bluuebunny/crossref_metadata_2025 huggingface dataset:
Excitation and inhibition in recurrent networks mediate collision avoidance in Xenopus tadpoles
Authors: Khakhalin Arseny S. , Koren David , Gu Jenny , Xu Heng , Aizenman Carlos D.
Published: July 2014

Information processing in the vertebrate brain is thought to be mediated through distributed neural networks, but it is still unclear how sensory stimuli are encoded and detected by these networks, and what role synaptic inhibition plays in this process. Here we used a collision avoidance behavior in Xenopus tadpoles as a model for stimulus discrimination and recognition. We showed that the visual system of the tadpole is selective for behaviorally relevant looming stimuli, and that the detection of these stimuli first occurs in the optic tectum. By comparing visually guided behavior, optic nerve recordings, excitatory and inhibitory synaptic currents, and the spike output of tectal neurons, we showed that collision detection in the tadpole relies on the emergent properties of distributed recurrent networks within the tectum. We found that synaptic inhibition was temporally correlated with excitation, and did not actively sculpt stimulus selectivity, but rather it regulated the amount of integration between direct inputs from the retina and recurrent inputs from the tectum. Both pharmacological suppression and enhancement of synaptic inhibition disrupted emergent selectivity for looming stimuli. Taken together these findings suggested that, by regulating the amount of network activity, inhibition plays a critical role in maintaining selective sensitivity to behaviorally‐relevant visual stimuli.
A hybrid frequency–time domain method for predicting multiaxial fatigue life of 7075‐T6 aluminium alloy under random loading
Authors: Ge J. , Sun Y. , Zhou S. , Zhang L. , Zhang Y. , Zhang Q.
Published: July 2014

A hybrid frequency–time domain method for predicting multiaxial fatigue life under random loading is developed on the basis of combination of the frequency domain and time domain analysis. The critical damage point of the structure is determined by the frequency domain equivalent stress method. Then, the fatigue life prediction is made in time domain by generating random load‐time histories from the power spectral density of the critical point. The method is validated with the random vibration fatigue test of 7075‐T6 aluminium alloy. It has been shown that the results of fatigue life calculated by hybrid method are well correlated with the experiment.
miRNA in hepatocellular carcinoma
Authors: Morishita Asahiro , Masaki Tsutomu
Published: July 2014

Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. Despite improvements in HCC therapy, the prognosis for HCC patients remains poor due to a high incidence of recurrence. An improved understanding of the pathogenesis of HCC development would facilitate the development of more effective outcomes for the diagnosis and treatment of HCC at earlier stages. miRNA are small, endogenous, non‐coding, ssRNA that are 21–30 nucleotides in length and modulate the expression of various target genes at the post‐transcriptional and translational levels. Aberrant expression of miRNA is common in various human malignancies and modulates cancer‐associated genomic regions or fragile sites. As for the relationship between miRNA and HCC, several studies have demonstrated that the aberrant expression of specific miRNA can be detected in HCC cells and tissues. However, little is known about the mechanisms of miRNA‐related cell proliferation and development. In this review, we summarize the central and potential roles of miRNA in the pathogenesis of HCC and elucidate new possibilities that may be useful as diagnostic and prognostic markers, as well as novel therapeutic targets in HCC.
Radiofrequency ablation combined with chemolipiodolization in a porcine liver: Comparison of the pharmacokinetic analysis with cisplatin powder and miriplatin
Authors: Ito Tomoyasu , Okubo Hironao , Kokubu Shigehiro , Miyazaki Akihisa , Ando Hitoshi , Fujimura Akio , Watanabe Sumio
Published: July 2014

Aim

To compare the pharmacokinetics of radiofrequency (RF) ablation with chemolipiodolization using cisplatin (CDDP) powder and miriplatin (MPT) in a porcine liver.

Methods

Twelve pigs were divided equally into four groups. After each CDDP powder‐lipiodol suspension (n = 6; groups A and B) or MPT‐lipiodol suspension (n = 6; groups C and D) was injected into the lateral left artery, one RF ablation was performed at the lateral left lobe of each pig. Six pigs (groups A and C) were killed on the same day as treatment, whereas the other pigs (groups B and D) were killed 7 days after the treatment. The platinum concentrations in venous blood were assayed at 15, 60 and 120 min, and 7 days after treatment. The platinum concentrations in the ablated area and the surrounding liver were also examined.

Results

Plasma platinum concentrations of the CDDP group peaked at 15 min, and then gradually diminished over time (μg units), while plasma platinum levels in the MPT group gradually increased over time (ng units). Liver tissue platinum concentrations of the CDDP group were significantly lower in non‐ablative areas than in ablated areas at days 0 and 7, while liver concentrations of the MPT group were significantly higher in non‐ablative areas than in ablated areas at day 7.

Conclusion

MPT may be a suitable chemotherapeutic agent to stagnate platinum in the surrounding liver.
It's the talk: a study of involvement initiatives in secure mental health settings
Authors: McKeown Mick , Jones Fiona , Wright Karen , Spandler Helen , Wright Joanna , Fletcher Holly , Duxbury Joy , McVittie Jolene , Simon  , Turton Wayne
Published: July 2014

Background

A study of involvement initiatives within secure mental health services across oneUKregion, where these have been organized to reflect alliances between staff and service users. There is little previous relevant international research, but constraints upon effective involvement have been noted.

Objective

To explore and evaluate involvement initiatives in secure mental health settings.

Design

A case study design with thematic analysis of qualitative interviews and focus groups.

Setting and participants

Data collection was carried out between October 2011 and February 2012 with 139 staff and service users drawn from a variety of secure mental health settings.

Findings

Our analysis offers four broad themes, titled: safety and security first?; bringing it all back home; it picks you up; it's the talk. The quality of dialogue between staff and services users was deemed of prime importance. Features of secure environments could constrain communication, and the best examples of empowerment took place in non‐secure settings.

Discussion

Key aspects of communication and setting sustain involvement. These features are discussed with reference to Jurgen Habermas's work on communicative action and deliberative democracy.

Conclusions

Involvement initiatives with service users resident in secure hospitals can be organized to good effect and the active role of commissioners is crucial. Positive outcomes are optimized when care is taken over the social space where involvement takes place and the process of involvement is appreciated by participants. Concerns over risk management are influential in staff support. This is germane to innovative thinking about practice and policy in this field.
Achieving patient‐centred care: the potential and challenge of the patient‐as‐professional role
Authors: Phillips Rebecca L , Short Alison , Kenning Annie , Dugdale Paul , Nugus Peter , McGowan Russell , Greenfield David
Published: July 2014

Background

The patient‐as‐professional concept acknowledges the expert participation of patients in interprofessional teams, including their contributions to managing and coordinating their care. However, little is known about experiences and perspectives of these teams.

Objective

To investigate (i) patients’ and carers’ experiences of actively engaging in interprofessional care by enacting the patient‐as‐professional role and (ii) clinicians’ perspectives of this involvement.

Design, setting and participants

A two‐phased qualitative study. In Phase 1, people with chronic disease (n = 50) and their carers (n = 5) participated in interviews and focus groups. Phase 2 involved interviews with clinicians (n = 14). Data were analysed thematically.

Findings

Patients and carers described the characteristics of the role (knowing about the condition, questioning clinicians, coordinating care, using a support network, engaging an advocate and being proactive), as well as factors that influence its performance (the patient–clinician partnership, benefits, barriers and applicability). However, both patients and carers, and clinicians cautioned that not all patients might desire this level of involvement. Clinicians were also concerned that not all patients have the required knowledge for this role, and those who do are time‐consuming. When describing the inclusion of the patient‐as‐professional, clinicians highlighted the patient and clinician's roles, the importance of the clinician–patient relationship and ramifications of the role.

Conclusion

Support exists for the patient‐as‐professional role. The characteristics and influencing factors identified in this study could guide patient engagement with the interprofessional team and support clinicians to provide patient‐centred care. Recognition of the role has the potential to improve health‐care delivery by promoting patient‐centred care.
The impact of DECISION+2 on patient intention to engage in shared decision making: secondary analysis of a multicentre clustered randomized trial
Authors: Couët Nicolas , Labrecque Michel , Robitaille Hubert , Turcotte Stéphane , Légaré France
Published: July 2014

Background

Training health professionals in shared decision making (SDM) may influence their patients' intention to engage in SDM.

Objective

To assess the impact of DECISION+2, a SDM training programme for family physicians about the use of antibiotics to treat acute respiratory infections (ARIs), on their patients' intention to engage in SDM in future consultations.

Design

Secondary analysis of a multicentre clustered randomized trial.

Setting and participants

Three hundred and fifty‐nine patients consulting family physicians about an ARI in nine family practice teaching units (FPTUs).

Intervention

DECISION+2 (two‐hour online tutorial, two‐hour workshop, and decision support tools) was offered in the experimental group (five FPTUs, 162 physicians, 181 patients). Usual care was provided in the control group (four FPTUs, 108 physicians, 178 patients).

Outcome measure

Change in patients' intention scores (range −3 to +3) between pre‐ and post‐consultation.

Results

The mean ± SD [median] scores of intention to engage in SDM were high in both study groups before consultation (DECISION+2 group: 1.4 ± 1.0 [1.7]; control group: 1.5 ± 1.1 [1.7]) and increased in both groups after consultation (DECISION+2 group: 2.1 ± 1.1 [2.7]; control group: 1.9 ± 1.2 [2.3]). Change of intention, classified as either increased, stable or decreased, was not statistically associated with the exposure to the DECISION+2 programme after adjusting for the cluster design (proportional odds ratio = 1.5; 95% confidence interval = 0.8–3.0).

Conclusion

DECISION+2 had no significant impact on patients' intention to engage in SDM for choosing to use antibiotics or not to treat an ARI in future consultations. Patient‐targeted interventions may be necessary to achieve this purpose.
Residents with mild cognitive decline and family members report health students ‘enhance capacity of care’ and bring ‘a new breath of life’ in two aged care facilities in Tasmania
Authors: Elliott Kate‐Ellen J. , Annear Michael J. , Bell Erica J. , Palmer Andrew J. , Robinson Andrew L.
Published: July 2014

Background

Care provided by student doctors and nurses is well received by patients in hospital and primary care settings. Whether the same is true for aged care residents of nursing homes with mild cognitive decline and their family members is unknown.

Objective

To investigate the perspectives of aged care residents with mild cognitive decline and their family members on interdisciplinary student placements in two residential aged care facilities (RACF) in Tasmania.

Design, setting and participants

A mixed methods design was employed with both qualitative and quantitative data collected. All participants were interviewed and completed a questionnaire on residents' quality of life, during or after a period of student placements in each facility (October–November, 2012). Qualitative data were coded for themes following a grounded theory approach, and quantitative data were analysed using SPSS.

Results

Twenty‐one participants (13 residents and 8 family members) were recruited. Four themes were identified from the qualitative data and included (i) increased social interaction and facility vibrancy; (ii) community service and personal development, (iii) vulnerability and sensitivity (learning to care) and (iv) increased capacity and the confidence of enhanced care. Residents' quality of life was reported to be mostly good in the presence of the students, despite their high care needs.

Conclusion

Residents with mild cognitive decline and their family members perceive a wide array of benefits of student provided care in RACFs including increased social interaction. Future quantitative research should focus on whether changes in care occur for residents as a result of student involvement.
A pharmacy asthma service achieves a change in patient responses from increased awareness to taking responsibility for their asthma
Authors: Naik-Panvelkar Pradnya , Saini Bandana , LeMay Kate S , Emmerton Lynne M , Stewart Kay , Burton Deborah L , Bosnic-Anticevich Sinthia Z , Krass Ines , Smith Lorraine D , Armour Carol L
Published: July 2014

Objectives

If novel health services are to be implemented and sustained in practice, the perceptions and views of patients form a critical part of their evaluation. The aims of this study were to explore patient’s perceptions and experiences with a pharmacy asthma service and to investigate if there was a change over time.

Methods

Interviews and focus groups were conducted with patients participating in the asthma service at three time points. Data were transcribed verbatim and thematically analyzed using a framework approach.

Key findings

The service led to an enhanced awareness and understanding of asthma, changes in participants’ beliefs and attitudes towards asthma management, changes in asthma-related health behaviours and improved self-efficacy. Participants were very positive about the service and the role of the pharmacist in asthma management. There was a shift in participant perceptions and views, from being at an abstract level in those who had completed just one visit of the service to a more experiential level in those who had experienced the entire comprehensive asthma service.

Conclusions

A sustained experience/multiple visits in a service may lead to more concrete changes in patient perceptions of severity, beliefs, health behaviours and enhanced self-efficacy and control. The study highlights a need for such asthma services in the community.
Homeodomain‐interacting protein kinase (Hipk) phosphorylates the small SPOC family protein Spenito
Authors: Dewald D. N. , Steinmetz E. L. , Walldorf U.
Published: July 2014

The Drosophila homeodomain‐interacting protein kinase (Hipk) is a versatile regulator involved in a variety of pathways, such as Notch and Wingless signalling, thereby acting in processes including the promotion of eye development or control of cell numbers in the nervous system. In vertebrates, extensive studies have related its homologue HIPK2 to important roles in the control of p53‐mediated apoptosis and tumour suppression. Spenito (Nito) belongs to the group of small SPOC family proteins and has a role, amongst others, as a regulator of Wingless signalling downstream of Armadillo. In the present study, we show that both proteins have an enzyme–substrate relationship, adding a new interesting component to the broad range of Hipk interactions, and we map several phosphorylation sites of Nito. Furthermore, we were able to define a preliminary consensus motif for Hipk target sites, which will simplify the identification of new substrates of this kinase.
Rhabdomyolysis in association with simvastatin and dosage increment in clarithromycin
Authors: Page S. R. , Yee K. C.
Published: July 2014

Clarithromycin is the most documented cytochrome P450 3A4 (CYP3A4) inhibitor to cause an adverse interaction with simvastatin. This particular case is of interest as rhabdomyolysis only occurred after an increase in the dose of clarithromycin. The patient developed raised cardiac biomarkers without any obvious cardiac issues, a phenomenon that has been linked to rhabdomyolysis previously. To date, there has been no reported effect of rhabdomyolysis on the structure and function of cardiac muscle. Clinicians need to be aware of prescribing concomitant medications that increase the risk of myopathy or inhibit the CYP3A4 enzyme. Our case suggests that troponin elevation could be associated with statin induced rhabdomyolysis, which may warrant further studies.
Novel finding of carbamazepine induced gall bladder granulomatous vasculitis
Authors: Haddad R. , O'Brien B. , Evans J. , Orr C.
Published: July 2014

We report a 63‐year‐old male patient who presented with eosinophilic granulomatous vasculitis of the gall bladder secondary to carbamazepine drug therapy. Following commencement of carbamazepine for treatment of partial seizures, the patient developed an allergic cutaneous drug rash. He continued to take carbamazepine postdischarge despite cessation by the treating team. He represented 7 weeks later with acute pancreatitis and cholecystis. Gall bladder histopathology showed a granulomatous vasculitis.
Salt Preferences of Normotensive and Hypertensive Older Individuals
Authors: Villela Patrícia Teixeira Meirelles , de‐Oliveira Eduardo Borges , Villela Paula Teixeira Meirelles , Bonardi José Maria Thiago , Bertani Rodrigo Fenner , Moriguti Júlio Cesar , Ferriolli Eduardo , Lima Nereida Kilza da Costa
Published: July 2014

The aim of this study was to evaluate the preference for salt in hypertensive and normotensive older individuals. Hypertensive (group 1: n=32, aged 73.7±6.3 years) or normotensive patients (group 2: n=26, aged 71.5±8.0 years) were submitted to a test to determine their preference for bread samples with different salt concentrations: 1.5%, 2.0% (usual concentration), and 2.7%, and were reevaluated 2 weeks later using the same salt concentrations, but with the addition of oregano. Twenty‐four–hour urinary sodium excretion (UNaV), blood pressure (BP), and body mass index (BMI) were obtained. Systolic BP, BMI, and UNaV were higher in group 1. In the first analysis, group 1 showed greater preference for the saltiest sample (P=.001). Comparing the first evaluation and the second, a greater preference for less salty samples was observed in both groups (P<.01). Hypertensive older patients consumed more salt and showed a greater salt preference than the normotensive patients. The use of the spice reduced the preference for salt in both groups.
Commentary: The strength of multivariate twin studies: testing for shared and distinctive aetiology among different sets of behavioural traits – reflections on Lewis et al. (2014)
Authors: Boomsma Dorret I.
Published: July 2014

This contribution discusses the article by Lewis et al. on the relationship between variation in normal personality and adolescent behavioural problems and puts the study into the perspective of the value of twin studies of multivariate behavioural traits, which enable the analyses of genetic pleiotropy and causality.
Editorial: ‘What's up, (R)DoC?’ – can identifying core dimensions of early functioning help us understand, and then reduce, developmental risk for mental disorders?
Authors: Sonuga‐Barke Edmund J. S.
Published: July 2014

In the US the National Institute of Mental Health (NIMH), the main funder of mental health research in the world, has recently changed its funding model to promote a radically new perspective for mental health science. This bold, and for some controversial, initiative, termed the Research Diagnostic Criteria (or RDoC for short), intends to shift the focus of research, and eventually clinical practice, away from existing diagnostic categories, as recently updated in the DSM‐5, towards ‘new ways of classifying psychopathology based on dimensions of observable behavior and neurobiological measures.’ This reorientation from discrete categorical disorder manifestations to underlying cross‐cutting dimensions of individual functioning has generated considerable debate across the community of mental health researchers and clinicians (with strong views voiced both pro and con). Given its pivotal role in defining the research agenda globally, there is little doubt that this US science funding initiative will also have ramifications for researchers and clinicians worldwide. In this Editorial we focus specifically on the translational potential of the dimensional RDoC approach, properly extended to developmental models of early risk, in terms of its value as a potential driver of early intervention/prevention models; in the current issue of the JCPP this is exemplified by a number of papers thata address the mapping of underlying dimensions of core functioning to disorder risk, providing evidence for their potential predictive power as early markers of later disorder processes.
Micro‐evolution of the hepatitis B virus genome in hepatitis B e‐antigen‐positive carriers: Comparison of genotypes B and C at various immune stages
Authors: Liu Chun‐Jen , Chen Ting‐Chih , Chen Pei‐Jer , Wang Hurng‐Yi , Tseng Tai‐Chung , Cheng Huei‐Ru , Liu Chen‐Hua , Chen Ding‐Shinn , Kao Jia‐Horng
Published: July 2014

Background and Aim

Patients with hepatitis B virus (HBV) genotype B infection experience hepatitis B e‐antigen (HBeAg) seroconversion at an earlier stage than do patients with genotype C infection. Therefore, this study investigated whether the differential phenotypes are related to HBV genomic evolution.

Methods

Thirty‐three HBeAg‐positive patients with a mean follow‐up of 3.1 years were enrolled: 16 at the immune tolerance stage (group I) and 17 at the immune clearance stage (group II). The evolution rates of paired viral genomes at enrollment and at the final follow‐up in the full‐length genome (μf), nonoverlapping regions (synonymous [μs] and nonsynonymous [μa]), and overlapping regions (μ) were calculated. The evolution rates were then compared according to serum alanine aminotransferase (ALT) levels and HBV genotype.

Results

The overall μf evolution rate was lower in group I than in group II (1.4 × 10−5 ± 3.3 × 10−5 vs 1.2 × 10−3 ± 1.2 × 10−3 nucleotide substitution/site/year, P < 0.001). We observed similar results for the μs, μa, and μ evolution rates. All evolution parameters were comparable between genotypes B and C. We determined a positive correlation between μa/y and the area under the average ALT time curve in genotype B (R2 = 0.6935, P < 0.0001), but not in genotype C (R2 = 0.1606, P = 0.124).

Conclusion

The evolution rate of the HBV genome is higher at the immune clearance stage than at the immune tolerance stage. Host immune selection might play a role in triggering evolution of genotype B.
PNPLA3 gene polymorphism and response to lifestyle modification in patients with nonalcoholic fatty liver disease
Authors: Shen Jiayun , Wong Grace Lai‐Hung , Chan Henry Lik‐Yuen , Chan Ruth Suk‐Mei , Chan Hoi‐Yun , Chu Winnie Chiu‐Wing , Cheung Bernice Ho‐Ki , Yeung David Ka‐Wai , Li Liz Sin , Sea Mandy Man‐Mei , Woo Jean , Wong Vincent Wai‐Sun
Published: July 2014

Background and Aim

Lifestyle modification is the cornerstone for the management of nonalcoholic fatty liver disease (NAFLD), and patatin‐like phospholipase 3 (PNPLA3) is one of the most important genetic determinants of NAFLD. We aimed to investigate the effect of PNPLA3 gene polymorphism on the response to lifestyle modification in NAFLD patients.

Methods

This was a post‐hoc analysis of a randomized controlled trial on a lifestyle modification program in community NAFLD patients. The PNPLA3 rs738409 gene polymorphism was correlated with changes in metabolic profile and intrahepatic triglyceride content (IHTG) as measured by proton magnetic resonance spectroscopy.

Results

One hundred and fifty‐four patients were equally randomized into the intervention and control groups. The presence of G allele was associated with greater reduction in IHTG (CC: 3.7 ± 5.2%, CG: 6.5 ± 3.6%), and GG: 11.3 ± 8.8% (Spearman's correlation, 0.34; P = 0.002), body weight (P = 0.030), waist‐to‐hip ratio (P = 0.024), total cholesterol (P = 0.031), and low‐density lipoprotein cholesterol (P = 0.009) in the intervention group. In contrast, PNPLA3 polymorphism had no impact on IHTG changes in the control group. By multivariable analysis, PNPLA3 genotype and body mass index (BMI) change were independently associated with IHTG reduction in the intervention group. Only BMI change was associated with IHTG reduction in the control group.

Conclusion

Although the PNPLA3 rs738409 GG genotype confers a higher risk of NAFLD, these patients are more sensitive to the beneficial effects of lifestyle modification and should be encouraged to do so.
Clinical role of Notch signaling pathway in intraductal papillary mucinous neoplasm of the pancreas
Authors: Ikemoto Tetsuya , Sugimoto Koji , Shimada Mitsuo , Utsunomiya Tohru , Morine Yuji , Imura Satoru , Arakawa Yusuke , Kanamoto Mami , Iwahashi Shu‐ichi , Saito Yu , Yamada Shinichiro
Published: July 2014

Background and Aim

This study was performed to elucidate the expression of the Notch signaling pathway and its correlations to clinicopathological factors of intraductal papillary mucinous neoplasms (IPMNs). It is incontrovertible that regulatory T cells (Tregs) play an important role in tumor immunity. However, the whole mechanism of control of peripheral Tregs remains unclear. It is also known that the Notch signaling pathway is involved in Treg suppressor function. Moreover, IPMNs have a high malignant potential.

Methods

Peripheral blood samples and resected specimens from 18 patients with IPMN were evaluated. All patients were pathologically diagnosed with IPMN. Resected specimens were immunohistochemically evaluated (anti‐Notch1, anti‐Notch2, and anti‐Notch2‐intracellular domain antibody staining) and compared in terms of clinicopathological factors. Peripheral Treg populations were analyzed with an automated flow cytometer.

Results

Disease‐free survival was significantly worse in the Notch1 high‐expression group (P = 0.023). Notch2 family expressions were higher in intraductal papillary mucinous carcinoma (IPMC) than in intraductal papillary mucinous adenoma (IPMA) (Notch2, P = 0.012; Notch2‐intracellular domain, P = 0.036). Jagged1 expression was significantly higher in IPMC than in IPMA (P < 0.05) and was significantly related to recurrence. The Treg population in peripheral blood was higher in patients with IPMC than in those with IPMA (P < 0.01).

Conclusions

Notch signaling, especially Jagged1 expression, reflects IPMN aggressiveness. Our data may suggest that the Notch signaling pathway is a key pathway that determines IPMN pathological aggressiveness and reflects the peripheral Treg population.
Mosapride treatment for functional dyspepsia: A meta‐analysis
Authors: Bang Chang Seok , Kim Jong Hyeok , Baik Gwang Ho , Kim Hyo Sun , Park Sang Hyun , Kim Eun Jin , Kim Jin Bong , Suk Ki Tae , Yoon Jai Hoon , Kim Yeon Soo , Kim Dong Joon
Published: July 2014

Background and Aim

The aim of this study was to assess the therapeutic effect of mosapride in patients with functional dyspepsia (FD).

Methods

Randomized controlled trials (RCTs) of mosapride for the treatment of FD performed between 2002 and 2013 were identified from databases. Symptom response rates were extracted and analyzed using risk ratios (RRs). A random effect model was applied based on Higgins I2 tests. Publication bias was evaluated using a funnel plot, Egger's test, trim and fill, and the rank correlation test.

Results

In total, 13 RCTs, which included 1091 mosapride‐treated patients and 1129 control patients (on placebo or other drugs), were identified and analyzed. Overall, mosapride showed an RR of 0.999 (95% confidence interval [CI]: 0.869–1.150, P = 0.992) for improving global efficacy or symptom‐based scores. In a sensitivity analysis of the high‐quality RCTs, mosapride showed an RR of 1.114 (95% CI: 1.011–1.227, P = 0.029). However, in the studies using the Rome III criteria for the diagnosis of FD, mosapride showed an RR of 0.906 (95% CI: 0.807–1.016, P = 0.092). In the studies having funding source, mosapride showed an RR of 1.131 (95% CI: 1.028–1.244, P = 0.012), whereas an RR of 0.966 (95% CI: 0.896–1.042, P = 0.367) was observed in the studies without funding source. Publication bias was not detected.

Conclusion

In this analysis, we could not find a significant effect of mosapride on FD. Inconsistent diagnostic criteria for FD and different assessment outcomes are causes of heterogeneity. Further studies using common validated outcomes or questionnaires and high‐quality RCTs will elucidate the real effect of this medication on FD.
Use of proton pump inhibitors decrease cellular oxidative burst in patients with decompensated cirrhosis
Authors: Garcia‐Martinez Irma , Francés Rubén , Zapater Pedro , Giménez Paula , Gómez‐Hurtado Isabel , Moratalla Alba , Lozano‐Ruiz Beatriz , Bellot Pablo , González‐Navajas José M , Such José
Published: July 2014

Background and Aims

Proton pump inhibitors (PPIs) are commonly used antisecretory drugs and have been linked to an increased risk of bacterial infections in cirrhosis. We investigated whether the treatment with PPIs in cirrhosis affects the oxidative burst activity of granulocytes and monocytes and its possible interference with serum norfloxacin (Nflx) levels in these patients.

Methods

70 patients with cirrhosis and ascitic fluid and 24 healthy controls were included in the study and distributed into groups according to the regular use of PPIs and/or norfloxacin. The blood granulocyte and monocyte's phagocytic activity and oxidative burst were evaluated by flow cytometry. Blood levels of norfloxacin were measured by HPLC and bacterial translocation was evaluated by detection of bacterial DNA in blood.

Results

Use of PPIs was associated with a decreased granulocyte and monocyte oxidative burst, but not of phagocytic activity, as compared with patients not receiving PPIs. PPIs use did not affect serum norfloxacin levels in patients. A not significant trend to an increased bacterial DNA translocation was observed in patients receiving PPIs, including patients simultaneously receiving norfloxacin.

Conclusions

PPIs significantly decrease cellular oxidative burst in cirrhosis. This fact may provide a pathogenic explanation to the reported high rates of bacterial infections in this setting, and strongly suggests that PPIs should only be used in patients with cirrhosis when clinically indicated.
Impact of renal insufficiency on patients with hepatocellular carcinoma undergoing radiofrequency ablation
Authors: Chen Chuan‐Fu , Liu Po‐Hong , Lee Yun‐Hsuan , Tsai Ya‐Ju , Hsu Chia‐Yang , Huang Yi‐Hsiang , Chiou Yi‐You , Huo Teh‐Ia
Published: July 2014

Background and Aim

Renal insufficiency (RI) is commonly seen in patients with hepatocellular carcinoma (HCC). We aimed to investigate the impact of RI on the long‐term survival of HCC patients undergoing radiofrequency ablation (RFA) and to determine the optimal staging strategy for these patients.

Methods

RI was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m2. A total of 123 and 344 patients with and without RI undergoing RFA, respectively, were enrolled. A one‐to‐one propensity score matching analysis with preset caliper width was performed. The prognostic ability of four currently used staging systems was compared by the Akaike information criterion (AIC).

Results

HCC patients with RI undergoing RFA were older (P < 0.001) and had significantly different baseline characteristics. Of all patients, RI was significantly associated with a decreased long‐term survival (P = 0.03). After matching in the propensity model, the baseline characteristics were similar between patients with (n = 92) and without (n = 92) RI. In the propensity model, RI was not significantly associated with a shortened survival (P = 0.273). In the Cox multivariate analysis, Child‐Turcotte‐Pugh class B or C was identified as the only independent predictor of poor prognosis. Among patients with RI undergoing RFA, the Taipei Integrated Scoring (TIS) system provided the highest homogeneity and lowest AIC value among the currently used staging systems.

Conclusions

The long‐term survival of HCC patients undergoing RFA is not affected by RI. The TIS staging system may provide a better prognostic prediction for HCC patients with RI undergoing RFA.
Randomized, controlled pharmacokinetic and pharmacodynamic evaluation of albinterferon in patients with chronic hepatitis B infection
Authors: Colvin Richard A , Tanwandee Tawesak , Piratvisuth Teerha , Thongsawat Satawat , Hui Aric Josun , Zhang Hongfei , Ren Hong , Chen Pei‐Jer , Chuang Wan‐Long , Sobhonslidsuk Abhasnee , Li Ruobing , Qi Yin , Praestgaard Jens , Han Yi , Xu Junfang , Stein Daniel S ,   the ABF656A2206 Study Group
Published: July 2014

Background and Aims

Albinterferon is a fusion of albumin and interferon‐α2b developed to improve the pharmacokinetics, convenience, and potential efficacy of interferon‐α for the treatment of chronic hepatitis infections.

Methods

This open‐label, randomized, active‐controlled, multicenter study investigated the safety and efficacy of albinterferon in patients with chronic hepatitis B virus (HBV) infection who were e‐antigen (HBeAg) positive. One hundred and forty‐one patients received one of four albinterferon doses/regimens or pegylated‐interferon‐α2a. Primary efficacy outcomes were changes in serum HBeAg and antibody, HBV‐DNA, and alanine aminotransferase. Principal safety outcomes were changes in laboratory values, pulmonary function, and adverse events.

Results

The study was prematurely terminated as phase III trials in hepatitis C infection indicated noninferior efficacy but inferior safety compared with pegylated‐interferon‐α2a. Here, all treatment groups had a significant reduction in HBV‐DNA from baseline. Reductions in HBV‐DNA were not significantly different, except the 1200 μg every 4 weeks albinterferon dose which was inferior compared with pegylated‐interferon‐α2a. The serum alanine aminotransferase levels decreased in all arms. The per‐patient incidence of adverse events was not significantly different for albinterferon (96.4–100%) and pegylated‐interferon‐α2a (93.1%). Total adverse events, however, were higher for albinterferon and correlated to dose. Decreased lung function was found in all arms (∼93% of patients), and was more common in some albinterferon groups.

Conclusions

Albinterferon doses with similar anti‐HBV efficacy to pegylated‐interferon‐α2a had higher rates of certain adverse events, particularly changes in lung diffusion capacity (http://www.clinicaltrials.gov number NCT00964665).
Association of interleukin 28B polymorphism and mutations in the NS5A region of hepatitis C virus genotype 2 with interferon responsiveness
Authors: Hayashi Kazuhiko , Katano Yoshiaki , Ishizu Yoji , Kuzuya Teiji , Honda Takashi , Ishigami Masatoshi , Itoh Akihiro , Hirooka Yoshiki , Ishikawa Tetsuya , Nakano Isao , Yoshioka Kentaro , Toyoda Hidenori , Kumada Takashi , Goto Hidemi
Published: July 2014

Background and Aim

The single nucleotide polymorphism (SNP) of interleukin 28B (IL28B) and the mutations in the NS5A region of hepatitis C virus (HCV) genotype 1 have been associated with response to interferon (IFN) therapy. However, these relationships in patients with HCV genotype 2 are not well understood. The aim of this study was to investigate whether the SNP of IL28B (rs8099917) and amino acid substitutions in the NS5A region in patients with HCV genotype 2 affect the response to IFN and ribavirin combination therapy.

Methods

The study enrolled 286 patients with chronic hepatitis C genotype 2. Patients received pegylated‐IFN‐alpha 2b once each week plus oral ribavirin daily for 24 weeks.

Results

Of the 286 patients, 215 (75.2%) achieved sustained virologic response (SVR). Rate of SVR was similar in patients with IL28B TT allele (76%) and those with TG or GG alleles (72%). Patients with SVR were younger than those without SVR (P < 0.001). SVR was achieved in 65.9% of patients with wild‐type IFN sensitivity‐determining region (ISDR) and 83.5% of patients with mutant type (P < 0.001). There were no significant differences in other factors, including sex, alanine aminotransferase, platelet count, HCV viral load, HCV genotype, and IL28B genotype. The factors related to SVR on multivariate analysis were age (P = 0.019) and ISDR (P = 0.003).

Conclusions

ISDR sequence variations are significantly associated with IFN responsiveness in patients with HCV genotype 2. The SNP of IL28B was not associated with SVR in patients with HCV genotype 2.
K+ retention in leaf mesophyll, an overlooked component of salinity tolerance mechanism: A case study for barley
Authors: Wu Honghong , Zhu Min , Shabala Lana , Zhou Meixue , Shabala Sergey
Published: July 2014

Plant salinity tolerance is a physiologically complex trait, with numerous mechanisms contributing to it. In this work, we show that the ability of leaf mesophyll to retain K+ represents an important and essentially overlooked component of a salinity tolerance mechanism. The strong positive correlation between mesophyll K+ retention ability under saline conditions (quantified by the magnitude of NaCl‐induced K+ efflux from mesophyll) and the overall salinity tolerance (relative fresh weight and/or survival or damage under salinity stress) was found while screening 46 barley (Hordeum vulgare L.) genotypes contrasting in their salinity tolerance. Genotypes with intrinsically higher leaf K+ content under control conditions were found to possess better K+ retention ability under salinity and, hence, overall higher tolerance. Contrary to previous reports for barley roots, K+ retention in mesophyll was not associated with an increased H+‐pumping in tolerant varieties but instead correlated negatively with this trait. These findings are explained by the fact that increased H+ extrusion may be needed to charge balance the activity and provide the driving force for the high affinity HAK/KUP K+ transporters required to restore cytosolic K+ homeostasis in salt‐sensitive genotypes.
Genetics of Guillain‐Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP): current knowledge and future directions
Authors: Blum Stefan , McCombe Pamela A.
Published: July 2014

Abstract

Guillain‐Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are thought to be autoimmune diseases. There have been many attempts to find a human leukocyte antigen (HLA) association with GBS and CIDP with little success. There have been studies of other plausible genes in GBS and CIDP and the role of these genes in GBS and CIDP and the data from these genetic studies is reviewed. Some of the genes that have been studied are immune related and some others have nervous system effects. The studies are limited by small numbers. Some of the genes show association with disease severity rather than disease susceptibility. The need for more detailed molecular studies of the role of HLA molecules and the need for modern genetic approaches to GBS and CIDP are explained.
Normal variation in cortical osteocyte lacunar parameters in healthy young males
Authors: Carter Yasmin , Suchorab Jessica L. , Thomas C. David L. , Clement John G. , Cooper David M. L.
Published: July 2014

The most abundant cell in bone, osteocytes form an interconnected system upon which the regulation of healthy bone relies. Although the complete nature of the role of osteocytes has yet to be defined, they are generally accepted to play a part in the sensing of load and the initiation of damage repair. A previous study conducted by our group identified variation of up to 30% in osteocyte lacunar density and morphological parameters between regions of a single cross‐section of human femoral shaft; that study, however, was limited to a single individual. The aim of the current study was to determine whether this pattern consistently occurs in healthy young male femora. Anterior, posterior, medial and lateral blocks were prepared from the proximal femoral shaft of seven males and synchrotron radiation micro‐CT imaged. Average lacunar densities (± SD) from the anterior, posterior, medial and lateral regions were 23 394 ± 1705, 30 180 ± 4860, 35 946 ± 5990 and 29 678 ± 6081 lacunae per mm3 of bone tissue, respectively. These values were significantly different between the anterior and both the medial and posterior regions (P < 0.05). The density of the combined anterior and posterior regions was also significantly lower (P = 0.006) than the density of the combined medial and lateral regions. Although no difference was found in predominant orientation, shape differences were found; with the combined anterior‐posterior regions having lacunae that were significantly more elongated and less flat than the combined medial‐lateral values (P < 0.001). As expected, in this larger study, there was a dramatic difference in lacunar density between the medial and anterior region (up to ~ 54%). The study clearly demonstrates that the high variation seen in osteocyte lacunar density as well as other lacunar parameters, noted in a number of biomechanical, age and pathology studies, are well within the range of normal variation; however, the reasons for and consequences of this variation remain unclear. Lacunar parameters including abundance and shape are being increasingly incorporated into computational modeling of bone biology and this paper represents a more comprehensive description of normal healthy lacunae.
The loss of a shared lifetime: a qualitative study exploring spouses’ experiences of losing couplehood with their partner with dementia living in institutional care
Authors: Førsund Linn Hege , Skovdahl Kirsti , Kiik Riina , Ytrehus Siri
Published: July 2014

Aims and objectives

To explore and describe spouses’ experiences of losing couplehood with their dementia‐afflicted partner living in institutional care.

Background

Despite the losses and experiences of discontinuity due to the cognitive decline caused by dementia, the feelings of belonging and reciprocity in close relationships are still crucial to many couples. However, these experiences of spouses with partners living in institutional care are not well documented and are thus the focus of this study.

Design

A constructivist grounded theory approach was used to capture the relational processes described by the spouses.

Methods

Conversational interviews were conducted with n = 10 spouses of dementia‐afflicted persons living in institutional care. Data were analysed using the constant comparative method.

Results

The spouses’ experiences of losing couplehood were primarily connected to separation from the partner and the sense of being alone. They were also related to the loss of the shared past and future. However, these experiences did not seem to be constant; short glimpses of connectedness, reciprocity and interdependence contributed to a feeling of couplehood, although these were only momentary.

Conclusions

The spouses’ experiences of losing couplehood were dynamic and were related to the couple's entire life. The spouses wavered between senses of loss and belonging to couplehood, depending on the conditions characterising the moment.

Relevance to clinical practice

Healthcare personnel must recognise the severity of some spouses’ experiences of losing couplehood and be aware of how these experiences can fluctuate and be situation dependent.
Enterovirus 71 outbreak in Northern Sydney, 2013: Case series and initial response
Authors: Horsley Emily , Just E , Torres C , Huhtinen E , Forssman B , Slade R
Published: July 2014

Aim

Enteroviruses are a common cause of childhood disease which may manifest in a variety of ways. Enterovirus 71 (EV71) is a subtype of enterovirus which can cause meningoencephalomyelitis resulting in neurological sequelae including lethargy, weakness, ataxia, sleep myoclonus, urinary retention and, in severe cases, cardiorespiratory collapse due to neurogenic pulmonary oedema. EV71 was responsible for outbreaks in South East Asia in 1997–1998, in Western Australia in 1999 and in Sydney in 2000–2001. In 2013, we are experiencing another EV71 outbreak in Sydney. This study describes the discovery of a new outbreak in Sydney's Northern Beaches, the clinical findings as well as the public health response.

Methods

Thirty‐seven children in total presented with presumed EV71 to the Northern Beaches Health Service from December 2012 to April 2013. Most children presented with a prodrome lasting 2–7 days prior to seeking medical attention. Sleep myoclonus was a common presenting sign occurring in 65%. Neurological signs were subtle in the majority of children and were at times missed by clinicians on a child's first presentation. Forty‐six per cent of children who presented to Northern Beaches Health Service during this outbreak required a transfer to a tertiary paediatric centre for more intensive care.

Results

The public health investigation was important in establishing that the disease was widespread throughout the community and not as a result to exposure to a single child care setting. Identification of risk factors enabled more targeted communication to medical practitioners, child care centres and parents within the local community.

Conclusions

EV71 is in Australia and all clinicians seeing children in primary, secondary and tertiary care centres need to be aware of the disease, the subtle nature of initial symptoms and the potentially devastating consequences.
Driving habits and risk factors for traffic accidents among sleep apnea patients – a European multi‐centre cohort study
Authors: Karimi Mahssa , Hedner Jan , Lombardi Carolina , Mcnicholas Walter T. , Penzel Thomas , Riha Renata L. , Rodenstein Daniel , Grote Ludger ,   the Esada Study Group
Published: July 2014

Obstructive sleep apnea is associated with increased motor vehicle accident risk, and improved detection of patients at risk is of importance. The present study addresses potential risk factors in the European Sleep Apnea Database and includes patients with suspected obstructive sleep apnea [n = 8476, age 51.5 (12.5) years, body mass index 31.0 (6.6) kg m−2, 82.4% driver's licence holders]. Driving distance (km year−1), driver's licence type, sleep apnea severity, sleepiness and comorbidities were assessed. Previously validated risk factors for accident history: Epworth Sleepiness Scale ≥16; habitual sleep time ≤5 h; use of hypnotics; and driving ≥15 000 km year−1 were analysed across European regions. At least one risk factor was identified in male and female drivers, 68.75 and 51.3%, respectively. The occurrence of the risk factors was similar across Europe, with only a lower rate in the eastern region (P = 0.001). The mean number of risk factors increased across classes of sleep apnea severity. Frequent driving was prevalent [14.0 (interquartile range 8.0–20.0) × 103 km year−1] and 32.7% of drivers had severe obstructive sleep apnea [apnea–hypopnea index 50.3 (38.8–66.0) n h−1]. Obesity, shorter sleep time and younger age were associated with increased traffic exposure (P ≤ 0.03). In conclusion, the risk factors associated with accident history were common among European patients with suspected obstructive sleep apnea, but varied between geographical regions. There was a weak covariation between occurrence of risk factors and clinically determined apnea severity but frequent driving, a strong risk factor for accidents, was over‐represented. Systematic evaluation of accident‐related risk factors is important to detect sleep apnea patients at risk for motor vehicle accidents.