bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated levels of interleukin‐33 are associated with allergic and eosinophilic asthma
Authors: Gasiuniene Edita , Janulaityte Ieva , Zemeckiene Zivile , Barkauskiene Diana , Sitkauskiene Brigita 
Published: October 2018

AbstractIL‐33 is a recently discovered cytokine which plays an important role in asthma pathogenesis.AimTo evaluate serum IL‐33 in patients with asthma and healthy controls, and to evaluate the association of IL‐33 with different asthma phenotypes.MethodsPatients with asthma (n = 115) and healthy subjects (n = 85) were included in the study. Subjects with asthma were divided into groups according to their phenotype: allergic/non‐allergic, eosinophilic/non‐eosinophilic, obese/non‐obese and severity according to GINA (mild, moderate and severe). The concentration of IL‐33 in serum was measured by standardized enzyme‐linked immunosorbent assay.ResultsThe level of IL‐33 was significantly higher in patients with asthma when compared to healthy subjects (672.73 ± 104.47 pg/mL vs 268.52 ± 27.56 pg/mL, P < 0.05). IL‐33 was also higher in the allergic asthma group patients when compared to non‐allergic asthmatics (844.61 ± 152.08 pg/mL vs 369.56 ± 77.94 pg/mL, P < 0.05). There was a significantly higher serum IL‐33 level in the eosinophilic asthma group when compared to the group of non‐eosinophilic asthma patients (1001.10 ± 199.11 pg/mL vs 337.49 ± 72.68 pg/mL, P < 0.01). We did not find a significant difference in serum IL‐33 level between different asthma severity groups, obese and non‐obese asthmatics.ConclusionIL‐33 is increased in asthma patients, particularly in some phenotypes: allergic asthma and eosinophilic asthma.
Effects of capsaicin application on the skin during resting exposure to temperate and warm conditions
Authors: Botonis Petros G. , Miliotis Panagiotis G. , Kounalakis Stylianos N. , Koskolou Maria D. , Geladas Nickos D. 
Published: October 2018

AbstractWe investigated thermoregulatory and cardiovascular responses at rest in a temperate (20°C) and in a warm (30°C) environment (40% RH) without and with the application of capsaicin on the skin. We hypothesized that regardless of environmental temperature, capsaicin application would stimulate heat loss and concomitantly deactivate heat conservation mechanisms, thus resulting in rectal temperature (Tre) and mean blood pressure decline due to excitation of heat‐sensitive TRPV1. Ten male subjects were exposed, while seated, for 30 minutes to 20.8 ± 1.0°C or to 30.6 ± 1.1°C: without (NCA) and with (CA) application of capsaicin patches on the skin. Thermoregulatory (Tre, proximal‐distal skin temperature gradient) and cardiovascular variables (modelflow technique) as well as oxygen uptake were continuously measured. The area under the curve for Tre decline at 20°C was smaller in CA (−2.1 ± 1.3 a.u.) than in NCA (−0.6 ± 1.1 a.u., P < 0.01, r = 0.8). Likewise, at 30°C it was smaller in CA (−2.2 ± 2.1 a.u.) compared to NCA (−0.8 ± 2.0 a.u., P = 0.02, r = 0.7). Local vasomotor tone and oxygen uptake, were significantly lower by 36.7% ± 94.2% and 12.3% ± 12.3%, respectively, with capsaicin compared to NCA (P = 0.05 and P < 0.01, respectively). Additionally, in 30°C CA mean arterial pressure was lower by 10.7% ± 5.9%, 8.9% ± 5.9%, and 10.6% ± 7.0% compared to 30°C NCA, 20°C NCA, and 20°C CA, respectively (P < 0.01, P = 0.02, and P < 0.01, respectively, d = 1.4‐1.8). In conclusion, capsaicin application on the skin induced vasodilation and Tre decline. At 30°C CA, thermal responses were accompanied by arterial hypotension most likely due to the interactive effects of both stressors (warm environment and capsaicin) on cutaneous vascular regulation.
Effect of isavuconazole on tacrolimus and sirolimus serum concentrations in allogeneic hematopoietic stem cell transplant patients: A drug‐drug interaction study
Authors: Kieu Van , Jhangiani Kristi , Dadwal Sanjeet , Nakamura Ryotaro , Pon Doreen 
Published: October 2018

AbstractIntroductionIsavuconazole, a triazole antifungal, is an inhibitor of cytochrome P450 3A4, which also metabolizes tacrolimus and sirolimus. In previous studies, isavuconazole administration increased tacrolimus and sirolimus area under the curve values by 2.3‐fold and 1.8‐fold, respectively, in healthy adults and tacrolimus concentration/dose (C/D) ratio by 1.3‐fold in solid organ transplant patients. We aimed to determine the magnitude of effect of isavuconazole administration on tacrolimus and sirolimus C/D ratios in allogeneic hematopoietic stem cell transplant (alloHSCT) patients.MethodsA retrospective, single‐center, single‐arm study in adult alloHSCT patients who received at least 10 days of combination therapy with isavuconazole and tacrolimus and/or sirolimus as inpatients or outpatients was conducted. Tacrolimus and sirolimus trough serum concentrations were measured up to twice weekly for up to 4 weeks.ResultsTwenty‐two patients receiving tacrolimus and twenty patients receiving sirolimus met the inclusion criteria. The mean C/D ratio increased from baseline by 1.42‐fold for tacrolimus during week 1 (P = 0.002) and up to 1.56‐fold for sirolimus during week 2 (P = 0.02). For the remaining timepoints, tacrolimus and sirolimus C/D ratios were not statistically significantly different from baseline.ConclusionIn alloHSCT patients, modest increases in tacrolimus and sirolimus C/D ratios from baseline were observed within the first 2 weeks after initiation of isavuconazole.
Donor‐derived strongyloidiasis after organ transplantation in Norway
Authors: Nordheim Espen , Olafsson Storrø Monica , Natvik Ane Kristine , Birkeland Kro Grete , Midtvedt Karsten , Varberg Reisæter Anna , Hagness Morten , Fevang Børre , Pettersen Frank O. 
Published: October 2018

AbstractStrongyloides stercoralis is an intestinal helminth which in humans can cause asymptomatic chronic infection maintained for decades through its auto‐infective cycle. During solid organ transplantation, recipients may unintentionally receive an organ infected with strongyloides. This is a very rare complication but may have deadly outcome if not detected. We hereby report two transplant recipients whom developed Strongyloides hyperinfection syndrome after organ transplantation from the same deceased donor. Recipient 1 was kidney transplanted and presented at day 65 post engraftment with diarrhea and subsequent septicemia and gastric retention. Larvae were detected in gastric aspirate. Recipient 2 was simultaneously kidney and pancreas transplanted and presented at day 90 post engraftment also with gastric retention and septicemia. Larvae were demonstrated on duodenal biopsy and stool sample. The clinical course was complicated with severe duodenal bleedings, gastric retention, meningitis, and prolonged hospitalization. Retrospective testing of pre‐transplant donor serum was positive for Strongyloides stercoralis antibodies. As a result of disease severity and gastric retention albenazole was administered via a jejunal tube and ivermectin subcutaneously in both recipients. S stercoralis was successfully eradicated and the transplants ended up with unaffected graft function. Following these two cases, we started systematic screening of all deceased donors for serum Strongyloides IgG in October 2016. After having screened 150 utilized donors one tested positive for Strongyloides, which initiated prophylactic ivermectin treatment to organ recipients. No symptoms or disease developed. Our center will continue to screen all donors as prophylactic treatment may avert this potentially lethal complication in cases of donor‐derived Strongyloides infection.
International validation of harmonized definitions for complications of blood donations
Authors: Land Kevin J. , Townsend Mary , Goldman Mindy , Whitaker Barbee I. , Perez Gabriela E. , Wiersum‐Osselton Jo C. 
Published: October 2018

BACKGROUNDIn December 2014, a multinational collaboration of hemovigilance experts from the International Society of Blood Transfusion (ISBT), the International Hemovigilance Network, and AABB published harmonized definitions of complications related to blood donation titled “Standard for Surveillance of Complications Related to Blood Donation.” Both mandatory and optional terms were included. The definitions are endorsed by the Alliance of Blood Operators and the European Blood Alliance.STUDY DESIGN AND METHODSThe objective of this study was to validate harmonized donor hemovigilance definitions with potential users. In June 2016, 30 real‐world cases were sent to potential users around the world along with the definitions, an answer sheet, and instructions on how to complete the validation exercise.RESULTSOverall, 54 responses from 25 countries were received, including over 400 comments. The results were presented for feedback at both ISBT and AABB meetings. Case diagnoses were consistent across most responders. Exceptions were rare adverse events, nonstandard presentations, or incomplete information. In general, the application of optional definitions, including severity grading and imputability, had the most variability.CONCLUSIONThe use of standardized terms in the donor setting serves to increase focus on donor safety, facilitate conversation, foster exchange of information, and frame questions for future research. Overall, the definitions provide adequate coverage of donor reactions; however, some terms require clarification. Severity grading and imputability and other optional terms need clear and objective definitions and instructions on when and how to use them. Additional feedback and final recommendations are summarized in this report.
Assessment of plasma lactate and core‐peripheral temperature gradient in association with stages of naturally occurring myxomatous mitral valve disease in dogs
Authors: Soares Felipe B. , Pereira‐Neto Gláucia B. , Rabelo Rodrigo C. 
Published: October 2018

AbstractObjectiveTo evaluate plasma lactate concentrations and core‐peripheral temperature gradients as perfusion parameters in dogs with heart failure caused by myxomatous mitral valve disease (MMVD) and to determine whether the above perfusion parameters are correlated with disease stages.DesignProspective observational study.SettingUniversity teaching hospital.AnimalsAfter excluding 129 dogs because of exclusion criteria, 7 dogs with heart failure classified as stage B2 and 10 dogs classified as stage C according to the American Heart Association (AHA)/American College of Cardiology (ACC) were included in the study. Six dogs without MMVD were evaluated as the control group.InterventionsNone.Measurements and Main ResultsAmong the evaluated parameters, the plasma lactate concentrations were increased in stage C (median 3.70 mmol/L [33.3 mg/dL], interquartile range (IQR) 0.72 mmol/L [6.5 mg/dL]) compared with those in the control (median 2.80 mmol/L [25.2 mg/dL], IQR 0.8 mmol/L [7.2 mg/dL];P= 0.024) and stage B2 groups (median 2.70 mmol/L [24.3 mg/dL], IQR 1.8 mmol/L [16.2 mg/dL];P= 0.045). Significant differences were not observed in the core‐peripheral temperature gradients among the control, stage B2, and stage C dogs.ConclusionsDogs with structural heart disease as a result of MMVD may have occult tissue hypoperfusion in stage C that is demonstrated by hyperlactatemia.
Rapid, Transient Fluconazole Resistance in
Candida albicans
Is Associated with Increased mRNA Levels of
CDR
Authors: Marr Kieren A. , Lyons Christopher N. , Rustad Tiger , Bowden Raleigh A. , White Theodore C. 
Published: October 2018

ABSTRACT

Fluconazole-resistant
Candida albicans
, a cause of recurrent oropharyngeal candidiasis in patients with human immunodeficiency virus infection, has recently emerged as a cause of candidiasis in patients receiving cancer chemotherapy and marrow transplantation (MT). In this study, we performed detailed molecular analyses of a series of
C. albicans
isolates from an MT patient who developed disseminated candidiasis caused by an azole-resistant strain 2 weeks after initiation of fluconazole prophylaxis (K. A. Marr, T. C. White, J. A. H. vanBurik, and R. A. Bowden, Clin. Infect. Dis. 25:908–910, 1997). DNA sequence analysis of the gene (
ERG11
) for the azole target enzyme, lanosterol demethylase, revealed no difference between sensitive and resistant isolates. A sterol biosynthesis assay revealed no difference in sterol intermediates between the sensitive and resistant isolates. Northern blotting, performed to quantify mRNA levels of genes encoding enzymes in the ergosterol biosynthesis pathway (
ERG7
,
ERG9
, and
ERG11
) and genes encoding efflux pumps (
MDR1
,
ABC1
,
YCF
, and
CDR
), revealed that azole resistance in this series is associated with increased mRNA levels for members of the ATP binding cassette (ABC) transporter superfamily,
CDR
genes. Serial growth of resistant isolates in azole-free media resulted in an increased susceptibility to azole drugs and corresponding decreased mRNA levels for the
CDR
genes. These results suggest that
C. albicans
can become transiently resistant to azole drugs rapidly after exposure to fluconazole, in association with increased expression of ABC transporter efflux pumps.
Evaluation of Antimicrobial and Lipopolysaccharide-Neutralizing Effects of a Synthetic CAP18 Fragment againstPseudomonas aeruginosain a Mouse Model
Authors: Sawa Teiji , Kurahashi Kiyoyasu , Ohara Maria , Gropper Michael A. , Doshi Vatsal , Larrick James W. , Wiener-Kronish Jeanine P. 
Published: October 2018

ABSTRACTCAP18 (cationic antimicrobial protein; 18 kDa) is a neutrophil-derived protein that can bind to and inhibit various activities of lipopolysaccharide (LPS). The 37 C-terminal amino acids of CAP18 make up the LPS-binding domain. A truncated 32-amino-acid C-terminal fragment of CAP18 had potent activity againstPseudomonas aeruginosain vitro. We studied the antimicrobial and LPS-neutralizing effects of this synthetic truncated CAP18 peptide (CAP18106–137) on lung injury in mice infected with cytotoxicP. aeruginosa. To determine its maximal effect, the CAP18106–137peptide was mixed with bacteria just prior to tracheal instillation, and lung injury was evaluated by determining the amount of leakage of an alveolar protein tracer (125I-albumin) into the circulation and by the quantification of lung edema. The lung injury caused by the instillation of 5 × 105CFU ofP. aeruginosawas significantly reduced by the concomitant instillation of CAP18106–137. However, the administration of CAP18106–137alone, without bacteria, induced lung edema, suggesting that it has some toxicity. Also, the peptide did not significantly reduce the number of bacteria that had been simultaneously instilled, nor did it significantly improve the survival of the infected mice. The addition of CAP18106–137to aztreonam along with the bacteria did decrease the level of antibiotic-induced release of inflammatory mediators including tumor necrosis factor alpha, interleukin-6, and nitric oxide and also improved the survival of the mice. Therefore, more investigations are needed to confirm the toxicities and the therapeutic benefits of CAP18106–137as an adjunctive therapy to antibiotics in the treatment of infections caused by gram-negative bacteria.
In Vitro Activity of Lumefantrine (Benflumetol) against Clinical Isolates of
Plasmodium falciparum
in Yaoundé, Cameroon
Authors: Basco Leonardo K. , Bickii Jean , Ringwald Pascal 
Published: October 2018

ABSTRACT

The in vitro antimalarial activity of the new Chinese synthetic drug, lumefantrine, also known as benflumetol (a fluorene derivative belonging to the aminoalcohol class), was determined by an isotopic microtest against 61 fresh clinical isolates of
Plasmodium falciparum
and compared with that of other established antimalarial agents. The geometric mean 50% inhibitory concentration of lumefantrine was 11.9 nmol/liter (95% confidence intervals, 10.4 to 13.6 nmol/liter; range, 3.3 to 25.6 nmol/liter). The in vitro activities of lumefantrine against the chloroquine-sensitive and the chloroquine-resistant isolates did not differ (
P
> 0.05). There was a significant positive correlation of responses between lumefantrine and two other aminoalcohols studied, mefloquine (
r
= 0.688) and halofantrine (
r
= 0.677), and between lumefantrine and artesunate (
r
= 0.420), suggesting a potential for in vitro cross-resistance. Our data suggest high in vitro activity of lumefantrine, comparable to that of mefloquine, and are in agreement with the promising results of preliminary clinical trials.
Chemoprophylaxis of Influenza A Virus Infections, with Single Doses of Zanamivir, Demonstrates that Zanamivir Is Cleared Slowly from the Respiratory Tract
Authors: Fenton Robert J. , Morley Peter J. , Owens Ian J. , Gower David , Parry Simon , Crossman Lee , Wong Tony 
Published: October 2018

ABSTRACT

Zanamivir (4-guanidino-2,4-dideoxy-2,3-dehydro-
N
-acetylneuraminic acid; Relenza; GG167) is a potent and highly specific neuraminidase (sialidase) inhibitor with inhibitory activity in vivo against both influenza A and B viruses. This compound has been extensively tested in both mouse and ferret models of influenza and has recently been approved for the treatment of influenza in Europe and Australasia. The compound markedly reduces the clinical course of disease in humans when given therapeutically by inhalation directly into the respiratory tract. In addition, experimental influenza infections in phase I clinical trials have shown the benefit of giving a single prophylactic dose of zanamivir in addition to a therapeutic regime. The studies reported here were designed to determine the persistence of zanamivir, as assessed by its antiviral activity in vivo, in the respiratory tracts of infected animals. We have shown that the prophylactic administration of zanamivir, when the drug is given in a single dose by the intranasal route, can significantly reduce lung virus titers in the mouse and can reduce both viral titers and symptoms in the ferret. Whole-body autoradiographical analyses of mice have indicated a long retention time for this compound in respiratory tract tissues when it is given in a single dose by the intranasal route. These results indicate that zanamivir may have clinical value as a prophylactic agent in protecting at-risk groups from influenza virus infection. In addition, these data may be useful in the design of prophylactic protocols for humans, in that the dosing schedule may only need to be intermittent to provide protection.
Safety and Single-Dose Pharmacokinetics of Abacavir (1592U89) in Human Immunodeficiency Virus Type 1-Infected Children
Authors: Hughes Walter , McDowell James A. , Shenep Jerry , Flynn Patricia , Kline Mark W. , Yogev Ram , Symonds William , Lou Yu , Hetherington Seth 
Published: October 2018

ABSTRACT

Abacavir (formerly 1592U89) is a potent 2′-deoxyguanosine analog reverse transcriptase inhibitor that has been demonstrated to have a favorable safety profile in initial clinical trials with adults with human immunodeficiency virus (HIV) type 1 infection. A phase I study was conducted to evaluate the pharmacokinetics and safety of abacavir following the administration of two single oral doses (4 and 8 mg/kg of body weight) to 22 HIV-infected children ages 3 months to 13 years. Plasma was collected for analysis at predose and at 0.5, 1, 1.5, 2, 2.5, 3, 5, and 8 h after the administration of each dose. Plasma abacavir concentrations were determined by high-performance liquid chromatography, and data were analyzed by noncompartmental methods. Abacavir was well tolerated by all subjects. The single abacavir-related adverse event was rash, which occurred in 2 of 22 subjects. After administration of the oral solution, abacavir was rapidly absorbed, with the time to the peak concentration in plasma occurring within 1.5 h postdosing. Pharmacokinetic parameter estimates were comparable among the different age groups for each dose level. The mean maximum concentration in plasma (
C
max
) and the mean area under the curve from time zero to infinity (AUC
0–∞
) increased by 16 and 45% more than predicted, respectively, as the abacavir dose was doubled from 4 to 8 mg/kg (
C
max
increased from 1.69 to 3.94 μg/ml, and AUC
0–∞
increased from 2.82 to 8.09 μg · h/ml). Abacavir was rapidly eliminated, with a mean elimination half-life of 0.98 to 1.13 h. The mean apparent clearance from plasma decreased from 27.35 to 18.88 ml/min/kg as the dose increased. Neither body surface area nor creatinine clearance were correlated with pharmacokinetic estimates at either dose. The extent of exposure to abacavir appears to be slightly lower in children than in adults, with the comparable unit doses being based on body weight. In conclusion, this study showed that abacavir is safe and well tolerated in children when it is administered as a single oral dose of 4 or 8 mg/kg.
Effects of the Hematoregulatory Peptide SK&F 107647 Alone and in Combination with Amphotericin B against Disseminated Candidiasis in Persistently Neutropenic Rabbits
Authors: Lyman Caron A. , Gonzalez Corina , Schneider Mark , Lee James , Walsh Thomas J. 
Published: October 2018

ABSTRACT

The effects of the hematoregulatory peptide SK&F 107647 were examined in a persistently and profoundly neutropenic rabbit model of disseminated candidiasis in order to determine its potential to enhance resistance against infection and its role as an adjunct to conventional antifungal chemotherapy. In healthy animals, SK&F 107647 elicited a time-dependent increase in CD11b-positive monocytes and neutrophils. When administered to neutropenic rabbits infected with
Candida albicans
, no significant differences in the number of CFU per gram in any of the tissues tested compared with the number in untreated control rabbits were detected. However, when SK&F 107647 was administered in combination with low doses of amphotericin B, there was a significant reduction in organism burden in the lungs, liver, spleen, and kidneys compared with the burdens in the organs of untreated control animals and in the lungs and kidneys compared with the burdens in the lungs and kidneys of animals treated with amphotericin B alone. These data suggest a potential role for this peptide as adjunctive therapy in combination with conventional antifungal agents in the treatment of disseminated candidiasis in the setting of profound and persistent neutropenia.
Prediction of school outcome after preterm birth: a cohort study
Authors: Odd David , Evans David , Emond Alan M 
Published: October 2018

Objective
To identify if the educational trajectories of preterm infants differ from those of their term peers.

Design
This work is based on the Avon Longitudinal Study of Parents and Children (ALSPAC). Educational measures were categorised into 10 deciles to allow comparison of measures across time periods. Gestational age was categorised as preterm (23–36 weeks) or term (37–42 weeks). Multilevel mixed-effects linear regression models were derived to examine the trajectories of decile scores across the study period. Gestational group was added as an interaction term to assess if the trajectory between educational measures varied between preterm and term infants. Adjustment for possible confounders was performed.

Subjects
The final dataset contained information on 12 586 infants born alive at between 23 weeks and 42 weeks of gestation.

Main outcome measures
UK mandatory educational assessments (SATs) scores throughout educational journal (including final GCSE results at 16 years of age).

Results
Preterm infants had on average lower Key Stage (KS) scores than term children (−0.46 (−0.84 to −0.07)). However, on average, they gained on their term peers in each progressive measure (0.10 (0.01 to 0.19)), suggesting ‘catch up’ during the first few years at school. Preterm infants appeared to exhibit the increase in decile scores mostly between KS1 and KS2 (p=0.005) and little between KS2 and KS3 (p=0.182) or KS3 and KS4 (p=0.149).

Conclusions
This work further emphasises the importance of early schooling and environment in these infants and suggests that support, long after the premature birth, may have additional benefits.