bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of hedgehog pathway reveals the regulatory role of SMO in gastric cancer cells
Authors: Yang Zixin , Lv Yingqian , Wang Long , Chen Yong , Han Jinzhu , Zhao Shan , Liu Wei
Published: November 2017

Previous studies report aberrant activation of the hedgehog signaling pathway in the progression of various cancers. This study aimed to investigate the expressions of smoothened and downstream glioma-associated oncogene homology-1 in gastric cancer and the underlying molecular mechanisms. Here, we first detected the expression in 58 cases of primary gastric cancer tissue and matched normal tissue specimens by western blot analysis and quantitative reverse transcription polymerase chain reaction. Cell proliferation and cycle were assayed in gastric cancer cells after blocking the hedgehog pathway by lentiviral-short hairpin RNA knockdown. In vitro inhibition of hedgehog pathway resulted in decreased cell proliferation and migration. Our studies demonstrate an important role for smoothened and glioma-associated oncogene homology-1 in gastric cancer and suggest inhibition of hedgehog pathway as a novel and potent strategy to treat gastric cancer patients.
ADAM9 expression promotes an aggressive lung adenocarcinoma phenotype
Authors: Kossmann Céline Mongaret , Annereau Maxime , Thomas-Schoemann Audrey , Nicco-Overney Carole , Chéreau Christiane , Batteux Frédéric , Alexandre Jérôme , Lemare François
Published: November 2017

A disintegrin and metalloproteinase 9 (ADAM9) possesses potent metastasis-inducing capacities and is highly expressed in several cancer cells. Previous work has shown that ADAM9 participates in the adhesive–invasive phenotype in lung cancer cells in vitro. In this study, we evaluated whether ADAM9 expression plays a critical role in metastatic processes in vivo and in angiogenesis. We first found that high ADAM9 expression was correlated with poor lung adenocarcinoma patient prognosis on Prognoscan data base. In vivo model based on intravenous injection in nude mice showed that a stable downregulation of ADAM9 in A549 (TrA549 A9-) cells was associated with a lower number of nodules in the lung, suggesting lower potentials for extravasation and metastasis. On a subcutaneous xenograft we showed that TrA549 A9− produced significantly smaller tumours and exhibited fewer neovessels. In addition, in vitro human umbilical vein endothelial cells exposed to supernatant from TrA549 A9− could reduce the formation of more vessel-like structures. To further understand the mechanism, a human antibody array analysis confirmed that five cytokines were downregulated in TrA549 A9− cells. Interleukin 8 was the most significantly downregulated, and its interaction with CXCR2 was implicated in angiogenesis on an in vitro model. These results emphasize the critical influence of ADAM9 on lung cancer progression and aggressiveness. ADAM9 should at least be a marker of cancer aggressiveness and a potential therapeutic target for cancer treatment.
Radiation-induced Epstein–Barr virus reactivation in gastric cancer cells with latent EBV infection
Authors: Nandakumar Athira , Uwatoko Futoshi , Yamamoto Megumi , Tomita Kazuo , Majima Hideyuki J , Akiba Suminori , Koriyama Chihaya
Published: November 2017

Epstein–Barr virus, a ubiquitous human herpes virus with oncogenic activity, can be found in 6%–16% of gastric carcinomas worldwide. In Epstein–Barr virus–associated gastric carcinoma, only a few latent genes of the virus are expressed. Ionizing irradiation was shown to induce lytic Epstein–Barr virus infection in lymphoblastoid cell lines with latent Epstein–Barr virus infection. In this study, we examined the effect of ionizing radiation on the Epstein–Barr virus reactivation in a gastric epithelial cancer cell line (SNU-719, an Epstein–Barr virus–associated gastric carcinoma cell line). Irradiation with X-ray (dose = 5 and 10 Gy; dose rate = 0.5398 Gy/min) killed approximately 25% and 50% of cultured SNU-719 cells, respectively, in 48 h. Ionizing radiation increased the messenger RNA expression of immediate early Epstein–Barr virus lytic genes (BZLF1 and BRLF1), determined by real-time reverse transcription polymerase chain reaction, in a dose-dependent manner at 48 h and, to a slightly lesser extent, at 72 h after irradiation. Similar findings were observed for other Epstein–Barr virus lytic genes (BMRF1, BLLF1, and BcLF1). After radiation, the expression of transforming growth factor beta 1 messenger RNA increased and reached a peak in 12–24 h, and the high-level expression of the Epstein–Barr virus immediate early genes can convert latent Epstein–Barr virus infection into the lytic form and result in the release of infectious Epstein–Barr virus. To conclude, Ionizing radiation activates lytic Epstein–Barr virus gene expression in the SNU-719 cell line mainly through nuclear factor kappaB activation. We made a brief review of literature to explore underlying mechanism involved in transforming growth factor beta–induced Epstein–Barr virus reactivation. A possible involvement of nuclear factor kappaB was hypothesized.
MicroRNA-200b suppresses the invasion and migration of hepatocellular carcinoma by downregulating RhoA and circRNA_000839
Authors: Wang Ben-gang , Li Jun-shuai , Liu Yong-feng , Xu Qian
Published: November 2017

MicroRNAs could mediate the targeted coding gene and the targeted non-coding RNA to form endogenous competition, which have an important regulatory role in tumorigenesis of many types of cancer, including hepatocellular carcinoma. The goal of this study was to characterize the role of miR-200b in the pathogenesis of hepatocellular carcinoma. We identified miR-200b that was predicted to regulate RhoA and circ_000839. Our data establish that miR-200b is expressed at a relatively low level in hepatocellular carcinoma ( p < 0.001). RhoA and circ_000839 are expressed at a relatively high level in hepatocellular carcinoma ( p < 0.001, respectively). Our mechanistic data indicate that RhoA is a direct target of miR-200b ( p < 0.001), binding of which affects the expression of invasion and migration in hepatocellular carcinoma cell lines ( p < 0.05). And correlation analysis showed that miR-200b was inversely correlated with RhoA and circ_000839 ( p = 0.012, p = 0.002, respectively), while RhoA was positively correlated with circ_000839 ( p < 0.001). Taken together, our data suggest that miR-200b could mediate RhoA gene and circ_000839 to form endogenous competition. And this is a direction for the association study of miR-200b and RhoA in the future.
XIAP 3′-untranslated region serves as a competitor for HMGA2 by arresting endogenous let-7a-5p in human hepatocellular carcinoma
Authors: Wu Wen-Yong , Tao Si-Qi , Wang Xiao-Nan , Lobie Peter E , Wu Zheng-Sheng
Published: November 2017

X-linked inhibitor of apoptosis protein functions as an intrinsic regulator of apoptosis by inhibition of caspase activity and possesses a pivotal role in human cancer development and progression. A growing body of literature has demonstrated that microRNAs lead to the degradation or translational repression of messenger RNAs by binding to the non-coding region of messenger RNA at the 3′-untranslated region. Here, we revealed that the expression of HMGA2 is upregulated with X-linked inhibitor of apoptosis protein after transfection of X-linked inhibitor of apoptosis protein 3′-untranslated region in hepatocellular carcinoma cells, suggesting that X-linked inhibitor of apoptosis protein 3′-untranslated region serves as a competitor for microRNAs and prevent the co-targeted messenger RNA, HMGA2, from being suppressed. We further identified that let-7a-5p could bind to both the X-linked inhibitor of apoptosis protein 3′-untranslated region and HMGA2 3′-untranslated region. Moreover, we demonstrated that the forced expression of X-linked inhibitor of apoptosis protein 3′-untranslated region increases the oncogenicity of hepatocellular carcinoma cells in vitro. Cell functional analyses were performed to examine the association of HMGA2 status and X-linked inhibitor of apoptosis protein 3′-untranslated region. We have also measured the functional readout of let-7a-5p and HMGA2, an assay often employed to provide substantial evidence for the effects of X-linked inhibitor of apoptosis protein 3′-untranslated region on hepatocellular carcinoma cells. In general, our findings suggest that X-linked inhibitor of apoptosis protein 3′-untranslated region serves as a competitive endogenous RNA for HMGA2 to activate hepatocellular carcinoma progression by arresting endogenous let-7a-5p.
Establishment of cholangiocarcinoma cell lines from patients in the endemic area of liver fluke infection in Thailand
Authors: Saensa-ard Sunitta , Leuangwattanawanit Saman , Senggunprai Laddawan , Namwat Nisana , Kongpetch Sarinya , Chamgramol Yaovalux , Loilome Watcharin , Khansaard Walaiporn , Jusakul Apinya , Prawan Auemduan , Pairojkul Chawalit , Khantikeo Narong , Yongvanit Puangrat , Kukongviriyapan Veerapol
Published: November 2017

Cholangiocarcinoma is a rare type of cancer which is an increasingly discernible health threat. The disease is usually very difficult in diagnosis and various treatment modalities are typically not effective. Cholangiocarcinoma is a complex and very heterogeneous malignancy characterized by tumor location, different risk factors, molecular profiling, and prognosis. Cancer cell lines represent an important tool for investigation in various aspects of tumor biology and molecular therapeutics. We established two cell lines, KKU-452 and KKU-023, which were derived from patients residing in the endemic area of liver fluke infection in Thailand. Both of tumor tissues have gross pathology of perihilar and intrahepatic mass-forming cholangiocarcinoma. Two cell lines were characterized for their biological, molecular and genetic properties. KKU-452 and KKU-023 cells are both adherent cells with epithelium morphology, but have some differences in their growth pattern (a doubling time of 17.9 vs 34.8 h, respectively) and the expression of epithelial bile duct markers, CK7 and CK19. Cytogenetic analysis of KKU-452 and KKU-023 cells revealed their highly complex karyotypes; hypertriploid and hypotetraploid, respectively, with multiple chromosomal aberrations. Both cell lines showed mutations in p53 but not in KRAS. KKU-452 showed a very rapid migration and invasion properties in concert with low expression of E-cadherin and high expression of N-cadherin, whereas KKU-023 showed opposite characters. KKU-023, but not KKU-452, showed in vivo tumorigenicity in xenografted nude mice. Those two established cholangiocarcinoma cell lines with unique characters may be valuable for better understanding the process of carcinogenesis and developing new therapeutics for the patients
MicroRNA–target cross-talks: Key players in glioblastoma multiforme
Authors: Toraih Eman Ali , Aly Nagwa Mahmoud , Abdallah Hoda Y , Al-Qahtani Saeed Awad , Shaalan Aly AM , Hussein Mohammad Hosny , Fawzy Manal Said
Published: November 2017

The role of microRNAs in brain cancer is still naive. Some act as oncogene and others as tumor suppressors. Discovery of efficient biomarkers is mandatory to debate that aggressive disease. Bioinformatically selected microRNAs and their targets were investigated to evaluate their putative signature as diagnostic and prognostic biomarkers in primary glioblastoma multiforme. Expression of a panel of seven microRNAs (hsa-miR-34a, hsa-miR-16, hsa-miR-17, hsa-miR-21, hsa-miR-221, hsa-miR-326, and hsa-miR-375) and seven target genes ( E2F3, PI3KCA, TOM34, WNT5A, PDCD4, DFFA, and EGFR) in 43 glioblastoma multiforme specimens were profiled compared to non-cancer tissues via quantitative reverse transcription–polymerase chain reaction. Immunohistochemistry staining for three proteins (VEGFA, BAX, and BCL2) was performed. Gene enrichment analysis identified the biological regulatory functions of the gene panel in glioma pathway. MGMT ( O-6-methylguanine-DNA methyltransferase) promoter methylation was analyzed for molecular subtyping of tumor specimens. Our data demonstrated a significant upregulation of five microRNAs (hsa-miR-16, hsa-miR-17, hsa-miR-21, hsa-miR-221, and hsa-miR-375), three genes ( E2F3, PI3KCA, and Wnt5a), two proteins (VEGFA and BCL2), and downregulation of hsa-miR-34a and three other genes ( DFFA, PDCD4, and EGFR) in brain cancer tissues. Receiver operating characteristic analysis revealed that miR-34a (area under the curve = 0.927) and miR-17 (area under the curve = 0.900) had the highest diagnostic performance, followed by miR-221 (area under the curve = 0.845), miR-21 (area under the curve = 0.836), WNT5A (area under the curve = 0.809), PDCD4 (area under the curve = 0.809), and PI3KCA (area under the curve = 0.800). MGMT promoter methylation status was associated with high miR-221 levels. Moreover, patients with VEGFA overexpression and downregulation of TOM34 and BAX had poor overall survival. Nevertheless, miR-17, miR-221, and miR-326 downregulation were significantly associated with high recurrence rate. Multivariate analysis by hierarchical clustering classified patients into four distinct groups based on gene panel signature. In conclusion, the explored microRNA–target dysregulation could pave the road toward developing potential therapeutic strategies for glioblastoma multiforme. Future translational and functional studies are highly recommended to better understand the complex bio-molecular signature of this difficult-to-treat tumor.
Genetic variants of SULT1A1 and XRCC1 genes and risk of lung cancer in Bangladeshi population
Authors: Tasnim Tasnova , Al-Mamun Mir Md Abdullah , Nahid Noor Ahmed , Islam Md Reazul , Apu Mohd Nazmul Hasan , Bushra Most Umme , Rabbi Sikder Nahidul Islam , Nahar Zabun , Chowdhury Jakir Ahmed , Ahmed Maizbha Uddin , Islam Mohammad Safiqul , Hasnat Abul
Published: November 2017

Lung cancer is one of the most frequently occurring cancers throughout the world as well as in Bangladesh. This study aimed to correlate the prognostic and/or predictive value of functional polymorphisms in SULT1A1 (rs9282861) and XRCC1 (rs25487) genes and lung cancer risk in Bangladeshi population. A case-control study was conducted which comprises 202 lung cancer patients and 242 healthy volunteers taking into account the age, sex, and smoking status. After isolation of genomic DNA, genotyping was done by polymerase chain reaction–restriction fragment length polymorphism method and the lung cancer risk was evaluated as odds ratio that was adjusted for age, sex, and smoking status. A significant association was found between SULT1A1 rs9282861 and XRCC1 rs25487 polymorphisms and lung cancer risk. In case of rs9282861 polymorphism, Arg/His (adjusted odds ratio = 5.06, 95% confidence interval = 3.05–8.41, p < 0.05) and His/His (adjusted odds ratio = 3.88, 95% confidence interval = 2.20–6.82, p < 0.05) genotypes were strongly associated with increased risk of lung cancer in comparison to the Arg/Arg genotype. In case of rs25487 polymorphism, Arg/Gln heterozygote (adjusted odds ratio = 4.57, 95% confidence interval = 2.79–7.46, p < 0.05) and Gln/Gln mutant homozygote (adjusted odds ratio = 4.99, 95% confidence interval = 2.66–9.36, p < 0.05) were also found to be significantly associated with increased risk of lung cancer. This study demonstrates that the presence of His allele and Gln allele in case of SULT1A1 rs9282861 and XRCC1 rs25487, respectively, involve in lung cancer prognosis in Bangladeshi population.
Cell-free DNA levels and correlation to stage and outcome following treatment of locally advanced rectal cancer
Authors: Boysen Anders Kindberg , Wettergren Yvonne , Sorensen Boe Sandahl , Taflin Helena , Gustavson Bengt , Spindler Karen-Lise Garm
Published: November 2017

Accurate staging of rectal cancer remains essential for optimal patient selection for combined modality treatment, including radiotherapy, chemotherapy and surgery. We aimed at examining the correlation of cell free DNA with the pathologic stage and subsequent risk of recurrence for patients with locally advanced rectal cancer undergoing preoperative chemoradiation. We examined 75 patients with locally advanced rectal cancer receiving preoperative chemoradiation. Blood samples for translational use were drawn prior to rectal surgery. The level of cell free DNA was quantified by digital droplet PCR and expressed as copy number of beta 2 microglobulin. We found a median level of cell free DNA in the AJCC stages I-III of 3100, 8300, and 10,700 copies/mL respectively. For patients with 12 sampled lymph nodes or above, the median level of cell free DNA were 2400 copies/mL and 4400 copies/mL (p = 0.04) for node negative and node positive disease respectively. The median follow-up was 39 months and 11 recurrences were detected (15%). The median level for patients with recurrent disease was 13,000 copies/mL compared to 5200 copies/mL for non-recurrent patients (p = 0.08). We have demonstrated a correlation between the level of total cell free DNA and the pathologic stage and nodal involvement. Furthermore, we have found a trend towards a correlation with the risk of recurrence following resection of localized rectal cancer.
Beta-mangostin from Cratoxylum arborescens activates the intrinsic apoptosis pathway through reactive oxygen species with downregulation of the HSP70 gene in the HL60 cells associated with a G0/G1 cell-cycle arrest
Authors: Omer Fatima Abdelmutaal Ahmed , Hashim Najihah Binti Mohd , Ibrahim Mohamed Yousif , Dehghan Firouzeh , Yahayu Maizatulakmal , Karimian Hamed , Salim Landa Zeenelabdin Ali , Mohan Syam
Published: November 2017

Xanthones are phytochemical compounds found in a number of fruits and vegetables. Characteristically, they are noted to be made of diverse properties based on their biological, biochemical, and pharmacological actions. Accordingly, the apoptosis mechanisms induced by beta-mangostin, a xanthone compound isolated from Cratoxylum arborescens in the human promyelocytic leukemia cell line (HL60) in vitro, were examined in this study. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was done to estimate the cytotoxicity effect of β-mangostin on the HL60 cell line. Acridine orange/propidium iodide and Hoechst 33342 dyes and Annexin V tests were conducted to detect the apoptosis features. Caspase-3 and caspase-9 activities; reactive oxygen species; real-time polymerase chain reaction for Bcl-2, Bax, caspase-3, and caspase-9 Hsp70 genes; and western blot for p53, cytochrome c, and pro- and cleavage-caspase-3 and caspase-9 were assessed to examine the apoptosis mechanism. Cell-cycle analysis conducted revealed that β-mangostin inhibited the growth of HL60 at 58 µM in 24 h. The administration of β-mangostin with HL60 caused cell morphological changes related to apoptosis which increased the number of early and late apoptotic cells. The β-mangostin-catalyzed apoptosis action through caspase-3, caspase-7, and caspase-9 activation overproduced reactive oxygen species which downregulated the expression of antiapoptotic genes Bcl-2 and HSP70. Conversely, the expression of the apoptotic genes Bax, caspase-3, and caspase-9 were upregulated. Meanwhile, at the protein level, β-mangostin activated the formation of cleaved caspase-3 and caspase-9 and also upregulated the p53. β-mangostin arrested the cell cycle at the G0/G1 phase. Overall, the results for β-mangostin showed an antiproliferative effect in HL60 via stopping the cell cycle at the G0/G1 phase and prompted the intrinsic apoptosis pathway.
Competition soft law in French and German courts
Authors: Georgieva Zlatina
Published: November 2017

Ten years after the decentralization of EU competition law enforcement, this paper aims to ascertain through empirical means whether Commission-issued competition guidelines and notices (soft law) actually help to enhance enforcement consistency at the national level. This is what the European Commission itself maintained in White Paper on Modernization in 1999. The main premise of the White Paper is that if soft law is to help enhance consistency (a goal central to the current regime), it needs to be treated consistently by national judiciaries within and across EU jurisdictions – a difficult task, however, given its lack of binding force. Therefore, to ascertain the extent to which and how national courts in two select jurisdictions – France and Germany – engage or refuse to engage with supranational soft law, a theoretical framework of ‘judicial recognition’ of soft law is superimposed on a sample of 84 national judgments. While not discouraging, the results show some significant discrepancies that require further attention.
The Single Supervisory Mechanism Regulation: Questions of ne bis in idem and implications for the further integration of the system of fundamental rights protection in the EU
Authors: van Bockel Bas
Published: November 2017

This article discusses the enforcement framework of Regulation No. 1024/2013 (the Single Supervisory Mechanism Regulation, or ‘SSMR’) in light of the potential ne bis in idem situations which may arise, both in the interaction between the different modes and instruments of enforcement available to the European Central Bank (ECB) and National Competent Authorities (NCAs) under the SSMR, as well as in relation to national laws. 1 Shared enforcement of the rules for credit institutions under the SSMR transcends the familiar legal divide between the EU and the Member States, and the division of tasks and competences between national and EU authorities that is characteristic of EU law. The question raised here is whether the integrated enforcement architecture of the SSMR is matched by a sufficiently integrated system of fundamental rights protection in the EU, as viewed through the ‘lens’ of the ne bis in idem principle.
‘The day after’
Authors: Nicolaides Phedon
Published: November 2017

The purpose of the two-year rule in Article 50 TEU is to prevent the remaining Member States from delaying the exit of the withdrawing Member State through stalling tactics. This article argues that the two-year period is a double-edge sword. It affords very little time to the withdrawing Member State to adjust its domestic legislation, regulatory system and administrative structure to be able to function effectively on the day after exit from the EU. The UK’s Great Repeal Bill proposes a ‘copy and paste’ approach. However, this approach is only a partial solution to the problem of the ‘exit-induced’ legal lacuna. With the use of two case studies, the article demonstrates that the UK will have to establish new regulatory procedures and redefine EU concepts inserted in national law. The UK will ‘regain control’ but will have to follow EU practice. At some point in the future it will also encounter the dilemma of diverging from EU practice and creating two sets of compliance standards for its companies.
A historical overview of the general implementation of the European Union Market Abuse Directive in the United Kingdom before Brexit and its future implications
Authors: Chitimira Howard
Published: November 2017

The European Union (EU) was arguably the first body to establish multinational anti-market abuse laws aimed at enhancing the detection and curbing of cross-border market abuse activities in its Member States. Put differently, the EU Insider Dealing Directive was adopted in 1989 and was the first law that harmonized the insider trading ban among the EU Member States. Thereafter, the European Union Directive on Insider Dealing and Market Manipulation (EU Market Abuse Directive) was adopted in a bid to improve and effectively discourage all forms of market abuse in the EU’s securities and financial markets. However, the EU Market Abuse Directive had its own gaps and flaws. In light of this, the Market Abuse Regulation and the Criminal Sanctions for Market Abuse Directive were enacted to repeal and replace the EU Market Abuse Directive in 2016. The article examines the adequacy of the EU Market Abuse Directive and its implementation in the United Kingdom (UK) prior to the UK’s vote to leave the European Union (Brexit). This is done to investigate the possible implications of the Brexit referendum outcome of 23 June 2016 on the future regulation of market abuse in the UK.
Child Care Leave 2.0 – Suggestions for the improvement of the EU Maternity and Parental Leave Directives from a rights perspective
Authors: Foubert Petra
Published: November 2017

In August 2015, the European Commission launched its ‘Roadmap for a new start to address the challenges of work-life balance faced by working families’. Whilst it now seems quite serious about setting up a coherent legal framework, with full respect for the equal opportunities for women and men in the labour market, two elements have remained absent from the debate, that is the fact that the main focus is still on the nuclear family, and the fact that the gendered division of care activities remains out of sight. This article intends to draw attention to these elements, hoping that the Commission could still take them into account with regard to the revision of the Maternity Leave Directive. The first section provides a critical overview of the current legislative framework. The second section then presents a number of suggestions for a new legislative framework that is not detrimental to women workers and that caters for all sorts of families.
The cultural open method of coordination
Authors: Psychogiopoulou Evangelia
Published: November 2017

Launched in 2008, the open method of coordination (OMC) in the policy area of culture in the European Union has been used to structure cultural cooperation between Member States, to promote the exchange of best practices and feed national and EU policies by making recommendations to national and European policy-makers. The purpose of this article is to investigate whether the cultural OMC has delivered on its objectives. Has the process been successful in structuring cooperation between Member States? Has it had an influence on Member States’ cultural policies and if yes, in what way(s)? Has it informed cultural activity in the EU, affecting the measures taken at EU level? Based on a broad range of EU policy documents, cultural OMC outputs and interviews held with the European institutions, Member States’ cultural authorities and OMC participants in the cultural field, this article presents an empirical analysis of the effects of the cultural OMC through two distinct cycles (2008-2010 and 2011-2014). The analysis seeks to deepen the understanding of policy coordination in culture – a policy area that is essentially reserved for Member States due to their sensitivities in this field.
‘From Rome to Rome’ – Cross-border employment contract. European Private International Law: Intertemporal law and foreign overriding mandatory laws
Authors: Rammeloo Stephan
Published: November 2017

To what extent are Greek saving laws, resulting in payment cuts in the public sector (that is employment conditions), capable of overriding the applicable (German) law? A dispute arising from an employment relationship between the Greek Republic and an employee habitually carrying out work in Germany, gave rise to preliminary questions having regard to the temporal scope of EU Regulation No. 593/2008 (the ‘Rome I Regulation’)1 and, closely related thereto, the functional reach of Article 9(3) of that Regulation in respect of ‘foreign’ mandatory laws, in light of the principle of sincere cooperation enshrined in Article 4(3) TEU. An analysis of the Advocate General’s Opinion and the Court of Justice of the European Union’s (CJEU) ruling is followed by critical commentary and suggestions for future EU legislative amendments to the Rome I regime.
The Job Content, Context, and Requirements of Regulated Home-Based Childcare Workers
Authors: Stitou Mariam , Bourgeault Ivy-Lynn , Kohen Dafna
Published: November 2017

Contrary to a large and growing literature on center-based childcare workers, we know little about the work and health experiences of those providing childcare services in their homes. This study examines the job content, context, and requirements of regulated Home-Based Childcare workers in Canada. It is based on the qualitative analysis of eleven individual semistructured interviews. These workers perform business administration tasks and more housekeeping and domestic work than those in the center-based childcare, which affect their health and well-being. In addition, they reported factors related to the context and the content of their job such as the high physical and mental efforts, the absence of contact with other adults during working hours, the lack of external help, the exposure to noise and bad odors, the interference of work with personal and family life, the precarious remuneration, and the lack of benefits as potential factors that may affect their health.
Injury Among Home Care Workers in Washington State
Authors: Hansell Allison K. , Knaster Elizabeth S. , Phillips Leslie E.
Published: November 2017

Home Care Aides (HCAs) have nearly four times the rate of injury as the general U.S. work force. In 2015, the Service Employees International Union 775 Benefits Group conducted a health and safety survey with 672 HCAs in Washington State. The goal was to identify the risk factors for injury and to better assess injury rates through self-report. Quantitative analyses assessed injury prevalence and barriers in reporting injury. Overall, 13 percent responded that they had ever had an injury that required medical attention while working as an HCA. These rates are significantly higher for HCAs employed by home care agencies compared with HCAs who work independently. Over a third reported moderate to high levels of hesitancy in reporting an on-the-job injury; these rates were even higher for independent providers. Study findings suggest that HCAs are well informed about appropriate next steps following workplace injury, but strong barriers may prevent them from attempting the reporting process.
Art and Social Work: History and Collaborative Possibilities for Interdisciplinary Synergy
Authors: Nissen Laura Burney
Published: November 2017

This article will stretch the boundaries of the interdisciplinary lens to consider the history of and current potential for the arts to enhance, advance, and amplify individual, family, and community social change goals of the social work profession. To begin, consider the following questions: What would inspire artists and social workers to intentionally work together to reveal new strengths, energy, and capacity in the areas we care about? What do the arts have to teach the profession of social work and vice versa? How have the arts already played a role in the profession, and what has impaired social work’s ability to make greater use of the strengths associated with the arts? How have other professions (public health, psychology, education, and others) incorporated partnerships with the arts? This article concludes with a call to action to advance the potential of the arts in coordination with social work and related disciplines.
All Awareness and No Action: Can Social Work Leverage Creative Arts’ Potential?
Authors: Travis Raphael
Published: November 2017

Social work is grounded with an emphasis on promoting the well-being being of individuals and families with an explicit recognition of how the environment plays a significant role in the unfolding of well-being. Unfortunately, the profession’s commitment to maintaining the infrastructure for social work research, education, and practice that helps students and professionals focus on the environmental forces that create, contribute to, and address problems of the living sometimes feels superficial. These trends have made it difficult to realize the effectiveness and promise of integrating creative arts into social work practice. The present article discusses how social work efforts with creative arts will have limited influence if their context, underlying assumptions, and framing are misaligned with the experiential realities of clients; if gatekeeping is too rigid or biased to effectively grow the arts-based infrastructure; and if the underlying assumptions that define well-being outcomes are proportionately narrow, deficit oriented, and short-term focused.
Resilience Among Nepali Widows After the Death of a Spouse: “That Was My Past and Now I Have to See My Present”
Authors: Hendrickson Zoé M. , Kim Jane , Tol Wietse A. , Shrestha Abina , Kafle Hari Maya , Luitel Nagendra P. , Thapa Lily , Surkan Pamela J.
Published: November 2017

Responses to the death of a spouse vary; although some are at increased risk of poorer physical and mental health outcomes, others have more resilient responses. In light of the limited scope of research on widows’ experiences in Nepal, a setting where widows are often marginalized, we explore themes of resilience in Nepali widows’ lives. Drawing from a larger qualitative study of grief and widowhood, a thematic narrative analysis was performed on narratives from four widows that reflected resilient outcomes. Individual assets and social resources contributed to these widows’ resilient outcomes. Forgetting, acceptance, and moving forward were complemented by confidence and strength. Social support and social participation were key to widows’ resilient outcomes. These four narratives reflect the sociocultural context that shape widows’ resilient outcomes in Nepal. Future studies on the emergent themes from this exploratory study will help identify how best to encourage resilient outcomes among widows.
“Gimme Shelter”: The Role of Democracy and Institutional Quality in Disaster Preparedness
Authors: Persson Tove Ahlbom , Povitkina Marina
Published: November 2017

Natural disasters cause suffering for millions of people around the globe every year, and as climate change unfolds, the likelihood of natural catastrophes is increasing. While weather shocks such as earthquakes, tornadoes, and floods are beyond our control, the governments’ capacity to protect populations largely determines the degree of human suffering in disasters. Democracies, with freedom of speech, broad public participation, and representation, are believed to protect their populations better than nondemocratic regimes. However, democratic institutions are insufficient for securing protection from disasters in contexts of corruption, poor planning, and public administration incompetence. We argue that the effect of democracy on the extent of human suffering in disasters is contingent on the ability of governments to implement their tasks or the quality of implementing institutions. We test this interaction hypothesis using time-series cross-sectional data from the Varieties of Democracy project, the Quality of Government dataset, and the Centre for Research on the Epidemiology of Disasters. The results show that more democracy is associated with fewer people being affected by natural disasters only in settings where institutional quality is high. When institutional quality is low, more people seem to suffer in democracies than in authoritarian states.
The Leviathan’s Conscience: Hobbesian Human Nature and Moral Judgment
Authors: Branstetter John
Published: November 2017

Hannah Arendt claims that Thomas Hobbes was responsible for constituting modern people as apolitical subjects who can no longer make independent moral judgments. The refusal to think that Hobbes allegedly engendered was a major factor in twentieth-century totalitarianism’s worst crimes. In her view, Hobbes’s Leviathan established the architecture of the totalitarian state and initiated the cultivation of people so incapable of exercising moral judgment that they stood idly by and let such a state commit horrors in their name. I argue that Hobbes rejected the proto-totalitarian form of domination Arendt attributes to him and expressed hope about the human capacities for practical judgment and moral improvement. Instead of creating thoughtless subjects which authorize any crime the state might commit, he suggests that the Leviathan should cultivate the public’s capacity for reason and judgment to make violence unnecessary. Considering Hobbes’s accounts of reason and science in light of his materialism shows that the Leviathan requires the exercise of individual moral thought and judgment to function properly. I suggest that the primary duty of the Hobbesian sovereign might be understood primarily in terms of the cultivation of individual judgment and reason rather than its suppression.
Predictive Associations Between Family System Characteristics and Emergent Protective Factors
Authors: Lenz A. Stephen , Oliver Marvarene
Published: November 2017

The present study was implemented to identify predictive relationships between family processes and the emergence of protective factors among young adults. There were 198 participants (119 women, 60%; 79 men, 40%) with a mean age of 18.29 years ( SD = .46) with predominately Hispanic/Latino ( n = 88; 44%) and Caucasian ( n = 80; 40%) ethnic identities who were enrolled at a medium-sized 4-year university in the Central Southern region of the United States. Simultaneous multiple regression analyses revealed differential predictive weight for types of family processes and emergent protective factors. Specifically, use of strengths and adaptability predicted a sense of mattering and repeated exposure to crises predicted resilience. Implications for family therapy and recommendations for further research are identified.
Building the Marital Muscle Groups
Authors: Sauerheber Jill Duba , Ponton Richard F.
Published: November 2017

Marriage enrichment is a wellness-based approach to strengthening key areas of marital success. This article develops the metaphor of marital muscle groups and integrates Adlerian theories of development and personality with Gottman’s behavioral approach to provide a model of enrichment that can be applied in a clinical setting. A case example illustrates the application of the approach.
Minimally Invasive Distal Metatarsal Diaphyseal Osteotomy (DMDO) for Chronic Plantar Diabetic Foot Ulcers
Authors: Biz Carlo , Gastaldo Stefano , Dalmau-Pastor Miki , Corradin Marco , Volpin Andrea , Ruggieri Pietro
Published: November 2017

Background:

The aims of this prospective study were first to evaluate the safety and effectiveness of minimally invasive distal metatarsal diaphyseal osteotomies (DMDOs) for treating a consecutive series of diabetic patients with chronic plantar diabetic foot ulcers (CPDFUs) and second to assess their clinical-functional and radiographic outcomes.

Methods:

A consecutive series of patients affected by diabetes mellitus with CPDFUs, not responsive to previous nonoperative management, underwent DMDO. The CPDFUs were evaluated using the University of Texas Diabetic Wound Classification System (UTDWC). Demographic parameters, Foot & Ankle Society (AOFAS) scores, visual analog scale (VAS) scores, healing times, and complications were recorded. Maestro et al criteria and bone callus formation were analyzed radiologically. Statistical analysis was carried out ( P < .05). Thirty consecutive enrolled patients with a mean age of 66.7 (range, 53-75) years presented 35 CPDFUs with a mean diameter of 16.3 mm and a mean duration of 10.3 months. The most frequent grade of the UTDWC was IIIB (42.9%).

Results:

All ulcers recovered with a mean healing time of 7.9 ± 4.0 (range, 4-17) weeks. AOFAS scores improved significantly from 55.3 to 81.4 points ( P < .001). At a mean follow-up of 25.3 months (range, 18-71), no cases of ulcer recurrence were recorded, while a major complication or a wound infection required longer healing time.

Conclusion:

Minimally invasive DMDO was a safe and effective method in promoting CPDFU healing, regardless of the grade of severity, by the reduction of the high plantar pressure under the metatarsal heads. This technique improved functional and radiographic outcomes with few complications.

Level of Evidence:

IV, case series.
Short-term Clinical and Radiographic Results of the Salto Mobile Total Ankle Prosthesis
Authors: Wan Dong Dong , Choi Woo Jin , Shim Dong Woo , Hwang Yeokgu , Park Yoo Jung , Lee Jin Woo
Published: November 2017

Background:

The mobile-bearing Salto total ankle prosthesis has been reported to have promising outcomes. However, clinical reports on this prosthesis are few, and most have been published by the inventors and disclosed consultants.

Methods:

We retrospectively reviewed 59 patients who received Salto prosthesis unilaterally. The average follow-up was 35.9 (range, 6-56) months. Clinical and radiologic results were evaluated. Clinical results were evaluated according to visual analog scale (VAS), American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score, Ankle Osteoarthritis Scale (AOS) pain and disability score, and ankle range of motion (ROM) in dorsiflexion/plantarflexion. In the radiographic evaluation, we measured the tibial angle (TA), talar angle (TAL), tibial slope, and talocalcaneal angle (TCA) on weightbearing radiographs.

Results:

By the last follow-up, 7 of 59 patients (11.9%) had undergone reoperation, and 3 of 59 implants (5.1%) had been removed. The prosthesis survival was 94.9% (95% CI, 89.1%-100%). With any reoperation as the endpoint of follow-up, the clinical success rate was 88.1% (95% CI, 79.4%-96.9%). The mean postoperative visual analog scale score, AOFAS ankle-hindfoot score, and Ankle Osteoarthritis Scale pain and disability score improved significantly ( P < .001). The ankle range of motion also improved from preoperative 33.4 ± 16.6 to 40.3 ± 15.5 postoperatively ( P < .001); however, there was no statistically significant change in plantarflexion ( P = .243). Radiolucent areas and osteolysis were found in 28 (47.5%) and 27 (45.8%) patients, respectively. Heterotopic ossification was observed in 13 patients (22.0%).

Conclusions:

In this series, early clinical and radiographic outcomes of this prosthesis were promising. We believe the early radiolucent lines were probably due to the gap at the implant and bone interface, and they disappeared at the time of osseous integration. However, longer follow-up is necessary to determine the long-term durability and survivorship of this implant, particularly given the high incidence of postoperative osteolysis.

Level of Evidence:

Level IV, case series.
Restoring Motor Functions After Stroke: Multiple Approaches and Opportunities
Authors: Raffin Estelle , Hummel Friedhelm C.
Published: November 2017

More than 1.5 million people suffer a stroke in Europe per year and more than 70% of stroke survivors experience limited functional recovery of their upper limb, resulting in diminished quality of life. Therefore, interventions to address upper-limb impairment are a priority for stroke survivors and clinicians. While a significant body of evidence supports the use of conventional treatments, such as intensive motor training or constraint-induced movement therapy, the limited and heterogeneous improvements they allow are, for most patients, usually not sufficient to return to full autonomy. Various innovative neurorehabilitation strategies are emerging in order to enhance beneficial plasticity and improve motor recovery. Among them, robotic technologies, brain-computer interfaces, or noninvasive brain stimulation (NIBS) are showing encouraging results. These innovative interventions, such as NIBS, will only provide maximized effects, if the field moves away from the “one-fits all” approach toward a “patient-tailored” approach. After summarizing the most commonly used rehabilitation approaches, we will focus on NIBS and highlight the factors that limit its widespread use in clinical settings. Subsequently, we will propose potential biomarkers that might help to stratify stroke patients in order to identify the individualized optimal therapy. We will discuss future methodological developments, which could open new avenues for poststroke rehabilitation, toward more patient-tailored precision medicine approaches and pathophysiologically motivated strategies.
Neonatal Arterial Ischemic Stroke: Risk Related to Family History, Maternal Diseases, and Genetic Thrombophilia
Authors: Arnaez Juan , Arca Gemma , Martín-Ancel Ana , Agut Thais , Garcia-Alix Alfredo
Published: November 2017

The objective of this study was to evaluate the heritability of neonatal arterial ischemic stroke (NAIS) in relation to family history of thromboembolic event, maternal diseases, and thrombophilia in both parents ( F5G1691A, F2G20210A, and MTHFRC677 T mutations). Forty-two consecutive infants ≥36 weeks of gestation <28 days of life with acute symptomatic NAIS and their parents, as well as 129 controls, were prospectively recruited. Information on maternal data (age, body mass index, oral contraception, migraine, epilepsy, hypertension, and immune disease) and a 3-generation pedigree regarding myocardial infarction, pulmonary embolism, cerebrovascular event, and deep vein thrombosis were obtained. Thrombophilia and maternal diseases did not differ between cases and controls, except for the use of oral contraceptives (more frequent in mothers of controls). No differences were found regarding each studied antecedent of thromboembolic event in the families. The NAIS group showed a higher presence of positive family history among second-degree maternal relatives than did the control infants (odds ratio 4.10; 95% confidence interval 1.29-12.99). Our study does not support the hypothesis that common genetic thrombophilia or familial predisposition to thromboembolic events is associated with the occurrence of idiopathic NAIS.
Inhibitor Risk Stratification and Individualized Treatment in Patients With Nonsevere Hemophilia A: A Single-Institution Practice Audit
Authors: Sun Haowei (Linda) , Chan Stella , Yenson Paul , Jackson Shannon
Published: November 2017

Inhibitor risk in nonsevere hemophilia A increases with cumulative factor VIII (FVIII) exposure days and high-risk mutations. A standardized approach to minimize inhibitor risk is warranted. Following establishment of a systematic approach to reduce inhibitor risk in nonsevere hemophilia, we evaluated the uptake of these strategies into clinical practice. All adult males with nonsevere hemophilia A followed by British Columbia Adult Hemophilia Program from 2004 to 2016 were included in this retrospective audit. Quality-of-care indicators on inhibitor prevention were examined. Of 108 patients, 18 patients had high-risk FVIII mutations for inhibitor development. Rates of FVIII genotyping and 1-deamino-8-d-arginine-vasopressin (DDAVP) testing in mild patients without contraindications were both over 90%, although DDAVP was used for surgical prophylaxis in only 70% of procedures. Inhibitor testing and clinic visits occurred at a median interval of 22 months. Over 80% of patients with high-risk mutations had documentation and education on their inhibitor risk. Our practice audit demonstrated a high level of recognition and patient education of individual inhibitor risk. Impact of our standardized approach on the incidence of inhibitor development is yet to be determined.