The Direct Anterior Approach: A Comprehensive Guide for the Learner and Educator

Total hip arthroplasty is one of the most widely performed procedures demonstrating excellent clinical outcomes and implant longevity. Enhanced imaging modalities, advancements in material science, and improvements in surgical technique have contributed to the global success of this procedure. One such technique has gained significant attention over the past decade – the direct anterior approach (DAA). First described by Carl Hueter in 1881, the DAA is now more commonly credited to Smith-Peterson. This technique demonstrates rapid recovery, reduced hospital length of stay, and enhanced stability. Despite these advantages, there is a well reported learning curve for surgeons, particularly for those who trained using an alternative surgical approach. In this chapter we explore a methodological approach to mitigate and decrease the learning curve; allowing for a safe and reproducible guide to teach surgeons how to transition to the DAA

Reporters for the analysis of N-glycosylation in \u3ci\u3eCandida albicans\u3c/i\u3e

A large proportion of Candida albicans cell surface proteins are decorated post-translationally by glycosylation. Indeed N-glycosylation is critical for cell wall biogenesis in this major fungal pathogen and for its interactions with host cells. A detailed understanding of N-glycosylation will yield deeper insights into host-pathogen interactions. However, the analysis of N-glycosylation is extremely challenging because of the complexity and heterogeneity of these structures. Therefore, in an attempt to reduce this complexity and facilitate the analysis of N-glycosylation, we have developed new synthetic C. albicans reporters that carry a single N-linked glycosylation site derived from Saccharomyces cerevisiae Suc2. These glycosylation reporters, which carry C. albicans Hex1 or Sap2 signal sequences plus carboxy-terminal FLAG3 and His6 tags, were expressed in C. albicans from the ACT1 promoter. The reporter proteins were successfully secreted and hyperglycosylated by C. albicans cells, and their outer chain glycosylation was dependent on Och1 and Pmr1, which are required for N-mannan synthesis, but not on Mnt1 and Mnt2 which are only required for O-mannosylation. These reporters are useful tools for the experimental dissection of N-glycosylation and other related processes in C. albicans, such as secretion

The Economic Burden of Non-fatal Musculoskeletal Injuries in Northeastern Tanzania

Background: Although musculoskeletal injuries have increased in sub-Saharan Africa, data on the economic burden of non-fatal musculoskeletal injuries in this region are scarce. Objective: Socioeconomic costs of orthopedic injuries were estimated by examining both the direct hospital cost of orthopedic care as well as indirect costs of orthopedic trauma using disability days and loss of work as proxies. Methods: This study surveyed 200 patients seen in the outpatient orthopedic ward of the Kilimanjaro Christian Medical Center, a tertiary hospital in Northeastern Tanzania, during the month of July 2016. Findings: Of the patients surveyed, 88.8% earn a monthly income of less than $250 and the majority of patients (73.7%) reported that the healthcare costs of their musculoskeletal injuries were a catastrophic burden to them and their family with 75.0% of patients reporting their medical costs exceeded their monthly income. The majority (75.3%) of patients lost more than 30 days of activities of daily living due to their injury, with a median (IQR) functional day loss of 90 (30). Post-injury disability led to 40.6% of patients losing their job and 86.7% of disabled patients reported a wage decrease post-injury. There were significant associations between disability and post-injury unemployment (p < .0001) as well as lower post-injury wages (p = .022). Conclusion: This exploratory study demonstrates that in this region of the world, access to definitive treatment post-musculoskeletal injury is limited and patients often suffer prolonged disabilities resulting in decreased employment and income

Reporters for the analysis of N-glycosylation in Candida albicans

Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.Peer reviewedPublisher PD

The duration of embryo culture after mouse IVF differentially affects cardiovascular and metabolic health in male offspring

Study question: Do the long-term health outcomes following IVF differ depending upon the duration of embryo culture before transfer?Summary answer: Using a mouse model, we demonstrate that in male but not female offspring, adverse cardiovascular (CV) health was more likely with prolonged culture to the blastocyst stage, but metabolic dysfunction was more likely if embryo transfer (ET) occurred at the early cleavage stage.What is known already: ART associate with increased risk of adverse CV and metabolic health in offspring, and these findings have been confirmed in animal models in the absence of parental infertility issues. It is unclear which specific ART treatments may cause these risks. There is increasing use of blastocyst, versus cleavage-stage, transfer in clinical ART which does not appear to impair perinatal health of children born, but the longer-term health implications are unknown.Study design, size, duration: Five mouse groups were generated comprising: (i) natural mating (NM)-naturally mated, non-superovulated and undisturbed gestation; (ii) IV-ET-2Cell-in-vivo derived two-cell embryos collected from superovulated mothers, with immediate ET to recipients; (iii) IVF-ET-2Cell-IVF generated embryos, from oocytes from superovulated mothers, cultured to the two-cell stage before ET to recipients; (iv) IV-ET-BL-in-vivo derived blastocysts collected from superovulated mothers, with immediate ET to recipients; (v) IVF-ET-BL-IVF generated embryos, from oocytes from superovulated mothers, cultured to the blastocyst stage before ET to recipients. Both male and female offspring were analysed for growth, CV and metabolic markers of health. There were 8-13 litters generated for each group for analyses; postnatal data were analysed by multilevel random effects regression to take account of between-mother and within-mother variation and litter size.Participants/materials, settings, methods: C57/BL6 female mice (3-4 weeks old) were used for oocyte production; CBA males for sperm with human tubal fluid medium were used for IVF. Embryos were transferred (ET) to MF1 pseudo-pregnant recipients at the two-cell stage or cultured in synthetic oviductal medium enriched with potassium medium to the blastocyst stage before ET. Control in-vivo embryos from C57BL6 × CBA matings were collected and immediately transferred at the two-cell or blastocyst stage. Postnatal assays included growth rate up to 27 weeks; systolic blood pressure (SBP) at 9, 15 and 21 weeks; lung and serum angiotensin-converting enzyme (ACE) activity at time of cull (27 weeks); glucose tolerance test (GTT; 27 weeks); basal glucose and insulin levels (27 weeks); and lipid accumulation in liver cryosections using Oil Red O imaging (27 weeks).Main results and the role of chance: Blastocysts formed by IVF developed at a slower rate and comprised fewer cells that in-vivo generated blastocysts without culture (P < 0.05). Postnatal growth rate was increased in all four experimental treatments compared with NM group (P < 0.05). SBP, serum and lung ACE and heart/body weight were higher in IVF-ET-BL versus IVF-ET-2Cell males (P < 0.05) and higher than in other treatment groups, with SBP and lung ACE positively correlated (P < 0.05). Glucose handling (GTT AUC) was poorer and basal insulin levels were higher in IVF-ET-2Cell males than in IVF-ET-BL (P < 0.05) with the glucose:insulin ratio more negatively correlated with body weight in IVF-ET-2Cell males than in other groups. Liver/body weight and liver lipid droplet diameter and density in IVF-ET-2Cell males were higher than in IVF-ET-BL males (P < 0.05). IVF groups had poorer health characteristics than their in-vivo control groups, indicating that outcomes were not caused specifically by background techniques (superovulation, ET). No consistent health effects from duration of culture were identified in female offspring.Large scale data: N/A.Limitations, reasons for caution: Results from experimental animal models cannot be extrapolated to humans. Nevertheless, they are valuable to develop conceptual models, in this case, in the absence of confounding parental infertility, in assessing the safety of ART manipulations.Wider implications of the findings: The study indicates that longer duration of embryo culture after IVF up to blastocyst before ET leads to increased dysfunction of CV health in males compared with IVF and shorter cleavage-stage ET. However, the metabolic health of male offspring was poorer after shorter versus longer culture duration. This distinction indicates that the origin of CV and metabolic health phenotypes after ART may be different. The poorer metabolic health of males after cleavage-stage ET coincides with embryonic genome activation occurring at the time of ET

UNMASC: Tumor-only variant calling with unmatched normal controls

Despite years of progress, mutation detection in cancer samples continues to require significant manual review as a final step. Expert review is particularly challenging in cases where tumors are sequenced without matched normal control DNA. Attempts have been made to call somatic point mutations without a matched normal sample by removing well-known germline variants, utilizing unmatched normal controls, and constructing decision rules to classify sequencing errors and private germline variants. With budgetary constraints related to computational and sequencing costs, finding the appropriate number of controls is a crucial step to identifying somatic variants. Our approach utilizes public databases for canonical somatic variants as well as germline variants and leverages information gathered about nearby positions in the normal controls. Drawing from our cohort of targeted capture panel sequencing of tumor and normal samples with varying tumortypes and demographics, these served as a benchmark for our tumor-only variant calling pipeline to observe the relationship between our ability to correctly classify variants against a number of unmatched normals. With our benchmarked samples, approximately ten normal controls were needed to maintain 94% sensitivity, 99% specificity and 76% positive predictive value, far outperforming comparable methods. Our approach, called UNMASC, also serves as a supplement to traditional tumor with matched normal variant calling workflows and can potentially extend to other concerns arising from analyzing next generation sequencing data

The Dome Technique for Managing Massive Anterosuperior Medial Acetabular Bone Loss in Revision Total Hip Arthroplasty: Short-Term Outcomes

PURPOSE: The dome technique is a technique used in performance of revision total hip arthroplasty (THA) involving intraoperative joining of two porous metal acetabular augments to fill a massive anterosuperior medial acetabular bone defect. While excellent outcomes were achieved using this surgical technique in a series of three cases, short-term results have not been reported. We hypothesized that excellent short-term clinical and patient reported outcomes could be achieved with use of the dome technique. MATERIALS AND METHODS: A multicenter case series was conducted for evaluation of patients who underwent revision THA using the dome technique for management of Paprosky 3B anterosuperior medial acetabular bone loss from 2013-2019 with a minimum clinical follow-up period of two years. Twelve cases in 12 patients were identified. Baseline demographics, intraoperative variables, surgical outcomes, and patient reported outcomes were acquired. RESULTS: The implant survivorship was 91% with component failure requiring re-revision in only one patient at a mean follow-up period of 36.2 months (range, 24-72 months). Three patients (25.0%) experienced complications, including re-revision for component failure, inter-prosthetic dual-mobility dissociation, and periprosthetic joint infection. Of seven patients who completed the HOOS, JR (hip disability and osteoarthritis outcome score, joint replacement) survey, five patients showed improvement. CONCLUSION: Excellent outcomes can be achieved using the dome technique for management of massive anterosuperior medial acetabular defects in revision THA with survivorship of 91% at a mean follow-up period of three years. Conduct of future studies will be required in order to evaluate mid- to long-term outcomes for this technique

Recognition and blocking of innate immunity cells by Candida albicans chitin

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