IMPROVE 2022 International Meeting on Pathway‐Related Obesity: Vision of Excellence

Nearly 90 clinicians and researchers from around the world attended the first IMPROVE 2022 International Meeting on Pathway-Related Obesity. Delegates attended in person or online from across Europe, Argentina and Israel to hear the latest scientific and clinical developments in hyperphagia and severe, early-onset obesity, and set out a vision of excellence for the future for improving the diagnosis, treatment, and care of patients with melanocortin-4 receptor (MC4R) pathway-related obesity. The meeting co-chair Peter Kühnen, Charité Universitätsmedizin Berlin, Germany, indicated that change was needed with the rapidly increasing prevalence of obesity and the associated complications to improve the understanding of the underlying mechanisms and acknowledge that monogenic forms of obesity can play an important role, providing insights that can be applied to a wider group of patients with obesity. World-leading experts presented the latest research and led discussions on the underlying science of obesity, diagnosis (including clinical and genetic approaches such as the role of defective MC4R signalling), and emerging clinical data and research with targeted pharmacological approaches. The aim of the meeting was to agree on the questions that needed to be addressed in future research and to ensure that optimised diagnostic work-up was used with new genetic testing tools becoming available. This should aid the planning of new evidence-based treatment strategies for the future, as explained by co-chair Martin Wabitsch, Ulm University Medical Center, Germany

Corporate Foundations in Europe

The objective is to give an insight into what we know and what we don't know about the current situation of corporate foundations. While we are able to put the spotlight on several interesting developments in the field, this chapter cannot give a comprehensive overview of corporate foundations in all European foundation sectors. As corporate foundations are predominantly public-benefit foundations and part of the nonprofit sector, it is useful to start with a brief overview of the European foundation sector. This may help to gain a first impression of the sector and possibly allows conclusions about the number and country-specific nature of corporate foundations, at least to give some indication about the environment corporate foundations act in

Rapid improvement of hepatic steatosis after initiation of leptin substitution in a leptin-deficient girl.

Background: Leptin deficiency is associated with severe obesity and metabolic disturbances. Increased liver fat content has been reported in only one case beforehand, even though hepatic steatosis is a typical comorbidity of common obesity. It is also frequent in patients with lipodystrophy where it resolves under leptin therapy. Subject and Methods: In 2010, we reported a leptin-deficient patient with a novel homozygous mutation in the leptin gene and severe hepatic steatosis. We have now studied serum changes and changes in liver fat content during the substitution with recombinant methionyl human leptin. Results: After 23 weeks of leptin substitution, elevated transaminases, total cholesterol and low-density lipoprotein levels normalized. After 62 weeks, homeostasis model assessment of insulin resistance improved from 10.7 to 6.0 and body fat mass dropped from 50.2 to 37.8%. Liver fat content was drastically reduced from 49.7 to 9.4%. The first changes in liver fat content were detectable after 3 days of therapy. Conclusion: Our patient showed a remarkable reduction of liver fat content during the treatment with recombinant methionyl human leptin. These changes occurred rapidly after initiation of the substitution, which implies that leptin has a direct effect on hepatic lipid metabolism in humans as it is seen in rodents

Leptin is not essential for obesity-associated hypertension.

Background and Objective: Hyperleptinemia is supposed to play a causal role in the development of obesity-associated hypertension, possibly via increased sympathetic tone. Hence patients with congenital leptin deficiency should be hypotensive and their low blood pressure should increase under leptin substitution. Subjects and Methods: To test this assumption, we examined ambulatory blood pressure, resting heart rate, Schellong test results, cold pressor test results, heart rate variability, catecholamine metabolites, and aldosterone levels in 6 patients with congenital leptin deficiency before as well as 2-7 days and 7-14 months after the start of leptin substitution. Ambulatory blood pressure was also examined in 3 patients with biallelic disease-causing variants in the leptin receptor gene. Results: Contrary to our expectations, even before leptin substitution, 1 patient with biallelic leptin receptor gene variants and 4 patients with leptin deficiency had been suffering from hypertension. Short-term substitution with leptin increased blood pressure further in 3 out of 4 patients (from 127.0 ± 11.7 to 133.8 ± 10.6 mm Hg), concomitant with an increase in resting heart rate as well as in heart rate during the Schellong test in all patients (from 87.6 ± 7.7 to 99.9 ± 11.0 bpm, p = 0.031, and from 102.9 ± 13.5 to 115.6 ± 11.3 bpm, p = 0.031, respectively). Furthermore, the systolic blood pressure response during the cold pressor test increased in 4 out of 6 patients. Unexpectedly, catecholamine metabolites and aldosterone levels did not increase. After long-term leptin substitution and weight loss, the resting heart rate decreased in 4 out of 6 patients compared to baseline, and in all patients below the heart rate seen immediately after the start of therapy (from 99.9 ± 11.0 to 81.7 ± 5.4 bpm; p = 0.031). Conclusions: These results show that obesity-associated hypertension does not depend on the presence of leptin. However, short-term leptin substitution can increase the blood pressure and heart rate in obese humans with leptin deficiency, indicating that leptin plays at least an additive role in obesity-associated hypertension. The mechanisms behind this are not clear but might include an increase in regional sympathetic tone

The Swiss Civil Society Sector in a Comparative Perspective

Switzerland has a strong nonprofit sector, with a long historical tradition and of high importance to the Swiss society. Elements such as independence, individual responsibility and self-help are social cornerstones which are deeply rooted in the mind of the Swiss population and have thus shaped Switzerland‟s entire social system. Over the centuries, these factors have led to the development of a large and significant civil society sector alongside the state (Helmig et al., 2009). The term “civil society sector” encompasses all nonprofit organizations (NPOs) existing between state and private firms, which are, in principle, sustained by private parties and do not pursue profit oriented goals (Etzioni, 1973; Levitt, 1973). Therefore, the civil society sector (or third sector) is best described as a complement to the two social constructs “state” and “economy”. NPOs point at the weaknesses in both state and economy, that consist of strong tendencies to rigid bureaucracy and the exclusive focus on profit maximization, respectively (Hansmann, 1980; Weisbrod, 1988). Meanwhile, in their way of functioning, they try to combine the strengths of the state and economy, which could be subsumed under predictability and public control on one side, and under flexibility and efficiency on the other (Seibel, 1990). To date, only a few details about the exact contribution of the NPOs to the total economic output of Switzerland are known. To some extent, this can be explained by the heterogeneous structure of the NPOs that constitute the Swiss civil society. This heterogeneous structure is visible not only in the difference in sheer size between large economic associations and small environmentalist groups, but also in the large scope of activities NPOs conduct, ranging from sports to advocacy to humanitarian aid abroad (Lichtsteiner et al., 2008). Because of this heterogeneity the civil society sector is seldom considered a separate sector as such. This working paper aims at narrowing down the term civil society sector in quantitative and qualitative terms, especially by discriminating between NPOs and organizations of the for-profit economic sector. The following chapter provides detail on the project‟s objectives, the approach to gathering and analyzing data, and the way in which NPOs have been defined for the purpose of this project. As a basis for this work, we used the guidelines of the Johns Hopkins Comparative Nonprofit Sector Project (CNP) that has been dealing with the comparative study of this sector since the early 1990s. The research project sought to document the Swiss NPOs quantitatively, following the methodological guidelines spelled out in the United Nations Handbook on Nonprofit Institutions in the System of National Accounts (United Nations, 2003) and to compare the Swiss findings to those from other countries surveyed by the CNP. It also seeks to describe the Swiss nonprofit sector qualitatively by putting this set of institutions into historical and political context. As a result the study provides the first comprehensive empirical overview of the nonprofit sector in Switzerland enabling the systematic comparison of the Swiss results to those from other countries. These major empirical findings about the scope and scale of Switzerland‟s civil society sector will be summarized in Chapter 2. Furthermore this chapter examines the comparisons of the Swiss findings to those of the over 40 countries on which comparable data is available. Introduction IV Chapter 3 draws the key historical factors that shaped the development of NPOs in Switzerland. Chapter 4 addresses the key issues the sector is presently confronted with, particularly in terms of the impact of government policy. Finally, Chapter 5 discusses some conclusions from the findings presented here and outlines their implications for public policy, NPOs, and research