bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain abscesses caused by Cladophialophora bantiana in a lung transplant patient: A case report and review of the literature
Authors: Gschwend Anthony , Dégot Tristan , Denis Julie , Sabou Alina M. , Jeung Mi Young , Zapata Emilie , Porzio Michele , Renaud‐Picard Benjamin , Herbrecht Raoul , Kessler Romain 
Published: October 2017

AbstractCladophialophora bantiana brain abscesses are rare, but are frequently and quickly lethal in transplanted patients. We report the case of a 63‐year‐old man who had undergone lung transplantation for chronic obstructive pulmonary disease and presented with headaches and a neurological deficit. Magnetic resonance imaging revealed multiple brain abscesses. C. bantiana was identified by DNA sequencing performed directly on cerebral tissue obtained by surgical biopsy. After 6 months of antifungal treatment, the brain abscesses were replaced by ischemic sequelae. The patient died suddenly 2 months later from a pulmonary bacterial infection. This is the second reported case of C. bantiana brain abscesses in a lung transplant recipient, to our knowledge, who experienced a long survival period with medical antifungal treatment alone. We review the literature and discuss our treatment.
Subcutaneous phaeohyphomycosis in kidney transplant recipients: A series of seven cases
Authors: Haridasan Satish , Parameswaran Sreejith , Bheemanathi Srinivas Hanuman , Chandrasekhar Laxmisha , Suseela Bibilash Babu , Singh Rakesh , Rabindranath Jayasurya , Padhi Rajesh Kumar , Sampath Ezhilnilavan , Dubey Avinash Kumar , Puthenpurackal Priyamvada Sivan Pillai 
Published: October 2017

AbstractBackgroundSuperficial and deep fungal infections are more frequent in transplant recipients primarily because of the failure of cell‐mediated immunity and lesser amount of antigen‐presenting Langerhans cells in their epidermis. Here, we report seven cases of post‐renal transplant subcutaneous phaeohyphomycosis, all of which manifested within 1 year after transplantation and were unresponsive to prolonged courses of itraconazole. This is the first case series, to our knowledge, of phaeohyphomycosis in transplant recipients in India.MethodWe performed a retrospective review of cases of phaeohyphomycosis among kidney transplant recipients for type of transplant, immunosuppression, histopathology, and treatment, with prospective follow‐up of healed lesion.ResultsAn overall incidence of 8.3% was noted, with a median duration of approximately 6 months post transplant to the onset of skin lesion. None of the lesions responded to itraconazole alone and 6/7 lesions were surgically excised. Histopathology showed various lesions and culture could isolate Neocytalidium and Exophiala jeanselmi in two cases.ConclusionDematiaceous fungi are increasingly implicated in cutaneous lesions in transplant recipients. Histopathology and surgical excision are the appropriate tools for diagnosis and treatment, respectively.
Rare and unusual presentation of Cladophialophora infection in a pulmonary transplant cystic fibrosis patient
Authors: Reynaud Quitterie , Dupont Damien , Nove‐Josserand Raphaële , Durupt Stephane , Persat Florence , Ader Florence , Grenet Dominique , Durieu Isabelle 
Published: October 2017

AbstractA 35‐year‐old woman with severe cystic fibrosis was admitted for sudden loss of strength in both legs, revealing a myelitis. The medullary lesion biopsy revealed phaeohyphomycosis caused by Cladophialophora species. Myelitis caused by Cladophialophora bantiana is a rare disease associated with high mortality.
The economic impact of the Trans‐Pacific Partnership: What have we learned from CGE simulation?
Authors: Gilbert John , Furusawa Taiji , Scollay Robert 
Published: October 2017

AbstractThe Trans‐Pacific Partnership (TPP) trade agreement, if were it to be successfully implemented, would be one of the largest regional agreements ever seen. It is the only exemplar to date of a “mega‐regional” FTA for which negotiations have been successfully concluded, and a landmark in evolving approaches to Asia–Pacific integration. As such, quantitative assessments of its potential effects are of considerable interest. One of the most widely used techniques for evaluating the economic impact of regional trading agreements is numerical simulation with computable general equilibrium, or CGE, models. There have now been a large number of papers written that use CGE methods to analyse the potential economic impact of the TPP agreement under varying theoretical and policy assumptions. In this paper we provide a synthesis of the key results that have emerged from the literature, and introduce some new simulation results of our own to anchor the discussion.
Empirical evaluation of river basin sustainability affected by inter‐basin water transfer using composite indicators
Authors: Kefayati Maryam , Saghafian Bahram , Ahmadi Azadeh , Babazadeh Hossein 
Published: October 2017

AbstractIn this study, a practical approach to evaluate the sustainability of river basins subjected to an inter‐basin water transfer project is developed. Selection of appropriate evaluation indicators is pivotal to such approach. To make use of huge amount of data, composite indicators of sustainability (CIS) should be utilised. The proposed approach relies on 15 sustainability indicators (SI) that cover three major criteria namely (economic, social and environmental), and aggregates them into eight different types of sustainability indices for a more robust outcome. Two scenarios were considered within the source and recipient basins. Furthermore, multivariate principal component analysis (PCA) was applied to determine principal and non‐principal indicators for the two river basins. The ability of CIS and PCA methods were verified via correlation and simple regression methods respectively. The results demonstrated that inter‐basin water transfer may improve sustainability, provided that a proper water resource management is enforced.
Plasma membrane Ca2+‐ATPase 1 is required for maintaining atrial Ca2+ homeostasis and electrophysiological stability in the mouse
Authors: Wang Yanwen , Wilson Claire , Cartwright Elizabeth J. , Lei Ming 
Published: October 2017

Key points
The role of plasma membrane Ca2+‐ATPase 1 (PMCA1) in Ca2+ homeostasis and electrical stability in atrial tissue has been investigated at both organ and cellular levels in mice with cardiomyocyte‐specific deletion of PMCA1 (PMCA1cko)
The PMCA1cko hearts became more susceptible to atrial arrhythmic stress conditions than PMCA1loxP/loxP hearts.
PMCA1 deficiency alters cellular Ca2+ homeostasis under both baseline and stress conditions.
PMCA1 is required for maintaining cellular Ca2+ homeostasis and electrical stability in murine atria under stress conditions.
AbstractTo determine the role of plasma membrane Ca2+‐ATPase 1 (PMCA1) in maintaining Ca2+ homeostasis and electrical stability in the atrium under physiological and stress conditions, mice with a cardiomyocyte‐specific deletion of PMCA1 (PMCA1cko) and their control littermates (PMCA1loxP/loxP) were studied at the organ and cellular levels. At the organ level, the PMCA1cko hearts became more susceptible to atrial arrhythmias under rapid programmed electrical stimulation compared with the PMCA1loxP/loxP hearts, and such arrhythmic events became more severe under Ca2+ overload conditions. At the cellular level, the occurrence of irregular‐type action potentials of PMCA1cko atrial myocytes increased significantly under Ca2+ overload conditions and/or at higher frequency of stimulation. The decay of Na+/Ca2+ exchanger current that followed a stimulation protocol was significantly prolonged in PMCA1cko atrial myocytes under basal conditions, with Ca2+ overload leading to even greater prolongation. In conclusion, PMCA1 is required for maintaining Ca2+ homeostasis and electrical stability in the atrium. This is particularly critical during fast removal of Ca2+ from the cytosol, which is required under stress conditions.
A Dynamic Stress Model Explains the Delayed Drug Effect in Artemisinin Treatment of Plasmodium falciparum
Authors: Cao Pengxing , Klonis Nectarios , Zaloumis Sophie , Dogovski Con , Xie Stanley C. , Saralamba Sompob , White Lisa J. , Fowkes Freya J. I. , Tilley Leann , Simpson Julie A. , McCaw James M. 
Published: October 2017

ABSTRACT

Artemisinin resistance constitutes a major threat to the continued success of control programs for malaria, particularly in light of developing resistance to partner drugs. Improving our understanding of how artemisinin-based drugs act and how resistance manifests is essential for the optimization of dosing regimens and the development of strategies to prolong the life span of current first-line treatment options. Recent short-drug-pulse
in vitro
experiments have shown that the parasite killing rate depends not only on drug concentration but also the exposure time, challenging the standard pharmacokinetic-pharmacodynamic (PK-PD) paradigm in which the killing rate depends only on drug concentration. Here, we introduce a dynamic stress model of parasite killing and show through application to 3D7 laboratory strain viability data that the inclusion of a time-dependent parasite stress response dramatically improves the model's explanatory power compared to that of a traditional PK-PD model. Our model demonstrates that the previously reported hypersensitivity of early-ring-stage parasites of the 3D7 strain to dihydroartemisinin compared to other parasite stages is due primarily to a faster development of stress rather than a higher maximum achievable killing rate. We also perform
in vivo
simulations using the dynamic stress model and demonstrate that the complex temporal features of artemisinin action observed
in vitro
have a significant impact on predictions for
in vivo
parasite clearance. Given the important role that PK-PD models play in the design of clinical trials for the evaluation of alternative drug dosing regimens, our novel model will contribute to the further development and improvement of antimalarial therapies.
Choosing Optimal Antifungal Agents To Prevent Fungal Infections in Nonneutropenic Critically Ill Patients: Trial Sequential Analysis, Network Meta-analysis, and Pharmacoeconomic Analysis
Authors: Wang Yan , Xie Jiao , Xing Yuanming , Chen Lu , Li Ying , Meng Ti , Dong Weihua , Wang Xue , Dong Yalin 
Published: October 2017

ABSTRACT
The use of antifungal interventions in critically ill patients prior to invasive fungal infection (IFI) being microbiologically confirmed and the preferred drug are still controversial. A systematic literature search was performed to identify randomized controlled trials (RCTs) that compared untargeted antifungal treatments applied to nonneutropenic critically ill patients. The primary outcomes were all-cause mortality and proven IFI rates. A random-effects model was used with trial sequential analyses (TSA), a network meta-analysis (NMA) was conducted to obtain indirect evidence, and a cost-effectiveness analysis using a decision-analytic model was completed from the patient perspective over a lifetime horizon. In total, 19 RCTs involving 2,556 patients (7 interventions) were included. Untargeted antifungal treatment did not significantly decrease the incidence of all-cause mortality (odds ratio [OR] = 0.89, 95% confidence interval [95%CI] = 0.70 to 1.14), but it did reduce the incidence of proven IFI (OR = 0.45, 95%CI = 0.29 to 0.71) relative to placebo/no intervention. The TSA showed that there was sufficient evidence supporting these findings. In the NMA, the only significant difference found for both primary outcomes was between fluconazole and placebo/no intervention in preventing proven IFI (OR = 0.35, 95%CI = 0.19 to 0.65). Based on drug and hospital costs in China, the incremental cost-effectiveness ratios per life-year saved for fluconazole, caspofungin, and micafungin relative to placebo/no intervention corresponded to US$889, US$9,994, and US$10,351, respectively. Untargeted antifungal treatment significantly reduced proven IFI rates in nonneutropenic critically ill patients but with no mortality benefits relative to placebo/no intervention. Among the well-tolerated antifungals, fluconazole remains the only one that is effective for IFI prevention and significantly cheaper than echinocandins.
Emergence of Various NDM-Type-Metallo-β-Lactamase-Producing Escherichia coli Clinical Isolates in Nepal
Authors: Shrestha Basudha , Tada Tatsuya , Shimada Kayo , Shrestha Shovita , Ohara Hiroshi , Pokhrel Bharat Mani , Sherchand Jeevan B. , Kirikae Teruo 
Published: October 2017

ABSTRACT

Of 250 clinical isolates of
Escherichia coli
obtained in Nepal, 38 were carbapenem resistant, with MICs of imipenem or meropenem of ≥4 μg/ml. All 38 isolates harbored the following
bla
NDM
s:
bla
NDM-1
,
bla
NDM-3
,
bla
NDM-4
,
bla
NDM-5
,
bla
NDM-7
,
bla
NDM-12
, and
bla
NDM-13
. Most of these isolates also harbored the 16S rRNA methylase gene(s)
armA
,
rmtB
, and/or
rmtC
.
The Alternative Sigma Factors SigE and SigB Are Involved in Tolerance and Persistence to Antitubercular Drugs
Authors: Pisu Davide , Provvedi Roberta , Espinosa Dulce Mata , Payan Jorge Barrios , Boldrin Francesca , Palù Giorgio , Hernandez-Pando Rogelio , Manganelli Riccardo 
Published: October 2017

ABSTRACT

The emergence and spread of drug-resistant
Mycobacterium tuberculosis
strains possibly threaten our ability to treat this disease in the future. Even though two new antitubercular drugs have recently been introduced, there is still the need to design new molecules whose mechanisms of action could reduce the length of treatment. We show that two alternative sigma factors of
M. tuberculosis
(SigE and SigB) have a major role in determining the level of basal resistance to several drugs and the amount of persisters surviving long-duration drug treatment. We also demonstrate that ethambutol, a bacteriostatic drug, is highly bactericidal for
M. tuberculosis
mutants missing either SigE or SigB. We suggest that molecules able to interfere with the activity of SigE or SigB not only could reduce
M. tuberculosis
virulence
in vivo
but also could boost the effect of other drugs by increasing the sensitivity of the organism and reducing the number of persisters able to escape killing.
Activity of Ceftolozane-Tazobactam and Ceftazidime-Avibactam against Beta-Lactam-Resistant Pseudomonas aeruginosa Isolates
Authors: Humphries Romney M. , Hindler Janet A. , Wong-Beringer Annie , Miller Shelley A. 
Published: October 2017

ABSTRACT

Ceftolozane-tazobactam (C/T) and ceftazidime-avibactam (CZA) MICs were evaluated for a collection of 309 beta-lactam-resistant isolates of
Pseudomonas aeruginosa
recovered from three institutions in the area of Los Angeles, CA. Overall, 12.0% of isolates were susceptible to imipenem, 15.9% were susceptible to meropenem, 20.7% were susceptible to piperacillin-tazobactam, 24.6% were susceptible to ceftazidime, 25.9% were susceptible to cefepime, 72.5% were susceptible to C/T, and 61.8% were susceptible to CZA. Among C/T-resistant isolates, 9.1% were CZA susceptible, whereas 36.4% of CZA-resistant isolates were susceptible to C/T.
Acquired Protective Immunity in Atlantic Salmon Salmo salar against the Myxozoan Kudoa thyrsites Involves Induction of MHIIβ
+
CD83
+
Antigen-Presenting Cells
Authors: Braden Laura M. , Rasmussen Karina J. , Purcell Sara L. , Ellis Lauren , Mahony Amelia , Cho Steven , Whyte Shona K. , Jones Simon R. M. , Fast Mark D. 
Published: October 2017

ABSTRACT

The histozoic myxozoan parasite
Kudoa thyrsites
causes postmortem myoliquefaction and is responsible for economic losses to salmon aquaculture in the Pacific Northwest. Despite its importance, little is known about the host-parasite relationship, including the host response to infection. The present work sought to characterize the immune response in Atlantic salmon during infection, recovery, and reexposure to
K. thyrsites
. After exposure to infective seawater, infected and uninfected smolts were sampled three times over 4,275 degree-days. Histological analysis revealed infection severity decreased over time in exposed fish, while in controls there was no evidence of infection. Following a secondary exposure of all fish, severity of infection in the controls was similar to that measured in exposed fish at the first sampling time but was significantly reduced in reexposed fish, suggesting the acquisition of protective immunity. Using immunohistochemistry, we detected a population of MHIIβ
+
cells in infected muscle that followed a pattern of abundance concordant with parasite prevalence. Infiltration of these cells into infected myocytes preceded destruction of the plasmodium and dissemination of myxospores. Dual labeling indicated a majority of these cells were CD83
+
/MHIIβ
+
. Using reverse transcription-quantitative PCR, we detected significant induction of cellular effectors, including macrophage/dendritic cells (
mhii
/
cd83
/
mcsf
), B cells (
igm
/
igt
), and cytotoxic T cells (
cd8
/
nkl
), in the musculature of infected fish. These data support a role for cellular effectors such as antigen-presenting cells (monocyte/macrophage and dendritic cells) along with B and T cells in the acquired protective immune response of Atlantic salmon against
K. thyrsites
.
The Electron Transport Chain Sensitizes Staphylococcus aureus and Enterococcus faecalis to the Oxidative Burst
Authors: Painter Kimberley L. , Hall Alex , Ha Kam Pou , Edwards Andrew M. 
Published: October 2017

ABSTRACT

Small-colony variants (SCVs) of
Staphylococcus aureus
typically lack a functional electron transport chain and cannot produce virulence factors such as leukocidins, hemolysins, or the antioxidant staphyloxanthin. Despite this, SCVs are associated with persistent infections of the bloodstream, bones, and prosthetic devices. The survival of SCVs in the host has been ascribed to intracellular residency, biofilm formation, and resistance to antibiotics. However, the ability of SCVs to resist host defenses is largely uncharacterized. To address this, we measured the survival of wild-type and SCV
S. aureus
in whole human blood, which contains high numbers of neutrophils, the key defense against staphylococcal infection. Despite the loss of leukocidin production and staphyloxanthin biosynthesis, SCVs defective for heme or menaquinone biosynthesis were significantly more resistant to the oxidative burst than wild-type bacteria in human blood or the presence of purified neutrophils. Supplementation of the culture medium of the heme-auxotrophic SCV with heme, but not iron, restored growth, hemolysin and staphyloxanthin production, and sensitivity to the oxidative burst. Since
Enterococcus faecalis
is a natural heme auxotroph and cause of bloodstream infection, we explored whether restoration of the electron transport chain in this organism also affected survival in blood. Incubation of
E. faecalis
with heme increased growth and restored catalase activity but resulted in decreased survival in human blood via increased sensitivity to the oxidative burst. Therefore, the lack of functional electron transport chains in SCV
S. aureus
and wild-type
E. faecalis
results in reduced growth rate but provides resistance to a key immune defense mechanism.
Risk of rehospitalisation and death for vulnerable New Zealand children
Authors: Oliver Jane , Foster Tim , Kvalsvig Amanda , Williamson Deborah A , Baker Michael G , Pierse Nevil 
Published: October 2017

ObjectivesThere is considerable need to improve the effectiveness of healthcare to reduce morbidity and mortality. Child hospitalisations are influenced by determinants of health, including the home environment. Our aims were: (1) To investigate whether children hospitalised with potentially avoidable conditions thought to be associated with the home have an increased risk of rehospitalisation and death, (2) To investigate whether children hospitalised with particular subgroups of potentially avoidable conditions have an increased risk of rehospitalisation and death, (3) To assess the usefulness of these subgroups for identifying at-risk children.DesignWe used four existing groups of potentially avoidable conditions developed based on expert opinion: 1. the potentially avoidable hospitalisations (PAH) group, associated with social/environmental conditions, 2. the potentially avoidable hospitalisations attributable (at least in part) to the home environment (PAHHE) group, 3. the crowding group, and 4. the Ministry of Health (MoH) group. We analysed national New Zealand hospital discharge data (2000–2014). Rehospitalisation and death were described using Kaplan-Meier curves. Group effectiveness for identifying at-risk children was assessed using Cox proportional hazard models with children hospitalised for non-PAH conditions as comparison.ResultsIn total, 1425085 hospital admissions occurred, for 683115 unique children. Rehospitalisation was relatively common (71.0%). Death was rare (0.6%). All groups performed moderately well identifying at-risk children. Children with PAH have increased risk of rehospitalisation (adjusted HR (aHR):2.30–3.60) and death (aHR:3.07–10.44). PAH group had highest sensitivity (75.1%). The MoH group has the highest positive predictive value (rehospitalisation: 86.2%, death: 2.5%).ConclusionsChildren in the MoH group are very likely to benefit from housing interventions. Rehospitalisation and early mortality are useful assessment measures. Rehospitalisation exerts a considerable burden, and child deaths are catastrophic.
Observational study on the palatability and tolerability of oral prednisolone and oral dexamethasone in children in Saudi Arabia and the UK
Authors: Aljebab Fahad , Alanazi Mofadhi , Choonara Imti , Conroy Sharon 
Published: October 2017

BackgroundShort-course oral corticosteroids are routinely used to treat acute asthma and croup. We evaluated their tolerability and palatability in Saudi Arabian (SA) and UK children.MethodsProspective observational/interview study (3 months in each country). Palatability was evaluated using a 5-point facial Hedonicscale and tolerability by direct questioning of patient/parents.ResultsIn SA, of 122 patients (2–10 years) recruited, 52 received prednisolone base tablets, 37 prednisolone sodium phosphate syrup and 33 received dexamethasone elixir. In the UK, of 133 patients (2–16 years), 38 received prednisolone base tablets (mainly crushed and dispersed), 42 prednisolone sodium phosphate soluble tablets and 53 received dexamethasone sodium phosphate oral solution.In both countries, dexamethasone had the highest palatability scores (SA mean: 1.97; UK mean: 3) and prednisolone base tablets had the lowest (SA mean: 1.12; UK mean: 1.39). Palatability scores improved for all formulations of prednisolone with each subsequent daily dose.In SA, prednisolone base tablets were associated with more nausea (24vs7 patients) and vomiting (5vs0 patients) than sodium phosphate syrup (p=0.008 and p=0.073, respectively). In the UK, vomiting occurred more frequently with prednisolone base (8 patients) than sodium phosphate soluble tablets (2 patients) (p=0.041).In both centres, dexamethasone was associated with less side effects. Vomiting (1vs0 patients), nausea (7vs3 patients) and abdominal pain (10vs8 patients) occurred more with dexamethasone sodium phosphate solution than dexamethasone elixir.ConclusionsDexamethasone sodium phosphate solution was the most palatable preparation. Prednisolone base tablets were rated least palatable and were least well tolerated. Palatability scores improved with each dose taken.