Miracle-dz/UniFAR-FTUs huggingface dataset:
Opposite Trends of Allergic Disorders and Respiratory Symptoms in Children over a Period of Large-Scale Ambient Air Pollution Decline

The aim of our study was to analyze a 15-year trend in the prevalence of allergic disorders and respiratory symptoms in children living in an urban area of Upper Silesia, Poland. Three cross-sectional studies (1993, 2002, and 2007) in children aged 7-10 showed a statistically significant increase in the prevalence of all physician-diagnosed allergic disorders (1993-2002-2007): asthma (3.4%-4.7%-8.5%); allergic rhinitis (9.1%-13.7%-17.4%); atopic dermatitis (3.6%-8.4%-8.9%); allergic conjunctivitis (4.3%-11.8%-14.9%); allergy to pollen (5.9%-12.3%-17.3%); allergy to food (5.5%-11.0%-17.0%). A simultaneous decreasing trend in the prevalence of coughing correlated with significant improvement of ambient air quality. However, the rising trends could result from both increasing incidence and improved diagnosis of allergic diseases.
Surgical treatment of pacemaker and defibrillator lead endocarditis: the impact of electrode lead extraction on outcome.

BACKGROUND Cardiac device (CD) endocarditis is an infrequent but potentially lethal infectious complication of permanent pacemakers or implantable cardioverter-defibrillators (ICDs), and mortality rates of 30 to 35% have been reported. Medical treatment has been suggested for the treatment of CD endocarditis, but there is increasing evidence that surgical treatment is to be preferred as the best approach to achieve eradication of the infection and reduce mortality. OBJECTIVE To evaluate the following: (1) the clinical and echocardiographic characteristics of patients with pacemaker or ICD endocarditis, (2) the outcome of this population depending on the mode of treatment (medical vs surgical treatment), and (3) the clinical, microbiological, echocardiographic, and therapeutic variables associated with patient outcome. DESIGN Prospective cohort study. SETTING Tertiary referral center in Barcelona, Spain. PATIENTS All consecutive patients with infectious endocarditis (IE) admitted to the study institution between 1990 and 2001 were prospectively evaluated by a multidisciplinary treatment team, and a definite diagnosis of CD endocarditis was established when cases met pathologic or clinical criteria according to the Duke criteria. RESULTS A total of 31 patients, 25 men and 6 women aged 61 +/- 15 years (mean +/- SD), with pacemaker or ICD endocarditis were identified among 669 consecutive patients (4.6%) with IE. During the study period, a total of 3,768 pacemakers and 460 ICDs were implanted in the study institution. In 22 cases of pacemaker endocarditis, the pacemaker was implanted in our institution, and 9 cases were referred from other institutions (incidences of endocarditis on pacemaker and ICD implanted in our institution of 0.58% and 0.65%, respectively). Medical treatment without removal of the pacing system was initially performed on seven patients; all of them (100%) had relapses of endocarditis, and one patient died. The remaining 24 patients underwent surgical removal of the pacing system; 1 patient had one relapse, 3 patients died after surgical treatment, and the others were successfully cured with no relapses after a mean follow-up of 38 +/- 9 months. Clinical, echocardiographic, microbiological, and therapeutic variables were evaluated in association with prognosis. The only prognostic factor for failure of treatment or mortality was the absence of surgical treatment (p < 0.0001). CONCLUSIONS Electrode lead endocarditis occurred in < 1% of pacemaker and ICD implants. Conservative treatment without explantation of all hardware failed in all patients, and surgical treatment during antibiotic therapy was effective in eradication of infection but was associated with a 12.5% mortality. The only patient characteristic associated with treatment failure or death was the absence of surgical removal of all infected hardware. Complete extraction of the pacemaker or ICD should be considered as standard therapy for most patients with CD endocarditis.
Ocular Features in 16 Brazilian Patients with Williams-Beuren Syndrome

Abstract Objectives: Williams-Beuren Syndrome (WBS) is a multisystem disorder caused by the deletion of contiguous genes on chromosome 7q11.23. Ophthalmologic abnormalities and deficits in visual motor integration are important features of WBS. Here we describe our experience with Brazilian WBS patients and their ophthalmologic features. Methods: Sixteen patients with confirmed WBS went through thorough ophthalmologic examination. Results: The most frequent ocular findings in our group of patients were stellate iris pattern (81.2%), hyperopic astigmatism (50%), hyperopia (37.5%), tortuosity of retinal vessel (37.5%) and strabismus (18.7%). Conclusions: This is the second report of ophthalmologic abnormalities in a group of Brazilian individuals with WBS. It is extremely valuable that specific populations are studied so that clinical diagnosis can be refined and management of patients can be driven to the most common presentations of the disease.
Effect of nature of forage on spontaneous lipolysis in milk from cows in late lactation

Summary Levels of free fatty acids (FFA) were determined in milk from cows after 7 months of lactation and 4 months of pregnancy immediately after milking (initial FFA) and after 22 h storage at 4 °C (FFA-22). During the pre-experimental period, cows were at pasture. When housed indoors (experimental period) they were fed hay or grass silage for 3 weeks. Then all cows received grass silage for 3 weeks (post-experimental period). Feeding hay did not increase FFA-22 content in milk compared with pasture, but grass silage feeding enhanced FFA-22 content in milk compared with pasture (+130 %) or hay (+93 %). Increased lipolysis with grass silage was not due to underfeeding of the cows because grass silage and hay were both of high nutritive value. As pasture, hay and grass silage were of the same type (native mountain grassland), the high level of lipolysis occurring with grass silage probably resulted from the method of forage conservation.
Intercellular communication via connexin43 gap junctions is required for ovarian folliculogenesis in the mouse.

The ovarian follicle in mammals is a functional syncytium, with the oocyte being coupled with the surrounding cumulus granulosa cells, and the cumulus cells being coupled with each other and with the mural granulosa cells, via gap junctions. The gap junctions coupling granulosa cells in mature follicles contain several different connexins (gap junction channel proteins), including connexins 32, 43, and 45. Connexin43 immunoreactivity can be detected from the onset of folliculogenesis just after birth and persists through ovulation. In order to assess the importance of connexin43 gap junctions for postnatal folliculogenesis, we grafted ovaries from late gestation mouse fetuses or newborn pups lacking connexin43 (Gja1(-)/Gja1(-)) into the kidney capsules of adult females and allowed them to develop for up to 3 weeks (this was necessitated by the neonatal lethality caused by the mutation). By the end of the graft period, tertiary (antral) follicles had developed in grafted normal (wild-type or heterozygote) ovaries. Most follicles in Gja1(-)/Gja1(-) ovaries, however, failed to become multilaminar, with the severity of the effect depending on strain background. Dye transfer experiments indicated that intercellular coupling between granulosa cells is reduced, but not abolished, in the absence of connexin43, consistent with the presence of additional connexins. These results suggest that coupling between granulosa cells mediated specifically by connexin43 channels is required for continued follicular growth. Measurements of oocyte diameters revealed that oocyte growth in mutant follicles is retarded, but not arrested, despite the arrest of folliculogenesis. The mutant follicles are morphologically abnormal: the zona pellucida is poorly developed, the cytoplasm of both granulosa cells and oocytes is vacuolated, and cortical granules are absent from the oocytes. Correspondingly, the mutant oocytes obtained from 3-week grafts failed to undergo meiotic maturation and could not be fertilized, although half of the wild-type oocytes from 3-week grafted ovaries could be fertilized. We conclude that connexin43-containing gap junction channels are required for expansion of the granulosa cell population during the early stages of follicular development and that failure of the granulosa cell layers to develop properly has severe consequences for the oocyte.
Incentives in Organizations: An Overview of Some of the Evidence and Theory

This paper begins with a review of the different forms of evidence on incentives in organizations. It is argued that it is not possible to understand modern organizations using one kind of data or empirical model. There is a need to combine standard regression studies with survey and laboratory evidence to obtain a complete picture of how modern organizations operate. The evidence that we have points to the importance of finding solutions to the problem of incomplete contracting in organizations. This contracting problem can help us understand why it has been so difficult to consistently estimate and test empirical incentive models. An implication of this work is the impossibility of specifying the solution to the optimal contract problem in advance. Rather, incentive problems in organizations must be based on a combination of past experience and experimentation. More work is needed to understand how the market can be used to select those organizations that find efficient solutions to the incomplete contracting problem.
Is there a place for the insertion of a JJ stent as a temporizing procedure for symptomatic partial congenital vesico‐ureteric junction obstruction in infancy?

Partial vesico-ureteric junction obstruction (VUJO) with hydroureteronephrosis is a relatively uncommon congenital anomaly compared with PUJ obstruction (PUJO) and in most cases can be managed conservatively. In a series of 105 000 consecutive pregnancies scanned over a 10-year period, there were only 16 babies with VUJO (two bilateral), compared with 52 with PUJO (six bilateral) [1]. We present two patients with severe recurrent UTIs, one with an episode of septicaemia, who responded well to the temporary insertion of a JJ stent.
Internalization and Down-regulation of Human Muscarinic Acetylcholine Receptor m2 Subtypes

Internalization and down-regulation of human muscarinic acetylcholine m2 receptors (hm2 receptors) and a hm2 receptor mutant lacking a central part of the third intracellular loop (I3-del m2 receptor) were examined in Chinese hamster ovary (CHO-K1) cells stably expressing these receptors and G protein-coupled receptor kinase 2 (GRK2). Agonist-induced internalization of up to 80–90% of hm2 receptors was demonstrated by measuring loss of [3H]N-methylscopolamine binding sites from the cell surface, and transfer of [3H]quinuclidinyl benzilate binding sites from the plasma membrane into the light-vesicle fractions separated by sucrose density gradient centrifugation. Additionally, translocation of hm2 receptors with endocytic vesicles were visualized by immunofluorescence confocal microscopy. Agonist-induced down-regulation of up to 60–70% of hm2 receptors was demonstrated by determining the loss of [3H]quinuclidinyl benzilate binding sites in the cells. The half-time (t½) of internalization and down-regulation in the presence of 10−4 m carbamylcholine was estimated to be 9.5 min and 2.3 h, respectively. The rates of both internalization and down-regulation of hm2 receptors in the presence of 10−6 m or lower concentrations of carbamylcholine were markedly increased by coexpression of GRK2. Agonist-induced internalization of I3-del m2 receptors was barely detectable upon incubation of cells for 1 h, but agonist-induced down-regulation of up to 40–50% of I3-del m2 receptors occurred upon incubation with 10−4 m carbamylcholine for 16 h. However, the rate of down-regulation was lower compared with wild type receptors (t½ = 9.9 versus2.3 h). These results indicate that rapid internalization of hm2 receptors is facilitated by their phosphorylation with GRK2 and does not occur in the absence of the third intracellular loop, but down-regulation of hm2 receptors may occur through both GRK2-facilitating pathway and third intracellular loop-independent pathways.
Apoptosis , Dedifferentiation , and Chromosomal Instability in Thyroid PCCL 3 Cells

The activating mutation BRAF is the most prevalent genetic alteration in papillary thyroid carcinomas (PTC). It is associated with advanced PTCs, suggesting that this oncoprotein confers thyroid cancers with more aggressive properties. BRAF is also observed in thyroid micropapillary carcinomas and may thus be an early event in tumor development. To explore its biological consequences, we established doxycycline-inducible BRAF-expressing clonal lines derived from well-differentiated rat thyroid PCCL3 cells. Expression of BRAF did not induce growth in the absence of thyrotropin despite increasing DNA synthesis, which is likely explained because of a concomitant increase in apoptosis. Thyrotropin-dependent cell growth and DNA synthesis were reduced by BRAF because of decreased thyrotropin responsiveness associated with inhibition of thyrotropin receptor gene expression. These results are similar to those obtained following conditional expression of RET/PTC. However, in contrast to RET/PTC, BRAF activation did not impair key activation steps distal to the thyrotropin receptor, such as forskolin-induced adenylyl cyclase activity or cyclic AMP– induced DNA synthesis. We reported previously that acute RET/PTC expression in PCCL3 cells did not induce genomic instability. By contrast, induction of BRAF expression increased the frequency of micronuclei by both clastogenic and aneugenic events. These data indicate that BRAF expression confers thyroid cells with little growth advantage because of concomitant activation of DNA synthesis and apoptosis. However, in contrast to RET/PTC, BRAF may facilitate the acquisition of secondary genetic events through induction of genomic instability, which may account for its aggressive properties. (Cancer Res 2005; 65(6): 2465-73)
Ethyl loflazepate: a prodrug from the benzodiazepine series designed to dissociate anxiolytic and sedative activities.

Ethyl loflazepate (Victan) is an original 1,4-benzodiazepine (BZD) being used as a potent, nonsedative, minor tranquillizer. Ethyl loflazepate was designed to be a prodrug that would gradually release within the organism an active 1,4-BZD. It was hypothesized that this type of pharmacokinetic profile would dissociate anxiolytic from sedative activities. Previously published pharmacokinetic studies performed in rats, baboons and humans have confirmed that ethyl loflazepate gradually releases in the plasma an active 1,4-BZD, descarboxyloflazepate. In the present study, the activity of ethyl loflazepate and its main plasmatic metabolites were examined in rodent models predictive of anxiolytic, anticonvulsant, myorelaxant and sedative properties. The activities of ethyl loflazepate and its metabolites were compared to those of reference BZDs: diazepam, bromazepam, nitrazepam, flunitrazepam, lorazepam, clorazepate. Ethyl loflazepate and its metabolites revealed the typical profile of activity of minor tranquillizers. The activity of ethyl loflazepate was long-lasting. The overall anxiolytic potency of ethyl loflazepate was similar to that of diazepam but ethyl loflazepate appeared to be less sedative than diazepam. Thus in the approach-avoidance conflict procedure in rats the threshold anxiolytic doses were 1 and 2 mg/kg i.p. for ethyl loflazepate and diazepam, respectively, whereas the threshold sedative doses were 16 and 8 mg/kg i.p., respectively. In vitro ethyl loflazepate exhibited a weak affinity for the BZD receptor site. In vivo ethyl loflazepate displaced [3H]-flunitrazepam from mice brain membranes with a potency comparable to that of lorazepam. In vitro, descarboxyloflazepate, the main plasmatic metabolites of ethyl loflazepate, revealed a 4-fold greater affinity for the BZD receptor than diazepam. (ABSTRACT TRUNCATED AT 250 WORDS)
arbocysteine regulates innate immune responses and senescence rocesses in cigarette smoke stimulated bronchial epithelial cells

Cigarette smoke represents the major risk factor for chronic obstructive pulmonary disease (COPD). Cigarette smoke extracts (CSE) alter TLR4 expression and activation in bronchial epithelial cells. Carbocysteine, an anti-oxidant and mucolytic agent, is effective in reducing the severity and the rate of exacerbations in COPD patients. The effects of carbocysteine on TLR4 expression and on the TLR4 activation downstream events are largely unknown. This study was aimed to explore whether carbocysteine, in a human bronchial epithelial cell line (16-HBE), counteracted some pro-inflammatory CSE-mediated effects. In particular, TLR4 expression, LPS binding, p21 (a senescence marker), IL-8 mRNA and release in CSE-stimulated 16-HBE as well as actin reorganization in neutrophils cultured with supernatants from bronchial epithelial cells which were stimulated with CSE and/or carbocysteine were assessed. TLR4 expression, LPS binding, and p21 expression were assessed by flow cytometry, IL-8 mRNA by Real Time PCR and IL-8 release by ELISA. Actin reorganization, a prerequisite for cell migration, was determined using Atto 488 phalloidin in neutrophils by flow cytometry and fluorescence microscopy. CSE increased: (1) TLR4, LPS binding and p21 expression; (2) IL-8 mRNA and IL-8 release due to IL-1 stimulation; (3) neutrophil migration. Carbocysteine in CSE stimulated bronchial epithelial cells, reduced: (1) TLR4, LPS binding and p21; (2) IL-8 mRNA and IL-8 release due to IL-1 stimulation; (3) neutrophil chemotactic migration. In conclusion, the present study provides compelling evidences that carbocysteine may contribute to control the inflammatory and senescence processes present in smokers.
Curvature of Swimming Fish Midlines as an Index of Muscle Strain Suggests Swimming Muscle Produces Net Positive Work.

The axial muscle used in steady swimming by fish is geometrically complex and this has required the study of in vivo muscle swimming mechanics to be done with largely inferential techniques. Currently there is some debate concerning the variation in muscle function in different regions of the body, and the importance of negative work production by muscles in posterior locations. We have used video taped kinematics of steady swimming in mackerel and then analysed the lateral flexion of the body that is thought to reflect the cycle of length change in the axial muscles. A comparison of several of the techniques used in the past to estimate muscle length changes are shown not to be equivalent. Specifically, we find that peak values of lateral deflection of the body are not correlated in time or axial position with peaks in curvature of the body midline. This is important because the timing of the muscle strain cycle is often inferred from such information. Having documented this observation in a swimming mackerel, we use analytical geometry to show that this result is a consequence of the curves that describe swimming fish midlines. Since this observation is shown to be the geometric consequence of an amplitude envelope that is not constant, it should therefore apply to other animals that propel themselves with axial undulations of increasing amplitude. Our minor result is that care must be taken when estimating the phase of swimming muscle strain from kinematics. Our major results is that appreciation of the geometric character of the kinematics these fish adopt may resolve much of the current debate concerning the mechanical performance of swimming muscle in fish. Specifically, using our estimate of the phase of muscle shortening and data on EMG timing in the mackerel we conclude that all axial muscles are activated before peak length and in a manner that should produce net positive work within each shortening cycle.Copyright 1998 Academic Press
Relations between body and waist circumference in American and Korean men and women

Heymsfield et al. (1) have confirmed that the squaring of height in calculating BMI is well justified. For large samples of men and women—non-Hispanic whites, non-Hispanic blacks, Mexican Americans, and Asian Koreans, they separately related body mass [body weight (BW)], fat mass (FM), and waist circumference (WC) to height, with b estimated by logarithmic regression. Some b values were adjusted for age and/or for percentage of fat (%fat) by including these with height as independent variables in the regressions. Here I distinguish the b values by subscripts so that, for example, bBW means b for BW. In most groups bBW (whether or not adjusted for age, but not for %fat) was lower in women than in men, as is generally true (2, 3). Here I integrate various ideas and quantitative evidence, extracting further information from the b values. The correlation coefficients, r, are all significant (P , 0.01). Adjustment for age was important. It increased bFM for all samples (Table 1, line 1), and presumably because BW includes FM, it increased bBW also, but to a lesser extent (line 2). Age had a striking influence in Korean women, probably because of generational differences in nutrition (1). Heymsfield et al. (1) discussed determinants of bBW in physical terms. In terms of statistics, bBW is determined by the SDs of log (BW) and log(height) and by r for log(BW) and log(height) (3). Thus,
A Novel Subtype of Prostacyclin Receptor in the Central Nervous System

Abstract: Recently, in the course of our search for the prostacyclin receptor in the brain, we found a novel subtype, designated as IP2, which was finely discriminated by use of the specific ligand (15R)‐16‐m‐tolyl‐17,18,19,20‐tetranorisocarbacyclin (15R‐TIC) and specifically localized in the rostral part of the brain. In the present study, the tritiated compound 15R‐[15‐3H]TIC was synthesized and utilized for more specific research on IP2. The specificity of binding to rat brain regions was confirmed by use of several prostacyclin derivatives including 15S‐TIC. Mapping of 15R‐ and 15S‐[3H]TIC binding in adjacent pairs of frozen sections of rat brain demonstrated a quite similar pattern of distribution in almost all rostral brain regions, indicating that the regions may contain only the IP2 subtype. On the other hand, 15R‐[3H]TIC binding was very faint as compared with 15S‐[3H]TIC binding in the caudal medullary region. High densities of 15R‐[3H]TIC binding sites were shown in the dorsal part of the lateral septal nucleus, thalamic nuclei, limbic structures, and some of the cortical regions. Scatchard plot analysis showed two components of high‐affinity 15R‐[3H]TIC binding in the rostral regions, one with a KD value at ∼1 nM and the other with ∼30 nM. These results strengthen our previous finding that a different subtype of prostacyclin receptor is expressed in the CNS, and the map with 15R‐[3H]TIC obtained here could guide further studies on the molecular and functional properties of the IP2.