Miracle-dz/UniFAR-FTUs huggingface dataset:
Blockade of Endothelin Receptors Reduces Diet-Induced Hypercholesterolemia and Atherosclerosis in Apolipoprotein E-Deficient Mice

Objective: Endothelin (ET)-1 has proatherogenic properties, since ET receptor antagonists reduce atherosclerotic lesions in animals. However, we recently demonstrated that ET-1 and ETB receptors are increased in atherosclerotic lesions. To further examine the effects of ETB receptor antagonism on atherogenesis, we investigated the chronic effects of the nonselective ETA/ETB receptor antagonist SB209670 on the development of atherosclerosis in apolipoprotein E (ApoE)-deficient mice. Methods: Ninety-four male mice (10 weeks of age) were randomly divided into four groups: mice fed a Western-type diet or a chow diet with SB209670 treatment (10 mg/kg/day) or placebo for 12 weeks. Results: In mice fed the Western-type diet, but not in mice fed the chow diet, treatment with SB209670 significantly attenuated the increase in plasma total cholesterol, predominantly in the very-low-density lipoprotein and intermediate-density lipoprotein fractions, without altering the plasma triglyceride level. Furthermore, treatment with SB209670 significantly reduced the extent of aortic atherosclerosis, by 53% in mice fed the Western-type diet and by 38% in mice fed the chow diet. Histological analysis revealed that SB209670 prevented the formation of atheromatous plaque lesions by inhibiting the fibroproliferative process. Conclusion: We found that chronic administration of SB209670 reduced diet-induced hypercholesterolemia and atherosclerosis in ApoE-deficient mice. Thus, nonselective ET receptor antagonists may have a therapeutic potential in the treatment of human atherosclerotic disease.
Sleep-disordered breathing in children with asthma: a systematic review on the impact of treatment

Background The objective was to perform a systematic review in order to describe the relationship between asthma and sleep-disordered breathing (SDB) in children, especially regarding the impact of treatment and management. Methods We performed an electronic search in MEDLINE, EMBASE, and LILACS database. Study inclusion criteria were the following: 1) studies that examined the relationship between asthma/wheezing and SDB/obstructive sleep apnea (OSA); and 2) studies conducted in children <18 years of age. Primary outcomes were the prevalence of asthma and SDB, the tests used for diagnosis, and the influence of their treatment and management. Results One thousand and twenty studies were identified, among which 32 were selected (n=143,343 children; 51% males; age [mean ± standard deviation] 8.4±2.5 years). Most studies (n=26) diagnosed SDB using questionnaires or clinical history. Nine studies performed a sleep study for diagnosing OSA. The diagnosis of asthma was based on clinical history (n=16), previous medical diagnosis (n=4), questionnaires (n=12), and spirometry (n=5). Children with asthma were more likely to develop habitual snoring and OSA, and children with SDB were more likely to develop asthma. Moreover, asthma was associated with more severe OSA, and the presence of SDB was associated with severe asthma. Treatment of SDB with adenotonsillectomy was associated with significant asthma improvement. Conclusion The relationship between asthma and SDB appears to be bidirectional, and adenotonsillectomy appears to improve asthma control. Future trials on how asthma treatment could impact on SDB are needed.
TIM-4 Expressed on APCs Induces T Cell Expansion and Survival1

TIM (T cell, Ig, mucin) proteins can regulate T cell immune responses. Tim-4 mRNA is not expressed in T cells, but exclusively in APCs. Tim-4 is a ligand for Tim-1 and Tim-4.Ig fusion protein was shown to either inhibit or expand T cells. However, the molecular basis for such opposite effects was not defined. By generating mAbs, we show that expression of Tim-4 protein is restricted to CD11c+ and CD11b+ cells and is up-regulated upon activation. We show that Tim-4 specifically phosphorylates Tim-1 and induces T cell expansion by enhancing cell division and reducing apoptosis. Tim-4 also induces the phosphorylation of signaling molecules LAT, Akt, and ERK1/2 in T cells. Tim-4, expressed on APCs, is a costimulatory molecule that promotes T cell expansion and survival by cross-linking Tim-1 on T cells.
[Influence of speech rate and loudness on speech intelligibility].

BACKGROUND contextual cues intrinsic to speech stimuli can have an influence on speech intelligibility measurements; however, the influence of cues that depend on the acoustic signal, such as speech rate and vocal loudness, need further investigation. AIM to examine whether possible reductions in the articulatory rate and increase in vocal loudness, associated to the production of different speech stimuli, can have an influence on speech intelligibility measurements. METHOD participants of this study were thirty normal speakers and sixty normal listeners. Speakers were recorded during the repetition of three lists of speech stimuli (sentences, words and pseudo words). The averages of the articulatory rate (syllables per second) and of the vocal loudness (decibel) were calculated for each speaker according to their performance in each repetition task. Speech intelligibility was measured based on the orthographic transcription of the speech samples; the score was calculated in terms of percentage of correctly transcribed words. RESULTS it was observed that articulatory rates were statistically different between the three types of stimuli; however, the stimuli produced with the lowest articulatory rate (pseudo words followed by words) did not present higher speech intelligibility scores. Vocal loudness was statistically higher during the repetition of pseudo words; however, this increase did not have an influence on the speech intelligibility scores. CONCLUSION the reduction of the articulatory rate or the increase of vocal loudness did not have an influence on the speech intelligibility measurements, indicating that contextual cues have a greater impact on speech intelligibility than the independent cues given by the acoustic signal.
Infant TGF-alpha genotype, orofacial clefts, and maternal periconceptional multivitamin use.

OBJECTIVE We previously demonstrated a strong association between periconceptional maternal cigarette smoking, infant transforming growth factor-alpha (TGFa) genotype, and risk of orofacial clefts. Because serum folate may be decreased by cigarette smoking and because maternal periconceptional use of multivitamins containing folic acid has been associated with a reduced risk of clefting, we explored whether a potential relation existed between infant TGFa genotype, maternal multivitamin use, and risk of orofacial cleft phenotypes. DESIGN Data were derived from a population-based case-control study of fetuses and live-born infants among a cohort of 1987 to 1989 California births (n = 548,844). Information concerning periconceptional multivitamin use was obtained via telephone interviews with mothers of 731 (84.7% of eligible) orofacial cleft case infants, and of 734 (78.2%) nonmalformed control infants. DNA was obtained from newborn screening bloodspots and genotyped for the Taql polymorphism of TGFa. Among infants of interviewed mothers, genotypes were available for 571 (78.1%) case infants and 640 (87.2%) control infants. SETTING The study encompassed all hospitals in selected California counties. MAIN OUTCOME MEASURE The main outcome measures were the risks of specific cleft phenotypes among infants with uncommon TGFa genotypes and whose mothers did not use multivitamins periconceptionally. RESULTS Compared with infants homozygous for the common TGFa genotype and whose mothers used multivitamins, increased clefting risks were observed for infants with the A2 genotype (homozygous or heterozygous) and whose mothers did not use multivitamins. Risk estimates were 3.0 (1.4-6.6 [95% confidence interval]) for isolated cleft lip with or without cleft palate (CLP), 2.4 (0.69-11.6) for multiple CLP, 2.6 (0.97-7.7) for isolated cleft palate (CP), 4.2 (1.3-16.2) for multiple CP, and 8.1 (2.6-27.7) for "known-syndrome" clefts. Clefting risks for infants with the A2 genotype and whose mothers used multivitamins were substantially smaller, as were the risks for infants with the A1 genotype whose mothers did not use multivitamins. CONCLUSION These data provide preliminary evidence for a gene-nutrient interaction in risk of clefting.
Surgical treatment of aortic coarctation in adults: Beneficial effect on arterial hypertension.

BACKGROUND The aim of this study was to determine the outcome after surgical repair of aortic coarctation in adults, analysing its effect on arterial blood pressure. METHODS Twenty-five adults (9 women, 16 men), mean age 43.4 years (19 to 70 years), underwent aortic coarctation surgical repair. All patients suffered from preoperative hypertension. Mean blood pressure was 182/97 mm Hg. Sixteen (64%) patients demonstrated reduced load capacity. Operative technique was resection and end-to-end anastomosis for 5 patients (20%), interposition of a Dacron-tube graft for 3 patients (12%), Dacron-patch dilatation was performed in 7 (28%) patients, and in 10 (40%) patients we performed an extra-anatomical bypass graft. RESULTS Early mortality occurred in 1 patient (4%). The mean blood pressure was reduced [systolic 182 mm Hg vs. 139 mm Hg (p < 0.001), diastolic 97 mm Hg vs. 83 mm Hg (p < 0.001)] in all patients. In 12 patients, blood pressure normalized immediately after surgery, in 7 patients it remained slightly elevated (systolic blood pressure between 140-160 mm Hg), and 1 patient suffered from prolonged arterial hypertension. Preoperatively, all patients were treated with antihypertensive drugs. Eleven of 20 patients received long-term medication during follow- up. In the remaining 4 patients, medication lists were unobtainable in retrospect. The mean follow-up was 7.1 years (min. 1.0 years; max. 16.6 years). One patient (5%) died from cardiac failure 12.4 years after the operation. On average, the New York Heart Association (NYHA) class was improved by 0.92. CONCLUSIONS The surgical repair of aortic coarctation in adults can be performed with low surgical risk. Surgery reduces hypertension and permits more effective medical treatment.
Evaluation of amiodarone versus metoprolol in treating atrial fibrillation after coronary artery bypass grafting

Introduction Atrial fibrillation (AF) is the most common arrhythmia affecting patients in open heart ICU after coronary artery bypass grafting (CABG). Most cardiac surgery textbooks recommend beta blockers as the drug of choice for treating such a condition while many experienced physicians and a number of anesthesiology references offer amiodarone as the drug of choice. Therefore, because of insufficient evidence and the aforementioned controversy, we decided to conduct a study evaluating these two antiarrhythmic medicines. Methods This is a double-blind, randomized, clinical trial performed on patients admitted for CABG at Amir al Momenin hospital in Arak province, Iran, who developed new onset AF after surgery. Based on the type of medication used, these patients were randomly divided into two groups: amiodarone (A) group and metoprolol (M) group. Each group consisted of 73 cases. All data were analyzed via SPSS 19. Results Among the results achieved in this study, amiodarone was successful in treating AF in 55 patients (73%), while metoprolol achieved normal rhythm in treating AF in 69 patients (92%). With a p-value of 0.04, it seems that metoprolol is more effective in treating AF. Conclusion Metoprolol seems to be a most efficacious medication for post-CABG AF (p-value = 0.004).
Inspiratory muscle training improves tidal volume and vital capacity after CABG surgery.

OBJECTIVE To evaluate lung function and respiratory muscle strength in the postoperative period and investigate the effect of inspiratory muscle training on measures of respiratory muscle performance in patients undergoing coronary artery bypass grafting. METHODS A randomized study with 47 patients undergoing coronary artery bypass grafting with cardiopulmonary bypass. They were divided into study group (SG) 23 patients and control group (CG) 24 patients, mean age 61.83 ± 8.61 and 66.33 ± 10.20 years, EuroSCORE SG 0.71 ± 0.0018 and CG 0.76 ± 0.0029, respectively. The study group underwent physical therapy and inspiratory muscle training with threshold IMT® and CG underwent conventional physiotherapy. We compared the maximal respiratory pressures (MIP and MEP), tidal volume (TV), vital capacity (VC) and peak expiratory flow (peak flow) preoperatively (Pre-OP), 1st (PO1) and 3rd (PO3) postoperative day. RESULTS There was a significant reduction in all variables measured on PO1 compared to preoperative values in both groups, MIP (P <0.0001), MEP (P <0.0001), TV SG (P <0.0004) and CG (P <0.0001) and VC SG (P <0.0001) and CG (P <0.0001) and peak flow (P <0.0001). At PO3, SG presented higher value of VC, GE 1230.4 ± 477.86 ml vs. GC 919.17 ± 394.47 ml (P=0.0222) and TV SG 608.09 ± 178.24 ml vs. CG 506.96 ± 168.31 ml (P= 0.0490). CONCLUSION Patients undergoing cardiac surgery experience reduced ventilatory capacity and respiratory muscle strength after surgery. Muscle training was performed to retrieve TV and VC in the PO3, in the trained group.
Potential association between endogenous leptin and sympatho‐vagal activities in young obese Japanese women

Leptin is an adipocyte‐derived hormone that decreases food intake and increases energy expenditure through the activation of the sympathetic nervous system (SNS). Notwithstanding recent intensive research, the underlying physiological mechanism of leptin as well as the etiology of obesity in humans remains elusive. The present study attempted to investigate the potential association between endogenous circulating leptin and sympatho‐vagal activities in age‐ and height‐matched obese and nonobese healthy young women. Plasma leptin concentrations were measured by radioimmunoassay. The autonomic nervous system activity was assessed during the resting condition by means of a recently devised power spectral analysis of heart rate variability, which serves to identify three separate frequency components, very low (VLO), low (LO), and high (HI). Plasma leptin concentrations were greater in the obese than in the control group (45.7 ± 5.89 vs. 11.2 ± 1.10 ng · ml−1, P < 0.01). As to the contribution of endogenous leptin to SNS activity, both the ratios of the VLO frequency component reflecting thermoregulatory sympathetic function and the global SNS index [(VLO + LO)/HI] to plasma leptin concentration were markedly reduced in the obese compared to the control group (VLO per leptin: 5.9 ± 1.39 vs. 37.8 ± 8.1 ms2 · ml · ng−1, P < 0.01; SNS index per leptin: 0.04 ± 0.008 vs. 0.33 ± 0.01 ml ċ· ng−1, P < 0.01). Additionally, a nonlinear regression analysis revealed that these ratios exponentially decreased as a function of body fat content (VLO per leptin r2 = 0.57, P < 0.01; SNS index per leptin r2 = 0.53, P < 0.01). Our data suggest that reduced sympathetic responsiveness to endogenous leptin production, implying peripheral leptin resistance, might be a pathophysiological feature of obesity in otherwise healthy young women. The findings regarding the association of leptin, body fat content, and SNS activity further indicate that the 30% of total body fat, which has been used as a criterion of obesity, might be a critical point at which leptin resistance is induced. Am. J. Hum. Biol. 15:8–15, 2003. © 2002 Wiley‐Liss, Inc.
Which Ratio of Areas Improves Vision Quality in Simultaneous Focus Optics?

Purpose To evaluate the impact of the center optical zone diameter (COZD) of center-near bifocal optics on the through-focus subjective quality of vision. Methods Subjective image quality was assessed by 14 young, normally sighted subjects. Computed images of three high-contrast 20/50 letters were generated, across a range of object vergences from +2 diopters (D) to −4 D in 0.25-D steps. The center near optical zone addition power was +2.50 D, and the diameter of this center zone was varied in 10% steps to cover from 0% (single vision distance) to 90% of the 4.5-mm pupil diameter. Subjects rated image clarity of these computed images on a 0 to 5 scale, through a 3-mm pupil to limit the effect of their own aberrations. Results To quantify the efficiency of bifocal optics, we calculated the area under the through-focus subjective quality of vision curve. A criterion higher than 2 was judged to be an acceptable level of quality of vision, normalized by the naked eye condition. The average benefit of the optical profiles is highly subject dependent (i.e., from 0.8 to 1.9), potentially explaining why some subjects are not satisfied with simultaneous vision multifocal corrections. Averaged across subjects, the best benefit (i.e., 1.42) was obtained with a COZD covering 40% of the pupil area, whereas the 20, 30, and 50% profiles provide slightly lower benefit (i.e., ∼1.35). A COZD covering 20% of the pupil area equalized distance and near quality of vision. Conclusions Quality of vision with bifocal optics is highly subject dependent. Peripheral rays do not seem to play an important role in the through-focus quality of vision, as the central pupil area is more heavily weighted in determining subjective image quality.
Structural Requirements for Expression of Factor Va Activity*

Thrombin activated factor Va (factor VIIa, residues 1–709 and 1546–2196) has an apparent dissociation constant (Kd,app) for factor Xa within prothrombinase of ∼0.5 nm. A protease (NN) purified from the venom of the snake Naja nigricollis nigricollis, cleaves human factor V at Asp697, Asp1509, and Asp1514 to produce a molecule (factor VNN) that is composed of a Mr 100,000 heavy chain (amino acid residues 1–696) and a Mr 80,000 light chain (amino acid residues 1509/1514–2196). Factor VNN, has a Kd,app for factor Xa of 4 nm and reduced clotting activity. Cleavage of factor VIIa by NN at Asp697 results in a cofactor that loses ∼60–80% of its clotting activity. An enzyme from Russell's viper venom (RVV) cleaves human factor V at Arg1018 and Arg1545 to produce a Mr 150,000 heavy chain and Mr 74,000 light chain (factor VRVV, residues 1–1018 and 1546–2196). The RVV species has affinity for factor Xa and clotting activity similar to the thrombin-activated factor Va. Cleavage of factor VNN at Arg1545 by α-thrombin (factor VNN/IIa) or RVV (factor VNN/RVV) leads to enhanced affinity of the cofactor for factor Xa (Kd,app ∼ 0.5 nm). A synthetic peptide containing the last 13 residues from the heavy chain of factor Va (amino acid sequence 697–709, D13R) was found to be a competitive inhibitor of prothrombinase with respect to prothrombin. The peptide was also found to specifically interact with thrombin-agarose. These data demonstrate that 1) cleavage at Arg1545 and formation of the light chain of factor VIIa is essential for high affinity binding and function of factor Xa within prothrombinase and 2) a binding site for prothrombin is contributed by amino acid residues 697–709 of the heavy chain of the cofactor.
Vagal nerve maturation in the fetal lamb: An ultrastructural and morphometric study

The maturation of the left vagal nerve was studied in the fetal lamb by transmission electron microscopy and by computer‐assisted morphometry of sections of the entire nerve at seven gestational ages between 79 and 145 days (term is 147 days) and in the adult ewe. The number of unmyelinated axons per Schwann cell progressively decreased from 25 to 55 at 79 days to 1 to 5 at near‐term. Unmyelinated axons of various sizes were enclosed within a single Schwann cell at all ages, but the mean axonal diameter increased in inverse relation to the number of unmyelinated axons. A few Schwann cells enclosed two myelinated axons, but in most instances myelination did not begin until a 1:1 ratio was achieved; some single axons with a Schwann cell remained unmyelinated in the adult. Myelinated fibers were rare at 79 days but myelination progressed rapidly thereafter until the adult ratio of myelinated: unmyelinated fibers was reached at about 100 days; myelinated axons were not uniformly distributed. The myelin sheaths and axons of small fibers progressively increased in diameter in late gestation, but new large fibers were not added. Early myelinating fibers and immature unmyelinated axons contained more microtubules than neurofilaments; neurofilaments predominated in mature axons with or without myelin. Cross‐linkages between neurofilaments were already evident by 79 days. Maturation of the vagal nerve thus occurs first by an increase in number of myelinated fibers and then by an increase in the size of each fiber in this fixed population. The bimodal distribution in the size histogram of myelinated fibers is not achieved until 134 days gestation and correlates well with physiological maturation of respiratory patterns. © 1993 Wiley‐Liss, Inc.
Can an ancestral condition for milk oligosaccharides be determined? Evidence from the Tasmanian echidna (Tachyglossus aculeatus setosus).

The monotreme pattern of egg-incubation followed by extended lactation represents the ancestral mammalian reproductive condition, suggesting that monotreme milk may include saccharides of an ancestral type. Saccharides were characterized from milk of the Tasmanian echidna Tachyglossus aculeatus setosus. Oligosaccharides in pooled milk from late lactation were purified by gel filtration and high-performance liquid chromatography using a porous graphitized carbon column and characterized by (1)H NMR spectroscopy; oligosaccharides in smaller samples from early and mid-lactation were separated by ultra-performance liquid chromatography and characterized by negative electrospray ionization mass spectrometry (ESI-MS) and tandem collision mass spectroscopy (MS/MS) product ion patterns. Eight saccharides were identified by (1)H NMR: lactose, 2'-fucosyllactose, difucosyllactose (DFL), B-tetrasaccharide, B-pentasaccharide, lacto-N-fucopentaose III (LNFP3), 4-O-acetyl-3'-sialyllactose [Neu4,5Ac(α2-3)Gal(β1-4)Glc] and 4-O-acetyl-3'-sialyl-3-fucosyllactose [Neu4,5Ac(α2-3)Gal(β1-4)[Fuc(α1-3)]Glc]. Six of these (all except DFL and LNFP3) were present in early and mid-lactation per ESI-MS, although some at trace levels. Four additional oligosaccharides examined by ESI-MS and MS/MS are proposed to be 3'-sialyllactose [Neu5Ac(α2-3)Gal(β1-4)Glc], di-O-acetyl-3'-sialyllactose [Neu4,5,UAc3(α2-3)Gal(β1-4)Glc where U = 7, 8 or 9], 4-O-acetyl-3'-sialyllactose sulfate [Neu4,5Ac(α2-3)Gal(β1-4)GlcS, where position of the sulfate (S) is unknown] and an unidentified 800 Da oligosaccharide containing a 4-O-acetyl-3'-sialyllactose core. 4-O-acetyl-3'-sialyllactose was the predominant saccharide at all lactation stages. 4-O-Acetylation is known to protect sialyllactose from bacterial sialidases and may be critical to prevent microbial degradation on the mammary areolae and/or in the hatchling digestive tract so that sialyllactose can be available for enterocyte uptake. The ability to defend against microbial invasion was probably of great functional importance in the early evolution of milk saccharides.