Effect of headless compression screw on construct stability for centre of rotation and angulation-based levelling osteotomy. Biomechanical testing in flexion and torsion.

OBJECTIVE: To compare the biomechanical properties of bone and implant constructs when used for the centre of rotation and angulation (CORA) based levelling osteotomy, with and without implantation of a trans-osteotomy headless compression screw tested under three-point flexural and torsional forces; thereby determining the contribution of a trans-osteotomy headless compression screw with regards to stability of the construct. METHODS: Experimental biomechanical study utilizing 12 pairs of cadaveric canine tibias. Using the CORA based levelling osteotomy (CBLO) procedure, the osteotomy was stabilized with either a standard non-locking CBLO bone plate augmented with a headless compression screw (HCS) or a CBLO bone plate alone. Tibial constructs were mechanically tested in three-point craniocaudal flexural testing or in torsion. RESULTS: In three-point flexural testing, the difference between the two constructs was not significant. In torsion, the difference in the angle of failure between constructs with a HCS (48.46°) and constructs without a HCS (81.65°) was significant (p = 0.036). Maximum torque achieved by constructs with a HCS (21.7 Nm) was greater than those without (18.7 Nm) (p = 0.056). Stiffness differences between both groups in torsion and bending were not significant. Use of a HCS did increase the stability of the CBLO construct in torsional testing, but not in flexural testing.

How Many Cultures Are Necessary to Identify Pathogens in the Management of Total Hip and Knee Arthroplasty Infections?

BACKGROUND: Identification of the infecting organism is critical to the successful management of deep prosthetic joint infections about the hip and the knee. However, the number of culture specimens and which culture specimens are best to identify these organisms is unknown. METHODS: We evaluated 113 consecutive patients with infected total hip and total knee arthroplasties and correlated the type of culture specimen and number of specimens taken during surgery to the likelihood of a positive culture result. From these data, we subsequently developed a model to maximize culture yield at the time of surgical intervention. After exclusions, 74 patients meeting the Musculoskeletal Infection Society criteria were left for final analysis. RESULTS: From this cohort, 63 of 74 patients had a positive culture result (85%). The odds of a fluid culture result being positive was 35 of 47 (0.75), whereas the likelihood of tissue cultures yielding a positive result was 164 of 245 (0.67; P = .313). The sample designated "best culture" specimen was the only culture with a positive result in 1 of 48 cases in which a best culture was identified. The optimal number of cultures needed to yield a positive test result was 4 (specificity = 0.61 and sensitivity = 0.63). Increasing the number of samples increases sensitivity but reduces specificity. CONCLUSION: A minimum of 4 tissue cultures from representative areas is necessary to maximize the chance of identifying the infecting organism during management of the infected total hip and total knee arthroplasties. The designation of the best culture specimen for additional testing is arbitrary and may not be clinically efficacious.

Evaluation of Commonly Used Products for Disinfecting Clipper Blades in Veterinary Practices: A Pilot Study.

Nosocomial infections are a concern of growing interest in veterinary medicine. Clipper blades have been confirmed as fomites for numerous potential pathogens and, as such, may be associated with wound and surgical site infections. The goal of this study was to evaluate the disinfectant capabilities of several commonly used clipper blade cleaning products. Seventy sterile clipper blades were inoculated with strains of Pseudomonas aeruginosa , Escherichia coli , and Staphylococcus aureus . Blades were then subjected to one of seven treatment groups for disinfecting. Quantitative cultures of remaining bacteria were performed. All blades in the control group showed large amounts of bacterial recovery. Culture results showed no recovery in blades soaked in alcohol or chlorhexidine or those sprayed with an ethanol/o-phenylphenol product, while moderate recovery was seen with all other treatments. These results show that persistent contamination of clipper blades can occur with the use of several commonly used disinfectant products. Further research is necessary to evaluate fungicidal capabilities as well as the effect of disinfection on clipper blade maintenance.

Metal-on-metal total hip arthroplasty: is there still a role in 2016?

The use of metal-on-metal (MoM) bearings in total hip arthroplasty (THA) was popularized due to its enhanced wear profile and the ability to use large femoral heads to reduce post-operative instability. However, enthusiasm for the bearing declined following serious complications encountered at the primary articulation. This review discusses the development of MoM and the subsequent unexpected downstream challenges, most notably elevated serum metal ion levels, aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL), pseudotumor formation, and subsequent soft tissue and bone destruction. Both patient centered risk factors as well as component design led to high early failure rates resulting in product recalls and an overall decline in the use of MoM. In 2016, there is not a role for large-head MoM bearing in THA. Alternatively, the bearing has shown promise in hip resurfacing procedures for carefully selected patients.

Dissecting the genetics of chronic mucus hypersecretion in smokers with and without COPD.

Smoking is a notorious risk factor for chronic mucus hypersecretion (CMH). CMH frequently occurs in chronic obstructive pulmonary disease (COPD). The question arises whether the same single-nucleotide polymorphisms (SNPs) are related to CMH in smokers with and without COPD. We performed two genome-wide association studies of CMH under an additive genetic model in male heavy smokers (≥20 pack-years) with COPD (n=849, 39.9% CMH) and without COPD (n=1348, 25.4% CMH), followed by replication and meta-analysis in comparable populations, and assessment of the functional relevance of significantly associated SNPs. Genome-wide association analysis of CMH in COPD and non-COPD subjects yielded no genome-wide significance after replication. In COPD, our top SNP (rs10461985, p=5.43×10(-5)) was located in the GDNF-AS1 gene that is functionally associated with the GDNF gene. Expression of GDNF in bronchial biopsies of COPD patients was significantly associated with CMH (p=0.007). In non-COPD subjects, four SNPs had a p-value <10(-5) in the meta-analysis, including a SNP (rs4863687) in the MAML3 gene, the T-allele showing modest association with CMH (p=7.57×10(-6), OR 1.48) and with significantly increased MAML3 expression in lung tissue (p=2.59×10(-12)). Our data suggest the potential for differential genetic backgrounds of CMH in individuals with and without COPD.

The effect of viscosity on cement penetration in total knee arthroplasty, an application of the squeeze film effect.

The authors present a prospective randomized blinded cadaver study designed to evaluate the engineering concept of a squeeze film effect and the effect of cement viscosity on cement penetration in total knee arthroplasty. This was done in response to an earlier clinical study demonstrating inferior tibial cement penetration using early, often liquid, phase cement. Paired cadaver tibias were implanted with the tibial component using either liquid or dough phase cement. Based on an AP fluoroscopic image, the dough phase cement penetrated deeper than liquid in all four zones. This was statistically significant in zones 1, 2 and 3. Deeper cement penetration has been shown to provide a stronger cement-bone interphase. As a result dough phase cement is recommended to obtain optimal cement penetration.

Scientific collaboration networks using biomedical text.

The combination of scientific knowledge and experience is the key success for biomedical research. This chapter demonstrates some of the strategies used to help in identifying key opinion leaders with the expertise you need, thus enabling an effort to increase collaborative biomedical research.

Stress injuries of the ischiopubic synchondrosis.

A 12-year-old competitive runner with enlarged symptomatic right-sided ischiopubic synchondrosis (IPS) is presented, highlighting the pertinent clinical and radiographic findings as well as the basic principles of conservative management and appropriate follow-up surveillance. Magnetic resonance imaging (MRI) studies revealed remarkable asymmetric enlargement of the right inferior pubic ramus with axial fat-suppressed proton density MRI demonstrating an irregular low signal intensity intramedullary line within the right ischiopubic junction. In symptomatic patients, a thorough review of radiologic imaging is warranted in order to confirm the diagnosis of IPS and investigate potential associated injuries. The pertinent radiographic findings vital to making an accurate diagnosis and treatment plan are reviewed.

Symptomatic ganglion cyst of the popliteus tendon treated with ultrasound-guided aspiration and steroid injection: a case report.

Ultrasound-guided aspiration of symptomatic ganglion cysts about peripheral joints is a valuable and routinely performed therapeutic modality. Intratendinous and peritendinous ganglia involving the popliteus tendon are rare, with only 3 cases previously reported. These ganglion cysts are usually small and can easily be mistaken for normal anatomy on magnetic resonance imaging (ie, small periarticular vessel or fluid within the popliteus tendon sheath), leading to delayed patient diagnosis and appropriate treatment.

Regulation of synaptic Pumilio function by an aggregation-prone domain.

We identified Pumilio (Pum), a Drosophila translational repressor, in a computational search for metazoan proteins whose activities might be regulated by assembly into ordered aggregates. The search algorithm was based on evolutionary sequence conservation patterns observed for yeast prion proteins, which contain aggregation-prone glutamine/asparagine (Q/N)-rich domains attached to functional domains of normal amino acid composition. We examined aggregation of Pum and its nematode ortholog PUF-9 by expression in yeast. A domain of Pum containing the Q/N-rich sequence, denoted as NQ1, the entire Pum N terminus, and the complete PUF-9 protein localize to macroscopic aggregates (foci) in yeast. NQ1 and PUF-9 can generate the yeast Pin+ trait, which is transmitted by a heritable aggregate. NQ1 also assembles into amyloid fibrils in vitro. In Drosophila, Pum regulates postsynaptic translation at neuromuscular junctions (NMJs). To assess whether NQ1 affects synaptic Pum activity in vivo, we expressed it in muscles. We found that it negatively regulates endogenous Pum, producing gene dosage-dependent pum loss-of-function NMJ phenotypes. NQ1 coexpression also suppresses lethality and NMJ phenotypes caused by overexpression of Pum in muscles. The Q/N block of NQ1 is required for these phenotypic effects. Negative regulation of Pum by NQ1 might be explained by formation of inactive aggregates, but we have been unable to demonstrate that NQ1 aggregates in Drosophila. NQ1 could also regulate Pum by a "dominant-negative" effect, in which it would block Q/N-mediated interactions of Pum with itself or with cofactors required for translational repression.

Thermal conductivity of multi-walled carbon nanotube sheets: radiation losses and quenching of phonon modes.

The extremely high thermal conductivity of individual carbon nanotubes, predicted theoretically and observed experimentally, has not yet been achieved for large nanotube assemblies. Resistances at tube-tube interconnections and tube-electrode interfaces have been considered the main obstacles for effective electronic and heat transport. Here we show that, even for infinitely long and perfect nanotubes with well-designed tube-electrode interfaces, excessive radial heat radiation from nanotube surfaces and quenching of phonon modes in large bundles are additional processes that substantially reduce thermal transport along nanotubes. Equivalent circuit simulations and an experimental self-heating 3omega technique were used to determine the peculiarities of anisotropic heat flow and thermal conductivity of single MWNTs, bundled MWNTs and aligned, free-standing MWNT sheets. The thermal conductivity of individual MWNTs grown by chemical vapor deposition and normalized to the density of graphite is much lower (kappa(MWNT) = 600 +/- 100 W m(-1) K(-1)) than theoretically predicted. Coupling within MWNT bundles decreases this thermal conductivity to 150 W m(-1) K(-1). Further decrease of the effective thermal conductivity in MWNT sheets to 50 W m(-1) K(-1) comes from tube-tube interconnections and sheet imperfections like dangling fiber ends, loops and misalignment of nanotubes. Optimal structures for enhancing thermal conductivity are discussed.

Histologic comparison of canine skin biopsies collected using monopolar electrosurgery, CO2 laser, radiowave radiosurgery, skin biopsy punch, and scalpel.

OBJECTIVE: To compare the histologic appearance of canine skin biopsies collected by use of a scalpel, skin biopsy punch, monopolar electrosurgery, CO2 laser, and radio wave radiosurgery in fully rectified wave form (RWRS). STUDY DESIGN: Experimental, randomized design. ANIMALS: Healthy adult grayhounds (n=4). METHODS: Skin biopsies were collected using 5 techniques. Cut margins of biopsy specimens and adjacent peripheral skin were evaluated using light microscopy to compare penetration of the dermis by tissue carbonization (char). RESULTS: No char occurred in skin specimens collected by biopsy punch and scalpel. Char penetration occurred in all specimens collected by electrosurgery, CO2 laser, and RWRS. Mean char penetration in skin biopsies collected by RWRS (0.158 mm) was significantly less than for monopolar electrosurgery (0.223 mm) and CO2 laser (0.215 mm). Mean char penetration in adjacent peripheral skin surrounding biopsies collected by RWRS (0.171 mm) was significantly less than monopolar electrosurgery (0.255 mm) but not less than CO2 laser (0.215 mm, P<.07). CONCLUSIONS: RWRS (blended waves in cut-coagulate mode) caused less lateral thermal damage to canine skin biopsies than monopolar electrosurgery and CO2 laser and less lateral thermal injury to peripheral skin than monopolar electrosurgery. CLINICAL RELEVANCE: Excision of canine skin biopsies with heat-generating devices may not allow reliable histologic interpretation, particularly when assessing margins of small biopsy specimens. RWRS may be less traumatic to canine skin than monopolar electrosurgery and CO2 laser when used to make incisions.

Comparison of normograde and retrograde intramedullary pinning of feline tibias.

This study evaluated the effects of normograde and retrograde intramedullary pinning of mid-diaphyseal fractures of the feline tibia on the anatomical structures of the stifle joint. Using the paired pelvic limbs from five mature feline cadavers, a transverse, mid-diaphyseal osteotomy was performed, and each tibia was pinned in a normograde or retrograde fashion. The stifle joints were examined to determine the pin exit site and measure the distance from the exit site to pertinent anatomical structures of the stifle joint. Neither normograde nor retrograde intramedullary pinning resulted in damage to the cruciate ligaments, menisci, intermeniscal ligament, femoral condyles, or joint capsule. The patellar tendon was penetrated in all five tibias during retrograde pin insertion.

Interaction between a G-patch protein and a spliceosomal DEXD/H-box ATPase that is critical for splicing.

Prp2 is an RNA-dependent ATPase that activates the spliceosome before the first transesterification reaction of pre-mRNA splicing. Prp2 has extensive homology throughout the helicase domain characteristic of DEXD/H-box helicases and a conserved carboxyl-terminal domain also found in the spliceosomal helicases Prp16, Prp22, and Prp43. Despite the extensive homology shared by these helicases, each has a distinct, sequential role in splicing; thus, uncovering the determinants of specificity becomes crucial to the understanding of Prp2 and the other DEAH-splicing helicases. Mutations in an 11-mer near the C-terminal end of Prp2 eliminate its spliceosome binding and splicing activity. Here we show that a helicase-associated protein interacts with this domain and that this interaction contributes to the splicing process. First, a genome-wide yeast two-hybrid screen using Prp2 as bait identified Spp2, which contained a motif with glycine residues found in a number of RNA binding proteins. SPP2 was originally isolated as a genetic suppressor of a prp2 mutant. In a reciprocal screen, Spp2 specifically pulled out the C-terminal half of Prp2. Mutations in the Prp2 C-terminal 11-mer that disrupted function or spliceosome binding also disrupted Spp2 interaction. A screen of randomly mutagenized SPP2 clones identified an Spp2 protein with a mutation in the G patch that could restore interaction with Prp2 and enhanced splicing in a prp2 mutant strain. The study identifies a potential mechanism for Prp2 specificity mediated through a unique interaction with Spp2 and elucidates a role for a helicase-associated protein in the binding of a DEXD/H-box protein to the spliceosome.

Role of the tendons of the biceps brachii and infraspinatus muscles and the medial glenohumeral ligament in the maintenance of passive shoulder joint stability in dogs.

OBJECTIVE: To objectively evaluate the effect of transecting the tendon of the biceps brachii muscle (BBT), tendon of the infraspinatus muscle (IFS), or medial glenohumeral ligament (MGHL) on shoulder joint stability in canine cadavers. SAMPLE POPULATION: 81 forelimbs from mature dogs. PROCEDURE: Cadaver forelimbs were placed in a testing frame and axially preloaded with 4 kg of weight. Shoulder joint stability was tested in neutral joint position, flexion, and extension before and after transection of the BBT (n = 37), IFS (37), or MGHL (7). Humeral translation relative to the glenoid was induced by applying a 3-kg load in each of 3 directions (cranial, lateral, and medial) and quantitatively measured by use of an electromagnetic motion tracking system. Peak translational data were compared in each joint position before and after transection of the BBT, IFS, or MGHL. RESULTS: When tested in neutral position, the cranial, lateral, and medial translation of the humerus was significantly increased after BBT transection. In the flexed position, translation of the humerus in the cranial and lateral directions was significantly increased after BBT transection. In the extended position, the medial translation of the humerus was significantly increased after BBT transection. Complete medial luxation of all humeral heads occurred following transection of the MGHL. CONCLUSIONS AND CLINICAL RELEVANCE: The BBT contributes to passive shoulder joint stability in dogs, particularly in the neutral and flexed positions. It also provides medial stability during shoulder joint extension. Complete luxation of the joint occurs when the MGHL is transected.

Definition of a spliceosome interaction domain in yeast Prp2 ATPase.

The Saccharomyces cerevisiae splicing factor Prp2 is an RNA-dependent ATPase required before the first transesterification reaction in pre-mRNA splicing. Prp2 binds to the spliceosome in the absence of ATP and is released following ATP hydrolysis. It contains three domains: a unique N-terminal domain, a helicase domain that is highly conserved in the DExD/H protein family, and a C-terminal domain that is conserved in spliceosomal DEAH proteins Prp2, Prp16, Prp22, and Prp43. We examined the role of each domain of Prp2 by deletion mutagenesis. Whereas deletions of either the helicase or C-terminal domain are lethal, deletions in the N-terminal domain have no detectable effect on Prp2 activity. Overexpression of the C-terminal domain of Prp2 exacerbates the temperature-sensitive phenotype of a prp2(Ts) strain, suggesting that the C-domain interferes with the activity of the Prp2(Ts) protein. A genetic approach was then taken to study interactions between Prp2 and the spliceosome. Previously, we isolated dominant negative mutants in the helicase domain of Prp2 that inhibit the activity of wild-type Prp2 when the mutant protein is overexpressed. We mutagenized one prp2 release mutant gene and screened for loss of dominant negative function. Several weak binding mutants were isolated and mapped to the C terminus of Prp2, further indicating the importance of the C terminus in spliceosome binding. This study is the first to indicate that amino acid substitutions outside the helicase domain can abolish spliceosome contact and splicing activity of a spliceosomal DEAH protein.

DExD/H-box proteins and their partners: helping RNA helicases unwind.

Members of the DExD/H-box family of RNA helicases are involved in many processes and complexes within the cell. While individual DExD/H helicase family members have been studied extensively, the mechanisms through which helicases affect multiprotein complexes are just beginning to be investigated. Because RNA helicases are both highly conserved and numerous in the cell, study of RNA helicase recruitment and modulation by cofactors is necessary for understanding the mechanisms of helicase action in vivo. This review will focus on cofactor-mediated regulation of helicase target specificity and activity.