Miracle-dz/UniFAR-FTUs huggingface dataset:
Cold and L-menthol-induced sensitization in healthy volunteers—a cold hypersensitivity analogue to the heat/capsaicin model

Abstract Topical high-concentration L-menthol is the only established human experimental pain model to study mechanisms underlying cold hyperalgesia. We aimed at investigating the combinatorial effect of cold stimuli and topical L-menthol on cold pain and secondary mechanical hyperalgesia. Analogue to the heat–capsaicin model on skin sensitization, we proposed that cold/menthol enhances or prolong L-menthol-evoked sensitization. Topical 40% L-menthol or vehicle was applied (20 minutes) on the volar forearms of 20 healthy females and males (age, 28.7 ± 0.6 years). Cold stimulation of 5°C for 5 minutes was then applied to the treated area 3 times with 40-minute intervals. Cold detection threshold and pain, mechanical hyperalgesia (pinprick), static and dynamic mechanical allodynia (von Frey and brush), skin blood flow (laser speckle), and temperature (thermocamera) were assessed. Cold detection threshold and cold pain threshold (CPT) increased after L-menthol and remained high after the cold rekindling cycles (P < 0.001). L-menthol evoked secondary hyperalgesia to pinprick (P < 0.001) particularly in females (P < 0.05) and also induced secondary allodynia to von Frey and brush (P < 0.001). Application of cold stimuli kept these areas enlarged with a higher response in females to brush after the third cold cycle (P < 0.05). Skin blood flow increased after L-menthol (P < 0.001) and stayed stable after cold cycles. Repeated application of cold on skin treated by L-menthol facilitated and prolonged L-menthol–induced cold pain and hyperalgesia. This model may prove beneficial for testing analgesic compounds when a sufficient duration of time is needed to see drug effects on CPT or mechanical hypersensitivity.
Granulocyte Elastase, Tumor Necrosis Factor-α and Urokinase Levels as Prognostic Markers in Severe Infection

Summary We have examined the prognostic value of the levels in the blood of granulocyte elastase-α1-proteinase inhibitor (E-α1-PI) complex, tumor necrosis factor-α (TNF-α) and urokinase-type plasminogen activator (u-PA) in 35 patients with severe infection upon admission to an Intensive Care Unit. Fourteen patients died. No differences for E-α1-PI complex were found between survivors and nonsurvivors, but in all patients the levels on admission were eight-fold higher than the reference value. TNF-α levels, measured by immunoassay, on admission were four times higher in the nonsurvivors than in the survivors (p = 0.0003) and correlated with the severity of the disease (APACHE II score, r = 0.43, p <0.05). TNF-α was not detectable by bioassay. Total u-PA antigen (u-PA Ag), plasmin-activatable single-chain u-PA (scu-PA) and inactive, nonactivatable u-PA (u-PA#) were on admission all two-fold higher in the nonsurvivors (p = 0.0006, 0.003 and 0.0003, respectively), while normal in the survivors. In both, survivors and nonsurvivors, the ratio between scu-PA and u-PA Ag was significantly decreased (p <0.001, compared to a reference group of healthy volunteers), indicative for enhanced conversion of scu-PA to active two-chain u-PA (tcu-PA) and inactive u-PA# during severe infectious disease. tcu-PA was detected in nine of the 35 patients, while virtually undetectable in controls. scu-PA correlated with the Child-Pugh score on admission (r = 0.42, p <0.05). TNF-α correlated with u-PA Ag (r = 0.38, p <0.05) and with u-PA# (r = 0.47, p <0.01). In a stepwise logistic regression analysis, documentation of infection and plasma levels of u-PA Ag contributed most significantly to prediction of patient outcome. Serum levels of TNF-α did not. These results suggest that, in addition to a number of other clinical and laboratory parameters, u-PA Ag can be used as a prognostic marker in patients with severe infection admitted to an Intensive Care Unit.
Racial/Ethnic Pay Disparities among Registered Nurses (RNs) in U.S. Hospitals: An Econometric Regression Decomposition.

OBJECTIVE To detect the presence of racial and ethnic pay disparities between minority and white hospital RNs using a national sample. DATA SOURCES/STUDY SETTING The National Sample Survey of Registered Nurses, 2008, which is representative at both the state and national level. STUDY DESIGN Cross-sectional data were analyzed using multivariate regression and regression decomposition. Differences between groups were decomposed into differences in the possession of characteristics and differences in the value of the same characteristic between different groups, the latter being a commonly used measure of wage discrimination. DATA COLLECTION/EXTRACTION METHODS As the majority of minority hospital RNs are employed within the most densely populated (central) counties of metropolitan statistical areas (MSAs), only hospital RNs employed in the central counties of MSAs were selected. PRINCIPAL FINDINGS Regression decomposition found that black and Hispanic RNs earned less than whites and Asians, while Asian RNs earned more than white RNs. The majority of pay variation between white RNs, versus Asian, black, or Hispanic RNs was due to unexplained differences in the value of the same characteristic between groups. CONCLUSIONS Differences in earnings between underrepresented and overrepresented hospital RNs is suggestive of discrimination.
Carbon dioxide sensitivity during hypoglycaemia‐induced, elevated metabolism in the anaesthetized rat

We have utilized an anaesthetized rat model of insulin‐induced hypoglycaemia to test the hypothesis that peripheral chemoreceptor gain is augmented during hypermetabolism. Insulin infusion at 0.4 U kg −1min−1 decreased blood glucose concentration significantly to 3.37 ± 0.12 mmol l−1. Whole‐body metabolism and basal ventilation were elevated without increase in P a,CO 2 (altered non‐significantly from the control level, to 37.3 ± 2.6 mmHg). Chemoreceptor gain, measured either as spontaneous ventilatory airflow sensitivity to P a,CO 2 during rebreathing, or by phrenic minute activity responses to altered P a,CO 2 induced by varying the level of artificial ventilation, was doubled during the period of hypermetabolism. This stimulatory effect was primarily upon the mean inspiratory flow rate, or phrenic ramp component of breathing and was reduced by 75% following bilateral carotid sinus nerve section. In vitro recordings of single carotid body chemoafferents showed that reducing superfusate glucose concentration from 10 mm to 2 mm reduced CO2 chemosensitivity significantly from 0.007 ± 0.002 Hz mmHg−1 to 0.001 ± 0.002 Hz mmHg−1. Taken together, these data suggest that the hyperpnoea observed during hypermetabolism might be mediated by an increase in the CO2 sensitivity of the carotid body, and this effect is not due to the insulin‐induced fall in blood glucose concentration.
Developmental outcomes in early school-age children with minimal hearing loss.

PURPOSE Previous research suggests that school-age children with minimal hearing loss (CMHL) are at risk for a variety of psychoeducational problems. However, CMHL are a heterogeneous group, and the profile of at-risk children is unknown. Data regarding the characteristics of early school-age CMHL are needed to extend previous findings and determine potential risk factors associated with psychoeducational difficulties. METHOD Psychoeducational outcomes were evaluated at baseline and longitudinally in age-matched groups of 27 CMHL (ages 4–10 years) and 26 children with normal hearing (CNH) using assessments of language, reading, behavior, speech recognition in noise, and cognition. Additional analyses were used to identify demographic characteristics among CMHL that are associated with psychoeducational difficulties. RESULTS At the earliest age tested, CMHL had greater teacher-rated attention difficulties in the classroom than CNH. Differences in the rate of psychoeducational development were not observed between groups. Among CMHL, psychoeducational difficulties were associated with delays in identification of hearing loss and low maternal education. CONCLUSIONS Classroom attention abilities should be monitored for early school-age CMHL. Late-identified CMHL and CMHL with low maternal education levels may be in particular need of academic and social support. Continued efforts for early identification of CMHL should be made to improve outcomes for these children.
Biochemical and Structural Studies of Malate Synthase fromMycobacterium tuberculosis *

Establishment or maintenance of a persistent infection by Mycobacterium tuberculosis requires the glyoxylate pathway. This is a bypass of the tricarboxylic acid cycle in which isocitrate lyase and malate synthase (GlcB) catalyze the net incorporation of carbon during growth of microorganisms on acetate or fatty acids as the primary carbon source. The glcB gene from M. tuberculosis, which encodes malate synthase, was cloned, and GlcB was expressed inEscherichia coli. The influence of media conditions on expression in M. tuberculosis indicated that this enzyme is regulated differentially to isocitrate lyase. Purified GlcB hadK m values of 57 and 30 μm for its substrates glyoxylate and acetyl coenzyme A, respectively, and was inhibited by bromopyruvate, oxalate, and phosphoenolpyruvate. The GlcB structure was solved to 2.1-Å resolution in the presence of glyoxylate and magnesium. We also report the structure of GlcB in complex with the products of the reaction, coenzyme A and malate, solved to 2.7-Å resolution. Coenzyme A binds in a bent conformation, and the details of its interactions are described, together with implications on the enzyme mechanism.
Comparison of electromagnetic and hadronic models generated using Geant 4 with antiproton dose measured in CERN

After proposing the idea of antiproton cancer treatment in 1984 many experiments were launched to investigate different aspects of physical and radiobiological properties of antiproton, which came from its annihilation reactions. One of these experiments has been done at the European Organization for Nuclear Research known as CERN using the antiproton decelerator. The ultimate goal of this experiment was to assess the dosimetric and radiobiological properties of beams of antiprotons in order to estimate the suitability of antiprotons for radiotherapy. One difficulty on this way was the unavailability of antiproton beam in CERN for a long time, so the verification of Monte Carlo codes to simulate antiproton depth dose could be useful. Among available simulation codes, Geant4 provides acceptable flexibility and extensibility, which progressively lead to the development of novel Geant4 applications in research domains, especially modeling the biological effects of ionizing radiation at the sub-cellular scale. In this study, the depth dose corresponding to CERN antiproton beam energy by Geant4 recruiting all the standard physics lists currently available and benchmarked for other use cases were calculated. Overall, none of the standard physics lists was able to draw the antiproton percentage depth dose. Although, with some models our results were promising, the Bragg peak level remained as the point of concern for our study. It is concluded that the Bertini model with high precision neutron tracking (QGSP_BERT_HP) is the best to match the experimental data though it is also the slowest model to simulate events among the physics lists.
TLR-4+ peripheral blood monocytes and cardiovascular events in patients with chronic kidney disease--a prospective follow-up study.

BACKGROUND Atherosclerosis is an inflammatory process mediated by circulating immune cells, including monocytes. There is accumulating evidence for the involvement of Toll-like receptor 4 (TLR-4) as a mediator of atherogenesis. METHODS We evaluated the association between CD14+/TLR-4+ monocytes in peripheral blood (flow cytometry) and future cardiovascular events (CVE), e.g. myocardial infarction, percutaneous transluminal coronary angioplasty (including stenting), aortocoronary bypass, stroke and angiographically verified stenosis of peripheral arteries and cardiovascular (CV) death, in 191 patients with chronic kidney disease Stage V receiving hemodialysis therapy. RESULTS At baseline, CD14+/TLR-4+ monocytes correlated significantly with age (r = 0.2; P = 0.007), high-sensitivity C-reactive protein (r = 0.2; P = 0.008) and mean arterial pressure (r = -0.2; P = 0.02), but not with gender (P = 0.5), smoking (P = 0.6) and the presence of diabetes (P = 0.5). During a median follow-up period of 36 [1-54] months, 79 (41%) patients experienced a CVE. A total of 55 patients died during the follow-up period, 25 of those due to a confirmed CV cause. Log-rank test did not reveal statistical significance for TLR-4+ monocytes concerning incident CVE (P = 0.3), CV death (P = 0.85) and overall death (P = 0.8). In a multiple Cox-regression analysis, we identified age (P = 0.003) and smoking (P = 0.001) as the only independent variables associated with incident CVE. CONCLUSIONS Unexpectedly, we could not detect an association between CD14+/TLR-4+ monocytes and incident CVE as well as CV death in stable hemodialysis patients. Further studies have to clarify the potential role of this cell population for CV outcome in this population.
Involvement of Nox2 and Nox4 NADPH oxidases in early brain injury after subarachnoid hemorrhage

Abstract Oxidative stress is responsible for a poor prognosis of subarachnoid hemorrhage (SAH) patients. Nox2 has been shown to participate in SAH-induced early brain injury (EBI). Nox4 is another major subtype of Nox family widely expressed in central nervous system (CNS). Here, we investigated the role of Nox4 and whether there was a synergistic effect of Nox2 and Nox4 in SAH-induced EBI. Clinical brain biopsies of four patients with traumatic brain injury (TBI) and perihematomal brain tissue from six subjects with SAH were examined. Gp91ds-tat (a specific inhibitor of Nox2), GKT137831 (a specific inhibitor of Nox4), and apocynin (a non-specific Nox inhibitor) were used to test the role of Nox2 and Nox4. The protein levels of Nox2 and Nox4 were elevated in rat neurons and astrocytes at 12 h after SAH, and in cultured brain microvascular endothelial cells at 24 h after exposure to OxyHb. Similarly, there were higher Nox2 and Nox4 protein levels in perihematomal neurons and astrocytes in SAH patients than that in brain tissue from subjects with TBI. In SAH rat model, gp91ds-tat and GKT137831 could reduce SAH-induced neuronal death and degeneration, whereas apocynin did not induce a more intense neuroprotection. Consistently, in in vitro SAH model, siRNA-mediated silencing of Nox2 and Nox4 suppressed the OxyHb-induced neuronal apoptosis, whereas Nox2 and Nox4 co-knockdown also did not show a remarkable overlay effect. In conclusion, Nox4 should contribute to the pathological processes in SAH-induced EBI, and there was not an overlay effect of Nox2 inhibition and Nox4 inhibition on preventing SAH-induced EBI.
Involvement of Hydrogen Peroxide in the Manganese-Induced Myocytes Mitochondrial Membrane Potential Loss

Isolated rat ventricular myocytes were incubated in different manganese concentrations and after that the reactive oxygen species (ROS) generation, the level of reduced glutathione (GSH), and the changes of mitochondrial membrane potential (Δψ m) were investigated by a flow cytometer (FACScan) as well as laser scanning confocal microscopy (LSCM). Results showed that, although the total ROS in the cell were increased after manganese treatment, hydrogen peroxide (H2O2) was the main elevated species while superoxide anion (O2·−) was nearly unchanged. The generation of H2O2 became obvious when the myocytes were incubated in the higher concentration of manganese. The content of GSH in myocytes also decreased after manganese exposure. When the myocytes were incubated with both manganese and GSH-ethylester (GSH-EE), which is permeable to the cell membrane, the generation of H2O2 decreased greatly. The loss of the mitochondrial membrane potential (Δψ m) was also induced by manganese incubation. However, with the existence of extracellular GSH-EE the Δψ m were rescued. The results suggested that manganese action may lead to the ROS stress upon myocytes which most probably rise from high generation of intracellular H2O2. GSH-EE could effectively clean the over-production of H2O2, indicating that the low level of intracellular GSH was another main reason to the high accumulation of H2O2. The mitochondrial membrane potential was also affected by manganese and rescued by GSH-EE, suggesting that H2O2 was also involved in the manganese damages to the mitochondrial membrane potential.
Abundance and distribution of fleas on desert rodents: linking Taylor's power law to ecological specialization and epidemiology

We investigated variation in the abundance-prevalence relationships of fleas among 17 different flea-host associations as well as among different species of hosts and fleas in the Negev desert. We explored variation in the value of exponent of Taylor's power relationship with changes in flea community size and flea specialization (host specificity and seasonal pattern of activity). We tested if a simple epidemiological model can reproduce the pattern of the abundance-prevalence relationship. We confirmed aggregated distribution of fleas within a population of host species as well as across a whole host community and the existence of a positive relationship between local flea abundance and their prevalence. Prevalence, mean abundance and variance of abundance were significantly higher in host specific than host opportunistic fleas. When ecological specialization was considered, based on a seasonal pattern of activity, these parameters were higher in year-round-active than seasonal fleas. The degree of flea specialization and flea community richness affected the pattern of the relationship between mean abundance and its variance. Power law slopes decreased with increasing richness of flea community. A simple epidemiological model based on mean flea abundance and degree of aggregation, corrected for host sample size, can predict the observed pattern of prevalence. In some cases, observed flea prevalence was higher than that predicted from the epidemiological model. The discrepancy of the observed prevalence from that predicted by the model can be explained by either a relatively low negative effect of flea parasitism on a host (at least, in terms of pathology) or strong resistance of a host to flea parasitism or both.
Fine‐needle aspiration findings in Castleman's disease

Castleman's disease of the hyaline vascular subtype is an uncommon lesion; experience with fine‐needle aspiration (FNA) of this tumor is limited to rare case reports. We describe the cytologic, flow cytometric, and immunohistochemical findings in two cases initially sampled by FNA. Two females, aged 40 and 26 yr, were found incidentally to have an oropharyngeal and a mediastinal mass, respectively. Neither complained of systemic symptoms, and both had a normal routine laboratory workup. FNA followed by surgical excision in both cases was consistent with Castleman's disease of the hyaline vascular type. In the appropriate clinical context, a mature small lymphoid population associated with larger atypical cells, which are consistent with follicular dendritic cells, can be suggestive of Castleman's disease. Confirmation of a polytypic B‐cell population by flow cytometry, supported by immunohistochemistry, is very helpful. However, definitive distinction from Hodgkin's lymphoma on FNA is probably not possible. Diagn. Cytopathol. 1999;21:57–60. © 1999 Wiley‐Liss, Inc.
Beyond the hippocampus

Objective: To examine volumetric changes in limbic structures in patients with probable AD using planimetric measures on MRI. Method: Limbic structures (i.e., hippocampus, amygdala, anterior thalamus, hypothalamus, mamillary bodies, basal forebrain, septal area, fornix, and cingulate, orbitofrontal, and parahippocampal cortices) were traced on 3D T1-weighted MR images of 40 patients with mild to moderate AD and 40 age-, sex-, and education-matched normal control subjects. Limbic volumes were compared between groups and the predictive ability was assessed. Results: Overall, limbic structures showed significant atrophy in AD patients compared with normal control subjects. Differences (p < 0.05) were found in all limbic regions except the anterior cingulate cortex. The greatest percentage volumetric losses occurred in the septal area (34%), hippocampus (28%), amygdala (21%), parahippocampal cortex (21%), and posterior cingulate cortex (20%). Combining volumetric measures of amygdala and septal area distinguished patients with AD from normal control subjects with 93% accuracy. Conclusions: These results verify that system-wide limbic degeneration occurs in patients with AD. In addition, atrophy in selected limbic structures was used to distinguish patients with AD from normal elderly individuals with over 90% accuracy in this select clinical sample. The measures require further exploration in samples more representative of those seen by primary care physicians before their utility can be accurately assessed.
Comparisons Between Alzheimer Disease, Frontotemporal Lobar Degeneration, and Normal Aging With Brain Mapping

Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD) are both common degenerative dementias in the under 65 age group. Although clinical criteria have been defined for both diseases, there is considerable overlap in clinical features, and hence, diagnosis still can be very difficult particularly in the early stages of the disease. As a result, there has been increasing interest in using magnetic resonance imaging to better characterize these diseases and to aid in diagnosis. Voxel-based morphometry (VBM) is an automated technique that assesses patterns of regional gray matter atrophy on magnetic resonance imaging between 2 groups of subjects. It is unbiased in that it looks throughout the whole brain and does not require any a priori assumptions concerning which structures to assess, giving it a significant advantage over traditional region of interest-based methods. Voxel-based morphometry has been widely used to assess patterns of regional atrophy in subjects with AD and FTLD. These studies have demonstrated specific patterns of regional loss in both diseases, compared the 2 diseases to look for differences that could be diagnostically useful, and have correlated regions of gray matter loss to cognitive and behavioral deficits in these subjects. This article will review the findings of these studies and discuss the role of VBM in these neurodegenerative diseases.
Transpedicular Convex Anterior Hemiepiphysiodesis and Posterior Arthrodesis for Progressive Congenital Scoliosis

Nine children with progressive congenital scoliosis underwent bilateral posterior spinal fusion supplemented with transpedicular convex anterior hemieplphysiodesis. The average preoperative curve was 52°. The average age at surgery was 9 years and 1 month and the average follow-up period was 3 years and 6 months. Curve progression was arrested in all cases, and curve correction greater than 10° was achieved in four patients.