bluuebunny/crossref_metadata_2025 huggingface dataset:
Effective use of a vessel‐sealing system for laparoscopic unroofing of liver cysts
Authors: Kanamoto Mami , Imura Satoru , Morine Yuji , Utsunomiya Tohru , Mori Hiroki , Arakawa Yusuke , Takasu Chie , Shimada Mitsuo
Published: January 2015

Introduction

Liver cysts that present with symptoms such as jaundice, abdominal pain, and intra‐cystic infection require treatment. In laparoscopic unroofing of liver cysts, appropriate treatment is needed in cases where the cystic walls contain vessels or bile ducts. A vessel‐sealing system can seal not only vessels, but also bile ducts. We experienced four cases in which laparoscopic unroofing of liver cysts was performed with a vessel‐sealing system.

Materials and Surgical Technique

Case 1 was a woman in her 70s who presented at our hospital with abdominal pressure. Abdominal CT showed liver cysts with a maximum diameter of 13 cm. Laparoscopic unroofing was performed with LigaSure Impact. Case 2 was a woman in her 50s with abdominal discomfort. CT showed a cyst 15 cm in diameter situated in the right lobe. We performed SILS using a LigaSure Blunt Tip to unroof the cyst. Case 3 was a man in his 80s with abdominal pain. CT showed a huge cyst 25 cm in diameter in the right lobe. We performed hybrid SILS with a LigaSure Blunt Tip to unroof the cysts. Case 4 was a woman in her 70s with upper abdominal pain. CT showed multiple cysts with a maximum diameter of 15 cm in the bilateral lobes. We performed hybrid SILS to successfully unroof her cysts. None of the cases experienced postoperative complications, such as bleeding or bile leakage, and none experienced recurrence of cysts.

Discussion

A laparoscopic unroofing using a vessel‐sealing system can be a minimally invasive and safe treatment for liver cysts.
Intraoperative fluorescent cholangiography using indocyanine green for laparoscopic fenestration of nonparasitic huge liver cysts
Authors: Kitajima Toshihiro , Fujimoto Yasuhiro , Hatano Etsuro , Mitsunori Yusuke , Tomiyama Koji , Taura Kojiro , Mizumoto Masaki , Uemoto Shinji
Published: January 2015

Bile duct injury is one of the known serious complications of laparoscopic fenestration for nonparasitic liver cysts. Herein, we report the case of a huge liver cyst for which we performed laparoscopic fenestration using intraoperative fluorescent cholangiography with indocyanine green. A 71‐year‐old woman with abdominal distention was referred to our hospital. CT demonstrated a 17 × 11.5‐cm simple cyst replacing the right lobe of the liver, so laparoscopic fenestration was performed. Although the biliary duct could not be detected because of compression by the huge cyst, fluorescent cholangiography with indocyanine green through endoscopic naso‐biliary drainage tube clearly delineated the intrahepatic bile duct in the remaining cystic wall. The patient had no complications at 3 months after surgery. Fluorescent cholangiography using indocyanine green is a safe and effective procedure to avoid bile duct injury during laparoscopic fenestration, especially in patients with a huge liver cyst.
Inguinal hernia repair: Toward Asian guidelines
Authors: Lomanto Davide , Cheah Wei‐Keat , Faylona Jose Macario , Huang Ching Shui , Lohsiriwat Darin , Maleachi Andy , Yang George Pei Cheung , Li Michael Ka‐Wai , Tumtavitikul Sathien , Sharma Anil , Hartung Rolf Ulrich , Choi Young Bai , Sutedja Barlian
Published: January 2015

Groin hernias are very common, and surgical treatment is usually recommended. In fact, hernia repair is the most common surgical procedure performed worldwide. In countries such as the USA, China, and India, there may easily be over 1 million repairs every year. The need for this surgery has become an important socioeconomic problem and may affect health‐care providers, especially in aging societies. Surgical repair using mesh is recommended and widely employed in Western countries, but in many developing countries, tissue‐to‐tissue repair is still the preferred surgical procedure due to economic constraints. For these reason, the development and implementation of guidelines, consensus, or recommendations may aim to clarify issues related to best practices in inguinal hernia repair in Asia. A group of Asian experts in hernia repair gathered together to debate inguinal hernia treatments in Asia in an attempt to reach some consensus or develop recommendations on best practices in the region. The need for recommendations or guidelines was unanimously confirmed to help overcome the discrepancy in clinical practice between countries; the experts decided to focus mainly on the technical aspects of open repair, which is the most common surgery for hernia in our region. After the identification of 12 main topics for discussion (indication, age, and sex; symptomatic and asymptomatic hernia: type of hernia; type of treatment; hospital admission; preoperative care; anesthesia; surgical technique; perioperative care; postoperative care; early complications; and long‐term complications), a search of the literature was carried out according to the five levels of the Oxford Classification of Evidence and the four grades of recommendation.
Conjugated fatty acids and methane production by rumen microbes when incubated with linseed oil alone or mixed with fish oil and/or malate
Authors: Li Xiang Z. , Gao Qing S. , Yan Chang G. , Choi Seong H. , Shin Jong S. , Song Man K.
Published: January 2015

We hypothesized that manipulating metabolism with fish oil and malate as a hydrogen acceptor would affect the biohydrogenation process of α‐linolenic acid by rumen microbes. This study was to examine the effect of fish oil and/or malate on the production of conjugated fatty acids and methane (CH4) by rumen microbes when incubated with linseed oil. Linseed oil (LO), LO with fish oil (LO‐FO), LO with malate (LO‐MA), or LO with fish oil and malate (LO‐FO‐MA) was added to diluted rumen fluid, respectively. The LO‐MA and LO‐FO‐MA increased pH and propionate concentration compared to the other treatments. LO‐MA and LO‐FO‐MA reduced CH4 production compared to LO. LO‐MA and LO‐FO‐MA increased the contents of c9,t11‐conjugated linoleic acid (CLA) and c9,t11,c15‐conjugated linolenic acid (CLnA) compared to LO. The content of malate was rapidly reduced while that of lactate was reduced in LO‐MA and LO‐FO‐MA from 3 h incubation time. The fold change of the quantity of methanogen related to total bacteria was decreased at both 3 h and 6 h incubation times in all treatments compared to the control. Overall data indicate that supplementation of combined malate and/or fish oil when incubated with linseed oil, could depress methane generation and increase production of propionate, CLA and CLnA under the conditions of the current in vitro study.
Effect of active immunization against GnRH‐I on the reproductive function in cat
Authors: Jiang Shudong , Hong Meizhen , Su Shiping , Song Min , Tian Yuan , Cui Pei , Song Shuang , Wang Yaoyao , Li Fubao , Fang Fugui
Published: January 2015

This study was designed to explore the effect of active immunization against maltose binding protein‐gonadotropin releasing hormone I hexamer (MBP‐GnRH‐I6) on the reproductive function in cats. Each immunized cat was administered twice intramuscularly in the neck at 16 and 20 weeks old. The concentrations of the testosterone and estradiol and the level of anti‐GnRH‐I antibody in the serum were measured by radioimmunoassay and ELISA, respectively. The results showed that the weight and size of testicles and ovaries, and the concentrations of serum testosterone and estradiol in the immunized animals were lower than those of the control cats (P < 0.05), but that the levels of anti‐GnRH‐I antibody were significant higher compared to control animals (P < 0.05). Testicular tissues from the immunized male cats showed that seminiferous tubules were depauperate with the lumen relatively empty and that the differentiation of spermatogonia was not obvious. Tissues from the immunized female cats showed that the ovaries had many primordial follicles and primary follicles, but no secondary follicle was observed. These results showed active immunization against MBP–GnRH‐I6 could make the gonads atrophy and reduce the concentrations of gonadal hormones, which suggested that MBP‐GnRH‐I6 was a very effective immunogen in the cat.
Central obesity is predictive of persistent storage lower urinary tract symptoms (LUTS) after surgery for benign prostatic enlargement: results of a multicentre prospective study
Authors: Gacci Mauro , Sebastianelli Arcangelo , Salvi Matteo , De Nunzio Cosimo , Tubaro Andrea , Vignozzi Linda , Corona Giovanni , McVary Kevin T. , Kaplan Steven A. , Maggi Mario , Carini Marco , Serni Sergio
Published: January 2015

Objective

To evaluate the impact of components of metabolic syndrome (MetS) on urinary outcomes after surgery for severe lower urinary tract symptoms (LUTS) due to benign prostatic enlargement (BPE), as central obesity can be associated with the development of BPE and with the worsening of LUTS.

Patients and Methods

A multicentre prospective study was conducted including 378 consecutive men surgically treated for large BPE with simple open prostatectomy (OP) or transurethral resection of the prostate (TURP), between January 2012 and October 2013. LUTS were measured by the International Prostate Symptom Score (IPSS), immediately before surgery and at 6–12 months postoperatively. MetS was defined according the USA National Cholesterol Education Program‐Adult Treatment Panel III.

Results

The improvement of total and storage IPSS postoperatively was related to diastolic blood pressure and waist circumference (WC). A WC of >102 cm was associated with a higher risk of an incomplete recovery of both total IPSS (odds ratio [OR] 0.343, P = 0.001) and storage IPSS (OR 0.208, P < 0.001), as compared with a WC of <102 cm. The main limitations were: (i) population selected from a tertiary centre, (ii) Use exclusively of IPSS questionnaire, and (iii) No inclusion of further data.

Conclusions

Increased WC is associated with persistent postoperative urinary symptoms after surgical treatment of BPE. Obese men have a higher risk of persistent storage LUTS after TURP or OP.
A novel urodynamic model for lower urinary tract assessment in awake rats
Authors: Schneider Marc P. , Hughes Francis M. , Engmann Anne K. , Purves J. Todd , Kasper Hansjörg , Tedaldi Marco , Spruill Laura S. , Gullo Miriam , Schwab Martin E. , Kessler Thomas M.
Published: January 2015

Objectives

To develop a urodynamic model incorporating external urethral sphincter (EUS) electromyography (EMG) in awake rats.

Materials and Methods

Bladder catheters and EUS EMG electrodes were implanted in female Sprague Dawley rats. Assessments were performed in awake, lightly restrained rats on postoperative day 12–14. Measurements were repeated in the same rat on day 16 under urethane anaesthesia. Urodynamics and EUS EMG were performed simultaneously. In addition, serum creatinine and bladder histology was assessed.

Results

No significant differences in urodynamic parameters were found between bladder catheter only vs bladder catheter and EUS EMG electrode groups. Urethane anaesthesia evoked prominent changes in both urodynamic parameters and EUS EMG. Serum creatinine was within the normal limits in all rats. Bladder weight and bladder wall thickness were significantly increased in both the bladder catheter only and the bladder catheter and EUS EMG group compared with controls.

Conclusions

Our novel urodynamic model allows repetitive measurements of both bladder and EUS function at different time points in the same rat under fully awake conditions and opens promising avenues to investigate lower urinary tract dysfunction in a translational approach.
Trimlines, blockfields and the vertical extent of the last ice sheet in southern Ireland
Authors: Ballantyne Colin K. , Stone John O.
Published: January 2015

Trimlines separating glacially abraded lower slopes from blockfield‐covered summits on Irish mountains have traditionally been interpreted as representing the upper limit of the last ice sheet during the Last Glacial Maximum (LGM). Cosmogenic 10Be exposure ages obtained for samples from glacially deposited perched boulders resting on blockfield debris on the summit area of Slievenamon (721 m a.s.l.) in southern Ireland demonstrate emplacement by the last Irish Ice Sheet (IIS), implying preservation of the blockfield under cold‐based ice during the LGM, and supporting the view that trimlines throughout the British Isles represent former englacial thermal regime boundaries between a lower zone of warm‐based sliding ice and an upper zone of cold‐based ice. The youngest exposure age (22.6±1.1 or 21.0±0.9 ka, depending on the 10Be production rate employed) is statistically indistinguishable from the mean age (23.4±1.2 or 21.8±0.9 ka) obtained for two samples from ice‐abraded bedrock at high ground on Blackstairs Mountain, 51 km to the east, and with published cosmogenic 36Cl ages. Collectively, these ages imply (i) early (24–21 ka) thinning of the last IIS and emergence of high ground in SE Ireland; (ii) relatively brief (1–3 ka) glacial occupation of southernmost Ireland during the LGM; (iii) decoupling of the Irish Sea Ice Stream and ice from the Irish midlands within a similar time frame; and (iv) that the southern fringe of Ireland was deglaciated before western and northern Ireland.
In vitro and in vivo regulation of synaptogenesis by the novel antidepressant spadin
Authors: Devader C , Khayachi A , Veyssière J , Moha ou Maati H , Roulot M , Moreno S , Borsotto M , Martin S , Heurteaux C , Mazella J
Published: January 2015

Background and Purpose

We have described a novel antidepressant peptide, spadin, that acts by blocking the TWIK‐related‐potassium channel, type 1 (TREK‐1). Here, we examined possible mechanisms of action of spadin at both molecular and cellular levels.

Experimental Approaches

Effects of spadin were measured in primary cultures of neurons or tissues from mice injected i.v. with spadin. Western blots, qPCR, histochemical and electrophysiological techniques were used.

Key Results

In vitro, spadin increased neuronal membrane potential and activated both the MAPK and PI3K signalling pathways, in a time‐ and concentration‐dependent manner. The latter pathway was involved in the protective effect of spadin against staurosporine‐induced apoptosis. Also, spadin enhanced both mRNA expression and protein of two markers of synaptogenesis, the post‐synaptic density protein of 95 kDalton (PSD‐95) and synapsin. We confirmed these effects on synaptogenesis by the observation that spadin treatment significantly increased the proportion of mature spines in cortical neurons. Finally, in vivo injections of spadin led to a rapid increase in both mRNA expression and protein level of brain‐derived neurotrophic factor (BDNF) in the hippocampus, confirming the antidepressant action of the peptide. We argue for a new role of spadin in synaptogenesis as both PSD‐95 and synapsin mRNA expression and protein levels were further enhanced in the hippocampus, following treatment in vivo with the peptide.

Conclusions and Implications

These findings provide new mechanisms of action for the rapidly acting antidepressant peptide spadin by stimulating expression of BDNF and synaptic proteins, both in vitro and in vivo.
The anti‐inflammatory mediator palmitoylethanolamide enhances the levels of 2‐arachidonoyl‐glycerol and potentiates its actions at TRPV1 cation channels
Authors: Petrosino Stefania , Schiano Moriello Aniello , Cerrato Santiago , Fusco Mariella , Puigdemont Anna , De Petrocellis Luciano , Di Marzo Vincenzo
Published: January 2015

Background and Purpose

Palmitoylethanolamide (PEA) is an endogenous congener of anandamide and potentiates its actions at cannabinoid CB1 and CB2 receptors, and at transient receptor potential vanilloid type‐1 (TRPV1) channels. The other endocannabinoid, 2‐arachidonoylglycerol (2‐AG), was recently suggested to act as a TRPV1 channel agonist. We investigated if PEA enhanced levels of 2‐AG in vitro or in vivo and 2‐AG activity at TRPV1 channels.

Experimental Approach

Endogenous lipid levels were measured by LC‐MS in (i) human keratinocytes incubated with PEA (10–20 μM, 40 min, 6 and 24 h, 37°C); (ii) the blood of spontaneously Ascaris suum hypersensitive beagle dogs given a single oral dose of ultramicronized PEA (30 mg·kg−1, 1, 2, 4 and 8 h from administration); (iii) the blood of healthy volunteers given a single oral dose of micronized PEA (300 mg, 2, 4 and 6 h from administration). Effects of 2‐AG at TRPV1 channels were assessed by measuring intracellular Ca2+ in HEK‐293 cells over‐expressing human TRPV1 channels.

Key Results

PEA elevated 2‐AG levels in keratinocytes (∼3‐fold) and in human and canine plasma (∼2 and ∼20‐fold respectively). 2‐AG dose‐dependently raised intracellular Ca2+ in HEK‐293‐TRPV1 cells in a TRPV1‐dependent manner and desensitized the cells to capsaicin. PEA only slightly enhanced 2‐AG activation of TRPV1 channels, but significantly increased 2‐AG‐induced TRPV1 desensitization to capsaicin (IC50 from 0.75 ± 0.04 to 0.45 ± 0.02 μM, with PEA 2 μM).

Conclusions and Implications

These observations may explain why several effects of PEA are attenuated by cannabinoid receptor or TRPV1 channel antagonists.

Linked Articles

This article is part of a themed section on Endocannabinoids. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.7/issuetoc
Effects of the novel BK (KCa1.1) channel opener GoSlo‐SR‐5‐130 are dependent on the presence of BKβ subunits
Authors: Large R J , Kshatri A , Webb T I , Roy S , Akande A , Bradley E , Sergeant G P , Thornbury K D , McHale N G , Hollywood M A
Published: January 2015

Background and Purpose

GoSlo‐SR compounds are efficacious BK (KCa1.1) channel openers, but little is known about their mechanism of action or effect on bladder contractility. We examined the effects of two closely related compounds on BK currents and bladder contractions.

Experimental Approach

A combination of electrophysiology, molecular biology and synthetic chemistry was used to examine the effects of two novel channel agonists on BK channels from bladder smooth muscle cells and in HEK cells expressing BKα alone or in combination with either β1 or β4 subunits.

Key Results

GoSlo‐SR‐5‐6 shifted the voltage required for half maximal activation (V1/2) of BK channels approximately −100 mV, irrespective of the presence of regulatory β subunits. The deaminated derivative, GoSlo‐SR‐5‐130, also shifted the activation V1/2 in smooth muscle cells by approximately −100 mV; however, this was reduced by ∼80% in HEK cells expressing only BKα subunits. When β1 or β4 subunits were co‐expressed with BKα, efficacy was restored. GoSlo‐SR‐5‐130 caused a concentration‐dependent reduction in spontaneous bladder contraction amplitude and this was abolished by iberiotoxin, consistent with an effect on BK channels.

Conclusions and Implications

GoSlo‐SR‐5‐130 required β1 or β4 subunits to mediate its full effects, whereas GoSlo‐SR‐5‐6 worked equally well in the absence or presence of β subunits. GoSlo‐SR‐5‐130 inhibited spontaneous bladder contractions by activating BK channels. The novel BK channel opener, GoSlo‐SR‐5‐130, is approximately fivefold more efficacious on BK channels with regulatory β subunits and may be a useful scaffold in the development of drugs to treat diseases such as overactive bladder.
The long‐acting β2‐adrenoceptor agonist, indacaterol, enhances glucocorticoid receptor‐mediated transcription in human airway epithelial cells in a gene‐ and agonist‐dependent manner
Authors: Joshi T , Johnson M , Newton R , Giembycz M A
Published: January 2015

Background and Purpose

Inhaled glucocorticoid (ICS)/long‐acting β2‐adrenoceptor agonist (LABA) combination therapy is a recommended treatment option for patients with moderate/severe asthma in whom adequate control cannot be achieved by an ICS alone. Previously, we discovered that LABAs can augment dexamethasone‐inducible gene expression and proposed that this effect may explain how these two drugs interact to deliver superior clinical benefit. Herein, we extended that observation by analysing, pharmacodynamically, the effect of the LABA, indacaterol, on glucocorticoid receptor (GR)‐mediated gene transcription induced by seven ligands with intrinsic activity values that span the spectrum of full agonism to antagonism.

Experimental Approach

BEAS‐2B human airway epithelial cells stably transfected with a 2× glucocorticoid response element luciferase reporter were used to model gene transcription together with an analysis of several glucocorticoid‐inducible genes.

Key Results

Indacaterol augmented glucocorticoid‐induced reporter activation in a manner that was positively related to the intrinsic activity of the GR agonist. This effect was demonstrated by an increase in response maxima without a change in GR agonist affinity or efficacy. Indacaterol also enhanced glucocorticoid‐inducible gene expression. However, the magnitude of this effect was dependent on both the GR agonist and the gene of interest.

Conclusions and Implications

These data suggest that indacaterol activates a molecular rheostat, which increases the transcriptional competency of GR in an agonist‐ and gene‐dependent manner without apparently changing the relationship between fractional GR occupancy and response. These findings provide a platform to rationally design ICS/LABA combination therapy that is based on the generation of agonist‐dependent gene expression profiles in target and off‐target tissues.
Regulation of μ and δ opioid receptor functions: involvement of cyclin‐dependent kinase 5
Authors: Beaudry H , Mercier‐Blais A‐A , Delaygue C , Lavoie C , Parent J‐L , Neugebauer W , Gendron L
Published: January 2015

Background and Purpose

Phosphorylation of δ opioid receptors (DOP receptors) by cyclin‐dependent kinase 5 (CDK5) was shown to regulate the trafficking of this receptor. Therefore, we aimed to determine the role of CDK5 in regulating DOP receptors in rats treated with morphine or with complete Freund's adjuvant (CFA). As μ (MOP) and DOP receptors are known to be co‐regulated, we also sought to determine if CDK5‐mediated regulation of DOP receptors also affects MOP receptor functions.

Experimental Approach

The role of CDK5 in regulating opioid receptors in CFA‐ and morphine‐treated rats was studied using roscovitine as a CDK inhibitor and a cell‐penetrant peptide mimicking the second intracellular loop of DOP receptors (C11‐DOPri2). Opioid receptor functions were assessed in vivo in a series of behavioural experiments and correlated by measuring ERK1/2 activity in dorsal root ganglia homogenates.

Key Results

Chronic roscovitine treatment reduced the antinociceptive and antihyperalgesic effects of deltorphin II (Dlt II) in morphine‐ and CFA‐treated rats respectively. Repeated administrations of C11‐DOPri2 also robustly decreased Dlt II‐induced analgesia. Interestingly, DAMGO‐induced analgesia was significantly increased by roscovitine and C11‐DOPri2. Concomitantly, in roscovitine‐treated rats the Dlt II‐induced ERK1/2 activation was decreased, whereas the DAMGO‐induced ERK1/2 activation was increased. An acute roscovitine treatment had no effect on Dlt II‐ or DAMGO‐induced analgesia.

Conclusions and Implications

Together, our results demonstrate that CDK5 is a key player in the regulation of DOP receptors in morphine‐ and CFA‐treated rats and that the regulation of DOP receptors by CDK5 is sufficient to modulate MOP receptor functions through an indirect process.
Correlation of circulating betatrophin concentrations with insulin secretion capacity, evaluated by glucagon stimulation tests
Authors: Tokumoto S. , Hamamoto Y. , Fujimoto K. , Yamaguchi E. , Okamura E. , Honjo S. , Ikeda H. , Wada Y. , Hamasaki A. , Koshiyama H.
Published: January 2015

Aim

To investigate the relationship between plasma betatrophin concentrations and insulin secretion capacity in people with Type 2 diabetes.

Methods

Glucagon stimulation tests (1 mg) were performed in 70 people with Type 2 diabetes after an overnight fast. Plasma betatrophin concentrations were measured using an enzyme‐linked immunosorbent assay. Insulin secretion capacity was evaluated by measuring increments of C‐peptide concentration in response to glucagon stimulation, and creatinine clearance was determined by comparing creatinine concentrations in serum and 24‐h urine samples.

Results

Plasma betatrophin concentrations were positively correlated with duration of Type 2 diabetes (r = 0.34, P = 0.003), and negatively correlated with increments of C‐peptide concentration (r = 0.37, P = 0.001) and creatinine clearance (r = 0.37, P = 0.001). The correlation with increments of C‐peptide concentration remained significant after adjustment for age and duration of Type 2 diabetes (r = 0.25, P = 0.037). Multivariate analysis identified age and increments of C‐peptide concentration as independent factors associated with plasma betatrophin levels.

Conclusion

Plasma betatrophin levels inversely correlate with insulin secretion capacity, suggesting that betatrophin levels are regulated by insulin secretion capacity in humans.
Is iatrogenic sleep disturbance worth the effort in Type 1 diabetes?
Authors: Barnard K. D. , Oliver N. , Adolfsson P. , Aldred C. , Kerr D.
Published: January 2015

What's new?

Chronic sleep disturbance is common for people with Type 1 diabetes.

Fear of nocturnal hypoglycaemia is causing frequent nocturnal blood glucose testing causing impaired sleep.

New strategies for the prevention of nocturnal hypoglycaemia need to be devised and tested.

The consequences of chronic sleep disturbance for people living with diabetes and their families needs to be appreciated by their clinical advisors.
Latent autoimmune diabetes of the adult: current knowledge and uncertainty
Authors: Laugesen E. , Østergaard J. A. , Leslie R. D. G. ,   the Danish Diabetes Academy Workshop and Workshop Speakers
Published: January 2015

Patients with adult‐onset autoimmune diabetes have less Human Leucocyte Antigen (HLA)‐associated genetic risk and fewer diabetes‐associated autoantibodies compared with patients with childhood‐onset Type 1 diabetes. Metabolic changes at diagnosis reflect a broad clinical phenotype ranging from diabetic ketoacidosis to mild non‐insulin‐requiring diabetes, also known as latent autoimmune diabetes of the adult (LADA). This latter phenotype is the most prevalent form of adult‐onset autoimmune diabetes and probably the most prevalent form of autoimmune diabetes in general. Although LADA is associated with the same genetic and immunological features as childhood‐onset Type 1 diabetes, it also shares some genetic features with Type 2 diabetes, which raises the question of genetic heterogeneity predisposing to this form of the disease. The potential value of screening patients with adult‐onset diabetes for diabetes‐associated autoantibodies to identify those with LADA is emphasized by their lack of clinically distinct features, their different natural history compared with Type 2 diabetes and their potential need for a dedicated management strategy. The fact that, in some studies, patients with LADA show worse glucose control than patients with Type 2 diabetes, highlights the need for further therapeutic studies. Challenges regarding classification, epidemiology, genetics, metabolism, immunology, clinical presentation and treatment of LADA were discussed at a 2014 workshop arranged by the Danish Diabetes Academy. The presentations and discussions are summarized in this review, which sets out the current ideas and controversies surrounding this form of diabetes.
Mass spectrometry evaluation of the hepcidin‐25 assay in the differential diagnosis of iron deficiency anaemia with concurrent inflammation and anaemia of inflammation in elderly patients
Authors: Karlsson Torbjörn
Published: January 2015

In this study, mass spectrometry was used to evaluate the hepcidin‐25 assay in the differential diagnosis of iron deficiency anaemia with concurrent inflammation and anaemia of inflammation in elderly patients using the absence of stainable bone marrow iron as the gold standard criterion for iron deficiency (ID). In addition, correlation coefficients for hepcidin‐25 vs. haematimetric and biochemical iron parameters, and C‐reactive protein (CRP) were determined. The optimal cut‐off for hepcidin‐25 was 31.5 ng/mL corresponding to a sensitivity and specificity of 82% and 95%, respectively, for ID. For ferritin, a sensitivity and specificity of 70% and 100%, respectively, correspond to an optimal cut‐off of 41.5 μg/L. Receiver operating characteristics curve analysis revealed that mass spectrometry analysis of hepcidin‐25 does not appear to be superior to ferritin in the diagnosis of ID in elderly anaemic patients with concurrent inflammation. Hepcidin‐25 shows a strong positive correlation with ferritin, and also correlates positively with CRP, in this patient population.
Hepcidin‐25 vs. conventional clinical biomarkers in the diagnosis of functional iron deficiency
Authors: Enko Dietmar , Wagner Helga , Kriegshäuser Gernot , Kimbacher Christine , Stolba Robert , Worf Elfriede , Halwachs‐Baumann Gabriele
Published: January 2015

Objectives

As hepcidin‐25 is considered as a key regulator of human iron homoeostasis, this study aimed to compare this parameter with conventional biomarkers and diagnostic tools of iron deficiency (ID).

Methods

In total, 233 hospitalised adult patients, who underwent routine blood testing for ID, were included. All subjects were investigated for hepcidin‐25, reticulocyte haemoglobin content (CHr), soluble transferrin receptor (sTfR)/log ferritin ratio (i.e. Thomas plot), sTfR, ferritin, transferrin saturation (TSAT), C‐reactive protein (CRP) and for complete blood cell count. Functional ID was defined as a CHr < 28 pg. Separate logistic regression models were calculated with all potential biomarkers to evaluate and compare the predictive performance with respect to functional ID in patients without (CRP ≤ 0.5 mg/dL) and with (CRP > 0.5 mg/dL) acute‐phase reaction, respectively.

Results

One hundred seventeen patients with CRP > 0.5 mg/dL showed a distinctly higher hepcidin‐25 median value [35.60 (range: 4.27–80.03) ng/mL] as compared to 116 patients with CRP ≤ 0.5 mg/dL [18.55 (range: 3.77–73.01) ng/mL]. With respect to functional ID, sTfR/log ferritin ratio and sTfR were of better positive predictive value (PPV) (sTfR/log ferritin ratio: 58.33% and 70.83%; sTfR: 60.00% and 60.00%) than when compared to hepcidin‐25 (PPV: 37.74% and 42.86%) and ferritin (PPV: 27.54% and 46.15%) in both subgroups.

Conclusions

The sTfR/log ferritin ratio, as well as sTfR, were better predictors of functional ID in patients with and without acute‐phase reaction as compared to hepcidin‐25 and ferritin.
Detection Model of Legally Registered Mafia Firms in Italy
Authors: Ravenda Diego , Argilés‐Bosch Josep M. , Valencia‐Silva Maika M.
Published: January 2015

This paper develops a model that can contribute to the detection of legally registered firms defined as Mafia firms (LMFs) due to having been confiscated by judicial authorities, in relation to alleged connections of their owners with Italian organized crime. The model correctly classifies 76.41% of firms within a matched sample of 852 firm‐years including LMFs and lawful firms. Furthermore, we present an analysis of financial statement characteristics of singular private firms which are socially irresponsible by nature and whose incentives, modus operandi and legal financial statement formats differ from those of listed companies. In particular, we show that specific accruals and earnings management proxies may provide more insight into accounting manipulation patterns of LMFs. More importantly, our paper can help practitioners and regulators identify accounting signals that can be used in risk assessment models or in the detection of criminal infiltrations and related illicit practices.
Glioblastomas, astrocytomas and oligodendrogliomas linked to Lynch syndrome
Authors: Therkildsen C. , Ladelund S. , Rambech E. , Persson A. , Petersen A. , Nilbert M.
Published: January 2015

Background and purpose

Brain tumors represent a rare and relatively uncharacterized tumor type in Lynch syndrome.

Methods

The national Danish Hereditary Nonpolyposis Colorectal Cancer Register was utilized to estimate the cumulative life‐time risk for brain tumors in Lynch syndrome, and the mismatch repair (MMR) status in all tumors available was evaluated.

Results

Primary brain tumors developed in 41/288 families at a median age of 41.5 (range 2–73) years. Biallelic MMR gene mutations were linked to brain tumor development in childhood. The risk of brain tumors was significantly higher (2.5%) in MSH2 gene mutation carriers compared to patients with mutations in MLH1 or MSH6. Glioblastomas predominated (56%), followed by astrocytomas (22%) and oligodendrogliomas (9%). MMR status was assessed in 10 tumors, eight of which showed MMR defects. None of these tumors showed immunohistochemical staining suggestive of the IDH1 R132H mutation.

Conclusion

In Lynch syndrome brain tumors occurred in 14% of the families with significantly higher risks for individuals with MSH2 gene mutations and development of childhood brain tumors in individuals with constitutional MMR defects.
White matter lesions and temporal lobe atrophy related to incidence of both dementia and major depression in 70‐year‐olds followed over 10 years
Authors: Gudmundsson P. , Olesen P. J. , Simoni M. , Pantoni L. , Östling S. , Kern S. , Guo X. , Skoog I.
Published: January 2015

Background and purpose

A number of studies have suggested associations between dementia and depression in older adults. One reason could be that these disorders share structural correlates, such as white matter lesions (WMLs) and cortical atrophy. No study has examined whether these lesions precede both dementia and depression independently of each other in the general population.

Methods

Whether WMLs and cortical atrophy on computed tomography predict dementia and depression was investigated in a population‐based sample of 70‐year‐olds (n = 380) followed over 10 years. Exclusion criteria were dementia, major depression, history of stroke and a Mini‐Mental State Examination score below 26 at baseline in 2000–2001. Dementia was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised, and depression according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition. Primary outcomes included dementia and major depression at 10‐year follow‐up.

Results

Adjusted logistic regression models, including both WMLs and temporal lobe atrophy, showed that moderate to severe WMLs [odds ratio (OR) 3.96, 95% confidence interval (CI) 1.23–12.76] and temporal lobe atrophy (OR 2.93, 95% CI 1.13–7.60) predicted dementia during a 10‐year follow‐up independently of major depression. Similarly, both moderate to severe WMLs (OR 3.84, 95% CI 1.25–11.76) and temporal lobe atrophy (OR 2.52, 95% CI 1.06–5.96) predicted depression even after controlling for incident dementia.

Conclusion

White matter lesions and temporal lobe atrophy preceded 10‐year incidence of both dementia and depression in 70‐year‐olds. Shared structural correlates could explain the reported associations between dementia and depression. These brain changes may represent independent and complementary pathways to dementia and depression. Strategies to slow progression of vascular pathology and neurodegeneration could indirectly prevent both dementia and depression in older adults.
Serum antibodies from epileptic patients react, at high prevalence, with simian virus 40 mimotopes
Authors: Faggioli R. , Mazzoni E. , Borgna‐Pignatti C. , Corallini A. , Turlà G. , Taronna A. P. , Fiumana E. , Martini F. , Tognon M.
Published: January 2015

Background and purpose

It has been demonstrated that inflammation may contribute to epileptogenesis and cause neuronal injury in epilepsy. In this study, the prevalence of antibodies to simian virus 40 (SV40), a kidney and neurotropic polyomavirus, was investigated in serum samples from 88 epileptic children/adolescents/young adults.

Methods

Serum antibodies reacting to specific SV40 peptides were analysed by indirect enzyme‐linked immunosorbent assay. Synthetic peptides corresponding to the epitopes of viral capsid proteins 1–3 were used as SV40 antigens.

Results

A significantly higher prevalence of antibodies against SV40 was detected in sera from epileptic patients compared to controls (41% vs. 19%). Specifically, the highest significant difference was revealed in the cohort of patients from 1.1 to 10 years old (54% vs. 21%), with a peak in the sub‐cohort of 3.1–6 years old (65% vs. 18%).

Conclusion

Our immunological data suggest a strong association between epilepsy and the SV40 infection.
Anti‐sulfatide IgM antibodies in peripheral neuropathy: to test or not to test?
Authors: Giannotta C. , Di Pietro D. , Gallia F. , Nobile‐Orazio E.
Published: January 2015

Background and purpose

Anti‐sulfatide immunoglobulin M (IgM) antibodies have been associated with different forms of neuropathies but their diagnostic role in neuropathy remains unclear.

Methods

The clinical association of increased titers of anti‐sulfatide IgM antibodies in 570 patients with neuropathy and related disorders examined in our laboratory since 2004 was reviewed. Sera were tested by enzyme‐linked immunosorbent assay at the initial serum dilution of 1:32 000 and titrated by serial two‐fold dilution. In all positive patients IgM antibodies to myelin‐associated glycoprotein (MAG) were also measured by western blot.

Results

High titers of anti‐sulfatide antibodies were found in 39 patients including 33 (85%) who also had anti‐MAG IgM. Six patients did not have anti‐MAG IgM including five in whom moderately increased anti‐sulfatide titers were associated with different forms of neuropathy. One patient with a demyelinating neuropathy and IgM monoclonal gammopathy had markedly increased anti‐sulfatide titers (1:256 000).

Conclusions

Increased titers of anti‐sulfatide IgM antibodies are not infrequent in patients with neuropathy where they are often associated with a concomitant reactivity to MAG. A selective reactivity to sulfatide, however, is rarely found and is associated with different forms of neuropathy limiting its usefulness in the diagnosis of neuropathy.
Cryptogenic stroke
Authors: Fonseca A. C. , Ferro J. M.
Published: January 2015

In about a quarter of ischaemic strokes the cause is undetermined, because the investigation is incomplete or delayed, because there are multiple causes or because the stroke is truly cryptogenic. Cryptogenic stroke can be further classified as non‐embolic or embolic. Embolic stroke of undetermined source can be due to paroxysmal atrial fibrillation, minor emboligenic cardiac conditions, atheroembolism, cancer associated and paradoxical embolism through a patent foramen ovale (PFO) or less often a pulmonary fistula. Currently, risk factor control, statins and antiplatelets are the main therapeutic measures to prevent recurrent stroke. There is no evidence to implement routine closure of PFO in patients with cryptogenic stroke. Direct anticoagulants are being evaluated in randomized controlled trials including embolic stroke of undetermined source patients. Advances in high resolution ultrasound or magnetic resonance imaging of extracranial and intracranial vessels and of the heart and prolonged heart rhythm monitoring will be instrumental techniques to identify arterial and cardiac hidden causes of stroke.
Elevation‐Related Differences in Parental Risk‐Taking Behavior are Associated with Cognitive Variation in Mountain Chickadees
Authors: Kozlovsky Dovid Y. , Branch Carrie L. , Pravosudov Vladimir V.
Published: January 2015

Breeding animals must balance their current reproductive effort with potential costs to their own survival and consequently to future reproduction. Life‐history theory predicts that variation in reproductive investment should be based on fecundity and life expectancy with longer‐lived species favoring their own survival over parental investment. Recently, variation in parental risk taking was also linked with differences in cognition suggesting a potential trade‐off between cognitive ability and risk taking. Here, we tested whether mountain chickadees from two different elevations with known differences in cognitive ability differ in their parental risk taking by comparing the responses of nesting birds to a potential predator. Higher elevations are associated with shorter breeding season limiting renesting opportunities, but chickadees at high elevations also have better cognitive abilities, which might be potentially associated with better survival. Compared to lower elevations, high‐elevation chickadees laid larger clutches, showed longer latencies to return to the nest in the presence of a hawk, had lower fledging success, and exhibited higher rate of complete nest failures. Nestling development among successful nests, however, was similar between elevations. These data are not consistent with life‐history hypothesis because birds at high elevation invest more in the clutch, while at the same time take less risk when facing potential danger to themselves, which could jeopardize their current reproductive success. These data, however, are consistent with the hypothesis that better cognitive abilities might be associated with less parental risk taking.
Broken nasotracheal tube aspiration in a horse during anaesthetic recovery
Authors: Potter J. , Allen K. , Macfarlane P. , Holopherne‐Doran D.
Published: January 2015

A horse was presented for soft palate thermocautery and surgical advancement of the larynx under general anaesthesia, following a history of respiratory noise and poor athletic performance. Physical examination prior to surgery was unremarkable. The horse was anaesthetised and a 20 mm cuffed endotracheal tube (ETT) used to intubate the trachea via the right nostril. The cuff was deflated at the end of the procedure and the tube secured in place around the head of the horse for the recovery. The horse was assisted to standing and during this process the end of the nasotracheal tube broke and was observed hanging from the head collar. The remainder of the tube was aspirated into the trachea of the horse. The remaining length of endotracheal tube was removed using a modified endoscopic technique. The horse recovered with no further problems. An unusual complication of a nasotracheal tube leftin situfor recovery in a horse is reported and possible reasons for this complication are discussed.
Endotracheal intubation in horses – are complications truly rare?
Authors: Trim C. M.
Published: January 2015

Endotracheal intubation is an essential component of general anaesthesia in horses to facilitate delivery of inhalation anaesthetic agent and oxygen, artificial ventilation, and prevent pulmonary aspiration of blood or gastric reflux. Experimental studies have identified a high incidence of tracheal mucosal injury after intubation resulting from direct trauma or local ischaemia from the pressure of the inflated cuff. Recommendations to minimise injury include gentle intubation, disconnection from the anaesthesia machine when moving the horse, and monitoring the endotracheal tube cuff pressure. New studies are needed to evaluate trachea and cuff pressure interactions under current practice conditions, including specialised ventilation modalities such as positive end‐expiratory pressure and continuous airway pressure.
Standing removal of the proximal aspect of an olecranon fracture in a mature horse
Authors: Elliott C. R. B. , Middleton B. G. A.
Published: January 2015

A 12‐year‐old 450 kgArgentine polo mare presented with a dropped elbow and an unwillingness to bear weight after being kicked by another horse on the lateral aspect of the upper left forelimb. The mare was subsequently diagnosed with a displaced olecranon fracture that did not readily conform to the standard classification systems. Referral for surgical treatment involving open reduction and internal fixation was declined due to financial constraints. Due to the mare being unsuitable for breeding, and conservative treatment of displaced olecranon fractures being deemed to have an overall poor prognosis for return to full athletic performance, another treatment option was sought. Given the fracture configuration, standing surgical removal of the large proximal fragment was performed. The mare returned to full athletic performance 12 months post operatively without lameness. This case report describes an alternative treatment option for selected olecranon fractures.
Treatment of aStandardbred racehorse for septic infraspinatus and intertubercular bursitis caused by haematogenous bacterial spread
Authors: O'Sullivan P. , Gudehus T. , Kamm L. , Bridge I. S.
Published: January 2015

This report describes the diagnosis and treatment of synovial sepsis of the infraspinatus and intertubercular (bicipital) bursae. The origin of infection was considered to be haematogenous spread from an ipsilateral foot abscess. The horse responded well to treatment and returned to full athletic function.
Letter to the Editor
Authors: Richards A. D.
Published: January 2015

See article by Preston et al.
Investigating the benefits of using circular die springs instead of rectangular die springs
Authors: Gonen D. , Oral A. , Cakir M. C.
Published: January 2015

Die springs with rectangular cross section (rectangular die springs) are common in the industry. However, the production of rectangular die springs is difficult, and the cost of production is high. In this study, we examined the use of die springs with circular cross section (circular die springs), which are both easier to produce and less costly, in place of rectangular ones. To this aim, the fatigue life values of both die spring with equivalent specifications were compared experimentally. The results obtained were transferred to the finite element methods software to run the simulation of the fatigue test. From the experimental results obtained, it has been observed that using circular die springs in place of rectangular die springs is always possible, provided that the springs are guided with cast polyamide guides.
Effects of Dietary Folate Intake on Migraine Disability and Frequency
Authors: Menon Saras , Lea Rodney A. , Ingle Sarah , Sutherland Michelle , Wee Shirley , Haupt Larisa M. , Palmer Michelle , Griffiths Lyn R.
Published: January 2015

Background

Migraine is a highly disabling disease affecting a significant proportion of the Australian population. The methylenetetrahydrofolate reductase (MTHFR) C677T variant has been associated with increased levels of homocysteine and risk of migraine with aura (MA). Folic acid (FA), vitamin B6, and B12 supplementation has been previously shown to reduce increased levels of homocysteine and decrease migraine symptoms. However, the influence of dietary folate intake on migraine has been unclear. The aim of the current study was to analyze the association of dietary folate intake in the form of dietary folate equivalent, FA, and total food folate (TFF) on migraine frequency, severity, and disability.

Methods

A cohort of 141 adult females of Caucasian descent with MA was genotyped for the MTHFR C677T variant using restriction enzyme digestion. Dietary folate information was collected from all participants and analyzed using the “FoodWorks” 2009 package. Folate consumption was compared with migraine frequency, severity, and disability using linear regression.

Results

A significant inverse relation was observed between dietary folate equivalent (R2 = 0.201, B = −0.002, P = .045, 95% confidence interval [CI] [−0.004, −0.001]) and FA (R2 = 0.255, B = −0.005, P = .036, 95% CI [−0.009, −0.002]) consumption and migraine frequency. It was also observed that in individuals with the CC genotype for the MTHFR C677T variant, migraine frequency was significantly linked to FA consumption (R2 = 0.106, B = −0.004, P = .029, 95% CI [−0.007, −0.004]).

Conclusions

The results from this study indicate that folate intake in the form of FA may influence migraine frequency in female MA sufferers.