bluuebunny/crossref_metadata_2025 huggingface dataset:
Type 2 diabetes promotes cell centrosome amplification and the role of AKT-ROS-dependent signalling of ROCK1 and 14-3-3σ
Authors: Wang Pu , Lu Yu Cheng , Wang Jie , Wang Lan , Yu Hanry , Li Yuan Fei , Kong Alice , Chan Juliana , Lee Shao Chin
Published: August 2017

Type2 diabetes is associated with oxidative stress which can cause cell centrosome amplification. The study investigated centrosome amplification in type 2 diabetes and the underlying mechanisms. We found that centrosome amplification was increased in the peripheral blood mononuclear cells (PBMC) from the type 2 diabetic patients, which correlated with the levels of fasting blood glucose and HbA1c. High glucose, insulin and palmitic acid, alone or in combinations, induced ROS production and centrosome amplification. Together, they increased AKT activation as well as the expression, binding and centrosome translation of ROCK1 and 14-3-3σ. Results from further analyses showed that AKT-ROS-dependent upregulations of expression, binding and centrosome translocation of ROCK1 and 14-3-3σ was the molecular pathway underlying the centrosome amplification induced by high glucose, insulin and palmitic acid. Moreover, the increases in AKT activation and ROS production as well as expression, binding and centrosome distribution of ROCK1 and 14-3-3σ were confirmed in the PBMC from the patients with type 2 diabetes. In conclusion, our results show that type 2 diabetes promotes cell centrosome amplification, and suggest that the diabetic pathophysiological factors-activated AKT-ROS-dependent signalling of ROCK1 and 14-3-3σ is the underlying molecular mechanism.
Identifying genetic determinants of complex phenotypes from whole genome sequence data
Authors: Long George S. , Hussen Mohammed , Dench Jonathan , Aris-Brosou Stéphane
Published: August 2017

A critical goal in biology is to relate the phenotype to the genotype, that is, to find the genetic determinants of various traits. However, while simple monofactorial determinants are relatively easy to identify, the underpinnings of complex phenotypes are harder to predict. While traditional approaches rely on genome-wide association studies based on Single Nucleotide Polymorphism data, the ability of machine learning algorithms to find these determinants in whole proteome data is still not well known. To better understand the applicability of machine learning in this case, we implemented two such algorithms, adaptive boosting (AB) and repeated random forest (RRF), and developed a chunking layer that facilitates the analysis of whole proteome data. We first assessed the performance of these algorithms and tuned them on an influenza data set, for which the determinants of three complex phenotypes (in-fectivity, transmissibility, and pathogenicity) are known based on experimental evidence. This allowed us to show that chunking improves runtimes by an order of magnitude. Based on simulations, we showed that chunking also increases sensitivity of the predictions, reaching 100% with as few as 20 sequences in a small proteome as in the influenza case (5k sites), but may require at least 30 sequences to reach 90% on larger alignments (500k sites). While RRF has less specificity than RF, it was never < 50%, and RRF sensitivity was significantly higher at smaller chunk sizes. We then used these algorithms to predict the determinants of three types of drug resistance (to Ciprofloxacin, Ceftazidime, and Gentamicin) in a bacterium,Pseudomonas aeruginosa. While both algorithms performed well in the case of the influenza data, results were more nuanced in the bacterial case, with RRF making more sensible predictions, with smaller errors rates, than AB. Altogether, we demonstrated that ML algorithms can be used to identify genetic determinants in small proteomes (viruses), even when trained on small numbers of individuals. We further showed that our RRF algorithm may deserve more scrutiny, which should be facilitated by the decreasing costs of both sequencing and phenotyping of large cohorts of individuals.
On the Structure and Mechanism of Two-Pore Channels
Authors: Kintzer Alexander F. , Stroud Robert M.
Published: August 2017

In eukaryotes, two-pore channels (TPC1-3) comprise a family of ion channels that regulate the conductance of Na+and Ca2+ions across cellular membranes. TPC1-3 form endolysosomal channels, but TPC3 can also function in the plasma membrane. TPC1/3 are voltage-gated channels, but TPC2 opens in response to binding endolysosome-specific lipid phosphatidylinositol-3,5-diphosphate (PI(3,5)P2). Filoviruses, such as Ebola, exploit TPC-mediated ion release as a means of escape from the endolysosome during infection. Antagonists that block TPC1/2 channel conductance abrogate filoviral infections. TPC1/2 form complexes with the mechanistic target of rapamycin complex 1 (mTORC1) at the endolysosomal surface that couple cellular metabolic state and cytosolic nutrient concentrations to the control of membrane potential and pH. We determined the X-ray structure of TPC1 fromArabidopsis thaliana(AtTPC1) to 2.87Å resolution–one of the two first reports of a TPC channel structure. Here we summarize these findings and the implications that the structure may have for understanding endolysosomal control mechanisms and their role in human health.

Abbreviations

mTORC1

Mechanistic target of rapamycin complex 1

TPC

Two-pore channel

PI(3,5)P2

Phosphatidylinositol-3,5-diphosphate

AtTPC1

Arabidopsis thalianaTPC1

NED19

Trans-Ned-19

VSD

Voltage-sensing domain

P1

Pore domain in S5-S6

P2

Pore domain in S11-S12

Cav

Voltage-gated calcium channel

Nav

Voltage-gated sodium channel

Kv

Voltage-gated potassium channel

NTD

N-terminal domain

CTD

C-terminal domain

EF

EF-hand domain

NAADP

Nicotinic acid adenine dinucleotide phosphate

PI(4,5)P2

Phosphatidylinositol-4,5-diphosphate

DHP

Dihydropyridine

PAA

Phenylalkylamine

BTZ

Benzothiazepine

Caa2+

Activating Ca2+-ion

Cai2+

Inhibitory Ca2+-ion

fou2

Fatty acid oxygenation up-regulated 2

SLC38a9

Sodium-coupled neutral amino acid transporter 9

NPC1

Niemann-Pick C1

PKA

Protein kinase A

PKC

Protein kinase C

PKG

Protein kinase G

H+

ATPase - Proton Pump

32P

– Phosphorus-32
Tetrahydrocannabinolic acid is a potent PPARγ agonist with neuroprotective activity
Authors: Nadal Xavier , del Río Carmen , Casano Salvatore , Palomares Belén , Ferreiro‐Vera Carlos , Navarrete Carmen , Sánchez‐Carnerero Carolina , Cantarero Irene , Bellido Maria Luz , Meyer Stefan , Morello Gaetano , Appendino Giovanni , Muñoz Eduardo
Published: August 2017

Background and Purpose

Phytocannabinoids are produced in Cannabis sativa L. in acidic form and are decarboxylated upon heating, processing and storage. While the biological effects of decarboxylated cannabinoids such as Δ9‐tetrahydrocannabinol have been extensively investigated, the bioactivity of Δ9‐tetahydrocannabinol acid (Δ9‐THCA) is largely unknown, despite its occurrence in different Cannabis preparations. Here we have assessed possible neuroprotective actions of Δ9‐THCA through modulation of PPARγ pathways.

Experimental Approach

The effects of six phytocannabinoids on PPARγ binding and transcriptional activity were investigated. The effect of Δ9‐THCA on mitochondrial biogenesis and PPARγ coactivator 1‐α expression was investigated in Neuro‐2a (N2a) cells. The neuroprotective effect was analysed in STHdhQ111/Q111 cells expressing a mutated form of the huntingtin protein and in N2a cells infected with an adenovirus carrying human huntingtin containing 94 polyQ repeats (mHtt‐q94). The in vivo neuroprotective activity of Δ9‐THCA was investigated in mice intoxicated with the mitochondrial toxin 3‐nitropropionic acid (3‐NPA).

Key Results

Cannabinoid acids bind and activate PPARγ with higher potency than their decarboxylated products. Δ9‐THCA increased mitochondrial mass in neuroblastoma N2a cells and prevented cytotoxicity induced by serum deprivation in STHdhQ111/Q111 cells and by mutHtt‐q94 in N2a cells. Δ9‐THCA, through a PPARγ‐dependent pathway, was neuroprotective in mice treated with 3‐NPA, improving motor deficits and preventing striatal degeneration. In addition, Δ9‐THCA attenuated microgliosis, astrogliosis and up‐regulation of proinflammatory markers induced by 3‐NPA.

Conclusions and Implications

Δ9‐THCA shows potent neuroprotective activity, which is worth considering for the treatment of Huntington's disease and possibly other neurodegenerative and neuroinflammatory diseases.
Variation in chick‐a‐dee calls of bridled titmice (Baeolophus wollweberi): Frequent use of non‐combinatorial calls in a combinatorial calling system
Authors: Jung Hwayoung , Freeberg Todd M.
Published: August 2017

Chick‐a‐dee calls of Poecile (chickadee) and Baeolophus (titmouse) species are complex in terms of the structural composition of note types and the diversity of messages. Studies so far have mainly focused on the calls of various chickadee and just one titmouse species—the tufted titmouse (B. bicolor). To begin to address this lack of titmouse data, our study investigated variation in note composition of calls of bridled titmice (B. wollweberi). We obtained calls from 26 flocks in the Chiricahua Mountains of Arizona in the overwintering flocking period. Bridled titmice produce proportionally more non‐combinatorial call variants than combinatorial call variants. The number of the single noted calls furthermore exceeded the number of multinote calls. In general, structural variation in the combinatorial calls appears to be comparable to calls of better‐studied chickadees and of tufted titmice, although bridled titmice appear to have a unique call length distribution. We also analyzed some behavioral associations with call variation and found that flight behavior and close interactions between individuals were associated with use of specific note types. Finally, we found microgeographic variation in note type use in these calls. We discuss some possible explanations for call complexity in this species.
Remote sensing as a tool to assess botanical composition, structure, quantity and quality of temperate grasslands
Authors: Wachendorf M. , Fricke T. , Möckel T.
Published: August 2017

Grassland systems frequently exhibit small‐scale botanical and structural heterogeneity with pronounced spatio‐temporal dynamics. These features present particular challenges for sensor applications, in addition to limitations posed by the high cost and low spatial resolution of many available remote‐sensing (RS) systems. There has been little commercial application ofRSfor practical grassland farming. This article considers the developments in sensor performance, data analysis and modelling over recent decades, identifies significant advances inRSfor grassland research and practice and reviews the most important sensor types and corresponding findings in research. Beside improvements of single sensor types, the development of systems with complementary sensors is seen as a very promising research area, and one that will help to overcome the limitations of single sensors and provide better information about grassland composition, yield and quality. From an agronomic point of view, thematic maps of farm fields are suggested as the central outcome ofRSand data analysis. These maps could represent the relevant grassland features and constitute the basis for various farm management decisions at strategic, tactical and operational levels. The overarching goal will be to generate low cost, appropriate and timely information that can be provided to farmers to support their decision‐making.
Diagnostic accuracy of instantaneous wave free‐ratio in clinical practice
Authors: Ding Wern Yew , Nair Satheesh , Appleby Clare
Published: August 2017

Aims

To evaluate the correlation between iFR and FFR in real‐world clinical practice.

Methods and Results

Retrospective, single‐centre study of 229 consecutive pressure‐wire studies (np = 158). Real‐time iFR and FFR measurements were performed for angiographically borderline stenoses. Functionally significant stenoses were defined as iFR <0.86 or FFR ≤0.80. An iFR between 0.86 and 0.93 was considered within the grey zone (Hybrid approach). Median iFR and FFR (IQR) were 0.92 (0.87‐0.95) and 0.83 (0.76‐0.89), respectively. Pearson's correlation coefficient was 0.75 (P < 0.001). Bland‐Altman plot showed a mean difference between iFR and FFR that remained consistent throughout the range of values. The optimal iFR cutoff was 0.91—sensitivity 80%, specificity 82% with ROC area under curve of 89%. Using the Hybrid iFR‐FFR strategy, we demonstrated high accuracy of iFR results—sensitivity 95%, specificity 96%, PPV 95%, and NPV 96%. In addition, this method would have avoided adenosine in 56% of patients. Mean follow‐up period was 17.2 (±3.4) months. All‐cause mortality was 3.2% (np = 5) and repeat intervention was required in six lesions (2.6%).

Conclusions

This study demonstrates that iFR is a valuable adjunct to FFR using the Hybrid iFR‐FFR strategy in a real‐world population. The use of adenosine may be avoided in about half the cases.
THE EFFECT OF EXTERNAL SUCTION AT THE DUST OUTLET OF A CYCLONE
Authors: Dewika M. , Rashid M. , Hasyimah N.
Published: August 2017

Cyclone is one of the most commonly used particulate dust collectors in industries. It employs centrifugal force generated by a spinning gas stream to separate the particulate matter from the carrier gas. However, cyclone is efficient to collect coarse rather than fine particulate size fraction. In this regard, a study was carried out to determine the effect of creating more negative pressure at the storage hopper of a 100 mm diameter laboratory scale cyclone. The negative pressure was created by drawing out a small portion of the gas stream by means of an air pump attached to the storage hopper.  Results showed that there was exponentially related between the pressure drop (ΔP) and the amount of gas stream drawn at the storage hopper, but with an increment of 2.6% with suction compared to without. Interestingly, it was observed that more of the fine particulate matter was drawn from the gas stream as the suction flow rate increases. This is due to the suction velocity which exceeds the terminal falling velocities of the fine particles size range. There was a reduction by weight in the fine particle emitted from the cyclone ranging between 14% to 52% by introduction of the suction. The finding serves as a basis for future work in reducing fine particulates from a cyclone separator.
Motion Video-Based Quantitative Analysis of the ‘lifting-Thrusting— Method: A Comparison between Teachers and Students of Acupuncture
Authors: Tang Wen-Chao , Yang Hua-Yuan , Liu Tang-Yi , Gao Ming , Xu Gang
Published: August 2017

Objective

To compare objective measures of needle manipulation between students and teachers of acupuncture using motion video analysis technology, to help support instructional acupuncture education.

Methods

A total of 30 teachers and 60 students participated in this study. Acupuncture needles were inserted at LI11 and motion videos were recorded for three subtypes of ‘lifting-thrusting’ manipulation: (1) ‘mild reinforcing-attenuating’; (2) ‘reinforcing’; and (3) ‘attenuating’. The videos were analysed using Simi Motion 3D software to acquire the movement parameters of four trace marks: ‘thumb tip’; ‘forefinger tip’; ‘forefinger middle joint’; and ‘forefinger base joint’. Differences between the two groups were compared using t-tests, X2 tests and/or rank-sum tests.

Results

Changes in the near-end interphalangeal joint were positively associated with a range of movement along the X axis. Motion parameters for the thumb tip, the proximal interphalangeal (PIP) joint of the forefinger and the X axis shaft swing near the end of the forefinger in the teacher group were higher than those in the student group. The teacher group featured smaller trough dispersion and smaller crest dispersion during ‘reinforcing’ and ‘attenuating’ manipulations, respectively.

Conclusions

The ‘lifting-thrusting’ manipulation could be simplified as a fixed-axis rotation using metacarpophalangeal joints in the thumb and forefinger as the shaft centre. Teachers opened at a larger angular variation for the PIP during the lifting and thrusting processes with better spatial control. Temporal control was similar between groups and therefore appears easier to grasp. Repetitive training might be helpful for improving athletic and spatial stability during needle manipulation.
Fifteen-minute consultation: Assessment, surveillance and management of hemihypertrophy
Authors: Mark Catherine , Hart Caroline , McCarthy Anthony , Thompson Andrew
Published: August 2017

This article aims to provide a structured and concise guide for the general paediatrician managing a child with hemihypertrophy. Hemihypertrophy is a relatively uncommon condition. The significance is that a proportion of those affected are at risk of developing malignancies in childhood. For these children regular surveillance is required. We have outlined how one might assess and investigate a child presenting with hemihypertrophy. We have also formulated a practicable surveillance strategy which is in line with the current Royal College of Paediatrics and Child Health (RCPCH) guideline ‘Wilms’ tumour surveillance in at-risk children’.
Effect of childhood coeliac disease on ninth grade school performance: evidence from a population-based study
Authors: Namatovu Fredinah , Strandh Mattias , Ivarsson Anneli , Nilsson Karina
Published: August 2017

Background

Coeliac disease might affect school performance due to its effect on cognitive performance and related health consequences that might increase school absenteeism. The aim of this study was to investigate whether children with coeliac disease performed differently on completion of ninth grade in school compared with children without coeliac disease.

Methods

Analysis was performed on a population of 445 669 children born in Sweden between 1991 and 1994 of whom 1767 were diagnosed with coeliac disease. School performance at ninth grade was the outcome and coeliac disease was the exposure. Other covariates included sex, Apgar score at 5 min, small for gestational age, year of birth, family type, parental education and income.

Results

There was no association between coeliac disease and school performance at ninth grade (adjusted coefficient −2.4, 95% CI 5.1 to 0.4). A weak association was established between late coeliac diagnosis and higher grades, but this disappeared after adjusting for parent socioeconomic conditions. Being small for gestational age affected performance negatively (adjusted coefficient −6.9, 95% CI 8.0 to 5.7). Grade scores were significantly lower in children living with a single parent (adjusted coefficient −20.6, 95% CI 20.9 to 20.2), compared with those with married/cohabiting parents. A positive association was found between scores at ninth grade and parental education and income.

Conclusion

Coeliac disease diagnosis during childhood is not associated with poor school performance at ninth grade.
What is MR spectroscopy?
Authors: Manias Karen Angela , Peet Andrew
Published: August 2017

1H-Magnetic Resonance Spectroscopy (MRS) is a novel advanced imaging technique used as an adjunct to MRI to reveal complementary non-invasive information about the biochemical composition of imaged tissue. Clinical uses in paediatrics include aiding diagnosis of brain tumours, neonatal disorders such as hypoxic-ischaemic encephalopathy, inherited metabolic diseases, traumatic brain injury, demyelinating conditions and infectious brain lesions. MRS has potential to improve diagnosis and treatment monitoring of childhood brain tumours and other CNS diseases, facilitate biopsy and surgical planning, and provide prognostic biomarkers. MRS is employed as a research tool outside the brain in liver disease and disorders of muscle metabolism. The range of clinical uses is likely to increase with growing evidence for added value. Multicentre trials are needed to definitively establish the benefits of MRS in specific clinical scenarios and integrate this promising new technique into routine practice to improve patient care. This article gives a brief overview of MRS and its potential clinical applications, and addresses challenges surrounding translation into practice.
Non-invasive method of monitoring retinal vasculitis in patients with birdshot chorioretinopathy using optical coherence tomography
Authors: Knickelbein Jared E , Tucker William , Kodati Shilpa , Akanda Marib , Sen H Nida
Published: August 2017

Background/aims

To investigate the utility of using montaged optical coherence tomography (OCT) thickness maps to monitor perivascular thickness as a marker of vasculitic activity in patients with large-vessel retinal vasculitis.

Methods

This is a retrospective cohort study of 22 eyes of 11 patients with a history of retinal vasculitis associated with birdshot chorioretinopathy (BCR). Patients had serial spectral domain 6×6 mm cube OCT scans centred on the fovea, optic nerve and proximal branches of the superior and inferior retinal vessels. OCT thickness change maps for each respective region were analysed. Changes in perivascular thickness were confirmed by assessing vasculitic activity on fluorescein angiography (FA), when clinically indicated.

Results

In three patients, montaged OCT scans were acquired at diagnosis and serially through initial treatment. In all three patients, montaged OCT demonstrated reduced perivascular thickening with oral prednisone treatment, which was confirmed by FA showing reduced vascular leakage in both eyes. Eight patients had serial montaged OCT scans after diagnosis and initial treatment of BCR. Four of these patients showed fluctuations in perivascular thickness during flares and treatment that were confirmed by either increased or decreased vascular leakage on FA. The other four patients remained quiet on their immunosuppressive treatment regimens, and no changes in perivascular thickness were detected.

Conclusions

Evaluating large-vessel perivascular thickness on OCT scans may be a useful method for non-invasively monitoring posterior pole large-vessel retinal vasculitis.
Active surveillance of choroidal neovascularisation in children: incidence, aetiology and management findings from a national study in the UK
Authors: Moosajee Mariya , Abbouda Alessandro , Foot Barnaby , Bunce Catey , Moore Anthony T , Acheson James
Published: August 2017

Background/Aims

To determine the UK incidence, demographics, aetiology, management and visual outcome for children developing choroidal neovascularisation (CNV).

Methods

A prospective population-based observational study of routine practice via the British Ophthalmological Surveillance Unit between January 2012 and December 2013 with subsequent 1-year follow-up in children under 16 years old with newly diagnosed CNV.

Results

Twenty-seven children with CNV were reported. The UK estimated annual incidence for those aged 16 and under was 0.21 per 100 000 (95% CI 0.133 to 0.299). The mean age was 11.1 years (SD 3.9, range 4–16). Fourteen were female. Seventy-seven per cent (22 patients) were Caucasian British. Twenty-three children (85%) had unilateral disease. The most common aetiology included inflammatory retinochoroidopathy (n=9), optic disc abnormalities (n=9) and idiopathic (n=5). Optical coherence tomography was performed in all cases and fundus fluorescein angiography in 61%. Management included observation only (n=10), anti-vascular endothelial growth factor (anti-VEGF) injection of bevacizumab (n=14) or ranibizumab (n=2), or both (n=1), and additional use of oral (n=1) and local (periocular n=2 and intravitreal n=2) steroids in five children with inflammatory retinochoroidopathy. The mean number of anti-VEGF injections was 2±1, with eight patients receiving only one injection. The mean (SD) best corrected visual acuity in LogMAR was 0.91 (0.53) at presentation and 0.74 (0.53) at 1-year follow-up (p=0.09).

Conclusion

This is the first population-based prospective study of CNV in children. This is a rare disorder with a poor visual prognosis irrespective of CNV location and the use of anti-VEGF therapy.
Traumatic brain injury, dry eye and comorbid pain diagnoses in US veterans
Authors: Lee Charity J , Felix Elizabeth R , Levitt Roy C , Eddy Christopher , Vanner Elizabeth A , Feuer William J , Sarantopoulos Constantine D , Galor Anat
Published: August 2017

Aims

The purpose of the study is to evaluate the relationship between dry eye (DE) and pain diagnoses in US veterans with and without traumatic brain injury (TBI).

Methods

Retrospective cohort study of veterans who were seen in the Veterans Administration Hospital (VA) between 1 January 2010 and 31 December 2014. Veterans were separated into two groups by the presence or absence of an International Classification of Diseases, Ninth Revision diagnosis of TBI and assessed for DE and other comorbidities. A dendrogram was used to investigate the linkage between TBI, DE, chronic pain and other comorbid conditions.

Results

Of the 3 265 894 veterans seen during the 5-year period, 3.97% carried a diagnosis of TBI. Veterans with TBI were more likely to have a diagnosis of DE compared with their counterparts without TBI (37.2% vs 29.1%, p<0.0005). The association was stronger between TBI and ocular pain (OR 3.08; 95% CI 3.03 to 3.13) compared with tear film dysfunction (OR 1.09; 95% CI 1.07 to 1.10). Those with TBI were also about twice as likely to have a diagnosis of chronic pain, headache, depression or post-traumatic stress disorder compared with their counterparts without TBI. Cluster analysis of TBI, DE and pain diagnoses of interest revealed that central pain syndrome, cluster headache, sicca syndrome, keratoconjunctivitis sicca and late effect of injury to the nervous system (as can be seen after TBI) were all closely clustered together.

Conclusions

DE and pain disorders occur at higher frequencies in patients with a diagnosis of TBI, suggesting a common underlying pathophysiology.
Intravitreal topotecan in the management of refractory and recurrent vitreous seeds in retinoblastoma
Authors: Rao Raksha , Honavar Santosh G , Sharma Vishal , Reddy Vijay Anand P
Published: August 2017

Background/aim

To evaluate the efficacy of intravitreal topotecan for refractory or recurrent vitreous seeds in retinoblastoma.

Methods

Intravitreal injection of topotecan hydrochloride (30 µg/0.15 mL) was provided every 3 weeks by the safety enhanced technique.

Results

The study included 17 consecutive patients with retinoblastoma with refractory or recurrent vitreous seeds. Five eyes (29%) belonged to International Classification of Retinoblastoma group C and 12 eyes (71%) belonged to group D. Primary treatment included triple drug intravenous chemotherapy for a mean of 10 cycles (median, 9 cycles; range, 6–18 cycles). Fifteen patients (88%) had undergone 56 periocular carboplatin injections with a mean of 4 injections (median, 3 injections; range, 1–8 injections), concurrent with intravenous chemotherapy. A total of 53 intravitreal topotecan injections were performed in 17 eyes of 17 consecutive patients with refractory or recurrent vitreous seeds with a mean of 3 injections (median, 3 injections; range, 2–6 injections). Complete regression of vitreous seeds was achieved in 17 of 17 eyes (100%). At a mean follow-up of 23.8 months (median, 24 months; range, 15.1–34.1 months), one eye (6%) with a recurrent retinal tumour needed enucleation, and the rest of the 16 eyes (94%) maintained complete regression. Final visual acuity could be reliably assessed in all 16 eyes (100%), of whom 12 eyes (75%) had visual acuity ≥20/200. None of the patients developed ocular or systemic complications.

Conclusion

Three-weekly intravitreal topotecan appears effective and safe in controlling focal or diffuse refractory or recurrent vitreous seeds in retinoblastoma.
Multicentred international review of orbital exenteration and reconstruction in oculoplastic and orbit practice
Authors: Zhang Ze , Ho Son , Yin Vivian , Varas Gonzalo , Rajak Saul , Dolman Peter J , McNab Alan , Heathcote J Godfrey , Valenzuela Alejandra
Published: August 2017

Background

Orbital exenteration is a disfiguring procedure reserved for life-threatening malignancies. This study examines the clinical course and outcomes of a large series of patients who underwent orbital exenteration for malignant periocular neoplasms.

Methods

This is a retrospective review of patients who underwent orbital exenteration from 1 July 2005 to 30 June 2015 at four tertiary referral centres in the USA, Australia and Canada. Demographics, indication for surgery, pathology, surgical technique, reconstruction type and outcomes were reviewed.

Results

Orbital exenteration was performed on 102 patients. The mean age at surgery was 67.5 years. The most common malignant tumours encountered were squamous cell carcinoma, melanoma and basal cell carcinoma. Seventy-six patients (75%) underwent reconstruction with a local myocutaneous flap, twelve with partial-thickness skin grafts (PTSG), or split skin graft, two had a free flap, and one had a dermis fat graft. Sixteen patients had combined procedures of two of the above. Complete removal of the tumour was achieved with clear margins in 81 cases. Of all patients, 72% were alive at 48 months or more.

Conclusion

The majority of orbital exenterations performed in this series were secondary to periocular malignancies with unsuccessful/insufficient previous treatments. Regional myocutaneous flaps, PTSG, full-thickness skin grafts and dermis fat grafts were all highly effective and durable reconstructive options, and were able to withstand radiation therapy without complications.
Pterygia are indicators of an increased risk of developing cutaneous melanomas
Authors: Crewe Julie M , Threlfall Tim , Clark Antony , Sanfilippo Paul G , Mackey David A
Published: August 2017

Aim

To investigate whether pterygium is an indicator of an increased risk of cutaneous melanoma (CM).

Methods

A matched-cohort study, using linked health administrative data sets to identify all hospital-treated pterygium in Western Australia (WA) between 1979 and 2014. We identified pterygium cases from hospital diagnosis and/or procedure International Classification of Diseases 9th revision (ICD-9) and 10th revision (ICD-10) codes and matched cases by age, sex and residential postcode to WA Electoral Roll controls with no known history of pterygium. Both cohorts were linked to the WA Cancer Registry and the WA Deaths Registry.

Results

23 625 people had pterygium treatment (64% male) in WA hospitals. The median age for pterygium diagnosis and/or treatment was 49 years (range 14–96). There were significantly more CM cases in the pterygium cohort compared with the control cohort (1083 vs 874; p<0.001). In a logistic regression analysis, there was a 24% increase in the odds of developing a CM in the pterygium cohort, compared with controls, after controlling for other predictors (OR 1.24, 95% CI 1.1 to 1.4). The incident rate ratio (IRR) of a malignant CM diagnosis was 20% greater in people who had treatment for a pterygium compared with controls (IRR 1.2, 95% CI 1.0 to 1.4).

Conclusion

The presence of a pterygium indicates a significantly increased risk of developing a CM. Eye care providers who see patients with developing pterygia should advise these patients of this increased risk and recommend regular skin surveillance.
Cumulative retention rate of adalimumab in patients with Behçet’s disease-related uveitis: a four-year follow-up study
Authors: Fabiani Claudia , Sota Jurgen , Vitale Antonio , Rigante Donato , Emmi Giacomo , Vannozzi Lorenzo , Bacherini Daniela , Lopalco Giuseppe , Guerriero Silvana , Gentileschi Stefano , Capozzoli Marco , Franceschini Rossella , Frediani Bruno , Galeazzi Mauro , Iannone Florenzo , Tosi Gian Marco , Cantarini Luca
Published: August 2017

Background/aims

Adalimumab (ADA) has been shown to be an effective treatment for Behçet’s disease (BD)-related uveitis. We aimed at evaluating the cumulative retention rate of ADA during a 48-month follow-up period in patients with BD-related uveitis, the impact of a concomitant use of disease modifying anti-rheumatic drugs (DMARDs) on ADA retention rate, and differences according to the various lines of biologic therapy (ie, first- vs second-line or more). Predictive factors of response to ADA were also investigated.

Methods

We enrolled patients diagnosed with BD-related uveitis and treated with ADA between January 2009 and December 2016. Cumulative survival rates were studied using the Kaplan-Meier plot, while the log-rank (Mantel-Cox) test was used to compare survival curves. Statistical analysis was performed to identify differences according to the response to ADA.

Results

54 consecutive patients (82 eyes) were eligible for analysis. The drug retention rate at 12- and 48-month follow-up was 76.9% and 63.5%, respectively. No statistically significant differences were identified according to the use of concomitant DMARDs (p=0.27) and to the different lines of ADA treatment (p=0.37). No significant differences were found between patients continuing and discontinuing ADA in terms of age (p=0.24), age at BD onset (p=0.81), age at uveitis onset (p=0.56), overall BD duration (p=0.055), uveitis duration (p=0.46), human leucocyte antigen-B51 positivity (p=0.51), and gender (p=0.47).

Conclusions

ADA retention rate in BD-related uveitis is excellent and is not affected by the concomitant use of DMARDs or by the different lines of biological therapy. Negative prognostic factors for BD uveitis do not impact ADA efficacy.
Limited understanding, limited services, limited resources: patients’ experiences with managing hypertension and diabetes in Cambodia
Authors: Jacobs Bart , Men Cheanrithy , Bigdeli Maryam , Hill Peter S
Published: August 2017

Introduction

Health system responses to the emergence of non-communicable diseases (NCDs) in many Southeast Asian nations, Cambodia included, have been insufficient. Little is known about how people suffering from such conditions behave in constrained contexts. We examined the experience of patients with NCDs as they seek care for their conditions and manage them.

Methods

In-depth interviews with 28 purposively selected patients with hypertension and/or diabetes using an interview guide to capture the trajectory followed by interviewees from the development and recognition of symptoms to adherence to treatment. A general outline of major topics to be discussed was used instead of a predetermined list of specific questions.

Results

All interviewees had experienced symptoms for a substantial period of time, sometimes many years, before being diagnosed. Initial treatment focused on symptoms instead of underlying conditions, often at considerable financial cost. Following diagnosis, many struggled to take medicines daily for their condition and adhering to the required behaviour changes. Many resorted to complementary medicine. Lack of financial resources was a common reason to discontinue treatment. Many reported loss of income and assets such as livestock and productive land and increasingly relied on others.

Conclusion

In order to assist people with NCDs in Cambodia, there is a need for a multipronged approach focusing on communities and healthcare providers. Information campaigns could focus on the timely recognition by communities of symptoms indicative of the conditions, together with instigating demand for routine screening at qualified health providers. Peer support is considerable, and locally adjusted approaches based on this principle should be considered.
The moderating role of personal resources in the relationship between psychosocial job demands and health: a cross-sectional study
Authors: Mayerl Hannes , Stolz Erwin , Großschädl Franziska , Rásky Éva , Freidl Wolfgang
Published: August 2017

Objective

The main objective of this research was to investigate the buffering effects of an individual’s physical, mental and social resources in the relationship between psychosocial job demands and (1) health symptoms, (2) mental strain and (3) the body mass index (BMI), respectively.

Methods

We performed moderated regression analysis to examine data from a large cross-sectional survey of an Austrian employee sample (n=9434).

Results

The results revealed a robust association between psychosocial job demands and health symptoms as well as mental strain, but only a weak relationship between psychosocial job demands and BMI. Although the personal resources showed a positive effect on health symptoms and mental strain, only weak evidence was found for the hypothesised interaction with psychosocial job demands. Solely the physical fitness of a person was found to mitigate the impact of psychosocial job demands on health symptoms.

Conclusions

In conclusion, personal resources substantially accounted for the prediction of health. However, the interactions between psychosocial job demands and personal resources only slightly contributed to explaining the variation in health.
Relationship between non-technical skills and technical performance during cardiopulmonary resuscitation: does stress have an influence?
Authors: Krage Ralf , Zwaan Laura , Tjon Soei Len Lian , Kolenbrander Mark W , van Groeningen Dick , Loer Stephan A , Wagner Cordula , Schober Patrick
Published: August 2017

Background

Non-technical skills, such as task management, leadership, situational awareness, communication and decision-making refer to cognitive, behavioural and social skills that contribute to safe and efficient team performance. The importance of these skills during cardiopulmonary resuscitation (CPR) is increasingly emphasised. Nonetheless, the relationship between non-technical skills and technical performance is poorly understood. We hypothesise that non-technical skills become increasingly important under stressful conditions when individuals are distracted from their tasks, and investigated the relationship between non-technical and technical skills under control conditions and when external stressors are present.

Methods

In this simulator-based randomised cross-over study, 30 anaesthesiologists and anaesthesia residents from the VU University Medical Center, Amsterdam, the Netherlands, participated in two different CPR scenarios in random order. In one scenario, external stressors (radio noise and a distractive scripted family member) were added, while the other scenario without stressors served as control condition. Non-technical performance of the team leader and technical performance of the team were measured using the ‘Anaesthetists’ Non-technical Skill’ score and a recently developed technical skills score. Analysis of variance and Pearson correlation coefficients were used for statistical analyses.

Results

Non-technical performance declined when external stressors were present (adjusted mean difference 3.9 points, 95% CI 2.4 to 5.5 points). A significant correlation between non-technical and technical performance scores was observed when external stressors were present (r=0.67, 95% CI 0.40 to 0.83, p<0.001), while no evidence for such a relationship was observed under control conditions (r=0.15, 95% CI −0.22 to 0.49, p=0.42). This was equally true for all individual domains of the non-technical performance score (task management, team working, situation awareness, decision-making).

Conclusions

During CPR with external stressors, the team’s technical performance is related to the non-technical skills of the team leader. This may have important implications for training of CPR teams.
Factors associated with the efficacy of polyp detection during routine flexible sigmoidoscopy
Authors: Maliampurakal Akash J , McMillan Donald C , Anderson John H , Horgan Paul G , Mansouri David
Published: August 2017

Objective

Flexible sigmoidoscopy reduces the incidence of colonic cancer through the detection and removal of premalignant adenomas. However, the efficacy of the procedure is variable. The aim of the present study was to examine factors associated with the efficacy of detecting polyps during flexible sigmoidoscopy.

Design and patients

Retrospective observational cohort study of all individuals undergoing routine flexible sigmoidoscopy in NHS Greater Glasgow and Clyde from January 2013 to January 2016.

Results

A total of 7713 patients were included. Median age was 52 years and 50% were male. Polyps were detected in 1172 (13%) patients. On multivariate analysis, increasing age (OR 1.020 (1.016–1.023) p<0.001), male sex (OR 1.23 (1.10–1.38) p<0.001) and the use of any bowel preparation (OR 3.55 (1.47–8.57) p<0.001) were associated with increasing numbers of polyps being detected. There was no significant difference in the number of polyps found in patients who had received an oral laxative preparation compared with an enema (OR 3.81 (1.57–9.22) vs 3.45 (1.43–8.34)), or in those who received sedation versus those who had not (OR 1.00 vs 1.04 (0.91–1.17) p=0.591). Furthermore, the highest number of polyps was found when the sigmoidoscope was inserted to the descending colon (OR 1.30 (1.04–1.63)).

Conclusions

Increasing age, male sex and the utilisation of any bowel preparation were associated with an increased polyp detection rate. However, the use of sedation or oral laxative preparation appears to confer no additional benefit. In addition, the results indicate that insertion to the descending colon optimises the efficacy of flexible sigmoidoscopy polyp detection.
Unrestricted faecal calprotectin testing performs poorly in the diagnosis of inflammatory bowel disease in patients in primary care
Authors: Conroy Samantha , Hale Melissa F , Cross Simon S , Swallow Kirsty , Sidhu Reena H , Sargur Ravishankar , Lobo Alan J
Published: August 2017

Background

Faecal calprotectin (FC) measurement distinguishes patients with inflammatory bowel disease (IBD) from those with irritable bowel syndrome but evidence of its performance in primary care is limited.

Aims

To assess the yield of IBD from FC testing in primary care.

Methods

Retrospective review of hospital records to assess the outcome following FC testing in primary care. Investigations for all patients undergoing FC testing in a single laboratory for 6 months from 1 October 2013 to 28 February 2014 were reviewed.

Results

410 patients (162 male; median age 42; range 16–91) were included. FC>50 µg/g was considered positive (FC+). 148/410 (36.1%; median age 44 (17–91)) were FC+ (median FC 116.5 µg/g (51–1770)). 122/148 FC-positive patients (82.4%) underwent further investigation. 97 (65.5%) underwent lower gastrointestinal endoscopy (LGIE), of which 7 (7.2%) had IBD. 49/262 (18.7%) FC-negative (FC−) patients (FC ≤50 µg/g) (median age 47 (19–76)) also underwent LGIE, of whom 3 (6.1%) had IBD.

IBD was diagnosed in 11/410 (2.7%; 4 ulcerative colitis, 3 Crohn’s disease, 4 microscopic colitis). 8/11 were FC+ (range 67–1170) and 3 FC−. At a 50 µg/g threshold, sensitivity for detecting IBD was 72.7%, specificity 64.9%, positive predictive value (PPV) 5.41% and negative predictive value 98.9%. Increasing the threshold to 100 µg/g reduced the sensitivity of the test for detecting IBD to 54.6%.

Conclusions

FC testing in primary care has low sensitivity and specificity with poor PPV for diagnosing IBD. Its use needs to be directed to those with a higher pretest probability of disease. Local services and laboratories should advise general practitioners accordingly.
Targeting the anterior superior iliac spine yields significantly longer bone marrow cores
Authors: Reed Louis , Attarian Shirin , Pendurti Gopichand , Singh Aditi P , Budhathoki Anjali , Abi-Aad Simon , Shah Urvi A , Kim Salem , Bachiashvili Kimo , Moon Jee Young , Kim Mimi , Elrafei Tarek , Alexis Karenza , Strakhan Marianna , Li Weijuan , Friedman Ellen
Published: August 2017

Pathologists and haematologists generally agree that the length of the biopsy core is a good surrogate for the diagnostic quality of the bone marrow. Previous studies suggested that the angulation of the biopsy needle from the posterior superior iliac spine (PSIS) could influence the length of the biopsy cores, targeting the anterior superior iliac spine (ASIS) from the PSIS would yield longer specimens than the traditional angulation technique (TAT), where the biopsy needle is directed straight in, perpendicular to the plane of the back. Twenty five adult haematology patients were prospectively recruited by haematologists-in-training (HITs), who were trained to target the ASIS using a lateral angulationtechnique (LAT). The mean length of biopsy cores was 16 mm and that was significantly longer (p=0.003) than a comparable group of bone marrow biopsies previously obtained by HITs using the TAT approach. These results support the LAT as a new standard of haematology practice.

Trial registration number

NCT 02524613
Diagnostic accuracy of interleukin 27 for tuberculous pleural effusion: two prospective studies and one meta-analysis
Authors: Wang Wen , Zhou Qiong , Zhai Kan , Wang Yao , Liu Jing-Yuan , Wang Xiao-Juan , Wang Zhen , Zhang Jian-Chu , Tong Zhao-Hui , Shi Huan-Zhong
Published: August 2017

Background

Accurate differentiating diagnosis is essential for choosing treatment for exudative pleural effusions.

Objective

To establish the diagnostic accuracy of interleukin 27 for tuberculous pleural effusion (TPE).

Methods

First, the concentrations of pleural interleukin 27, interferon-gamma and adenosine deaminase were compared between 51 patients with TPE and 103 with non-TPEs (Beijing cohort), and their diagnostic values were evaluated. These were further verified in another independent population (Wuhan cohort, n=120). In the second part of the study, we performed a meta-analysis.

Results

With a cut-off value of 591.4 ng/L in the Beijing cohort, the area under the curve, sensitivity, specificity, positive predictive value and negative predictive value of interleukin 27 to diagnose TPE were 0.983 (95% CI 0.947 to 0.997), 96.1% (86.5% to 99.5%), 99.0% (94.7% to 100%), 98.0 (89.4 to 99.9) and 98.1 (93.3 to 99.8), respectively. Excellent diagnostic accuracy of interleukin 27 was also found in the Wuhan cohort and was further confirmed in the meta-analysis. The diagnostic performance of interleukin 27 was comparable to that of interferon-gamma and was more accurate than that of adenosine deaminase. Since the post-test probability of a negative result was always <0.1%, a negative test was considered to exclude TPE in all tuberculosis prevalence settings.

Conclusions

Interleukin 27 can be used to diagnose TPE in a high prevalence setting, and a negative result can also be reliably used to rule out TPE in all prevalence settings.
Molecular epidemiology of Pseudomonas aeruginosa in an unsegregated bronchiectasis cohort sharing hospital facilities with a cystic fibrosis cohort
Authors: Mitchelmore Philip J , Randall Joanna , Bull Matthew J , Moore Karen A , O’Neill Paul A , Paszkiewicz Konrad , Mahenthiralingam Eshwar , Scotton Chris J , Sheldon Christopher D , Withers Nicholas J , Brown Alan R
Published: August 2017

While Pseudomonas aeruginosa (PA) cross-infection is well documented among patients with cystic fibrosis (CF), the equivalent risk among patients with non-CF bronchiectasis (NCFB) is unclear, particularly those managed alongside patients with CF. We performed analysis of PA within a single centre that manages an unsegregated NCFB cohort alongside a segregated CF cohort. We found no evidence of cross-infection between the two cohorts or within the segregated CF cohort. However, within the unsegregated NCFB cohort, evidence of cross-infection was found between three (of 46) patients. While we do not presently advocate any change in the management of our NCFB cohort, longitudinal surveillance is clearly warranted.