Should return to pivoting sport be avoided for the secondary prevention of osteoarthritis after anterior cruciate ligament reconstruction? A prospective cohort study with MRI, radiographic and symptomatic outcomes.

OBJECTIVE: To evaluate if returning to pivoting sport following anterior cruciate ligament reconstruction (ACLR) is associated with longitudinal structural and symptomatic osteoarthritis outcomes. DESIGN: Eighty-one adults aged 18-50 years were followed prospectively 1- to 5-years post-ACLR. Return to pivoting sport was assessed at 1-, 3- and 5-years. Longitudinal changes in osteoarthritis features were evaluated from 1- and 5-year magnetic resonance imaging (MRI)s using MRI Osteoarthritis Knee Score (MOAKS). Radiographic osteoarthritis and self-reported knee symptoms, function and quality of life were assessed using the Osteoarthritis Research Society International (OARSI) atlas and Knee injury Osteoarthritis Outcome Score (KOOS), respectively, at 5 years post-ACLR. Generalised linear models (adjusted for baseline characteristics) assessed whether returning to pivoting sport was associated with risk of worsening osteoarthritis features on MRI, radiographic osteoarthritis and KOOS. RESULTS: Thirty participants returned to pivoting sport 1-year post-ACLR and 50 returned at any time (i.e., 1-, 3- or 5-years). Returning to pivoting sport was not associated with worsening of any MRI osteoarthritis feature (risk ratio (RR) range: 0.59-2.91) or 5-year KOOS (ß range: -2.73-3.69). Returning to pivoting sport at 1-year and up to 5-years post-ACLR was associated with a 50% (RR 0.49, 95%CI 0.10-2.37) and 40% (RR 0.60, 95%CI 0.16-2.17) reduced risk of radiographic osteoarthritis, respectively, but these risk reductions were inconclusive due to wide confidence intervals. CONCLUSION: After ACLR, returning to pivoting sport was not associated with increased risk of worsening knee osteoarthritis features on MRI, radiographic osteoarthritis or knee symptoms. Participation in pivoting sport need not be avoided as part of osteoarthritis secondary prevention strategies.

Global Microscopic Description of Nucleon-Nucleus Scattering with Quantified Uncertainties.

We develop for the first time a microscopic global nucleon-nucleus optical potential with quantified uncertainties suitable for analyzing nuclear reaction experiments at next-generation rare-isotope beam facilities. Within the improved local density approximation and without any adjustable parameters, we begin by computing proton-nucleus and neutron-nucleus optical potentials from a set of five nuclear forces from chiral effective field theory for 1800 target nuclei in the mass range 12≤A≤242 for energies between 0 MeV

Imputation of Assay Bioactivity Data Using Deep Learning.

We describe a novel deep learning neural network method and its application to impute assay pIC50 values. Unlike conventional machine learning approaches, this method is trained on sparse bioactivity data as input, typical of that found in public and commercial databases, enabling it to learn directly from correlations between activities measured in different assays. In two case studies on public domain data sets we show that the neural network method outperforms traditional quantitative structure-activity relationship (QSAR) models and other leading approaches. Furthermore, by focusing on only the most confident predictions the accuracy is increased to R2 > 0.9 using our method, as compared to R2 = 0.44 when reporting all predictions.

Knee kinematics and kinetics are associated with early patellofemoral osteoarthritis following anterior cruciate ligament reconstruction.

OBJECTIVE: Patellofemoral osteoarthritis (PFOA) commonly occurs following anterior cruciate ligament reconstruction (ACLR). Our study aimed to compare knee kinematics and kinetics during a hop-landing task between individuals with and without early PFOA post-ACLR. DESIGN: Forty-five individuals (mean ± SD 26 ± 5 years) 1-2 years post-ACLR underwent 3T isotropic MRI scans and 3D biomechanical assessment of a standardised forward hop task. Knee kinematics (initial contact, peak, excursion) in all three planes and sagittal plane kinetics (peak) were compared between 15 participants with early PFOA (MRI-defined patellofemoral cartilage lesion) and 30 participants with no PFOA (absence of patellofemoral cartilage lesion on MRI) using analysis of covariance (ANCOVA), adjusted for age, BMI, sex and the presence of early tibiofemoral OA. RESULTS: Compared to participants without PFOA, those with early PFOA exhibited smaller peak knee flexion angles (mean difference, 95% confidence interval [CI]: -5.2°, -9.9 to -0.4; P = 0.035) and moments (-4.2 Nm/kg.m, -7.8 to -0.6; P = 0.024), and greater knee internal rotation excursion (5.3°, 2.0 to 8.6; P = 0.002). CONCLUSIONS: Individuals with early PFOA within the first 2-years following ACLR exhibit distinct kinematic and kinetic features during a high-load landing task. These findings provide new information regarding common post-ACLR biomechanical patterns and PFOA. Since management strategies, such as altering knee load, are more effective during the early stages of disease, this knowledge will help to inform clinical management of early PFOA post-ACLR.

Polycyclic aromatic hydrocarbons in residential dust and risk of childhood acute lymphoblastic leukemia.

Several polycyclic aromatic hydrocarbons (PAHs) are known or probable human carcinogens. We evaluated the relationship between PAH exposure and risk of childhood acute lymphoblastic leukemia (ALL) using concentrations in residential dust as an exposure indicator. We conducted a population-based case-control study (251 ALL cases, 306 birth-certificate controls) in Northern and Central California from 2001 to 2007. We collected residential dust using a high volume small surface sampler (HVS3) (n=185 cases, 212 controls) or by sampling from participants' household vacuum cleaners (n=66 cases, 94 controls). We evaluated log-transformed concentrations of 9 individual PAHs, the summed PAHs, and the summed PAHs weighted by their carcinogenic potency (the toxic equivalence). We calculated odds ratios (ORs) and 95% confidence intervals (CI) using logistic regression adjusting for demographic characteristics and duration between diagnosis/reference date and dust collection. Among participants with HVS3 dust, risk of ALL was not associated with increasing concentration of any PAHs based on OR perln(ng/g). Among participants with vacuum dust, we observed positive associations between ALL risk and increasing concentrations of benzo[a]pyrene (OR perln[ng/g]=1.42, 95% CI=0.95, 2.12), dibenzo[a,h]anthracene (OR=1.98, 95% CI=1.11, 3.55), benzo[k]fluoranthene (OR=1.71, 95% CI=0.91, 3.22), indeno[1,2,3-cd]pyrene (OR=1.81, 95% CI=1.04, 3.16), and the toxic equivalence (OR=2.35, 95% CI=1.18, 4.69). The increased ALL risk among participants with vacuum dust suggests that PAH exposure may increase the risk of childhood ALL; however, reasons for the different results based on HVS3 dust samples deserve further study.

Stored swine manure and swine faeces as reservoirs of antibiotic resistance genes.

Inclusion of low levels of antibiotics in the feed of domestic food animals promotes improved growth, animal performance and overall health benefits. However, this practice has come under scrutiny due to concerns over such feeding on bacterial antibiotic resistance (AR) and potential impact on human health. There is a paucity of data on the types and levels of AR genes that may be present in agricultural practices. Using PCR detection of AR genes, this study demonstrates that both stored swine manure and swine faeces harbour a variety of AR genes, and bacterial members of these communities contain genes that may move between micro-organisms. Thus, both ecosystems may serve as reservoirs of AR genes.

Microbial production of volatile sulphur compounds in the large intestine of pigs fed two different diets.

AIMS: To investigate the production of volatile sulphur compounds (VSC) in the segments of the large intestine of pigs and to assess the impact of diet on this production. METHODS AND RESULTS: Pigs were fed two diets based on either wheat and barley (STD) or wheat and dried distillers grains with solubles (DDGS). Net production of VSC and potential sulphate reduction rate (SRR) (sulphate saturated) along the large intestine were determined by means of in vitro incubations. The net production rate of hydrogen sulphide and potential SRR increased from caecum towards distal colon and were significantly higher in the STD group. Conversely, the net methanethiol production rate was significantly higher in the DDGS group, while no difference was observed for dimethyl sulphide. The number of sulphate-reducing bacteria and total bacteria were determined by quantitative PCR and showed a significant increase along the large intestine, whereas no diet-related differences were observed. CONCLUSION: VSC net production varies widely throughout the large intestine of pigs and the microbial processes involved in this production can be affected by diet. SIGNIFICANCE AND IMPACT OF THE STUDY: This first report on intestinal production of all VSC shows both spatial and dietary effects, which are relevant to both bowel disease- and odour mitigation research.

The genome sequence of Bifidobacterium longum subsp. infantis reveals adaptations for milk utilization within the infant microbiome.

Following birth, the breast-fed infant gastrointestinal tract is rapidly colonized by a microbial consortium often dominated by bifidobacteria. Accordingly, the complete genome sequence of Bifidobacterium longum subsp. infantis ATCC15697 reflects a competitive nutrient-utilization strategy targeting milk-borne molecules which lack a nutritive value to the neonate. Several chromosomal loci reflect potential adaptation to the infant host including a 43 kbp cluster encoding catabolic genes, extracellular solute binding proteins and permeases predicted to be active on milk oligosaccharides. An examination of in vivo metabolism has detected the hallmarks of milk oligosaccharide utilization via the central fermentative pathway using metabolomic and proteomic approaches. Finally, conservation of gene clusters in multiple isolates corroborates the genomic mechanism underlying milk utilization for this infant-associated phylotype.

Development and comparison of SYBR Green quantitative real-time PCR assays for detection and enumeration of sulfate-reducing bacteria in stored swine manure.

AIMS: To develop and evaluate primer sets targeted to the dissimilatory sulfite reductase gene (dsrA) for use in quantitative real-time PCR detection of sulfate-reducing bacteria (SRB) in stored swine manure. METHODS AND RESULTS: Degenerate primer sets were developed to detect SRB in stored swine manure. These were compared with a previously reported primer set, DSR1F+ and DSR-R, for their coverage and ability to detect SRB communities in stored swine manure. Sequenced clones were most similar to Desulfovibrio sp. and Desulfobulbus sp., and these SRB populations differed within different manure ecosystems. Sulfur content of swine diets was shown to affect the population of Desulfobulbus-like Group 1 SRB in manure. CONCLUSIONS: The newly developed assays were able to enumerate and discern different groups of SRB, and suggest a richly diverse and as yet undescribed population of SRB in swine manure. SIGNIFICANCE AND IMPACT OF THE STUDY: The PCR assays described here provide improved and efficient molecular tools for quantitative detection of SRB populations. This is the first study to show population shifts of SRB in swine manure, which are a result of either the effects of swine diets or the maturity of the manure ecosystem.

Gene expression does not change significantly in C3H 10T(1/2) cells after exposure to 847.74 CDMA or 835.62 FDMA radiofrequency radiation.

In vitro experiments with C3H 10T(1/2) mouse cells were performed to determine whether Frequency Division Multiple Access (FDMA) or Code Division Multiple Access (CDMA) modulated radiofrequency (RF) radiations induce changes in gene expression. After the cells were exposed to either modulation for 24 h at a specific absorption rate (SAR) of 5 W/ kg, RNA was extracted from both exposed and sham-exposed cells for gene expression analysis. As a positive control, cells were exposed to 0.68 Gy of X rays and gene expression was evaluated 4 h after exposure. Gene expression was evaluated using the Affymetrix U74Av2 GeneChip to detect changes in mRNA levels. Each exposure condition was repeated three times. The GeneChip data were analyzed using a two-tailed t test, and the expected number of false positives was estimated from t tests on 20 permutations of the six sham RF-field-exposed samples. For the X-ray-treated samples, there were more than 90 probe sets with expression changes greater than 1.3-fold beyond the number of expected false positives. Approximately one-third of these genes had previously been reported in the literature as being responsive to radiation. In contrast, for both CDMA and FDMA radiation, the number of probe sets with an expression change greater than 1.3-fold was less than or equal to the expected number of false positives. Thus the 24-h exposures to FDMA or CDMA RF radiation at 5 W/kg had no statistically significant effect on gene expression.

Sequential development of aneuploidy, keratin modifications, and gamma-glutamyltransferase expression in mouse skin papillomas.

To elucidate the role and timing of expression of different premalignant and malignant markers in tumor promotion, we correlated alterations in keratin patterns and gamma-glutamyltransferase (GGT) expression with the chromosomal status of individual mouse skin papillomas. Papillomas were induced by 7,12-dimethylbenz[a]anthracene initiation and 12-O-tetradecanoylphorbol-13-acetate promotion. Individual tumors were randomly sampled at 20 and 35 weeks of promotion. Each tumor was cytogenetically analyzed and serial paraffin sections were used for GGT detection, immunoblotting, and immunohistochemistry studies. Monospecific antibodies elicited against keratins K1 (Mr 67,000) and K14 (Mr 55,000) were used to analyze keratin modifications. Most tumors at 20 weeks of promotion, although exhibiting aneuploidy, still presented high levels of the K1 differentiation-associated keratin. Later during promotion those tumors bearing the highest aneuploidy indexes were those that showed a marked decrease in or absence of the K1 protein. Furthermore, those same tumors with the highest levels of genomic alterations also exhibited foci of GGT activity. These results support the idea that the majority of papillomas under continuous promotion are progressing toward malignancy. Aneuploidy seems to precede detectable keratin modifications, and GGT activity appears to be the latest marker to be expressed.

Nucleotide sequences of xylan-inducible xylanase and xylosidase/arabinosidase genes from Bacteroides ovatus V975.

The nucleotide sequences of the xylI and xsa genes of Bacteroides ovatus V975, encoding xylanase and xylosidase activities, were determined. Both genes are part of a xylan-inducible operon, the sequenced region of which also contains a partial open reading frame upstream of the xylanase gene. Deduced amino acid sequence similarly analyses indicate that the xylanase belongs to the Family F series of glycosyl hydrolases.

Interrupted catalytic domain structures in xylanases from two distantly related strains of Prevotella ruminicola.

Two xylanases from the rumen anaerobic bacterium Prevotella ruminicola were found to possess highly unusual structures in which family 10 catalytic domains are interrupted by unrelated sequences. XynC from P. ruminicola B(1)4 carries a 160 amino-acid insertion, while a P. ruminicola D31d xylanase carries an unrelated region of 280 amino acids, containing an imperfect 130 amino-acid duplication. Both regions of family 10 similarity were shown to be essential for activity of the D31d enzyme.

7 alpha-Dehydroxylation of cholic acid by cell extracts of Eubacterium species V.P.I. 12708.

NADH:flavin oxidoreductase and 7 alpha-dehydroxylase were induced 5- and 90-fold, respectively, by cholic acid in cultures of Eubacterium species V.P.I. 12708. Assays of 7 alpha-dehydroxylase activity in the presence of various cofactors revealed that optimal activity was obtained in the presence of NAD+ plus FADH2. The pH optima of 7 alpha-dehydroxylase activity in whole cells and cell extracts were 7.0. The similar induction pattern of these two enzymes and the apparent cofactor requirements for 7 alpha-dehydroxylation suggest a relationship between 7 alpha-dehydroxylase and NADH:flavin oxidoreductase.

A rapid luminescently monitored enzyme immunoassay for IgE.

A novel halophenol-enhanced luminol-peroxide luminescent detection method for horseradish peroxidase has been tested in an enzyme immunoassay for IgE. The luminescent enzyme immunoassay was reproducible (within-batch CV, 3.9-13.2%) and values obtained on serum samples showed good agreement with those obtained by colorimetric enzyme immunoassay. The major advantages of the luminescent detection method are that it is rapid, 30 s compared with 30 min for the colorimetric assay using o-phenylenediamine, and the luminescent signal is intense and stable for several minutes.

Membrane-induced secondary structures of neuropeptides: a comparison of the solution conformations adopted by agonists and antagonists of the mammalian tachykinin NK1 receptor.

We present what we believe to be the first documented example of an inducement of distinctly different secondary structure types onto agonists and antagonists selective for the same G-coupled protein receptor using the same membrane-model matrix wherein the induced structures are consistent with those suggested to be biologically active by extensive analogue studies and conventional binding assays. 1H NMR chemical shift assignments for the mammalian NK1 receptor-selective agonists alpha-neurokinin (NKA) and beta-neurokinin (NKB) as well as the mammalian NK1 receptor-selective antagonists [d-Pro2,d-Phe7,d-Trp9]SP and [d-Arg1, d-Pro2,d-Phe7,d-His9]SP have been determined at 600 MHz in sodium dodecyl sulfate (SDS) micelles. The SDS micelle system simulates the membrane-interface environment the peptide experiences when in the proximity of the membrane-embedded receptor, allowing for conformational studies that are a rough approximation of in vivo conditions. Two-dimensional NMR techniques were used to assign proton resonances, and interproton distances were estimated from the observed nuclear Overhauser effects (NOEs). The experimental distances were used as constraints in a molecular dynamics and simulated annealing protocol using the modeling package DISCOVER to generate three-dimensional structures of the two agonists and two antagonists when present in a membrane-model environment to determine possible prebinding ligand conformations. It was determined that (1) NKA is helical from residues 6 to 9, with an extended N-terminus; (2) NKB is helical from residues 4 to 10, with an extended N-terminus; (3) [d-Pro2,d-Phe7,d-Trp9]SP has poorly defined helical properties in the midregion and a beta-turn structure in the C-terminus (residues 6-9); and (4) [d-Arg1,d-Pro2, d-Phe7,d-His9]SP has a helical structure in the midregion (residues 4-6) and a well-defined beta-turn structure in the C-terminus (residues 6-10). Attempts have been made to correlate the observed conformational differences between the agonists and antagonists to their binding potencies and biological activity.

Solution structures in SDS micelles and functional activity at the bullfrog substance P receptor of ranatachykinin peptides.

A set of novel tachykinin-like peptides has been isolated from bullfrog brain and gut. These compounds, ranatachykinin A (RTKA), ranatachykinin B (RTKB), and ranatachykinin C (RTKC), were named for their source, Rana catesbeiana, and their homology to the tachykinin peptide family. We present the first report of the micelle-bound structures and pharmacological actions of the RTKs. Generation of three-dimensional structures of the RTKs in a membrane-model environment using (1)H NMR chemical shift assignments, two-dimensional NMR techniques, and molecular dynamics and simulated annealing procedures allowed for the determination of possible prebinding ligand conformations. RTKA, RTKB, and RTKC were determined to be helical from the midregion to the C-terminus (residues 4-10), with a large degree of flexibility in the N-terminus and minor dynamic fraying at the end of the C-terminus. The pharmacological effects of the RTKs were studied by measuring the elevation of intracellular Ca(2+) in Chinese hamster ovarian cells stably transfected with the bullfrog substance P receptor (bfSPR). All of the RTKs tested elicited Ca(2+) elevations with a rank order of maximal effect of RTKA >/= SP > RTKC >/= RTKB. A high concentration (1 microM) of the neuropeptides produced varying degrees of desensitization to a subsequent challenge with the same or different peptide, while a low concentration (1 pM) produced sensitization at the bfSPR. Our data suggest differences in amino acid side chains and their charged states at the C-terminal sequence or differences in secondary structure at the N-terminus, which do not overlap according to the findings in this paper, may explain the differing degree and type of receptor activation seen at the bfSPR.

The "hustle": socioeconomic deprivation, urban drug trafficking, and low-income, African-American male gender identity.

OBJECTIVE: Drug trafficking seems to be both prevalent and associated with considerable morbidity and mortality among inner-city African-American males. Survey data has indicated the possible importance of economic need in the rapid emergence of drug trafficking in this population. In the present study, an historical-cultural approach is used to examine this economic relationship further and to explore the role that drug trafficking plays in a society that has permitted its successful and rapid growth. METHODOLOGY: Data were obtained from interviews of approximately 600 African-Americans residing in inner-city neighborhoods in Washington, DC and Baltimore during nine drug- and acquired immunodeficiency syndrome-related studies conducted over 4 years. RESULTS AND CONCLUSIONS: From the perspective of the study participants, the need to provide economic support for one's family as well as to achieve some sense of status, respect, and reputation among one's peers are two core constructs of masculine identity in the United States. The historical and worsening inequities in access to economic resources and power by African-American males are viewed as significantly reducing the opportunity for economic success through more social or legal enterprises. Pursuit of nonmainstream activities (such as drug trafficking) is perceived as offering an opportunity for economic advancement and for establishing a power base for individuals who have been denied access to mainstream opportunities.

External quality assessment of clinical laboratories in the United Kingdom.

A review is given of the National External Quality Assessment Schemes (NEQASs) in various pathology disciplines in the United Kingdom, with a discussion of the relative roles of the DHSS, individual laboratory scientists, and the relevant professional bodies. Principles of operation and scientific problems in the design of NEQASs in different disciplines are described and contrasted, and some comparisons with the experience in other European countries and the USA are drawn.

Adsorption of serum calcium by plastic sample cups.

Sera left overnight in plastic AutoAnalyzer sample cups may give low calcium values; the effect is attributed to adsorption of calcium onto the walls of the vessel. The adsorption is brought about by a rise in the pH of the sera, and factors which promote the rise in pH increase the adsorption. This phenomenon is of practical importance because as much as 10% of the calcium in the serum may be adsorbed. Adsorption occurs particularly onto the walls of polystyrene cups, and when polypropylene cups were used the adsorption was reduced. The phenomenon cannot be evaluated or controlled by the use of control sera. In order to avoid the sampling error, serum for calcium analysis should be used fresh or stored at 4 degrees C under conditions such that any change in pH is minimal. Sera should not be left to stand in AutoAnalyzer cups at room temperature for longer than three hours before analysis.