bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the Adequacy of Small Solute Clearance for Various Dialysis Modalities, with Inclusion of Residual Native Kidney Function
Authors: Chin Andrew I. , Depner Thomas A. , Daugirdas John T. 
Published: February 2017

AbstractMeasurement of small molecule clearance remains important in the clinical care of patients requiring long‐term dialysis. Many patients maintain a significant degree of residual native kidney function and may have nontraditional schedules with or without combined dialysis modalities. In this review, we examine and outline methods for comparing small molecule clearances among various dialysis prescriptions and modalities, with inclusion of residual kidney urea clearance.
Trust in the System? Factors that Impact Citizens’ View of Courts in the United Kingdom
Authors: Hansen Michael A. 
Published: February 2017

ObjectiveThe objective of this study was to test the individual and parliamentary constituency factors that impact the level of trust that British citizens have in the courts.MethodsBy using a Bayesian hierarchical model, this article is able to calculate the effect of variables that exist at both levels.ResultsAt the individual level, the main explanatory variable is the amount of trust a citizen holds for other institutions, and at the constituency level, crime rate has an effect on a citizen's level of trust in the courts.ConclusionPrevious findings related to citizen attitudes and support for courts in the United States transfer well to the United Kingdom.
Disability, Voter Turnout, and Polling Place Accessibility
Authors: Schur Lisa , Ameri Mason , Adya Meera 
Published: February 2017

ObjectivePolling place inaccessibility may contribute to the disability gap in voter turnout, both directly by making voting more difficult for people with disabilities, and indirectly by sending the message that people with disabilities are not expected to participate in the political sphere. We explore the role of polling place inaccessibility by examining voter turnout and reports of voting difficulties among people with and without disabilities in the 2012 elections.MethodWe use the Census Bureau's Voting and Registration Supplement (VRS) and a newly constructed national household survey following the 2012 elections.ResultsConsistent with past findings, the disability turnout gap is reduced but not eliminated when controlling for standard predictors of voter turnout. Nearly, one‐third (30 percent) of voters with disabilities reported difficulty in voting at a polling place in 2012, compared to only 8 percent of voters without disabilities. We find that difficulties in voting predict lower perceptions of the influence people with disabilities have in the political process. This in turn is a significant predictor of voter turnout among people with disabilities, supporting the idea that voting difficulties depress turnout. Majorities of people both with and without disabilities said they would prefer voting in person in a polling place in the next election.ConclusionThe results point to the potential role of polling place accessibility in voter turnout, and the gains from wider adoption of best practices to reduce barriers and make the voting process more fully accessible.
The Ties that Bind Beyond the Battlefield: An Examination of the Diffusion Patterns of Veterans Treatment Courts
Authors: Easterly Bianca 
Published: February 2017

ObjectivesThe growing number of veterans on court dockets with mental health and substance abuse issues has resulted in the proliferation of veterans treatment courts (VTCs). Given the ubiquity of substance abuse and mental illness across communities, it is unclear why some local courts innovate and, more importantly, why some do so earlier than others.MethodsUsing data from 2008 to 2014, the study applies event history modeling to investigate the extent to which, if any, presiding judges’ connection to the armed forces, either personally or through immediate family members (e.g., parents, children), accelerates the adoption of states’ initial VTCs.ResultsFindings show significant support for both the hastening effect of personal knowledge of the military and, to a lesser extent, the increased presence VA Community‐Based Outpatient Clinics have on VTC innovation.ConclusionsJudges’ social group membership and the availability of government resources in a community influence court organization innovation.
Guinea worm infection in northern Nigeria: reflections on a disease approaching eradication
Authors: Greenwood Brian , Greenwood Alice , Bradley Andrew 
Published: February 2017

SummaryGlobal eradication of the guinea worm (Dracunculus medinensis) is near, although perhaps delayed a little by the discovery of a transmission cycle in dogs. It is therefore an appropriate time to reflect on the severe impact of this infection on the life of the communities where it was endemic prior to the start of the global eradication programme in 1981. From 1971 to 1974, we conducted a series of unpublished studies on guinea worm in a group of villages in Katsina State, northern Nigeria, where the infection was highly endemic. These studies demonstrated the high rate of infection in affected communities, the frequent recurrence of the infection in some subjects and the long‐standing disability that remained in some infected individuals. Immunological studies showed a high level of immediate hypersensitivity to adult worm and larval antigens but a downregulation of Th1‐type T‐cell responses to worm antigens. Freeing communities such as those described in this article from the scourge of guinea worm infection for good will be an important public health triumph.
Requirement of extracellular Ca2+ binding to specific amino acids for heat‐evoked activation of TRPA1
Authors: Kurganov Erkin , Saito Shigeru , Tanaka Saito Claire , Tominaga Makoto 
Published: February 2017

Key points
We found that extracellular Ca2+, but not other divalent cations (Mg2+ and Ba2+) or intracellular Ca2+, is involved in heat‐evoked activation of green anole (ga) TRPA1.
Heat‐evoked activation of chicken (ch) and rat snake (rs) TRPA1 does not depend solely on extracellular Ca2+.
Neutralization of acidic amino acids on the outer surface of TRPA1 by extracellular Ca2+ is important for heat‐evoked large activation of gaTRPA1, chTRPA1 and rsTRPA1.
AbstractTransient receptor potential ankyrin 1 (TRPA1) is a homotetrameric non‐selective cation‐permeable channel that has six transmembrane domains and cytoplasmic N‐ and C‐termini. The N‐terminus is characterized by an unusually large number of ankyrin repeats. Although the 3‐dimensional structure of human TRPA1 has been determined, and TRPA1 channels from insects to birds are known to be activated by heat stimulus, the mechanism for temperature‐dependent TRPA1 activation is unclear. We previously reported that extracellular Ca2+, but not intracellular Ca2+, plays an important role in heat‐evoked TRPA1 activation in green anole lizards (gaTRPA1). Here we focus on extracellular Ca2+‐dependent heat sensitivity of gaTRPA1 by comparing gaTRPA1 with heat‐activated TRPA1 channels from rat snake (rsTRPA1) and chicken (chTRPA1). In the absence of extracellular Ca2+, rsTRPA1 and chTRPA1 are activated by heat and generate small inward currents. A comparison of extracellular amino acids in TRPA1 identified three negatively charged amino acid residues (glutamate and aspartate) near the outer pore vestibule that are involved in heat‐evoked TRPA1 activation in the presence of extracellular Ca2+. These results suggest that neutralization of acidic amino acids by extracellular Ca2+ is important for heat‐evoked activation of gaTRPA1, chTRPA1, and rsTRPA1, which could clarify mechanisms of heat‐evoked channel activation.
Simplified Reversed Chloroquines To Overcome Malaria Resistance to Quinoline-Based Drugs
Authors: Gunsaru Bornface , Burgess Steven J. , Morrill Westin , Kelly Jane X. , Shomloo Shawheen , Smilkstein Martin J. , Liebman Katherine , Peyton David H. 
Published: February 2017

ABSTRACT

Building on our earlier work of attaching a chemosensitizer (reversal agent) to a known drug pharmacophore, we have now expanded the structure-activity relationship study to include simplified versions of the chemosensitizer. The change from two aromatic rings in this head group to a single ring does not appear to detrimentally affect the antimalarial activity of the compounds. Data from
in vitro
heme binding and
β
-hematin inhibition assays suggest that the single aromatic RCQ compounds retain activities against
Plasmodium falciparum
similar to those of CQ, although other mechanisms of action may be relevant to their activities.
Results from a Patient-Based Health Education Intervention in Reducing Antibiotic Use for Acute Upper Respiratory Tract Infections in the Private Sector Primary Care Setting in Singapore
Authors: Lee Magdalene Hui Min , Pan Darius Shaw Teng , Huang Joyce Huixin , Chen Mark I-Cheng , Chong Joash Wen Chen , Goh Ee Hui , Jiang Lili , Leo Yee Sin , Lee Tau Hong , Wong Chia Siong , Loh Victor Weng Keong , Lim Fong Seng , Poh Adrian Zhongxian , Tham Tat Yean , Wong Wei Mon , Yu Yue 
Published: February 2017

ABSTRACT

We investigated the efficacy of patient-targeted education in reducing antibiotic prescriptions for upper respiratory tract infections (URTIs) among adults in the private primary care setting in Singapore. Our randomized controlled trial enrolled patients aged 21 years and above presenting at general practitioner (GP) clinics with URTI symptoms for 7 days or less. Intervention arm patients were verbally educated via pamphlets about the etiology of URTIs, the role of antibiotics in treating URTIs, and the consequences of inappropriate antibiotic use. Control arm patients were educated on influenza vaccinations. Both arms were compared regarding the proportions prescribed antibiotics and the patients' postconsultation views. A total of 914 patients consulting 35 doctors from 24 clinics completed the study (457 in each arm). The demographics of patients in both arms were similar, and 19.1% were prescribed an antibiotic, but this varied from 0% to 70% for individual GPs. The intervention did not significantly reduce antibiotic prescriptions (odds ratio [OR], 1.20; 95% confidence interval [CI], 0.83–1.73) except in patients of Indian ethnicity (OR, 0.28; 95% CI, 0.09–0.93). Positive associations between the intervention and the view that antibiotics were not needed most of the time for URTIs (
P
= 0.047) and on being worried about the side effects of antibiotics (
P
= 0.018) were restricted to the Indian subgroup. GPs in limited liability partnerships or clinic chains prescribed less (OR, 0.36; 95% CI, 0.14 to 0.92), while certain inappropriate patient responses were associated with the receipt of antibiotics. Follow-up studies to investigate differences in responses to educational programs between ethnicities and to explore GP-targeted interventions are recommended.
Towards Selective Mycobacterial ClpP1P2 Inhibitors with Reduced Activity against the Human Proteasome
Authors: Moreira Wilfried , Santhanakrishnan Sridhar , Ngan Grace J. Y. , Low Choon Bing , Sangthongpitag Kanda , Poulsen Anders , Dymock Brian W. , Dick Thomas 
Published: February 2017

ABSTRACT

Mycobacterium tuberculosis
is responsible for the greatest number of deaths worldwide due to a bacterial agent. We recently identified bortezomib (Velcade; compound 1) as a promising antituberculosis (anti-TB) compound. We showed that compound 1 inhibits the mycobacterial caseinolytic proteases P1 and P2 (ClpP1P2) and exhibits bactericidal activity, and we established compound 1 and ClpP1P2 as an attractive lead/target couple. However, compound 1 is a human-proteasome inhibitor currently approved for cancer therapy and, as such, exhibits significant toxicity. Selective inhibition of the bacterial protease over the human proteasome is desirable in order to maintain antibacterial activity while reducing toxicity. We made use of structural data in order to design a series of dipeptidyl-boronate derivatives of compound 1. We tested these derivatives for whole-cell ClpP1P2 and human-proteasome inhibition as well as bacterial-growth inhibition and identified compounds that were up to 100-fold-less active against the human proteasome but that retained ClpP1P2 and mycobacterial-growth inhibition as well as bactericidal potency. The lead compound, compound 58, had low micromolar ClpP1P2 and anti-
M. tuberculosis
activity, good aqueous solubility, no cytochrome P450 liabilities, moderate plasma protein binding, and low toxicity in two human liver cell lines, and despite high clearance in microsomes, this compound was only moderately cleared when administered intravenously or orally to mice. Higher-dose oral pharmacokinetics indicated good dose linearity. Furthermore, compound 58 was inhibitory to only 11% of a panel of 62 proteases. Our work suggests that selectivity over the human proteasome can be achieved with a drug-like template while retaining potency against ClpP1P2 and, crucially, anti-
M. tuberculosis
activity.
Application of Fluoroquinolone Resistance Score in Management of Complicated Urinary Tract Infections
Authors: Shah Ansal , Justo Julie Ann , Bookstaver P. Brandon , Kohn Joseph , Albrecht Helmut , Al-Hasan Majdi N. 
Published: February 2017

ABSTRACT

The fluoroquinolone resistance score (FQRS) predicts the probability of fluoroquinolone resistance with good discrimination. The score has been derived from patients with bloodstream infections caused by Gram-negative bacteria and is based on fluoroquinolone use within the past 6 months, among other clinical and health care exposure criteria. This study aims to examine the utility of the FQRS in patients with complicated urinary tract infections (cUTI) and determine whether extension of prior fluoroquinolone use to 12 months improves model discrimination. Adults with cUTI at Palmetto Health in central South Carolina, USA, from 1 April 2015 through 31 July 2015 were prospectively identified. Multivariate logistic regression was used to examine the association between prior fluoroquinolone use and resistance. Among 238 patients, 54 (23%) had cUTI due to fluoroquinolone-resistant bacteria. Overall, the median age was 66 years, 162 (68%) patients were women, and 137 (58%) patients had cUTI due to
Escherichia coli
. Prior exposure to fluoroquinolones within 3 months (adjusted odds ratio [aOR], 23.4; 95% confidence interval [CI], 8.2 to 76.8;
P
< 0.001) and within 3 to 12 months (aOR, 13.2; 95% CI, 3.1 to 68.4;
P
< 0.001) was independently associated with fluoroquinolone resistance compared to no prior use. The area under the receiver operating characteristic curve for the FQRS increased from 0.73 to 0.80 when prior fluoroquinolone use was extended from 6 to 12 months. FQRSs of ≥2 and ≥3 had negative predictive values of 91% and 90%, respectively. The modified FQRS stratifies patients with cUTI on the basis of the predicted probability of fluoroquinolone resistance with very good discrimination. Application of the modified FQRS may improve antimicrobial utilization in patients with acute pyelonephritis.
Prevalence and Molecular Characterization of
mcr-1
-Positive Salmonella Strains Recovered from Clinical Specimens in China
Authors: Cui Mingquan , Zhang Jinfei , Gu Zhen , Li Ruichao , Chan Edward Wai-chi , Yan Meiyin , Wu Congming , Xu Xuebin , Chen Sheng 
Published: February 2017

ABSTRACT

The recently discovered colistin resistance element,
mcr-1
, adds to the list of antimicrobial resistance genes that rapidly erode the antimicrobial efficacy of not only the commonly used antibiotics but also the last-line agents of carbapenems and colistin. This study investigated the prevalence of the mobile colistin resistance determinant
mcr-1
in
Salmonella
strains recovered from clinical settings in China and the transmission potential of
mcr-1
-bearing mobile elements harbored by such isolates. The
mcr-1
gene was recoverable in 1.4% of clinical isolates tested, with the majority of them belonging to
Salmonella enterica
serotype Typhimurium. These isolates exhibited diverse pulsed-field gel electrophoresis (PFGE) profiles and high resistance to antibiotics other than colistin and particularly to cephalosporins. Plasmid analysis showed that
mcr-1
was carried on a variety of plasmids with sizes ranging from ∼30 to ∼250 kb, among which there were conjugative plasmids of ∼30 kb, ∼60 kb, and ∼250 kb and nonconjugative plasmids of ∼140 kb, ∼180 kb, and ∼240 kb. Sequencing of representative
mcr-1
-carrying plasmids revealed that all conjugative plasmids belonged to the IncX4, IncI2, and IncHI2 types and were highly similar to the corresponding types of plasmids reported previously. Nonconjugative plasmids all belonged to the IncHI2 type, and the nontransferability of these plasmids was attributed to the loss of a region carrying partial or complete
tra
genes. Our data revealed that, similar to the situation in
Escherichia coli
,
mcr-1
transmission in
Salmonella
was accelerated by various plasmids, suggesting that transmission of
mcr-1
-carrying plasmids between different species of
Enterobacteriaceae
may be a common event.
A Redox-Responsive Transcription Factor Is Critical for Pathogenesis and Aerobic Growth of Listeria monocytogenes
Authors: Whiteley Aaron T. , Ruhland Brittany R. , Edrozo Mauna B. , Reniere Michelle L. 
Published: February 2017

ABSTRACT

Bacterial pathogens have evolved sophisticated mechanisms to sense and adapt to redox stress in nature and within the host. However, deciphering the redox environment encountered by intracellular pathogens in the mammalian cytosol is challenging, and that environment remains poorly understood. In this study, we assessed the contributions of the two redox-responsive, Spx-family transcriptional regulators to the virulence of
Listeria monocytogenes
, a Gram-positive facultative intracellular pathogen. Spx-family proteins are highly conserved in
Firmicutes
, and the
L. monocytogenes
genome contains two paralogues,
spxA1
and
spxA2
. Here, we demonstrate that
spxA1
, but not
spxA2
, is required for the oxidative stress response and pathogenesis. SpxA1 function appeared to be conserved with the
Bacillus subtilis
homologue, and resistance to oxidative stress required the canonical CXXC redox-sensing motif. Remarkably,
spxA1
was essential for aerobic growth, demonstrating that
L. monocytogenes
SpxA1 likely regulates a distinct set of genes. Although the Δ
spxA1
mutant did not grow in the presence of oxygen in the laboratory, it was able to replicate in macrophages and colonize the spleens, but not the livers, of infected mice. These data suggest that the redox state of bacteria during infection differs significantly from that of bacteria growing
in vitro
. Further, the host cell cytosol may resemble an anaerobic environment, with tissue-specific variations in redox stress and oxygen concentration.
THE ADDED VALUE OF A MULTICOUNTRY NETWORK FOR PROMOTING ETHICAL AND REGULATORY STANDARDS IN CLINICAL TRIALS IN LOW- AND MIDDLE-INCOME COUNTRIES: THE EXPERIENCE OF THE ‘SWITCHING THE POLES NETWORK’
Authors: Ravinetto Raffaella , Tinto Halidou , Diro Ermias , Mahendrahata Yodi , Okebe Joseph , Rijal Suman , Garcia Coralith , Sundar Shyam , Ndayisaba Gilles , Sopheak Thai , Ngoduc Thang , Loen Harry Van , Jacobs Jan , D'Alessandro Umberto , Boelaert Marleen , Buvé Anne 
Published: February 2017

BackgroundIn 2008, we created the ‘Switching The Poles’ Clinical Research Network, by joining the forces of non-commercial clinical research groups in Benin, Burkina Faso, Cambodia, Cuba, the Democratic Republic of Congo, Ethiopia, India, Indonesia, Nepal, Peru, Rwanda, The Gambia and Vietnam. Our aim was to strengthen capacity to conduct non-commercial clinical trials that comply with ethical/regulatory standards.MethodsOur capacity building initiatives were designed to directly benefit the implementation of clinical trials, including various EDCTP-sponsored projects, e.g. 4ABC (7 countries), PREGACT (4), Microbicide Safety Biomarkers (3) and Ring Plus (1). Our training, coaching and networking activities targeted young researchers from the South as well as research professionals who are traditionally ‘neglected’ in trainings, such as data managers and laboratory staff. There were several thematic packages: Good Clinical Practice (GCP), Good Clinical Laboratory Practice, data management (DM), monitoring, and informed consent.ResultsWe developed a theoretical and practice-based GCP training that was adopted by WANETAM Plus in 2013, and a set of standardised DM procedures. Data managers used to working on their own, now benefit from an e-platform (admitnetwork.org) for collaboration and peer advice. We started coaching clinical monitors, for facilitating reciprocal monitoring schemes. We publicly spoke out about ethical issues, e.g. ethical review of externally-sponsored trials, voluntariness in informed consent in vulnerable populations, and provided recommendations to the International Conference of Harmonization in its revision of GCP Guidelines. The inclusion of partners from so many diverse countries and settings resulted in cross-fertilisation and mutual learning. The Networks' small size facilitated interpersonal collaboration.ConclusionsOur experience shows that a relatively small, but focused international network provides an excellent platform for supporting young researchers across different professional disciplines and helps to strengthen capacity for clinical research. This approach has enabled partners in low- and middle-income countries to successfully conduct harmonised GCP-compliant clinical trials.
CYTOLOGICAL PROFILE OF RED BLOOD CELLS IN HIV-INFECTED PATIENTS: CASE OF THE DOUALA GENERAL HOSPITAL (CAMEROON)
Authors: Bidias Amel , Ndjonka Dieudonné , Olemba Clémence , Souleymanou Arabo 
Published: February 2017

BackgroundHaematological abnormalities have been documented as strong independent predictors of morbidity and mortality in HIV-infected individuals. Those infected with HIV without antiretroviral treatment (ART) have a high prevalence of abnormal blood cells. HIV-1 induced dyserythropoiesis in conjunction with the effects of HIV-related inflammation and/or chronic immune activation. The objective of the study is to identify and characterise the different red cell morphological changes that occur during the evolution of HIV infection in patients according to clinical, biological and therapeutic variables.MethodsA total of 232 patients infected by HIV were included in this cross-sectional and descriptive study conducted at the Douala General Hospital (Cameroon) from June to December 2015. All the patients were screened for red blood cells abnormalities. Blood samples were taken in EDTA tubes for full blood counts (FBC) and blood films. chi-square test was used to compare the variables, and the statistical significance level adopted was p-value under 0.05.ResultsThree quarters of patients in our study had abnormal quantitative or qualitative red blood cells, giving a prevalence of 77.5%. The mean value of haemoglobin was 11.9 g/dl with a prevalence of anemia at 61.2% for all participants. The main red blood cells abnormalities were the anisocytosis (43.1%), the anisochromia (34.5%), the macrocytosis (24.1%), the microcytosis (13.8%), the hypochromia (12.9%) and the poikilocytosis (12.5%). These abnormalities are statistically significant and are dependent on the severity of the anaemia the WHO clinical stage, the ART duration and the medication regime with all p< 0.05.ConclusionsThe frequency of cytological abnormalities of red blood cells is high during HIV infection and proportional to the severity of the anemia, the duration of antiretroviral therapy diet and its clinical evolution stage. We recommend that reading blood films is systematic of FBC prescription in the monitoring of HIV-infected patients.