Important Trends in UCP3 Investigation

Membrane uncoupling protein 3 (UCP3), a member of the mitochondrial uncoupling protein family, was discovered in 1997. UCP3′s properties, such as its high homology to other mitochondrial carriers, especially to UCP2, its short lifetime and low specificity of UCP3 antibodies, have hindered progress in understanding its biological function and transport mechanism over decades. The abundance of UCP3 is highest in murine brown adipose tissue (BAT, 15.0 pmol/mg protein), compared to heart (2.7 pmol/mg protein) and the gastrocnemius muscle (1.7 pmol/mg protein), but it is still 400-fold lower than the abundance of UCP1, a biomarker for BAT. Investigation of UCP3 reconstituted in planar bilayer membranes revealed that it transports protons only when activated by fatty acids (FA). Although purine nucleotides (PN) inhibit UCP3-mediated transport, the molecular mechanism differs from that of UCP1. It remains a conundrum that two homologous proton-transporting proteins exist within the same tissue. Recently, we proposed that UCP3 abundance directly correlates with the degree of FA β-oxidation in cell metabolism. Further development in this field implies that UCP3 may have dual function in transporting substrates, which have yet to be identified, alongside protons. Evaluation of the literature with respect to UCP3 is a complex task because (i) UCP3 features are often extrapolated from its “twin” UCP2 without additional proof, and (ii) the specificity of antibodies against UCP3 used in studies is rarely evaluated. In this review, we primarily focus on recent findings obtained for UCP3 in biological and biomimetic systems

Workshop on Stakeholder Engagement Strategy (WKSHOES)

The ICES Workshop on Stakeholder Engagement Strategy (WKSHOES) met online 22-24 June 2021 with the objective to organize the background information needed for SCICOM and ACOM to develop a formal ICES Stakeholder Engagement Strategy. Stakeholder engagement has taken an increasingly important role in ICES. There was a strong consensus in the workshop that stakeholder engagement is essential to ICES’ work, as has been captured by the most recent ICES Strategic, Science, and Advisory Plans. The question is how to do it best. While WKSHOES recognized the essential nature of stakeholder engagement for addressing environmental challenges, understanding human impacts and values, the group discussed the valid concern that if stakeholder engagement is done incorrectly, it could compromise the perceived objectivity of ICES science and its independence. Workshop participants challenged the idea of objective or “pure” science, but also recognized the practical need to have ICES advice be transparent and science-based. Participants also understand that when providing advice, tradeoffs have to be made that are informed by the different weights that stakeholders place on various management objectives. A key question related to a potential stakeholder engagement strategy is “Who is a stakeholder?” This report discusses several definitions and roles. A central challenge for ICES is recognizing that the network of stakeholders is a subset of the people impacted by ICES science and advice. The Stakeholder Engagement Strategy should therefore primarily focus on ensuring that people who are part of the ICES network have clear roles and responsibilities and that ICES performs its work fairly and transparently. However, participants also recognize the need to increase opportunities for diverse resource users and citizens to have clear avenues to engage with the different aspects of the ICES network. Considering and promoting diversity and inclusion and avoiding implicit bias are crucial in this process. It is also essential to define clear goals for stakeholder engagement in general, and tangible objectives for each engagement activity in particular. Engagement objectives already formulated in various ICES documents are outlined in this report, as well as recommendations for guiding principles that provide the overarching frame of reference for engagement. This Report serves as the primary output from WKSHOES, and represents the knowledge and opinions of workshop participants. WKSHOES recommends that in order to both complete the development of the strategy and conduct successful stakeholder engagement about it, a suite of communication activities is needed that should best be coordinated from a central contact point within ICES. WKSHOES recommends that after ACOM and SCICOM draft the strategy and obtain input from the ICES Council, a diversity of stakeholders should be invited to provide input on the WKSHOES report and the development of the Engagement Strategy. ICES should solicit input from stakeholders by early 2022 to agree on the contents of the Strategy and how it will be implemented. WKSHOES also recommends that a future Expert Group address the ongoing need to develop and communicate effective stakeholder engagement methods within the ICES network.Peer reviewe

MRI features of idiopathic intracranial hypertension are not prognostic of visual and headache outcome

Abstract Background In idiopathic intracranial hypertension (IIH), certain MRI features are promising diagnostic markers, but whether these have prognostic value is currently unknown. Methods We included patients from the Vienna-Idiopathic-Intracranial-Hypertension (VIIH) database with IIH according to Friedman criteria and cranial MRI performed at diagnosis. Presence of empty sella (ES), perioptic subarachnoid space distension (POSD) with or without optic nerve tortuosity (ONT), posterior globe flattening (PGF) and transverse sinus stenosis (TSS) was assessed and multivariable regression models regarding visual outcome (persistent visual impairment/visual worsening) and headache outcome (headache improvement/freedom of headache) were fitted. Results We included 84 IIH patients (88.1% female, mean age 33.5 years, median body mass index 33.7). At baseline, visual impairment was present in 70.2% and headache in 84.5% (54.8% chronic). Persistent visual impairment occurred in 58.3%, visual worsening in 13.1%, headache improvement was achieved in 83.8%, freedom of headache in 26.2%. At least one MRI feature was found in 78.6% and 60.0% had ≥3 features with POSD most frequent (64.3%) followed by TSS (60.0%), ONT (46.4%), ES (44.0%) and PGF (23.8%). In multivariable models, there was no association of any single MRI feature or their number with visual impairment, visual worsening, headache improvement or freedom. Visual impairment at baseline predicted persistent visual impairment (odds ratio 6.3, p<0.001), but not visual worsening. Chronic headache at baseline was significantly associated with lower likelihood of headache freedom (odds ratio 0.48, p=0.013), but not with headache improvement. Conclusions MRI features of IIH are neither prognostic of visual nor headache outcome

Treatment with GLP-1 receptor agonists is associated with significant weight loss and favorable headache outcomes in idiopathic intracranial hypertension

Abstract Background In idiopathic intracranial hypertension (IIH), sustained weight loss is the main pillar in modifying disease course, whereby glucagon-like peptide-1 receptor agonists (GLP-1-RAs) could present an attractive treatment option. Methods In this open-label, single-center, case–control pilot study, patients with IIH (pwIIH) and a body mass index (BMI) of ≥ 30 kg/m2 were offered to receive a GLP-1-RA (semaglutide, liraglutide) in addition to the usual care weight management (UCWM). Patients electing for UCWM only served as a control group matched for age-, sex- and BMI (1:2 ratio). The primary endpoint was the percentage weight loss at six months (M6) compared to baseline. Secondary endpoints included the rate of patients with a weight loss of ≥ 10%, monthly headache days (MHD), the rate of patients with a ≥ 30% and ≥ 50% reduction in MHD, visual outcome parameters, and adverse events (AEs). Results We included 39 pwIIH (mean age 33.6 years [SD 8.0], 92.3% female, median BMI 36.3 kg/m2 [IQR 31.4–38.3]), with 13 patients being treated with GLP-1-RAs. At M6, mean weight loss was significantly higher in the GLP-1-RA group (–12.0% [3.3] vs. –2.8% [4.7]; p < 0.001). Accordingly, weight loss of ≥ 10% was more common in this group (69.2% vs. 4.0%; p < 0.001). Median reduction in MHD was significantly higher in the GLP-1-RA group (–4 [–10.5, 0.5] vs. 0 [–3, 1]; p = 0.02), and the 50% responder rate was 76.9% vs. 40.0% (p = 0.04). Visual outcome parameters did not change significantly from baseline to M6. Median reduction in acetazolamide dosage was significantly higher in the GLP-1-RA group (–16.5% [–50, 0] vs. 0% [–25, 50]; p = 0.04). AEs were mild or moderate and attributed to gastrointestinal symptoms in 9/13 patients. None of the AEs led to premature treatment discontinuation. Conclusions This open-label, single-center pilot study suggests that GLP-1-RAs are an effective and safe treatment option for achieving significant weight loss with a favorable effect on headache, leading to reduced acetazolamide dosage in pwIIH. Graphical Abstrac

Additional file 1 of Treatment with GLP-1 receptor agonists is associated with significant weight loss and favorable headache outcomes in idiopathic intracranial hypertension

Additional file 1