bluuebunny/crossref_metadata_2025_split huggingface dataset:
Calcineurin inhibitors dampen humoral immunity by acting directly on naive B cells
Authors: De Bruyne R , Bogaert D , De Ruyck N , Lambrecht B N , Van Winckel M , Gevaert P , Dullaers M 
Published: February 2015

SummaryCalcineurin inhibitors (CNI), used frequently in solid organ transplant patients, are known to inhibit T cell proliferation, but their effect on humoral immunity is far less studied. Total and naive B cells from healthy adult donors were cultured in immunoglobulin (Ig)A- or IgG/IgE-promoting conditions with increasing doses of cyclosporin, tacrolimus, rapamycin or methylprednisolone. The effect on cell number, cell division, plasmablast differentiation and class-switching was tested. To examine the effect on T follicular helper (Tfh) cell differentiation, naive CD4+ T cells were cultured with interleukin (IL)-12 and titrated immunosuppressive drug (IS) concentrations. Total B cell function was not affected by CNI. However, naive B cell proliferation was inhibited by cyclosporin and both CNI decreased plasmablast differentiation. Both CNI suppressed IgA, whereas only cyclosporin inhibited IgE class-switching. Rapamycin had a strong inhibitory effect on B cell function. Strikingly, methylprednisolone, increased plasmablast differentiation and IgE class-switching from naive B cells. Differentiation of Tfh cells decreased with increasing IS doses. CNI affected humoral immunity directly by suppressing naive B cells. CNI, as well as rapamycin and methylprednisolone, inhibited the in-vitro differentiation of Tfh from naive CD4+ T cells. In view of its potent suppressive effect on B cell function and Tfh cell differentiation, rapamycin might be an interesting candidate in the management of B cell mediated complications post solid organ transplantation.
Specific overexpression of tumour necrosis factor-α-induced protein (TNFAIP)9 in CD14+CD16− monocytes in patients with rheumatoid arthritis: comparative analysis with TNFAIP3
Authors: Takai C , Matsumoto I , Inoue A , Umeda N , Tanaka Y , Kurashima Y , Wada Y , Narita I , Sumida T 
Published: February 2015

SummaryThe tumour necrosis factor (TNF)-α-induced proteins (TNFAIP)9 and TNFAIP3 play an important pathogenic role in murine arthritis. To clarify their pathophysiological roles in patients with rheumatoid arthritis (RA), we examined their expression and localization in peripheral blood mononuclear cells (PBMC). TNFAIP9 and TNFAIP3 mRNA expression was determined in PBMC of RA patients and healthy subjects (control). Flow cytometry was used to analyse the main TNFAIP9- and TNFAIP3-expressing cell populations. TNFAIP9 and TNFAIP3 mRNA expression levels were examined in vitro on CD14+ cells stimulated with TNF-α and lipopolysaccharide (LPS). The expression levels of TNFAIP9 and TNFAIP3 mRNA were also measured before and 12 weeks after treatment with tocilizumab and abatacept. TNFAIP9 expression was significantly higher, while TNFAIP3 expression was lower in PBMC of RA (n = 36) than the control (n = 24) (each P &lt; 0·05). TNFAIP9 was expressed on CD14+ cells, especially in human leucocyte antigen D-related (HLA-DR)+CD14brightCD16−cells, while TNFAIP3 was expressed mainly on CD3+ T cells. TNF-α and LPS induced TNFAIP9 and TNFAIP3 in human CD14+monocytes in vitro. Treatment with tocilizumab (n = 13), but not abatacept (n = 11), significantly reduced TNFAIP9 mRNA expression in PBMC, which was associated with reduction in the number of circulating CD14bright monocytes. The expression of TNFAIP9 in CD14+ cells was specifically elevated in patients with RA, regulated by TNF-α and LPS, and suppressed by tocilizumab, while TNFAIP3 in PBMC showed different localization and induction patterns.
Current landscape of direct‐to‐consumer genetic testing and its role in ophthalmology: a review
Authors: Sanfilippo Paul G , Kearns Lisa S , Wright Philip , Mackey David A , Hewitt Alex W 
Published: February 2015

AbstractThe sequencing of the human genome has seen the emergence of the direct‐to‐consumer (DTC) genetic‐testing market, which allows individuals to obtain information about their genetic profile and its many health and lifestyle implications. Genetics play an important role in the development of many eye diseases, however, little information is available describing the influence of the DTC industry in ophthalmology. In this review, we examined DTC companies providing genetic test products for eye disease. Of all eye conditions, the majority of DTC companies provided susceptibility testing or risk assessment for age‐related macular degeneration (AMD). For the 15 companies noted to offer products, we found considerable variation in the cost, scope and clarity of informational content of DTC genetic testing for ophthalmic conditions. The clinical utility of these tests remains in question, and the American Academy of Ophthalmology recommendations against routine testing for many conditions probably still apply.
A break‐even analysis of major ear surgery
Authors: Wasson J.D. , Phillips J.S. 
Published: February 2015

ObjectivesTo determine variables which affect cost and profit for major ear surgery and perform a break‐even analysis.DesignRetrospective financial analysis.SettingUK teaching hospital.ParticipantsPatients who underwent major ear surgery under general anaesthesia performed by the senior author in main theatre over a 2‐year period between dates of 07 September 2010 and 07 September 2012.Main outcome measuresIncome, cost and profit for each major ear patient spell. Variables that affect major ear surgery profitability.ResultsSeventy‐six patients met inclusion criteria. Wide variation in earnings, with a median net loss of £−1345.50 was observed. Income was relatively uniform across all patient spells; however, theatre time of major ear surgery at a cost of £953.24 per hour varied between patients and was the main determinant of cost and profit for the patient spell. Bivariate linear regression of earnings on theatre time identified 94% of variation in earnings was due to variation in theatre time (r = −0.969; P < 0.0001) and derived a break‐even time for major ear surgery of 110.6 min. Theatre time was dependent on complexity of procedure and number of OPCS4 procedures performed, with a significant increase in theatre time when three or more procedures were performed during major ear surgery (P = 0.015).ConclusionFor major ear surgery to either break‐even or return a profit, total theatre time should not exceed 110 min and 36 s.
Restoring normoglycaemia by use of a very low calorie diet in long‐ and short‐duration Type 2 diabetes
Authors: Steven S. , Taylor R. 
Published: February 2015

AbstractAimsTo establish whether an 8‐week very‐low‐calorie diet could improve glycaemic control in Type 2 diabetes of long duration.MethodsA total of 29 people with Type 2 diabetes [short‐duration group (diabetes duration < 4 years), n = 15; long‐duration group (diabetes duration > 8 years), n = 14] completed an 8‐week very‐low‐calorie diet, with assessments of fasting anthropometry, blood tests and blood pressure at baseline and weeks 1, 4 and 8 of the diet.ResultsSimilar weight loss was achieved in the short‐ and long‐duration groups (14.8 ± 0.8% and 14.4 ± 0.7% respectively; P = 0.662). The glucose response to acute calorie restriction was heterogeneous in the long‐duration group with some responding similarly to those in the short‐duration group, some responding, but only slowly, and others not responding at all. Overall, HbA1c concentration in the short‐ vs. long‐duration groups fell to 44 ± 2 vs. 64 ± 6 mmol/l (6.2 ± 0.2 vs. 8.0 ± 0.5%; P = 0.002). Fasting plasma glucose levels decreased to 5.8 ± 0.2 vs. 8.4 ± 1.1 mmol/l (P = 0.024) respectively. A total of 87% of the short‐duration group and 50% of the long‐duration group achieved non‐diabetic fasting plasma glucose levels at week 8. Clinically significant improvements in blood pressure and lipid profile were seen regardless of diabetes duration.ConclusionIn people with Type 2 diabetes of > 8 years' duration, a therapeutic trial of a very‐low‐calorie diet may be undertaken with a 50% chance of achieving non‐diabetic fasting glucose levels off all antidiabetic therapies.
Practical approach to non‐alcoholic fatty liver disease in patients with diabetes
Authors: Tai F. W. D. , Syn W.‐K. , Alazawi W. 
Published: February 2015

AbstractThe prevalence of Type 2 diabetes is expected to increase in parallel with obesity rates and the ageing population. Recent studies show that Type 2 diabetes is associated with a twofold increase in the risk of non‐alcoholic fatty liver disease, a leading cause of chronic liver disease. Individuals with non‐alcoholic steatohepatitis, a more advanced stage of non‐alcoholic fatty liver disease, are specifically at risk of developing fibrosis/cirrhosis (end‐stage liver disease) and hepatocellular carcinoma; therefore, identifying individuals (with Type 2 diabetes) who are likely to develop hepatic complications is paramount. In the present clinical review, we discuss the potential impact of non‐alcoholic fatty liver disease diagnosis on Type 2 diabetes, and the putative risk factors for developing non‐alcoholic steatohepatitis and non‐alcoholic steatohepatitis fibrosis. We highlight the limitations of currently used tools in non‐alcoholic fatty liver disease diagnosis and staging, and provide an insight into future developments in the field. We present an example of a non‐alcoholic fatty liver disease screening protocol and discuss the therapeutic options currently available to our patients.
Normal pregnancy outcome after first‐trimester exposure to liraglutide in a woman with Type 2 diabetes
Authors: Greco D. 
Published: February 2015

AbstractBackgroundData from animal studies suggest that glucagon‐like peptide‐1 analogues should not be used in pregnancy, but there have been no reports to date of their effects in human pregnancy. The aim of the present report was to describe a case of exposure to liraglutide during the first trimester of pregnancy in a patient with Type 2 diabetes mellitus.Case reportA 37‐year‐old woman with Type 2 diabetes mellitus who had been taking liraglutide for 2 years was admitted in the 13th week of gestation. Liraglutide was immediately discontinued and intensive insulin therapy instituted. The woman gave birth to a healthy child after completing an uneventful gestation period.ConclusionAlthough the present normal pregnancy outcome does not mean that glucagon‐like peptide‐1 analogues are safe to use in pregnancy, this report contributes to the limited knowledge regarding human exposure to these drugs during pregnancy in women with diabetes.
Negative appraisals of insulin therapy are common among adults with Type 2 diabetes using insulin: Results from Diabetes MILES – Australia cross‐sectional survey
Authors: Holmes‐Truscott E. , Skinner T. C. , Pouwer F. , Speight J. 
Published: February 2015

AbstractAimTo identify insulin therapy appraisals among adults with Type 2 diabetes using insulin and how negative appraisals relate to clinical, self‐care and psychosocial outcomes.MethodsDiabetes MILES – Australia 2011 was a national survey of adults with diabetes, focused on behavioural and psychosocial issues. Subgroup analyses were conducted on the responses of 273 adults with Type 2 diabetes using insulin (46% women; mean ± sd age: 59 ± 9 years; diabetes duration: 12 ± 7 years; years using insulin: 4 ± 4). They completed validated measures of insulin therapy appraisals (ITAS), depression (PHQ–9), anxiety (GAD–7), diabetes distress (PAID) and diabetes‐specific self‐efficacy (DES–SF).ResultsInsulin was perceived to be very important, and its benefits (e.g. improves health) were endorsed by most (82%). Fifty‐one per cent believed that taking insulin means their diabetes has become worse; 51% that insulin causes weight gain; 39% that they have ‘failed to manage’ their diabetes. Those with the greatest and least ‘ITAS negative’ scores did not differ by diabetes duration or years using insulin, or by average number of insulin injections or blood glucose checks per day. Those with more negative insulin appraisals were significantly younger (Mean Diff. = 5 years, P < 0.001), less satisfied with recent blood glucose levels (P < 0.001, d = 0.63), had reduced diabetes‐specific self‐efficacy (P < 0.001, d = 0.7), and were more likely to report depressive symptoms, anxiety or diabetes distress (all P < 0.001, d = 0.65–1.1).ConclusionsNegative insulin therapy appraisals are common among adults with Type 2 diabetes using insulin, and are associated with lower general and diabetes‐specific emotional well‐being, reduced diabetes‐specific self‐efficacy and satisfaction with blood glucose.
Gender‐based differences in glycaemic control and hypoglycaemia prevalence in patients with type 2 diabetes: results from patient‐level pooled data of six randomized controlled trials
Authors: Kautzky‐Willer A. , Kosi L. , Lin J. , Mihaljevic R. 
Published: February 2015

AimsTo determine the impact of gender on glycaemic control and hypoglycaemia in insulin‐naïve patients with type 2 diabetes (T2DM).MethodsData were pooled from six randomized clinical trials of insulin glargine or NPH insulin in insulin‐naïve, inadequately controlled patients. Female [n = 1251; mean glycated haemoglobin (HbA1c) level 8.99%, age 56.91 years, diabetes duration 9.84 years] and male patients (n = 1349; mean HbA1c 8.9%, age 57.47 years, diabetes duration 10.13 years) were started on and treated with insulin glargine or NPH insulin for 24–36 weeks. HbA1c and fasting blood glucose levels, percent achieving HbA1c target of <7% and insulin dose change were recorded.ResultsFor both men and women, HbA1c levels were significantly reduced over time (p < 0.001); a significantly greater HbA1c reduction was observed in men than in women (−1.36 vs. −1.22; p = 0.002). Significantly fewer women achieved target HbA1c of <7% (p < 0.001). At the study end, women had a significantly higher insulin dose/kg than men (0.47 vs. 0.42 U/kg; p < 0.001). The incidence rates of severe and severe nocturnal hypoglycaemia were significantly higher in women (3.28% vs. 1.85%; p < 0.05 and 2.24% vs. 0.59%; p < 0.001, respectively). Women were more likely to experience severe hypoglycaemia [odds ratio (OR) 1.80; 95% confidence interval (CI) 1.08, 3.00; p = 0.02] and severe nocturnal hypoglycaemia (OR: 3.80; 95% CI 1.72, 8.42; p = 0.001).ConclusionsThese observations confirm studies that found a smaller improvement in HbA1c and greater hypoglycaemia in women during insulin treatment. Physicians should be aware of the need to determine and closely monitor dosing, particularly in women, to optimize the balance between glycaemic control and hypoglycaemia risk.
Circulating and urinary microRNA profile in focal segmental glomerulosclerosis: a pilot study
Authors: Ramezani Ali , Devaney Joseph M. , Cohen Scott , Wing Maria R. , Scott Richard , Knoblach Susan , Singhal Rishi , Howard Lilian , Kopp Jeffrey B. , Raj Dominic S. 
Published: February 2015

AbstractBackgroundMicroRNAs (miRNAs) are noncoding RNA molecules that play important roles in the pathogenesis of various kidney diseases. We investigated whether patients with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) have distinct circulating and urinary miRNA expression profiles that could lead to potential development of noninvasive biomarkers of the disease.Materials and methodsExosome miRNAs were extracted from plasma and urine samples of patients with primary FSGS (n = 16) or MCD (n = 5) and healthy controls (n = 5). Differences in miRNA abundance were examined using Affymetrix GeneChip miRNA 3.0 arrays. QRT‐PCR was used to validate the findings from the array.ResultsComparison analysis of FSGS versus MCD revealed 126 and 155 differentially expressed miRNAs in plasma and in urine, respectively. Only 38 of these miRNAs were previously cited, whereas the remaining miRNAs have not been described. Comparison analysis showed that a significant number of miRNAs were downregulated in both plasma and urine samples of patients with FSGS compared to those with MCD. Plasma levels of miR‐30b, miR‐30c, miR‐34b, miR‐34c and miR‐342 and urine levels of mir‐1225‐5p were upregulated in patients with MCD compared to patients with FSGS and controls (P < 0·001). Urinary levels of mir‐1915 and miR‐663 were downregulated in patients with FSGS compared to MCD and controls (P < 0·001), whereas the urinary levels of miR‐155 were upregulated in patients with FSGS when compared to patients with MCD and controls (P < 0·005).ConclusionsPatients with FSGS and MCD have a unique circulating and urinary miRNA profile. The diagnostic and prognostic potential of miRNAs in FSGS and MCD warrants further studies.
Increasing rate of atrial fibrillation from 2003 to 2011 in patients with ischaemic stroke: results from 55 551 patients in a nationwide registry
Authors: Jespersen S. F. , Christensen L. M. , Christensen A. , Christensen H. 
Published: February 2015

Background and purposeThe general awareness of atrial fibrillation is increasing. The key to prevent atrial fibrillation related stroke is oral anticoagulation therapy; however, it has often been proposed that oral anticoagulation therapy is under‐utilized despite indication. The aim of the study was to examine the trends in atrial fibrillation rate in patients after acute ischaemic stroke and to determine whether the use of oral anticoagulation therapy increased from 2003 to 2011.MethodsIn the nationwide Danish Stroke Registry 55 551 patients (≥18 years) admitted with acute ischaemic stroke were identified. Frequency analysis and linear regression were used to assess trends in atrial fibrillation diagnosis and oral anticoagulation therapy prescription.ResultsA total of 17.1% (n = 9482) of ischaemic stroke patients had atrial fibrillation. The relative frequency of atrial fibrillation increased significantly during the study period (16.3%–20.1%). The prescription rate of oral anticoagulation therapy had a yearly increase five times higher than the atrial fibrillation rate.ConclusionFrom 2003 to 2011 atrial fibrillation detection rate increased significantly, which was followed by a more marked increase in the use of oral anticoagulation therapy, most probably reflecting an increased awareness and questioning assumed current under‐use of oral anticoagulation therapy in secondary stroke prevention.
ICD coding for epilepsy: Past, present, and future—A report by the International League Against Epilepsy Task Force on ICD codes in epilepsy
Authors: Jette Nathalie , Beghi Ettore , Hesdorffer Dale , Moshé Solomon L. , Zuberi Sameer M. , Medina Marco T. , Bergen Donna 
Published: February 2015

SummaryThe World Health Organization (WHO) International Classification of Diseases (ICD) has been used to classify causes of morbidity and mortality such as epilepsy for more than 50 years. The aims of this critical commentary are to do the following: (1) Introduce the ICD classification, summarize the ICD‐9 and ICD‐10 codes for epilepsy and seizures, and discuss the challenges of mapping epilepsy codes between these two versions; (2) discuss how the ICD‐9 and ICD‐10 relate to the revised International League Against Epilepsy (ILAE) terminology and concepts for classification of seizures and epilepsies; (3) discuss how ICD‐coded data have been used for epilepsy care and research and briefly examine the potential impact of the international ICD‐10 clinical modifications on research; (4) discuss the upcoming ICD‐11 codes and the role of the epilepsy community in their development; and (5) discuss how the ICD‐11 will conform more closely to the current ILAE terminology and classification of the epilepsies and seizures and its potential impact on clinical care, surveillance, and public health and research.
Neuropeptide FF and prolactin‐releasing peptide decrease cortical excitability through activation of NPFF receptors
Authors: Buffel Ine , Meurs Alfred , Portelli Jeanelle , Raedt Robrecht , De Herdt Veerle , Sioncke Lynn , Wadman Wytse , Bihel Frederic , Schmitt Martine , Vonck Kristl , Bourguignon Jean‐Jacques , Simonin Frederic , Smolders Ilse , Boon Paul 
Published: February 2015

SummaryObjectiveDrugs with a novel mechanism of action are needed to reduce the number of people with epilepsy that are refractory to treatment. Increasing attention is paid to neuropeptide systems and several anticonvulsant neuropeptides have already been described, such as galanin, ghrelin, and neuropeptide Y (NPY). Many others, however, have not been investigated for their ability to affect epileptic seizures. In this study, the potential anticonvulsant activities of three members of the RF‐amide neuropeptide family, neuropeptide FF (NPFF), prolactin‐releasing peptide (PrRP), and kisspeptin (Kp) and other receptor ligands (NPFF1/2R, GPR10, and GRP54, respectively) were tested in the motor cortex stimulation model.MethodsA train of pulses with increasing intensity (0–10 mA over 150 s, 50 Hz, pulse width 2 msec) was delivered to the motor cortex of rats. The threshold intensity for eliciting a motor response (i.e., motor threshold) was determined through behavioral observation and used as a measure for cortical excitability. The threshold was determined before, during, and after the intracerebroventricular (i.c.v.) administration of various NPFF1/2R, GPR10, and GPR54 receptor ligands.ResultsNPFF and PrRP significantly increased the motor threshold by a maximum of 143 ± 27 and 83 ± 13 μA, respectively, for the doses of 1 nmol/h (p < 0.05). The increase of motor threshold by NPFF and PrRP was prevented by pretreatment and co‐treatment with the NPFF1/2R antagonist RF9. Pretreatment with a selective NPFF1R antagonist also prevented the threshold increase induced by NPFF. Kp did not increase motor threshold.SignificanceIntracerebroventricular infusion of NPFF or PrRP decreases cortical excitability in rats through activation of NPFFRs. Furthermore, the NPFF1R is required for the NPFF‐induced decrease in cortical excitability.
Diagnosis and treatment of carpometacarpal desmopathy in a horse
Authors: Porter E. G. , Brokken M. T. , Holmes S. P. 
Published: February 2015

SummaryA 9‐year‐old Warmblood gelding underwent magnetic resonance (MR) imaging of the carpal and proximal metacarpal regions for evaluation of prolonged right forelimb lameness. Magnetic resonance findings were indicative of desmopathy of the right lateral carpometacarpal ligament and the interosseous ligament between the third and fourth metacarpal bones. Based on the MR findings and lack of response to conservative therapy, surgery using a drilling technique was performed to facilitate fusion of the right carpometacarpal joint. After surgery and a 6‐month rest and rehabilitation programme, the horse returned to soundness. This case report describes a unique combination of lateral carpal/proximal metacarpal soft tissue injuries that resulted in prolonged lameness and were treated with facilitated arthrodesis of the carpometacarpal joint. These soft tissue injuries should be considered as a differential diagnosis in horses with lameness localised to the proximal metacarpal/distal carpal region.