bluuebunny/crossref_metadata_2025 huggingface dataset:
Chromatin accessibility changes betweenArabidopsisstem cells and mesophyll cells illuminate cell type-specific transcription factor networks
Authors: Sijacic Paja , Bajic Marko , McKinney Elizabeth C. , Meagher Richard B. , Deal Roger B.
Published: November 2017

Background

Cell differentiation is driven by changes in transcription factor (TF) activity and subsequent alterations in transcription. To study this process, differences in TF binding between cell types can be deduced by methods that probe chromatin accessibility. We used cell type-specific nuclei purification followed by the Assay for Transposase Accessible Chromatin (ATAC-seq) to delineate differences in chromatin accessibility and TF regulatory networks between stem cells of the shoot apical meristem (SAM) and differentiated leaf mesophyll cells ofArabidopsis thaliana.

Results

Chromatin accessibility profiles of SAM stem cells and leaf mesophyll cells were highly similar at a qualitative level, yet thousands of regions of quantitatively different chromatin accessibility were also identified. We found that chromatin regions preferentially accessible in mesophyll cells tended to also be substantially accessible in the stem cells as compared to the genome-wide average, whereas the converse was not true. Analysis of genomic regions preferentially accessible in each cell type identified hundreds of overrepresented TF binding motifs, highlighting a set of TFs that are likely important for each cell type. Among these, we found evidence for extensive co-regulation of target genes by multiple TFs that are preferentially expressed in one cell type or the other. For example, a set of zinc-finger TFs appear to control a suite of growth-and development-related genes specifically in stem cells, while another TF set co-regulates genes involved in light responses and photosynthesis specifically in mesophyll cells. Interestingly, the TFs within both of these sets also show evidence of extensively co-regulating each other.

Conclusions

Quantitative analysis of chromatin accessibility differences between stem cells and differentiated mesophyll cells allowed us to identify TF regulatory networks and downstream target genes that are likely to be functionally important in each cell type. Our findings that mesophyll cell-enriched accessible sites tend to already be substantially accessible in stem cells, but not vice versa, suggests that widespread regulatory element accessibility may be important for the developmental plasticity of stem cells. This work also demonstrates the utility of cell type-specific chromatin accessibility profiling in quickly developing testable models of regulatory control differences between cell types.
DO CELLMATES MATTER? A CAUSAL TEST OF THE SCHOOLS OF CRIME HYPOTHESIS WITH IMPLICATIONS FOR DIFFERENTIAL ASSOCIATION AND DETERRENCE THEORIES
Authors: HARRIS HEATHER M. , NAKAMURA KIMINORI , BUCKLEN KRISTOFER BRET
Published: November 2017

In the schools of crime hypothesis, social interactions between inmates are assumed to produce criminogenic rather than deterrent prison peer effects, thus implicating them in the persistence of high recidivism rates and null or criminogenic prison effects. We assess the validity of the schools of crime hypothesis by estimating prison peer effects that result from differential cellmate associations in a male, first‐time release cohort from the Pennsylvania Department of Corrections. To isolate causal prison peer effects in the presence of essential heterogeneity, we use a semiparametric local instrumental variables estimation strategy. Our results do not support the school of crime hypothesis. In our sample, prison peer effects produced in interaction with more criminally experienced cellmates are always null or deterrent rather than criminogenic. Although we do not explicitly test for the operant conditioning mechanisms theorized to underlie social influence in the context of differential association, we argue that, under the assumption that the differential association context relates positively to the direction of peer influence, our universally noncriminogenic estimates exclude direct reinforcement, vicarious reinforcement, and direct punishment as potential drivers of prison peer effects produced in interaction with more criminally experienced cellmates. Our results support the assertion that operant conditioning mechanisms connect differential association and deterrence theories.
AGE, PERIOD, AND COHORT EFFECTS ON DEATH PENALTY ATTITUDES IN THE UNITED STATES, 1974–2014
Authors: ANDERSON AMY L. , LYTLE ROBERT , SCHWADEL PHILIP
Published: November 2017

In this article, we further the understanding of both changes in public opinion on capital punishment in the United States and changes in the factors associated with public opinion on the death penalty. Support for the death penalty may be motivated by events happening during specific time periods, and it can vary across birth cohorts as a result of cohort‐specific socialization processes, demographic changes, and formative events that are specific to each generation. An explication of the sources of and variation in death penalty attitudes over time would benefit from the accounting for the age of the respondent, the year of the survey response, and the birth cohort of the respondent. We improve on previous research by using multiple approaches including hierarchical age–period–cohort models and data from the General Social Survey (N = 41,474) to examine changes in death penalty attitudes over time and across birth cohorts. The results showed curvilinear age effects, strong period effects, and weak cohort effects on death penalty support. The violent crime rate explained much of the variation in support for the death penalty across periods. The examination of subgroup differences suggests that support for the death penalty is becoming concentrated among Whites, Protestants, and Republicans.
DOES THE GENDER GAP IN DELINQUENCY VARY BY LEVEL OF PATRIARCHY? A CROSS‐NATIONAL COMPARATIVE ANALYSIS
Authors: SAVOLAINEN JUKKA , APPLIN SAMANTHA , MESSNER STEVEN F. , HUGHES LORINE A. , LYTLE ROBERT , KIVIVUORI JANNE
Published: November 2017

We examined cross‐national variation in the gender differential in offending, which is often referred to as the gender gap in crime. Analyses were directed toward two empirical questions: 1) Is the gender gap narrower in less patriarchal sociocultural settings, and if so, 2) is this outcome a result of higher levels of offending on the part of girls, lower levels of offending on the part of boys, or some combination thereof? To address these questions, we compiled a multilevel, cross‐national data set combining information on self‐reported offending from the second International Self Report Delinquency Survey (ISRD‐2) with normative and structural indicators of societal levels of patriarchy. The results from regression equations showed the gender gap in delinquency to be narrower at reduced national levels of patriarchy. The predicted probabilities calculated from regression coefficients suggested that this narrowing is a result of increased offending among girls and, to some extent, of decreased offending among boys in less patriarchal nations. Sensitivity checks with alternative model specifications confirmed these patterns but also identified a potential outlier. We discuss the implications of these descriptive findings for etiological research and theory.
Early Recurrence of First Unprovoked Seizures in Children
Authors: Goldberg Leah R. , Kernie Catherine G. , Lillis Kathleen , Bennett Jonathan , Conners Gregory , Macias Charles G. , Callahan James , Akman Cigdem , Allen Hauser W. , Kuppermann Nathan , Dayan Peter S.
Published: November 2017

Objectives

The risk of early seizure recurrences after first unprovoked seizures in children is largely unknown. We aimed to determine the rate of seizure recurrence within 14 days of first unprovoked seizures in children and identify associated risk factors. Secondarily, we aimed to determine the risk of recurrence at 48 hours and 4 months.

Methods

We conducted a secondary analysis of a multicenter cohort study of children 29 days to 18 years with first unprovoked seizures. Emergency department (ED) clinicians completed standardized histories and physical examinations. The primary outcome, recurrent seizure at 14 days, and the secondary outcomes, recurrence at 48 hours and 4 months, were assessed by telephone follow‐up and medical record review. For each recurrence time point, we excluded those patients for whom no seizure had recurred but chronic antiepileptic drugs had been initiated.

Results

A total of 475 patients were enrolled in the parent study. Of evaluable patients for this secondary analysis, 26 of 392 (6.6%, 95% confidence interval [CI] = 4.4%–9.6%) had recurrences within 48 hours of the incident seizures, 58 of 366 (15.8%, 95% CI = 12.3%–20.0%) had recurrences within 14 days, and 107 of 340 (31.5%, 95% CI = 26.6%–36.7%) had recurrences within 4 months. On logistic regression analysis, age younger than 3 years was independently associated with a higher risk of 14‐day recurrence (adjusted odds ratio [OR] = 2.1, 95% CI = 1.2–3.7; p = 0.01). Having had more than one seizure within the 24 hours prior to ED presentation was independently associated with a higher risk of seizure recurrence at 48 hours (adjusted OR = 4.3, 95% CI = 1.9–9.8; p < 0.001).

Conclusions

Risk of seizure recurrence 14 days after first unprovoked seizures in children is substantial, with younger children at higher risk. Prompt completion of an electroencephalogram and evaluation by a neurologist is appropriate for these children.
The prevalence, incidence, and gender and age‐specific incidence of problem gambling: results of the Swedish longitudinal gambling study (Swelogs)
Authors: Abbott Max , Romild Ulla , Volberg Rachel
Published: November 2017

Aims

To estimate the prevalence, incidence and gender and age‐specific incidence of problem gambling in the Swedish adult population.

Design

Longitudinal cohort study with linkage to register data.

Setting

Sweden.

Participants

Stratified random sample aged 16–84 years at baseline (n = 8165) re‐assessed a year later (n = 6021).

Measurements

Problem gambling (life‐time and past 12 months) was measured by the South Oaks Gambling Screen–Revised (SOGS‐R). Past 12‐month (current) problem gambling was also measured by the Problem Gambling Severity Index (PGSI).

Findings

The SOGS‐R combined current pathological and problem gambling prevalence rate (PR) was 2.1 [95% confidence interval (CI) = 1.8–2.4] at baseline and 1.7 (1.4–2.0) at follow‐up, approximately half the corresponding life‐time estimates.[Correction added on 22 Dec 2017, after first online publication: In the preceding sentence, the SOGS‐R combined current pathological and problem gambling prevalence rate (PR) was incorrectly reported as being double the corresponding life‐time rate. It has been corrected in this version.] PGSI combined current problem and moderate‐risk gambling PRs were 2.2 (1.9–2.5) at baseline and 1.9 (1.6–2.2) at follow‐up. Combined incidence rates (IRs) were 1.0 (0.8–1.3) (SOGS‐R) and 1.4 (1.1–1.7) (PGSI), with more than three‐quarters being new cases. While first‐time IRs did not vary by gender, males had a higher relapse IR and proportionately more females were new cases. The young adult IR was more than double the older adult IR; similar proportions were new cases.

Conclusions

The actual incidence of problem gambling relapse in Sweden is likely to be higher than estimated. The profile of problem gambling in Sweden is likely to change over time, with increased proportions of women and older adults.
Efficacy of a web‐based intervention with and without guidance for employees with risky drinking: results of a three‐arm randomized controlled trial
Authors: Boß Leif , Lehr Dirk , Schaub Michael Patrick , Paz Castro Raquel , Riper Heleen , Berking Matthias , Ebert David Daniel
Published: November 2017

Aims

To test the efficacy of a web‐based alcohol intervention with and without guidance.

Design

Three parallel groups with primary end‐point after 6 weeks.

Setting

Open recruitment in the German working population.

Participants

Adults (178 males/256 females, mean age 47 years) consuming at least 21/14 weekly standard units of alcohol (SUA) and scoring ≥ 8/6 on the Alcohol Use Disorders Identification Test.

Intervention

Five web‐based modules including personalized normative feedback, motivational interviewing, goal setting, problem‐solving and emotion regulation during 5 weeks. One intervention group received an unguided self‐help version (n=146) and the second received additional adherence‐focused guidance by eCoaches (n=144). Controls were on a waiting list with full access to usual care (n=144).

Measurements

Primary outcome was weekly consumed SUA after 6 weeks. SUA after 6 months was examined as secondary outcome, next to numbers of participants drinking within the low‐risk range, and general and work‐specific mental health measures.

Findings

All groups showed reductions of mean weekly SUA after 6 weeks (unguided: −8.0; guided: −8.5; control: −3.2). There was no significant difference between the unguided and guided intervention (P=0.324). Participants in the combined intervention group reported significantly fewer SUA than controls [B=−4.85, 95% confidence interval (CI)=−7.02 to −2.68, P < 0.001]. The intervention groups also showed significant reductions in SUA consumption after 6 months (B=−5.72, 95% CI=−7.71 to −3.73, P < 0.001) and improvements regarding general and work‐related mental health outcomes after 6 weeks and 6 months.

Conclusions

A web‐based alcohol intervention, administered with or without personal guidance, significantly reduced mean weekly alcohol consumption and improved mental health and work‐related outcomes in the German working population.
Cost‐effectiveness of personal tailored risk information and taster sessions to increase the uptake of the NHS stop smoking services: the Start2quit randomized controlled trial
Authors: Wu Qi , Gilbert Hazel , Nazareth Irwin , Sutton Stephen , Morris Richard , Petersen Irene , Galton Simon , Parrott Steve
Published: November 2017

Aims

To assess the cost‐effectiveness of a two‐component intervention designed to increase attendance at the NHS Stop Smoking Services (SSSs) in England.

Design

Cost‐effectiveness analysis alongside a randomized controlled trial (Start2quit).

Setting

NHS SSS and general practices in England.

Participants

The study comprised 4384 smokers aged 16 years or more identified from medical records in 99 participating practices, who were motivated to quit and had not attended the SSS in the previous 12 months.

Intervention and comparator

Intervention was a personalized and tailored letter sent from the general practitioner (GP) and a personal invitation and appointment to attend a taster session providing information about SSS. Control was a standard generic letter from the GP advertising SSS and asking smokers to contact the service to make an appointment.

Measurements

Costs measured from an NHS/personal social services perspective, estimated health gains in quality‐adjusted life‐years (QALYs) measured with EQ‐5D and incremental cost per QALY gained during both 6 months and a life‐time horizon.

Findings

During the trial period, the adjusted mean difference in costs was £92 [95% confidence interval (CI) = –£32 to –£216) and the adjusted mean difference in QALY gains was 0.002 (95% CI = –0.001 to 0.004). This generates an incremental cost per QALY gained of £59 401. The probability that the tailored letter and taster session is more cost‐effective than the generic letter at 6 months is never above 50%. In contrast, the discounted life‐time health‐care cost was lower in the intervention group, while the life‐time QALY gains were significantly higher. The probability that the intervention is more cost‐effective is more than 83% using a £20 000–30 000 per QALY‐gained decision‐making threshold.

Conclusions

An intervention designed to increase attendance at the NHS Stop Smoking Services (tailored letter and taster session in the services) appears less likely to be cost‐effective than a generic letter in the short term, but is likely to become more cost‐effective than the generic letter during the long term.
Risk factors for asthma after infant bronchiolitis
Authors: Törmänen S. , Lauhkonen E. , Riikonen R. , Koponen P. , Huhtala H. , Helminen M. , Korppi M. , Nuolivirta K.
Published: November 2017

Background

Five studies carried out after bronchiolitis at less than 24 months of age, with a follow‐up of more than 10 years, reported that atopic dermatitis, family asthma, early‐life exposure to tobacco smoke and rhinovirus aetiology were early‐life risk factors for later asthma. This study evaluated the long‐term outcome at 11‐13 years of age of children who were hospitalized for bronchiolitis in early infancy.

Methods

We previously prospectively followed 166 children hospitalized for bronchiolitis at less than 6 months of age until 5‐7 years of age. The current study included a structured questionnaire, parental interviews, clinical examinations and bronchodilation test of 138 of those children at 11‐13 years of age.

Results

Respiratory syncytial virus caused 66% of the bronchiolitis cases, and nearly half of the patients were exposed to tobacco smoke in early life. Doctor‐diagnosed asthma was present in 13% of the former bronchiolitis patients at 11‐13 years of age. Maternal asthma was the only independently significant risk factor in early life (adjusted OR 3.45, 95% CI 1.07‐11.74), as was allergic rhinitis at 5‐7 years of age (adjusted OR 4.06, 95% CI 1.35‐12.25).

Conclusions

After bronchiolitis at less than 6 months of age, the risk of doctor‐diagnosed asthma at 11‐13 years was about twice that of the general Finnish population. Maternal asthma was the only independently significant early‐life risk factor for current asthma at 11‐13 years of age.
A systematic review of the incidence of and risk factors for postoperative atrial fibrillation following general surgery
Authors: Chebbout R. , Heywood E. G. , Drake T. M. , Wild J. R. L. , Lee J. , Wilson M. , Lee M. J.
Published: November 2017

Atrial fibrillation is a common cardiac arrhythmia and can occur de novo following a surgical procedure. It is associated with increased inpatient and long‐term mortality. There is limited evidence concerning new‐onset atrial fibrillation following abdominal surgery. This study aimed to identify the prevalence of and risk factors for postoperative atrial fibrillation in the general surgical population. A systematic search of the Embase, MEDLINE and Cochrane (CENTRAL) databases was conducted. Studies were included in the review if they reported cases of new‐onset atrial fibrillation within 30 days of the index operation. Results were evaluated qualitatively due to substantial clinical heterogeneity. Incidence rates were pooled using a weighted random‐effects meta‐analysis model. A total of 835 records were initially identified, from which 32 full texts were retrieved. Following review, 13 studies were included that involved 52,959 patients, of whom 10.94% (95%CI 7.22–15.33) developed atrial fibrillation. Five studies of patients undergoing oesophagectomy (n = 376/1923) had a weighted average rate of 17.66% (95%CI 12.16–21.47), compared with 7.63% (95%CI 4.39–11.98) from eight studies of non‐oesophageal surgery (n = 2927/51,036). Identified risk factors included: increasing age; history of cardiac disease; postoperative complications, particularly, sepsis, pneumonia and pleural effusions. New‐onset postoperative atrial fibrillation is common, and is more frequent after surgery involving the thorax. Future work should focus on stratifying risk to allow targeted prophylaxis of atrial fibrillation and other peri‐operative complications.
Monitoring foveal sparing in geographic atrophy with fluorescence lifetime imaging ophthalmoscopy – a novel approach
Authors: Sauer Lydia , Klemm Matthias , Peters Sven , Schweitzer Dietrich , Schmidt Johanna , Kreilkamp Lukas , Ramm Lisa , Meller Daniel , Hammer Martin
Published: November 2017

Purpose

To investigate fundus autofluorescence (FAF) lifetimes in geographic atrophy (GA) with a focus on macular pigment (MP) and foveal sparing.

Methods

The study included 35 eyes from 28 patients (mean age 79.2 ± 8.0 years) with GA. A 30° retinal field, centred at the macula, was investigated using fluorescence lifetime imaging ophthalmoscopy (FLIO). The FLIO technology is based on a Heidelberg Engineering Spectralis system. Decays of FAF were detected in a short (498–560 nm, SSC) and long (560–720 nm, LSC) spectral channel. The mean fluorescence lifetime, τm, was calculated from a three‐exponential approximation of the FAF decays. Macular optical coherence tomography (OCT) scans as well as fundus photography were recorded.

Results

Review of FLIO data reveals specific patterns of significantly prolonged τm in regions of GA (SSC 616 ± 343 ps, LSC 615 ± 154 ps) as compared to non‐atrophic regions. Large τm differences between the fovea and atrophic areas correlate with better visual acuity (VA). Shorter τm at the fovea than within other non‐atrophic regions indicates sparing, which was identified in 16 eyes. Seventy per cent of patients treated with lutein supplementation showed foveal sparing, whereas the rate among non‐supplemented patients was 22%.

Conclusion

Using FLIO, we present a novel way to detect foveal sparing, investigate MP, and analyse variability of τm in different foveal regions (including the prognostic valuable border region) in GA. These findings support the potential utility of FLIO in monitoring disease progression. The findings also highlight the possibly protective effect of lutein supplementation, with implication in recording the presence and distributional pattern of MP.
BRAF V600E, TERT promoter mutations and CDKN2A/B homozygous deletions are frequent in epithelioid glioblastomas: a histological and molecular analysis focusing on intratumoral heterogeneity
Authors: Nakajima Nozomi , Nobusawa Sumihito , Nakata Satoshi , Nakada Mitsutoshi , Yamazaki Tatsuya , Matsumura Nozomi , Harada Kenichi , Matsuda Hadzki , Funata Nobuaki , Nagai Shoichi , Nakamura Hideo , Sasaki Atsushi , Akimoto Jiro , Hirato Junko , Yokoo Hideaki
Published: November 2017

Epithelioid glioblastoma (E‐GBM) is a rare aggressive variant of IDH‐wildtype glioblastoma newly recognized in the 2016 World Health Organization classification, composed predominantly of monotonous, patternless sheets of round cells with laterally positioned nuclei and plump eosinophilic cytoplasm. Approximately 50% of E‐GBM harbor BRAF V600E, which is much less frequently found in other types of glioblastomas. Most E‐GBM are recognized as primary/de novo lesions; however, several E‐GBM with co‐ or pre‐existing lower‐grade lesions have been reported. To better understand associations between E‐GBM and the lower‐grade lesions, we undertook a histological and molecular analysis of 14 E‐GBM, 10 of which exhibited lower‐grade glioma‐like components (8 E‐GBM with co‐existing diffuse glioma‐like components, 1 E‐GBM with a co‐existing PXA‐like component and 1 E‐GBM with a pre‐existing PXA). Molecular results demonstrated that the prevalence of BRAF V600E, TERT promoter mutations and CDKN2A/B homozygous deletions in E‐GBM were 13/14 (93%), 10/14 (71%) and 11/14 (79%), respectively, and concurrent BRAF V600E, TERT promoter mutations and CDKN2A/B homozygous deletions were observed in 7/14 (50%) of E‐GBM. These alterations were also frequently seen in the lower‐grade lesions irrespective of the histology. Genetic analysis including array comparative genomic hybridization performed for 5 E‐GBM with co‐ and pre‐existing lower‐grade components revealed that all molecular changes found in the lower‐grade components were also observed in the E‐GBM components, and additional changes were detected in the E‐GBM components. In conclusion, E‐GBM frequently exhibit BRAF V600E, TERT promoter mutations and CDKN2A/B homozygous deletions and these alterations tend to coexist in E‐GBM. Taken together with the facts that only one PXA preceded E‐GBM among these lower‐grade lesions, and that co‐occurrence of BRAF V600E, TERT promoter mutations and CDKN2A/B homozygous deletions have been reported to be rare in conventional lower‐grade diffuse gliomas, the diffuse glioma‐like components may be distinct infiltrative components of E‐GBM, reflecting intratumoral heterogeneity.
Activation of plasmacytoid dendritic cells by apoptotic particles – mechanism for the loss of immunological tolerance in Sjögren's syndrome
Authors: Ainola M , Porola P , Takakubo Y , Przybyla B , Kouri V P , Tolvanen T A , Hänninen A , Nordström D C
Published: November 2017

Sjögren's syndrome (SS) is a common autoimmune disease targeting salivary and lacrimal glands. It is strongly female-dominant, characterized by low oestrogen levels combined with a local intracrine dihydrotestosterone defect. We hypothesized that these hormonal deficits lead to increased apoptosis of the epithelial cells and plasmacytoid dendritic cell (pDC)-mediated proinflammatory host responses. Expression of Toll-like receptors (TLRs)-7 and -9 and cytokine profiles was studied in pDCs treated with apoptotic particles collected in consecutive centrifugation steps of media from apoptotic cells. Expression and localization of SS autoantigens in these particles was also analysed. Furthermore, the effects of sex steroids were studied in pDCs cultured with several concentrations of dihydrotestosterone and 17-β-oestradiol, and in saliva of patient treated with dehydroepiandrosterone. Apoptosis of the epithelial cells led to cleavage and translocation of SS-autoantigens, α-fodrin and SS-A, into apoptotic particles. The apoptosis-induced apoptotic particles also contained another SS-autoantigen, hy1-RNA. These particles were internalized by pDCs in a size-dependent manner and affected TLR-7 and -9 expression and the production of proinflammatory cytokines. The analysed androgens protected cells from apoptosis, influenced redistribution of autoantigens and diminished the apoptotic particle-stimulated increase of the TLRs in pDCs. Our findings suggest that the formation of apoptotic particles may play a role in loss of immune tolerance, manifested by production of autoantibodies and the onset of autoinflammation in SS.
Hypersensitivity pneumonitis due to unclean continuous positive airway pressure equipment
Authors: Chang Hsu‐Chao , Lan Chou‐Chin , Wu Yao‐Kuang , Su Wen‐Lin , Yang Mei‐Chen
Published: November 2017

Hypersensitivity pneumonitis is a potentially fatal immunological lung disease caused by occupational or environmental exposure to specific antigens. Here, we report on an obstructive sleep apnea patient whose hypersensitivity pneumonitis was aggravated because of the use of unclean continuous positive airway pressure equipment. This report shows that careful history taking is important when diagnosing hypersensitivity pneumonitis. Sleep specialists should be aware of the risks related to unclean continuous positive airway pressure equipment use, and obstructive sleep apnea patients should be instructed and monitored in the regular cleaning of their equipment.
Endobronchial ultrasound‐guided transbronchial needle aspiration with the flexible 19‐gauge needle
Authors: Trisolini Rocco , Natali Filippo , Ferrari Marco , Livi Vanina , Paioli Daniela , Romagnoli Micaela , Cancellieri Alessandra
Published: November 2017

Introduction and Objectives

Endosonography has become standard of care in the diagnostic work‐up of mediastinal lymphadenopathy and peribronchial lung lesions, but its success rate in some specific settings/conditions may be hampered by limited needle flexibility and size. We report on our initial experience with the 19G Flex needle, characterized by larger size and greater flexibility as compared with the currently available cytology needles.

Methods

Retrospective review of prospectively collected data on the first 13 consecutive patients submitted to endosonography with the 19G Flex needle. Patients were included if they had: (a) suspicion of a histologically complex disease (ie, lymphoma); (b) suspicion of an advanced lung cancer possibly requiring extensive genotyping; (c) a lesion whose sampling with a 22G needle had failed because of lack of visibility when the needle was loaded into the scope.

Results

The 13 patients enrolled had a mean age of 58.15 ± 17 years and a male to female ratio of 8:5. Target lesions (mean size 18.6 ± 6.4 mm) were lymphadenopathies (9 patients), lung lesions (3 patients) and a pleural nodule (1 patient). Histology core/s and a definite diagnosis (adenocarcinoma, 4 cases; lymphoma, 2; mesothelioma, 2, metastases from extrathoracic tumors, 2; non‐small‐cell lung cancer not otherwise specifiable, 1; small cell carcinoma, 1; sarcoidosis, 1) were obtained in 100% of patients. A single case of self‐resolving bleeding was the only complication we observed.

Conclusions

Preliminary results obtained with the dedicated Flex 19G needle are promising, as sample size/quality is satisfactory and the needle influence on scope flexibility is minimal.
Regional differences in the incidence of tuberculosis among patients with newly diagnosed diabetes mellitus
Authors: Yang Bo Ram , Kang Young Ae , Heo Eun Young , Koo Bo Kyung , Choi Nam‐Kyong , Hwang Seung‐sik , Lee Chang‐Hoon
Published: November 2017

Objective

There are regional differences in the burden of tuberculosis (TB). Although these differences might be explained by regional differences in the risk factors of TB, whether such risk factors are actually associated with the regional differences in the TB burden remains unclear. This study aimed to investigate the relationship between the risk factors of and regional differences in TB incidence.

Methods

A cohort study applying nationwide claims database in Republic of Korea included patients newly diagnosed with type 2 diabetes mellitus (DM) in 2009. The main outcome was the incidence of TB defined based on the diagnostic codes combined with anti‐tuberculosis treatment repeated within 90 days. Sixteen regions were categorized into 3 groups according to the age‐ and sex‐standardized TB incidence rates. Multivariate logistic regression analysis adjusted for risk factors was performed to identify the determinants of the regional differences in TB incidence.

Results

Among 331 601 participants newly diagnosed with type 2 DM and with no history of previous TB, 1216 TB cases were observed. The regional TB incidence rates ranged between 2.3 and 5.9/1000 patients. Multivariate analyses did not identify any determinants of regional differences in the TB incidence among the various risk factors, including age, sex, health care utilization, co‐morbidities, medication and treatment and complications of DM. Similarly, temperature, humidity and latent TB infection rate also did not affect the results.

Conclusions

Although substantial regional differences in the TB incidence rate were observed among patients with newly diagnosed DM, no determinants of regional difference were identified among the risk factors.
Sleep quality and quality of life in patients with moderate to very severe chronic obstructive pulmonary disease
Authors: Akinci Buket , Aslan Gökşen Kuran , Kiyan Esen
Published: November 2017

Introduction

Chronic obstructive pulmonary disease (COPD) is highly associated with obstructive sleep apnea (OSA). Poor sleep quality is found to be related with decreased quality of life (QoL) in patients with COPD but no study assessed this relationship on the basis of nocturnal sleep parameters.

Objectives

The aim of this study is to explore the relationships between sleep quality, daytime sleepiness and QoL in patients suffering from moderate to very severe COPD with and without sleep apnea assessed objectively and to compare sleep quality, QoL and daytime sleepiness in patients suffering from COPD with and without sleep apnea.

Methods

Fifty‐one patients with stable moderate to very severe COPD (mean age, 59.8 ± 8.1 years) included in the study. The parameters of polygraphic sleep studies (Stardust II, Philips‐Respironics) were noted. Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), The Modified Medical Research Council Dyspnea and SF‐36 Health Quality Survey were performed.

Results

The rate of OSA was 74.5% (Apnea‐Hypopnea Index, >5). out of all the patients, 94% had poor sleep quality (PSQI, >5). Negative correlations were found between PSQI and physical role, social function and mental health of SF‐36 subgroups (P < .05). There was no correlation between PSQI, ESS, SF‐36, dyspnea and polygraphic parameters (P > .05). In the comparison of patients with or without OSA, the vitality of SF‐36 subgroup was found lower in patients with OSA (P < .05).

Conclusions

In conclusion, irrespective of OSA, patients with COPD are suffering from poor sleep quality and poor sleep quality negatively affects the QoL. Also, COPD and OSA association causes worsened vitality in the terms of health‐related QoL.
The liver recipient with acute renal dysfunction: A single institution evaluation of the simultaneous liver‐kidney transplant candidate
Authors: Yadav Kunal , Serrano Oscar K. , Peterson Kent J. , Pruett Timothy L. , Kandaswamy Raja , Bangdiwala Ananta , Ibrahim Hassan , Israni Ajay , Lake John , Chinnakotla Srinath
Published: November 2017

The Organ Procurement Transplant Network (OPTN) listing criteria for simultaneous liver‐kidney transplant (SLK) are not well defined. Concerns remain about rising numbers of SLKs, which divert quality kidneys from candidates awaiting kidney transplants (KT). We performed a retrospective review of liver transplants (LTs) at our center from 2004 to 2014; 127 recipients (liver transplant alone; 102 LTA, 25 SLK) were identified with short‐term preoperative kidney dysfunction (creatinine >4 mg/dL or preoperative hemodialysis [HD] for <6 weeks). Both cohorts had comparable baseline demographic characteristics with the exception of higher model for end‐stage liver disease (MELD) score in the LTA group (41.4 vs 32.9, P < .0001) and higher incidence of pre‐LT diabetes in the SLK cohort (52% vs 26.5%, P = .0176). Duration of pre‐LT HD was higher in SLK recipients, but the difference was not statistically significant (P = .39). Renal nonrecovery (RNR) rate in LTA cohort was low (<5%). No significant difference was noted in 1‐year mortality, liver graft rejection/failure, or length of stay (LOS) between the cohorts. Thus, it appears that liver recipients with short‐term (<6 weeks) HD or AKI without HD have comparable outcomes between LTA and SLK. With provisions for a KT safety net, as proposed by OPTN, LTA may be the most adequate option for these patients.
Consistent increase in the prevalence and female ratio of multiple sclerosis over 15 years in northern Japan
Authors: Houzen H. , Kondo K. , Horiuchi K. , Niino M.
Published: November 2017

Background and purpose

The prevalence of multiple sclerosis (MS) is considered to be lower in East Asia than in Western countries. An increasing trend has been reported globally for the prevalence of MS. We investigated the changes in the prevalence and clinical characteristics of MS in the Tokachi province of Hokkaido, northern Japan from 2001 to 2016.

Methods

Prevalence was determined on 31 March 2016. Data‐processing sheets were collected from all MS‐related institutions in Tokachi province. We applied Poser's diagnostic criteria for MS as used in our previous three studies. Cases of neuromyelitis optica spectrum disorders were excluded.

Results

In 2016, the crude MS prevalence was 18.6/100 000 (95% confidence interval, 14.3–23.8) in northern Japan. Over the last 15 years, the prevalence of MS in the same area was 8.1, 12.6 and 16.2 in 2001, 2006 and 2011, respectively. The female:male ratio was 3.57, which increased from 2.63 in 2001. The ratios of primary progressive, relapsing–remitting and secondary progressive MS types were 2%, 84% and 14%, respectively.

Conclusion

Our results demonstrated a consistent increase in MS prevalence among the northern Japanese population, particularly in females, and relatively lower rates of progressive MS in northern Japan than in Western countries.
Influence of glutamate‐evoked pain and sustained elevated muscle activity on blood oxygenation in the human masseter muscle
Authors: Suzuki Shunichi , Arima Taro , Kitagawa Yoshimasa , Svensson Peter , Castrillon Eduardo
Published: November 2017

This study aimed to investigate the effect of glutamate‐evoked masseter muscle pain on intramuscular oxygenation during rest and sustained elevated muscle activity (SEMA). Seventeen healthy individuals participated in two sessions in which they were injected with glutamate and saline in random order. Each session was divided into three, 10‐min periods. During the first (period 1) and the last (period 3) 10‐min periods, participants performed five intercalated 1‐min bouts of masseter SEMA with 1‐min periods of ‘rest’. At onset of the second 10‐min period, glutamate (0.5 ml, 1 M; Ajinomoto, Tokyo, Japan) or isotonic saline (0.5 ml; 0.9%) was injected into the masseter muscle and the participants kept the muscle relaxed in a resting position for 10 min (period 2). The hemodynamic characteristics of the masseter muscle were recorded simultaneously during the experiment by a laser blood‐oxygenation monitor. The results demonstrated that glutamate injections caused significant levels of self‐reported pain in the masseter muscle; however, this nociceptive input did not have robust effects on intramuscular oxygenation during rest or SEMA tasks. Interestingly, these findings suggest an uncoupling between acute nociceptive activity and hemodynamic parameters in both resting and low‐level active jaw muscles. Further studies are needed to explore the pathophysiological significance of blood‐flow changes for persistent jaw‐muscle pain conditions.
TNF stimulates IL‐6, CXCL8 and VEGF secretion from human keratinocytes via activation of mTOR, inhibited by tetramethoxyluteolin
Authors: Patel Arti B. , Tsilioni Irene , Weng Zuyi , Theoharides Theoharis C.
Published: November 2017

Psoriasis is an autoimmune skin disease characterized by keratinocyte hyperproliferation and chronic inflammation. The pathogenesis of psoriasis involves proinflammatory cytokines, such as tumor necrosis factor (TNF), but the mechanism of keratinocyte activation is not well understood. Here, we show that TNF (10 or 50 ng/mL) stimulates a significant (P < .0001) gene expression and secretion of proinflammatory IL‐6, CXCL8 and VEGF from both cultured human HaCaT and normal epidermal human keratinocytes (NHEKs). This effect occurs via activation of the mammalian target of rapamycin (mTOR) signalling complex as shown by Western blot analysis and phospho‐ELISAs. Pretreatment with the novel natural flavonoid tetramethoxyluteolin (10‐100 μmol L−1) significantly (P < .0001) inhibits gene expression and secretion (P < .0001) of all 3 mediators in a concentration‐dependent manner. Moreover, tetramethoxyluteolin (50 μmol L−1) appears to be a potent inhibitor of the phosphorylated mTOR substrates (pmTORSer2448, pp70S6KThr389 and p4EBP1Thr37/46) as compared to known mTOR inhibitors in keratinocytes. The present findings indicate that TNF stimulates skin inflammation via mTOR signalling. Inhibition by tetramethoxyluteolin may be used in the treatment for psoriasis.
Distinguishing Characteristics of Headache in Nontraumatic Subarachnoid Hemorrhage
Authors: Mac Grory Brian , Vu Linh , Cutting Shawna , Marcolini Evadne , Gottschalk Christopher , Greer David
Published: November 2017

Introduction

Subarachnoid hemorrhage (SAH) is a life‐threatening emergency that is frequently missed due to its varied and often subtle presentation. The most common presentation of SAH is with a severe headache. The classical adjective used in SAH is “thunderclap”; however, this has not been well defined in the literature, rendering it a challenge to triage patients in clinical practice presenting with severe headache.

Methods

We undertook a prospective, observational study at a tertiary academic medical center examining the clinical characteristics of the presenting headache in SAH. We enrolled patients through the emergency department and from the neurosciences intensive care unit, and documented clinical features of the headache including the time to peak intensity, location, associated symptoms, and activities that caused worsening.

Results

One hundred and fifty‐eight subjects were enrolled, of whom 20 patients had SAH and 138 did not. Notable distinguishing features on history included occipital location (55% in the SAH group vs 22% in the non‐SAH group, P < .001), “stabbing” quality (35% in the SAH group vs 5% in the non‐SAH group, P < .001), presence of prior headache (50% in the SAH group vs 83% in the non‐SAH group, P = .002), and associated meningismus (80% in the SAH group and 42% in the non‐SAH group, P = .002). Sixty‐five percent of patients with SAH reported that their headache peaked within 1 second of onset, compared with only 10% of those without SAH (P < .001).

Conclusion

This is the first study that has sought to examine in detail the clinical characteristics of the presenting headache in SAH. Our study suggests that the clinical features of headache with SAH are distinct from those associated with other headache syndromes, and that this may prove useful in the acute care setting in triaging patients with a chief complaint of headache.
Openness, inclusion and transparency in the practice of public involvement in research: A reflective exercise to develop best practice recommendations
Authors: Brown Laura J.E. , Dickinson Tommy , Smith Stuart , Brown Wilson Christine , Horne Maria , Torkington Kate , Simpson Paul
Published: November 2017

Context

Reflective accounts of public involvement in research (PI) are important for helping researchers plan and deliver more effective PI activities. In particular, there is a need to address power differentials between team members that can prohibit effective and meaningful involvement.

Objective

To critically reflect on the PI practices that underpinned our research project on intimacy and sexuality in care homes, to develop a series of recommendations for improving future PI activities.

Setting

The research team comprised five academics from nursing, public health, sociology and psychology, and two members of the public with experience of sex education, and lesbian, gay, bisexual and trans issues in older populations. In order to address power differentials within the group, we developed an approach to PI practice that was grounded in values of openness, inclusion and transparency.

Method

Reflective commentaries on the strengths and weaknesses of the team's approach to PI were gathered through interviews and open‐ended questionnaires with research team members. These views were collated and discussed at a workshop comprising research team members and an additional member of the public to generate recommendations for future PI practice.

Results

A number of strengths and limitations of our approach to PI were identified. Clear recommendations for improving PI practice were developed for three broad areas of identified difficulty: (i) communication within and between meetings; (ii) the roles and responsibilities of team members; and (iii) PI resources and productivity.

Discussion and conclusion

These recommendations add to the developing body of guidance for conducting effective PI.
Investigating social motivations, opportunity and ability to participate in communities of virtual co‐creation
Authors: Bettiga Debora , Lamberti Lucio , Noci Giuliano
Published: November 2017

Communities of virtual co‐creation are emerging as a new form of consumer engagement, where through a collaborative and interactive process, ideas and knowledge from consumer are applied differently to create new value for the consumers themselves, the company and all stakeholders. The aim of this paper is to explore the drivers, namely motivation, opportunity and ability, of consumer willingness to participate in communities of virtual co‐creation. The role of social motivations, that is, altruism and social reputation, particularly relevant inside online communities, is investigated. Data were collected through an online survey on 180 consumers from diverse nationalities. The unit of analysis was a virtual co‐creation activity for food products. Findings show that consumer motivation and ability have a relevant influence on willingness to participate in co‐creation projects, while opportunity has not. In particular, ability showed to be the most relevant factor, suggesting that virtual co‐creation initiatives should be properly designed to facilitate the engagement of consumers. Further, results indicate that consumers' motivations are driven by both altruism and social reputation, where altruism plays a greater role. This confirms that social relations are key motivational drivers in virtual communities, where value is created through interaction with like‐minded people, exchange of information and experiences, provision of support.
The maternal 14 bp Ins/Del polymorphism in HLA‐G is not associated with preeclampsia risk
Authors: Ferreira L. C. , Lopes T. P. B. , Guimarães T. B. , Gomes C. E. M. , Jeronimo S. M. B.
Published: November 2017

The effect of HLA‐G 14 bp Ins/Del polymorphism (rs371194629) on the risk of preeclampsia has been assessed in several populations, yet the results are still conflicting. Lack of power due to small sample sizes is a common cause of inconsistencies in genetic association studies. We aimed to test whether the maternal polymorphism is associated with preeclampsia, eclampsia or HELLP syndrome (acronym for Hemolysis, Elevation of Liver enzymes, Low Platelets). To achieve a statistical power greater than 0.90, a total of 741 women (332 controls, 246 preeclampsia, 57 eclampsia and 106 HELLP) were genotyped for the 14‐bp Ins/Del polymorphism. The genetic association with disease status was assessed by Fisher's exact test and odds ratio (OR) estimates using logistic regression model adjusted for maternal age and parity status. Allele and genotype distributions were the same between control and case groups (p > .05). The polymorphism was not associated with the risk of developing preeclampsia [OR = 0.93 (0.72–1.19); p = .541], or eclampsia [OR = 0.90 (0.60–1.38); p = .628] nor HELLP syndrome [OR = 0.92 (0.66–1.28); p = .628]. This well‐powered study clearly demonstrates that the maternal HLA‐G 14‐bp Ins/Del polymorphism is not associated with preeclampsia risk. However, as the offspring genotypes were not evaluated here, we could not rule out the effect of the foetal genotype on the preeclampsia pathogenesis.
Cyclophosphamide‐induced tolerance in kidney transplantation avoids long‐term immunosuppressive therapy
Authors: Takeuchi Ario , Kato Koji , Akashi Koichi , Eto Masatoshi
Published: November 2017

There has recently been remarkable progress in immunosuppressive agents, such as tacrolimus and cyclosporine. Therefore, the rate of organ establishment has improved in transplantation. However, immunosuppressive agents generally suppress the function of T cells. Thus, opportunistic infections, such as cytomegalovirus infection, are still a major problem in kidney transplantation. Induction of specific tolerance to avoid immunosuppressive drug therapy after kidney transplantation is considered as the ultimate goal of transplantation. Various factors induce tolerance that involves establishment of hematopoietic chimerism and various cell subsets. In particular, we have carried out various studies regarding the cyclophosphamide‐induced tolerance system. Tolerance is induced after establishment of hematopoietic chimerism after donor bone marrow transplantation. At the clinical stage, kidney transplantation before administration of cyclophosphamide after transfusion of bone marrow to create hematopoietic chimera is considered to be one of the most successful protocols. Furthermore, recent studies have shown the involvement of multiple populations of immune cells in preserving immunological tolerance and promoting long‐term renal grafts. The present review focuses on how cyclophosphamide and other immune factors induce tolerance in kidney transplantation.