Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of the efficacy of albendazole sulphoxide and praziquantel in combination on Taenia crassiceps cysts: in vitro studies.

OBJECTIVES Praziquantel and albendazole are currently used for chemotherapeutic treatment of neurocysticercosis. Albendazole has been found to be more effective than praziquantel; however, it is well known that not all patients will show a complete resolution of cysts. Searching for more effective treatments, this study was designed to evaluate the effect of the combination of praziquantel and albendazole sulphoxide in a Taenia crassiceps in vitro model as well as the kind of interaction between both drugs. METHODS In order to determine the concentration that produced 50% effect (EC50), T. crassiceps cysts were incubated in culture medium containing praziquantel (0.005-0.04 microg/mL), albendazole sulphoxide (0.021-0.16 microg/mL) or the combination of praziquantel and albendazole sulphoxide in a fixed-dose ratio (1:1). The experimental concentration (EC50Exp) of the combination was determined from the concentration-response curve constructed from the combined drug treatment. Isobolographic analyses were used to define the nature of the interaction between praziquantel and albendazole sulphoxide. Morphological and ultrastuctural alterations after different treatments over the parasite tissue were observed by light and transmission electron microscopy. RESULTS The changes in ultrastructure were more marked with the praziquantel and albendazole sulphoxide combination. Also the cysticidal effect of the combination was observed earlier than that of each drug alone. When isobolographic analysis was employed, we found that the experimental EC50 value (0.042 microg/mL) was not significantly different from the theoretical EC50 value (0.035 microg/mL), which indicates an additive interaction between praziquantel and albendazole sulphoxide. CONCLUSIONS Our study suggests that the combination of praziquantel and albendazole sulphoxide could potentially improve the current neurocysticercosis treatment.
Helicobacter pylori gamma-glutamyl transpeptidase is a pathogenic factor in the development of peptic ulcer disease.

BACKGROUND & AIMS gamma-Glutamyl transpeptidase (GGT) has been reported to be a virulence factor of Helicobacter pylori associated with bacterial colonization and cell apoptosis. But its mechanism of pathogenesis is not firmly established. This study aims to examine its role in H pylori-mediated infection. METHODS Various H pylori isogenic mutants were constructed by a polymerase chain reaction (PCR) approach. H pylori native GGT protein (HP-nGGT) was purified with ion-exchange and gel-filtration chromatography. Generation of H2O2 was measured with fluorimetric analysis, whereas nuclear factor-kappaB (NF-kappaB) activation was determined by luciferase assay and Western blot. Cytokine production was examined by enzyme-linked immunoabsorbent assay and real-time PCR. DNA damage was assessed with comet assay and flow cytometry. The GGT activity of 98 H pylori isolates was analyzed by an enzymatic assay. RESULTS Purified HP-nGGT generated H2O2 in primary gastric epithelial cells and AGS gastric cancer cells, resulting in the activation of NF-kappaB and up-regulation of interleukin-8 (IL-8) production. In addition, HP-nGGT caused an increase in the level of 8-OH-dG, indicative of oxidative DNA damage. In contrast, Deltaggt showed significantly reduced levels of H2O2 generation, IL-8 production, and DNA damage in cells compared with the wild type (P<.05). The clinical importance of GGT was indicated by significantly higher (P<.001) activity in H pylori isolates obtained from patients with peptic ulcer disease (n=54) than isolates from patients with nonulcer dyspepsia (n=44). CONCLUSION Our findings provide evidence that GGT is a pathogenic factor associated with H pylori-induced peptic ulcer disease.
Participants’ experiences of hospital-based peer support groups for stroke patients and carers

Purpose: The aim was to examine stroke patients’, carers’ and volunteer supporters’ experiences of peer support groups during hospital rehabilitation. Methods: Semi-structured interviews and questionnaires were analysed by inductive thematic analysis. Participants also answered a standardised Therapeutic Factors Inventory (TFI). Results: Five superordinate themes emerged for patients, carers and volunteer supporters. Three themes related to group processes; ‘practical issues’ (five subthemes), ‘staff presence’, ‘similarity-difference’, and comparison with other group members. ‘Value of peers’ (five subthemes) described beneficial outcomes. The ‘similarity-difference’ theme and four subthemes under ‘value of peers’ were related to items from the TFI which drew agreement from most participants. The supporters had some unique themes; two were concerned with group organisation, one was the experience of ‘being helpful to others’ and one described the experiences of training. As well as its links with themes, agreement with TFI items revealed experiences that did not emerge as themes; feeling secure, expressing emotions and increased independence. Conclusions: Participation in the group was experienced as beneficial by participants. Benefits included helpful information, advice, making new connections and increased awareness of stroke. Participants identified important group processes such as upward and downward comparison. Responses to the TFI suggested that attendance brought therapeutic gains. Implications for Rehabilitation Peer support groups for stroke survivors and their carers, provided early during in-patient rehabilitation, are experienced as beneficial by survivors, carers and peer supporters alike. Peers supporters with similar backgrounds and experiences to the stroke survivors and carers are experienced as the most helpful. The inclusion of staff in the groups is viewed as important and helpful by participants. Therapeutic benefits experienced in the groups include: empowerment and inspiration; sense of belonging; learning new ways to cope; feeling helpful; feeling secure; being able to express feelings; a sense of increased agency and independence.
A longitudinal etiologic model for symptoms of anxiety and depression in women

Background Designed as state measures to monitor treatment response, symptoms of anxiety and depression (SxAnxDep) also have trait-like characteristics. No comprehensive etiologic model for SxAnxDep has illuminated the inter-relationship between their state- and trait-like characteristics, while including key predictor variables. Method In a prospective three-wave study of 2395 female twins from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders (VATSPSUD), we examined, using structural equation modeling, how genes, childhood and past-year environmental stressors, personality and episodes of major depression (MD) and generalized anxiety disorder (GAD) influence SxAnxDep. Results The best-fit model, which explained 68–74% of the variance in SxAnxDep, revealed two etiologic pathways. Stable levels of SxAnxDep resulted largely from neuroticism, which in turn was influenced by genetic and early environment risk factors. Occasion-specific influences resulted from stressful events mediated through episodes of MD or GAD. These two pathways, which had approximately equal influences on levels of SxAnxDep, were substantially correlated because the genetic, early environmental and personality factors that impacted on stable symptom levels also predisposed to event exposure and disorder onset. No significant interaction was seen between the two pathways. Conclusions SxAnxDep in women in the general population arise from two inter-related causal pathways. The first, the ‘trait-like’ pathway, reflects genetic and early environmental risk factors, and is mediated largely through personality. The second pathway is mediated through episodes of MD and GAD, and is the result of both recent environmental adversities and trait-like factors that influence event exposure and the probability of disorder onset.
Study of degradation of sulphur compounds and depletion of metal passivators during thermal ageing of mineral oil

Presence of sulphur compounds in mineral transformer oil poses serious problems of corrosion of copper conductors. Thermal degradation of sulphur compounds like DBDS, 2- mercaptobenzothiozole and depletion of metal passivators like Irgamet 39 and BTA in mineral oil are complex processes. This paper presents results of investigations on degradation of mineral oil with these additives under thermal ageing in air and nitrogen. Efforts are made to explain independently the observed degradation of DBDS, 2-mercaptobenzothiozole and depletion of Irgamet 39 and BTA over a range of temperatures. The effect of sulphur compounds on the performance and depletion of BTA and Irgamet 39 are also explained. Irgamet 39 and BTA deplete in oil under thermal ageing to lower levels, but continue to protect copper from corrosion due to their adsorption by paper which acts as reservoir of metal passivators. The advantages and limitations in the use of Irgamet 39 and BTA are also discussed. To further substantiate the results of the study, effect of these additives on acid formation, interfacial tension and copper ion concentration are discussed.
RSA in Spine: A Review

Study Design: Systematic review of literature. Objectives: This systematic review was conducted to investigate the accuracy of radiostereometric analysis (RSA), its assessment of spinal motion and disorders, and to investigate the limitations of this technique in spine assessment. Methods: Systematic review in all current literature to invesigate the role of RSA in spine. Results: The results of this review concluded that RSA is a very powerful tool to detect small changes between 2 rigid bodies such as a vertebral segment. The technique is described for animal and human studies for cervical and lumbar spine and can be used to analyze range of motion, inducible displacement, and fusion of segments. However, there are a few disadvantages with the technique; RSA percutaneous procedure needs to be performed to implant the markers (and cannot be used preoperatively), one needs a specific knowledge to handle data and interpret the results, and is relatively time consuming and expensive. Conclusions: RSA should be looked at as a very powerful research instrument and there are many questions suitable for RSA studies.
Positive and Negative Aspects of the Human Immunodeficiency Virus Protease: Development of Inhibitors versus Its Role in AIDS Pathogenesis

SUMMARY In this review we summarize multiple aspects of the human immunodeficiency virus (HIV) protease from both structural and functional viewpoints. After an introductory overview, we provide an up-to-date status report on protease inhibitors (PI). This proceeds from a discussion of PI structural design, to how PI are optimally utilized in highly active antiretroviral triple therapy (one PI along with two reverse transcriptase inhibitors), the emergence of PI resistance, and the natural role of secretory leukocyte PI. Then we switch to another focus: the interaction of HIV protease with other genes in acute and persistent infection, which in turn may have an effect on AIDS pathogenesis. We conclude with a discussion on future directions in HIV treatment, involving multiple-target anti-HIV therapy, vaccine development, and novel reactivation-inhibitory reagents.
Increased lung matrix metalloproteinase‐9 levels in extremely premature baboons with bronchopulmonary dysplasia

Matrix metalloproteinases (MMPs) regulate the formation of normal lung architecture. Extremely premature infants exposed to hyperoxia and mechanical ventilation often develop lung inflammation and injury. We hypothesized that an imbalance between MMPs and their tissue inhibitors plays a key role. Our hypothesis was tested to: 1) examine the ontogeny of lung MMPs and tissue inhibitors of metalloproteinases (TIMPs); and 2) determine the effects of hyperoxia and mechanical ventilation on lung MMPs and TIMPs in premature newborn baboons developing chronic lung disease/bronchopulmonary dysplasia (CLD/BPD). Lung specimens were obtained from five groups of gestational controls (GCs) sacrificed at 125, 140, 160, 175, and 185 (term) days of gestation, one fetal baboon model of CLD/BPD delivered at 125 days, and two at 140 days of gestation. Paraffin‐embedded lung tissue sections were examined for pathological changes, and frozen lung specimens were analyzed for MMPs‐1, ‐2, ‐8, and ‐9; TIMPs‐1 and ‐2; and messenger RNA expression of type I collagen. In GCs, MMP‐1 and ‐9 were elevated in the last trimester, whereas MMP‐2 and ‐8 levels were decreased. Significant changes in lung architecture were noted in the BPD models. MMP‐1 was increased in the 125‐day model, but decreased in both 140‐day models. MMP‐8 and collagen mRNA levels were decreased, while MMP‐9 and MMP‐9 to TIMP‐1 ratios were increased in all BPD models. We conclude that an imbalance between MMP‐9 and TIMP‐1 leading to excessive MMP‐9 activity contributes to lung inflammation and edema in CLD/BPD. © 2004 Wiley‐Liss, Inc.
Prognostic significance of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 in voided urine samples from patients with transitional cell carcinoma of the bladder.

PURPOSE To study the role of urinary matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in bladder cancer and their relationship to tumor progression. EXPERIMENTAL DESIGN MMP-1 and TIMP-1 were measured by ELISA in urine samples from 131 patients with bladder tumors (7 cis, 74 Ta, 29 T1, and 21 T2-T4; 46 G(1), 41 G(2), and 37 G(3)), 5 patients with prostate cancer, 33 patients with benign lower urinary tract disorders, and 36 healthy volunteers. Complete clinical data were available for 100 patients with bladder cancer with a median follow-up time of 24 months (range: 4-39 months). RESULTS MMP-1 was detected in urine samples from 21 of 131 (16%) patients with bladder cancer but was undetectable in samples from all other groups (P < 0.0001). Urinary MMP-1 was detected in a higher percentage of patients with T2-T4 tumors and G(3) tumors than patients with cis/Ta/T1 or G(1)-G(2) tumors (P = 0.04 and P = 0.0074, respectively). Patients with detectable concentrations of urinary MMP-1 had higher rates of disease progression (P = 0.04) and death from bladder cancer (P = 0.02) than patients with undetectable urinary MMP-1. All patient groups had higher urinary TIMP-1 concentrations than healthy volunteers (P = 0.02). Patients with muscle-invasive tumors had higher concentrations of urinary TIMP-1 than patients with cis/Ta/T1 tumors (P = 0.037), but there was no association between TIMP-1 and tumor grade. Urinary TIMP-1 levels strongly correlated with tumor size (P = 0.0002). Progression-free survival rates were lower for patients with urinary TIMP-1 concentrations above the median (1.8 ng/ml, P = 0.04), but urinary TIMP-1 levels were not related to disease-specific survival. Patients with T2-T4 tumors and G(3) tumors had significantly lower urinary MMP-1:TIMP-1 ratios than patients with Ta/T1 bladder tumors (P = 0.039) or G(1)-G(2) tumors (P = 0.0415). CONCLUSIONS Where urinary MMP-1 is detectable, the patient is more likely to have a bladder tumor of advanced stage or grade and may be at increased risk of disease progression and death of bladder cancer. The relationship between urinary TIMP-1, muscle-invasion, and disease progression in bladder cancer is at variance with its role as an inhibitor of MMPs and warrants additional evaluation.
INTRASPECIFIC COMPETITION AND THE EVOLUTION OF VIRULENCE IN A PARASITIC TREMATODE

Abstract Intrahost competition between parasite genotypes has been predicted to be an important force shaping parasite ecology and evolution and has been extensively cited as a mechanism for the evolution of increased parasite virulence. However, empirical evidence demonstrating the existence and nature of intraspecific competition is lacking for many parasites. Here, we compared within-host competitiveness between genetic strains of Schistosoma mansoni with high (HIGH-V) or low (LOW-V) virulence to their intermediate snail host, Biomphalaria glabrata. Groups of snails were exposed to either one or the other of two parasite strains, or a mixed infection of both strains, and the resulting progeny were identified using a molecular marker. In two separate experiments investigating simultaneous and sequential infections, we demonstrated that the lifetime reproductive success of parasite strain HIGH-V was reduced in the presence of a faster replicating parasite genotype, LOW-V, regardless of whether it was in a majority or minority in the initial inoculum of the simultaneous exposure or of its relative position in the sequential exposure experiment. Thus, we demonstrate competition between parasite genotypes and asymmetry in competitive success between parasite strains. Moreover, since the less virulent strain investigated here had a competitive advantage, we suggest that a high frequency of multiple infections could favor the evolution of less, rather than more, virulent parasites in this system.
Effect of circumferential plasma-spray porous coating on the rate of femoral osteolysis after total hip arthroplasty.

BACKGROUND Osteolysis of the femur has been a serious problem associated with some designs of total hip-replacement implants; it frequently leads to failure of the femoral component. We evaluated the effect of a circumferential plasma-spray porous coating on the rate of osteolysis in a study that included two groups of hips, each of which received an implant with the same design except for the extent of the porous coating. Our goal was to determine the possible role of circumferential porous coating in protecting the bone-implant interface from osteolysis. METHODS A series of consecutive primary total hip replacements performed with insertion of the Mallory-Head implant without cement was divided into two study groups. The first 126 hips (Group 1) were treated with a femoral stem that had a noncircumferential plasma-spray porous titanium coating. The next ninety hips (Group 2) were treated with a circumferentially coated stem of the same design. The average duration of radiographic follow-up was 7.8 years in Group 1 and 7.5 years in Group 2. RESULTS The average rate of polyethylene wear was similar for the two groups (0.187 millimeter per year in Group 1 and 0.189 millimeter per year in Group 2). The prevalence of osteolysis in Group 1 (40 percent; fifty of 126 hips) was significantly higher than that in Group 2 (10 percent; nine of ninety hips) (p < 0.001). Osteolysis remote from the joint space (distal to zones 1 and 7) was found in 11 percent (fourteen) of the hips in Group 1 but in none of those in Group 2 (p = 0.0004). The average total area of osteolysis in Group 1 (5.0 square centimeters) was significantly larger than that in Group 2 (2.9 square centimeters) (p < 0.05). CONCLUSIONS A circumferential plasma-spray titanium porous coating on the femoral component of a total hip-replacement prosthesis inserted without cement appears to provide an effective barrier preventing wear debris from gaining access to the endosteal surface of the femur and the greater trochanter. This finding supports the hypothesis of the so-called effective joint space, which predicts that wear debris from the joint bearing can migrate, driven by intracapsular pressures, to all areas to which joint fluid has access and thus can result in osteolysis. The reduction of the prevalence of osteolysis and the elimination of osteolysis from the zones remote from the joint space by the use of a circumferential plasma-spray porous coating indicates that the femur was effectively sealed off from the joint space. We believe that the durability and longevity of the femoral component should be enhanced by the use of such a coating.
Low Back Pain in Patients Treated Surgically for Scoliosis: Longer Than Sixteen-Year Follow-up

Study Design. A retrospective study. Objective. To evaluate long-term outcome regarding low back pain (LBP) in patients treated surgically for scoliosis. Summary of Background Data. Measures of long-term outcome after surgery for scoliosis have focused mainly on radiologic changes. However, subjective symptoms such as LBP after surgical treatment are of great concern to patients who undergo surgical treatment for scoliosis. Methods. Thirty-two patients treated surgically for scoliosis between 1976 and 1989 were included in this study. The mean duration of follow-up was 21.1 years. Eighteen patients had adolescent idiopathic scoliosis, 8 had congenital scoliosis, and 6 had symptomatic scoliosis. We evaluated long-term outcome by direct interview. Degree of LBP was evaluated by visual analogue scale score and Moskowitz classification in addition to clinical and radiologic evaluation. Patients were also asked to complete the SF-36 questionnaire. Results. Mean visual analogue scale score at the latest follow-up was 21 (0–80), and 15% of patients had occasional or frequent LBP in Moskowitz classification. On the SF-36, score for bodily pain was not markedly different from that for age-matched controls. Among radiologic findings, level of distal fusion had no effect on the incidence or severity of LBP. Furthermore, preoperative Cobb angle, latest Cobb angle, and degenerative changes of subjacent segment each exhibited no correlation with degree of LBP, either. On the other hand, sagittal balance was a factor affecting LBP following scoliosis surgery. Conclusion. We evaluated long-term outcomes regarding LBP following scoliosis surgery. Regardless of residual back deformity, LBP was found to be no more frequent than in the normal population in Japan. Positive sagittal balance at the latest follow-up was a factor significantly contributing to LBP following scoliosis surgery.
THE DIFFERENTIAL REGIONAL EFFECTS OF MONETARY AND FISCAL POLICIES IN BRAZIL

The aim of this paper is to examine whether monetary and fiscal policies have symmetric effects across the regions of Brazil. For this, I use a SVAR model in which a Bayesian sign restrictions approach is adopted to identify the shocks. The results indicate that regional products tend to have similar reactions to monetary policy shocks, but asymmetric responses to fiscal policy shocks. Moreover, monetary policy shocks have more influence on economic activity than fiscal policy shocks in all regions.