bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased efficacy of omalizumab in atopic dermatitis patients with wild‐type filaggrin status and higher serum levels of phosphatidylcholines
Authors: Hotze M. , Baurecht H. , Rodríguez E. , Chapman‐Rothe N. , Ollert M. , Fölster‐Holst R. , Adamski J. , Illig T. , Ring J. , Weidinger S.
Published: October 2013

Omalizumab, a monoclonal antibody targeting IgE, is an established therapy for severe allergic asthma and has shown efficacy in chronic spontaneous urticaria. Small‐scale studies indicated some beneficial effect also in atopic dermatitis (AD). To evaluate the efficacy of omalizumab in AD and to identify markers associated with treatment response, we conducted a prospective 28‐week open‐label trial on 20 adults with moderate‐to‐severe AD. Our results confirm previous observations of a positive response in a subgroup of patients and suggest that responders are characterized by the absence of filaggrin mutations and altered lipid metabolite profiles with high levels of various glycerophospholipids.
Chlorhexidine droplet splash from a skin preparation gallipot: effect of height of pouring
Authors: Evans L. , Cunningham M. , Tilakaratna P.
Published: October 2013

Chlorhexidine contamination of equipment used in central neuraxial anaesthesia has been implicated in causing adhesive arachnoiditis. We measured the extent of chlorhexidine splash during pouring into a gallipot (antiseptic skin preparation container) from heights of 5 cm, 10 cm, 15 cm and 20 cm. Twenty experiments were performed at each height. Measurements made up to a horizontal distance of 40 cm radius from the gallipot showed a median (IQR [range]) maximum spread of splash droplets ≥ 2 mm diameter of 26.2 (10.2–36.4 [0–40]) cm. The 40‐cm radius measurement area was divided into 5‐cm‐wide zones to assess spread. At pouring heights of 15 cm and 20 cm, all zones were contaminated. These results demonstrate that pouring chlorhexidine into a gallipot generates significant splash, and we recommend that this should be avoided near equipment used for neuraxial anaesthesia.
Electrocardiographic Findings in Accessory Right Precordial Leads in Adults and Seniors with Notched S Waves in Lead V1—A Preliminary Study
Authors: Zhong‐qun Zhan , Nikus Kjell C. , Pérez‐Riera Andrés Ricardo , Chong‐quan Wang
Published: October 2013

Background

Atypical right bundle branch block (RBBB) may present with an rS pattern and notched S wave in lead V1. The notched S wave may represent slowed conduction or delayed activation of the right ventricular conduction system or ventricular myocardium.

Methods

We retrospectively analyzed the QRS patterns in accessory right precordial leads (from V3R to V5R) in 15 adults/senior individuals with notched S wave in lead V1.

Results

In the right accessory precordial leads, 13 showed triphasic QRS pattern with final R′ wave in their QRS complexes. This QRS pattern in association with notched S wave in lead V1 is suggestive of the presence of RBBB (incomplete or complete).

Conclusions

A notched S wave in lead V1 and in the right precordial accessory leads associated with a final R′ wave suggests the possibility of concealed RBBB (incomplete or complete).
Non‐surgical interventions for the management of type 2 dens fractures: a systematic review
Authors: Sime David , Pitt Veronica , Pattuwage Loyal , Tee Jin , Liew Susan , Gruen Russell
Published: October 2013

Background

Non‐surgical immobilization strategies for type 2 odontoid fractures vary considerably, with some surgeons preferring rigid collars, halothoracic bracing or the Minerva brace. Choice of device should be informed by the effectiveness in achieving union, whilst minimizing mortality and complications.

Objectives

Perform a systematic review evaluating the efficacy of non‐surgical interventions for type 2 odontoid fractures.

Data Sources

MEDLINE (OvidSP), EMBASE (OvidSP) and The Cochrane Library, ClinicalTrials.gov, Current Controlled Trials.

Methods

We conducted a systematic review of studies directly comparing the halothoracic brace and cervical collars or the Minerva brace for union, mortality and complications. Studies were appraised for quality and bias, and results were pooled for analysis.

Results

Our search identified 1794 citations, 13 of which met inclusion criteria. There were no randomized or prospective studies. All studies were small, retrospective and observational. Our results demonstrate a greater likelihood of developing stable union (osseous and fibrous); relative risk (RR) 1.27 (95% confidence intervals (CI) 1.03 to 1.57; P = 0.03); and airway complications; RR 7.52 (95% CI 1.39 to 40.83; P = 0.02) with halothoracic bracing compared with cervical collar. In patients >65, there was a greater risk of airway complications; RR 7.50 (0.96–58.36; P = 0.05). No other significant differences were identified.

Conclusion

Evidence to support selection of non‐surgical immobilization in type 2 odontoid fractures is poor. Osseous union has traditionally been the benchmark for ‘successful’ treatment; however, evidence of association between union and improved outcomes is lacking. We highlight the need for a randomized study to promote evidence‐based decision‐making in the non‐surgical management of this injury.
Developmental competence of oocytes isolated from surplus medulla tissue in connection with cryopreservation of ovarian tissue for fertility preservation
Authors: Wilken‐Jensen Helle N. , Kristensen Stine G. , Jeppesen Janni V. , Yding Andersen Claus
Published: October 2013

Objective

Evaluating the developmental competence of immature oocytes collected from surplus medulla tissue in connection with ovarian tissue cryopreservation for fertility preservation.

Design

Cohort comparative study.

Setting

University laboratory in Denmark from 2011–2012.

Population

69 girls and women (0–38 years of age) who each had one ovary cryopreserved for fertility preservation.

Methods

Ovaries were obtained directly from the local hospital or from collaborating hospitals (two to five hours' transport on ice). Immature oocytes were aspirated from large antral follicles visible on the ovaries, and collected from the saline solution, containing surplus medulla tissue, following dissection of the ovarian cortical tissue for cryopreservation. The immature oocytes were cultured for 48 h in an Embryoscope™ Time‐lapse System or in culture dishes overlaid with liquid paraffin using commercial and in‐house supplemented culture media.

Main outcome measures

Maturation rate for immature oocytes reaching metaphase II.

Results

With a maturation rate of 3.1%, only 21 of 682 immature oocytes reached metaphase II. Immature oocytes from ovaries that had been transported on ice for two to five hours performed significantly poorer than those recovered immediately after surgery. Addition of epidermal growth factor and follicle fluid from human small antral follicles to the culture medium did not augment the maturation rate. Immature oocytes cultured in the Embryoscope performed significantly better than those in conventional culture dishes.

Conclusions

In vitro maturation of immature oocytes should only be attempted clinically from visible antral follicles and where the ovary is not subjected to a cooling period prior to recovery of immature oocytes.
Intensity of menstrual pain and estimated angle of uterine flexion
Authors: Cagnacci Angelo , Grandi Giovanni , Cannoletta Marianna , Xholli Anjeza , Piacenti Ilaria , Volpe Annibale
Published: October 2013

Objective

To assess the impact of ultrasound‐estimated uterus position on the intensity of pelvic pain.

Design

Descriptive analytical study.

Setting

Tertiary university gynecology unit.

Population

181 consecutive patients with pelvic pain.

Methods

Each woman underwent physical examination, transvaginal sonography and filled self‐administered questionnaires on pain using a 10‐cm visual analog scale (VAS).

Main outcome measures

Visual analog scale score of menstrual pain, intermenstrual pain and dyspareunia was related to uterine version (ante‐ or retroversion) and the angle of uterine flexion (actual angle between cervix and uterine body) evaluated by transvaginal sonography.

Results

Estimated uterine version was not associated with the intensity of any type of pain. The estimated angle of flexion was higher in retroverted than in anteverted uteri (182.3° ± 50.3° vs. 142.3° ± 24.2°, p < 0.0001). Intensity of menstrual pain was lowest with flexion between 150° and 210° (4.9 ± 3.1) (p = 0.002), intermediate with flexion <150° (6.3 ± 2.8) and highest with flexion ≥210° (7.9 ± 2.3). Severe menstrual pain was more prevalent with flexion ≥210° (77.7%) than between 150° and 210° (31.4%; p = 0.0008) or <150° (45.2%; p = 0.005). The intensity of intermenstrual pain and dyspareunia were not associated with the angle of flexion. In multiple regression analysis, the angle of flexion was independently related only to the intensity of menstrual pain (r = 0.272; p = 0.002).

Conclusions

In women with pelvic pain, ultrasound‐estimated uterine flexion represents an independent risk for intense menstrual pain.
Exercise Performance of Chronic Heart Failure Patients in the Early Period of Support by an Axial‐Flow Left Ventricular Assist Device as Destination Therapy
Authors: Compostella Leonida , Russo Nicola , Setzu Tiziana , Compostella Caterina , Bellotto Fabio
Published: October 2013

Axial‐flow left ventricular assist devices (LVADs) are increasingly used as destination therapy in end‐stage chronic heart failure (CHF), as they improve survival and quality of life. Their effect on exercise tolerance in the early phase after implantation is still unclear. The aim of this study was to evaluate the effect of LVADs on the exercise capacity of a group of CHF patients within 2 months after initiation of circulatory support. Cardiopulmonary exercise test data were collected for 26 consecutive LVAD‐implanted CHF patients within 2 months of initiation of assistance; the reference group consisted of 30 CHF patients not supported by LVAD who were evaluated after an episode of acute heart failure. Both LVAD and reference groups showed poor physical performance; LVAD patients achieved lower workload (LVAD: 36.3 ± 9.0 W, reference: 56.6 ± 18.2 W, P < 0.001) but reached a similar peak oxygen uptake (peak VO2; LVAD: 12.5 ± 3.0 mL/kg/min, reference: 13.6 ± 2.9 mL/kg/min, P = ns) and similar percentages of predicted peak VO2 (LVAD: 48.8 ± 13.9%, reference: 54.2 ± 15.3%, P = ns). While the values of the O2 uptake efficiency slope were 12% poorer in LVAD patients than in reference patients (1124.2 ± 226.3 vs. 1280.2 ± 391.1; P = ns), the kinetics of VO2 recovery after exercise were slightly better in LVAD patients (LVAD: 212.5 ± 62.5, reference: 261.1 ± 80.2 sec, P < 0.05). In the first 2 months after initiation of circulatory support, axial‐flow LVAD patients are able to sustain a low‐intensity workload; though some cardiopulmonary exercise test parameters suggest persistence of a marked physical deconditioning, their cardiorespiratory performance is similar to that of less compromised CHF patients, possibly due to positive hemodynamic effects beginning to be produced by the assist device.
HeartWare Ventricular Assist Device as Bridge to Transplant in Children and Adolescents
Authors: Padalino Massimo A. , Bottio Tomaso , Tarzia Vincenzo , Bortolussi Giacomo , Cerutti Alessia , Vida Vladimiro L. , Gerosa Gino , Stellin Giovanni
Published: October 2013

Limited options do exist for mechanical circulatory support as a bridge to transplantation in the pediatric population. This is especially true when it comes to intracorporeal technologies. We describe our successful experience with the use of HeartWare ventricular assist devices (HeartWare, Inc., Framingham, MA, USA) in three patients <16 years of age, as a successful and feasible bridge to transplant in patients weighing greater than 20 kg.
Effective Use of Alteplase for Occluded Tunneled Venous Catheter in Hemodialysis Patients
Authors: Mendes Marcela L. , Castro João H. , Silva Tricya N. , Barretti Pasqual , Ponce Daniela
Published: October 2013

Despite their propensity for significant infectious and mechanical complications, tunneled central venous catheters (CVCs) have become a common means of vascular access in the world for patients requiring chronic hemodialysis for end‐stage renal disease. The objective of this study was to explore if cryopreserved solutions of the thrombolytic agent alteplase could be used as an effective, safe, and economically reasonable alternative in hemodialysis patients with occluded tunneled CVC. Patients requiring chronic hemodialysis and presenting with occluded tunneled CVC received a sufficient volume of the alteplase solution to fill the occluded catheter. To make alteplase economically feasible, it was diluted to 1‐mg/mL aliquots and they were stored at −20°C until use. Eighty‐one patients accounting for 179 attempted clearances were assessable for efficacy. One hundred forty‐seven (82.1%) of the 179 catheter clearance attempts resulted in successful catheter clearance after one dose. Twenty‐seven (15.1%) of all occluded CVCs were successful after two doses whereas five (2.8%) were not. No adverse events were reported. Cryopreserved 1‐mg/mL aliquots of alteplase are safe and effective in the clearance of occluded CVC for hemodialysis patients.
Quantitation of Fetal Heart Function With Tissue Doppler Velocity Imaging—Reference Values for Color Tissue Doppler Velocities and Comparison With Pulsed Wave Tissue Doppler Velocities
Authors: Saini Ashish P. , Ural Serdar , Pauliks Linda B.
Published: October 2013

Quantitative assessment of fetal heart function has been difficult. Increasingly, tissue Doppler imaging (TDI) is used to measure fetal cardiac function noninvasively. There are two principal techniques, spectral pulsed wave (PW) TDI and color TDI (CTDI). Published reference values for fetal myocardial velocities are based on spectral PW TDI only. However, previous phantom, adult, and animal studies have shown that PW TDI velocities are systematically higher than CTDI velocities. There are no fetal studies so far. We hypothesized that myocardial velocities derived by PW TDI and CTDI are significantly different in the fetus. This prospective observational study included 91 fetuses (gestational age 28.6 ± 6.6 weeks; range 19–40 weeks) seen for routine prenatal ultrasound. From apical 4‐chamber views, tricuspid ring (right ventricle), lateral and septal mitral ring were sampled by PW TDI and CTDI. Bland–Altman analysis was used for comparisons. PW and CTDI S′ velocities correlated strongly in all three cardiac segments (r = 0.6 to 0.9; P < 0.01). There was a systematic bias toward higher velocities with PW TDI versus CTDI (bias 0.96 cm/s; 95% CI 1.08–0.85 cm/s). However, the strength of the correlation and bias varied depending on the region of the fetal heart sampled. PW TDI and CTDI velocity measurements are feasible in the fetus and correlate well. However, PW TDI velocities are higher than CTDI velocities with significant regional variation. This precludes a mathematical conversion of PW to CTDI in vivo. As PW TDI and color TDI vary, different reference values for fetal CTDI velocities were generated.
Comparison of a new portable digital meniscometer and optical coherence tomography in tear meniscus radius measurement
Authors: Bandlitz Stefan , Purslow Christine , Murphy Paul J. , Pult Heiko
Published: October 2013

Purpose

Non‐invasive measurement of tear meniscus radius (TMR) is useful in the assessment of tear volume for dry eye diagnosis. This study investigates the agreement between a new, portable, slit‐lamp mounted, digital meniscometer (PDM) and optical coherence tomography (OCT) in the measurement of human TMR.

Methods

Images of the tear meniscus at the centre of the lower lid of 30 normal subjects (8M, 22F; mean age 27.5 SD ± 9.6 years) were taken using the PDM and the OCT. On the PDM and OCT images, TMR was measured using imagej 1.46b software. The meniscus on the OCT images was subdivided vertically into three equal sections and the radius calculated for each: bottom (BTMR), centre (CTMR) and top (TTMR). The relationship between PDM and OCT measurements was analysed using Spearman's rank coefficient, and differences between PDM and OCT subsection measurements were evaluated using Bland–Altman plots.

Results

Tear meniscus radius measured with the PDM (0.25 ± 0.06 mm) and OCT (0.29 ± 0.09 mm) was significantly correlated (r = 0.675; p < 0.001). The mean differences between TMR using the PDM and the subsections from OCT showed that TMR measured with PDM was greater for BTMR (0.07 mm; CI 0.05–0.10; p < 0.001), similar for CTMR (−0.01 mm; CI −0.04 to 0.02; p = 0.636) and steeper for TTMR (−0.07 mm; CI −0.10 to −0.04; p < 0.001).

Conclusions

Portable digital meniscometer and OCT measurements of the TMR are significantly correlated, suggesting that the new PDM is a useful surrogate for OCT in this respect. The PDM appears to measure the radius of the central section of the tear meniscus.
Using a safe taxi service to transport newborn babies home from hospital
Authors: Eventov‐Friedman S , Bar‐Oz B , Zisk‐Rony RY
Published: October 2013

Aim

To evaluate an intervention to enhance parents' use of car safety seats (CSSs) for their newborn baby's first journey home from the hospital in a population not usually exposed to television, internet and mainstream printed media.

Methods

Parents of newborn babies who did not bring a CSS to the hospital before their baby was discharged were lent a CSS to use in a ‘safe taxi’ service. All taxi drivers were trained to install the CSS safely. The intervention was evaluated using preprogramme questionnaires and follow‐up interviews 4–8 weeks after discharge.

Results

Twelve parents participated in the intervention during the study period (January to April 2011) and in the evaluation process. Eleven couples were Jewish and one was Muslim. Most (75%) reported that they had not previously used CSS routinely and the reason was not financial. Following the ‘safe taxi’ intervention, 83% reported the use of CSS when travelling in all vehicles (excluding buses). On follow‐up, most participants reported that the intervention increased their awareness and the use of CSS.

Conclusion

The intervention, targeted at this specific population, was well received by the parents, increased awareness, changed practices and assured that more newborns travelled home safely in a CSS.
Estimating reliable paediatric reference intervals in clinical chemistry and haematology
Authors: Ridefelt Peter , Hellberg Dan , Aldrimer Mattias , Gustafsson Jan
Published: October 2013

Very few high‐quality studies on paediatric reference intervals for general clinical chemistry and haematology analytes have been performed. Three recent prospective community‐based projects utilising blood samples from healthy children in Sweden, Denmark and Canada have substantially improved the situation.

Conclusion

The present review summarises current reference interval studies for common clinical chemistry and haematology analyses.
Review of insulin treatment in stress‐related hyperglycaemia in children without preexisting diabetes
Authors: Ng Sze May , Balmuri Sirisha
Published: October 2013

A systematic review was undertaken to assess the effect of using insulin therapy in the treatment for stress hyperglycaemia in children without preexisting diabetes in: achieving normoglycaemia, improving symptoms associated with hyperglycaemia and survival, and to determine if any adverse effects were associated with the use of insulin therapy.

Conclusion

There is currently insufficient evidence for the routine use of insulin therapy in stress hyperglycaemia compared with conventional care in children without preexisting diabetes.
White matter microstructure is influenced by extremely preterm birth and neonatal respiratory factors
Authors: Alexandrou Georgios , Mårtensson Gustaf , Skiöld Beatrice , Blennow Mats , Ådén Ulrika , Vollmer Brigitte
Published: October 2013

Aim

The aim of this study was to investigate whether prematurity per se or perinatal risk factors explain altered brain structure after preterm birth, in extremely preterm (EPT) infants without focal brain lesions.

Methods

A population‐based cohort of 58 EPT infants [gestational age (GA) <27 + 0 weeks] was examined with diffusion magnetic resonance imaging at term‐equivalent age and compared with 14 term‐born controls. Associations of diffusion measures with prematurity and neonatal risk factors were explored. Data were analysed with tract‐based spatial statistics (TBSS) for whole‐brain analysis and region‐of‐interest (ROI) analysis.

Results

Whole‐brain analyses showed lower fractional anisotropy (FA) and higher mean diffusivity (MD) in several white matter (WM) tracts in the preterms, which was essentially confirmed by ROI analyses. Within the preterm GA range (23 + 0 to 26 + 6 weeks), GA at birth was not significantly associated with diffusion measures. Bronchopulmonary dysplasia predicted lower FA in the corpus callosum and right inferior longitudinal fasciculus; mechanical ventilation >2 days was predictive of higher MD in the right external capsule.

Conclusion

White matter microstructure is influenced by preterm birth and by neonatal respiratory factors, whereas the degree of prematurity within the EPT range appears to be of less importance.
Early discontinuation of thyroxine therapy is possible in most very low‐birthweight infants with hypothyroidism detected by screening
Authors: Lim Gina , Lee Youn Kyung , Han Heon‐Seok
Published: October 2013

Aim

To determine the feasibility of discontinuing thyroid hormone treatment earlier than recommended by the current guidelines for congenital hypothyroidism.

Methods

We retrospectively reviewed the medical records of very low‐birthweight (VLBW) infants born at Chungbuk National University Hospital from January 2006 to December 2010. Infants were divided into two groups – hypothyroid and normal thyroid – on the basis of the thyroid function test results. Infants in the hypothyroid group were treated with levothyroxine (L‐T4) and attempts to discontinue this therapy began when they were about 2 years old.

Results

Of the 216 infants born during the study period, 20 died and 196 were included in the study. Of these, 46 were in the hypothyroid group and 150 were in the normal thyroid group. Thirty‐nine infants were taken off L‐T4 therapy at around 2 years of age. All were successfully weaned off L‐T4 and retained normal thyroid function. Tc‐99 m thyroid scans were performed in 32 infants, and no distinct abnormality was noted.

Conclusion

Thyroid dysfunction in VLBW infants was common in our cohort and most cases were transient. Attempts to discontinue this therapy could begin at around the age of two or earlier when low doses of L‐T4 have achieved maintenance.
Postoperative emesis after laparoscopic pyloromyotomy in infantile hypertrophic pyloric stenosis
Authors: Castellani C , Peschaut T , Schippinger M , Saxena AK
Published: October 2013

Aim

This study aimed to determine the causes of postoperative emesis (PE) in neonates with infantile hypertrophic pyloric stenosis (IHPS) after laparoscopic pyloromyotomy (LP).

Methods

Retrospective review of the hospital database for infants with IHPS managed between 2000 and 2010 was performed. Relevant data were collected from the clinical records in the Medocs® system and used for statistical analysis.

Results

During the 10‐year period, 95 patients with IHPS were identified and 43 (36 boys and seven girls) fulfilled the inclusion criteria. PE occurred in 21 infants (48.8%), of which nine presented with manifestations of enteric infections, with confirmed diagnosis in four. PE was significantly higher in the fast track feeding protocol (FTFP) group 12/15 compared with the conventional slow feeding protocol (CSFP) group 8/21 (p = 0.019). Gastro‐oesophageal reflux (GER) confirmed by 24‐h impedance monitoring was responsible for PE in three. Operative revision for suspected incomplete pyloromyotomy was performed in five infants. However, incomplete myotomy could only be confirmed in two infants during surgery.

Conclusion

Postoperative emesis in IHPS after LP requires careful evaluation as it can be a result of enteric viral infections, aggressive feeding protocols or GER. Decisions to perform reoperations for incomplete myotomy after LP due to PE are challenging.
The relationship between body growth and pulmonary function in children with cystic fibrosis
Authors: Woestenenk Janna W , Stellato Rebecca K , Terheggen−Lagro Suzanne W , van der Ent Cornelis K , Houwen Roderick HJ
Published: October 2013

Aim

To measure the weight and height of children with cystic fibrosis (CF) from 2 to 10 years of age and to investigate the relationship between these parameters and forced expiratory volume in 1 sec (FEV1) beginning at 6 years of age.

Methods

Weight and height were expressed as z‐scores for weight‐for‐age (WFA), height‐for‐age (HFA), height‐adjusted‐for‐target‐height (HFA/TH) and weight‐for‐height (WFH). The children were categorised as having a z−score ≥0, between 0 and −1, or <−1 based on z‐scores at 2 years of age. The cross‐sectional and longitudinal relationships between FEV1 and WFA, HFA, HFA/TH and WFH were determined and the predictive value of these parameters for FEV1.

Results

We enrolled 156 CF children. Their mean weight and height were below the average for the healthy population. Both WFA and WFH increased with age (primarily before the age of 6), while the reduction in HFA and HFA/TH persisted. Importantly, the yearly decline in FEV1 was significantly slowed [by 1.8 and 1.9% for each unit increase in WFA and WFH (p < 0.015)] in children who gained weight.

Conclusion

CF patients aged 2 to 10 years have long‐term impaired growth. Nevertheless, weight gain slowed the decline in FEV1 in these patients.
Lipotoxicity and the role of maternal nutrition
Authors: Pruis M. G. M. , van Ewijk P. A. , Schrauwen‐Hinderling V. B. , Plösch T.
Published: October 2013

Intrauterine malnutrition predisposes the offspring towards the development of type 2 diabetes and cardiovascular disease. To explain this association, the Developmental Origins of Health and Disease hypothesis was introduced, meaning that subtle environmental changes during embryonic and foetal development can influence post‐natal physiological functions. Different mechanisms, including epigenetics, are thought to be involved in this foetal programming, but the link between epigenetics and disease is missing. There is increasing evidence that ectopic lipid accumulation and/or lipotoxicity is induced by foetal programming. The aim of this review is to provide insights into the mechanisms underlying lipotoxicity through programming, which contributes to the increase in hepatic and cardiac metabolic risk.
Adenosine increases LPS‐induced nuclear factor kappa B activation in smooth muscle cells via an intracellular mechanism and modulates it via actions on adenosine receptors
Authors: Yang J. , Zheng X. , Haugen F. , Darè E. , Lövdahl C. , Schulte G. , Fredholm B. B. , Valen G.
Published: October 2013

Aim

In inflamed and damaged cardiovascular tissues, local extracellular adenosine concentrations increase coincidentally with activation of the transcription factor nuclear factor kappa B (NFκB). To investigate whether adenosine influences NFκB activation in vascular smooth muscle cells (VSMCs) and, if so, to examine the role of its receptors.

Methods

VSMCs were isolated from NFκB–luciferase reporter mice, cultured and then treated by lipopolysaccharide (LPS) to activate NFκB signalling. Adenosine, adenosine receptor agonists and antagonists, adenosine deaminase and uptake inhibitors were used together with LPS to evaluate the role of adenosine and its receptors on NFκB activation, which was assessed by luciferase activity and NFκB target gene expression.

Results

Adenosine potentiated LPS‐induced NFκB activation. This was dependent on adenosine uptake and enhanced by an adenosine deaminase inhibitor, suggesting that intracellular adenosine plays an important role. Non‐selective adenosine receptor agonists (2Cl‐Ado and NECA) inhibited NFκB activation induced by LPS. Selective A1 or A2A antagonist given alone could not completely antagonize the NECA effect, indicating that the inhibitory effect was due to multiple adenosine receptors. The activation of the A3 receptor further increased LPS‐induced NFκB activation.

Conclusions

Adenosine increases LPS‐induced nuclear factor kappa B activation in smooth muscle cells via an intracellular mechanism and decreases it via actions on A1 and A2A receptors. These results provide novel insights into the role of adenosine as a regulator of inflammation‐induced NFκB activation.
Autophagy is altered in skeletal and cardiac muscle of spontaneously hypertensive rats
Authors: Bloemberg D. , McDonald E. , Dulay D. , Quadrilatero J.
Published: October 2013

Aim

Autophagy is a subcellular degradation mechanism important for muscle maintenance. Hypertension induces well‐characterized pathological changes to the heart and is associated with impaired function and increased apoptotic signalling in skeletal muscle. We examined whether essential hypertension affects several autophagy markers in skeletal and cardiac muscle.

Methods

Immunoblotting and qRT‐PCR were used to measure autophagy‐related proteins/mRNA in multiple skeletal muscles as well as left ventricle (LV) of spontaneously hypertensive rats (SHR) and normotensive Wistar–Kyoto rats (WKY).

Results

Skeletal muscles of hypertensive rats had decreased (P < 0.01) cross‐sectional area of type I fibres (e.g. soleus WKY: 2952.9 ± 64.4 μm2 vs. SHR: 2579.9 ± 85.8 μm2) and a fibre redistribution towards a ‘fast’ phenotype. Immunoblot analysis revealed that some SHR skeletal muscles displayed a decreased LC3II/I ratio (P < 0.05), but none showed differences in p62 protein. LC3 and LAMP2 mRNA levels were increased approx. 2–3‐fold in all skeletal muscles (P < 0.05), while cathepsin activity, cathepsin L mRNA and Atg7 protein were increased 16–17% (P < 0.01), 2–3‐fold (P < 0.05) and 29–49% (P < 0.01), respectively, in fast muscles of hypertensive animals. Finally, protein levels of BAG3, a marker of chaperone‐assisted selective autophagy, were 18–25% lower (P < 0.05) in SHR skeletal muscles. In the LV of SHR, LC3I and p62 protein were elevated 34% (P < 0.05) and 47% (P < 0.01), respectively. Furthermore, p62 mRNA was 68% higher (P < 0.05), while LAMP2 mRNA was 45% lower (P < 0.05), in SHR cardiac muscle. There was no difference in Beclin1, Atg7, Bnip3 or BAG3 protein in the LV between strains.

Conclusion

These results suggest that autophagy is altered in skeletal and cardiac muscle during hypertension.
PPARγ activation inhibits cerebral arteriogenesis in the hypoperfused rat brain
Authors: Duelsner A. , Gatzke N. , Hillmeister P. , Glaser J. , Zietzer A. , Nagorka S. , Janke D. , Pfitzner J. , Stawowy P. , Meyborg H. , Urban D. , Bondke Persson A. , Buschmann I. R.
Published: October 2013

Aims

PPARγ stimulation improves cardiovascular (CV) risk factors, but without improving overall clinical outcomes. PPARγ agonists interfere with endothelial cell (EC), monocyte and smooth muscle cell (SMC) activation, function and proliferation, physiological processes critical for arterial collateral growth (arteriogenesis). We therefore assessed the effect of PPARγ stimulation on cerebral adaptive and therapeutic collateral growth.

Methods

In a rat model of adaptive cerebral arteriogenesis (3‐VO), collateral growth and function were assessed (i) in controls, (ii) after PPARγ stimulation (pioglitazone 2.8 mg kg−1; 10 mg kg−1 compared with metformin 62.2 mg kg−1 or sitagliptin 6.34 mg kg−1) for 21 days or (iii) after adding pioglitazone to G‐CSF (40 μg kg−1 every other day) to induce therapeutic arteriogenesis for 1 week. Pioglitazone effects on endothelial and SMC morphology and proliferation, monocyte activation and migration were studied.

Results

PPARγ stimulation decreased cerebrovascular collateral growth and recovery of hemodynamic reserve capacity (CVRC controls: 12 ± 7%; pio low: −2 ± 9%; pio high: 1 ± 7%; metformin: 9 ± 13%; sitagliptin: 11 ± 12%), counteracted G‐CSF‐induced therapeutic arteriogenesis and interfered with EC activation, SMC proliferation, monocyte activation and migration.

Conclusion

Pharmacologic PPARγ stimulation inhibits pro‐arteriogenic EC activation, monocyte function, SMC proliferation and thus adaptive as well as G‐CSF‐induced cerebral arteriogenesis. Further studies should evaluate whether this effect may underlie the CV risk associated with thiazolidinedione use in patients.
The adrenergic regulation of proximal tubular Na+/H+ exchanger 3 in the rat
Authors: Healy V. , Thompson C. , Johns E. J.
Published: October 2013

Aim

This study in the anaesthetized rat investigated how renal sympathetic nerve activity and catecholamine release influenced NHE3 abundance and activity in proximal tubular brush border membranes using both in vivo and in vitro approaches.

Methods

Renal excretory function and brush border NHE3 abundance and activity were measured in rat kidneys which underwent renal denervation, renal nerve electrical stimulation and renal infusion of phenylephrine and the NHE3 inhibitor S1661. NHE3 activity and cell surface abundance were also measured in primary cultures of proximal tubular cells treated with noradrenaline and prazosin.

Results

Acute renal denervation caused a natriuresis and diuresis, which occurred with a reduction in NHE3 abundance and activity in the brush border membranes. By contrast, low‐level electrical stimulation of the renal innervation causing an antinatriuresis and antidiuresis increased NHE3 activity in the brush border membranes. Intrarenal infusion of phenylephrine caused an antinatriuresis and antidiuresis, while blockade of NHE3 activity, using local infusion of the blocker S1661, caused a natriuresis and diuresis. Exposure of primary cultures of proximal tubular cells to noradrenaline increased brush border NHE3 abundance and activity which was blocked by prior exposure to prazosin, indicating it as an α1‐adrenoceptor‐mediated mechanism.

Conclusion

Together, these findings demonstrate that the renal sympathetic nerves not only have a direct action to modulate tubular sodium reabsorption via stimulation of the NHE transporter, but also have an indirect effect, whereby NHE3 abundance is increased within the brush border membrane, thereby increasing the capacity for fluid reabsorption.
A Brief Self‐Affirmation Study to Improve the Experience of Minority Patients
Authors: Burgess Diana J. , Taylor Brent C. , Phelan Sean , Spoont Michele , van Ryn Michelle , Hausmann Leslie R.M. , Do Tam , Gordon Howard S.
Published: October 2013

Background: There is evidence that Black patients may experience stereotype threat—apprehension about being negatively stereotyped—in healthcare settings, which might adversely affect their behavior in clinical encounters. Recent studies conducted outside of healthcare have shown that a brief self‐affirmation intervention, in which individuals are asked to focus on and affirm their valued characteristics and sources of personal pride, can reduce the negative effects of stereotype threat on academic performance and on interpersonal communication. Methods: This randomised controlled trial examined whether a self‐affirmation (SA) intervention would decrease the negative effects of stereotype threat (negative mood, lower state self‐esteem, greater perceptions of racial discrimination) and increase communication self‐efficacy among Black primary care patients. Self‐affirmation was induced by having patients complete a 32‐item values affirmation questionnaire. Results: Patients in the SA condition had lower levels of performance self‐esteem and social self‐esteem than patients in the control. There were no differences between the SA and the control groups on negative mood, communication self‐efficacy, and perceptions of discrimination. Conclusions: Our SA intervention lowered state self‐esteem among Black patients. Future research is needed to determine the type of SA task that is most effective for this population.
Physical Activity and Psychological Health in Breast Cancer Survivors: An Application of Basic Psychological Needs Theory
Authors: Mack Diane E. , Meldrum Lindsay S. , Wilson Philip M. , Sabiston Catherine M.
Published: October 2013

Objective: The role of psychological need satisfaction in terms of understanding the mechanisms through which leisure‐time physical activity (LTPA) is associated with psychological health in breast cancer survivors who have recently completed treatment was examined. Methods: Adopting a longitudinal two‐wave design, female breast cancer survivors (N = 144) completed self‐report instruments of LTPA, psychological need satisfaction, and psychological health at two points separated by 3 months. The first test administration period was 6 months following the completion of primary treatment. Results: Change score analyses demonstrated that greater LTPA across the 3‐month period was associated with greater perceptions of well‐being (rs ranged from .17 to .20) and lower ill‐being (rs ranged from −.06 to −.21). Results of multiple mediation analyses demonstrated that psychological need fulfillment underpinned the LTPA–well‐being relationship only. Conclusions: Collectively these findings indicate that increased engagement in LTPA represents one factor associated with greater psychological health in breast cancer survivors, with fulfilling the psychological need for relatedness most salient in understanding this relationship. Continued investigation into the mechanisms associated with reductions in ill‐being in breast cancer survivors appear justified.
Investigation of child maltreatment: Survey among junior school pupils in Henan province of China
Authors: Shen Lijuan , Zhang Yingli , Liang Wei , Zhang Yalin
Published: October 2013

Introduction

This study is to examine the prevalence of child maltreatment and its association with attachment and self‐esteem among junior schools students in Henan province of China.

Methods

Seven hundred thirty‐six pupils were selected from two public schools. Data were collected with the self‐reported questionnaires of the basic demographic information, the Revised Inventory of Parent and Peer Attachment, the Rosenberg Self‐Esteem Scale, and the Childhood Trauma Questionnaire. Data were analyzed using SPSS 17.0.

Result

In this study, the prevalence of emotional neglect, physical neglect, sexual abuse, emotional abuse, and physical abuse were 22.8%, 38.0%, 11.0%, 10.6%, and 7.1%, respectively. There was a significant difference between male and female pupils in the prevalence of the physical neglect (Pearson χ2 = 16.27, P < 0.01), sexual abuse (χ2 = 15.38, P < 0.01), and physical abuse (χ2 = 11.55, P < 0.01). In addition, physical neglect was the most common reported by pupils in the child maltreatment. Drinking habit of the mother was a significantly risk factor for emotional abuse, emotional neglect, and physical neglect.

Conclusion

Child abuse is still a severe social and psychological problem, and child neglect is more common than child abuse. It is noteworthy that mothers with drinking habit were more likely to abuse their own children than fathers with drinking habit.
Review article: the association of diet with onset and relapse in patients with inflammatory bowel disease
Authors: Spooren C. E. G. M. , Pierik M. J. , Zeegers M. P. , Feskens E. J. M. , Masclee A. A. M. , Jonkers D. M. A. E.
Published: October 2013

Background

The role of diet in inflammatory bowel disease (IBD) is supported by migration studies and increasing incidences in line with Westernisation.

Aim

To give a complete overview of studies associating habitual diet with the onset or relapses in ulcerative colitis (UC) or Crohn's disease (CD).

Methods

A structured search in Pubmed, the Cochrane Library and EMBASE was performed using defined key words, including only full text papers in English language.

Results

Forty‐one studies were identified, investigating onset (n = 35), relapses (n = 5) or both (n = 1). Several studies reported high intake of sugar or sugar‐containing foods (n = 7 UC, n = 12 CD), and low intake of fruits and/or vegetables (n = 5 UC, n = 10 CD) to be associated with an increased onset risk. However, these findings could not be confirmed by similar or higher numbers of other studies. A possible protective role was found for grain‐derived products in CD onset, but results were inconsistent for dietary fibre in UC and CD and grain‐derived products in UC. No definite conclusions could be drawn for unsaturated fatty acids (UFA), protein and energy intake due to limited and/or inconsistent results. Six studies reported on diet and relapse risk, of which only two (n = 1 UC, n = 1 CD) had a prospective follow‐up.

Conclusions

The current evidence is not sufficient to draw firm conclusions on the role of specific food components or nutrients in the aetiology of IBD. Furthermore, large prospective studies into the role of habitual diet as a trigger of relapses are needed, to identify new therapeutic or preventive targets.
A trial of mercaptopurine is a safe strategy in patients with inflammatory bowel disease intolerant to azathioprine: an observational study, systematic review and meta‐analysis
Authors: Kennedy N. A. , Rhatigan E. , Arnott I. D. R. , Noble C. L. , Shand A. G. , Satsangi J. , Lees C. W.
Published: October 2013

Background

Thiopurines maintain remission and modify disease course in inflammatory bowel disease. Use is limited by intolerance and subsequent drug withdrawal in approximately 17% of patients treated with azathioprine. Previous case series have addressed the success rates of re‐treatment with mercaptopurine in these individuals.

Aims

To determine the rate of tolerance when trialling mercaptopurine in azathioprine‐intolerant patients and the factors predictive of success, and to perform a systematic review and meta‐analysis of these data with other published data sets.

Methods

A retrospective observational study of 149 patients with IBD (82 with Crohn's disease and 67 with ulcerative colitis) previously intolerant of azathioprine subsequently treated with mercaptopurine was performed. A meta‐analysis was undertaken of all published studies of mercaptopurine use in azathioprine‐intolerant patients (455 patients in 11 included studies).

Results

Mercaptopurine was tolerated by 58% of azathioprine‐intolerant patients in the Edinburgh cohort. In the meta‐analysis, 68% tolerated mercaptopurine. A higher proportion of those in the meta‐analysis with GI toxicity (62%) or hepatotoxicity (81%) were able to tolerate mercaptopurine than those with flu‐like illness (36%). Among those patients who ceased mercaptopurine for further adverse effects, 59% experienced the same adverse effect as they had with azathioprine.

Conclusions

This meta‐analysis shows that switching to mercaptopurine is a safe therapeutic strategy for over two‐thirds of azathioprine‐intolerant patients and may help optimise immunomodulatory therapy in inflammatory bowel disease. A trial of mercaptopurine should be attempted in IBD patients (except those with acute pancreatitis or bone marrow aplasia) before considering thiopurine intolerance.
The outcome of patients with oesophageal eosinophilic infiltration after an eight‐week trial of a proton pump inhibitor
Authors: Vazquez‐Elizondo G. , Ngamruengphong S. , Khrisna M. , DeVault K. R. , Talley N. J. , Achem S. R.
Published: October 2013

Background

Current diagnostic guidelines recommend that eosinophilic oesophagitis (EoE) should be diagnosed only after GERD is excluded by a lack of response to a trial of acid suppression. There is limited information available providing outcome data about the effectiveness of this approach.

Aim

To examine the impact of double‐dose proton pump inhibitor (PPI) therapy on symptoms, endoscopic and histological features in patients with documented oesophageal eosinophilia consistent with EoE (≥15 eosinophils/high‐power field).

Methods

Sixty consecutive symptomatic patients with documented oesophageal eosinophilia received open‐label omeprazole 20 mg orally twice daily before meals for 8 weeks. Clinical, endoscopic and histological (resolution: 0–5 eosinophils/HPF, partial improvement: 5–14 eosinophils/HPF), or no improvement: (≥15 eosinophils/HPF) evaluation was repeated at the end of this period. An expert GI pathologist, unaware of the study aims, reviewed all slides.

Results

Clinical improvement occurred in 43 (71.6%), endoscopic signs were reduced in 34 (61.8%) and normalised in 12 (21.8%), and histologically, 34 (56.6%) improved, while 15 (25%) obtained complete resolution. Overall, 22 patients (36.7%) obtained both complete clinical and histological remission.

Conclusions

More than 50% of patients with documented oesophageal eosinophilic infiltration in the EoE range improved when treated with a double‐dose PPI trial for 8 weeks. These findings support the published guidelines recommending a PPI trial prior to diagnosing EoE, and confirm the existence of an eosinophilic oesophageal infiltrationPPI‐responsive population.
Fieldwork amid geographies of openness and closure
Authors: Mohammad Robina , Sidaway James D
Published: October 2013

This commentary on the set of papers on ‘Field methods in “closed contexts” ’ situates the papers within debates in geography about the interrelated politics, praxis and ethics of fieldwork across cultural, political and economic disjuncture and reflects on the geography of openness and closure.
Importance of Family Values Differences Between Husbands and Wives in Determining Depression in Foreign Wives in Korean Multicultural Families: Examining the Moderating Effect of Social Support
Authors: Won Seojin , Kim Hyemee
Published: October 2013

Differences in value systems are often grounds for conflict in relationships. This is particularly the case for international marriages where spouses hold potentially different family values. This study thus investigated the effect of family values differences between Korean husbands and foreign wives on depression of the wives. It also attempted to examine the moderating effect of family, friend, and formal support. Findings showed that family values differences affected the wives' depression and family support had a significant moderating effect. Researchers recommended that practitioners should be attentive to values differences between the spouses when working with multicultural families.