Miracle-dz/UniFAR-FTUs huggingface dataset:
Graft Loss and CLAD-Onset Is Hastened by Viral Pneumonia After Lung Transplantation

Background Community-acquired respiratory virus (CARV) infections occur frequently after lung transplantation and may adversely impact outcomes. We hypothesized that while asymptomatic carriage would not increase the risk of chronic lung allograft dysfunction (CLAD) and graft loss, severe infection would. Methods All lung transplant cases between January 2000 and July 2013 performed at our center were reviewed for respiratory viral samples. Each isolation of virus was classified according to clinical level of severity: asymptomatic, symptomatic without pneumonia, and viral pneumonia. Multivariate Cox modeling was used to assess the impact of CARV isolation on progression to CLAD and graft loss. Results Four thousand four hundred eight specimens were collected from 563 total patients, with 139 patients producing 324 virus-positive specimens in 245 episodes of CARV infection. Overall, the risk of CLAD was elevated by viral infection (hazard ratio [HR], 1.64; P < 0.01). This risk, however, was due to viral pneumonia alone (HR, 3.94; P < 0.01), without significant impact from symptomatic viral infection (HR, 0.97; P = 0.94) nor from asymptomatic viral infection (HR, 0.99; P = 0.98). The risk of graft loss was not increased by asymptomatic CARV infection (HR, 0.74; P = 0.37) nor symptomatic CARV infection (HR, 1.39; P = 0.41). Viral pneumonia did, however, significantly increase the risk of graft loss (HR, 2.78; P < 0.01). Conclusions With respect to CARV, only viral pneumonia increased the risk of both CLAD and graft loss after lung transplantation. In the absence of pneumonia, respiratory viruses had no impact on measured outcomes.
Air pollution and childhood respiratory health: exposure to sulfate and ozone in 10 Canadian rural communities.

This study was designed to examine differences in the respiratory health status of preadolescent school children, aged 7-11 years, who resided in 10 rural Canadian communities areas of moderate and low exposure to regional sulfate and ozone pollution. Five of the communities were located in central Saskatchewan, a low-exposure region, and five were located in southwestern Ontario, an area with moderately elevated exposures resulting from long-range atmospheric transport of polluted air masses. In this cross-sectional study, the child's respiratory symptoms and illness history were evaluated using a parent-completed questionnaire, administered in September 1985. Respiratory function was assessed once for each child in the schools between October 1985 and March 1986, by the measurement of pulmonary function for forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1.0), peak expiratory flow rate (PEFR), mean forced expiratory flow rate during the middle half of the FVC curve (FEF25-75), and maximal expiratory flow at 50% of the expired vital capacity (V50max). The 1986 annual mean of the 1-hr daily maxima of ozone was higher in Ontario (46.3 ppb) than in Saskatchewan (34.1 ppb), with 90th percentile concentrations of 80 ppb in Ontario and 47 ppb in Saskatchewan. Summertime 1-hr daily maxima means were 69.0 ppb in Ontario and 36.1 ppb in Saskatchewan. Annual mean and 90th percentile concentrations of inhalable sulfates were three times higher in Ontario than in Saskatchewan; there were no significant differences in levels of inhalable particles (PM10) or particulate nitrates. Levels of sulfur dioxide (SO2) and nitrogen dioxide (NO2) were low in both regions. After controlling for the effects of age, sex, parental smoking, parental education, and gas cooking, no significant regional differences were observed in rates of chronic cough or phlegm, persistent wheeze, current asthma, bronchitis in the past year, or any chest illness that kept the child at home for 3 or more consecutive days during the previous year. Children living in southwestern Ontario had statistically significant (P < 0.01) mean decrements of 1.7% in FVC and 1.3% in FEV1.0 compared with Saskatchewan children, after adjusting for age, sex, weight, standing height, parental smoking, and gas cooking. There were no statistically significant regional differences in the pulmonary flow parameters (P > 0.05).
Unconscious High-Level Information Processing

Theories about the neural correlates and functional relevance of consciousness have traditionally assigned a crucial role to the prefrontal cortex in generating consciousness as well as in orchestrating high-level conscious control over behavior. However, recent neuroscientific findings show that prefrontal cortex can be activated unconsciously. The depth, direction, and scope of these activations depend on several top-down factors such as the task being probed (task-set, strategy) and on (temporal/spatial) attention. Regardless, such activations—when mediated by feedforward activation only—do not lead to a conscious sensation. Although unconscious, these prefrontal activations are functional, in the sense that they are associated with behavioral effects of cognitive control, such as response inhibition, task switching, conflict monitoring, and error detection. These findings challenge the pivotal role of the prefrontal cortex in consciousness. Instead, it appears that specific brain areas (or cognitive modules) may support specific cognitive functions but that consciousness is independent of this. Conscious sensations arise only when the brain areas involved engage in recurrent interactions enabling the long-lasting exchange of information between brain regions. Moreover, recent evidence suggests that also the state of consciousness, for example, in vegetative state patients or during sleep and anesthesia, is closely related to the scope and extent of residual recurrent interactions among brain regions.
Drug Resistance Mutations in HIV-1-Infected Subjects during Protease Inhibitor-Containing Highly Active Antiretroviral Therapy with Nelfinavir or Indinavir

Objectives The aim of this retrospective study was to evaluate treatment outcome and characterize the pattern of genotype mutations in subjects with treatment failure on highly active antiretroviral therapy (HAART) containing nelfinavir or indinavir. Study design and methods The database of the Swiss HIV Cohort Study was screened for all subjects naive to protease inhibitor (PI) treatment who started HAART with nelfinavir or indinavir, responded initially (HIV-RNA <400 copies/ml) and received >24 weeks of treatment. Responders with subsequent treatment failure (HIV-RNA >1000 copies/ml, bordered by HIV-RNA >400 copies/ml) were selected for genotypic analysis. Results Initial treatment response, maintenance of response and subsequent virological failure were observed at a comparable frequency in 1143 nelfinavir and 1555 indinavir subjects. Of the treatment-naive patients, 13% who took nelfinavir and 16% who took indinavir had HIV-RNA >1000 copies/ml at least once. These values increased to 24 and 27%, respectively, for reverse transcriptase inhibitor-experienced subjects. Genotypic analysis in a subset of subjects with virological failure identified 30N as the only primary mutation in the nelfinavir subjects (8 out of 21, 38%) whereas isolated or combined 82A/T and 46I/L mutations were detected in the indinavir subjects (9 out of 20, 45%). Conclusions In this population of previously PI-naive subjects, the rate of virological failure and the frequency of resistance mutations at the time of virological failure were comparable in subjects receiving nelfinavir- or indinavir-containing HAART. In nelfinavir subjects, 30N was the only primary mutation whereas isolated or combined 82A/T and 46I/L mutations were detected in indinavir subjects.
Biofeedback on heart rate variability in cardiac rehabilitation: practical feasibility and psycho-physiological eff ects

Objective Biofeedback is a self-regulation therapy by which the patient learns how to optimize the functioning of his autonomic nervous system. It has been applied to patients with various cardiovascular disorders. The purpose of this study was to investigate the practical feasibility and the psychophysiological effects of biofeedback applied to heart rate variability (HRV biofeedback) in order to increase cardiac coherence in coronary artery disease (CAD) patients participating in a cardiac rehabilitation programme. Methods and results In this randomised and controlled study, 31 CAD patients were randomly assigned to an experimental or to a control group. The experimental group participated in a programme of 10 sessions of cardiac coherence biofeedback training, in addition to the rehabilitation programme. The control group participated in the usual cardiac rehabilitation programme only. Physiological variables (systolic and diastolic blood pressure, SDNN) and psychosocial variables (anxiety, depression, type D personality) were measured at the start and at the end of the programme in both groups. Statistical comparisons assessed the inter and intra group differences. The small sample size precludes any fi rm conclusions concerning the effect of cardiac coherence biofeedback on physiological or psychological variables. However, we observed a significant increase of the percentage of cardiac coherence, in relation with an increased SDNN index. Conclusions Our study demonstrated the practical feasibility of cardiac coherence biofeedback training in CAD patients. Further research is desirable to investigate the potential benefit of cardiac coherence biofeedback as an adjunct to stress management in cardiac rehabilitation.
The association between common genetic variation in the FTO gene and metabolic syndrome in Han Chinese.

BACKGROUND Genome-wide association studies for type 2 diabetes mellitus (T2DM) identified FTO gene as a locus conferring increased risk for common obesity in many populations with European ancestry. However, the involvement of FTO gene in obesity or T2DM related metabolic traits has not been consistently established in Chinese populations. The objective of this study was to investigate the association of FTO genetic polymorphisms with metabolic syndrome (MetS) in Han Chinese. METHODS We tested 41 FTO single nucleotide polymorphisms (SNPs) for association between FTO and MetS-related traits. There were a total of 236 unrelated subjects (108 cases and 128 controls), grouped according to the International Diabetes Federation (IDF) criteria. RESULTS Of the 41 SNPs examined, only SNP rs8047395 exhibited statistical significance (P = 0.026) under a recessive model, after Bonferroni adjustment for multiple testing (OR 1.64, 95%CI 1.11-2.42; P = 0.014). The common distributions of this polymorphism among Chinese--with a minor allele frequency (MAF) of 36% in the control group versus 48% in the MetS group--greatly improved our test power in a relatively small sample size for an association study. Previously identified obesity- (or T2DM-) associated FTO SNPs were less common in Han Chinese and were not associated with MetS in this study. No significant associations were found between our FTO SNPs and any endophenotypes of MetS. CONCLUSIONS A more common risk-conferring variant of FTO for MetS was identified in Han Chinese. Our study substantiated that genetic variations in FTO locus are involved in the pathogenesis of MetS.
Bifidobacterial Diversity and the Development of New Microbial Source Tracking Indicators

ABSTRACT Many studies suggest a close relationship between species of Bifidobacterium and their hosts. Thus, species such as B. adolescentis and B. thermacidophilum subsp. porcinum have been proposed as potential indicators of human and porcine fecal pollution. The diversity of bifidobacteria in wastewaters (human and animal) and slurries is analyzed using nested PCR followed by denaturant gradient gel electrophoresis (DGGE). The sewage samples showed similar DGGE patterns. The predominant bands were recognized as B. adolescentis, B. longum, and two unidentified species related to B. adolescentis. A single band detected in poultry samples was identified as B. saeculare. Bifidobacterial diversity was higher within porcine and bovine samples. The main bands in porcine samples were identified as B. minimum, an unknown species, and B. thermophilum/B. thermacidophilum subsp. porcinum. The latter species was also identified among the main bands in bovine samples together with B. pseudolongum and B. ruminantium. We then attempted to isolate the host-specific strains. DGGE bands were examined to develop specific probes to screen environmental samples by colony hybridization and further isolation of strains from positively hybridized colonies. Bifidobacterial strains that are host associated by DGGE bands to human and pig were successfully isolated from the environment: B. adolescentis from human sewage samples and the unidentified species related to pig from slurries and slaughterhouse wastewater. Neither the poultry-associated B. saeculare nor the ruminant-associated B. pseudolongum could be isolated with the current methodology, suggesting either a low prevalence in the samples or failure of the culture to grow in the media used.
Ascorbic acid for anemia management in hemodialysis patients: a systematic review and meta-analysis.

BACKGROUND Ascorbic acid is believed to improve anemia in patients with end-stage renal disease, but its overall effectiveness is unclear. STUDY DESIGN Systematic review and meta-analysis. SETTING & POPULATION Adult hemodialysis patients. SELECTION CRITERIA FOR STUDIES Randomized clinical trials of ascorbic acid use in addition to standard anemia management. INTERVENTION Ascorbic acid. OUTCOMES Weighted mean difference (WMD) for change in hemoglobin level, recombinant human erythropoietin (rHuEPO) dose, transferrin saturation and ferritin level and adverse events. RESULTS Of 157 potentially relevant studies, 6 studies (n = 326 patients) met the inclusion criteria. Combining the 3 randomized clinical trials involving patients with baseline hemoglobin levels <11 g/dL, change in hemoglobin level was greater for ascorbic acid use compared with standard care (WMD, 0.9 g/dL; 95% CI, 0.5-1.2 g/dL). Compared with standard care, ascorbic acid use also was associated with a statistically significant decrease in rHuEPO dose (WMD, -17.1 U/kg/wk; 95% CI, -26.0 to -8.2 U/kg/wk) and improvement in transferrin saturation (WMD, 7.9%; 95% CI, 5.2-10.5%), with no change in ferritin concentration. Adverse events had questionable relevance to ascorbic acid use; no study reported oxalate levels or occurrence of oxalosis. LIMITATIONS Small number of studies, heterogeneity between study populations, and study durations were short. Adverse events were poorly reported. CONCLUSIONS Although the studies are limited by small numbers of subjects, short durations of follow-up, and variable quality, these results suggest that compared with standard care, ascorbic acid use may result in an increase in hemoglobin concentration and transferrin saturation and decrease in rHuEPO requirements. Longer term studies are required to confirm these results, provide information about adverse events, and determine whether these changes translate into improved patient outcomes and cost-effectiveness.
Eccentric exercise‐induced morphological changes in the membrane systems involved in excitation—contraction coupling in rat skeletal muscle

Physiological evidence suggests that excitation‐contraction (E—C) coupling failure results from eccentric contraction‐induced muscle injury because of structural and morphological damage to membrane systems directly associated with the E—C coupling processes within skeletal muscle fibres. In this study using rats, we observed the ultrastructural features of the membrane systems of fast‐twitch (FT) and slow‐twitch (ST) muscle fibres involved in E—C coupling following level and downhill running exercise. Our aim was to find out whether mechanically mediated events following eccentric exercise caused disorder in the membrane systems involved in E—C coupling, and how soon after exercise such disorder occurred. We also compared the morphological changes of the membrane systems between ST and FT muscle fibres within the same muscles. Single muscle fibres were dissected from triceps brachii muscles of male Fischer 344 rats after level or downhill (16 deg decline) motor‐driven treadmill running (18 m min−1, 5 min running with 2 min rest interval, 18 bouts). All single muscle fibres were histochemically classified into ST or FT fibres. The membrane systems were visualized using Ca2+–K3Fe(CN)6–OsO4 techniques, and observed by high voltage electron microscopy (120–200 kV). There were four obvious ultrastructural changes in the arrangement of the transverse (t)‐tubules and the disposition of triads after the downhill running exercise: (1) an increase in the number of longitudinal segments of the t‐tubule network, (2) changes in the direction and disposition of triads, (3) the appearance of caveolar clusters, and (4) the appearance of pentads and heptads (close apposition of two or three t‐tubule elements with three or four elements of terminal cisternae of the sarcoplasmic reticulum). The caveolar clusters appeared almost exclusively in the ST fibres immediately after downhill running exercise and again 16 h later. The pentads and heptads appeared almost exclusively in the FT fibres, and their numbers increased dramatically 2–3 days after the downhill running exercise. The eccentric exercise led to the formation of abnormal membrane systems involved in E–C coupling processes. These systems have unique morphological features, which differ between ST and FT fibres, even within the same skeletal muscle, and the damage appears to be concentrated in the FT fibres. These observations also support the idea that eccentric exercise‐ induced E–C coupling failure is due to physical and chemical disruption of the membrane systems involved in the E–C coupling process in skeletal muscle.
Paths to panic disorder/agoraphobia: an exploratory analysis from age 3 to 21 in an unselected birth cohort.

OBJECTIVE To evaluate childhood temperamental traits and early illness experiences in the etiology of adult panic disorder with agoraphobia. METHOD Evaluated temperamental and illness experience factors, at ages 3 through 18, as predictors of panic and agoraphobia at ages 18 or 21 in an unselected sample (N = 992). Analyses were conducted with classification trees. RESULTS Experience with respiratory ill health predicted panic/agoraphobia relative to other anxiety disorders and healthy controls. Also, temperamental emotional reactivity at age 3 predicted panic/agoraphobia in males but did not predict other anxiety disorders, compared with healthy controls. Furthermore, temperament and ill health interacted with gender. CONCLUSIONS Results are discussed in terms of cognitive theories of fear of physical symptoms and biological models of respiratory disturbance for panic/agoraphobia.
SIRT1 Suppresses Activator Protein-1 Transcriptional Activity and Cyclooxygenase-2 Expression in Macrophages*

SIRT1 (Sirtuin type 1), a mammalian orthologue of yeast SIR2 (silent information regulator 2), has been shown to mediate a variety of calorie restriction (CR)-induced physiological events, such as cell fate regulation via deacetylation of the substrate proteins. However, whether SIRT1 deacetylates activator protein-1 (AP-1) to influence its transcriptional activity and target gene expression is still unknown. Here we demonstrate that SIRT1 directly interacts with the basic leucine zipper domains of c-Fos and c-Jun, the major components of AP-1, by which SIRT1 suppressed the transcriptional activity of AP-1. This process requires the deacetylase activity of SIRT1. Notably, SIRT1 reduced the expression of COX-2, a typical AP-1 target gene, and decreased prostaglandin E2 (PGE2) production of peritoneal macrophages (pMΦs). pMΦs with SIRT1 overexpression displayed improved phagocytosis and tumoricidal functions, which are associated with depressed PGE2. Furthermore, SIRT1 protein level was up-regulated in CR mouse pMΦs, whereas elevated SIRT1 decreased COX-2 expression and improved PGE2-related macrophage functions that were reversed following inhibition of SIRT1 deacetylase activity. Thus, our results indicate that SIRT1 may be a mediator of CR-induced macrophage regulation, and its deacetylase activity contributes to the inhibition of AP-1 transcriptional activity and COX-2 expression leading to amelioration of macrophage function.
High-resolution structures of a heterochiral coiled coil

Significance d polypeptides represent an attractive platform for biomedical applications because of their resistance to proteolytic degradation. However, the structural principles that underlie associations between L- and D-protein partners remain poorly understood because there has been very little atomic-resolution structural characterization of such heterochiral assemblies. Here we report two X-ray crystal structures of the racemic form of an α-helical peptide derived from the influenza M2 protein. Both structures contain large heterochiral coiled–coil interfaces. The ubiquity and regularity of coiled coils has inspired extensive design effort directed toward homochiral tertiary and quaternary structures, and we anticipate that the insights from these crystal structures will facilitate the design of an analogous rich set of heterochiral proteins and assemblies. Interactions between polypeptide chains containing amino acid residues with opposite absolute configurations have long been a source of interest and speculation, but there is very little structural information for such heterochiral associations. The need to address this lacuna has grown in recent years because of increasing interest in the use of peptides generated from d amino acids (d peptides) as specific ligands for natural proteins, e.g., to inhibit deleterious protein–protein interactions. Coiled–coil interactions, between or among α-helices, represent the most common tertiary and quaternary packing motif in proteins. Heterochiral coiled–coil interactions were predicted over 50 years ago by Crick, and limited experimental data obtained in solution suggest that such interactions can indeed occur. To address the dearth of atomic-level structural characterization of heterochiral helix pairings, we report two independent crystal structures that elucidate coiled-coil packing between l- and d-peptide helices. Both structures resulted from racemic crystallization of a peptide corresponding to the transmembrane segment of the influenza M2 protein. Networks of canonical knobs-into-holes side-chain packing interactions are observed at each helical interface. However, the underlying patterns for these heterochiral coiled coils seem to deviate from the heptad sequence repeat that is characteristic of most homochiral analogs, with an apparent preference for a hendecad repeat pattern.
A proton magnetic resonance spectroscopy investigation of the dorsolateral prefrontal cortex in acute mania

Several neurochemical abnormalities have been reported in bipolar disorder (BD), but the exact mechanisms that underlie its pathophysiology remain to be elucidated. Proton magnetic resonance spectroscopy (1HMRS) allows in vivo measurements of certain neurometabolites in the human brain. 1HMRS was used to investigate the dorsolateral prefrontal cortex (DLPFC) in bipolar subjects during a manic or mixed phase. N‐acetyl‐L‐aspartate (NAA), choline‐containing molecules (Cho), creatine plus phosphocreatine (Cr) and myoinositol (Ino) were measured.