Miracle-dz/UniFAR-FTUs huggingface dataset:
The role of ultrasound elastography in preoperative localization of parathyroid lesions: a new assisting method to preoperative parathyroid ultrasonography

Background After the definition of minimally invasive procedures, preoperative localization of parathyroid lesions is now crucial. False‐positive results up to 30% were reported by B‐mode grayscale ultrasonography (US) in localization of parathyroid lesions. Parathyroid adenomas are relatively stiff lesions. Ultrasound elastography (USE) can accurately evaluate tissue stiffness and might detect the stiff parathyroid lesions.
Sympathetic and parasympathetic interaction in vascular and secretory control of the nasal mucosa in anaesthetized dogs

1 In dogs anaesthetized with pentobarbitone, electrical stimulation of the parasympathetic nerve fibres to the nasal mucosa evoked frequency dependent increases in both nasal arterial blood flow and nasal secretion. Blood flow was measured using a transonic flow probe placed around the artery. 2 Sympathetic nerve stimulation for 3 min at 10 Hz evoked significant and prolonged (> 30 min) attenuation of the vasodilator and secretory responses to subsequent parasympathetic stimulation. 3 Intravenous and intranasal administration of the neuropeptide Y (NPY) analogue N‐acetyl [Leu28,Leu31] NPY 24–36, a selective NPY Y2 receptor agonist (20 nmol kg−1), significantly attenuated both vasodilator and secretory effects of subsequent parasympathetic nerve stimulation. When given intravenously, the inhibitory effect of this Y2 receptor agonist on vascular and secretory effects of parasympathetic nerve stimulation was rapid in onset (5 min) and lasted for more than 60 min. The modulatory effect of the Y2 receptor agonist was also seen with intranasal administration, but was slower in onset (15 min), and lasted less than 45 min. The effects of the intranasal pretreatment with the Y2 receptor agonist were significantly prolonged in the presence of the endopeptidase inhibitor phosphoramidon (10 nm). 4 Atropine pretreatment did not significantly reduce the change in vascular conductance evoked by parasympathetic nerve stimulation. Subsequent pretreatment with the NPY Y2 receptor agonist N‐acetyl [Leu28,Leu31] NPY 24–36 reduced the stimulation induced increase in conductance by 30%. Nasal secretion was reduced by 70% following pretreatment with atropine and a further 30% by pretreatment with the NPY Y2 receptor agonist. Dose dependent vasodilator and secretory effects of local intra‐arterial infusion of acetylcholine and vasoactive intestinal peptide were not modified by the NPY Y2 agonist. 5 Total protein and albumin concentration were measured in nasal lavage fluid collected after nerve stimulation. Atropine pretreatment increased the percentage of the total protein that was albumin in nasal lavage fluid. Neither sympathetic nerve stimulation nor Y2 receptor agonist pretreatment further modified the albumin exudation (a marker of vascular permeability) in nasal fluid lavage collected after parasympathetic nerve stimulation. 6 We propose that sympathetic nerve stimulation releases NPY, which acts on Y2 receptors, probably located on parasympathetic nerve endings, to attenuate both vasodilatation and nasal secretion evoked by subsequent parasympathetic nerve stimulation. This effect is also observed after pretreatment with the Y2‐selective NPY analogue N‐acetyl [Leu28,Leu31] NPY 24–36.
Fibroblast growth factor 23 predicts coronary calcification and poor prognosis in patients with chronic kidney disease stages 3-5D.

OBJECTIVE To investigate the relationship of fibroblast growth factor-23 (FGF23) to coronary calcification and prognosis in patients with chronic kidney disease (CKD) stages 3-5D. METHOD We determined serum levels of intact FGF23 in 150 patients with CKD stages 3-5D, using an enzyme-linked immunosorbent assay (ELISA). The coronary calcification was detected with multi-slice CT, and its relationship to FGF23 was analyzed. These patients were followed up over a period of 35±3 months. RESULT Serum FGF23 levels of patients with CKD stages 3-5D were significantly higher than those of the healthy control group (p<0.01). There was a significant positive correlation between serum FGF23 levels and coronary calcification score (CaS) (r=0.177, p<0.05). Age, dialysis vintage, and FGF23 levels were independent risk factors for coronary calcification in patients with CKD stages 3-5D. Receiver-operating characteristic (ROC) curves showed that the sensitivity and specificity of FGF23 were 62.5% and 75.9%, respectively, for diagnosing coronary calcification, with an area of 0.705 under the curve (p<0.01). Kaplan-Meier analysis revealed that survival rates were significantly better in patients with lower FGF23 levels (p<0.05). In Cox regression analysis, FGF23 levels and severe coronary calcification (CaS>400) were independent risk factors for all-cause mortality. CONCLUSION Serum FGF23 level in patients with CKD stages 3-5D was significantly higher than in the healthy controls. These increased FGF23 levels are likely associated with coronary calcification and poor prognosis.
E- and P-Selectin Are Not Required for the Development of Experimental Autoimmune Encephalomyelitis in C57BL/6 and SJL Mice1

In multiple sclerosis and in its animal model experimental autoimmune encephalomyelitis (EAE), inflammatory cells migrate across the endothelial blood-brain barrier (BBB) and gain access to the CNS. It is well-established that α4 integrins are actively involved in leukocyte recruitment across the BBB during EAE. In contrast, the role of endothelial E- and P-selectin in this process has been a controversial issue. In this study, we demonstrate that P-selectin protein can be detected in meningeal blood vessel endothelial cells in healthy SJL and C57BL/6 mice and on rare parenchymal CNS blood vessels in C57BL/6, but not SJL, mice. During EAE, expression of P-selectin but not E-selectin was found up-regulated on inflamed CNS microvessels surrounded by inflammatory infiltrates irrespective of their meningeal or parenchymal localization with a more prominent immunostaining detected in C57BL/6 as compared with SJL mice. P-selectin immunostaining could be localized to CNS endothelial cells and to CD41-positive platelets adhering to the vessel wall. Despite the presence of P-selectin in wild-type mice, E/P-selectin-deficient SJL and C57BL/6 mice developed clinical EAE indistinguishable from wild-type mice. Absence of E- and P-selectin did neither influence the activation of myelin-specific T cells nor the composition of the cellular infiltrates in the CNS during EAE. Finally, endothelial-specific tetracycline-inducible expression of E-selectin at the BBB in transgenic C57BL/6 mice did not alter the development of EAE. Thus, E- and P-selectin are not required for leukocyte recruitment across the BBB and the development of EAE in C57BL/6 and in SJL mice.
Retrospective Evaluation of Tiagabine Overdose

Background. Tiagabine is an anticonvulsant that blocks reuptake of the inhibitory neurotransmitter GABA. There are no published studies or case series of tiagabine overdoses. Methods. The records of six poison centers and one statewide poison center network were searched for all exposures to tiagabine for the years 2000–2002. Inclusion criterion was a human tiagabine exposure with follow-up to a known outcome; exclusion criterion was multiple drug ingestion. Results. 57 cases met the inclusion criterion. Thirty-seven patients were female (67%). Mean and median ages were 30.5 years (S.D. ± 18.5) and 31 years, respectively, with a range of 2 to 80 years. Seven patients were ≤ 6 years. Neurologic symptoms were common: lethargy, seizures (multiple), status epilepticus, seizure (single), coma, confusion, agitation, tremors, dizziness, dystonias/abnormal posturing, and hallucinations. Other symptoms included respiratory depression, tachycardia, hypertension, and hypotension. Therapies included benzodiazepines, mechanical ventilation, phenytoin, phenobarbital, diphenhydramine, and dopamine. The mean onset and duration of symptoms were 1.3 hours (± 0.5, range 1–2 hours) and 9.1 hours (± 3.8, range 4–24 hours), respectively. Dose ingested by history was known for 38 patients (67%). The lowest dose with the development of multiple seizures and coma was 96 mg. This occurred in a 36-year-old female with a history of epilepsy. The lowest dose with symptoms in a child was 8 mg, in a 6-year-old with drowsiness. Mean dose of those with and without symptoms was 102 mg and 10 mg, respectively. The mean dose for patients experiencing seizures was 224 mg (± 172, range 96 to 680 mg). The mean dose for patients experiencing coma and respiratory depression was 270 mg (± 204, range 96 to 680 mg). Fifty-two patients (91%) were evaluated in the ED of whom 43 were admitted for medical care. Conclusion. Seizures and altered mental status were common with tiagabine overdose, with rapid onset and resolution of symptoms. In this series, seizures did not occur until the ingestion was greater than three times the maximum recommended daily dose.
Are prematurity and environmental factors determinants for developing childhood-onset systemic lupus erythematosus?

Abstract Objective: The objective of this study is to evaluate the influence of exposure to air pollutants and inhalable environmental elements during pregnancy and after birth until childhood-onset systemic lupus erythematosus(cSLE) diagnosis. Methods: This case–control study comprised 30 cSLE patients and 86 healthy controls living in the Sao Paulo metropolitan area. A structured and reliable questionnaire (kappa index for test-retest was 0.78) assessed demographic data, gestational and perinatal-related-factors, and exposure to inhalable elements during pregnancy and after birth (occupational exposure to inhalable particles and/or volatile vapor, and/or tobacco, as well as, the presence of industrial activities or gas stations near the home/work/daycare/school). Tropospheric pollutants included: particulate matter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3) and carbon monoxide (CO). Results: The median current age was similar between cSLE patients and healthy controls [16.0 (5–21) versus 15.0 (4–21) years, p = . 32], likewise the frequency of female gender (87% versus 78%, p = .43). The frequencies of prematurity (30% versus 6%, p = .001), maternal occupational exposure during pregnancy (59% versus 12%, p < .001), exposure to volatile vapor (48% versus 8%, p < .001) and fetal smoking (maternal and/or secondhand) (37% versus 19%, p = .008) were significantly higher in cSLE patients compared with controls. In a multivariate analysis regarding the gestation period, maternal occupational exposure (OR 13.5, 95% CI 2.5–72.4, p = .002), fetal smoking (OR 8.6, 95%CI 1.6–47, p = .013) and prematurity (OR 15.8, 95%CI 1.9–135.3, p = .012) remained risk factors for cSLE development. Furthermore, exposure to secondhand smoking during pregnancy and after birth (OR 9.1, 95%CI 1.8–42.1, p = .002) was also a risk factor for cSLE development. Conclusions: Prematurity and environmental factors were risk factors for developing cSLE.
Relation between cellular doxorubicin binding ability to nuclear DNA and histologic response to preoperative chemotherapy in patients with osteosarcoma

Although chemosensitivity to antiosteosarcoma agents is the most important prognostic factor in human osteosarcoma, none of the many chemosensitivity tests reported previously are reliable and clinically useful. In this study, the authors investigated the reliability and clinical availability of doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) binding assay (ABA) as a new chemosensitivity test for osteosarcoma.
Pertussis knowledge, attitude and practices among European health care professionals in charge of adult vaccination

Despite successful infant vaccination programmes, pertussis remains endemic in many countries. Waning immunity leaves adolescents and adults susceptible to disease and potential reservoirs of infection allowing transmission to vulnerable infants. Misdiagnosis leads to significant underestimation of disease burden and inappropriate treatment. This online survey of 517 European health care professionals (HCP) examined their knowledge, attitudes and practices regarding pertussis and adult vaccination. Compared with other vaccine-preventable diseases, HCPs did not perceive pertussis as a serious disease in adults and there was a low perceived need for adult vaccination; only 17% mentioned pertussis as a disease they would usually vaccinate adults against. Pertussis incidence was considered to be low. Although the majority of HCPs agreed that vaccination is useful to prevent pertussis transmission from adults to susceptible infants, respondents discussed pertussis vaccination with ≤5% of patients; 58% respondents had never prescribed a pertussis vaccine to adults. The perceived low incidence of pertussis in adults and the lack of official guidelines/ recommendations were cited as key reasons for not administering pertussis boosters. Despite only taking place in four countries, our results suggest that the incidence and burden of adult pertussis is not reflected in the attitudes of European HCPs to the disease. Awareness of adult pertussis, its diagnosis and guidance on pertussis boosters should be raised to protect adults and vulnerable infants and to manage the consequences of waning pertussis immunity.
CCR5 genotypes in sexually active couples discordant for human immunodeficiency virus type 1 infection status.

Persons who are homozygous for the delta32 polymorphism of the CCR5 chemokine receptor gene are highly protected against human immunodeficiency virus type 1 (HIV-1) infection. Previous studies described 54 HIV-1-discordant couples in whom no virus transmission occurred despite extensive sexual contact. The possible role of the delta32 polymorphism in the lack of HIV-1 transmission between these partners was studied. No participants were homozygous for the delta32 allele, but the proportion that was heterozygous was higher among HIV-1-seronegative than HIV-1-seropositive partners (28% vs. 11%, P = .05). This association was seen in heterosexual couples (P = .03) but not in homosexual couples (P = .74). Among white persons, who are most likely to carry the delta32 allele, 38.9% of HIV-1-uninfected and 5.6% of HIV-1-infected heterosexual partners were heterozygous (P = .04). These data are consistent with a possible association between the heterozygous delta32 genotype in heterosexual sex partners and partial protection against HIV-1 infection, and they emphasize the importance of analyzing different risk groups in studies of host factors that influence infection.
Emerging indications of endoscopic radiofrequency ablation

Introduction Radiofrequency ablation (RFA) is a well-validated treatment of dysplastic Barrett's esophagus. Other indications of endoscopic RFA are under evaluation. Results Four prospective studies (total 69 patients) have shown that RFA achieved complete remission of early esophageal squamous intra-epithelial neoplasia at a rate of 80%, but with a substantial risk of stricture. In the setting of gastric antral vascular ectasia, two prospective monocenter studies, and a retrospective multicenter study, (total 51 patients), suggest that RFA is efficacious in terms of reducing transfusion dependency. In the setting of chronic hemorrhagic radiation proctopathy, a prospective monocenter study and a retrospective multicenter study (total 56 patients) suggest that RFA is an efficient treatment. A retrospective comparative study (64 patients) suggests that RFA improves stents patency in malignant biliary strictures. Conclusions Endoscopic RFA is an upcoming treatment modality in early esophageal squamous intra-epithelial neoplasia, as well as in gastric, rectal, and biliary diseases.
Model for mechanical to neural transduction in the auditory receptor.

We describe a model for transduction of displacement of the basilar membrane to activity of auditory nerve fibers. The model is physiologically oriented. Quanta (“vesicles”) are added to a population inside an urn (hair cell) at a fixed average rate. They are removed from the population with a probability proportional to the number of quanta in the population and related in a simple manner to the instantaneous amplitude of the input signal (displacement). The removal of a quantum results in an event (action potential) with a probability related to time elapsed since the preceding event (refractory period). Apart from refractoriness, the model is completely specified by three parameters which determine spontaneous and maximum firing rates and the time constant of recovery after intense stimulation. The model is more compatible with observed activity of the auditory nerve than threshold‐crossing models. An important feature of auditory‐nerve data reproduced by the model is the level normalization observed at moderate to high stimulus intensities. The model reproduces features of period, PST, and interval histograms in response to pure and complex tones, tone bursts, and noise. We present results both from analysis and from computer simulation of the model.
The role of the cannabinoid type 1 receptor and down‐stream cAMP/DARPP‐32 signal in the nucleus accumbens of methamphetamine‐sensitized rats

Blockade of the cannabinoid type 1 (CB1) receptor could suppress methamphetamine self‐administration; however, the cellular mechanism remains unclear. In this study, we intended to investigate the significance of brain CB1 receptors on the development of behavioral sensitization to methamphetamine. Male Sprague‐Dawley rats treated with chronic methamphetamine (4 mg/kg, i.p.) for either 7 or 14 days developed behavioral sensitization to methamphetamine (1 mg/kg) at withdrawal day 7. A progressive decrease in numbers of CB1 receptor (both Bmax and mRNA) but increase in binding affinity (Kd) was noticed during withdrawal days 3 to 7. Microinjection of CB1 antagonist [5‐(4‐bromophenyl)‐1‐(2,4‐dichlorophenyl)‐4‐ethyl‐N‐(1‐piperidinyl)‐1H‐pyrazole‐3‐carboxamide] into the nucleus accumbens (NAc) at withdrawal day 7, significantly suppressed the behavioral sensitization to methamphetamine. In NAc brain slices preparation, acute incubation with CB1 agonist (1R,3R,4R)‐3‐[2‐hydroxy‐4‐(1,1‐dimethylheptyl)phenyl]‐4‐(3‐hydroxypropyl)cyclohexan‐1‐ol (CP 55940) dose‐dependently enhanced cAMP accumulation in sensitized rats; no change was noticed in control groups. Consequently, treatment of CP 55940 induced a dose‐dependent (10 nmol/L–10 μmol/L) phosphorylation on down‐stream dopamine and cAMP‐regulated phosphoprotein of Mr 32 000 (DARPP‐32)/Thr34 in sensitized rats, while only 10 μmol/L CP 55940 was able to enhance the phosphoDARPP‐32/T34 in control groups. Alternatively, both basal activity of calcineurin (PP‐2B) and CP 55940‐induced changes in the amount of PP‐2B in the NAc were both decreased in sensitized rats, but not in controls. Overall, we demonstrated that brain CB1 receptor and its down‐stream cAMP/DARPP‐32/T34/PP‐2B signaling are profoundly altered in methamphetamine‐sensitized animals.
The effects of leptin on REM sleep and slow wave deltain rats are reversed by food deprivation

Leptin (ob protein) is an adipose tissue derived circulating hormone that acts at specific receptors in the hypothalamus to reduce food intake. The protein is also critically involved in energy balance and metabolic status. Here the effect of leptin on sleep architecture in rats was evaluated because food consumption and metabolic status are known to influence sleep. Sprague‐Dawley rats were chronically implanted with electrodes for EEG and EMG recording and diurnal sleep parameters were quantified over 9‐h periods following leptin administration. Murine recombinant leptin (rMuLep) was administered systemically to rats that either had undergone 18 h of prior food deprivation or had received food ad libitum. In the normally fed rats, leptin significantly decreased the duration of rapid eye movement sleep (REMS) by about 30% and increased the duration of slow wave sleep (SWS) by about 13%, the latter effect reflecting enhanced power in the delta frequency band. These results are consistent with studies that have linked changes in metabolic rate with effects on sleep. Leptin administration has previously been shown to alter neuroendocrine parameters that could have mediated these changes in sleep architecture. Unexpectedly, prior food deprivation negated the effect of leptin on both REMS and SWS, a result that emphasizes the significance of the apparent coupling between sleep parameters and energy status.
A dynamic checkpoint in oxidative lesion discrimination by formamidopyrimidine–DNA glycosylase

In contrast to proteins recognizing small-molecule ligands, DNA-dependent enzymes cannot rely solely on interactions in the substrate-binding centre to achieve their exquisite specificity. It is widely believed that substrate recognition by such enzymes involves a series of conformational changes in the enzyme–DNA complex with sequential gates favoring cognate DNA and rejecting nonsubstrates. However, direct evidence for such mechanism is limited to a few systems. We report that discrimination between the oxidative DNA lesion, 8-oxoguanine (oxoG) and its normal counterpart, guanine, by the repair enzyme, formamidopyrimidine-DNA glycosylase (Fpg), likely involves multiple gates. Fpg uses an aromatic wedge to open the Watson–Crick base pair and everts the lesion into its active site. We used molecular dynamics simulations to explore the eversion free energy landscapes of oxoG and G by Fpg, focusing on structural and energetic details of oxoG recognition. The resulting energy profiles, supported by biochemical analysis of site-directed mutants disturbing the interactions along the proposed path, show that Fpg selectively facilitates eversion of oxoG by stabilizing several intermediate states, helping the rapidly sliding enzyme avoid full extrusion of every encountered base for interrogation. Lesion recognition through multiple gating intermediates may be a common theme in DNA repair enzymes.
Children learn separate aspects of speech production at different rates: evidence from spectral moments.

One theoretical perspective on speech development holds that segmental structure gradually emerges in the utterances of children as their first words, realized as roughly specified patterns of gesture, are differentiated into patterns of precisely specified and carefully coordinated gestures. The purpose of the present study was to test one aspect of this theoretical position, namely that children's articulatory gestures are not as precisely specified as are those of adults. In addition, a related hypothesis was tested, namely that some patterns of gesture achieve adultlike precision sooner than others. To test these hypotheses, the first, third, and fourth spectral moments were derived for fricative (/s/ and /integral of) and for stop-burst (/t/ and /k/) noises in the speech samples of children (3 to 7 years of age) and of adults. First spectral moments for fricatives showed stronger consonant effects (i.e., /s/ vs /integral of/) for adults' than for children's samples. This acoustic finding replicated a previous result [Nittrouer et al, J. Speech Hear. Res. 32, 120-132 (1989)], and provided support for the hypothesis that some articulatory gestures are not as precisely specified in children's speech as in that of adults. First spectral moments for /t/ and /k/ revealed no age-related differences in the magnitude of the consonant effect, providing support for the hypothesis that some gestures achieve mature status sooner than others. Although not a focus of the present study, it was also found that children's /k/ first moments varied more than adults' as a function of vowel environment (/i/, /a/, or /u/). Thus further support was obtained for a finding described elsewhere: For at least some articulatory gestures, there is greater influence of one on another for children's than for adults' speech [e.g., Nittrouer et al., J. Speech Hear. Res. 32, 120-132 (1989); S. Nittrouer, J. Speech Hear. Res. 36, 959-971 (1993)].