A fruitful fly forward : the role of the fly in drug discovery for neurodegeneration

AD, Alzheimer’s disease; APP, amyloid precursor protein; BBB, blood brain barrier; GFP, green fluorescent protein; HTS, high-throughput screening; HD, Huntington’s disease; LB, Lewy bodies; PD, Parkinson’s disease; PolyQ, Polyglutamine; RNAi, RNA interference; SNCA, α-synuclein gene; UAS, Upstream Activating Sequence.peer-reviewe

Neurological diseases and stem cell transplantation - review paper

Stem cells and their potentials for therapy are major areas of research. The literature on the subject is expanding at a very rapid pace and the great prospectives offered by these remarkable cells are continuously being unravelled. The use of stem cells vis-à-vis neurological diseases is of particular interest since many such diseases have a poor prognosis and generally decrease considerably the quality of life. Treatment of neurological diseases is complicated by the lack of regeneration of the nervous system, the neuroanatomical complexity, the presence of the blood-brain barrier and the possible spread of excitotoxicity. Hence, more effective ways how to intervene on these pathological processes are required. This review highlights, the fundamental aspects of stem cell biology, with a special reference to neural stem cells and their niches. Dysmyelinating diseases and invasive brain tumours are specifically considered since, they are presumed candidates for successful clinical application of stem cell therapy.peer-reviewe

Heavy quarkonium hybrids from Coulomb gauge QCD

Using the non-relativisitc reduction of Coulomb gauge QCD we compute spectrum of the low mass hybrid mesons containing a heavy quark-antiquark pair. The gluon degrees of freedom are treated in the mean field approximation calibrated to the gluelump spectrum. We discuss the role of the non-abelian nature of the QCD Coulomb interaction in the ordering of the spin-parity levels.Comment: 12 pages, 6 figure

Generalized gangliosidosis in Malta

The purpose of this paper is to describe the clinical features of four cases of generalized gangliosidosis, two of which in siblings. In two of the cases, and in one of the siblings, B-galactosidase deficiency was demonstrated in blood and urine samples. The point that emerges from these cases is the realization that the clinical distinction between the various ganglioside lipidoses is now no 'longer possible, even in the clinically 'typical' case the resemblance to one or other of the classical Tay-Sachs or Niemann Pick is meaningless without the aid of specialized enzymatic tests. Moreover, the dramatic finding of the cherry-red spots in the retina is now no longer pathognomonic of classical Tay-Sachs disease, as was formerly widely held by clinicians. In every case the exact metabolic defect should be pin-pointed before a definite diagnosis can be made. It therefore becomes mandatory to investigate all patients in this group by special chemical techniques.peer-reviewe

Risk Allocation in Toll Highway Concessions in Spain: Lessons from Economic Recession

Spain has a long tradition of encouraging toll highways by granting concessions to private companies. Concessions in Spain have been characterized by a willingness to transfer considerable risk to the private sector. Traffic demand, acquisition of the right-of-way, and financial risk have often been allocated to the private sector. From 1996 to 2011, 16 toll highway concessions, covering a total distance of 835 km, were awarded by the central government of Spain with this approach. Some of those highways started their operations just before the economic recession began. The recession had negative consequences for Spain's economy. The gross domestic product per capita plummeted, and the unemployment rate increased from 9% to 20% of the working population in just 2 years. The recession also had severe consequences for the economic performance of toll highway concessions. Traffic levels declined at a much greater rate than did the gross domestic product. In addition, the conditions imposed by the financial markets on borrowers became much stricter because of the liquidity crisis. This study analyzes the impact that the economic recession ultimately had on the performance of toll highway concessions in Spain and the actions that the government adopted to avoid the bankruptcy of the concessionaires. It was found that the economic recession helped identify some deficiencies in how risk had been allocated in Spain. The measures that both Spain and the European Union are adopting so as to improve risk allocation are discussed

Congenital malformations survey : a preliminary report

A congenital malformation may be defined as any developmental defect which is present on clinical examination at the time of birth or within the first few months of life. The purpose of this paper is to give a preliminary report on the congenital malformations, major and minor, found in the first 1000 consecutive deliveries at St. Luke's Hospital, Malta over a period of one year. This preliminary survey indicates that the incidence of major and minor congenital malformations in babies born at St. Luke's Hospital is in the region of 2% (20 out of 1016 total births) and 10% (106 out of 1016 total births) respectively. This is similar to that reported from other countries. It is concluded that in spite of alleged inbreeding in a relatively small island population, there is probably no greater incidence of major and minor anomalies in the Maltese islands.peer-reviewe

A case of anorectal agenesis : postoperative complications

An analysis of the postoperative complications of a case of ano-rectal agenesis is here presented. The multiplicity of factors involved, with special emphasis on protein-calorie malnutrition, together with the importance of team-work in the management of this case, is emphasised. The postoperative care of a seriously ill child who has undergone major surgery and may be suffering from multiple complications, necessitates close liaison between the surgeon, the pediatrician and the laboratory and nursing staff. It is clear from the comments about this case that the utmost attention to detail is crucial in the management of such casespeer-reviewe

Presentation and management of diabetic ketoacidosis in adults in Malta

Aim: The aim of this audit was to assess adherence to local guideline in the management of Diabetic Ketoacidosis (DKA). Method: Patients admitted with DKA between April 2013 and March 2015 were identified and data was retrospectively collected from patients’ confidential files and Isoft®. Data collected included initial parameters recorded and biochemical investigations taken (initial and subsequent assessment of pH, HCO3-, blood glucose, potassium levels and urinary ketones), insulin regime started and intravenous fluid administered. Results: During the established time period 40 cases of DKA were identified in 18 patients. Median age was 33 years with a female preponderance of 60%. Six patients had newly diagnosed diabetes mellitus while 8 patients had more than one admission of DKA. All cases had capillary blood glucose monitoring (BGM) and/or venous random blood (plasma) glucose (RBG) checked and pH and HCO3- recorded on admission. 0.9% sodium chloride was the intravenous fluid started in all cases (as recommended by the guideline) and a median of 6.75L was prescribed during the first 24 hours. The median time spent on intravenous insulin infusion was 42.7 hours while the median time to pH >7.30, HCO3- >15mmol/L and negligible urinary ketones were 6.88, 12.83 and 34.5 hours respectively. Subcutaneous insulin was started at a median time of 48.21 hours from initiation of DKA protocol. Conclusion: This audit showed good adherence to local guideline. The great discrepancy between the time to pH >7.3 and the time to negligible urinary ketones highlights the need to introduce tools to measure systemic ketone production in the management of DKA with an update in the current local clinical practice guideline.peer-reviewe

Major incident triage: Derivation and comparative analysis of the Modified Physiological Triage Tool (MPTT).

BACKGROUND: Triage is a key principle in the effective management at a major incident. There are at least three different triage systems in use worldwide and previous attempts to validate them, have revealed limited sensitivity. Within a civilian adult population, there has been no work to develop an improved system. METHODS: A retrospective database review of the UK Joint Theatre Trauma Registry was performed for all adult patients (>18years) presenting to a deployed Military Treatment Facility between 2006 and 2013. Patients were defined as Priority One if they had received one or more life-saving interventions from a previously defined list. Using first recorded hospital physiological data (HR/RR/GCS), binary logistic regression models were used to derive optimum physiological ranges to predict need for life-saving intervention. This allowed for the derivation of the Modified Physiological Triage Tool-MPTT (GCS≥14, HR≥100, 12<RR≥22). A comparison of the MPTT and existing triage tools was then performed using sensitivities and specificities with 95% confidence intervals. Differences in performance were assessed for statistical significance using a McNemar test with Bonferroni correction. RESULTS: Of 6095 patients, 3654 (60.0%) had complete data and were included in the study, with 1738 (47.6%) identified as priority one. Existing triage tools had a maximum sensitivity of 50.9% (Modified Military Sieve) and specificity of 98.4% (Careflight). The MPTT (sensitivity 69.9%, 95% CI 0.677-0.720, specificity 65.3%, 95% CI 0.632-0.675) showed an absolute increase in sensitivity over existing tools ranging from 19.0% (Modified Military Sieve) to 45.1% (Triage Sieve). There was a statistically significant difference between the performance (p<0.001) between the MPTT and the Modified Military Sieve. DISCUSSION & CONCLUSION: The performance characteristics of the MPTT exceed existing major incident triage systems, whilst maintaining an appropriate rate of over-triage and minimising under-triage within the context of predicting the need for a life-saving intervention in a military setting. Further work is required to both prospectively validate this system and to identify its performance within a civilian environment, prior to recommending its use in the major incident setting