Miracle-dz/UniFAR-FTUs huggingface dataset:
SPECIAL TOPIC Intracrine Renin-Angiotensin System: A New Paradigm in Cardiovascular and Renal Control Novel roles of nuclear angiotensin receptors and signaling mechanisms

Gwathmey TM, Alzayadneh EM, Pendergrass KD, Chappell MC. Novel roles of nuclear angiotensin receptors and signaling mechanisms. Am J Physiol Regul Integr Comp Physiol 302: R518–R530, 2012. First published December 14, 2011; doi:10.1152/ajpregu.00525. 2011. —The renin-angiotensin system (RAS) constitutes an important hormonal system in the physiological regulation of blood pressure. The dysregulation of the RAS is considered a major influence in the development and progression of cardiovascular disease and other pathologies. Indeed, experimental and clinical evidence indicates that blockade of this system with angiotensin-converting enzyme (ACE) inhibitors or angiotensin type 1 receptor (AT1R) antagonists is an effective therapy to attenuate hypertension and diabetic renal injury, and to improve heart failure. Originally defined as a circulating system, multiple tissues express a complete RAS, and compelling evidence now favors an intracellular system involved in cell signaling and function. Within the kidney, intracellular expression of the three predominant ANG receptor subtypes is evident in the nuclear compartment. The ANG type 1 receptor (AT1R) is coupled to the generation of reactive oxygen species (ROS) through the activation of phosphoinositol-3 kinase (PI3K) and PKC. In contrast, both ANG type 2 (AT2R) and ANG-(1–7) (AT7R) receptors stimulate nitric oxide (NO) formation, which may involve nuclear endothelial NO synthase (eNOS). Moreover, blockade of either ACE2—the enzyme that converts ANG II to ANG-(1–7)—or the AT7 receptor exacerbates the ANG II-ROS response on renal nuclei. Finally, in a model of fetal programmed hypertension, the nuclear ROS response to ANG II is enhanced, while both AT2 and AT7 stimulation of NO is attenuated, suggesting that an imbalance in the intracellular RAS may contribute to the development of programming events. We conclude that a functional intracellular or nuclear RAS may have important implications in the therapeutic approaches to cardiovascular disease.
Estimation of Short-Term Effects of Air Pollution on Stroke Hospital Admissions in Southern Sweden

Background: Short-term exposure to high levels of air pollution can increase stroke risk. In this study we investigated the short-term effects of air pollution on hospital admissions for stroke in a setting where pollutant levels are rather low. We also addressed methodological issues in evaluating the short-term effects of air pollution. Methods: Daily admissions of ischemic (n = 11,267) and hemorrhagic (n = 1,681) stroke were obtained from a Swedish quality register for stroke, Riks-Stroke. We used two types of exposure data: (1) daily measured background levels of ozone, temperature and particles with a diameter <10 µm (PM10) and (2) modeled levels of a mixture of NO and NO2 (NOx) at the residential address of each individual. Results: We estimated a 13% (95% confidence interval, 4–22%) increased risk for hospital admissions for ischemic stroke for levels of PM10 above 30 µg/m3 compared to <15 µg/m3, whereas temperature above 16°C decreased the risk. No consistent associations were found for hemorrhagic stroke or for ischemic stroke and ozone or NOx. Conclusion: Particulate air pollution and temperature seemed to be associated with ischemic stroke hospital admissions. Individual exposure modeling facilitates a detailed exposure assessment but may also be more prone to misclassification errors. The time series and case crossover approaches yielded similar effect estimates.
Effects of Reduced Dialysate Calcium on Calcium-Phosphorus Product and Bone Metabolism in Hemodialysis Patients

Background: The safety of using reduced calcium dialysate (RDC) in hemodialysis (HD) patients is controversial due to related changes in bone metabolism. In the present study we investigated whether an 18-month treatment period with RDC may induce significant changes in calcium-phosphorus product (CaxP), bone metabolism, and components of the insulin-like growth factor (IGF) system in HD patients. Study Design: In this prospective study, 13 HD patients with biochemical signs of diminished or low-normal bone turnover and high CaxP due to high serum calcium level were treated by lowering dialysate calcium from 3.5 to 2.5 mEq/l for 18 months. By specific immunometric assays, serum levels of intact parathyroid hormone (PTH), bone alkaline phosphatase (B-ALP), pyridinoline (PYR), desoxypyridinoline (D-PYR), 25-OH-vitamin D3 (25-vit D3), 1,25-(OH)2-vitamin D3 (1,25-vit D3), free IGF-I, IGF-II, and IGF-binding protein (IGFBP)-1 to -6 were measured. Results: CaxP decreased significantly from 5.62 (baseline) to 3.95 mmol2/l2 (at 18 months), whereas PTH increased from 81 ± 57 pg/ml at baseline to 236 ± 188 at 12 months (p < 0.01), remaining in this range thereafter. Parameters of bone resorption (PYR) as well as formation (B-ALP) significantly increased during RDC, with peak levels after 12 months. Despite increasing doses of oral alfacalcidol, levels of 25-vit D3 and 1,25-vit D3 subsequently declined during RDC. In parallel with the changes in bone markers, free IGF-I levels decreased (baseline: 1.9 ± 0.9 ng/ml, after 18 months: 1.1 ± 0.7; p < 0.01). The decline of free IGF-I correlated with decreasing levels of IGFBP-3 and increasing levels of IGFBP-1/-4. Conclusion: The treatment with RDC effectively lowered CaxP and stimulated bone formation and resorption. The different changes in bone markers and IGF system components mirror the complex effects on bone metabolism.
Adenovirus infection in patients with Kawasaki disease

Two outbreaks of Kawasaki disease at different times and areas (Kyoto in 1982 and Sapporo in 1985) of Japan were studied retrospectively for the presence of antibodies to adenoviruses and herpesviruses. Only 2 of 12 (16.7%) consecutive acute phase sera of patients from the outbreak in 1982 and 1 of 10 (10.0%) sera from 1985 showed positive antibodies for the common adenovirus antigen by a complement fixation (CF) test, whereas 10 of 16 (62.5%) age‐ and sex‐matched controls during the outbreak of Kawasaki disease in 1985 were seropositive by the CF test. In contrast, using a recently developed enzyme‐linked immunosorbent assay (ELISA), 9 patients (75.0%) in 1982 and 9 patients (90.0%) in 1985 had antibodies to adenovirus type 2. In addition, 5 of 10 (50.0%) of the 1982 and 6 of 9 (66.7%) of the 1985 patients who were seronegative for CF antibodies were positive for IgM antibodies to adenovirus type 2. Fifteen (93.8%) controls were positive for antibodies to adenovirus type 2 by ELISA and only two sera showed negative CF antibodies with positive IgM antibodies to adenovirus type 2. Sequential sera from 4 patients in 1985 had either IgM or IgG antibodies by ELISA and eventually three became seropositive by the CF test in time. Additionally, no significant difference was noted with antibody status to herpes simplex virus type 1 and 2 (HSV‐1 and HSV‐2), varicella zoster virus (VZV), and cytomegalovirus (CMV) between patients and controls. In contrast, antibodies to Epstein‐Barr virus (EBV) were found in only one of 22 (4.5%) patients, whereas 13 (81.3%) controls were seropositive for EBV. These findings suggests that the primary infection with adenovirus type 2 may be associated with Kawasaki disease in patients who are seronegative for EBV.
Spontaneous local alpha oscillations predict motion‐induced blindness

Bistable visual illusions are well suited for exploring the neuronal states of the brain underlying changes in perception. In this study, we investigated oscillatory activity associated with ‘motion‐induced blindness’ (MIB), which denotes the perceptual disappearance of salient target stimuli when a moving pattern is superimposed on them (Bonneh et al., ). We applied an MIB paradigm in which illusory target disappearances would occur independently in the left and right hemifields. Both illusory and real target disappearance were followed by an alpha lateralization with weaker contralateral than ipsilateral alpha activity (~10 Hz). However, only the illusion showed early alpha lateralization in the opposite direction, which preceded the alpha effect present for both conditions and coincided with the estimated onset of the illusion. The duration of the illusory disappearance was further predicted by the magnitude of this early lateralization when considered over subjects. In the gamma band (60–80 Hz), we found an increase in activity contralateral relative to ipsilateral only after a real disappearance. Whereas early alpha activity was predictive of onset and length of the illusory percept, gamma activity showed no modulation in relation to the illusion. Our study demonstrates that the spontaneous changes in visual alpha activity have perceptual consequences.
New targets in the treatment of anorexia nervosa

The pathophysiology of anorexia nervosa (AN) is complex and involves alterations of serotonin, dopamine and histamine neurotransmitters. In addition, receptor activity is disturbed, presumably in response to the neurotransmitter changes. These alterations are reviewed in relation to symptomatology and outcome of AN. Neuropeptide and peripheral orexigenic and satiety peptide research is in its infancy but holds much promise to shed light on the pathophysiological mechanisms involved in this illness. Current drug therapies have not demonstrated the efficacy desired in the treatment of AN. Current therapies are reviewed and new drug targets are explored. Compounds that interact with serotonin, histamine and dopamine receptors may offer unique treatment opportunities. In the future, the manipulation of peptides may add to the therapeutic potential of pharmacotherapy.
Consumer Culture and Political Ideology Plots in Social Media Campaigns

ABSTRACT A number of studies are devoted to explicating global consumer culture and political ideology plots in traditional advertising. Nevertheless, studies of these plots in social media campaigns are scarce. In order to fill this gap, our study examines consumer culture and political ideology plots utilized by global brands in social media advertisements targeted to US Millennials. Employing semiotic analysis, a series of advertisements from automotive, food and beverage, electronics, personal care products, fast food, athletics and financial sectors were evaluated and interpreted. Our findings uncovered one unique main plot labeled “identity-of-self” and three subplots: 1) successful and young living, 2) Peter Pan syndrome, and 3) purposeful connectedness. Implications for practice and directions for future work are suggested.
Influence of diet on oral health in young adults--pilot study.

INTRODUCTION Diet is a factor that can modify, among others, the course of caries, dental erosive lesions and periodontal disease. It is important to know the influence of diet on the clinical oral condition in young adults. MATERIAL AND METHODS 20 women and 20 men aged 19-21 participated in the study. During a clinical examination of the patients the following clinical indices were estimated: Ap- proximal Plaque Index (API), Bleeding on Probing (BOP) and DMFT indices. The frequency and quality of food products consumed were noted in a special questionnaire. Results with p ≤ 0.05 were considered statistically significant. RESULTS The average API value for the female participants was 77.37%, BOP--23.84% and DMFT--9.9. The t-test results for independent samples showed that women who consumed meat and meat products two times a week or more, had statistically higher API (p = 0.01) and BOP (p = 0.05) values, than the mean value for these indexes. Women who consumed grain products and grain-based products two times a week or more, had higher API values compared to the mean value for this index (p = 0.02). The average API value for the male participants was 34.25%, BOP--10.15% and DMFT--9.05, respectively. Men who consumed milk and dairy products three times a week or less had statistically lower API (p = 0.05) and BOP values (p = 0.02), relative to the mean index values. CONCLUSIONS The chemical composition and texture of the food intake can affect oral health. Besides instruction in oral hygiene, doctors and dentists should also assess the eating habits of their patients.
Prevalence and socio-demographic correlates of daily cigarette smoking in Poland: Results from the Global Adult Tobacco Survey (2009–2010)

ObjectivesThe aim of the study was to evaluate the prevalence and socio-demographic correlates of daily cigarette smoking among adults in Poland.Materials and MethodsA nationally representative household study was implemented between 2009 and 2010 to explore smoking pattern among the population aged 15 years and older. The smoking status and socio-demographic data were determined based on the Global Adult Tobacco Survey (GATS) questionnaire. Out of the 14000 households selected for the survey, 7840 sampled persons completed the interviews, including 2162 respondents who declared daily smoking of cigarettes. Logistic regression models were applied to assess factors related to daily cigarette smoking.ResultsOver 33% of men and 21% of women (p < 0.01) reported tobacco smoking on a daily basis. The significantly higher risk of smoking on a daily basis was observed among the male and female 20–59 years of age compared to the 60 or older population (p < 0.05). For men and women with the lower educational (primary/vocational/secondary) level, the risk of smoking was significantly higher than for the subjects with university degree (p < 0.05). The unemployed men smoked daily significantly more frequently than the employed ones (OR = 1.8; 95% CI: 1.4–2.4). This association was not observed among women (p > 0.05). The residents of urban areas smoked significantly more frequently than people living in rural settings (p < 0.05). ConclusionsActions to tackle socio-economic inequalities in smoking need to be intensified. The antismoking efforts should be focused on the population of Poles at large and people with lower educational levels, unemployed men, and residents of large urban settings in particular. The tobacco control interventions should also address the population of women at reproductive age.
The Role of Interferons in Inflammation and Inflammasome Activation

Inflammation is an essential physiological process, which enables survival during infection and maintains tissue homeostasis. Interferons (IFNs) and pro- and anti-inflammatory cytokines are crucial for appropriate response to pathogens, damaged cells, or irritants in inflammatory response. The inflammasom is multiprotein complex, which initiates cleavage of pro-inflammatory cytokines IL-1β and IL-18 into active forms. In addition, inflammasomes initiate pyroptotic cell death. In the present review, I summarize and analyze recent findings regarding the cross talk of IFNs and inflammasomes.
Effects of a movement and swimming program on vital capacity and water orientation skills of children with cerebral palsy

Swimming and aquatic exercise are known for their effects on respiration in normal and asthmatic people. The purpose of the present study was to evaluate the effect of a 6‐month movement and swimming program on the respiratory function and water orientation skills of children with cerebral palsy (CP). Forty‐six kindergarten children aged 5 to 7 years were assigned either to a treatment or control group. The intervention program consisted of swimming sessions twice weekly and sessions of group physical activity in a gym once weekly, each session lasting 30 minutes, for a period of 6 months. Children in the control group were treated (30 minutes, 4 days per week) with Bobath physical therapy. The children in the treatment and control groups had comparable disability types, age, and anthropometric measurements. A 2 × 2 (group × test period) repeated measures ANOVA design confirmed a significant effect of interaction of time with group. The results also confirmed that children with CP have reduced lung function compared with normative data for children in the same age category. The treatment program improved baseline vital capacity results by 65%, while children in the control group improved by only 23%. The movement and swimming exercise program had a better effect than a physical therapy routine implemented in a previous study, consisting of respiratory exercise alone.
Intra-arterially administered papaverine for the treatment of symptomatic cerebral vasospasm.

OBJECTIVE We examined the therapeutic benefits of intra-arterially administered papaverine for treatment of symptomatic cerebral vasospasm after subarachnoid hemorrhage (SAH). Recent advances in microcatheter technology have facilitated endovascular approaches to vessels experiencing vasospasm after SAH. However, despite numerous encouraging anecdotal reports, no rigorous examination of the efficacy of these procedures has been published. Intra-arterial infusion of papaverine has become part of the standard management of vasospasm at some centers. METHODS We examined a series of 31 patients undergoing papaverine infusion for the treatment of symptomatic vasospasm after SAH. The patients were a subgroup of the series enrolled in the North American Trial of Tirilizad for Aneurysmal Subarachnoid Hemorrhage. These individuals were matched with patients from the same trial who exhibited similar clinical characteristics (including the degree of vasospasm and the modified Glasgow Coma Scale scores measured at the time of admission and on the day of papaverine infusion) but received medical management alone for vasospasm. RESULTS Logistic regression analysis comparing these two groups showed no statistical difference in the 3-month Glasgow Outcome Scale scores between patients receiving papaverine and control subjects (58% favorable outcomes for control subjects versus 45% for patients receiving papaverine). CONCLUSION Although isolated series documenting clinical successes have prompted the increased use of papaverine as a treatment for vasospasm after SAH, this series suggests that, as it is currently being used, the drug does not provide added benefits, compared with medical treatment of vasospasm alone. This result does not preclude the possibility that alterations in the timing of or indications for drug treatment might produce beneficial effects.
Altered ceramide acyl chain length and ceramide synthase gene expression in Parkinson's disease

Genetic studies have provided increasing evidence that ceramide homeostasis plays a role in neurodegenerative diseases including Parkinson's disease (PD). It is known that the relative amounts of different ceramide molecular species, as defined by their fatty acyl chain length, regulate ceramide function in lipid membranes and in signaling pathways. In the present study we used a comprehensive sphingolipidomic case‐control approach to determine the effects of PD on ceramide composition in postmortem brain tissue from the anterior cingulate cortex (a region with significant PD pathology) and the occipital cortex (spared in PD), also assessing mRNA expression of the major ceramide synthase genes that regulate ceramide acyl chain composition in the same tissue using quantitative PCR. In PD anterior cingulate cortex but not occipital cortex, total ceramide and sphingomyelin levels were reduced from control levels by 53% (P < 0.001) and 42% (P < 0.001), respectively. Of the 13 ceramide and 15 sphingomyelin molecular lipid species identified and quantified, there was a significant shift in the ceramide acyl chain composition toward shorter acyl chain length in the PD anterior cingulate cortex. This PD‐associated change in ceramide acyl chain composition was accompanied by an upregulation of ceramide synthase‐1 gene expression, which we consider may represent a response to reduced ceramide levels. These data suggest a significant shift in ceramide function in lipid membranes and signaling pathways occurs in regions with PD pathology. Identifying the regulatory mechanisms precipitating this change may provide novel targets for future therapeutics. © 2013 International Parkinson and Movement Disorder Society
Differential Mechanisms of Impairment of Remote Memory in Alzheimer’s and Frontotemporal Dementia

This paper describes retrograde memory performances of 12 Alzheimer’s disease (AD) patients and 12 frontotemporal dementia (FTD) patients. First of all, we observed that FTD and AD patients did not differ for language tests (verbal fluency tests and oral denomination 80), for semantic memory tests, for logical memory test and Benton visual memory test and differed for anterograde verbal memory and frontal tests. Concerning retrograde memory, there was no difference between AD and FTD patients in retrograde memory scores (autobiographical memory interview, Crovitz’s task, French public events interview battery) and both FTD and AD patients exhibited a retrieval deficit in their remote memory. We observed that the mechanisms of remote memory deficit was different in FTD and in AD patients. We observed no classical paradigm of Ribot for FTD patient’s remote informations, and they appeared to have lost of access to memories and executive difficulties. In AD, the results indicated these patients’ ability to learn new information and to search semantic memory failed.
Activation of hepatocyte growth factor activator zymogen (pro‐HGFA) by human kallikrein 1‐related peptidases

Hepatocyte growth factor activator (HGFA) is a serine protease and a potent activator of prohepatocyte growth factor/scatter factor (pro‐HGF/SF), a multifunctional growth factor that is critically involved in tissue morphogenesis, regeneration, and tumor progression. HGFA circulates as a zymogen (pro‐HGFA) and is activated in response to tissue injury. Although thrombin is considered to be an activator of pro‐HGFA, alternative pro‐HGFA activation pathways in tumor microenvironments remain to be identified. In this study, we examined the effects of kallikrein 1‐related peptidases (KLKs), a family of extracellular serine proteases, on the activation of pro‐HGFA. Among the KLKs examined (KLK2, KLK3, KLK4 and KLK5), we identified KLK4 and KLK5 as novel activators of pro‐HGFA. Using N‐terminal sequencing, the cleavage site was identified as the normal processing site, Arg407–Ile408. The activation of pro‐HGFA by KLK5 required a negatively charged substance such as dextran sulfate, whereas KLK4 could process pro‐HGFA without dextran sulfate. KLK5 showed more efficient pro‐HGFA processing than KLK4, and was expressed in 50% (13/25) of the tumor cell lines examined. HGFA processed by these KLKs efficiently activated pro‐HGF/SF, and led to cellular scattering and invasion in vitro. The activities of both KLK4 and KLK5 were strongly inhibited by HGFA inhibitor type 1, an integral membrane Kunitz‐type serine protease inhibitor that inhibits HGFA and other pro‐HGF/SF‐activating proteases. These data suggest that KLK4 and KLK5 mediate HGFA‐induced activation of pro‐HGF/SF within tumor tissue, which may thereafter trigger a series of events leading to tumor progression via the MET receptor.