Clinical outcomes of extra-articular tenodesis/anterolateral reconstruction in the ACL injured knee

Purpose: The role of concomitant extra-articular procedures in improving the outcome of ACL reconstruction has experienced a recent resurgence in interest. The aim of this article is to highlight the differences in philosophies and outcomes of historical non-anatomic reconstructions and contemporary, anatomical anterolateral reconstruction. Methods: A narrative review was performed using PubMed/MEDLINE using the keywords "lateral extra-articular tenodesis" and "anterolateral ligament reconstruction". Results: Results of search strategy: 37 studies [13 reporting clinical outcomes of isolated lateral extra-articular tenodesis (LET) in ACL deficient knees and 23 comparing isolated anterior cruciate ligament reconstruction (ACLR) with ACLR + LET] and one study on anterolateral ligament (ALL) reconstruction were identified as relevant and included in the review. Results of literature review: Isolated extra-articular reconstructions are rarely performed in contemporary practice. They are associated with a high rate of persistent anterior instability and early degenerative change. Combined ACL reconstruction and lateral extra-articular tenodeses results in a significant reduction in the prevalence of residual pivot shift, but the majority of the studies do not demonstrate any significant difference with respect to patient-reported outcome measures and return to sport. Although several authors report a trend towards decreased graft rupture rates, significant differences were not demonstrated in most studies. In a single clinical study, combined anatomic ACL and anterolateral ligament reconstruction was reported to be associated with a three-fold reduction in graft rupture rates and improved return to sport compared to isolated ACL graft choices. Conclusions: Historically performed, combined ACL reconstruction and lateral extra-articular tenodeses are associated with improved knee kinematics. Although a trend towards decreased graft rupture rates is reported by several authors, the majority did not demonstrate a significant difference, likely as a result of small and underpowered studies using postoperative immobilisation and delayed rehabilitation protocols. More recently, combined ACLR and ALL reconstruction has been shown to be associated with significant improvements in graft failure and return to sport rates when compared to isolated ACLR. However, these results are from a single clinical series with only medium-term follow-up. Level of evidence: IV

Cholesteryl hemiazelate causes lysosome dysfunction impacting vascular smooth muscle cell homeostasis

In atherosclerotic lesions, vascular smooth muscle cells (VSMCs) represent half of the foam cell population, which is characterized by an aberrant accumulation of undigested lipids within lysosomes. Loss of lysosome function impacts VSMC homeostasis and disease progression. Understanding the molecular mechanisms underlying lysosome dysfunction in these cells is, therefore, crucial. We identify cholesteryl hemiazelate (ChA), a stable oxidation end-product of cholesteryl-polyunsaturated fatty acid esters, as an inducer of lysosome malfunction in VSMCs. ChA-treated VSMCs acquire a foam-cell-like phenotype, characterized by enlarged lysosomes full of ChA and neutral lipids. The lysosomes are perinuclear and exhibit degradative capacity and cargo exit defects. Lysosome luminal pH is also altered. Even though the transcriptional response machinery and autophagy are not activated by ChA, the addition of recombinant lysosomal acid lipase (LAL) is able to rescue lysosome dysfunction. ChA significantly affects VSMC proliferation and migration, impacting atherosclerosis. In summary, this work shows that ChA is sufficient to induce lysosomal dysfunction in VSMCs, that, in ChA-treated VSMCs, neither lysosome biogenesis nor autophagy are triggered, and, finally, that recombinant LAL can be a therapeutic approach for lysosomal dysfunction

The RING-CH ligase K5 antagonizes restriction of KSHV and HIV-1 particle release by mediating ubiquitin-dependent endosomal degradation of tetherin

Tetherin (CD317/BST2) is an interferon-induced membrane protein that inhibits the release of diverse enveloped viral particles. Several mammalian viruses have evolved countermeasures that inactivate tetherin, with the prototype being the HIV-1 Vpu protein. Here we show that the human herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) is sensitive to tetherin restriction and its activity is counteracted by the KSHV encoded RING-CH E3 ubiquitin ligase K5. Tetherin expression in KSHV-infected cells inhibits viral particle release, as does depletion of K5 protein using RNA interference. K5 induces a species-specific downregulation of human tetherin from the cell surface followed by its endosomal degradation. We show that K5 targets a single lysine (K18) in the cytoplasmic tail of tetherin for ubiquitination, leading to relocalization of tetherin to CD63-positive endosomal compartments. Tetherin degradation is dependent on ESCRT-mediated endosomal sorting, but does not require a tyrosine-based sorting signal in the tetherin cytoplasmic tail. Importantly, we also show that the ability of K5 to substitute for Vpu in HIV-1 release is entirely dependent on K18 and the RING-CH domain of K5. By contrast, while Vpu induces ubiquitination of tetherin cytoplasmic tail lysine residues, mutation of these positions has no effect on its antagonism of tetherin function, and residual tetherin is associated with the trans-Golgi network (TGN) in Vpu-expressing cells. Taken together our results demonstrate that K5 is a mechanistically distinct viral countermeasure to tetherin-mediated restriction, and that herpesvirus particle release is sensitive to this mode of antiviral inhibition

No Benefit from Chronic Lithium Dosing in a Sibling-Matched, Gender Balanced, Investigator-Blinded Trial Using a Standard Mouse Model of Familial ALS

Background: In any animal model of human disease a positive control therapy that demonstrates efficacy in both the animal model and the human disease can validate the application of that animal model to the discovery of new therapeutics. Such a therapy has recently been reported by Fornai et al. using chronic lithium carbonate treatment and showing therapeutic efficacy in both the high-copy SOD1G93A mouse model of familial amyotrophic lateral sclerosis (ALS), and in human ALS patients. Methodology/Principal Findings: Seeking to verify this positive control therapy, we tested chronic lithium dosing in a sibling-matched, gender balanced, investigator-blinded trial using the high-copy (average 23 copies) SOD1G93A mouse (n = 27–28/group). Lithium-treated mice received single daily 36.9 mg/kg i.p. injections from 50 days of age through death. This dose delivered 1 mEq/kg (6.94 mg/kg/day lithium ions). Neurological disease severity score and body weight were determined daily during the dosing period. Age at onset of definitive disease and survival duration were recorded. Summary measures from individual body weight changes and neurological score progression, age at disease onset, and age at death were compared using Kaplan-Meier and Cox proportional hazards analysis. Our study did not show lithium efficacy by any measure. Conclusions/Significance: Rigorous survival study design that includes sibling matching, gender balancing, investigato

Acidente com material perfurocortante entre profissionais de enfermagem de um hospital universitário

Os riscos ocupacionais a que os profissionais da equipe de enfermagem estão sujeitos no desempenho de suasfunções são consideráveis. Assim estabeleceu-se como objetivo deste estudo analisar os acidentes perfurocortantesno período de 2002 a 2006, envolvendo a equipe de enfermagem de um hospital universitário, para compreender ocontexto em que ocorrem. A utilização destas informações pode ser ferramenta de prevenção. Estudo descritivo,retrospectivo quantitativo e qualitativo. Na análise quantitativa foi utilizada estatística descritiva e na qualitativao discurso do sujeito coletivo. Por meio das fichas de notificação do Núcleo de Vigilância Epidemiológica doHospital, foi possível identificar acidentes do gênero no período pesquisado. Entrevistas foram direcionadas àsvítimas de acidentes que tiveram como paciente-fonte portador de Síndrome da Imunodeficiência Adquirida/Vírus da Imunodeficiência Humana, hepatite B e C. Os achados demonstraram que ainda persiste um grau significativodo desconhecimento ou banalização dos acidentes entre profissionais da saúde

A synthesis of bacterial and archaeal phenotypic trait data.

A synthesis of phenotypic and quantitative genomic traits is provided for bacteria and archaea, in the form of a scripted, reproducible workflow that standardizes and merges 26 sources. The resulting unified dataset covers 14 phenotypic traits, 5 quantitative genomic traits, and 4 environmental characteristics for approximately 170,000 strain-level and 15,000 species-aggregated records. It spans all habitats including soils, marine and fresh waters and sediments, host-associated and thermal. Trait data can find use in clarifying major dimensions of ecological strategy variation across species. They can also be used in conjunction with species and abundance sampling to characterize trait mixtures in communities and responses of traits along environmental gradients

Temperature Effects on Gametophyte Life-History Traits and Geographic Distribution of Two Cryptic Kelp Species

A major determinant of the geographic distribution of a species is expected to be its physiological response to changing abiotic variables over its range. The range of a species often corresponds to the geographic extent of temperature regimes the organism can physiologically tolerate. Many species have very distinct life history stages that may exhibit different responses to environmental factors. In this study we emphasized the critical role of the haploid microscopic stage (gametophyte) of the life cycle to explain the difference of edge distribution of two related kelp species. Lessonia nigrescens was recently identified as two cryptic species occurring in parapatry along the Chilean coast: one located north and the other south of a biogeographic boundary at latitude 29–30°S. Six life history traits from microscopic stages were identified and estimated under five treatments of temperature in eight locations distributed along the Chilean coast in order to (1) estimate the role of temperature in the present distribution of the two cryptic L. nigrescens species, (2) compare marginal populations to central populations of the two cryptic species. In addition, we created a periodic matrix model to estimate the population growth rate (λ) at the five temperature treatments. Differential tolerance to temperature was demonstrated between the two species, with the gametophytes of the Northern species being more tolerant to higher temperatures than gametophytes from the south. Second, the two species exhibited different life history strategies with a shorter haploid phase in the Northern species contrasted with considerable vegetative growth in the Southern species haploid stage. These results provide strong ecological evidence for the differentiation process of the two cryptic species and show local adaptation of the life cycle at the range limits of the distribution. Ecological and evolutionary implications of these findings are discussed