The proposed function of Cdc4p, an essential contractile ring protein in Schizosaccharomyces pombe, is that of a myosin essential light chain. However, five conditionally lethal cdc4 alleles exhibit complementation in diploids. Such interallelic complementation is not readily explained if the sole function of Cdc4p is that of a myosin essential light chain. Complementation of cdc4 alleles could occur only if different mutant forms can assemble into an active oligomeric complex or if Cdc4p has more than one essential function. To search for other proteins that may interact with Cdc4p, we performed a two-hybrid screen and identified two such candidates: one similar to Saccharomyces cerevisiae Vps27p and the other a putative phosphatidylinositol (PI) 4-kinase. Binding of Cdc4p to the latter and to myosin heavy chain (Myo2p) was confirmed by immunosorbent assays. Deletion studies demonstrated interaction between the Cdc4p C-terminal domain and the PI 4-kinase C-terminal domain. Furthermore, interaction was abolished by the Cdc4p C-terminal domain point mutation, Gly 107 to Ser. This allele also causes failure of cytokinesis. Ectopic expression of the PI 4-kinase C-terminal domain caused cytokinesis defects that were most extreme in cells carrying the G107S allele. We suggest that Cdc4p plays multiple roles in cytokinesis and that interaction with a PI 4-kinase may be important for contractile ring assembly and/or function.

Smoking many cigarettes per day (CPD) and short interval to first cigarette (TTF) after waking are two of the most heritable smoking phenotypes and comprise the Heavy Smoking Index (HSI). These phenotypes are often used as proxies for nicotine dependence (ND) and are associated with smoking cessation outcomes. Case-control and genome-wide association studies have reported links between single nucleotide polymorphisms (SNPs) in the alpha-5 and -3 nicotinic receptor subunit (CHRNA5 and CHRNA3) genes and CPD but few have examined TTF or cessation outcomes. In this study we longitudinally assessed 1301 European-American smokers at four time-points from 1988 to 2005. One CHRNA5 (rs16969968) and two CHRNA3 (rs1051703, rs6495308) SNPs were examined for their ability to predict smokers who ‘ever’ reported ND based on three phenotypic classifications: 1) 25+ CPD, 2) TTF < 10 minutes, and 3) HSI ≥ 4. In a subsample of 1157 quit attempters, we also examined each SNP’s ability to predict ‘ever’ quitting for a period of >6 months. Demographically adjusted logistic regressions showed significant allelic and genotypic associations between all three SNPs and CPD but not TTF, HSI, or smoking cessation. Carriers of both the rs16969968-AA and rs6495308-TT genotypes had approximately two-fold greater odds for ND defined using CPD or TTF. Results suggest nicotinic receptor variants are associated with greater odds of ND according to CPD and to a lesser extent TTF. Research examining the effect of nicotinic receptor genetic variation on ND phenotypes beyond CPD is warranted.

Introduction: The purpose of this study was to perform a meta-analysis for long-term patient-reported outcome (PRO) measures in Matrix-induced Autologous Chondrocyte Implantation (MACI) patients using the Knee Injury and Osteoarthritis Outcome Score (KOOS) model. Materials and Methods: A literature search under the PubMed/Medline and Embase databases was conducted. Statistical significance was determined between the mean pre- and postoperative scores at each time point (1-, 2-, and 5-years). Cohen’s d analysis was used to measure the effect size (ES) in each group when compared to preoperative measurements to determine clinical responsiveness. Results: KOOS subscales at all long-term postoperative follow ups measured in this study showed significant (p-value <0.001) improvement when compared to preoperative scores. Furthermore, apart from KOOS sports and recreation (KOOS-SR) at 1-year postoperative follow up that showed a medium ES (ES, 0.761), all other KOOS subscales at long-term follow up periods showed a large (>0.8) ES on mean preoperative KOOS. Conclusion: Review of the literature demonstrate an absence of large meta-analyses for long-term PRO measures with the MACI procedure. It was found that all subscales were largely responsive when evaluated at >2 years after surgery. Based on these results, MACI is an effective treatment option for patients with symptomatic, full-thickness cartilage defects about the knee.

Introduction. Acute compartment syndrome (ACS) occurs secondary to increasing pressure within a fascial compartment that exceeds perfusion pressure. This can be caused by spontaneous hematomas, which can be secondary to prolonged anticoagulation therapy. Eliquis® has not been associated with ACS of the thigh in any of the currently published literature. Identifying ACS early is important because it can reduce the risk of permanent structural damage, limb amputations, and mortality rates. Case Report. A 43-year-old male with past medical history of unprovoked Deep Vein Thrombosis (DVT) eight months prior to presentation on Eliquis® presented to the emergency department for significant right thigh pain after riding a roller coaster. There was increased tone/firmness of the anterior compartment and tenderness on palpation of the proximal two-thirds of the anterior thigh. Imaging, clinical findings, and Stryker needle measurements confirmed ACS secondary to hematoma, which required fasciotomy and evacuation of the hematoma. The patient was temporarily switched to aspirin for DVT prophylaxis postoperatively to prevent new hematoma formation. Six weeks later, the patient arrived at the ED with a DVT that was treated with Eliquis®. Eight months later, the same patient presented with acute right thigh pain that started while lying in bed. A diagnosis of recurrent ACS in the right anterior thigh was made, requiring a fasciotomy. Surgery was successful without any complications. Discussion. Eliquis® is associated with an increased risk of hematoma formation, which can lead to ACS. This is a rare adverse effect that providers should be aware of because it requires early management to prevent ACS-associated complications. This is significant because no currently published literature has identified an association of Eliquis® with ACS in the thigh. In cases of atraumatic ACS, we were unable to find any protocols advocating for or against the use of DVT prophylaxis postfasciotomy in the literature.

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Clofarabine (CLO), a purine nucleoside analog with promising efficacy in acute myeloid leukemia (AML), inhibits the ribonucleotide reductase, p53R2. We have shown that p53R2 mRNA is up-regulated by decitabine (DEC), another drug with promising activity in AML. We developed a pharmacodynamic model to characterize the interaction between CLO and DEC on an AML cell line and down-regulated p53R2 protein to understand its role. These results confirm a role for p53R2 in both CLO and DEC mechanism of action, demonstrate synergism between these two drugs in this AML model and support the use of this combination in a future clinical trial.

Distal radius buckle fractures (DRBFs) are the most common pediatric fractures and resemble the rounded portion of a Greek pillar or torus. They result from compressive forces applied to a child’s highly plastic radius. DRBFs lack cortical and physeal disruption, which makes them relatively stable. In this review, we discuss angled DRBFs, a hypothesized subset of buckle fractures that results from an off-center compressive force. Some authors refute the existence of angled DRBFs, instead proposing new criteria for DRBF classification: measuring more than 1 cm away from the physis with two to three inflection points. Without universal diagnostic criteria, misdiagnosis is common, and the utilization of flexible treatment modalities is infrequent. Rigid immobilization with short-arm casting continues to be the mainstay of treatment in clinical practice. Yet, new protocols implementing removable elastic bandages have had comparable results to casting, including reduced healthcare expenditure, less stiffness, and improved convenience and patient tolerability. Despite the discrepancies in categorizing DRBFs, complication rates remain low, and diagnostic confusion insignificantly affects clinical outcomes. Angled DRBFs have been theorized to have intraphyseal extension, making them unstable Salter-Harris fractures. Radiographic evidence supporting or denying this claim is limited. Further research is essential to determine the stability of the angled DRBF subtype and whether they should continue to be defined and managed as buckle fractures.

It is estimated that there are over 6.2 million American‐bred rabbits owned as domesticated pets in the United States. However, variation in the vasculature of domesticated rabbits is not well studied and could therefore lead to complications during surgeries. This study examined the variation in the origin of the vertebral artery. In rabbits, the vertebral artery (right and left) typically branch off of the subclavian artery (right and left respectively), travels superiorly through the neck with spinal processes branching off of it to supply the spinal cord. The bilateral vertebral arteries then continue to travel cranially, through the foramen magnum. Here, they join to become the basilar artery, which aids in supplying the brain with blood. Through dissection of commercially available preserved rabbits, a new variation was found in the left vertebral artery: an anastomosis between the left subclavian artery and the left common carotid artery. No variation was found in the right vertebral artery. These results will potentially help veterinarian surgeons perform cardiovascular and cerebral surgeries with less complications, thus increasing survival rates.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.