Miracle-dz/UniFAR-FTUs huggingface dataset:
Standardizing dose in dosimetric bronchial challenge tests

Recent technical recommendations on bronchial challenge testing aim at standardized assessment of provocative dose of causing 20% decrease in FEV1 (PD20). The aim of this study was to investigate the effect of mode of nebulization on the output of a computerized dosimeter (APS) and to compare PD20 obtained by two different dosimetric systems in vivo. The output of the APS system was tested during continuous nebulization, and using simulated breaths, for intermittent actuations with four different durations. Using output data, a modified methacholine challenge protocol was applied for APS and compared with a standard set‐up using Spira dosimeter in 14 asthmatic patients attending duplicate methacholine challenges using both systems, within median (range) 3 (1–6) days apart. The calculated output (mg min−1) with all the intermittent mode settings was significantly higher (P<0·001) than in the continuous mode, and in the intermittent mode, the output was dependent of the pulse duration. The PD20 values assessed with the APS and Spira systems were significantly correlated (r = 0·69; P<0·007), without systematic difference in the geometric means (P = 0·10). A moderate to good agreement was found for assessment of significant hyperresponsiveness. The results suggest that in dosimetric systems for bronchial challenge tests, the output of the nebulizer is dependent on the mode of nebulization, and this should be considered when standardizing the dose between devices and protocols. As long as the delivered dose is determined for the specified nebulization mode of the protocol, it may be possible to obtain comparable results between different devices.
Randomized comparison of cefepime and ceftazidime for treatment of skin, surgical wound, and complicated urinary tract infections in hospitalized subjects

We undertook a prospective, randomized open comparison of the broad-spectrum cephalosporins cefepime and ceftazidime in treatment of hospitalized subjects with skin or wound infections and complicated nosocomial urinary tract infections. Cefepime treatment (dosage, 2.0 g intravenously twice daily for 4 to 28 days) was successful in 36 (90%) of 40 infections of the skin and skin structure or wounds and in 16 (84%) of 19 nosocomial urinary tract infections. Ceftazidime treatment, 2.0 g every 8 h, was successful in 34 (96%) of 36 infections of the skin and skin structure and in 15 (88%) of 17 urinary tract infections. Microbiological eradication rates of each agent overall and for Pseudomonas aeruginosa were greater than 90%. In the cefepime group, one death occurred, contributed to by an enterococcal superinfection acquired during study drug therapy, and there were two mild and transient adverse experiences observed. Cefepime was comparable to ceftazidime in treatment of infections of the skin and skin structure requiring hospitalization and of complicated nosocomial urinary tract infections.
Ankle instability effects on joint position sense when stepping across the active movement extent discrimination apparatus.

CONTEXT Individuals with and without functional ankle instability have been tested for deficits in lower limb proprioception with varied results. OBJECTIVE To determine whether a new protocol for testing participants' joint position sense during stepping is reliable and can detect differences between participants with unstable and stable ankles. DESIGN Descriptive laboratory study. SETTING University clinical laboratory. PATIENTS OR OTHER PARTICIPANTS Sample of convenience involving 21 young adult university students and staff. Ankle stability was categorized by score on the Cumberland Ankle Instability Tool; 13 had functional ankle instability, 8 had healthy ankles. INTERVENTION(S) Test-retest of ankle joint position sense when stepping onto and across the Active Movement Extent Discrimination Apparatus twice, separated by an interim test, standing still on the apparatus and moving only 1 ankle into inversion. MAIN OUTCOME MEASURE(S) Difference in scores between groups with stable and unstable ankles and between test repeats. RESULTS Participants with unstable ankles were worse at differentiating between inversion angles underfoot in both testing protocols. On repeated testing with the stepping protocol, performance of the group with unstable ankles was improved (Cohen d = 1.06, P = .006), whereas scores in the stable ankle group did not change in the second test (Cohen d = 0.04, P = .899). Despite this improvement, the unstable group remained worse at differentiating inversion angles on the stepping retest (Cohen d = 0.99, P = .020). CONCLUSIONS The deficits on proprioceptive tests shown by individuals with functional ankle instability improved with repeated exposure to the test situation. The learning effect may be the result of systematic exposure to ankle-angle variation that led to movement-specific learning or increased confidence when stepping across the apparatus.
The effect of maternal and paternal immune challenge on offspring immunity and reproduction in a cricket

Trans‐generational immune priming is the transmission of enhanced immunity to offspring following a parental immune challenge. Although within‐generation increased investment into immunity demonstrates clear costs on reproductive investment in a number of taxa, the potential for immune priming to impact on offspring reproductive investment has not been thoroughly investigated. We explored the reproductive costs of immune priming in a field cricket, Teleogryllus oceanicus. To assess the relative importance of maternal and paternal immune status, mothers and fathers were immune‐challenged with live bacteria or a control solution and assigned to one of four treatments in which one parent, neither or both parents were immune‐challenged. Families of offspring were reared to adulthood under a food‐restricted diet, and approximately 10 offspring in each family were assayed for two measures of immunocompetence. We additionally quantified offspring reproductive investment using sperm viability for males and ovary mass for females. We demonstrate that parental immune challenge has significant consequences for the immunocompetence and, in turn, reproductive investment of their male offspring. A complex interaction between maternal and paternal immune status increased the antibacterial immune response of male offspring. This increased immune response was associated with a reduction in son's sperm viability, implicating a trans‐generational resource trade‐off between investment into immunocompetence and reproduction. Our data also show that these costs are sexually dimorphic, as daughters did not demonstrate a similar increase in immunity, despite showing a reduction in ovary mass.
Predicting early onset of male antisocial behavior from preschool behavior.

METHODS Data from a large longitudinal study of boys who were between kindergarten and age 13 years were used to (1) test whether Gray's and Cloninger's personality dimensions measured in kindergarten predicted the early onset of stable, highly delinquent behavior; (2) test whether 1, 2, or 3 dimensions were needed; and (3) test the predictive value of a categorical approach. RESULTS The impulsivity dimension was the best predictor of the early onset of stable, highly delinquent behavior. Anxiety and reward dependence made significant but weaker contributions. The categorical approach corroborated Cloninger's suggestion that boys who are high in impulsivity, low in anxiety, and low in reward dependence would be more at risk for delinquent involvement. Boys who were high in impulsivity and low in anxiety but high in reward dependence were much less at risk for delinquency. Differences in antisocial behavior among extreme kindergarten personality groups were stable from ages 11 to 13 years. CONCLUSIONS The behavioral activating system appears to be the major dimension underlying the propensity toward early onset of antisocial behavior, but both the behavioral inhibition system and the need for social rewards play important roles. The behavioral style (personality) that results from the interplay of these systems is clearly in place by the kindergarten year. Preventive efforts should target preschool children with at-risk behavior profiles. However, longitudinal-experimental studies with at least yearly assessments between birth and school-entry age are needed to understand the extent to which the behavioral styles are antecedent to preschool disruptive behavior disorders.
Coinfection With HIV-1 and Human T-Cell Lymphotropic Virus Type II in Intravenous Drug Users Is Associated With Delayed Progression to AIDS

Human T-cell lymphotropic virus (HTLV) type II has spread among intravenous drug users (IDUs), many of whom are coinfected with HIV-1. We have investigated the rate of HTLV-II infection in 3574 Italian IDUs screened for HIV-1, HTLV-I, and HTLV-II from 1986 to the present. HTLV-II proviral load was determined by a real-time polymerase chain reaction specifically designed for tax amplification. The frequency of HTLV-II infection was 6.7% among HIV-1-positive subjects and 1.1% among HIV-1-negative subjects (P < 0.0001). For examination of AIDS progression, a group of 437 HIV-1-monoinfected subjects and another group of 96 HIV-1/HTLV-II-coinfected subjects were monitored. Enrollees were matched at entry by CD4 cell counts and followed for an average of 13 years. HIV-1/HTLV-II coinfection was associated with older age (P < 0.0001) and higher CD4 (P < 0.0001) and CD8 (P < 0.001) cell counts compared with monoinfected IDUs. The number of long-term nonprogressors for AIDS was significantly higher (P < 0.0001) among coinfected patients (13 [13.5%] of 96 patients) than HIV monoinfected patients (5 [1.1%] of 437 patients), showing that HTLV-II exerts a protective role. An increased incidence of liver disease and hepatitis C virus positivity among coinfected IDUs was observed. Five coinfected subjects undergoing antiretroviral therapy showed a significant (P < 0.05) increase in HTLV-II proviral load concomitant to a decrease in HIV-1 viremia, suggesting that the treatment is ineffective against HTLV-II infection.
Effects of Subchronic Exposures to Concentrated Ambient Particles (CAPs) in Mice: III. Acute and Chronic Effects of CAPs on Heart Rate, Heart-Rate Fluctuation, and Body Temperature

Abstract Normal mice (C57) and mice prone to develop atherosclerosis (ApoE−/−) were implanted with electrocardiograph (EKG), core body temperature, and motion transmitters and were exposed daily for 6 h to Tuxedo, NY, concentrated ambient particles (CAPs) for 5 days/wk during the spring and summer of 2003. Time series of 5-min EKG monitoring and body-temperature measurements were obtained for each animal in the CAPs and filtered air sham exposure groups. Our hypothesis was that chronic exposure could cause cumulative health effects. We used our recently developed nonparametric method to estimate the daily time periods that mean heart rates (HR), body temperature, and physical activity differed significantly between the CAPs and sham exposed groups. CAPs exposure most affected heart rate between 1:30 a.m. and 4:30 a.m. With the response variables being the average heart rate, body temperature, and physical activity, we adopted a two-stage modeling approach to obtain the estimates of chronic and acute effects on the changes of these three response variables. In the first stage, a time-varying model estimated daily crude effects. In the second stage, the true means of the estimated crude effects were modeled with a polynomial function of time for chronic effects, a linear term of daily CAPs exposure concentrations for acute effects, and a random component for unknown noise. A Bayesian framework combined these two stages. There were significant decreasing patterns of HR, body temperature, and physical activity for the ApoE−/− mice over the 5 mo of CAPs exposure, with smaller and nonsignificant changes for the C57 mice. The chronic effect changes of the three response variables for ApoE−/− mice were maximal in the last few weeks. There was also a significant relationship between CAPs exposure concentration and short-term change of heart rate in ApoE−/− mice during exposure. Response variables were also defined for examining fluctuations of 5-min heart rates within long (i.e., 3–6 h) and short time periods (i.e., ∼ 15 min). The results for the ApoE−/− mice showed that heart- rate fluctuation within the longer periods increased to 1.35-fold by the end of exposure experiment, while the heart-rate fluctuation within 15 min decreased to 0.7-fold.
Ultrasound guidance allows accurate needle placement and aspiration from small joints in patients with early inflammatory arthritis.

OBJECTIVES To compare the accuracy of palpation-guided and high frequency ultrasound-guided needle placement in small joints and to develop a technique to obtain synovial fluid from these joints for diagnosis and research. METHODS The accuracy of needle placement during palpation-guided proximal interphalangeal (PIP) or metacarpophalangeal (MCP) joint injection was assessed. This was compared with the accuracy of ultrasound-guided needle placement. A joint lavage technique was developed to obtain synovial fluid from these joints. RESULTS Needle positioning was intra-articular in 59% of palpation-guided injections (6/12 PIP and 4/5 MCP joints). No fluid could be aspirated prior to injection. With ultrasound guidance, initial needle placement was intra-articular in 96% of cases (24/26 PIP and 27/27 MCP joints). Synovial fluid cells were lavaged from 63% of joints (19/25 PIP and 14/27 MCP joints). In only one case was a large effusion seen and this was aspirated directly. CONCLUSIONS The use of high frequency ultrasound to guide needle placement within a small joint allows for significantly greater accuracy than a palpation-guided approach. When followed by lavage, synovial fluid cells and diluted synovial fluid can be obtained from the majority of small joints. This has important clinical and research implications.
Dynamic signaling for neural stem cell fate determination

Central nervous system (CNS) development starts from neural stem cells (NSCs) which ultimately give rise to the three major cell types (neurons, oligodendrocytes and astrocytes) of the CNS. NSCs are specified in space- and time-related fashions, becoming spatially heterogeneous and generating a progressively restricted repertoire of cell types. Mammalian NSCs produce different cell types at different time points during development under the influence of multiple signaling pathways. These pathways act in a dynamic web mode to determine the fate of NSCs via modulating the expression and activity of distinct set of transcription factors which in turn trigger the transcription of neural fate-associated genes. This review thus introduces the major signal pathways、transcription factors and their cross-talks and coordinative interactions in NSC fate determination.
Inflammation-mediated skin tumorigenesis induced by epidermal c-Fos

Briso et al. find that c-fos expression in the mouse epidermis is sufficient to promote inflammation-mediated epidermal hyperplasia. c-Fos transcriptionally controls mmp10 and s100a7a15 expression in keratinocytes, promoting CD4 T-cell recruitment to the skin. Combining c-fos expression with the carcinogen DMBA leads to the development of highly invasive SCCs, which was prevented by the anti-inflammatory drug sulindac. Human SCCs display a correlation between c-FOS and MMP10 and S100A15 proteins as well as CD4 T-cell infiltration. This work reveals promising therapeutic strategies to treat SCCs.
EFFECTS OF CANNABINOID RECEPTOR ACTIVATION ON RABBIT BISECTED VAS DEFERENS STRIPS

1. In the present study, the effects of anandamide and WIN 55,212‐2, cannabinoid receptor agonists, were investigated on electrical field stimulation (EFS)‐induced biphasic twitch responses obtained from the epididymal and prostatic portions of rabbit vas deferens strips.
Human Mutation within Per-Arnt-Sim (PAS) Domain-containing Protein Kinase (PASK) Causes Basal Insulin Hypersecretion

Background: The glucose sensor PAS kinase (PASK) plays a fundamental role in pancreatic islet physiology. Results: A single amino acid substitution in the human PASK kinase domain stimulates enzyme activity and increases insulin secretion at low glucose. Conclusion: A rare, naturally occurring mutation in PASK modulates insulin release in man. Significance: We provide direct genetic evidence for a role for PASK in controlling insulin secretion in man. PAS kinase (PASK) is a glucose-regulated protein kinase involved in the control of pancreatic islet hormone release and insulin sensitivity. We aimed here to identify mutations in the PASK gene that may be associated with young-onset diabetes in humans. We screened 18 diabetic probands with unelucidated maturity-onset diabetes of the young (MODY). We identified two rare nonsynonymous mutations in the PASK gene (p.L1051V and p.G1117E), each of which was found in a single MODY family. Wild type or mutant PASKs were expressed in HEK 293 cells. Kinase activity of the affinity-purified proteins was assayed as autophosphorylation at amino acid Thr307 or against an Ugp1p-derived peptide. Whereas the PASK p.G1117E mutant displayed a ∼25% increase with respect to wild type PASK in the extent of autophosphorylation, and a ∼2-fold increase in kinase activity toward exogenous substrates, the activity of the p.L1051V mutant was unchanged. Amino acid Gly1117 is located in an α helical region opposing the active site of PASK and may elicit either: (a) a conformational change that increases catalytic efficiency or (b) a diminished inhibitory interaction with the PAS domain. Mouse islets were therefore infected with adenoviruses expressing wild type or mutant PASK and the regulation of insulin secretion was examined. PASK p.G1117E-infected islets displayed a 4-fold decrease in glucose-stimulated (16.7 versus 3 mm) insulin secretion, chiefly reflecting a 4.5-fold increase in insulin release at low glucose. In summary, we have characterized a rare mutation (p.G1117E) in the PASK gene from a young-onset diabetes family, which modulates glucose-stimulated insulin secretion.
Therapeutic benefit of melatonin in experimental feline uveitis

Abstract: Uveitis is a frequent ophthalmic disorder which constitutes one of the main causes of blindness in domestic cats. The aim of this report was to analyze the effect of melatonin on experimentally induced uveitis in cats. Bacterial lipopolysaccharide (LPS) was injected intravitreally into one eye from intact cats, while the contralateral eye was injected with vehicle. Melatonin was orally administered every 24 hr to a group of ten cats, from 24 hr before until 45 days after intravitreal injections. Eyes were evaluated by means of clinical evaluation, intraocular pressure (IOP), blood–ocular barrier integrity (via measurement of protein concentration and cell content in samples of aqueous humor [AH]), electroretinogram (ERG), and histological examination of the retinas. In LPS‐treated eyes, several clinical signs were observed until day 45 postinjection. The treatment with melatonin significantly decreased clinical signs and prevented the reduction in IOP induced by LPS. In LPS‐injected eyes, melatonin significantly preserved the blood–ocular barrier integrity, as shown by a decrease in the number of infiltrating cells and protein concentration in the AH. Mean amplitudes of scotopic ERG a‐ and b‐waves were significantly reduced in eyes injected with LPS, whereas melatonin significantly prevented the effect of LPS. At 45 days after injection, LPS induced alterations in photoreceptors and at the middle portion of the retina, whereas melatonin preserved the retinal structure. These results indicate that melatonin prevented clinical, biochemical, functional, and histological alterations induced by LPS injection. Thus, melatonin might constitute a useful tool for the treatment of feline uveitis.
Artemether-lumefantrine (six-dose regimen) for treating uncomplicated falciparum malaria.

BACKGROUND The World Health Organization recommends artemether-lumefantrine for treating uncomplicated malaria. We sought evidence of superiority of the six-dose regimen over existing treatment regimens as well as its effectiveness in clinical situations. OBJECTIVES To evaluate the six-dose regimen of artemether-lumefantrine for treating uncomplicated falciparum malaria. SEARCH STRATEGY We searched the Cochrane Infectious Diseases Group Specialized Register (April 2005), CENTRAL (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to April 2005), EMBASE (1974 to April 2005), LILACS (1982 to April 2005), conference proceedings, and reference lists of articles. We also contacted experts in malaria research and the pharmaceutical company that manufactures artemether-lumefantrine. SELECTION CRITERIA Randomized controlled trials comparing six doses of artemether-lumefantrine administered orally with standard treatment regimens (single drug or combination), or supervised with unsupervised treatment, for uncomplicated falciparum malaria. DATA COLLECTION AND ANALYSIS Two authors independently applied inclusion criteria to potentially relevant trials, assessed trial quality, and extracted data, including adverse events. Total failure by day 28 (day 42 for sulfadoxine-pyrimethamine and day 63 for mefloquine) was the primary outcome. MAIN RESULTS Nine trials (4547 participants) tested the six-dose regimen. Total failure at day 28 for artemether-lumefantrine was lower when compared with amodiaquine (270 participants, 1 trial), amodiaquine plus sulfadoxine-pyrimethamine (507 participants, 1 trial), but not with chloroquine plus sulfadoxine-pyrimethamine (201 participants, 2 trials). In comparisons with artemisinin derivative combinations, artemether-lumefantrine performed better than amodiaquine plus artesunate (668 participants, 2 trials), worse than mefloquine plus artesunate (270 participants, 4 trials), and no differently to dihydroartemisinin-napthoquine-trimethoprim (89 participants, 1 trial). AUTHORS' CONCLUSIONS The six-dose regimen of artemether-lumefantrine appears more effective than antimalarial regimens not containing artemisinin derivatives.