STUDY DESIGN: Experimental.
SAMPLE POPULATION: Fourteen equine cadaver limbs/horses.
METHODS: Simulated fractures were repaired with 2 lag screws under 4-Nm insertion torque (linear repair). Computed tomography (CT) imaging was performed with the leg unloaded and loaded to forces generated while walking. The fracture repair was revised to include 3 lag screws placed with the same insertion torque (triangular repair) prior to CT. The width of the fracture gap was assessed qualitatively by 2 observers and graded on the basis of gap measurements relative to the average voxel size at dorsal, mid, and palmar P1 sites. Interobserver agreement was assessed with Cohen's κ. The effect of repair type, loading condition, and measurement site on fracture gap grades was evaluated by using Kendall's τ-b correlation coefficients and paired nonparametric tests. Significance was set at P ≤ .05.
RESULTS: Agreement between loading and fracture gap widening was fair in triangular (κ = 0.53) and excellent in linear (κ = 0.81) repairs. Loading resulted in fracture gap distraction in linear repairs (Plinear = .008). Triangular repairs reduced fractures better irrespective of loading (Punloaded = .003; Ploaded
MAIN BODY: We argue that broader consideration of lactation, incorporating evolutionary, comparative and anthropological aspects, could provide new insights into breastfeeding practices and problems, enhance research and ultimately help to develop novel approaches to improve initiation and maintenance. Our current focus on breastfeeding as a strategy to improve health outcomes must engage with the evolution of lactation as a flexible trait under selective pressure to maximise reproductive fitness. Poor understanding of the dynamic nature of breastfeeding may partly explain why some women are unwilling or unable to follow recommendations.
CONCLUSIONS: We identify three key implications for health professionals, researchers and policymakers. Firstly, breastfeeding is an adaptive process during which, as in other mammals, variability allows adaptation to ecological circumstances and reflects mothers' phenotypic variability. Since these factors vary within and between humans, the likelihood that a 'one size fits all' approach will be appropriate for all mother-infant dyads is counterintuitive; flexibility is expected. From an anthropological perspective, lactation is a period of tension between mother and offspring due to genetic 'conflicts of interest'. This may underlie common breastfeeding 'problems' including perceived milk insufficiency and problematic infant crying. Understanding this - and adopting a more flexible, individualised approach - may allow a more creative approach to solving these problems. Incorporating evolutionary concepts may enhance research investigating mother-infant signalling during breastfeeding; where possible, studies should be experimental to allow identification of causal effects and mechanisms. Finally, the importance of learned behaviour, social and cultural aspects of primate (especially human) lactation may partly explain why, in cultures where breastfeeding has lost cultural primacy, promotion starting in pregnancy may be ineffective. In such settings, educating children and young adults may be important to raise awareness and provide learning opportunities that may be essential in our species, as in other primates.
OBJECTIVE: Here we synthesize 10 chalcone derivatives to be evaluated their in vitro enzymatic inhibition activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE).
METHODS: The synthesis was carried out using Claissen-Schimdt condensation and the in vitro assay was conducted using Ellman Method.
RESULTS: Compounds 2b and 4b demonstrated as the best IC50 of 9.3 μM and 68.7 μM respectively, towards AChE and BChE inhibition. Molecular docking studies predicted that this activity might be due to the interaction of the chalcones with important amino acid residues in the binding site of AChE such as SER200 and in that of BChE, such as TRP82, SER198, TRP430, TYR440, LEU286 and VAL288.
CONCLUSION: Chalcone can be used as the scaffold for cholinesterase inhibitor, in particularly either fluorine or nitro group to be augmented at the para-position of Ring B, whereas the hydrophobic chain is necessary at the meta-position of Ring B.