Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of wheezing phenotypes with fractional exhaled nitric oxide in children

Asthma comprises a heterogeneous group of disorders characterized by airway inflammation, airway obstruction, and airway hyperresponsiveness (AHR). Airway inflammation, which induces AHR and recurrence of asthma, is the main pathophysiology of asthma. The fractional exhaled nitric oxide (FeNO) level is a noninvasive, reproducible measurement of eosinophilic airway inflammation that is easy to perform in young children. As airway inflammation precedes asthma attacks and airway obstruction, elevated FeNO levels may be useful as predictive markers for risk of recurrence of asthma. This review discusses FeNO measurements among early-childhood wheezing phenotypes that have been identified in large-scale longitudinal studies. These wheezing phenotypes are classified into three to six categories based on the onset and persistence of wheezing from birth to later childhood. Each phenotype has characteristic findings for atopic sensitization, lung function, AHR, or FeNO. For example, in one birth cohort study, children with asthma and persistent wheezing at 7 years had higher FeNO levels at 4 years compared to children without wheezing, which suggested that FeNO could be a predictive marker for later development of asthma. Preschool-aged children with recurrent wheezing and stringent asthma predictive indices also had higher FeNO levels in the first 4 years of life compared to children with wheezing and loose indices or children with no wheeze, suggesting that FeNO measurements may provide an additional parameter for predicting persistent wheezing in preschool children. Additional large-scale longitudinal studies are required to establish cutoff levels for FeNO as a risk factor for persistent asthma.
Evaluation of 11 PCR Assays for Species-Level Identification of Campylobacter jejuni and Campylobacter coli

ABSTRACT We examined the sensitivity and specificity of 11 PCR assays described for the species identification of Campylobacter jejuni and Campylobacter coli by using 111 type, reference, and field strains of C. jejuni, C. coli, and Campylobacter lari. For six assays, an additional 21 type strains representing related Campylobacter, Arcobacter, and Helicobacter species were also included. PCR tests were initially established in the laboratory by optimizing conditions with respect to five type and reference strains of C. jejuni, C. coli, and C. lari. One PCR test for C. coli failed to give appropriate results during this initial setup phase and was not evaluated further. The remaining 10 assays were used to examine heated lysate and purified DNA templates as appropriate of well-characterized type, reference, and field strains of C. jejuni (n = 62), C. coli (n = 34), and C. lari (n = 15). The tests varied considerably in their sensitivity and specificity for their respective target species. No assay was found to be 100% sensitive and/or specific for all C. jejuni strains tested, but four assays for C. coli gave appropriate responses for all strains examined. Between one and six strains of C. jejuni gave amplicons in four of seven C. jejuni PCR tests only where purified DNA was used as the template; corresponding results were seen with one strain of C. coli in each of three assays for the latter species. Our findings indicate that a polyphasic strategy for PCR-based identification should be used to identify C. jejuni and C. coli strains. The data may assist laboratories in selecting assays suited for their needs and in designing evaluations of future PCR tests aimed to identify these species.
Leucine and phenylalanine kinetics during mixed meal ingestion: a multiple tracer approach.

To estimate whole body and splanchnic metabolism of dietary amino acids, phenylalanine and leucine kinetics were determined simultaneously in six normal volunteers before and during the constant administration of a complete mixed meal, employing multiple tracers of these amino acids. L-[5,5,5-2H]leucine and L-[2,6-3H]-phenylalanine were infused intravenously; L-[1-13C]leucine and L-[1-14C]phenylalanine were administered orally with the meal. During the meal, steady-state leucine concentration rose from 136 +/- 6 to 190 +/- 14 mumol/l (P less than 0.01), phenylalanine from 44 +/- 4 to 61 +/- 6 mumol/l (P less than 0.01), total leucine rate of appearance (Ra) from 1.29 +/- 0.03 to 1.77 +/- 0.07 (P less than 0.01, +37 +/- 3%), and phenylalanine Ra from 0.73 +/- 0.05 to 0.80 +/- 0.07 mumol.kg-1.min-1 (P less than 0.05, +8 +/- 3%). Splanchnic uptake of dietary phenylalanine was greater (P less than 0.001) than that of leucine (58 +/- 4 vs. 25 +/- 4%, respectively), 44 +/- 3% of circulating leucine derived from the diet vs. 20 +/- 2% of circulating phenylalanine (P less than 0.01). Endogenous leucine and phenylalanine Ra were significantly suppressed (P less than 0.05). In summary: 1) splanchnic uptake of dietary phenylalanine is onefold greater than that of leucine; 2) dietary contribution to systemic phenylalanine Ra is about half of that to leucine Ra; and 3) endogenous appearance of both leucine and phenylalanine after the meal is suppressed. In conclusion, splanchnic metabolism of dietary leucine and phenylalanine differs markedly and can be quantitated in vivo without catheterization.
Attenuation of G protein‐mediated inhibition of N‐type calcium currents by expression of caveolins in mammalian NG108–15 cells

1 Caveolins are integral proteins of glycolipid/cholesterol‐rich plasmalemmal caveolae domains, where, they may function as a plasma membrane scaffold onto which many classes of signalling molecules, including receptors and heterotrimeric G proteins, can assemble. To ascertain whether caveolins influence G protein‐mediated signal transduction, we stably expressed caveolin‐1 and −3 isoforms in the neuroblastoma × glioma NG108–15 hybrid cell line, lacking endogenous caveolins. Subsequently, using whole‐cell voltage clamp methods, we examined whether the modulation of N‐type voltage‐gated Ca2+ channels by Go protein‐coupled, δ‐type opioid receptors might be affected by recombinant caveolin expression. 2 In transfected NG108–15 cells, caveolins localized at the plasma membrane and, upon subcellular fractionation on sucrose density gradients, they co‐localized in Triton‐resistant, low buoyancy fractions, with endogenous Go protein α‐subunits. 3 The voltage‐dependent inhibition of ω‐conotoxin GVIA‐sensitive Ba2+ currents following either activation of δ‐opioid receptors by the agonist [o‐pen2,o‐pen5]‐enkephalin (DPDPE), or direct stimulation of G proteins with guanosine 5′‐O‐(thiotriphosphate) (GTPγS) was significantly attenuated in caveolin‐expressing cells. The kinetics of Ca2+ channel inhibition were also modified by caveolins. 4 Overall, these results suggest that caveolins may negatively affect G protein‐dependent regulation of voltage‐gated N‐type Ca2+ channels, presumably by causing a reduction of the available pool of activated G proteins.
Effect of diagnostic criteria on the prevalence of peripheral arterial disease. The San Luis Valley Diabetes Study.

BACKGROUND The ankle/brachial systolic blood pressure index (ABI), a noninvasive measure of peripheral arterial disease (PAD), is widely used in epidemiological studies. However, the normal ranges of the ABI in healthy populations and ABI criteria for the diagnosis of PAD in large population studies have not been critically evaluated. METHODS AND RESULTS The San Luis Valley Diabetes Study (SLVDS) was designed to evaluate the prevalence and complications of non-insulin-dependent diabetes mellitus (NIDDM) in a biethnic population. The present study was conducted as part of the SLVDS to assess the prevalence of vascular disease in 1280 nondiabetic control subjects and 430 patients with NIDDM. The ABI criteria for PAD were developed in 403 healthy individuals with a low risk for cardiovascular disease. In these low-risk subjects, the average resting ABI value was 0.07 lower in women than in men. In both sexes, the dorsalis pedis ABI was 0.04 lower than in the posterior tibial artery, and the left leg ABI was 0.02 lower than the right leg ABI (all differences, P < .05). In the low-risk subjects, ABI values were lower after exercise than at rest and had similar differences by sex and leg as observed at rest. Using specific abnormal cutoff points for the ABI, we evaluated three criteria for PAD in the overall population: two abnormal vessels in the same leg at rest (both dorsalis pedis and posterior tibial arteries), one abnormal vessel per leg at rest, and an ABI abnormality only after exercise. Subjects classified with PAD by the two-vessel criterion had a higher frequency of claudication and the physical finding of an absent pulse compared with subjects without PAD or patients with PAD defined by the one-vessel or exercise criterion. Use of the two-vessel criterion identified an increased risk of PAD with increasing age, NIDDM, smoking, hypertension, and elevated cholesterol levels. In contrast, the one-vessel PAD criterion was associated only with increasing age and smoking, and exercise-diagnosed PAD was not associated with any cardiovascular risk factor except for male sex. CONCLUSIONS In low-risk subjects, the normal distribution and lower abnormal cutoff point values of the ABI differed by type of test, sex, ankle vessel, and leg. When these specific abnormal cutoff points were applied to the SLVDS population, the two-vessel abnormal criterion described patients with typical clinical characteristics of PAD and the expected associations of PAD with cardiovascular risk factors. These clinical characteristics and cardiovascular risk factor associations were less evident with PAD diagnosed by the one-vessel or exercise criterion. Therefore, an abnormal dorsalis pedis and posterior tibial ABI in the same leg at rest should be used for the diagnosis of PAD in epidemiological studies.
Regional Cerebral Blood Flow during and after 2 Hours of Middle Cerebral Artery Occlusion in the Rat

In this study we explored if the secondary bioenergetic failure, which occurs a few hours after recirculation, following transient middle cerebral artery occlusion (MCAO) in rats, is caused by a compromised reflow. We induced 2 hours of MCAO and measured CBF at the end of the ischemia, as well as 15 minutes, 1, 2, and 4 hours after the start of recirculation, using autoradiographic or tissue sampling 14C-iodoantipyrine techniques. After 2 hours of MCAO, the autoradiographically measured CBF in the ischemic core areas was reduced to 3 to 5% of contralateral values. The reduction in CBF was less in neighboring, penumbral areas. After recirculation, flow already normalized in core tissues after 15 minutes, and remained close to normal for the 4 hours recirculation period studied. However, in penumbral tissues, recovery CBF values were usually below normal. The results show that tissues that are heavily compromised by the 2-hour period of ischemia and are destined to incur infarction, show a “relative hyperemia” during recirculation. In fact, some areas of the previously densely ischemic tissue showed overt hyperperfusion. This finding raises the question whether the relative or absolute hyperemia reflects events that are pathogenetically important. Because drugs that clearly ameliorate the final damage incurred fail to alter the relative hyperperfusion of previously ischemic tissues, it is concluded that vascular events in the reperfusion period do not play a major role in causing the final damage.
Mutant Lrp1 Knock-In Mice Generated by Recombinase-Mediated Cassette Exchange Reveal Differential Importance of the NPXY Motifs in the Intracellular Domain of LRP1 for Normal Fetal Development

ABSTRACT Lrp1 knock-in mice carrying either a wild-type allele or three different mutated alleles encoding the multifunctional endocytic receptor LRP1 were generated by recombinase-mediated cassette exchange (RMCE). Reinsertion by RMCE of a wild-type allele led to a normal pattern and level of gene expression and a completely normal phenotype, indicating that the RMCE procedure itself is neutral with respect to the function of the gene locus. In contrast, reinsertion of mutated LRP1 alleles carrying either inactivating mutations in the proximal NPXY motif (NPTY→AATA) of the cytoplasmic domain or in the furin cleavage site (RHRR→AHAA) caused distinctive liver phenotypes: respectively, either a late fetal destruction of the organ causing perinatal death or a selective enlargement of von-Kupffer cell lysosomes reminiscent of a mild lysosomal storage without an apparent negative effect on animal survival. Notably, mutation of the distal NPXY motif overlapping with an YXXL motif (NPVYATL→AAVAATL) did not cause any obvious pathological effect. The mutations showed no effect on the LRP1 expression level; however, as expected, the proteolytic maturation of LRP1 into its two subunits was significantly impaired, although not completely abolished, in the furin cleavage mutant. These data demonstrate that RMCE is a reliable and efficient approach to generate multiple mutant knock-in alleles for in vivo functional analysis of individual domains or motifs of large multidomain proteins. Its application in Lrp1 reveals dramatically variant phenotypes, of which further characterization will definitively contribute to our understanding of the biology of this multifunctional receptor.
Screening tests for antinuclear antibodies (ANA): selective use of central nuclear antigens as a rational basis for screening by ELISA.

Rational, fully automated ELISA screening tests for ANA have become accessible for routine use. Full length, recombinant or purified naturally expressed antigens can be selected to deliver well defined screening tests, designed to detect ANAs of established clinical significance, while unknown specificities with no clear biological impact are omitted. By comparing results of ANA screening by immunofluorescence (IIF) on tissue section with HEp-2 cells, a correlation of 88% was revealed, while 86% of HEp-2-positive sera bound tissue sections. Eighty-nine percent of HEp-2 ANA-positive sera bound in ANA ELISA I. Seventy-five percent of ANAs detected in ELISA I also bound in ELISA II. These correlations were statistically significant. ANAs detected in ANA ELISA I were all detected upon retesting in both ANA screening ELISA systems, and also by antigen-specific ELISAs. Specific ANAs defined by ELISA, immunodiffusion or Crithidia tests were detected in both ANA ELISA tests. These data demonstrate that most ANAs detected by immunofluorescence tests contain a dominating repertoire of specificities covered by the ANA ELISA systems. The sensitivity of the different ELISA tests can easily be adjusted to internationally defined consensus levels, and screening for ANA using both ELISA systems detects expected ANA specificities in ongoing international quality assessment programs.
Arterial baroreflex dynamics in normotensive and spontaneously hypertensive rats.

To investigate dynamic or frequency-dependent characteristics of arterial baroreflex control of efferent sympathetic nerve activity in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY), we assessed the transfer function from aortic pressure (AP) to renal sympathetic nerve activity (RSNA) using a "white-noise technique. " In pentobarbital sodium-anesthetized rats, we recorded RSNA as the output, while AP was randomly perturbed to impose input pressure changes with broad frequencies. We calculated the transfer function from AP to RSNA over the frequency range of 0.01-5 Hz through the spectral analysis of the input and output. The results indicated that the gain, phase shift, and coherence of the transfer function for SHR and for WKY were similar and statistically indistinguishable. The gain was relatively constant below 0.05 Hz but increased steadily by fivefold as frequency increased in the frequency range of 0.05-0.8 Hz. The phase was out of phase where coherence was high. The coherence was high (greater than 0.5) in the frequency range of 0.04-0.8 and 1.00-1.03 Hz but was low in other frequencies. These results suggest that dynamic or frequency-dependent characteristics of arterial baroreflex control of RSNA were not altered in SHR as compared with WKY.
New Strategies for Medical Management of Castration-Resistant Prostate Cancer

Although advanced prostate cancer patients respond very well to front-line androgen deprivation, failure to hormonal therapy most often occurs after a median time of 18–24 months. The care of castration-resistant prostate cancer (CRPC) has significantly evolved over the past decade, with the onset of first-line therapy with docetaxel. Although numerous therapy schedules have been investigated alongside docetaxel, in either first-line or salvage therapy, results were dismal. However, CRPC chemotherapy is currently evolving, with, on the one hand, new agents targeting androgen metabolism and, on the other hand, significant progress in chemotherapy drugs, particularly for second-line therapy. The aim of the present review is to describe the current treatments for CRPC chemotherapy alongside their challengers that might shortly become new standards. In this article, we discuss the most recent data from clinical trials to provide the reader with a comprehensive, state-of-the-art overview of CRPC chemotherapy and hormonal therapy.
Early lexical and phonological acquisition and its relationships.

PURPOSE Verifying likely relationships between lexical and phonological development of children aged between 1 year to 1 year, 11 months and 29 days, who were enrolled in public kindergarten schools of Santa Maria (RS). METHODS The sample consisted of 18 children of both genders, with typical language development and aged between 1 year to 1 year, 11 months and 29 days, separated in three age subgroups. Visual recordings of spontaneous speech of each child were collected and then lexical analysis regarding the types of the said lexical items and phonological assessment were performed. The number of sounds acquired and partially acquired were counted together, and the 19 sounds and two all phones of Brazilian Portuguese were considered. To the statistical analysis, the tests of Kruskal-Wallis and Wilcoxon were used, with significance level of prelace_LT0. 05. RESULTS When compared the means relating to the acquired sounds and mean of the acquired and partially acquired sounds percentages, there was difference between the first and the second age subgroup, and between the first and the third subgroup. In the comparison of the said lexical items means among the age subgroups, there was difference between the first and the second subgroup, and between the first and the third subgroup again. In the comparison between the said lexical items and acquired and partially acquired sounds in each age subgroup, there was difference only in the age subgroup of 1 year and 8 months to 1 year, 11 months and 29 days, in which the sounds highlighted. CONCLUSION The phonological and lexical domains develop as a growing process and influence each other. The Phonology has a little advantage.
Assessing the Automaticity of the Exogenous Orienting of Tactile Attention

We examined whether or not abrupt tactile onsets are capable of exogenously capturing tactile spatial attention when visual spatial attention is focused elsewhere. In experiment 1, we compared performance under dual-task conditions (where participants performed a tactile exogenous cuing task and a rapid serial visual presentation—RSVP—task at the same time) with their performance under single-task conditions (where the participants had to perform only the cuing task, although the RSVP stream was still presented in the background) and to a no-stream condition (where only the cuing task was presented). Tactile cuing was completely suppressed in both the dual-task and single-task conditions, showing that exogenous tactile spatial orienting is modulated by visual-spatial attention, which hence appears to be far from truly automatic. In experiment 2, we demonstrated that the abolishment of exogenous tactile orienting was not caused by the transient presentation of abrupt onset stimuli (letters). These results therefore show that exogenous spatial attentional orienting toward abrupt peripheral tactile stimuli is possible as long as perceptual resources are not depleted by a perceptually demanding (RSVP) task.
Hepatitis C Virus-Linked Mitochondrial Dysfunction Promotes Hypoxia-Inducible Factor 1α-Mediated Glycolytic Adaptation

ABSTRACT Hepatitis C virus (HCV) infection induces a state of oxidative stress by affecting mitochondrial-respiratory-chain activity. By using cell lines inducibly expressing different HCV constructs, we showed previously that viral-protein expression leads to severe impairment of mitochondrial oxidative phosphorylation and to major reliance on nonoxidative glucose metabolism. However, the bioenergetic competence of the induced cells was not compromised, indicating an efficient prosurvival adaptive response. Here, we show that HCV protein expression activates hypoxia-inducible factor 1 (HIF-1) by normoxic stabilization of its α subunit. In consequence, expression of HIF-controlled genes, including those coding for glycolytic enzymes, was significantly upregulated. Similar expression of HIF-controlled genes was observed in cell lines inducibly expressing subgenomic HCV constructs encoding either structural or nonstructural viral proteins. Stabilization and transcriptional activation of HIF-1α was confirmed in Huh-7.5 cells harboring cell culture-derived infectious HCV and in liver biopsy specimens from patients with chronic hepatitis C. The HCV-related HIF-1α stabilization was insensitive to antioxidant treatment. Mimicking an impairment of mitochondrial oxidative phosphorylation by treatment of inducible cell lines with oligomycin resulted in stabilization of HIF-1α. Similar results were obtained by treatment with pyruvate, indicating that accumulation of intermediate metabolites is sufficient to stabilize HIF-1α. These observations provide new insights into the pathogenesis of chronic hepatitis C and, possibly, the HCV-related development of hepatocellular carcinoma.
Autosomal Genome-Wide Linkage Analysis to Identify Loci for Gallbladder Wall Thickness in Mexican Americans

ABSTRACT The significance of gallbladder wall thickness (GBWT) in regard to gallbladder disease (GBD) is not completely understood. Thickening of the gallbladder wall has been observed in patients with acute calculous and acalculous cholecystitis and chronic cholecystitis. However, various pathologic processes, such as gallbladder cancer and nonbiliary disorders such as liver cirrhosis and viral hepatitis, could also cause thickening of the gallbladder wall. To date, there is no report available on the genetic factors influencing GBWT. Therefore we sought to estimate the heritability (h2) of GBWT and to perform a genome-wide search to identify the susceptibility genes for GBWT, using data from the San Antonio Family Diabetes/Gallbladder Study (SAFDGS), a family study of Mexican Americans. GBWT was measured by ultrasound. After adjusting for the significant effects of age, sex, GBD (i.e., asymptomatic gallstones), metabolic syndrome, and duration of type 2 diabetes (T2DM), GBWT was found to be under significant and appreciable additive genetic influences (h2 ± SE = 0.38 ± 0.09, P ≤ 0.0001). The strongest evidence for linkage occurred between markers D11S912 and D11S968 on chromosome 11q24–q25 (LOD = 2.7), where we have already shown suggestive evidence for linkage of GBD (LOD = 2.7) in a subset of our SAFDGS data. Potential evidence for linkage occurred at markers D1S1728 (1p31.1; LOD = 1.4) and D16S748 (16p13.1; LOD = 1.4), respectively. In conclusion, our study provides suggestive evidence for linkage of GBWT on chromosome 11q in Mexican Americans, and future tasks of mapping susceptibility gene(s) for GBD and its related traits, such as GBWT, in this chromosomal region can be fruitful.