Miracle-dz/UniFAR-FTUs huggingface dataset:
Fractalkine/CX3CL1 modulates GABAA currents in human temporal lobe epilepsy

The chemokine fractalkine/CX3CL1 and its receptor CX3CR1 are widely expressed in the central nervous system (CNS). Recent evidence showed that CX3CL1 participates in inflammatory responses that are common features of CNS disorders, such as epilepsy. Mesial temporal lobe epilepsy (MTLE) is the prevalent form of focal epilepsy in adults, and hippocampal sclerosis (HS) represents the most common underlying pathologic abnormality, as demonstrated at autopsy and postresection studies. Relevant features of MTLE are a characteristic pattern of neuronal loss, as are astrogliosis and microglia activation. Several factors affect epileptogenesis in patients with MTLE, including a lack of γ‐aminobutyric acid (GABA)ergic inhibitory efficacy. Therefore, experiments were designed to investigate whether, in MTLE brain tissues, CX3CL1 may influence GABAA receptor (GABAAR) mediatedtransmission, with a particular focus on the action of CX3CL1 on the use‐dependent decrease (rundown) of the GABA‐evoked currents (IGABA), a feature underlying the reduction of GABAergic function in epileptic tissue.
Hepatoprotective effects of Juglans regia extract against CCl4-induced oxidative damage in rats

Abstract Context: Different parts of the walnut [Juglans regia L. (Juglandaceae)] have been used in folk medicine for protection against liver injury, although its actual efficacy remains uncertain. Objective: The present study investigated the protective effect of walnut leaf extract against carbon tetrachloride (CCl4)-induced liver damage in rats. Materials and methods: The rats were randomly divided into seven groups: control, CCl4 (i.p., 0.5 mL/kg b.w., 50% CCl4 in olive oil), walnut extract (at dose level of 0.2 g/kg b.w.) alone, walnut extract (at dose levels of 0.05, 0.1, 0.2 and 0.4 g/kg b.w.) with CCl4, and treatment was carried out accordingly. On the 28th day, rats were sacrificed and blood was withdrawn by cardiac puncture. Liver damage was assessed by serum biochemical parameters (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and albumin), antioxidant enzymes (superoxide dismutase and catalase) and histopathological observation. Results: Administration of walnut leaf extract (ranging from 0.2 to 0.4 g/kg b.w.) significantly lowered serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase levels in CCl4-treated rats. Walnut leaf extract increased antioxidant enzymes, including superoxide dismutase and catalase. Histopathological examination of livers showed that walnut leaves extract reduced fatty degeneration, cytoplasmic vacuolization and necrosis in CCl4-treated rats. Discussion and conclusion: These results suggest that walnut extract has a protective effect over CCl4-induced oxidative damage in rat liver. These results demonstrate that walnut extract acts as a good hepatoprotective and antioxidant agent in attenuating hepatocellular damage.
α-Synuclein Blocks ER-Golgi Traffic and Rab1 Rescues Neuron Loss in Parkinson's Models

Alpha-synuclein (αSyn) misfolding is associated with several devastating neurodegenerative disorders, including Parkinson's disease (PD). In yeast cells and in neurons αSyn accumulation is cytotoxic, but little is known about its normal function or pathobiology. The earliest defect following αSyn expression in yeast was a block in endoplasmic reticulum (ER)–to–Golgi vesicular trafficking. In a genomewide screen, the largest class of toxicity modifiers were proteins functioning at this same step, including the Rab guanosine triphosphatase Ypt1p, which associated with cytoplasmic αSyn inclusions. Elevated expression of Rab1, the mammalian YPT1 homolog, protected against αSyn-induced dopaminergic neuron loss in animal models of PD. Thus, synucleinopathies may result from disruptions in basic cellular functions that interface with the unique biology of particular neurons to make them especially vulnerable.
Identification of Proteins Differentially Expressed in Human Monocytes Exposed to Porphyromonas gingivalis and Its Purified Components by High-Throughput Immunoblotting

ABSTRACT To characterize the roles of Porphyromonas gingivalis and its components in disease processes, we investigated the cytokine profiles induced by live P. gingivalis, its lipopolysaccharide (LPS), and its major fimbrial protein, fimbrillin (FimA). A cytokine antibody array revealed that human monocyte-derived macrophages were induced to produce chemokines (e.g., monocyte chemoattractant protein 1, macrophage inflammatory protein 1β [MIP-1β], and MIP-3α) as early as 1 h after exposure to P. gingivalis, with production declining after 24 h of exposure. As expected, an extensive repertoire of inflammatory mediators increased subsequent to infection, most predominantly tumor necrosis factor alpha (TNF-α), interleukin 1β (IL-1β), IL-6, IL-10, and granulocyte-macrophage colony-stimulating factor. The induction of cytokines by P. gingivalis was not triggered simply by bacterial cell surface components, since purified P. gingivalis LPS and FimA induced similar patterns of cytokines, while the pattern of cytokines induced by live P. gingivalis was significantly different, indicating that the host defense system senses live bacteria differently than it does the cell surface components LPS and FimA. To further understand the mechanisms by which live P. gingivalis and its components exert their effects, we used a high-throughput immunoblot screening approach (Becton-Dickinson PowerBlot) to analyze intracellular proteins involved in P. gingivalis infection in human macrophages. Exposure of human macrophages to either live P. gingivalis, its LPS, or its FimA protein led to the up-regulation of 12, 8, and 10 proteins and the down-regulation of 15, 8, and 17 proteins, respectively. The expression of proteins involved in gene transcription (e.g., monocyte enhancer factor 2D [MEF2D], signal transducer and activator of transcription 1 [STAT1], STAT3, STAT6, and IL enhancer binding factors [ILF3]), of protein kinases (e.g., mitogen-activated protein kinase 3 [MAPK3], MAP3K8, double-stranded RNA-activated protein kinase [PRKR], and MAP2K4), and of proteins involved in immune responses (e.g., TNF super family member 6 [TNFSF6] and interferon-induced protein with tetratricopeptide repeat 4 [IFIT4]), apoptosis (e.g., genes associated with retinoid interferon-induced mortality 19 [GRIM19]), and other fundamental cellular processes (e.g., clathrin heavy-chain polypeptide, culreticulin, and Ras-associated protein RAB27A) was found to be modulated differentially by P. gingivalis, LPS, and FimA. These differential changes are interpreted as preferential signal pathway activation in host immune/inflammatory responses to P. gingivalis infection.
Medication dispensing errors at a public pediatric hospital.

OBJECTIVE assess the safety of medication dispensing processes through the dispensing error rate. METHOD Cross-sectional study carried out at a pharmaceutical service of a pediatric hospital in Espírito Santo, Brazil. Data collection was performed between August and September 2006, totaling 2620 prescribed medication doses. Any deviation from the medical prescription in dispensing medication was considered a dispensing error. THE CATEGORIES OF MEDICATION ERRORS WERE: content, labeling, and documentation errors. The dispensing error rate was computed by dividing the number of errors by the total of dispensed doses. RESULTS From the 300 identified errors, 262 (87.3 %) were content errors. The rate of errors in the labeling and documentation categories was 33 (11%) and 5 (1.7%), respectively. CONCLUSION The total dispensing error rate was higher than rates reported in international studies. The most frequent category was "content error".
Independently from mitral regurgitation, Barlow disease may cause left ventricular enlargement and thereby anticipation of surgery.

Sir: We read the article ‘Anatomic characteristics of bileaflet mitral valve prolapse – Barlow disease – in patients undergoing mitral valve repair’ by Rostagno et al. (2014) with great interest. In this article, they shared their surgical observations about bileaflet mitral valve prolapse (MVP) in terms of mitral valve repair. We appreciated their experiences on mitral valve repair in patients having MVP. However, we have some doubts about the timing of surgery. They reported that almost half of the patients were in New York Heart Association functional class (NYHA) I or II and that the left ventricular (LV) end-diastolic and end-systolic diameters of the patients were 58.02±6.14 and 34.81±6.88 mm, respectively. Moreover, LV ejection fraction of the patients were 62.32±7.11%. All of the above mentioned findings suggest the possibility that surgical intervention was premature in some patients according to guidelines (Vahanian et al., 2012). This may result from the good experience of the surgical team in the repair procedures for MVP. They may desire that mitral regurgitation (MR) disappears before impairment in systolic function of LV. This may have logical reasons. Instead of replacement, they repair mitral valves, thereby i) patients take not so much surgical risk, and ii) they are protected the patients from the negative effects of long-term mechanical valve. It is well known that capabilities may sometimes influence decision-making process. However, there is no randomized clinical trial investigating the optimal timing for surgical intervention in patients with MR who are candidate for mitral valve repair. In this context, new studies investigating the optimal timing for surgery are needed for patients with MR having high probability to undergo mitral valve repair. Furthermore, we previously conducted a research on patients with classic MVP (Yiginer et al., 2012) and demonstrated that patients with classic bileaflet MVP have
An evidence-based appraisal of reflux disease management — the Genval Workshop Report

This report summarises conclusions from an evidence-based workshop which evaluated major clinical strategies for the management of the full spectrum of gastro-oesophageal reflux disease, with an emphasis on medical management. The disease was defined by the presence of oesophageal mucosal breaks or by the occurrence of reflux induced symptoms severe enough to impair quality of life. Endoscopy negative patients were recognised as the most common subgroup; most of these patients can be diagnosed by a well structured symptom analysis. There is a consistent hierarchy of effectiveness of available initial and long term therapies that applies for all patient subgroups. Lifestyle measures were judged to be of such low efficacy that they were rejected as a primary therapy for all patient subgroups. Proton pump inhibitor therapy was considered the initial medical treatment of choice because of its clearly superior efficacy which results in the most prompt achievement of desirable outcomes at the lowest overall medical cost. It was acknowledged that most of patients require long term management and that any maintenance therapy should be chosen by step down to the regimen that is still effective, but least costly. Endoscopic monitoring of routine long term therapy was considered inappropriate, on the basis that control of symptoms is an acceptably reliable indicator of healing in patients with oesophagitis. Laparoscopic antireflux surgery was recognised as a significant therapeutic advance, the results of which, however, depend substantially on the experience of the surgeon. There are currently no published direct comparisons of cost and efficacy outcomes of optimal medical and surgical therapies for reflux disease. To a significant degree, the choice between medical and surgical therapy should depend on informed patient preference. Substantial advances have occurred recently in the understanding and treatment of reflux disease. By contrast, there has been relatively little research into the best …
Bradycardia, increased cardiac output, and reversal of pulmonary hypertension in altitude natives living at sea level.

Eleven healthy young men native to high altitude underwent haemodynamic studies at their original place of residence and after two years' residence at sea level. The investigation sought to determine the long-term effects of the suppression of the hypoxic stimulus upon heart rate, cardiac output, and pulmonary artery pressure of highlanders. For comparative purposes the influence of oxygen inhalation at high altitude was also studied. The heart rate fell at sea level and bradycardia was seen in most of the cases. The fall in heart rate is probably related to an increase in the predominance of the parasympathetic nervous sys-
Reduced Toxicity, High Performance Monopropellant at the U.S. Air Force Research Laboratory

Abstract : Current programs are aiming to develop reduced toxicity monopropellant formulations to replace spacecraft hydrazine monopropellant. The Air Force Research Laboratory's (AFRL's) approach to replacing hydrazine is the synthesis and development of energetic compounds/formulations with substantially less vapor toxicity and superior performance (specific impulse and density). Characterization and testing of these high energy density materials is an essential part of the screening process for viable advanced propellants. Hazardous handling characteristics, undesirable physical properties or unacceptable sensitivity behaviors must also be identified and/or modified to further development by a potential user. AFRL has successfully identified a novel monopropellant (designated AF-M315E) that shows great promise as an avenue toward replacement of hydrazine monopropellant for spacecraft propulsion. Hazard and safety/sensitivity, stability, and toxicity studies have been conducted on the monopropellant and will be described. The results from AF-M315E indicate that a >50% improvement in propulsion system performance over hydrazine is achievable while simultaneously providing a safer environment for the general public, ground personnel, crews and flight participants.
Proteomic Characterization of Enterohemorrhagic Escherichia coli O157:H7 in the Oxidation‐Induced Viable but Non‐Culturable State

Enterohemorrhagic Escherichia coli (EHEC) O157 strain F2, a food isolate of an outbreak, is resistant to oxidative stress, but has increased stress‐sensitivity after passage through mice. The stress‐sensitive variant of F2 (designated MP37) has decreased culturability, but retains membrane integrity under stress conditions, indicating that the cells enter a viable but non‐culturable (VBNC) state. Proteomic analyses revealed that MP37 in the VBNC state had decreased levels of some oxidation‐responsive factors (AhpCF, AceF), but it markedly increased levels of outer membrane protein W (OmpW). Because F2 expressed higher levels of some ribosome‐associated proteins (RaiA, S6, Bcp) than MP37, the effect of animal passage on the induction of the VBNC state in the EHEC O157 cells might be due to ribosomal activity.
Septated cystic tumors of the pancreas: Is it possible to treat them by endoscopic ultrasonography-guided intervention?

Objectives. Endoscopic ultrasonography (EUS)-guided intervention has recently been tried in the treatment of cystic tumors of the pancreas. Factors that can influence the treatment response include cyst wall thickness and the presence of septation and mural nodules. This study aimed to evaluate the effectiveness of EUS-guided ethanol lavage with paclitaxel injection (EUS-EP) in the treatment of septated cystic tumors of the pancreas. Methods. Ten patients with oligolocular septated cystic tumors underwent EUS-EP and the treatment response was analyzed by measuring cyst volume before and more than 6 months after treatment. Results. The 10 patients comprised 7 women and 3 men, of mean age 38.4 years (range 22–54 years). Median tumor diameter was 29.5 mm (range 20–68 mm), while median tumor volume was 5.07 ml (range 1.51–68.74 ml). Median carcinoembryonic antigen and amylase concentrations in the cyst fluid were 39.2 ng/ml (range 1–8,190 ng/ml) and 115.5 U/L (range 5–75,633 U/L), respectively. Three tumors were diagnosed as mucinous cystic neoplasms, four as serous cystadenomas, and three as indeterminate cysts. Median tumor volume had decreased to 0.54 ml (range 0.00–12.42 ml). Complete resolution was achieved in six patients and partial resolution in two, whereas two patients had persistent cysts. Two patients with persistent cysts underwent surgical resection, and focal remnant neoplastic epithelial lining was observed on the resected specimens. Conclusions. EUS-EP resulted in complete resolution in 6 of 10 patients with septated cystic tumors. Careful patient selection and tailored intervention are required to maximize the therapeutic efficacy of this procedure.
Insulin resistance and cancer: Epidemiological evidence

Over the last 60 years, Japanese people have experienced a rapid and drastic change in lifestyle, including diet. Suspicions have been raised that so‐called ‘Westernization’, characterized by a high‐calorie diet and physical inactivity, is associated with increasing trends in the incidence of cancer of the colon, liver, pancreas, prostate, and breast, as well as type 2 diabetes. Epidemiological evidence from our prospective study, the Japan Public Health Center‐based Prospective (JPHC) study, and systematic literature reviews generally support the idea that factors related to diabetes or insulin resistance are associated with an increased risk of colon (mostly in men), liver, and pancreatic cancers. These cancers are inversely associated with physical activity and coffee consumption, which are known to decrease the risk of type 2 diabetes. The suggested mechanism of these effects is that insulin resistance and the resulting chronic hyperinsulinemia and increase in bioavailable insulin‐like growth factor 1 (IGF1) stimulate tumor growth. In contrast, associations with diabetes are less clear for cancer of the colon in women, and breast and prostate, which are known to be related to sex hormones. The effect of insulin resistance or body fat on sex‐hormone production and bioavailability may modify their carcinogenic effect differently from cancers of the colon in men, and liver and pancreas. In conclusion, there is substantial evidence to show that cancers of the colon, liver, and pancreas are associated with insulin resistance, and that these cancers can be prevented by increasing physical activity, and possibly coffee consumption.
Intestinal crypt clonogens: a new interpretation of radiation survival curve shape and clonogenic cell number

Abstract. Estimates of the clonogen content (number of microcolony‐forming cells) of murine intestinal crypts using microcolony assays show an apparent dependence on the radiation dose used in the assay of clonogen content. Crypt radiation survival curves often show increased curvature beyond that expected on the basis of the conventional linear‐quadratic model. A novel form of crypt survival curve shape is proposed based on two contributory mechanisms of crypt killing. Six previously published sets of microcolony data were re‐analysed using a dual‐kill model, where target cells are killed by two contributory mechanisms, each described by a linear‐quadratic function of dose. The data were analysed as two series – high‐dose rate and low‐dose rate irradiation. The data were fitted to the models using direct maximization of a quasi‐likelihood, explicitly allowing for overdispersion. The dual‐kill model can reproduce both the apparent dose‐dependence of the clonogen estimates and the high‐dose curvature of the dose–response curves. For both series of data the model was a significantly better fit to the data than the standard linear‐quadratic model, with no evidence of any systematic lack of fit. The parameters of the clonogenic cell component of the model are consistent with other studies that suggest a low clonogen number (somewhat less than five) per crypt. The model implies that there is a secondary mechanism decreasing clonogen survival, and hence increasing clonogen number estimates, at high doses. The mechanisms underlying the modification of the dose–response are unclear, and the implied mechanisms of, for example, slow growth, induced either directly in the surviving cells or indirectly through stromal injury or bystander effects are only speculative. Nevertheless, the model fits the data well, demonstrating that there is greater kill at high doses in these experimental series than would be expected from the conventional linear‐quadratic model. This alternative model, or another model with similar behaviour, needs to be considered when analysing in detail and interpreting microcolony data as a function of dose. The implied low number of ≤ 5 of these regenerative and relatively radioresistant clonogenic cells is distinct from a similar number of much more radiosensitive precursor stem cells which undergo early apoptosis after doses around 1 Gy.
VISUAL ILLUSIONS OF MOVEMENT.

Abstract : The autokinetic, oculogyral, and oculogravic illusions all involve apparent motion or displacement of the visual field with respect to an observer. It is shown that these illusions are related to involuntary eye movements, occurring either spontaneously as in the autokinetic illusion, or in response to the special stimuli associated with the other two illusions. During fixation the visual sensation of movement seems to be produced by, or related to, the pattern of efferent activity aimed at the group of extraocular muscles which will act as antagonists to the involuntary eye movement referred to.
Changes in joint cartilage aggrecan after knee injury and in osteoarthritis.

OBJECTIVE To determine the concentrations of aggrecan fragments in synovial fluid from patients with knee joint injury, osteoarthritis (OA), or acute pyrophosphate arthritis (PPA; pseudogout), and to test their relative reactivity with the 846 epitope, a putative marker of cartilage aggrecan synthesis. METHODS Samples of knee joint fluid from 385 patients and 9 healthy-knee volunteers were obtained in a cross-sectional study. Study groups were acute PPA/ pseudogout (n = 60), anterior cruciate ligament (ACL) rupture (n = 159), meniscus lesion (n = 129), and primary knee OA (n = 37). The 846 epitope on aggrecan was assayed by competitive solution-phase radioimmunoassay. Aggrecan fragments were assayed by enzyme-linked immunosorbent assay using a monoclonal antibody (1-F21). Cartilage oligomeric matrix protein (COMP), C-propeptide of type II collagen (CPII), bone sialoprotein, matrix metalloproteinases 1 and 3, and tissue inhibitor of metalloproteinases 1 were previously quantified by immunoassays. RESULTS Reactivity of the 846 epitope was increased in all study groups compared with the reference group, and was highest in patients with primary OA. The median levels (in microg fetal aggrecan equivalents/ml) of the epitope were 0.28 (range 0.24-0.47) in the reference group, 0.48 (range 0.26-1.32) in PPA/pseudogout, 0.61 (range 0.12-2.87) in ACL rupture, 0.53 (range 0.22-3.02) in meniscus lesion, and 0.68 (range 0.31-4.31) in primary OA. The 846 epitope reactivity per microg aggrecan fragments in the joint fluid was higher in late-stage OA than in early-stage OA. Epitope 846 reactivity correlated positively with several markers of matrix turnover, particularly with COMP (r(s) = 0.421) and CPII (r(s) = 0.307). CONCLUSION The observed differences in 846 epitope reactivity in synovial fluid, and its concentration in relation to aggrecan and other markers of matrix turnover, were consistent with marked ongoing changes in aggrecan turnover after joint injury and in the development of OA. OA is thus a disease characterized by dynamic changes in tissue macromolecule turnover, which is reflected by measurable changes in aggrecan epitopes in the synovial fluid.