Miracle-dz/UniFAR-FTUs huggingface dataset:
Matrix Metalloproteinase Processing of CXCL11/I-TAC Results in Loss of Chemoattractant Activity and Altered Glycosaminoglycan Binding*

The CXCR3 chemokine receptor regulates the migration of Th1 lymphocytes and responds to three ligands: CXCL9/MIG, CXCL10/IP-10, and CXCL11/I-TAC. We screened for potential regulation of T cell responses by matrix metalloproteinase (MMP) processing of these important chemokines. The most potent of the CXCR3 ligands, CXCL11, was identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry as a substrate of the PMN-specific MMP-8, macrophage-specific MMP-12, and the general leukocyte MMP-9. The 73-amino acid residue CXCL11 is processed at both the amino and carboxyl termini to generate CXCL11-(5–73), -(5–63), and -(5–58) forms. NH2-terminal truncation results in loss of agonistic properties, as shown in calcium mobilization and chemotaxis experiments using CXCR3 transfectants and human T lymphocytes. Moreover, CXCL11-(5–73) is a CXCR3 antagonist and interestingly shows enhanced affinity to heparin. However, upon COOH-terminal truncation to position 58 there is loss of antagonist activity and heparin binding. Together this highlights an unexpected site for receptor interaction and that the carboxyl terminus is critical for glycosaminoglycan binding, an essential function for the formation of chemokine gradients in vivo. Hence, MMP activity might regulate CXCL11 tissue gradients in two ways. First, the potential of CXCL11-(5–73) to compete active CXCL11 from glycosaminoglycans might lead to the formation of an antagonistic haptotactic chemokine gradient. Second, upon further truncation, MMPs disperse the CXCL11 gradients in a novel way by proteolytic loss of a COOH-terminal GAG binding site. Hence, these results reveal potential new roles in down-regulating Th1 lymphocyte chemoattraction through MMP processing of CXCL11.
Pros and cons of using the Mental Health Act for severe eating disorders in adolescents.

BACKGROUND In England and Wales the compulsory treatment of young people with severe eating disorders is controversial. There is a concern that such treatment may impair patient autonomy and negatively influence the outcome. In this study, based in a specialist hospital, we compared patients treated under parental consent with those detained under the Mental Health Act: their characteristics and outcome up to 12 months after discharge. RESULTS 34 patients were informal (treated under parental consent) (age: 16.2 +/- 1.3 years) and 16 were treated under Section 3 of the Mental Health Act (age: 16.2 +/- 1) in a 3-year period. Detained patients had an earlier age of onset (12.2 +/- 5 vs. 14.3 +/- 1.8) and more previous hospitalisation. On admission, their psychosocial functioning (Children's Global Assessment Scale (C-GAS): 13.6 +/- 2 vs. 26.9 +/- 9; Health of the Nation Outcome Scale for Children and Adolescents (HONOSCA): 41.7 +/- 5 vs. 31.9 +/- 5) were worse than voluntary patients', they had a higher level of co-morbid depression (BDI: 38.1 +/- 15.6 vs. 26.6 +/- 12.4) and a higher rate of suicidal behaviour. All physical and psychosocial measures improved substantially and clinically significantly by discharge and there was no statistically significant difference at this stage between the two patient groups. Two informal patients died within a year after discharge (6.3%), but there were no deaths amongst the detained patients. COMMENTS In contrast with previous findings in adults, the outcome for detained patients was similar to that for informal patients, despite the former having more severe presentation on admission. There was no evidence of higher mortality in the detained group.
Oral Calcium Supplements Do Not Affect the Progression of Aortic Valve Calcification or Coronary Artery Calcification

Background: The use of oral calcium supplementation among the elderly for prevention and treatment of osteoporosis and osteopenia is increasing. The incidence of aortic valve disease and coronary artery disease also is increasing. No study thus far has been done to demonstrate whether this affects the progression of calcification in both the valves and vasculature. We sought to determine whether ingestion of oral calcium supplementation has an effect on aortic valve calcification (AVC) and coronary artery calcification (CAC). Methods: We performed an independent assessment of AVC, CAC, and calcium supplementation among patients enrolled in the Epidemiology of Coronary Artery Calcification study who were >60 years of age and had baseline and 4-year follow-up AVC data. In this population-based study of Olmsted County (Minnesota) residents, AVC and CAC scores were determined prospectively by electron beam computed tomography. We evaluated baseline demographic data and analyzed whether those patients using calcium supplementation had a higher rate of progression of both AVC and CAC. Results: We identified 257 patients (mean age, 67.8 ± 5.2 years), 144 of whom were women. Twenty-five patients (all women) reported using calcium supplements. Analysis of the 144 women (25 taking calcium supplementation) showed there was no difference in the progression of AVC (mean difference in baseline and follow-up AVC score; no supplement versus supplement, 30 ± 9 vs 39 ± 28; P = .73) or CAC (mean difference in baseline and follow-up CAC score; no supplement vs supplement, 47 ± 15 vs 112 ± 22; P = .154). There were no significant differences between the 2 groups with regard to baseline AVC, serum calcium, renal function, diabetes, hypertension, cholesterol, or body mass index. Conclusion: In this community-based observational study with a 4-year follow-up, no significant increased progression of AVC or CAC was found in women taking oral calcium supplementation. Larger prospective, randomized studies are needed to confirm these findings.
Neuropsychology of first-episode schizophrenia: initial characterization and clinical correlates.

OBJECTIVE Neuropsychological impairments are well documented in schizophrenia and are important targets of treatment. Information about the severity and pattern of deficits after treatment for the first psychotic episode and about relationships between these deficits and syndromal characteristics remains limited. METHOD Comprehensive neuropsychological assessments including 41 individual tests were given to 94 patients with first-episode schizophrenia after initial stabilization of psychosis and to a comparison group of 36 healthy volunteers. Profiles of neuropsychological deficits and the relationship of deficits to sex and handedness were examined. Correlations of neuropsychological deficit with a broad range of historical and clinical characteristics, including outcome, were explored. RESULTS Patients had a large generalized neuropsychological deficit (1.5 standard deviations compared to healthy volunteers). Patients also had, superimposed on the generalized deficit, subtle relative deficits (less than 0.5 standard deviation compared to their own average profile) in memory and executive functions. Learning/memory dysfunction best distinguished patients from healthy individuals; after accounting for this difference, only motor deficits further distinguished the groups. Patients with higher neuropsychological ability had only memory deficits, and patients with lower ability had both memory and executive deficits. No sex differences were observed beyond the normal advantage for men in motor speed. Dextral patients had less severe generalized deficit. Severity of residual symptoms was associated with greater generalized deficit. Executive and attentional deficits were most linked to global functional impairment and poor outcome. CONCLUSIONS The results document a large generalized deficit, and more subtle differential deficits, in clinically stabilized first-episode patients. Learning/memory deficits were observed even in patients with less severe generalized deficit, but the pattern was unlike the amnestic syndrome and probably reflects different mechanisms. Executive and attentional deficits marked the more severely disabled patients, and may portend relatively poor outcome. Failure to develop typical patterns of cerebral dominance may increase the risk for greater generalized deficit.
Therapeutic Benefit of a Dissociated Glucocorticoid and the Relevance of In Vitro Separation of Transrepression from Transactivation Activity

Glucocorticoids (GCs) are the mainstay of asthma therapy; however, major side effects limit their therapeutic use. GCs influence the expression of genes either by transactivation or transrepression. The antiinflammatory effects of steroids are thought to be due to transrepression and the side effects, transactivation. Recently, a compound, RU 24858, has been identified that demonstrated dissociation between transactivation and transrepression in vitro. RU 24858 exerts strong AP-1 inhibition (transrepression), but little or no transactivation. We investigated whether this improved in vitro profile results in the maintenance of antiinflammatory activity (evaluated in the Sephadex model of lung edema) with reduced systemic toxicity (evaluated by loss in body weight, thymus involution, and bone turnover) compared with standard GCs. RU 24858 exhibits comparable antiinflammatory activity to the standard steroid, budesonide. However, the systemic changes observed indicate that transactivation events do occur with this GC with similar potency to the standard steroids. In addition, the GCs profiled showed no differentiation on quantitative osteopenia of the femur. These results suggest that in vitro separation of transrepression from transactivation activity does not translate to an increased therapeutic ratio for GCs in vivo or that adverse effects are a consequence of transrepression.
Evaluating the Survival Benefit of Kidney Retransplantation

Background. The magnitude of the survival benefit associated with kidney retransplantation has not been well studied. Methods. Using data from the Canadian Organ Replacement Register (CORR), we studied patients (n=3,067) initiating renal replacement therapy during 1981–1998 who had received a transplant and experienced graft failure (GF). Such patients were followed until death, loss to follow-up or the end of the observation period (December 31, 1998). Using Cox regression, we estimated the post-GF covariate-adjusted hazard ratio (HR) for retransplant versus dialysis, and determined whether the contrast differed across patient subgroups. Through nonproportional hazards models, we also examine patterns in the retransplant/dialysis HR with time following retransplant. Results. Overall, retransplantation is associated with a covariate-adjusted 50% reduction in mortality, relative to remaining on dialysis (HR=0.50; P<0.0001). This benefit is most pronounced in the 18- to 59-year age group. Retransplanted patients were at significantly higher risk of death relative to patients on dialysis only during the first month posttransplant (HR=1.66; P=0.047), and experienced significantly reduced mortality thereafter. Conclusions. Following primary graft failure, retransplantation is associated with significantly reduced mortality rates among Canadian end-stage renal disease patients. Further study should be undertaken to assess the applicability of our findings to other patient populations.
VEGF‐C and VEGF‐D expression in neuroendocrine cells and their receptor, VEGFR‐3, in fenestrated blood vessels in human tissues

Recently, vascular endothelial growth factor receptor 3 (VEGFR‐3) has been shown to provide a specific marker for lymphatic endothelia in certain human tissues. In this study, we have investigated the expression of VEGFR‐3 and its ligands VEGF‐C and VEGF‐D in fetal and adult tissues. VEGFR‐3 was consistently detected in the endothelium of lymphatic vessels such as the thoracic duct, but fenestrated capillaries of several organs including the bone marrow, splenic and hepatic sinusoids, kidney glomeruli and endocrine glands also expressed this receptor. VEGF‐C and VEGF‐D, which bind both VEGFR‐2 and VEGFR‐3 were expressed in vascular smooth muscle cells. In addition, intense cytoplasmic staining for VEGF‐C was observed in neuroendocrine cells such as the α cells of the islets of Langerhans, prolactin secreting cells of the anterior pituitary, adrenal medullary cells, and dispersed neuroendocrine cells of the gastrointestinal tract. VEGF‐D was observed in the innermost zone of the adrenal cortex and in certain dispersed neuroendocrine cells. These results suggest that VEGF‐C and VEGF‐D have a paracrine function and perhaps a role in peptide release from secretory granules of certain neuroendocrine cells to surrounding capillaries. —Partanen, T. A. , Arola, J., Saaristo, A. , Jussila, L. , Ora, A. , Miettinen, M. , Stacker, S. A. , Achen, M. G. , Alitalo, K. VEGF‐C and VEGF‐D expression in neuroendocrine cells and their receptor, VEGFR‐3, in fenestrated blood vessels in human tissues. FASEB J. 14, 2087–2096 (2000)
Vitamin B supplementation, homocysteine levels, and the risk of cerebrovascular disease

Objective: To perform a meta-analysis on the effect of lowering homocysteine levels via B vitamin supplementation on cerebrovascular disease risk. Methods: Using clinical trials published before August 2012 to assess stroke events, we used relative risks (RRs) with 95% confidence intervals (95% CIs) to measure the association between B vitamin supplementation and endpoint events using a fixed-effects model and χ2 tests. We included 14 randomized controlled trials with 54,913 participants in this analysis. Results: We observed a reduction in overall stroke events resulting from reduction in homocysteine levels following B vitamin supplementation (RR 0.93; 95% CI 0.86–1.00; p = 0.04) but not in subgroups divided according to primary or secondary prevention measures, ischemic vs hemorrhagic stroke, or occurrence of fatal stroke. There were beneficial effects in reducing stroke events in subgroups with ≥3 years follow-up time, and without background of cereal folate fortification or chronic kidney disease (CKD). Some trials that included CKD patients reported decreased glomerular filtration rate with B vitamin supplementation. We conducted detailed subgroup analyses for cyanocobalamin (vitamin B12) but did not find a significant benefit regarding intervention dose of vitamin B12 or baseline blood B12 concentration. Stratified analysis for blood pressure and baseline participant medication use showed benefits with >130 mm Hg systolic blood pressure and lower antiplatelet drug use in reducing stroke risk. Conclusions: B vitamin supplementation for homocysteine reduction significantly reduced stroke events, especially in subjects with certain characteristics who received appropriate intervention measures.
Clinical, pathological, immunohistochemical and molecular characterization of feline chronic gingivostomatitis

Objectives This study presents the clinical, pathological, immunohistochemical and molecular characterization of 26 cats with feline chronic gingivostomatitis (FCG). Methods Oral mucosal biopsies, blood and swabs were collected from cats presenting with oral lesions. The tissue sections were submitted for histopathology and immunohistochemical analysis for feline calicivirus (FCV), feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV). The swabs were subjected to PCR analysis for FCV, and blood for FeLV and FIV. Results The main clinical findings were dysphagia (88.2%), halitosis (76.5%), sialorrhea (47.1%), weight loss (41.2%), intense oral discomfort (35.3%), oral hemorrhage (17.6%), and lackluster and fragile coat (11.8%). Gross inspection revealed bilateral lesions across the palatoglossal fold to the lateral tongue base. The lesions were diffuse, proliferative, intensely red and friable, and bled easily upon examination in 80.8% of cases. In 23.1% of cases, the lesions were multifocal to coalescent, at times forming multiple vesicles on a reddened, edematous palatoglossal fold. Microscopic examination showed that 15.4% of lesions had moderate (grade 2) and 84.6% had severe (grade 3) inflammation. Immunohistochemistry revealed the presence of FeLV antigens in the epithelium and the inflammatory infiltrate of 30.8% of the cats with FCG. FCV antigens were not detected in the FCG lesions. Conclusions and relevance The FCG cases analyzed could not be correlated with FCV. It is possible that FeLV plays a role as a causal agent of lesions in cases where the presence of the virus has been confirmed by immunohistochemistry in epithelial samples.
Estimation of serum zinc, copper, and iron in the patients of oral submucous fibrosis

Introduction: The role of trace elements in various diseases has been a matter of controversy with various authors reporting on conflicting data. They are receiving much attention in the detection of oral cancer and precancer as they are found to be significantly altered and have an important role in carcinogenesis. Trace elements have been extensively studied in the recent years to assess whether they have any modifying effect in the etiology of oral malignant conditions. Materials and Methods: A study was conducted on fifty subjects with clinically diagnosed oral submucous fibrosis (OSMF) and fifty controls with no apparent lesions of the oral mucosa and without any areca nut-related oral habit. Results: The level of serum zinc was significantly (P < 0.0001) lower among cases (73.48 ± 24.21) compared with controls (119.48 ± 52.78). However, the serum copper level was significantly (P < 0.0001) higher among cases (155.50 ± 40.13) than controls (100.40 ± 24.52). The level of serum iron was observed to be lower among the cases (66.57 ± 27.76) as compared to controls (94.19 ± 35.70), and the difference was statistically significant. Conclusion: It can be concluded from this study that serum zinc, copper, and iron levels could be used as a potential prognostic and diagnostic markers in OSMF patients.
The Relationship Between Helicobacter pylori Infection, the Virulence Genotypes of the Infecting Strain and Gastric Cancer in the African Setting

The relationship between Helicobacter pylori infection and gastric carcinoma remains controversial, especially in the African setting where infection is common, while gastric cancer is perceived to be uncommon, the basis of the so called ‘African enigma’. This discrepancy between infection and the development of disease is commonly attributed to differences in host, environment and bacterial factors. Interest in the bacterial factors has focused on heterogeneity in the so‐called ‘virulence genes’.
Incidence of and Risk Factors for Clinically Significant Methicillin-Resistant Staphylococcus aureus Infection in a Cohort of HIV-Infected Adults

Objectives:Outbreaks of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) have been noted in multiple sites in the United States. This study's purpose was to estimate trends in the incidence of and risk factors for clinically significant MRSA (CS-MRSA) infection in a cohort of HIV-infected adults. Design:A retrospective clinic-based cohort (January 1, 2000-December 31, 2003) study. Methods:We ascertained all initial episodes of CS-MRSA and categorized them by primary site. Incidence rates were estimated by half year. Risk factors for CA-MRSA infection were identified using Cox modeling. Results:Of 126 potential events, 94 were CS. Their primary sources were 83% skin or soft tissue, 10% blood, 6% respiratory, and 1.0% other sites. Among these, 60% were CA and 40% were nosocomial. Of antibiotics tested, only cotrimoxazole resistance was associated with nosocomial acquisition. The 3455 patients contributed 7003 person-years at risk. The incidence of CS-MRSA infection increased 6.2-fold from the first to the last half year. In multivariate analysis, independent predictors of CA-MRSA infection included HIV transmission by men who have sex with men or by injection drug use, CD4 count <50 cells/μL, log10 HIV plasma viral load, and absence of cotrimoxazole prophylaxis. Conclusions:The incidence of initial CS-MRSA events increased more than 6-fold in a 4-year period. The associations between CA-MRSA infection and HIV severity indicators merit examination in other cohorts.
Assessment of Reporting Quality in Randomised Controlled Trials of Acupuncture for Post-Stroke Rehabilitation Using the Consort Statement and Stricta Guidelines

Objectives To evaluate the completeness of reporting of randomised controlled trials (RCTs) of acupuncture for post-stroke rehabilitation in order to provide information to facilitate transparent and more complete reporting of acupuncture RCTs in this field. Methods Multiple databases were searched from their inception through September 2015. Quality of reporting for included papers was assessed against a subset of criteria adapted from the Consolidated Standards for Reporting Trials (CONSORT) 2010 statement and the Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA) guidelines. Each item was scored 1 if it was reported, or 0 if it was not clearly stated. Descriptive statistical analysis was performed. Cohen's κ-statistics were calculated to assess agreement between the two reviewers. Results A total of 87 RCTs were included in the full text. Based on CONSORT, good reporting was evident for items “Randomised’ in the title or abstract’, ‘Participants’, ‘Statistical methods’, ‘Recruitment’, ‘Baseline data’, and ‘Outcomes and estimation’, with positive rates >80%. However, the quality of reporting for the items ‘Trial design’, ‘Outcomes’, ‘Sample size’, ‘Allocation concealment’, ‘Implementation’, ‘Blinding’, ‘Flow chart’, ‘Intent-to-treat analysis’, and ‘Ancillary analyses’ was very poor with positive rates <10%. Based on STRICTA, the items ‘Number of needle insertions per subject per session’, ‘Responses sought’, and ‘Needle type’ had poor reporting with positive rates <50%. Substantial agreement was observed for most items and good agreement was observed for some items. Conclusions The reporting quality of RCTs in acupuncture for post-stroke rehabilitation is unsatisfactory and needs improvement.
Transplant Outcomes and Economic Costs Associated with Patient Noncompliance to Immunosuppression

We describe factors associated with immunosuppression compliance after kidney transplantation and examine relationships between compliance with allograft outcomes and costs. Medicare claims for immunosuppression in 15 525 renal transplant recipients with at least 1 year of graft function were used to calculate compliance as medication possession ratio. Compliance was categorized by quartiles as poor, fair, good and excellent. We modeled adjusted associations of clinical factors with the likelihood of persistent compliance by multiple logistic regressions (aOR), and estimated associations of compliance with subsequent graft and patient survival with Cox proportional hazards (aHR). Adolescent recipients aged 19–24 years were more likely to be persistently noncompliant compared to patients aged 24–44 years (aOR 1.49 [1.06–2.10]). Poor (aHR 1.80 [1.52–2.13]) and fair (aHR 1.63[1.37–1.93]) compliant recipients were associated with increased risks of allograft loss compared to the excellent compliant recipients. Persistent low compliance was associated with a $12 840 increase in individual 3‐year medical costs. Immunosuppression medication possession ratios indicative of less than the highest quartile of compliance predicted increased risk of graft loss and elevated costs. These findings suggest that interventions to improve medication compliance among kidney transplant recipients should emphasize the benefits of maximal compliance, rather than discourage low compliance.