The promise of a community-based approach to managing severe malnutrition: A case study from Ethiopia

BACKGROUND: Community-based therapeutic care (CTC) is a new strategy in the arsenal of techniques to manage complex nutritional emergencies in rural communities. The CTC approach uses a newly developed ready-to-use therapeutic food, Plumpynut, to rehabilitate severely malnourished children in their home communities. Emerging literature has suggested the CTC strategy yielded results that were superior to those of programs limited to therapeutic feeding centers, as measured by rates of coverage and numbers of children rehabilitated. OBJECTIVE: To compare the effectiveness of the CTC strategy in combination with conventional treatments for acute malnutrition. The expectation was that this program would support the growing consensus on the effectiveness of CTC strategies. METHODS: Data from monitoring the initial phase of program implementation were reviewed to ascertain program impact. The number of children participating and the outcome of their participation were assessed. RESULTS: Families became key participants in the rehabilitation of their children, and communities became strengthened through the mobilization of local networks and the improved knowledge base of local health workers. Recovery rates were comparable with international standards, and coverage far exceeded that of traditional center-based care. CONCLUSIONS: CTC is an important tool to effectively address nutritional emergencies and may be a valuable entry point for long-term development, since it fosters capacity building and improvement in local communities. CTC programs may eventually be viewed as the entry point for more sustained development-oriented interventions, thus helping make the transition from relief to development.     

Changes in the volatile composition of red wines during aging in oak barrels due to microoxygenation treatment applied before malolactic fermentation

Microoxygenation is a wine-making technique consisting in the addition of small and controlled amounts of oxygen. This study has examined the effect of this technique on the volatile composition of two red single variety wines during two successive vintages. The microoxygenation treatment was applied at the end of alcoholic fermentation and before beginning malolactic fermentation. Once the microoxygenation treatment had finished, wines were aged in new American oak barrels for 12 months. The results obtained showed that the microoxygenation treatment did not cause significant changes in the varietal and fermentation volatile compounds, however microoxygenation slowed down the extraction of some of the volatile compounds extracted from wood. A varietal and vintage effect was also observed for some of the compounds studied.     

Antioxidant potential of single-variety red wines aged in the barrel and in the bottle

Wine constitutes a dynamic system in continuous evolution, in which numerous reactions involving polymerization and condensation take place between its phenolic compounds during the ageing process, which undoubtedly affect its structure and, very probably, its antioxidant effect. This study set out to evaluate the effect of ageing on the antioxidant potential of wine. A group of 162 wines were studied, of varying ages, which had undergone different ageing processes, both in the barrel and in the bottle, and which were prepared from different grape varieties and vintages. Total antioxidant capacity (ABTS, DPPH, DMPD, ORAC and FRAP), scavenger activity (HRSA and SRSA) and the biomarkers of oxidative stress (DNA-damage and ABAP-LP) were all analysed. The assay methods showed different behaviours for the same wines, thus the young wines presented higher indices for ABTS, DPPH and DMPD, whereas those that were aged showed higher indices for ABAP-LP and ORAC. Finally, the antioxidant potential of the wines in the study appeared not to be influenced by other factors, such as microoxygenation or grape variety.     

Colloidal synthesis of Au nanoparticles using polyelectrolytes with 1,3,4-thiadiazole as reducing agents

Heterocyclic compounds are well known for their biological activity and coordination properties. Some heterocyclic compounds have been employed in the stabilization against coalescence of metallic nanoparticles in colloidal solutions, for example, tetrazole, triazole, and pyrazole. The aim of this work is to design new polyelectrolytes with heterocyclic pendant groups useful as reducing agents of Au³⁺ and as stabilizing agents for the synthesis of colloidal Au nanoparticles. Thus, polyelectrolytes with thiosemicarbazone and 1,3,4-thiadiazole pendant groups were used as reducing agents of Au³⁺ ions and stabilizing agents of Au nanoparticles. The voltammetry study of the polyelectrolytes showed that one with thiosemicarbazone pendant groups is the better reducing agent than polyelectrolytes with heterocyclic pendant groups. The polyelectrolytes can control the growth of the nanoparticles, obtaining structures with an average size of 9 nm. In this study, it was concluded that the nature of the heterocyclic group does not have an effect on the shape of nanoparticles and quasi-spherical nanoparticles were obtained with all polyelectrolytes. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47790.     

Interrelated Mechanism by Which the Methide Quinone Celastrol,Obtained from the Roots of Tripterygium wilfordii,Inhibits Main Protease 3CLpro of COVID-19 and Acts as Superoxide Radical Scavenger

We describe the potential anti coronavirus disease 2019 (COVID-19) action of the methide quinone inhibitor, celastrol. The related methide quinone dexamethasone is, so far, among COVID-19 medications perhaps the most effective drug for patients with severe symptoms. We observe a parallel redox biology behavior between the antioxidant action of celastrol when scavenging the superoxide radical, and the adduct formation of celastrol with the main COVID-19 protease. The related molecular mechanism is envisioned using molecular mechanics and dynamics calculations. It proposes a covalent bond between the S(Cys145) amino acid thiolate and the celastrol A ring, assisted by proton transfers by His164 and His41 amino acids, and a π interaction from Met49 to the celastrol B ring. Specifically, celastrol possesses two moieties that are able to independently scavenge the superoxide radical: the carboxylic framework located at ring E, and the methide-quinone ring A. The latter captures the superoxide electron, releasing molecular oxygen, and is the feature of interest that correlates with the mechanism of COVID-19 inhibition. This unusual scavenging of the superoxide radical is described using density functional theory (DFT) methods, and is supported experimentally by cyclic voltammetry and X-ray diffraction.     

Beyond “Big Eaters”: The Versatile Role of Alveolar Macrophages in Health and Disease

Macrophages act as immune scavengers and are important cell types in the homeostasis of various tissues. Given the multiple roles of macrophages, these cells can also be found as tissue resident macrophages tightly integrated into a variety of tissues in which they fulfill crucial and organ-specific functions. The lung harbors at least two macrophage populations: interstitial and alveolar macrophages, which occupy different niches and functions. In this review, we provide the latest insights into the multiple roles of alveolar macrophages while unraveling the distinct factors which can influence the ontogeny and function of these cells. Furthermore, we will highlight pulmonary diseases, which are associated with dysfunctional macrophages, concentrating on congenital diseases as well as pulmonary infections and impairment of immunological pathways. Moreover, we will provide an overview about different treatment approaches targeting macrophage dysfunction. Improved knowledge of the role of macrophages in the onset of pulmonary diseases may provide the basis for new pharmacological and/or cell-based immunotherapies and will extend our understanding to other macrophage-related disorders.     

Prenatal THC Does Not Affect Female Mesolimbic Dopaminergic System in Preadolescent Rats

Cannabis use among pregnant women is increasing worldwide along with permissive sociocultural attitudes toward it. Prenatal cannabis exposure (PCE), however, is associated with adverse outcome among offspring, ranging from reduced birth weight to child psychopathology. We have previously shown that male rat offspring prenatally exposed to Δ9-tetrahydrocannabinol (THC), a rat model of PCE, exhibit extensive molecular, cellular, and synaptic changes in dopamine neurons of the ventral tegmental area (VTA), resulting in a susceptible mesolimbic dopamine system associated with a psychotic-like endophenotype. This phenotype only reveals itself upon a single exposure to THC in males but not females. Here, we characterized the impact of PCE on female behaviors and mesolimbic dopamine system function by combining in vivo single-unit extracellular recordings in anesthetized animals and ex vivo patch clamp recordings, along with neurochemical and behavioral analyses. We find that PCE female offspring do not show any spontaneous or THC-induced behavioral disease-relevant phenotypes. The THC-induced increase in dopamine levels in nucleus accumbens was reduced in PCE female offspring, even when VTA dopamine activity in vivo and ex vivo did not differ compared to control. These findings indicate that PCE impacts mesolimbic dopamine function and its related behavioral domains in a sex-dependent manner and warrant further investigations to decipher the mechanisms determining this sex-related protective effect from intrauterine THC exposure.     

Synthesis and SAR of Tetracyclic Inhibitors of Protein Kinase CK2 Derived from Furocarbazole W16

The serine/threonine kinase CK2 modulates the activity of more than 300 proteins and thus plays a crucial role in various physiological and pathophysiological processes including neurodegenerative disorders of the central nervous system and cancer. The enzymatic activity of CK2 is controlled by the equilibrium between the heterotetrameric holoenzyme CK2α₂β₂ and its monomeric subunits CK2α and CK2β. A series of analogues of W16 ((3aR,4S,10S,10aS)-4-{[(S)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]carbonyl}-10-(3,4,5-trimethoxyphenyl)-4,5,10,10a-tetrahydrofuro[3,4-b]carbazole-1,3(3aH)-dione ((+)- 3 a )) was prepared in an one-pot, three-component Levy reaction. The stereochemistry of the tetracyclic compounds was analyzed. Additionally, the chemically labile anhydride structure of the furocarbazoles 3 was replaced by a more stable imide ( 9 ) and N-methylimide ( 10 ) substructure. The enantiomer (−)- 3 a (K_i=4.9 μM) of the lead compound (+)- 3 a (K_i=31 μM) showed a more than sixfold increased inhibition of the CK2α/CK2β interaction (protein-protein interaction inhibition, PPII) in a microscale thermophoresis (MST) assay. However, (−)- 3 a did not show an increased enzyme inhibition of the CK2α₂β₂ holoenzyme, the CK2α subunit or the mutated CK2α′ ^C336S subunit in the capillary electrophoresis assay. In the pyrrolocarbazole series, the imide (−)- 9 a (K_i=3.6 μM) and the N-methylimide (+)- 10 a (K_i=2.8 μM) represent the most promising inhibitors of the CK2α/CK2β interaction. However, neither compound could inhibit enzymatic activity. Unexpectedly, the racemic tetracyclic pyrrolocarbazole (±)- 12 , with a carboxy moiety in the 4-position, displays the highest CK2α/CK2β interaction inhibition (K_i=1.8 μM) of this series of compounds.     

Design,Synthesis, and Characterization of Macrocyclic Inhibitors of the Proprotein Convertase Furin

The activation of viral glycoproteins by the host protease furin is an essential step in the replication of numerous pathogenic viruses. Thus, effective inhibitors of furin could serve as broad-spectrum antiviral drugs. A crystal structure of an inhibitory hexapeptide derivative in complex with furin served as template for the rational design of various types of new cyclic inhibitors. Most of the prepared derivatives are relatively potent furin inhibitors with inhibition constants in the low nanomolar or even sub-nanomolar range. For seven derivatives the crystal structures in complex with furin could be determined. In three complexes, electron density was found for the entire inhibitor. In the other cases the structures could be determined only for the P6/P5-P1 segments, which directly interact with furin. The cyclic derivatives together with two non-cyclic reference compounds were tested as inhibitors of the proteolytic activation and replication of respiratory syncytial virus in cells. Significant antiviral activity was found for both linear reference inhibitors, whereas a negligible efficacy was determined for the cyclic derivatives.