SARS-COV-2 recombinant Receptor-Binding-Domain (RBD) induces neutralizing antibodies against variant strains of SARS-CoV-2 and SARS-CoV-1.

SARS-CoV-2 is the etiological agent of COVID19. There are currently several licensed vaccines approved for human use and most of them target the spike protein in the virion envelope to induce protective immunity. Recently, variants that spread more quickly have emerged. There is evidence that some of these variants are less sensitive to neutralization in vitro, but it is not clear whether they can evade vaccine induced protection. In this study, we tested SARS-CoV-2 spike RBD as a vaccine antigen and explored the effect of formulation with Alum/MPLA or AddaS03 adjuvants. Our results show that RBD induces high titers of neutralizing antibodies and activates strong cellular immune responses. There is also significant cross-neutralization of variants B.1.1.7 and B.1.351 and to a lesser extent, SARS-CoV-1. These results indicate that recombinant RBD can be a viable candidate as a stand-alone vaccine or as a booster shot to diversify our strategy for COVID19 protection.

Acute high-dose titanium dioxide nanoparticle exposure alters gastrointestinal homeostasis in mice.

Human exposure to a wide variety of engineered nanoparticles (NPs) is on the rise and use in common food additives increases gastrointestinal (GI) exposure. Host health is intricately linked to the GI microbiome and immune response. Perturbations in the microbiota can affect energy harvest, trigger inflammation and alter the mucosal barrier leading to various disease states such as obesity and inflammatory bowel diseases. We hypothesized that single high-dose titanium dioxide (TiO2 ) NP exposure in mice would lead to dysbiosis and stimulate mucus production and local immune populations. Juvenile mice (9-10 weeks) were gavaged with 1 g/kg TiO2 NPs and examined for changes in mucosa-associated bacteria abundance, inflammatory cytokines, mucin expression and body mass. Our data provide support that TiO2 NP ingestion alters the GI microbiota and host defenses promoting metabolic disruption and subsequently weight gain in mice.

US of Right Upper Quadrant Pain in the Emergency Department: Diagnosing beyond Gallbladder and Biliary Disease.

Acute cholecystitis is the most common diagnosable cause for right upper quadrant abdominal (RUQ) pain in patients who present to the emergency department (ED). However, over one-third of patients initially thought to have acute cholecystitis actually have RUQ pain attributable to other causes. Ultrasonography (US) is the primary imaging modality of choice for initial imaging assessment and serves as a fast, cost-effective, and dynamic modality to provide a definitive diagnosis or a considerably narrowed list of differential possibilities. Multiple organ systems are included at standard RUQ US, and a variety of ultrasonographically diagnosable disease processes can be identified, including conditions of hepatic, pancreatic, adrenal, renal, gastrointestinal, vascular, and thoracic origin, all of which may result in RUQ pain. In certain cases, subsequent computed tomography, magnetic resonance (MR) imaging, MR cholangiopancreatography, or cholescintigraphy may be considered, depending on the clinical situation and US findings. Familiarity with the spectrum of disease processes outside of the gallbladder and biliary tree that may manifest with RUQ pain and recognition at US of these alternative conditions is pivotal for early diagnosis and appropriate management. Diagnosis at the time of initial US can reduce unnecessary imaging and its consequences, including excess cost, radiation exposure, nephrotoxic contrast medium use, and time to diagnosis, thereby translating into improved patient care and outcome. This article (a) reviews the causes of RUQ pain identifiable at US using an organ-system approach, (b) illustrates the US appearance of select conditions from each organ system with multimodality imaging correlates, and (c) discusses the relevant pathophysiology and treatment of these entities to aid in efficient direction of management. Online supplemental material is available for this article. ©RSNA, 2018.

Role of the E2 Hypervariable Region (HVR1) in the Immunogenicity of a Recombinant Hepatitis C Virus Vaccine.

Current evidence supports a protective role for virus-neutralizing antibodies in immunity against hepatitis C virus (HCV) infection. Many cross-neutralizing monoclonal antibodies have been identified. These antibodies have been shown to provide protection or to clear infection in animal models. Previous clinical trials have shown that a gpE1/gpE2 vaccine can induce antibodies that neutralize the in vitro infectivity of all the major cell culture-derived HCV (HCVcc) genotypes around the world. However, cross-neutralization appeared to favor certain genotypes, with significant but lower neutralization against others. HCV may employ epitope masking to avoid antibody-mediated neutralization. Hypervariable region 1 (HVR1) at the amino terminus of glycoprotein E2 has been shown to restrict access to many neutralizing antibodies. Consistent with this, other groups have reported that recombinant viruses lacking HVR1 are hypersensitive to neutralization. It has been proposed that gpE1/gpE2 lacking this domain could be a better vaccine antigen to induce broadly neutralizing antibodies. In this study, we examined the immunogenicity of recombinant gpE1/gpE2 lacking HVR1 (ΔHVR1). Our results indicate that wild-type (WT) and ΔHVR1 gpE1/gpE2 antigens induced antibodies targeting many well-characterized cross-genotype-neutralizing epitopes. However, while the WT gpE1/gpE2 vaccine can induce cross-genotype protection against various genotypes of HCVcc and/or HCV-pseudotyped virus (HCVpp), antisera from ΔHVR1 gpE1/gpE2-immunized animals exhibited either reduced homologous neutralization activity compared to that of the WT or heterologous neutralization activity similar to that of the WT. These data suggest that ΔHVR1 gpE1/gpE2 is not a superior vaccine antigen. Based on previously reported chimpanzee protection data using WT gpE1/gpE2 and our current findings, we are preparing a combination vaccine including wild-type recombinant gpE1/gpE2 for clinical testing in the future.IMPORTANCE An HCV vaccine is an unmet medical need. Current evidence suggests that neutralizing antibodies play an important role in virus clearance, along with cellular immune responses. Previous clinical data showed that gpE1/gpE2 can effectively induce cross-neutralizing antibodies, although they favor certain genotypes. HCV employs HVR1 within gpE2 to evade host immune control. It has been hypothesized that the removal of this domain would improve the production of cross-neutralizing antibodies. In this study, we compared the immunogenicities of WT and ΔHVR1 gpE1/gpE2 antigens as vaccine candidates. Our results indicate that the ΔHVR1 gpE1/gpE2 antigen confers no advantages in the neutralization of HCV compared with the WT antigen. Previously, we showed that this WT antigen remains the only vaccine candidate to protect chimpanzees from chronic infection, contains multiple cross-neutralizing epitopes, and is well tolerated and immunogenic in humans. The current data support the further clinical development of this vaccine antigen component.

Thermally Stable, High Performance Transfer Doping of Diamond using Transition Metal Oxides.

We report on optimisation of the environmental stability and high temperature operation of surface transfer doping in hydrogen-terminated diamond using MoO3 and V2O5 surface acceptor layers. In-situ annealing of the hydrogenated diamond surface at 400 °C was found to be crucial to enhance long-term doping stability. High temperature sheet resistance measurements up to 300 °C were performed to examine doping thermal stability. Exposure of MoO3 and V2O5 transfer-doped hydrogen-terminated diamond samples up to a temperature of 300 °C in ambient air showed significant and irreversible loss in surface conductivity. Thermal stability was found to improve dramatically however when similar thermal treatment was performed in vacuum or in ambient air when the oxide layers were encapsulated with a protective layer of hydrogen silsesquioxane (HSQ). Inspection of the films by X-ray diffraction revealed greater crystallisation of the MoO3 layers following thermal treatment in ambient air compared to the V2O5 films which appeared to remain amorphous. These results suggest that proper encapsulation and passivation of these oxide materials as surface acceptor layers on hydrogen-terminated diamond is essential to maximise their environmental and thermal stability.

Polycyclic aromatic hydrocarbon contamination and source profiling in watersheds serving three small Wisconsin, USA cities.

Polycyclic aromatic hydrocarbons (PAHs) continue to be common environmental contaminants. The anthropogenic sources of these compounds are broadly classed as petrogenic and pyrogenic, but more importantly specific sources including activities such as coal burning, oil spills, and application of coal tar sealants can be identified based on several types of data analysis. Several studies have focused on PAHs in sediments of lakes, streams, and stormwater ponds in larger urban areas, finding contamination arising from a number of different sources and correlating well to land use in the nearby watershed. We report here a study of PAH concentrations and source identification for river and lakebed sediments in and upstream of three smaller Wisconsin municipalities: Eau Claire (Eau Claire River), Stevens Point (Plover River), and Racine (Root River). PAH concentrations increased with increasing developed land cover and impervious surface. Concentrations within the cities and upstream agricultural or residential areas do not rise to the level found in larger urban areas or stormwater ponds servicing industrial or commercial land use, but can rise to a level that exceeds the Threshold Effects Concentration (TEC). Concentrations in areas with natural landcovers were very low, with the exception of one sample in a wetland with unusually high organic content. Multiple lines of evidence indicate that coal tar-based pavement sealants are a primary source of the contamination in all three cities. PAH concentrations reported here are likely conservative, and these results indicate that even smaller cities using detention ponds as a stormwater management practice should be prepared for costs of contaminated sediment disposal.

Native Folding of a Recombinant gpE1/gpE2 Heterodimer Vaccine Antigen from a Precursor Protein Fused with Fc IgG.

A recombinant strain HCV1 (hepatitis C virus [HCV] genotype 1a) gpE1/gpE2 (E1E2) vaccine candidate was previously shown by our group to protect chimpanzees and generate broad cross-neutralizing antibodies in animals and humans. In addition, recent independent studies have highlighted the importance of conserved neutralizing epitopes in HCV vaccine development that map to antigenic clusters in E2 or the E1E2 heterodimer. E1E2 can be purified using Galanthis nivalis lectin agarose (GNA), but this technique is suboptimal for global production. Our goal was to investigate a high-affinity and scalable method for isolating E1E2. We generated an Fc tag-derived (Fc-d) E1E2 that was selectively captured by protein G Sepharose, with the tag being removed subsequently using PreScission protease. Surprisingly, despite the presence of the large Fc tag, Fc-d E1E2 formed heterodimers similar to those formed by GNA-purified wild-type (WT) E1E2 and exhibited nearly identical binding profiles to HCV monoclonal antibodies that target conserved neutralizing epitopes in E2 (HC33.4, HC84.26, and AR3B) and the E1E2 heterodimer (AR4A and AR5A). Antisera from immunized mice showed that Fc-d E1E2 elicited anti-E2 antibody titers and neutralization of HCV pseudotype viruses similar to those with WT E1E2. Competition enzyme-linked immunosorbent assays (ELISAs) showed that antisera from immunized mice inhibited monoclonal antibody binding to neutralizing epitopes. Antisera from Fc-d E1E2-immunized mice exhibited stronger competition for AR3B and AR5A than the WT, whereas the levels of competition for HC84.26 and AR4A were similar. We anticipate that Fc-d E1E2 will provide a scalable purification and manufacturing process using protein A/G-based chromatography. IMPORTANCE: A prophylactic HCV vaccine is still needed to control this global disease despite the availability of direct-acting antivirals. Previously, we demonstrated that a recombinant envelope glycoprotein (E1E2) vaccine (genotype 1a) elicited cross-neutralizing antibodies from human volunteers. A challenge for isolating the E1E2 antigen is the reliance on GNA, which is unsuitable for large scale-up and global vaccine delivery. We have generated a novel Fc domain-tagged E1E2 antigen that forms functional heterodimers similar to those with native E1E2. Affinity purification and removal of the Fc tag from E1E2 resulted in an antigen with a nearly identical profile of cross-neutralizing epitopes. This antigen elicited anti-HCV antibodies that targeted conserved neutralizing epitopes of E1E2. Owing to the high selectivity and cost-effective binding capacity of affinity resins for capture of the Fc-tagged rE1E2, we anticipate that our method will provide a means for large-scale production of this HCV vaccine candidate.

The impact of trainee involvement on outcomes in low-dose-rate brachytherapy for prostate cancer.

PURPOSE: To determine the impact of fellow, resident, or medical student (MS) involvement on outcomes in patients undergoing permanent (125)I prostate seed implant. METHODS AND MATERIALS: The study population consisted of men with clinically localized low/intermediate-risk prostate cancer treated with low-dose-rate permanent interstitial brachytherapy. Cases were stratified according to resident, fellow, MS, or attending involvement. Outcomes were compared using analysis of variance, logistic regression, and log rank tests. RESULTS: A total of 291 patients were evaluated. Fellows, residents, and MS were involved in 47 (16.2%), 231 (79.4%), and 34 (11.7%) cases, respectively. Thirteen (4.4%) cases were completed by an attending physician alone. There was no difference in freedom from biochemical failure when comparing the resident, fellow, or attending alone groups (p = 0.10). There was no difference in V100 (volume of the prostate receiving 100% of the prescription dose) outcomes when comparing resident cases to fellow cases (p = 0.72) or attending alone cases (p = 0.78). There was no difference in D90 (minimum dose covering 90% of the postimplant volume) outcomes when comparing resident cases to fellow cases (p = 0.74) or attending alone cases (p = 0.58). When examining treatment toxicity, fellow cases had higher rates of acute Grade 2 + GU toxicity (p = 0.028). With the exception of higher urethra D90 among PGY 2-3 cases (p = 0.02), dosimetric outcomes were similar to cases with PGY 4-5 resident participation. There was no difference in outcomes for cases with and without MS participation. CONCLUSIONS: Interstitial prostate seed implants can be safely performed by trainees with appropriate supervision. Hands-on brachytherapy training is effective and feasible for trainees.

Caveolin 1 is critical for abdominal aortic aneurysm formation induced by angiotensin II and inhibition of lysyl oxidase.

Although AngII (angiotensin II) and its receptor AT1R (AngII type 1 receptor) have been implicated in AAA (abdominal aortic aneurysm) formation, the proximal signalling events primarily responsible for AAA formation remain uncertain. Caveolae are cholesterol-rich membrane microdomains that serve as a signalling platform to facilitate the temporal and spatial localization of signal transduction events, including those stimulated by AngII. Cav1 (caveolin 1)-enriched caveolae in vascular smooth muscle cells mediate ADAM17 (a disintegrin and metalloproteinase 17)-dependent EGFR (epidermal growth factor receptor) transactivation, which is linked to vascular remodelling induced by AngII. In the present study, we have tested our hypothesis that Cav1 plays a critical role for the development of AAA at least in part via its specific alteration of AngII signalling within caveolae. Cav1-/- mice and the control wild-type mice were co-infused with AngII and ß-aminopropionitrile to induce AAA. We found that Cav1-/- mice with the co-infusion did not develop AAA compared with control mice in spite of hypertension. We found an increased expression of ADAM17 and enhanced phosphorylation of EGFR in AAA. These events were markedly attenuated in Cav1-/- aortas with the co-infusion. Furthermore, aortas from Cav1-/- mice with the co-infusion showed less endoplasmic reticulum stress, oxidative stress and inflammatory responses compared with aortas from control mice. Cav1 silencing in cultured vascular smooth muscle cells prevented AngII-induced ADAM17 induction and activation. In conclusion, Cav1 appears to play a critical role in the formation of AAA and associated endoplasmic reticulum/oxidative stress, presumably through the regulation of caveolae compartmentalized signals induced by AngII.

Symptomatic cardiac toxicity is predicted by dosimetric and patient factors rather than changes in 18F-FDG PET determination of myocardial activity after chemoradiotherapy for esophageal cancer.

PURPOSE: To determine factors associated with symptomatic cardiac toxicity in patients with esophageal cancer treated with chemoradiotherapy. MATERIAL AND METHODS: We retrospectively evaluated 102 patients treated with chemoradiotherapy for locally advanced esophageal cancer. Our primary endpoint was symptomatic cardiac toxicity. Radiation dosimetry, patient demographic factors, and myocardial changes seen on (18)F-FDG PET were correlated with subsequent cardiac toxicity. Cardiac toxicity measured by RTOG and CTCAE v3.0 criteria was identified by chart review. RESULTS: During the follow up period, 12 patients were identified with treatment related cardiac toxicity, 6 of which were symptomatic. The mean heart V20 (79.7% vs. 67.2%, p=0.05), V30 (75.8% vs. 61.9%, p=0.04), and V40 (69.2% vs. 53.8%, p=0.03) were significantly higher in patients with symptomatic cardiac toxicity than those without. We found the threshold for symptomatic cardiac toxicity to be a V20, V30 and V40 above 70%, 65% and 60%, respectively. There was no correlation between change myocardial SUV on PET and cardiac toxicity, however, a greater proportion of women suffered symptomatic cardiac toxicity compared to men (p=0.005). CONCLUSIONS: A correlation did not exist between percent change in myocardial SUV and cardiac toxicity. Patients with symptomatic cardiac toxicity received significantly greater mean V20, 30 and 40 values to the heart compared to asymptomatic patients. These data need validation in a larger independent data set.

Screening-level ecological and human health risk assessment of polycyclic aromatic hydrocarbons in stormwater detention pond sediments of Coastal South Carolina, USA.

Screening-level ecological and human health assessments were performed for polycyclic aromatic hydrocarbon (PAH) contamination in the sediments of 19 stormwater detention ponds located in coastal South Carolina. For ecological screening benchmarks, we used threshold and probable effect concentrations (TEC and PEC) derived from consensus-based sediment quality guidelines for individual PAH analytes and equilibrium partitioning sediment benchmarks-toxic units (SigmaESB-TU) derived for PAH mixtures. For human health benchmarks, we used preliminary remediation goals (PRGs). Sediments of five stormwater ponds (four commercial ponds and one residential pond with a large drainage area) exceeded PEC values for several PAH analytes and the SigmaESB-TU safe value of 1 for PAH mixtures. These same five stormwater ponds also exceeded the PRG values for five carcinogenic PAH analytes. These results suggest that the PAH levels in sediments from certain commercial and residential ponds have the potential to pose moderate to high risks for adverse, chronic effects to benthic organisms in situ and an increased risk of cancer to humans ex situ following excavation and on-site disposal. We recommend that sediment from these stormwater ponds be tested prior to excavation to determine the appropriate method of disposal. We also recommend that regulatory agencies enforce guidelines for periodic sediment removal as this should reduce both in situ and ex situ risks resulting from sediment PAH exposure.

An intraoperative real-time sleeved seed technique for permanent prostate brachytherapy.

PURPOSE: To describe a novel technique that integrates customized sleeved seed production to reduce seed migration using preloaded needles with real-time intraoperative dosimetric planning for patients treated with iodine-125 (I-125) permanent prostate seed implants. METHODS AND MATERIALS: Customized seed-spacer sequences were calculated for patients in real time based on an intraoperative transrectal ultrasound-guided volume study. Using a Fox Chase Cancer Center modified Best Iodine-125 seed loader (Best Medical, Springfield, VA), the seeds and spacers were inserted into a hollow suture material (sleeve) and then loaded into the implant needles. Needles were placed sequentially under transrectal ultrasound guidance with sagittal plane visualization of the dropped sleeved seeds. RESULTS: This technique was successfully implemented allowing intraoperative planning to be combined with real-time sleeved seed production. CONCLUSIONS: The use of sleeves for seeds combined with real-time intraoperative planning allowed for the intraoperative customization of implants with the practical advantages of linked seeds.

Functional roles of osteoactivin in normal and disease processes.

Osteoactivin (OA) protein was discovered in bone cells a decade ago. Recent literature suggests that osteoactivin is crucial for the differentiation and functioning of different cell types, including bone-forming osteoblasts and bone-resorbing osteoclast cells. Here, we review the literature to date on various regulatory functions of osteoactivin, as well as its discovery, structure, expression, and function in different tissues and cells. The transcriptional regulation of osteoactivin and its mechanism of action in normal and diseased conditions with special emphasis on bone are also covered in this review. In addition, we touch on the therapeutic potential of osteoactivin in cancer and bone diseases.

A survey of metal and pesticide levels in stormwater retention pond sediments in coastal South Carolina.

During the summer of 2007, sediment samples were collected from 16 stormwater detention ponds and 2 reference ponds located in coastal South Carolina. The sediments were analyzed for more than 30 pesticides with current and historical uses, six polybrominated diphenyl ethers (PBDEs), and seven metals. The results are compared with established screening assessment parameters, with copper found to be the contaminant of highest concern. Lead levels were found to correlate well with pond drainage area, while copper and zinc levels correlated with both pond drainage area and pond surface area. Chlorpyrifos levels were found to correlate with pond surface area. Our results also show that ponds draining commercial areas were likely to have higher levels of zinc and lead in the sediments compared to other pond classes.

Polycyclic aromatic hydrocarbon contamination in stormwater detention pond sediments in coastal South Carolina.

The purpose of this study was to characterize the polycyclic aromatic hydrocarbon (PAH) contamination in the sediments of stormwater detention ponds in coastal South Carolina. Levels of the sum of PAH analytes were significantly higher in the sediments of commercial ponds compared to that of reference, golf course, low-density residential, and high-density residential ponds. Isomer ratio analysis suggested that the predominant source of PAHs were pyrogenic; however, many ponds had a PAH signature consistent with mixed uncombusted and combusted PAH sources. PAH levels in these sediments could be modeled using both pond drainage area and pond surface area. These results demonstrate that the sediment from most commercial ponds, and a few residential and golf course ponds, were moderately contaminated with PAHs. PAH levels in these contaminated ponds exceeded between 42% and 75% of the ecological screening values for individual PAH analytes established by US EPA Region IV, suggesting that they may pose a toxicological risk to wildlife.

Induction of broad CD4+ and CD8+ T-cell responses and cross-neutralizing antibodies against hepatitis C virus by vaccination with Th1-adjuvanted polypeptides followed by defective alphaviral particles expressing envelope glycoproteins gpE1 and gpE2 and nonstructural proteins 3, 4, and 5.

Broad, multispecific CD4(+) and CD8(+) T-cell responses to the hepatitis C virus (HCV), as well as virus-cross-neutralizing antibodies, are associated with recovery from acute infection and may also be associated in chronic HCV patients with a favorable response to antiviral treatment. In order to recapitulate all of these responses in an ideal vaccine regimen, we have explored the use of recombinant HCV polypeptides combined with various Th1-type adjuvants and replication-defective alphaviral particles encoding HCV proteins in various prime/boost modalities in BALB/c mice. Defective chimeric alphaviral particles derived from the Sindbis and Venezuelan equine encephalitis viruses encoding either the HCV envelope glycoprotein gpE1/gpE2 heterodimer (E1E2) or nonstructural proteins 3, 4, and 5 (NS345) elicited strong CD8(+) T-cell responses but low CD4(+) T helper responses to these HCV gene products. In contrast, recombinant E1E2 glycoproteins adjuvanted with MF59 containing a CpG oligonucleotide elicited strong CD4(+) T helper responses but no CD8(+) T-cell responses. A recombinant NS345 polyprotein also stimulated strong CD4(+) T helper responses but no CD8(+) T-cell responses when adjuvanted with Iscomatrix containing CpG. Optimal elicitation of broad CD4(+) and CD8(+) T-cell responses to E1E2 and NS345 was obtained by first priming with Th1-adjuvanted proteins and then boosting with chimeric, defective alphaviruses expressing these HCV genes. In addition, this prime/boost regimen resulted in the induction of anti-E1E2 antibodies capable of cross-neutralizing heterologous HCV isolates in vitro. This vaccine formulation and regimen may therefore be optimal in humans for protection against this highly heterogeneous global pathogen.

Hepatitis C virus envelope glycoprotein immunization of rodents elicits cross-reactive neutralizing antibodies.

Neutralizing antibody responses elicited during infection generally confer protection from infection. Hepatitis C virus (HCV) encodes two glycoproteins E1 and E2 that are essential for virus entry and are the major target for neutralizing antibodies. To assess whether both glycoproteins are required for the generation of a neutralizing antibody response, rodents were immunized with a series of glycoproteins comprising full length and truncated versions. Guinea pigs immunized with HCV-1 genotype 1a E1E2p7, E1E2 or E2 generated high titer anti-glycoprotein antibody responses that neutralized the infectivity of HCVpp and HCVcc expressing gps of the same genotype as the immunizing antigen. Less potent neutralization of viruses bearing the genotype 2 strain J6 gps was observed. In contrast, immunized mice demonstrated reduced anti-gp antibody responses, consistent with their minimal neutralizing activity. Immunization with E2 alone was sufficient to induce a high titer response that neutralized HCV pseudoparticles (HCVpp) bearing diverse glycoproteins and cell culture grown HCV (HCVcc). The neutralization titer was reduced 3-fold by the presence of lipoproteins in human sera. Cross-competition of the guinea pig anti-E1E2 immune sera with a panel of epitope mapped anti-E2 monoclonal antibodies for binding E2 identified a series of epitopes within the N-terminal domain that may be immunogenic in the immunized rodents. These data demonstrate that recombinant E2 and E1E2 can induce polyclonal antibody responses with cross-reactive neutralizing activity, supporting the future development of prophylactic and therapeutic vaccines.

Reliability, validity, and responsiveness of the IKDC score for meniscus injuries of the knee.

PURPOSE: The purpose of this study was to determine the psychometric properties of the International Knee Documentation Committee (IKDC) score for meniscus injuries of the knee. METHODS: Test-retest reliability, content validity, construct validity, and responsiveness to change were determined for the IKDC score. Knees were excluded if they had ligament pathology or a chondral defect greater than Outerbridge grade 2. All patients had meniscus pathology requiring treatment. The study comprised 4 subsets of patients. Group A consisted of 31 patients who completed an IKDC form at least 2 years after surgery for meniscus pathology and were then retested within 4 weeks of the primary questionnaire. Group B contained 264 patients with preoperative IKDC scores that were used for construct and content validity. Group C contained 50 patients who had a preoperative IKDC score and completed a short form 12 survey. Group D contained 100 patients with preoperative and postoperative IKDC scores used to measure responsiveness. RESULTS: The overall IKDC score showed acceptable test-retest reliability with an interclass correlation of 0.95. There were acceptable floor and ceiling effects. All constructs tested showed significant differences. These included lower IKDC score with the following: lower activity level, difficulty with activities of daily living, difficulty with sports, abnormal knee function, and complex/degenerative meniscus tears. Responsiveness to change showed a large effect size (2.11) and a large response mean (1.5) for the overall score. The SE of the measurement was 3.19, and the minimum detectable change was 8.8 points. CONCLUSIONS: The overall IKDC score showed overall acceptable psychometric performance for outcome measures of meniscus injuries of the knee. LEVEL OF EVIDENCE: Level III, testing of previously developed diagnostic criteria in nonconsecutive patients.

Genetic variation in comC, the gene encoding competence-stimulating peptide (CSP) in Streptococcus mutans.

The genetic variability in comC, the gene encoding the quorum-sensing molecule, competence-stimulating peptide (CSP) in Streptococcus mutans is reported. Seven comC alleles encoding three distinct mature CSPs were identified among 36 geographically diverse strains, although, compared with Streptococcus pneumoniae, the amount of predicted amino acid sequence variation is low. In agreement with other studies, significant variation was found in the natural competence for DNA uptake in these strains. However, there was no correlation between the CSP genotype and the ability to transform these strains. Representative strains encoding each of the CSP variants became competent in response to synthetic CSPs of each type. Therefore, in contrast to S. pneumoniae, comC alleles in S. mutans are functionally equivalent and there is no evidence of pherotype specificity.