Prader–Willi Syndrome and Hypogonadism: A Review Article

Prader-Labhart-Willi syndrome (PWS) is a rare genetic disorder characterized by intellectual disability, behavioural problems, hypothalamic dysfunction and specific dysmorphisms. Hypothalamic dysfunction causes dysregulation of energy balance and endocrine deficiencies, including hypogonadism. Although hypogonadism is prevalent in males and females with PWS, knowledge about this condition is limited. In this review, we outline the current knowledge on the clinical, biochemical, genetic and histological features of hypogonadism in PWS and its treatment. This was based on current literature and the proceedings and outcomes of the International PWS annual conference held in November 2019. We also present our expert opinion regarding the diagnosis, treatment, care and counselling of children and adults with PWS-associated hypogonadism. Finally, we highlight additional areas of interest related to this topic and make recommendations for future studies.     

Physical and oxidative stability of n-3 delivery emulsions added seaweed-based polysaccharide extracts from Nordic brown algae Saccharina latissima

Enriching foods with long-chain n-3 polyunsaturated fatty acids requires a delivery emulsion system, which is both thermodynamically and oxidatively stable. The antioxidant and stabilizing properties of three types of polysaccharide extracts from brown algae Saccharina latissima with a mixed composition of polysaccharides (SA: 98% sodium alginate, SF: 90% alginate and 9% fucoidan, SL: 14.5% fucoidan, 9.5% laminarin, and co-extracted nonpolysaccharides) were evaluated. SA, SF, SL, and REF (added commercial sodium alginate) showed in vitro ferrous ion chelating ability in the order: SA (99%) > SL (78%) > REF (31%) > SF (16%). The difference in antioxidant activity between SA, REF, and SF appeared related to structural differences of alginate (M/G ratio). A storage trial was conducted using 70% (w/w) fish oil-in-water delivery emulsions added sodium caseinate (NaCas) (0.23 wt%) as emulsifier in combination with SA, SF, SL, or commercial NaAlg (REF) in different concentrations (C1 = 0.1, C2 = 0.2, C3 = 0.3, and C4 = 0.4 wt%). A control with only NaCas was included (CON). The physical (e.g., creaming and droplet-size distribution) and oxidative (peroxide value and volatiles) stability of the emulsions, were evaluated (12 days, dark at 20˚C). Acceptable physical stability (creaming index) was found for REF (all concentrations), SF = 0.2 wt% (C2), SL and SA = 0.3 wt% (C3) and 0.4 wt% (C4). In general, the oxidative stability decreased by adding REF, SA, and SF (except for REF at C1), as prooxidant activity was observed. However, SA showed antioxidant activity against the formation of 2-ethylfuran. SL showed antioxidant activity in decreasing the formation of volatile compounds in emulsions when added in concentrations above 0.2 wt%.     

Formation of Supramolecular Gels from Host–Guest Interactions between PEGylated Chitosan and α-Cyclodextrin

Chitosan-based hydrogels are prepared via the formation of polypseudorotaxanes (PPR), by selectively threading α-cyclodextrin (α-CD) macrocycles onto polymeric chains, which, through the formation of microcrystalline domains, act as junction points for the network. Specifically, host–guest inclusion complexes are formed between α-CD and PEGylated chitosan (PEG-Ch), resulting in the formation of supramolecular gels. PEG-grafted chitosan is obtained with a reaction yield of 79.8%, a high degree of grafting (50.9% GW) and water solubility (≈16 mg mL⁻¹), as assessed by turbidimetry. A range of compositions for mixtures of PEG-Ch solutions (0.2–0.8% w/w) and α-CD solutions (2−12% w/w, or 0.04–0.2% mol) are studied. Regardless of PEG content, gels are not formed at low α-CD concentrations (<4%). Dynamic rheology measurements reveal stiff gels (G’ above 15k) and a narrow linear viscoelastic region, reflecting their brittleness. The highest elastic modulus is obtained for a hydrogel composition of 0.4% PEG-Ch and 6% α-CD. Steady-state measurements, cycling between low and high shear rates, confirm the thixotropic nature of the gels, demonstrating their capacity to fully recover their mechanical properties after being exposed to high stress, making them good candidates to use as in-situ gel-forming materials for drug delivery to topical or parenteral sites.     

Comparison of online,hands-on,and a combined approach for teaching cautery disbudding technique to dairy producers

The use of pain control for disbudding and dehorning is important from both an animal and industry perspective. Best practices include the use of local anesthetic, commonly given as a cornual nerve block (CNB), and a nonsteroidal anti-inflammatory drug. The proportion is decreasing, but many dairy producers do not use local anesthesia, perhaps in part due to lack of knowledge of the CNB technique. Although this skill is typically learned in person from a veterinarian, alternative methods may be useful. The objective of this trial was to determine if there were differences in the efficacy of online training (n = 23), hands-on training (n = 20), and a combined approach (n = 23) for teaching producers to successfully administer a CNB and disbud a calf. The primary outcome was block efficacy, defined as a lack of established pain behaviors during iron application. Secondary outcomes were background knowledge (assessed by a written quiz), CNB and disbudding technique (evaluated by rubric scoring), time taken, and self-confidence before and after evaluation. Associations between training group and outcome were assessed with logistic regression, ordered logistic regression, and Cox-proportional hazard models, with a random effect for workshop. Block efficacy was not different between training groups, with 91% successful in both combined and online groups, and 75% in the hands-on trained group. Online learners had poorer technical scores than hands-on trainees. The combined group was not different from hands-on. Time to block completion tended to be longer for the online group (62 ± 11 s), whereas time to disbudding completion was not different between hands-on (41 ± 5 s) or combined trainees (41 ± 5 s). The combined group had the highest pre-evaluation confidence score, and remained higher after evaluation than online but was not different than hands-on. Although we saw some statistical differences between groups, absolute differences were small and block efficacy was similar. This suggests online training can be a useful tool for motivated producers who lack access to hands-on training.     

Improvement of Modified Wood Properties with Addition of Chestnut Tannins in Lactic Acid-Based Treatments

Wood modification treatments based on lactic acid oligomers (OLA) and monomers (LA) enhance beech dimensional stability (up to 70%) and biological resistance (less than 3% weight loss according to EN113). Chestnut wood tannins natural biological activity might improve the modified wood durability with milder curing conditions. Treatment consisted of the impregnation of monomers or oligomers mixtures followed by curing (140?°C/160?°C for 48h). Tannins addition is almost inconsequential with oligomeric-based treatment but improved the monomeric-based treatment. In this case, modified wood biological resistance and product persistence were increased. OLA impregnated wood cured at 160?°C was always the best performing treatment regarding dimensional stability and durability, but the addition of tannins in LA systems conferred promising properties to wood allowing simplification of the modification process.     

Musical constraint satisfaction problems solved with adaptive search

Constraint Programming (CP) allows to model and solve combinatory problems by specifying some partial information on variables, unknowns of the problem. We have studied musical constraint problems, either stated by contemporary composers, or of musical analysis, or instrumentation, in collaboration with IRCAM (french Institute for Research and Coordination Acoustics / Music). Fourteen such problems have been modeled and solved, which allowed to give a detailed typology. This has been used to conceive and implement OMClouds, a library in the Computer Assisted Composition environment OpenMusic. It is based on a local search algorithm called adaptive search. Its architecture allows in particular to define a constraint problem visually, to solve it, and eventually to edit partial or approached results during the resolution process.     

The neuroarchitecture of the circadian clock in the brain of Drosophila melanogaster

Neuroethologists try to assign behavioral functions to certain brain centers, if possible down to individual neurons and to the expression of specific genes. This approach has been successfully applied for the control of circadian rhythmic behavior in the fruit fly Drosophila melanogaster. Several so-called "clock genes" are expressed in specific neurons in the lateral and dorsal brain where they generate cell-autonomous molecular circadian oscillations. These clusters are connected with each other and contribute differentially to the control of behavioral rhythmicity. This report reviews the latest work on characterizing individual circadian pacemaker neurons in the fruit fly's brain that control activity and pupal eclosion, leading to the questions by which neuronal pathways they are synchronized to the external light-dark cycle, and how they impose periodicity on behavior.     

A Subtractive Photoresist Platform for Micro‐ and Macroscopic 3D Printed Structures

The selective removal of structural elements plays a decisive role in 3D printing applications enabling complex geometries. To date, the fabrication of complex structures on the microscale is severely limited by multistep processes. Herein, a subtractive photoresist platform technology that is transferable from microscopic 3D printing via direct laser writing to macroscopic structures via stereolithography is reported. All resist components are readily accessible and exchangeable, offering fast adaptation of the resist's property profile. The micro‐ and macroprinted structures can be removed in a facile fashion, without affecting objects based on standard photoresists. The cleavage is analyzed by time‐lapse optical microscopy as well as via in‐depth spectroscopic assessment. The mechanical properties of the printed materials are investigated by nanoindentation. Critically, the power of the subtractive resist platform is demonstrated by constructing complex 3D objects with flying features on the microscale.