Robotic-Assisted Conversion of Unicompartmental Knee Arthroplasty to Total Knee Arthroplasty.

Background: Unicompartmental knee arthroplasty (UKA) procedures have become much more common in the United States in recent years, with >40,000 UKAs performed annually. However, it is estimated that 10% to 40% of UKAs fail and thus require conversion to total knee arthroplasty (TKA). In the field of total joint arthroplasty, robotic-assisted surgeries have demonstrated advantages such as better accuracy and precision of implant positioning and improved restoration of a neutral mechanical axis.

Early Radiographic and Clinical Outcomes of an Additive-Manufactured Acetabular Component.

Background: Additive manufacturing has recently gained popularity and is widely adopted in the orthopaedic industry. However, there is a paucity of literature on the radiographic and clinical outcomes of these relatively novel components. The aim of this study was to assess the 2-year clinical and radiographic outcomes of a specific additive-manufactured acetabular component in primary total hip arthroplasty.

Motivations and Barriers for Women Orthopaedic Surgeons Considering Arthroplasty Fellowship.

Background: Arthroplasty is one of the least gender-diverse orthopaedic subspecialties. While previous studies have looked at factors influencing fellowship choices for women, few studies have attempted to understand the decision for or against arthroplasty specifically. Working to better understand fellowship choice is a critical step in the process of increasing women recruitment.

Direct Anterior Cup-Half Cage for Revision and Complex Primary Total Hip Arthroplasty: Surgical Technique.

As surgeons' comfort with the direct anterior approach (DAA) for total hip arthroplasty continues to increase, there is a growing interest in performing complex surgeries through this approach. Acetabular bone loss and/or pelvic discontinuity in the primary or revision setting often requires specialized implants such as a cup-cage construct. We describe our surgical technique for implanting modified cup-half cages through the DAA and show 2 case examples of how this technique was utilized in the setting of complex acetabular bone loss.

Occupational Hazards to the Joint Replacement Surgeon: Radiation Exposure.

Background: Intraoperative fluoroscopy is an essential tool to assist orthopedic surgeons in accurately and safely implanting hardware. In arthroplasty cases, its use is on the rise with the increasing popularity of the direct anterior (DA) approach for THA. However, exposure of ionizing radiation poses a potential health risk to surgeons.

Talar-tarsal Stabilisation: Goals and Initial Outcomes.

Background: While surgical stabilisation of the subtalar joint (arthroeresis) in children remains controversial in the USA, it is widely practised worldwide, with reportedly good outcomes. We are presenting a series of patients who met our criteria for calcaneal lengthening, but whose parents chose the less invasive option of talo-tarsal stabilisation (TTS). The goal of this surgery was to forestall or prevent hindfoot osteotomy.

Can I Ski Doc?: Return to Skiing Following Total Joint Arthroplasty.

Background: Currently, there are little data on performance, safety, or return to downhill skiing after total joint arthroplasty (TJA). This leaves surgeons with little information for patient counseling regarding skiing.

Methods: An online survey was sent to 4360 patients who had undergone at least 1 primary TJA at a single academic center over the past 10 years (4 surgeons).

Behavioural Indicators of Intra- and Inter-Specific Competition: Sheep Co-Grazing with Guanaco in the Patagonian Steppe.

In extensive livestock production, high densities may inhibit regulation processes, maintaining high levels of intraspecific competition over time. During competition, individuals typically modify their behaviours, particularly feeding and bite rates, which can therefore be used as indicators of competition. Over eight consecutive seasons, we investigated if variation in herd density, food availability, and the presence of a potential competitor, the guanaco (), was related with behavioural changes in domestic sheep in Chilean Patagonia.

High Rates of Spacer Fracture in the Setting of Extended Trochanteric Osteotomy With a Specific Thin-Core Articulating Antibiotic Hip Spacer.

Background: Two-stage revision remains the standard of care for prosthetic joint infection after total hip arthroplasty. However, there are substantial complications associated with articulating antibiotic hip spacers. Handmade and molded spacers have been shown to have higher rates of spacer fracture than antibiotic-coated prostheses (ACPs).

Feed-forward regulation adaptively evolves via dynamics rather than topology when there is intrinsic noise.

In transcriptional regulatory networks (TRNs), a canonical 3-node feed-forward loop (FFL) is hypothesized to evolve to filter out short spurious signals. We test this adaptive hypothesis against a novel null evolutionary model. Our mutational model captures the intrinsically high prevalence of weak affinity transcription factor binding sites.

Inhibiting mitochondrial phosphate transport as an unexploited antifungal strategy.

The development of effective antifungal therapeutics remains a formidable challenge because of the close evolutionary relationship between humans and fungi. Mitochondrial function may present an exploitable vulnerability because of its differential utilization in fungi and its pivotal roles in fungal morphogenesis, virulence, and drug resistance already demonstrated by others. We now report mechanistic characterization of ML316, a thiohydantoin that kills drug-resistant Candida species at nanomolar concentrations through fungal-selective inhibition of the mitochondrial phosphate carrier Mir1.

A Fungal-Selective Cytochrome bc Inhibitor Impairs Virulence and Prevents the Evolution of Drug Resistance.

To cause disease, a microbial pathogen must adapt to the challenges of its host environment. The leading fungal pathogen Candida albicans colonizes nutrient-poor bodily niches, withstands attack from the immune system, and tolerates treatment with azole antifungals, often evolving resistance. To discover agents that block these adaptive strategies, we screened 300,000 compounds for inhibition of azole tolerance in a drug-resistant Candida isolate.

Luminidependens (LD) is an Arabidopsis protein with prion behavior.

Prion proteins provide a unique mode of biochemical memory through self-perpetuating changes in protein conformation and function. They have been studied in fungi and mammals, but not yet identified in plants. Using a computational model, we identified candidate prion domains (PrDs) in nearly 500 plant proteins.

Scalable and cost-effective NGS genotyping in the cloud.

Background: While next-generation sequencing (NGS) costs have plummeted in recent years, cost and complexity of computation remain substantial barriers to the use of NGS in routine clinical care. The clinical potential of NGS will not be realized until robust and routine whole genome sequencing data can be accurately rendered to medically actionable reports within a time window of hours and at scales of economy in the 10's of dollars.

Results: We take a step towards addressing this challenge, by using COSMOS, a cloud-enabled workflow management system, to develop GenomeKey, an NGS whole genome analysis workflow.

Cross-kingdom chemical communication drives a heritable, mutually beneficial prion-based transformation of metabolism.

In experimental science, organisms are usually studied in isolation, but in the wild, they compete and cooperate in complex communities. We report a system for cross-kingdom communication by which bacteria heritably transform yeast metabolism. An ancient biological circuit blocks yeast from using other carbon sources in the presence of glucose.

An evolutionarily conserved prion-like element converts wild fungi from metabolic specialists to generalists.

[GAR(+)] is a protein-based element of inheritance that allows yeast (Saccharomyces cerevisiae) to circumvent a hallmark of their biology: extreme metabolic specialization for glucose fermentation. When glucose is present, yeast will not use other carbon sources. [GAR(+)] allows cells to circumvent this "glucose repression.

COSMOS: Python library for massively parallel workflows.

Summary: Efficient workflows to shepherd clinically generated genomic data through the multiple stages of a next-generation sequencing pipeline are of critical importance in translational biomedical science. Here we present COSMOS, a Python library for workflow management that allows formal description of pipelines and partitioning of jobs. In addition, it includes a user interface for tracking the progress of jobs, abstraction of the queuing system and fine-grained control over the workflow.

PLAAC: a web and command-line application to identify proteins with prion-like amino acid composition.

Unlabelled: Prions are self-templating protein aggregates that stably perpetuate distinct biological states and are of keen interest to researchers in both evolutionary and biomedical science. The best understood prions are from yeast and have a prion-forming domain with strongly biased amino acid composition, most notably enriched for Q or N. PLAAC is a web application that scans protein sequences for domains with P: rion- L: ike A: mino A: cid C: omposition.

Fitness trade-offs restrict the evolution of resistance to amphotericin B.

The evolution of drug resistance in microbial pathogens provides a paradigm for investigating evolutionary dynamics with important consequences for human health. Candida albicans, the leading fungal pathogen of humans, rapidly evolves resistance to two major antifungal classes, the triazoles and echinocandins. In contrast, resistance to the third major antifungal used in the clinic, amphotericin B (AmB), remains extremely rare despite 50 years of use as monotherapy.

Yeast reveal a "druggable" Rsp5/Nedd4 network that ameliorates α-synuclein toxicity in neurons.

α-Synuclein (α-syn) is a small lipid-binding protein implicated in several neurodegenerative diseases, including Parkinson's disease, whose pathobiology is conserved from yeast to man. There are no therapies targeting these underlying cellular pathologies, or indeed those of any major neurodegenerative disease. Using unbiased phenotypic screens as an alternative to target-based approaches, we discovered an N-aryl benzimidazole (NAB) that strongly and selectively protected diverse cell types from α-syn toxicity.

Heritable remodeling of yeast multicellularity by an environmentally responsive prion.

Prion proteins undergo self-sustaining conformational conversions that heritably alter their activities. Many of these proteins operate at pivotal positions in determining how genotype is translated into phenotype. But the breadth of prion influences on biology and their evolutionary significance are just beginning to be explored.

Inhibiting GPI anchor biosynthesis in fungi stresses the endoplasmic reticulum and enhances immunogenicity.

In fungi, the anchoring of proteins to the plasma membrane via their covalent attachment to glycosylphosphatidylinositol (GPI) is essential and thus provides a valuable point of attack for the development of antifungal therapeutics. Unfortunately, studying the underlying biology of GPI-anchor synthesis is difficult, especially in medically relevant fungal pathogens because they are not genetically tractable. Compounding difficulties, many of the genes in this pathway are essential in Saccharomyces cerevisiae.

Prions are a common mechanism for phenotypic inheritance in wild yeasts.

The self-templating conformations of yeast prion proteins act as epigenetic elements of inheritance. Yeast prions might provide a mechanism for generating heritable phenotypic diversity that promotes survival in fluctuating environments and the evolution of new traits. However, this hypothesis is highly controversial.

The spontaneous appearance rate of the yeast prion [PSI+] and its implications for the evolution of the evolvability properties of the [PSI+] system.

Epigenetically inherited aggregates of the yeast prion [PSI+] cause genomewide readthrough translation that sometimes increases evolvability in certain harsh environments. The effects of natural selection on modifiers of [PSI+] appearance have been the subject of much debate. It seems likely that [PSI+] would be at least mildly deleterious in most environments, but this may be counteracted by its evolvability properties on rare occasions.