bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes of preterm birth and evidence synthesis
Authors: Marlow Neil
Published: January 2018

This commentary is on the systematic review by Pascal et al. on pages 342–355 of this issue.
How to assess goals in intrathecal baclofen therapy
Authors: Bonouvrié Laura A
Published: January 2018

This commentary is on the original article by Liew et al. on pages 367–373 of this issue.
Flash forward: a review of flash glucose monitoring
Authors: Leelarathna L. , Wilmot E. G.
Published: January 2018

The FreeStyle Libre flash glucose monitor became available on prescription (subject to local health authority approval) in all four nations of the UK from November 2017, a watershed moment in the history of diabetes care. Calibration free, the FreeStyle Libre is a disc worn on the arm for 14 days which is designed largely to replace the recommended 4–10 painful finger‐stick blood glucose tests required each day for the self‐management of diabetes. This review discusses clinical data from randomized and observational studies, considers device accuracy metrics and deliberates its popularity and the potential challenges that this new device brings to diabetes care in the UK. In randomized trials, FreeStyle Libre use is associated with a reduction in hypoglycaemia and, in observational studies, improvements in HbA1c levels. User satisfaction is high and adverse events are low. Accuracy of the FreeStyle Libre is comparable to currently available real‐time continuous glucose monitors in adults, children and during pregnancy; the cost of the FreeStyle Libre is lower. Glucose data can be visualized in multiple devices and platforms, and summarized in an ambulatory glucose profile to aid pattern recognition and insulin dose adjustment. There is a need for appropriate education, of both users and healthcare professionals, to harness the full benefits. Further randomized studies to assess the long‐term impact on HbA1c, particularly in those with high baseline HbA1c and in specific age groups, such as adolescents and young adults, are warranted. The potential impact on complications, is yet to be realized.
Diabetes technology: improving care, improving patient‐reported outcomes and preventing complications in young people with Type 1 diabetes
Authors: Prahalad P. , Tanenbaum M. , Hood K. , Maahs D. M.
Published: January 2018

With the evolution of diabetes technology, those living with Type 1 diabetes are given a wider arsenal of tools with which to achieve glycaemic control and improve patient‐reported outcomes. Furthermore, the use of these technologies may help reduce the risk of acute complications, such as severe hypoglycaemia and diabetic ketoacidosis, as well as long‐term macro‐ and microvascular complications. In addition, diabetes technology can have a beneficial impact on psychosocial health by reducing the burden of diabetes. Unfortunately, diabetes goals are often unmet and people with Type 1 diabetes too frequently experience acute and long‐term complications of this condition, in addition to often having less than ideal psychosocial outcomes. Increasing realization of the importance of patient‐reported outcomes is leading to diabetes care delivery becoming more patient‐centred. Diabetes technology in the form of medical devices, digital health and big data analytics have the potential to improve clinical care and psychosocial support, resulting in lower rates of acute and chronic complications, decreased burden of diabetes care, and improved quality of life.
INTRODUCTION TO THE SYMPOSIUM—CONTESTS: THEORY AND EVIDENCE
Authors: Chowdhury Subhasish M. , Malueg David A.
Published: January 2018

This Symposium consists of five studies in the area of “Contests.” These peer‐reviewed papers were among a larger set of research presented at the 2016 conference “Contests: Theory and Evidence” at the University of East Anglia in Norwich, United Kingdom, and represent that research in terms of both the questions raised and the techniques used to address them. (JEL C7, C9, D9)
Box–Cox‐chord transformations for community composition data prior to beta diversity analysis
Authors: Legendre Pierre , Borcard Daniel
Published: January 2018

In studies of spatial or temporal beta diversity, community composition data, often containing many zeros, must be transformed in some way before they are analysed by multivariate methods of data analysis. Data are transformed to reduce the skewness of species distributions and make dissimilarities double‐zero asymmetrical. Criteria have recently been proposed to determine which dissimilarity functions (or the corresponding data transformations) can be used for beta diversity assessment. The chord transformation is often used as the preliminary transformation for frequency data. When the Euclidean distance is computed on chord‐transformed data, a chord dissimilarity matrixDis produced, which obeys the proposed criteria. The Hellinger transformation, i.e. the chord transformation applied to square‐root transformed frequencies, is also often used with community composition data prior to multivariate analyses; it leads to the Hellinger dissimilarity, which is another widely usedDfunction in beta diversity studies. Among the data transformations often used in simple or multivariate data analysis, the Box–Cox method provides a useful series of transformations to make data distributions more symmetrical, where exponent 1 is the absence of a transformation, exponent 0.5 is the square‐root, exponent 0.25 is the fourth‐root, and the log transformation is the limit of the Box–Cox function corresponding to exponent 0. Combining the two previous ideas, this paper proposes to combine any transformation of the Box–Cox family with exponent in the [0,1] range with the chord transformation. In particular, one can compute the loge(y + 1) transformation of a community composition (or other frequency) data table and follow with a chord transformation. ADmatrix can be computed from the doubly‐transformed data. The transformations andDfunctions in that family inherit the properties of the chord dissimilarity, and this ensures that they all follow the necessary criteria for beta diversity assessment that have recently been proposed.
Survey of diagnostic and treatment practices for multiple sclerosis (MS) in Europe. Part 2: Progressive MS, paediatric MS, pregnancy and general management
Authors: Fernández O. , Delvecchio M. , Edan G. , Fredrikson S. , Giovannoni G. , Hartung H.‐P. , Havrdova E. , Kappos L. , Pozzilli C. , Soerensen P. S. , Tackenberg B. , Vermersch P. , Comi G.
Published: January 2018

Background and purpose

The European Charcot Foundation supported the development of a set of surveys to understand current practice patterns for the diagnosis and management of multiple sclerosis (MS) in Europe. Part 2 of the report summarizes survey results related to secondary progressive MS (SPMS), primary progressive MS (PPMS), pregnancy, paediatric MS and overall patient management.

Methods

A steering committee of MS neurologists developed case‐ and practice‐based questions for two sequential surveys distributed to MS neurologists throughout Europe.

Results

Respondents generally favoured changing rather than stopping disease‐modifying treatment (DMT) in patients transitioning from relapsing−remitting MS to SPMS, particularly with active disease. Respondents would not initiate DMT in patients with typical PPMS symptoms, although the presence of ≥1 spinal cord or brain gadolinium‐enhancing lesion might affect that decision. For patients considering pregnancy, respondents were equally divided on whether to stop treatment before or after conception. Respondents strongly favoured starting DMT in paediatric MS with active disease; recommended treatments included interferon, glatiramer acetate and, in John Cunningham virus negative patients, natalizumab. Additional results regarding practice‐based questions and management are summarized.

Conclusions

Results of part 2 of the survey of diagnostic and treatment practices for MS in Europe largely mirror results for part 1, with neurologists in general agreement about the treatment and management of SPMS, PPMS, pregnancy and paediatric MS as well as the general management of MS. However, there are also many areas of disagreement, indicating the need for evidence‐based recommendations and/or guidelines.
Investor heterogeneity and trading
Authors: Knyazeva Anzhela , Knyazeva Diana , Kostovetsky Leonard
Published: January 2018

Institutional investors play a crucial role in the information environment of firms. We argue that heterogeneity in the information ability of institutional investors has a significant impact on trading around information releases. We propose novel measures of within‐firm investor heterogeneity and find that investor heterogeneity increases abnormal trading volume around news, holding constant the average levels of investor sophistication. We also find larger spread reductions around announcements for firms with greater investor heterogeneity. The effect of investor heterogeneity on trading continues to hold after accounting for total institutional ownership, the presence of certain types of institutional investors, and analyst coverage.
Effects of age and diet on glucose and insulin dynamics in the horse
Authors: Rapson J. L. , Schott H. C. , Nielsen B. D. , McCutcheon L. J. , Harris P. A. , Geor R. J.
Published: January 2018

Background

Age and diet may affect insulin sensitivity (SI) but these factors have received limited investigation in horses.

Objectives

To measure minimal model parameters during an insulin‐modified frequently sampled intravenous glucose tolerance test (FSIGTT) after adaptation to a forage only diet (HAY) or forage supplemented with either starch/sugar‐rich (SS) or oil/fibre‐rich (FF) concentrate feeds; and to assess glucose and insulin responses to a standardised meal challenge (SMC, 4 g/kg BW ofSS) after diet adaptation in adult and aged mares.

Study design

Latin square design with eight adult (5–12 years) and nine aged (>19 years) healthy mares.

Methods

Diets were fed for 6 weeks, and theFSIGTTandSMCwere performed after 31–32 and 41 days on each diet respectively. Data were analysed by a mixedANOVAfor repeated measures.

Results

Acute insulin response to glucose (AIRg) was greater andSIwas lower in aged horses, compared with adults, regardless of diet. BothAIRg andSIwere greater in aged mares after adaptation toSS, as compared withHAY. Similar trends, although not statistically significant, were observed after adaptation toSSin adult mares. Peak insulin concentration and area under the insulin vs. time curve during theSMCwere greater in aged than adult mares with all diets. Furthermore, area under the glucose vs. time curve was lower after adaptation toSS, when compared with other diets, in both groups.

Main limitations

Transient weight loss occurred at the beginning of the study and only one sex was included. Incomplete ingestion of theSMCby four mares was another limitation.

Conclusions

Insulin responses to i.v. and enteral nonstructural carbohydrate challenge increase with age in healthy horses, regardless of diet fed.
Mouldable, thermoplastic, glue‐on frog‐supportive shoes change hoof kinetics in normal and obese Shetland ponies
Authors: Sleutjens J. , Serra Bragança F. M. , van Empelen M. W. , ten Have R. E. , de Zwaan J. , Roelfsema E. , Oosterlinck M. , Back W.
Published: January 2018

Background

Obesity and hyperinsulinaemia are frequently encountered in the equine population and risk factors for the development of laminitis. There are many options for hoof support that claim a beneficial effect, but often the scientific evidence is scarce.

Objectives

To quantify the effect of frog‐supportive shoes on hoof kinetics in normal and obese ponies.

Study design

Controlled in vivo trial.

Methods

Ten Shetland mares (n = 10) with a normal (n = 5) or obese (n = 5) body condition were led over a dynamically calibrated pressure plate before (T0), immediately after (T1) and 72 h (T2) after application of the shoes. The following locomotor variables were measured: stance duration (StDur), vertical impulse (VI), peak vertical force (PVF), time to PVF and time from PVF to lift off. The hoof print was divided into a toe and heel region and the StDur toe–heel index was calculated. The toe–heel hoof balance curves of the vertical force were plotted throughout the stance phase.

Results

The VI and PVF increased significantly 72 h after application of the shoes, when compared with T0 and T1. The StDur toe–heel index and toe–heel balance curves were significantly different between the normal and obese ponies. These variables became more comparable between the groups after application of the frog‐supportive shoes.

Main limitations

It would have been interesting to measure the effect of the shoe in patients with acute laminitis. However, this would have had major welfare implications.

Conclusions

The obese ponies moved more carefully than the normal group, demonstrated by a decreased loading of the toe area. The data illustrate that the ponies became more comfortable 72 h after application of the shoes, with a pronounced effect in the obese group. Thus, these results suggest that frog‐supportive shoes could be beneficial, especially for obese ponies.
Seasonal changes in epidermal ceramides are linked to impaired barrier function in acne patients
Authors: Pappas Apostolos , Kendall Alexandra C. , Brownbridge Luke C. , Batchvarova Nikoleta , Nicolaou Anna
Published: January 2018

Acne skin demonstrates increased transepidermal water loss (TEWL) compared with healthy skin, which may be due, in part, to altered ceramide (CER) levels. We analysed ceramides in the stratum corneum of healthy and acne skin, and studied seasonal variation over the course of a year. Using ultraperformance liquid chromatography with electrospray ionisation and tandem mass spectrometry (UPLC/ESI‐MS/MS), we identified 283 ceramides. Acne‐affected skin demonstrated overall lower levels of ceramides, with notable reductions in CER[NH] and CER[AH] ceramides, as well as the acylceramides CER[EOS] and CER[EOH]; these differences were more apparent in the winter months. Lower ceramide levels reflected an increase in TEWL in acne, compared with healthy skin, which partly resolves in the summer. Individual ceramide species with 18‐carbon 6‐hydroxysphingosine (H) bases (including CER[N(24)H(18)], CER[N(26)H(18)], CER[A(24)H(18)], CER[A(26)H(18)]) were significantly reduced in acne skin, suggesting that CER[NH] and CER[AH] species may be particularly important in a healthy skin barrier.
Expression analysis of HMGB1 in histological samples of malignant pleural mesothelioma
Authors: Rrapaj Eltjona , Trisolini Elena , Bertero Luca , Salvo Michela , Indellicato Rossella , Andorno Silvano , Garcia‐Manteiga Jose M , Rena Ottavio , Boldorini Renzo L
Published: January 2018

Aims

High mobility group box 1 (HMGB1) is a chromatin structural protein, expressed ubiquitously in the nuclei of mammalian cells. When transported extracellularly, it acts as a tumour suppressor and oncogenic protein. In malignant pleural mesothelioma (MPM), high serum levels of HMGB1 have been related to a poor prognosis. Conversely, the significance of HMGB1 expression in MPM tissues is still unclear.

Methods and results

Biopsy samples from 170 patients with MPM were assessed by immunohistochemistry and reverse transcription–polymerase chain reaction (RT–PCR) to evaluate HMGB1 protein and gene expression. The expression level of HMGB1 protein was scored using a semiquantitative system that sums the intensity (0–3) and the percentage (from 0 to 4) of positively stained cells in nuclei, cytoplasm and in both. The final score was considered as high (>3) or low (<3) expression. Gene expression levels were calculated using the ΔΔCt method. High expression levels of HMGB1 as total (P = 0.0011) and cytoplasmic score (P = 0.0462) were related to a worse disease‐specific survival (DSS) in the entire cohort and in the clinicopathological subgroups. No significant correlation was found between HMGB1 gene expression and DSS.

Conclusions

These findings indicate that HMGB1 may be a useful prognostic biomarker in MPM when detected by immunohistochemistry. Conversely, as it is also expressed in normal and reactive mesothelial cells, HMGB1 cannot be considered a diagnostic biomarker in histological samples of mesothelioma.
Radiotherapy regimens in patients with nonmelanoma head and neck skin cancers
Authors: Dundar Yusuf , Cannon Richard B. , Hunt Jason P. , Monroe Marcus , Suneja Gita , Hitchcock Ying J.
Published: January 2018

Background

To assess the effectiveness and outcomes of adjuvant radiotherapy regimens for nonmelanoma skin cancers (NMSC) of the head and neck, particularly for elderly patients.

Methods

A retrospective review of patients with head and neck NMSC was conducted. Radiotherapy dose per fraction regimens included ≤200, 240–250, 300–400, and 500–600 cGy. Demographics, tumor characteristics, local control (LC), regional control (RC), and survival outcomes were analyzed.

Results

Of the 90 patients with 140 disease sites, 76.6% were squamous cell carcinoma, 15.5% were basal cell carcinoma, and 7.7% were other histologies. The mean age at diagnosis was 72.1 years old. The most common location was preauricular (20.0%), followed by temple, scalp, cheek, and forehead. The overall LC and RC rates were 88.8% and 88.8%, respectively by patients, and 92.8% and 86.4%, respectively by treatment sites. Age, primary tumor location, T classification, N classification, overall stage, perineural invasion, comorbid disease, skull base invasion, and radiotherapy subgroup were significantly associated with disease‐free and overall survival (P < 0.05). LC and RC were not significantly different among the radiotherapy dose subgroups. The mean survival was longer in patients treated with 240–250 cGy/fraction (50.3 months). There was no significant difference in radiotherapy toxicity between the subgroups.

Conclusion

Short‐term radiotherapy regimens for patients with locally or regionally advanced head and neck NMSC appear feasible and effective, particularly in elderly patients or those that cannot tolerate the length of standard regimens.
The impact of closed-loop electronic medication management on time to first dose: a comparative study between paper and digital hospital environments
Authors: Austin Jodie A , Smith Ian R , Tariq Amina
Published: January 2018

Closed-loop electronic medication management systems (EMMS) are recognised as an effective intervention to improve medication safety, yet evidence of their effectiveness in hospitals is limited. Few studies have compared medication turnaround time for a closed-loop electronic versus paper-based medication management environment.

Objective

To compare medication turnaround times in a paper-based hospital environment with a digital hospital equipped with a closed-loop EMMS, consisting of computerised physician order entry, profiled automated dispensing cabinets packaged with unit dose medications and barcode medication administration.

Method

Data were collected during 2 weeks at three private hospital sites (one with closed-loop EMMS) within the same organisation network in Queensland, Australia. Time between scheduled and actual administration times was analysed for first dose of time-critical and non-critical medications located on the ward or sourced via pharmacy.

Key findings

Medication turnaround times at the EMMS site were less compared to the paper-based sites (median, IQR: 35 min, 8–57 min versus 120 min, 30–180 min, P < 0.001). For time-critical medications, 77% were administered within 60 min of scheduled time at the EMMS site versus 38% for the paper-based sites. Similar difference was observed for non-critical medications, 80% were administered within 60 min of their scheduled time at the EMMS site versus 41% at the paper-based facilities.

Conclusion

The study indicates medication turnaround times utilising a closed-loop EMMS are less compared to paper-based systems. This improvement may be attributable to increased accessibility of medications using automated dispensing cabinets and electronic medication administration records flagging tasks to nurses in real time.
High‐temperature mechanical behavior of ZrB2‐based composites with micrometer‐ and nano‐sized SiC particles
Authors: Guo Shuqi
Published: January 2018

Using micrometer‐ and nano‐sized SiC particles as reinforcement phase, two ZrB2‐SiC composites with high strength up to 1600°C were prepared using high‐energy ball milling, followed by hot pressing. The composite microstructure comprised finer equiaxed ZrB2 and SiC grains and intergranular amorphous phase. The temperature dependency of flexure strength related to the initial particle size of SiC. In the case of micrometer‐sized SiC, the high‐temperature strength was improved up to 1500°C compared to room‐temperature strength, but the strength degraded at 1600°C, with strength values of 600‐770 MPa. In the case of nano‐sized SiC, the enhanced high‐temperature strength was observed up to 1600°C, with strength values of 680‐840 MPa.
Freeze casting for near‐net‐shaping of dense zirconium diboride ceramics
Authors: Leo Silvia , Jukes Laura , Pinches Samuel , Tallon Carolina , Franks George V.
Published: January 2018

Zirconium diboride (ZrB2) was formed into dense complex shapes using freeze casting as a near‐net‐shaping technique. Aqueous‐based formulations were compared with nonaqueous (cyclohexane) based formulations in terms of rheological behavior, particle packing in the green body, sintered density, macroscale porosity, and cracking. The influence of particle solids concentration and freezing rate was investigated. The aqueous formulations were found to be deficient in that they produced macroscale porosity that could not be eliminated during sintering resulting in low density and large pores in the final shaped objects. The nonaqueous‐based system was able to produce complex shaped objects with significantly reduced macroscale porosity. The higher concentration of solids in the nonaqueous‐based formulations was primarily responsible for the reduced macroscale porosity and enabled higher sintered densities (up to 90%‐91.5% of theoretical density for fast freezing). The microstructure of the ZrB2 formed at fast freezing rates and high solids content typically had isolated pores in the order of 5‐10 μm in size, mainly found along grain boundaries (grain sizes between 20 and 50 μm). Although this rapid freezing produced denser components, it tended to produce objects with internal cracks. When slower freezing rates were used, intricate complex shaped objects could be produced without cracks but their density was only between 65% and 80% of theoretical density.
Higher arterial stiffness is associated with lower cognitive performance in patients with hypertension
Authors: Muela Henrique C.S. , Costa‐Hong Valeria A. , Yassuda Mônica S. , Moraes Natália C. , Memória Claudia M. , Machado Michel F. , Bor‐Seng‐Shu Edson , Nogueira Ricardo C. , Mansur Alfredo J. , Massaro Ayrton R. , Nitrini Ricardo , Macedo Thiago A. , Bortolotto Luiz A.
Published: January 2018

Cognitive impairment and elevated arterial stiffness have been described in patients with arterial hypertension, but their association has not been well studied. We evaluated the correlation of arterial stiffness and different cognitive domains in patients with hypertension compared with those with normotension. We evaluated 211 patients (69 with normotension and 142 with hypertension). Patients were age matched and distributed according to their blood pressure: normotension, hypertension stage 1, and hypertension stage 2. Cognitive function was assessed using the Mini‐Mental State Examination, Montreal Cognitive Assessment, and a battery of neuropsychological evaluations that assessed six main cognitive domains. Pulse wave velocity was measured using a Complior device, and carotid properties were assessed by radiofrequency ultrasound. Central arterial pressure and augmentation index were obtained using applanation tonometry. The hypertension stage 2 group had higher arterial stiffness and worse performance either by Mini‐Mental State Examination (26.8±2.1 vs 27.3±2.1 vs 28.0±2.0, P=.003) or the Montreal Cognitive Assessment test (23.4±3.5 vs 24.9±2.9 vs 25.6±3.0, P<.001). On multivariable regression analysis, augmentation index, intima‐media thickness, and pulse wave velocity were the variables mainly associated with lower cognitive performance at different cognitive domains. Cognitive impairment in different domains was associated with higher arterial stiffness.
Hypertension and frailty in older adults
Authors: Aprahamian Ivan , Sassaki Eduardo , dos Santos Marília F. , Izbicki Rafael , Pulgrossi Rafael C. , Biella Marina M. , Borges Ana Camila N. , Sassaki Marcela M. , Torres Leonardo M. , Fernandez Ícaro S. , Pião Olívia A. , Castro Paula L. M. , Fontenele Pedro A. , Yassuda Mônica S.
Published: January 2018

The association between hypertension and frailty syndrome in older adults remains unclear. There is scarce information about the prevalence of hypertension among frail elderly patients or on its relationship with frailty. Up to one quarter of frail elderly patients present without comorbidity or disability, yet frailty is a leading cause of death. The knowledge and better control of frailty risk factors could influence prognosis. The present study evaluated: (1) the prevalence of hypertension in robust, prefrail, and frail elderly; and (2) factors that might be associated with frailty including hypertension. A cross‐sectional study was conducted in 619 older adults at a university‐based outpatient center. Study protocol included sociodemographic data, measures of blood pressure and body mass index, frailty screening according to the internationally validated FRAIL (fatigue, resistance, ambulation, illnesses, and loss of weight) scale, number of comorbidities, drug use assessment, physical activity, cognitive status, and activities of daily living. Ordinal logistic regression was used to evaluate factors associated with frailty. Prevalence of hypertension and frailty was 67.3% and 14.8%, respectively, in the total sample. Hypertension was more prevalent in the prefrail (72.5%) and frail (83%) groups than among controls (51.7%). Hypertension, physical activity, number of prescribed drugs, and cognitive performance were significantly associated with frailty status. Hypertension presented an odds ratio of 1.77 towards frailty (95% confidence interval, 1.21–2.60; P = .002). Hypertension was more prevalent in frail elderly patients and was significantly associated with frailty. Intensive control of hypertension could influence the trajectory of frailty, and this hypothesis should be explored in future prospective clinical trials.
T‐cell papulosis associated with B‐cell malignancy: a distinctive clinicopathologic entity
Authors: Visseaux L. , Durlach A. , Barete S. , Beylot‐Barry M. , Bonnet N. , Chassine A. , Franck N. , Herve G. , Leclec'h C. , Machet L. , Ingen‐Housz‐Oro S. , Petrella T. , Vergier B. , Ortonne N. , Grange F.
Published: January 2018

Background

A distinctive eruption referred to as ‘insect bite‐like reaction’ or ‘eosinophilic dermatosis of haematological malignancy’ has been described during the course of haematological B‐cell malignancies (BCM). However, its clinical evolution, histopathological features and pathogenesis remain unclear.

Objectives

To characterize this eruption and to investigate its pathogenesis and relationship with the underlying BCM.

Methods

In this multicenter retrospective study of the French Study Group on Cutaneous Lymphomas, 37 patients with a BCM and a cutaneous eruption consisting in chronic and/or recurrent papules, papulo‐vesicles and/or nodules were included. Clinical, histopathological, immunohistochemical and molecular data were reviewed.

Results

No significant insect bite history or seasonal predominance was recorded. Patients had pruritic papules (81%), papulo‐vesicles (43%) and nodules (38%), often predominated in the head and neck region (84%), without complete remission periods in most cases (57%). The predominant associated BCM was chronic lymphocytic leukaemia (73%). Histological and immunohistochemical review showed a dense dermal lymphocytic infiltrate predominantly composed of T lymphocytes (100%), with frequent eosinophils (77.6%); a perivascular and periadnexal (most often folliculotropic) pattern (77.6%), sometimes suggestive of a folliculotropic mycosis fungoides; clusters of tumour B cells were identified in 47% of cases using appropriate phenotyping markers. In 10/14 cases (71.4%) tested for B‐cell IgH gene rearrangement, a B‐cell clone was identified in skin lesions (identical to the blood clone in nine cases), whereas no T‐cell clone was present.

Conclusion

We propose the denomination ‘T‐cell papulosis associated with B‐cell malignancy’ (TCP‐BCM) for this distinctive eruption. Although resulting in various histopathological pictures, it can be easily recognized by clinicians and may be identified by informed pathologists relying on some key features. An extravasation of tumour B cells with skin‐homing properties associated with a secondary, predominant, T‐cell immune reaction could explain the clinicopathologic aspect and the prolonged regressive and recurrent course of the disease.
Pigmented fungiform lingual papillae: dermoscopic and clinical features
Authors: Chessa M.A. , Patrizi A. , Sechi A. , Virdi A. , Leuzzi M. , Neri I.
Published: January 2018

The tongue is covered by fungiform, filiform and circumvallate papillae. Fungiform papillae may be mainly pigmented in dark‐skinned individuals. A single‐centre study aimed to examine the clinical and dermoscopic features of pigmented fungiform papulae of the tongue (PFPT) in children, and a concise review of the literature has been performed. The clinical and anamnestic data of eight children affected by PFPT visited at the Pediatric Dermatology Unit of Bologna between 2010 and 2017, and a systemic review of all studies of PFPT published on PubMed up to 31 August 2017 has been collected and analysed. The results of our data were consistent with the literature review: dark brown to black coloured pinhead papules or bumps were observed in all cases of PFPT, and three types of clinical patterns have been detected. Moreover, the dermoscopic examination showed a cobblestone‐like distribution and rose petal pattern. PFPT could be associated with hyperpigmentation of other sites such as the proximal nail folds and gums, and an intrafamiliar transmission is also possible. Clinical and dermoscopic features of PFPT may help clinicians to recognize this ethnic, acquired and benign condition.
Comparative Effectiveness and Safety of Cognitive Enhancers for Treating Alzheimer's Disease: Systematic Review and Network Metaanalysis
Authors: Tricco Andrea C. , Ashoor Huda M. , Soobiah Charlene , Rios Patricia , Veroniki Areti Angeliki , Hamid Jemila S. , Ivory John D. , Khan Paul A. , Yazdi Fatemeh , Ghassemi Marco , Blondal Erik , Ho Joanne M. , Ng Carmen H. , Hemmelgarn Brenda , Majumdar Sumit R. , Perrier Laure , Straus Sharon E.
Published: January 2018

Background/Objectives

To examine the comparative effectiveness and safety of cognitive enhancers for Alzheimer's disease (AD).

Design

Systematic review and Bayesian network metaanalysis (NMA).

Setting

MEDLINE, EMBASE, Cochrane Library, CINAHL, Ageline (inception–March 2016).

Participants

Individuals with AD in randomized controlled trials (RCTs), quasi‐RCTs, and nonrandomized studies.

Intervention

Any combination of donepezil, rivastigmine, galantamine, or memantine.

Measurements

Two reviewers independently screened titles, abstracts, and full‐texts; abstracted data; and appraised risk of bias.

Results

Twenty thousand three hundred forty‐three citations were screened, and 142 studies were included (110 RCTs, 21 non‐RCTs, 11 cohort studies). NMA found that donepezil (Mini‐Mental State Examination: mean difference (MD) = 1.39, 95% credible interval (CrI) = 0.53–2.24), donepezil+memantine (2.59, 95% CrI = 0.12–4.98), and transdermal rivastigmine (2.02, 95% CrI = 0.02–4.08) improved cognition more than placebo. NMA found that donepezil (Alzheimer's Disease Assessment Scale–cognitive: MD = −3.29, 95% CrI = −4.57 to −1.99) and galantamine (MD = −2.13, 95% CrI = −3.91 to −0.27) improved cognition more than placebo. NMA found that donepezil+memantine (MD = −5.23, 95% CrI = −8.72 to −1.56) improved behavior more than placebo. NMA found that donepezil (MD = −0.32, 95% CrI = −0.46 to −0.19), donepezil+memantine (MD = −0.57, 95% CrI = −0.95 to −0.21), oral rivastigmine (MD = −0.38, 95% CrI = −0.56 to −0.17), and galantamine (MD = −3.79, 95% CrI = −6.98 to −0.59) improved global status more than placebo. NMA found that galantamine decreased the odds of mortality (odds ratio = 0.56, 95% CrI = 0.36–0.87). No agent increased risk of serious adverse events, falls, or bradycardia. Some increased risk of headache (oral rivastigmine), diarrhea (oral rivastigmine, donepezil), nausea (oral rivastigmine, donepezil, galantamine), and vomiting (oral rivastigmine, donepezil, galantamine).

Conclusion

An exhaustive review of the literature involving 142 studies demonstrated that cognitive enhancers in general have minimal effects on cognition according to minimal clinically important difference and global ratings. The drugs appear safe, but this must be interpreted cautiously because trial participants may have less comorbidity and fewer adverse effects than those treated with these drugs in clinical practice.
Liquidity Risk, Bank Networks, and the Value of Joining the Federal Reserve System
Authors: ANDERSON HAELIM , CALOMIRIS CHARLES W. , JAREMSKI MATTHEW , RICHARDSON GARY
Published: January 2018

Reducing systemic liquidity risk related to seasonal loan demand was one reason for founding the Federal Reserve System. Nevertheless, less than 8% of state‐chartered banks joined the Fed in its first decade. Banks facing high liquidity risk from seasonal loan demand were more likely to join the Fed in its first decade. We also find evidence consistent with the notion that banks could obtain some indirect access to the discount window through interbank transfers. Some banks apparently joined the Fed to pass through discount window liquidity to other banks via the interbank network.  Joining the Fed increased member banks’ lending.
Kisspeptin neurones in the posterodorsal medial amygdala modulate sexual partner preference and anxiety in male mice
Authors: Adekunbi D. A. , Li X. F. , Lass G. , Shetty K. , Adegoke O. A. , Yeo S. H. , Colledge W. H. , Lightman S. L. , O'Byrne K. T.
Published: January 2018

The posterodorsal medial amygdala (MePD) is a neural site in the limbic brain involved in regulating emotional and sexual behaviours. There is, however, limited information available on the specific neuronal cell type in the MePD functionally mediating these behaviours in rodents. The recent discovery of a significant kisspeptin neurone population in the MePD has raised interest in the possible role of kisspeptin and its cognate receptor in sexual behaviour. The present study therefore tested the hypothesis that the MePD kisspeptin neurone population is involved in regulating attraction towards opposite sex conspecifics, sexual behaviour, social interaction and the anxiety response by selectively stimulating these neurones using the novel pharmacosynthetic DREADDs (designer receptors exclusively activated by designer drugs) technique. Adult male Kiss‐Cre mice received bilateral stereotaxic injections of a stimulatory DREADD viral construct (AAV‐hSyn‐DIO‐hM3D(Gq)‐mCherry) targeted to the MePD, with subsequent activation by i.p. injection of clozapine‐N‐oxide (CNO). Socio‐sexual behaviours were assessed in a counter‐balanced fashion after i.p. injection of either saline or CNO (5 mg kg‐1). Selective activation of MePD kisspeptin neurones by CNO significantly increased the time spent by male mice in investigating an oestrous female, as well as the duration of social interaction. Additionally, after CNO injection, the mice appeared less anxious, as indicated by a longer exploratory time in the open arms of the elevated plus maze. However, levels of copulatory behaviour were comparable between CNO and saline‐treated controls. These data indicate that DREADD‐induced activation of MePD kisspeptin neurones enhances both sexual partner preference in males and social interaction and also decreases anxiety, suggesting a key role played by MePD kisspeptin in sexual motivation and social behaviour.
Striving to meet targets for ideal treatment of acute myocardial infarction in Brazil: Data from the Midwest region
Authors: Carvalho Gustavo , Rassi Salvador , Guérios Enio , Curado Fernando A. M. , Bastos Ana Tereza
Published: January 2018

Objectives

To evaluate the systematic chain of care for patients with acute ST‐elevation myocardial infarction (STEMI) referred for primary angioplasty in a capital city in Midwestern Brazil.

Background

Acute myocardial infarction is recognized as an important cause of morbidity and mortality and as a public health problem worldwide. Early specialized care is crucial for a good prognosis.

Methods

All STEMI patients receiving care through the public health system at two tertiary care centers from March 2012 to June 2014 were retrospectively analyzed. Symptom onset‐to‐balloon time and door‐to‐balloon time were analyzed and compared with current guideline recommendations.

Results

A total of 835 patients were included. Median symptom onset‐to‐balloon time was 32 h. A total of 783 (94%) patients had had symptoms for more than 12 h and 507 (61%) for more than 24 h. Only 51 (6%) patients arrived within 12 h of symptom onset and were treated with primary angioplasty. Among these patients, median door‐to‐balloon time was 37 min, in accordance with guideline recommendations.

Conclusion

Treatment of STEMI through the public health system in a capital city in Midwestern Brazil falls short of the recommended guidelines due to failure in the initial links of the chain of care. This potentially reversible failure has an important impact on patient outcomes and on health care burden.
Alcohol use and personality change in middle and older adulthood: Findings from the Health and Retirement Study
Authors: Luchetti Martina , Terracciano Antonio , Stephan Yannick , Sutin Angelina R.
Published: January 2018

Objective

Personality is known to predict alcohol consumption, but how alcohol use is related to personality change is less clear, especially at older ages. The present study examined the effects of level of alcohol consumption and history of dependence on change in the Five‐Factor Model personality traits in a national cohort of Americans aged over 50.

Method

Over 10,000 adults who participated in 2006–2008 waves of the Health and Retirement Study reported on personality and alcohol use and were followed over 4 years.

Results

Latent difference score models indicated decreases in Extraversion to be attenuated for individuals categorized as light‐to‐moderate drinkers at baseline, whereas decreases in Conscientiousness were accentuated by having experienced alcohol dependence symptoms. Moreover, personality difference scores correlated with changes in the amount of alcohol consumed at follow‐up.

Conclusions

The findings suggest that patterns of alcohol consumption are associated with changes in personality across the second half of the life span.
Developing a strawberry lexicon to describe cultivars at two maturation stages
Authors: Oliver Penelope , Cicerale Sara , Pang Edwin , Keast Russell
Published: January 2018

The sensory profile of strawberries is documented as being influenced by cultivar, maturation stage, and environment. Thus, internationally bred strawberries grown in Australia will have a flavor profile adapted to the Australian environment. The objective of this research was to devise a strawberry lexicon relevant to the sensory characteristics of commercially available strawberries grown in Australia. A quantitative descriptive analysis (QDA) trained panel developed a lexicon consisting of two appearance, eight aroma, ten flavor, and five textural/mouthfeel attributes to describe the strawberries. The panel subsequently applied the developed lexicon to describe the sensory attributes of six strawberry cultivars of two flowering types, grown in Australia and harvested at two different maturation stages. A principal component analysis (PCA) determined three dimensions of which the attributes explained 86% of the variance. There were significant differences identified between strawberries, attributable to flowering type, cultivar and maturation stage, validating the developed lexicon to discriminate strawberries.

Practical applications

Strawberries are a commonly consumed berry, with an abundance of cultivars grown worldwide. The sensory profile of strawberries is dependent upon the cultivar and environmental conditions of which the strawberry is grown. This research has identified differences attributable to maturation stage, cultivar, and flowering type. Therefore, the development of a sensory lexicon via this research, applicable to the environmental conditions where cultivars are grown, will assist ongoing breeding programs in developing strawberries expressing flavors shown to be associated with liking.
Anion exchanger 3 in dorsal root ganglion contributes to nerve injury-induced chronic mechanical allodynia and thermal hyperalgesia
Authors: Pérez-Rodríguez Marian J , Velazquez-Lagunas Isabel , Pluma-Pluma Alejandro , Barragán-Iglesias Paulino , Granados-Soto Vinicio
Published: January 2018

Objective

To determine the role of anion exchanger 3 (AE3) in dorsal root ganglion (DRG) in nerve injury-induced chronic nociception in the rat.

Methods

Spared nerve injury (SNI) was used to induce neuropathic pain. Von Frey filaments and Hargreaves test were used to assess tactile allodynia and thermal hyperalgesia, respectively. Drugs were given by intrathecal administration. Western blotting was used to determine AE3 expression in DRG.

Key findings

SNI produced long-lasting mechanical allodynia and thermal hyperalgesia. AE3 was found in DRG of sham-operated rats. SNI enhanced baseline AE3 expression in L4 and L5 DRGs at days 7 and 14, respectively. In contrast, SNI did not affect AE3 expression in L6 DRG. AE3 expression returned to baseline levels 21 days after SNI. Intrathecal 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS) (5–50 μg) pretreatment prevented SNI-induced allodynia and, at a lesser extent, hyperalgesia. Moreover, DIDS (50 μg) reduced SNI-induced AE3 upregulation in L4, but not L5, DRGs. Intrathecal DIDS (5–50 μg) or anti-AE3 antibody (1 μg), but not vehicle, post-treatment (6 days) partially reversed SNI-induced allodynia and hyperalgesia. DIDS or anti-AE3 antibody post-treatment diminished SNI-induced AE3 upregulation in L4 and L5 DRGs.

Conclusions

Data suggest that AE3 is present in DRG and contributes to mechanical allodynia and thermal hyperalgesia in neuropathic rats.
Lansoprazole prevents the progression of liver fibrosis in non-alcoholic steatohepatitis model rats
Authors: Nishi Toshio , Yamamoto Yuta , Yamagishi Naoko , Iguchi Mikitaka , Tamai Hideyuki , Ito Takao , Tsuruo Yoshihiro , Ichinose Masao , Kitano Masayuki , Ueyama Takashi
Published: January 2018

Objectives

We previously demonstrated that lansoprazole provided hepatoprotection in a drug-induced hepatitis animal model partially through the Nrf2/HO-1 pathway. Here, we examined whether lansoprazole could also provide hepatoprotection in a rat model of non-alcoholic steatohepatitis (NASH).

Methods

Six-week-old rats were fed a normal chow or a choline-deficient amino acid-defined (CDAA) diet to establish a rat model of NASH. The groups fed a CDAA diet for 5 weeks were subcutaneously administered either a vehicle or a lansoprazole suspension for 4 weeks beginning the second week of the experiment.

Key findings

Bridging fibrosis was observed in the livers of almost all the NASH model rats (six of seven), but it was not always observed in NASH model rats (one of seven) continuously administered lansoprazole. The serum aspartate aminotransferase level elevated by the CDAA diet was significantly decreased following lansoprazole administration. Lansoprazole also increased the expression of Nrf2, but not HO-1, in the liver of NASH model rats. Lansoprazole decreased the level of activated TGF-β protein. Furthermore, interleukin-6 gene and protein expression were decreased.

Conclusions

Lansoprazole inhibits hepatic fibrogenesis, at least during the early stages, in CDAA diet-induced NASH model rats. The mechanisms might be associated with cytokine suppression but not the inhibition of reactive oxygen species.
Antigastritis effects of Armillariella tabescens (Scop.) Sing. and the identification of its anti-inflammatory metabolites
Authors: Lee Seulah , Lee Dahae , Park Jun Yeon , Seok Soonja , Jang Tae Su , Park Hyun Bong , Shim Sang Hee , Kang Ki Sung , Kim Ki Hyun
Published: January 2018

Objectives

This study demonstrates the biological and chemical analysis of the mushroom Armillariella tabescens (Scop.) Sing. (Tricholomataceae).

Methods

Chemical structures of the isolates were determined by 1D and 2D NMR, and ESI-MS, as well as comparison with previously reported data. All isolates were tested for anti-inflammatory effects based on their ability to inhibit LPS-stimulated nitric oxide (NO) production in RAW264.7 cells.

Key findings

We found that the MeOH extract of the fruiting bodies of A. tabescens showed antigastritis activity against ethanol-induced gastric damage in rats and notably reduced the gastric damage index compared to control in a concentration-dependent manner. Chemical investigation of the MeOH extract led to the isolation of four steroids (1–4), three alkaloids (5–7), two nucleic acids (8–9) and four fatty acids (10–13). This is the first study to report the identification of all isolates, except for compound 7, from A. tabescens. Compounds 1, 2, 3, 4 and 10 showed inhibition on LPS-stimulated NO production. Treatment with compound 10 inhibited expression of iNOS, COX-2, phospho-IKKα, IKKα, phospho-IκBα, IκBα and NF-kappa B in LPS-stimulated RAW264.7 cells.

Conclusions

Compound 10 likely contributes to the health benefits of A. tabescens as an antigastritis agent through its anti-inflammatory effects.
Dysphagia secondary to focal inflammatory myopathy and consequent dorsiflexion of the tongue in a dog
Authors: Strøm P. C. , Marks S. L. , Rivera J. A. , Shelton G. D.
Published: January 2018

A 14‐month‐old female pitbull terrier mix was presented for evaluation of dysphagia of 8 months’ duration secondary to intermittent dorsiflexion of the tongue apex. Physical and neurological examinations were unremarkable with the exception of the dorsiflexed tongue. Serum creatine kinase activity was increased (703 IU/L, reference interval: 55 to 257 IU/L), and electromyography of the tongue demonstrated areas of fibrillation potentials. Histopathology of the tongue showed myopathic changes with excessive variability in myofibre size and endomysial fibrosis. Cytochemical stains verified mixed mononuclear cells throughout the endomysium and perimysium consistent with a chronic inflammatory myopathy. No improvement was reported following prednisone administration; although the dog was able to prehend kibble, it needed assistance when drinking water. This is the first report documenting a focal lingual myopathy in a non‐corgi breed and highlights the utility of determining creatine kinase activity and obtaining tongue biopsies when warranted in dysphagic animals.