The Sight Loss and Vision Priority Setting Partnership (SLV-PSP): overview and results of the research prioritisation survey process

Objectives: The Sight Loss and Vision Priority Setting Partnership aimed to identify research priorities relating to sight loss and vision through consultation with patients, carers and clinicians. These priorities can be used to inform funding bodies’ decisions and enhance the case for additional research funding. Design: Prospective survey with support from the James Lind Alliance. Setting: UK-wide National Health Service (NHS) and non-NHS. Participants: Patients, carers and eye health professionals. Academic researchers were excluded solely from the prioritisation process. The survey was disseminated by patient groups, professional bodies, at conferences and through the media, and was available for completion online, by phone, by post and by alternative formats (Braille and audio). Outcome measure: People were asked to submit the questions about prevention, diagnosis and treatment of sight loss and eye conditions that they most wanted to see answered by research. Returned survey questions were reviewed by a data assessment group. Priorities were established across eye disease categories at final workshops. Results: 2220 people responded generating 4461 submissions. Sixty-five per cent of respondents had sight loss and/or an eye condition. Following initial data analysis, 686 submissions remained which were circulated for interim prioritisation (excluding cataract and ocular cancer questions) to 446 patients/carers and 218 professionals. The remaining 346 questions were discussed at final prioritisation workshops to reach agreement of top questions per category. Conclusions: The exercise engaged a diverse community of stakeholders generating a wide range of conditions and research questions. Top priority questions were established across 12 eye disease categories. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial

Decreased Toll-like receptor 8 expression and lower TNF-alpha synthesis in infants with acute RSV infection

<p>Abstract</p> <p>Background</p> <p>Toll-like receptors (TLRs) are part of the innate immune system, able to recognize pathogen-associated molecular patterns and activate immune system upon pathogen challenge. Respiratory syncytial virus (RSV) is a RNA virus particularly detrimental in infancy. It could cause severe lower respiratory tract disease and recurrent infections related to inadequate development of anti-viral immunity. The reason could be inadequate multiple TLRs engagement, including TLR8 in recognition of single-stranded viral RNA and diminished synthesis of inflammatory mediators due to a lower expression.</p> <p>Methods</p> <p>Intracellular TLR8 expression in peripheral blood monocytes from RSV-infected infants was profiled and compared to healthy adults and age matched controls. Whether the observed difference in TLR8 expression is a transitory effect, infants in convalescent phase (4-6 weeks later) were retested. Specific TLR8-mediated TNF-α production in monocytes during an acute and convalescent phase was analyzed.</p> <p>Results</p> <p>RSV-infected and healthy infants had lower percentage of TLR8-expressing monocytes than healthy adults whereas decreased of TLR8 protein levels were detected only for RSV-infected infant group. Lower protein levels of TLR8 in monocytes from RSV-infected infants, compared to healthy infants, negatively correlated with respiratory frequency and resulted in lower TNF-α synthesis upon a specific TLR8 stimulation. In the convalescent phase, levels of TLR8 increased, accompanied by increased TNF-α synthesis compared to acute infection.</p> <p>Conclusions</p> <p>Lower TLR8 expression observed in monocytes, during an acute RSV infection, might have a dampening impact on early anti-viral cytokine production necessary to control RSV replication, and subsequently initiate an adaptive Th1 type immune response leading to severe disease in infected infants.</p

The thiol antioxidant 1,2-dithiole-3-thione stimulates the expression of heat shock protein 70 in dopaminergic PC12 cells

In Parkinson's disease (PD), the pathogenic factors oxidative stress and protein aggregation interact and culminate in the apoptotic death of (mainly catecholaminergic) neurons. The dithiolethiones comprise thiol antioxidants that are well known for their activation of the expression of a wide collection of cytoprotective genes, including genes coding for antioxidant enzymes. Given the observation that heat shock proteins (HSPs), in particular the heat shock protein 72 (HSP72), protects against cellular degeneration in various models of PD, the ability of the unsubstituted dithiolethione 1,2-dithiole-3-thione (D3T) to stimulate heat shock protein gene and protein expression was studied using the dopaminergic PC12 cell line. As anticipated, D3T stimulated the expression of the antioxidant enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1). Quantitative PCR analysis revealed that D3T stimulates the expression of the inducible, cytoplasmic HSP72. Moreover, D3T strongly potentiated HSP72 gene and protein expression in heat-stressed cells. Taken together, our data show that, in addition to antioxidant enzymes, D3T stimulates the expression of HSP72, a chaperone shown to be neuroprotective in various models of PD, in particular under conditions of cellular stress. Thus, the broad range manipulation of endogenous cellular defense mechanisms, through D3T, may represent an innovative approach to therapeutic intervention in PD

Rapportcijfers Voor Voetballers: Zin Of Onzin?

Veel Nederlanders nemen zondagavond en maandagochtend de voetbaluitslagen door. Met collega's worden de verrichtingen van de favoriete teams doorgenomen: de helden van het weekend bejubeld en de scheidsrechters (indien nodig) beschimpt. Het aardige van voetballen is dat iedereen er een mening over heeft, niet noodzakelijkerwijze gebaseerd op kennis van zaken. De voetballers worden overigens niet alleen beoordeeld door het publiek in de stadions en tijdens de gesprekken op maandag, ze krijgen ook rapportcijfers in een landelijk ochtendblad en een weekblad. In deze notitie analyseren we die rapportcijfers; met name gaan we na in hoeverre de beoordelingen tussen beiden bladen overeenstemmen. Die rapportcijfers dienen overigens niet alleen ter vermaak van de lezers: op basis van de rapportcijfers wordt een prestigieuze prijs als 'De voetballer van het jaar' uitgereikt en het gemiddelde rapportcijfer van 5.8 was voor Volendam een van de redenen om Danny den Ouden te ontslaan.