bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proton‐dependent zinc release from intracellular ligands
Authors: Kiedrowski Lech 
Published: March 2014

AbstractIn cultured cortical and hippocampal neurons when intracellular pH drops from 6.6 to 6.1, yet unclear intracellular stores release micromolar amounts of Zn2+ into the cytosol. Mitochondria, acidic organelles, and/or intracellular ligands could release this Zn2+. Although exposure to the protonophore FCCP precludes reloading of the mitochondria and acidic organelles with Zn2+, FCCP failed to compromise the ability of the intracellular stores to repeatedly release Zn2+. Therefore, Zn2+‐releasing stores were not mitochondria or acidic organelles but rather intracellular Zn2+ ligands. To test which ligands might be involved, the rate of acid‐induced Zn2+ release from complexes with cysteine, glutathione, histidine, aspartate, glutamate, glycine, and carnosine was investigated; [Zn2+] was monitored in vitro using the ratiometric Zn2+‐sensitive fluorescent probe FuraZin‐1. Carnosine failed to chelate Zn2+ but did chelate Cu2+; the remaining ligands chelated Zn2+ and upon acidification were releasing it into the medium. However, when pH was decreasing from 6.6 to 6.1, only zinc–cysteine complexes rapidly accelerated the rate of Zn2+ release. The zinc–cysteine complexes also released Zn2+ when a histidine‐modifying agent, diethylpyrocarbonate, was applied at pH 7.2. Since the cytosolic zinc–cysteine complexes can contain micromolar amounts of Zn2+, these complexes may represent the stores responsible for an acid‐induced intracellular Zn2+ release.
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This study aimed at identifying intracellular stores which release Zn2+ when pHi drops from 6.6 to 6.1. It was found that these stores are not mitochondria or acidic organelles, but rather intracellular Zn2+ ligands. When the pH was decreasing from 6.6 to 6.1, only zinc–cysteine complexes showed a rapid acceleration in the rate of Zn2+ release. Therefore, the stores responsible for an acid‐induced intracellular Zn2+ release in neurons may be the cytosolic zinc–cysteine complexes.
National Trends in the Treatment of Penile Prosthesis Infections by Explantation Alone vs. Immediate Salvage and Reimplantation
Authors: Zargaroff Sherwin , Sharma Vidit , Berhanu Daniel , Pearl Jeff A. , Meeks Joshua J. , Dupree James M. , Le Brian V. , Cashy John , McVary Kevin T. 
Published: March 2014

Abstract

Introduction
A penile prosthesis infection (PPI) is either treated with explantation of the prosthesis with a possible delayed reimplantation or a salvage procedure with an immediate reimplantation of the prosthesis.

Aim
We used a large, all-payer national database to investigate the use of the salvage procedure in the setting of PPI.

Methods
The study used years 2000–2009 of the Nationwide Inpatient Sample to identify PPIs treated with immediate salvage or explantation alone. Admissions were then stratified by various parameters to compare differences in the salvage rates.

Main Outcome Measures
Salvage Rate of Penile Prosthesis infection.

Results
A total of 1,557 patients were treated with an explantation only (82.7%) or salvage (17.3%) for PPI, a proportion that remained stable over the study period. The patients treated with salvage were younger (60.4 vs. 65.1 years), more likely to be discharged home (87.3% vs. 61.9%), and were less likely to have a severe presentation (7.2% vs. 31.6%) than those who were explanted only (P &lt; 0.001). These factors were confirmed on multivariate regression analysis. The regression also revealed that treatment at rural hospitals had lower odds of salvage than treatment at urban teaching hospitals. Race, comorbid diabetes, and insurance status did not independently affect the salvage rate. There was no significant difference in total hospital charges between groups.

Conclusions
Salvage rates have remained low over the past decade. Our study elucidated several factors decreasing the chances of salvage after PPI including age, severity of presentation, and hospital setting.
Use of hepatitis B surface and “e” antigen quantification during extensive treatment with tenofovir in patients co‐infected with HIV‐HBV
Authors: Boyd Anders , Maylin Sarah , Gozlan Joël , Delaugerre Constance , Simon François , Girard Pierre‐Marie , Lacombe Karine 
Published: March 2014

AbstractBackground & AimsIn patients infected with hepatitis B virus (HBV) and HIV, hepatitis B ‘e’ antigen (qHBeAg) and hepatitis B surface antigen quantification (qHBsAg) may be used to predict short‐term HBeAg and HBsAg loss, respectively. To determine if these quantifiable markers also provide accurate prediction of antigen loss during long‐term, extensive tenofovir (TDF) treatment and to further establish qHBsAg profiles associated with HBsAg seroconversion.MethodsProspective study of 111 co‐infected, antiretroviral‐experienced patients undergoing a TDF‐containing regimen for >12 months. HBV‐DNA viral load, qHBeAg [Paul Ehrlich Institute Units (PEIU)/ml] and qHBsAg were quantified at baseline and every 6–12 months. Sensitivity (Se) and specificity (Sp) of qHBeAg criteria were calculated using a time‐dependent receiver operator characteristic curve, and qHBsAg profiles were developed using a group‐based trajectory model.ResultsAfter a median 74.2 months (IQR: 33.1–94.7) of TDF treatment, four patients had HBsAg seroconversion. Among the 78 (70.3%) HBeAg‐positive patients, cumulative proportion with HBeAg loss was 42.0% (n = 23) at month 96. Baseline qHBeAg ≤100 PEIU/ml was the only significant factor for HBeAg loss (adjusted‐HR = 2.36, 95% CI: 1.02–5.46) in multivariable analysis. In terms of predicting HBeAg‐loss until month 96, qHBeAg ≤10 PEIU/ml was more accurate when evaluated at month 24 (Se = 0.73, Sp = 0.80) than month 12 (Se = 0.48, Sp = 0.90). All four patients with HBsAg seroconversion had profiles with large decreases in qHBsAg (>2 log10 IU/ml), not necessarily occurring during the first 12 months, which was infrequent in patients without seroconversion (8.4%, P < 0.001).ConclusionsQuantifying hepatitis ‘e’ antigen during the first 2 years of TDF treatment is a practical tool in predicting long‐term HBeAg loss. Non time‐specific declines in qHBsAg may be a useful indicator of HBsAg seroconversion.
Isolation and characterisation of the fungusSpiromastix asexualissp. nov. from discospondylitis in aGermanShepherd dog, and review ofSpiromastixwith the proposal of the new orderSpiromastixales (Ascomycota)
Authors: Rizzo L. , Sutton D. A. , Wiederhold N. P. , Thompson E. H. , Friedman R. , Wickes B. L. , Cano‐Lira J. F. , Stchigel A. M. , Guarro J. 
Published: March 2014

SummaryThe genusSpiromastixconsists of several fungal species that have been isolated from soil and animal dung in various parts of the world. However, these species are considered to be of low pathogenic potential, as no cases of infections caused by these fungi have been reported. Here, we describe the clinical course of discospondylitis in a dog from which a fungus was cultured from a biopsy and identified as aSpiromastixspecies by morphologic characteristics and sequencing. Phylogenetic analysis determined this to be a new species,Spiromastix asexualis, which is described, and a new order,Spiromastixales, is proposed.
Cognitive analytic therapy: A review of the outcome evidence base for treatment
Authors: Calvert Rachel , Kellett Stephen 
Published: March 2014

PurposeThis study reviews the quality of the extant outcome evidence for cognitive analytic therapy (CAT) to inform clinical practice and to stimulate a future CAT research strategy.MethodAn electronic search identified CAT efficacy and effectiveness studies and these were subject to systematic review. The methodological quality of studies meeting inclusion criteria were appraised using two validated research study quality checklists and studies were fitted to an established model of psychotherapy evaluation.ResultsTwenty‐five outcome studies met the inclusion criteria, including five randomized controlled trials. The CAT evidence base is predominated by small‐scale practice‐based studies, in typically complex and severe clinical populations – 44% were focal to the treatment of personality disorder. Although the quality of extant CAT evidence is generally sound (52% of studies were high quality), the depth and breadth of the evidence base is currently limited. Where comparisons with other modalities are available, CAT appears largely equivocal.ConclusionsCognitive analytic therapy is a popular and promising intervention for complex presentations. However, the evidence base currently lacks wider credibility due to having largely bypassed the rigours of the controlled phase of the hourglass model of psychotherapy evaluation. There is a particular need for further CAT outcome research with common mental health problems.Practitioner points

CAT can be an effective intervention across a range of mental health difficulties.

Consider a 24‐session CAT contract for those patients presenting with complex and severe difficulties.

Practice research networks could make a significant contribution to the CAT evidence base.
Association of leptin/receptor and TNF‐α gene variants with adolescent obesity in Malaysia
Authors: Ng Zoe Yi , Veerapen Muthu Kumar , Hon Wei Min , Lim Renee Lay Hong 
Published: March 2014

AbstractBackgroundLeptin (LEP) G‐2548A (rs7799039), leptin receptor (LEPR) Q223R (rs1137101) and tumor necrosis factor (TNF)‐α G‐308A (rs1800629) gene variants have been reported to be associated with obesity, although results for subjects from different countries have been controversial. The aim of this study was to determine the prevalence of overweight and obesity in Malaysian adolescents and the association of these polymorphisms with overweight and obese or over‐fat adolescents.MethodsA total of 613 adolescents (241 Malay, 219 Chinese, 153 Indian) were enrolled. Anthropometric measurements of body mass index (BMI) and body fat percentage were used to classify subjects as controls (non‐overweight/obese or normal fat) or as cases (overweight/obese or over‐fat). Genomic DNA was extracted from oral buccal mucosa cells for genotyping using polymerase chain reaction–restriction fragment length polymorphism and data obtained were statistically analyzed.ResultsA total of 23.3% of subjects were overweight/obese whereas 11.4% were over‐fat; there were significantly more overweight/obese and over‐fat Indian and Malay adolescents compared to Chinese (P < 0.001). A allele was the minor one for LEPR Q223R and TNF‐α G‐308A in all ethnic groups, whereas G allele was minor for LEP G‐2548A in Chinese and Malay adolescents, except for Indian adolescents. Indian male adolescents with AA genotype for LEP G‐2548A were associated with overweight/obesity (P = 0.025; odds ratio, 3.64; 95% confidence interval: 1.15–11.54). Despite the lack of association observed for LEPR Q223R and TNF‐α G‐308A, Indian and Chinese subjects with AA risk genotype for LEPR Q223R/LEP G‐2548A and TNF‐α G‐308A/LEP G‐2548A, respectively, had increased mean BMI (P = 0.049, P = 0.016).ConclusionsGenotype distribution and association of these polymorphisms with overweight/obesity vary between ethnic groups and genders. Nevertheless, the LEP G‐2548A risk allele may be associated with overweight/obese Indian male adolescents in Malaysia.
Shūrà and Democracy: Two Sides of the Same Coin?
Authors: Soage Ana Belén 
Published: March 2014

AbstractSince the beginning of the modern period – usually called the Renaissance (Nahda in Arabic) – prominent pre‐Islamists and Islamists such as Jamāl al‐Dīn al‐Afghānī, Rashīd Ridā and Yūsuf al‐Qaradāwī have condemned the political oppression that prevails in much of the Muslim world and attributed its backwardness to that oppression. For many of those authors, the solution is the implementation of the old Arab institution of consultation (shūrà), which is mentioned in the Koran and has been associated with the Western parliamentary system. But were those Islamist authors just trying to encourage the adoption of Western‐style democracy in Muslim lands by painting it with the brush of Islam? Can we really conceive shūrà as a form of democracy? And what about those who espouse shūrà but reject democracy? The present paper looks at that institution in its historical context and offers the opinion of several renowned contemporary Islamist thinkers on its prospects.
Benefits of sulfamethoxazole‐trimethoprim prophylaxis on rates of sepsis after kidney transplant
Authors: Horwedel T.A. , Bowman L.J. , Saab G. , Brennan D.C. 
Published: March 2014

AbstractBackgroundThe use of potent immunosuppression increases the risk of infectious complications following kidney transplantation. Sulfamethoxazole‐trimethoprim (SMX/TMP) is an inexpensive broad‐spectrum antimicrobial agent used in our center as lifelong prophylaxis against Pneumocystis jirovecii, unless contraindicated. This study evaluated the clinical impact of SMX/TMP prophylaxis compared with no prophylaxis with SMX/TMP (NoPPx), but with alternative agents.MethodsThis was a retrospective cohort analysis of renal transplant recipients (RTR) transplanted from January 2002 through December 2010. Patients were divided into SMX/TMP group and NoPPX group, based on whether they received prophylaxis with SMX/TMP or not, and rates of sepsis were compared between groups. We also analyzed the pathogens and source implicated in these episodes, as well as the dose of SMX/TMP. Rates were compared using multivariate logistic regression.ResultsWith a mean follow‐up of 4.8 (± 2.5) years, 63 cases of sepsis occurred in 1224 patients (5.1%), and 60% of these cases had a urinary source. The risk of sepsis was significantly reduced with prophylaxis vs. NoPPx (13.3% vs. 4.3% for SMX/TMP, P < 0.001), and this association was maintained through multivariate regression. Sepsis was associated with a numerically increased risk of graft loss and death that was not significantly affected by use of SMX/TMP.ConclusionsProphylaxis with SMX/TMP is an inexpensive way to reduce the incidence of sepsis in RTR.
Hypothesis On The Source, Transmission and Characteristics of Infection of Avian Influenza A (H7N9) Virus – Based On Analysis of Field Epidemiological Investigation and Gene Sequence Analysis
Authors: Ling F. , Chen E. , Liu Q. , Miao Z. , Gong Z. 
Published: March 2014

SummaryOn 31 March 2013, the National Health and Family Planning Commission announced that human infections with influenza A (H7N9) virus had occurred in Shanghai and Anhui provinces, China. H7N9 cases were later detected in Jiangsu and Zhejiang provinces. It was estimated that the virus first spread northward along the route taken by migratory birds and then spread to neighbouring provinces with the sale of poultry. Epidemiological studies were carried out on samples from the external environment of infected cases, transmission routes, farmers markets and live poultry markets. Phylogenetic study of viral sequences from human and avian infections in Zhejiang showed that those from Shanghai and Jiangsu provinces along Taihu Lake were highly homologous with those from the external environment. This suggests that avian viruses carried by waterfowl combined with the virus carried by migratory birds, giving rise to avian influenza virus H7N9, which is highly pathogenic to humans. It is possible that the virus was transmitted by local wildfowl to domestic poultry and then to humans, or spread further by means of trading in wholesale poultry markets. As the weather has turned warm, and with measures adopted to terminate poultry trade and facilitate health communication, the epidemic in the first half of the year has been kept under control. However, the infection source in the triangular area around Taihu Lake still remains. The H7N9 epidemic will probably hit the area later in the year and next spring when the migratory birds return and may even spread to other areas. Great importance should therefore be attached to the wildfowl in Taihu Lake as the repository and disseminator of the virus: investigation and study of this population is essential.
Miltefosine Increases Lipid and Protein Dynamics in Leishmania amazonensis Membranes at Concentrations Similar to Those Needed for Cytotoxicity Activity
Authors: Moreira Rodrigo Alves , Mendanha Sebastião Antonio , Fernandes Kelly Souza , Matos Grazzielle Guimaraes , Alonso Lais , Dorta Miriam Leandro , Alonso Antonio 
Published: March 2014

ABSTRACT

Miltefosine (MT) is a membrane-active alkylphospholipid licensed for the topical treatment of breast cancer skin metastases and the oral treatment of leishmaniasis, although its mechanism of action remains unclear. Electron paramagnetic resonance (EPR) spectroscopy of a spin-labeled lipid and a thiol-specific spin label in the plasma membrane of
Leishmania
promastigotes showed that MT causes dramatic increases in membrane dynamics. Although these alterations can be detected using a spin-labeled lipid, our experimental results indicated that MT interacts predominantly with the protein component of the membrane. Cell lysis was also detected by analyzing the supernatants of centrifuged samples for the presence of spin-labeled membrane fragments and cytoplasmic proteins. Using a method for the rapid incorporation of MT into the membrane, these effects were measured immediately after treatment under the same range of MT concentrations that cause cell growth inhibition. Cytotoxicity, estimated via microscopic counting of living and dead cells, indicated ∼70% cell death at the concentration of MT at which EPR spectroscopy detected a significant change in membrane dynamics. After this initial impact on the number of viable parasites, the processes of cell death and growth continued during the first 4 h of incubation. The EPR spectra of spin-labeled membrane-bound proteins were consistent with more expanded and solvent-exposed protein conformations, suggesting a detergent-like action. Thus, MT may form micelle-like structures around polypeptide chains, and proteins with a higher hydrophobicity may induce the penetration of hydrophilic groups of MT into the membrane, causing its rupture.
Characterization of the Population Pharmacokinetics of Ampicillin in Neonates Using an Opportunistic Study Design
Authors: Tremoulet Adriana , Le Jennifer , Poindexter Brenda , Sullivan Janice E. , Laughon Matthew , Delmore Paula , Salgado Andrea , Ian-U Chong Sandy , Melloni Chiara , Gao Jamie , Benjamin Daniel K. , Capparelli Edmund V. , Cohen-Wolkowiez Michael 
Published: March 2014

ABSTRACT

Although ampicillin is the most commonly used drug in neonates, developmental pharmacokinetic (PK) data to guide dosing are lacking. Ampicillin is primarily renally eliminated, and developmental changes are expected to influence PK. We conducted an open-label, multicenter, opportunistic, prospective PK study of ampicillin in neonates stratified by gestational age (GA) (≤34 or >34 weeks) and postnatal age (PNA) (≤7 or >7 days). Drug concentrations were measured by tandem mass spectrometry. PK data were analyzed using population nonlinear mixed-effects modeling in NONMEM 7.2. Monte Carlo simulations were conducted to determine the probability of target attainment for the time in which the total steady-state ampicillin concentrations remained above the MIC (
T
>MIC) for 50%, 75%, and 100% of the dosing interval. A total of 142 PK samples from 73 neonates were analyzed (median [range] GA, 36 [24 to 41] weeks; PNA, 5 [0 to 25] days). The median ampicillin dose was 200 (100 to 350) mg/kg/day. Postmenstrual age and serum creatinine were covariates for ampicillin clearance (CL). A simplified dosing regimen of 50 mg/kg every 12 h for GA of ≤34 weeks and PNA of ≤7 days, 75 mg/kg every 12 h for GA of ≤34 weeks and PNA of ≥8 and ≤28 days, and 50 mg/kg every 8 h for GA of >34 weeks and PNA of ≤28 days achieved the prespecified surrogate efficacy target in 90% of simulated subjects. Ampicillin CL was associated with neonatal development. A simplified dosing regimen stratified by GA and PNA achieves the desired surrogate therapeutic target in the vast majority of neonates.
Application of Qualitative and Quantitative Real-Time PCR, Direct Sequencing, and Terminal Restriction Fragment Length Polymorphism Analysis for Detection and Identification of Polymicrobial 16S rRNA Genes in Ascites
Authors: Krohn Sandra , Böhm Stephan , Engelmann Cornelius , Hartmann Jan , Brodzinski Annika , Chatzinotas Antonis , Zeller Katharina , Prywerek Delia , Fetzer Ingo , Berg Thomas 
Published: March 2014

ABSTRACT

Qualitative and quantitative 16S rRNA gene-based real-time PCR and direct sequencing were applied for rapid detection and identification of bacterial DNA (bactDNA) in 356 ascites samples. bactDNA was detected in 35% of samples, with a mean of 3.24 log copies ml
−1
. Direct sequencing of PCR products revealed 62% mixed chromatograms predominantly belonging to Gram-positive bacteria. Terminal restriction fragment length polymorphism (T-RFLP) results of a sample subset confirmed sequence data showing polymicrobial DNA contents in 67% of bactDNA-positive ascites samples.
Diagnostic Accuracy of Xpert MTB/RIF for Extrapulmonary Tuberculosis Specimens: Establishing a Laboratory Testing Algorithm for South Africa
Authors: Scott Lesley Erica , Beylis Natalie , Nicol Mark , Nkuna Gloria , Molapo Sebaka , Berrie Leigh , Duse Adriano , Stevens Wendy Susan 
Published: March 2014

ABSTRACT

South Africa implemented Xpert MTB/RIF as the initial diagnostic test for pulmonary tuberculosis (TB). Xpert MTB/RIF's accuracy for diagnosing extrapulmonary tuberculosis (EPTB) was investigated. EPTB specimens (
n
= 7,916) from hospitalized patients received over a 6-month period at a high-throughput TB referral laboratory in Johannesburg were investigated. Large-volume specimens were centrifuged, tissue biopsy specimens homogenized, and all specimens checked for growth of contaminating bacteria on blood agar. Contaminated samples received NALC-NaOH (
N
-acetyl-
l
-cysteine–sodium hydroxide) decontamination prior to liquid culture. Residual specimens (volumes > 1 ml) after inoculation of culture (
n
= 1,175) were tested using the Xpert MTB/RIF sputum protocol. Using culture as the reference, Xpert MTB/RIF's overall sensitivity was 59% (95% confidence interval [95% CI], 53% to 65%) and specificity was 92% (CI, 90% to 94%), with the highest sensitivities of 91% (95% CI, 78% to 97%) for pus, 80% (95% CI, 56% to 94%) for lymph node aspirates, and 51% (95% CI, 44% to 58%) for fluids (ascitic, 59%; pleural, 47%). A difference in sensitivities was noticed between specimens classified as having a thick (87% [95% CI, 76% to 94%]) versus clear (watery) (48% [95% CI, 36% to 61%]) appearance. This was unchanged with traces of blood (52% [95% CI, 44% to 60%]) or precentrifugation (57% [95% CI, 28% to 82%]) among clear specimens. Xpert MTB/RIF generated an additional 124 specimen results that were contaminated by Mycobacterial Growth Indicator Tubes (MGIT; 10.5%) and diagnosed rifampin (RIF) resistance earlier (9.6% [25/260]). Xpert MTB/RIF's performance on EPTB specimens provides very promising results and should be considered for incorporation into national TB guidelines. Xpert MTB/RIF is less affected by contaminating bacteria and reduces laboratory labor and diagnostic delay compared to traditional methods.