bluuebunny/crossref_metadata_2025 huggingface dataset:
Indications for intervention during active surveillance of prostate cancer: a comparison of the Johns Hopkins and Prostate Cancer Research International Active Surveillance (PRIAS) protocols
Authors: Kates Max , Tosoian Jeffrey J. , Trock Bruce J. , Feng Zhaoyong , Carter H. Ballentine , Partin Alan W.
Published: June 2014

Objective

To analyse how patients enrolled in our biopsy based surveillance programme would fare under the Prostate Cancer Research International Active Surveillance (PRIAS) protocol, which uses PSA kinetics.

Patients and Methods

Since 1995, 1125 men with very‐low‐risk prostate cancer have enrolled in the AS programme at the Johns Hopkins Hospital (JHH), which is based on monitoring with annual biopsy. The PRIAS protocol uses a combination of periodic biopsies (in years 1, 4, and 7) and prostate‐specific antigen doubling time (PSADT) to trigger intervention. Patients enrolled in the JHH AS programme were retrospectively reviewed to evaluate how the use of the PRIAS protocol would alter the timing and use of curative intervention.

Results

Over a median of 2.1 years of follow up, 38% of men in the JHH AS programme had biopsy reclassification. Of those, 62% were detected at biopsy intervals corresponding to the PRIAS criteria, while 16% were detected between scheduled PRIAS biopsies, resulting in a median delay in detection of 1.9 years. Of the 202 men with >5 years of follow‐up, 11% in the JHH programme were found to have biopsy reclassification after it would have been identified in the PRIAS protocol, resulting in a median delay of 4.7 years to reclassification. In all, 12% of patients who would have undergone immediate intervention under PRIAS due to abnormal PSA kinetics would never have undergone reclassification on the JHH protocol and thus would not have undergone definitive intervention.

Conclusions

There are clear differences between PSA kinetics‐based AS programmes and biopsy based programmes. Further studies should address whether and how the differences in timing of intervention impact subsequent disease progression and prostate cancer mortality.
Controlling the activation of the Bv8/prokineticin system reduces neuroinflammation and abolishes thermal and tactile hyperalgesia in neuropathic animals
Authors: Maftei D , Marconi V , Florenzano F , Giancotti L A , Castelli M , Moretti S , Borsani E , Rodella L F , Balboni G , Luongo L , Maione S , Sacerdote P , Negri L , Lattanzi R
Published: June 2014

Background and Purpose

Chemokines are involved in neuroinflammation and contribute to chronic pain processing. The new chemokine prokineticin 2 (PROK2) and its receptors (PKR1 and PKR2) have a role in inflammatory pain and immunomodulation. In the present study, we investigated the involvement of PROK2 and its receptors in neuropathic pain.

Experimental Approach

Effects of single, intrathecal, perineural and s.c. injections of the PKR antagonist PC1, or of 1 week s.c. treatment, on thermal hyperalgesia and tactile allodynia was evaluated in mice with chronic constriction of the sciatic nerve (CCI). Expression and localization of PROK2 and of its receptors at peripheral and central level was evaluated 10 days after CCI, following treatment for 1 week with saline or PC1. IL‐1β and IL‐10 levels, along with glia activation, were evaluated.

Key Results

Subcutaneous, intrathecal and perineural PC1 acutely abolished the CCI‐induced hyperalgesia and allodynia. At 10 days after CCI, PROK2 and its receptor PKR2 were up‐regulated in nociceptors, in Schwann cells and in activated astrocytes of the spinal cord. Therapeutic treatment with PC1 (s.c., 1 week) alleviated established thermal hyperalgesia and allodynia, reduced the injury‐induced overexpression of PROK2, significantly blunted nerve injury‐induced microgliosis and astrocyte activation in the spinal cord and restored the physiological levels of proinflammatory and anti‐inflammatory cytokines in periphery and in spinal cord.

Conclusion and Implications

The prokineticin system contributes to pain modulation via neuron–glia interaction. Sustained inhibition of the prokineticin system, at peripheral or central levels, blocked both pain symptoms and some events underlying disease progression.
PAR1‐dependent COX‐2/PGE2 production contributes to cell proliferation via EP2 receptors in primary human cardiomyocytes
Authors: Chien Peter Tzu‐Yu , Hsieh Hsi‐Lung , Chi Pei‐Ling , Yang Chuen‐Mao
Published: June 2014

Background and Purpose

Different protease‐activated receptors (PARs) activated by thrombin are involved in cardiovascular disease, via up‐regulation of inflammatory proteins including COX‐2. However, the mechanisms underlying thrombin‐regulated COX‐2 expression in human cardiomyocytes remain unclear.

Experimental Approach

Human cardiomyocytes were used in the study. Thrombin‐induced COX‐2 protein and mRNA expression, and signalling pathways were determined by Western blot, real‐time PCR and COX‐2 promoter luciferase reporter assays, and pharmacological inhibitors or siRNAs. PGE2 generation and cell proliferation were also determined.

Key Results

Thrombin‐induced COX‐2 protein and mRNA expression, promoter activity and PGE2 release was attenuated by the PAR1 antagonist (SCH79797) or the inhibitors of proteinase activity (PPACK), MEK1/2 (U0126), p38 MAPK (SB202190) or JNK1/2 (SP600125), and transfection with small interfering RNA (siRNA) of PAR1, p38, p42 or JNK2. These results suggested that PAR1‐dependent MAPKs participate in thrombin‐induced COX‐2 expression in human cardiomyocytes. Moreover, thrombin stimulated phosphorylation of MAPKs, which was attenuated by PPACK and SCH79797. Furthermore, thrombin‐induced COX‐2 expression was blocked by the inhibitors of AP‐1 (tanshinone IIA) and NF‐κB (helenalin). Moreover, thrombin‐stimulated phosphorylation of c‐Jun/AP‐1 and p65/NF‐κB was attenuated by tanshinone IIA and helenalin, respectively, suggesting that thrombin induces COX‐2 expression via PAR1/MAPKs/AP‐1 or the NF‐κB pathway. Functionally, thrombin increased human cardiomyocyte proliferation through the COX‐2/PGE2 system linking to EP2 receptors, as determined by proliferating cell nuclear antigen and cyclin D1 expression.

Conclusions and Implications

These findings demonstrate that MAPKs‐mediated activation of AP‐1/NF‐κB pathways is, at least in part, required for COX‐2/PGE2/EP2‐triggered cell proliferation in human cardiomyocytes.
Quercetin attenuates doxorubicin cardiotoxicity by modulating Bmi‐1 expression
Authors: Dong Qinghua , Chen Long , Lu Qunwei , Sharma Sherven , Li Lei , Morimoto Sachio , Wang Guanyu
Published: June 2014

Background and Purpose

Doxorubicin‐based chemotherapy induces cardiotoxicity, which limits its clinical application. We previously reported the protective effects of quercetin against doxorubicin‐induced hepatotoxicity. In this study, we tested the effects of quercetin on the expression of Bmi‐1, a protein regulating mitochondrial function and ROS generation, as a mechanism underlying quercetin‐mediated protection against doxorubicin‐induced cardiotoxicity.

Experimental Approach

Effects of quercetin on doxorubicin‐induced cardiotoxicity was evaluated using H9c2 cardiomyocytes and C57BL/6 mice. Changes in apoptosis, mitochondrial function, oxidative stress and related signalling were evaluated in H9c2 cells. Cardiac function, serum enzyme activity and reactive oxygen species (ROS) generation were measured in mice after a single injection of doxorubicin with or without quercetin pre‐treatment.

Key Results

In H9c2 cells, quercetin reduced doxorubicin‐induced apoptosis, mitochondrial dysfunction, ROS generation and DNA double‐strand breaks. The quercetin‐mediated protection against doxorubicin toxicity was characterized by decreased expression of Bid, p53 and oxidase (p47 and Nox1) and by increased expression of Bcl‐2 and Bmi‐1. Bmi‐1 siRNA abolished the protective effect of quercetin against doxorubicin‐induced toxicity in H9c2 cells. Furthermore, quercetin protected mice from doxorubicin‐induced cardiac dysfunction that was accompanied by reduced ROS levels and lipid peroxidation, but enhanced the expression of Bmi‐1 and anti‐oxidative superoxide dismutase.

Conclusions and Implications

Our results demonstrate that quercetin decreased doxorubicin‐induced cardiotoxicity in vitro and in vivo by reducing oxidative stress by up‐regulation of Bmi‐1 expression. The findings presented in this study have potential applications in preventing doxorubicin‐induced cardiomyopathy.
A novel 1,2‐benzenediamine derivative FC‐99 suppresses TLR3 expression and ameliorates disease symptoms in a mouse model of sepsis
Authors: Gong Wei , Hu Erling , Dou Huan , Song Yuxian , Yang Liu , Ji Jianjian , Li Erguang , Tan Renxiang , Hou Yayi
Published: June 2014

Background and Purpose

Sepsis is a clinical condition characterized by overwhelming systemic inflammation with high mortality rate and high prevalence, but effective treatment is still lacking. Toll‐like receptor 3 (TLR3) is an endogenous sensor, thought to regulate the amplification of immune response during sepsis. Modulators of TLR3 have an advantage in the treatment of sepsis. Here, we aimed to explore the mechanism of a monosubstituted 1,2‐benzenediamine derivative FC‐99 {N1‐[(4‐methoxy)methyl]‐4‐methyl‐1,2‐benzenediamine}on modulating TLR3 expression and its therapeutic potential on mouse model of sepsis.

Experimental Approach

Cells were pretreated with FC‐99 followed by poly(I:C) or IFN‐α stimulation; TLR3 and other indicators were assayed. Female C57BL/6 mice were subjected to sham or caecal ligation puncture (CLP) surgery after i.p. injection of vehicle or FC‐99; serum and tissues were collected for further experiments.

Key Results

FC‐99 suppressed inflammatory response induced by poly(I:C) with no effect on cell viability or uptake of poly(I:C). FC‐99 also inhibited TLR3 expression induced by not only poly(I:C) but also by exogenous IFN‐α. This inhibition of FC‐99 was related to the poly(I:C)‐evoked IRF3/IFN‐α/JAK/STAT1 signalling pathway. In CLP‐induced model of sepsis, FC‐99 administration decreased mice mortality and serum levels of inflammatory factors, attenuated multiple organ dysfunction and enhanced bacterial clearance. Accordingly, systemic and local expression of TLR3 was reduced by FC‐99 in vivo.

Conclusion and Implications

FC‐99 reversed TLR3 expression and ameliorate CLP‐induced sepsis in mice. Thus, FC‐99 will be a potential therapeutic candidate for sepsis.
Invisible populations: LGBTQ people and federal health policy in Canada
Authors: Mulé Nick J. , Smith Miriam
Published: June 2014

This article reviews the state of federal health policy discourse toward the LGBTQ population in Canada. Despite the advent of greater attention to diversity and gender mainstreaming in federal public policy and the shift to legalized rights protections for LGBTQ people, symbolized by policies such as same‐sex marriage, LGBTQ health concerns continue to be marginalized in federal health policy. Based on a systematic review of federal policy documents and websites as well as a small number of interviews with federal policy‐makers, the research demonstrates the extent to which LGBTQ health concerns are rendered invisible in federal health policy. The article suggests several ways in which a commitment to gender‐based policy analysis could be expanded to take account of diverse health needs of LGBTQ Canadians.
Design, Synthesis and Evaluation of Rhodanine Derivatives as Aldose Reductase Inhibitors
Authors: Agrawal Yogesh P. , Agrawal Mona Y. , Gupta Arun K.
Published: June 2014

Aldose reductase (ALR) enzyme plays a significant role in conversion of excess amount of glucose into sorbitol in diabetic condition, inhibitors of which decrease the secondary complication of diabetes mellitus. To understand the structural interaction of inhibitors with ALR enzyme and develop more effective ALR inhibitors, a series of substituted 5‐phenylbenzoate containing N‐substituted rhodanine derivatives were synthesized and evaluated for their in vitro ALR inhibitory activity. Docking studies of these compounds were carried out, which revealed that the 5‐phenylbenzoate moiety deeply influenced the key π‐π stacking while 4‐oxo‐2‐thioxothiazolidines contributed in hydrogen bond interactions. The phenyl ring of benzylidene system occupied in specific pocket constituted from Phe115, Phe122, Leu300 and Cys303 while the rhodanine ring forms a tight net of hydrogen bond with Val47 at anionic binding site of the enzyme. The structural insights obtained from the docking study gave better understanding of rhodanine and macromolecular interaction and will help us in further designing and improving of ALR inhibitory activity of rhodanine analogs.
The protein tyrosine phosphatase PTPN22 controls forkhead box protein 3 T regulatory cell induction but is dispensable for T helper type 1 cell polarization
Authors: Fousteri G , Jofra T , Debernardis I , Stanford S M , Laurenzi A , Bottini N , Battaglia M
Published: June 2014

Protein tyrosine phosphatases (PTPs) regulate T cell receptor (TCR) signalling and thus have a role in T cell differentiation. Here we tested whether the autoimmune predisposing gene PTPN22 encoding for a PTP that inhibits TCR signalling affects the generation of forkhead box protein 3 (FoxP3)+ T regulatory (Treg) cells and T helper type 1 (Th1) cells. Murine CD4+ T cells isolated from Ptpn22 knock-out (Ptpn22  KO) mice cultured in Treg cell polarizing conditions showed increased sensitivity to TCR activation compared to wild-type (WT) cells, and subsequently reduced FoxP3 expression at optimal-to-high levels of activation. However, at lower levels of TCR activation, Ptpn22  KO CD4+ T cells showed enhanced expression of FoxP3. Similar experiments in humans revealed that at optimal levels of TCR activation PTPN22 knock-down by specific oligonucleotides compromises the differentiation of naive CD4+ T cells into Treg cells. Notably, in vivo Treg cell conversion experiments in mice showed delayed kinetic but overall increased frequency and number of Treg cells in the absence of Ptpn22. In contrast, the in vitro and in vivo generation of Th1 cells was comparable between WT and Ptpn22  KO mice, thus suggesting PTPN22 as a FoxP3-specific regulating factor. Together, these results propose PTPN22 as a key factor in setting the proper threshold for FoxP3+ Treg cell differentiation.
Twelve‐Year Retrospective Follow‐Up of Machined Implants in the Posterior Maxilla: Radiographic and Peri‐Implant Outcome
Authors: Simion Massimo , Gionso Luca , Grossi Giovanni Battista , Briguglio Francesco , Fontana Filippo
Published: June 2014

Purpose

To retrospectively evaluate the survival rate of machined implants in sinus‐lifted posterior maxilla after 12 years, with special reference to radiographic outcome and peri‐implantitis.

Materials and Methods

From 37 possible candidates, 29 patients with 59 implants were evaluated. Implants were placed in the posterior maxilla in combination with a sinus elevation procedure (27 patients) or 6 months after sinus elevation (2 patients). Marginal bone level changes were radiographically evaluated at baseline and 1, 7, and 12 years post‐loading. Probing depth was measured; presence/absence of plaque and bleeding on probing were recorded.

Results

Four out of 59 implants failed in 4 out of 29 patients (cumulative survival rate = 93.2%). The mean bone loss was 0.78 mm (± 0.88) after 12 years. Changes in the mean bone level were statistically significant between baseline and all the other follow‐up intervals (p < .001). Statistically significant differences could be demonstrated for the first‐ to 12th‐year interval (p < .05) and for the seventh‐ to 12th‐year interval (p < 0.001). No statistically significant differences could be demonstrated at the first‐ to seventh‐year interval (p = .32). The mean overall probing depth was 2.9 ± 0.66 mm. Probing depth was moderately correlated with the marginal bone changes at 7 year and after 12 year follow up (p = .05). No signs of peri‐implantitis were reported during the 12‐year follow‐up period.

Conclusions

This follow‐up demonstrates a very good prognosis when implants with machined surfaces are used. The frequencies of implant failures were very small. Within the limits of the results from this study, the risk of peri‐implantitis in the posterior maxilla might be considered a minor problem when implants with machined surfaces are used.
MicroRNAs as oncogenes or tumour suppressors in oesophageal cancer: potential biomarkers and therapeutic targets
Authors: Huang J. , Zhang S.‐Y. , Gao Y.‐M. , Liu Y.‐F. , Liu Y.‐B. , Zhao Z.‐G. , Yang K.
Published: June 2014

MicroRNAs are a class of small, non‐coding RNAs that can negatively regulate protein‐coding genes, and are associated with almost all known physiological and pathological processes, especially cancer. The number of studies documenting miRNA expression patterns in malignancy continues to expand rapidly, with continuously gained critical information regarding how aberrantly expressed miRNAs may contribute to carcinogenesis. miRNAs can influence cancer pathogenesis, playing a potential role as either oncogenes or tumour suppressors. Recently, several miRNAs have been reported to exert different regulatory functions in oesophageal cancer – the carcinoma typically arising from the epithelial lining of the oesophagus. These miRNAs also have potential clinical applications towards developing biomarkers or targets for possible use in diagnosis or therapy in oesophageal cancer. In this review, we have summarized the two (oncogenic or tumour suppressive) roles of miRNAs here, and their applications as potential biomarkers or therapeutic targets, which may illuminate future treatment for oesophageal cancer.
Association of COPD exacerbation frequency with gene expression of pattern recognition receptors in inflammatory cells in induced sputum
Authors: Kinose Daisuke , Ogawa Emiko , Kudo Megumi , Marumo Satoshi , Kiyokawa Hirofumi , Hoshino Yuma , Hirai Toyohiro , Chin Kazuo , Muro Shigeo , Mishima Michiaki
Published: June 2014

Background

Bacteria and viruses are major causes of chronic obstructive pulmonary disease (COPD) exacerbations. Molecular components of these pathogens are recognized by pattern‐recognition receptors (PRRs) expressed by various cells in the airway, which leads to initiation of inflammatory processes. Expression levels of PRRs in airway inflammatory cells are expected to affect susceptibility to COPD exacerbation.

Aims

This prospective observational study was conducted to detect any association between exacerbation and PRR expression.

Methods

Thirty‐one male COPD patients were recruited. At baseline, clinical history, lung function measurements, peripheral blood samples and induced sputum were obtained. Using sputum samples, we performed gene expression analysis of TLR2, TLR3, TLR4, NOD1, NOD2, RIG‐I and MDA‐5 by quantitative reverse transcription‐polymerase chain reaction in addition to quantitative bacterial culture. COPD exacerbations were assessed based on Anthonisen's criteria using symptom diaries for the following 1‐year period.

Results

During 1‐year follow‐up period, 13 patients experienced at least one exacerbation, but 18 patients did not. Those with exacerbations tended to be more severe COPD and showed larger neutrophil fraction in their induced sputum. Among PRRs, only TLR3 gene expression was increased in COPD patients with exacerbation compared with those without exacerbations. Multivariate logistic regression analysis including neutrophil fraction and TLR3 gene expression as predictor variables demonstrated that only an increase of neutrophil fraction, but not TLR3 gene expression, was a significant predictor for COPD exacerbation.

Conclusion

TLR3 expression in inflammatory cells might affect the susceptibility to COPD exacerbation.
Dedicated ‘cannabis only’ treatment clinics in New South Wales, Australia: Client and treatment characteristics and associations with first‐time treatment seeking
Authors: Copeland Jan , Allsop David
Published: June 2014

Introduction and Aims

Over the past decade, there has been significant investment in dedicated cannabis‐only treatment clinics in New South Wales. This study aims to describe the characteristics of clients and compares first‐time treatment seeking history and treatment completion rates between dedicated and non‐dedicated clinics.

Design and Methods

An observational study of administrative information from 209 012 drug and alcohol treatment episodes from services reporting to the New South Wales Alcohol and Other Drug Treatment Services Minimum Dataset, July 2003–June 2008.

Results

Across all episodes, cannabis was the second most prevalent primary drug of concern (17.8%, n = 37 242). The majority of clients primarily seeking treatment for cannabis were male (69.4%, 26 088), with a mean age of 29 years. Counselling was the most common cannabis treatment (34.1%, n = 12 713), with 11.6% (n = 1476) of those receiving counselling having done so at a cannabis clinic. Those treated in cannabis clinics were older (30.12 years vs. 27.95 years; P < 0.0001); had shorter episode durations (10.95 weeks vs. 12.71 weeks; P < 0.0001); and were more likely to be naïve to treatment (53.7% vs. 47.7%; P < 0.0001). Indigenous Australian treatment seekers were more likely to complete cannabis treatment in a dedicated cannabis clinic (49.6%) than in a non‐dedicated clinic (40.5%; P < 0.05).

Discussion and Conclusion

Cannabis clinics have attracted groups traditionally difficult to attract and retain in treatment. As the cohort of daily cannabis users age, it is important that service models are attractive to older clients, new to treatment. Rigorous, prospective research examining client treatment outcomes are now warranted. [Copeland J, Allsop D. Dedicated ‘cannabis only’ treatment clinics in New South Wales, Australia: Client and treatment characteristics and associations with first‐time treatment seeking. Drug Alcohol Rev 2014;33:565–71]
General overview of the disaster management framework in Cameroon
Authors: Bang Henry Ngenyam
Published: June 2014

Efficient and effective disaster management will prevent many hazardous events from becoming disasters. This paper constitutes the most comprehensive document on the natural disaster management framework of Cameroon. It reviews critically disaster management in Cameroon, examining the various legislative, institutional, and administrative frameworks that help to facilitate the process. Furthermore, it illuminates the vital role that disaster managers at the national, regional, and local level play to ease the process. Using empirical data, the study analyses the efficiency and effectiveness of the actions of disaster managers. Its findings reveal inadequate disaster management policies, poor coordination between disaster management institutions at the national level, the lack of trained disaster managers, a skewed disaster management system, and a top‐down hierarchical structure within Cameroon's disaster management framework. By scrutinising the disaster management framework of the country, policy recommendations based on the research findings are made on the institutional and administrative frameworks.
Cyclone shelters and their locational suitability: an empirical analysis from coastal Bangladesh
Authors: Mallick Bishawjit
Published: June 2014

Bangladesh is one of the poorest and the most disaster‐prone countries in Asia; it is important, therefore, to know how its disaster reduction strategies are organised and planned. Cyclone shelters comprise a widely acceptable form of infrastructural support for disaster management in Bangladesh. This paper attempts to analyse empirically their use during cyclones in a sample study area along the southwest coastal belt of the country. It shows how the location of a cyclone shelter can determine the social power structure in coastal Bangladesh. The results reveal that the establishment of cyclone shelters in the studied communities is determined by neither a right‐based nor a demand‐based planning approach; rather, their creation is dependent on the socio‐political affluence of local‐level decision‐makers. The paper goes on to demonstrate that socially vulnerable households (defined, for example, by income or housing conditions) are afforded disproportionately less access to cyclone shelters as compared to less socially vulnerable households.
Social dimensions of science–humanitarian collaboration: lessons from Padang, Sumatra, Indonesia
Authors: Shannon Rachel , Hope Max , McCloskey John , Crowley Dominic , Crichton Peter
Published: June 2014

This paper contains a critical exploration of the social dimensions of the science–humanitarian relationship. Drawing on literature on the social role of science and on the social dimensions of humanitarian practice, it analyses a science–humanitarian partnership for disaster risk reduction (DRR) in Padang, Sumatra, Indonesia, an area threatened by tsunamigenic earthquakes. The paper draws on findings from case study research that was conducted between 2010 and 2011. The case study illustrates the social processes that enabled and hindered collaboration between the two spheres, including the informal partnership of local people and scientists that led to the co‐production of earthquake and tsunami DRR and limited organisational capacity and support in relation to knowledge exchange. The paper reflects on the implications of these findings for science–humanitarian partnering in general, and it assesses the value of using a social dimensions approach to understand scientific and humanitarian dialogue.
Attitude before method: disability in vulnerability and capacity assessment
Authors: Twigg John
Published: June 2014

Many agencies working on disaster risk reduction use vulnerability and capacity assessment (VCA) to identify vulnerable groups, to assess their needs and capacities, and to develop appropriate programmes and policies. In theory, VCA offers a good opportunity to incorporate disabled people's needs and resources in counter‐disaster programming. This paper seeks to establish and explain the extent to which disability is included in VCA in practice. It reviews VCA reports and findings, formal VCA guidance, and other methodological literature. The review indicates that disability is a neglected issue in VCA practice and that manuals and guidelines, while promoting the general ideal of inclusiveness, are insufficiently aware of the challenges to achieving this in practice and do not offer enough guidance on how to reach and include disabled people. Ways of overcoming these problems are suggested. However, the real challenge may be to change core attitudes and perceptions of disability within implementing organisations.
Parenting in Fukushima City in the post‐disaster period: short‐term strategies and long‐term perspectives
Authors: Goto Aya , Reich Michael R. , Suzuki Yuriko , Tsutomi Hiroshi , Watanabe Eiko , Yasumura Seiji
Published: June 2014

Growing evidence indicates the adverse psychological and welfare consequences of nuclear power accidents particularly among parents of small children. However, little has been published about the public health experiences of and practical countermeasures to deal with such consequences for parents of small children in the aftermath of disasters. Based on our past research efforts to develop parenting support programmes in Fukushima City, we describe here the discussions and resulting strategies that developed from collaborative efforts between university researchers and public health nurses after the Fukushima nuclear plant accident caused by the Great East Japan Earthquake. The processes presented here may be useful to improve national and international preparedness to protect the health of parents and children in future nuclear disasters.
Multi‐level functionality of social media in the aftermath of the Great East Japan Earthquake
Authors: Jung Joo‐Young , Moro Munehito
Published: June 2014

This study examines the multi‐level functionalities of social media in the aftermath of the Great East Japan Earthquake of 11 March 2011. Based on a conceptual model of multi‐level story flows of social media (Jung and Moro, 2012), the study analyses the multiple functionalities that were ascribed to social media by individuals, organisations, and macro‐level social systems (government and the mass media) after the earthquake. Based on survey data, a review of Twitter timelines and secondary sources, the authors derive five functionalities of social media: interpersonal communications with others (micro level); channels for local governments; organisations and local media (meso level); channels for mass media (macro level); information sharing and gathering (cross level); and direct channels between micro‐/meso‐ and macro‐level agents. The study sheds light on the future potential of social media in disaster situations and suggests how to design an effective communication network to prepare for emergency situations.
The tsunami's impact on mortality in a town severely damaged by the 2011 Great East Japan Earthquake
Authors: Nagata Satoko , Teramoto Chie , Okamoto Reiko , Koide Keiko , Nishida Masumi , Suzuki Ruriko , Nomura Michie , Tada Toshiko , Kishi Emiko , Sakai Yoko , Jojima Noriko , Kusano Emiko , Iwamoto Saori , Saito Miki , Murashima Sachiyo
Published: June 2014

This study identifies the relationship between tsunami damage and mortality through a demographic pyramid of a town severely damaged by the tsunami following the Great East Japan Earthquake of 11 March 2011. It uses cross‐sectional data collection. Volunteers visited all households, including shelters, and asked residents about the whereabouts of family members and neighbours. The information was collated with lists of evacuees and the dead to confirm the whereabouts of all residents about 50 days after the disaster. Demographic pyramids for the whole population based on pre‐ and post‐disaster data were drawn. In all, 1,412 (8.8 per cent) were dead or missing, 60.2 per cent of whom were aged 65 and over and 37.5 per cent aged 75 and over, suggesting that the very old should be located beyond the reach of tsunamis. The mortality rate of children was lower than that in other studies, which may indicate the efficacy of disaster evacuation drills.
Effect of exogenously administered glucagon versus spontaneous endogenous counter‐regulation on glycaemic recovery from insulin‐induced hypoglycaemia in patients with type 2 diabetes treated with a novel glucokinase activator, AZD1656, and metformin
Authors: Krentz A. J. , Morrow L. , Petersson M. , Norjavaara E. , Hompesch M.
Published: June 2014

Aims

To study the effect of exogenous i.m. glucagon on recovery from controlled insulin‐induced hypoglycaemia in patients with type 2 diabetes treated with the novel glucokinase activator AZD1656, in combination with metformin.

Methods

This was a single‐centre randomized, open, two‐way crossover phase I, automated glucose clamp (Biostator®; Life Science Instruments, Elkhart, MD, USA) study (NCT00817271) in eight patients (seven men and one woman, mean age 58.6 years, body mass index 28.1 kg/m2). All patients received a stable dose of metformin twice daily, ranging from 1000 to 2250 mg. A 2‐day titration phase commenced with 40 mg AZD1656 twice daily, escalating to 80 mg twice daily if tolerated. This was followed by a single dose of 80 or 160 mg AZD1656, administered on days 5 and 8 when metabolic studies were performed. After an overnight fast on days 5 and 8, controlled hypoglycaemia was induced using an exogenous i.v. infusion of insulin. Plasma glucose was lowered in a stepwise fashion over 3 h to attain a target nadir of 2.7 mmol/l. This was sustained for 30 min, at the end of which the hypoglycaemic clamp was released. In random sequence, patients either received an i.m. injection of 1 mg glucagon or were allowed to recover from hypoglycaemia by endogenous counter‐regulation. To avoid prolonged hypoglycaemia, a reverse glucose clamp was applied from 4 to 6 h post‐dose.

Results

Three patients received 40 mg AZD1656 twice daily and five patients 80 mg twice daily. Mean plasma glucose at 20 min after release of the hypoglycaemic clamp was significantly lower (3.1 ± 0.3 mmol/l) for AZD1656 alone than for AZD1656 + glucagon (4.9 ± 0.8 mmol/l; p < 0.001 between the groups). Catecholamine and cortisol responses were similar on the AZD1656 + glucagon and AZD alone study days. Growth hormone response was 18% lower for AZD1656 alone (p = 0.01), consistent with the effect of a pharmacological dose of glucagon on growth hormone secretion. No safety or tolerability concerns were observed during treatment with AZ1656.

Conclusions

Exogenous glucagon was effective as a rescue treatment for hypoglycaemia induced during treatment with AZD1656, given in combination with metformin in patients with type 2 diabetes.
Safety of closed‐loop therapy during reduction or omission of meal boluses in adolescents with type 1 diabetes: a randomized clinical trial
Authors: Elleri D. , Maltoni G. , Allen J. M. , Nodale M. , Kumareswaran K. , Leelarathna L. , Thabit H. , Caldwell K. , Wilinska M. E. , Calhoun P. , Kollman C. , Dunger D. B. , Hovorka Roman
Published: June 2014

We evaluated the safety and efficacy of closed‐loop therapy with meal announcement during reduction and omission of meal insulin boluses in adolescents with type 1 diabetes (T1D).

Twelve adolescents with T1D [six male; mean (s.d.) age 15.9 (1.8) years; mean (s.d.) glycated haemoglobin (HbA1c) 77 (27) mmol/mol] were studied in a randomized crossover study comparing closed‐loop therapy with meal announcement with conventional pump therapy over two 24‐h stays at a clinical research facility. Identical meals were given on both occasions. The evening meal insulin bolus was calculated to cover half of the carbohydrate content of the meal and no bolus was delivered for lunch. Plasma glucose levels were in the target range of 3.9–10 mmol/l for a median [interquartile range (IQR)] of 74 (55,86)% of the time during closed‐loop therapy with meal announcement and for 62 (49,75)% of the time during conventional therapy (p = 0.26). Median (IQR) time spent with plasma glucose levels > 10 mmol/l [23 (13,39) vs. 27 (10,50)%; p = 0.88] or < 3.9 mmol/l [1(0,4) vs. 5 (1,10)%; p = 0.24] and mean [standard deviation (SD)] glucose levels [8.0 (7.6,9.3) vs. 7.7 (6.6,10.1) mmol/l, p = 0.79] were also similar. In conclusion, these results assist home testing of closed‐loop delivery with meal announcement in adolescents with poorly controlled T1D who miscalculate or miss meal insulin boluses.
Efficacy and safety of dapagliflozin monotherapy in Japanese patients with type 2 diabetes inadequately controlled by diet and exercise
Authors: Kaku K. , Kiyosue A. , Inoue S. , Ueda N. , Tokudome T. , Yang J. , Langkilde A. M.
Published: June 2014

Aims

To evaluate the efficacy and safety of the selective sodium glucose co‐transporter 2 inhibitor dapagliflozin in Japanese patients with type 2 diabetes mellitus (T2DM) inadequately controlled by diet and exercise.

Methods

Patients received placebo or dapagliflozin (5 or 10 mg) once daily for 24 weeks. The primary outcome measure was change from baseline in glycated haemoglobin (HbA1c).

Results

Patients (N = 261) had modestly elevated baseline HbA1c (mean ≈ 7.5%) and most had mild or moderate renal impairment (estimated glomerular filtration rate range 43–103 ml/min/1.73 m2). Greater reductions in mean HbA1c level were observed with dapagliflozin (5 mg, −0.41%; 10 mg, −0.45%) than with placebo (−0.06%) at week 24 and these were greater in patients with higher baseline HbA1c levels. Fasting plasma glucose (FPG) was also significantly reduced with dapagliflozin (5 mg, −8.6 mg/dl; 10 mg, −13.7 mg/dl) compared with placebo (+5.8 mg/dl). Dapagliflozin significantly reduced body weight (5 mg, −2.13 kg; 10 mg, −2.22 kg) compared with placebo (−0.84 kg). Overall, 47.7 and 64.8% of patients with dapagliflozin 5 and 10 mg, respectively, and 51.7% with placebo experienced ≥1 adverse event, mostly mild or moderate, and unrelated to study treatment. Two patients on dapagliflozin 10 mg reported hypoglycaemia. Four patients across all groups reported events suggestive of genital infection and four of urinary tract infection. No events of pyelonephritis were reported.

Conclusion

Dapagliflozin (5 and 10 mg) was well tolerated and effective in reducing HbA1c, FPG and body weight over 24 weeks in Japanese patients with T2DM inadequately controlled by diet and exercise.
Saddle fit and management: An investigation of the association with equine thoracolumbar asymmetries, horse and rider health
Authors: Greve L. , Dyson S.
Published: June 2014

Reasons for performing study

No previous studies have investigated interrelationships between saddle fit/management, equine thoracolumbar asymmetries, rider and horse health.

Objectives

To assess associations between data obtained by clinical assessment and those provided by riders via a questionnaire.

Study design

Clinical assessment of a convenience sample of horses and riders compared with a Web‐based questionnaire survey (n = 205).

Methods

Horse thoracolumbar asymmetries at predetermined sites, the presence of lameness (in hand and/or ridden), saddle slip, saddle fit/management and rider straightness were assessed. Kappa statistics were used to assess the relationship between categorical clinical data and questionnaire data from riders. Spearman's correlation was used to investigate associations between outcomes from clinical assessment (horse, saddle and rider data) and information provided by riders.

Results

There was a 40.5% (205 of 506) questionnaire response rate. Thirty horses (14.6%) had saddle slip, which was significantly associated with hindlimb lameness or gait abnormalities (P<0.001), but only 2 riders had considered a link between saddle slip and lameness. Rider back pain was common (38.5%) and associated with ill‐fitting saddles (P = 0.03) and either a quadrupedally reduced cranial phase of the step or a stiff, stilted canter (P = 0.006). Well‐fitted saddles were associated with frequent saddle fit checks (P = 0.004). Minor thoracolumbar asymmetries (P = 0.04) were negatively associated with ill‐fitting saddles and positively associated with rider skill level (P = 0.001).

Conclusions

The interaction between the horse, saddle and rider is complex. Ill‐fitting saddles and a stiff, stilted canter or quadrupedally reduced cranial phase of the step are associated with rider back pain. Equine back pain and minor thoracolumbar asymmetries are associated with ill‐fitting saddles. Saddle fit should be checked more often than once yearly to lower the number of ill‐fitting saddles. Riders, trainers and other professionals involved in equine care and performance need better education to recognise ill‐fitting saddles, lameness, saddle slip and rider crookedness.
Topical application of rapamycin ointment ameliorates Dermatophagoides farina body extract‐induced atopic dermatitis in NC/Nga mice
Authors: Yang Fei , Tanaka Mari , Wataya‐Kaneda Mari , Yang Lingli , Nakamura Ayumi , Matsumoto Shoji , Attia Mostafa , Murota Hiroyuki , Katayama Ichiro
Published: June 2014

Atopic dermatitis (AD), a chronic inflammatory skin disease characterized by relapsing eczema and intense prurigo, requires effective and safe pharmacological therapy. Recently, rapamycin, an mTOR (mammalian target of rapamycin) inhibitor, has been reported to play a critical role in immune responses and has emerged as an effective immunosuppressive drug. In this study, we assessed whether inhibition of mTOR signalling could suppress dermatitis in mice. Rapamycin was topically applied to inflamed skin in a murine AD model that was developed by repeated topical application of Dermatophagoides farina body (Dfb) extract antigen twice weekly for 7 weeks in NC/Nga mice. The efficacy of topical rapamycin treatment was evaluated immunologically and serologically. Topical application of rapamycin reduced inflammatory cell infiltration in the dermis, alleviated the increase of serum IgE levels and resulted in a significant reduction in clinical skin condition score and marked improvement of histological findings. In addition, increased mTOR phosphorylation in the lesional skin was observed in our murine AD model. Topical application of rapamycin ointment inhibited Dfb antigen‐induced dermatitis in NC/Nga mice, promising a new therapy for atopic dermatitis.
Perturbations in the carbon budget of the tropics
Authors: Grace John , Mitchard Edward , Gloor Emanuel
Published: June 2014

The carbon budget of the tropics has been perturbed as a result of human influences. Here, we attempt to construct a ‘bottom‐up’ analysis of the biological components of the budget as they are affected by human activities. There are major uncertainties in the extent and carbon content of different vegetation types, the rates of land‐use change and forest degradation, but recent developments in satellite remote sensing have gone far towards reducing these uncertainties. Stocks of carbon as biomass in tropical forests and woodlands add up to 271 ± 16 Pg with an even greater quantity of carbon as soil organic matter. Carbon loss from deforestation, degradation, harvesting and peat fires is estimated as 2.01 ± 1.1 Pg annum−1; while carbon gain from forest and woodland growth is 1.85 ± 0.09 Pg annum−1. We conclude that tropical lands are on average a small carbon source to the atmosphere, a result that is consistent with the ‘top‐down’ result from measurements in the atmosphere. If they were to be conserved, they would be a substantial carbon sink. Release of carbon as carbon dioxide from fossil fuel burning in the tropics is 0.74 Pg annum−1 or 0.57 MgC person−1 annum−1, much lower than the corresponding figures from developed regions of the world.
Introduction to the religious lives of migrant minorities: a transnational and multi‐sited perspective
Authors: VÁSQUEZ MANUEL A. , DEWIND JOSH
Published: June 2014

This introduction describes the evolution of the conceptual framework that guided the research and analysis of findings from an international research project bringing a multi‐sited and transnational perspective to the study of the religious lives of migrant minorities. The project began by identifying potential contributions that studies of religion, migration and diversity offered one another. To research these issues, the project members investigated the lives of migrants who identify themselves as Christians, Muslims, Hindus and Buddhists, who live as minorities within three urban contexts, and whose different national regimes for governing migrant and religious diversity have been shaped historically by the British Empire (London, Johannesburg, Kajang‐Kuala Lumpur). The researchers employed a biographic method of investigation in order to examine how migrants organized their religious lives within individual, familial, communal, urban, national and transnational spheres. To understand the intertwining between migratory and religious aspects of the migrants' lives on each of these levels, the project members focused their analysis of the research findings in relation to three themes: migratory and spiritual journeys, sacred and secular place‐making, and the circulation of people, objects, practices, and faiths. The introduction highlights how each of the articles in this collection both reflect and contribute to this intellectual framing in order to understand the interplay between religion, migration, and diversity.
Case of cholangiocellular carcinoma in a patient with glycogen storage disease type Ia
Authors: Kanamori Hiroyuki , Nakade Yukiomi , Yamamoto Takaya , Kobayashi Yuji , Sato Ken , Ito Kiyoaki , Ohashi Tomohiko , Nakao Noiku , Ishii Norimitsu , Takahashi Emiko , Yokoi Toyoharu , Nakao Haruhisa , Kurokawa Tsuyoshi , Yamaguchi Chikara , Yoneda Masashi
Published: June 2014

Glycogen storage disease (GSD) type Ia is caused by a deficiency in glucose‐6‐phosphatase. Long‐term complications, including renal disease, gout, osteoporosis and pulmonary hypertension, develop in patients with GSD type Ia. In the second or third decade, 22–75% of GSD type Ia patients develop hepatocellular adenoma (HCA). In some of these patients, the HCA evolves into hepatocellular carcinoma. However, little is known about GSD type Ia patients with HCA who develop cholangiocellular carcinoma (CCC). Here, we report for the first time, a patient with GSD type Ia with HCA, in whom intrahepatic CCC was developed.
Safe and cost‐effective control of post‐transplantation recurrence of hepatitis B
Authors: Takaki Akinobu , Yagi Takahito , Yamamoto Kazuhide
Published: June 2014

A combination of hepatitis B immunoglobulin (HBIG) and nucleoside/nucleotide analogs (NUC) is the current standard of care for controlling hepatitis B recurrence after orthotopic liver transplantation (OLT). However, long‐term HBIG administration is associated with several unresolved issues, including limited availability and extremely high cost, and thus several protocols for treatment with low‐dose HBIG combined with NUC or HBIG‐free regimens have been developed. This article reviews recent advances in post‐OLT hepatitis B virus (HBV) control and future methodological directions. New NUC such as entecavir, tenofovir or lamivudine plus adefovir dipivoxil combinations induce a very low frequency of viral resistance. The withdrawal of HBIG after several months of OLT under new NUC continuation also has permissible effects. Even after HBV reactivation, NUC can usually achieve viral control when viral markers are strictly followed up. Another approach is to induce self‐producing anti‐HBV antibodies via vaccination with a hepatitis B surface antigen vaccine. However, HBV vaccination is not sufficiently effective in patients to treat liver cirrhosis type B after OLT because immune tolerance to the virus has already continued for several decades. Trials of its safety and cost‐effectiveness are required. This review advocates a safe and economical approach to controlling post‐OLT HBV recurrence.
Acute cellular rejection versus recurrent hepatitis C after liver transplantation: Clinical and pathological features driving a rational diagnostic approach
Authors: de la Peña‐Moral Jesús M. , Pons Jose A. , Tome Santiago , Gude Francisco , Miras Manuel , Bermejo Juan , Ramirez Pablo , Berenguer Marina , Varo Evaristo , Forteza Jeronimo , Parrilla Pascual
Published: June 2014

Aim

The aim of our study was develop and validate an algorithm system based on morphological features for finding the differences between recurrent hepatitis C virus (HCV) and acute cellular rejection (ACR) in liver biopsies of HCV‐transplanted patients.

Methods

Two hundred and eighty‐eight liver biopsies were analyzed from 121 patients transplanted for HCV. A diagnostic consensus was reached between clinicians and pathologists in 214 biopsies for the diagnosis of recurrent HCV or ACR. A random sample of 114 liver biopsies (derivation cohort) was taken to generate the diagnostic tree and was subsequently evaluated using the validation cohort in 100 liver biopsies by recursive partitioning analysis of morphological variables and time since transplantation.

Results

The presence of endotheliitis together with a time of less than 6 weeks since LT definitely excluded recurrent HCV. After obtaining the regression tree, diagnostic accuracy was 96% and 93% in the derivation and validation cohort, respectively. Both cases surpassed the pathologist's original diagnosis, which had a diagnostic accuracy of 91% (P < 0.05, for both comparisons).

Conclusion

A recursive partitioning analysis of the morphological features in liver biopsies from HCV‐transplanted patients may be useful for easily distinguishing between recurrent HCV and ACR.