bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aging impacts CD103+CD8+ T cell presence and induction by dendritic cells in the genital tract
Authors: Rodriguez‐Garcia Marta , Fortier Jared M. , Barr Fiona D. , Wira Charles R. 
Published: February 2018

SummaryAs women age, susceptibility to systemic and genital infections increases. Tissue‐resident memory T cells (TRMs) are CD103+CD8+ long‐lived lymphocytes that provide critical mucosal immune protection. Mucosal dendritic cells (DCs) are known to induce CD103 expression on CD8+ T cells. While CD103+CD8+ T cells are found throughout the female reproductive tract (FRT), the extent to which aging impacts their presence and induction by DCs remains unknown. Using hysterectomy tissues, we found that endometrial CD103+CD8+ T cells were increased in postmenopausal compared to premenopausal women. Endometrial DCs from postmenopausal women were significantly more effective at inducing CD103 expression on allogeneic naïve CD8+ T cells than DCs from premenopausal women; CD103 upregulation was mediated through membrane‐bound TGFβ signaling. In contrast, cervical CD103+ T cells and DC numbers declined in postmenopausal women with age. Decreases in DCs correlated with decreased CD103+ T cells in endocervix, but not ectocervix. Our findings demonstrate a previously unrecognized compartmentalization of TRMs in the FRT of postmenopausal women, with loss of TRMs and DCs in the cervix with aging, and increased TRMs and DC induction capacity in the endometrium. These findings are relevant to understanding immune protection in the FRT and to the design of vaccines for women of all ages.
Accuracy of point‐of‐care HbA1c testing in pregnant women
Authors: Culliney Katherine , McCowan Lesley M.E. , Okesene‐Gafa Karaponi , Murphy Rinki , Rowan Janet , Taylor Rennae S. , Mckinlay Christopher J.D. ,   the HUMBA Study Group
Published: February 2018

BackgroundIn New Zealand, it is recommended that all pregnant women have a haemoglobin A1c (HbA1c) test performed with their booking antenatal bloods to identify previously unrecognised diabetes. However, screening rates in some groups are low. Use of a point‐of‐care device may improve compliance with screening.AimTo assess the accuracy of the COBAS b101 point‐of‐care system referenced against a laboratory method, for measurement of HbA1c levels in pregnant women.Materials and methodsConvenience sample of 40 obese pregnant women enrolled in a clinical trial. HbA1c was assayed in paired capillary and venous whole blood samples using the COBAS b101 point‐of‐care system and Primus Ultra2 high performance liquid chromatography laboratory analyser, respectively. The accuracy of the point‐of‐care system was assessed by Bland–Altman analysis.ResultsThe mean (SD) laboratory HbA1c was 35.9 (2.0) mmol/mol. The COBAS b101 point‐of‐care system, compared with the laboratory reference method, had a small negative bias for HbA1c (−1.0 mmol/mol, 95% CI −2.0 to −0.03, P = 0.03) and relatively wide 95% limits of agreement (−7.2 to 5.1 mmol/mol).ConclusionIn conclusion, we found that in pregnancy, the COBAS b101 point‐of‐care system has a small negative bias and modest point accuracy for HbA1c. When used to screen for previously unrecognised diabetes in pregnancy, appropriate COBAS b101 HbA1c point‐of‐care HbA1c thresholds for a negative and positive result are 7 mmol/mol below and 5 mmol/mol above the clinical threshold, respectively. Values between these limits should be confirmed by laboratory testing.
One‐year longitudinal study found a bidirectional relationship between physical activity and sleep disturbance in teenage Estonian girls
Authors: Raudsepp L 
Published: February 2018

AbstractAimStudies have shown that physical activity (PA) declines during adolescence, especially among girls. We examined the relationship between changes in PA and sleep disturbance over the school year, including any bidirectional relationship between these two factors.MethodsThis longitudinal study focused on teenage girls who had a mean age of 13.2 ± 0.2 years at baseline and were drawn from five randomly selected schools in the city of Tartu, Estonia. Sleep disturbance and PA were subjectively assessed using the self‐reported 3‐Day Physical Activity Recall and the Insomnia Severity Index, at four intervals throughout the school year. Latent growth curve analyses were used to evaluate longitudinal and bidirectional associations between PA and sleep disturbance.ResultsAssessments were carried out at three‐monthly intervals from September 2015 to June 2016. Sleep disturbance increased and PA decreased over the school year. At baseline, higher PA was related to lower sleep disturbance. Changes in PA corresponded with changes in sleep disturbance. A negative bidirectional relationship between sleep disturbance and PA over time was also found.ConclusionThese results suggest that increasing PA may be an effective strategy for improving the quality of sleep in girls during early adolescence.
Comparative cardiovascular safety of nonsteroidal anti‐inflammatory drugs in patients with hypertension: a population‐based cohort study
Authors: Dong Yaa‐Hui , Chang Chia‐Hsuin , Wu Li‐Chiu , Hwang Jing‐Shiang , Toh Sengwee 
Published: February 2018

AimsPrevious studies have suggested that nonsteroidal anti‐inflammatory drugs (NSAIDs) may be associated with higher cardiovascular risks. However, few have been active comparison studies that directly assessed the potential differential cardiovascular risk between NSAID classes or across individual NSAIDs. We compared the risk of major cardiovascular events between cyclooxygenase 2 (COX‐2)‐selective and nonselective NSAIDs in patients with hypertension.MethodsWe conducted a cohort study of patients with hypertension who initiated COX‐2‐selective or nonselective NSAIDs in a population‐based Taiwanese database. The outcomes included hospitalization for the following major cardiovascular events: ischaemic stroke, acute myocardial infarction, congestive heart failure, transient ischaemic attack, unstable angina or coronary revascularization. We followed patients for up to 4 weeks, based on the as‐treated principle. We used inverse probability weighting to control for baseline and time‐varying covariates, and estimated the on‐treatment hazard ratios (HRs) and 95% conservative confidence interval (CIs).ResultsWe identified 2749 eligible COX‐2‐selective NSAID users and 52 880 eligible nonselective NSAID users. The HR of major cardiovascular events comparing COX‐2‐selective with nonselective NSAIDs after adjusting for baseline and time‐varying covariates was 1.07 (95% CI 0.65, 1.74). We did not observe a differential risk when comparing celecoxib to diclofenac (HR 1.17; 95% CI 0.61, 2.25), ibuprofen (HR 1.36; 95% CI 0.58, 3.18) or naproxen (HR 0.75; 95% CI 0.23, 2.44). There was an increased risk with COX‐2‐selective NSAIDs, however, when comparing COX‐2‐selective NSAIDs with mefenamic acid (HR 2.11; 95% CI 1.09, 4.09).ConclusionsOur results provide important information about the comparative cardiovascular safety of NSAIDs in patients with hypertension.
Physiologically‐based pharmacokinetic modelling of a CYP2C19 substrate, BMS‐823778, utilizing pharmacogenetic data
Authors: Gong Jiachang , Iacono Lisa , Iyer Ramaswamy A. , Humphreys William G. , Zheng Ming 
Published: February 2018

AimsPrevious studies demonstrated direct correlation between CYP2C19 genotype and BMS‐823778 clearance in healthy volunteers. The objective of the present study was to develop a physiologically‐based pharmacokinetic (PBPK) model for BMS‐823778 and use the model to predict PK and drug–drug interaction (DDI) in virtual populations with multiple polymorphic genes.MethodsThe PBPK model was built and verified using existing clinical data. The verified model was simulated to predict PK of BMS‐823778 and significance of DDI with a strong CYP3A4 inhibitor in subjects with various CYP2C19 and UGT1A4 genotypes.ResultsThe verified PBPK model of BMS‐823778 accurately recovered observed PK in different populations. In addition, the model was able to capture the exposure differences between subjects with different CYP2C19 genotypes. PK simulation indicated higher exposures of BMS‐823778 in CYP2C19 poor metabolizers who were also devoid of UGT1A4 activity, compared to those with normal UGT1A4 functionality. Moderate DDI with itraconazole was predicted in subjects with wild‐type CYP2C19 or UGT1A4. However, in subjects without CYP2C19 or UGT1A4 functionality, significant DDI was predicted when BMS‐823778 was coadministered with itraconazole.ConclusionsA PBPK model was developed using clinical data that accurately predicted human PK in different population with various CYP2C19 phenotypes. Simulations with the verified PBPK model indicated that UGT1A4 was probably an important clearance pathway in CYP2C19 poor metabolizers. DDI with itraconazole is likely to be dependent on the genotypes of CYP2C19 and UGT1A4.
Incorporation ofGSTA1genetic variations into a population pharmacokinetic model for IV busulfan in paediatric hematopoietic stem cell transplantation
Authors: Nava Tiago , Kassir Nastya , Rezgui Mohamed Aziz , Uppugunduri Chakradhara Rao Satyanarayana , Huezo‐Diaz Curtis Patricia , Duval Michel , Théoret Yves , Daudt Liane E. , Litalien Catherine , Ansari Marc , Krajinovic Maja , Bittencourt Henrique 
Published: February 2018

AimsThe aim of this study is to develop a population pharmacokinetic (PopPK) model for intravenous busulfan in children that incorporates variants ofGSTA1, gene coding for the main enzyme in busulfan metabolism.MethodsBusulfan concentration–time data was collected from 112 children and adolescents (median 5.4 years old, range: 0.1–20) who received intravenous busulfan during the conditioning regimen prior to stem cell transplantation. Weight, sex, baseline disease (malignantvs.non‐malignant), age, conditioning regimen andGSTA1diplotypes were evaluated as covariates of pharmacokinetic parameters by using nonlinear mixed effects analysis. The ability to achieve the target AUC24h(3600–6000 μM min−1) was assessed by estimating the first dose based on the present PopPK model and by comparing the results with other available models in children.ResultsA one‐compartment model with first‐order elimination best described the data. Allometric scaling of weight and a factor of busulfan metabolism maturation were included in the base model.GSTA1diplotypes were found to be a significant covariate of busulfan clearance, which was 7% faster in rapid metabolizers and 12% slower in poor metabolizers, in comparison with normal ones. Busulfan doses calculated using the parameters of the proposed PopPK model were estimated to achieve the target AUC in 85.2% of the cases (95% CI 78.7–91.7%).ConclusionThis is the first PopPK for busulfan that successfully incorporatedGSTA1genotype in a paediatric population. Its use may contribute to better prediction of busulfan exposure in children and adolescents since the first dose, by tailoring the dose according to the individual metabolic capacity.
Tension‐free vaginal tape for treatment of pure urodynamic stress urinary incontinence: efficacy and adverse effects at 17‐year follow‐up
Authors: Braga Andrea , Caccia Giorgio , Sorice Paola , Cantaluppi Simona , Coluccia Anna Chiara , Di Dedda Maria Carmela , Regusci Luca , Ghezzi Fabio , Uccella Stefano , Serati Maurizio 
Published: February 2018

ObjectiveTo assess the efficacy and safety of retropubic tension‐free vaginal tape (TVT) 17 years after implantation for the treatment of female pure stress urinary incontinence (SUI).Patients and MethodsA prospective study was conducted in two urogynaecological units in two countries. All consecutive women with urodynamically proven pure SUI treated by TVT were included. Patients with mixed incontinence and/or anatomical evidence of pelvic organ prolapse were excluded. Data regarding subjective outcomes (International Consultation on Incontinence Questionnaire–Short Form, Patient Global Impression of Improvement, and patient satisfaction scores), objective cure (stress test) rates, and adverse events were collected during follow‐up. Univariable analysis was performed to investigate outcomes.ResultsA total of 52 women underwent TVT implantation. At 17‐year follow‐up, 46 women (88.4%) were available for the evaluation. We did not find any significant change in surgical outcomes during this time. At 17 years after surgery, 41 of 46 women (89.1%) declared themselves cured (P = 0.98). Similarly, at 17‐year evaluation, 42 of 46 women (91.4%) were objectively cured. No significant deterioration in objective cure rates was observed over time (P for trend 0.50). The univariate analysis did not find any risk factor statistically associated with the recurrence of SUI. Of the 46 women, 15 (32.6%) reported the onset of de novo overactive bladder at 17‐year follow‐up. No other late complications were reported.ConclusionsThe 17‐year results of this study showed that TVT is a highly effective and safe option for the treatment of SUI.
Differential effects of oxycodone and venlafaxine on resting state functional connectivity—A randomized placebo‐controlled magnetic resonance imaging study
Authors: Hansen Tine M. , Lelic Dina , Olesen Anne E. , Drewes Asbjørn Mohr , Frøkjær Jens B. 
Published: February 2018

SummaryAimDifferent mechanisms may be involved in the antinociceptive effects of oxycodone (opioid) and venlafaxine (serotonin‐norepinephrine reuptake inhibitor), and the aim of this study was to investigate the effect of these drugs on brain functional connectivity.MethodsResting state functional magnetic resonance imaging was acquired in 20 healthy volunteers before and after a 5‐day treatment with oxycodone, venlafaxine, or placebo in a randomized, double‐blind, crossover study. Functional connectivity analyses were performed between four predefined seeds (dorsal anterior cingulate cortex, rostral anterior cingulate cortex, posterior insula, and prefrontal cortex), and the whole brain.ResultsThe overall interpretation was that there were differences between the effects of oxycodone and venlafaxine on functional connectivity. Oxycodone mainly showed decreased functional connectivity between limbic structures and to supralimbic areas (all P < 0.05). Venlafaxine also showed decreased functional connectivity between limbic structures and to supralimbic areas, but increased functional connectivity to structures in the midbrain and brain stem was also found (all P < 0.05).ConclusionsOxycodone and venlafaxine showed differential effects on resting‐state functional connectivity as compared to placebo. This supports that the two drugs exert different mechanisms, and that the drugs in combination may exert additive effects and could potentially improve pain therapy.
Serum brain‐derived neurotrophic factor in children with coeliac disease
Authors: Margoni Daphne , Michalakakou Kelly , Angeli Eleni , Pervanidou Panagiota , Kanaka‐Gantenbein Christina , Chrousos George , Papassotiriou Ioannis , Roma Eleftheria 
Published: February 2018

AbstractBackgroundBrain‐derived neurotrophic factor (BDNF) is a neurotrophin that has a protective role in the nervous system and is involved in neural plasticity. It is abundant in the central nervous system, but is also expressed in the gastrointestinal tract. Coeliac disease (CD), characterised by intestinal inflammation, has some comorbidity with neurologic and mental disorders. The aim of this study was to evaluate circulating BDNF concentrations in patients with CD at diagnosis or on a gluten‐free diet (GFD) for longer than 1 year and in healthy controls (HC).Materials and methodsFifty newly diagnosed patients with CD (aged 8.6 ± 3.7 years, 64.0% females), thirty‐nine patients on GFD for longer than 1 year (aged 10.4 ± 3.4 years, 71.8% females) and 36 HC (aged 8 ± 1.7 years, 33.3% females) were included in the study. Along with anthropometric evaluation and standard blood chemistry, serum BDNF levels were measured by a specific immunoenzymatic assay.ResultsPatients at diagnosis and on GFD had significantly higher BDNF levels (26 110 ± 8204 and 28 860 ± 7992 pg/mL), respectively, than HC (19 630 ± 8093 pg/mL, P < .001 for both CD groups). Patients on GFD had significantly higher BDNF levels than those at diagnosis (P = .02).ConclusionsSerum BDNF concentrations were higher in patients with CD than in HC, regardless of their status of gluten consumption. This could be attributed either to a potential protective response to the inflammation of the intestine or to chronic stress.
Insecticidal potential of Bacillus thuringiensis for the biological control of neotropical brown stink bug
Authors: Schünemann Rogério , Roggia Samuel , Muraro Dionei Schmidt , Knaak Neiva , Fiuza Lidia Mariana 
Published: February 2018

AbstractEuschistus heros (Hemiptera: Pentatomidae) is considered a major insect pest in soybean production in Brazil. The indiscriminate application of pesticides to fields leads to reduction in biodiversity, selection of resistant populations, emergence of new pest outbreaks, and damage to non‐target organisms. The objective of this research was to evaluate the effects of exposure to Cry proteins present in new isolates of Bacillus thuringiensis Berliner, commercial formulations, and Bt soybean on E. heros development. The feeding preference of E. heros for Bt‐ vs. non‐Bt soybean was also evaluated. All treatments caused significant mortality to E. heros except the Bt soybean. Tests with combinations of isolated Bt‐toxins indicated that combinations had greater efficacy than other treatments (>98% mortality). The results demonstrate that E. heros is susceptible to B. thuringiensis toxins, which may contribute to the management of this insect in soybean agro‐ecosystems.
Role of potentially inappropriate medication use in rehabilitation outcomes for geriatric patients after strokes
Authors: Kose Eiji , Hirai Toshiyuki , Seki Toshiichi , Hayashi Hiroyuki 
Published: February 2018

AimThe effect of the use of potentially inappropriate medications (PIM) on mortality and functional outcome after strokes is unclear in Japan. The aim of the present study was to establish whether treatment with PIM affects functional improvements among geriatric patients convalescing after strokes.MethodsThis retrospective longitudinal study included consecutive geriatric patients admitted and discharged from convalescent rehabilitation wards for stroke between 2010 and 2016. Demographic data, laboratory data and the Functional Independence Measure (FIM) were analyzed. We used the 2015 American Geriatrics Society Beers Criteria to screen for PIM, and the primary outcome was motor FIM gain. Multivariate regression analysis was carried out to analyze the relationship between PIM use and functional recovery.ResultsIn total, 272 participants (102 men, 170 women; median age 79 years, interquartile range 72–85 years) were included in the present study. Multivariate regression analysis of motor FIM gain, adjusting for confounding factors, showed that PIM use was independently and negatively correlated with motor FIM gain. In particular, anticholinergic drugs (such as antipsychotics, antidepressants and first‐generation antihistamines) were significantly increased from admission to discharge.ConclusionIncreased PIM use during hospitalization might be a predictor of reduced functional improvement in geriatric patients after strokes. Geriatr Gerontol Int 2018; 18: 321–328.
Both B‐1a and B‐1b cells exposed to Mycobacterium tuberculosis lipids differentiate into IgM antibody‐secreting cells
Authors: Ordoñez Ciara , Savage Hannah P. , Tarajia Musharaf , Rivera René , Weeks‐Galindo Cheyenne , Sambrano Dilcia , Riley Lee , Fernandez Patricia L. , Baumgarth Nicole , Goodridge Amador 
Published: February 2018

SummaryTuberculosis is an infectious disease caused by Mycobacterium tuberculosis. The cellular immune response to mycobacteria has been characterized extensively, but the antibody response remains underexplored. The present study aimed to examine whether host or bacterial phospholipids induce secretion of IgM, and specifically anti‐phospholipid IgM, antibodies by B cells and to identify the responsible B‐cell subset. Here we show that peritoneal B cells responded to lipid antigens by secreting IgM antibodies. Specifically, stimulation with M. tuberculosis H37Rv total lipids resulted in significant induction of total and anti‐phosphatidylcholine IgM. Similarly, IgM antibody production increased significantly with stimulation by whole Mycobacterium bovis bacillus Calmette–Guérin. The B‐1 subset was the dominant source of IgM antibodies after exposure to cardiolipin. Both CD5+ B‐1a and CD5− B‐1b cell subsets secreted total IgM antibodies after exposure to M. tuberculosis H37Rv total lipids in vitro. Overall, our results suggest that the poly‐reactive B‐1 cell repertoire contributes to non‐specific anti‐phospholipid IgM antibody secretion in response to M. tuberculosis lipids.
The effect of pre‐pregnancy lifestyle counselling on food intakes and association between food intakes and gestational diabetes in high‐risk women: results from a randomised controlled trial
Authors: Valkama A. J. , Meinilä J. , Koivusalo S. , Lindström J. , Rönö K. , Stach‐Lempinen B. , Kautiainen H. , Eriksson J. G. 
Published: February 2018

AbstractBackgroundHealthy diets before and during pregnancy have been suggested to reduce the risk of gestational diabetes (GDM). Several lifestyle intervention studies for pregnant women have reported dietary improvements after counselling. However, evidence concerning the effect of counselling initiated before pregnancy on diets is limited.MethodsThis randomised controlled study explored whether pre‐pregnancy lifestyle counselling influenced food intakes, as well as whether changes in food intakes were associated with GDM. The participants comprised 75 women with prior GDM and/or a body mass index ≥ 30 kg m–2. Women were randomised into a control or an intervention group, and their food intakes were followed from pre‐pregnancy to early pregnancy using a food frequency questionnaire. The control and intervention groups were combined to assess the association between changes in food intakes and GDM. The diagnosis of GDM was based on a 75‐g oral glucose tolerance test conducted in the first and second trimester of pregnancy.ResultsPre‐pregnancy lifestyle counselling showed no major overall effect on food intakes. The intake of low‐fat cheese increased significantly in women who did not develop GDM compared to women who did after adjusting for potential confounders (P = 0.028). This association was not observed for regular‐fat cheese.ConclusionsThe findings obtained in the present study suggest that an increased intake of low‐fat but not regular‐fat cheese between pre‐pregnancy and early pregnancy is associated with a lower risk of GDM in high‐risk women.
Polymorphisms of cytochrome P450 2B6 (CYP2B6) in cynomolgus and rhesus macaques
Authors: Uno Yasuhiro , Uehara Shotaro , Yamazaki Hiroshi 
Published: February 2018

AbstractBackgroundCytochrome P450 2B6 (CYP2B6) is an important drug‐metabolizing enzyme and is expressed in liver. Although human CYP2B6 variants account for variable enzyme properties among individuals and populations, CYP2B6 genetic variants have not been investigated in cynomolgus macaques, widely used in drug metabolism studies.MethodsCYP2B6 was resequenced in 120 cynomolgus macaques and 23 rhesus macaques by direct sequencing.ResultsTwenty‐three non‐synonymous variants were found, of which 12 and 3 were unique to cynomolgus macaques and rhesus macaques, respectively. By functional characterization using the 14 variant proteins, 8 variants (V114I, R253C, M435I, V459M, L465P, C475S, R487C, and R487H) showed different rate (>1.5‐fold) of testosterone 16β‐hydroxylation to wild type. However, the four variants (M435I, L465P, C475S, and R487H) were analyzed in liver microsomes, and the catalytic rates were not substantially different from wild type.ConclusionsMacaque CYP2B6 was polymorphic, and the genotype could partly account for variable enzyme activities of macaque CYP2B6.