Miracle-dz/UniFAR-FTUs huggingface dataset:
Rab11 Family Interacting Protein 2 Associates with Myosin Vb and Regulates Plasma Membrane Recycling*

Plasma membrane recycling is an important process necessary for maintaining membrane composition. The motor protein myosin Vb regulates plasma membrane recycling through its association with Rab11a. Overexpression of the tail of myosin Vb disrupts trafficking out of plasma membrane recycling systems and leads to the accumulation of Rab11a in both polarized and non-polarized cells. We have investigated the association of Rab11 family interacting protein 2 (Rab11-FIP2) with myosin Vb as an adapter protein between Rab11a and myosin Vb. Immunofluorescence studies indicated a colocalization of endogenous Rab11-FIP2 with green fluorescent protein-myosin Vb tail overexpressed in Madin-Darby canine kidney (MDCK) cells. Yeast two hybrid assays showed that amino acids 129–356 of Rab11-FIP2 were important for binding to myosin Vb tail.In vitro association assays and co-transfection experiments in both MDCK and HeLa cells confirmed this result but further refined the binding site to amino acids 129–290 of Rab11-FIP2. Like myosin Vb, functional studies indicated that Rab11-FIP2 is also important for normal plasma membrane recycling. Green fluorescent protein-Rab11-FIP2 (129–512), which lacks its amino-terminal C2 domain, functioned as a dominant negative acting truncation that caused accumulation of Rab11a and disrupted IgA trafficking in MDCK cells and transferrin trafficking in HeLa cells. The ternary association of myosin Vb and Rab11-FIP2 with Rab11a suggests that a multimeric protein complex is involved in vesicle trafficking through plasma membrane recycling systems.
Fatty Liver and Uric Acid Levels Predict Incident Coronary Heart Disease but Not Stroke among Atomic Bomb Survivors in Nagasaki

Relationships between fatty liver and coronary heart disease (CHD) and stroke risk remain ill defined. We investigated whether fatty liver is a predictor of CHD and stroke risk. Until December 2000 we followed 2,024 atomic bomb survivors (775 men: 62.0±9.9 years old; 1,249 women: 63.2±8.4 years old) who had basic examinations between November 1990 and October 1992 for clinical and laboratory CHD risk factors and fatty liver and who were initially free of CHD and stroke. Forty-nine cases of CHD and 84 cases of stroke were observed. At the time of the baseline examinations, significant clinical associations were found between fatty liver and obesity (p<0.001), hypertension (p<0.001), dyslipidemia (p<0.001), and glucose intolerance (p<0.001). A slight but nonsignificant association was found between fatty liver and hyperuricemia (p=0.07) as well. By using multiple Cox regression analyses, age (relative risk [RR] 1.05, 95% confidence interval [CI] 1.01–1.08), smoking (RR 2.20, 95% CI 1.02–4.74), hyperuricemia (RR 2.30, 95% CI 1.08–4.89), and fatty liver (RR 2.53, 95% CI 1.06–6.06) were shown to be significant predictors of CHD, whereas age (RR 1.08, 95% CI 1.06–1.10), smoking (RR 2.06, 95% CI 1.14–3.72), and hypertension (RR 2.14, 95% CI 1.38–3.30) predicted stroke risk. Fatty liver, which clusters clinical and laboratory CHD risk factors, is an independent predictor of CHD, but not of stroke. Fatty liver should be followed as a feature of metabolic syndrome, with the aim of preventing CHD.
Moral Motivation Based on Multiple Developmental Structures: An Exploration of Cognitive and Emotional Dynamics

ABSTRACT Intrapersonal variability and multiplicity in the complexity of moral motivation were examined from Dynamic Systems and Self-Determination Theory perspectives. L. Kohlberg's (1969) stages of moral development are reconceptualized as soft-assembled and dynamically transformable process structures of motivation that may operate simultaneously within person in different degrees. Moral motivation is conceptualized as the real-time process of self-organization of cognitive and emotional dynamics out of which moral judgment and action emerge. A detailed inquiry into intrapersonal variation in moral motivation is carried out based on the differential operation of multiple motivational structures. A total of 74 high school students and 97 college students participated in the study by completing a new questionnaire, involving 3 different hypothetical moral judgments. As hypothesized, findings revealed significant multiplicity in the within-person operation of developmental stage structures, and intrapersonal variability in the degrees to which stages were used. Developmental patterns were found in terms of different distributions of multiple stages between high school and college samples, as well as the association between age and overall motivation scores. Differential relations of specific emotions to moral motivation revealed and confirmed the value of differentiating multiple emotions. Implications of the present theoretical perspective and the findings for understanding the complexity of moral judgment and motivation are discussed.
Transfusion rate using intravenous tranexamic acid in hip revision surgery.

INTRODUCTION Hip revision surgery is associated with a high probability of the necessity for a blood transfusion. Different studies support the use of tranexamic acid (TXA) to decrease the rate of transfusions in primary hip surgery. Nevertheless, the use of this drug in hip revision surgery has not yet been widely accepted. The aim of our study was to establish the rate of blood transfusion with and without TXA in hip revision surgery. METHODS We retrospectively studied 125 hip revision surgery patients operated on between 2011 and 2014. We divided our series into 2 groups: the TXA group with 61 patients (in which a 1000 mg dose of TXA was used before the skin incision and a second identical dose after skin closure) and a control group with 64 patients. We analysed the red blood cell (RBC) transfusion rates and their odds risk as well as the presence of collateral complications. RESULTS Average RBC transfusion was 2.7 units/patient (range 0-6) in the control group compared to 1.6 units/patient (range 0-6) in the TXA group. A 90.11% (odds ratio [OR] 0.098; confidence interval [CI] 0.02-0.04; p<0.0029) odds risk reduction for transfusion of at least 1 unit of erythrocyte blood cell was observed in the TXA group. Complications associated with the TXA were similar in both groups. INTERPRETATION The benefits of TXA have been shown in elective hip replacement. In this study, TXA proved to be safe and efficacious in reducing the need for transfusions following revision total hip arthroplasty.
Outcomes of primary percutaneous coronary intervention (PCI) in a tertiary care cardiac centre.

OBJECTIVE To determine the outcomes of primary percutaneous coronary intervention (PCI) in a tertiary care cardiac centre. METHODS Medical records of 104 consecutive patients presented in our hospital between January 2006 to December 2007 with acute ST elevation myocardial infarction (STEMI) and treated with primary PCI as a mode of reperfusion were reviewed. The primary end point was in hospital mortality and secondary end points were 30 day mortality, myocardial infarction, recurrent angina and congestive cardiac failure, from discharge to one month follow up. RESULTS The procedural success was 97%. Six (5.8%) patients died during hospital stay including one on table death. Out of six patients who died, five (83.3%) had cardiogenic shock. No mortality was observed in the 30 days follow up from discharge while other complications like myocardial infarction, recurrent angina and congestive cardiac failure were 1%, 1% and 5% respectively. CONCLUSIONS Our findings suggest that favourable outcomes, matching the international data can be achieved in our patients with primary PCI in the management of life threatening illness like STEMI despite all the limitations. Primary PCI as a preferred method of reperfusion strategy fieeds to be practiced more often in our part of the world.
Serum Estradiol and Sex Hormone‐Binding Globulin and the Risk of Hip Fracture in Elderly Women: The EPIDOS Study

It has been suggested that low serum 17β‐estradiol (E2) and sex hormone‐binding globulin (SHBG) may predict hip fracture in postmenopausal women. We have investigated the predictive value of serum E2 and SHBG concentrations and urinary deoxypyridinoline (D‐Pyr) and type I collagen breakdown products (CTX) in a large prospective cohort of 7598 healthy elderly ambulatory women (EPIDOS study), aged 75 years or more. We performed a nested case control study, by matching 212 patients with incident hip fracture with 636 controls. Mean follow‐up was 3.3 years (maximum, 4.9 years). Women having serum E2 below the limit of detection (3 pg/ml), that is, 2% of the population, were not at higher risk, with a relative hazard (RH) of 1.59 (95% CI = 0.45‐5.55). Women having serum E2 below 5, 6, 7, or 8 pg/ml, in the lowest quartile, or below the median had no increased risk of hip fracture. In contrast, women having serum E2 in the highest quartile (i.e., ≥10 pg/ml) were protected, with an RH of 0.66 (0.44‐0.98) that did not remain significant after adjustment for weight (RH = 0.71 [0.47‐1.06]). High serum SHBG values with different cut‐offs tended to be associated with an increased risk of hip fracture. Women in the highest quartile had an RH of 2.5 (1.37‐4.61), compared with those in the lowest quartile, that decreased markedly after adjustment for body weight (1.61 [0.99‐2.62]). The highest quartile of the ratio E2/SHBG, which is an index of free E2, was associated with a lower hip fracture risk (RH = 0.6 [0.4‐0.91]) that was no longer significant after adjustment for weight. In contrast, urinary D‐Pyr and CTX, when elevated above the upper limit of premenopausal values, were predictive of hip fracture, with an RH of 2.07 (1.49‐2.9) and 1.67 (1.19‐2.32), respectively, even after adjustment for body weight, serum E2, and SHBG. We conclude that in healthy elderly French women over 75 years of age, serum E2 and E2/SHBG in the highest quartile are associated with a lower risk of hip fracture and that this association is explained by a higher body weight. In addition, serum levels of E2 and SHBG do not account for the increased risk of hip fracture associated with high levels of bone resorption markers.
Incretin hormones: Their role in health and disease

Incretin hormones are gut peptides that are secreted after nutrient intake and stimulate insulin secretion together with hyperglycaemia. GIP (glucose‐dependent insulinotropic polypeptide) und GLP‐1 (glucagon‐like peptide‐1) are the known incretin hormones from the upper (GIP, K cells) and lower (GLP‐1, L cells) gut. Together, they are responsible for the incretin effect: a two‐ to three‐fold higher insulin secretory response to oral as compared to intravenous glucose administration. In subjects with type 2 diabetes, this incretin effect is diminished or no longer present. This is the consequence of a substantially reduced effectiveness of GIP on the diabetic endocrine pancreas, and of the negligible physiological role of GLP‐1 in mediating the incretin effect even in healthy subjects. However, the insulinotropic and glucagonostatic effects of GLP‐1 are preserved in subjects with type 2 diabetes to the degree that pharmacological stimulation of GLP‐1 receptors significantly reduces plasma glucose and improves glycaemic control. Thus, it has become a parent compound of incretin‐based glucose‐lowering medications (GLP‐1 receptor agonists and inhibitors of dipeptidyl peptidase‐4 or DPP‐4). GLP‐1, in addition, has multiple effects on various organ systems. Most relevant are a reduction in appetite and food intake, leading to weight loss in the long term. Since GLP‐1 secretion from the gut seems to be impaired in obese subjects, this may even indicate a role in the pathophysiology of obesity. Along these lines, an increased secretion of GLP‐1 induced by delivering nutrients to lower parts of the small intestines (rich in L cells) may be one factor (among others like peptide YY) explaining weight loss and improvements in glycaemic control after bariatric surgery (e.g., Roux‐en‐Y gastric bypass). GIP and GLP‐1, originally characterized as incretin hormones, have additional effects in adipose cells, bone, and the cardiovascular system. Especially, the latter have received attention based on recent findings that GLP‐1 receptor agonists such as liraglutide reduce cardiovascular events and prolong life in high‐risk patients with type 2 diabetes. Thus, incretin hormones have an important role physiologically, namely they are involved in the pathophysiology of obesity and type 2 diabetes, and they have therapeutic potential that can be traced to well‐characterized physiological effects.
Effective taper criterion for the full veneer crown preparation in preclinical prosthodontics.

PURPOSE Effective taper criteria must define a realistic, measurable goal that the student can visualize and achieve. Six degrees is widely accepted as the taper criterion for the full veneer crown preparation. However, studies show the actual taper of most preparations to be greater than 12 degrees. The purpose of this study was to determine whether 12 degrees is an effective taper criterion for the full veneer crown preparation in preclinical prosthodontics instruction. MATERIALS AND METHODS A group of 191 full veneer crown preparations with 6 degrees as the taper criterion, and a group of 130 full veneer crown preparations with 12 degrees as the taper criterion were evaluated. All preparations were accomplished by preclinical dental students working on typodonts under examination conditions. RESULTS The overall mean taper for each group exceeded the targeted criterion. The overall mean taper for the 6 degrees group was 14,490. When 12 degrees was the criterion, the overall mean taper was 15,580. The t test results indicate significant differences (p < .0001) between the targeted criterion and the actual preparation mean taper in all samples except one: the faciolingual measurements in the 12 degrees group. The faciolingual measurement of 12,920 was not statistically significantly different (.0542) from the targeted criterion of 12 degrees. CONCLUSION The use of a 12 degrees taper criterion did not result in preclinical students achieving the goal of a 12 degrees taper. However, a 12 degrees criterion is more realistic than a 6 degrees criterion for full veneer crown preparations.
Organisational readiness: exploring the preconditions for success in organisation-wide patient safety improvement programmes

Background Patient safety has been high on the agenda for more than a decade. Despite many national initiatives aimed at improving patient safety, the challenge remains to find coherent and sustainable organisation-wide safety-improvement programmes. In the UK, the Safer Patients' Initiative (SPI) was established to address this challenge. Important in the success of such an endeavour is understanding ‘readiness’ at the organisational level, identifying the preconditions for success in this type of programme. This article reports on a case study of the four NHS organisations participating in the first phase of SPI, examining the perceptions of organisational readiness and the relationship of these factors with impact by those actively involved in the initiative. Materials and methods A mixed-methods design was used, involving a survey and semistructured interviews with senior executive leads, the principal SPI programme coordinator and the four operational leads in each of the SPI clinical work areas in all four organisations taking part in the first phase of SPI. Conclusions This preliminary work would suggest that prior to the start of organisation-wide quality- and safety-improvement programmes, organisations would benefit from an assessment of readiness with time spent in the preparation of the organisational infrastructure, processes and culture. Furthermore, a better understanding of the preconditions that mark an organisation as ready for improvement work would allow policymakers to set realistic expectations about the outcomes of safety campaigns.
Structure and mechanism of Escherichia coli glutathionylspermidine amidase belonging to the family of cysteine; histidine‐dependent amidohydrolases/peptidases

The bifunctional Escherichia coli glutathionylspermidine synthetase/amidase (GspSA) catalyzes both the synthesis and hydrolysis of Gsp. Its amidase domain (GspA), which catalyzes the hydrolysis of Gsp into glutathione and spermidine, plays an important role in redox sensing and protein S‐thiolation. To gain insight of the regulation and catalytic mechanism of and further understand the recycling of the Gsp dimer and Gsp‐S‐protein adducts, we solved two crystal structures of GspA and GspSA both with the C59A mutation and bound with the substrate, Gsp. In both structures, Cys59, His131, and Glu147 form the catalytic triad, which is similar to other cysteine proteases. Comparison of the GspA_Gsp complex and apo GspSA structures indicates that on binding with Gsp, the side chains of Asn149 and Gln58 of the amidase domain are induced to move closer to the carbonyl oxygen of the cleaved amide bond of Gsp, thereby participating in catalysis. In addition, the helix‐loop region of GspA, corresponding to the sequence 30YSSLDPQEYEDDA42, involves in regulating the substrate binding. Our previous study indicated that the thiol of Cys59 of GspA is only oxidized to sulfenic acid by H2O2. When comparing the active site of GspA with those of other cysteine proteases, we found that limited space and hydrophobicity of the environment around Cys59 play an important role to inhibit its further oxidation. The structural results presented here not only elucidate the catalytic mechanism and regulation of GspA but also help us to design small molecules to inhibit or probe for the activity of GspA.
Long- and Short-Term Exposure to PM2.5 and Mortality: Using Novel Exposure Models

Background: Many studies have reported associations between ambient particulate matter (PM) and adverse health effects, focused on either short-term (acute) or long-term (chronic) PM exposures. For chronic effects, the studied cohorts have rarely been representative of the population. We present a novel exposure model combining satellite aerosol optical depth and land-use data to investigate both the long- and short-term effects of PM2.5 exposures on population mortality in Massachusetts, United States, for the years 2000–2008. Methods: All deaths were geocoded. We performed two separate analyses: a time-series analysis (for short-term exposure) where counts in each geographic grid cell were regressed against cell-specific short-term PM2.5 exposure, temperature, socioeconomic data, lung cancer rates (as a surrogate for smoking), and a spline of time (to control for season and trends). In addition, for long-term exposure, we performed a relative incidence analysis using two long-term exposure metrics: regional 10 × 10 km PM2.5 predictions and local deviations from the cell average based on land use within 50 m of the residence. We tested whether these predicted the proportion of deaths from PM-related causes (cardiovascular and respiratory diseases). Results: For short-term exposure, we found that for every 10-µg/m3 increase in PM 2.5 exposure there was a 2.8% increase in PM-related mortality (95% confidence interval [CI] = 2.0–3.5). For the long-term exposure at the grid cell level, we found an odds ratio (OR) for every 10-µg/m3 increase in long-term PM2.5 exposure of 1.6 (CI = 1.5–1.8) for particle-related diseases. Local PM2.5 had an OR of 1.4 (CI = 1.3–1.5), which was independent of and additive to the grid cell effect. Conclusions: We have developed a novel PM2.5 exposure model based on remote sensing data to assess both short- and long-term human exposures. Our approach allows us to gain spatial resolution in acute effects and an assessment of long-term effects in the entire population rather than a selective sample from urban locations.
Presence and seasonal variation of trihalomethanes (THMs) levels in drinking tap water in Mostaganem Province in northwest Algeria

Background The use of chlorine to disinfect water, produces various disinfection byproducts such as trihalomethanes (THMs). These compounds are formed when free available chlorine reacts with natural organic matter in raw water during water disinfection. Epidemiologic studies have shown an association between long-term exposure to THMs and an increased risk of cancer, all of them are suspected of having carcinogenic effects. Aim The aim of this study was to determine the presence of THMs in the drinking tap water of Mostaganem Province (Algeria) in order to assess the seasonal variation in trihalomethane levels in tap water and to identify the season of high risk to the consumer. Methods This analytical study was conducted in Mostaganem Province, Algeria in March, July, September and December 2015. Primarily, we proceeded to collect 30 samples from different areas of Mostaganem Province which were marked with a higher level of residual chlorine for the year 2015; secondly, we utilised the HS-SPME method for determination of trihalomethanes in drinking tap water over a period of four months. For comparison of trihalomethanes values, we used ANOVA. Results The results obtained show variability in total THM concentrations from one district to another, with a maximum of 198 μg/l recorded in the Achaacha district during July, but the lowest value 07.84 μg/l is noted at Salamandre city during the same period, noting that these values decrease progressively during the winter period. Conclusion Our drinking tap water samples include a large quantity of THMs with different concentrations, where the dibromochloromethane and the bromoform constitute the major portion of THMs.
Circumvention of P‐glycoprotein‐mediated drug resistance in human leukaemic cells by non‐immunosuppressive cyclosporin D analogue, SDZ PSC 833

Summary. Cyclosporin A (CSA) exhibits greater multidrug resistance (MDR) modulating activity in vitro than other MDR modulators such as verapamil and quinidine. However, the immunosuppressive and nephrotoxic effects of CSA may limit its clinical use. PSC 833, a new cyclosporin D derivative, exerts a higher MDR reversal activity but lacks toxic or immunosuppressive effects. The drug‐resistant sublines K/DAV10. ,, K/DAU200. K/DAU30o. K/DAU40o, K/ DAU500 and K/DAU60o have been derived from the drug‐sensitive parental cell line, K562 cl.6 and CEM/VLB100 is a drug‐resistant derivative of CCRF‐CEM. We report a comparison of the effects of PSC 833 and CSA on daunorubicin (DAU) transport kinetics and chemosensitivity in these cell lines. Both CEM/VBL100 and KS62 cl.6 DAU‐resistant cells displayed high levels of P‐glycoprotein (PGP), decreased DAU accumulation and increased DAU efflux when compared to their parental cells. PSC 833 was 1‐6‐, 3‐4‐, 4‐9‐ and 4‐6‐fold more effective than CSA in reversing DAU resistance in higher resistance CEM/VLB10o, K/DAU40o, K/DAU500 and K/DAU60o cells respectively. DAU transport kinetics showed that PSC 833 was more effective than CSA in increasing cellular DAU accumulation and decreasing DAU efflux in higher resistant leukaemia subclones. PSC 833 could restore DAU retention at lower doses and was more active than CSA in all the resistant cells. A 89‐100% restoration of intracellular DAU retention were gained by PSC 833 at 1‐0ftM in K562 cl.6 DAU‐resistant sublines, whereas a 73‐100% restoration of DAU retention was obtained by CSA only at 30‐0 β, M in the same resistant sublines. PSC 833 at 3‐0/XM is sufficient to restore full DAU retention in all resistant cells. CSA, however, even at 30‐0 pM, cannot confer full restoration of DAU retention in higher resistance K562 cl.6/DAU sublines. By measuring MDR modulator‐mediated short‐term inhibition of PGP function, PSC 833 was found to be at least 10‐30 times more active than CSA. As no effect on DAU retention and sensitivity has been found in sensitive parental cells with PSC 833, it is suggested that PSC 833 may act by blocking the effluxing function of PGP in the resistant leukaemia cells.