bluuebunny/crossref_metadata_2025 huggingface dataset:
Early combination therapy for the treatment of type 2 diabetes mellitus: systematic review and meta‐analysis
Authors: Phung O. J. , Sobieraj D. M. , Engel S. S. , Rajpathak S. N.
Published: November 2013

Aims

Guidelines for type 2 diabetes recommend add‐on agents when metformin alone fails to provide adequate glycaemic control. However, early combination therapy may benefit health outcomes. We conducted a systematic review and meta‐analysis to investigate this question.

Methods

We searched MEDLINE and Cochrane CENTRAL (up to July 2012) without language restrictions. We sought randomized controlled trials (RCTs) evaluating initial combination therapy with metformin versus metformin monotherapy in patients with untreated type 2 diabetes. Weighted mean differences (WMDs) for changes from baseline and relative risks (RRs) [with 95% confidence intervals (CIs)] were calculated using random‐effects model.

Results

In 15 RCTs (N = 6693), the mean age range was 48.4–62.7 years; mean baseline glycosylated haemoglobin (A1c) was 7.2–9.9% and mean diabetes duration was 1.6–4.1 years, with median follow‐up of 6 months and with 13 comparisons for A1c change, 14 comparisons for A1c goal attainment of <7% and 13 comparisons for change in fasting plasma glucose (FPG). Drugs combined with metformin included thiazolidinediones (TZDs), insulin secretagogues, dipeptidyl peptidase‐4 (DPP‐4) inhibitors or sodium glucose transporterase (SGLT‐2) inhibitors. Compared to metformin alone, combination therapy with metformin provided statistically significant reductions in A1c (WMD −0.43%, 95% CI −0.56, −0.30), increases in attainment of A1c goal of less than 7% (RR 1.40, 95% CI 1.33–1.48) and reductions in FPG (WMD −14.30 mg/dl, 95% CI −16.09, −12.51).

Conclusions

These results suggest a potential benefit of initial combination therapy on glycaemic outcomes in diabetes compared to metformin monotherapy across a wide range of baseline A1c levels. Further research should explore if early combination treatment may also affect longer term health outcomes in diabetes.
A randomized controlled trial of the efficacy and safety of saxagliptin as add‐on therapy in patients with type 2 diabetes and inadequate glycaemic control on metformin plus a sulphonylurea
Authors: Moses R. G. , Kalra S. , Brook D. , Sockler J. , Monyak J. , Visvanathan J. , Montanaro M. , Fisher S. A.
Published: November 2013

Aims

To evaluate the efficacy and safety of saxagliptin as add‐on therapy in adults with type 2 diabetes with inadequate glycaemic control on metformin plus a sulphonylurea.

Methods

In this 24‐week, multicentre, randomized, parallel‐group, double‐blind study, outpatients aged ≥18 years with type 2 diabetes, body mass index ≤40 kg/m2 and inadequate glycaemic control, received saxagliptin 5 mg or placebo once‐daily added to background medication consisting of a stable maximum tolerated dose of metformin plus a sulphonylurea. The primary end point was change in glycated haemoglobin (HbA1c) from baseline to week 24. Safety and tolerability assessments included adverse events (AEs), hypoglycaemia and body weight.

Results

A total of 257 patients were randomized, treated and included in the safety analysis (saxagliptin, n = 129; placebo, n = 128); 255 were included in the efficacy analysis (saxagliptin, n = 127; placebo, n = 128). HbA1c reduction was greater with saxagliptin versus placebo [between‐group difference in adjusted mean change from baseline, −0.66%; 95% confidence interval (CI), −0.86 to −0.47 (7 mmol/mol, −9.4 to −5.1); p < 0.0001]. The proportion of patients with ≥1 AE was 62.8% with saxagliptin and 71.7% with placebo. In the saxagliptin and placebo groups, rates of reported hypoglycaemia were 10.1 and 6.3%, respectively, and rates of confirmed hypoglycaemia (symptoms + glucose < 2.8 mmol/l) were 1.6 and 0%. Mean change in body weight was 0.2 kg for saxagliptin and −0.6 kg for placebo (p = 0.0272).

Conclusion

Addition of saxagliptin 5 mg/day in patients inadequately controlled on metformin and sulphonylurea effectively improved glycaemic control and was well tolerated.
Caffeic acid, naringenin and quercetin enhance glucose‐stimulated insulin secretion and glucose sensitivity in INS‐1E cells
Authors: Bhattacharya S. , Oksbjerg N. , Young J. F. , Jeppesen P. B.
Published: November 2013

Aims

Caffeic acid, naringenin and quercetin are naturally occurring phenolic compounds (PCs) present in many plants as secondary metabolites. The aim of this study was to investigate their effect on glucose‐stimulated insulin secretion (GSIS) in INS‐1E cells and to explore their effect on expression of genes involved in β‐cell survival and function under normoglycaemic and glucotoxic conditions.

Methods

For acute studies, INS‐1E cells were grown in 11 mM glucose (72 h) and then incubated with the PCs (1 h) with 3.3/16.7 mM glucose; whereas, for chronic studies, the cells were grown in 11 mM glucose (72 h) with/without the PCs, and then incubated with 3.3/16.7 mM glucose (1 h); thereafter, GSIS was measured. For GSIS and gene expression studies (GES) under glucotoxic conditions, two sets of cells were grown in 11/25 mM glucose with/without the PCs (72 h): one was used for GES, using real time RT‐PCR, and the other was exposed to 3.3/16.7 mM glucose, followed by measurement of GSIS.

Results

The study demonstrated that the PCs can enhance GSIS under hyperglycaemic and glucotoxic conditions in INS‐1E cells. Moreover, these compounds can differentially, yet distinctly change the expression profile of genes [Glut2 (glucose transporter 2), Gck (glucokinase), Ins1 (insulin 1), Ins2, Beta2 (neurogenic differentiation protein 1), Pdx1 (pancreatic and duodenal homeobox protein 1), Akt1 (RAC‐α serine/threonine‐protein kinase encoding gene), Akt2 (RAC‐β serine/threonine‐protein kinase encoding gene), Irs1 (insulin receptor substrate 1), Acc1 (acetyl CoA carboxylase 1), Bcl2 (β‐cell lymphoma 2 protein), Bax (Bcl‐2 associated X protein), Casp3 (Caspase 3), Hsp70 (heat shock protein 70), and Hsp90] involved in β‐cell stress, survival and function.

Conclusion

The results indicate that the PCs tested enhance GSIS and glucose sensitivity in INS‐1E cells. They also modulate gene expression profiles to improve β‐cell survival and function during glucotoxicity.
The Incumbency Effects of Signalling
Authors: Caselli Francesco , Cunningham Tom , Morelli Massimo , de Barreda Inés Moreno
Published: November 2013

Much literature on political behaviour treats politicians as motivated by re‐election, choosing actions to signal their types to voters. We identify a novel implication of incumbent signalling. Because incumbents only care about clearing a re‐election hurdle, signals will tend to cluster just above the threshold needed for re‐election. This generates a skew distribution of signals leading to an incumbency advantage in the probability of election. We also solve for the optimal threshold when voters have the ability to commit.
Left Ventricular Mechanics in Adolescents and Young Adults with a History of Kawasaki Disease: Analysis by Three‐Dimensional Speckle Tracking Echocardiography
Authors: Yu Wei , Wong Sophia J. , Cheung Yiu‐fai
Published: November 2013

Background

Myocardial fibrosis and perfusion abnormalities can occur in patients with Kawasaki disease (KD). We explored using the new three‐dimensional speckle tracking echocardiography (3DSTE) the left ventricular (LV) mechanics in adolescents and young adults with a history of KD.

Methods

Twenty‐five KD patients (18 males) aged 17.0 ± 5.2 years, 14 with (group I) and 11 without (group II) coronary aneurysms, were studied. The 3D volume datasets were acquired for quantification of LV global 3D strain, global and regional area strain, systolic dyssynchrony index (SDI), twist, twist gradient (twist/LV length), and ejection fraction.

Results

The results were compared with those of 14 age‐matched controls. Of the 14 group I patients, 6 had left, 2 had right, and 6 had both left and right coronary aneurysms. Compared with controls, group I patients had significantly lower LV systolic global 3D strain (43.7 ± 7.3% vs. 50.4 ± 6.6%, P = 0.02), twist (8.7 ± 1.3° vs. 11.4 ± 2.0°, P < 0.001), and twist gradient (1.5 ± 0.3°/cm vs. 1.9 ± 0.4°/cm, P = 0.01), greater SDI (6.8 ± 1.9% vs. 4.7 ± 1.9%, P < 0.001), and similar ejection fractions. Six patients in group I had perfusion defects, who had global 3DSTE parameters similar to those of the 8 patients without perfusion abnormalities (all P > 0.05). For group II patients, only the global area strain was significantly lower than that of controls (37.6 ± 3.5% vs. 40.7 ± 3.6%, P = 0.038).

Conclusion

In adolescents and young adults with a history of KD, impairment of LV mechanics occurs and is worse in patients with than those without coronary complications.
Repeated Neurological Complications during Dialysis – A Case for Echo?
Authors: Groves Danja S. , Harding Ulf , Lanckohr Christian , Gottschalk Antje , Kern John A. , Schmidt Christoph
Published: November 2013

Mini‐Abstract

A 65‐year old woman presented with acute or chronic renal failure and signs of right heart failure. Renal replacement therapy—using a surgically placed dialysis catheter via the left jugular vein—was repeatedly complicated by altered flows of the dialysis unit, impaired consciousness, new onset of seizures and left‐sided hemiparesis. The tip of the dialysis catheter was detected on transesophageal echocardiography within the lumen of the ascending aorta. Further imaging of the neck vessels demonstrated a primary placement of the catheter in the left common carotid artery. This incident underscores the value of ultrasound guidance for placement of intravascular catheters.
The landscape genetics of syntopic topminnows (Fundulus notatus and F. olivaceus) in a riverine contact zone
Authors: Earnest Kate , Scott Jason , Schaefer Jake , Duvernell David
Published: November 2013

The metapopulation dynamics of a species are influenced by the spatial arrangement of preferred habitats across a landscape. Increasing habitat patchiness can result in greater population subdivision, leading to more pronounced population genetic structure. Therefore, even subtle differences in habitat preferences among species could lead to substantial differences in genetic structure. Members of the Fundulus notatus species complex of topminnows include a headwater specialist and a large river specialist with broadly overlapping geographical distributions. Both species are often found in the same drainage systems, but partially isolated by divergent habitat preferences. The purpose of this research was to determine whether distribution along a stream continuum in a contact zone influences population genetic patterns in two species of topminnow (Fundulus olivaceus and Fundulus notatus). Fish were collected in the summers of 2010–2012, and habitat data were collected in summer 2012, within all major tributaries of the Saline River in southern Illinois. In total, 523 fish were genotyped using seven microsatellite loci to assess genetic variation. Species distributions in F. notatus and F. olivaceus were associated with habitat factors that covaried with cumulative drainage area. Populations of F. olivaceus showed a greater level of genetic structure reflected in a significant pattern of isolation by distance, while populations of F. notatus showed no such pattern. Spatial autocorrelation analysis revealed that at an individual level, both species became increasingly divergent with waterway distance. Overall, clear interspecific differences in habitat preferences were translated into measurable but relatively subtle differences in population genetic structure.
Cost‐effectiveness analysis of preoperative transfusion in patients with sickle cell disease using evidence from the TAPS trial
Authors: Spackman Eldon , Sculpher Mark , Howard Jo , Malfroy Moira , Llewelyn Charlotte , Choo Louise , Hodge Renate , Johnson Tony , Rees David C. , Fijnvandraat Karin , Kirby‐Allen Melanie , Davies Sally , Williamson Lorna
Published: November 2013

The study's objective was to assess the cost‐effectiveness of preoperative transfusion compared with no preoperative transfusion in patients with sickle cell disease undergoing low‐ or medium‐risk surgery. Seventy patients with sickle cell disease (HbSS/Sß0thal genotypes) undergoing elective surgery participated in a multicentre randomised trial, Transfusion Alternatives Preoperatively in Sickle Cell Disease (TAPS). Here, a cost‐effectiveness analysis based on evidence from that trial is presented. A decision‐analytic model is used to incorporate long‐term consequences of transfusions and acute chest syndrome. Costs and health benefits, expressed as quality‐adjusted life years (QALYs), are reported from the ‘within‐trial’ analysis and for the decision‐analytic model. The probability of cost‐effectiveness for each form of management is calculated taking into account the small sample size and other sources of uncertainty. In the range of scenarios considered in the analysis, preoperative transfusion was more effective, with the mean improvement in QALYs ranging from 0.018 to 0.206 per patient, and also less costly in all but one scenario, with the mean cost difference ranging from −£813 to £26. All scenarios suggested preoperative transfusion had a probability of cost‐effectiveness >0.79 at a cost‐effectiveness threshold of £20 000 per QALY.
Influence of masticatory hypofunction on the alveolar bone and the molar periodontal ligament space in the rat maxilla
Authors: Denes Balazs J. , Mavropoulos Anestis , Bresin Andrea , Kiliaridis Stavros
Published: November 2013

Previous studies have established that complete absence of masticatory function results in a narrower alveolar process and periodontal ligament (PDL). The aim of our study was to investigate, for the first time, both the alveolar process and the PDL in masticatory hypofunction. Twenty‐six rats, 3 wk of age, were randomly assigned to either a hard‐ or a soft‐diet group (n = 13 each group). The rats were killed after 6 wk and their skulls were scanned using micro‐computed tomography (micro‐CT). We measured the cross‐sectional width of the space occupied by the PDL, as well as the cross‐sectional alveolar socket surface (AS) and the cross‐sectional root surface (RS). We also measured the width of the alveolar process. The alveolar process was narrower, the PDL width was thinner, and the AS was smaller in rats fed a soft diet compared with rats fed a hard diet. The PDL width was correlated to the alveolar process width and the AS. The narrower alveolar process found in rats fed a soft diet is the result of alterations to both the alveolar bone and the PDL. The correlation between them provides evidence that a reduction of occlusal loading induces a simultaneous response in both tissues.
Role ofNMDAreceptors in the trigeminal pathway, and the modulatory effect of magnesium in a model of rat temporomandibular joint arthritis
Authors: Cavalcante André L. C. , Siqueira Rafaelly M. P. , Araujo Joana C. B. , Gondim Delane V. , Ribeiro Ronaldo A. , Quetz Josiane S. , Havt Alexandre , Lima Aldo A. M. , Vale Mariana L.
Published: November 2013

Temporomandibular joint (TMJ) arthritis is a common cause of orofacial pain. In the present study, the modulatory effects ofN‐methyl‐d‐aspartate receptors (NMDA‐Rs) and magnesium were investigated inTMJarthritis hypernociception. Male Wistar rats received an intra‐articular injection of carrageenan (Cg) in theTMJ, and mechanical hypernociception was measured. TheNMDA‐Rantagonist,MK‐801, and magnesium chloride (MgCl2) were administered before arthritis induction. Magnesium deficiency was promoted by feeding rats a synthetic magnesium‐free diet for 9 d before injection ofCg. TheCg induced mechanical hypernociception that lasted for 120 h. MK‐801 inhibited this hypernociceptive state. MgCl2pretreatment preventedCg‐induced hypernociception and altered the nociceptive threshold in the absence ofCg. Magnesium deficiency increased hypernociception and induced spontaneous hypernociceptive behavior. TMJ arthritis increased the expression ofmRNAfor allNMDA‐Rsubunits and immunostaining of phosphorylatedNR1 (phospho‐NR1). MgCl2inhibited expression ofNR2B mRNAand phospho‐NR1 immunostaining and increased expression of NR3mRNA. Magnesium deficiency increased expression of bothNR1 andNR3mRNAs and phospho‐NR1 immunostaining in the trigeminal subnucleus caudalis. We found that magnesium modulates nociceptive behavior and inducesNMDA‐Rsubunit rearrangement in the subnucleus caudalis. The present results may lead to a better understanding of central processing in the nociceptive trigeminal pathway and the development of new approaches to treat orofacial pain with aTMJorigin.
The specificity and kinetic mechanism of branched‐chain amino acid aminotransferase from Escherichia coli studied with a new improved coupled assay procedure and the enzyme's potential for biocatalysis
Authors: Yu Xuejing , Wang Xingguo , Engel Paul C.
Published: November 2013

Branched‐chain amino acid aminotransferase (BCAT) plays a key role in the biosynthesis of hydrophobic amino acids (such as leucine, isoleucine and valine), and its substrate spectrum has not been fully explored or exploited owing to the inescapable restrictions of previous assays, which were mainly based on following the formation/consumption of the specific branched‐chain substrates rather than the common amino group donor/acceptor. In our study, detailed measurements were made using a novel coupled assay, employing (R)‐hydroxyglutarate dehydrogenase from Acidaminococcus fermentans as an auxiliary enzyme, to provide accurate and reliable kinetic constants. We show that Escherichia coli BCAT can be used for asymmetric synthesis of a range of non‐natural amino acids such as l‐norleucine, l‐norvaline and l‐neopentylglycine and compare the kinetic results with the results of molecular modelling. A full two‐substrate steady‐state kinetic study for several substrates yields results consistent with a bi‐bi ping‐pong mechanism, and detailed analysis of the kinetic constants indicates that, for good 2‐oxoacid substrates, release of 2‐oxoglutarate is much slower than release of the product amino acid during the transamination reaction. The latter is in fact rate‐limiting under conditions of substrate saturation.

Database

Branched‐chain amino acid aminotransferase EC 2.6.1.42; (R)‐2‐hydroxyglutarate dehydrogenase EC 1.1.99.2
Structure‐based analysis of thermodynamic and mechanical properties of cavity‐containing proteins – case study of plant pathogenesis‐related proteins of class 10
Authors: Chwastyk Mateusz , Jaskolski Mariusz , Cieplak Marek
Published: November 2013

We provide theoretical comparisons of the physical properties of eighteen proteins with the pathogenesis‐related proteins of class 10 (PR‐10) fold, which is characterized by a large hydrophobic cavity enclosed between a curved β‐sheet and a variable α‐helix. Our novel algorithm to calculate the volume of internal cavities within protein structures is used to demonstrate that, although the sizes of the cavities of the investigated PR‐10 proteins vary significantly, their other physical properties, such as thermodynamic and mechanical parameters or parameters related to folding, are very close. The largest variations (in the order of 20%) are predicted for the optimal folding times. We show that, on squeezing, the PR‐10 proteins behave differently from typical virus capsids.
Worldwide Reported Use of IV Tissue Plasminogen Activator for Acute Ischemic Stroke
Authors: Berkowitz Aaron L. , Mittal Manoj K. , McLane Hannah C. , Shen Gordon C. , Muralidharan RajaNandini , Lyons Jennifer L. , Shinohara Russell T. , Shuaib Ashfaq , Mateen Farrah J.
Published: November 2013

Background and Purpose

Intravenous tissue plasminogen activator is the most effective treatment for acute ischemic stroke, and its use may therefore serve as an indicator of the available level of acute stroke care. The greatest burden of stroke is in low- and middle-income countries, but the extent to which intravenous tissue plasminogen activator is used in these countries is unreported.

Summary of Review

A systematic review was performed searching each country name AND ‘stroke’ OR ‘tissue plasminogen activator’ OR ‘thrombolysis’ using PubMed, Embase, Global Health, African Index Medicus, and abstracts published in the International Journal of Stroke (Jan. 1, 1996–Oct. 1, 2012). The reported use of intravenous tissue plasminogen activator was then analyzed according to country-level income status, total expenditure on health per capita, and mortality and disability-adjusted life years due to stroke. There were 118 780 citations reviewed. Of 214 countries and independent territories, 64 (30%) reported use of intravenous tissue plasminogen activator for acute ischemic stroke in the medical literature: 3% (1/36) low-income, 19% (10/54) lower-middle-income, 33% (18/54) upper-middle-income, and 50% (35/70) high-income-countries (test for trend, P < 0·001). When considering country-level determinants of reported intravenous tissue plasminogen activator use for acute ischemic stroke, total healthcare expenditure per capita (odds ratio 3·3 per 1000 international dollar increase, 95% confidence interval 1·4–9·9, P = 0·02) and reported mortality rate from cerebrovascular disease (odds ratio 1·02, 95% confidence interval 0·99–1·06, P = 0·02) were significant, but reported disability-adjusted life years from cerebrovascular diseases and gross national income per capita were not ( P > 0·05). Of the 10 countries with the highest disability-adjusted life years due to stroke, only one reported intravenous tissue plasminogen activator use.

Conclusions

By reported use, intravenous tissue plasminogen activator for acute ischemic stroke is available to some patients in approximately one-third of countries. Access to advanced acute stroke care is most limited where the greatest burden of cerebrovascular disease is reported.
Popular Music and Copyright Law in the Sixties
Authors: Bellido Jose
Published: November 2013

Copyright and its relationship with popular music is one of the most disputed issues amongst music and copyright scholars. While some have accused copyright of being blind (or deaf) to the particularities of popular music, others have defended its significance within the industry. This article contributes to this debate by tracing the networks of connections between lawyers, musicians, and clerks that emerged in a formative period in British pop music (the Sixties). It considers how their collaborative efforts and strategies to present evidence in copyright infringement trials were articulated in an attempt to influence music copyright infringement tests in Britain. By highlighting the concrete geographical and temporal contexts from which these networks emerged and their particular contingencies, the article also casts a new light on the impact of the legal profession on copyright, showing a practice‐oriented and historically situated way of observing differences between French and British copyright systems.
Visible Light Transparency for Polycrystalline Ceramics of MgO·2Al2O3 and MgO·2.5Al2O3 Spinel Solid Solutions
Authors: Sutorik Anthony C. , Cooper Christopher , Gilde Gary
Published: November 2013

Magnesium aluminate spinel solid solutions with the alumina‐rich compositions MgO·2Al2O3 and MgO·2.5Al2O3 have been prepared as polycrystalline ceramics with average in‐line transmissions at 550 nm of 85.5 ± 0.3% and 80.9 ± 0.4%, respectively. Starting powders are prepared from combinations of high purity Mg(OH)2 and γ‐Al2O3 thoroughly mixed in an aqueous slurry, and the solids are collected, dried, calcined, mixed with LiF sintering aid, and sieved. The optimum amount of LiF added varies with the alumina composition of the spinel solid solution. The powders are sintered into dense ceramics by hot pressing at 1600°C under vacuum and 20 MPa uniaxial load followed by hot isostatic pressing at 1850°C under 200 MPa in Ar. Both compositions exhibit exaggerated grain growth with average sizes well over 500 μm. Knoop hardness measurements are 11.2 ± 0.3 GPa for MgO·2Al2O3 and 11.0 ± 0.4 GPa for MgO·2.5Al2O3.
Families Supporting a Child with Intellectual or Developmental Disabilities: The Current State of Knowledge
Authors:   Families Special Interest Research Group of IASSIDD
Published: November 2013

This IASSIDD Position Paper provides a concise authoritative summary of (i) existing scientific knowledge regarding the situation, challenges and well‐being of families that include a child with intellectual and/or developmental disabilities, and (ii) priorities for future research. IASSIDD (www.iassidd.org) is the leading global organisation for researchers and research centres that seek to improve the understanding of and improve the lives of people with intellectual or developmental disabilities, their families and those who support them. The paper and the recommendations it contains have been developed through an iterative process led by IASSIDD's Families Special Interest Research Group (SIRG). During this process, all members of the Families SIRG and all members of IASSIDD's ruling council have had the opportunity to comment on drafts of this paper. The final Position Paper was adopted by the Council of IASSIDD on 9 July 2012.
Prevalence of human Papillomavirus DNA in eyebrow hairs plucked from patients with psoriasis treated with TNF inhibitors
Authors: Bellaud G. , Gheit T. , Pugin A. , Prétet J. L. , Tommasino M. , Mougin C. , Aubin F.
Published: November 2013

Background

Tumour necrosis factor alpha (TNF‐α) inhibitors are associated with an increased risk of infections and with a still debatable risk of skin cancer. Furthermore, cutaneous human papillomavirus (HPV) infection may be involved in skin cancer.

Objectives

Our primary objective was to assess the HPV DNA prevalence in psoriasis patients treated with TNF inhibitors and the secondary objective was to assess the same parameter before and during treatment.

Methods

Plucked eyebrow hairs were collected from 151 consecutive patients with moderate to severe chronic plaque psoriasis, including 48 patients treated with anti‐TNF‐α agents, 21 patients treated with methotrexate (MTX) and 82 patients with no previous systemic treatment. Among them, 38 patients were subsequently treated with either MTX or anti‐TNF‐α agents. HPV genotyping was performed using the HPV type‐specific E7 PCR bead‐based multiplex allowing the detection of 27 genus‐α types, 25 genus‐β types, 16 genus‐γ types and one single genus‐μ type. Follow‐up provided a total of 972.7 person‐months of overall exposure for patients treated with TNF inhibitors and 326.9 person‐months for patients treated with MTX.

Results

Our data confirm the high prevalence of β‐HPV infection in healthy skin of psoriasis patients (68.9%), with no significant difference between untreated patients (64.6%), patients treated with MTX (76.2%) and patients treated with anti‐TNF‐α agents (72.9%). The mean number of different HPV types and the distribution of HPV types were similar in different groups of patients. Moreover, in prospectively treated patients, we did not observe any change in the HPV DNA prevalence in the distribution of HPV types and the number of HPV types after a mean duration of treatment of 332 ± 39.8 days.

Conclusion

Despite the small number of patients in our cohort, our results are quite encouraging in view of the increased use of anti‐TNF‐α agents in different auto inflammatory immune diseases.
Surgical residents' perceptions of patient safety climate in Dutch teaching hospitals
Authors: Martowirono Kartinie , Wagner Cordula , Bijnen A. Bart
Published: November 2013

Rationale, aims and objectives

Explicit attention to patient safety during surgical training is needed to improve patient safety. A positive safety climate is associated with greater patient safety and is a requisite for safety teaching at the workplace. The Safety Climate Survey (SCS) measures perceptions of safety climate. This study aims to take a first step in validating the SCS for use among surgical residents in the Netherlands and to highlight opportunities for safety climate improvement through changes in surgical training in the Netherlands. It therefore assesses (1) if the SCS can be used to assess surgical residents' perceptions of the safety climate in Dutch teaching hospitals; and (2) how, according to SCS results, these residents perceive the safety climate in Dutch teaching hospitals.

Methods

In a cross‐sectional study conducted in February 2011, a Dutch translation of the SCS was administered to all general surgical residents in the Netherlands. Face validity and internal consistency were assessed, as were overall mean, means per item and significant differences in means between different groups of respondents.

Results

In total, 306 of 390 (78%) residents completed the questionnaire. The SCS showed good face validity and internal consistency (Cronbach's alpha = 0.87). Residents reported an overall mean of 3.95 (standard deviation 0.51) out of a maximum score of 5.00, and 52% reported an overall mean of 4.00 or higher. Women and residents working in university hospitals gave significantly lower scores. Significant differences were also found among hospitals and among regions. Majority of the items scored less than 4.00.

Conclusions

The SCS is potentially useful to measure surgical residents' perceptions of the patient safety climate in Dutch teaching hospitals. There is considerable room for improvement of the patient safety climate. Surgical training should include better feedback, formal patient safety teaching sessions at the workplace and specific attention to patient safety during the introduction in a new hospital, and supervisors should encourage surgical residents to report any patient safety concern they may have.
Comorbidity of postural orthostatic tachycardia syndrome and chronic fatigue syndrome in an Australian cohort
Authors: Reynolds G. K. , Lewis D. P. , Richardson A. M. , Lidbury B. A.
Published: November 2013

Objective

Patients with chronic fatigue syndrome (CFS) are frequently diagnosed with comorbid postural orthostatic tachycardia syndrome (POTS), suggesting a shared pathogenesis. The aim of this study was to examine the relationship between demographic characteristics, autonomic functioning and fatigue levels amongst CFS patients with and without comorbid POTS.

Design and setting

All patients presenting to the CFS Discovery Clinic between 2009 and 2012 completed a 20‐min standing task as part of their initial assessment. Heart rate and pulse pressure were recorded at baseline, at 2‐min intervals poststanding, at the end of the task and following a recovery period. Average heart rate and pulse pressure variability were calculated from this data. Age, gender, length of illness and self‐reported fatigue scores were also recorded. POTS patients were diagnosed by an orthostatic increase in heart rate >30 beats per min, concomitant symptoms of orthostatic intolerance and no orthostatic hypotension. Differences in autonomic functioning between POTS and CFS patients were compared using independent samples t‐tests, whilst logistic and linear regressions were performed to examine the contribution of autonomic functioning to task completion and perceived fatigue, respectively.

Results

Comorbidity of CFS and POTS (CFS‐POTS) was observed in 11% (33/306) of patients. CFS‐POTS patients were significantly younger (P < 0.001), had a shorter length of illness (P = 0.034), experienced greater task difficulty (P = 0.002) and were able to stand for significantly shorter periods compared to the CFS‐only patients (P < 0.001). CFS‐POTS patients experienced significantly lower baseline diastolic blood pressure (P = 0.002), significantly higher heart rate and lower pulse pressures at each standing measurement. Early heart rate changes (P = 0.002) and overall heart rate change (P < 0.001) were significant predictors of completion status, whereas heart rate variability (P < 0.001) and female gender (P < 0.001) were significant predictors of increased perceived task difficulty.

Conclusions

Haemodynamic and demographic differences between CFS‐POTS and CFS‐only patients suggest that the former group reflects a distinct subgroup of the CFS population. The findings highlight the utility of screening younger patients with fatigue for POTS, and identified heart rate variability as an important marker of fatigue for CFS patients in general.
Effect of non‐surgical periodontal treatment on short chain fatty acid levels in gingival crevicular fluid of patients with generalized aggressive periodontitis
Authors: Lu R. , Meng H. , Gao X. , Xu L. , Feng X.
Published: November 2013

Background and Objective

Short chain fatty acids (SCFAs) play important roles in periodontal diseases. However, the concentrations of SCFAs in gingival crevicular fluid of patients with aggressive periodontitis are not known. The aim of this intervention study was to investigate the influences of non‐surgical periodontal therapy on levels of SCFAs in the gingival crevicular fluid of patients with generalized aggressive periodontitis (G‐AgP), and analyze the concentrations of SCFAs in sites with or without the detected putative periodontal pathogens.

Material and Methods

Eighty gingival crevicular fluid samples (four per subject) were collected on filter paper strips from patients with G‐AgP (n = 20; mean age 24.5 years), before and at 2 wk, 2, 4 and 6 mo after non‐surgical periodontal treatment. Eighty gingival crevicular fluid samples (four per subject) were collected from periodontally healthy controls (n = 20; mean age 26.2 years). Concentrations of formic acid, succinic acid, acetic acid, lactic acid, propionic acid, butyric acid and isovaleric acid from the supernatant of gingival crevicular fluid samples were measured by high performance capillary electrophoresis. Porphyromonas gingivalis, Treponema denticola, Aggregatibacter actinomycetemcomitans, Prevotella intermedia and Fusobacterium nucleatum from the precipitate of the same pretreatment samples of gingival crevicular fluids were analyzed by polymerase chain reaction amplification.

Results

The clinical parameters of patients with G‐AgP during the 6 mo after non‐surgical periodontal treatment were improved remarkably. The formic acid concentration increased significantly after treatment; the level of formic acid was lower in the P. gingivalis‐, T. denticola‐, P. intermedia‐ or F. nucleatum‐positive sites compared with the negative sites. The concentrations of acetic acid, propionic acid and butyric acid reduced significantly after treatment and reached the lowest level at 2 wk post‐treatment, although showed a tendency to increase after 2 mo post‐treatment, and the three SCFA levels were significantly higher in P. gingivalis‐, T. denticola‐, P. intermedia‐ or F. nucleatum‐positive sites compared with those in the negative sites.

Conclusion

Non‐surgical periodontal treatment resulted in a significant decrease of acetic acid, propionic acid, butyric acid levels and increase of formic acid level in gingival crevicular fluids in patients with G‐AgP, accompanied by improvement in clinical parameters. A marked lower level of formic acid, as well as higher levels of acetic acid, propionic acid and butyric acid in gingival crevicular fluid of patients with G‐AgP was consistent with periodontal pathogen infection.
Effect of the concentration of phenothiazine photosensitizers in antimicrobial photodynamic therapy on bone loss and the immune inflammatory response of induced periodontitis in rats
Authors: Garcia V. G. , Longo M. , Gualberto Júnior E. C. , Bosco A. F. , Nagata M. J. H. , Ervolino E. , Theodoro L. H.
Published: November 2013

Background and Objective

Antimicrobial therapy can suppress periodontal pathogens and increase the effectiveness of conventional mechanical treatment. The aim of this study was to assess bone loss and the immune inflammatory response of rats under the influence of two photosensitizing agents (MB and TBO) at two different concentrations in antimicrobial photodynamic therapy (aPDT), used as an adjuvant therapy in the treatment of periodontitis.

Material and Methods

Periodontitis was induced in the mandibular first molars of 162 rats. The animals were divided into nine groups: G1 – scaling and root planing (SRP); G2 – SRP plus 100 μg/mL of methylene blue (MB); G3 – SRP plus 10 mg/mL of MB; G4 – SRP plus 100 μg/mL of toluidine blue (TBO); G5 – SRP plus 10 mg/mL of TBO; G6 – SRP plus 100 μg/mL of MB and laser; G7 – SRP plus 10 mg/mL of MB and laser; G8 – SRP plus 100 μg/mL of TBO and laser; and G9 – SRP plus 10 mg/mL of TBO and laser. Six animals from each group were euthanized 7, 15, or 30 d after treatment. Bone loss (BL) in the furcation region was evaluated using histomorphometric and immunohistochemical analyses to detect the receptor activator of nuclear factor‐Κappa B ligand (RANKL), osteoprotegerin (OPG) and tartrate‐resistant acid phosphatase (TRAP).

Results

There was significantly less BL in animals treated with aPDT using low concentrations of MB and TBO at 7, 15 and 30 d. Immunohistochemical analysis revealed decreased RANKL and increased OPG in the aPDT groups and decreased TRAP‐positive cells in G6 and G8.

Conclusions

aPDT, using low concentrations of MB and TBO, was the most effective adjuvant therapy to SRP, acting indirectly as a downregulator of the molecular mechanisms that control bone resorption in periodontitis.
Green tea extract and its major constituent, epigallocatechin‐3‐gallate, induce epithelial beta‐defensin secretion and prevent beta‐defensin degradation by Porphyromonas gingivalis
Authors: Lombardo Bedran T. B. , Feghali K. , Zhao L. , Palomari Spolidorio D. M. , Grenier D.
Published: November 2013

Background and Objective

Antimicrobial peptides, such as beta‐defensins, secreted by gingival epithelial cells, are thought to play a major role in preventing periodontal diseases. In the present study, we investigated the ability of green tea polyphenols to induce human beta‐defensin (hBD) secretion in gingival epithelial cells and to protect hBDs from proteolytic degradation by Porphyromonas gingivalis.

Material and Methods

Gingival epithelial cells were treated with various amounts (25–200 μg/mL) of green tea extract or epigallocatechin‐3‐gallate (EGCG). The secretion of hBD1 and hBD2 was measured using ELISAs, and gene expression was quantified by real‐time PCR. The treatments were also carried out in the presence of specific kinase inhibitors to identify the signaling pathways involved in hBD secretion. The ability of green tea extract and EGCG to prevent hBD degradation by proteases of P. gingivalis present in a bacterial culture supernatant was evaluated by ELISA.

Results

The secretion of hBD1 and hBD2 was up‐regulated, in a dose‐dependent manner, following the stimulation of gingival epithelial cells with a green tea extract or EGCG. Expression of the hBD gene in gingival epithelial cells treated with green tea polyphenols was also increased. EGCG‐induced secretion of hBD1 and hBD2 appeared to involve extracellular signal‐regulated kinase 1/2 and p38 mitogen‐activated protein kinase. Lastly, green tea extract and EGCG prevented the degradation of recombinant hBD1 and hBD2 by a culture supernatant of P. gingivalis.

Conclusion

Green tea extract and EGCG, through their ability to induce hBD secretion by epithelial cells and to protect hBDs from proteolytic degradation by P. gingivalis, have the potential to strengthen the epithelial antimicrobial barrier. Future clinical studies will indicate whether these polyphenols represent a valuable therapeutic agent for treating/preventing periodontal diseases.
Modeling Population Health
Authors: Bauer Susanne
Published: November 2013

Risk reasoning has become the common‐sense mode of knowledge production in the health sciences. Risk assessment techniques of modern epidemiology also co‐shape the ways genomic data are translated into population health. Risk computations (e.g., in preventive medicine, clinical decision‐support software, or web‐based self‐tests), loop results from epidemiological studies back into everyday life. Drawing from observations at various European research sites, I analyze how epidemiological techniques mediate and enact the linkages between genomics and public health. This article examines the epidemiological apparatus as a generative machine that is socially performative. The study design and its reshuffling of data and categories in risk modeling recombine old and new categories from census to genomics and realign genes/environment and nature/culture in novel and hybrid ways. In the Euro‐American assemblage of risk reasoning and related profiling techniques, the individual and the population are no longer separate but intimately entangled.
Introduction
Authors: Taussig Karen‐Sue , Gibbon Sahra Elizabeth
Published: November 2013

We introduce this special issue ofMedial Anthropology Quarterlyon public health genomics by exploring both the unique contribution of ethnographic sensibility that medical anthropologists bring to the study of genomics and some of the key insights offered by the essays in this collection. As anthropologists, we are concerned with the power dynamics and larger cultural commitments embedded in practices associated with public health. We seek to understand, first, the broad significance of genomics as a cultural object and, second, the social action set into motion as researchers seek to translate genomic knowledge and technology into public health benefits.
Race, Risk, and Recreation in Personal Genomics: The Limits of Play
Authors: Lee Sandra Soo‐Jin
Published: November 2013

Despite the mantra that genetics has moved beyond race, the burgeoning industry of genetic ancestry reveals how genetics has offered new technology through which individuals can link to intersections in time and space in complex ways that recapitulate understandings of racial order, origins, and group membership. This article focuses on the trope of “recreation” asserted in the marketing of ancestry genetic tests and examines the suggestion of self‐discovery through the recovery of lost kin. Themes of recreation and re‐creation paradoxically suggest both passivity of self‐revelation and the power to re‐act and re‐create one's self in light of a different, more enlightened future. Direct‐to‐consumer personal genetics testing companies play guardian to this consumer play, providing tailored genetic scripts and highlighting how consumers might use their information. This article critically examines the play with concepts of ancestry, ethnicity, and genetic variation and their implications for public understanding of the relationship between race and genetics.
For the Sake of Others: Reciprocal Webs of Obligation and the Pursuit of Transplantation as a Caring Act
Authors: Heinemann Laura Lynn
Published: November 2013

This article highlights reciprocal webs of care and moral obligations toward kin during transplantation, using an expansive notion of “care” to include both its obvious and more hidden forms. Evidence from 24 months of ethnographic fieldwork among transplant patients, their loved ones, and clinical personnel in the U.S. Midwest suggests that patients are simultaneously caregivers to others and are considered vital members of reciprocal webs of care without whom their kin networks could not effectively operate. Transplantation can become a person's main, perhaps only hope of fulfilling ongoing obligations to others, so pursuing a transplant becomes not a matter of choice, but rather a moral orientation. A potential implication of these findings is that rather quotidian and conventional (even if contested) notions of what kin ought to do and be for each other may be among the underpinnings of high‐tech biomedical practices like transplantation.
Canary Grasses (Phalaris, Poaceae): biogeography, molecular dating and the role of floret structure in dispersal
Authors: Voshell Stephanie M. , Hilu Khidir W.
Published: November 2013

Canary grasses (Phalaris, Poaceae) include 21 species, widely spread throughout the temperate and subtropical regions of the world with two centres of diversity: the Mediterranean Basin and western North America. The genus contains annual and perennial, endemic, cosmopolitan, wild, and invasive species with diploid, tetraploid and hexaploid cytotypes. As such, Phalaris presents an ideal platform to study diversification via historic hybridization and polyploidy events, and geographical dispersal in grasses. We present the first empirical phylogeographic study for Phalaris testing current, intuitive hypotheses on the centres of origin, historic dispersal events and diversification within a geological timeframe. Bayesian methods (beast, version 1.6.2) were used to establish divergence dates, and dispersal–vicariance analyses (rasp, version 2.1b) were implemented for ancestral node reconstructions. Our phylogeographic results indicate that the genus emerged during the Miocene epoch [20.6–8.4 Ma (million years ago)] in the Mediterranean basin followed by dispersal and vicariance events to Africa, Asia and the Americas. We propose that a diploid ancestor of P. arundinacea migrated to western North America via the Bering Strait, where further diversification emerged in the New World. It appears that polyploidy played a major role in the evolution of the genus in the Old World, while diversification in the New World followed a primarily diploid pathway. Dispersal to various parts of the Americas followed different routes. Fertile florets with hairy protruding sterile lemmas showed significant correlation with wider geographical distribution.
Why do off‐shored Indian call centre workers want to leave their jobs?
Authors: Deery Stephen , Nath Vandana , Walsh Janet
Published: November 2013

Employee turnover is a major problem in off‐shored Indian call centres. Agents who service Western customers often face hostility and racial abuse because of who they are and where they are located. A substantial part of job‐related training focuses on teaching employees to manage their identity and modify their accent. Based on a sample (n = 211) of Indian call centre workers servicing international customers, we explore these issues and investigate how they affect employee turnover intentions. The study utilises Taylor and Bain's (2005) distinction between factors particular to the Indian context and those more generic to the call centre labour process to better understand the drivers of turnover. We found that a number of distinctive factors including accent modification difficulty, stigma consciousness, racial abuse and perceived favouritism were associated with turnover intentions. The study also revealed that certain job‐related factors related to intentions to leave, including routinisation and poor promotional opportunities.
Limitations and vulnerabilities of the neonatal cardiovascular system: considerations for anesthetic management
Authors: Wolf Andrew R. , Humphry Adrian T.
Published: November 2013

Development of the cardiovascular system through the last trimester of pregnancy and the subsequent neonatal period is profound. Morphological changes within the myocardium make the heart vulnerable to challenges such as fluid shifts and anesthetic drugs. The sensitivity of the myocardium to metabolic challenges and potential harm of drugs needed to maintain adequate blood pressure and cardiac output are highlighted. Traditional monitoring under anesthesia has focussed on maintaining oxygenation and heart rate in the neonate with less attention paid to blood pressure, cardiac output, and more importantly organ well‐being. There is now a better understanding of the limitations of blood pressure homeostasis in the neonate and the potential consequences of marginal hypoperfusion. This article highlights some of these vulnerabilities particularly as they relate to anesthesia and surgery in the very young.