Miracle-dz/UniFAR-FTUs huggingface dataset:
Critical Role for Perforin-, Fas/FasL-, and TNFR1-Mediated Cytotoxic Pathways in Down-Regulation of Antigen-Specific T Cells during Persistent Viral Infection

ABSTRACT Viral persistence following infection with invasive strains of lymphocytic choriomeningitis virus (LCMV) can be achieved by selective down-regulation of virus-specific T lymphocytes. High viral burden in the onset of infection drives responding cells into functional unresponsiveness (anergy) that can be followed by their physical elimination. In this report, we studied down-regulation of the virus-specific CD8+-T-cell response during persistent infection of adult mice with LCMV, with emphasis on the role of perforin-, Fas/FasL-, or tumor necrosis factor receptor 1 (TNFR1)-mediated cytolysis in regulating T-cell homeostasis. The results reveal that the absence of perforin, Fas-ligand, or TNFR1 has no significant effect on the kinetics of proliferation and functional inactivation of virus-specific CD8+ T cells in the onset of chronic LCMV infection. However, these molecules play a critical role in the homeostatic regulation of T cells, influencing the longevity of the virus-specific CD8+-T-cell population once it has become anergic. Thus, CD8+ T cells specific to the dominant LCMV NP396–404 epitope persist in an anergic state for at least 70 days in perforin-, FasL-, or TNFR1-deficient mice, but they were eliminated by day 30 in C57BL/6 controls. These effects were additive as shown by a deficit of apoptotic death of NP396–404 peptide-specific CD8+ T cells in mice lacking both perforin and TNFR1. This suggests a role for perforin-, FasL-, and TNFR1-mediated pathways in down-regulation of the antiviral T cell response during persistent viral infection by determining the fate of antigen-specific T cells. Moreover, virus-specific anergic CD8+ T cells in persistently infected C57BL/6 mice contain higher levels of Bcl-2 and Bcl-XL than functionally intact T cells generated during acute LCMV infection. In the case of proapoptotic factors, Bax expression did not differ between T-cell populations and Bad was below the limit of detection in all samples. As expression of the Bcl-2 family members controls susceptibility to apoptosis, this finding may provide a molecular basis for the survival of anergic cells under conditions of prolonged antigen stimulation.
Outpatient Management of Continuous Peripheral Nerve Catheters Placed Using Ultrasound Guidance: An Experience in 620 Patients

BACKGROUND:Continuous peripheral nerve block (CPNB) is an optimal choice for analgesia after orthopedic procedures, but is not commonly used in outpatients because of concern regarding the possibility of catheter-related complications. In addition, it may be difficult to provide adequate patient access to physicians in this setting. We present 620 outpatients who were treated with CPNB using an established protocol. METHODS:All catheters were placed using direct ultrasound visualization. These patients received extensive oral and written preoperative instruction and were provided continuous telephone access to the anesthesiologist during the postoperative period. All patients were also contacted at home by telephone on the first postoperative day. In addition, each patient was seen and examined by the surgeon within 2 wk of hospital discharge. RESULTS:Of the 620 patients, there were 190 interscalene (brachial plexus), 206 fascia iliaca (femoral nerve), and 224 popliteal fossa (sciatic nerve) catheters. Two patients (0.3%) had complications related to the nerve block. In both of these patients, the symptoms resolved within 6 wk of surgery. Twenty-six patients (4.2%) required postoperative interventions by the anesthesiologist. One patient returned to the hospital for catheter removal. CONCLUSIONS:In this large series of outpatients treated with CPNB, there were surprisingly few interventions requiring an anesthesiologist. Likewise, patients were able to manage and remove their catheters at home without additional follow-up. This suggests that with adequate instruction and telephone access to health care providers, patients are comfortable with managing and removing CPNB catheters at home.
Effects of the Introduction of the WHO “Surgical Safety Checklist” on In-Hospital Mortality: A Cohort Study

Objective:To evaluate the effect of implementation of the WHO's Surgical Safety Checklist on mortality and to determine to what extent the potential effect was related to checklist compliance. Background:Marked reductions in postoperative complications after implementation of a surgical checklist have been reported. As compliance to the checklists was reported to be incomplete, it remains unclear whether the benefits obtained were through actual completion of a checklist or from an increase in overall awareness of patient safety issues. Methods:This retrospective cohort study included 25,513 adult patients undergoing non-day case surgery in a tertiary university hospital. Hospital administrative data and electronic patient records were used to obtain data. In-hospital mortality within 30 days after surgery was the main outcome and effect estimates were adjusted for patient characteristics, surgical specialty and comorbidity. Results:After checklist implementation, crude mortality decreased from 3.13% to 2.85% (P = 0.19). After adjustment for baseline differences, mortality was significantly decreased after checklist implementation (odds ratio [OR] 0.85; 95% CI, 0.73–0.98). This effect was strongly related to checklist compliance: the OR for the association between full checklist completion and outcome was 0.44 (95% CI, 0.28–0.70), compared to 1.09 (95% CI, 0.78–1.52) and 1.16 (95% CI, 0.86–1.56) for partial or noncompliance, respectively. Conclusions:Implementation of the WHO Surgical Checklist reduced in-hospital 30-day mortality. Although the impact on outcome was smaller than previously reported, the effect depended crucially upon checklist compliance.
Nicotine Activation of α4* Receptors: Sufficient for Reward, Tolerance, and Sensitization

The identity of nicotinic receptor subtypes sufficient to elicit both the acute and chronic effects of nicotine dependence is unknown. We engineered mutant mice with α4 nicotinic subunits containing a single point mutation, Leu9′ → Ala9′ in the pore-forming M2 domain, rendering α4* receptors hypersensitive to nicotine. Selective activation of α4* nicotinic acetylcholine receptors with low doses of agonist recapitulates nicotine effects thought to be important in dependence, including reinforcement in response to acute nicotine administration, as well as tolerance and sensitization elicited by chronic nicotine administration. These data indicate that activation of α4* receptors is sufficient for nicotine-induced reward, tolerance, and sensitization.
Analysis of Causality Between Economic Growth, Energy Consumption and Carbon Dioxide Emissions in 4 ASEAN Countries

Economic growth and energy consumption in 4 ASEAN countries increase in every year. Energy consumption in 4 ASEAN countries is dominated by fossil fuels which increases the carbon dioxide emission. This study examines the causality relationship between economic growth, energy consumption and carbon dioxide emissions in 4 ASEAN countries during the period of 1975 -2013. Methods in this study using Granger Causality and Vector Error Correction Model. The result shows that economic growth and energy consumption in Indonesia and Singapore are not interconnected. While in Malaysia and Thailand, there is a direct causal relationship. A one direction relationship between economic growth and carbon dioxide emissions happened in Indonesia and Thailand, while in Malaysia and Singapore did not exist. Causal relationship between energy consumption and carbon dioxide emissions occurs Indonesia, whereas in other countries did’t exist. The respond of every variables on the shock in other variables are different in each country.
Arthroscopic débridement for osteoarthritis of the knee.

BACKGROUND The role of arthroscopic débridement in the treatment of osteoarthritis of the knee remains to be defined, and few clinical and radiographic characteristics have been quantitatively associated with the outcome. The hypothesis of this study was that the outcome of arthroscopic débridement for osteoarthritis of the knee is associated with preoperative clinical and radiographic features and intraoperative characteristics and that there are subsets of patients who are more and less likely to respond favorably to the treatment. METHODS We performed a cross-sectional study of a consecutive cohort of 122 patients who underwent arthroscopic débridement for the treatment of osteoarthritis of the knee that had been unresponsive to anti-inflammatory therapy. One hundred and ten patients were followed for a mean of thirty-four months. Pain was assessed with the pain domain of the Knee Society scoring system. Radiographs were scored with the Kellgren-Lawrence method, and limb alignment and the widths of the medial and lateral joint spaces were measured. The severity of cartilage lesions was scored intraoperatively with a modified Noyes grading system. Specific methods of data collection and analysis were incorporated to minimize bias. RESULTS Fifty-two (90%) of fifty-eight knees with mild arthritis, normal alignment, and a joint space width of > or = 3 mm were improved after arthroscopic débridement. Conversely, only five (25%) of twenty knees with severe arthritis, limb malalignment, and a joint space width of < 2 mm had substantial relief of symptoms. Of seventy-two patients who had improvement, forty-four (61%) had it within six months after the arthroscopy. The severity of the lesion was highly predictive of the clinical outcome both in patients with mild arthritis and in those with severe arthritis. CONCLUSIONS The severity of the arthritis, as assessed preoperatively with radiography and intraoperatively by rating the severity of cartilage lesions, influences the clinical outcome of arthroscopic débridement of an osteoarthritic knee. Knees with severe arthritis fare poorly, whereas those with mild arthritis fare well. We could not predict the outcome for knees with moderate arthritis. We believe that these observations are relevant for establishing indications for arthroscopy in patients with osteoarthritis of the knee and may be useful for designing studies with a more rigorous experimental design.
The Cytotoxic Effect of Combined Hyperthermia and Taxane Chemotherapy on Ovarian Cancer Cells: Results of an in vitro Study

Purpose: Hyperthermic intraperitoneal chemotherapy (HIPEC) is under continuous evaluation as a potential treatment for ovarian cancer. The purpose of this study was to evaluate the effect of chemotherapy, drug concentration and temperature. Materials and Methods: We examined the combined effects of hyperthermia and taxane chemotherapy on the clonogenic survival of the human ovarian carcinoma SHIN-3 cell line in vitro. Results: When hyperthermia was combined with chemotherapy, the median lethal dose (LD50) was equivalent regardless of the duration of exposure, and was independent of the exposure temperature. Taxanes showed a similar LD50 over the temperature range tested. Conclusions: In our study, hyperthermia does not increase the cytotoxic effects of taxanes, at least for the concentrations and durations tested.
Occurrence, presentation and treatment of candidemia

Candida is one of the most common causes of nosocomial bloodstream infections. Candidemia is not confined to hematological patients, intensive care units or abdominal surgery wards, but it is remarkably frequent in the internal medicine setting. High mortality associated with candidemia can be reduced by prompt, appropriate antifungal therapy. The epidemiology of species has been shifting toward non-albicans strains. Significant improvements in nonculture-based diagnostic methods, such as serological markers, have been made in recent years, and novel diagnostic techniques should be further studied to enable early pre-emptive therapy. Treatment guidelines indicate that echinocandins are at present the best choice for patients who are severely ill or possibly infected with fluconazole-resistant strains.
Emission of iodine-containing volatiles by selected microalgae species

Abstract. In this study we present the results of an emission study of different phytoplankton samples in aqueous media treated with elevated ozone levels. Halocarbon measurements show that the samples tested released bromoform and different iodocarbons, including iodomethane, iodochloromethane and diiodomethane. Iodide and iodate levels in the liquid phase were representative of concentrations of surface water in a natural environment. Measurement of volatile iodine (I2) emissions from two diatom samples (Mediopyxis helysia and Porosira glacialis) and the background sample (F/2 medium from filtered natural seawater) showed that the quantity of evolved I2 depends on the ozone concentration in the air. This behaviour was assumed to be caused by the oxidation reaction mechanism of iodide with ozone. The I2 emission flux agrees with model calculations at different iodide concentrations. The I2 emission of a natural plankton concentrate sample was, however, very low compared to other samples and showed no dependence on ozone. The reason for this was shown to be the low iodide concentration in the algal suspension, which seems to be the limiting factor in the oxidative formation of I2.
Contribution of Proteus mirabilis urease to persistence, urolithiasis, and acute pyelonephritis in a mouse model of ascending urinary tract infection

Proteus mirabilis, a significant cause of bacteriuria and acute pyelonephritis in humans, produces urease. This high-molecular-weight, multimeric, cytoplasmic enzyme hydrolyzes urea to ammonia and carbon dioxide. To assess the role of urease in colonization, urolithiasis, and acute pyelonephritis in an animal model of ascending urinary tract infection, we compared a uropathogenic strain of P. mirabilis with its isogenic urease-negative mutant, containing an insertion mutation within ureC, the gene encoding the large subunit of the enzyme. Mice challenged transurethrally with the parent strain developed significant bacteriuria and urinary stones. The urease-negative mutant had a 50% infective dose of 2.7 x 10(9) CFU, a value more than 1,000-fold greater than that of the parent strain (2.2 x 10(6) CFU). The urease-positive parent strain reached significantly higher concentrations and persisted significantly longer in the bladder and kidney than did the mutant. Indeed, in the kidney, the parent strain increased in concentration while the mutant concentration fell so that, by 1 week, the parent strain concentration was 10(6) times that of the mutant. Similarly, the urease-positive parent produced significantly more severe renal pathology than the mutant. The initial abnormalities were in and around the pelvis and consisted of acute inflammation and epithelial necrosis. By 1 week, pyelitis was more severe, crystals were seen in the pelvis, and acute pyelonephritis, with acute interstitial inflammation, tubular epithelial cell necrosis, and in some cases abscesses, had developed. By 2 weeks, more animals had renal abscesses and radial bands of fibrosis. We conclude that the urease of P. mirabilis is a critical virulence determinant for colonization, urolithiasis, and severe acute pyelonephritis.
Nanostructured Ferroelectrics: Fabrication and Structure–Property Relations

With the continued demand for ultrahigh density ferroelectric data storage applications, it is becoming increasingly important to scale the dimension of ferroelectrics down to the nanometer‐scale region and to thoroughly understand the effects of miniaturization on the materials properties. Upon reduction of the physical dimension of the material, the change in physical properties associated with size reduction becomes extremely difficult to characterize and to understand because of a complicated interplay between structures, surface properties, strain effects from substrates, domain nucleation, and wall motions. In this Review, the recent progress in fabrication and structure‐property relations of nanostructured ferroelectric oxides is summarized. Various fabrication approaches are reviewed, with special emphasis on a newly developed stencil‐based method for fabricating ferroelectric nanocapacitors, and advantages and limitations of the processes are discussed. Stress‐induced evolutions of domain structures upon reduction of the dimension of the material and their implications on the electrical properties are discussed in detail. Distinct domain nucleation, growth, and propagation behaviors in nanometer‐scale ferroelectric capacitors are discussed and compared to those of micrometer‐scale counterparts. The structural effect of ferroelectric nanocapacitors on the domain switching behavior and cross‐talk between neighboring capacitors under external electric field is reviewed.
Psychopathology, hypnotizability, and dissociation.

OBJECTIVE The purpose of the study was to replicate and extend previous findings regarding the hypnotizability of different clinical groups. METHOD The authors compared the differential hypnotizability of four psychiatric groups--patients with dissociative disorders (N = 17), schizophrenia (N = 13), mood disorders (N = 13), and anxiety disorders (N = 14)--and one normal group of college students (N = 63). Hypnotizability was assessed by four different measures: the eye roll sign and the induction score of the Hypnotic Induction Profile, the Stanford Hypnotic Susceptibility Scale, Form C, and two self-ratings of hypnotizability. RESULTS As predicted, dissociative disorder patients had significantly higher hypnotizability scores on all measures than all other groups. Schizophrenic patients, on the other hand, had significantly lower scores than normal subjects on the eye roll sign and induction score but not on the other measures of hypnotizability. Some other unpredicted between-group differences were also found. Nevertheless, despite the between-group differences, the intercorrelations between the various hypnotizability measures within the normal group were very similar to those observed in the combined patient groups. CONCLUSIONS The findings suggest that routine hypnotizability assessment may be useful in the differential diagnosis of patients with dissociative disorders.
The Diagnosis and Treatment of Antisynthetase Syndrome

Antisynthetase syndrome is an autoimmune condition, characterized by antibodies directed against an aminoacycl transfer RNA synthetase along with clinical features that can include interstitial lung disease (ILD), myositis, Raynaud’s phenomenon, and arthritis. There is a higher prevalence and increased severity of ILD in patients with antisynthetase syndrome, as compared with dermatomyositis and polymyositis, inflammatory myopathies with which it may overlap phenotypically. The diagnosis is made by a multidisciplinary approach, synthesizing rheumatology and pulmonary evaluations, along with serologic, radiographic, and occasionally muscle and/or lung biopsy results. Patients with antisynthetase syndrome often require multimodality immunosuppressive therapy to control the muscle and/or pulmonary manifestations of their disease. The long-term care of these patients mandates careful attention to the adverse effects and complications of chronic immunosuppressive therapy, and disease-related sequelae that can include progressive ILD necessitating lung transplantation, pulmonary hypertension, malignancy, and a decreased survival. It is expected that a greater awareness of the clinical features of this syndrome will allow for an earlier diagnosis and appropriate treatment to improve outcomes in patients with antisynthetase syndrome.
A Metal-induced Conformational Change and Activation of HIV-1 Integrase*

Retroviral integrases are composed of three independently folding domains whose organization relevant to one another is largely unknown. As an approach to understanding its structure, we have investigated the effect of the required metal cofactor(s), Mn2+ or Mg2+, on the conformation of human immunodeficiency virus type 1 (HIV-1) integrase (IN) using monoclonal antibodies (mAbs) that are specific for each of these three domains. Upon the addition of increasing concentrations of the divalent cations to immobilized HIV-1 IN in ELISA assays, binding of mAbs specific for either the C-terminal domain or for an epitope in the catalytic core domain was lost, whereas binding of an N terminus-specific mAb was unaffected. Size exclusion chromatography of a nonaggregating derivative of HIV-1 IN showed that the oligomeric state of the protein did not change under conditions in which recognition of the core and C terminus-specific mAbs was lost. Preincubation with Mn2+ increased the resistance of HIV-1 IN to proteolytic digestion and produced a digestion pattern that was significantly different from that observed with the apoprotein. A derivative that lacked the N-terminal domain, IN(50–288), exhibited the same metal-dependent changes observed with the full-length protein, whereas the isolated catalytic core domain IN(50–212) did not. From this we conclude that the metal-induced conformational change comprises a reorganization of the core and C-terminal domains. Preincubation with Mn2+ increased the specific activity of HIV-1 IN 5-fold. Enzymatic activity was inhibited by the conformation-sensitive C terminus-specific mAb, but this inhibition was reduced greatly if the enzyme was first preincubated with metal ions. Thus, it appears that apo-HIV-1 IN exists predominantly in an inactive conformation that is converted into a catalytically competent form upon the addition of metal ions.
HIV‐1 infection in young men in northern Thailand

Objectives:To determine risk factors for HIV-1 infection in young men in northern Thailand. Methods:At enrollment into a prospective study, data were collected from a self-administered questionnaire and serologic testing on a cohort of 1115 young men selected by lottery for conscription. Results:The overall HIV-1 infection rate was 6.9%; however, the rate was 15.3% among the 387 (34.7%) men who had been living in the upper north subregion of Thailand compared with 2.5% for the remaining 728 men (P< 0.001). A history of sex with female prostitutes was reported by 74.7% of men and increased frequency of this type of sex was highly associated with HIV-1 infection and a history of sexually transmitted disease (STD) symptoms (x2 for trend, P< 0.001). In stratified and multivariate analyses, however, history of STD symptoms, reported by 42.5% of the cohort, was most strongly associated with HIV-1 infection. Only 42.8% of men who reported sex with prostitutes had used condoms more than half the time. Conclusions:Young men in the general population in northern Thailand are at high risk for HIV-1 infection via sex with female prostitutes; STD are highly associated with HIV-1 infection. Increasing condom use and controlling STD should be immediate goals of HIV control programs.