bluuebunny/crossref_metadata_2025 huggingface dataset:
Obesity, but not metabolic syndrome, negatively affects outcome in bipolar disorder
Authors: McElroy S. L. , Kemp D. E. , Friedman E. S. , Reilly‐Harrington N. A. , Sylvia L. G. , Calabrese J. R. , Rabideau D. J. , Ketter T. A. , Thase M. E. , Singh V. , Tohen M. , Bowden C. L. , Bernstein E. E. , Brody B. D. , Deckersbach T. , Kocsis J. H. , Kinrys G. , Bobo W. V. , Kamali M. , McInnis M. G. , Leon A. C. , Faraone S. , Nierenberg A. A. , Shelton R. C.
Published: June 2015

Objective

Examine the effects of obesity and metabolic syndrome on outcome in bipolar disorder.

Method

The Comparative Effectiveness of a Second Generation Antipsychotic Mood Stabilizer and a Classic Mood Stabilizer for Bipolar Disorder (Bipolar CHOICE) study randomized 482 participants with bipolar disorder in a 6‐month trial comparing lithium‐ and quetiapine‐based treatment. Baseline variables were compared between groups with and without obesity, with and without abdominal obesity, and with and without metabolic syndrome respectively. The effects of baseline obesity, abdominal obesity, and metabolic syndrome on outcomes were examined using mixed effects linear regression models.

Results

At baseline, 44.4% of participants had obesity, 48.0% had abdominal obesity, and 27.3% had metabolic syndrome; neither obesity, nor abdominal obesity, nor metabolic syndrome were associated with increased global severity, mood symptoms, or suicidality, or with poorer functioning or life satisfaction. Treatment groups did not differ on prevalence of obesity, abdominal obesity, or metabolic syndrome. By contrast, among the entire cohort, obesity was associated with less global improvement and less improvement in total mood and depressive symptoms, suicidality, functioning, and life satisfaction after 6 months of treatment. Abdominal obesity was associated with similar findings. Metabolic syndrome had no effect on outcome.

Conclusion

Obesity and abdominal obesity, but not metabolic syndrome, were associated with less improvement after 6 months of lithium‐ or quetiapine‐based treatment.
An unusual urticarial eruption: Familial cold autoinflammatory syndrome
Authors: Nguyen Rebecca , Robinson Aaron , Nicholls Katherine , Varigos George , Dolianitis Con
Published: June 2015

This is a case of a 26‐year‐old Caucasian woman with a lifelong history of an episodic urticaria associated with arthralgia, precipitated by exposure to cold. She had no other significant past medical history. She reported several family members with a history of very similar episodic eruptions without definitive diagnoses. An examination showed an urticarial eruption over her limbs with no other systemic findings. A baseline full blood examination, serology and autoimmune screen were normal. A skin biopsy was consistent with urticaria, with dermal oedema and a perivascular infiltrate. Following genetic testing, she was found to be heterozygous for a mutation, p.Ala439Val in the NLRP3 gene, known to cause familial cold autoinflammatory syndrome (FCAS), which typically presents with urticaria, conjunctivitis and arthralgia, as described in this patient. FCAS is one subtype of a group of conditions known as cryopyrin‐associated periodic syndromes (CAPS). CAPS are rare, autosomal dominant inherited conditions with a spectrum of phenotypes, characterised by increased interleukin‐1β release with subsequent local and systemic proinflammatory and pyrogenic effects.
Dermal desmoplastic fibroblastoma presenting as a large sacral mass
Authors: Hu Stephen Chu‐Sung , Lin Chi‐Ling
Published: June 2015

Desmoplastic fibroblastoma (collagenous fibroma) is a rare and recently recognised benign tumour. Most desmoplastic fibroblastomas arise in the subcutaneous tissue or skeletal muscle. Involvement of the dermis is extremely rare. We describe an unusual case of dermal desmoplastic fibroblastoma presenting as a large sacral mass in a 16‐year‐old male. An awareness of this entity is necessary to avoid confusion with other benign and malignant soft tissue neoplasms.
Skin protection behaviour and sex differences in melanoma location in patients with multiple primary melanomas
Authors: Warren Matthew , McMeniman Erin , Adams Agnieszka , De'Ambrosis Brian
Published: June 2015

Background/Objectives

Previous studies have shown that sunscreen usage, sun‐protection measures and self‐examination rates in patients with single primary melanomas (SPM) are similar to that in the general population. This study hypothesises that these rates would be different in a population with multiple primary melanomas (MPM). We further hypothesise that there would be a sex difference in melanoma location in patients with MPM. The objectives of this study were to determine skin protection measures, self‐examinations and melanoma location in a cohort of patients with MPM.

Methods

A survey was conducted on 137 patients with MPM examining their sun‐protection measures, skin self‐examination rates and medical and phenotypic characteristics. These data were combined with a review of their medical records to examine the patients' skin cancer history.

Results

Patients with MPM had higher rates of skin self‐evaluation (74% vs 22%), sunscreen usage (70% vs 45%) and other sun‐protection measures (95% vs 46%) than has been published for patients with a history of a SPM. We have also shown that women have a higher risk of developing melanomas on their arms (p < 0.01) and lower legs (p < 0.05) than men.

Conclusions

This report showed the rates of skin self‐examination, sunscreen usage and other sun‐protection methods in patients with MPM is higher than in studies of patients with SPM. It also highlighted sex differences in terms of melanoma location for patients with MPM. Further studies to examine the cause of the differences in these forms of protective behaviour could help improve the utilisation of these important preventative measures in all patients.
How effective and acceptable is Web 2.0 Balint group participation for general practitioners and general practitioner registrars in regional Australia? A pilot study
Authors: Koppe Hilton , van de Mortel Thea F. , Ahern Christine M.
Published: June 2015

Objective

General practitioners (GPs) and general practice registrars report work‐related stress. Balint groups may improve coping mechanisms. However, attendance at a face‐to‐face Balint group is difficult for rural doctors due to distance constraints. The study aim was to evaluate online Balint groups for rural doctors and determine effect size for a full‐scale trial.

Design

A mixed‐methods approach, including a pre–post controlled trial and thematic analysis of qualitative data.

Setting

Rural primary care.

Participants

Thirteen GPs and 8 general practice registrars completed the study.

Interventions

Balint groups were delivered over 8–9 fortnightly online sessions. GPs and GP registrars participated in separate groups. Data were collected on work‐related affect, psychological medicine skills and professional isolation using the Warr's Work‐Related Affect Scale, the Psychological Medicine Inventory, and a professional isolation scale.

Main outcome measures

Change scores on Warr's Work‐Related Affect Scale, the Psychological Medicine Inventory, and a professional isolation scale.

Results

Balint participants' scores were significantly higher post‐intervention on the Psychological Medicine Inventory (mean 6.49 (±0.20) versus 5.43 (±0.26); P < 0.01) and Warr's Work‐Related Affect (mean 4.09 (±0.09) versus 3.60 (±0.12); P < 0.01) scales than control group scores. Effect size on these scales ranged from 0.46 to 0.50. The greatest challenge was technical problems related to insufficient broadband speed.

Conclusions

Online Balint groups appear to improve rural doctors' psychological medicine skills and work‐related affect. New data on effect size will inform a full‐scale trial. Improved national broadband infrastructure may enhance online support opportunities for rural doctors.
Restoration of sand grasslands by topsoil removal and self‐greening
Authors: Gilhaus Kristin , Vogt Vera , Hölzel Norbert
Published: June 2015

Questions

Is topsoil removal in combination with year‐round grazing a suitable method to restore and maintain nutrient‐poor open sand grasslands and wet heaths on ex‐arable land? Are there constraints in terms of animal nutrition?

Location

Pastures on ex‐arable land in pleistocene lowlands of Northwestern Germany, 120–160 m a.s.l.

Methods

We sampled vegetation, soil nutrient status and above‐ground biomass properties in 42 quadrats in a restored sand grassland and wet heath site and ten quadrats in an old sand grassland nearby. Data were analyzed using ordination, ANOVA and a generalized linear model.

Results

Soil phosphorus and nitrogen were significantly reduced by topsoil removal to the level of target communities. A remarkably high number of typical and endangered sand grassland species established, presumably from the seed/spore bank. Compared to old, seasonally grazed sand grassland, higher species diversity could be observed after topsoil removal. Reasons may be the raised pH as a heritage of arable cultivation and the very open vegetation structures enhancing early successional species. Year‐round grazing preserved open vegetation structures, but was not able to fully suppress birch encroachment in early stages of succession.

Conclusions

Our study showed that combining topsoil removal, self‐greening via recruitment from the seed/spore bank and subsequent year‐round grazing might be particularly successful approaches for the restoration of endangered sand grasslands and wet heaths on ex‐arable land. However, additional measures might be necessary to prevent undesired shrub encroachment in the first years after topsoil removal. Due to relatively low biomass quantity and quality of sand grasslands even in summer, we propose supplementary feeding in winter or a restriction to seasonal grazing to meet the requirements of animal welfare.
Drug‐Related Inadvertent Deaths in a University Hospital – A Declining Trend
Authors: Lapatto‐Reiniluoto Outi , Patinen Laura , Niemi Mikko , Backman Janne T. , Neuvonen Pertti J.
Published: June 2015

We studied the incidence of fatal adverse drug reactions (ADRs) in a tertiary hospital to find out which drugs were involved. The secondary objective was to compare the data from the same hospital published 12 years earlier. All 1708 death cases in the Helsinki University Central Hospital during the year 2012 were retrospectively evaluated. All suspected drug‐related deaths, excluding suicides, were scrutinized by an expert panel using the WHO ADR probability classification. Of all cases, 52 (3.0%) were classified as certainly or probably drug related and 24 (1.4%) as possibly drug related. Together, these corresponded to 0.02% of all hospital admissions. The most commonly involved drugs in certain or probable cases were cytostatics (18 cases, 1.1% of all cases) and antithrombotics (17, 1.0%). Twelve years earlier, these caused 27 (1.8%) and 22 (1.5%) cases, respectively. Non‐steroidal anti‐inflammatory drugs (NSAIDs) and glucocorticoids caused less (2 and 0 cases) fatal ADRs than earlier (12 and 4 cases, p = 0.048 and p = 0.005, respectively). Most of the ADRs leading to death were present already in admission and affected seriously ill or elderly patients. Hospital‐born fatal ADRs occurred in 0.003% of patients. In conclusion, cytostatics and antithrombotics are still the leading causes of fatal ADRs, but NSAIDs and glucocorticoids seem to cause fatal ADRs less often than previously. The incidence of fatal ADRs in 2012 was 3.0% of all deaths, suggesting a decline compared to the 2000 value (5.0%). Improved awareness, prevention and treatment of ADRs and safer medicines may explain these declining trends.
PAX5 alterations in genetically unclassified childhood Precursor B‐cell acute lymphoblastic leukaemia
Authors: Stasevich Irina , Inglott Sarah , Austin Nicola , Chatters Steve , Chalker Jane , Addy Dilys , Dryden Carryl , Ancliff Philip , Ford Anthony , Williams Owen , Kempski Helena
Published: June 2015

Here, we report a high incidence of PAX5 abnormalities observed in 32/68 (47%) of patients with genetically unclassified childhood precursor B‐cell acute lymphoblastic leukaemia (pre‐B ALL). Various deletions, gains, mutations and rearrangements of PAX5 comprised 45%, 12%, 29% and 14%, respectively, of the abnormalities found. 28% of patients showed more than one abnormality of the gene, implying bi‐allelic impairment of PAX5. Novel PAX5‐RHOXF2, PAX5‐ELK3 and PAX5‐CBFA2T2 rearrangements, which lead to aberrant expression of PAX5, were also identified. PAX5 rearrangements demonstrated a complex mechanism of formation including concurrent duplications/deletions of PAX5 and its partner genes. Finally, the splice variant c.1013‐2A>G, seen in two patients with loss of one PAX5 allele, was confirmed to be germ‐line in one patient and somatic in the other. PAX5 alterations were also found to be clinically associated with a higher white blood cell count (P = 0·015). These findings contribute to the knowledge of PAX5 alterations and their role in the pathogenesis of pre‐B ALL.
Guideline on aspects of cancer‐related venous thrombosis
Authors: Watson Henry G. , Keeling David M. , Laffan Mike , Tait Robert Campbell , Makris Mike ,   the British Committee for Standards in Haematology
Published: June 2015

The guideline was drafted by a writing group identified by the Haemostasis and Thrombosis Task Force of the British Committee for Standards in Haematology (BCSH). All the authors are consultants in haematology in the UK. A search was performed of PubMed and Embase using the term ‘cancer’ combined with ‘thrombosis’, ‘treatment’, ‘prophylaxis’ and ‘clinical presentation’. The search covered articles published up until December 2014. Only human studies were included and articles not written in English were excluded. References in recent reviews were also examined. The writing group produced the draft guideline, which was subsequently revised by consensus by members of the Haemostasis and Thrombosis Task Force of the BCSH and the BCSH executive. The guideline was then reviewed by the sounding board of the British Society for Haematology (BSH). This comprises 50 or more members of the BSH who have reviewed the guidance and commented on the content and application to the UK setting. The ‘GRADE’ system was used to quote levels and grades of evidence, details of which can be found at: http://www.bcshguidelines.com/BCSH_PROCESS/EVIDENCE_LEVELS_AND_GRADES_OF_RECOMMENDATION/43_GRADE.html. The objective of this guideline is to provide healthcare professionals with clear guidance on the prevention and management of venous thromboembolism (VTE) in patients with cancer and to advise on an approach to screening for cancer in patients with unprovoked VTE in whom cancer was not initially suspected based on clinical grounds.
Growth in neurofibromatosis 1 microdeletion patients
Authors: Ning X. , Farschtschi S. , Jones A. , Kehrer‐Sawatzki H. , Mautner V.‐F. , Friedman J. M.
Published: June 2015

Microdeletions of the entire NF1 gene and surrounding genomic region occur in about 5% of patients with neurofibromatosis 1 (NF1). NF1 microdeletion patients usually have more cutaneous and plexiform neurofibromas and a higher risk of developing malignant peripheral nerve sheath tumors than other people with NF1. Somatic overgrowth has also been observed in NF1 microdeletion patients, an observation that is remarkable because most NF1 patients are smaller than average for age and sex. We studied longitudinal measurements of height, weight, and head circumference in 56 patients with NF1 microdeletions and 226 NF1 patients with other kinds of mutations. Although children with NF1 microdeletions were much taller than non‐deletion NF1 patients at all ages after 2 years, the lengths of deletion and nondeletion NF1 patients were similar in early infancy. NF1 microdeletion patients tended to be heavier than other NF1 patients, but height or weight more than 3 standard deviations above the mean for age and sex was infrequent in children with NF1 microdeletions. Head circumference and age of puberty were similar in deletion and non‐deletion NF1 patients. The pattern of growth differs substantially in deletion and non‐deletion NF1 patients, but the pathogenic basis for this difference is unknown.
Life with a stoma after curative resection for rectal cancer: a population‐based cross‐sectional study
Authors: Feddern M.‐L. , Emmertsen K. J. , Laurberg S.
Published: June 2015

Aim

The aim of the investigation was to examine life with a stoma after rectal cancer surgery.

Method

This was a population‐based, cross‐sectional study of patients with a stoma treated for rectal cancer from 2001 to 2007. A questionnaire was mailed to patients who had undergone abdominoperineal excision, Hartmann's procedure and anterior resection with a permanent stoma.

Results

Informative answers were obtained from 644 (88%) of 732 patients. Most (91%) managed the stoma on their own. There was an impact of the stoma on the quality of life in 68% of patients but this was minor in 50%. Leakage of the appliance was reported in 59%, and 58% of patients were disturbed by the smell of faeces. A parastomal hernia was reported in 57% and pain at the stoma site in 30%. There was no association between the impact of the stoma on the quality of life and gender, type of surgery, use of radiochemotherapy or the interval from surgery.

Conclusion

Most patients reported little or no impact on quality of life resulting from the stoma, but many patients were disturbed by the smell or leakage of faeces. The parastomal hernia rate was extremely high.
Efficacy and safety of bone marrow‐derived cell transplantation for spinal cord injury: a systematic review and meta‐analysis of clinical trials
Authors: Li Xiao Chuan , Zhong Cheng Fan , Deng Gui Bin , Liang Rong Wei , Huang Chun Ming
Published: June 2015

Purpose

Bone marrow‐derived cells (BMDCs) for clinical transplantation were carried out many years in treating spinal cord injury (SCI) without a clear conclusion. This study aimed to evaluate the safety and efficacy of BMDC transplantation in treatment of SCI patients.

Method

Electronic databases, including PubMed, EMBASE, MEDLINE, and the Cochrane library, were searched to identify clinical therapeutic trials studying the application of BMDC transplantation in SCI.

Results

Overall the quality of the 24 studies was low, including one Grade I level of evidence, six Grade II levels, three Grade III levels, and 14 Grade IV levels. With a maximum of six‐yr follow‐up, the procedure‐related complications were minor and temporary, without serious adverse events (p = 0, n = 594). AIS improvement rate was analyzed in favor of BMDCs 6.13 (95% CI, 3.0–12.51; p < 0.001). In patient with complete (AIS A) and chronic SCI, the application of cell transplantation numbers between n × (107–108) seemed to be more beneficial (p < 0.05 for all groups).

Conclusions

Based on short‐medium terms following up, BMDC transplantation appears to be safe and valid in SCI patients, more effective in chronic and complete injury. Nonetheless, prospective, randomized trials in larger cohorts are still needed.
Switching STudy of Kidney TRansplant PAtients with Tremor to LCP‐TacrO (STRATO): an open‐label, multicenter, prospective phase 3b study
Authors: Langone Anthony , Steinberg Steven M. , Gedaly Roberto , Chan Laurence K. , Shah Tariq , Sethi Kapil D. , Nigro Vincenza , Morgan John C. ,   STRATO Investigators
Published: June 2015

Tremor is a common side effect of tacrolimus correlated with peak‐dose drug concentration. LCPT, a novel, once‐daily, extended‐release formulation of tacrolimus, has a reduced Cmax with comparable AUC exposure, requiring a ~30% dose reduction vs. immediate‐release tacrolimus. In this phase 3b study, kidney transplant recipients (KTR) on a stable dose of tacrolimus and with a reported clinically significant tremor were offered a switch to LCPT. Tremor pre‐ and seven d post‐conversion was evaluated by independent, blinded movement disorder neurologists using the Fahn–Tolosa–Marin (FTM) scale and by an accelerometry device; patients completed the QUEST (quality of life in essential tremor) and the Patient Global Impression of Change. There were 38 patients in the mITT population. A statistically and clinically significant improvement in tremor (FTM score, amplitude as measured by the accelerometry device and QOL [p‐values < 0.05]) resulted post‐conversion. Change in QUEST was significantly (p = 0.006) correlated (R = 0.44) with change in FTM; 78.9% of patients reported an improvement after switching to LCPT (p < 0.0005). To our knowledge this is the first trial in KTR that utilizes a sophisticated and reproducible measurement of tremor. Results suggest LCPT is associated with clinically meaningful improvement of hand tremor and may be an alternative management approach in lieu of further dose reduction of immediate‐release tacrolimus for patients experiencing tremor.
Incidence and care‐related costs of severe hypoglycaemia requiring emergency treatment in Andalusia (Spain): the PAUEPAD project
Authors: Barranco R. J. , Gomez‐Peralta F. , Abreu C. , Delgado M. , Palomares R. , Romero F. , Morales C. , de la Cal M. A. , Garcia‐Almeida J. M. , Pasquel F. , Umpierrez G. E.
Published: June 2015

Aims

Hypoglycaemia is a serious medical emergency. The need for emergency medical service care and the costs of hypoglycaemic emergencies are not completely known.

Methods

This was a retrospective observational study using Public Company for Health Emergencies (EPES) data for hypoglycaemia in 2012. The EPES provides emergency medical services to the entire population of Andalusia, Spain (8.5 million people). Data on event type, onsite treatments, emergency room visits or hospitalization were collected. Medical costs were estimated using the public rates for healthcare services.

Results

From a total of 1 137 738 emergency calls that requested medical assistance, 8683 had a primary diagnosis of hypoglycaemia (10.34 per 10 000 person‐years). The incidence of severe hypoglycaemic episodes requiring emergency treatment in the estimated population with diabetes was 810 episodes per 10 000 person‐years. A total of 7479 episodes (86%) required an emergency team to visit the patient's residence. The majority of cases (64%) were addressed in the residence, although 1784 (21%) cases were transferred to hospital. A total of 5564 events (65%) involved patients aged > 65 years. Overall mortality was 0.32% (28 cases). The total annual cost of attending a hypoglycaemic episode was €6 093 507, leading to an estimated mean direct cost per episode of €702 ± 565. Episodes that required hospital treatment accounted for 49% of the total costs.

Conclusions

Hypoglycaemia is a common medical emergency that is associated with high emergency medical service utilization, resulting in a significant economic impact on the health system.
The Utility of Systolic and Diastolic Echocardiographic Parameters for Predicting Coronary Artery Disease Burden as Defined by the SYNTAX Score
Authors: Liu Shuangbo , Moussa Motaz , Wassef Anthony W. , Hiebert Brett M. , Hussain Farrukh , Jassal Davinder S.
Published: June 2015

Background

Early identification of high‐grade ischemia based on echocardiographic diastolic abnormalities may be clinically useful in the acute coronary syndrome (ACS) setting. This could provide the clinician with an awareness of the burden of coronary artery disease (CAD) before angiography is performed to allow for early intervention of suspected ischemic lesions. The objective of the study was to assess whether 2D transthoracic echocardiography (TTE)‐derived tissue Doppler imaging parameters can predict the severity of CAD in comparison with the cardiac catheterization‐derived SYNTAX score.

Methods

A retrospective study of 74 stable angina or patients with ACS was performed in 2012 at a single tertiary care center. In all study subjects, TTE and angiography were performed within 6 months of each other without revascularization in the interim.

Results

The study population included a total of 74 patients (mean age 67 ± 12 years) with 77% presenting with an ACS. The median SYNTAX score was 24.0 (6.0–35.0). The E‐wave velocity was higher, and deceleration time (DT) was lower in the high SYNTAX group in comparison with the low/intermediate SYNTAX group (P = 0.045 and P = 0.001, respectively). Septal mitral annular S′ was lower in the high SYNTAX group (P = 0.02). After multivariate analysis, E/A ratio (OR 0.03, 95% 0.00–0.36, P = 0.0067), DT (OR 0.93, 95% CI 0.89–0.97, P = 0.0001) and septal annular S′‐wave velocity (OR 0.34, 95% CI 0.16–0.71, P = 0.0038) remained strong predictors of a high SYNTAX score.

Conclusion

Early identification of systolic and diastolic dysfunction based on echocardiographic parameters may be of important clinical significance for predicting CAD burden prior to invasive angiography.
Effects of plant volatiles on electrophysiological and behavioral responses ofCryptorrhynchus lapathi
Authors: Cao Qing‐Jie , Yu Jia , Ran Ya‐Li , Chi De‐Fu
Published: June 2015

Electroantennogram (EAG), Y‐tube olfactometer, and wind tunnel bioassays were conducted to test the electrophysiological and behavioral responses ofCryptorrhynchus lapathiL. (Coleoptera:Curculionidae) to six individual volatiles and seven essential oils (compounded volatiles). The aim of this study was to select effective plant compounds that can be used in the development of semiochemical‐based push–pull methods for the control of this harmful insect. Male and femaleC. lapathidisplayed strongEAGresponses to linoleic acid, α‐pinene, (Z)‐3‐hexen‐1‐ol, geraniol, turpentine oil, and salicylaldehyde. Y‐tube olfactometer assays indicated that salicylaldehyde and α‐pinene elicited strong repellent effects on femaleC. lapathi. Linoleic acid and (Z)‐3‐hexen‐1‐ol showed greater luring effects on male and femaleC. lapathicompared with the control. Turpentine oil was stronger repellent, and geraniol showed stronger luring effects on maleC. lapathithan the control. Wind tunnel assays with both male and femaleC. lapathiindicated that salicylaldehyde, α‐pinene, and turpentine oil elicited repellent effects compared with the control. Linoleic acid, (Z)‐3‐hexen‐1‐ol, and geraniol were stronger lures of both male and femaleC. lapathithan the control. These results provide a basis for the further development ofC. lapathiluring and repellent agents.
Assassin bugs of the subfamily Diaspidiinae (Heteroptera: Reduviidae): distribution and potential ecological niches
Authors: Chłond Dominik , Bugaj‐Nawrocka Agnieszka
Published: June 2015

The prediction and definition of the conditions for the potentially suitable ecological niche of the subfamily Diaspidiinae was the main goal of this study. Our research was based on 283 specimens of all known species of assassin bugs belonging to the subfamily Diaspidiinae stored in European museum collections and a set of 21 environmental variables in the form of a 1 × 1 km grid covering Africa and Madagascar. Based on occurrence localities, as well as a digital elevation model and layer of the tree cover‐continuous fields, information about the distribution of each species is given. Using Maxent software, potentially useful ecological niches were modeled, which allowed for the creation of a map of the potential distribution of the members of this subfamily and for determining their climatic preferences. A jackknife test showed that annual precipitation, annual temperature range and tree cover‐continuous fields were the most important environmental variables affecting the distribution of the subfamily Diaspidiinae. An analysis of climatic preferences suggested that the representatives of the subfamily were linked mainly to the tropical climate. An analysis of environmental variables also showed that the subfamily preferred areas with herbaceous vegetation and some trees, and this preference is probably caused by the food preferences of their prey. On the basis of the museum data on the species occurrence, as well as ecological niche modeling methods, we provided new and valuable information on potentially suitable habitat and the possible range of distribution of the subfamily Diaspidiinae along with its climatic preferences.
Drug–drug interaction between clobazam and cannabidiol in children with refractory epilepsy
Authors: Geffrey Alexandra L. , Pollack Sarah F. , Bruno Patricia L. , Thiele Elizabeth A.
Published: June 2015

Objective

Under an expanded access investigational new drug (IND) trial, cannabidiol (CBD) is being studied as a possible adjuvant treatment of refractory epilepsy in children. Of the 25 subjects in the trial, 13 were being treated with clobazam (CLB). Because CLB and CBD are both metabolized in the cytochrome P450 (CYP) pathway, we predicted a drug–drug interaction, which we evaluate in this article.

Methods

Thirteen subjects with refractory epilepsy concomitantly taking CLB and CBD under IND 119876 were included in this study. Demographic information was collected for each subject including age, sex, and etiology of seizures, as well as concomitant antiepileptic drugs (AEDs). CLB, N‐desmethylclobazam (norclobazam; nCLB), and CBD levels were measured over the course of CBD treatment. CLB doses were recorded at baseline and at weeks 4 and 8 of CBD treatment. Side effects were monitored.

Results

We report elevated CLB and nCLB levels in these subjects. The mean (± standard deviation [SD]) increase in CLB levels was 60 ± 80% (95% confidence interval (CI) [−2–91%] at 4 weeks); the mean increase in nCLB levels was 500 ± 300% (95% CI [+90–610%] at 4 weeks). Nine of 13 subjects had a >50% decrease in seizures, corresponding to a responder rate of 70%. The increased CLB and nCLB levels and decreases in seizure frequency occurred even though, over the course of CBD treatment, CLB doses were reduced for 10 (77%) of the 13 subjects. Side effects were reported in 10 (77%) of the 13 subjects, but were alleviated with CLB dose reduction.

Significance

Monitoring of CLB and nCLB levels is necessary for clinical care of patients concomitantly on CLB and CBD. Nonetheless, CBD is a safe and effective treatment of refractory epilepsy in patients receiving CLB treatment.
Equine allogeneic umbilical cord blood derived mesenchymal stromal cells reduce synovial fluid nucleated cell count and induce mild self‐limiting inflammation when evaluated in an lipopolysaccharide induced synovitis model
Authors: Williams L. B. , Koenig J. B. , Black B. , Gibson T. W. G. , Sharif S. , Koch T. G.
Published: June 2015

Reasons for performing study

Improvement has been reported following intra‐articular (i.a.) injection of mesenchymal stromal cells (MSCs) in several species. These observations have led to the use of i.a.MSCs in equine practice with little understanding of the mechanisms by which perceived improvement occurs.

Objectives

To evaluate the effect of i.a. allogeneic umbilical cord blood (CB‐) derivedMSCs using a lipopolysaccharide (LPS) induced synovitis model. We hypothesised that i.a.CB‐MSCs would reduce the inflammatory response associated withLPSinjection.

Study design

Randomised, blinded experimental study.

Methods

Feasibility studies evaluated i.a.LPSorCB‐MSCs alone into the tarsocrural joint. In the principal study, middle carpal joint synovitis was induced bilaterally with LPS and thenCB‐MSCs were injected into one middle carpal joint. Lameness, routine synovial fluid analysis, and synovial fluid biomarkers were evaluated at 0, 8, 24, 48 and 72 h.

Results

LPSinjection alone resulted in transient lameness and signs of inflammation. In joints untreated withLPS, injection of 30 millionCB‐MSCs resulted in mild synovitis that resolved without treatment. Mild (grade 1–2) lameness in theCB‐MSC‐treated limb was observed in 2 horses and severe lameness (grade 4) in the 3rd, 24 h post injection. Lameness did not correlate with synovitis induced byCB‐MSCinjection. Simultaneous injection ofLPSandCB‐MSCs resulted in significant reduction in synovial fluid total nucleated, neutrophil and mononuclear cell numbers compared with contralateralLPS‐only joints. No difference was detected in other parameters associated with synovial fluid analysis or in synovial fluid biomarkers. The incidence of lameness was only different from baseline at 8 h, where horses were lame inCB‐MSClimbs.

Conclusions

AllogeneicCB‐MSCs reduced synovial fluid cell populations and stimulated mild self‐limiting inflammation in the synovitis model. Continued evaluation of the effects of i.a.CB‐MSCtherapy on synovitis in horses is needed to evaluate anti‐ and proinflammatory properties ofCB‐MSCs. Immediate interests are dose, timing of treatment, and treatment frequency.
Linking coastal aquaculture of meagre Argyrosomus regius and Western Mediterranean coastal fisheries through escapes incidents
Authors: Arechavala‐Lopez P. , Valero‐Rodriguez J. M. , Peñalver‐García J. , Izquierdo‐Gomez D. , Sanchez‐Jerez P.
Published: June 2015

Escape incidents in coastal aquaculture lead to economic losses for farmers and may have indirect socio‐economic effects on local fisheries. In this study, the relationship of meagre, Argyrosomus regius (Asso), production in open‐sea cages and coastal small‐scale fisheries was analysed through captures of escapes, which are easily detected because this species is considered locally absent in native communities in Western Mediterranean regions. Scale reading showed that 100% of captured meagre were escapees. The existence of a direct relationship, in terms of biomass, between the development of meagre coastal aquaculture and the increase of captures of this species by local fisheries was demonstrated. The spatial distribution of meagre captures suggested that there is a local environmental and economic interaction between meagre aquaculture and fisheries through escapees. Monitoring the presence of locally absent species such as meagre within landings might help to assess the magnitude of escapes, the potential economic effects on local aquaculture and fishery industries, and the potential adverse ecological impacts on local ecosystems.
Head morphology and piscivory of European eels, Anguilla anguilla, predict their probability of infection by the invasive parasitic nematode Anguillicoloides crassus
Authors: Pegg Josephine , Andreou Demetra , Williams Chris F. , Britton J. Robert
Published: June 2015

The morphology of animal body structures influences their function; intrapopulation plasticity in diet composition can occur where head morphology limits gape size. The European eel, Anguilla anguilla, a critically endangered catadromous fish, shows significant intrapopulation variations in head width, with broader headed individuals being more piscivorous.

Infection of eels during their freshwater phase by Anguillicoloides crassus, an invasive nematode parasite, involves paratenic fish hosts. We tested the relationships between their infection status, head functional morphology (as head width/total length ratio; HW:TL) and the proportion of fish in diet (estimated by stable isotope mixing models) across three populations.

The extent of piscivory in the diets of individual eels increased significantly as their HW:TL ratios increased. There were no significant differences between infected and uninfected eels in their total lengths and hepatic–somatic indices. However, the HW:TL ratios of infected eels were significantly higher than those of uninfected eels and, correspondingly, their diet comprised a higher proportion of fish.

Logistic regression revealed that head morphology and diet were significant predictors of infection status, with models correctly assigning up to 78% of eels to their infection status. Thus, eel head functional morphology significantly influenced their probability of being infected by invasive A. crassus, most likely through increased exposure to fish paratenic hosts. Accordingly, the detrimental consequences of infections are likely to be focussed on those individuals in freshwater populations whose functional morphology enables greater specialisation in piscivory.
Putative calcium‐binding domains of the Caenorhabditis elegans BK channel are dispensable for intoxication and ethanol activation
Authors: Davis S. J. , Scott L. L. , Ordemann G. , Philpo A. , Cohn J. , Pierce‐Shimomura J. T.
Published: June 2015

Alcohol modulates the highly conserved, voltage‐ and calcium‐activated potassium (BK) channel, which contributes to alcohol‐mediated behaviors in species from worms to humans. Previous studies have shown that the calcium‐sensitive domains, RCK1 and the Ca2+ bowl, are required for ethanol activation of the mammalian BK channel in vitro. In the nematode Caenorhabditis elegans, ethanol activates the BK channel in vivo, and deletion of the worm BK channel, SLO‐1, confers strong resistance to intoxication. To determine if the conserved RCK1 and calcium bowl domains were also critical for intoxication and basal BK channel‐dependent behaviors in C. elegans, we generated transgenic worms that express mutated SLO‐1 channels predicted to have the RCK1, Ca2+ bowl or both domains rendered insensitive to calcium. As expected, mutating these domains inhibited basal function of SLO‐1 in vivo as neck and body curvature of these mutants mimicked that of the BK null mutant. Unexpectedly, however, mutating these domains singly or together in SLO‐1 had no effect on intoxication in C. elegans. Consistent with these behavioral results, we found that ethanol activated the SLO‐1 channel in vitro with or without these domains. By contrast, in agreement with previous in vitro findings, C. elegans harboring a human BK channel with mutated calcium‐sensing domains displayed resistance to intoxication. Thus, for the worm SLO‐1 channel, the putative calcium‐sensitive domains are critical for basal in vivo function but unnecessary for in vivo ethanol action.
The initial stage of reversal learning is impaired in mice hemizygous for the vesicular glutamate transporter (VGluT1)
Authors: Granseth B. , Andersson F. K. , Lindström S. H.
Published: June 2015

Behavioral flexibility is a complex cognitive function that is necessary for survival in changeable environments. Patients with schizophrenia or Parkinson's disease often suffer from cognitive rigidity, reducing their capacity to function in society. Patients and rodent models with focal lesions in the prefrontal cortex (PFC) show similar rigidity, owing to the loss of PFC regulation of subcortical reward circuits involved in behavioral flexibility. The vesicular glutamate transporter (VGluT1) is preferentially expressed at modulatory synapses, including PFC neurons that project to components of the reward circuit (such as the nucleus accumbens, NAc). VGluT1+/− mice display behavioral phenotypes matching many symptoms of schizophrenia, and VGluT1 expression is reduced in the PFC of patients with schizophrenia and Parkinson's disease. Thus, it appears likely that VGluT1‐expressing synapses from PFC play a key role in behavioral flexibility. To examine this hypothesis, we studied behavioral flexibility in VGluT1+/− mice by testing reversal learning in a visual discrimination task. Here, we show that VGluT1+/− mice acquired the initial visual discrimination at the same rate as controls. However, they failed to suppress responses to the previously rewarded stimulus following reversal of reward contingencies. Thus, our genetic disruption of modulatory glutamatergic signaling, including that arising from PFC, appears to have impaired the first stage of reversal learning (extinguishing responses to previously rewarded stimuli). Our data show that this deficit stems from a preservative phenotype. These findings suggest that glutamatergic regulation from the cortex is important for behavioral flexibility and the disruption of this pathway may be relevant in diseases such as schizophrenia.
Pigment‐dispersing factor signaling in the circadian system of Caenorhabditis elegans
Authors: Herrero A. , Romanowski A. , Meelkop E. , Caldart C. S. , Schoofs L. , Golombek D. A.
Published: June 2015

The neuropeptide pigment‐dispersing factor (PDF) is important for the generation and entrainment of circadian rhythms in the fruitfly Drosophila melanogaster. Recently two pdf homologs, pdf‐1 and pdf‐2, and a PDF receptor, pdfr‐1, have been found in Caenorhabditis elegans and have been implicated in locomotor activity. In this work, we have studied the role of the PDF neuropeptide in the circadian system of C. elegans and found that both pdf‐1 and pdf‐2 mutants affect the normal locomotor activity outputs. In particular, loss of pdf‐1 induced circadian arrhythmicity under both light–dark (LD) and constant dark (DD) conditions. These defects can be rescued by a genomic copy of the pdf‐1 locus. Our results indicate that PDF‐1 is involved in rhythm generation and in the synchronization to LD cycles, as rhythmic patterns of activity rapidly disappear when pdf‐1 mutants are recorded under both entrained and free‐running conditions. The role of PDF‐2 and the PDF receptors is probably more complex and involves the interaction between the two pdf paralogues found in the nematode.
Supporting quality public and patient engagement in health system organizations: development and usability testing of the Public and Patient Engagement Evaluation Tool
Authors: Abelson Julia , Li Kathy , Wilson Geoff , Shields Kristin , Schneider Colleen , Boesveld Sarah
Published: June 2015

Objectives

Only rudimentary tools exist to support health system organizations to evaluate their public and patient engagement (PPE) activities. This study responds to this gap by developing a generic evaluation tool for use in a wide range of organizations.

Methods

The evaluation tool was developed through an iterative, collaborative process informed by a review of published and grey literature and with the input of Canadian PPE researchers and practitioners. Over a 3‐year period, structured e‐mail, telephone and face‐to‐face exchanges, including a modified Delphi process, were used to produce an evaluation tool that includes core principles of high‐quality engagement, expected outcomes for each principle and three unique evaluation questionnaires that were tested and revised with input from 65 end users.

Results

The tool is structured around four core principles of ‘quality engagement’: (i) integrity of design and process; (ii) influence and impact; (iii) participatory culture; and (iv) collaboration and common purpose. Three unique questionnaires were developed to assess each of these four evaluation domains from the following perspectives: (i) those who participate in PPE activities; (ii) those who plan, execute or sponsor PPE activities within organizations; and (iii) those who provide the leadership and capacity for PPE within their organizations.

Conclusions

This is the first known collaboration of researchers and practitioners in the co‐design of a comprehensive PPE evaluation tool aimed at three distinct respondent groups and for use in a wide range of health system organization settings.
In vitro and in vivo dermal absorption assessment of acetyl aspartic acid: a compartmental study
Authors: Duracher L. , Visdal‐Johnsen L. , Mavon A.
Published: June 2015

Synopsis

Objective

The purpose of this study was to evaluate the dermal absorption of acetyl aspartic acid (A‐A‐A) through an in vitro and in vivo evaluation with human skin after 6 and 24 h of topical application of a cosmetic formulation containing A‐A‐A at 1%.

Methods

The in vitro experiment was carried out using the Franz diffusion cells system with ex vivo human skin samples. The profile of diffusion of A‐A‐A was evaluated after 6 and 24 h. The in vivo experiment was performed on human volunteers following a tape‐stripping protocol after 6 h of topical application. A‐A‐A was quantified in the main skin compartments, that is the skin surface, the stratum corneum, the skin and the receptor fluid using LC‐MS analysis.

Results

The 24‐h in vitro experiment confirmed the great penetration potential of A‐A‐A in all skin compartments. After 6 h of topical application, the removed tape strips from both in vitro and in vivo experiments were analysed and the profile of diffusion of A‐A‐A was determined, allowing also an in vitro/in vivo comparison. The diffusion profile observed on the in vitro skin penetration test is highly representative of the in vivo situation evaluated on volunteers.

Conclusion

The combination of in vitro with in vivo data confirmed that A‐A‐A has the capacity to diffuse through the skin after topical application and reach the dermis as the targeted skin layer for potential anti‐ageing benefits.
Pre‐clinical formulation screening, development and stability of acetyl aspartic acid for cosmetic application
Authors: Cattley K. , Duracher L. , Camattari P. , Mavon A. , Grooby S.
Published: June 2015

Synopsis

Background

Acetyl aspartic acid (A‐A‐A) was discovered through gene array analysis with corresponding connectivity mapping (Cmap). Using an in silico and in vitro approach, A‐A‐A was found increased keratinocyte regeneration, inhibited dermal expression of MMP making this compound a potential active ingredient for cosmetic application.

Objectives

To determine the conditions to successfully formulate A‐A‐A for skin delivery investigation and in vivo clinical assessment by the systematic approach of pre‐formulation testing of the active, screening of formulation type on active delivery and stability evaluations.

Methods

Analytical evaluation of A‐A‐A was undertaken using LC‐MS ESI method. Formulation stability was evaluated using Brookfield viscometer, pH analysis, optical microscopy and organoleptic evaluations.

Results

Analytical evaluation of A‐A‐A shows that pH significantly impacts chemical stability of the molecule. A‐A‐A containing formulae show minimal differences to vehicle product throughout the testing.

Conclusion

A‐A‐A is an active that can be successfully formulated in a cosmetic o/w emulsion within defined pH considerations.
Expression and significance of cortactin and HDAC6 in human prostatic foamy gland carcinoma
Authors: Hou Huilian , Zhao Le , Chen Wei , Li Jing , Zuo Qinqin , Zhang Guanjun , Zhang Xuebin , Li Xu
Published: June 2015

Cortactin, the cytoplasmic substrate of HDAC6, is known to play an actin cytoskeletal regulatory role which is implicated in the motility of cancer cells, and thus in cancer progression. Its activity is found to be regulated by HDAC6. However, the significance of cortactin and HDAC6 remains unclear in uncommon histologic variant human prostatic foamy gland carcinoma (PfCa). In this study, we aimed to identify the expression and potential role of cortactin and HDAC6 in PfCa. Therefore, 16 PfCa specimens containing 48 foci with distinctive lesions were collected to identify the status of cortactin and HDAC6 by immunohistochemistry. Their correlation between clinicopathological characteristics and prognostic values were further analysed. The effect of cortactin and HDAC6 on prostate cancer cell migration and invasion was then evaluated in IA8 cells. The results showed that expression of cortactin and HDAC6 was significantly higher in PfCa foci, compared to that of high‐grade prostatic intraepithelial neoplasia (HGPIN) foci and benign foci (P < 0.05). Cortactin and HDAC6 were associated with poor prognosis of patients with PfCa (P < 0.05). Multivariable Cox regression analysis showed HDAC6 level was a significant prognostic factor for survival of patients with PfCa (β = 1.200, Wald value = 7.282, P = 0.007, 95% CI = 1.389–7.941, P < 0.01, β > 0). Both knocking down cortactin and inhibition of HDAC6 activity with tubacin reduced in vitro migration and invasion ability of IA8 cells substantially. Furthermore, HDAC6 has prognostic value for patients with PfCa. Dysregulation of cortactin and HDAC6 is implicated in the invasiveness and migration of prostate cancer cells.