The evolution of labour law in the new member states of the European Union : 1995-2005 - country studies on Cyprus and Malta

This Report traces the development of Labour Law and the implications for Industrial Relations, as well as social and employment policy more generally, in the two small Mediterranean countries of Cyprus and Malta during the period 1995–2005. This period was particularly important for the two countries as it coincided with their efforts for accession to the European Union (EU) and the process of harmonisation with the Acquis Communautaire. Since their independence in 1960 and 1964 respectively for Cyprus and Malta, successive Governments in each country – working with the social partners – had sought to steer a policy of social cohesion to underpin their development efforts. Whilst these strategies were successful in fostering a long period of economic growth and peaceful labour relations, a major outcome was the existence of relatively inflexible labour markets. Liberalisation and globalisation of international markets, coupled with the pressure exerted by the accession process, which required the implementation of the Acquis Communautaire necessitated a series of changes with far reaching implications in social and economic affairs. Naturally the framework of Labour Law – and labour practices thereof – came under increasing pressure to adapt and reform. The Executive Summary describes the main aims and objectives of the Report on the evolution of Labour Law in Cyprus and Malta in the period 1995-2005, and provides an outline of the component chapters. Specifically the Report is divided into three chapters. The first and second chapters consist of the individual Reports on Cyprus and Malta respectively. These constitute the main body of the Report and investigate the evolution of Labour Law in the two countries separately and the implications for Industrial Relations, employment and social policy. The third chapter provides a concluding overview of the two countries’ experiences and an evaluation of the state of implementation of the Acquis Communautaire in the fields examined.peer-reviewe

Novel HDAC6 inhibitors increase tubulin acetylation and rescue axonal transport of mitochondria in a model of Charcot-Marie-Tooth Type 2F

Disruption of axonal transport causes a number of rare, inherited axonopathies and is heavily implicated in a wide range of more common neurodegenerative disorders, many of them age- related. Acetylation of α-tubulin is one important regulatory mechanism, influencing microtubule stability and motor protein attachment. Of several strategies so far used to enhance axonal transport, increasing microtubule acetylation through inhibition of the deacetylase enzyme HDAC6 has been one of the most effective. Several inhibitors have been developed and tested in animal and cellular models but better drug candidates are still needed. Here we report the development and characterisation of two highly potent HDAC6 inhibitors, which show low toxicity, promising pharmacokinetic properties, and enhance microtubule acetylation in the nanomolar range. We demonstrate their capacity to rescue axonal transport of mitochondria in a primary neuronal culture model of the inherited axonopathy Charcot- Marie-Tooth Type 2F, caused by a dominantly acting mutation in heat shock protein beta 1.Funding for this work was provided by Takeda Development Centre Europe Ltd. M.P.C. is funded by the John and Lucille van Geest Foundation

Skin Biopsy in the Context of Dermatological Diagnosis: A Retrospective Cohort Study

Background. Skin biopsy is an established method for allying the dermatologist in overcoming the diagnostic dilemmas which occur during consultations. However neither do all skin biopsies produce a conclusive diagnosis nor the dermatologists routinely perform this procedure to every patient they consult. The aim of this study was to investigate the favourable clinical diagnoses set by dermatologists when performing skin biopsy, the diagnoses reached by the dermatopathologists after microscopic examination, and the relationship between them and finally to comment on the instances that skin biopsy fails to fulfill the diagnostic task. Methods. Six thousand eight hundred and sixteen biopsy specimens were reviewed and descriptive statistics were performed. Results. The mean age of the patients was 54.58 ± 0.26 years, the most common site of biopsy was the head and neck (38.3%), the most frequently proposed clinical diagnoses included malignancies (19.28%), and the most prevalent pathological diagnosis was epitheliomas (21.9%). After microscopic examination, a specific histological diagnosis was proposed in 83.29% of the cases and a consensus between clinical and histological diagnoses was observed in 68% of them. Conclusions. Although there are cases that skin biopsy exhibits diagnostic inefficiency, it remains a valuable aid for the dermatology clinical practice

Enhancement of endogenous midbrain neurogenesis by microneurotrophin BNN-20 after neural progenitor grafting in a mouse model of nigral degeneration

We have previously shown the neuroprotective and pro-neurogenic activity of microneurotrophin BNN-20 in the substantia nigra of the “weaver” mouse, a model of progressive nigrostriatal degeneration. Here, we extended our investigation in two clinically-relevant ways. First, we assessed the effects of BNN-20 on human induced pluripotent stem cell-derived neural progenitor cells and neurons derived from healthy and parkinsonian donors. Second, we assessed if BNN-20 can boost the outcome of mouse neural progenitor cell intranigral transplantations in weaver mice, at late stages of degeneration. We found that BNN-20 has limited direct effects on cultured human induced pluripotent stem cell-derived neural progenitor cells, marginally enhancing their differentiation towards neurons and partially reversing the pathological phenotype of dopaminergic neurons generated from parkinsonian donors. In agreement, we found no effects of BNN-20 on the mouse neural progenitor cells grafted in the substantia nigra of weaver mice. However, the graft strongly induced an endogenous neurogenic response throughout the midbrain, which was significantly enhanced by the administration of microneurotrophin BNN-20. Our results provide straightforward evidence of the existence of an endogenous midbrain neurogenic system that can be specifically strengthened by BNN-20. Interestingly, the lack of major similar activity on cultured human induced pluripotent stem cell-derived neural progenitors and their progeny reveals the in vivo specificity of the aforementioned pro-neurogenic effect

First treatment of mycosis fungoides by total skin electron beam (TSEB) therapy in Greece

BackgroundMycosis fungoides (MF), the most common subtype of cutaneous T-Cell Lymphoma (CTCL), is a rare chronic skin neoplasia. Total skin electron irradiation has been employed along with a variety of other topical or systemic treatments for MF management.AimTo report the first case treated by TSEB irradiation protocol in Greece.Materials and methodsA fractionated 36[[ce:hsp sp="0.25"/]]Gy total skin electron beam (TSEB) therapy was prescribed to a 65-years-old male patient with mycosis fungoides (MF), stage IIB, refractory to several treatments during a 20-year period. Dose uniform delivery was monitored by thermo-luminescence dosimetry.Results and discussionThe homogeneous skin dose distribution resulted in a complete clinical response. Limited, irradiation-oriented, side effects appeared.ConclusionsThe first TSEB irradiation prescription in Greek medical chronicles was proved effective in this case of tumor stage MF (T3-IIB), which had been refractory to several single or combination treatments

Cardiac Resynchronisation Therapy and Cellular Bioenergetics: Effects Beyond Chamber Mechanics

Cardiac resynchronisation therapy is a cornerstone in the treatment of advanced dyssynchronous heart failure. However, despite its widespread clinical application, precise mechanisms through which it exerts its beneficial effects remain elusive. Several studies have pointed to a metabolic component suggesting that, both in concert with alterations in chamber mechanics and independently of them, resynchronisation reverses detrimental changes to cellular metabolism, increasing energy efficiency and metabolic reserve. These actions could partially account for the existence of responders that improve functionally but not echocardiographically. This article will attempt to summarise key components of cardiomyocyte metabolism in health and heart failure, with a focus on the dyssynchronous variant. Both chamber mechanics-related and -unrelated pathways of resynchronisation effects on bioenergetics – stemming from the ultramicroscopic level – and a possible common underlying mechanism relating mechanosensing to metabolism through the cytoskeleton will be presented. Improved insights regarding the cellular and molecular effects of resynchronisation on bioenergetics will promote our understanding of non-response, optimal device programming and lead to better patient care

European Physician Survey Characterizing the Clinical Pathway and Treatment Patterns of Patients Post-Myocardial Infarction

Introduction: The 2019 European Society of Cardiology and European Atherosclerosis Society (2019 ESC/EAS) guidelines stress the importance of managing low-density lipoprotein cholesterol (LDL-C) after myocardial infarction (MI) to reduce the risk of cardiovascular events. Information on guideline implementation is limited. The aim of this survey was to describe current clinical practice regarding LDL-C management in the first year post-MI across Europe, improving understanding of the role of ESC/EAS guidelines on clinical practice. Methods: A qualitative web-based cross-sectional physician survey about the patient pathway and LDL-C management post-MI was conducted in 360 physicians from France, Italy, Germany, The Netherlands, Spain, and the UK (n = 60/country) between December 2019 and June 2020. Secondary and primary care physicians (SCPs/PCPs) described their experiences treating patients post-MI over the preceding 2months. Results: Physicians reported that on average 90.7% of patients not prescribed lipid-lowering therapy (LLT) before an MI initiated LLT as inpatients; for patients already taking LLT, treatment was intensified for 64.7% of inpatients post-MI. SCPs reported prescribing higher-intensity statins and/or ezetimibe for between 72.3% (Italy) and 88.6% (UK) of patients post-MI. More than 80.0% of SCPs and 51.2% of PCPs stated that they would initiate a change in LLT immediately if patients did not achieve their LDL-C treatment goal by 12weeks post-MI; 82.0% of SCPs and 55.1% of PCPs reported referring to 2019 ESC/EAS guidelines for management of patients post-MI. Barriers to initiating PCSK9 inhibitors (PCSK9is) included prior prescription of a maximally tolerated dose of statin (49.4%) and/or ezetimibe (38.9%), requirement to reach threshold LDL-C levels (44.9%), and pre-authorization requirements (30.4%). Conclusion: Differences in clinical practice post-MI were reported across the countries surveyed, including divergence between 2019 ESC/EAS and local guidelines. Increased use of innovative medicines to achieve LDL-C goals should reduce risk of subsequent cardiovascular events in very high-risk patients post-MI

In Utero Gene Therapy (IUGT) Using GLOBE Lentiviral Vector Phenotypically Corrects the Heterozygous Humanised Mouse Model and Its Progress Can Be Monitored Using MRI Techniques

Funder: UK Thalassaemia SocietyAbstract: In utero gene therapy (IUGT) to the fetal hematopoietic compartment could be used to treat congenital blood disorders such as β-thalassemia. A humanised mouse model of β-thalassemia was used, in which heterozygous animals are anaemic with splenomegaly and extramedullary hematopoiesis. Intrahepatic in utero injections of a β globin-expressing lentiviral vector (GLOBE), were performed in fetuses at E13.5 of gestation. We analysed animals at 12 and 32 weeks of age, for vector copy number in bone marrow, peripheral blood liver and spleen and we performed integration site analysis. Compared to noninjected heterozygous animals IUGT normalised blood haemoglobin levels and spleen weight. Integration site analysis showed polyclonality. The left ventricular ejection fraction measured using magnetic resonance imaging (MRI) in treated heterozygous animals was similar to that of normal non-β-thalassemic mice but significantly higher than untreated heterozygous thalassemia mice suggesting that IUGT ameliorated poor cardiac function. GLOBE LV-mediated IUGT normalised the haematological and anatomical phenotype in a heterozygous humanised model of β-thalassemia

Static and dynamic mechanics of the murine lung after intratracheal bleomycin

<p>Abstract</p> <p>Background</p> <p>Despite its widespread use in pulmonary fibrosis research, the bleomycin mouse model has not been thoroughly validated from a pulmonary functional standpoint using new technologies. Purpose of this study was to systematically assess the functional alterations induced in murine lungs by fibrogenic agent bleomycin and to compare the forced oscillation technique with quasi-static pressure-volume curves in mice following bleomycin exposure.</p> <p>Methods</p> <p>Single intratracheal injections of saline (50 μL) or bleomycin (2 mg/Kg in 50 μL saline) were administered to C57BL/6 (<it>n </it>= 40) and Balb/c (<it>n </it>= 32) mice. Injury/fibrosis score, tissue volume density (TVD), collagen content, airway resistance (<it>R_N</it>), tissue damping (<it>G</it>) and elastance coefficient (<it>H</it>), hysteresivity (<it>η</it>), and area of pressure-volume curve (PV-A) were determined after 7 and 21 days (inflammation and fibrosis stage, respectively). Statistical hypothesis testing was performed using one-way ANOVA with LSD <it>post hoc </it>tests.</p> <p>Results</p> <p>Both C57BL/6 and Balb/c mice developed weight loss and lung inflammation after bleomycin. However, only C57BL/6 mice displayed cachexia and fibrosis, evidenced by increased fibrosis score, TVD, and collagen. At day 7, PV-A increased significantly and <it>G </it>and <it>H </it>non-significantly in bleomycin-exposed C57BL/6 mice compared to saline controls and further increase in all parameters was documented at day 21. <it>G </it>and <it>H</it>, but not PV-A, correlated well with the presence of fibrosis based on histology, TVD and collagen. In Balb/c mice, no change in collagen content, histology score, TVD, <it>H </it>and <it>G </it>was noted following bleomycin exposure, yet PV-A increased significantly compared to saline controls.</p> <p>Conclusions</p> <p>Lung dysfunction in the bleomycin model is more pronounced during the fibrosis stage rather than the inflammation stage. Forced oscillation mechanics are accurate indicators of experimental bleomycin-induced lung fibrosis. Quasi-static PV-curves may be more sensitive than forced oscillations at detecting inflammation and fibrosis.</p