investigate the coagulation profile of COVID-19 patients. Methods: This was a cross-sectional study conducted using a retrospective research design. We recruited patients with COVID-19 admitted to a hospital from June 15th to July 7th, 2020. Upon patients' entering a blood sample was drawn from each patient for assessing patient’s coagulation profile (PT, PTT, INR, Platelet count); and a chest high-resolution computed tomography (HRCT) scan was performed for each patient. The study patients were divided in to sever group (CO-RADS score 5) and non-sever group (CO-RADS score <5). Results: Thirty-six patients (20 males and 16 females) with a mean age of 54.7±17.5 years were studied. Of them, 11 cases (30.56%) had severe pulmonary involvement. Also, the coagulation profiles were longer in the severe group than non-sever group. As well, the means of platelet count that were 232.440 per microliter in the non-severe group and 289.180 per microliter in the severe and non-sever groups, respectively; but still not statistically significant (p>0.05). The Area under the ROC Curve (AUC) for PT and INR was 0.615 and 0.611, respectively. The AUC for platelet count was 0.680 (95% CI: 0.501 to 0.859) and had an acceptable discriminating power. Conclusions: In this study, we did not find any statistically significant relationship between the results of coagulation tests and the severity of pulmonary involvement according to HRCT scan findings in COVID-19 patients. But further analyses suggest that, except PTT, the other coagulation tests (PT, INR, and platelet count) may discriminate severe COVID-19 patients
Gender Differences in COVID-19 Deceased Cases in Jahrom City, South of Iran
Objective: To evaluate the clinical and epidemiological features of deceased patients and comparing the discrepancies between male and female patients based on high prevalence of coronavirus disease 2019 (COVID-19), its irreversible effects and the rising mortality rate in Jahrom city. Methods: This is a descriptive-analytical retrospective study that was conducted from the beginning of March 2020 to the end of November 2020. The study population were included all patients with COVID-19 who admitted to Peymaniyeh Hospital in Jahrom and died of COVID-19. Clinical and demographic data were collected from medical records and analyzed by SPSS software. Results: In this study, 61 patients (57.54%) were men and 45 patients (42.36%) were women. The mean age was 68.7±18.33 in men and 68.82±14.24 in women. The mean hospitalization length was 9.69±7.75 days in men and 9.69±7.75 days in women patients. There was no statistically significant difference between men and women patients (p>0.05). The results showed that 17 (27.87%) men and 28 (45.9%) of women patients had hypertension and the prevalence of this disease was significantly higher in women than men (p=0.01). In this study, 7 (11.48%) men and 13 (21.31%) women had hyperlipidemia. The frequency of hyperlipidemia in women caseswas significantly higher than in men patients (p=0.024). Men cases’ diastolic blood pressure (mean=77.53) was significantly higher than women’s diastolic blood pressure at the same time with a mean of 71.42 (p <0.05). Conclusion: The findings of the study represented the mortality rate in men which is higher than women patients. The prevalence of underlying diseases such as hypertension and hyperlipidemia were higher in women than men. Despite higher mortality among women, symptoms such as fever and dyspnea were less common in women than men
Loss of expression of TGF-βs and their receptors in chronic skin lesions induced by sulfur mustard as compared with chronic contact dermatitis patients
<p>Abstract</p> <p>Background</p> <p>Sulfur mustard (SM) is a blister-forming agent that has been used as a chemical weapon. Sulfur mustard can cause damage in various organs, especially the skin, respiratory system, and eyes. Generally, the multiple complications of mustard gas result from its alkalizing potency; it reacts with cellular components like DNA, RNA, proteins, and lipid membranes.</p> <p>TGF-β is a multi-functional cytokine with multiple biological effects ranging from cell differentiation and growth inhibition to extracellular matrix stimulation, immunosuppression, and immunomodulation. TGF-β has 3 isoforms (TGF-β 1, 2, 3) and its signaling is mediated by its receptors: R1, R2 and intracellular Smads molecules.</p> <p>TGF-β has been shown to have anti-inflammatory effects. TGF-βs and their receptors also have an important role in modulation of skin inflammation, proliferation of epidermal cells, and wound healing, and they have been implicated in different types of skin inflammatory disorders.</p> <p>Methods</p> <p>Seventeen exposed SM individuals (48.47 ± 9.3 years), 17 chronic dermatitis patients (46.52 ± 14.6 years), and 5 normal controls (44.00 ± 14.6 years) were enrolled in this study.</p> <p>Evaluation of TGF-βs and their receptors expressions was performed by semiquantitative RT-PCR. Only TGF1was analyzed immunohistochemically.</p> <p>Results</p> <p>Our results showed significant decreases in the expression percentages of TGF-β 1, 2 and R1, R2 in chemical victims in comparison with chronic dermatitis and normal subjects and significant decreases in the intensity of R1 and R2 expressions in chemical victims in comparison with chronic dermatitis and normal controls. (P value < 0.05)</p> <p>Conclusions</p> <p>TGF-βs and their receptors appear to have a noticeable role in chronic inflammatory skin lesions caused by sulfur mustard.</p
Global, regional, and national burden of stroke and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019
Background
Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels.
Methods
We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level.
Findings
In 2019, there were 12·2 million (95% UI 11·0–13·6) incident cases of stroke, 101 million (93·2–111) prevalent cases of stroke, 143 million (133–153) DALYs due to stroke, and 6·55 million (6·00–7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8–12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1–6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0–73·0), prevalent strokes increased by 85·0% (83·0–88·0), deaths from stroke increased by 43·0% (31·0–55·0), and DALYs due to stroke increased by 32·0% (22·0–42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0–18·0), mortality decreased by 36·0% (31·0–42·0), prevalence decreased by 6·0% (5·0–7·0), and DALYs decreased by 36·0% (31·0–42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0–24·0) and incidence rates increased by 15·0% (12·0–18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5–3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5–3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57–8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97–3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01–1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7–90·8] DALYs or 55·5% [48·2–62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3–48·6] DALYs or 24·3% [15·7–33·2]), high fasting plasma glucose (28·9 million [19·8–41·5] DALYs or 20·2% [13·8–29·1]), ambient particulate matter pollution (28·7 million [23·4–33·4] DALYs or 20·1% [16·6–23·0]), and smoking (25·3 million [22·6–28·2] DALYs or 17·6% [16·4–19·0]).
Interpretation
The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries.publishedVersio
Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019
Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings In 2019, there were 12.2 million (95% UI 11.0-13.6) incident cases of stroke, 101 million (93.2-111) prevalent cases of stroke, 143 million (133-153) DALYs due to stroke, and 6.55 million (6.00-7.02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11.6% 10.8-12.2] of total deaths) and the third-leading cause of death and disability combined (5.7% 5.1-6.2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70.0% (67.0-73.0), prevalent strokes increased by 85.0% (83.0-88.0), deaths from stroke increased by 43.0% (31.0-55.0), and DALYs due to stroke increased by 32.0% (22.0-42.0). During the same period, age-standardised rates of stroke incidence decreased by 17.0% (15.0-18.0), mortality decreased by 36.0% (31.0-42.0), prevalence decreased by 6.0% (5.0-7.0), and DALYs decreased by 36.0% (31.0-42.0). However, among people younger than 70 years, prevalence rates increased by 22.0% (21.0-24.0) and incidence rates increased by 15.0% (12.0-18.0). In 2019, the age-standardised stroke-related mortality rate was 3.6 (3.5-3.8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3.7 (3.5-3.9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62.4% of all incident strokes in 2019 (7.63 million 6.57-8.96]), while intracerebral haemorrhage constituted 27.9% (3.41 million 2.97-3.91]) and subarachnoid haemorrhage constituted 9.7% (1.18 million 1.01-1.39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79.6 million 67.7-90.8] DALYs or 55.5% 48.2-62.0] of total stroke DALYs), high body-mass index (34.9 million 22.3-48.6] DALYs or 24.3% 15.7-33.2]), high fasting plasma glucose (28.9 million 19.8-41.5] DALYs or 20.2% 13.8-29.1]), ambient particulate matter pollution (28.7 million 23.4-33.4] DALYs or 20.1% 16.6-23.0]), and smoking (25.3 million 22.6-28.2] DALYs or 17.6% 16.4-19.0]). Interpretation The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries
Weakness of will and its connection with practical reasons
This thesis pursues two main goals. First, it aspires to develop a plausible account of weakness of will that can make sense of our attribution of weakness of will to a range of cases. My proposal to account for weakness of will is that weakness of will arises when the agent withdraws (abandons, revises or acts against) her practical commitment(s) without a good enough normative reason. The idea that a proper analysis of weakness of will involves, among other things, the claims about good enough normative reasons leads us to the second purpose of this thesis. This is to consider what happens when the proposed account of weakness of will is conjoined with a theory of reasons. The motivation for doing so has twofold. First, I take it to be a completion of my proposed account since I believe that a proper understanding of weakness of will needs to make use of the notion of practical reasons. Second, this will be an attempt to bridge the gap between two relatively independent debates, the dispute over “weakness of will” and “practical reasons”; and I take this to be a distinctive contribution of my thesis. To elaborate my proposal further by adding to it a theory of reasons, I will combine the proposed account of weakness of will with Humeanism and Kantianism in turn, and consider the implications of the resulting conjoint view