Inflammatory responses to platelet-activating factor in human skin

Since its discovery over 20 years ago, platelet- activating factor (PAF) has been the subject of intensive research. In particular, its role in pathophysiology has provoked as much controversy as research interest. The pharmacological profile and ubiquity of PAF have made it a candidate for involvement in a number of inflammatory processes. No clear evidence has been demonstrated however to establish a role in disease in man, although clinical caution about its potential toxic effects has limited the number of available experimental human models. One particular tissue which lends itself to examination of the effects of PAF is the skin. A series of studies has been undertaken to define accurately the characteristics of the acute responses to PAF in human skin and to study the role of histamine in these responses. By way of comparison, the acute responses to other inflammatory mediators (PGE2, substance P, and CGRP) has also been investigated. The effects of histamine antagonism, and depletion on the PAF responses have been examined together with evaluation of local histamine release from the skin after PAF treatment. Additionally, a comparison of the PAF-induced responses in atopic and non-atopic subjects has been undertaken. As a consequence of these studies, quantitative methods have been validated as sensitive and reproducible techniques for evaluating hyperalgesia and histamine-type flare and weal responses in the skin. Using the hyperalgesia model, intradermally injected PAF failed to cause hyperalgesia in the skin. Conversely intradermal PGE2 was shown to provoke dose- related hyperalgesia, which was associated with spreading erythema, lasting for 2-3 hours. Apart from at high doses where the effect was marginal when compared with PGE2, the neuropeptides substance P and CGRP also failed to produce hyperalgesia in the skin. Using the flare and weal model, PAF, substance P and PGE2 were associated with dose-related histamine-like weal and flare responses, although the PGE2 responses were considerably weaker. CGRP did not produce these responses and instead caused a local intense erythema, similar to the later effect of PGE2. Evaluation of the effects of H1-antagonism and histamine depletion, and the quantification of local histamine release have demonstrated that the PAF responses in the skin are largely mediated by histamine. Indomethacin was also found to have a small inhibitory effect on the PAF responses implicating secondary prostaglandin release. The acute inflammatory responses to intradermal PAF have been shown to be similar in atopic subjects compared with non-atopics using the techniques described above. Baseline plasma histamine, however, was found to be higher in atopic subjects

Local survival outcomes in metastatic renal cell carcinoma

A quarter of patients who develop renal cell carcinoma will have metastatic disease at presentation. The role of cytoreductive surgery in these patients is a topic of debate. The aim of this study was to analyse survival outcomes of patients treated in Malta who did and did not receive a nephrectomy. Data was gathered retrospectively from the Malta Cancer Registry and Mortality Data at the Department of Health Information, records of multidisciplinary team meetings held within the urology department at Mater Dei Hospital, hospital imaging and patient records. Data gathered included: patient demographics, date of diagnosis, TNM staging, tumour histology, Fuhrman grade, time to treatment and modality of treatment. Exclusions included: • Localized disease relapsing after surgery • Non-renal cell histological subtypes • Presence of metastasis at diagnosis not certain • Concomitant primary tumours 77 patients diagnosed over 5 years between 04.03.2005 and 13.2.2009 were included. The age at presentation ranged from 30 to 88 years, with a median age of 67 years. 11 were incidental findings and 47 were symptomatic. The most prevalent symptoms were abdominal pain and gross haematuria. Five-year cancer specific survival in patients who received a nephrectomy was significantly better at 65%, compared to patients who did not undergo surgery (32%) P value <0.05, CI 95%. These results where compared favourably with SEER data outcomespeer-reviewe

Structural and compositional variations of basic Cu(II) chlorides in the herbertsmithite and gillardite structure field.

© 2017 The Mineralogical Society. This document is the author’s final accepted version of the journal article. You are advised to consult the published version if you wish to cite from it

Health-related quality of life of children with attention-deficit/hyperactivity disorder versus children with diabetes and healthy controls

The impact of attention-deficit/hyperactivity disorder (ADHD) on health-related quality of life (HRQoL) is reported to be similar to that of other mental health and physical disorders. In this cross-sectional study, we hypothesized that children with ADHD and children with type 1 diabetes mellitus (T1DM) would have significantly worse HRQoL compared with healthy children, and that better clinical status in ADHD and T1DM would be associated with better HRQoL. Children were recruited from three outpatient services in Scotland. Responses to two frequently used validated HRQoL instruments, the Paediatric Quality of Life Inventory (PedsQL) and Child Health and Illness Profile-child edition (CHIP-CE), were obtained from parents/carers and children (6–16 years) with/without ADHD or T1DM. Child and parent/carer-completed HRQoL measurements were evaluated for 213 children with ADHD, 58 children with T1DM and 117 healthy children (control group). Significantly lower self and parent/carer ratings were observed across most PedsQL (P < 0.001) and CHIP-CE (P < 0.05) domains (indicating reduced HRQoL) for the ADHD group compared with the T1DM and control groups. Parent/carer and child ratings were significantly correlated for both measures of HRQoL (PedsQL total score: P < 0.001; CHIP-CE all domains: P < 0.001), but only with low-to-moderate strength. Correlation between ADHD severity and HRQoL was significant with both PedsQL and CHIP-CE for all parent/carer (P < 0.01) and most child (P < 0.05) ratings; more ADHD symptoms were associated with poorer HRQoL. These data demonstrate that ADHD has a significant impact on HRQoL (as observed in both parent/carer and child ratings), which seems to be greater than that for children with T1DM

Towards a quality education for all

This document summarises the recommendations being proposed in the NCF and examines the implications of such recommendations. There can only be a meaningful strategy for the implementation of the NCF once the recommendations are debated and the full impact of their implications understood. This process of consultation needs to include all stakeholders in a professionally engaging manner. Moreover, the consultation and implementation strategies need to be based on the full understanding of a change management process. This document will therefore map out the way forward by presenting: • a summary of the recommendations being proposed by the NCF; • implications of these recommendations for implementation; • ideas about the management of change which underpin the consultation and implementation strategies the NCF would like to promote; • a strategy for the consultation process following the publication of the draft NCF; and • a proposed timeline for the implementation process of the NCF, following consultation and agreement with the wider educational community about the way forward.peer-reviewe

Physical Health, Media Use, and Mental Health in Children and Adolescents With ADHD During the COVID-19 Pandemic in Australia

Objective: To examine the impact of COVID-19 restrictions among children with attention-deficit/hyperactivity disorder (ADHD). Methods: Parents of 213 Australian children (5–17 years) with ADHD completed a survey in May 2020 when COVID-19 restrictions were in place (i.e., requiring citizens to stay at home except for essential reasons). Results: Compared to pre-pandemic, children had less exercise (Odds Ratio (OR) = 0.4; 95% CI 0.3–0.6), less outdoor time (OR = 0.4; 95% 0.3–0.6), and less enjoyment in activities (OR = 6.5; 95% CI 4.0–10.4), while television (OR = 4.0; 95% CI 2.5–6.5), social media (OR = 2.4; 95% CI 1.3–4.5), gaming (OR = 2.0; 95% CI 1.3–3.0), sad/depressed mood (OR = 1.8; 95% CI 1.2–2.8), and loneliness (OR = 3.6; 95% CI 2.3–5.5) were increased. Child stress about COVID-19 restrictions was associated with poorer functioning across most domains. Most parents (64%) reported positive changes for their child including more family time. Conclusions: COVID-19 restrictions were associated with both negative and positive impacts among children with ADHD

Nikteb...

Ġabra ta’ poeżiji u proża li tinkludi: L-iben il-ħali ta’ David Agius Muscat – Kaptan ta’ Kit Azzopardi – Il-lanterna ta’ Charles Bezzina – Li kelli mmur lura ta’ Ġorġ Borg – Firda ta’ Ġorġ Borg – Garden fairy ta’ Charles Briffa – Sejf jinfidlek ruħek ta’ Charles Briffa – Waqt ta’ Joseph Buttigieg – Vjaġġ ta’ John Caruana – Ċaqlembuta ta’ Antoine Cassar – Ħaġa tqila ta’ Carmel G. Cauchi – F’tarf il-blat ta’ Leanne Ellul – Int ta’ Victor Fenech – Pippin u l-bojja ta’ Charles Flores – L-arloġġ ta’ Joe Friggieri – Il-fjur tal-ġakaranda ta’ Joe Friggieri – Fjur tal-kaktus ta’ Joel Galea – Biss is-skiet ta’ Joel Galea – Għalissa ta’ Maria Grech Ganado – Ilsna ta’ Maria Grech Ganado – Is-sried ixoqqna fin fin ta’ Adrian Grima – Ħsieb ħalliel... ta’ Patrick Sammut – Lament lil ommi ta’ Salv Sammut – Hekk kif tinħass ġol-arja x-xitwa ta’ Lillian Sciberras – F’għajnejha, il-ħarsa siekta ta’ Clare Azzopardi – Għad jagħdab l-irdum ta’ Paul P. Borg – Forsi...xi darba ta’ Charles Casha – Faxxa ngħas ta’ Sergio Grech – Il-mejda tal-mogħdija ta’ Pierre J. Mejlak – Min jaf bi Stojan Kurepa? ta’ Immanuel Mifsud – L-eħrex jum tal-gwerra ta’ Maurice Mifsud Bonnici – Il-vażett tal-bewsiet ta’ Rita Saliba – Pjanu ta’ Trevor Żahra – Il-ħalliel ta’ Guy de Maupassant, traduzzjoni ta’ Toni Aquilina – Salvu tal-pasturi ta’ Francis Ebejer, traduzzjoni ta’ Steve Borg – Sunetti ta’ William Shakespeare, traduzzjoni ta’ Oliver Friggieri – Nikteb... ta’ Nizar Qabbani, traduzzjoni ta’ Kevin Saliba.peer-reviewe

Antiparkinsonian effects of the "Radiprodil and Tozadenant" combination in MPTP-treated marmosets

Investigate a combination of two clinically tested drugs, the NR2B antagonist Radiprodil and the A2A antagonist Tozadenant in the MPTP-treated marmoset model of Parkinson's Disease (PD).In PD, there remains a need for the development of non-dopaminergic drugs to effectively treat the motor symptoms without the induction of L-Dopa-induced motor complications.Clinically relevant doses of Radiprodil and Tozadenant were given both alone and in combination without the addition of L-Dopa, and the antiparkinsonian efficacy of the treatments was assessed in a primate model of PD.When compared to the drugs tested alone, the drug combination led to a significant increase of motor activity and an improvement of motor disability in MPTP-treated marmosets. In addition, the motor restoration brought about by the combination was almost completely devoid of dyskinesia. Interestingly, treated primates were not overstimulated, but were able to move normally when motivated by the exploration of novel objects.We have demonstrated in a primate model that, the "Radiprodil/Tozadenant" combination significantly improves motor activity, extending previous results obtained in unilaterally lesioned 6-OHDA-rats. The strength of the preclinical data accumulated so far suggests that the use of such an A2A and NR2B antagonist combination could bring significant motor improvement to PD patients, without inducing the motor complications induced by L-Dopa therapy. Although encouraging, these preclinical data need to be confirmed in the clinic