Miracle-dz/UniFAR-FTUs huggingface dataset:
Viral Interference with Antigen Presentation Does Not Alter Acute or Chronic CD8 T Cell Immunodominance in Murine Cytomegalovirus Infection1

Both human CMV and murine CMV (MCMV) elicit large CD8 T cell responses, despite the potent effects of viral genes that interfere with the MHC class I (MHC I) pathway of Ag presentation. To investigate the impact of immune evasion on CD8 T cell priming, we infected mice with wild-type (wt) MCMV or a mutant lacking its MHC I immune evasion genes, Δm4+m6+m152 MCMV. In acute infection, the two viruses elicited a CD8 T cell response to 26 peptide epitopes that was virtually identical in total size, kinetics, and immunodominance hierarchy. This occurred despite results demonstrating that primary DCs are susceptible to the effects of MCMV’s MHC I immune evasion genes. Eight months later, responses to both wt and mutant MCMV displayed the same CD8 T cell “memory inflation” and altered immunodominance that characterize the transition to chronic MCMV infection in C57BL/6 mice. Taken together, these findings suggest either that cross-priming dominates over direct CD8 T cell priming in both acute and chronic MCMV infection, or else that the MHC I immune evasion genes of MCMV are unable to alter direct CD8 T cell priming in vivo. At 2 years postinfection, differences in CD8 T cell immunodominance emerged between individual mice, but on average there were only slight differences between wt and mutant virus infections. Overall, the data indicate that the presence or absence of MHC I immune evasion genes has remarkably little impact on the size or specificity of the MCMV-specific CD8 T cell response over an entire lifetime of infection.
Prevalence of Copied Information by Attendings and Residents in Critical Care Progress Notes*

Objectives:To determine the prevalence and mechanism of copying among ICU physicians using an electronic medical record. Design:Retrospective cohort study. Setting:Medical ICU of an urban, academic medical center. Patients:Two thousand sixty-eight progress notes of 135 patients generated by 62 residents and 11 attending physicians between August 1, 2009, and December 31, 2009. Interventions:None. Measurements and Main Results:EIghty-two percent of all residents and 74% of all attending notes contained greater than or equal to 20% copied information (p = 0.001). Although residents authored more copied notes than attendings, residents copied less information between notes than attendings (55% vs. 61%, p < 0.001). Following greater than or equal to 1 day off, residents copied less often from their own prior notes compared to attendings (66% vs. 94%, p < 0.001). Of the copied information following a day off, there was no difference in the amount of information copied into notes of residents (59%) or attendings (61%, p = 0.17). In a regression model of attending notes, no patient factors were associated with copying. However, the levels of copying among attendings varied from 41% to 82% (p < 0.001). Conclusions:Copying among attendings and residents was common in this ICU-based cohort, with residents copying more frequently and attendings copying more information per note. The only factor that was independently associated with attending copying was the attending. Further studies should focus on further elucidating the factors influencing copying in the ICU and the effects of copying on patient outcomes.
Two-stage vs single-stage management for concomitant gallstones and common bile duct stones.

AIM To evaluate the safety and effectiveness of two-stage vs single-stage management for concomitant gallstones and common bile duct stones. METHODS Four databases, including PubMed, Embase, the Cochrane Central Register of Controlled Trials and the Science Citation Index up to September 2011, were searched to identify all randomized controlled trials (RCTs). Data were extracted from the studies by two independent reviewers. The primary outcomes were stone clearance from the common bile duct, postoperative morbidity and mortality. The secondary outcomes were conversion to other procedures, number of procedures per patient, length of hospital stay, total operative time, hospitalization charges, patient acceptance and quality of life scores. RESULTS Seven eligible RCTs [five trials (n = 621) comparing preoperative endoscopic retrograde cholangiopancreatography (ERCP)/endoscopic sphincterotomy (EST) + laparoscopic cholecystectomy (LC) with LC + laparoscopic common bile duct exploration (LCBDE); two trials (n = 166) comparing postoperative ERCP/EST + LC with LC + LCBDE], composed of 787 patients in total, were included in the final analysis. The meta-analysis detected no statistically significant difference between the two groups in stone clearance from the common bile duct [risk ratios (RR) = -0.10, 95% confidence intervals (CI): -0.24 to 0.04, P = 0.17], postoperative morbidity (RR = 0.79, 95% CI: 0.58 to 1.10, P = 0.16), mortality (RR = 2.19, 95% CI: 0.33 to 14.67, P = 0.42), conversion to other procedures (RR = 1.21, 95% CI: 0.54 to 2.70, P = 0.39), length of hospital stay (MD = 0.99, 95% CI: -1.59 to 3.57, P = 0.45), total operative time (MD = 12.14, 95% CI: -1.83 to 26.10, P = 0.09). Two-stage (LC + ERCP/EST) management clearly required more procedures per patient than single-stage (LC + LCBDE) management. CONCLUSION Single-stage management is equivalent to two-stage management but requires fewer procedures. However, patient's condition, operator's expertise and local resources should be taken into account in making treatment decisions.
Nanomaterials in the environment: Behavior, fate, bioavailability, and effects

The recent advances in nanotechnology and the corresponding increase in the use of nanomaterials in products in every sector of society have resulted in uncertainties regarding environmental impacts. The objectives of this review are to introduce the key aspects pertaining to nanomaterials in the environment and to discuss what is known concerning their fate, behavior, disposition, and toxicity, with a particular focus on those that make up manufactured nanomaterials. This review critiques existing nanomaterial research in freshwater, marine, and soil environments. It illustrates the paucity of existing research and demonstrates the need for additional research. Environmental scientists are encouraged to base this research on existing studies on colloidal behavior and toxicology. The need for standard reference and testing materials as well as methodology for suspension preparation and testing is also discussed.
Pulse laser assisted optical tweezers for biomedical applications

Optical tweezers which enables to trap micron to nanometer sized objects by radiation pressure force is utilized for manipulation of particles under a microscope and for measurement of forces between biomolecules. Weak force of optical tweezers causes some limitations such as particle adhesion or steric barrier like lipid membrane in a cell prevent further movement of objects. For biomedical applications we need to overcome these difficulties. We have developed a technique to exert strong instantaneous force by use of a pulse laser beam and to assist conventional optical tweezers. A pulse laser beam has huge instantaneous laser power of more than 1000 times as strong as a conventional continuous-wave laser beam so that the instantaneous force is strong enough to break chemical bonding and molecular force between objects and obstacles. We derive suitable pulse duration for pulse assist of optical tweezers and demonstrate particle manipulation in difficult situations through an experiment of particle removal from sticky surface of glass substrate.
Serum prealbumin is an independent predictor of mortality in systemic sclerosis outpatients.

OBJECTIVE Serum prealbumin is a recognized marker of malnutrition, but its role in the prognosis of patients with SSc has not yet been investigated. The aim of the present multicentre prospective study was to investigate the association between prealbumin and mortality, independent of clinical features, in a cohort of SSc outpatients. METHODS Patients were followed up according to standard clinical guidelines with visits at least every 6 months. Data collected included records of skin and internal organ involvement, survival and causes of death. RESULTS During a median follow-up of 48 months [interquartile range (IQR) 25-58], 34/299 patients (11%) died. In univariable survival analysis, age; male sex; lung, gastrointestinal or multiple visceral organ involvement (two or more); co-morbidities (two or more) and low serum prealbumin were significant predictors of mortality. In bivariable Cox models, alternatively adjusted for significant predictors, prealbumin was independently and significantly associated with the outcome. Mortality rates were particularly influenced by low prealbumin in patients without significant co-morbidities or multiple organ involvement. CONCLUSION In SSc patients, low serum prealbumin is an independent predictor of mortality, particularly in those without significant internal organ involvement. Further research on this nutritional marker is warranted.
Attenuated T-Lymphocyte Response to HIV Therapy in Individuals Receiving HMG-CoA Reductase Inhibitors

Abstract Purpose: The protease inhibitor class of antiretroviral agents is associated with the unwanted side effect of hypertriglyceridemia, which is usually treated with either HMG-CoA reductase inhibitors (statins) or fibrates. However, since statin therapy is intrinsically immunomodulatory, we questioned whether the T-cell response of patients who received PI-based therapy plus statin differed from the response of patients on PI therapy alone or on PI therapy with a fibrate. Method: Retrospective cohort study. Results: Thirty-five patients who had received ritonavir/saquinavir (R/S)-based antiretroviral therapy for 5 or more years were evaluated and stratified into four treatment groups: patients on R/S alone (n = 9), patients on R/S and stavudine/lamivudine (d4T/3TC) (n = 10), patients on R/S with or without d4T/3TC and statin (n = 11), or patients on R/S with or without d4T/3TC and fibrate (n = 5). All patients had suppressed levels of viral replication at all time points. T-cell responses were similar in all four groups before they were exposed to lipid-lowering agents. After the addition of lipid-lowering agents, absolute CD4 T-cell responses were lower in the statin group than in all other groups (p < .05), when measured after 6, 12, and 18 months of treatment. Conclusion: These data suggest that T-cell responses are influenced by the choice of anti-lipid agent and suggest that a prospective comparison is needed to determine the clinical relevance of these findings.
Measurement of Acetaminophen‐Protein Adducts in Children and Adolescents with Acetaminophen Overdoses

Acetaminophen‐protein adducts are biomarkers of acetaminophen toxicity present in the centrilobular region of the liver of laboratory animals following the administration of toxic doses of acetaminophen. These biomarkers are highly specific for acetaminophen‐induced hepatic injury and correlate with hepatic transaminase elevation. The objective of this prospective, multicenter study was to evaluate the clinical application of the measurement of acetaminophen‐protein adducts in pediatric acetaminophen overdose patients. Serum samples were obtained from 51 children and adolescents with acetaminophen overdose at the time ofrou‐ tine blood sampling for clinical monitoring. Six subjects developed “severe” hepatotoxicity (transaminase elevation > 1000IU/L), and 6 subjects had transaminase elevation of 100 to 1000 IU/L. Acetaminophen‐protein adducts were detected in the serum of only 1 study subject, a patient with marked transaminase elevation (> 6000 IU/L) and high riskforthe development of hepatotoxicity according to the Rumack nomogram. While this study provides further support for the occurrence of covalent binding of acetaminophen to hepatic protein in humans following acetaminophen overdose, the detection of acetaminophen‐protein adducts in serum with the current methodology requires significant biochemical evidence of hepatocellular injury.
Intraductal papillary mucinous tumors of the pancreas: imaging studies and treatment strategies.

OBJECTIVE We analyzed clinicopathologic and imaging features and the prognosis of intraductal papillary mucinous tumor (IPMT) of the pancreas to identify imaging findings indicative of malignancy and to establish the optimal treatment strategy. SUMMARY BACKGROUND DATA In IPMT, preoperative differentiation between adenoma and adenocarcinoma is often difficult. Appropriate treatment based on pathologic study and surgical outcome has not been adequately documented. METHODS Forty-one patients with IPMT underwent surgery; 15 with adenoma and 26 with adenocarcinoma; main duct type in 13, combined type in 12, and branch duct type in 16. RESULTS In malignant IPMT, deep invasion was found in 62% and lymph node metastasis in 23% (peripancreatic nodes in 19% and distant nodes in 4%). Tumors with mural nodules (86%) had a significantly higher incidence of carcinoma than tumors without nodules (37%). IPMT with a main pancreatic duct > or =15 mm or tumor diameter > or =30 mm (branch duct type) showed a high prevalence of adenocarcinoma. Main duct (54%) and combined (58%) type tumor, and tumors with mural nodules (64%) often showed invasion. All five branch duct tumors less than 30 mm without nodules were adenomas. However, imaging studies could not definitely distinguish adenocarcinomas from adenomas. Complete resection was possible for all adenomas and 88% of adenocarcinomas. Five-year survival rates for patients with adenomas and adenocarcinomas were 100% and 82%, respectively. CONCLUSIONS IPMT has a favorable prognosis, regardless of deep invasion or node metastasis. IPMT requires peripancreatic node dissection in addition to complete tumor excision. Node dissection may be omitted for branch duct tumors less than 30 mm without mural nodules.
Characteristics of CD59 up‐regulation induced in porcine endothelial cells by αGal ligation and its association with protection from complement

Abstract: Background: Activation of endothelial cells may result in proinflammatory and procoagulant changes, or in changes that protect the endothelial cells (EC) from injurious insults. Stimulation of porcine EC with human anti‐porcine antibodies, or lectins from Bandeiraea simplicifolia that bind terminal Galα(1–3)Gal (abbreviated αGal), can induce EC protection from cytotoxicity by human complement. These EC also exhibit up‐regulation of CD59 protein and mRNA expression. Porcine CD59 has been reported to protect porcine cells from human complement. Therefore we investigated the specificity requirements and other characteristics of the induced CD59 up‐regulation, as well as the role of up‐regulated CD59 in lectin‐induced protection of EC from human complement. Methods: Aortic EC were incubated in vitro with αGal‐binding lectins B. simplicifolia lectin I isolectin B4 (IB4) and B. simplicifolia lectin I (BS‐I) and CD59 expression was assessed by flow cytometry and enzyme linked immunosorbent assay (ELISA). Binding requirement was studied using disaccharides containing either αgalactosyl or βgalactosyl moieties to inhibit CD59 up‐regulation. Protection from complement killing was assessed after incubation of EC with human serum as a source of anti‐porcine antibodies and complement. The role of CD59 in lectin‐induced protection was studied in the presence of an anti‐pig CD59 antibody and after removal of CD59 using phosphatidylinositol (PI)‐specific phospholipase C (PI‐PLC). Results: We found that induction of CD59 up‐regulation required specific binding of the lectin to terminal αGal and was not induced either by soluble factors that may be released from EC by stimulation with the lectin or by TNF‐α, IFN‐γ, or IL‐1α. Unstimulated or BS‐I‐treated EC showed little or no expression of decay accelerator factor (DAF). Removal of membrane‐associated CD59 (and other proteins that are associated with the membrane through PI linkage) with PI‐PLC from EC that had been exposed to lectin restored their complement sensitivity to various degrees, depending on the extent of lectin‐induced protection. Cytotoxicity was completely restored in cells that exhibited partial protection induced with lectin at low doses or for a short period of time. However, EC that were fully resistant to complement did not regain sensitivity to complement after removal of CD59. Changes in CD59 expression did not modify the degree of C9 binding. Conclusion: Induction of CD59 expression required specific binding of the lectin to terminal αGal and was not induced by soluble factors that may be released from EC by lectin stimulation. Increased CD59 expression may contribute to this form of protection from complement; however, mechanisms other than CD59 up‐regulation appear to be essential for the development of full protection.
Articular mobility in ballet dancers

A follow-up study of ballet dancers was conducted to determine the influence of 4 years additional training on articular mobility using Beighton's method. The score increased in 25 (45.5%) of the 55 dancers reexamined. Acquired forward flexion accounted for this increase in 21 (84%) of the 25 dancers. These 21 dancers had had significantly less training than had the 30 dancers who could forward flex when examined initially (P < 0.0001), showing that forward flexion is acquired through train ing. There were significantly more hypermobile individ uals among dancers who had continued dancing than among those who had stopped (P < 0.03). However, only 2 (16.7%) of 12 dancers who had progressed in their careers were hypermobile. We conclude that 1) most ballet dancers are able to forward flex, 2) forward flexion is usually acquired and develops after 4 or more years of training, 3) the mobility score may assist in predicting who will continue dancing, but that 4) there is no association between hypermobility and dancing excellence.
Perceptions of Parental Caring Predict Health Status in Midlife: A 35-Year Follow-up of the Harvard Mastery of Stress Study

Objective This study examined how the perception of parental caring, obtained from undergraduates, relates to subsequent health over the ensuing 35 years. Methods In the early 1950s, initial ratings of parental caring were obtained from a sample of healthy, Harvard undergraduate men who participated in the Harvard Mastery of Stress Study. In a 35 year prospective, follow-up investigation, detailed medical and psychological histories and medical records were obtained. Results Subjects identified in midlife as suffering from illnesses such as coronary artery disease, hypertension, duodenal ulcer, and alcoholism, gave their parents significantly lower ratings (p <.00003) on perceived parental caring items (loving, just, fair, hardworking, clever, strong) while in college. This effect was independent of subject's age, family history of illness, smoking behavior, the death and/or divorce of parents, and marital history of subjects. Furthermore, 87% of subjects who rated both their mothers and fathers low in parental caring had diagnosed diseases in midlife, whereas only 25% of subjects who rated both their mothers and fathers high in parental caring had diagnosed diseases in midlife. Conclusions Since parents are usually the most meaningful source of social support for much of early life, the perception of parental caring, and parental loving itself, may have important regulatory and predictive effects on biological and psychological health and illness.
Activation of PKA/CREB Signaling is Involved in BMP9-Induced Osteogenic Differentiation of Mesenchymal Stem Cells

Background/Aims: BMP9 is highly capable of promoting osteogenic differentiation of mesenchymal stem cells (MSCs) although the molecular mechanism involved is largely unknown. Here, we explored the detail role of PKA/CREB signaling in BMP9-induced osteogenic differentiation. Methods: Activation status of PKA/CREB signaling is assessed by nonradioactive assay and Western blot. Using PKA inhibitors and a dominant negative protein of CREB (A-CREB), we investigated the effect of PKA/CREB signaling on BMP9-induced osteogenic differentiation. Results: We found that BMP9 promotes PKA activity and enhances CREB phosphorylation in MSCs. BMP9 is shown to down-regulate protein kinase A inhibitor γ (PKIγ) expression. We demonstrated that PKA inhibitors suppress BMP9-induced early osteogenic marker alkaline phosphatase (ALP) activity in MSCs as well as late osteogenic markers osteopontin (OPN), osteocalcin (OCN) and matrix mineralization. We found that PKA inhibitor reduces BMP9-induced Runx2 activation and p38 phosphorylation in MSCs. Lastly, interference of CREB function by A-CREB decreased BMP9-induced osteogenic differentiation as well. Conclusion: Our results revealed that BMP9 may activate PKA/CREB signaling in MSCs through suppression of PKIγ expression. It is noteworthy that inhibition of PKA/CREB signaling may impair BMP9-induced osteogenic differentiation of MSCs, implying that activation of PKA/CREB signaling is required for BMP9 osteoinductive activity.
EL COMPORTAMIENTO DE LOS EMPRENDEDORES ESPAÑOLES EN 2008

La literatura economica especializada de las ultimas decadas ha venido senalando el papel relevante que desempenan los emprendedores, no solo ante el crecimiento economico, sino tambien en el mercado de trabajo, siendo una alternativa, en este ambito, a las medidas keynesianas de expansion de la demanda y a las de oferta que proponen flexibilizar dicho mercado. El objetivo de este articulo es mostrar los datos sobre emprendedores que nos ofrece el informe GEM (Global Entrepreneurship Monitor) de 2008, mostrando las actuaciones que se podrian realizar para mejorar su situacion.
Local reactions during allergen immunotherapy do not require dose adjustment.

BACKGROUND The recent World Health Organization position paper on allergen immunotherapy states that local reactions to immunotherapy are not predictive of subsequent systemic reactions. Nevertheless, in clinical practice dose adjustment after local reactions continues to be recommended, presumably in an effort to prevent future systemic reactions. OBJECTIVE We sought to determine whether dose adjustment versus no adjustment for local reactions during allergen immunotherapy influences the occurrence of subsequent systemic reactions. METHODS In a single-site allergy clinic before October 1, 1997, local reactions after allergen vaccine injection resulted in adjustment of the subsequent dose. After October 1, 1997, no dose adjustments were made for immediate and late local reactions. For the same 9-month period before and after the change in local reaction dose-adjustment policy, systemic reaction rates were compared retrospectively. For individuals experiencing a systemic reaction, local reaction rates and local reactions immediately preceding a systemic reaction were also compared before and after the policy change. RESULTS Comparing the 9-month period (October 1996-June 1997) preceding the policy change and the 9 months (October 1997-June 1998) after the change in policy, the systemic reaction rates (0.80% and 1.01%, respectively) were not statistically different (P =.24). Among those experiencing a systemic reaction, the rate of local reactions was unchanged (7.3% and 4.7%, respectively; P =.07), and the rate of local reactions immediately preceding a systemic reaction did not increase (18.8% and 10.5%, respectively; P =.37). The sensitivity of a local reaction predicting a systemic reaction at the next immunotherapy dose was 15%. CONCLUSIONS A local reaction is a very insensitive predictor for a subsequent systemic reaction at the next allergen vaccine dose. Dose adjustment for most local reactions is unnecessary and may delay therapy, increase costs, and put the patient at increased risk of dose administration errors.