Medializing Calcaneal Osteotomy for progressive collapsing foot deformity alters the three-dimensional subtalar joint alignment.

BACKGROUND: A medializing calcaneal osteotomy (MCO) is considered as one of the key inframalleolar osteotomies to correct progressive collapsing foot deformity (PCFD). While many studies were able to determine the post-operative hind- and midfoot alignment, alternations of the subtalar joint alignment remained obscured by superposition on plain radiography. Therefore, we aimed to assess the hind-, midfoot- and subtalar joint alignment pre- compared to post-operatively using 3D weightbearing CT (WBCT) imaging. METHODS: Seventeen patients with a mean age of 42 ± 17 years were retrospectively analyzed. Inclusion criteria consisted of PCFD deformity corrected by a medializing calcaneal osteotomy (MCO) as main procedure and imaged by WBCT before and after surgery. Exclusion criteria were patients who had concomitant calcaneal lengthening osteotomies, mid-/hindfoot fusions, hindfoot coalitions, and supramalleolar procedures. Image data were used to generate 3D models and compute the hindfoot (HA), midfoot (MA) - and subtalar joint (STJ) alignment in the coronal, sagittal and axial plane, as well as distance maps. RESULTS: Pre-operative measurements of the HA and MA improved significantly relative to their post-operative equivalents p < 0.05). The post-operative STJ alignment showed significant inversion (2.8° ± 1.7), abduction (1.5° ± 1.8), and dorsiflexion (2.3° ± 1.7) of the talus relative to the calcaneus (p < 0.05) compared to the pre-operative alignment. The displacement between the talus and calcaneus relative to the sinus tarsi increased significantly (0.6 mm±0.5; p < 0.05). CONCLUSION: This study detected significant changes in the sagittal, coronal, and axial plane alignment of the subtalar joint, which corresponded to a decompression of the sinus tarsi. These findings contribute to our clinical practice by demonstrating the magnitude of alteration in the subtalar joint alignment that can be expected after PCFD correction with MCO as main procedure.

Analysis of the Evolution of Pandemic Influenza A(H1N1) Virus Neuraminidase Reveals Entanglement of Different Phenotypic Characteristics.

The influenza A virus (IAV) neuraminidase (NA) is essential for virion release from cells and decoy receptors and an important target of antiviral drugs and antibodies. Adaptation to a new host sialome and escape from the host immune system are forces driving the selection of mutations in the NA gene. Phylogenetic analysis shows that until 2015, 16 amino acid substitutions in NA became fixed in the virus population after introduction in the human population of the pandemic IAV H1N1 (H1N1pdm09) in 2009. The accumulative effect of these substitutions, in the order in which they appeared, was analyzed using recombinant proteins and viruses in combination with different functional assays. The results indicate that NA activity did not evolve to a single optimum but rather fluctuated within a certain bandwidth. Furthermore, antigenic and enzymatic properties of NA were intertwined, with several residues affecting multiple properties. For example, the substitution K432E in the second sialic acid binding site, next to the catalytic site, was shown to affect catalytic activity, substrate specificity, and the pH optimum for maximum activity. This substitution also altered antigenicity of NA, which may explain its selection. We propose that the entanglement of NA phenotypes may be an important determining factor in the evolution of NA.IMPORTANCE Since its emergence in 2009, the pandemic H1N1 influenza A virus (IAV) has caused significant disease and mortality in humans. IAVs contain two envelope glycoproteins, the receptor-binding hemagglutinin (HA) and the receptor-destroying neuraminidase (NA). NA is essential for virion release from cells and decoy receptors, is an important target of antiviral drugs, and is increasingly being recognized as an important vaccine antigen. Not much is known, however, about the evolution of this protein upon the emergence of the novel pandemic H1N1 virus, with respect to its enzymatic activity and antigenicity. By reconstructing the evolutionary path of NA, we show that antigenic and enzymatic properties of NA are intertwined, with several residues affecting multiple properties. Understanding the entanglement of NA phenotypes will lead to better comprehension of IAV evolution and may help the development of NA-based vaccines.

N-Glycolylneuraminic Acid as a Receptor for Influenza A Viruses.

A species barrier for the influenza A virus is the differential expression of sialic acid, which can either be α2,3-linked for avians or α2,6-linked for human viruses. The influenza A virus hosts also express other species-specific sialic acid derivatives. One major modification at C-5 is N-glycolyl (NeuGc), instead of N-acetyl (NeuAc). N-glycolyl is mammalian specific and expressed in pigs and horses, but not in humans, ferrets, seals, or dogs. Hemagglutinin (HA) adaptation to either N-acetyl or N-glycolyl is analyzed on a sialoside microarray containing both α2,3- and α2,6-linkage modifications on biologically relevant N-glycans. Binding studies reveal that avian, human, and equine HAs bind either N-glycolyl or N-acetyl. Structural data on N-glycolyl binding HA proteins of both H5 and H7 origin describe this specificity. Neuraminidases can cleave N-glycolyl efficiently, and tissue-binding studies reveal strict species specificity. The exclusive manner in which influenza A viruses differentiate between N-glycolyl and N-acetyl is indicative of selection.

The hind- and midfoot alignment computed after a medializing calcaneal osteotomy using a 3D weightbearing CT.

PURPOSE: A medializing calcaneal osteotomy (MCO) is a surgical procedure frequently performed to correct an adult acquired flatfoot (AAFD) deformity. However, most studies are limited to a 2D analysis of 3D deformity. Therefore, the aim is to perform a 3D assessment of the hind- and midfoot alignment using a weightbearing CT (WBCT) preoperatively as well as postoperatively. METHODS: Eighteen patients with a mean age of 49.4 years (range 18-67) were prospectively included in a pre-post-study design. A MCO was performed and a WBCT was obtained pre- and postoperative. Images were converted into 3D models to compute linear and angular measurements, respectively, in millimeters (mm) and degrees (°), based on previously reported landmarks of the hind- and midfoot alignment. A regression analysis was performed between the displacement of a MCO and the obtained postoperative correction. RESULTS: The mean 3D hindfoot angle improved significantly preoperative compared to postoperative (p < 0.001). This appeared according to a linear relation with the amount of medial translation in a MCO (R2 = 0.84, p < 0.001). The axes of the tibia showed significant coronal as well as axial changes (p < 0.05). Analysis of the midfoot showed significant changes in the navicular height and rotation as well as the Méary angle (p < 0.05). Additionally, a linear trend between the midfoot measurements and amount of medial translation in a MCO was observed, but not significant (p > 0.05). CONCLUSION: This study demonstrates an effective 3D correction of an AAFD by a MCO according to a linear relationship. The concomitant formula can be used to perform a preoperative planning. The novelty is the comparative 3D weightbearing CT assessment of both the computed hind- and midfoot alignment after a medializing calcaneus osteotomy. This could improve accuracy of the currently performed preoperative planning in clinical practice.

Efficient catalysts for asymmetric Mannich reactions.

Efficient chiral catalysts for direct asymmetric three-component Mannich reactions of ketones, aldehydes and an amine (p-anisidine) have been developed. The corresponding ß-amino carbonyl compounds (Mannich adducts) were obtained in good chemical yields and excellent enantio- and diastereoselectivities. The reaction conditions have been optimized by invoking ultrasonication and the influence of some structural moieties of the catalysts on the chemical yield and stereoselectivity of the Mannich products has been evaluated.