Total knee arthroplasty using computer-assisted navigation in patients with deformities of the femur and tibia: A report of 5 cases

Anatomic aberrations of the femur and tibia secondary to trauma, congenital defects, and prior surgery present challenges for the reconstructive knee surgeon because of an altered mechanical axis and distorted anatomic landmarks. Five patients with arthritis of the knee and extra-articular femoral and/or tibial deformity, retained hardware, or intramedullary (IM) implants underwent total knee arthroplasty using a computer navigation system. The navigation system obviated the need for an IM guide, and the normal mechanical axis of the patients was restored. Extensive dissection for hardware removal or osteotomy was not necessary in these patients. In these 5 cases, a navigation system proved to be an effective tool for restoration of limb alignment in the presence of significant extra-articular deformities and/or IM hardware. Thus, it provides an alternative approach to the traditional IM instrumentation for treating these patients in an effective manner

Hydrogenation reactions of carbon on Earth: linking methane, margarine, and life

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in McGlynn, S. E., Glass, J. B., Johnson-Finn, K., Klein, F., Sanden, S. A., Schrenk, M. O., Ueno, Y., & Vitale-Brovarone, A. Hydrogenation reactions of carbon on Earth: linking methane, margarine, and life. American Mineralogist, 105(5), (2020): 599-608, doi:10.2138/am-2020-6928CCBYNCND.Hydrogenation reactions are a major route of electron and proton flow on Earth. Interfacing geology and organic chemistry, hydrogenations occupy pivotal points in the Earth’s global geochemical cycles. Some examples of hydrogenation reactions on Earth today include the production and consumption of methane in both abiotic and biotic reactions, the reduction of protons in hydrothermal settings, and the biological synthesis and degradation of fatty acids. Hydrogenation reactions were likely important for prebiotic chemistry on the early Earth, and today serve as one of the fundamental reaction classes that enable cellular life to construct biomolecules. An understanding and awareness of hydrogenation reactions is helpful for comprehending the larger web of molecular and material inter-conversions on our planet. In this brief review we detail some important hydrogenation and dehydrogenation reactions as they relate to geology, biology, industry, and atmospheric chemistry. Such reactions have implications ranging from the suite of reactions on early Earth to industrial applications like the production of hydrocarbon fuel.S.E.M. is supported by NSF Award 1724300 and JSPS KAKENHI Grant JP18H01325. A.V.B. is supported by ANR T-ERC, CNRS INSU-SYSTER, and Rita Levi Montalcini by MIUR. J.B.G. is supported by NASA Exobiology Grant NNX14AJ87G and 80NSSC19K0477. F.K. is supported by NSF-OCE award 1634032 and 1427274. M.O.S. is supported by the NASA Astrobiology Institute Rock-Powered Life Grant NNA15BB02A

Encephalitic alphaviruses exploit caveola-mediated transcytosis at the blood-brain barrier for central nervous system entry

Venezuelan and western equine encephalitis viruses (VEEV and WEEV, respectively) invade the central nervous system (CNS) early during infection, via neuronal and hematogenous routes. While viral replication mediates host shutoff, including expression of type I interferons (IFN), few studies have addressed how alphaviruses gain access to the CNS during established infection or the mechanisms of viral crossing at the blood-brain barrier (BBB). Here, we show that hematogenous dissemination of VEEV and WEEV into the CNS occurs via caveolin-1 (Cav-1)-mediated transcytosis (Cav-MT) across an intact BBB, which is impeded by IFN and inhibitors of RhoA GTPase. Use of reporter and nonreplicative strains also demonstrates that IFN signaling mediates viral restriction within cells comprising the neurovascular unit (NVU), differentially rendering brain endothelial cells, pericytes, and astrocytes permissive to viral replication. Transmission and immunoelectron microscopy revealed early events in virus internalization and Cav-1 association within brain endothelial cells. Cav-1-deficient mice exhibit diminished CNS VEEV and WEEV titers during early infection, whereas viral burdens in peripheral tissues remained unchanged. Our findings show that alphaviruses exploit Cav-MT to enter the CNS and that IFN differentially restricts this process at the BBB

A Bright Submillimeter Source in the Bullet Cluster (1E0657--56) Field Detected with BLAST

We present the 250, 350, and 500 micron detection of bright submillimeter emission in the direction of the Bullet Cluster measured by the Balloon-borne Large Aperture Submillimeter Telescope (BLAST). The 500 micron centroid is coincident with an AzTEC 1.1 mm point-source detection at a position close to the peak lensing magnification produced by the cluster. However, the 250 micron and 350 micron centroids are elongated and shifted toward the south with a differential shift between bands that cannot be explained by pointing uncertainties. We therefore conclude that the BLAST detection is likely contaminated by emission from foreground galaxies associated with the Bullet Cluster. The submillimeter redshift estimate based on 250-1100 micron photometry at the position of the AzTEC source is z_phot = 2.9 (+0.6 -0.3), consistent with the infrared color redshift estimation of the most likely IRAC counterpart. These flux densities indicate an apparent far-infrared luminosity of L_FIR = 2E13 Lsun. When the amplification due to the gravitational lensing of the cluster is removed, the intrinsic far-infrared luminosity of the source is found to be L_FIR <= 10^12 Lsun, consistent with typical luminous infrared galaxies.Comment: Accepted for publication in the Astrophysical Journal. Maps are available at http://blastexperiment.info

Late effects of clubfoot deformity in adolescent and young adult patients whose initial treatment was an extensive soft-tissue release: Topic review and clinical case series

Children with congenital clubfoot often have residual deformity, pain, and limited function in adolescence and young adulthood. These patients represent a heterogeneous group that often requires an individualized management strategy. This article reviews the available literature on this topic while proposing a descriptive classification system based on a review of patients at our institution who underwent surgery for problems related to previous clubfoot deformity during the period between January 1999 and January 2012. Seventy-two patients (93 feet) underwent surgical treatment for the late effects of clubfoot deformity at an average age of 13 years (range 9 to 19 years). All patients had been treated at a young age with serial casting, and most had at least one previous surgery on the affected foot or feet. Five common patterns of pathology identified were as follows: undercorrection, overcorrection, dorsal bunion, anterior ankle impingement, and lateral hindfoot impingement. Management pathways for each group of the presenting problems is described. To our knowledge, this topic review represents the largest report of adolescent and young adult patients with residual clubfoot deformity in the literature

Over half of the far-infrared background light comes from galaxies at z >= 1.2

Submillimetre surveys during the past decade have discovered a population of luminous, high-redshift, dusty starburst galaxies. In the redshift range 1 <= z <= 4, these massive submillimetre galaxies go through a phase characterized by optically obscured star formation at rates several hundred times that in the local Universe. Half of the starlight from this highly energetic process is absorbed and thermally re-radiated by clouds of dust at temperatures near 30 K with spectral energy distributions peaking at 100 microns in the rest frame. At 1 <= z <= 4, the peak is redshifted to wavelengths between 200 and 500 microns. The cumulative effect of these galaxies is to yield extragalactic optical and far-infrared backgrounds with approximately equal energy densities. Since the initial detection of the far-infrared background (FIRB), higher-resolution experiments have sought to decompose this integrated radiation into the contributions from individual galaxies. Here we report the results of an extragalactic survey at 250, 350 and 500 microns. Combining our results at 500 microns with those at 24 microns, we determine that all of the FIRB comes from individual galaxies, with galaxies at z >= 1.2 accounting for 70 per cent of it. As expected, at the longest wavelengths the signal is dominated by ultraluminous galaxies at z > 1.Comment: Accepted to Nature. Maps available at http://blastexperiment.info

The Structure of Episodic Memory: Ganeri's ‘Mental Time Travel and Attention’

We offer a framework for assessing what the structure of episodic memory might be, if one accepts the Buddhist denial of persisting selves. This paper is a response to Jonardon Ganeri's paper "Mental time travel and attention", which explores Buddhaghosa's ideas about memory. (It will eventually be published with a reply by Ganeri)

Novel mutations expand the clinical spectrum of DYNC1H1-associated spinal muscular atrophy

OBJECTIVE To expand the clinical phenotype of autosomal dominant congenital spinal muscular atrophy with lower extremity predominance (SMA-LED) due to mutations in the dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) gene. METHODS Patients with a phenotype suggestive of a motor, non-length-dependent neuronopathy predominantly affecting the lower limbs were identified at participating neuromuscular centers and referred for targeted sequencing of DYNC1H1. RESULTS We report a cohort of 30 cases of SMA-LED from 16 families, carrying mutations in the tail and motor domains of DYNC1H1, including 10 novel mutations. These patients are characterized by congenital or childhood-onset lower limb wasting and weakness frequently associated with cognitive impairment. The clinical severity is variable, ranging from generalized arthrogryposis and inability to ambulate to exclusive and mild lower limb weakness. In many individuals with cognitive impairment (9/30 had cognitive impairment) who underwent brain MRI, there was an underlying structural malformation resulting in polymicrogyric appearance. The lower limb muscle MRI shows a distinctive pattern suggestive of denervation characterized by sparing and relative hypertrophy of the adductor longus and semitendinosus muscles at the thigh level, and diffuse involvement with relative sparing of the anterior-medial muscles at the calf level. Proximal muscle histopathology did not always show classic neurogenic features. CONCLUSION Our report expands the clinical spectrum of DYNC1H1-related SMA-LED to include generalized arthrogryposis. In addition, we report that the neurogenic peripheral pathology and the CNS neuronal migration defects are often associated, reinforcing the importance of DYNC1H1 in both central and peripheral neuronal functions

Synthesis and structural characterization of a mimetic membrane-anchored prion protein

During pathogenesis of transmissible spongiform encephalopathies (TSEs) an abnormal form (PrPSc) of the host encoded prion protein (PrPC) accumulates in insoluble fibrils and plaques. The two forms of PrP appear to have identical covalent structures, but differ in secondary and tertiary structure. Both PrPC and PrPSc have glycosylphospatidylinositol (GPI) anchors through which the protein is tethered to cell membranes. Membrane attachment has been suggested to play a role in the conversion of PrPC to PrPSc, but the majority of in vitro studies of the function, structure, folding and stability of PrP use recombinant protein lacking the GPI anchor. In order to study the effects of membranes on the structure of PrP, we synthesized a GPI anchor mimetic (GPIm), which we have covalently coupled to a genetically engineered cysteine residue at the C-terminus of recombinant PrP. The lipid anchor places the protein at the same distance from the membrane as does the naturally occurring GPI anchor. We demonstrate that PrP coupled to GPIm (PrP-GPIm) inserts into model lipid membranes and that structural information can be obtained from this membrane-anchored PrP. We show that the structure of PrP-GPIm reconstituted in phosphatidylcholine and raft membranes resembles that of PrP, without a GPI anchor, in solution. The results provide experimental evidence in support of previous suggestions that NMR structures of soluble, anchor-free forms of PrP represent the structure of cellular, membrane-anchored PrP. The availability of a lipid-anchored construct of PrP provides a unique model to investigate the effects of different lipid environments on the structure and conversion mechanisms of PrP