Видалення металоконструкцій: проблему вирішено?

Up to 30-35 % of operations for removal of hardware pass with unforeseen difficulties, and often with complications. For instance, the risk of a subcapital fracture of the femur after the removal of a proximal nail or DHS in elderly people reaches 70 %. Refractures are most commonly observed after the removal of plates from the forearm diaphysis. According to different authors, the frequency of such refractures is 20-40 %. Diverse scientific information, absence of any clear indications and contraindications for removal of implants at the present period of time lead scientists to continue both discussions and researches in this direction in order to create a definite algorithm of actions in different clinical situations.До 30–35 % операций по удалению металлоконструкций протекают с непредвиденными сложностями, и часто с осложнениями. Так, риск субкапитального перелома бедренной кости после удаления проксимального гвоздя или DHS у пожилых пациентов достигает 70 %. Наиболее часто встречаются рефрактуры после удаления пластин из диафиза предплечья. По данным разных авторов, их частота составляет 20–40 %. Неоднозначная научная информация, отсутствие ныне четких показаний и противопоказаний к удалению имплантатов наталкивает ученых на продолжение как дискуссии, так и исследований по этому направлению с целью выработки определенного алгоритма действий в различных клинических ситуациях.До 30–35 % операцій з видалення металоконструкцій перебігають з непередбачуваними складнощами і часто з ускладненнями. Так, ризик субкапітального перелому стегнової кістки після видалення проксимального цвяха або DHS у літніх пацієнтів досягає 70 %. Найчастіше трапляються рефрактури після видалення пластин із діафіза передпліччя. Як свідчать різні автори, їх частота становить 20–40 %. Неоднозначна наукова інформація, відсутні дотепер чіткі показання і протипоказання до видалення імплантатів спонукає науковців до продовження як дискусії, так і нових досліджень в цьому напрямкові з метою розроблення певного алгоритму дій у різних клінічних ситуаціях

Computational Design of a pH Stable Enzyme: Understanding Molecular Mechanism of Penicillin Acylase's Adaptation to Alkaline Conditions

<div><p>Protein stability provides advantageous development of novel properties and can be crucial in affording tolerance to mutations that introduce functionally preferential phenotypes. Consequently, understanding the determining factors for protein stability is important for the study of structure-function relationship and design of novel protein functions. Thermal stability has been extensively studied in connection with practical application of biocatalysts. However, little work has been done to explore the mechanism of pH-dependent inactivation. In this study, bioinformatic analysis of the Ntn-hydrolase superfamily was performed to identify functionally important subfamily-specific positions in protein structures. Furthermore, the involvement of these positions in pH-induced inactivation was studied. The conformational mobility of penicillin acylase in <i>Escherichia coli</i> was analyzed through molecular modeling in neutral and alkaline conditions. Two functionally important subfamily-specific residues, Gluβ482 and Aspβ484, were found. Ionization of these residues at alkaline pH promoted the collapse of a buried network of stabilizing interactions that consequently disrupted the functional protein conformation. The subfamily-specific position Aspβ484 was selected as a hotspot for mutation to engineer enzyme variant tolerant to alkaline medium. The corresponding Dβ484N mutant was produced and showed 9-fold increase in stability at alkaline conditions. Bioinformatic analysis of subfamily-specific positions can be further explored to study mechanisms of protein inactivation and to design more stable variants for the engineering of homologous Ntn-hydrolases with improved catalytic properties.</p></div

The network of hydrogen bonding interactions between the two β-layers of the αββα-core B1 domain in Ntn-hydrolases.

<p>(A) Glutarylamidase from <i>Pseudomonas sp</i>., (B) N-acyl homoserine lactone acylase PvdQ from <i>Pseudomonas aeruginosa</i>, and (C) penicillin acylase from <i>Alcaligenes faecalis</i>.</p

Structural stability of the wild type <i>Ec</i>PA at pH 7.5 and 10.0.

<p>Root mean square deviation (RMSD) for each enzyme variant has been averaged over three independent MD runs. The mean and standard deviation are shown in angstroms. N_res – number of amino acid residues in a structural domain. Δ_RMSD  =  RMSD_pH10 – RMSD_pH7.5 and <i>f</i>  =  <i>f</i>(RMSD_pH7.5 ≥ RMSD_pH10) were calculated as explained in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0100643#s4" target="_blank">Methods</a>, section 2. Lower <i>f</i> values indicate a significant destabilizing effect of the alkaline pH compared to neutral conditions while Δ_RMSD estimates the degree of destabilization.</p

Root mean square deviation (RMSD) of different structural domains during 50 ns MD simulations.

<p>Results are shown for <i>Ec</i>PA and its Dβ484N mutant at different pH. Each curve is averaged over three independent MD trajectories.</p

Modeling of the wild type (WT) and the mutant (Dβ484N) <i>Ec</i>PA stability at pH 10.0.

<p>Root mean square deviation (RMSD) for each enzyme variant has been averaged over three independent MD runs. The mean and standard deviation are shown in angstroms. N_res – number of amino acid residues in a structural unit. Δ_RMSD  =  RMSD_Dβ484N – RMSD_WT and <i>f</i>  =  <i>f</i>(RMSD_Dβ484N ≥ RMSD_WT) were calculated as explained in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0100643#s4" target="_blank">Methods</a>, section 2. Lower <i>f</i> values indicate a significant stabilizing effect of the mutation compared to the wild type enzyme while Δ_RMSD estimates the degree of stabilization.</p

The globalizability of temporal discounting

Economic inequality is associated with extreme rates of temporal discounting, which is a behavioral pattern where individuals choose smaller, immediate financial gains over larger, delayed gains. Such patterns may feed into rising global inequality, yet it is unclear if they are a function of choice preferences or norms, or rather absence of sufficient resources to meet immediate needs. It is also not clear if these reflect true differences in choice patterns between income groups. We test temporal discounting and five intertemporal choice anomalies using local currencies and value standards in 61 countries. Across a diverse sample of 13,629 participants, we found highly consistent rates of choice anomalies. Individuals with lower incomes were not significantly different, but economic inequality and broader financial circumstances impact population choice patterns

The globalizability of temporal discounting.

Economic inequality is associated with preferences for smaller, immediate gains over larger, delayed ones. Such temporal discounting may feed into rising global inequality, yet it is unclear whether it is a function of choice preferences or norms, or rather the absence of sufficient resources for immediate needs. It is also not clear whether these reflect true differences in choice patterns between income groups. We tested temporal discounting and five intertemporal choice anomalies using local currencies and value standards in 61 countries (N = 13,629). Across a diverse sample, we found consistent, robust rates of choice anomalies. Lower-income groups were not significantly different, but economic inequality and broader financial circumstances were clearly correlated with population choice patterns

The globalizability of temporal discounting

Economic inequality is associated with preferences for smaller, immediate gains over larger, delayed ones. Such temporal discounting may feed into rising global inequality, yet it is unclear whether it is a function of choice preferences or norms, or rather the absence of sufficient resources for immediate needs. It is also not clear whether these reflect true differences in choice patterns between income groups. We tested temporal discounting and five intertemporal choice anomalies using local currencies and value standards in 61 countries (N = 13,629). Across a diverse sample, we found consistent, robust rates of choice anomalies. Lower-income groups were not significantly different, but economic inequality and broader financial circumstances were clearly correlated with population choice patterns