Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of a fully automated serum assay for total N-terminal propeptide of type I collagen in postmenopausal osteoporosis.

BACKGROUND Biochemical markers of bone turnover can provide prognostic information about the risk of fracture and may be useful for monitoring efficacy of antiresorptive and anabolic therapy in osteoporosis. We evaluated the performance of a fully automated assay for serum total N-terminal propeptide of type I collagen (P1NP), a marker of bone formation. METHODS Serum P1NP was measured on the Elecsys 2010 automated analyzer (Roche) in 230 healthy premenopausal women, age 30-49 years, 179 postmenopausal women with osteoporosis participating in the previously published 1 year randomized Parathyroid Hormone and Alendronate for Osteoporosis study of full-length parathyroid hormone (PTH 1-84, >100 microg/day subcutaneously; n = 119) or oral alendronate 10 mg/day (n = 60), and 64 healthy men, age 40 to 65 years. RESULTS The within-run and between-run (total) imprecision (CVs) were < or =1.7% (n = 20) and 4.4% (n = 15), respectively. The median within-person variability of results (3 measurements over 3 months in 15 postmenopausal women) was 7.2%, resulting in a least significant change (LSC) value of 20%. Serum P1NP concentrations were 74% (P <0.0001) higher in postmenopausal women than in premenopausal controls. After 3 months of treatment, 83% and 88% of patients treated with PTH 1-84 and alendronate, respectively, demonstrated changes of serum P1NP that exceeded the LSC. CONCLUSION The automated assay for serum total P1NP is precise and sensitive enough to detect changes that exceed the LSC in a majority of postmenopausal women after 3 months of treatment with PTH 1-84 or alendronate. Because of its convenience and high throughput, this bone formation marker may be useful for the monitoring of patients with osteoporosis.
Family‐based association study of the serotonin‐6 receptor gene (C267T polymorphism) in schizophrenia

The expression of serotonin type 6 receptor (5‐HT6) in limbic and cortical regions of the brain, and its high affinity for atypical antipsychotics suggest that its encoding gene may play a role in the pathogenesis of schizophrenia. We firstly performed a meta‐analysis of the C267T polymorphism of the 5‐HT6 gene in schizophrenia, based on four different case/control studies, and showed that the allelic distribution is not significantly different between patients and controls, even when taking into account the role of between samples heterogeneity. We then recruited 103 trios (patients with Diognostic and Statistical Manual Mental Disorders, 4th ed. (DSM‐IV) diagnosis of schizophrenia and their parents), and investigated the C267T polymorphism of the 5‐HT6 receptor gene with regard to family‐based association study approach (haplotype relative risk (HRR) and transmission disequilibrium test (TDT)). We found no excess of transmission of one allele from the parents to their affected children, using the HRR (P = 0.60), as well as no evidence for linkage between C267T polymorphism and schizophrenia, using the TDT (P = 0.71). Furthermore, the 267T allele frequency was comparable in the different subgroups defined on age at onset, family history of schizophrenia, treatment response, and subtypes of patients based on positive versus negative predominant symptoms. These data do not support the idea that the 5‐HT6 receptor gene plays a major role in the etiopathogenesis of schizophrenia. © 2003 Wiley‐Liss, Inc.
Physiological Mapping of Local Inhibitory Inputs to the Hypothalamic Paraventricular Nucleus

Local inhibitory synaptic inputs to neurons of the rat hypothalamic paraventricular nucleus (PVN) were studied by using glutamate microstimulation and conventional intracellular and whole-cell patch-clamp recordings in coronal, horizontal, and parasagittal slices of rat hypothalamus. PVN cells were classified as magnocellular or parvocellular neurons on the basis of electrophysiological andpost hoc immunohistochemical analyses; GABA-producing neurons were localized with in situ hybridization. Glutamate microstimulation of different sites around the PVN evoked volleys of postsynaptic potentials in 43% of the PVN neurons tested. Some responses to stimulation at each site were blocked by bicuculline, suggesting that they were mediated by the activation of presynaptic GABA neurons. In the coronal plane, presynaptic inhibitory sites were located lateral to the PVN and ventral to the fornix, corresponding to the lateral hypothalamic area and the posterior bed nucleus of the stria terminalis (BNST). In the horizontal plane, presynaptic inhibitory sites were found rostral, lateral, and caudal to the nucleus, corresponding to parts of the anterior hypothalamic area, the posterior BNST, the medial preoptic area, and the dorsomedial hypothalamus. In the parasagittal plane, presynaptic inhibitory neurons were revealed at sites rostral and caudal to the nucleus, corresponding to the medial preoptic area and the dorsomedial hypothalamus, and in a site dorsal to the optic chiasm that included the suprachiasmatic nucleus. These presynaptic sites each contained GABA-producing neurons based on in situ hybridization with a glutamic acid decarboxylase riboprobe and together formed a three-dimensional ring around the PVN. Unexpectedly, both magnocellular and parvocellular neurons received inhibitory synaptic inputs from common sites.
Impaired creatinine secretion after an intravenous creatinine load is an early characteristic of the nephropathy of sickle cell anaemia.

BACKGROUND The capacity to increase the tubular secretion of creatinine (TS(cr)) after an intravenous creatinine load (stimulated TS(cr)) has been found to be impaired in subclinical reduction of renal mass. We decided to investigate if this response was impaired in sickle cell anaemia (SCA) patients before there was evidence of deterioration of renal function. METHODS Studies were done in 16 patients with homozygous SCA who had normal or supranormal glomerular filtration rate (GFR) and in 20 normal controls of similar median age (23 years). The tubular stress test (TST) consisted of 30-min clearance periods ([(125)I]iothalamate and creatinine) done before (baseline) and after (three successive post-stimulation periods) the intravenous infusion of 88.4 micromol (10 mg) of creatinine per kg of body weight. RESULTS Baseline studies showed that the SCA patients had higher GFR and lower serum creatinine concentration. After stimulation there were no changes in GFR. In contrast, creatinine clearance increased 2.3 times in normal but not in SCA patients (P<0.001) and the TS(cr) in the first post-stimulation period was 161+/-83 nmol/kg/min in SCA patients vs 286+/-93.2 in normal controls (P<0.001). The mean TS(cr) post-stimulation was also reduced in patients with SCA (123+/-52 nmol/kg/min vs 179+/-50 in normal controls, P<0.001). Since SCA patients had lower P(cr) values, separate analysis was made of post-load clearance periods in which P(cr) was comparable in patients and in normal controls (range 177-265 micromol/l or 2-3 mg/dl) and the reduction in TS(cr) was also present in SCA patients in these study periods. CONCLUSION Patients with SCA have impaired response to the TST before there are reductions in glomerular filtration. Therefore, a reduction in the tubular secretory reserve capacity represents an early event in the nephropathy of this condition.
Credit Conditions and the Effects of Economic Shocks : Amplification and Asymmetries

In this paper we address three empirical questions related to credit conditions. Do they change the dynamic interactions of economic variables by characterizing different regimes? Do they amplify the effects of economic shocks? Do they generate asymmetries in the effects of economic shocks depending on the size and sign of the shock? To answer these questions, we introduce endogenous regime switching in the parameters of a large Multivariate Autoregressive Index (MAI) model, where all variables react to a set of observable common factors. We develop Bayesian estimation methods and show how to compute responses to common structural shocks. We find that credit conditions do act as a trigger variable for regime changes. Moreover, demand and supply shocks are amplified when they hit the economy during periods of credit stress. Finally, good shocks seem to have more positive effects during stress time, in particular on unemployment.
Experiences and Outcomes of a Women's Leadership Development Program: A Phenomenological Investigation.

Women’s leadership training programs provide organizations opportunities to value women leaders as organizational resources. This qualitative research utilized phenomenological methodology to examine lived experiences of seven alumni of a women’s-only leadership program. We conducted semi-structured interviews to clarify what learning elements were most beneficial in furthering an individuals’ leadership role. Emerging research themes included perceptional and personal agency changes within participants. Women’s leadership programs provided an opportunity for cognitive, affective, and behavioral growth; engaging learning activities, social capital development, and relational model methodologies were perceived as most helpful in leadership development. Action learning techniques, fostering interconnectedness, and philosophical leadership development activities were critical elements in leadership development. Insights gained from this study provided perspective on the unique experiences of women in a leadership training program.
Acute lung injury during bacterial or fungal sepsis

We compared physiological and ultrastructural indices of acute lung injury (ALI) during septic shock caused by taxonomically diverse pathogens to distinguish ALI due to endogenous inflammatory mediators vs. microbial exotoxins or other factors. Conscious rats were infected i.v. with gram‐negativeEscherichia coli(EC, serotype 055:B5), exotoxin‐C producing gram‐positiveStaphylococcus aureus (SA), or yeast‐phaseCandida albicans(CA, a clinical isolate). Viable inocula of 1010 EC, 1010 SA, or 109 CA caused lethal shock in <24 h, but distinct types of ALI were noted after bacteria vs. fungi. Within 0.5 h of EC infection, leukocytes marginated in the lung vasculature; by death at 6–14 h, animals were hyperoxemic but not acidemic, and showed slight interstitial edema with increased wet/dry weight ratios (W/D = 5.22 ± 0.10, mean ± SE, vs. 4.86 ± 0.07 in controls, P <0.05). Similarly mild ALI occurred after 1010 SA. In contrast, within 0.5 h of CA infection, yeast were visible within lung intravascular leukocytes. By death at 6–12 h, CA animals showed hyperoxic acidemia and moderate ALI with capillary obstruction, interstitial hemorrhage, and elevated lung W/D (5.52 ± 0.13, P <0.05 vs. controls) associated with yeast‐mycelial transformation. Prior neutropenia accelerated mortality and worsened ALI after CA, with hypoxemic acidemia, increased lung W/D (7.23 ± 0.34, P <0.05 vs. other groups), capillary occlusion, perivascular and alveolar hemorrhage, and septal disruption by mycelia. Bacteremia induced large increases in serum tumor necrosis factor‐α (TNF) and interleukin‐1α within 1.5 h, but these cytokines remained low in CA animals, even at death. Neither survival nor ALI after EC or CA was altered by pentoxifylline, which attentuated TNF production, or by cyclooxygenase inhibition with ibuprofen. Thus, overall ALI severity correlated with physiological indices of pulmonary function, but ultrastructural changes correlated better with pathogen type than circulating cytokine or eicosanoid mediators. Whereas lethal bacteremia induced early cytokinemia and mild ALI with or without bacterial exotoxins, moderate ALI apparently was mediated by fungal exotoxins during lethal candidemia, which worsened during neutropenia due to enhanced mycelial proliferation. © 1993 Wiley‐Liss, Inc.
Cultural Fit and the Choice of International Market Entry Scale of Chinese Firms

ABSTRACT Previous research on how cultural distance impacts the choice of entry mode shows contradictory findings. This study uses a strategic fit perspective to examine the impact of distinct cultural factors as predictors of equity entry scale of Chinese firms. Findings from a sample of 667 Chinese firms demonstrate that the effects of cultural fit on equity entry scale vary across cultural dimensions. Whereas a collectivism cultural fit motivates Chinese investors to secure a high-equity entry scale in foreign firms, a lower power distance cultural fit (“misfit”) leads to higher entry involvement.
Muscle conduction velocity, strength, neural activity, and morphological changes after eccentric and concentric training

This study compared the effects of concentric and eccentric training on neuromuscular adaptations in young subjects. Twenty‐two men and women were assigned to one of two groups: concentric (CON, n = 11) and eccentric (ECC, n = 11) training. Training consisted of 6 weeks of isokinetic exercise, performed twice weekly, starting with two sets of eight repetitions, and progressing to five sets of 10 repetitions. Subjects were tested in strength variables [concentric, eccentric, and isometric peak torque (PT), and rate of force development (RFD)], muscle conduction velocity (CV), neuromuscular activity, vastus lateralis (VL) muscle thickness, and echo intensity as determined by ultrasonography. There were similar increases in the concentric and eccentric PTs in both the CON and ECC groups (P < 0.01), but only the ECC group showed an increase in isometric PT (P < 0.001). Similarly, both groups exhibited increased VL muscle thickness, CV, and RFD, and reduced VL echo intensity (P < 0.05). Significant correlations were observed among the relative changes in the neuromuscular outcomes and training variables (e.g., total work, average PT) (r = 0.68–0.75, P < 0.05). The results showed that both training types similarly improved dynamic PT, CV, RFD, and muscle thickness and quality during the early weeks of training.
Are avian blood parasites pathogenic in the wild? A medication experiment in blue tits (Parus caeruleus)

The Hamilton and Zuk hypothesis on haemoparasite–mediated sexual selection and certain studies of reproductive costs are based on the assumption that avian blood parasite infections are detrimental to their hosts. However, there is no experimental evidence demonstrating harmful effects of blood parasites on fitness in wild populations, it even having been suggested that they may be non–pathogenic. Only an experimental manipulation of natural blood parasite loads may reveal their harmful effects. In this field experiment we reduced through medication the intensity of infection by Haemoproteus majoris and the prevalence of infection by Leucocytozoon majoris in blue tits (Parus caeruleus), and demonstrated detrimental effects of natural levels of infection by these common parasite species on host reproductive success and condition. The fact that some of the costs of infection were paid by offspring indicates that blood parasites reduce parental working capacity while feeding nestlings. Medicated females may be able to devote more resources to parental care through being released from the drain imposed upon them by parasites and/or through a reduced allocation to an immune response. Therefore, this work adds support to previous findings relating host's life–history traits and haematozoan infections.
Tonic Regulation of GABAergic Synaptic Activity on Vasopressin Neurones by Cannabinoids

Synaptic activity in magnocellular neurosecretory neurones is influenced by the retrograde (i.e. somatodendritic) release of vasopressin, oxytocin and cannabinoids (CBs). For oxytocin neurones, oxytocin exerts constitutive effects on pre‐synaptic activity through its ability to release CBs post‐synaptically. In the present study, we examined evoked inhibitory post‐synaptic currents (eIPSCs) and spontaneous inhibitory post‐synaptic currents (sIPSCs) in identified vasopressin (VP) neurones in coronal slices from virgin rats to determine: (i) the extent to which CBs may also tonically modulate VP synaptic activity; and (ii) to determine whether depolarisation‐induced suppression of inhibition was present in VP neurones, and if so, whether it was mediated by VP or CBs. The CB1 antagonists AM251 (1 μm) and SR14171 (1 μm) consistently increased the frequency of sIPSCs in VP neurones without affecting their amplitude, suggesting a tonic CB presence. This effect on frequency was independent of action potential activity, and blocked by chelating intracellular calcium with 10 mm ethylene glycol tetraacetic acid (EGTA). AM251 also increased the amplitude of eIPSCs and decreased the paired‐pulse ratio (PPR) in VP neurones‐effects that were completely blocked with even low (1 mm EGTA) internal calcium chelation. Bouts of evoked firing of VP neurones consistently suppressed sIPSCs but had no effect on eIPSCs or the PPR. This depolarisation‐induced suppression of IPSCs was reduced by AM251, and was totally blocked by 10 μm of the mixed vasopressin/oxytocin antagonist, Manning compound. We then tested the effect of vasopressin on IPSCs at the same time as blocking CB1 receptors. Vasopressin (10–100 nm) inhibited sIPSC frequency but had no effect on sIPSC or eIPSC amplitudes, or on the PPR, in the presence of AM251. Taken together, these results suggest a tonic, pre‐synaptic inhibitory modulation of IPSCs in VP neurones by CBs that is largely dependent on post‐synaptic calcium, and an inhibitory effect of VP on IPSCs that is independent of CB release.
In vitro investigations of tumor targeting with (99m)Tc-labeled antisense DNA.

UNLABELLED One objective of this investigation was to determine whether chemical modifications of oligonucleotides to permit radiolabeling with gamma- or positron emitters interferes with hybridization and target cell accumulation. A second objective was to establish to a reasonable extent whether cellular accumulation of radiolabeled oligonucleotides can be explained by an antisense mechanism. METHODS An 18mer uniform phosphorothioate DNA antisense to the messenger RNA (mRNA) of the type I regulatory subunit alpha of cyclic adenosine monophosphate-dependent protein kinase A (RI alpha) was conjugated with the N-hydroxysuccinimidyl derivative of S-acetylmercaptoacetyltriglycine (MAG3) through a primary amine/linker and investigated in vitro in cell culture. RESULTS By surface plasmon resonance, the association kinetics between native (i.e., without amine/linker) DNA and MAG3-amide/linker-DNA were identical. Melting temperatures were also identical for native DNA, amine/linker-DNA, and MAG3-amide/linker-DNA, indicating that these chemical modifications had no detectable influence on hybridization. However, cellular accumulation of (99m)Tc-MAG3-DNA was lower than that of (35)S-MAG3-DNA, suggesting that chemical modifications can have an important influence on cellular accumulation. In tissue culture studies of ACHN tumor cells (a human renal adenocarcinoma cell type), an antisense effect was suggested by 3 findings: an increased accumulation of (35)S- or (99m)Tc-labeled antisense versus sense DNA, an increased accumulation of (99m)Tc-antisense DNA in another RI alpha-positive tumor cell line (LS174T) but not in a murine transfected control cell line (HC-2), and the disappearance of the increased cellular accumulation of (99m)Tc-antisense DNA with increasing dosage of antisense DNA. Higher than expected cellular accumulations of about 10(5) antisense DNAs per cell over 24 h suggest stabilization of the target mRNA or increased mRNA production by the presence of the antisense DNA. In support of this suggestion, we observed, first, an increased incorporation of uridine-5'-triphosphate into RNA in cells exposed to the antisense DNA but not to the control DNA and, second, an increase in target mRNA expression in cells exposed to the antisense DNA but not to the control DNA. CONCLUSION This evidence suggests tumor cell accumulation by an antisense mechanism. Moreover, the high level of DNA accumulation suggests that a rapid target mRNA turnover or transcription rate may be an important determinant of tumor counting rates.
Neostigmine Decreases Bupivacaine Use by Patient-Controlled Epidural Analgesia During Labor: A Randomized Controlled Study

BACKGROUND: Intrathecal neostigmine not only produces analgesia but also severe nausea. In contrast, epidural neostigmine enhances opioid and local anesthetic analgesia without causing nausea. Previous studies examined only single epidural neostigmine bolus administration and did not assess the efficacy of continuous epidural infusion or several aspects of maternal and fetal safety. We therefore tested the hypothesis that epidural neostigmine in combination with bupivacaine by continuous infusion during labor would reduce the amount of bupivacaine required. METHODS: Twelve healthy women scheduled for elective cesarean delivery were assigned to receive epidural neostigmine, 40 μg (first six subjects) or 80 μg (second six subjects) as a single bolus, with fetal heart rate (FHR) and uterine contractions monitored for 20 min. In a subsequent experiment, 40 healthy laboring women were randomized to receive bupivacaine 1.25 mg/mL alone or with neostigmine 4 μg/mL by patient-controlled epidural analgesia. The primary outcome measure was hourly bupivacaine use. RESULTS: Epidural neostigmine bolus did not alter baseline FHR, induce contractions, or produce nausea. Epidural neostigmine infusion reduced bupivacaine requirement by 19% in all patients and 25% in those with >4 h of treatment (P < 0.05 for both) but might have contributed to the incidence of mild sedation. Mode of delivery, incidence of maternal nausea, and FHR abnormality were similar between groups. CONCLUSIONS: These data show that adding epidural neostigmine 4 μg/mL reduces the hourly bupivacaine requirement by 19%–25% with patient-controlled epidural analgesia during labor. Administered as a bolus and by continuous infusion at the studied doses, epidural neostigmine does not cause nausea and does not induce uterine contractions or FHR abnormalities, but mild sedation can occur.
The effect of CYP2C9 and VKORC1 genetic polymorphisms on warfarin dose requirements in a pediatric population

Objective: The aim was to investigate the frequency of genetic polymorphisms of cytochrome P4502C9 (CYP2C9) and vitamin K epoxide reductase complex subunit1 (VKORC1) and determine the effect of these polymorphisms on warfarin dose requirements in pediatric patients. Methods: Fifty-eight pediatric patients with cardiac disease, thrombophilia, or other conditions, taking a stable warfarin dose, aged 0.2–18 years, and with international normalized ratio (INR) between 2 and 3 and 149 healthy children as a control group were included in this prospective, observational study. Patients receiving drugs that interact with warfarin, having chronic liver or renal disease, obesity, or thyroid dysfunctions were excluded. Polymerase chain reaction (real time and restriction fragment length polymorphism) was used to analyze the CYP2C9*2, CYP2C9*3, and VKORC1 polymorphisms. The ideal warfarin dose was calculated according to the patient’s age, height, and the presence of CYP2C9*2, CYP2C9*3, and VKORC1 genetic polymorphisms. The mean daily administered doses and ideal doses were compared. Analysis of variance, Student’s t-test, logistic regression analysis, and Pearson’s correlation analysis were used for statistical analyses. Results: The frequency of the CYP2C9 and VKORC1 genetic polymorphisms was determined as CYP2C9*1/*1 (54.6%), *1/*2 (16.4%), *1/*3 (24.2%), *2/*3 (2.9%), *3/*3 (1.9%), wild-type VKORC1 (26.6%), heterozygote alleles (52.7%), and mutant alleles (20.8%). Patients with allelic variants were found to require lower warfarin doses, and a 64.5% correlation was found between the calculated ideal doses and the administered warfarin doses. Conclusion: Considering CYP2C9 and VKORC1 genetic polymorphisms prior to commencing warfarin treatment will make it easier to reach target INRs and reduce the rate of complications.