Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical CVVH model removes endothelium-derived microparticles from circulation

Background Endothelium-derived microparticles (EMPs) are submicron vesicles released from the plasma membrane of endothelial cells in response to injury, apoptosis or activation. We have previously demonstrated EMP-induced acute lung injury (ALI) in animal models and endothelial barrier dysfunction in vitro. Current treatment options for ALI are limited and consist of supportive therapies. We hypothesize that standard clinical continuous venovenous hemofiltration (CVVH) reduces serum EMP levels and may be adapted as a potential therapeutic intervention. Materials and methods EMPs were generated from plasminogen activation inhibitor-1 (PAI-1)-stimulated human umbilical vein endothelial cells (HUVECs). Flow cytometric analysis was used to characterize EMPs as CD31- and annexin V-positive events in a submicron size gate. Enumeration was completed against a known concentration of latex beads. Ultimately, a concentration of ~650,000 EMP/mL perfusate fluid (total 470 mL) was circulated through a standard CVVH filter (pore size 200 μm, flow rate 250 mL/hr) for a period of 70 minutes. 0.5 mL aliquots were removed at 5- to 10-minute intervals for flow cytometric analysis. EMP concentration in the dialysate was measured at the end of 4 hours to better understand the fate of EMPs. Results A progressive decrease in circulating EMP concentration was noted using standard CVVH at 250 mL/hr (a clinical standard rate) from a 470 mL volume modelling a patient's circulation. A 50% reduction was noted within the first 30 minutes. EMPs entering the dialysate after 4 hours were 5.7% of the EMP original concentration. Conclusion These data demonstrate that standard CVVH can remove EMPs from circulation in a circuit modelling a patient. An animal model of hemofiltration with induction of EMP release is required to test the therapeutic potential of this finding and potential of application in early treatment of ALI.
Grappling with herpes: Herpes gladiatorum

Initial reports of herpes gladiatorum, a skin infection of wrestlers caused by herpes simplex virus (HSV), fo cused on case histories and clinical presentations of this disease. To more adequately address broader ep idemiologic questions concerning this skin infection, we surveyed members of four southeastern college wres tling teams, sampled high school and college athletic trainers nationwide, and obtained serum specimens from members of one college wrestling team for HSV antibody studies. Nine of 48 (18.8%) college wrestlers in the southeastern athletic conference reported histo ries of herpes gladiatorum. Wrestlers with a prior history of oral HSV infection (cold sores) were less likely to report HSV skin infection than wrestlers without cold sores (RR = 0.25; 95% C.I. 0.03 to 1.8), while wrestlers with exposure to opponents with cutaneous HSV le sions were at high risk to develop herpes gladiatorum (RR = 9.4; 95% C.I. 2.2 to 40.0). The national survey of athletic trainers indicated that 7.6% of college wres tlers and 2.6% of high school wrestlers had HSV skin infection during the 1984-85 season. Herpes gladiato rum is a common problem among college wrestlers, and morbidity associated with this skin disease can be significant.
Vibration and large deformation simulation analysis of graphene membrane for nanomechanical applications

This paper reports an efficient and accurate simulation method for vibrations and deformations of single- and multi-layer graphene membranes. In this method, a graphene membrane is modelled by a 2-D plate element whose thickness is changeable in COMSOL Multiphysics. The graphene is regarded as a linear isotropic elastic material, and the load-deformation behaviour is approximated as a doubly clamped bridge model or a clamped circular membrane. By comparing the simulation results using 2-D plate and another SHELL element with the experiment data respectively, we find that the average errors of 1st-order frequency using 2-D plate and SHELL element for the same membrane are 4% and 43%. Therefore, the simulation method using 2-D plate element is precise and efficient for the nanomechanical analysis of graphene sheets. With the proposed simulation method, the vibrations and nonlinear deformations of the circular and square graphene membranes are analyzed with different dimensions and thicknesses. These simulation results can be the guideline for the nanomechanical device design.
Antifungal effects of the nonlinear pharmacokinetics of cilofungin, a 1,3-beta-glucan synthetase inhibitor, during continuous and intermittent intravenous infusions in treatment of experimental disseminated candidiasis

Cilofungin (LY-121019) is a fungicidal cell wall-active 1,3-beta-glucan synthetase inhibitor with a short plasma half-life and saturable nonlinear plasma pharmacokinetics. To optimize the in vivo efficacy of this compound, we studied the effects of its linear and nonlinear pharmacokinetics during continuous versus intermittent intravenous infusion of cilofungin in the treatment of experimental disseminated candidiasis in persistently granulocytopenic rabbits. Six groups of rabbits were studied, untreated controls (n = 32) and five cilofungin dosage regimen groups consisting of the following: 25 mg/kg of body weight intravenously twice daily (VLoINT) (n = 9); 50 mg/kg twice daily (LoINT) (n = 9); 90 mg/kg twice daily (HiINT) (n = 11); 5 mg/kg/h for 18 h/day (LoCI) (n = 7); and 10 mg/kg/h for 18 h/day (HiCI) (n = 7). All regimens achieved plasma concentrations exceeding the MIC for Candida albicans (0.25 microgram/ml). In vitro timed kill assays found that the fungicidal activity and rate of kill by cilofungin above the MIC for C. albicans was concentration dependent. At the lower dosage regimens (VLoINT, LoINT, and LoCI), cilofungin followed linear plasma pharmacokinetics, whereas at higher doses (HiCI and HiINT), nonlinear kinetics consistent with a saturated elimination pathway(s) were observed. Only HiCI and HiINT produced a 10(3)- to 10(4)-fold reduction in CFU per gram in candidiasis of the brain (P less than or equal to 0.001). HiCI and HiINT also significantly reduced infection in the choroid (P less than or equal to 0.05). All regimens, except VLoInt, significantly (P less than or equal to 0.01) reduced tissue infections in lung, liver, spleen, and kidney. However, only the regimens with nonlinear saturation kinetics (HiCI and HiINT) produced a 10(6) reduction in the spleen and a > 10(5) reduction of C. albicans in the kidney and liver. A simple doubling of the dosage from LoCI to HiCI resulted in tissue concentrations that were 10 times higher and a 10(2)- to 10(4)-fold-greater antifungal effect. There was a direct correlation (r2 = 0.83) between tissue concentrations of cilofungin and antifungal activity. Thus, continuous and intermittent infusion dosage regimens that elicit nonlinear saturation plasma pharmacokinetics of cilofungin were associated with increased antifungal activity against experimental disseminated candidiasis.
Antifibrogenic effect of a deletion variant of hepatocyte growth factor on liver fibrosis in rats

Hepatic fibrosis, which may lead to cirrhosis, is associated with most chronic liver diseases. Current therapies for hepatic fibrosis are, however, generally ineffective. In this report we assessed the efficacy of the treatment of hepatic fibrosis with a naturally occurring deletion variant of hepatocyte growth factor (dHGF). The administration of dHGF increased liver weight and suppressed the increase of hepatic collagen content in rats treated with dimethylnitrosamine (DMN) to induce hepatic fibrosis. Furthermore, dHGF exerted its mitogenic and antifibrogenic activities even after the liver fibrosis had been established with DMN. Northern blot analysis showed that dHGF suppressed the increase of messenger RNA (mRNA) levels of procollagen α2(I), αl(III), α1(IV), transforming growth factor β1 (TGF‐β1), desmin (a marker of hepatic lipocytes), and α‐smooth muscle (sm)‐actin (a marker of activated hepatic lipocytes). In addition to suppressing the elevated TGF‐β1, mRNA level in hepatic fibrosis, dHGF had a potent ability to decrease TGF‐β1 mRNA level even in a normal liver. Immunohistochemical analysis revealed that desmin‐positive cells and α‐sm‐actin‐positive cells were increased in the hepatic fibrosis, whereas neither cells were seen in livers of DMN‐treated rats given dHGF. We conclude that dHGF prevents and improves the DMN‐induced hepatic fibrosis in rats by reducing mRNA levels of procollagens and TGF‐β1, by inhibiting an activation of hepatic lipocytes, and by stimulating liver regeneration. dHGF may be useful for and applicable to the treatment of fibrosis in chronic liver diseases.
TGF-β blockade depletes T regulatory cells from metastatic pancreatic tumors in a vaccine dependent manner

Our neoadjuvant clinical trial of a GM-CSF secreting allogeneic pancreas tumor vaccine (GVAX) revealed the development of tertiary lymphoid aggregates (TLAs) within the pancreatic ductal adenocarcinoma (PDA) tumor microenvironment 2 weeks after GVAX treatment. Microarray studies revealed that multiple components of the TGF-β pathway were suppressed in TLAs from patients who survived greater than 3 years and who demonstrated vaccine-enhanced mesothelin-specific T cell responses. We tested the hypothesis that combining GVAX with TGF-β inhibitors will improve the anti-tumor immune response of vaccine therapy. In a metastatic murine model of pancreatic cancer, combination therapy with GVAX vaccine and a TGF-β blocking antibody improved the cure rate of PDA-bearing mice. TGF-β blockade in combination with GVAX significantly increased the infiltration of effector CD8+ T lymphocytes, specifically anti-tumor-specific IFN-γ producing CD8+ T cells, when compared to monotherapy controls (all p < 0.05). TGF-β blockade alone did not deplete T regulatory cells (Tregs), but when give in combination with GVAX, GVAX induced intratumoral Tregs were depleted. Therefore, our PDA preclinical model demonstrates a survival advantage in mice treated with an anti-TGF-β antibody combined with GVAX therapy and provides strong rational for testing this combinational therapy in clinical trials.
Accents of English 2 : The British Isles

Volume II: The British Isles: Preface Typographical conventions and phonetic symbols Part IV. England: 12. RP revisited 13. London 14. The south 15. The north Part V. The Celtic Countries: 16. Wales 17. Scotland 18. Ireland Sources and further reading References Index.
Characteristics and Outcome of Cancer Patients Admitted to the ICU in England, Wales, and Northern Ireland and National Trends Between 1997 and 2013*

Objective: To describe trends in outcomes of cancer patients with an unplanned admission to the ICU between 1997 and 2013 and to identify risk factors for mortality of those admitted between 2009 and 2013. Design: Retrospective analysis. Setting: Intensive Care National Audit & Research Centre Case Mix Programme Database including data of ICUs in England, Wales, and Northern Ireland. Patients: Patients (99,590) with a solid tumor and 13,538 patients with a hematological malignancy with an unplanned ICU admission between 1997 and 2013; 39,734 solid tumor patients and 6,652 patients with a hematological malignancy who were admitted between 2009 and 2013 were analyzed in depth. Interventions: None. Measurements and Main Results: In solid tumor patients admitted between 2009 and 2013, hospital mortality was 26.4%. Independent risk factors for hospital mortality were metastatic disease (odds ratio, 1.99), cardiopulmonary resuscitation before ICU admission (odds ratio, 1.63), Intensive Care National Audit & Research Centre Physiology score (odds ratio, 1.14), admission for gastrointestinal (odds ratio, 1.12), respiratory (odds ratio, 1.48) or neurological (odds ratio, 1.65) reasons, and previous ICU admission (odds ratio, 1.18). In patients with a hematological malignancy admitted between 2009 and 2013, hospital mortality was 53.6%. Independent risk factors for hospital mortality were age (odds ratio, 1.02), cardiopulmonary resuscitation before ICU admission (odds ratio, 1.90), Intensive Care National Audit & Research Centre Physiology Score (odds ratio, 1.12), admission for hematological (odds ratio, 1.48) or respiratory (odds ratio, 1.56) reasons, bone marrow transplant (odds ratio, 1.53), previous ICU admission (odds ratio, 1.43), and mechanical ventilation within 24 hours of admission (odds ratio, 1.33). Trend analysis showed a significant decrease in ICU and hospital mortality and length of stay between 1997 and 2013 despite little change in severity of illness during this time. Conclusions: Between 1997 and 2013, the outcome of cancer patients with an unplanned admission to ICU improved significantly. Among those admitted between 2009 and 2013, independent risk factors for hospital mortality were age, severity of illness, previous cardiopulmonary resuscitation, previous ICU admission, metastatic disease, and admission for respiratory reasons.
Expression of nuclear factor-kappaB in Helicobacter pylori-infected gastric mucosa detected with southwestern histochemistry.

BACKGROUND The transcription factor nuclear factor-kappaB (NF-kappaB) plays a pivotal role in inflammatory responses by upregulating mRNA expression of, for example, proinflammatory cytokines and chemokines. Although in vitro studies have shown that Helicobacter pylori can induce NF-kappaB activation in gastric cancer cell lines, there is little information on cellular localization of NF-kappaB in H. pylori-infected gastric mucosa. METHODS H. pylori-infected and -negative patients with various endoscopic findings were examined. NF-kappaB expression was studied by means of Southwestern histochemistry, a new method of localizing transcription factors. Labeled double-stranded oligo-DNA with specific consensus sequence for the NF-kappaB binding site was reacted with frozen sections from gastric biopsy specimens. We compared mucosal interleukin-8 (IL-8) and IL-1beta levels as measured with enzyme-linked immunosorbent assay with the degree of NF-kappaB expression. RESULTS NF-kappaB expression was often evident in nuclei of epithelial cells in H. pylori-infected gastric mucosa. The degree of NF-kappaB expression on the epithelium was significantly more severe in H. pylori-infected than in -negative mucosa. The degree of NF-kappaB expression also correlated with mucosal IL-8 levels but not with IL-8. CONCLUSIONS H. pylori infection increases the expression of NF-kappaB in gastric mucosa, suggesting that NF-kappaB is involved in inflammatory responses to H. pylori.
Steroid withdrawal in mycophenolate mofetil-treated renal allograft recipients.

BACKGROUND Acute rejection is an inherent risk of the withdrawal of steroids in renal allograft recipients. Mycophenolate mofetil is a potent immunosuppressant that, when given with cyclosporine (CsA), reduces the incidence of acute rejection and may facilitate discontinuation of steroids without increasing the risk of rejection. METHODS In an open pilot study, steroids were withdrawn from 26 adult cadaveric kidney transplant recipients. Corticosteroids were discontinued between 4 and 30 (mean 17) months after transplantation, and steroid-free follow-up ranged from 7 to 18 (mean 10) months. RESULTS Mean CsA doses, CsA blood levels, and serum creatinine at the time of steroid withdrawal and at last patient visit after cessation of steroids were 4.2+/-1.2 mg/kg/day and 3+/-0.8 mg/kg/day (P<0.001), 170+/-53 ng/ml and 113+/-34 ng/ml (P<0.001), and 133+/-36 microM/L and 130+/-37 microM/L (NS), respectively. No rejection episodes occurred after steroid withdrawal. CONCLUSIONS This open study shows that corticosteroids can be safely and successfully withdrawn from renal allograft recipients receiving CsA and mycophenolate mofetil.
Summary of Studies of Abused Infants and Children Later Homicidal, and Homicidal, Assaulting later Homicidal, and Sexual Homicidal Youth and Adults

To study the risks of abuse, violence, and homicide, 5 studies of groups at risk for violence are summarized. 192 Abused Infants, 181 Abused Children, 127 Homicidal Youth, 425 Assaulters, 223 Rapists, and 223 Molesters were randomly selected and tracked in court, probation, medical, and school records, then compared with carefully matched groups of Controls and (in older groups) Nonviolent Delinquents. In adolescence or adulthood, these groups were classified into Later Homicidal (N = 234), Later Violent or Nonviolent Delinquent, and Later Nondelinquent subgroups for more detailed comparisons. Shao's bootstrapped logistic regressions were applied to identify risks for commission of homicide. Significant predictors for all homicidal cases in these samples were number of court contacts, poorer executive function, lower social maturity, alcohol abuse, and weapon possession. Predictors for the 373 Abused cases (Infants and Children) were court contacts, injury, burn, poisoning, fetal substance exposure, and parental alcohol abuse. Predictors for the 871 Violent Delinquent cases (Assaulters, Rapists, Molesters) were court contacts, poorer executive function, and lower social maturity. Accuracies of prediction from the regressions ranged from 81% for homicidal sex offenders to 87 to 99% for other homicidal groups.
Left atrial mechanical functions in patients with the metabolic syndrome

Objective Metabolic syndrome (MS) is a cluster of risk factors leading to cardiometabolic diseases. The aim of the present study was to investigate the eff ect of MS on left atrial function, which is an important determinant of left ventricular fi lling. Methods Left atrial (LA) volumes were measured echocardiographically in 32 MS patients and 32 age- and sex-matched controls. LA volumes were determined at the time of mitral valve opening (maximal, Vmax), at the onset of atrial systole (p wave on the electrocardiogram, Vp) and at the mitral valve closure (minimal, Vmin) according to the biplane area-length method in apical 4-chamber and 2-chamber view. All volumes were corrected to the body surface area, and following left atrial emptying functions were calculated. LA passive emptying volume = Vmax – Vp, LA passive emptying fraction = LA passive emptying volume/Vmax. Conduit volume = LV stroke volume – (Vmax – Vmin), LA active emptying volume = Vp – Vmin, LA active emptying fraction = LA active emptying volume/Vp , LA total emptying volume = (Vmax –Vmin), LA total emptying fraction = LA total emptying volume/Vmax. Results LA maximal volume and LA presystolic volume were signifi cantly higher in MS patients than in controls (P < 0.001). But LA minimum volume was signifi cantly lower in MS patients than in controls (P < 0.001). Although LA passive emptying volume (P < 0.03), LA passive emptying fraction (P < 0.001) and conduit volume (P < 0.001) were found to be signifi cantly lower in MS patients than in controls, LA active emptying volume (P < 0.001) and LA active emptying fraction (P < 0.001) were signifi cantly greater in MS patients than in controls. Conclusion In our study, metabolic syndrome was associated with increased left atrial volume, decreased left atrial passive emptying function and increased pump function. Increased left atrial pump function represents a compensatory mechanism in patients with MS. Thus, these results underline the importance of maintaining a sinus rhythm in these patients.
Hip Abductor Muscle Weakness in Individuals with Gluteal Tendinopathy.

PURPOSE This study aimed to compare hip abductor muscle strength between individuals with symptomatic, unilateral gluteal tendinopathy (GT), and asymptomatic controls. METHODS Fifty individuals with GT age between 35 and 70 yr and 50 sex- and age-comparable controls were recruited from the community. Maximal isometric strength (torque normalized to body mass) of the hip abductors was recorded in the supine position using an instrumented manual muscle tester. A two-way mixed ANCOVA, with covariates of self-reported pain during testing and pain limiting maximum effort, was used to compare hip abductor strength of the symptomatic and asymptomatic hip between GT and control individuals. Data were expressed as mean and SD, with the pairwise comparisons expressed as mean differences and 95% confidence intervals. RESULTS Individuals with GT demonstrated significantly lower hip abductor torque of both their symptomatic and asymptomatic hip than healthy controls (both P < 0.05), with mean strength deficits of 0.35 N·m·kg (32%) on the symptomatic hip and 0.25 N·m·kg (23%) on the asymptomatic hip. In individuals with GT, the symptomatic hip was significantly weaker than the asymptomatic hip with a mean strength deficit of 0.09 N·m·kg (11%) (P < 0.05). CONCLUSIONS People with unilateral GT demonstrate significant weakness of the hip abductor muscles bilaterally when compared with healthy controls. Although it is not clear whether hip weakness precedes GT or is a consequence of the condition, the findings provide a basis to consider hip abductor muscle weakness in the treatment plan for management of GT.
Associations between diagnoses, impairments, disability and handicap in a population of elderly people.

BACKGROUND 'Handicap' is the disadvantage for an individual that results from ill-health. It represents an important outcome in chronic disabling disease, but has proved difficult to measure until recently. The strength of association between handicap and other health status measures, and the relative contributions of health and socioeconomic variables to handicap have not been studied previously. METHODS We undertook a cross-sectional survey of all people > 65 years old in a defined geographical area of North London. The interview was based on the short-CARE psychiatric survey tool, and in addition included measures of physical health and disability, the London Handicap Scale, income, social support and housing. In all, 654 residents (74%) from a register of 889 were interviewed. A random sample of 225 had additional data collected which are reported in this analysis. RESULTS Strength of association with handicap scores increased progressively from diagnosis to impairment to disability. Variation in handicap with diagnosis was explained by impairment, and variation with impairment was mostly explained by disability. Age, housing quality, social support and income were associated with handicap score, but confounding by these did not explain the association between handicap and other aspects of disablement. Disease-associated variables explained quantitatively much more variation in handicap than socioeconomic variables. CONCLUSIONS The most potent influences on handicap are disease and disability, justifying the high priority given by health services to detection, treatment and rehabilitation. Where this is not possible handicap may be reduced to some extent through socioeconomic intervention.
Can interposition of a silicone implant after sapheno-femoral ligation prevent recurrent varicose veins?

OBJECTIVES To investigate whether a silicone implant at the sapheno-femoral ligation site could prevent recurrent varicosities. MATERIALS AND METHODS Two non-randomised groups of patients were studied prospectively. In group A 173 patients and 212 limbs had sapheno-femoral ligation, while 172 patients and 210 limbs additionally had a piece (2x3cm) of silicone sheet sutured to the saphenous stump to cover the anterior half of the common femoral vein. The implant was fixed in apposition to the deep vein by carefully closing the cribriform fascia. Colour duplex scanning was performed after 2 and 12 months. RESULTS In the no implant group neovascularisation was observed in 35 (17%) after 12 months, but only in 13 (6%) limbs treated with a silicone implant (p<0.05). CONCLUSIONS Interposition of a partition of silicone implant seems to lower the incidence of neovascularisation one year after saphenofemoral ligation. This technique may constitute an efficient method to prevent recurrence at the correctly ligated saphenous stump.