Addressing the most neglected diseases through an open research model: The discovery of fenarimols as novel drug candidates for eumycetoma

Eumycetoma is a chronic infectious disease characterized by a large subcutaneous mass, often caused by the fungus Madurella mycetomatis. A combination of surgery and prolonged medication is needed to treat this infection with a success rate of only 30%. There is, therefore, an urgent need to find more effective drugs for the treatment of this disease. In this study, we screened 800 diverse drug-like molecules and identified 215 molecules that were active in vitro. Minimal inhibitory concentrations were determined for the 13 most active compounds. One of the most potent compounds, a fenarimol analogue for which a large analogue library is available, led to the screening of an additional 35 compounds for their in vitro activity against M. mycetomatis hyphae, rendering four further hit compounds. To assess the in vivo potency of these hit compounds, a Galleria mellonella larvae model infected with M. mycetomatis was used. Several of the compounds identified in vitro demonstrated promising efficacy in vivo in terms of prolonged larval survival and/or reduced fungal burden. The results presented in this paper are the starting point of an Open Source Mycetoma (MycetOS) approach in which members of the global scientific community are invited to participate and contribute as equal partners. We hope that this initiative, coupled with the promising new hits we have reported, will lead to progress in drug discovery for this most neglected of neglected tropical diseases

Addressing the most neglected diseases through an open research model: The discovery of fenarimols as novel drug candidates for eumycetoma

Eumycetoma is a chronic infectious disease characterized by a large subcutaneous mass, often caused by the fungus Madurella mycetomatis. A combination of surgery and prolonged medication is needed to treat this infection with a success rate of only 30%. There is, the

Human total, basal and activity energy expenditures are independent of ambient environmental temperature

ower ambient temperature (Ta) requires greater energy expenditure to sustain body temperature. However, effects of Ta on human energetics may be buffered by environmental modification and behavioral compensation. We used the IAEA DLW database for adults in the USA (n = 3213) to determine the effect of Ta (−10 to +30°C) on TEE, basal (BEE) and activity energy expenditure (AEE) and physical activity level (PAL). There were no significant relationships (p > 0.05) between maximum, minimum and average Ta and TEE, BEE, AEE and PAL. After adjustment for fat-free mass, fat mass and age, statistically significant (p < 0.01) relationships between TEE, BEE and Ta emerged in females but the effect sizes were not biologically meaningful. Temperatures inside buildings are regulated at 18–25°C independent of latitude. Hence, adults in the US modify their environments to keep TEE constant across a wide range of external ambient temperatures

Dietary fruits and vegetables and cardiovascular diseases risk

Diet is likely to be an important determinant of cardiovascular disease (CVD) risk. In this article, we will review the evidence linking the consumption of fruit and vegetables and CVD risk. The initial evidence that fruit and vegetable consumption has a protective effect against CVD came from observational studies. However, uncertainty remains about the magnitude of the benefit of fruit and vegetable intake on the occurrence of CVD and whether the optimal intake is five portions or greater. Results from randomized controlled trials do not show conclusively that fruit and vegetable intake protects against CVD, in part because the dietary interventions have been of limited intensity to enable optimal analysis of their putative effects. The protective mechanisms of fruit and vegetables may not only include some of the known bioactive nutrient effects dependent on their antioxidant, anti-inflammatory, and electrolyte properties, but also include their functional properties, such as low glycemic load and energy density. Taken together, the totality of the evidence accumulated so far does appear to support the notion that increased intake of fruits and vegetables may reduce cardiovascular risk. It is clear that fruit and vegetables should be eaten as part of a balanced diet, as a source of vitamins, fiber, minerals, and phytochemicals. The evidence now suggests that a complicated set of several nutrients may interact with genetic factors to influence CVD risk. Therefore, it may be more important to focus on whole foods and dietary patterns rather than individual nutrients to successfully impact on CVD risk reduction. A clearer understanding of the relationship between fruit and vegetable intake and cardiovascular risk would provide health professionals with significant information in terms of public health and clinical practice

Human total, basal and activity energy expenditures are independent of ambient environmental temperature

Lower ambient temperature (Ta) requires greater energy expenditure to sustain body temperature. However, effects of Ta on human energetics may be buffered by environmental modification and behavioral compensation. We used the IAEA DLW database for adults in the USA (n = 3213) to determine the effect of Ta (−10 to +30°C) on TEE, basal (BEE) and activity energy expenditure (AEE) and physical activity level (PAL). There were no significant relationships (p > 0.05) between maximum, minimum and average Ta and TEE, BEE, AEE and PAL. After adjustment for fat-free mass, fat mass and age, statistically significant (p < 0.01) relationships between TEE, BEE and Ta emerged in females but the effect sizes were not biologically meaningful. Temperatures inside buildings are regulated at 18–25°C independent of latitude. Hence, adults in the US modify their environments to keep TEE constant across a wide range of external ambient temperatures

Kalium ondergeschoven kindje

Gegevens m.b.t. het kaliumgehalte van drijfmest en adviezen voor de kaliumbemesting. In tabellen: de effecten van verschillende mestbewerkingstechnieken op het kaliumgehalte van zeugenmest; de geadviseerde kalibemesting op zand voor verschillende gewassen, afhankelijk van de kalitoestand van de bodem; de samenstelling van zeugendrijfmest en van de dikke en dunne fractie na bezinking; de aanvoer van stikstof, fosfaat en kali bij een mestgift van drijfmest en dunne fractie op basis van 150 kg werkzame N per h

The Public Health Status and Foresight report 2014: Four normative perspectives on a healthier Netherlands in 2040.

Policy-oriented foresight reports aim to inform and advise decision-makers. In value-laden areas such as public health and healthcare, deliberative scenario methods are clearly needed. For the sixth Dutch Public Health Status and Forecasts-report (PHSF-2014), a new approach of co-creation was developed aiming to incorporate different societal norms and values in the description of possible future developments. The major future trends in the Netherlands were used as a starting point for a deliberative dialogue with stakeholders to identify the most important societal challenges for public health and healthcare. Four societal challenges were identified: 1) To keep people healthy as long as possible and cure illness promptly, 2) To support vulnerable people and enable social participation, 3) To promote individual autonomy and freedom of choice, and 4) To keep health care affordable. Working with stakeholders, we expanded these societal challenges into four corresponding normative scenarios. In a survey the normative scenarios were found to be recognizable and sufficiently distinctive. We organized meetings with experts to explore how engagement and policy strategies in each scenario would affect the other three societal challenges. Possible synergies and trade-offs between the four scenarios were identified. Public health foresight based on a business-as-usual scenario and normative scenarios is clearly practicable. The process and the outcomes support and elucidate a wide range of strategic discussions in public health