bluuebunny/crossref_metadata_2025 huggingface dataset:
Growth of thymic epithelial tumors and thymic cysts: Differential radiological points
Authors: Kim Hyungjin , Yoon Soon Ho , Kim Jihang , Lee Kyung Won , Choi Ye Ra , Cho Hyoun , Goo Jin Mo
Published: February 2019

Background

The growth rate of thymic epithelial tumors (TETs) and thymic cysts was investigated to determine whether they can be differentiated and clinico‐radiological predictors of interval growth was identified.

Methods

This retrospective study included 122 patients with pathologically proven thymic cysts (n = 56) or TETs (n = 66) who underwent two serial chest computed tomography scans at least eight weeks apart. Average diameters and attenuation were measured, volume‐doubling times (VDTs) were calculated, and clinical characteristics were recorded. VDTs were compared using the log‐rank test. Predictors of growth were analyzed using the log‐rank test and Cox regression analysis.

Results

The frequency of growth did not differ significantly between TETs and thymic cysts (P = 0.279). The VDT of thymic cysts (median 324 days) was not significantly different from that of the TETs (median 475 days; P = 0.808). Water attenuation (≤ 20 Hounsfield units) predicted growth in thymic cysts (P = 0.016; hazard ratio 13.2, 95% confidence interval 1.6–107.3), while lesion size (> 17.2 mm) predicted growth in TETs (P = 0.008 for size, P = 0.029 for size*time). For the growing lesions, the positive and negative predictive values of water attenuation for thymic cysts were 93% and 80%, respectively.

Conclusion

The frequencies of interval growth and VDTs were indistinguishable between TETs and thymic cysts. Water attenuation and lesion size predicted growth in thymic cysts and TETs, respectively. Among the growing lesions, water attenuation was a differential feature of thymic cysts.
Age‐dependent DNA methylation patterns on the Y chromosome in elderly males
Authors: Lund Jesper B. , Li Shuxia , Christensen Kaare , Mengel‐From Jonas , Soerensen Mette , Marioni Riccardo E. , Starr John , Pattie Alison , Deary Ian J. , Baumbach Jan , Tan Qihua
Published: February 2019

The Y chromosome, a sex chromosome that only exists in males, has been ignored in traditional epigenetic association studies for multiple reasons. However, sex differences in aging‐related phenotypes and mortality could suggest a critical role of the sex chromosomes in the aging process. We obtained blood‐based DNA methylation data on the Y chromosome for 624 men from four cohorts and performed a chromosome‐wide epigenetic association analysis to detect Y‐linked CpGs differentially methylated over age and cross‐validated the significant CpGs in the four cohorts. We identified 40–219 significant CpG sites (false discovery rate <0.05) with >82% of them hypermethylated with increasing age, which is in strong contrast to the patterns reported on the autosomal chromosomes. Comparing the rate of change in the Y‐linked DNA methylation across cohorts that represent different age intervals revealed a trend of acceleration in DNA methylation with increasing age. The age‐dependent DNA methylation patterns on the Y chromosome were further examined for their association with all‐cause mortality with results suggesting that the predominant pattern of age‐related hypermethylation on the Y chromosome is associated with reduced risk of death.
Cannabidiol modulates the expression of neuroinflammatory factors in stress‐ and drug‐induced reinstatement of methamphetamine in extinguished rats
Authors: Karimi‐Haghighi Saeideh , Dargahi Leila , Haghparast Abbas
Published: February 2019

Methamphetamine (METH) is a highly potent and addictive psychostimulant that is frequently abused worldwide. Although the biggest challenge to the efficient treatment of drug dependence is relapse, its mechanism is completely unclear. Plenty of evidence suggests that inflammation contributes to drug‐induced reward especially in brain regions that are involved in the reward system, but there is no document about relapse. Cannabidiol (CBD) is a nonpsychoactive cannabinoid that has powerful anti‐inflammatory and immunosuppressive properties. A previous research in our laboratory has demonstrated that CBD prevents reinstatement of METH even in 24‐hour rapid eye movement (REM) sleep‐deprived (RSD) rats. The aim of this study was to assess whether CBD prevents reinstatement of METH through change of gene expression of cytokines such as interleukin‐1β, interleukin‐6, interleukin‐10, and tumor necrosis factor α (TNF‐α) in extinguished rats. Real‐time polymerase chain reaction (PCR) was used in this research to assay gene expression of cytokines. We found that stress‐ and drug‐induced reinstatement of METH enhanced mRNA expression of cytokines in the prefrontal cortex (PFC) and hippocampus. Furthermore, CBD treatment significantly reduced the mRNA expression of cytokines in the PFC and hippocampus, but CBD treatment in RSD rats increased expression of cytokines in the hippocampus. It seems that enhancement of cytokines leads to change in neurotransmission and so triggers reinstatement of METH.
Resuscitation planning on a subacute geriatric evaluation and management ward
Authors: Strasser Rupert , Smith Roger , Yates Paul , Reid David , Katz Benny
Published: February 2019

Objectives

To describe the use of acute resuscitation plans (ARPs) among patients on a subacute geriatric ward and to identify factors associated with use of ARPs in these patients.

Methods

The hospital records of all patients admitted to the geriatric medicine ward in 2016 were retrospectively audited.

Results

An ARP was completed before separation for 333/442 (75.3%) admissions. In the event of arrest, 240 (54.3%) patients had an ARP specifying “care of the dying”, 93 (21.0%) had an ARP specifying “cardiopulmonary resuscitation” and 109 (24.7%) had no resuscitation plan. Age 85‐94 years (OR 1.65, P = 0.04) and ≥95 years (OR 9.59, P = 0.003), as well as Charlson index of comorbidity ≥2 (OR 3.4, P < 0.001), Australian‐born (OR 2.09, P = 0.002) and admission during October‐December (OR 3.81, P < 0.001) were independently associated with increased use of ARPs.

Conclusions

Acute resuscitation plan use was associated with older age, higher comorbidity, birth in Australia and admission later in the year.
Lung disease in STAT3 hyper‐IgE syndrome requires intense therapy
Authors: Kröner Carolin , Neumann Jens , Ley‐Zaporozhan Julia , Hagl Beate , Meixner Iris , Spielberger Benedikt D. , Dückers Gregor , Belohradsky Bernd H. , Niehues Tim , Borte Michael , Rosenecker Joseph , Kappler Matthias , Nährig Susanne , Reu Simone , Griese Matthias , Renner Ellen D.
Published: February 2019

Background

Pulmonary complications are responsible for high morbidity and mortality rates in patients with the rare immunodeficiency disorder STAT3 hyper‐IgE syndrome (STAT3‐HIES). The aim of this study was to expand knowledge about lung disease in STAT3‐HIES.

Methods

The course of pulmonary disease, radiological and histopathological interrelations, therapeutic management, and the outcome of 14 STAT3‐HIES patients were assessed.

Results

The patients’ quality of life was compromised most by pulmonary disease. All 14 patients showed first signs of lung disease at a median onset of 1.5 years of age. Lung function revealed a mixed obstructive‐restrictive impairment with reduced FEV1 and FVC in 75% of the patients. The severity of lung function impairment was associated with Aspergillus fumigatus infection and prior lung surgery. Severe lung tissue damage, with reduced numbers of ATP‐binding cassette sub‐family A member 3 (ABCA3) positive type II pneumocytes, was observed in the histological assessment of two deceased patients. Imaging studies of all patients above 6 years of age showed severe airway and parenchyma destruction. Lung surgeries frequently led to complications, including fistula formation. Long‐term antifungal and antibacterial treatment proved to be beneficial, as were inhalation therapy, chest physiotherapy, and exercise. Regular immunoglobulin replacement therapy tended to stabilize lung function.

Conclusions

Due to its severity, pulmonary disease in STAT3‐HIES patients requires strict monitoring and intensive therapy.
Reliability of frailty assessment in the critically ill: a multicentre prospective observational study
Authors: Pugh R. J. , Battle C. E. , Thorpe C. , Lynch C. , Williams J. P. , Campbell A. , Subbe C. P. , Whitaker R. , Szakmany T. , Clegg A. P. , Lone N. I.
Published: February 2019

Demand for critical care among older patients is increasing in many countries. Assessment of frailty may inform discussions and decision making, but acute illness and reliance on proxies for history‐taking pose particular challenges in patients who are critically ill. Our aim was to investigate the inter‐rater reliability of the Clinical Frailty Scale for assessing frailty in patients admitted to critical care. We conducted a prospective, multi‐centre study comparing assessments of frailty by staff from medical, nursing and physiotherapy backgrounds. Each assessment was made independently by two assessors after review of clinical notes and interview with an individual who maintained close contact with the patient. Frailty was defined as a Clinical Frailty Scale rating > 4. We made 202 assessments in 101 patients (median (IQR [range]) age 69 (65–75 [60–80]) years, median (IQR [range]) Acute Physiology and Chronic Health Evaluation II score 19 (15–23 [7–33])). Fifty‐two (51%) of the included patients were able to participate in the interview; 35 patients (35%) were considered frail. Linear weighted kappa was 0.74 (95%CI 0.67–0.80) indicating a good level of agreement between assessors. However, frailty rating differed by at least one category in 47 (47%) cases. Factors independently associated with higher frailty ratings were: female sex; higher Acute Physiology and Chronic Health Evaluation II score; higher category of pre‐hospital dependence; and the assessor having a medical background. We identified a good level of agreement in frailty assessment using the Clinical Frailty Scale, supporting its use in clinical care, but identified factors independently associated with higher ratings which could indicate personal bias.
In vitro aging of boar spermatozoa: role of sperm proximity and seminal plasma
Authors: Luther A.‐M. , Waberski D.
Published: February 2019

Background

Knowledge on the effect of seminal plasma on sperm function in extended semen during in vitro storage is lacking.

Objectives

The aim was to examine the interactive role of sperm concentration and seminal plasma concentration on boar sperm function during in vitro aging.

Material and methods

Experiment 1: Twenty‐one boar ejaculates were aliquoted with Beltsville Thawing Solution into five semen doses containing between 32.5 and 8.5 × 106 sperm/mL. Experiment 2: Semen samples (n = 8) containing 18 × 106 or 10 × 106 sperm/mL with their natural amount of seminal plasma and 10 × 106 sperm/mL substituted with autologous seminal plasma to the same concentration as in doses with 18 × 106 sperm/mL were prepared. Experiment 3: Four variants of semen doses containing 18 × 106 or 10 × 106 sperm/mL with either 10% or 0.5% (v/v) seminal plasma were used. Lipid peroxidation was assessed using Bodipy 581/591 in samples (n = 8) with two different sperm concentrations. Semen was examined during 144‐h storage at 17 °C by computer‐assisted semen analysis and flow cytometry.

Results

Experiment 1: 3D kinematic patterns revealed a concentration‐ and time‐dependent loss of sperm kinematics in samples with < 23 × 106 sperm/mL (p < 0.05). Percent viable spermatozoa with high mitochondria membrane potential were lower (p < 0.05) in samples with < 15 × 106 sperm/mL. Experiment 2: Seminal plasma supplementation in samples with 10 × 106 sperm/mL did not restore the loss of sperm kinematics (p > 0.05). Experiment 3: At 144 h, motility was lowest in samples containing 10 × 106 sperm/mL and 10% (v/v) seminal plasma (p < 0.05). Sperm lipid peroxidation did not differ between samples with different sperm concentration.

Conclusion

Long‐term exposure to seminal plasma has a negative impact on in vitro‐aged boar spermatozoa. Reduced sperm‐to‐sperm proximity but not the reduction of seminal plasma limits sperm function in long‐term stored boar semen.
Romiplostim in adult patients with newly diagnosed or persistent immune thrombocytopenia (ITP) for up to 1 year and in those with chronic ITP for more than 1 year: a subgroup analysis of integrated data from completed romiplostim studies
Authors: Kuter David J. , Newland Adrian , Chong Beng H. , Rodeghiero Francesco , Romero Monica T. , Pabinger Ingrid , Chen Yuqi , Wang Kejia , Mehta Bhakti , Eisen Melissa
Published: February 2019

The thrombopoietin receptor agonist romiplostim is approved for second‐line use in chronic immune thrombocytopenia (ITP), but its effects in patients with ITP for ≤1 year are not well characterized. This analysis of pooled data from 9 studies included patients with ITP for ≤1 year (n = 311) or >1 year (n = 726) who failed first‐line treatments and received romiplostim, placebo or standard of care. In subgroup analysis by ITP duration, patient incidences for platelet response at ≥75% of measurements were higher for romiplostim [ITP ≤1 year: 74% (204/277); ITP >1 year: 71% (450/634)] than for placebo/standard of care [ITP ≤1 year: 18% (6/34); ITP >1 year: 9% (8/92)]. Of patients with ≥9 months on study, 16% with ITP ≤1 year and 6% with ITP >1 year discontinued romiplostim and maintained platelet counts ≥50 × 109/l for ≥6 months without ITP treatment (treatment‐free remission). Independent of ITP duration, rates of serious adverse events and bleeding were lower with romiplostim than placebo/standard of care and thrombotic events occurred at similar rates. In this analysis, romiplostim and placebo/standard of care had similar safety profiles and romiplostim increased platelet counts in patients with either ITP ≤1 year or ITP >1 year, with more treatment‐free remission in those with ITP ≤1 year.
An ethical inquiry of support workers' experiences related to sexuality in the context of intellectual disabilities in Quebec, Canada
Authors: Pariseau‐Legault Pierre , Holmes Dave , Ouellet Guillaume , Vallée‐Ouimet Sandrine
Published: February 2019

Accessible summary

Support workers' attitudes towards the sexuality of people with intellectual disabilities are important. They can influence the support people with intellectual disabilities receive regarding their affective and sexual life.

Six support workers talked about their personal experiences. They talked about what they found easy and difficult when helping people with intellectual disabilities express their sexual life and needs.

They said that sexuality is a right, a health matter and an important need. They also said it was sometimes difficult to include sexuality in their work.

They also said they often feel insecure and uncertain about how to help because sexuality is a difficult subject to talk about. They wanted to help people make their own decisions, but also wanted to protect them if needed.

Background

In the last decade, the evolution of support workers' attitudes towards the affective and sexual lives of people with intellectual disabilities has been described as increasingly positive. However, restrictive attitudes targeting affective and sexual life are still documented.

Material and methods

This study aimed to explore the ethical implications of support workers' experiences concerning sexuality in the context of intellectual disabilities in everyday practice. This inquiry was guided by the following research questions: (a) In the context of intellectual disabilities, what meanings do service users' sexuality have for support workers? (b) How are those meanings translated into practice? Inspired by critical phenomenology, in‐depth individual interviews with support workers were conducted and analysed.

Results

One superordinate theme (Negotiating Interventions) and three themes were identified: “Crossing Organizational Borders,” “A Duty to Act Despite Uncertainty” and “Navigating Competing and Contradictory Discourses.”

Conclusion

Support workers' experiences related to sexuality in the context of intellectual disabilities are influenced by how they define their role in a clinical context. This role is influenced by how affective and sexual life is included in practices, local policies and interdisciplinary work. Despite positive attitudinal changes, sexuality is still regarded as a sensitive topic capable of endangering both service users and support workers.
Anatomical analysis of zygomatic bone in ectodermal dysplasia patients with oligodontia
Authors: Wang Haowei , Hung Kuofeng , Zhao Kai , Wang Yueping , Wang Feng , Wu Yiqun
Published: February 2019

Background

Abnormalities of some facial bones derived from the ectomesenchyme have been found in ectodermal dysplasia (ED) patients, but the characteristics of the zygoma are unknown.

Purpose

Comparison between ED patients and normal individuals to understand the anatomical features of the zygoma in ED patients.

Materials and Methods

Thirty patients diagnosed with ED based on clinical features and/or gene sequence tests and 80 normal individuals were recruited from 2016 to 2018. The thickness of the zygomatic body at 12 points on the superior, middle, and inferior areas and the length of four lines were measured on a three‐dimensional cone beam computed tomography image. Differences between ED patients and normal individuals were then compared.

Results

The zygomatic thicknesses and lengths were smaller in ED patients than in normal individuals. For ED patients, the largest thicknesses on the superior, middle, and inferior areas of the zygoma were 8.47 ± 1.49, 7.03 ± 1.56, and 5.99 ± 1.22 mm.

Conclusion

The development of zygomatic thickness on the inferior area and the zygomatic length were insufficient in ED patients with oligodontia. Consequently, zygomatic hypoplasia presented difficulties for the “quad approach” to zygomatic implants in this group of patients.
Profitability or Industrial Relations: What Explains Manufacturing Performance across Indian States?
Authors: Karak Anirban , Basu Deepankar
Published: February 2019

This article begins with a critique of the well‐known claim by Besley and Burgess concerning the negative impact of labour regulation on organized sector manufacturing performance in India. In the second part of the article, the authors use a state‐level panel data set for the period 1969–2005 to analyse the relative importance of profitability (rate of profit as a percentage of the total replacement cost of capital stock) and industrial disputes (man‐days lost to all industrial disputes as a percentage of total workers employed) to explain cross‐state variations of manufacturing performance in India's organized sector. Using three different measures of manufacturing performance — net value added, investment and employment — they find that profitability is more significant than industrial disputes in explaining the variation of manufacturing sector performance across Indian states. The findings presented here therefore question the uncritical acceptance of Besley and Burgess's results in the literature on labour regulation.
First two cases of Zenker's diverticulum treated with flexible endoscopic septum division in Japan
Authors: Kuwai Toshio , Ishaq Sauid
Published: February 2019

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Effects of valsartan, benazepril and their combination in overt nephropathy of type 2 diabetes: A prospective, randomized, controlled trial
Authors: Ruggenenti Piero , Trillini Matias , P. Barlovic Drazenka , Cortinovis Monica , Pisani Antonio , Parvanova Aneliya , Iliev Ilian P. , Ruggiero Barbara , Rota Stefano , Aparicio Maria C. , Perna Annalisa , Peraro Francesco , Diadei Olimpia , Gaspari Flavio , Carrara Fabiola , Stucchi Nadia , Martinetti Davide , Janez Andrej , Gregoric Nadan , Riccio Eleonora , Bossi Antonio C. , Trevisan Roberto , Manunta Paolo , Battaglia Giovanni , David Salvatore , Aucella Filippo , Belviso Antonio , Satta Andrea , Remuzzi Giuseppe ,   on behalf of the VALID Study Organization
Published: February 2019

Aims

To evaluate whether angiotensin‐converting enzyme (ACE) inhibitor and angiotensin II receptor blocker (ARB) combination therapy is more nephroprotective than ACE inhibitor or ARB monotherapy in people with type 2 diabetes and overt nephropathy.

Materials and methods

In this prospective, randomized, open, blind‐endpoint phase III trial sponsored by the Italian Drug Agency, 103 consenting patients with type 2 diabetes, aged >40 years, with serum creatinine levels 159 to 309 μmol/L, spot morning urinary albumin–creatinine ratio > 1000 mg/g (or > 500 mg/g in those on ACE inhibitor or ARB therapy at inclusion) were stratified by centre and randomized to 4.5‐year treatment with valsartan 320 mg/d (n = 36), benazepril 20 mg/d (n = 34) or halved doses of both medications (n = 33). The primary endpoint was end‐stage renal disease (ESRD). Modified intention‐to‐treat analyses were performed.

Results

Recruitment took place between June 2007 and February 2013 at 10 centres in Italy and one in Slovenia. A total of 77 participants completed the study and 26 were prematurely withdrawn. During a median (interquartile range) of 41 (18–54) months, 12 participants on benazepril (35.3%) and nine on combination therapy (27.3%) progressed to ESRD, versus five on valsartan (13.9%). Differences between benazepril (hazard ratio [HR] 3.59, 95% confidence interval [CI] 1.25–10.30; P = 0.018) or combination therapy (HR 3.28, 95% CI 1.07–10.0; P = 0.038) and valsartan were significant, even after adjustment for age, gender and baseline serum creatinine, systolic blood pressure and 24‐hour proteinuria (HR 5.16, 95% CI 1.50–17.75, P = 0.009 and HR 4.75, 95% CI 1.01–22.39, P = 0.049, respectively). Adverse events were distributed similarly among the groups.

Conclusions

In people with type 2 diabetes with nephropathy, valsartan (320 mg/d) safely postponed ESRD more effectively than benazepril (20 mg/d) or than halved doses of both medications.
Lower rates of cardiovascular events and mortality associated with liraglutide use in patients treated with basal insulin: A DEVOTE subanalysis (DEVOTE 10)
Authors: Brown‐Frandsen Kirstine , Emerson Scott S. , McGuire Darren K. , Pieber Thomas R. , Poulter Neil R. , Pratley Richard E. , Zinman Bernard , Ranthe Mattis F. , Grøn Randi , Lange Martin , Moses Alan C. , Örsy Petra , Buse John B. ,   on behalf of the DEVOTE Study Group
Published: February 2019

Aim

To compare the associations between concomitant liraglutide use versus no liraglutide use and the risk of major adverse cardiovascular events (MACE) and all‐cause mortality among patients receiving basal insulin (either insulin degludec [degludec] or insulin glargine 100 units/mL [glargine U100]) in the Trial Comparing Cardiovascular Safety of Insulin Degludec versus Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events (DEVOTE).

Materials and Methods

Patients with type 2 diabetes and high cardiovascular risk were randomized 1:1 to degludec or glargine U100. Hazard ratios for MACE/mortality were calculated using a Cox regression model adjusted for treatment and time‐varying liraglutide use at any time during the trial, without interaction. Sensitivity analyses were adjusted for baseline covariates including, but not limited to, age, sex, smoking and prior cardiovascular disease.

Results

At baseline, 436/7637 (5.7%) patients were treated with liraglutide; after baseline, 187/7637 (2.4%) started and 210/7637 (2.7%) stopped liraglutide. Mean liraglutide exposure from randomization was 530.2 days. Liraglutide use versus no liraglutide use was associated with significantly lower hazard rates for MACE [0.62 (0.41; 0.92)95%CI] and all‐cause mortality [0.50 (0.29; 0.88)95%CI]. There was no significant difference in the rate of severe hypoglycaemia with versus without liraglutide use. Multiple sensitivity analyses yielded similar results.

Conclusions

Use of liraglutide was associated with significantly lower risk of MACE and death in patients with type 2 diabetes and high cardiovascular risk using basal insulin.
The Maronite Leadership’s Approach toward Syria, 1970–2011: Between Integration, Separation, and Pragmatism
Authors: Naor Dan
Published: February 2019

The Maronite–Syria relationship is troublesome, and one can say that the two sides are diametrical opposites. The Maronites, in general, represent the aspiration for an independent Lebanon, while Syria considers Lebanon a part of “Greater Syria” and aspires to annex the Lebanese territories. The Maronite community has consistently resisted these aspirations. However, the Maronite community is not a coherent one, which is reflected in its approach toward Syria. In fact, the Maronite leadership has adopted three different approaches toward Syria: an integrative one that aspires to full cooperation with Syria; a separatist one that strongly considers Lebanon and Syria to be separate states; and a pragmatist one that adheres to intimate or unfriendly ties according to local Lebanese interests. This article introduces the three Maronite approaches and claims that one cannot disassociate these approaches, especially the pragmatist one, from the Syrian policy toward Lebanon, which includes changing alliances according to Syria’s political interests. Moreover, the article suggests that these approaches will remain in place regardless of which Maronite leader supports each one and regardless of who will rule in Syria.
The influence of the mandibular gonial angle on the occurrence of mandibular angle fracture
Authors: Dhara Vasantha , Kamath Abhay T. , Vineetha Ravindranath
Published: February 2019

Background/Aims

Angle fractures represent the largest percentage of mandibular fractures. They pose as a unique entity because of their codependent morphological dynamic factors, rendering the understanding of the mechanism, and treatment challenging. The aim of this study was to analyze the association between the mandibular gonial angle and the risk of mandibular angle fracture while highlighting its clinical relevance.

Materials and Methods

A retrospective analysis of radiographs of patients treated for mandibular fractures was done. The factors studied were as follows: the presence of a high gonial angle and an impacted third molar. The outcome was mandibular angle fracture. The gonial angle was measured using Planmeca Digital Software 3.7.0.R. Status of the third molar was also noted. Data obtained were analyzed using SPSS 22 (IBM Corp, Armonk, NY).

Results

The sample comprised 70 mandibular fractures (32 angle fractures and 38 non‐angle fractures). The mean gonial angle in the angle fracture group was 128.5 ± 5.4º which was 10.2° larger than in the non‐angle group (mean 118.5 ± 4.4º; P = 0.0001). Patients with a high gonial angle were 8.7 times more likely to sustain an angle fracture than those with normal or low gonial angles. A statistically significant relationship between the presence of impacted third molar and patients sustaining mandibular angle fractures was noted (P = 0.0001).

Conclusion

Subjects with a high gonial angle and an impacted third molar are at an increased risk for mandibular angle fracture due to direct and indirect morphological factors.
Local range boundaries vs. large‐scale trade‐offs: climatic and competitive constraints on tree growth
Authors: Anderegg Leander D. L. , HilleRisLambers Janneke
Published: February 2019

Species often respond to human‐caused climate change by shifting where they occur on the landscape. To anticipate these shifts, we need to understand the forces that determine where species currently occur. We tested whether a long‐hypothesised trade‐off between climate and competitive constraints explains where tree species grow on mountain slopes. Using tree rings, we reconstructed growth sensitivity to climate and competition in range centre and range margin tree populations in three climatically distinct regions. We found that climate often constrains growth at environmentally harsh elevational range boundaries, and that climatic and competitive constraints trade‐off at large spatial scales. However, there was less evidence that competition consistently constrained growth at benign elevational range boundaries; thus, local‐scale climate‐competition trade‐offs were infrequent. Our work underscores the difficulty of predicting local‐scale range dynamics, but suggests that the constraints on tree performance at a large‐scale (e.g. latitudinal) may be predicted from ecological theory.
Intravenous thrombolysis in stroke mimics: results from the SITS International Stroke Thrombolysis Register
Authors: Keselman B. , Cooray C. , Vanhooren G. , Bassi P. , Consoli D. , Nichelli P. , Peeters A. , Sanak D. , Zini A. , Wahlgren N. , Ahmed N. , Mazya M. V.
Published: February 2019

Background and purpose

Patients with stroke mimics (SM), i.e. conditions with stroke‐like symptoms, may risk harm if treated with intravenous thrombolysis (IVT). Current guidelines state low risk of intracerebral hemorrhage based on studies comprising a total of <400 SM cases. We aimed to compare safety and outcomes following IVT between patients with acute ischaemic stroke and mimicking conditions.

Methods

We included IVT‐treated ischaemic stroke patients in the SITS International Stroke Thrombolysis Register 2003–2017, examined with magnetic resonance imaging 22–36 h after treatment. Outcomes were parenchymal hematoma (PH) after treatment, symptomatic intracerebral hemorrhage (SICH) per Safe Implementation of Thrombolysis in Stroke Monitoring Study (SITS‐MOST), Second European Co‐operative Stroke Study (ECASS II) and National Institutes of Neurological Disorders and Stroke Study (NINDS) criteria, death and modified Rankin Scale score (mRS) at 3 months.

Results

Of 10 436 patients, 429 mimics (4.1%) were identified. The most common types were functional (30.8%), migraine (17.5%) and seizure (14.2%). Patients with mimics had fewer cerebrovascular risk factors and lower median National Institutes of Health Stroke Scale score [7 (interquartile range, 5–10) vs. 8 (5–14), P < 0.001]. Among mimics versus stroke patients, PH was seen in 1.2% vs. 5.1% (P < 0.001), SICH NINDS in 0.5% vs. 3.9% (P < 0.001), SICH ECASS II in 0.2% vs. 2.1% (P = 0.007) and SICH SITS‐MOST in 0% vs. 0.5% (P = 0.28). Modified Rankin Scale score 0–1 at 3 months was present in 84.1% vs. 57.7% (P < 0.001) and death within 3 months in 2.6% vs. 5.4% (P = 0.028) of mimics and stroke patients, respectively.

Conclusions

This large observational study indicated that PH and SICH following IVT in patients with SM are uncommon.
Mixed evidence for adaptation to environmental pollution
Authors: Loria Alessandra , Cristescu Melania E. , Gonzalez Andrew
Published: February 2019

Adaptation to pollution has been studied since the first observations of heavy metal tolerance in plants decades ago. To document micro‐evolutionary responses to pollution, researchers have used phenotypic, molecular genetics, and demographic approaches. We reviewed 258 articles and evaluated the evidence for adaptive responses following exposure to a wide range of pollutants, across multiple taxonomic groups. We also conducted a meta‐analysis to calculate the magnitude of phenotypic change in invertebrates in response to metal pollution. The majority of studies that reported differences in responses to pollution were focused on phenotypic responses at the individual level. Most of the studies that used demographic assays in their investigations found that negative effects induced by pollution often worsened over multiple generations. Our meta‐analysis did not reveal a significant relationship between metal pollution intensity and changes in the traits studied, and this was probably due to differences in coping responses among different species, the broad array of abiotic and biotic factors, and the weak statistical power of the analysis. We found it difficult to make broad statements about how likely or how common adaptation is in the presence of environmental contamination. Ecological and evolutionary responses to contamination are complex, and difficult to interpret in the context of taxonomic, and methodological biases, and the inconsistent set of approaches that have been used to study adaptation to pollution in the laboratory and in the field. This review emphasizes the need for: (a) long‐term monitoring programs on exposed populations that link demography to phenotypic, genetic, and selection assays; (b) the use of standardized protocols across studies especially for similar taxa. Approaches that combine field and laboratory studies offer the greatest opportunity to reveal the complex eco‐evolutionary feedback that can occur under selection imposed by pollution.
Effects of vatinoxan on cardiorespiratory function and gastrointestinal motility during constant‐rate medetomidine infusion in standing horses
Authors: Tapio H. , Raekallio M. R. , Mykkänen A. , Männikkö S. , Scheinin M. , Bennett R. C. , Vainio O.
Published: February 2019

Background

Medetomidine suppresses cardiovascular function and reduces gastrointestinal motility in horses mainly through peripheral α2‐adrenoceptors. Vatinoxan, a peripheral α2‐antagonist, has been shown experimentally to alleviate the adverse effects of some α2‐agonists in horses. However, vatinoxan has not been investigated during constant‐rate infusion (CRI) of medetomidine in standing horses.

Objectives

To evaluate effects of vatinoxan on cardiovascular function, gastrointestinal motility and on sedation level during CRI of medetomidine.

Study design

Experimental, randomised, blinded, cross‐over study.

Methods

Six healthy horses were given medetomidine hydrochloride, 7 μg/kg i.v., without (MED) and with (MED+V) vatinoxan hydrochloride, 140 μg/kg i.v., followed by CRI of medetomidine at 3.5 μg/kg/h for 60 min. Cardiorespiratory variables were recorded and borborygmi and sedation levels were scored for 120 min. Plasma drug concentrations were measured. The data were analysed using repeated measures ANCOVA and paired t‐tests as appropriate.

Results

Initially heart rate (HR) was significantly lower and mean arterial blood pressure (MAP) significantly higher with MED compared with MED+V. For example at 10 min HR (mean ± s.d.) was 26 ± 2 and 31 ± 5 beats/minute (P = 0.04) and MAP 129 ± 15 and 103 ± 13 mmHg (P<0.001) respectively. At 10 min, cardiac index was lower (P = 0.02) and systemic vascular resistance higher (P = 0.001) with MED than with MED+V. Borborygmi were reduced after MED; this effect was attenuated by vatinoxan (P<0.001). All horses were sedated with medetomidine, but the mean sedation scores were reduced with MED+V until 20 min (6.8 ± 0.8 and 4.5 ± 1.5 with MED and MED+V, respectively, at 10 min, P = 0.001). Plasma concentration of dexmedetomidine was significantly lower in the presence of vatinoxan (P = 0.01).

Main limitations

Experimental study with healthy, unstimulated animals.

Conclusions

Vatinoxan administered i.v. with a loading dose of medetomidine improved cardiovascular function and gastrointestinal motility during medetomidine CRI in healthy horses. Sedation was slightly yet significantly reduced during the first 20 min..

The Summary is available in Portuguese – see Supporting Information
Associations between an educational attainment polygenic score with educational attainment in an African American sample
Authors: Rabinowitz Jill A. , Kuo Sally I.‐C. , Felder William , Musci Rashelle J. , Bettencourt Amie , Benke Kelly , Sisto Danielle Y. , Smail Emily , Uhl George , Maher Brion S. , Kouzis Anthony , Ialongo Nicholas S.
Published: February 2019

Polygenic propensity for educational attainment has been associated with higher education attendance, academic achievement and criminal offending in predominantly European samples; however, less is known about whether this polygenic propensity is associated with these outcomes among African Americans. Using an educational attainment polygenic score (EA PGS), the present study examined whether this score was associated with post‐secondary education, academic achievement and criminal offending in an urban, African American sample. Three cohorts of participants (N = 1050; 43.9% male) were initially recruited for an elementary school‐based universal prevention trial in a Mid‐Atlantic city and followed into young adulthood. Standardized tests of reading and math achievement were administered in first grade. At age 20, participants reported on their level of education attained, and records of incarceration were obtained from Maryland's Criminal Justice Information System. In young adulthood, DNA was collected and extracted from blood or buccal swabs and genotyped. An EA PGS was created using results from a large‐scale genome‐wide association study on educational attainment. A higher EA PGS was associated with a greater log odds of post‐secondary education. The EA PGS was not associated with reading achievement, although a significant relationship was found with math achievement in the third cohort. These findings contribute to the dearth of molecular genetics work conducted in African American samples and highlight that polygenic propensity for educational attainment is associated with higher education attendance.
Heterogeneity and incorporation of chromium isotopes in recent marine molluscs (Mytilus)
Authors: Bruggmann Sylvie , Klaebe Robert M. , Paulukat Cora , Frei Robert
Published: February 2019

The mollusc genus Mytilus is abundant in various modern marine environments and is an important substrate for palaeo‐proxy work. The redox‐sensitive chromium (Cr) isotope system is emerging as a proxy for changes in the oxidation state of the Earth's atmosphere and oceans. However, potential isotopic offsets between ambient sea water and modern biogenic carbonates have yet to be constrained. We measured Cr concentrations ([Cr]) and isotope variations (δ53Cr) in recent mollusc shells (Mytilus) from open and restricted marine environments and compared these to ambient sea water δ53Cr values. We found a large range in mollusc [Cr] (12–309 ppb) and δ53Cr values (−0.30 to +1.25‰) and in the offset between δ53Cr values of mollusc shells and ambient sea water (, −0.17 to −0.91‰). Step digestions of cultivated Mytilus edulis specimens indicate that Cr is mainly concentrated in organic components of the shell (periostracum: 407 ppb, n = 2), whereas the mollusc carbonate minerals contain ≤3 ppb Cr. Analyses of individual Cr‐hosting phases (i.e., carbonate minerals and organic matrix) did not reveal significant differences in δ53Cr values, and thus, we suggest that Cr isotope fractionation may likely take place prior to rather than during biomineralisation of Mytilus shells. Heterogeneity of δ53Cr values in mollusc shells depends on sea water chemistry (e.g., salinity, food availability, faeces). The main control for δ53Cr values incorporated into shells, however, is likely vital effects (in particular shell valve closure time) since Cr can be partially or quantitatively reduced in sea water trapped between closed shell valves. The δ53Cr values recorded in Mytilus shells may thus be de‐coupled from the redox conditions of ambient sea water, introducing additional heterogeneity that needs to be better constrained before using δ53Cr values in mollusc shells for palaeo‐reconstructions.
Land‐sparing agriculture sustains higher levels of avian functional diversity than land sharing
Authors: Cannon Patrick G. , Gilroy James J. , Tobias Joseph A. , Anderson Alex , Haugaasen Torbjørn , Edwards David P.
Published: February 2019

The ecological impacts of meeting rising demands for food production can potentially be mitigated by two competing land‐use strategies: off‐setting natural habitats through intensification of existing farmland (land sparing), or elevating biodiversity within the agricultural matrix via the integration of “wildlife‐friendly” habitat features (land sharing). However, a key unanswered question is whether sparing or sharing farming would best conserve functional diversity, which can promote ecosystem stability and resilience to future land‐use change. Focusing on bird communities in tropical cloud forests of the Colombian Andes, we test the performance of each strategy in conserving functional diversity. We show that multiple components of avian functional diversity in farmland are positively related to the proximity and extent of natural forest. Using landscape and community simulations, we also show that land‐sparing agriculture conserves greater functional diversity and predicts higher abundance of species supplying key ecological functions than land sharing, with sharing becoming progressively inferior with increasing isolation from remnant forest. These results suggest low‐intensity agriculture is likely to conserve little functional diversity unless large blocks of adjacent natural habitat are protected, consistent with land sparing. To ensure the retention of functionally diverse ecosystems, we urgently need to implement mechanisms for increasing farmland productivity whilst protecting spared land.
The dielectric property and phase transition of Sr‐doping effect of Ba1−xSrxTi0.9Mn0.1O3‐δ ceramic
Authors: Lei Chien‐Ming , Siao Ya‐Shan
Published: February 2019

In this work, we prepare Ba1−xSrxTi0.9Mn.01O3‐δ (x = 0.00, 0.01, 0.03, 0.05, and 0.07) ceramics by the mixed oxide method and study the relationship between phase transition and dielectric property of the ceramics. The phase of the samples transformed from a hexagonal phase to mixed phases due to the increase in Sr doping amount. The X‐ray diffraction (XRD) profiles and Raman spectra of the samples also show the same phase transformation due to increasing Sr doping amount. The XRD pattern of the undoped sample indicates a single h‐BaTiO3 phase with P63/mmc symmetric space group, while the samples with high Sr doping amounts have a mixed phase with t‐BaTiO3 with P4mm symmetric space group. The scanning electron microscopy images show two types of BaTiO3 grains, which grew with increasing sintering temperature. With increasing Sr concentration, the K‐values (relative dielectric constant) of the ceramics increased, while the Qxf values (the quality factor multiplied by frequency) decreased, which indicate that the microwave dielectric property is related to phase transformation.
Unusual findings of acute myeloid leukemia with inv(3)(q21q26.2) or t(3;3)(q21;q26.2): A multicenter study
Authors: Gong Xubo , Yu Teng , Tang Qiusu , Fu Yanbiao , Wu Jie , Zhu Yongze , Tu Hongxiang , Ge Haifeng , Lu Xingguo , Gong Donghua , Zhao Xiaoying
Published: February 2019

Introduction

AML with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2) [inv(3)/t(3;3)] was very rare. Currently, most reports of AML‐inv(3)/t(3;3) were from Western countries, and few reports were from Asian countries. Racial differences in patients with AML‐inv(3)/t(3;3) are still unknown.

Methods

Between January 1996 and April 2018, a total of 37 AML cases with inv(3)/t(3;3) were studied retrospectively. They were collected from 2229 primary AML cases performed with conventional cytogenetic analysis (37/2229, 1.66%).

Results

Here, some differences were found by comparing our data with those from Western countries. In our series, AML with inv(3)(q21q26) had a lower incidence than that with t(3;3)(q21;q26) (11 vs 26 cases). Our patients seemed to be more younger (median, 43 years) and have lower hemoglobin concentrations (median, 73 g/L) and higher platelet count (median, 351 × 109/L). A higher incidence of acute monoblastic and monocytic leukemia (45.9%) was observed in our patients. Immunophenotypic studies showed that CD38 (30.8%) was not so frequently expressed as that in the earlier reports. Mutations analysis showed a high frequency of NRAS mutations (45.0%), followed by SF3B1(15.0%), GATA2(15.0%), FLT3‐ITD(10.0%), C‐Kit/D816(5.0%), and CEBPA(5.0%), without mutation of NPM1(Exon12)or JAK2V617.

Conclusion

Ethnic differences do exist between the Chinese and Western patients with AML‐inv(3)/t(3;3), and more attention should be paid involving different ethnic populations and geographic regions.
Establishment and molecular characterization of decitabine‐resistant K562 cells
Authors: Wen Xiang‐Mei , Zhang Ting‐Juan , Ma Ji‐Chun , Zhou Jing‐Dong , Xu Zi‐Jun , Zhu Xiao‐Wen , Yuan Qian , Ji Run‐Bi , Chen Qin , Deng Zhao‐Qun , Lin Jiang , Qian Jun
Published: February 2019

The clinical activity of decitabine (5‐aza‐2‐deoxycytidine, DAC), a hypomethylating agent, has been demonstrated in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients. However, secondary resistance to this agent often occurs during treatment and leads to treatment failure. It is important to clarify the mechanisms underlying the resistance for improving the efficacy. In this study, by gradually increasing concentration after a continuous induction of DAC, we established the DAC‐resistant K562 cell line (K562/DAC) from its parental cell line K562. The proliferation and survival rate of K562/DAC was significantly increased, whereas the apoptosis rate was remarkably decreased than that of K562 after DAC treatment. In K562/DAC, a total of 108 genes were upregulated and 118 genes were downregulated by RNA‐Seq. In addition, we also observed aberrant expression of DDX43/H19/miR‐186 axis (increased DDX43/H19 and decreased miR‐186) in K562/DAC cells. Ectopic expression of DDX43 in parental K562 cells rendered cells resistant to the DAC. Taken together, we successfully established DAC‐resistant K562 cell line which can serve as a good model for investigating DAC resistance mechanisms, and DDX43/H19/miR‐186 may be involved in DAC resistance in K562.
β‐arrestin 2 negatively regulates NOD2 signalling pathway through association with TRAF6 in microglia after cerebral ischaemia/reperfusion injury
Authors: Chen Lin , Kong Lingjun , Wei Xinbing , Wang Yimeng , Wang Bing , Zhang Xiumei , Sun Jinpeng , Liu Huiqing
Published: February 2019

We previously reported that nucleotide‐binding oligomerization domain‐containing protein (NOD) 2 was involved in the inflammatory responses to cerebral ischaemia/reperfusion (I/R) insult. However, the mechanism by which NOD2 participates in brain ischaemic injury and the regulation of NOD2 in the process are still obscure. Increased β‐arrestin 2 (ARRB2) expression was observed in microglia following cerebral I/R in wild‐type mice besides the up‐regulation of NOD2 and TRAF6. Stimulation of NOD2 by muramyl dipeptide (MDP) in BV2 cells induced the activation of NF‐κB by the phosphorylation of p65 subunit and the degradation of IκBα. Meanwhile, the protein level of Cyclooxygenase‐2 (COX‐2), the protein expression and activity of MMP‐9 were significantly increased in BV2 cells after administration of MDP. Furthermore, overexpression of ARRB2 significantly suppressed the inflammation induced by MDP, silence of ARRB2 significantly enhanced the inflammation induced by MDP in BV2 cells. In addition, we observed endogenous interaction of TRAF6 and ARRB2 after stimulation of MDP or cerebral I/R insult, indicating ARRB2 negatively regulates NOD2‐triggered inflammatory signalling pathway by associating with TRAF6 in microglia after cerebral I/R injury. Finally, the in vivo study clearly confirmed that ARRB2 negatively regulated NOD2‐induced inflammatory response, as ARRB2 deficiency exacerbated stroke outcomes and aggravated the NF‐κB signalling pathway induced by NOD2 stimulation after cerebral I/R injury. These findings revealed ARRB2 negatively regulated NOD2 signalling pathway through the association with TRAF6 in cerebral I/R injury.