Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of HIV-1 genes in podocytes alone can lead to the full spectrum of HIV-1-associated nephropathy.

BACKGROUND Human immunodeficiency virus (HIV)-1-associated nephropathy (HIVAN) is characterized by collapsing focal and segmental glomerulosclerosis (FSGS) and microcystic tubular dilatation. HIV-1 infection is also associated with other forms of nephropathy, including mesangial hyperplasia. Since HIV-1 gene products are detected in podocytes and other renal cells, it remains uncertain whether podocyte-restricted HIV-1 gene expression can account for the full spectrum of renal lesions involving nonpodocytes. METHODS To define the role of podocyte-restricted HIV-1 gene expression in the progression of HIVAN, we generated transgenic mice that express nonstructural HIV-1 genes selectively in podocytes. RESULTS Four of the seven founder mice developed proteinuria and nephropathy. In a subsequently established transgenic line, reverse transcription-polymerase chain reaction (RT-PCR) analysis detected mRNAs for vif, vpr, nef, and spliced forms of tat and rev, but not vpu, in the kidney. In situ hybridization localized HIV-1 RNA to the podocyte. Transgenic mice on FVB/N genetic background exhibited cuboidal morphology of podocytes with reduced extension of primary and foot processes at 2 weeks of age. After 3 weeks of age, these mice developed massive and nonselective proteinuria with damage of podocytes and other glomerular cells and, after 4 weeks of age, collapsing FSGS and microcystic tubular dilatation. In marked contrast, transgenic mice with C57BL/6 genetic background showed either normal renal histology or only mild mesangial expansion without overt podocyte damage. CONCLUSION The present study demonstrates that podocyte-restricted expression of HIV-1 gene products is sufficient for the development of collapsing glomerulosclerosis in the setting of susceptible genetic background.
Polymorphisms of the chicken antiviral MX gene

The Mx gene was originally found in laboratory mice in an infection experiment using influenza virus (Lindermann, 1962). Almost all of the mouse strains in that experiment died from the infection, and only the A2G strain had resistance to the virus. This resistant character was shown to be inherited as a single autosomal dominant trait (Lindermann et al., 1963; Lindermann, 1964; Haller et al., 1979). A congenic mouse strain was established by introducing the Mx+ allele of the A2G resistant strain into the Mx– sensitive inbred strain BALB/c (Staeheli et al., 1984). By immunizing parental BALB/c mice with extracts of interferon (IFN)-treated cultured cells from congenic BALB/c-Mx+ mice, a specific antibody against Mx protein was obtained (Horisberger et al., 1983; Staeheli et al., 1985). The Mx protein was detected in the nucleus of IFN-α/β-treated mouse cells by immunofluorescence using the anti-Mx antibody (Dreiding et al., 1985). Thereafter, by using the antibody as an indicator, cDNA encoding the Mx protein was cloned from a cDNA library constructed from IFN-treated cells of congenic BALB/c-Mx+ mice (Staeheli et al., 1986a). IFN-treated Mx+ mouse cells contained a 3.5-kb Mx mRNA in the Northern blot, while Mx– cells failed to express the transcript. The functional Mx+ gene from an A2G mouse was found to contain 14 exons and encode 631 amino acids. The Mx– allelic mouse strains were found to be missing sequence of exons 9 through 11 or to contain a point mutation that converts lysine at position 389 to a stop codon (Staeheli et al., 1988). If these polymorphisms of the Mx gene could be detected in domestic animals, it would be possible to produce breeds that show resistance to infectious diseases.
Cognitive-behavioral therapy augmentation of SSRI reduces cortisol levels in older adults with generalized anxiety disorder: A randomized clinical trial.

OBJECTIVES Elevated cortisol in stress and aging, such as has been seen in late-life anxiety disorders, is postulated to accelerate cognitive and physiological decline in this large and increasing population. Selective serotonin-reuptake inhibitors (SSRIs) and cognitive-behavioral therapy (CBT) are both effective treatments for generalized anxiety disorder (GAD) in older adults. On the other hand, there is very little research examining the effect of combining these therapies on peak cortisol levels. For the current analyses, we examined the effectiveness of CBT augmentation on peak cortisol levels in older adults diagnosed with GAD. METHODS The sample consisted of 42 individuals with late-life GAD who received an acute course of the SSRI escitalopram and then entered a 16-week randomized phase. Twenty-one participants were randomized to receive 16 sessions of CBT in addition to continuing escitalopram and the remaining 21 participants continued on escitalopram without CBT. Generalized estimating equations were performed to assess the effectiveness of CBT augmentation on peak cortisol levels (30 min after waking). RESULTS Older adults with GAD who received both escitalopram and CBT demonstrated a significant reduction in peak cortisol levels at posttreatment compared to the group who received escitalopram without CBT augmentation. CONCLUSIONS CBT augmentation of SSRI treatment reduced peak cortisol levels for older adults with GAD. Since persistently high cortisol levels in aging are thought to increase age-related cognitive and medical problems, our findings suggest that there may be a benefit to health and cognition of CBT augmentation for late-life anxiety disorders.
Efficacy and safety of rivastigmine in patients with Alzheimer's disease: international randomised controlled trial.

OBJECTIVES To assess the effects of rivastigmine on the core domains of Alzheimer's disease. DESIGN Prospective, randomised, multicentre, double blind, placebo controlled, parallel group trial. Patients received either placebo, 1-4 mg/day (lower dose) rivastigmine, or 6-12 mg/day (higher dose) rivastigmine. Doses were increased in one of two fixed dose ranges (1-4 mg/day or 6-12 mg/day) over the first 12 weeks with a subsequent assessment period of 14 weeks. SETTING 45 centres in Europe and North America. PARTICIPANTS 725 patients with mild to moderately severe probable Alzheimer's disease diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, and the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association. OUTCOME MEASURES Cognitive subscale of the Alzheimer's disease assessment scale, rating on the clinician interview based impression of change incorporating caregiver information scale, and the progressive deterioration scale. RESULTS At the end of the study cognitive function had deteriorated among those in the placebo group. Scores on the Alzheimer's disease assessment scale improved in patients in the higher dose group when compared with patients taking placebo (P<0.05). Significantly more patients in the higher dose group had improved by 4 points or more than had improved in the placebo group (24% (57/242) v 16% (39/238)). Global function as rated by the clinician interview scale had significantly improved among those in the higher dose group compared with those taking placebo (P<0.001), and significantly more patients in the higher dose group showed improvement than did in the placebo group (37% (80/219) v 20% (46/230)). Mean scores on the progressive deterioration scale improved from baseline in patients in the higher dose group but fell in the placebo group. Adverse events were predominantly gastrointestinal, of mild to moderate severity, transient, and occurred mainly during escalation of the dose. 23% (55/242) of those in the higher dose group, 7% (18/242) of those in the lower dose group, and 7% (16/239) of those in the placebo group discontinued treatment because of adverse events. CONCLUSIONS Rivastigmine is well tolerated and effective. It improves cognition, participation in activities of daily living, and global evaluation ratings in patients with mild to moderately severe Alzheimer's disease. This is the first treatment to show compelling evidence of efficacy in a predominantly European population.
Progressive Band Dimensionality Expansion and Reduction Via Band Prioritization for Hyperspectral Imagery

Processing enormous hyperspectral data results in high computational complexity. Band selection (BS) is one common practice to accomplish this goal. However, determining the number of bands to be selected and finding appropriate bands for BS are very challenging since it requires an exhaustive search. Instead of directly dealing with these two issues, this paper introduces a new approach, called progressive band dimensionality process (PBDP) which performs progressive band dimensionality expansion and reduction via band prioritization (BP) which prioritizes the hyperspectral bands according to their priority scores calculated by a specific BP criterion. Two dual processes, referred to as forward PBDP (FPBDP) which performs band expansion in a forward manner and backward PBDP (BPBDP) which performs band dimensionality reduction in a backward manner. By virtue of its progressive nature the PBDP can be implemented by high computing performance while avoiding excessive computing time required by finding an optimal subset from all possible band subset combinations out of full bands. As a consequence, PBDP provides band selection with an advantage of not being trapped in high computational complexity resulting from solving combinatorial mathematics problems. A key to success in PBDP is how to design BP criteria to meet various applications. To address this need, four categories of BP are derived from different designing rationales, second order statistics, higher-order statistics, classification, and band correlation/dependence.
Following tracheal intubation, mucus flow is reversed in the semirecumbent position: Possible role in the pathogenesis of ventilator–associated pneumonia

Objectives: Critically ill intubated patients are positioned in the semirecumbent position to prevent pneumonia. In tracheally intubated sheep, we investigated the effects of gravitational force on tracheal mucus transport and on bacterial colonization of the respiratory system. Design: Prospective randomized animal study. Setting: Animal research facility at the National Institutes of Health. Subjects: Sixteen healthy sheep. Interventions: Spontaneously breathing or mechanically ventilated sheep were randomized to be positioned with the orientation of the trachea above (40 degrees, trachea-up) or below (5 degrees, trachea-down) horizontal. Measurements and Main Results: Tracheal mucus velocity was measured through radiographic tracking of radiopaque tantalum disks, insufflated into the trachea. After 24 hrs, sheep were euthanized, and samples from the airways and lungs were taken for microbiological analysis. The proximal trachea was colonized in all sheep. In trachea-down sheep, all mucus moved toward the glottis at a mean velocity of 2.1 ± 1.1 mm/min. When mucus reached the endotracheal tube, it either entered the endotracheal tube or was lodged at the inflated endotracheal tube cuff. In all trachea-up sheep, abnormal tracheal mucus clearance was found. Mucus, mostly on the nondependent part of the trachea, moved toward the glottis at an average velocity of 2.2 ± 2.0 mm/min and constantly accumulated at the inflated endotracheal tube cuff. From the proximal trachea, mucus eventually moved toward the lungs on the dependent part of the trachea, leading to an “intratracheal route” of colonization of the lungs. Pneumonia was found in 6/8 of trachea-up sheep and the same microorganisms were isolated from the lungs and the proximal trachea. No pneumonia was found in trachea-down sheep (p = .007). Conclusions: The study indicates that following tracheal intubation gravitational force influences tracheal mucus clearance. When the trachea is oriented above horizontal, a flow of mucus from the proximal trachea toward the lungs is highly associated with bacterial colonization of the airways and pneumonia.
The Effect of Ezetimibe and Simvastatin on Monocyte Cytokine Release in Patients With Isolated Hypercholesterolemia

Apart from reducing plasma lipids, ezetimibe may produce non-lipid-related pleiotropic effects. The aim of this article was to compare the effect of ezetimibe and simvastatin on monocyte cytokine release and systemic inflammation in isolated hypercholesterolemic patients. One hundred thirty-four subjects with isolated hypercholesterolemia were allocated to 1 of 4 treatment groups treated for 90 days with, respectively, ezetimibe, simvastatin, ezetimibe plus simvastatin, or placebo. Monocyte cytokine release was determined at baseline and after 30 and 90 days of treatment. Compared with placebo, all the remaining treatment options reducedmonocyte release of tumor necrosis factor-α, interleukin-1β, interleukin-6, and monocyte chemoattractant protein-1, which was accompanied by a reduction in plasma C-reactive protein levels. In subjects receiving both simvastatin and ezetimibe, posttreatment monocyte cytokine release and plasma C-reactive protein levels did not differ from those observed in 30 matched healthy subjects. Monocyte-suppressing and systemic-anti-inflammatory effects were more expressed in simvastatin- than in ezetimibe-treated patients and strongest when both the agents were administered together. The results obtained suggest that simvastatin may be a better treatment option than ezetimibe in isolated hypercholesterolemic patients and that hypercholesterolemic patients of high cardiovascular risk may benefit the most from combined treatment with simvastatin and ezetimibe.
Contextualizing Parasympathetic Hyperactivity in Functionally Overreached Athletes With Perceptions of Training Tolerance.

PURPOSE Heart-rate variability (HRV) as a measure of autonomic function may increase in response to training interventions leading to increases or decreases in performance, making HRV interpretation difficult in isolation. This study aimed to contextualize changes in HRV with subjective measures of training tolerance. METHODS Supine and standing measures of vagally mediated HRV (root-mean-square difference of successive normal RR intervals [RMSSD]) and measures of training tolerance (Daily Analysis of Life Demands for Athletes questionnaire, perception of energy levels, fatigue, and muscle soreness) were recorded daily during 1 wk of light training (LT), 2 wk of heavy training (HT), and 10 d of tapering (T) in 15 male runners/ triathletes. HRV and training tolerance were analyzed as rolling 7-d averages at LT, HT, and T. Performance was assessed after LT, HT, and T with a 5-km treadmill time trial (5TTT). RESULTS Time to complete the 5TTT likely increased after HT (effect size [ES] ± 90% confidence interval = 0.16 ± 0.06) and then almost certainly decreased after T (ES = -0.34 ± 0.08). Training tolerance worsened after HT (ES ≥ 1.30 ± 0.41) and improved after T (ES ≥ 1.27 ± 0.49). Standing RMSSD very likely increased after HT (ES = 0.62 ± 0.26) and likely remained higher than LT at the completion of T (ES = 0.38 ± 0.21). Changes in supine RMSSD were possible or likely trivial. CONCLUSIONS Vagally mediated HRV during standing increased in response to functional overreaching (indicating potential parasympathetic hyperactivity) and also to improvements in performance. Thus, additional measures such as training tolerance are required to interpret changes in vagally mediated HRV.
Prematurity and programming: contribution of neonatal Intensive Care Unit interventions

Contemporary clinical practice for the care of the prematurely born babies has markedly improved their rates of survival so that most of these babies are expected to grow up to live a healthy functional life. Since the clinical follow-up is of short duration (years), only limited data are available to relate non-communicable diseases in adult life to events and interventions in the neonatal period. The major events that could have a programming effect include: (1) intrauterine growth restriction; (2) interruption of pregnancy with change in redox and reactive oxygen species (ROS) injury; (3) nutritional and pharmacological protocols for clinical care; and (4) nutritional care in the first 2 years resulting in accelerated weight gain. The available data are discussed in the context of perturbations in one carbon (methyl transfer) metabolism and its possible programming effects. Although direct evidence for genomic methylation is not available, clinical and experimental data on impact of redox and ROS, of low protein intake, excess methionine load and vitamin A, on methyl transfers are reviewed. The consequences of antenatal and postnatal administration of glucocorticoids are presented. Analysis of the correlates of insulin sensitivity at older age, suggests that premature birth is the major contributor, and is compounded by gain in weight during infancy. We speculate that premature interruption of pregnancy and neonatal interventions by affecting one carbon metabolism may cause programming effects on the immature baby. These can be additive to the effects of intrauterine environment (growth restriction) and are compounded by accelerated growth in early infancy.
CORONARY ARTERY DISEASE Original Studies Effects of Aspiration Thrombectomy on Necrosis Size and Ejection Fraction After Transradial Percutaneous Coronary Intervention in Acute ST-Elevation Myocardial Infarction

Background: The use of routine aspiration thrombectomy in primary percutaneous coronary intervention (PCI) remains controversial. Methods: Patients in the EArly Discharge after Transradial Stenting of CoronarY Arteries in Acute Myocardial Infarction (n 5 105) study were treated with aspirin, clopidogrel, and abciximab within 6 hr of symptoms onset. Operators were allowed to use 6 Fr Export aspiration catheter at their discretion. In this observational analysis, we compared acute and late results in patients treated with and without thrombectomy using cardiac biomarkers, angiographic, cardiovascular magnetic resonance (CMR), and clinical parameters. Results. Patients in the thrombectomy group (n 5 44) had longer symptoms to balloon time (196 6 86 min vs. 164 6 62, P 5 0.039) and higher incidence of preprocedural TIMI flow grade 0 or 1 (84% vs. 64%, P 5 0.028). Following PCI, both groups had similar incidence of TIMI flow grade 3 (93 vs. 92%, P 5 0.73) and myocardial blush grade 2 or 3 (80 vs. 77%, P 5 0.86), respectively. Patients in thrombectomy group had significantly higher post-PCI maximum values of creatine kinase-MB (P 5 0.0007) and troponin T (P 5 0.0010). Accordingly, post-PCI myocardial necrosis by CMR was higher (P 5 0.0030) in patients in the thrombectomy group. At 6-month follow-up, necrosis size remained higher (20.7% 6 13.3% vs. 13.5% 6 11.1%, P 5 0.012) in the thrombectomy group. Ejection fraction at 6 months was 65% 6 9% in patients in thrombectomy group compared to 70% 6 11% in patients without (P 5 0.070). Results were not affected by initial TIMI flow or symptoms to balloon time. Clinical events remained comparable in both groups at 12 months follow-up. Conclusion: In patients with ST-segment elevation myocardial infarction presenting within 6 hr of symptoms and undergoing primary angioplasty with maximal antiplatelet therapy, acute and late results did not suggest significant benefit for additional aspiration thrombectomy, irrespective of initial TIMI flow or total ischemic time. VC 2010 Wiley-Liss, Inc.
Learning Sets in an Invertebrate

Eight isopods, Porcellio scaber, were trained with water reinforcement to turn in a T-maze to criterion of correct responses. They were then tested through nine reversals of the turning response. An analysis of variance indicated that mean errors to criterion declined significantly over reversals (F = 4.78, d.f. = 9/63, P < .001).
[Fosinopril up-regulates and ameliorates the Ang II induced down-expression of klotho gene in NRK-52E].

OBJECTIVE To investigate the effect of fosinopril (Fos) on regulating klotho gene expression and elucidate the mechanism of Fos regulating the Angiotensin II (AngII) -induced down-expression of klotho gene. METHODS Culture cells, NRK-52E, were incubated with media either AngII or Fos or both of all. Experimental groups incubated with Fos (10(-5) mol/L) were divided according to variant points of time for 0 (control), 3, 6, 12, 24 h. Different concentration of Fos was selected to incubated with culture cells for 0 (control), 10(-9) 10(-8), 10(-7), 10(-6), 10(-5) mol/L at the optimal time point (24 h). Five groups, which were A: control; B: AngII (10(-7) mol/L); C: Fos(10(-5) mol/L); D: AngII (10(-7) mol/L) + Fos(10(-5) mol/L) and E: Cells pretreated with Fos(10(-5) mol/L)12 h incubated with AngII (10(-7) mol/L) were divided to observe the effect of Fos on expression of klotho induced by AngII. RT-PCR and immunohistochemistry (IHC) were applied to evaluate the klotho mRNA and protein expression, respectively. RESULTS Fos up-regulated klotho mRNA in time-dependent manner, and independent of dose-dependent manner; AngII obviously decreased the levels of kloltho mRNA and protein expression in NRK-52E as compared to the control (P < 0.05), the down-regulating effect was reversed by incubating both with AngII and Fos (P < 0.05), and Fos could inhibit the down-regulated expression of klotho gene induced by Ang II in NRK-52E. CONCLUSION Fosinopril up-regulates klotho mRNA in time-dependent manner, and inhibits the down-regulated expression of klotho gene induced by Ang II.
Improved Inactivation of Nonenveloped Enteric Viruses and Their Surrogates by a Novel Alcohol-Based Hand Sanitizer

ABSTRACT Norovirus is the leading cause of food-related illness in the United States, and contamination of ready-to-eat items by food handlers poses a high risk for disease. This study reports the in vitro (suspension test) and in vivo (fingerpad protocol) assessments of a new ethanol-based hand sanitizer containing a synergistic blend of polyquaternium polymer and organic acid, which is active against viruses of public health importance, including norovirus. When tested in suspension, the test product reduced the infectivity of the nonenveloped viruses human rotavirus (HRV), poliovirus type 1 (PV-1), and the human norovirus (HNV) surrogates feline calicivirus (FCV) F-9 and murine norovirus type 1 (MNV-1) by greater than 3 log10 after a 30-s exposure. In contrast, a benchmark alcohol-based hand sanitizer reduced only HRV by greater than 3 log10 and none of the additional viruses by greater than 1.2 log10 after the same exposure. In fingerpad experiments, the test product produced a 2.48 log10 reduction of MNV-1 after a 30-s exposure, whereas a 75% ethanol control produced a 0.91 log10 reduction. Additionally, the test product reduced the infectivity titers of adenovirus type 5 (ADV-5) and HRV by ≥3.16 log10 and ≥4.32 log10, respectively, by the fingerpad assay within 15 s; and PV-1 was reduced by 2.98 log10 in 30 s by the same method. Based on these results, we conclude that this new ethanol-based hand sanitizer is a promising option for reducing the transmission of enteric viruses, including norovirus, by food handlers and care providers.