Carotid artery disease screening : assessment of criteria

The Department of Radiology at St. Luke’s Hospital has provided a screening service for stroke related disease since April 1991. This consisted of Duplex Ultrasound screening (DUS) for Extracranial Carotid Artery Disease (ECAD) followed by angiography or intra-arterial digital subtraction angiography (lADSA) or digital intravenous angiography (DIVA) if ultrasound screening was positive for significant disease. The aim of this study was to evaluate in the local context, the various criteria for assessment already established overseas and to devise the best combination of these criteria to improve the detection of disease, thus improving the quality of the•local screening service. 504 patients have been screened for stroke related disease. Twelve patients (6M : 6F) with significant disease, who were considered for surgery, were referred for angiography, IADSA or DIVA. Comparison of these two modalities, DUS and vascular study, were made on 22 sides for the Multicentre Criteria (MCC), the Modified Seattle Criteria (MSC) and the Modified Washington Criteria (MWC). The accuracy, sensitivity, specificity, positive predictive value and negative predictive value were calculated for the MCC, the MSC and the MWC for peak systolic velocity. For the MCC the end diastolic velocity, the systolic velocity ratio and the diastolic velocity ratio were also compiled. The highest precision for extra cranial carotid artery disease screening can be achieved by a combination of the MCC or MSC for peak systolic velocity and with the systolic velocity ratio for the MCC.peer-reviewe

Five years of peripheral percutaneous transluminal angioplasty : the St Luke’s Hospital experience

This article reviews the first series of 54 cases of Percutaneous Transluminal Angioplasty on the peripheral vasculature performed at the Radiological/Surgical Department at St. Luke’s Hospital, Malta, over a five year period. After describing in detail the technique used, the indications and the objective criteria utilised for assessment are reviewed and analysed. The two year patency rate for femoro-popliteal and iliac stenoses was 93% and 86% respectively, while for corresponding occlusions, the figures were 42% and 0% respectively. Thus, while the results were very encouraging for femoro-popliteal stenoses and occlusions, they were unacceptable for iliac occlusions. As expected the major risk factors were smoking, diabetes mellitus and associated ischaemic heart or cerebrovascular disease. This series had no mortality and there was minimal morbidity, mainly at the site of arterial access. Elective surgery for iliac re-stenosis was only required in one patient.peer-reviewe

The rise of pertussis in Malta in 2011 : a case for adolescent and adult pertussis booster vaccination

Notwithstanding the high rates of pertussis infant vaccination coverage in developed countries, Bortedella pertussis infections are manifesting a changing epidemiological pattern of disease. Of notable concern is the rise of pertussis in adolescents and adults. This changing picture is largely attributable to waning immunity after natural infection or vaccination. The belief that pertussis is chiefly a childhood disease is a common misconception. A significant rise of pertussis cases in Malta in older age groups was recorded in 2011. The addition of an adolescent and/or an adult booster dose against pertussis should be strongly considered.peer-reviewe

Investigating the role for IL-21 in rabies virus vaccine-induced immunity.

Over two-thirds of the world\u27s population lives in regions where rabies is endemic, resulting in over 15 million people receiving multi-dose post-exposure prophylaxis (PEP) and over 55,000 deaths per year globally. A major goal in rabies virus (RABV) research is to develop a single-dose PEP that would simplify vaccination protocols, reduce costs associated with RABV prevention, and save lives. Protection against RABV infections requires virus neutralizing antibodies; however, factors influencing the development of protective RABV-specific B cell responses remain to be elucidated. Here we used a mouse model of IL-21 receptor-deficiency (IL-21R-/-) to characterize the role for IL-21 in RABV vaccine-induced immunity. IL-21R-/- mice immunized with a low dose of a live recombinant RABV-based vaccine (rRABV) produced only low levels of primary or secondary anti-RABV antibody response while wild-type mice developed potent anti-RABV antibodies. Furthermore, IL-21R-/- mice immunized with low-dose rRABV were only minimally protected against pathogenic RABV challenge, while all wild-type mice survived challenge, indicating that IL-21R signaling is required for antibody production in response to low-dose RABV-based vaccination. IL-21R-/- mice immunized with a higher dose of vaccine produced suboptimal anti-RABV primary antibody responses, but showed potent secondary antibodies and protection similar to wild-type mice upon challenge with pathogenic RABV, indicating that IL-21 is dispensable for secondary antibody responses to live RABV-based vaccines when a primary response develops. Furthermore, we show that IL-21 is dispensable for the generation of Tfh cells and memory B cells in the draining lymph nodes of immunized mice but is required for the detection of optimal GC B cells or plasma cells in the lymph node or bone marrow, respectively, in a vaccine dose-dependent manner. Collectively, our preliminary data show that IL-21 is critical for the development of optimal vaccine-induced primary but not secondary antibody responses against RABV infections

Mitochondrial Mislocalization Underlies Aβ42-Induced Neuronal Dysfunction in a Drosophila Model of Alzheimer's Disease

The amyloid-β 42 (Aβ42) is thought to play a central role in the pathogenesis of Alzheimer's disease (AD). However, the molecular mechanisms by which Aβ42 induces neuronal dysfunction and degeneration remain elusive. Mitochondrial dysfunctions are implicated in AD brains. Whether mitochondrial dysfunctions are merely a consequence of AD pathology, or are early seminal events in AD pathogenesis remains to be determined. Here, we show that Aβ42 induces mitochondrial mislocalization, which contributes to Aβ42-induced neuronal dysfunction in a transgenic Drosophila model. In the Aβ42 fly brain, mitochondria were reduced in axons and dendrites, and accumulated in the somata without severe mitochondrial damage or neurodegeneration. In contrast, organization of microtubule or global axonal transport was not significantly altered at this stage. Aβ42-induced behavioral defects were exacerbated by genetic reductions in mitochondrial transport, and were modulated by cAMP levels and PKA activity. Levels of putative PKA substrate phosphoproteins were reduced in the Aβ42 fly brains. Importantly, perturbations in mitochondrial transport in neurons were sufficient to disrupt PKA signaling and induce late-onset behavioral deficits, suggesting a mechanism whereby mitochondrial mislocalization contributes to Aβ42-induced neuronal dysfunction. These results demonstrate that mislocalization of mitochondria underlies the pathogenic effects of Aβ42 in vivo

Comparison of Heterologous Prime-Boost Strategies against Human Immunodeficiency Virus Type 1 Gag Using Negative Stranded RNA Viruses.

This study analyzed a heterologous prime-boost vaccine approach against HIV-1 using three different antigenically unrelated negative-stranded viruses (NSV) expressing HIV-1 Gag as vaccine vectors: rabies virus (RABV), vesicular stomatitis virus (VSV) and Newcastle disease virus (NDV). We hypothesized that this approach would result in more robust cellular immune responses than those achieved with the use of any of the vaccines alone in a homologous prime-boost regimen. To this end, we primed BALB/c mice with each of the NSV-based vectors. Primed mice were rested for thirty-five days after which we administered a second immunization with the same or heterologous NSV-Gag viruses. The magnitude and quality of the Gag-specific CD8(+) T cells in response to these vectors post boost were measured. In addition, we performed challenge experiments using vaccinia virus expressing HIV-1 Gag (VV-Gag) thirty-three days after the boost inoculation. Our results showed that the choice of the vaccine used for priming was important for the detected Gag-specific CD8(+) T cell recall responses post boost and that NDV-Gag appeared to result in a more robust recall of CD8(+) T cell responses independent of the prime vaccine used. However, the different prime-boost strategies were not distinct for the parameters studied in the challenge experiments using VV-Gag but did indicate some benefits compared to single immunizations. Taken together, our data show that NSV vectors can individually stimulate HIV-Gag specific CD8(+) T cells that are effectively recalled by other NSV vectors in a heterologous prime-boost approach. These results provide evidence that RABV, VSV and NDV can be used in combination to develop vaccines needing prime-boost regimens to stimulate effective immune responses

Genetic correlations between wellbeing, depression and anxiety symptoms and behavioral responses to the emotional faces task in healthy twins

© 2018 Elsevier BV. This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/ This author accepted manuscript is made available following 12 month embargo from date of publication (March 2018) in accordance with the publisher’s archiving policyCurrently there is a very limited understanding of how mental wellbeing versus anxiety and depression symptoms are associated with emotion processing behaviour. For the first time, we examined these associations using a behavioural emotion task of positive and negative facial expressions in 1668 healthy adult twins. Linear mixed model results suggested faster reaction times to happy facial expressions was associated with higher wellbeing scores, and slower reaction times with higher depression and anxiety scores. Multivariate twin modelling identified a significant genetic correlation between depression and anxiety symptoms and reaction time to happy facial expressions, in the absence of any significant correlations with wellbeing. We also found a significant negative phenotypic relationship between depression and anxiety symptoms and accuracy for identifying neutral emotions, although the genetic or environment correlations were not significant in the multivariate model. Overall, the phenotypic relationships between speed of identifying happy facial expressions and wellbeing on the one hand, versus depression and anxiety symptoms on the other, were in opposing directions. Twin modelling revealed a small common genetic correlation between response to happy faces and depression and anxiety symptoms alone, suggesting that wellbeing and depression and anxiety symptoms show largely independent relationships with emotion processing at the behavioral level

Good distribution practice training for medical device industry

In 2017 the European Parliament initiated the process towards a safer regulatory framework for medical devices with the change from Directives to Regulations. The EU Medical Device Regulation 2017/745 came into force into 2020 and In-Vitro Diagnostic Regulation 2017/746 and is coming into force within 2022.peer-reviewe

Developing a risk management course for forensic professionals

Forensic science provides continued impartial, robust and reproducible analysis of data and laboratory results through a rigorous scientific approach which is subsequently presented to judiciary systems. Appropriate risk management is one of the pillars of good quality systems supporting forensic scientists in their daily work.peer-reviewe