Miracle-dz/UniFAR-FTUs huggingface dataset:
ANG II dependence of tubuloglomerular feedback responsiveness in hypertensive ren-2 transgenic rats.

The present study was performed to determine the angiotensin II (ANG II) dependence of stop-flow pressure (SFP) tubuloglomerular feedback responses in hypertensive transgenic rats [strain name: TGR(mRen2)27] harboring the mouse ren-2 renin gene. SFP feedback responses to increases in late proximal perfusion rate were assessed in pentobarbital-anesthetized male ren-2 transgenic rats during control conditions and after administration of the AT1 receptor antagonist, L-158,809 (1 mg/kg iv). During control conditions, increases in late proximal perfusion rate elicited flow-dependent decreases in SFP. The magnitude of the maximal SFP feedback response to a late proximal perfusion rate of 40 nl/min averaged 16.1 +/- 1.4 mmHg (n = 7), a value higher than that normally observed in normotensive rats. Administration of L-158,809 decreased mean arterial blood pressure (174 +/- 6 vs. 117 +/- mmHg, P < 0.01, n = 10) and attenuated the magnitude of the maximal SFP feedback response by 84 +/- 4% (16.1 +/- 1.4 vs. 2.6 +/- 0.5 mmHg, P < 0.01, n = 7). In contrast, mechanical reduction of renal arterial pressure from 179 +/- 5 to 113 +/- 1 mmHg (P < 0.01, n = 7) attenuated the magnitude of the maximal SFP feedback response by only 43 +/- 5% (14.4 +/- 1.9 vs. 7.9 +/- 0.7 mmHg, P < 0.01, n = 7), indicating that approximately one-half of the attenuation of SFP feed-back responses elicited by AT1 receptor blockade was due to removal of the stimulatory effect of ANG II on the sensitivity of the tubuloglomerular feedback mechanism. (ABSTRACT TRUNCATED AT 250 WORDS)
Radiofrequency ablation followed by conventional radiotherapy for medically inoperable stage I non-small cell lung cancer.

PURPOSES The standard treatment of stage I non-small cell lung cancer (NSCLC) is surgical resection. Some patients are poor surgical candidates due to severe comorbid medical conditions. Radiotherapy alone has historically been used in this patient population with limited success. Radiofrequency ablation (RFA) is an image-guided, thermally mediated ablative technique recently applied to lung tumors. Combination therapy with both these treatments has not been previously performed. We report our experience with combined CT-guided RFA and conventional radiotherapy in 24 medically inoperable patients with a minimum of 2-year study follow-up in surviving patients. PATIENTS AND METHODS Twenty-four consecutive, medically inoperable patients with biopsy-proven, stage I NSCLC were treated with CT-guided RFA followed by radiotherapy to a dose of 66 Gy. RFA was performed with a single or cluster cool-tip F electrode; 21 patients were staged before therapy using fluorodeoxyglucose-positron emission tomography. RESULTS There were 14 women and 10 men (median age, 76 years; range, 58 to 85 years). The histologic subtypes were squamous cell (n = 13), adenocarcinoma (n = 5), and undifferentiated (n = 6). All patients received RFA followed by three-dimensional conformal radiotherapy. There were no treatment-related deaths or grade 3/4 toxicities. Pneumothorax requiring chest tubes developed in three patients (12.5%). At a mean follow-up period of 26.7 months (range, 6 to 65 months), 14 patients (58.3%) died, with cumulative survival rates of 50% and 39% at the end of 2 years and 5 years, respectively. Ten of the deaths were cancer related. Two patients had local recurrence (8.3%), while nine patients had systemic metastatic disease. Three patients died of respiratory failure with no evidence of active disease, and one patient died of a cerebrovascular accident at 18-month follow-up. Pleural effusions developed after treatment in six patients (25%), which proved to be malignant in one patient. CONCLUSION RFA followed by conventional radiotherapy is feasible in this population of medically inoperable stage I NSCLC patients. Procedural complication rates are low, and no additional major toxicities were seen despite the addition of RFA. Local control and survival rates appear to be better than with radiotherapy alone.
Vesicular Stomatitis Virus M Protein Mutant Stimulates Maturation of Toll-Like Receptor 7 (TLR7)-Positive Dendritic Cells through TLR-Dependent and -Independent Mechanisms

ABSTRACT Wild-type (wt) vesicular stomatitis virus (VSV) strains stimulate plasmacytoid dendritic cells (pDC) through Toll-like receptor 7 (TLR7) and its adaptor molecule, MyD88. Granulocyte-macrophage colony-stimulating factor-derived DC (G-DC), which do not express TLR7, are unresponsive to wt VSV due to inhibition of cellular gene expression by the matrix (M) protein. In contrast to its recombinant wt (rwt) counterpart, an M protein mutant of VSV, rM51R-M virus, stimulates maturation of G-DC independently of MyD88. These results suggest that, as in the case of G-DC, rM51R-M virus may stimulate pDC by mechanisms distinct from that by rwt virus. Studies presented here demonstrate that both rwt and rM51R-M viruses induced maturation of TLR7-positive DC derived by culture in the presence of Flt3L (F-DC), with the subsequent expression of type I interferon (IFN). F-DC are a mixture of myeloid (CD11b+) and plasmacytoid (B220+) DC, both of which respond to TLR7 ligands. Separated CD11b+ and B220+ F-DC responded to both rwt and rM51R-M viruses. Both viruses were also defective at inhibiting host gene expression in F-DC, including the expression of genes involved in the antiviral response. The data from F-DC generated from IFN receptor knockout mice demonstrated that the maturation of F-DC induced by rwt virus was dependent on the type I IFN response, while maturation induced by rM51R-M virus was partially dependent on this molecule. Therefore, activation of the type I IFN pathway appears to be important for not only inducing an antiviral response but also for stimulating maturation of F-DC upon virus infection. Importantly, F-DC from TLR7 and MyD88 knockout mice did not undergo maturation in response to rwt virus, while maturation induced by rM51R-M virus was largely independent of both molecules. These results indicate that although both viruses induce F-DC maturation, F-DC detect and respond to rM51R-M virus by means that are distinct from rwt virus. Specifically, this mutant virus appears capable of inducing DC maturation in a wide variety of DC subsets through TLR-dependent and independent mechanisms.
The metabolic effects of lopinavir/ritonavir in HIV-negative men

Background: Therapy with HIV protease inhibitors (PI) has been shown to worsen glucose and lipid metabolism, but whether these changes are caused by direct drug effects, changes in disease status, or body composition is unclear. Therefore, we tested the effects of the PI combination lopinavir and ritonavir on glucose and lipid metabolism in HIV-negative subjects. Methods: A dose of 400 mg lopinavir/100 mg ritonavir was given twice a day to 10 HIV-negative men. Fasting glucose and insulin, lipid and lipoprotein profiles, oral glucose tolerance, insulin sensitivity by euglycemic hyperinsulinemic clamp, and body composition were determined before and after lopinavir/ritonavir treatment for 4 weeks. Results: On lopinavir/ritonavir, there was an increase in fasting triglyceride (0.89 ± 0.15 versus 1.63 ± 0.36 mmol/l; P = 0.007), free fatty acid (FFA; 0.33 ± 0.04 versus 0.43 ± 0.06 mmol/l; P = 0.001), and VLDL cholesterol (15.1 ± 2.6 versus 20 ± 3.3 mg/dl; P = 0.05) levels. There were no changes in fasting LDL, HDL, IDL, lipoprotein (a), or total cholesterol levels. Fasting glucose, insulin, and insulin-mediated glucose disposal were unchanged, but on a 2 h oral glucose tolerance test glucose and insulin increased. There were no changes in weight, body fat, or abdominal adipose tissue by computed tomography. Conclusion: Treatment with 4 weeks of lopinavir/ritonavir in HIV-negative men causes an increase in triglyceride levels, VLDL cholesterol, and FFA levels. Lopinavir/ritonavir leads to a deterioration in glucose tolerance at 2 h, but there is no significant change in insulin-mediated glucose disposal rate by euglycemic hyperinsulinemic clamp.
Calciphylaxis: a still unmet challenge.

INTRODUCTION Calcific uremic arteriolopathy (CUA), also known as calciphylaxis, is a rare disease most frequently occurring in patients with advanced chronic kidney disease (CKD). The clinical picture is typically characterized by very painful skin lesions and ulcerations following calcification and occlusion of small cutaneous arterioles. CUA is life-threatening due to infections and concomitant cardiovascular diseases. METHODS We performed a literature search for the terms calciphylaxis and calcific uremic arteriolopathy and summarized current state-of-the-art knowledge about pathophysiology, clinical picture, course of the disease, as well as treatment options. We have filled out the literature data with our personal treatment experiences. RESULTS A combination of various local and systemic risk factors are necessary to cause the development of calciphylaxis. This pathophysiological cascade is still incompletely understood. Patients with advanced CKD and dialysis patients are especially at risk to develop CUA. Regarding therapy, no randomized prospective trials are available, and treatment is rather based on pathophysiological considerations as well as on evidence derived from case reports or case series. Therapy focuses on optimized dialysis treatment, control of chronic kidney disease-mineral and bone disorder parameters, experimental anticalcification strategies and wound care. CONCLUSION Facing the still deleterious outcome of patients with calciphylaxis, further studies on prophylaxis as well as treatment are urgently needed. Current treatment strategies may help ameliorate the course of the disease in some patients. However, it is still unclear if they are able to decrease mortality.
Expression of the receptor for advanced glycation end products in oligodendrocytes in response to oxidative stress

Demyelination is a common result of oxidative stress in the nervous system, and we report here that the response of oligodendrocytes to oxidative stress involves the receptor for advanced glycation end products (RAGE). RAGE has not previously been reported in neonatal rat oligodendrocytes (NRO), but, by using primers specific for rat RAGE, we were able to show expression of messenger RNA (mRNA) for RAGE in NRO, and a 55‐kDa protein was detected by Western blotting with antibodies to RAGE. Neonatal rat oligodendrocytes stained strongly for RAGE, suggesting membrane localization of RAGE. Addition of low concentrations of hydrogen peroxide (100 μM) initiated 55‐kDa RAGE shedding from the cell membrane and the appearance of “soluble” 45‐kDa RAGE in the culture medium, followed by restoration of RAGE expression to normal levels. Increasing hydrogen peroxide concentration (>200 μM) resulted in no restoration of RAGE, and the cells underwent apoptosis and necrosis. We further confirmed the observation in a human oligodendroglioma‐derived (HOG) cell line. Both the antioxidant N‐acetyl‐L‐cysteine and the broad‐spectrum metalloproteases inhibitor TAPI0 were able partially to inhibit shedding of RAGE, suggesting involvement of metalloproteases in cleavage to produce soluble RAGE. The level of 55‐kDa RAGE in autopsy brain of patients undergoing neurodegeneration with accompanying inflammation [multiple sclerosis and neuronal ceroid‐lipofuscinosis (Batten's disease)] was much lower than that in age‐matched controls, suggesting that shedding of RAGE might occur as reactive oxygen species accumulate in brain cells and be part of the process of neurodegeneration. © 2008 Wiley‐Liss, Inc.
VITAMIN A SUPPLEMENTATION INDUCES OXIDATIVE STRESS AND DECREASES THE IMMUNOCONTENT OF CATALASE AND SUPEROXIDE DISMUTASE IN RAT LUNGS

Lungs require an adequate supply of vitamin A for normal embryonic development, postnatal maturation, and maintenance and repair during adult life. However, recent intervention studies revealed that supplementation with retinoids resulted in a higher incidence of lung cancer, although the mechanisms underlying this effect are still unknown. Here, the authors studied the effect of vitamin A supplementation on oxidative stress parameters in lungs of Wistar rats. Vitamin A supplementation either at therapeutic (1000 and 2500 IU/kg) or excessive (4500 and 9000 IU/kg) doses for 28 days induced lipid peroxidation, protein carbonylation, and oxidation of protein thiol groups, as well as change in catalase (EC 1.11.1.6; CAT) and superoxide dismutase (EC 1.15.1.1, SOD) activities and immunocontents. These results altogether suggest that vitamin A supplementation causes significant changes in redox balance the free radical status in lungs, which are frequently associated to severe lung dysfunction.
Relaxin polymorphisms associated with metabolic disturbance in patients treated with antipsychotics

People with schizophrenia have an increased risk of metabolic syndrome, with consequent elevated morbidity and mortality, largely due to cardiovascular disease. Metabolic disorders comprise obesity, dyslipidemia and elevated levels of triglycerides, hypertension, and disturbed insulin and glucose metabolism. The elevated risk of metabolic syndrome in individuals suffering from schizophrenia is believed to be multifactorial, related to a genetic predisposition, lifestyle characteristics and treatment with antipsychotic medications. Relaxin 3 (RLN3, also known as INSL7) is a recently identified member of the insulin/relaxin superfamily that plays a role in the regulation of appetite and body weight control. RLN3 stimulates relaxin-3 receptor 1 (relaxin/insulin-like family peptide receptor 3, RXFP3) and relaxin receptor 2 (relaxin/insulin-like family peptide receptor 4, RXFP4). We have investigated the role of ten polymorphisms in these genes (RLN3 rs12327666, rs1982632, and rs7249702, RLN3R1 rs42868, rs6861957, rs7702361, and rs35399, and RLN3R2 rs11264422, rs1018730 and rs12124383) in the occurrence of metabolic syndrome phenotypes (obesity, diabetes, hypercholesterolemia, hypertrigyceridemia, and hypertension) in a cross-sectional cohort of 419 US Caucasian patients treated with antipsychotic drugs. We found several associations between relaxin polymorphisms and hypecholesterolemia, obesity and diabetes, suggesting a role for the relaxin/insulin pathway in the development of metabolic disturbance observed in patients treated with antipsychotics.
Performance analysis of brazilian public and philanthropic hospitals

This paper presents the results of a research that aimed at identifying optimal performance standards of Brazilian public and philanthropic hospitals. In order to carry out the analysis, a model based on Data Envelopment Analysis (DEA) was developed. We collected financial data from hospitals’ financial statements available on the internet, as well as operational data from the Information Technology Department of the Brazilian Public Health Care System – SUS (DATASUS). Data from 18 hospitals from 2007 to 2011 were analyzed. Our DEA model used both operational and financial indicators (variables). In order to develop this model, two indicators were considered inputs: Values (in Brazilian Reais) of Fixed Assets and Planned Capacity. On the other hand, the following indicators were considered outputs: Net Margin, Return on Assets and Institutional Mortality Rate. As regards the proposed model, there were five hospitals with optimal performance and four hospitals were considered inefficient, upon the analysis of the variables, considering the analyzed period. Analysis of the weights indicated the most relevant variables for determining efficiency and scale variable values, which is an important tool to aid the decision-making by hospital managers. Finally, the scale variables determined the returns on production, indicating that 14 hospitals work with scale diseconomies. This may indicate inefficiency in the resource management of the Brazilian public health-care system, by analyzing this set of proposed variables. Classification- JEL:
Modulational instability in the full-dispersion Camassa–Holm equation

We determine the stability and instability of a sufficiently small and periodic travelling wave to long-wavelength perturbations, for a nonlinear dispersive equation which extends a Camassa–Holm equation to include all the dispersion of water waves and the Whitham equation to include nonlinearities of medium-amplitude waves. In the absence of the effects of surface tension, the result qualitatively agrees with the Benjamin–Feir instability of a Stokes wave. In the presence of the effects of surface tension, it qualitatively agrees with those from formal asymptotic expansions of the physical problem and improves upon that for the Whitham equation, predicting the critical wave number at the strong surface tension limit. We discuss the modulational stability and instability in the Camassa–Holm equation and other related models.
Old Age and the Hepatic Sinusoid

Morphological changes in the hepatic sinusoid with old age are increasingly recognized. These include thickening and defenestration of the liver sinusoidal endothelial cell, sporadic deposition of collagen and basal lamina in the extracellular space of Disse, and increased numbers of fat engorged, nonactivated stellate cells. In addition, there is endothelial up‐regulation of von Willebrand factor and ICAM‐1 with reduced expression of caveolin‐1. These changes have been termed age‐related pseudocapillarization. The effects of old age on Kupffer cells are inconsistent, but impaired responsiveness is likely. There are functional implications of these aging changes in the hepatic sinusoid. There is reduced sinusoidal perfusion, which will impair the hepatic clearance of highly extracted substrates. Blood clearance of a variety of waste macromolecules takes place in liver sinusoidal endothelial cells (LSECs). Previous studies indicated either that aging had no effect, or reduced the endocytic capacity of LSECs. However, a recent study in mice showed reduced endocytosis in pericentral regions of the liver lobules. Reduced endocytosis may increase systemic exposure to potential harmful waste macromolecules such as advanced glycation end products Loss of fenestrations leads to impaired transfer of lipoproteins from blood to hepatocytes. This provides a mechanism for impaired chylomicron remnant clearance and postprandial hyperlipidemia associated with old age. Given the extensive range of substrates metabolized by the liver, age‐related changes in the hepatic sinusoid and microcirculation have important systemic implications for aging and age‐related diseases. Anat Rec, 291:672–683, 2008. © 2008 Wiley‐Liss, Inc.
Molecular Targeting of Alzheimer's Amyloid Plaques for Contrast-Enhanced Magnetic Resonance Imaging

Smart molecular probes for both diagnostic and therapeutic purposes are expected to provide significant advances in clinical medicine and biomedical research. We describe such a probe that targets beta-amyloid plaques of Alzheimer's disease and is detectable by magnetic resonance imaging (MRI) because of contrast imparted by gadolinium labeling. Three properties essential for contrast enhancement of beta-amyloid plaques on MRI exist in this smart molecular probe, putrescine-gadolinium-amyloid-beta peptide: (1) transport across the blood-brain barrier following intravenous injection conferred by the polyamine moiety, (2) binding to plaques with molecular specificity by putrescine-amyloid-beta, and (3) magnetic resonance imaging contrast by gadolinium. MRI was performed on ex vivo tissue specimens at 7 T at a spatial resolution approximating plaque size (62.5 microm(3)), in order to prove the concept that the probe, when administered intravenously, can selectively enhance plaques. The plaque-to-background tissue contrast-to-noise ratio, which was precisely correlated with histologically stained plaques, was enhanced more than nine-fold in regions of cortex and hippocampus following intravenous administration of this probe in AD transgenic mice. Continuing engineering efforts to improve spatial resolution are underway in MRI, which may enable in vivo imaging at the resolution of individual plaques with this or similar contrast probes. This could enable early diagnosis and also provide a direct measure of the efficacy of anti-amyloid therapies currently being developed.
International cooperation of emergency services : limiting and facilitating factors between the Netherlands and Germany

The purpose of this research was to explore the underlying factors of international cooperation of emergency services in the Netherlands and Germany. This study builds upon contextual distances (Dawes et al. 2012). These distances have been examined through the use of a qualitative research design in which 10 professionals from the Netherlands and Germany in the field of international cooperation of police and security regions were interviewed. Data was analysed by a process of several coding rounds. The results show that there are four general categories with several subcategories which prove to be important within international cooperation of emergency services; communication (media, language, organisational procedures and culture), resources (technical, organisational and financial), organisational factors (operational, relational factors, geographical situation, political influence) and personal factors (intention and personal network). In addition, this research argues that influential factors on international cooperation can be seen as facilitating or limiting. The main facilitating factors of international cooperation are the similarities in shared elements, geographical situation, personal intention and benefits which arise from the resources organisations have to offer each other. Problematic and limiting remain the factors related to communication such as the differences in culture, media and organisational procedures.
The relationship of Hammondia hammondi and Sarcocystis mucosa to other heteroxenous cyst-forming coccidia as inferred by phylogenetic analysis of the 18S SSU ribosomal DNA sequence

The complete sequence of the 18S small subunit (SSU) ribosomal DNA of Hammondia hammondi and Sarcocystis mucosa was obtained and compared to SSU rDNA sequences of Neospora caninum, Toxoplasma gondii, Besnoitia besnoiti, 2 species of Frenkelia, 3 species of Isospora, and 13 species of Sarcocystis. Analyses showed that H. hammondi and T. gondii are monophyletic and that these taxa shared a common ancestor with N. caninum and B. besnoiti. The weight of evidence shows that S. mucosa, S. neurona, and Frenkelia species form a clade thereby supporting the conclusion that Sarcocystis is paraphyletic.
Fetal anticonvulsant syndromes and polymorphisms in MTHFR, MTR, and MTRR

The malformations found in fetal anticonvulsant syndromes (FACS) are associated with folic acid deficiency and methylene‐tetrahydrofolate reductase (MTHFR) polymorphisms in the general population. To investigate a possible association between FACS and MTHFR genotype, we recruited 200 mothers who had taken anti‐epileptic drugs in pregnancy, and delivered at Aberdeen Maternity Hospital over a 26‐year period. Clinical findings in the mothers and their 337 children were documented. A clinical algorithm was devised to diagnose FACS objectively. Case‐parent triads were genotyped for polymorphisms in MTHFR, serine hydroxymethyl transferase (SHMT1), methionine synthase (MTR), and methionine synthase reductase (MTRR), and analyzed by log‐linear regression. No effect of the child's genotype on congenital malformation, neurodevelopmental disorder or FACS was detected using this method. The risk of having a child with congenital malformation or FACS was three to four times higher for mothers who were MTHFR 677TT homozygotes compared with MTHFR 677CC homozygotes. MTR 2756A > G and MTRR 66A > G genotype frequencies in children with FACS and neurodevelopmental disorder were different from those in healthy blood donor controls. © 2007 Wiley‐Liss, Inc.