Miracle-dz/UniFAR-FTUs huggingface dataset:
Antimicrobial-impregnated discs for prevention of intravenous catheter-related infections

Problem statement: Healthcare-associated infections are the 5th leading cause of death in the United States. Catheter-Related Bloodstream Infections (CRBSIs) comprise 14% of all healthcare-associated infections and contribute to increased mortality and financial costs. Antimicrobial-impregnated sponge discs to be used surrounding the catheter insertion site are a newer addition to the options available for the prevention of catheter-related infections. Approach: This review critically appraises the literature regarding the utility of antimicrobial-impregnated discs. We performed a literature search using the MEDLINE (1948-November 2011) database. Only controlled clinical trials were included and the electronic database search was performed using the following MeSH and keyword search terms: (“Biopatch” or “chlorhexidine”) and (“dressing” or “sponge”) and (“catheter”). Results: Our search yielded eight trials. Chlorhexidine-impregnated discs are effective in preventing catheter colonization in hospitalized patients and outpatients; however, effectiveness in preventing CRBSIs may be limited to hospitalized, critically ill patients. Although many studies have evaluated the effectiveness of several pharmaceutical agents for the prevention of catheter-related infections, there are still significant gaps in the literature regarding these infections, including the effectiveness of Polyhexamethylene Biguanide (PHMB)-impregnated discs and the cost-effectiveness of PHMB-impregnated discs compared to chlorhexidine-impregnated discs. It is also unclear if antimicrobial-impregnated discs are effective in specific populations, like in outpatients, patients at high risk compared to low risk patients and patients with long-term catheters. Conclusion: Chlorhexidine-impregnated discs should be utilized for the duration of catheterization in high risk, critically ill patients and in hospitals where catheter-related infection rates are persistently high despite other preventative strategies. Futher investigation of the effectiveness of these discs in other populations and of other antimicrobial-impregnated discs is needed.
Diagnostic yield and adverse effects of MRI-guided free-hand brain biopsies through a mini-burr hole in dogs with encephalitis.

BACKGROUND The diagnosis of encephalitis is usually presumptive based on MRI, cerebrospinal fluid analysis, or both. A definitive diagnosis based on histopathology, however, is required for optimizing treatment strategies. OBJECTIVE To investigate the diagnostic yield and adverse effects of minimally invasive brain biopsies in dogs with encephalitis. ANIMALS Seventeen dogs with suspected encephalitis, based on MR imaging and cerebrospinal fluid analysis. METHODS Retrospective study. Minimally invasive, free-hand brain biopsy specimens were taken from forebrain lesions through a 4-mm burr hole using a Sedan side-cutting needle. Routine histopathological examination was performed. The adverse effects were assessed by MRI evaluations after biopsy procedure (12/17) and by sequential neurological examinations. RESULTS The overall diagnostic yield with regard to a specific type of encephalitis was 82%. Encephalitis was evident in an additional 12%, but a specific disease could not be determined. There were no deaths caused by the biopsy procedure itself, but the indirect case fatality rate was 6%. Morbidity was 29%, including stupor, seizures, tetraparesis, hemiparesis, ataxia, and loss of conscious proprioception. All these signs resolved within 3-14 days. CONCLUSIONS AND CLINICAL IMPORTANCE Minimally invasive brain biopsy in dogs with suspected encephalitis leads to a definite diagnosis in the majority of dogs, allowing for a specific treatment. The advantages of a definite diagnosis outweigh potential case fatality rate and temporary neurological deficits.
Loss of subtelomeric sequence associated with a terminal inversion duplication of the short arm of chromosome 4.

We report on a 4(1/2)-year-old girl, who presented with multiple minor anomalies consistent with trisomy for 4p. GTG-banding identified a de novo terminal inversion duplication of distal 4p, dup(4)(p16.3p15.3). Fluorescence in situ hybridization (FISH) with a wcp4 probe confirmed the chromosome 4 origin of the additional material. FISH with a 4p subtelomere probe, D4F26, showed no signal on the dup(4) chromosome identifying a deletion of this region. Molecular analysis of 4p STS loci confirmed the subtelomeric deletion and showed loss of the paternal allele in this region. The paternal origin of the deleted region and homozygosity for one of the two paternal alleles within the region of the duplication suggests that a sister chromatid rearrangement on the paternal chromosome 4 was involved in the formation of the dup(4) chromosome. To date, the best characterized mechanisms of formation of chromosome duplications are terminal inversion duplications of 8p, which were shown to be derived from rearrangements at maternal meiosis-I. Our data show that mechanisms other than a maternal meiosis-I rearrangement can lead to the formation of terminal inversion duplications. FISH analysis with the appropriate subtelomeric probes is warranted in terminal inversion duplications to check for associated deletions.
No Kinetic Differences During Variations of the Power Clean in Inexperienced Female Collegiate Athletes

Abstract Comfort, P, McMahon, JJ, and Fletcher, C. No kinetic differences during variations of the power clean in inexperienced female collegiate athletes. J Strength Cond Res 27(2): 363–368, 2013—Previous research has identified that the second pull phase of the clean generates the greatest power output and that the midthigh variations of the power clean also result in the greatest force and power output in male athletes; however, no research has compared the kinetics of the variations of the power clean in women. The aim of this investigation was to identify any differences between variations of the clean, across a range of loads, in inexperienced female collegiate athletes. Sixteen healthy female collegiate athletes (age 19 ± 2.3 years; height 166.5 ± 3.22 cm; body mass 62.25 ± 4.52 kg; 1 repetition maximum [1RM] power clean 51.5 ± 2.65 kg) performed 3 repetitions of 3 variations (power clean, hang power clean, midthigh power clean) of the power clean at 60, 70, and 80% of their predetermined 1RM power clean, in a randomized and counterbalanced order. A 2-way analysis of variance (3 × 3; load × variation) revealed no significant differences (p > 0.05) in peak power, peak vertical force (Fz) or rate of force development (RFD) between loads or variations of the power clean. There appears to be no advantage in terms of peak power, Fz, or RFD between variations of the clean, in inexperienced female athletes, it is suggested, therefore, that inexperienced athletes intermittently perform different variations of the clean to ensure all round development and technical competence in each variation of the exercise.
An Important Role for Type III Interferon (IFN-λ/IL-28) in TLR-Induced Antiviral Activity1

Type III IFNs (IFN-λ/IL-28/29) are cytokines with type I IFN-like antiviral activities, which remain poorly characterized. We herein show that most cell types expressed both types I and III IFNs after TLR stimulation or virus infection, whereas the ability of cells to respond to IFN-λ was restricted to a narrow subset of cells, including plasmacytoid dendritic cells and epithelial cells. To examine the role of type III IFN in antiviral defense, we generated IL-28Rα-deficient mice. These mice were indistinguishable from wild-type mice with respect to clearance of a panel of different viruses, whereas mice lacking the type I IFN receptor (IFNAR−/−) were significantly impaired. However, the strong antiviral activity evoked by treatment of mice with TLR3 or TLR9 agonists was significantly reduced in both IL-28RA−/− and IFNAR−/− mice. The type I IFN receptor system has been shown to mediate positive feedback on IFN-αβ expression, and we found that the type I IFN receptor system also mediates positive feedback on IFN-λ expression, whereas IL-28Rα signaling does not provide feedback on either type I or type III IFN expression in vivo. Finally, using bone-marrow chimeric mice we showed that TLR-activated antiviral defense requires expression of IL-28Rα only on nonhemopoietic cells. In this compartment, epithelial cells responded to IFN-λ and directly restricted virus replication. Our data suggest type III IFN to target a specific subset of cells and to contribute to the antiviral response evoked by TLRs.
Diclofenac Sodium, a Nonselective Nonsteroidal Anti-Inflammatory Drug Aggravates Doxorubicin-Induced Cardiomyopathy in Rats

The cardiotoxic effects of selective cyclo-oxygenase-2 inhibitors are well documented. Recently, concerns have been raised over the cardiovascular safety of nonselective nonsteroidal anti-inflammatory drugs. The aim of this study was to assess the cardiac effects of diclofenac sodium on doxorubicin-induced cardiomyopathy in rats. Male Wistar rats were treated with doxorubicin (15 mg/kg intraperitoneally, single dose), diclofenac sodium (2.5 and 10 mg/kg/day, respectively, by gavage for 5 days) alone and doxorubicin + diclofenac sodium treatment, 24 hours after doxorubicin administration. Doxorubicin-induced a significant (P < 0.001) increase in the serum lactate dehydrogenase, cardiac thiobarbituric acid-reactive substance and catalase levels and a significant (P < 0.001) decrease in the cardiac glutathione and superoxide dismutase levels, which were significantly (P < 0.001) aggravated by diclofenac sodium treatment. Diclofenac sodium alone also showed a significant change in these parameters compared with the control. Ultrastructural studies showed that doxorubicin causes apoptosis in myocardium, which was characterized by condensation of chromatin network at the margins of nuclear membrane. Apoptosis induced by doxorubicin was exacerbated by diclofenac sodium treatment. Thus, our study indicates that diclofenac sodium, a nonaspirin nonsteroidal anti-inflammatory drug, is not free from cardiotoxicity and aggravates doxorubicin-induced cardiomyopathy in rats.
RNA polymerase III and RNA polymerase II promoter complexes are heterochromatin barriers in Saccharomyces cerevisiae

The chromosomes of eukaryotes are organized into structurally and functionally discrete domains. Several DNA elements have been identified that act to separate these chromatin domains. We report a detailed characterization of one of these elements, identifying it as a unique tRNA gene possessing the ability to block the spread of silent chromatin in Saccharomyces cerevisiae efficiently. Transcriptional potential of the tRNA gene is critical for barrier activity, as mutations in the tRNA promoter elements, or in extragenic loci that inhibit RNA polymerase III complex assembly, reduce barrier activity. Also, we have reconstituted the Drosophila gypsy element as a heterochromatin barrier in yeast, and have identified other yeast sequences, including the CHA1 upstream activating sequence, that function as barrier elements. Extragenic mutations in the acetyltransferase genes SAS2 and GCN5 also reduce tRNA barrier activity, and tethering of a GAL4/SAS2 fusion creates a robust barrier. We propose that silencing mediated by the Sir proteins competes with barrier element‐associated chromatin remodeling activity.
Characterization of a novel Mycobacterium bovis secreted antigen containing PGLTS repeats

Serum from naturally infected cattle was used to identify a novel Mycobacterium bovis antigen from an expression library. The first recombinant product identified was a fusion protein with lacZ (55 kDa). A clone containing the whole gene was also obtained. This clone expressed a 38-kDa protein. A rabbit serum against the recombinant antigen reacts in M. bovis supernatants with two proteins of 36 and 34 kDa. The new protein was called P36/P34. The gene cloned has a deduced amino acid sequence with a predicted molecular mass of 28 kDa, showing a characteristic signal sequence for exportation. The protein bears partial homology to a 28-kDa protein from M. leprae. An interesting feature of the P36/P34 sequence is that it contains several PGLTS repeats, which are not present in the M. leprae protein. Antigenic determinants seem also to be conserved between the two proteins because sera from leprosy patients recognized the recombinant M. bovis protein. The discrepancy among the molecular mass deduced from the sequence (28 kDa), that of the recombinant protein in Escherichia coli (38 kDa), and that of the native protein in M. bovis (36 and 34 kDa) could be attributed to posttranslational modifications or to the high proline content that may alter the migration properties of the protein. This antigen seems to be immunodominant during bovine tuberculosis, because 8 of 9 serum specimens from diseased cattle are reactive. The homology among the M. leprae 28-kDa protein, the protein described in this article, and a recently described M. tuberculosis protein suggests the existence of a new protein family in mycobacteria.
Risk of reoperation for mitral bioprosthesis dysfunction.

BACKGROUND AND AIM OF THE STUDY Today, when a mitral valve replacement is required, more patients and surgeons choose a bioprosthesis. Yet, the rationale of this choice is unclear in patients in whom age represents a predicting factor for reoperation. The study aim was to define the risk factors for reoperation after mitral bioprosthesis failure. METHODS A total of 282 consecutive patients (202 women, 80 men; mean age at surgery 61 years; range: 28-88 years) who underwent reoperation for mitral bioprosthesis failure between 1990 and 2006 was reviewed. Surgery was undertaken because of bioprosthesis degeneration (91%), prosthetic valve infective endocarditis (6%), paravalvular leak (2%), or other causes (1%). Emergency procedures were performed in 7% of cases. Associated procedures included tricuspid valve surgery in 16% of patients (tricuspid valve repair in 11%, tricuspid valve replacement in 5%) and coronary artery bypass graft in 5%. Almost one-fifth of patients (18%) had undergone more than one previous mitral valve replacement. RESULTS The overall operative mortality was 7.4% (n = 21). Factors identified (by multivariate analysis) as predictors of operative death included: presence of diabetes mellitus (odds ratio (OR) = 8.69, 95% CI 2.55-29.61; p = 0.001), chronic obstructive pulmonary disease (OR = 9.01, 95% CI 1.72-47.18; p = 0.009), NYHA class III/IV (OR 5.46, 95% CI 1.41-21.16; p = 0.01), and pulmonary artery pressure > 60 mmHg (OR = 3.13, 95% CI 1.10-8.94; p = 0.03). Associated procedures were not significant risk factors for mortality. New prostheses were mechanical in 68% of cases, and bioprostheses in 32%. CONCLUSION One reoperation for mitral bioprosthesis dysfunction is acceptable if the patient can be expected to survive to reoperation while free from comorbidities and the severe effects of mitral disease. The application of strict selective criteria to recipients at the first valve replacement, combined with a close follow up, may allow this goal to be achieved.
Activation of Notch signaling pathway in HIV-associated nephropathy

Objective:HIV-associated nephropathy (HIVAN) is characterized by the development of glomerulosclerosis and is associated with glomerular epithelial cell proliferation. It has recently been shown that activation of the Notch signaling pathway in podocytes results in glomerulosclerosis and podocyte proliferation. To determine whether Notch signaling is involved in renal disorder associated with HIVAN, we evaluated the expression of Notch receptors in HIVAN. Design:We evaluated the expression of the Notch signaling pathway using an HIV-transgenic (HIV-Tg) rat model of HIVAN, and biopsy samples from HIVAN and normal controls. Methods:Paraffin sections and kidney lysates were used for immunohistochemistry, immunofluorescence and western blot analysis. Results:A collapsing variant of glomerulosclerosis and focal segmental sclerosis was observed in HIV-Tg rats. Glomeruli of HIV-Tg rats demonstrated activation of Notch1 and Notch4, as determined by the presence of the intracellular domains. In addition, we observed increased expression of the Notch target protein, hairy enhancer of split homolog-1 in glomeruli of these animals. The expression of the Groucho homolog transducin-like enhancer protein 4, a Notch effector protein, and the homeodomain protein cut homeobox 1 were also significantly increased in glomeruli of HIV-Tg rats, and this was associated with decreased expression of the cyclin kinase inhibitor p27. Intriguingly, renal biopsy samples from HIVAN patients also showed upregulation of cleaved Notch1 and Notch4 in the glomeruli compared with the expression in normal kidneys. Conclusion:Our results demonstrate activation of Notch signaling pathway in HIVAN, thereby underscoring its role in disease pathogenesis.
Preliminary identification of a low molecular weight serological mediator in chronic idiopathic urticaria

Sixteen patients with chronic idiopathic urticaria were skin tested with their own serum, 10 with autologous plasma and five with serum that had been heated to 56° C to inactivate complement. Eight showed a weal and flare response to whole serum, four to plasma and five to heat‐treated serum. All serum‐positive patients showed the same response to their own plasma and to heated serum, indicating that the mediator concerned is not generated by clotting and is not dependent on a functioning complement pathway. Three control subjects were negative to autologous serum, plasma and heated serum. Local tachyphylaxis was demonstrated in five serum‐positive patients on reinjection of the same site with autologous serum on 3 consecutive days. This raises the possibility that the serological mediator may be acting by mast cell degranulation or directly on receptors in blood vessels and that repeated injections could induce a change in the number of receptors. Passage of whole autologous serum from four serum‐positive patients through ultrafiltration membranes showed that fractions with a molecular weight of less than 30,000 daltons were still able to produce a positive skin test response, but those less than 1000 daltons were not. All serum fractions from two serum‐negative patients and three normal controls were negative. Whole autologous serum from five serum‐positive patients and two control subjects was separated by column chromatography. On skin testing with pooled fractions, the greatest response was produced by fractions of 10,000–15,000 daltons in the serum‐positive patients, but there was no response in the controls.
The cost-effectiveness of hepatitis A vaccination in patients with chronic hepatitis C viral infection in the United States

OBJECTIVE:Hepatitis A vaccination is recommended for patients with chronic hepatitis C. Our aim was to analyze the cost-effectiveness of hepatitis A vaccination in these patients. The specific strategies evaluated were: no vaccination, targeted vaccination, and universal vaccination.METHODS:Clinical estimates were based on published data. Costs estimates were based on published data and institutional Medicare reimbursement rates. Health-related quality-of-life weights were derived from published data and expert estimates. The target population consisted of patients 45 yr of age with chronic hepatitis C followed every 6 months until death. We adopted a societal perspective.RESULTS:Compared with no vaccination, targeted vaccination was associated with an incremental cost-effectiveness ratio of $51,000 per quality-adjusted life-year. The incremental cost-effectiveness ratio of universal vaccination compared with targeted vaccination was $3,900,000 per quality-adjusted life-year. The results were particularly sensitive to the incidence of hepatitis A, probability of fulminant hepatic failure, and costs of hepatitis A antibody screening and vaccination.CONCLUSIONS:Targeted vaccination for hepatitis A in patients with chronic hepatitis C may be a cost-effective strategy to decrease the morbidity and mortality associated with hepatitis A superinfection. Universal vaccination is not a cost-effective alternative to targeted vaccination in this target population.
“They treated me like a leper”

OBJECTIVE: Hepatitis C virus is the most prevalent chronic blood-borne infection in the United States, typically acquired through contaminated blood products or needle sharing. We hypothesized that patients with chronic hepatitis C infection experience stigmatization independent of mode of acquisition and that it negatively affects quality of life.DESIGN: Cross-sectional observation study.SETTING: Specialty clinic in a tertiary referral hospital.PATIENTS: Two hundred and ninety outpatients diagnosed with chronic hepatitis C infection and seen in a hepatology clinic. Thirty participants were excluded because of missing data.MEASUREMENTS AND MAIN RESULTS: Patients were asked to complete a demographic profile, a semistructured interview, the Sickness Impact Profile, and the Hospital Anxiety Depression Scale. A team of two blinded coders analyzed the interviews. A total of 147 of the 257 study patients experienced stigmatization that they attributed to the disease. Women were more likely to report perceived stigmatization than men (P < .05). Age, education, professional status, and mode of infection did not influence the likelihood of stigmatization. Stigmatization was associated with higher anxiety (P<.01) and depression (P<.01), worsened quality of life (P<.01), loss of control (P<.01), and difficulty coping (P<.01). Individuals who experienced stigmatization also mentioned problems in their health care (P<.01) and work environment (P<.01) as well as with family members (P<.01). CONCLUSION: Stigmatization is a very common emotionally burdensome experience for patients with hepatitis C, which can erode social support. As it penetrates even into the health care environment, physicians and other care providers should be aware of the existence and impact of such negative stere-otyping.
Bioactivation of 3- n -Butylphthalide (NBP) via Sulfation of Its Major Metabolite 3-Hydroxy-NBP: Mediated Mainly by Sulfotransferase 1A1

: 3- n -Butylphthalide (NBP) [(±)-3-butyl-1(3 H )-isobenzofuranone] is an anti-cerebral ischemia drug. Moderate observed in clinic. 3- N -acetylcysteine-NBP, one of the major metabolites, has been detected in human urine, indicating the formation of reactive metabolite. The aim of the present study is to elucidate the formation mechanism of reactive metabolite and its association with the hepatotoxicity of NBP. The in vitro incubations revealed that 3-GSH-NBP was observed only in fresh rat liver homogenate rather than in liver microsomes, liver cytosol, or liver S9 supplemented with NADPH and GSH. 3-GSH-NBP was also detected when 3'-phosphoadenosine-5'-phosphosulfate was added in GSH-fortified human liver cytosol (HLC). The formation of 3-GSH-NBP was 39.3-fold higher using 3-hydroxy-NBP (3-OH-NBP) as the substrate than NBP. Sulfotransferases (SULT) inhibitors 2,6-dichloro-4-nitrophenol (DCNP) and quercetin suppressed 3-GSH-NBP formation in HLC by 75% and 82%, respectively, suggesting that 3-OH-NBP sulfation was involved in 3-GSH-NBP formation. Further SULT phenotyping revealed that SULT1A1 is the major isoform responsible for the sulfation. Dose-dependent toxicity was observed in primary rat hepatocytes exposed to 3-OH-NBP with an IC 50 of approximately 168 μ M. Addition of DCNP and quercetin significantly increased cell viability, whereas L-buthionine-sulfoximine (a GSH depletor) decreased cell viability. Overall, our study revealed the underlying mechanism for the bioactivation of NBP