Miracle-dz/UniFAR-FTUs huggingface dataset:
Inter-arm blood pressure difference and mortality: a cohort study in an asymptomatic primary care population at elevated cardiovascular risk.

BACKGROUND Differences in blood pressure between arms are associated with increased cardiovascular mortality in cohorts with established vascular disease or substantially elevated cardiovascular risk. AIM To explore the association of inter-arm difference (IAD) with mortality in a community-dwelling cohort that is free of cardiovascular disease. DESIGN AND SETTING Cohort analysis of a randomised controlled trial in central Scotland, from April 1998 to October 2008. METHOD Volunteers from Lanarkshire, Glasgow, and Edinburgh, free of pre-existing vascular disease and with an ankle-brachial index ≤0.95, had systolic blood pressure measured in both arms at recruitment. Inter-arm blood pressure differences were calculated and examined for cross-sectional associations and differences in prospective survival. Outcome measures were cardiovascular events and all-cause mortality during mean follow-up of 8.2 years. RESULTS Based on a single pair of measurements, 60% of 3350 participants had a systolic IAD ≥5 mmHg and 38% ≥10 mmHg. An IAD ≥5 mmHg was associated with increased cardiovascular mortality (adjusted hazard ratio [HR] 1.91, 95% confidence interval [CI] = 1.19 to 3.07) and all-cause mortality (adjusted HR 1.44, 95% CI = 1.15 to 1.79). Within the subgroup of 764 participants who had hypertension, IADs of ≥5 mmHg or ≥10 mmHg were associated with both cardiovascular mortality (adjusted HR 2.63, 95% CI = 0.97 to 7.02, and adjusted HR 2.96, 95% CI = 1.27 to 6.88, respectively) and all-cause mortality (adjusted HR 1.67, 95% CI = 1.05 to 2.66, and adjusted HR 1.63, 95% CI = 1.06 to 2.50, respectively). IADs ≥15 mmHg were not associated with survival differences in this population. CONCLUSION Systolic IADs in blood pressure are associated with increased risk of cardiovascular events, including mortality, in a large cohort of people free of pre-existing vascular disease.
Detrimental hemodynamic and inflammatory effects of microparticles originating from septic rats

Résumé en anglais Objective: Microparticles (MPs) are membrane vesicles with procoagulant and proinflammatory properties released during cell activation and might be potentially involved in the pathophysiology of septic shock. This study was designed to assess the effects of MPs from septic origin on the systemic hemodynamics as well as on the inflammatory, oxidative, and nitrosative stresses.Design: A prospective, randomized, controlled experimental study with repeated measurements. Setting: Investigational animal laboratory. Subjects: Forty healthy rats were randomly allocated to three groups: 10 animals inoculated with MPs isolated from control rats (cMPs), 15 animals inoculated with MPs isolated from sham rats (shMPs), and 15 animals inoculated with MPs isolated from rats with peritonitis (sMPs). Interventions: Rats were anesthetized, mechanically ventilated, and infused with the same amount of cMPs, shMPs, or sMPs. We measured the heart rate, mean arterial pressure, carotid artery, and portal vein blood flows. Hemodynamic parameters were recorded during 7 hours, and then animals were killed. Aorta and heart were harvested for further in vitro tissue analyses. Measurements and Main Results: 1) The cellular origin (phenotype) but not the circulating concentration of MPs was different in septic rats, characterized by a significant increase in leukocyte-derived MPs. 2) sMPs but not cMPs or shMPs decreased mean arterial pressure without any effect on carotid artery and portal vein blood flows. 3) Rats inoculated with sMPs exhibited an increase in superoxide ion production and nuclear factor kappa B activity, overexpression of inducible nitric oxide synthase with subsequent nitric oxide overproduction and decrease in endothelial nitric oxide synthase activation. Conclusions: Rats with sepsis induced by peritonitis exhibited a specific phenotype of MPs. Inoculation of sMPs in healthy rats reproduced hemodynamic, septic inflammatory patterns, associated with oxidative and nitrosative stresses.
Purα Is Essential for Postnatal Brain Development and Developmentally Coupled Cellular Proliferation As Revealed by Genetic Inactivation in the Mouse

ABSTRACT The single-stranded DNA- and RNA-binding protein, Purα, has been implicated in many biological processes, including control of transcription of multiple genes, initiation of DNA replication, and RNA transport and translation. Deletions of the PURA gene are frequent in acute myeloid leukemia. Mice with targeted disruption of the PURA gene in both alleles appear normal at birth, but at 2 weeks of age, they develop neurological problems manifest by severe tremor and spontaneous seizures and they die by 4 weeks. There are severely lower numbers of neurons in regions of the hippocampus and cerebellum of PURA−/− mice versus those of age-matched +/+ littermates, and lamination of these regions is aberrant at time of death. Immunohistochemical analysis of MCM7, a protein marker for DNA replication, reveals a lack of proliferation of precursor cells in these regions in the PURA−/− mice. Levels of proliferation were also absent or low in several other tissues of the PURA−/− mice, including those of myeloid lineage, whereas those of PURA+/− mice were intermediate. Evaluation of brain sections indicates a reduction in myelin and glial fibrillary acidic protein labeling in oligodendrocytes and astrocytes, respectively, indicating pathological development of these cells. At postnatal day 5, a critical time for cerebellar development, Purα and Cdk5 were both at peak levels in bodies and dendrites of Purkinje cells of PURA+/+ mice, but both were absent in dendrites of PURA−/− mice. Purα and Cdk5 can be coimmunoprecipitated from brain lysates of PURA+/+ mice. Immunohistochemical studies reveal a dramatic reduction in the level of both phosphorylated and nonphosphorylated neurofilaments in dendrites of the Purkinje cell layer and of synapse formation in the hippocampus. Overall results are consistent with a role for Purα in developmentally timed DNA replication in specific cell types and also point to a newly emerging role in compartmentalized RNA transport and translation in neuronal dendrites.
Lot-to-lot consistency study of the fully liquid pentavalent DTwP-HepB-Hib vaccine Quinvaxem® demonstrating clinical equivalence, suitability of the vaccine as a booster and concomitant administration with measles vaccine

This double-blind, randomized study evaluated the immunogenicity and safety of three production lots of the fully liquid combination DTwP-Hep-Hib vaccine, Quinvaxem® (Crucell, The Netherlands) in 360 healthy infants aged 42–64 d old given at 6, 10 and 14 weeks of age (Core Study). The Core Study was followed by an open-label Booster Phase evaluating immunogenicity and safety of a booster dose of Quinvaxem® given with either concomitant or deferred measles vaccine in 227 infants who completed the Core Study. One month after the third dose of Quinvaxem® immune responses reflecting seroprotection or seroconversion were observed in more than 90% of infants for all three vaccine lots. Quinvaxem® elicited a strong booster response as demonstrated by a large increase in antibodies against all antigens, which appeared to be unaffected by concomitant administration of the measles vaccine. Safety results were in line with previous reports for Quinvaxem® with no unexpected adverse events (AEs) being reported. In the Core Study and Booster Phase, Quinvaxem® was well tolerated. No study vaccine-related serious AEs were reported. Thus, Quinvaxem® was immunogenic and well-tolerated when administered to infants according to a 6–10–14 week vaccination schedule. The three production lots had consistent reactogenicity and immunogenicity profiles. The booster dose of Quinvaxem® was also immunogenic and safe, regardless of whether a monovalent measles vaccine was administered concomitantly or one month later. NOTE: Correction published in April 2013, Volume 9, Issue 4: www.landesbioscience. com/journals/vaccines/article/24580/
Prognostic significance of the Ki-67 labeling index in growth hormone-secreting pituitary adenomas.

CONTEXT Ki-67 is a marker of proliferation activity associated with invasiveness and prognosis in human tumors. OBJECTIVE The aim of the study was to evaluate the Ki-67 index prognostic relevance in a group of acromegalic patients who underwent transsphenoidal surgery for a GH-secreting pituitary adenoma. MATERIAL AND METHODS We selected 68 consecutive acromegalic patients referred to our hospital during a 5-yr period. The Ki-67 index was determined by immunohistochemistry on tissue samples obtained from each adenoma after surgery. Those patients who were not completely cured after surgery began medical therapy with somatostatin analogs (SSAs). Periodical pituitary magnetic resonance imaging and hormonal evaluation were performed during the follow-up. RESULTS Twenty-eight of 68 patients were cured after surgery (41%). Among the 40 patients treated with SSAs, 13 were considered uncontrolled. Pituitary magnetic resonance imaging showed residual/recurrent disease in 25 of 68 patients after 6 months. No correlation was found between Ki-67 index and age, tumor size, GH, or IGF-I plasma levels. Tumors described as having cavernous sinus invasion had a higher mean Ki-67 index as compared with noninvasive tumors (P < 0.01). The Ki-67 index was significantly lower in tumors in patients cured after surgery as compared with patients considered not cured (P < 0.01) and in tumors in patients controlled by SSA therapy as compared with patients considered as uncontrolled (P < 0.05). CONCLUSION The Ki-67 labeling index may predict clinical outcome in postsurgical management of acromegalic patients. We suggest routine Ki-67 evaluation in GH-secreting pituitary adenomas.
Evaluation of Unbiased Next-Generation Sequencing of RNA (RNA-seq) as a Diagnostic Method in Influenza Virus-Positive Respiratory Samples

ABSTRACT Unbiased nontargeted metagenomic RNA sequencing (UMERS) has the advantage to detect known as well as unknown pathogens and, thus, can significantly improve the detection of viral, bacterial, parasitic, and fungal sequences in public health settings. In particular, conventional diagnostic methods successfully identify the putative pathogenic agent in only 30% to 40% of respiratory specimens from patients with acute respiratory illness. Here, we applied UMERS to 24 diagnostic respiratory specimens (bronchoalveolar lavage [BAL] fluid, sputum samples, and a swab) from patients with seasonal influenza infection and 5 BAL fluid samples from patients with pneumonia that tested negative for influenza to validate RNA sequencing as an unbiased diagnostic tool in comparison to conventional diagnostic methods. In addition to our comparison to PCR, we evaluated the potential to retrieve comprehensive influenza virus genomic information and the capability to detect known superinfecting pathogens. Compared to quantitative real-time PCR for influenza viral sequences, UMERS detected influenza viral sequences in 18 of 24 samples. Complete influenza virus genomes could be assembled from 8 samples. Furthermore, in 3 of 24 influenza-positive samples, additional viral pathogens could be detected, and 2 of 24 samples showed a significantly increased abundance of individual bacterial species known to cause superinfections during an influenza virus infection. Thus, analysis of respiratory samples from known or suspected influenza patients by UMERS provides valuable information that is relevant for clinical investigation.
Identification of a type I nitroreductase gene in non-virulent Trypanosoma rangeli

ABSTRACT Trypanosomatid type I nitroreductases (NTRs), i.e., mitochondrial enzymes that metabolise nitroaromatic pro-drugs, are essential for parasite growth, infection, and survival. Here, a type I NTR of non-virulent protozoan Trypanosoma rangeli is described and compared to those of other trypanosomatids. The NTR gene was isolated from KP1(+) and KP1(-) strains, and its corresponding transcript and 5’ untranslated region (5’UTR) were determined. Bioinformatics analyses and nitro-drug activation assays were also performed. The results indicated that the type I NTR gene is present in both KP1(-) and KP1(+) strains, with 98% identity. However, the predicted subcellular localisation of the protein differed among the strains (predicted as mitochondrial in the KP1(+) strain). Comparisons of the domains and 3D structures of the NTRs with those of orthologs demonstrated that the nitroreductase domain of T. rangeli NTR is conserved across all the strains, including the residues involved in the interaction with the FMN cofactor and in the tertiary structure characteristics of this oxidoreductase protein family. mRNA processing and expression were also observed. In addition, T. rangeli was shown to be sensitive to benznidazole and nifurtimox in a concentration-dependent manner. In summary, T. rangeli appears to have a newly discovered functional type I NTR.
Comparative Analysis of Two Meningococcal Immunotyping Monoclonal Antibodies by Resonant Mirror Biosensor and Antibody Gene Sequencing

ABSTRACT Lipooligosaccharide (LOS) is a major surface component of the cell walls of Neisseria meningitidis, which is important for its roles in pathogenesis and antigenic variation, as a target for immunological typing, and as a possible vaccine component. Although the structures of many antigenic variants have been determined, routine immunological typing of these molecules remains problematic. Resonant mirror analysis was combined with gene sequencing to characterize two monoclonal antibodies (MAbs) used in typing panels that were raised against the same LOS immunotype, L3,7,9. The two MAbs (MAb 4A8-B2 and MAb 9-2-L379) were of the same immunoglobulin subtype, but while MAb 9-2-L379 was more than a 1,000-fold more sensitive in immunotyping assays of both whole meningococcal cells and purified LOS, MAb 4A8-B2 was more specific for immunotype L3,7,9. The differences in sensitivity were a consequence of MAb 9-2-L379 having a 44-fold-faster association constant than MAb 4A8-B2. Comparison of the amino acid sequences of the variable chains of the MAbs revealed that they had very similar heavy chains (81% amino acid sequence identity) but diverse light chains (54% sequence identity). The differential binding kinetics and specificities observed with these MAbs were probably due to differences in the epitopes recognized, and these were probably a consequence of the different immunization protocols used in their production.
Association of XRCC1, XRCC3, and XPD genetic polymorphism with an increased risk of hepatocellular carcinoma because of the hepatitis B and C virus

Objective The south-east Asian and sub-Saharan African populations are the most susceptible to hepatocellular carcinoma (HCC). We aimed to establish whether XRCC1, XRCC3, and XPD are associated with liver cancer in Pakistan and to examine the interaction of hepatitis B virus (HBV) or hepatitis C virus (HCV) with repaired genes in the occurrence of liver cancer. Materials and methods We enrolled 74 healthy individuals, 75 had either HBV or HCV, and 50 were HCC patients. The characteristic information of all the study participants were collected through a standard interviewer-administered questionnaire. The PCR-RFLP was used to identify the genotype of the patients. Results The results of our study indicated that the patients infected with HBV or HCV had a four or three-fold greater risk of developing liver cancer. Patients older than 55 years of age had a significantly higher risk of developing cancer compared with younger patients. The homozygous wild types Arg/Arg for 280 and Thr/Thr for 241 were more frequent in the controls than in the cases. The allelic frequency of mutant 280His and 399Gln was more pronounced among HCC cases than the controls or the HBV-infected patients. Conclusion The frequency of the XPD gene in the controls was in Hardy–Weinberg equilibrium, indicating that the gene played a protective role in the Pakistani population. XRCC1 or XRCC3 was associated with liver cancer in the Pakistani population; however, the XPD gene played a vital role in the repair of DNA damage.
What Constitutes an Effective but Safe Initial Dose of Lidocaine to Test a Thoracic Epidural Catheter?

To investigate the effects of age and dose on the spread of thoracic epidural anesthesia, we placed thoracic epidural catheters in 50 surgical patients divided into groups by age (Group I [young], 18–51 yr; Group II [old], 56–80 yr) and randomly assigned patients to receive either 5 mL (A) or 9 mL (B) of 2% lidocaine (plain) injected via the epidural catheter. Hemodynamic variables were measured (heart rate, mean arterial blood pressure, noninvasive impedance cardiac index) at baseline and every 5 min for 30 min. Detectable blockade occurred within 8 min after injection of 3 + 2 mL or 3 + 6 mL in 48 of 50 patients. Maximum spread of analgesia to pinprick occurred 15–23 min after completion of local anesthetic injection and was significantly different between age and volume groups by two-way analysis of variance (Group IA [young 5], 10.9 ± 4.0 dermatomes; Group IIB [young 9], 13.9 ± 4.5 dermatomes; Group IIA [old 5], 14.1 ± 5.6 dermatomes; and Group IIB [old 9], 17.4 ± 5.1dermatomes). Minor decreases in mean arterial blood pressure (8%–17%) and heart rate (4%–11%) were noted. Two patients in the Old 9 group required IV ephedrine or ephedrine/atropine to treat hypotension and bradycardia. We conclude that given the rapid onset (3–8 min), extensive spread (11–14 dermatomal segments), and consistent hemodynamic stability, thoracic epidural anesthesia should be initiated with lidocaine 100 mg (5 mL 2% lidocaine) to establish proper location of the catheter in the epidural space in both younger and older patients.
D-dimer testing to determine the duration of anticoagulation therapy.

BACKGROUND The optimal duration of oral anticoagulation in patients with idiopathic venous thromboembolism is uncertain. Testing of D-dimer levels may play a role in the assessment of the need for prolonged anticoagulation. METHODS We performed D-dimer testing 1 month after the discontinuation of anticoagulation in patients with a first unprovoked proximal deep-vein thrombosis or pulmonary embolism who had received a vitamin K antagonist for at least 3 months. Patients with a normal D-dimer level did not resume anticoagulation, whereas those with an abnormal D-dimer level were randomly assigned either to resume or to discontinue treatment. The study outcome was the composite of recurrent venous thromboembolism and major bleeding during an average follow-up of 1.4 years. RESULTS The D-dimer assay was abnormal in 223 of 608 patients (36.7%). A total of 18 events occurred among the 120 patients who stopped anticoagulation (15.0%), as compared with 3 events among the 103 patients who resumed anticoagulation (2.9%), for an adjusted hazard ratio of 4.26 (95% confidence interval [CI], 1.23 to 14.6; P=0.02). Thromboembolism recurred in 24 of 385 patients with a normal D-dimer level (6.2%). Among patients who stopped anticoagulation, the adjusted hazard ratio for recurrent thromboembolism among those with an abnormal D-dimer level, as compared with those with a normal D-dimer level, was 2.27 (95% CI, 1.15 to 4.46; P=0.02). CONCLUSIONS Patients with an abnormal D-dimer level 1 month after the discontinuation of anticoagulation have a significant incidence of recurrent venous thromboembolism, which is reduced by the resumption of anticoagulation. The optimal course of anticoagulation in patients with a normal D-dimer level has not been clearly established. (ClinicalTrials.gov number, NCT00264277 [ClinicalTrials.gov].).
Incidence and injury characteristics of traumatic brain injury: Comparison between children, adults and seniors in Israel

Abstract Aim: To assess the incidence and injury characteristics of hospitalized trauma patients diagnosed with TBI. Methods: A retrospective study of all injured hospitalized patients recorded in the National Trauma Registry at 19 trauma centres in Israel between 2002–2011. Incidence and injury characteristics were examined among children, adults and seniors. Results: The annual incidence rate of hospitalized TBI for the Israeli population in 2011 was 31.8/100 000. Age-specific incidence was highest among seniors with a dramatic decrease in TBI-related mortality rate among them. Adults, in comparison to children and seniors, had higher rates of severe TBI, severe and critical injuries, more admission to the intensive care unit, underwent surgery, were hospitalization for more than 2 weeks and were discharged to rehabilitation. After adjusting for age, gender, ethnicity, mechanism of injury and injury severity score, TBI-related in-hospital mortality was higher among seniors and adults compared to children. Conclusion: Seniors are at high risk for TBI-related in-hospital mortality, although adults had more severe and critical injuries and utilized more hospital resources. However, seniors showed the most significant reduction in mortality rate during the study period. Appropriate intervention programmes should be designed and implemented, targeted to reduce TBI among high risk groups.
Diagnosis of Traumatic Optic Neuropathy: Application of Diffusion Tensor Magnetic Resonance Imaging

Background: Using diffusion tensor imaging, we evaluated the directional diffusivities of the optic nerve in patients with traumatic optic neuropathy (TON). Methods: Our study consisted of 12 patients with unilateral TON, 6 patients with severe traumatic brain injury (comparison group A), and 6 patients with normal conventional brain magnetic resonance imaging (comparison group B). The contralateral optic nerve in patients with TON also was evaluated (comparison group C). Two trauma radiologists, blinded to the clinical diagnosis, independently obtained the directional diffusivities. The intraorbital optic nerve was divided into anterior and posterior segments to evaluate intersegmental differences in directional diffusivities. Results: The mean axial diffusivity (AD) in both optic nerve segments and the mean diffusivity (ADC) in the posterior segment on the affected side were significantly lower and differentiated subjects with TON from those in comparison groups A and B. Area under the receiver operating characteristic curve was 0.762, 0.746, and 0.737 for posterior AD, anterior AD, and posterior ADC, respectively. The mean AD, mean diffusivity, and radial diffusivity were lower in the affected nerves in comparison to the contralateral nerve (comparison group C), but the values did not reach statistical significance. Conclusion: Decreased AD and mean diffusivity in the posterior segment of the optic nerve may serve as a biomarker of axonal damage in patients with TON and merits further investigation as a predictor of initial visual acuity and potential visual recovery.
Evidence that the murine AIDS defective virus does not encode a superantigen

The T-cell receptor repertoire was analyzed in C57BL/6 mice upon infection with helper-free stocks of the pathogenic murine AIDS (MAIDS) defective virus in order to demonstrate if, as previously reported, this virus encodes a superantigen. A polyclonal T-cell stimulation involving T cells expressing multiple V beta subsets occurred within the first week of infection, while late in the disease we could note only a 50% deletion of V beta 5 CD8+ cells. Transfection of the MAIDS virus genomic DNA into fibroblasts and B cells expressing major histocompatibility complex class II molecules failed to show any stimulation of cells expressing the specific V beta (V beta 5) previously reported to respond to MAIDS virus-infected cells. In addition, mice lacking V beta 5 cells did not show any significant decrease in susceptibility to the disease compared with mice expressing V beta 5 and bred on the same genetic background. Our in vivo and in vitro results fail to demonstrate a role for a superantigen encoded by the MAIDS defective viral genome in the pathogenesis of MAIDS.