Miracle-dz/UniFAR-FTUs huggingface dataset:
Elevated plasma lipoprotein-associated phospholipase A₂ activity is associated with plaque rupture in patients with coronary artery disease.

BACKGROUND Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) has recently been shown to be positively related to coronary events in patients with coronary artery disease (CAD). However, direct evidence about the relationship between circulation Lp-PLA(2) activity and vulnerable plaque in patients with CAD remains lacking. METHODS Plasma Lp-PLA(2) activity was determined in 146 consecutive patients with CAD who underwent clinically-indicated coronary angiography and preinterventional intravascular ultrasound (IVUS). RESULTS Eighty-three patients were included in the final analysis after the initial screening. Sixty (72.3%) were acute coronary syndrome (ACS) patients and 23 (27.7%) were stable angina pectoris (SAP) patients. Plaque rupture occurred in 39 (47.0%) patients, and 34 (87.2%) were from ACS patients and 5 (12.8%) from SAP patients. There were no significant differences in clinical and angiographic characteristics between patients with plaque rupture and those without plaque rupture, except for smoking, high-sensitive C-reactive protein (hs-CRP) level and Lp-PLA(2) activity (all P < 0.05). IVUS measurement uncovered that patients with plaque rupture had more frequent positive remodeling (74.4% vs. 43.2%, P = 0.004), soft plaques (64.1% vs. 36.4%, P = 0.012) and higher remodeling index (1.13 ± 0.16 vs. 0.99 ± 0.11, P = 0.041) as compared with those without plaque rupture. Multivariate Logistic regression analysis showed that plasma Lp-PLA(2) activity was independently associated with plaque rupture after adjusting for smoking, positive remodeling and soft plaque (Model 1: odds ratio (OR) 1.13, 95% confidence interval (CI): 1.06 - 1.20) or adjusting for smoking, hs-CRP level, positive remodeling and soft plaque (Model 2: OR 1.11, 95%CI: 1.04 - 1.19). CONCLUSIONS Plasma Lp-PLA(2) activity is associated with plaque rupture in patients with CAD, independently of traditional CAD risk factors, hs-CRP level and IVUS parameters. Lp-PLA(2) may be a risk marker for vulnerable plaques.
Peroxisomal Hydrogen Peroxide Is Coupled to Biotic Defense Responses by ISOCHORISMATE SYNTHASE1 in a Daylength-Related Manner1[C][W][OA]

While it is well established that reactive oxygen species can induce cell death, intracellularly generated oxidative stress does not induce lesions in the Arabidopsis (Arabidopsis thaliana) photorespiratory mutant cat2 when plants are grown in short days (SD). One interpretation of this observation is that a function necessary to couple peroxisomal hydrogen peroxide (H2O2)-triggered oxidative stress to cell death is only operative in long days (LD). Like lesion formation, pathogenesis-related genes and camalexin were only induced in cat2 in LD, despite less severe intracellular redox perturbation compared with SD. Lesion formation triggered by peroxisomal H2O2 was modified by introducing secondary mutations into the cat2 background and was completely absent in cat2 sid2 double mutants, in which ISOCHORISMATE SYNTHASE1 (ICS1) activity is defective. In addition to H2O2-induced salicylic acid (SA) accumulation, the sid2 mutation in ICS1 abolished a range of LD-dependent pathogen responses in cat2, while supplementation of cat2 with SA in SD activated these responses. Nontargeted transcript and metabolite profiling identified clusters of genes and small molecules associated with the daylength-dependent ICS1-mediated relay of H2O2 signaling. The effect of oxidative stress in cat2 on resistance to biotic challenge was dependent on both growth daylength and ICS1. We conclude that (1) lesions induced by intracellular oxidative stress originating in the peroxisomes can be genetically reverted; (2) the isochorismate pathway of SA synthesis couples intracellular oxidative stress to cell death and associated disease resistance responses; and (3) camalexin accumulation was strictly dependent on the simultaneous presence of both H2O2 and SA signals.
Antibiotic combinations in polymicrobic diabetic foot infections.

OBJECTIVE The aim of this study was to evaluate synergistic potential of antibiotic combinations against pathogenic microorganisms isolated from patients with diabetic foot wounds. RESEARCH DESIGN AND METHODS 272 diabetic foot patients were studied prospectively over a two-year period. Tissue curettage samples from ulcer base were processed microbiologically to isolate aerobic as well as anaerobic pathogens. [775 isolates] Antibiotic susceptibility testing [MIC/MBC], from amongst these organisms revealed 75 multiresistant organisms, of which only 69 strains could be further studied to assess synergistic effect of various antibiotic combinations by the microtitre checkerboard assay technique. RESULTS The checkerboard synergy studies showed that overall, synergy could be demonstrated in 21.74% to 59.57%. Amongst the 14 combinations tested, it was found that four combinations could be of worthwhile clinical significance, namely Amikacin/Piperacillin [AK + PP] [77.50%]; Ampicillin-Sulbactum/Piperacillin [AS + PP] [76.92%]; Ampicillin Sulbactum/Cefoperazone [AS + CP] [74.47%], and Ofloxacillin/Cefotaxime [OF + CT] [71.43%]. CONCLUSIONS Amikacin/Piperacillin is a combination that has been proven to be of synergistic potential. This study not only confirms this observation but also showed that Ampitum-Sulbactum in combination with either Piperacillin or Cefoperazone was equally efficacious. Furthermore, it was also observed that Ofloxacillin/Cefotaxime combination could be almost equally useful. The study thus emphasizes that antibiotic combinations which are synergistic can be of great clinical significance in the management of patients with diabetic foot infections.
N‐methyl‐d‐aspartate receptor‐mediated increase of neurogenesis in adult rat dentate gyrus following stroke

Neurogenesis in the adult rat dentate gyrus was studied following focal ischemic insults produced by middle cerebral artery occlusion (MCAO). Animals were subjected to either 30 min of MCAO, which causes damage confined to the striatum, or 2 h of MCAO, which leads to both striatal and cortical infarction. When compared to sham‐operated rats, MCAO‐rats showed a marked increase of the number of cells double‐labelled for 5‐bromo‐2′‐deoxyuridine‐5′‐monophosphate (BrdU; injected during 4–6 days postischemia) and neuronal‐specific antigen (NeuN; a marker of postmitotic neurons) in the ipsilateral dentate granule cell layer and subgranular zone at 5 weeks following the 2 h insult. Only a modest and variable increase of BrdU‐labelled cells was found after 30 min of MCAO. The enhanced neurogenesis was not dependent on cell death in the hippocampus, and its magnitude was not correlated to the degree of cortical damage. Systemic administration of the N‐methyl‐d‐aspartate (NMDA) receptor blocker dizocilpine maleate (MK‐801) completely suppressed the elevated neurogenesis following 2 h of MCAO. Our findings indicate that stroke leads to increased neurogenesis in the adult rat dentate gyrus through glutamatergic mechanisms acting on NMDA receptors. This modulatory effect may be mediated through changes in the levels of several growth factors, which occur after stroke, and could influence various regulatory steps of neurogenesis.
Induction of anterior chamber-associated immune deviation by corneal allografts placed in the anterior chamber.

PURPOSE Although mice with long-accepted orthotopic corneal allografts display donor-specific anterior chamber-associated immune deviation (ACAID), this deviant response is not detected until well after the fate of the grafts is decided. To determine the efficiency with which corneal tissue itself can induce ACAID, allogeneic corneal segments were inserted into anterior chambers (AC) of normal mouse eyes. METHODS Central corneas from normal eyes of C57BL/6 (allogeneic) and BALB/c (syngeneic) donors were cut into wedge-shaped fragments measuring approximately 0.3 x 2.0 mm (in some experiments the corneal epithelium was removed) and inserted into the AC adjacent to recipient endothelium. Recipients of these fragments were evaluated for donor-specific delayed hypersensitivity (DH) and ACAID, and fragment-containing eyes were tested for their capacity to support ACAID to an irrelevant antigen. RESULTS Syngeneic and allogeneic corneas survived indefinitely in the AC without evidence of inflammation or rejection. Although fragments of cornea (with or without epithelial layers) placed at extraocular sites were potent inducers of DH, within the eye only epithelium-bearing grafts induced DH. Moreover, this DH response was short-lived. Recipients of allogeneic corneal fragments in the AC developed ACAID by 8 weeks, but not at 1 week. Moreover, fragment-containing eyes supported ACAID induction when bovine serum albumin was injected into the AC. CONCLUSIONS Anterior chamber-associated immune deviation can be induced by allogeneic corneal tissue inserted into the AC, but its onset is delayed. The delay may be dictated by persistence of donor epithelium on the graft, which promotes DH. Once the epithelium is lost, DH disappears and ACAID emerges. Anterior chamber-associated immune deviation may contribute to the maintenance of corneal allograft viability.
Protective role of BCG vaccination against tuberculous meningitis in Indian children: a reappraisal.

BACKGROUND The protective role of BCG vaccination against tuberculous meningitis (TBM) is still controversial in India, largely due to the presence of other predisposing factors such as age, nutritional and socioeconomic status, and household contact. Very few Indian studies have focused on the interaction between BCG and these factors on the occurrence of TBM. METHODS We did an unmatched hospital-based case-control study with prospective enrolment. Children with TBM diagnosed on the basis of predefined criteria were enrolled as cases. For each case, two children admitted on the same day and who did not have any neurological symptoms were enrolled as controls. Demographic data and information on predisposing factors for tuberculosis were collected for both cases and controls and the presence of a BCG scar was charted. Cases and controls were compared by univariate followed by multivariate analysis to obtain significant independent predictors for the occurrence of TBM. To assess the interaction between other predisposing factors and protective efficacy of BCG, a stratified analysis was also done. RESULTS A total of 91 cases and 182 controls were enrolled over a one-year study period, of which 37 cases and 111 controls had a BCG scar. The crude odds ratio for the occurrence of TBM in the absence of a BCG scar was 2.28 (range: 1.32-3.94). The time elapsed since vaccination was significantly longer in the cases. Also, the proportion with a household contact was significantly higher in the cases, the mean age of the cases was higher than that of the controls, and the mean weight and height for age percentage were significantly lower. The cases had a significantly lower socioeconomic status. On multivariate analysis, the significant independent predictors for the occurrence of TBM were positive household contact with tuberculosis (adjusted OR 4.26; 95% CCI 2.26-8.04), absent BCG scar (adjusted OR 1.98; 95%ClI 1.09-3.57) and rural residence (adjusted OR 2.07; 95% ClI 1.02-4.17). CONCLUSION Vaccination with BCG was found to be protective even after controlling for the effect of other variables. Stratified analysis showed that protection due to BCG failed to reach significance for those > 5 years of age, if the weight was <6 0% of that expected for age, in the presence of a household contact with tuberculosis, and in socioeconomic classes III, IV and V.
Well-Informed Patients with End-Stage Renal Disease Prefer Peritoneal Dialysis to Hemodialysis

One hundred and one azotemic patients, from March 1988 to March 1992, expected to be in need of active treatment of uremia within the next 6 months, were invited to four information meetings concerning conservative treatment of uremia, hemodialysis, peritoneal dialysis, and transplantation. Eighty-three percent of the invited patients attended. Another 13 started active treatment of uremia after receiving individualized information. At the end of the observation period, 37 of 97 patients had chosen continuous ambulatory peritoneal dialysis (CAPD), and 23 hemodialysis. Twenty-nine had not yet decided which mode of active treatment of uremia they wanted, and 4 patients had died. Patients choosing CAPD had a mean age of 52 years, compared to 59 years for those choosing hemodialysis. Thirty-six of 37 patients who had chosen CAPD and 19 of 23 patients who had chosen hemodialysis had started treatment. The cumulative patient and technique survival at 12 months for CAPD was 92% and 66%, and for hemodialysis 700/0 and 70%, respectively. The patients were asked to give their views on their choice of active treatment of uremia and the information meetings once they had started treatment. Eighty-six percent of the patients did not want to change their chosen therapy, and 88% of the patients found the Information provided adequate. When patients with renal insufficiency are given adequate Information, the majority prefer peritoneal dialysis to hemodialysis and are very satisfied with their choice.
Response of choroidal blood flow in the foveal region to hyperoxia and hyperoxia-hypercapnia.

PURPOSE Arterial carbon dioxide tension and arterial oxygen tension are important determinants of retinal and cerebral blood flow. In the present study the hypothesis that changes in arterial blood gases also influence choroidal blood flow was tested. METHODS The effect of breathing different mixtures of oxygen (O(2)) and carbon dioxide (CO(2)) on choroidal blood flow in the foveal region was investigated in healthy subjects. The study was performed in a randomized, double-masked four way cross-over design in 16 subjects. Using a compact laser Doppler flowmeter, red blood cell velocity (ChBVel), volume (ChBVol), and flow (ChBF) in the choroidal vasculature were measured during the breathing of various mixtures of O(2)and CO(2) (hyperoxia-hypercapnia): 100% O(2), 97%O(2)+3%CO(2), 95%O(2)+5%CO(2) (carbogen) and 92%O(2)+8%CO( 2). Arterial oxygen tension (pO(2)) and carbon dioxide tension (pCO(2)) were measured from arterialized blood samples from the earlobe. RESULTS Breathing 100% O(2) had no significant effect on ChBVel (-3.7%), ChBVol (+1.7%) and ChBF (-4.3%). Addition of 3% CO(2) to O(2) also produced no significant change on these blood flow parameters. In contrast, carbogen significantly increased ChBVel (10.0 +/- 4.4%, 95% CI, p < 0.001) and ChBF (12.5 +/- 11.7%, p = 0.002). The effect of 92% O(2) + 8% CO(2) was more pronounced since it significantly increased ChBVel and ChBF by 15.5 +/- 7.5% (p < 0.001) and 16.2 +/- 11.0% (p < 0.001), respectively. None of the gas mixtures induced a significant change in ChBVol. The increase in ChBF was approximately 1.5% per 1 mmHg increase in pCO(2). CONCLUSIONS This study demonstrates that, in healthy subjects, pCO(2) is an important determinant of foveal choroidal blood flow, whereas pO(2) has little impact on it.
The metabolic syndrome in schizophrenia: is inflammation a contributing cause?

This non-systematic review of the literature summarizes the evidence that inflammation plays a major role in the psychopathology of schizophrenia and in the mechanisms that contribute to physical ill health that is commonly associated with schizophrenia. The impact of prenatal infections on the developing brain, the possible genetic link between the human lymphocyte antigen gene, inflammation, heart disease and diabetes, together with the increase in pro-inflammatory cytokines in the blood and cerebrospinal fluid provide convincing evidence that inflammation is a major factor in the pathology of this disorder. The changes in immune-related markers and specific neurotransmitters associated with the positive symptoms of schizophrenia are described. In addition, the possible mechanism whereby structural changes occur in the brain is associated with the neurotoxic effects of pro-inflammatory cytokines, together with the neurotoxic metabolites from the tryptophan–kynurenine pathway that is activated by pro-inflammatory cytokines, is also discussed. The role of effective antipsychotic drug treatment in attenuating the inflammatory response is described. However, evidence is limited regarding the causal connection between atypical antipsychotic drugs and the changes in glucose and lipid metabolism that could trigger the onset of physical ill health, including diabetes and heart disease. Indeed, there is evidence that there is a metabolic predisposition to diabetes in patients with schizophrenia that is exacerbated by obesity and thereby contributes to cardiovascular disease and other co-morbid illnesses. It is concluded that the effects of inflammatory mediators on the brain causally contribute to the pathology of schizophrenia and the ill health that accompanies the disorder.
Cost-effectiveness of osimertinib in the UK for advanced EGFR-T790M non-small cell lung cancer

Abstract Aim: This study presents the cost-utility analysis that was developed to inform the NICE health technology assessment of osimertinib vs platinum-based doublet chemotherapy (PDC) in patients with EGFR-T790M mutation-positive non-small cell lung cancer (NSCLC) who have progressed on epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. Methods and materials: A partitioned survival model with three health states (progression-free, progressed disease, and death) from a UK payer perspective and over lifetime (15 years) was developed. Direct costs included disease management, treatment-related (acquisition, administration, monitoring, adverse events), and T790M testing costs. Efficacy and safety data were taken from clinical trials AURA extension and AURA2 for osimertinib and IMPRESS for PDC. An adjusted indirect treatment comparison was applied to reduce the potential bias in the non-randomized comparison. Parametric functions were utilized to extrapolate survival beyond the observed period. Health state utility values were calculated from EQ-5D data collected in the trials and valued using UK tariffs. Resource use and costs were based on published sources. Results: Osimertinib was associated with a gain of 1.541 quality-adjusted life-years (QALYs) at an incremental cost of £64,283 vs PDC (incremental cost-effectiveness ratio [ICER]: £41,705/QALY gained). Scenario analyses showed that none of the plausible scenarios produced an ICER above £44,000 per QALY gained, and probabilistic sensitivity analyses demonstrated a 63.4% probability that osimertinib will be cost-effective at a willingness-to-pay threshold of £50,000. Limitations: The analysis is subject to some level of uncertainty inherent to phase 2 single-arm data and the immaturity of the currently available survival data for osimertinib. Conclusions: Osimertinib may be considered a cost-effective treatment option compared with PDC in the second-line setting in patients with EGFR-T790M mutation-positive NSCLC from a UK payer perspective. Further data from the ongoing AURA clinical trial program will reduce the inherent uncertainty in the analysis.
ELUCIDATING THE FUNCTIONS OF SIALYLATION IN DROSOPHILA MELANOGASTER

Elucidating the Functions of Sialylation in Drosophila melanogaster. (August 2011) Mindy Nicole Carnahan, B.S., University of Illinois at Urbana-Champaign Chair of Advisory Committee: Dr Vladislav M. Panin Sialylation is an important carbohydrate modification of glycoconjugates, which introduces sialic acids (SA). The relatively large nine-carbon, negatively charged sugars are typically located at the termini of carbohydrate chains. SA‟s are often required for functionally important molecular and cellular interactions including virus-host interactions, tumor progression and malignancy, immune system development and function, and nervous system development and function. However, the study of sialylation in vertebrates, including man, encounters serious obstacles associated with the complexity of vertebrates‟ biology and limitations of available experimental approaches. Drosophila is a useful model system with many advantages including quick generation time, a large number of progeny, simplified glycosylation and neurophysiology, and ease of genetic manipulations. The primary focus of this thesis is on the functions of Drosophila melanogaster CMP sialic acid synthetase (DmCSAS) and sialyltransferase (DSiaT) in the central nervous system (CNS).
The effect of stability and change in health behaviors on trajectories of body mass index in older Americans: a 14-year longitudinal study.

BACKGROUND Obesity is increasingly prevalent among older adults, yet little is known about the impact of health behaviors on the trajectories of body weight in this age group. METHODS We examined the effect of time-varying smoking, physical activity (PA), alcohol use, and changes thereof, on the 14-year (1992-2006) trajectory of body- mass index (BMI) in a cohort of 10,314 older adults from the Health and Retirements Study, aged 51-61 years at baseline. Hierarchical linear modeling (HLM) quantifies the effect of smoking, PA, and alcohol use (user status, initiation and cessation) on intercept and rate-of-change in BMI trajectory, and tests for variations in the strength of association between each behavior and BMI. RESULTS Over 14 years (82,512 observations), BMI increased approximated by a quadratic function. Smoking and PA (user status and initiation) were associated with significantly lower BMI trajectories over time. Cessation of smoking and PA resulted in higher BMI trajectories over time. The weight-gaining effect of smoking cessation increased, while the strength of association between BMI trajectories and PA or alcohol use were constant over time. Socio-economic and health status differences explained the effects of alcohol use on BMI trajectory. CONCLUSIONS In older adults, smoking and PA, and changes thereof, vary in their long-term effect on trajectories of BMI. Barring increases in PA levels, older smokers who quit today are expected to gain significantly more weight than two decades ago. This knowledge is essential for the design of smoking cessation, physical activityPA, and weight-control interventions in older adults.
Motor unit number estimation and neuromuscular fidelity in 3 stages of sarcopenia

Introduction: Loss of motor units (MUs) and alterations in MU properties are major factors in development of sarcopenia. The purpose of this study was to compare MU properties among 3 groups categorized as either pre‐sarcopenic (n = 7), sarcopenic (n = 7), or severely sarcopenic (n = 5), all with similarly aged subjects (75–82 years). Methods: Using decomposition‐enhanced quantitative electromyography, MU number estimates and neuromuscular stability measures of near‐fiber (NF) jitter and jiggle were derived in addition to contractile properties of ankle dorsiflexors. Results: MU number estimates were similar across groups; however, maximal voluntary strength in the severe sarcopenia group was 27% and 37% less than the sarcopenic and pre‐sarcopenic groups, respectively. Moreover, NF jiggle was 31% greater in the severe group compared with pre‐sarcopenia, NF jitter was 43% greater in the severe group compared with the pre‐sarcopenic group. Conclusion: Unlike MU number estimates, strength and MU stability differed across groups and related to degree of sarcopenia. Muscle Nerve 55: 676–684, 2017