bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Electroacupuncture on Thermal Pain Threshold and Expression of Calcitonin-Gene Related Peptide, Substance P and γ-Aminobutyric Acid in the Cervical Dorsal Root Ganglion of Rats with Incisional Neck Pain
Authors: Qiao Li-na , Liu Jun-ling , Tan Lian-hong , Yang Hai-long , Zhai Xu , Yang Yong-sheng
Published: June 2017

Objective

Acupuncture therapy effectively reduces post-surgical pain, but its mechanism of action remains unclear. The aim of this study was to investigate whether expression of γ-aminobutyric acid (GABA) and the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) in the primary sensory neurons of cervical dorsal root ganglia (DRG) are involved in electroacupuncture (EA)-induced analgesia in a rat model of incisional neck pain.

Methods

The pain model was established by making a longitudinal midline neck incision in 60 rats. Another 15 rats underwent sham surgery (normal group). Post-incision, 15 rats remained untreated (model group) and 45 rats underwent EA (frequency 2/100 Hz, intensity 1 mA) at bilateral LI18, LI4-PC6 or ST36-GB34 (n=15 each) for 30 min at 4 hours, 24 hours, and 48 hours post-surgery, followed by thermal pain threshold (PT) measurement. 30 min later, the rats were euthanased and cervical (C3-6) DRGs removed for measurement of immunoreactivity and mRNA expression of SP/CGRP and the GABAergic neuronal marker glutamic acid decarboxylase 67 (GAD67).

Results

Thermal PT was significantly lower in the model group versus the normal group and increased in the LI18 and LI4-PC6 groups but not the ST36-GB34 group compared with the model group. Additionally, EA at LI18 and LI4-PC6 markedly suppressed neck incision-induced upregulation of mRNA/protein expression of SP/CGRP, and upregulated mRNA/protein expression of GAD67 in the DRGs of C3-6 segments.

Conclusions

EA at LI18/LI4-PC6 increases PT in rats with incisional neck pain, which is likely related to downregulation of pronociceptive mediators SP/CGRP and upregulation of the inhibitory transmitter GABA in the primary sensory neurons of cervical DRGs.
Stability of visual outcome between 2 and 5 years following corneal transplantation in the UK
Authors: Chow Sing-Pey , Hopkinson Cathy L , Tole Derek M , Jones Mark N , Cook Stuart D , John Armitage W
Published: June 2017

Background and Aims

Many studies of corneal transplantation focus on graft failure or rejection as endpoints, or report visual outcomes at one postoperative time point. We aimed to study the stability of visual outcomes between 2 and 5 years following corneal transplantation.

Methods

All patients with keratoconus (868) or Fuchs endothelial dystrophy (FED) (569) receiving their first corneal transplant for visual purposes in the UK between January 2003 and December 2009 were included. The probability of visual improvement or deterioration (gain or loss of ≥2 Snellen lines, respectively) between 2 and 5 years after keratoplasty was modelled by multivariable logistic regression.

Results

The majority of keratoconus patients with a penetrating keratoplasty (PK) or deep anterior lamellar keratoplasty maintained their visual acuity (651/868; 75%) while 15% (133/868) improved and 10% (84/868) deteriorated. Similarly, most patients with FED who received a PK maintained their vision (395/569; 70%) while 18% (105/569) improved and 12% (68/569) deteriorated.
One-year outcome of intravitreal ziv-aflibercept therapy for non-responsive neovascular age-related macular degeneration
Authors: Braimah Imoro Zeba , Agarwal Komal , Mansour Ahmad , Chhablani Jay
Published: June 2017

Aim

To evaluate 12-month outcome of intravitreal ziv-aflibercept (IVZ) therapy in eyes with neovascular age-related macular degeneration (nAMD) that are non-responsive to bevacizumab and ranibizumab.

Methods

This retrospective study included 16 eyes (14 patients) with nAMD who were on prior treatment with bevacizumab and ranibizumab and were treated with as-needed IVZ (1.25 mg/0.05 mL) for 12 months. The primary outcome measure was the mean change in best corrected visual acuity (BCVA) and secondary outcome measures included mean change in central macular thickness (CMT), retinal pigment epithelial detachment (RPED) heights, longest treatment free interval, presence of subretinal fluid (SRF) and intraretinal fluid (IRF) and adverse events.

Results

There was no change in the mean logarithm of minimum angle of resolution (logMAR) BCVA at baseline and following treatment with IVZ therapy (p=0.978). The mean number of IVZ injections during 12 months was 5.9±3.3, and the mean number of antivascular endothelial growth factors (VEGFs) injections prior to switching to IVZ was 8.4±4.7. The mean treatment free interval was longer during IVZ therapy (114.4±67.1 days) compared with 76.3±54.6 days before IVZ therapy (p=0.03). Five (31.25%) eyes had visual gains of at least 0.1 logMAR, 3 (18.75%) eyes had stable BCVA (within 0.1 logMAR) and 8 (50%) eyes had BCVA decline of at least 0.1 logMAR. There was no significant difference in the mean CMT, RPED heights and presence of IRF and SRF at 12 months compared with baseline. No adverse events were noted.

Conclusion

IVZ increased the treatment free interval in non-responders but no significant change in visual and anatomic outcomes.
Retinal vessels functionality in eyes with central serous chorioretinopathy
Authors: Tomasso Livia , Benatti Lucia , Rabiolo Alessandro , Carnevali Adriano , Zucchiatti Ilaria , Querques Lea , Bandello Francesco , Querques Giuseppe
Published: June 2017

Purpose

To analyse static characteristics and dynamic functionality of retinal vessels in eyes with central serous chorioretinopathy (CSCR) by means of Dynamic Vessel Analyzer (DVA).

Methods

Patients presenting with treatment-naïve CSCR and normal subjects (controls) matched for age and sex between May 2015 and November 2015 were enrolled in the study. Participants underwent a complete ophthalmological examination, including dynamic and static retinal vessels analysis by DVA.

Results

A total of 28 eyes of 28 subjects (14 eyes for each group) were included in the analysis. Dynamic analysis during stimulation by flickering light showed mean venous dilation of 3.3%±2.0% in patients with CSCR and 5.5%±2.6% in controls (p=0.0258); mean arterial dilation did not differ between patients and controls (3.2%±2.5% and 4.2%±1.5%, p=0.2). No differences were reported at static retinal analysis between patients with CSCR and control subjects. Subfoveal choroidal thickness as evaluated by optical coherence tomography was 438.6±86.1 µm in CSCR eyes, significantly increased compared with control subjects (301.5±72.5 µm, p=0.0001).

Conclusions

Dynamic analysis revealed a reduced retinal venous dilation in response to flicker light stimulation in CSCR eyes. The decreased retinal vein response to flicker light stimulation, possibly due to increased sympathetic tone and potentially leading to venous stasis, together with the increased choroidal thickness may help understand CSCR and give insights in its pathogenesis.
Is glycemia control in Canadians with diabetes individualized? A cross-sectional observational study
Authors: Coons Michael J , Greiver Michelle , Aliarzadeh Babak , Meaney Christopher , Moineddin Rahim , Williamson Tyler , Queenan John , Yu Catherine H , White David G , Kiran Tara , Kane Jennifer J
Published: June 2017

Objective

Diabetes guidelines recommend individualized glycemic targets: tighter control in younger, healthier patients and consideration of more moderate control in the elderly and those with coexisting illnesses. Our objective was to examine whether glycemic control varied by age and comorbidities in Canadian primary care.

Research design and methods

Cross-sectional study using data from the electronic medical records of 537 primary care providers across Canada; 30 416 patients with diabetes, aged 40 or above, with at least one encounter and one hemoglobin A1c (HbA1c) measurement between 1 January 2012 and 31 December 2013. The outcome was the most recent HbA1c, categorized into three levels of control: tight (<7.0% or <53 mmol/mol), moderate (7.0%–8.5%, 53 mmol/mol–69.5 mmol/mol) and uncontrolled (>8.5% or >69.5 mmol/mol). We adjusted for several factors associated with glycemic control including treatment intensity.

Results

Younger patients (aged 40–49) were more likely to have moderate as opposed to tight control than the older patients (aged 80+) (OR 1.28; 95% CI 1.11 to 1.49, p=0.001). The youngest were also more likely to have uncontrolled as opposed to moderately controlled glycemia (OR 3.39; 95% CI 2.75 to 4.17, p<0.0001). Patients with no or only one comorbidity were more likely to have moderate as opposed to tight control than those with three or more comorbidities (OR 1.66;95% CI 1.46 to 1.90, p<0.0001).

Conclusions

Levels of glycemic control, given age and comorbidities appear to differ from guideline recommendations. Research is needed to understand these discrepancies and develop methods to assist providers in personalizing glycemic targets.
Cross-sectional study of factors associated with community health centre use in a recently urbanised community in Chengdu, China
Authors: Liu Danping , Meng Hongdao , Dobbs Debra , Conner Kyaien O , Hyer Kathryn , Li Ningxiu , Ren Xiaohui , Gao Bo
Published: June 2017

Objectives

Public investment in community health centres (CHCs) has been increasing as a response to rapid urbanisation in China. The objectives of this study were: (1) to examine factors associated with CHC use among residents from a recently urbanised community in western China and (2) to describe satisfaction with CHC among users.

Design

Cross-sectional design.

Setting

A community recently converted to urban status with a newly constructed CHC in Southwest China.

Participants

A random sample of 2259 adults in the Hezuo community in Chengdu, China, completed the survey in 2013.

Outcome measures

Trained staff interviewed study participants in their homes using structured questionnaires. The survey included questions regarding sociodemographics, health status, access to and usage of healthcare, health behaviours and CHC use. The Andersen’s behavioural model of health service use was used to guide multivariable logistic regression modelling in identifying predisposing, enabling and need factors associated with the likelihood of using CHC. Descriptive statistics were used to describe residents’ satisfaction with the CHC.

Results

A total of 71.8% of the respondents reported using the CHC during the past year. Factors influencing adults’ CHC use included: gender, marital status, education level and knowledge of one’s blood pressure (predisposing factors); annual household per capita income and walking time to the CHC (enabling factors) and self-rated health as well as physical activities (need factors). CHC users reported modest satisfaction across various aspects of the CHC.

Conclusions

Neighbourhood CHC in urban areas provides important services to these residents living in a recently urbanised community. All three categories of factors in the Andersen model help explain the likelihood of CHC use. There is much room for improvement in CHC to enhance customer satisfaction. Future research is needed to improve access to CHCs and promote their use in urbanised populations with low to modest education.
Effect of physical activity and dietary restriction interventions on weight loss and the musculoskeletal function of overweight and obese older adults with knee osteoarthritis: a systematic review and mixed method data synthesis
Authors: Alrushud Asma S , Rushton Alison B , Kanavaki Archontissa M , Greig Carolyn A
Published: June 2017

Background

Despite the clinical recommendation of exercise and diet for people with knee osteoarthritis (OA), there are no systematic reviews synthesising the effectiveness of combining physical activity and dietary restriction interventions on the musculoskeletal function of overweight and obese older adults with knee OA.

Objective

To evaluate the effectiveness of combined physical activity and dietary restriction programmes on body weight, body mass index (BMI) and the musculoskeletal function of overweight and obese older adults with knee OA.

Information sources

A detailed search strategy was applied to key electronic databases (Ovid, Embase, Web of Science andCumulative Index to Nursing and Allied Health Literature (CINAHL)) for randomised controlled trials (RCTs) published in English prior to 15 January 2017.

Participants

Participants with BMI ≥25 kg/m2, aged ≥55 years of age and with radiographic evidence of knee OA.

Interventions

Physical activity plus dietary restriction programmes with usual care or exercise as the comparators.

Outcome measures

Primary outcome measures were body weight, BMI or musculoskeletal function. Secondary outcome measures were pain and quality of life.

Results

One pilot and two definitive trials with n=794 participants were included. Two articles reporting additional data and outcome measures for one of the RCTs were identified. All included RCTs had an unclear risk of bias. Meta-analysis was only possible to evaluate mobility (6 min walk test) at 6 months and the pooled random effect 15.05 (95% CI −11.77 to 41.87) across two trials with n=155 participants did not support the combined intervention programme. Narrative synthesis showed clear differences in favour of a reduced body weight and an increased 6 min walk in the intervention group compared with control groups.

Conclusion

The quality of evidence of benefit of combining exercise and dietary interventions in older overweight/obese adults with knee OA is unclear.

Trail registration number

CRD42015019088 and ISRCTN,ISRCTN12906938.
Development and validation of a risk stratification model for prediction of disability and hospitalisation in patients with heart failure: a study protocol
Authors: García-Olmos Luis , Rodríguez-Salvanés Francisco , Batlle-Pérez Maurice , Aguilar-Torres Río , Porro-Fernández Carlos , García-Cabello Alfredo , Carmona Montserrat , Ruiz-Alonso Sergio , Garrido-Elustondo Sofía , Alberquilla Ángel , Sánchez-Gómez Luis María , Sánchez de Madariaga Ricardo , Monge-Navarrete Elena , Benito-Ortiz Luis , Baños-Pérez Nicolás , Simón-Puerta Amaya , López Rodríguez Ana Belén , Martínez-Álvarez Miguel Ángel , Velilla-Celma María Ángeles , Bernal-Gómez María Isabel
Published: June 2017

Background

Chronic heart failure (CHF) reduces quality of life and causes hospitalisation and death. Identifying predictive factors of such events may help change the natural history of this condition.

Aim

To develop and validate a stratification system for classifying patients with CHF, according to their degree of disability and need for hospitalisation due to any unscheduled cause, over a period of 1 year.

Methods and analysis

Prospective, concurrent, cohort-type study in two towns in the Madrid autonomous region having a combined population of 1 32 851. The study will include patients aged over 18 years who meet the following diagnostic criteria: symptoms and typical signs of CHF (Framingham criteria) and left ventricular ejection fraction (EF)<50% or structural cardiac lesion and/or diastolic dysfunction in the presence of preserved EF (EF>50%).

Outcome variables will be(a) Disability, as measured by the WHO Disability Assessment Schedule V.2.0 Questionnaire, and (b) unscheduled hospitalisations. The estimated sample size is 557 patients, 371 for predictive model development (development cohort) and 186 for validation purposes (validation cohort). Predictive models of disability or hospitalisation will be constructed using logistic regression techniques. The resulting model(s) will be validated by estimating the probability of outcomes of interest for each individual included in the validation cohort.

Ethics and dissemination

The study protocol has been approved by the Clinical Research Ethics Committee of La Princesa University Teaching Hospital (PI-705). All results will be published in a peer-reviewed journal and shared with the medical community at conferences and scientific meetings.
Serious gaming during multidisciplinary rehabilitation for patients with complex chronic pain or fatigue complaints: study protocol for a controlled trial and process evaluation
Authors: Vugts Miel A P , Joosen Margot C W , Mert Agali , Zedlitz Aglaia , Vrijhoef Hubertus J M
Published: June 2017

Introduction

Many individuals suffer from chronic pain or functional somatic syndromes and face boundaries for diminishing functional limitations by means of biopsychosocial interventions. Serious gaming could complement multidisciplinary interventions through enjoyment and independent accessibility. A study protocol is presented for studying whether, how, for which patients and under what circumstances, serious gaming improves patient health outcomes during regular multidisciplinary rehabilitation.

Methods and analysis

A mixed-methods design is described that prioritises a two-armed naturalistic quasi-experiment. An experimental group is composed of patients who follow serious gaming during an outpatient multidisciplinary programme at two sites of a Dutch rehabilitation centre. Control group patients follow the same programme without serious gaming in two similar sites. Multivariate mixed-modelling analysis is planned for assessing how much variance in 250 patient records of routinely monitored pain intensity, pain coping and cognition, fatigue and psychopathology outcomes is attributable to serious gaming. Embedded qualitative methods include unobtrusive collection and analyses of stakeholder focus group interviews, participant feedback and semistructured patient interviews. Process analyses are carried out by a systematic approach of mixing qualitative and quantitative methods at various stages of the research.

Ethics and dissemination

The Ethics Committee of the Tilburg School of Social and Behavioural Sciences approved the research after reviewing the protocol for the protection of patients’ interests in conformity to the letter and rationale of the applicable laws and research practice (EC 2016.25t). Findings will be presented in research articles and international scientific conferences.

Trial registration number

A prospective research protocol for the naturalistic quasi-experimental outcome evaluation was entered in the Dutch trial register (registration number: NTR6020; Pre-results).
Improving medicines reconciliation rates at Ashford and St. Peter's Hospitals NHS Foundation Trust
Authors: Doolub Reshmee
Published: June 2017

Medicines reconciliation is integral to patient safety, symptom control and reducing patient anxiety. During a 3-month period on the respiratory ward at St. Peter's Hospital, 54% of drug charts were not reconciled with pre-admission medicines at the point of discharge for admissions up to 17 days. Only 18% were reconciled within 24 hours of admission. 50% of drug charts were missing 0-2 pre-admission medicines and 50% were missing 3-5 pre-admission medicines. The most common medicines that were not reconciled included topical applications which included eye, ear, nasal and skin applications (14%); vitamins i.e. vitamin B12 and thiamine, analgesia, PRN inhalers (11% individually); antidepressants and lipid regulators (6% individually); amongst a range of other medications including antiplatelets, calcium channel blockers, ACE inhibitors and diuretics.

Two interventions were carried out to improve the rate of medicines reconciliation onto hospital drug charts with pre-admission medicines. These were: 1) a green sticker placed in the medical notes by the pharmacist when drug charts were incomplete, which required a date and signature from the doctor when the drug chart had been reconciled 2) the placing of the loose medicines reconciliation record (a list of pre-admission medicines retrieved from a reliable source usually by the pharmacist) to the front of the drug chart. These measures were designed to alert the doctors that the drug chart was incomplete.

After 2 PDSA cycles, the results showed positive outcomes. In 75% of the cases where the interventions were used, medicines reconciliation was complete at the point of discharge with 34% of drug charts reconciled within 24 hours of admission. Of the 25% of drug charts that were not reconciled despite the use of the interventions, 100% of them were missing 0-2 medicines however 0% were missing 3-5 medicines. This highlights that the interventions were effective in improving the rates of medicines reconciliation.
Health-related shame: an affective determinant of health?
Authors: Dolezal Luna , Lyons Barry
Published: June 2017

Despite shame being recognised as a powerful force in the clinical encounter, it is underacknowledged, under-researched and undertheorised in the contexts of health and medicine. In this paper we make two claims. The first is that emotional or affective states, in particular shame, can have a significant impact on health, illness and health-related behaviours. We outline four possible processes through which this might occur: (1) acute shame avoidance behaviour; (2) chronic shame health-related behaviours; (3) stigma and social status threat and (4) biological mechanisms. Second, we postulate that shame's influence is so insidious, pervasive and pernicious, and so critical to clinical and political discourse around health, that it is imperative that its vital role in health, health-related behaviours and illness be recognised and assimilated into medical, social and political consciousness and practice. In essence, we argue that its impact is sufficiently powerful for it to be considered an affective determinant of health, and provide three justifications for this. We conclude with a proposal for a research agenda that aims to extend the state of knowledge of health-related shame.
Optimal thresholds for ischemic penumbra predicted by computed tomography perfusion in patients with acute ischemic stroke treated with mechanical thrombectomy
Authors: Kameda Katsuharu , Uno Junji , Otsuji Ryosuke , Ren Nice , Nagaoka Shintaro , Maeda Kazushi , Ikai Yoshiaki , Gi Hidefuku
Published: June 2017

Background and purpose

Optimal thresholds for ischemic penumbra detected by CT perfusion (CTP) in patients with acute ischemic stroke (AIS) have not been elucidated. In this study we investigated optimal thresholds for salvageable ischemic penumbra and the risk of hemorrhagic transformation (HT).

Methods

A total of 156 consecutive patients with AIS treated with mechanical thrombectomy (MT) at our hospital were enrolled. Absolute (a) and relative (r) CTP parameters including cerebral blood flow (aCBF and rCBF), cerebral blood volume (aCBV and rCBV), and mean transit time (aMTT and rMTT) were evaluated for their value in detecting ischemic penumbra in each of seven arbitrary regions of interest defined by the major supplying blood vessel. Optimal thresholds were calculated by performing receiver operating characteristic curve analysis in 47 patients who achieved Thrombolysis In Cerebral Infarction (TICI) grade 3 recanalization. The risk of HT after MT was evaluated in 101 patients who achieved TICI grade 2b–3 recanalization.

Results

Absolute CTP parameters for distinguishing ischemic penumbra from ischemic core were as follows: aCBF, 27.8 mL/100 g/min (area under the curve 0.82); aCBV, 2.1 mL/100 g (0.75); and aMTT, 7.30 s (0.70). Relative CTP parameters were as follows: rCBF, 0.62 (0.81); rCBV, 0.83 (0.87); and rMTT, 1.61 (0.73). CBF was significantly lower in areas of HT than in areas of infarction (aCBF, p<0.01; rCBF, p<0.001).

Conclusions

CTP may be able to predict treatable ischemic penumbra and the risk of HT after MT in patients with AIS.
Extending the indications for transvenous approach embolization for superficial brain arteriovenous malformations
Authors: Viana Dinark Conceição , de Castro-Afonso Luis Henrique , Nakiri Guilherme Seizem , Monsignore Lucas Moretti , Trivelato Felipe Padovani , Colli Benedicto Oscar , Abud Daniel Giansante
Published: June 2017

Introduction

Transarterial embolization is the standard endovascular treatment strategy for intracranial arteriovenous malformations (AVMs). The transvenous approach has been indicated for the embolization of deep AVMs meeting a set of strict eligibility criteria. The present study aims to assess the safety and efficacy of the transvenous approach for superficial AVMs.

Methods

A retrospective series of 12 patients presenting with cortical AVMs were treated by endovascular embolization using a transvenous approach with a curative intent.

Results

Nine patients (75%) had ruptured AVMs at admission. The mean nidus size was 1.9 cm, six patients (50%) had a nidus in eloquent areas and the median Spetzler–Martin grade was 2. The rate of immediate angiographic occlusion of the AVMs was 91.6% (11/12). One patient in whom immediate angiographic occlusion was not achieved showed spontaneous occlusion at the 6-month follow-up. No procedural or clinical complications were observed. The mean and median modified Rankin scale (mRS) scores at discharge were 1.7 and 2 (range 0–3, SD=0.96), and the mean and median mRS scores at 6 months were 1.6 and 2 (0–3, 1.16). Nine patients (75%) were independent (mRS ≤2) at discharge and 11 patients (91.6%) were independent (mRS ≤2) at the 6-month follow-up.

Conclusions

The curative transvenous embolization of superficial intracranial AVMs is feasible and appears safe and effective when strict anatomical selection is respected. This technique extends the current indications for transvenous embolization of intracranial AVMs and may improve cure rates while reducing embolization-related complications.
Gastrointestinal manifestations of neuroendocrine tumours: their investigation and management
Authors: Sagar Vandana M , Cooper Sheldon C , Johnson Jill , Shetty Shishir , Shah Tahir
Published: June 2017

The incidence of neuroendocrine tumours (NETs) is on the rise in the UK. Patients with NETs need to be managed by a team of clinical specialties. There are a number of challenging gastrointestinal (GI) manifestations related to NETs that can occur in these patients, but a limited literature base exists to guide clinicians.

Whilst life expectancy can be several years for patients with NETs, the GI symptoms can have a significant impact on their quality of life. It is therefore imperative to be familiar with the common GI manifestations associated with NETs, so symptoms can be appropriately managed with an overall aim of restoring the patient’s quality of life.
Contaminated fingers: a potential cause of Chlamydia trachomatis-positive urine specimens
Authors: Giffard Philip M , Lilliebridge Rachael A , Wilson Judith , Murray Gerald , Phillips Samuel , Tabrizi Sepehr N , Garland Suzanne M , Martin Louise , Singh Gurmeet , Tong Steven Y C , Holt Deborah C , Andersson Patiyan
Published: June 2017

Objectives

The detection of an STI agent in a urogenital tract (UGT) specimen from a young child is regarded as being indicative of sexual abuse. However, the probabilities of contamination events that could conceivably lead to STI positive specimens in the absence of sexual contact are unclear. The objective was to estimate the potential for fingers that have come in contact with Chlamydia trachomatis-positive urine to detectably contaminate C. trachomatis-negative urine.

Methods

The study design was based on self-experimentation. Dilutions of C. trachomatis elementary bodies (EBs) were prepared. A participant contacted an EB dilution then a urine surrogate specimen. The experiment was performed by three participants using three C. trachomatis isolates, of genotype E, F and B. Two surrogate urine contact methods were used to mimic contamination of a carer assisting with a child’s urine collection. All EB dilutions and urine surrogate specimens were subjected to C. trachomatis assay and quantification in a real-time PCR-based diagnostic system.

Results

The amplimer crossing point (Cq) for EB dilutions was 10.0±1.6 less than for corresponding finger contacted urine specimens, which corresponds to ~10 µL of EB suspension transferred. This was largely independent of participant identity, C. trachomatis strain or EB dilution. Hand decontamination led to large reductions in EBs transferred, but transfer remained consistently detectable. Recent Cq data from C. trachomatis-positive clinical urine specimens were collated, and 20% clearly contained sufficient C. trachomatis to detectably contaminate another specimen by finger-mediated transfer, as in this experiment.

Conclusions

This study directly demonstrated the potential for urine contaminated fingers to convert a C. trachomatis-negative urine specimen to C. trachomatis positive as a result of contact. Accordingly, procedures for urine specimen collection, particularly from children, need to be designed to prevent contamination.
Quantifying inorganic nitrogen uptake capacity among ectomycorrhizal fungal species using MIFE microelectrode ion flux measurements: theory and applications
Authors: Hawkins B.J. , Kranabetter J.M.
Published: June 2017

A growing appreciation of the intimate association between trees and a wide diversity of mycorrhizal fungi in forest ecosystems is leading to the view that trees and their associated mycorrhizal symbionts should be considered meta-organisms or holobionts. For ectomycorrhizal associations, nitrogen (N) mobilization and uptake is a major contribution from the fungal partners. This paper reviews the traditional methods of measuring N uptake by ectomycorrhizae, and describes the application of microelectrode ion flux measurement of nitrogen uptake using the MIFETM technique to ectomycorrhizal fungi associated with forest trees. From results obtained with microelectrode ion flux measurement thus far, we argue that plant N uptake capacity should be considered an exogenous trait, related to the functional diversity among ectomycorrhizal species and communities, rather than a function of host plant root physiology, alone.
Interface between fungi and green algae in lichen associations
Authors: Piercey-Normore Michele D. , Athukorala Sarangi N.P.
Published: June 2017

It is widely recognized that the lichen is the product of a fungus and a photosynthetic partner (green alga or cyanobacterium), but its acceptance was slow to develop throughout history. The development of powerful microscopic and other lab techniques enabled better understanding of the interface between symbionts, beginning with the contentious concept of the dual nature of the lichen thallus. Even with accelerating progress in understanding the interface between symbionts, much more work is needed to reach a level of knowledge consistent with that of other fungal interactions. This minireview describes the interface between algal and fungal symbionts in lichens, including the appearance of interacting symbionts, our current understanding of communication between symbionts, and emerging new concepts in light of the challenges and debates that have provided lichenology with an enriched history. Communication between symbionts occurs before physical contact, which has been studied through microscopy, movement of molecules between symbionts, and gene expression studies. New discoveries include the interaction with more than one alga in a lichen thallus as well as other unrelated fungi and bacteria typically found on or within the thallus. This minireview briefly describes our current state of knowledge and highlights new directions for further study.
Experimental Analysis of Students’ Satisfaction Factors in E-Learning Environment: A Case Study on Saudi Arabian University
Authors: Abdel-Jaber Hussein
Published: June 2017

Despite the proliferation of studies outlining the immense benefits obtained from e-learning, the understanding of students’ satisfaction with e-learning in developing countries is still unclear. Therefore, this paper investigates the relationship between Saudi students’ satisfaction with online courses and a number of individual, as well as institutional characteristics cited as robust predictors of students’ satisfaction in the educational literature. These include: students’ levels of internet self-efficacy, self-regulated learning, assessment of course and instructors’ interactivity and their evaluation of the Learning Management System (LMS) used. The results indicated that students’ internet self-efficacy and self-regulated learning constitute critical factors influencing students’ satisfaction with e-learning. Further, students’ assessment of course, as well as instructors’ interactivity are found to marginally affect perceived satisfaction with e-learning among Saudi students. The LMS used (Blackboard) seemed to be the weakest factor influencing students’ experience with online education. Overall, based on the results obtained and in order to maximise the benefits of e-learning; this paper recommends for Saudi universities to extensively use LMS to increase the interactions among primary stakeholders: students–instructors, students–students and students–LMS.
Tectonic Evolution of the Eastern Black Sea and Caucasus: an introduction
Authors: Sosson Marc , Stephenson Randell , Adamia Shota
Published: June 2017

This Special Publication presents the results of 15 different studies in the Black Sea–Caucasus segment of the Alpine–Tethys orogenic realm. The main focus of these studies is the style and timing of key tectonic events occurring primarily during the area's post-Pangaean evolution. The methodologies encompass: geophysics, including active and passive crustal-scale seismology and common depth point reflection seismic profiling (both onshore and marine), palaeomagnetism and magnetostratigraphy; field geology, including biostratigraphic recorrelation; radiochronology; igneous rock geochemistry, including analyses of the obducted ophiolites; and low-temperature thermochronology. The geological record of the area is essentially one of sedimentary basins formed in an extensional back-arc setting and their subsequent compressional deformation during the closure of at least two branches of the Neotethys Ocean system.
Multiharmonic Small-Signal Modeling of Low-Power PWM DC-DC Converters
Authors: Wang Ya , Gao Di , Tannir Dani , Dong Ning , Fang G. Peter , Dong Wei , Li Peng
Published: June 2017

Small-signal models of pulse-width modulation (PWM) converters are widely used for analyzing stability and play an important role in converter design and control. However, existing small-signal models either are based on averaged DC behaviors, and hence are unable to capture frequency responses that are faster than the switching frequency, or greatly approximate these high-frequency responses. We address the severe limitations of the existing models by proposing a multiharmonic model that provides a complete small-signal characterization of both DC averages and high-order harmonic responses. The proposed model captures important high-frequency overshoots and undershoots of the converter response, which are otherwise unaccounted for by the existing techniques. In two converter examples, the proposed model corrects the misleading results of the existing models by providing truthful characterization of the overall converter AC response and offers important guidance for converter design and closed-loop control.
Age or ischemia uncouples the blood flow response, tissue acidosis, and direct current potential signature of spreading depolarization in the rat brain
Authors: Menyhárt Ákos , Zölei-Szénási Dániel , Puskás Tamás , Makra Péter , Bari Ferenc , Farkas Eszter
Published: June 2017

Spreading depolarization (SD) events contribute to lesion maturation in the acutely injured human brain. Neurodegeneration related to SD is thought to be caused by the insufficiency of the cerebral blood flow (CBF) response; yet the mediators of the CBF response, or their deficiency in the aged or ischemic cerebral cortex, remain the target of intensive research. Here, we postulated that tissue pH effectively modulates the magnitude of hyperemia in response to SD, the coupling of which is prone to be dysfunctional in the aged or ischemic cerebral cortex. To test this hypothesis, we conducted systematic correlation analysis between the direct current (DC) potential signature of SD, SD-associated tissue acidosis, and hyperemic element of the CBF response in the isoflurane-anesthetized, young or old, and intact or ischemic rat cerebral cortex. The data demonstrate that the amplitude of the SD-related DC potential shift, tissue acidosis, and hyperemia are tightly coupled in the young intact cortex; ischemia and old age uncouples the amplitude of hyperemia from the amplitude of the DC potential shift and acidosis; the duration of the DC potential shift, hyperemia and acidosis positively correlate under ischemia alone; and old age disproportionally elongates the duration of acidosis with respect to the DC potential shift and hyperemia under ischemia. The coincidence of the variables supports the view that local CBF regulation with SD must have an effective metabolic component, which becomes dysfunctional with age or under ischemia. Finally, the known age-related acceleration of ischemic neurodegeneration may be promoted by exaggerated tissue acidosis.

NEW & NOTEWORTHY The hyperemic element of the cerebral blood flow response to spreading depolarization is effectively modulated by tissue pH in the young intact rat cerebral cortex. This coupling becomes dysfunctional with age or under ischemia, and tissue acidosis lasts disproportionally longer in the aged cortex, making the tissue increasingly more vulnerable.
Making the Case for Investment in Rural Cancer Control: An Analysis of Rural Cancer Incidence, Mortality, and Funding Trends
Authors: Blake Kelly D. , Moss Jennifer L. , Gaysynsky Anna , Srinivasan Shobha , Croyle Robert T.
Published: June 2017

Estimates of those living in rural counties vary from 46.2 to 59 million, or 14% to 19% of the U.S. population. Rural communities face disadvantages compared with urban areas, including higher poverty, lower educational attainment, and lack of access to health services. We aimed to demonstrate rural–urban disparities in cancer and to examine NCI-funded cancer control grants focused on rural populations. Estimates of 5-year cancer incidence and mortality from 2009 to 2013 were generated for counties at each level of the rural–urban continuum and for metropolitan versus nonmetropolitan counties, for all cancers combined and several individual cancer types. We also examined the number and foci of rural cancer control grants funded by NCI from 2011 to 2016. Cancer incidence was 447 cases per 100,000 in metropolitan counties and 460 per 100,000 in nonmetropolitan counties (P < 0.001). Cancer mortality rates were 166 per 100,000 in metropolitan counties and 182 per 100,000 in nonmetropolitan counties (P < 0.001). Higher incidence and mortality in rural areas were observed for cervical, colorectal, kidney, lung, melanoma, and oropharyngeal cancers. There were 48 R- and 3 P-mechanism rural-focused grants funded from 2011 to 2016 (3% of 1,655). Further investment is needed to disentangle the effects of individual-level SES and area-level factors to understand observed effects of rurality on cancer. Cancer Epidemiol Biomarkers Prev; 26(7); 992–7. ©2017 AACR.
The Premenopausal Breast Cancer Collaboration: A Pooling Project of Studies Participating in the National Cancer Institute Cohort Consortium
Authors: Nichols Hazel B. , Schoemaker Minouk J. , Wright Lauren B. , McGowan Craig , Brook Mark N. , McClain Kathleen M. , Jones Michael E. , Adami Hans-Olov , Agnoli Claudia , Baglietto Laura , Bernstein Leslie , Bertrand Kimberly A. , Blot William J. , Boutron-Ruault Marie-Christine , Butler Lesley , Chen Yu , Doody Michele M. , Dossus Laure , Eliassen A. Heather , Giles Graham G. , Gram Inger T. , Hankinson Susan E. , Hoffman-Bolton Judy , Kaaks Rudolf , Key Timothy J. , Kirsh Victoria A. , Kitahara Cari M. , Koh Woon-Puay , Larsson Susanna C. , Lund Eiliv , Ma Huiyan , Merritt Melissa A. , Milne Roger L. , Navarro Carmen , Overvad Kim , Ozasa Kotaro , Palmer Julie R. , Peeters Petra H. , Riboli Elio , Rohan Thomas E. , Sadakane Atsuko , Sund Malin , Tamimi Rulla M. , Trichopoulou Antonia , Vatten Lars , Visvanathan Kala , Weiderpass Elisabete , Willett Walter C. , Wolk Alicja , Zeleniuch-Jacquotte Anne , Zheng Wei , Sandler Dale P. , Swerdlow Anthony J.
Published: June 2017

Breast cancer is a leading cancer diagnosis among premenopausal women around the world. Unlike rates in postmenopausal women, incidence rates of advanced breast cancer have increased in recent decades for premenopausal women. Progress in identifying contributors to breast cancer risk among premenopausal women has been constrained by the limited numbers of premenopausal breast cancer cases in individual studies and resulting low statistical power to subcategorize exposures or to study specific subtypes. The Premenopausal Breast Cancer Collaborative Group was established to facilitate cohort-based analyses of risk factors for premenopausal breast cancer by pooling individual-level data from studies participating in the United States National Cancer Institute Cohort Consortium. This article describes the Group, including the rationale for its initial aims related to pregnancy, obesity, and physical activity. We also describe the 20 cohort studies with data submitted to the Group by June 2016. The infrastructure developed for this work can be leveraged to support additional investigations. Cancer Epidemiol Biomarkers Prev; 26(9); 1360–9. ©2017 AACR.
Clinical Implications of Monitoring Circulating Tumor DNA in Patients with Colorectal Cancer
Authors: Schøler Lone V. , Reinert Thomas , Ørntoft Mai-Britt W. , Kassentoft Christine G. , Árnadóttir Sigrid S. , Vang Søren , Nordentoft Iver , Knudsen Michael , Lamy Philippe , Andreasen Ditte , Mortensen Frank V. , Knudsen Anders R. , Stribolt Katrine , Sivesgaard Kim , Mouritzen Peter , Nielsen Hans J. , Laurberg Søren , Ørntoft Torben F. , Andersen Claus L.
Published: June 2017

Purpose: We investigated whether detection of ctDNA after resection of colorectal cancer identifies the patients with the highest risk of relapse and, furthermore, whether longitudinal ctDNA analysis allows early detection of relapse and informs about response to intervention.

Experimental Design: In this longitudinal cohort study, we used massively parallel sequencing to identify somatic mutations and used these as ctDNA markers to detect minimal residual disease and to monitor changes in tumor burden during a 3-year follow-up period.

Results: A total of 45 patients and 371 plasma samples were included. Longitudinal samples from 27 patients revealed ctDNA postoperatively in all relapsing patients (n = 14), but not in any of the nonrelapsing patients. ctDNA detected relapse with an average lead time of 9.4 months compared with CT imaging. Of 21 patients treated for localized disease, six had ctDNA detected within 3 months after surgery. All six later relapsed compared with four of the remaining patients [HR, 37.7; 95% confidence interval (CI), 4.2–335.5; P < 0.001]. The ability of a 3-month ctDNA analysis to predict relapse was confirmed in 23 liver metastasis patients (HR 4.9; 95% CI, 1.5–15.7; P = 0.007). Changes in ctDNA levels induced by relapse intervention (n = 19) showed good agreement with changes in tumor volume (κ = 0.41; Spearman ρ = 0.4).

Conclusions: Postoperative ctDNA detection provides evidence of residual disease and identifies patients at very high risk of relapse. Longitudinal surveillance enables early detection of relapse and informs about response to intervention. These observations have implications for the postoperative management of colorectal cancer patients. Clin Cancer Res; 23(18); 5437–45. ©2017 AACR.
Dual Inhibition of HDAC and Tyrosine Kinase Signaling Pathways with CUDC-907 Inhibits Thyroid Cancer Growth and Metastases
Authors: Kotian Shweta , Zhang Lisa , Boufraqech Myriem , Gaskins Kelli , Gara Sudheer Kumar , Quezado Martha , Nilubol Naris , Kebebew Electron
Published: June 2017

Purpose: There is currently no standard therapy for anaplastic thyroid cancer (ATC) and poorly differentiated thyroid cancer (PDTC), which account for two-thirds of thyroid cancer–related deaths. Driver mutations in the PI3K/AKT and RAF/RAS/MEK/ERK pathways are common in ATC and PDTC. Histone deacetylases (HDAC) regulate cancer initiation and progression. Our aim was to determine the therapeutic efficacy of simultaneously targeting these pathways in thyroid cancer with a single agent and to evaluate biomarkers of treatment response.

Experimental Design: CUDC-907 is a first-in-class compound, functioning as a dual inhibitor of HDACs and the PI3K/AKT pathway. We investigated its antiproliferative effect in vitro and in vivo.

Results: CUDC-907 significantly inhibited cellular proliferation in thyroid cancer cell lines, induced G2–M arrest with decreased levels of the checkpoint regulators cyclin B1, AURKA, AURKB, PLK1, and increased p21 and p27. Treatment induced apoptosis with increased caspase-3/7 activity and decreased survivin levels and decreased cellular migration and invasion. CUDC-907 treatment caused H3 hyperacetylation and decreased HDAC2 expression. HDAC2 was upregulated in ATC and other thyroid cancer histologic subtypes. CUDC-907 treatment reduced both p-AKT and p-ERK1/2 levels. Finally, CUDC-907 treatment, in a metastatic mouse model of thyroid cancer, showed significant inhibition of growth and metastases, and tumors from treated mice had decreased HDAC2 expression, suggesting that this may be a useful biomarker of response.

Conclusions: Dual inhibition of HDAC and the tyrosine kinase signaling pathways with CUDC-907 is a promising treatment strategy for advanced, metastatic thyroid cancer. Clin Cancer Res; 23(17); 5044–54. ©2017 AACR.
Intratumor Heterogeneity: Novel Approaches for Resolving Genomic Architecture and Clonal Evolution
Authors: Gupta Ravi G. , Somer Robert A.
Published: June 2017

High-throughput genomic technologies have revealed a remarkably complex portrait of intratumor heterogeneity in cancer and have shown that tumors evolve through a reiterative process of genetic diversification and clonal selection. This discovery has challenged the classical paradigm of clonal dominance and brought attention to subclonal tumor cell populations that contribute to the cancer phenotype. Dynamic evolutionary models may explain how these populations grow within the ecosystem of tissues, including linear, branching, neutral, and punctuated patterns. Recent evidence in breast cancer favors branching and punctuated evolution driven by genome instability as well as nongenetic sources of heterogeneity, such as epigenetic variation, hierarchal tumor cell organization, and subclonal cell–cell interactions. Resolution of the full mutational landscape of tumors could help reconstruct their phylogenetic trees and trace the subclonal origins of therapeutic resistance, relapsed disease, and distant metastases, the major causes of cancer-related mortality. Real-time assessment of the tumor subclonal architecture, however, remains limited by the high rate of errors produced by most genome-wide sequencing methods as well as the practical difficulties associated with serial tumor genotyping in patients. This review focuses on novel approaches to mitigate these challenges using bulk tumor, liquid biopsies, single-cell analysis, and deep sequencing techniques. The origins of intratumor heterogeneity and the clinical, diagnostic, and therapeutic consequences in breast cancer are also explored. Mol Cancer Res; 15(9); 1127–37. ©2017 AACR.