Interactions between megakaryocytes and tumour cells in the bone marrow vascular stem cell niche promote tumour growth and metastasis

Specialized bone marrow microenvironments (vascular and osteoblastic 'niches') regulate normal haematopoietic stem/progenitor cells. Recently, the vascular niche has also been implicated as an area for preferential engraftment of malignant cells. The cellular and molecular factors that regulate the vascular niche and, in particular, the role of megakaryocytes are poorly understood. The aim of my work was to investigate the role of megakaryocytes in homing and engraftment of malignant cells to the bone marrow vascular niche using mouse models. C57Bl/6 wild-type and megakaryocyte-deficient, thrombopoietin (TPO)-/- mice were injected with B16 melanoma or EL4 lymphoma cell lines and the megakaryocyte-vascular niche investigated by immunohistochemistry, confocal microscopy, in vitro culture, co-cultures and gene expression by RT-PCR. In wild-type mice injected with B16 melanoma, platelet size and megakaryocyte numbers significantly increased (P<0.02). B16 tumour cells were found to produce the thrombopoietic factors VEGF, SCF and IL11. Bone marrow sinusoids were almost universally surrounded by one of more megakaryocytes tightly abutting the vascular endothelium, forming the megakaryocyte-vascular niche. Metastatic B16 cells were observed in close association with megakaryocytes in the vascular niche, consistent with this being a port of entry to the bone marrow. In TPO-/- mice, tumour growth and metastasis was markedly retarded and no tumour cells were seen in the bone marrow, suggesting that megakaryocytes play a functional role in metastasis. In TPO-/- bone marrow, vessels were more tortuous and larger in diameter (P=0.01); and expression of PF4, TSP1, VEGF and TGFβ was 70%- 90% lower, suggesting that a major proportion of angiogenic regulatory factors is producted by megakaryocytes in the bone marrow in wild-type mice. Furthermore, in wild-type mice, expression of VEGF and TGFβ significantly increased during tumour growth and metastasis while PF4 expression decreased (P<0.05). Megakaryocyte-conditioned medium (MCM) enhanced the proliferation rate of B16 cells (P<0.001) and also was highly chemotactic for B16 cells (P<0.001), an effect mediated by pertussis toxin-sensitive Gi-protein receptors and reduced in the absence of TSP1. Co-culture with B16 cells increased megakaryocyte expression of VEGF, TGFβ and TSP1 and decreased PF4, consistent with the in vivo observations, while cocultured B16 cells displayed increased expression of VEGF and TGFβ and adhesion integrins. Moreover, pretreating B16 cells with MCM prior to tail vein injection enhanced metastatic engraftment. To investigate the role of megakaryocytes in human malignancy, trephine bone marrow biopsies from patients with metastatic carcinoma were examined. Increased megakaryocyte numbers and abnormal megakaryocyte clustering were observed in the majority of patients, suggesting that megakaryocyte-tumour interactions may also occur in the setting of human metastatic disease. In conclusion, my findings suggest that megakaryocytes contribute to the integrity and function of the bone marrow vascular niche and that cellular/molecular cross talk between megakaryocytes and tumour cells may promote metastasis. Targeting these interactions may be useful as adjunctive therapy in metastatic disease

Fibular stress fracture in a female cross-country runner : a case report

Stress fractures are probably the most feared class of injuries amongst endurance athletes, especially runners, since they require lengthy rehabilitation periods and temporary but drastic modifications of their training regime. A detailed literature review is presented with the aim of highlighting the importance of athlete education as well as pre-participation screening in female athletes for one or more components of the triad.peer-reviewe

Spiritual care at the end of life: whose job is it?

Interest in and recognition of the function of religious and spiritual coping in adjustment to serious illness has been growing. In particular, there has been increasing interest in the importance of understanding and valuing patients' individual spirituality as a function of providing appropriate support, particularly as part of nursing practice. This stems partly from the influence and application of palliative care principles in a range of care settings and not just hospices. Four decades of professional rhetoric have emphasised the importance of care for the 'whole' person in terms of spiritual as well as psychological, physical and social needs, without evaluating its impacts on patients or considering whether this approach is realistic in every case. Professional ideology within palliative care has been dominant in influencing a culture of openness between professional health workers and dying patients in their care, with attention to spiritual needs an increasing part of professionals' remit. New ways to both assess and address spiritual concerns as part of overall quality of life are being developed by health care practitioners as part of a package of support for people with critical and terminal illness (Randall and Downie, 2006; Watts, 2008). For this support to be meaningful, however, it is necessary to determine which dimensions of spirituality are relevant and the ways in which the human spirit can be celebrated in the face of life-threatening illness (Cobb and Legood, 2008). The ultimate value of such exploration is to make it possible for us to die the way we live (Hockey, 2002)

An unexpected cause of palmar paraesthesia in a soldier : a case report

Athletes presenting with neurological symptoms merit thorough assessments that in most cases will include investigations with one or more imaging modality. Imaging is especially useful in atypical presentations of neurological pathology (both acute and chronic) as was the instance in the presented case report. The case of a 22-year-old male soldier is presented who presented with a two week history of paraesthesia involving his right hand. After being assessed by the military medical officer, a presumptive diagnosis of cervical radiculopathy was made and appropriate treatment was prescribed. Symptoms persisted despite treatment and following an inconclusive cervical X-Ray, a magnetic resonance scan was booked that confirmed the diagnosis of multiple sclerosis. The patient was admitted to hospital and started on intravenous methylprednisolone and beta-interferon therapy with resolution of his symptoms. This case highlights the usefulness of imaging in confirming diagnosis, especially in atypical presentations of pathology afflicting the neurological system. Atypical symptoms, lack of response to standard therapy and inconclusive initial radiological investigations, should prompt the physician to carry out further detailed imaging modalities. The choice of the latter will need to reflect the working differential diagnoses. With reference to the presented case, imaging plays a role not only in diagnosis but also in assessing response to treatment and disease progression.peer-reviewe

The impact of non-performing loans on the profitability of listed Euro-Mediterranean commercial banks

This paper is based on the unpublished Thesis by Psaila, A. (2019) “The Impact of Non Performing Loans on the profitability of listed Euro-Mediterranean commercial banks” supervised by Dr. S. Grima. An earlier version of this article has been presented in ICABE 2019 www.icabe.grPurpose: To analyze the impact of NPLs on listed commercial bank’s profitability, in particular their ROA (Return on Assets), in the Euro-Mediterranean area. We aim to determine whether the change in the level of NPLs in listed commercial banks is either positively or negatively impacting the ROA of the concerned banks. Furthermore, knowing that the liquidity and the solvency of a bank are both equally important to maintain a robust financial position, a Liquidity (LQDT) and Solvency (SLVT) ratio were considered to help explain the variances with NPLs and ROA. Design/Methodology/Approach: We adopted a purposive research design using panel data (2013-2017) from data published on Thomson Reuters Eikon or annual reports of the 35 listed commercial banks in the Euro-Mediterranean region. We used descriptive statistics and four regression models, namely; the Pooled OLS regression model, Fixed Effects (FE), Random Effects (RE) and the Arellano-Bond (AB), through STATA/IC 15.1. Findings: Findings show that there is a negative impact of NPLs on ROA, indicating that problematic loans negatively impact listed commercial bank’s profitability in the EuroMediterranean region. Also, it was indicated that the Solvency ratio (SLVT) is the only controlling factor that can significantly explain variances within NPLs and ROA. Practical Implications: These results carry with them significant consequences for the bank’s financial stability within the Euro-Mediterranean countries and the role of the risk management function of listed commercial banks.peer-reviewe

The role of sports and exercise medicine in the military

Background Military training is notorious for being physically intensive interspersed by limited recovery periods, culminating in a high frequency of training-related injuries. Confusion may arise when military personnel are compared to athletes in other sporting disciplines in view of different training regimes employed by the military according to the set standard of the respective army. Hence, in line with other sporting disciplines having a designated medical team of sports and exercise professionals that is experienced in that particular field, this article discusses the importance of having such a team in the military. Objective The benefits of having a designated sports and exercise medicine set-up are discussed vis-à-vis the military. Methods A literature review of injuries related to military training comparing different armies is presented. Audit work attained from a military sports and exercise clinic is presented, listing injury type (acute or overuse) as well as the anatomical areas involved to highlight the specifics of injury outcomes in this population. Results A total of 72% of injuries listed were overuse in nature with a high propensity of injuries recorded in the lower limbs, in keeping with the methods of training employed by armies worldwide. Conclusion The availability of a designated sports and exercise clinic in a military setting can serve various purposes, not only through the provision of a service that is specific to military personnel and which therefore complements the ongoing training structures, but also through the provision of guidance in the planning of training regimes as well as in pre-training medical screening.peer-reviewe

The Ehlers-Danlos syndrome

A case study of a nineteen year old female illustrates the main features of the Ehlers-Danlos syndrome. This is a rare syndrome, the characteristic features of which are hyper elasticity and fragility of the skin, hyperextensibility of joints and fragility of blood vessels. Musculo-skeletal, ocular and internal manifestations are present in some cases. The main feature of this case was severe bleeding from minor trauma. The Kyphoscoliosis was first noticed in childhood but had become worse in her teens and she had evidence of respiratory insufficiency secondary to the marked chest deformity. No treatment is known. Surgical procedures may present a problem as the tissues are friable and difficult to suture. Meticulous techniques and pressure dressing are desirable.peer-reviewe

The value of X-ray chest screening

Paper read at the 1973 Annual Meeting of the Association of Physicians and Surgeons of Malta. Two cases of serious thoracic disease were discovered on routine Chest X-Ray screening in 150 schoolboys: one student being found to be suffering from ganglioneuroma, the other from coarctation of the aorta. Both were symptom free and both required thoracic surgery. The purpose of this paper is to emphasize and illustrate a well-known fact; the value of screening in the community. The example used is Chest X-Ray Screening.peer-reviewe

Spirituality in psychotherapy : a hidden dimension : an exploratory study

Many in the caring professions consider spirituality to be a fundamental dimension of human experience and identity. Consequently, some claim that this dimension cannot be ignored in disciplines such as psychotherapy that deals with the human being and with human experience. Moreover, the increase in secularisation and the emphasis on the subjective and the personal in people's experience of spirituality and religion, have led to an increased interest in psychotherapy, counselling and other forms of activities and professions that deal more closely with the personal and subjective. Other themes that connect spirituality and psychotherapy include: spirituality is related to a person's mental health; people make meaning which assumes that they are spiritual beings; and spirituality and psychotherapy both involve enlightenment and meaning-making. For some, spirituality is manifest in psychotherapy either because of spiritual concerns that are raised by clients in the psychotherapeutic process, as a resource, or as a form of pathology. For others, therapy is a spiritual encounter. The research is a qualitative exploratory study of the experience and perception of the spiritual dimension of psychotherapy of Maltese practitioners. The study was held with two groups of Maltese psychotherapists and clinical and counselling psychologists. Each group attended a series of four focus/study group sessions. Key areas explored include the participants' conception of spirituality and religion and their understanding and experience of the spiritual dimension in counselling and psychotherapy. Broadly, the study focused on the ways in which spirituality may become manifest' and express itself in the psychotherapeutic process, the roles and experiences of the therapist and the client regarding spirituality in counselling and psychotherapy and the identification of the factors that may contribute to the spiritual dimension of counselling and psychotherapy. The findings are presented as two main domains, that of 'understanding spirituality and religion in a postmodern context' and 'spirituality and psychotherapy'. The latter is divided into four themes that are facets of the domain 'spirituality and psychotherapy'. These are a) understanding spirituality and religion, b) the therapeutic relationship as sacred space, c) the being: it is who the therapist is that counts and d) applications in clinical practice. The findings are discussed in relation to the literature and to the Maltese context

An integrated approach to the management of health care in Malta

A successful health care programme depends directly on the team work of a group of people who care about and who care for patients in the management of their sickness with the aim of allaying the symptoms in all' cases and of a complete cure whenever possible. This team is made up of general practitioners, hospital medical officers, consultants, pharmacists, dentists, physiotherapists, occupational therapists, speech therapists, nurses and social workers. According to the front cover of the Pharmaceutical Journal of September 18th, 1982, in the 16th Century the physician and pharmacist worked closely together, but today we rarely see them depicted together. This might be so in other countries, but I am pleased to say, it is not the case in Malta. The pharmacist is an important member of the team looking after the sick. His place as a prominent member of this team has been enhanced by a working programme planned between the Department of Medicine and the Department of Pharmacy of our University under the auspices of the Ministry of Health. This working programme will be discussed later in this paper; at this stage I am going to dwell on the situation in Malta vis-a-vis the traditional relationship between the pharmacist and the physician.peer-reviewe