bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maternal sleep practices and stillbirth: Findings from an international case‐control study
Authors: O’Brien Louise M. , Warland Jane , Stacey Tomasina , Heazell Alexander E. P. , Mitchell Edwin A. ,   the STARS Consortium
Published: January 2019

AbstractBackgroundLate stillbirth, which occurs ≥28 weeks’ gestation, affects 1.3‐8.8 per 1000 births in high‐income countries. Of concern, most occur in women without established risk factors. Identification of potentially modifiable risk factors that relate to maternal behaviors remains a priority in stillbirth prevention research. This study aimed to investigate, in an international cohort, whether maternal sleep practices are related to late stillbirth.MethodsAn Internet‐based case‐control study of women who had a stillbirth ≥28 weeks’ gestation within 30 days before completing the survey (n = 153) and women with an ongoing third‐trimester pregnancy or who had delivered a live born child within 30 days (n = 480). Bivariate and multivariate logistic regressions were used to determine unadjusted and adjusted odds ratios (OR and aOR, respectively) with 95% confidence intervals (95% CIs) for stillbirth.ResultsSleeping >9 hours per night in the previous month was associated with stillbirth (aOR 1.75 [95% CI 1.10‐2.79]), as was waking on the right side (2.27 [1.31‐3.92]). Nonrestless sleep in the last month was also found to be associated with stillbirth (1.73 [1.03‐2.99]), with good sleep quality in the last month approaching significance (1.64 [0.98‐2.75]). On the last night of pregnancy, not waking more than one time was associated with stillbirth (2.03 [1.24‐3.34]). No relationship was found with going to sleep position during pregnancy, although very few women reported settling in the supine position (2.4%).ConclusionsLong periods of undisturbed sleep are associated with late stillbirth. Physiological studies of how the neuroendocrine and autonomic system pathways are regulated during sleep in the context of late pregnancy are warranted.
School‐related subjective well‐being promotes subsequent adaptability, achievement, and positive behavioural conduct
Authors: Putwain David W. , Loderer Kristina , Gallard Diahann , Beaumont Joanna 
Published: January 2019

BackgroundPrevious studies have shown that subjective well‐being and adaptability are linked to adaptive educational outcomes, including higher achievement and lower anxiety. It is not presently clear, however, how school‐related subjective well‐being and adaptability are related, or predict behavioural outcomes such as student conduct.AimThe aim of the present study was to test a bidirectional model of school‐related subjective well‐being and adaptability, and how they relate to achievement and behavioural conduct.MethodData were collected from 539 Year 12 students over four waves. Achievement and behavioural conduct were measured in the first wave of data collection (T1), school‐related subjective well‐being and adaptability at the second and third waves (T2 and T3), and achievement and behavioural conduct again in the fourth wave of data collection (T4).ResultsA structural equation model showed that T2 school‐related subjective well‐being predicted higher T3 adaptability, but not vice versa. T3 school‐related subjective well‐being predicted greater T4 achievement and positive behavioural conduct, and T3 adaptability predicted greater T4 positive behavioural conduct.ConclusionSchool‐related subjective well‐being promotes adaptability, achievement, and positive behavioural conduct, and adaptability is also related to positive behavioural conduct. Attempts to foster well‐being and adaptability could show educational gains for students.
A short perspective on the long road to effective treatments for Alzheimer's disease
Authors: Reynolds David S. 
Published: January 2019

Globally, there are approximately 47 million people living with dementia, and about two thirds of those have Alzheimer's disease (AD). Age is the single biggest risk factor for the vast majority of sporadic AD cases, and because the world's population is aging, the number of people living with AD is set to rise dramatically over the coming decades. There are currently no disease‐modifying treatments for AD, and the few symptomatic agents available have limited impact on the disease. Perhaps surprisingly, there is relatively little activity in the AD research and development field compared with other diseases with a high mortality burden, such as cancer. There is enormous economic incentive to discover and develop the first disease‐modifying treatment, but previous failure has significantly reduced further industrial investment in this field. The short review looks at the historical path trodden to develop treatments and reflects on the journey down the road to truly effective treatments for people living with AD.Linked ArticlesThis article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc
1,2,3,4,6‐Penta‐O‐galloyl‐β‐d‐glucose modulates perivascular inflammation and prevents vascular dysfunction in angiotensin II‐induced hypertension
Authors: Mikolajczyk Tomasz P. , Nosalski Ryszard , Skiba Dominik S. , Koziol Joanna , Mazur Magdalena , Justo‐Junior Amauri S. , Kowalczyk Paulina , Kusmierczyk Zofia , Schramm‐Luc Agata , Luc Kevin , Maffia Pasquale , Graham Delyth , Kiss Anna K. , Naruszewicz Marek , Guzik Tomasz J. 
Published: January 2019

AbstractBackground and PurposeHypertension is a multifactorial disease, manifested by vascular dysfunction, increased superoxide production, and perivascular inflammation. In this study, we have hypothesized that 1,2,3,4,6‐penta‐O‐galloyl‐β‐d‐glucose (PGG) would inhibit vascular inflammation and protect from vascular dysfunction in an experimental model of hypertension.Experimental ApproachPGG was administered to mice every 2 days at a dose of 10 mg·kg−1 i.p during 14 days of Ang II infusion. It was used at a final concentration of 20 μM for in vitro studies in cultured cells.Key ResultsAng II administration increased leukocyte and T‐cell content in perivascular adipose tissue (pVAT), and administration of PGG significantly decreased total leukocyte and T‐cell infiltration in pVAT. This effect was observed in relation to all T‐cell subsets. PGG also decreased the content of T‐cells bearing CD25, CCR5, and CD44 receptors and the expression of both monocyte chemoattractant protein 1 (CCL2) in aorta and RANTES (CCL5) in pVAT. PGG administration decreased the content of TNF+ and IFN‐γ+ CD8 T‐cells and IL‐17A+ CD4+ and CD3+CD4−CD8− cells. Importantly, these effects of PGG were associated with improved vascular function and decreased ROS production in the aortas of Ang II‐infused animals independently of the BP increase. Mechanistically, PGG (20 μM) directly inhibited CD25 and CCR5 expression in cultured T‐cells. It also decreased the content of IFN‐γ+ CD8+ and CD3+CD4−CD8− cells and IL‐17A+ CD3+CD4−CD8− cells.Conclusion and ImplicationPGG may constitute an interesting immunomodulating strategy in the regulation of vascular dysfunction and hypertension.Linked ArticlesThis article is part of a themed section on Immune Targets in Hypertension. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.12/issuetoc
Sex differences in schizophrenia, bipolar disorder, and post‐traumatic stress disorder: Are gonadal hormones the link?
Authors: Gogos Andrea , Ney Luke J. , Seymour Natasha , Van Rheenen Tamsyn E. , Felmingham Kim L. 
Published: January 2019

In this review, we describe the sex differences in prevalence, onset, symptom profiles, and disease outcome that are evident in schizophrenia, bipolar disorder, and post‐traumatic stress disorder. Women with schizophrenia tend to exhibit less disease impairment than men. By contrast, women with post‐traumatic stress disorder are more affected than men. The most likely candidates to explain these sex differences are gonadal hormones. This review details the clinical evidence that oestradiol and progesterone are dysregulated in these psychiatric disorders. Notably, existing data on oestradiol, and to a lesser extent, progesterone, suggest that low levels of these hormones may increase the risk of disease development and worsen symptom severity. We argue that future studies require a more inclusive, considered analysis of gonadal steroid hormones and the intricacies of the interactions between them, with methodological rigour applied, to enhance our understanding of the roles of steroid hormones in psychiatric disorders.LINKED ARTICLESThis article is part of a themed section on The Importance of Sex Differences in Pharmacology Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.21/issuetoc
The effect of agriculture on the seasonal dynamics and functional diversity of benthic biofilm in tropical headwater streams
Authors: Taniwaki Ricardo H. , Matthaei Christoph D. , Cardoso Tatima K. M. , Ferraz Silvio F. B. , Martinelli Luiz A. , Piggott Jeremy J. 
Published: January 2019

AbstractTropical streams are one of the most endangered ecosystems in the world due to the constant pressures from human activities. Among these activities, agriculture represents a land use that is crucial for human development but also a key driver of stream degradation and biodiversity decline in the tropics. Against this background, we investigated indirect effects of agriculture (alterations in stream flow and nutrient availability) and climate characteristics (water temperature) on benthic biofilm communities in tropical streams (São Paulo State, Brazil). Three first‐order streams draining catchments dominated by agricultural land use (sugarcane for bioenergy production, pasture) with some remaining riparian forest were studied for 1 year. We focused on the relationships of benthic biofilm biomass, algal biomass, diatom community, and functional structure with streamflow dynamics, nitrate concentrations, and water temperature. Our results indicate that these biological responses were mainly mediated by flow and water temperature and not by resource availability in the studied headwater streams. This result could be explained by the heavy rains and elevated runoff generation in these tropical catchments under agricultural influence, which might override the known effects of nutrient enrichment on benthic biofilm communities. Considering forecast climate and land‐use changes in tropical streams, our findings may suggest potential shifts in benthic biofilm communities, with functional consequences for aquatic food webs in these environments.Abstract in Brazilian Portuguese is available with online material.
Phase II trial of aflibercept with FOLFIRI as a second‐line treatment for Japanese patients with metastatic colorectal cancer
Authors: Denda Tadamichi , Sakai Daisuke , Hamaguchi Tetsuya , Sugimoto Naotoshi , Ura Takashi , Yamazaki Kentaro , Fujii Hirofumi , Kajiwara Takeshi , Nakajima Takako Eguchi , Takahashi Shin , Otsu Satoshi , Komatsu Yoshito , Nagashima Fumio , Moriwaki Toshikazu , Esaki Taito , Sato Takeo , Itabashi Michio , Oki Eiji , Sasaki Toru , Sunaga Yoshinori , Ziti‐Ljajic Samira , Brillac Claire , Yoshino Takayuki 
Published: January 2019

Aflibercept targets vascular endothelial growth factor. The present study involved assessing the efficacy, safety and pharmacokinetics of aflibercept plus 5‐fluorouracil/levofolinate/irinotecan (FOLFIRI) as a second‐line treatment for metastatic colorectal cancer (mCRC) in Japanese patients. Aflibercept (4 mg/kg) plus FOLFIRI was administered every 2 weeks in 62 patients with mCRC until disease progression, unacceptable toxicity or patient withdrawal. Tumors were imaged every 6 weeks. The primary endpoint was objective response rate (ORR); secondary endpoints were progression‐free survival, overall survival, safety, and pharmacokinetics of aflibercept, irinotecan and 5‐fluorouracil. A total of 60 patients were evaluated for ORR; 50 had received prior bevacizumab. The ORR was 8.3% (95% confidence interval [CI]: 1.3%‐15.3%), and the disease control rate (DCR) was 80.0% (69.9%‐90.1%). The median progression‐free survival was 5.42 months (4.14‐6.70 months) and the median overall survival was 15.59 months (11.20‐19.81 months). No treatment‐related deaths were observed, and no significant drug‐drug interactions were found. The most common treatment‐emergent adverse events were neutropenia and decreased appetite. Free aflibercept had a mean maximum concentration (coefficient of variation) of 73.2 μg/mL (15%), clearance of 0.805 L/d (22%) and volume of distribution of 6.2 L (18%); aflibercept bound with vascular endothelial growth factor had a clearance of 0.162 L/d (9%) (N = 62). Aflibercept did not significantly affect the pharmacokinetics of irinotecan or 5‐fluorouracil: The clearance was 11.1 L/h/m2 (28%) for irinotecan and, at steady state, 72.6 L/h/m2 (56%) for 5‐fluorouracil (N = 10). Adding aflibercept to FOLFIRI was shown to be beneficial and well‐tolerated in Japanese patients with mCRC. ClinicalTrials.gov Identifier: NCT01882868.
Nitric oxide inhibits autophagy and promotes apoptosis in hepatocellular carcinoma
Authors: Zhang XiaoGang , Jin Li , Tian Zhen , Wang Jing , Yang Yuan , Liu JinFeng , Chen Yi , Hu ChunHua , Chen TianYan , Zhao YingRen , He YingLi 
Published: January 2019

Hepatocellular carcinoma (HCC) is the second most common cause of cancer‐related mortality worldwide. The expression of nitric oxide synthase (NOS) and the inhibition of autophagy have been linked to cancer cell death. However, the involvement of serum nitric oxide (NO), the expression of NOS and autophagy have not been investigated in HCC. In the present study, we first established that the NO level was significantly higher in hepatitis B virus‐related HCC than in the liver cirrhosis control (53.60 ± 19.74 vs 8.09 ± 4.17 μmol/L, t = 15.13, P < 0.0001). Using immunohistochemistry, we found that the source of NO was at least partially attributed to the expression of inducible NOS and endothelial NOS but not neuronal NOS in the liver tissue. Furthermore, in human liver cancer cells, NO‐induced apoptosis and inhibited autophagy. Pharmacological inhibition of autophagy also induced apoptosis, whereas the induction of autophagy could ameliorate NO‐induced apoptosis. We also found that NO regulates the switch between apoptosis and autophagy by disrupting the Beclin 1/Vps34 association and by increasing the Bcl‐2/Beclin 1 interaction. Overall, the present findings suggest that increased NOS/NO promotes apoptosis through the inhibition of autophagy in liver cancer cells, which may provide a novel strategy for the treatment of HCC.
Validation of childhood asthma predictive tools: A systematic review
Authors: Colicino Silvia , Munblit Daniel , Minelli Cosetta , Custovic Adnan , Cullinan Paul 
Published: January 2019

SummaryBackgroundThere is uncertainty about the clinical usefulness of currently available asthma predictive tools. Validation of predictive tools in different populations and clinical settings is an essential requirement for the assessment of their predictive performance, reproducibility and generalizability. We aimed to critically appraise asthma predictive tools which have been validated in external studies.MethodsWe searched MEDLINE and EMBASE (1946‐2017) for all available childhood asthma prediction models and focused on externally validated predictive tools alongside the studies in which they were originally developed. We excluded non‐English and non‐original studies. PROSPERO registration number is CRD42016035727.ResultsFrom 946 screened papers, eight were included in the review. Statistical approaches for creation of prediction tools included chi‐square tests, logistic regression models and the least absolute shrinkage and selection operator. Predictive models were developed and validated in general and high‐risk populations. Only three prediction tools were externally validated: the Asthma Predictive Index, the PIAMA and the Leicester asthma prediction tool. A variety of predictors has been tested, but no studies examined the same combination. There was heterogeneity in definition of the primary outcome among development and validation studies, and no objective measurements were used for asthma diagnosis. The performance of tools varied at different ages of outcome assessment. We observed a discrepancy between the development and validation studies in the tools’ predictive performance in terms of sensitivity and positive predictive values.ConclusionsValidated asthma predictive tools, reviewed in this paper, provided poor predictive accuracy with performance variation in sensitivity and positive predictive value.
Hyponatraemia in patients with community‐acquired pneumonia; prevalence and aetiology, and natural history of SIAD
Authors: Cuesta Martin , Slattery David , Goulden Eirena L. , Gupta Saket , Tatro Elizabeth , Sherlock Mark , Tormey William , O'Neill Shane , Thompson Christopher J. 
Published: January 2019

SummaryObjectiveHyponatraemia is common in community‐acquired pneumonia (CAP) and is associated with increased mortality. The mechanism of hyponatraemia in CAP is not completely understood and treatment is therefore ill‐defined. We aimed to define the causation of hyponatraemia in CAP.DesignProspective, single‐centre, observational study of all patients with CAP and hyponatraemia (≤ 130 mmol/L) during a 9‐month period.PatientsThe prevalence of each subtype of hyponatraemia, and the associated mortality, was determined in 143 admissions with CAP (Study 1). A sub‐cohort of patients with SIAD (n = 10) was prospectively followed, to document the natural history of SIAD associated with CAP (Study 2).MeasurementsIn Study 2, blood and urine were collected on day 1, 3, 5 and 7 following admission for measurement of plasma vasopressin, sodium, osmolality and urine osmolality.ResultsIn study 1, 143/1723(8.3%) of CAP patients had hyponatraemia (≤130 mmol/L). About 66 had SIAD (46%), 60(42%) had hypovolaemic hyponatraemia (HON), 13(9%) had hypervolaemic hyponatraemia (HEN) and 4(3%) patients had hyponatraemia due to glucocorticoid hormone deficiency. Mortality was higher in the HEN than in the HON, SIAD or normonatraemic groups (P < 0.01). In Study 2, plasma sodium concentration normalized in 8/10 (80%) by day 7. Two patients with persistent hyponatraemia were discovered to have underlying bronchiectasis.ConclusionsHyponatraemia in CAP is most commonly secondary to SIAD or hypovolaemia. HEN is less common, but has worse prognosis. Prospective observation demonstrates that in SIAD, plasma AVP and sodium concentrations normalize with antimicrobials; failure of reversal of suggests underlying lung disease, such as bronchiectasis.
Comparison between radioiodine therapy and single‐session radiofrequency ablation of autonomously functioning thyroid nodules: A retrospective study
Authors: Cervelli Rosa , Mazzeo Salvatore , Boni Giuseppe , Boccuzzi Antonio , Bianchi Francesca , Brozzi Federica , Santini Pierina , Vitti Paolo , Cioni Roberto , Caramella Davide 
Published: January 2019

SummaryObjectiveTo compare the efficacy of Radioiodine (RI) and Radiofrequency ablation (RFA) in the treatment of autonomously functioning thyroid nodules (AFTNs). End‐points: nodule volume reduction (NVR) and thyroid function normalization.Design, patients and measurementsTwenty‐two patients (2:20 M:F; 51.9 ± 13.9 years) affected by 25 AFTNs, treated by RFA were retrospectively compared with 25 patients (8:17 M:F; 57.2 ± 12.8 years) affected by a single AFTN treated by RI. Both group showed analogous characteristics as to age, gender, toxic/pretoxic phase and pretreatment nodule volume (calculated by the ellipsoid formula). Thyroid hormone levels and autoimmune thyroid profile were assessed before treatment. A fixed RI activity of 555 MBq (15 mCi) was administered. RFA was performed with an 18G, single‐tipped electrode, by the “modified moving shot technique.” Thyroid hormones were assessed and the nodule post‐treatment volume calculated 12 months after treatment.ResultsNo statistical difference was found between the post‐treatment NVR by comparing RI and RFA (P = 0.69). The volume reduction rates were 68.4 ± 28.9% and 76.4 ± 16.9% after RI and RFA, respectively. As to the thyroid function, 5/25 patients developed clinical hypothyroidism after RI. After RFA, all the 22 patients silenced their AFTN and normalized the thyroid hormones. Subclinical hypothyroidism was recorded in two patients after both RI and RFA. Thus, the functional therapeutic success, defined as the restoration of euthyroidism, was achieved in 18/25 (72%) patients treated by RI and in 20/22 (90.9%) treated by RFA.ConclusionsNo statistical difference in NVR was found between RI and RFA. All patients responded to RI but 5/25 were “over‐treated” developing hypothyroidism. RFA was effective in all patients with no case of post‐treatment clinical hypothyroidism. No radiation exposure and lower risk of post‐treatment hypothyroidism might make RFA the favourite option especially for young patients.
Prehabilitation is feasible in patients with rectal cancer undergoing neoadjuvant chemoradiotherapy and may minimize physical deterioration: results from the REx trial
Authors: Moug S. J. , Mutrie N. , Barry S. J. E. , Mackay G. , Steele R. J. C. , Boachie C. , Buchan C. , Anderson A. S. 
Published: January 2019

AbstractAimRectal cancer patients undergoing neoadjuvant chemoradiotherapy (NACRT) experience physical deterioration and reductions in their quality of life. This feasibility study assessed prehabilitation (a walking intervention) before, during and after NACRT to inform a definitive multi‐centred randomized clinical trial (REx trial).MethodsPatients planned for NACRT followed by potentially curative surgery were approached (August 2014–March 2016) (www.isrctn.com; 62859294). Prior to NACRT, baseline physical and psycho‐social data were recorded using validated tools. Participants were randomized to either the intervention group (exercise counselling session followed by a 13–17 week telephone‐guided walking programme) or a control group (standard care). Follow‐up testing was undertaken 1–2 weeks before surgery.ResultsOf the 296 screened patients, 78 (26%) were eligible and 48 (61%) were recruited. N = 31 (65%) were men with a mean age of 65.9 years (range 33.7–82.6). Mean intervention duration was 14 weeks with 75% adherence. n = 40 (83%) completed follow‐up testing. Both groups recorded reductions in daily walking but the reduction was less in the intervention group although not statistically significant. Participants reported high satisfaction and fidelity to trial procedures.ConclusionThis study demonstrates that prehabilitation is feasible in rectal cancer patients undergoing NACRT. Good recruitment, adherence, retention and patient satisfaction rates support the development of a fully powered trial. The effects of the intervention on physical outcomes were promising.