Miracle-dz/UniFAR-FTUs huggingface dataset:
Treatment of Latent Syphilis in HIV-infected Patients with 10 d of Benzylpenicillin G Benethamine: A Prospective Study in Maputo, Mozambique

Neurosyphilis has been reported in HIV-infected patients previously treated with penicillin G benzathine, which does not achieve treponemicidal levels in cerebrospinal fluid. Therapy combining benzylpenicillin G and its repository form benzylpenicillin G benethamine could be a potentially effective alternative enhanced regimen for treating latent syphilis in HIV-infected patients because peak serum and cerebrospinal fluid concentrations would be achieved early post-administration by the former molecule and sustained for 24 h due to the prolonged half-life of the latter. In this study, 23 asymptomatic HIV and Treponema pallidum co-infected patients received 10 d of combined therapy (2 M IU intramuscular once daily) and were followed up at 3, 6 and 12 months. None experienced side effects or clinical symptoms. Of the 18 patients who were evaluated 1 y later, 8 (44.4%) exhibited serological treatment failure, defined as a positive serum rapid plasma reagin test. In conclusion, a 10-d regimen combining penicillin G and penicillin G benethamine seems to be of no benefit compared to currently recommended treatment.
Potent and Selective Peptide-based Inhibition of the G Protein Gαq*

In contrast to G protein-coupled receptors, for which chemical and peptidic inhibitors have been extensively explored, few compounds are available that directly modulate heterotrimeric G proteins. Active Gαq binds its two major classes of effectors, the phospholipase C (PLC)-β isozymes and Rho guanine nucleotide exchange factors (RhoGEFs) related to Trio, in a strikingly similar fashion: a continuous helix-turn-helix of the effectors engages Gαq within its canonical binding site consisting of a groove formed between switch II and helix α3. This information was exploited to synthesize peptides that bound active Gαq in vitro with affinities similar to full-length effectors and directly competed with effectors for engagement of Gαq. A representative peptide was specific for active Gαq because it did not bind inactive Gαq or other classes of active Gα subunits and did not inhibit the activation of PLC-β3 by Gβ1γ2. In contrast, the peptide robustly prevented activation of PLC-β3 or p63RhoGEF by Gαq; it also prevented G protein-coupled receptor-promoted neuronal depolarization downstream of Gαq in the mouse prefrontal cortex. Moreover, a genetically encoded form of this peptide flanked by fluorescent proteins inhibited Gαq-dependent activation of PLC-β3 at least as effectively as a dominant-negative form of full-length PLC-β3. These attributes suggest that related, cell-penetrating peptides should effectively inhibit active Gαq in cells and that these and genetically encoded sequences may find application as molecular probes, drug leads, and biosensors to monitor the spatiotemporal activation of Gαq in cells.
Mitofusin-1 protein is a generally expressed mediator of mitochondrial fusion in mammalian cells

Mitochondrial fusion may regulate mitochondrial morphogenesis and underlie complementation between mitochondrial genomes in mammalian cells. The nuclear encoded mitochondrial proteins Mfn1 and Mfn2 are human homologues of the only known protein mediators of mitochondrial fusion, the Drosophila Fzo GTPase and Saccharomyces cerevisiae yFzo1p. Although the Mfn1 and Mfn2 genes were broadly expressed, the two genes showed different levels of mRNA expression in different tissues. Two Mfn1 transcripts were detected at similar levels in a variety of human tissues and were dramatically elevated in heart, while Mfn2 mRNA was abundantly expressed in heart and muscle tissue but present only at low levels in many other tissues. Human Mfn1 protein localized to mitochondria and participated in a high molecular weight, detergent extractable protein complex. Forced expression of Mfn1 in cultured cells caused formation of characteristic networks of mitochondria. Introduction of a point mutation in the conserved G1 region of the predicted GTPase domain (Mfn1K88T) dramatically decreased formation of mitochondrial networks upon Mfn1 overexpression, suggesting that network formation required completion of the Mfn1 GTPase cycle. Conversely, a protein variant carrying a point mutation in the G2 motif of the Mfn1 GTPase domain acted as a dominant negative: overexpression of Mfn1T109A resulted in fragmentation of mitochondria. We propose that Mfn1T109A interferes with fusion activity of endogenous Mfn1 protein, possibly by binding necessary cofactors, so to allow unopposed mitochondrial fission. Thus, Mfn1 appears to be a key player in mediating mitochondrial fusion and morphology in mammalian cells.
Atmospheric Scintillation at Dome C, Antarctica: Implications for Photometryand Astrometry

We present low‐resolution turbulence profiles of the atmosphere above Dome C, Antarctica, measured with the MASS instrument during 25 nights in 2004 March–May. Except for the lowest layer, Dome C has significantly less turbulence than Cerro Tololo and Cerro Pachón. In particular, the integrated turbulence at 16 km is always less than the median values at the two Chilean sites. From these profiles we evaluate the photometric noise produced by scintillation, and the atmospheric contribution to the error budget in narrow‐angle differential astrometry. In comparison with the two midlatitude sites in Chile, Dome C offers a potential gain of about 3.6 in both photometric precision (for long integrations) and narrow‐angle astrometry precision. These gain estimates are preliminary, being computed with average wind‐speed profiles, but the validity of our approach is confirmed by independent data. Although the data from Dome C cover a fairly limited time frame, they lend strong support to expectations that Dome C will offer significant advantages for photometric and astrometric studies.
Hybrid cascode compensation for two-stage CMOS operational amplifiers

This paper presents the analysis of a hybrid cascode compensation scheme which is used in two-stage CMOS operational transconductance amplifiers (OTAs). The open loop signal transfer function is derived to allow the accurate estimation of the poles and zeros. This analytical approach shows that the nondominant poles and zeros of the hybrid cascode compensation are about 40 percent greater than the conventional cascode compensation. Circuit level simulation results are provided to show the accuracy of the calculated expressions and also the usefulness of the proposed cascode compensation technique.
Women's Health in Northeast Thailand: Working at the Interface Between the Local and the Global

SUMMARY An important first step in translating global statements about women's right to health into action programs is an assessment of the interface between local health culture and public health/medical practice. In this paper, we present the findings of an ongoing research project focusing on women's sexual and reproductive health in Northeast Thailand. The project is a prototype illustrating how formative research may be used to guide intervention development as well as midcourse correction. Examples are provided which clearly illustrate why cultural understandings of gynecological health are important to consider before introducing women's health programs. One case featured describes how an iatrogenic fear of cervical cancer has emerged from public health messages and screening programs. A hybrid model of cancer has evolved from preexisting local ideas, resulting in an exaggerated sense of risk wherein women fear that a wide range of common problems may potentially transform into this fatal disease. We argue that public health needs to be held accountable for what transpires when health messages are introduced into a community. Monitoring of community response is necessary. In the second half of the paper we describe efforts to increase community understanding of women's health problems, create gender and culturally sensitive health care services, and enhance the technical and communication skills of health staff.
Clinical outcomes in statin treatment trials: a meta-analysis.

OBJECTIVE To determine the risk of cardiovascular events and death in patients receiving statin treatment for cholesterol regulation. METHODS Systematic review and meta-analysis of all randomized controlled trials that were published as of April 15, 1997. Primary or secondary prevention trials or regression trials were eligible. MAIN OUTCOME MEASURES All-cause mortality, fatal myocardial infarction (MI) or stroke, nonfatal MI or stroke, angina, and withdrawal from the studies. Both random- and fixed-effects models were run for the outcomes of interests, and results are expressed as odds ratios (ORs). Sensitivity analyses tested the impact of the study type and duration, statin treatment type, and control arm event rates. Intent-to-treat denominators were used whenever they were available, and the number needed to treat was calculated when appropriate. RESULTS Seventeen studies (21 303 patients) were included (2 secondary prevention studies, 5 mixed primary-secondary prevention population studies, and 10 regression trials). Treatment groups included lovastatin (t = 5), pravastatin (t = 10), and simvastatin (t = 3). For all-cause mortality, the OR was 0.76 (95% confidence interval [CI], 0.67-0.86) in favor of receiving statin treatment; for fatal MI, the OR was 0.61 (95% CI, 0.48-0.78); for nonfatal MI, the OR was 0.69 (0.54-0.88); for fatal stroke, the OR was 0.77 (95% CI, 0.57-1.04); for nonfatal stroke, the OR was 0.69 (95% CI, 0.54-0.88); and for angina, the OR was 0.70 (95% CI, 0.65-0.76). CONCLUSIONS Patients who received statin treatment demonstrated a 20% to 30% reduction in death and major cardiovascular events compared with patients who received placebo. This advantage was generally present across study types and statin treatment types and for patients with less severe dyslipidemias. The benefit in clinical outcomes was noticeable as early as 1 year.
Aged garlic extract induces proliferation and ameliorates gentamicin‐induced toxicity in LLC‐PK1 cells

Gentamicin (GM)‐induced nephrotoxicity limits the use of this antibiotic. It has been shown that aged garlic extract (AGE) and S‐allylcysteine (SAC), the most abundant organosulfur compound in AGE, ameliorate GM‐induced nephrotoxicity in rats. The present communication evaluated the effect of AGE and SAC on proliferation and on GM‐induced toxicity and genotoxicity of porcine kidney epithelial cell line (LLC‐PK1 cells). The cells were preincubated with different concentrations of AGE or SAC for 12 h before incubation with 8 mm GM for an additional 72 h. At the end of this time, cell viability, genotoxicity and proliferation were evaluated. AGE stimulated cell proliferation and protected LLC‐PK1 cells from GM‐mediated toxicity and genotoxicity. SAC partially prevented only GM‐induced genotoxicity. These results suggest that the stimulation of cell proliferation could possibly be one of the mechanisms involved in the in vitro protective effect of AGE in GM‐induced toxicity of LLC‐PK1 cells. Copyright © 2006 John Wiley & Sons, Ltd.
Association Between Resistin Level and Renal Function in Patients Undergoing Coronary Artery Bypass Graft Surgery

Aim The purpose of this study was to evaluate the association between resistin levels and renal function in patients undergoing coronary artery bypass graft (CABG) surgery. Methods Thirty-seven consecutive patients (mean ± SD, age 60 ± 10 years, 29 (78%) male) undergoing CABG surgery at our department were enrolled into our study. Blood samples were taken to examine quantities of resistin level and other blood parameters the day before surgery. The patients were categorized into 2 groups: lower resistin level (group 1) or higher resistin level (group 2) according to the median value of 9 ng/mL. Results Mean ± SD resistin level, glomerular filtration rate (GFR), and urea and creatinine levels were 9.5 ± 4.2 ng/mL, 78 ± 25 mL/min per 1.73 m2, 42 ± 14 mg/dL, and 1.08 ± 0.2 mg/dL, respectively. Resistin showed significant correlation with serum levels of urea (r = 0.448l P = 0.005), creatinine (r = 0.367; P = 0.026), inverse correlation with GFR (r = −0.398; P = 0.015), statin usage (r = −0.393; P = 0.016), and β-blocker usage (r = −0.365; P = 0.026). In the multivariate logistic regression model, only GFR (odds ratio, 0.960; 95 confidence interval, 0.928-0.993; P = 0.018) remained independently associated with higher resistin levels after adjustment of other potential confounders in patients undergoing CABG surgery. According to the receiver operating characteristics curve analysis, the optimal cutoff value of GFR to predict higher resistin levels was found as 91 mL/min or less per 1.73 m2, with 100% sensitivity and 61.1% specificity. Conclusion The present study demonstrated that a lower glomerular filtration rate was associated with higher circulating resistin levels, independent of coronary heart disease risk factors in patients undergoing CABG surgery.
The Results and Complications of Cranial Bone Reconstruction in Patients With Craniosynostosis

AbstractThe aim of this study was to report the treatment results and complications of cranial bone reconstruction in patients with craniosynostosis at the Seoul National University Children’s Hospital over the 14-year period from 1996 to 2009. A retrospective study was undertaken on 96 cases of 94 consecutive patients diagnosed with craniosynostosis, operated on between 1996 and 2009. The authors collected the data regarding age at surgery, operative time, duration of hospitalization, and follow-up period. Surgical results including the amount of blood loss, signs related to increased intracranial pressure, aesthetic results, cranial index, and complications were evaluated. The authors compared these results with those of the past 10-year period from 1986 to 1995 at the same hospital. There were 81 patients with single synostosis and 13 patients with multiple synostoses. The age of patients ranged from 3 months to 130 months (mean, 27.9 months). The mean operative time was 7.54 ± 1.77 hours. The duration of hospital stay ranged from 5 to 70 days with a mean period of 8.97 days. The intraoperative loss of hemoglobin ranged from 0 to 9.2 g/dL (mean, 2.35 g/dL). The symptoms of increased intracranial pressure were improved after cranioplasty. With regard to aesthetic results, 94 patients were classified into category I and 2 into category IV. The cranial index decreased from 88.0% ± 1.2% to 86.9% ± 1.1% on average. There were 34 minor complications in 28 operations (29.2%). There were statistically significant differences in age at surgery, operative time, duration of hospital stay, and reoperation rate between the recent 14-year study and the past 10-year study. We observed good surgical results and low complications of cranial bone reconstruction in patients with craniosynostosis. The results of the recent 14-year operations were better than those of the past 10-year operations.
Sparse-partial wavelength conversion in wavelength-routed all-optical networks

Wavelength conversion has been shown as one of the key techniques that can improve the blocking performance in a wavelength-routed all-optical network. Given that wavelength converters nowadays are still very expensive, how to make effective use of the limited number of wavelength converters becomes an important issue. In this paper, we propose a novel sparse-partial wavelength conversion (SPWC) architecture with the inherent flexibility that can facilitate network carriers to migrate the optical backbone to support wavelength conversion. We demonstrate that this architecture can significantly save the number of wavelength converters while still achieving excellent blocking performance. We further investigate the wavelength converter placement problem. Simulation results indicate that, with appropriate wavelength assignment and wavelength converter placement scheme, the performance of the wavelength-routed all-optical network with only 1-5% of wavelength conversion capability is very close to that of the networks with full-complete wavelength conversion capability.
Superior survival associated with transplantation of matched unrelated versus one-antigen-mismatched unrelated or highly human leukocyte antigen-disparate haploidentical family donor marrow grafts for the treatment of hematologic malignancies: establishing a treatment algorithm for recipients of alt

The purpose of this study was to compare transplantation outcomes in patients with hematologic malignancies who received marrow grafts from either phenotypically matched unrelated, one-antigen-mismatched unrelated, or highly human leukocyte antigen (HLA)-disparate family donors. Between 1993 and 2000, 139 patients underwent transplantation from unrelated donors (81 matched and 58 mismatched) and 48 patients received marrow grafts from family donors that were mismatched at 2, 3, or 4 of 8 HLA loci. All patients received a standardized conditioning regimen and a graft-versus-host disease (GVHD) prophylaxis schedule with the exception of recipients of haploidentical marrow grafts, who received antithymocyte globulin after bone marrow transplantation as additional immunosuppression. There was no statistically significant difference in the rate of engraftment, or the cumulative incidences of acute and chronic GVHD between any of the 3 groups. The 2-year cumulative incidence of relapse was lower in matched unrelated patients (25%, P =.01) and mismatched unrelated patients (26%, P =.014) than in haploidentical patients (42%). Transplant-related mortality was significantly higher in recipients of mismatched unrelated grafts (45%, P =.01) and haploidentical grafts (42%, P =.001) compared with recipients of matched unrelated marrow grafts (23%). This resulted in a significantly higher probability of overall survival for matched unrelated patients (58%) versus either mismatched unrelated (34%, P =.01) or haploidentical (21%, P =.002) patients. There was no statistically significant difference in survival between patients who received mismatched unrelated grafts versus those who received haploidentical grafts. This study supports a donor selection algorithm whereby patients who lack a closely matched family donor be offered a phenotypically matched unrelated donor if available. There is no apparent advantage to using a mismatched unrelated versus a highly HLA-disparate family donor.
Introduction of Aromatic Ring-Containing Substituents in Cyclic Nucleotides Is Associated with Inhibition of Toxin Uptake by the Hepatocyte Transporters OATP 1B1 and 1B3

Analogs of the cyclic nucleotides cAMP and cGMP have been extensively used to mimic or modulate cellular events mediated by protein kinase A (PKA), Exchange protein directly activated by cAMP (Epac), or protein kinase G (PKG). We report here that some of the most commonly used cyclic nucleotide analogs inhibit transmembrane transport mediated by the liver specific organic anion transporter peptides OATP1B1 and OATP1B3, unrelated to actions on Epac, PKA or PKG. Several cAMP analogs, particularly with 8-pCPT-substitution, inhibited nodularin (Nod) induced primary rat hepatocyte apoptosis. Inhibition was not mediated by PKA or Epac, since increased endogenous cAMP, and some strong PKA- or Epac-activating analogs failed to protect cells against Nod induced apoptosis. The cAMP analogs inhibiting Nod induced hepatocyte apoptosis also reduced accumulation of radiolabeled Nod or cholic acid in primary rat hepatocytes. They also inhibited Nod induced apoptosis in HEK293 cells with enforced expression of OATP1B1 or 1B3, responsible for Nod transport into cells. Similar results were found with adenosine analogs, disconnecting the inhibitory effect of certain cAMP analogs from PKA or Epac. The most potent inhibitors were 8-pCPT-6-Phe-cAMP and 8-pCPT-2′-O-Me-cAMP, whereas analogs like 6-MB-cAMP or 8-Br-cAMP did not inhibit Nod uptake. This suggests that the addition of aromatic ring-containing substituents like the chloro-phenyl-thio group to the purines of cyclic nucleotides increases their ability to inhibit the OATP-mediated transport. Taken together, our data show that aromatic ring substituents can add unwanted effects to cyclic nucleotides, and that such nucleotide analogs must be used with care, particularly when working with cells expressing OATP1B1/1B3, like hepatocytes, or intact animals where hepatic metabolism can be an issue, as well as certain cancer cells. On the other hand, cAMP analogs with substituents like bromo, monobutyryl were non-inhibitory, and could be considered an alternative when working with cells expressing OATP1 family members.
Clinical and epidemiological research

Ann Rheum Dis 2012;71:38–44. doi:10.1136/annrheumdis-2011-200344 38 ABSTRACT Objectives To assess the effect of a temporary interruption in subcutaneous (SC) abatacept on immunogenicity, safety and effi cacy in patients with active rheumatoid arthritis despite methotrexate in a phase III trial. Methods Following a 12-week open-label introduction (period I; intravenous abatacept loading dose and weekly fi xed-dose SC abatacept 125 mg), patients were randomised 2:1 to double-blind SC placebo or SC abatacept for 12 weeks (period II). At the end of period II, patients receiving SC abatacept continued treatment and patients on placebo were reintroduced to SC abatacept (12-week open-label period III). The co-primary end points were ELISA-detected immunogenicity rate and safety at the end of period II. Effi cacy was also monitored. Results Of 167 patients entering period I, 72% qualifi ed for period II; during periods II and III, three patients discontinued treatment. Mean (SD) disease duration was 6.6 (6.5) years and Disease Activity Score 28 was 4.8 (0.8). The primary end point was met, with a nonsignifi cant increase in immunogenicity upon withdrawal (7/73 placebo vs 0/38 abatacept in period II; p=0.119) which was reversed upon reintroduction of SC abatacept (2/73 vs 1/38, end period III). Safety was comparable regardless of withdrawal, with no unexpected events upon reintroduction. Two patients experienced reactions at the SC injection site. On withdrawal, patients experienced slight worsening in effi cacy which improved following reintroduction. Conclusions Overall immunogenicity to SC abatacept is low, consistent with intravenous abatacept, and is not signifi cantly affected by a 3-month interruption and reintroduction. This stop–start schedule was well tolerated, with little impact on safety and effi cacy. These are important considerations for the clinical use of SC abatacept. ClinicalTrials gov Identifi er NCT00533897