Miracle-dz/UniFAR-FTUs huggingface dataset:
Randomized evaluation of fibrinogen vs placebo in complex cardiovascular surgery (REPLACE): a double-blind phase III study of haemostatic therapy.

BACKGROUND Single-dose human fibrinogen concentrate (FCH) might have haemostatic benefits in complex cardiovascular surgery. METHODS Patients undergoing elective aortic surgery requiring cardiopulmonary bypass were randomly assigned to receive FCH or placebo. Study medication was administered to patients with a 5 min bleeding mass of 60-250 g after separation from bypass and surgical haemostasis. A standardized algorithm for allogeneic blood product transfusion was followed if bleeding continued after study medication. RESULTS 519 patients from 34 centres were randomized, of whom 152 (29%) met inclusion criteria for study medication. Median (IQR) pretreatment 5 min bleeding mass was 107 (76-138) and 91 (71-112) g in the FCH and placebo groups, respectively (P=0.13). More allogeneic blood product units were administered during the first 24 h after FCH, 5.0 (2.0-11.0), when compared with placebo, 3.0 (0.0-7.0), P=0.026. Fewer patients avoided transfusion in the FCH group (15.4%) compared with placebo (28.4%), P=0.047. The FCH immediately increased plasma fibrinogen concentration and fibrin-based clot strength. Adverse event rates were comparable in each group. CONCLUSIONS Human fibrinogen concentrate was associated with increased allogeneic blood product transfusion, an unexpected finding contrary to previous studies. Human fibrinogen concentrate may not be effective in this setting when administered according to 5-minute bleeding mass. Low bleeding rates and normal-range plasma fibrinogen concentrations before study medication, and variability in adherence to the complex transfusion algorithm, may have contributed to these results. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov identifier no. NCT01475669; EudraCT trial no. 2011-002685-20.
Diagnostic value of plasma and urinary 2-hydroxyglutarate to identify patients with isocitrate dehydrogenase-mutated glioma.

BACKGROUND Mutant isocitrate dehydrogenase (IDH) 1/2 enzymes can convert α-ketoglutarate into 2-hydroxyglutarate (2HG). The aim of the present study was to explore whether 2HG in plasma and urine could predict the presence of IDH1/2 mutations in patients with glioma. MATERIALS AND METHODS All patients had histological confirmation of glioma and a recent brain magnetic resonance imaging scan showing the neoplastic lesion. Plasma and urine samples were taken from all patients, and the 2HG concentrations were determined using liquid chromatography tandem mass spectrometry. RESULTS A total of 84 patients were enrolled: 38 with R132H-IDH1 mutated and 46 with wild type. Among the 38 patients with mutant IDH1, 21 had high-grade glioma and 17 had low-grade glioma. Among the 46 patients with IDH1 wild-type glioma, 35 and 11 had high- and low-grade glioma, respectively. In all patients, we analyzed the mean 2HG concentration in the plasma, urine, and plasma/urine ratio (Ratio_2HG). We found a significant difference in the Ratio_2HG between patients with and without an IDH1 mutation (22.2 ± 8.7 vs. 15.6 ± 6.8; p < .0001). The optimal cutoff value for Ratio_2HG to identify IDH1 mutation was 19 (sensitivity, 63%; specificity, 76%; accuracy, 70%). In the patients with high-grade glioma only, the optimal cutoff value was 20 (sensitivity, 76%; specificity, 89%; accuracy, 84%; positive predictive value, 80%; negative predictive value, 86%). In 7 of 7 patients with high-grade glioma, we found a correlation between the Ratio_2HG value and the response to treatment. CONCLUSION Ratio_2HG might be a predictor of the presence of IDH1 mutation. The measurement of 2HG could be useful for disease monitoring and also to assess the treatment effects in these patients.
Functional analysis of the lysis genes of Staphylococcus aureus phage P68 in Escherichia coli.

Double-stranded DNA phages of both Gram-positive and Gram-negative bacteria typically use a holin-endolysin system to achieve lysis of their host. In this study, the lysis genes of Staphylococcus aureus phage P68 were characterized. P68 gene lys16 was shown to encode a cell-wall-degrading enzyme, which causes cell lysis when externally added to clinical isolates of S. aureus. Another gene, hol15, was identified embedded in the -1 reading frame at the 3' end of lys16. The deduced Hol15 protein has three putative transmembrane domains, and thus resembles class I holins. An additional candidate holin gene, hol12, was found downstream of the endolysin gene lys16 based on two predicted transmembrane domains of the encoded protein, which is a typical trait of class II holins. The synthesis of either Hol12 or Hol15 resulted in growth retardation of Escherichia coli, and both hol15 and hol12 were able to complement a phage lambda Sam mutation. The hol15 gene has a dual start motif beginning with the codons Met1-Lys2-Met3. Evidence is presented that the hol15 gene encodes a lysis inhibitor (anti-holin) and a lysis effector (actual holin). As depolarization of the membrane converted the anti-holin to a functional holin, these studies suggested that hol15 functions as a typical dual start motif class I holin. The unusual arrangement of the P68 lysis genes is discussed.
S1P3‐mediated Akt activation and crosstalk with platelet‐derived growth factor receptor (PDGFR)

Akt plays a pivotal role in cell survival and tumorigenesis. We investigated the potential interaction between sphingosine‐1‐phosphate (S1P) and platelet‐derived growth factor (PDGF) in the Akt signaling pathway. Using mouse embryonic fibroblasts (MEFs) from S1P receptor knockout mice, we show here that S1P3 was required for S473 phosphorylation of Akt by S1P. In addition, S1P‐stimulated activation of Akt, but not ERK, was blocked by a PDGF receptor (PDGFR)‐specific inhibitor, AG1296, suggesting a S1P3‐mediated specific crosstalk between the Akt signaling pathways of S1P and PDGFR in MEFs. We investigated this crosstalk under different conditions and found that both Akt and ERK activation induced by S1P, but not lysophosphatidic acid (LPA), in HEY ovarian cancer cells required PDGFR but not epidermal growth factor receptor (EGFR) or insulin‐like growth factor‐I receptor (IGFR). Importantly, S1P induced a Gi‐dependent tyrosine phosphorylation of PDGFR in HEY cells. This dependence on PDGFR in S1P‐induced Akt activation was also observed in A2780, T47D, and HMEC‐1 cells (which express S1P3), but not in PC‐3 or GI‐101A cells (which do not express S1P3), further supporting that S1P3 mediates the crosstalk between S1P and PDGFR. This is the first report demonstrating a unique interaction between S1P3 and PDGFR, in addition to demonstrating a specific role for S1P3 in S1P‐induced Akt activation.
Reconstitution of Phosphatidylserine Transport from Chemically Defined Donor Membranes to Phosphatidylserine Decarboxylase 2 Implicates Specific Lipid Domains in the Process*

Phosphatidylserine (PtdSer) is transported from its site of synthesis in the endoplasmic retiuculum to the locus of PtdSer decarboxylase 2 (Psd2p) in the Golgi/vacuole and decarboxylated to form phosphatidylethanolamine. Recent biochemical and genetic evidence has implicated the C2 domain of Psd2p and a membrane-bound form of the phosphatidylinositol binding/transfer protein, PstB2p, as essential for this transport process. We devised a reconstituted system in which chemically defined donor membranes function to transfer PtdSer to the biological acceptor membranes containing Psd2p. The transfer of PtdSer is poor when the donor membranes have a high degree of curvature but markedly enhanced when the membranes are relatively planar (≥400-nm diameter). PtdSer transfer is also dependent upon both the bulk and the surface concentrations of the lipid, with pure PtdSer vesicles acting as the most efficient donors at all concentrations. The lipid transfer from donor membranes containing either 100% PtdSer or 50% PtdSer at a fixed concentration (e.g. 250 μm PtdSer) differs by a factor of 20. Surface dilution of PtdSer by choline, ethanolamine, glycerol, and inositol phospholipids markedly inhibits PtdSer transfer, whereas phosphatidic acid (PtdOH) stimulates the transfer. Most importantly, the transfer of PtdSer from liposomes to Psd2p fails to occur in acceptor membranes from strains lacking PstB2p or the C2 domain of Psd2p. These data support a model for PtdSer transport from planar domains highly enriched in PtdSer or in PtdSer plus PtdOH.
Opposing actions of neuropeptide Y and light on the expression of circadian clock genes in the mouse suprachiasmatic nuclei

The circadian clockwork of the hypothalamic suprachiasmatic nuclei (SCN) is synchronized by light and by nonphotic cues. The core timing mechanism is cell‐autonomous, based on an autoregulatory transcriptional/translational feedback loop of circadian genes and their products. This study investigated the effects of neuropeptide Y (NPY), a potent nonphotic resetting cue, and its interaction with light in regulating clock gene expression in the SCN in vivo. Injection of NPY adjacent to the SCN and transfer to darkness 7 h before scheduled lights out, shifted the circadian activity–rest cycle. Exposure to light for 1 h immediately after NPY infusion blocked this behavioural response. NPY‐induced shifts were accompanied by suppression of both mPer1 and mPer2 mRNA in the SCN, assessed 3 h after infusion. mPer mRNAs were not altered 1 h after infusion. Levels of mClock mRNA or mCLOCK immunoreactivity in the SCN were not affected by NPY at either time point. In parallel to the behavioural response, the NPY‐induced suppression of mPer genes in the SCN was attenuated when a light pulse was delivered immediately after the infusion. These results identify mPer1 and mPer2 as molecular targets for both photic and nonphotic (NPY‐induced) resetting of the clockwork, and support a synthetic model of circadian entrainment based upon convergent up‐ and downregulation of mPer expression.
Church Membership and Social Insurance: Evidence from the Great Mississippi Flood of 1927

Religious communities are key providers of social insurance. This paper focuses on the devastating impact of the Great Mississippi Flood of 1927 to investigate how an increase in the demand for social insurance affects church membership. We find a significant increase in church membership in flooded counties. This effect is stronger in counties with severe economic losses and where access to credit was limited. We also document that fundamental denominations gained more members in flooded counties, which is consistent with the theory of club goods emphasizing the efficient provision of mutual insurance in stricter religious communities.
Stressful life events, family support and successful ageing in the Biafran War generation

Objectives: Although the developing countries contribute substantially to the population of the elderly, little is known about ageing in populous countries like Nigeria, particularly the Biafran War generation (BWG). Some of those who witnessed the Biafran War (also known as Nigerian Civil War) as children are well into late adulthood, while the majority of this pre-war/wartime cohort who are in their golden years will enter into later life in less than a decade from now. The aim of the present research was to examine the role of stressful life events and family support in successful ageing of the BWG. Method: Data were collected using a self-administered survey completed by 453 members of the BWG who were ≥45 years. The survey included measures such as the Successful Ageing Inventory, Life Events Inventory, and family support subscale of Family Dynamics Scale. Hierarchical multiple regression analyses were conducted to test the hypotheses of the study. Results: The three dimensions of stressful life events (health events, interpersonal events and work-related/financial events) had moderate negative relationships with successful ageing. Family support was moderately and positively associated with successful ageing. For the moderation hypotheses, family support was a significant moderator of only the relationship between work-related stressful life events and successful ageing, especially for the <65 years subgroup. Conclusion: Growing old can be a very positive experience for both the individual and the society. Family support provides social protection for older people, in the face of difficult socio-economic circumstances.
[Immunologic histochemical observation of anti-crypt keratin of cryptic epithelium of tonsilla in children with chronic tonsillitis].

OBJECTIVE To investigate anti-crypt keratin (CK) immunologic histochemical changes in children with chronic tonsillitis. METHOD Removed tonsilla were fixed by 10% formaldehyde. Immunologic histochemical method was used to determine the changes of anti-broad spectrum (KD 68, 56, 56, 50) CKSP. RESULT In 230 cases, obvious keratosis was 90.9%, no keratosis was 9.1%, 3 cases were found with fungus filaments and bacteria in the bottom of crypts. Anti-broad spectrum and hypermolecule CK of tonsil cryptic epithelium were positive reaction, anti-broad spectrum CK of cryptic keratosis in all cases was positive reaction. CONCLUSION During the period of episode, cryptic epitheliums of tonsilla was destroyed repeatly, therefore, immunoglobulin production was reduce. Because the immune function of tonsilla was reduced, bacteria and virus might be invade into organism. This reduplicative malignant circles must be interrupted or blocked only by tonsillectomy.
Immunopathology and Infectious Diseases Effect of Macrophage Migration Inhibitory Factor ( MIF ) in Human Placental Explants Infected with Toxoplasma gondii Depends on Gestational Age

From the Instituto de Ciências Biomédicas,* and the Departamento de Ginecologia e Obstetrícia, Faculdade de Medicina, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil; the Departamento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil; and the Dipartimento di Fisiologia, Università Degli Studi di Siena, Siena, Italy
Nurse-perceived time pressure and patient-perceived care quality.

AIMS To examine how time pressure among nurses influences patient-perceived care quality. BACKGROUND Although nurses worldwide face increased time pressure in the workplace, no studies have addressed how workplace time pressure influences patient-perceived care quality. Patient-perceived care quality predicts patient intent to revisit the hospital if care is required, warranting investigation as to whether nurse-perceived time pressure decreases patient-perceived care quality. METHODS A cross-sectional design and survey method were adopted. The data analysis was based on 229 nurse-patient sets drawn from a medical centre in northern Taiwan. Each set comprised one nurse and three patients. RESULTS The study results demonstrate that time pressure among nurses reduces patient-perceived reliability/accountability, responsiveness and assurance. The test results, however, did not indicate a significant negative association between time pressure and patient-perceived empathy and tangibles. CONCLUSION Time pressure among nurses may reduce patient perception of care quality in terms of reliability/accountability, responsiveness and assurance. IMPLICATIONS FOR NURSING MANAGEMENT To enhance patient perception of care quality, nursing managers need to devise means to reduce nurse-perceived time pressure.
Excellent agreement between C-reactive protein measurement methods in end-stage renal disease patients--no additional power for mortality prediction with high-sensitivity CRP.

BACKGROUND The conventional method for C-reactive protein (CRP) measurement is an immunoturbidimetric assay (imCRP, detection limit > or =3 mg/l). However, high-sensitivity CRP (hsCRP, detection limit >0.1 mg/l) has been advocated as preferable biomarker for cardiovascular risk assessment. The aim of this study was to determine agreement between imCRP and hsCRP in end-stage renal disease (ESRD) patients, and to examine whether the association between CRP and mortality is comparable when using imCRP or hsCRP. METHODS Patients from a prospective follow-up study among incident ESRD patients (NECOSAD) with serum CRP available at 3 months of follow-up were included [n = 840, 60% male, mean (SD) age 59 (15) years]. Agreement between imCRP and hsCRP was determined by intraclass correlation coefficient (ICC) and by Cohen's kappa (kappa) for CRP dichotomized to the presence (CRP >10 mg/l) or absence of systemic inflammation. The association between CRP and mortality was determined by Cox regression analysis and c-statistic. RESULTS ICC between imCRP and hsCRP was 0.78, which improved to 0.86 after correction for systematic differences between measurement methods. Systemic inflammation was present in 28.2% and absent in 67.6% of patients according to both methods (discordant in 4.2%), resulting in good agreement between the two methods (kappa = 0.90). Patients with systemic inflammation had a significantly increased mortality risk compared with patients without systemic inflammation [HR(im,adj) = 1.49 (95%CI 1.14-1.93) and HR(hs,adj) = 1.53 (1.18-2.0)]. Predictive capacity of mortality was similar for both CRP methods [c-statistic(adj) 0.83 (0.79-0.86)]. CONCLUSION The agreement between imCRP and hsCRP in patients with ESRD is very good. Furthermore, the association between CRP and mortality in ESRD patients is similar when using imCRP and hsCRP. These data suggest that there is no need to use a high-sensitivity method for the determination of inflammatory status in ESRD patients.
The Psychiatric Care of People with Intellectual Disabilities: The Perceptions of Consultant Psychiatrists in Victoria

Objective: This study was undertaken to establish the perceptions of psychiatrists regarding the care of people with intellectual disabilities. Method: A 28-item self-administered questionnaire was developed, piloted and sent on two occasions to 467 psychiatrists who receive the newsletter of the Victorian branch of the Royal Australian and New Zealand College of Psychiatrists. The questionnaire incorporated a Likert scale to document the opinions of the respondents. Results: A response rate of 51.1 % was achieved. The respondents indicated that, in their opinion, people with intellectual disabilities receive a poor standard of care in the inpatient and community setting. To improve this situation, the following strategies were recommended: the development of improved liaison between services; improved training for all personnel who provide services to people with intellectual disabilities; the development of greater resources; and support for professionals working in the area. The study also indicates that there is a core group of very interested psychiatrists who are currently practising and that people with intellectual disabilities are accessing private psychiatric services. In addition, the results suggest that diagnostic overshadowing is not a major barrier to psychiatric assessment, and that disorders which were presumed to be commonly overlooked by doctors (such as depression) are in fact frequently being diagnosed. Conclusions: Despite some positive findings, the majority of psychiatrists who responded held major concerns about the situation of people with intellectual disabilities. To improve the care provided to these people, it is recommended that these concerns are addressed by the psychiatric profession and responsible government departments in conjunction with university departments of psychiatry.
A Short Period of Mannitol Stress but Not LiCl Stress Led to Global Translational Repression in Plants

In plant cells, high salinity stress induces rapid inhibition of general protein synthesis. In this study, we found that treatment with mannitol, but not lithium stress, led to rapid global translational repression, suggesting that a rapid response at the level of translation might be induced by the osmotic but not the ionic components of salinity stress.
Clostridium Difficile Colitis: Increasing Incidence, Risk Factors, and Outcomes in Solid Organ Transplant Recipients

Background Clostridium difficile-associated diarrhea (CDAD) is an increasingly important diagnosis in solid organ transplant recipients, with rising incidence and mortality. We describe the incidence, risk factors, and outcomes of colectomy for CDAD after solid organ transplantation. Methods Patients with CDAD were identified from a prospective transplant database. Complicated Clostridium difficile colitis (CCDC) was defined as CDAD associated with graft loss, total colectomy, or death. Results From 1999 to 2010, we performed solid organ transplants for 1331 recipients at our institution. The incidence of CDAD was 12.4% (165 patients); it increased from 4.5% (1999) to 21.1% (2005) and finally 9.5% (2010). The peak frequency of CDAD was between 6 and 10 days posttransplantation. Age more than 55 years (hazard ratio [HR]: 1.47, 95% confidence interval [CI]=1.16–1.81), induction with antithymocyte globulin (HR: 1.43, 95% CI=1.075–1.94), and transplant other than kidney alone (liver, heart, pancreas, or combined kidney organ) (HR: 1.41, 95% CI=1.05–1.92) were significant independent risk factors for CDAD. CCDC occurred in 15.8% of CDAD cases. Independent predictors of CCDC were white blood cell count more than 25,000/&mgr;L (HR: 1.08, 95% CI=1.025–1.15) and evidence of pancolitis on computed tomography scan (HR: 2.52, 95% CI=1.195–5.35). Six patients with CCDC underwent colectomy with 83% patient survival and 20% graft loss. Of the medically treated patients with CCDC (n=20), the patient survival was 35% with 100% graft loss. Conclusions We have identified significant risk factors for CDAD and predictors of progression to CCDC. Furthermore, we found that colectomy can be performed with excellent survival in selected patients.
Shell bone histology indicates terrestrial palaeoecology of basal turtles

The palaeoecology of basal turtles from the Late Triassic was classically viewed as being semi-aquatic, similar to the lifestyle of modern snapping turtles. Lately, this view was questioned based on limb bone proportions, and a terrestrial palaeoecology was suggested for the turtle stem. Here, we present independent shell bone microstructural evidence for a terrestrial habitat of the oldest and basal most well-known turtles, i.e. the Upper Triassic Proterochersis robusta and Proganochelys quenstedti. Comparison of their shell bone histology with that of extant turtles preferring either aquatic habitats or terrestrial habitats clearly reveals congruence with terrestrial turtle taxa. Similarities in the shell bones of these turtles are a diploe structure with well-developed external and internal cortices, weak vascularization of the compact bone layers and a dense nature of the interior cancellous bone with overall short trabeculae. On the other hand, ‘aquatic’ turtles tend to reduce cortical bone layers, while increasing overall vascularization of the bone tissue. In contrast to the study of limb bone proportions, the present study is independent from the uncommon preservation of appendicular skeletal elements in fossil turtles, enabling the palaeoecological study of a much broader range of incompletely known turtle taxa in the fossil record.