Miracle-dz/UniFAR-FTUs huggingface dataset:
Protection Against Programmed Electrical Stimulation-Induced Ventricular Tachycardia and Sudden Cardiac Death by NE-10064, a Class III Antiarrhythmic Drug

Summary: The electrophysiologic and antifibrillatory properties of NE-10064 were studied in vivo in a conscious canine model of sudden cardiac death. Purpose bred male mongrel dogs weighing 14.5-21.5 kg were anesthetized, and surgical anterior myocardial infarction (MI) was induced by a 2-h occlusion, with reperfusion, of the left anterior descending coronary artery (LAD). Three to 5 days after induction of anterior wall MI, animals were subjected to testing by programmed electrical stimulation (PES). As compared with predrug incidence (12 of 12), NE-10064 (10 mg/kg intravenously, i.v.) reduced (p<0.05) the incidence (8 of 12) of PES-induced ventricular tachycardia (VT). All but 1 control animal remained inducible after vehicle (5% dextrose in water). The cycle length of induced VT was not prolonged by NE-10064 (0.245 ± 0.046 s predrug vs. 0.301 ± 0.060 s postdrug). NE-10064 increased ventricular effective refractory period (VERP 166 ± 5 ms predrug vs. 194 ± 13 ms postdrug, p=0.013), prolonged QTc interval (310 ± 12 ms predrug vs. 350 ± 16 ms postdrug, p=0.004) and prolonged the effective refractory period (ERP) of noninfarcted myocardium (p=0.045). The drug did not affect ECG-indexes of conduction velocity: QRS and P-R intervals were not affected, nor were activation delay and conduction time of noninfarcted and infarcted myocardium. In the sudden cardiac death protocol, NE-10064 protected (p=0.018) against ischemia-induced ventricular fibrillation (VF, 75% survival with drug vs. 25% survival without drug). NE-10064 afforded protection (p=0.040) throughout 14 h posterolateral ischemia in the presence of the previous anterior infarct. The data show that the antiarrhythmic activity of NE-10064 was associated with a significant antifibrillatory effect that may be related to its class III electrophysiologic actions
Analytical Method for DFIG Transients During Voltage Dips

Electromagnetic transients resulting from voltage dips not only present challenges for low-voltage ride-through (LVRT) of doubly fed induction generators (DFIGs) in wind turbines (WTs) but also introduce complications for protective relays in power systems. Analysis of the voltage-dip response is a fundamental requirement for methodologies targeting LVRT performance and is also useful for power system development. To date, it has not been feasible to take into account the interval between voltage dip and crowbar triggering, and, consequently, the accuracy of the analytical results has been compromised. In this paper, a concept of equivalent fault source is presented with which the transient process during voltage dips is decomposed into one response to the equivalent stator fault source and the other response to the equivalent rotor fault source. The former results from dips in the supply voltage, while the latter arises from variations in both the rotor resistance and the control voltage produced by crowbar activation. This makes it feasible to incorporate the interval, i.e., the triggering delay, into the analytical solution. Additionally, this decomposition approach allows for the physical mechanisms behind the individual transient components to be more clearly understood. With the explicit analytical formulas, some intrinsic characteristics of the transients are identified. The comparative accuracy and advantages of this analytical method over the conventional approaches is demonstrated through simulations using a 2-MW DFIG for commercial WTs and further verified experimentally on a laboratory-scale test rig.
Frequent Recovery and Broad Genotype 2 Diversity Characterize Hepatitis C Virus Infection in Ghana, West Africa

ABSTRACT Hepatitis C virus (HCV) infection is thought to mostly become chronic and rarely resolves. HCV infection was serologically screened in 4,984 samples from Ghanaian blood donors, and 1.3% prevalence was found. At least 53% of confirmed anti-HCV carriers had no detectable viral RNA and were considered to have cleared the virus and recovered from the infection. Confirmation was authenticated by the presence of antibodies specific to at least two viral antigens, mostly NS3 and E2. Reactivity to HCV core antigens was lower in Ghanaian than United Kingdom blood donors. The minority of chronically infected donors carried a viral load significantly lower than an unselected comparative group of United Kingdom blood donors (2.5 × 105 versus 2.9 × 106 IU/ml; P = 0.004). HCV genotype 2 was largely predominant (87%). Sequence clustering was similarly broad in the E1/E2 and NS5 regions. The phylogenetic diversity and the incapacity to distinguish subtypes within genotype 2 in our and others' West African strains suggested that West Africa may be the origin of HCV genotype 2. The genetic diversity extended to the identification of strains clearly separated from known subtypes of genotype 2 and genotype 1. One strain appears to be part of a new HCV genotype. HCV infection in Ghana is characterized by a high rate of recovery and the predominance of broadly divergent genotype 2 strains.
The Synthesis and In Vivo Pharmacokinetics of Fluorinated Arachidonic Acid: Implications for Imaging Neuroinflammation

Arachidonic acid (AA) is found in high concentrations in brain phospholipids and is released as a second messenger during neurotransmission and much more so during neuroinflammation and excitotoxicity. Upregulated brain AA metabolism associated with neuroinflammation has been imaged in rodents using [1-14C]AA and with PET in Alzheimer disease patients using [1-11C]AA. Radiotracer brain AA uptake is independent of cerebral blood flow, making it an ideal tracer despite altered brain functional activity. However, the 20.4-min radioactive half-life of 11C-AA and challenges of routinely synthesizing 11C fatty acids limit their translational utility as PET biomarkers. Methods: As a first step to develop a clinically useful 18F-fluoroarachidonic acid (18F-FAA) with a long radioactive half-life of 109.8 min, we report here a high-yield stereoselective synthetic method of nonradioactive 20-19F-FAA. We tested its in vivo pharmacokinetics by infusing purified nonradioactive 19F-FAA intravenously for 5 min at 2 doses in unanesthetized mice and measured its plasma and brain distribution using gas chromatography–mass spectrometry. Results: Incorporation coefficients of injected 19F-FAA into brain phospholipids (ratio of brain 19F-FAA concentration to plasma input function) were 3- to 29-fold higher for choline glycerophospholipid and phosphatidylinositol than for ethanolamine glycerophospholipid and phosphatidylserine at each of the 2 tested doses. The selectivities and values of incorporation coefficients were comparable to those reported after [1-14C]AA (the natural arachidonate) infusion in mice. Conclusion: These results suggest that it would be worthwhile to translate our stereoselective synthetic method for 19F-FAA to synthesize positron-emitting 18F-FAA for human brain AA metabolism in neuroinflammatory disorders such as Alzheimer disease.
Training Attention-Switching Ability in Adults With ADHD

Objective: Children with ADHD show attention-switching impairment. The present study assessed attention-switching ability in adults with ADHD, the extent to which this ability can be improved via targeted training, and the degree to which training extends to novel tasks of attention-switching. Method: Adults with ADHD (n = 16) and adults without ADHD (n = 18) were divided into training and non-training groups. Training groups performed six blocks of four different attention-switching tasks, while non-training groups completed non-switching, “filler” tasks. Lastly, the four groups were tested on two novel attention-switching tasks. Results: Adults with ADHD showed impaired attention-switching, relative to non-ADHD adults, but training significantly improved attention-switching in both ADHD and non-ADHD training groups. Finally, training effects transferred to new tasks of attention-switching. Conclusion: Adults with ADHD show attention-switching impairments, but deficits may be ameliorated with short-term, targeted training. Research has implications for cognitive training in ADHD.
Regional differences in sympathetic activation in lean and obese normotensive individuals with obstructive sleep apnoea

Objective: Obstructive sleep apnoea (OSA) is characterized by a marked sympathetic overdrive, as documented by the elevated sympathetic nerve firing rate detected in peripheral muscle nerves. No data are available, however, on the behaviour of sympathetic drive in vascular regional districts other than the muscle circulation. Design and methods: In 66 middle-aged normotensive individuals classified according to BMI, waist-to-hip ratio and apnoea–hypopnea index as lean individuals without (n = 20) or with (n = 14) OSA and as obese individuals without (n = 13) or with (n = 19) OSA, we measured blood pressure, heart rate, muscle sympathetic nerve activity (MSNA) and skin sympathetic nerve activity (SSNA), respectively, via microneurography. Measurements also included SSNA responses to an emotional stimulus. Results: The four groups were matched for age, sex and blood pressure values. Both in lean and obese individuals, presence of OSA was accompanied by MSNA values significantly greater than those found in non-OSA individuals. In contrast, no significant difference was found in SSNA values between OSA and non-OSA patients both in the lean and in the obese groups. This was the case also for the SSNA responses to an emotional arousal. Conclusion: These data provide the first evidence that in OSA, the adrenergic overdrive seen in the muscle circulation is not detected in cutaneous circulation and thus it cannot be regarded as a generalized phenomenon affecting the whole cardiovascular system. Further studies are needed to clarify whether in OSA, sympathetic drive of other vascular districts, such as the coronary, renal or cerebral circulation, is activated or normal.
Instability of the Upper Cervical Spine in Down Syndrome

Summary This study of 64 Down syndrome children at British Columbia's Children's Hospital established that ligamentous laxity of the upper cervical spine may exist at more than one location. Instability at the atlantooccipital level is common and must be considered along with the previously documented atlantoaxial instability. Treatment should depend on room available for the spinal cord instead of absolute values of displacement.
Ligand-Selective Potentiation of Rat Mineralocorticoid Receptor Activation Function 1 by a CBP-Containing Histone Acetyltransferase Complex

ABSTRACT The rat mineralocorticoid receptor (MR) has two activation functions in distinct regions of the A/B domain, designated activation function 1a (AF-1a; amino acids 1 to 169) and AF-1b (amino acids 451 to 600). Since the p160 family protein TIF2, a known component of the AF-2 coactivator complex, potentiates the transactivation function of AF-1b but not that of AF-1a, it is likely that some other, novel protein complex interacts with the AF-1a region. Therefore, we attempted to identify such coactivator complexes from HeLa nuclear extracts by biochemical purification using a glutathione S-transferase-MR AF-1a fusion protein. Purified AF-1a region-interacting proteins were found to contain RNA helicase A (RHA) and CBP. Further analysis showed that RHA interacted with the AF-1a region directly and then recruited a complex with histone acetyltransferase (HAT) activity that contained CBP. For full-length MR, aldosterone, but not hydrocortisone, was found to induce the binding of RHA/CBP complexes to the AF-1a region, as well as to allow the cooperative potentiation of MR transcriptional activity by RHA and CBP. In addition, a chromatin immunoprecipitation assay showed that aldosterone-bound MR, but not hydrocortisone-bound MR, recruited RHA/CBP complexes to native MR target gene promoters. Our results suggested that an altered conformation of the A/B region induced by aldosterone, but not hydrocortisone, might determine the accessibility of MR AF-1a to RHA/CBP complexes.
Magnetic Resonance Imaging and CT Scanning in Multiple Sclerosis

Prior to the development of cranial computed tomography (CT), the major role for neuroimaging was the exclusion of other pathologic processes that might mimic multiple sclerosis (MS). Cerebral angiography was generally normal or showed nonspecific mass effect with no evidence for arteriopathy or venopathy. Pneumoencephalography was either normal or defined dilated sulci and ventricles with longstanding disease. Myelography was normal even in the face of significant myelopathic clinical findings and only revealed cord (intramedullary) swelling or complete block on rare occasions with acute, severe disease. All of these techniques had the additional disadvantage of being traumatic and thus potentially leading to iatrogenic exacerbation of the disease process. With the advent of high resolution, cross-sectional imaging over the past decade, a powerful approach was made available for the diagnosis of demyelinating disease. These imaging methods are safe, relatively noninvasive, and able to provide exquisitely detailed anatomic information of even submillimeter structures routinely. Information obtained by CT or magnetic resonance (MR) imaging is thus an in vivo representation of gross pathology. Precise pathoanatomic studies in living patients have the additional advantage of permitting repeated examinations during the various stages of lesion development and of providing a better understanding of the dynamics (e.g., bloodbrain barrier integrity) of this remitting and exacerbating disease process. As both the specificity and sensitivity of CT and MR imaging improve, the results of these tests will need to be integrated into the diagnostic criteria schemas used to detect, prognose, and evaluate therapeutic response in demyelinating disease. ’ It is, however, important to recognize that the positive information derived from CT or M R imaging, if not used in careful conjunction with clinical acumen, may further complicate rather than facilitate patient care. The additional psychosocial dilemma exists of the patient with a minimal neurologic deficit or complete remission with an unequivocally abnormal imaging study.
Weight Change and Workplace Absenteeism in the HealthWorks Study

Objective: Little is known about the relationship between weight change and workplace absenteeism. The purpose of this study was to examine the degree to which weight change predicted 2-year absenteeism. Methods: A longitudinal analysis of 1,228 employees enrolled in a worksite-randomized controlled trial was performed. Participants were all working adults in the Minneapolis, MN, area (USA). Results: The final model indicated a significant interaction between weight change and baseline BMI. The difference in absenteeism ranged from (mean ± SE) 3.2 ± 1.2 days among healthy weight employees who maintained their weight to 6.6 ± 1.1 days among obese employees who gained weight (and slightly higher among healthy weight employees who lost weight). The adjusted model also indicated that participants who were male, not depressed, nonsmokers, and had lower baseline absenteeism had significantly less workplace absenteeism relative to participants who were female, depressed, smokers, and had higher baseline absenteeism. Conclusion: Absenteeism was generally low in this sample, but healthy weight employees who maintained their body weight over 2 years had the fewest number of sick days. More research is needed in this area, but future workforce attendance interventions may be improved by focusing on the primary prevention of weight gain in healthy weight employees.
A Randomized Controlled Trial of Postthoracotomy Pulmonary Rehabilitation in Patients with Resectable Lung Cancer

Introduction: Little is known about the effects of rehabilitation for patients with lung cancer after thoracotomy. The primary objective of this study was to evaluate the effect of a multidisciplinary rehabilitation program on quality of life (QOL) and secondary objectives were to determine its effects on pain and exercise capacity and the feasibility of combining rehabilitation with adjuvant chemotherapy. Methods: Patients who had undergone a thoracotomy for lung cancer were randomized between rehabilitation and usual care. Rehabilitation consisted of twice-weekly training for 12 weeks starting 1 month after hospital discharge, scheduled visits to pain specialists, and medical social work. QOL and pain were measured with validated questionnaires at baseline and after 1, 3, 6, and 12 months. Exercise tolerance was assessed at baseline and after 3 months with a 6-minute walking distance test. Results: The study closed prematurely because of the introduction of video-assisted thoracoscopic surgery. Of 57 randomized patients, 49 patients (23 active and 26 control) were analyzed. QOL was not significantly different between groups, although, the active group reported more pain after 3 and 6 months and more limitations because of physical problems after 3 months. In the active group, 6-minute walking distance improved by 35 m from preoperative baseline, as opposed to the control group that showed a decline by 59 m (p = 0.024 for difference). Patients treated with adjuvant chemotherapy showed decreased attendance at training sessions. Conclusion: Rehabilitation did not result in a better QOL. Exercise tolerance improved at the cost of more pain and more limitations because of physical problems. We suggest that rehabilitation is better postponed for 3 to 4 months after hospital discharge.
Dose, dose-rate and field size effects on cell survival following exposure to non-uniform radiation fields

For the delivery of intensity-modulated radiation therapy (IMRT), highly modulated fields are used to achieve dose conformity across a target tumour volume. Recent in vitro evidence has demonstrated significant alterations in cell survival occurring out-of-field which cannot be accounted for on the basis of scattered dose. The radiobiological effect of area, dose and dose-rate on out-of-field cell survival responses following exposure to intensity-modulated radiation fields is presented in this study. Cell survival was determined by clonogenic assay in human prostate cancer (DU-145) and primary fibroblast (AG0-1522) cells following exposure to different modulated field configurations delivered using a X-Rad 225 kVp x-ray source. Uniform survival responses were compared to in- and out-of-field responses in which 25–99% of the cell population was shielded. Dose delivered to the out-of-field region was varied from 1.6–37.2% of that delivered to the in-field region using different levels of brass shielding. Dose rate effects were determined for 0.2–4 Gy min−1 for uniform and modulated exposures with no effect seen in- or out-of-field. Survival responses showed little dependence on dose rate and area in- and out-of-field with a trend towards increased survival with decreased in-field area. Out-of-field survival responses were shown to scale in proportion to dose delivered to the in-field region and also local dose delivered out-of-field. Mathematical modelling of these findings has shown survival response to be highly dependent on dose delivered in- and out-of-field but not on area or dose rate. These data provide further insight into the radiobiological parameters impacting on cell survival following exposure to modulated irradiation fields highlighting the need for refinement of existing radiobiological models to incorporate non-targeted effects and modulated dose distributions.
Ligation of Cell Surface-Associated Glucose-Regulated Protein 78 by Receptor-Recognized Forms of α2-Macroglobulin: Activation of p21-Activated Protein Kinase-2-Dependent Signaling in Murine Peritoneal Macrophages1

Previous studies of the plasma proteinase inhibitor α2-macroglobulin (α2M) demonstrated that α2M-proteinase complexes (α2M*) modulate immune responses and promotes macrophage locomotion and chemotaxis. α2M* binds to cell surface-associated glucose-regulated protein 78 (GRP78), which activates downstream signaling events. The role of p21-activated protein kinase-1 and -2 (PAK-1 and -2) in promoting cellular motility is well documented. In the current study, we examined the ability of α2M* to activate PAK-1 and PAK-2. Upon macrophage stimulation with α2M*, PAK-2 is autophosphorylated, resulting in increased kinase activity; however, PAK-1 is negligibly affected. α2M*-stimulated macrophages showed a marked elevation in the levels of Rac·GTP. Receptor tyrosine phosphorylation upon binding of α2M* to GRP78, recruits PAK-2 to the plasma membrane via the adaptor protein NCK. Consistent with this hypothesis, silencing of GRP78 gene expression greatly attenuated the levels of membrane-associated PAK-2 and NCK. PAK-2 activity was markedly decreased by inhibition of tyrosine kinases and PI3K before α2M* stimulation. We further demonstrate that phosphorylation of Lin-11, Isl-1, Mec-3 (LIM) kinase and cofilin is promoted by treating macrophages with α2M*. Thus, α2M* regulates activation of the PAK-2-dependent motility mechanism in these cells.
Triploid Grass Carp: Status and Management Implications

Abstract Triploid grass carp are becoming readily available from commercial producers, who are capable of examining the fish individually to ensure that only triploids are shipped. Moreover, carefully controlled programs in Florida and other states have demonstrated that permitting procedures that require 100% triploids can work. Federal involvement in certification has lessened the load at the state level. Research has indicated that triploids feed and behave similarly to their diploid parents, which makes them effective biological plant control agents. Theory and the available empirical evidence suggest that triploid grass carp will be functionally sterile and will not establish self-sustaining populations. Judicious use of the triploid grass carp is advised because of their propensity to migrate and their predicted longevity (10–15 years). Their greatest benefit will be in reducing costs and reducing the quantities of potentially hazardous herbicides introduced into waters where plants historically hav.
Early physical activity provides sustained bone health benefits later in childhood.

PURPOSE This study examined the potential effect of early childhood moderate and vigorous physical activity (MVPA) on later bone health. METHODS Three hundred and thirty-three children, participating in the Iowa Bone Development Study, were studied at ages 5, 8, and 11 yr. MVPA (min x d(-1)) was measured using an accelerometry-based physical activity monitor. Bone mineral content (BMC; g) of the whole body, lumbar spine, and hip was measured using dual-energy x-ray absorptiometry. Mixed regression models were used to test whether MVPA at age 5 yr had an effect on BMC at ages 8 and 11 yr after adjustment for concurrent height, weight, age, maturity, and MVPA. The analysis was repeated to control for bone outcomes at age 5 yr. Mixed-model least-squares mean values at the person level of covariates for age group were used to compare the BMC at ages 8 and 11 yr of children in the highest and lowest quartiles of MVPA at age 5 yr. RESULTS For boys and girls, MVPA at age 5 yr predicted BMC adjusted for concurrent height, weight, age, maturity, and MVPA at ages 8 and 11 yr (P < 0.05). When the analysis was repeated to also control for BMC at age 5 yr, the effect of MVPA at age 5 yr was significant for boys but not for girls. Boys and girls in the highest quartile of MVPA at age 5 yr had 4%-14% more BMC at ages 8 and 11 yr than those in the lowest quartile of MVPA at age 5 yr (P < 0.05). CONCLUSIONS These results provide support for the benefits of early MVPA on sustained bone health during childhood especially for boys. Results indicate the importance of increasing MVPA as a strategy to improve BMC later in childhood.