Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Potassium Ions on Action Potential Conduction in A- and C-Fibers of Rat Spinal Nerves

Potassium ions in dentifrices for treating 'hypersensitive' dentin are believed to act directly on intradental nerves by raising extracellular potassium ion concentration ([K+]o) sufficiently to prevent action potential generation by axonal accommodation. However, the [K+]o necessary to block nerve conduction is not precisely known, nor is it certain that K+ can diffuse from a dentifrice in sufficient amounts to inactivate intradental nerves. To establish more accurately the [K+]o required to block nerve conduction under controlled conditions, we studied the effects of increased [K+]o on the sizes of compound action potentials (CAP) recorded from rat spinal nerves in vitro. [K+]o was increased by the addition of either KCl or KNO3 to Krebs' solutions applied to the central portion of the nerves. CAP attenuation increased in a dose-dependent manner as [K+]o was raised in the 8 to 64 mmol/L range, and complete block was generally produced with solutions containing at least 32 mmol/L K+. CAP attenuation was reversible, and recovery times increased with increasing [K+]o. The effects of KCl and KNO3 solutions were the same for all [K+]o tested. Half-maximal (50%) reduction in the Aβ-fiber component of the CAP occurred with 17.4 mmol/L K+, and with 17.8 mmol/L and 19.3 mmol/L K+, respectively, for the AS- and C-fiber components. Control experiments with glucose and choline chloride confirmed that the conduction block observed with increased [K+]o was not due to increased solution osmolarity or ionic strength. Assuming that intradental axons are as sensitive to altered [K+]o as spinal nerve axons, we suggest that for K+ in dentifrices to block intradental nerve conduction: (1) [K+]o in excess of 8 mmol/L would have to be achieved around nerve axons in the inner dentin or peripheral pulp, and (2) increases in [K+]o of these magnitudes would have to be maintained in order for intradental nerve inactivation to be sustained.
PROSPECTIVE RANDOMIZED CONTROLLED TRIAL OF COMBINATION RANIBIZUMAB (LUCENTIS) AND BROMFENAC (XIBROM) FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Pilot Study

Purpose: To evaluate whether bromfenac eyedrops and ranibizumab intravitreal injections would provide added efficacy over ranibizumab alone. Methods: This was a single-site, multiinvestigator, prospective, open-label, interventional, Phase II study of patients with new or recurrent exudative/neovascular age-related macular degeneration. Thirty eyes were enrolled consecutively and were randomized in a ratio of 2:1 to combination therapy with intravitreal ranibizumab and topical bromfenac, and ranibizumab alone. All patients received ranibizumab monthly therapy for 4 months then as needed monthly in accordance with standard of care. Patients receiving bromfenac self-administered 1 drop twice a day for 12 months. Patients were followed for 12 months. Results: There were no safety concerns with the combination therapy. No statistically significant differences were identified in Early Treatment Diabetic Retinopathy Study best-corrected visual acuity or the number of injections required. However, the mean 12-month change in central macular thickness in the combination group was −81.56 μm while in the ranibizumab group alone the change was −42.50 μm (P = 0.03). The proportion of eyes experiencing a decrease in CMT of 50 μm or more was also significantly higher in those receiving combination therapy (P = 0.046). Conclusion: This pilot study is the first to prospectively identify a biologic signal that may indicate combination therapy with an easily administered well-tolerated eyedrop and ranibizumab is efficacious for the treatment of neovascular age-related macular degeneration. Further studies are warranted to validate this finding.
Heterogeneity of mucosal mast cell infiltration in subgroups of patients with esophageal chest pain

Although there is growing evidence that an increase in mucosal mast cells (MMCs) in the small and large intestine is associated with visceral hypersensitivity, few studies have evaluated MMCs in humans with esophageal symptoms. The aim of this study was to investigate esophageal MMC distribution in patients with non‐cardiac chest pain (NCCP) and to examine the association between the number of gut MMCs and other functional gastrointestinal disorders.
Soluble E‐selectin in sera of patients with atopic dermatitis and psoriasis—correlation with disease activity

Summary E‐selectin endothelial leucocyte adhesion molecule‐1 is expressed on endothelial cells in distinct inflammatory skin diseases. E‐selectin mediates the adhesion between activated endothelium and different inflammatory cells. To evaluate soluble E‐selectin as a marker of disease activity in patients with atopic dermatitis and psoriasis, the concentration of soluble E‐selectin, determined by ELISA, was studied in sera of patients before and after treatment and compared with normal non‐atopic controls. The disease severity was established using clinical scoring systems. Levels of soluble E‐selectin were significantly elevated in sera of patients with atopic dermatitis and psoriasis (as compared with controls). Clinical improvement, after treatment, in patients with atopic dermatitis, but not in psoriasis, was associated with a significant decrease in serum levels of soluble E‐selectin. There was a significant correlation of soluble E‐selectin and disease activity in patients with atopic dermatitis. These data indicate that soluble E‐selectin is another parameter to evaluate the inflammatory response in atopic dermatitis and psoriasis. Determination of soluble E‐selectin may be a useful measure of disease activity in atopic dermatitis.
Differences between elderly voluntary and involuntary admitted psychiatric patients in Greece

ABSTRACT Background: Involuntary psychiatric admission is a controversial issue with legislation varying from country to country. Research on elderly individuals being involuntary admitted has been limited. This study aims first at assessing whether elderly involuntary admitted patients (IAPs) differ with regard to demographic, psychopathological, and behavioral characteristics from voluntary admitted psychiatric patients (VAPs) and second to assess whether the former group should be treated in a different (special) way. Methods: Forty IAPs were compared to 39 VAPs with regard to sociodemographic data, DSM-IV diagnosis, as well as behavioral issues recorded by the Patient–Staff Conflict Checklist – Shift Report (PSCC-SR). All patients were aged 60 years and over and were admitted in the psychiatric departments of four general hospitals in Athens. The study period lasted 12 months. Results: VAPs were more likely to be suffering from mood disorders, while IAPs presented higher rates of delirium. From the 20 items of the PSCC-SR, differences were found only in two: IAPs presented more aggressive behavior during the first few days of admission whereas VAPs had committed recent suicide attempt just before admission. Conclusion: From the clinical point of view, IAPs presented with delirium and more aggressive behavior, whereas, the VAPs presented with higher rates of mood disorder and suicidality. However, from the medicolegal point of view, our findings lend support to the argument of either setting a limited time frame for involuntary admission in elderly patients, and/or allowing for elderly individuals with acute organic conditions to be treated against their will.
Epidemiology of infective endocarditis in a large Belgian non-referral hospital

Abstract Objectives: Guidelines for diagnosis of infective endocarditis are largely based upon epidemiological studies in referral hospitals. Referral bias, however, might impair the validity of guidelines in non-referral hospitals. Recent studies in non-referral care centres on infective endocarditis are sparse. We conducted a retrospective epidemiological study on infective endocarditis in a large non-referral hospital in a Belgian city (Kortrijk). Methods: The medical record system was searched for all cases tagged with a putative diagnosis of infective endocarditis in the period 2003–2010. The cases that fulfilled the modified Duke criteria for probable or definite infective endocarditis were included. Results: Compared to referral centres, an older population with infective endocarditis, and fewer predisposing cardiac factors and catheter-related infective endocarditis is seen in our population. Our patients have fewer prosthetic valve endocarditis as well as fewer staphylococcal endocarditis. Our patients undergo less surgery, although mortality rate seems to be highly comparable with referral centres, with nosocomial infective endocarditis as an independent predictor of mortality. Conclusion: The present study suggests that characteristics of infective endocarditis as well as associative factors might differ among non-referral hospitals and referral hospitals.
Retinoic Acid Receptor Antagonist Inhibits CD38 Antigen Expression on Human Hematopoietic Cells In Vitro

The CD34+ CD38- subset of human hematopoietic stem cells are crucial for long-term ex-vivo expansion; conditions that decreased this specific sub-population reduced the self-renewal capacity and shortened the duration of the proliferative phase of the culture. Retinoids, such as all-trans retinoic acid (ATRA), have been shown to induce CD38 expression. ATRA present in serum may be responsible for the high CD38 of cells grown in serum-containing medium. In the present study we analyzed the effects of AGN 194310, a retinoic acid receptor pan-antagonist, on CD38 expression of human hematopoietic cells. Normal cells (cord blood derived CD34+ cells) and abnormal cells (myeloid leukemic lines) were studied when grown in either serum-containing or serum-free media. The results showed that both serum and ATRA enhanced differentiation and, thereby, reduced the proportion of CD34+ CD38- cells and total CD34+ cell expansion. AGN reversed these effects of serum and ATRA: it delayed differentiation and increased CD34+ CD38- cells. These results suggest that physiological ATRA levels in serum may prevent efficient cell expansion. AGN, by neutralizing ATRA, improves cell expansion in serum-containing cultures, thus making AGN a useful agent for ex vivo expansion of stem cells and other specific sub-populations for research and clinical use.
Detection of Ebola virus in oral fluid specimens during outbreaks of Ebola virus hemorrhagic fever in the Republic of Congo.

BACKGROUND Patients who have refused to provide blood samples has meant that there have been significant delays in confirming outbreaks of Ebola virus hemorrhagic fever (EVHF). During the 2 EVHF outbreaks in the Republic of Congo in 2003, we assessed the use of oral fluid specimens versus serum samples for laboratory confirmation of cases of EVHF. METHODS Serum and oral fluid specimens were obtained from 24 patients with suspected Ebola and 10 healthy control subjects. Specimens were analyzed for immunoglobulin G antibodies by enzyme-linked immunosorbent assay (ELISA) and for Ebola virus by antigen detection ELISA and reverse-transcriptase polymerase chain reaction (RT-PCR). Oral fluid specimens were collected with a commercially available collection device. RESULTS We failed to detect antibodies against Ebola in the oral fluid specimens obtained from patients whose serum samples were seropositive. All patients with positive serum RT-PCR results also had positive results for their oral fluid specimens. CONCLUSIONS This study demonstrates the usefulness of oral fluid samples for the investigation of Ebola outbreaks, but further development in antibodies and antigen detection in oral fluid specimens is needed before these samples are used for filovirus surveillance activities in Africa.
USP18 protects against hepatic steatosis and insulin resistance through its deubiquitinating activity

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, impaired insulin sensitivity, and chronic low‐grade inflammation. However, the pathogenic mechanism of NAFLD is poorly understood, which hinders the exploration of possible treatments. Here, we report that ubiquitin‐specific protease 18 (USP18), a member of the deubiquitinating enzyme family, plays regulatory roles in NAFLD progression. Expression of USP18 was down‐regulated in the livers of nonalcoholic steatohepatitis patients and high‐fat diet (HFD)–induced or genetically obese mice. When challenged with HFD, hepatocyte‐specific USP18 transgenic mice exhibited improved lipid metabolism and insulin sensitivity, whereas mice knocked out of USP18 expression showed adverse trends regarding hepatic steatosis and glucose metabolic disorders. Furthermore, the concomitant inflammatory response was suppressed in USP18–hepatocyte‐specific transgenic mice and promoted in USP18–hepatocyte‐specific knockout mice treated with HFD. Mechanistically, hepatocyte USP18 ameliorates hepatic steatosis by interacting with and deubiquitinating transforming growth factorβ‐activated kinase 1 (TAK1), which inhibits TAK1 activation and subsequently suppresses the downstream c‐Jun N‐terminal kinase and nuclear factor kappa B signaling pathways. This is further validated by alleviated steatotic phenotypes and highly activated insulin signaling in HFD‐fed USP18–hepatocyte‐specific knockout mice administered a TAK1 inhibitor. The therapeutic effect of USP18 on NAFLD relies on its deubiquitinating activity because HFD‐fed mice injected with active‐site mutant USP18 failed to inhibit hepatic steatosis. Conclusion: USP18 associates with and deubiquitinates TAK1 to protect against hepatic steatosis, insulin resistance, and the inflammatory response. (Hepatology 2017;66:1866–1884)
Hepatitis C virus replicates in peripheral blood mononuclear cells of patients with occult hepatitis C virus infection

Background: Occult hepatitis C virus (HCV) infection is characterised by the presence of HCV-RNA in the liver in the absence of anti-HCV, and serum viral RNA. Up to 70% of these patients also have HCV-RNA in peripheral blood mononuclear cells (PBMC) but it is not known if HCV is replicating in these cells. Aim: We studied possible HCV replication in PBMC of 18 patients with an occult HCV infection who were selected on the basis of HCV-RNA positivity in PBMC. Methods: Detection of HCV-RNA positive and negative strands in PBMC was done by strand specific reverse transcriptase-polymerase chain reaction (RT-PCR) and by in situ hybridisation. Results: The presence of HCV-RNA positive strand in PBMC was confirmed in all patients by strand specific RT-PCR and by in situ hybridisation. Mean percentage of PBMC which had the HCV-RNA positive strand was 3.3% (95% confidence interval (CI) 2.1–4.4) The HCV-RNA negative strand was found in the PBMC of 11/18 (61%) patients by strand specific RT-PCR and confirmed by in situ hybridisation, and the percentage of PBMC harbouring the HCV-RNA negative strand was 3.1% (95% CI 0.8–5.5). There was a significant correlation (p = 0.001, r = 0.84) between the percentage of PBMC with the HCV-RNA positive strand and that of PBMC with the HCV-RNA negative strand. Conclusion: HCV replicates in the PBMC of patients with occult HCV infection and thus, although these patients do not have serum HCV-RNA, they could be potentially infectious.
Effect of generic drug competition on the price of prescription drugs in Ontario.

OBJECTIVE To analyse the potential effect of generic drug competition on prices in Ontario to assess the costs and benefits associated with Bill C-22 (An Act to amend the Patent Act). DESIGN Comparison of the cost of the least and most expensive versions of all products sold by more than one manufacturer in 1991. The number of brand-name and generic drug companies marketing each of the products was recorded. RESULTS Of 1599 products 437 (27.3%) were made by more than one company. Almost half (44.6%) of the 437 were sold by two companies. The more companies that sold a drug the greater the difference in price between the least and most expensive versions. Similarly, as the proportion of generic drug companies in competition increased, the greater the price difference. When competition was between generic drug companies only, the price spread was smaller than when it was between brand-name drug companies only. CONCLUSIONS Generic drug competition can result in savings to the Ontario Drug Benefit Plan. A more in-depth analysis of the potential savings is necessary to fully assess the costs and benefits associated with Bill C-22.
Analysis of connexin expression during mouse Schwann cell development identifies Connexin29 as a novel marker for the transition of neural crest to precursor cells

Connexins are transmembrane proteins forming gap junction channels for direct intercellular and, for example in myelinating glia cells, intracellular communication. In mature myelin‐forming Schwann cells, expression of multiple connexins, i.e. connexin (Cx) 43, Cx29, Cx32, and Cx46 (after nerve injury) has been detected. However, little is known about connexin protein expression during Schwann cell development. Here we use histochemical methods on wildtype and Cx29lacZ transgenic mice to investigate the developmental expression of connexins in the Schwann cell lineage. Our data demonstrate that in the mouse Cx43, Cx29, and Cx32 protein expression is activated in a developmental sequence that is clearly correlated with major developmental steps in the lineage. Only Cx43 was expressed from neural crest cells onwards. Cx29 protein expression was absent from neural crest cells but appeared as neural crest cells generated precursors (embryonic day 12) both in vivo and in vitro. This identifies Cx29 as a novel marker for cells of the defined Schwann cell lineage. The only exception to this were dorsal roots, where the expression of Cx29 was delayed four days relative to ventral roots and spinal nerves. Expression of Cx32 commenced postnatally, coinciding with the onset of myelination. Thus, the coordinated expression of connexin proteins in cells of the embryonic and postnatal Schwann cell lineage might point to a potential role in peripheral nerve development and maturation. © 2006 Wiley‐Liss, Inc.
Regulation of Epidermal Growth Factor-induced Connexin 43 Gap Junction Communication by Big Mitogen-activated Protein Kinase 1/ERK5 but Not ERK1/2 Kinase Activation*

The gap junction protein, Cx43, plays a pivotal role in coupling cells electrically and metabolically, and the putative phosphorylation sites that modulate its function are reflected as changes in gap junction communication. Growth factor stimulation has been correlated with a decrease in gap junction communication and a parallel activation of ERK1/2; the inhibition of epidermal growth factor (EGF)-induced Cx43 gap junction uncoupling was observed by using the MEK1/2 inhibitor, PD98059. Because 1) BMK1/ERK5, another MAPK family member also activated by growth factors, possesses a phosphorylation motif similar to ERK1/2, and 2) it has been reported that PD98059 can inhibit not only MEK1/2-ERK1/2 but also MEK5-BMK1 activation, we investigated whether BMK1 can regulate EGF-induced Cx43 gap junction uncoupling and phosphorylation, comparing this to the role of ERK1/2 on Cx43 function and phosphorylation induced by EGF. Selective activation or inactivation of ERK1/2 by using a constitutively active form or a dominant negative form of MEK1 did not regulate Cx43 gap junction coupling. In contrast, we found that BMK1, selectively activated by constitutively active MEK5α, induced gap junction uncoupling, and the inhibition of BMK1 activation by transfection of dominant negative BMK1 prevented EGF-induced gap junction uncoupling. Activated BMK1 selectively phosphorylates Cx43 on Ser-255 in vitro and in vivo, but not on S279/S282, which are reported as the consensus phosphorylation sites for MAPK. Furthermore, by co-immunoprecipitation, we found that BMK1 directly associates with Cx43 in vivo. These data indicate that BMK1 is more important than ERK1/2 in EGF-mediated Cx43 gap junction uncoupling by association and Cx43 Ser- 255 phosphorylation.
Transmission routes of hepatitis B virus infection in chronic hepatitis B patients in The Netherlands

The Netherlands is a low endemic country for hepatitis B virus (HBV). Rotterdam, a city in The Netherlands harbors a large group of chronic hepatitis B (CHB) patients of which most are born abroad. The study included 464 consecutive CHB patients who were reported to the Municipal Public Health Service in Rotterdam from January 1, 2002 to September 15, 2005. The HBV genotypes, possible transmission routes of infection and travel history of CHB patients born in The Netherlands, were compared with those CHB patients living in The Netherlands but who were foreign‐born, taking into account the ethnicity of the mother. Of the 464 patients with CHB infection, 14% were Dutch‐born and 86% were foreign‐born. The CHB patients in the Dutch‐born group had genotypes A (35%), B (15%), C (11%), D (37%), and G (2%). In the foreign‐born group, the distribution of genotypes was A (20%), B (15%), C (11%), D (40%), and E (15%). In the Dutch‐born group, sexual transmission accounted for a larger proportion of infections (P < 0.0001) compared to the foreign‐born group, whereas perinatal transmission is reported to be higher in the foreign‐born group and in the Dutch‐born group with a foreign mother. The genotypes of the chronic HBV strains determined corresponded well with the HBV genotypes expected from the countries of origin of the patients or their mothers. Genotypes A and D are predominant in CHB patients in The Netherlands. J. Med. Virol. 80:399–404, 2008. © 2008 Wiley‐Liss, Inc.
Coenzyme Q protects Caenorhabditis elegans GABA neurons from calcium-dependent degeneration

Mitochondria are key regulators of cell viability and provide essential functions that protect against neurodegenerative disease. To develop a model for mitochondrial-dependent neurodegeneration in Caenorhabditis elegans, we used RNA interference (RNAi) and genetic ablation to knock down expression of enzymes in the Coenzyme Q (CoQ) biosynthetic pathway. CoQ is a required component of the ATP-producing electron transport chain in mitochondria. We found that reduced levels of CoQ result in a progressive uncoordinated (Unc) phenotype that is correlated with the appearance of degenerating GABA neurons. Both the Unc and degenerative phenotypes emerge during late larval development and progress in adults. Neuron classes in motor and sensory circuits that use other neurotransmitters (dopamine, acetylcholine, glutamate, serotonin) and body muscle cells were less sensitive to CoQ depletion. Our results indicate that the mechanism of GABA neuron degeneration is calcium-dependent and requires activation of the apoptotic gene, ced-4 (Apaf-1). A molecular cascade involving mitochondrial-initiated cell death is also consistent with our finding that GABA neuron degeneration requires the mitochondrial fission gene, drp-1. We conclude that the cell selectivity and developmental progression of CoQ deficiency in C. elegans indicate that this model may be useful for delineating the role of mitochondrial dysfunction in neurodegenerative disease.