Microbiologic Diagnosis of Prosthetic Shoulder Infection by Use of Implant Sonication

We recently described a sonication technique for the diagnosis of prosthetic knee and hip infections. We compared periprosthetic tissue culture to implant sonication followed by sonicate fluid culture for the diagnosis of prosthetic shoulder infection. One hundred thirty-six patients undergoing arthroplasty revision or resection were studied; 33 had definite prosthetic shoulder infections and 2 had probable prosthetic shoulder infections. Sonicate fluid culture was more sensitive than periprosthetic tissue culture for the detection of definite prosthetic shoulder infection (66.7 and 54.5%, respectively; P = 0.046). The specificities were similar (98.0% and 95.1%, respectively; P = 0.26). Propionibacterium acnes was the commonest species detected among culture-positive definite prosthetic shoulder infection cases by periprosthetic tissue culture (38.9%) and sonicate fluid culture (40.9%). All subjects from whom P. acnes was isolated from sonicate fluid were male. We conclude that sonicate fluid culture is useful for the diagnosis of prosthetic shoulder infection.

Deletion of TRPC4 and TRPC6 in Mice Impairs Smooth Muscle Contraction and Intestinal Motility In Vivo.

BACKGROUND & AIMS: Downstream effects of muscarinic receptor stimulation in intestinal smooth muscle include contraction and intestinal transit. We thought to determine whether classic transient receptor potential (TRPC) channels integrate the intracellular signaling cascades evoked by the stimulated receptors and thereby contribute to the control of the membrane potential, Ca-influx, and cell responses. METHODS: We created trpc4-, trpc6-, and trpc4/trpc6-gene-deficient mice and analyzed them for intestinal smooth muscle function in vitro and in vivo. RESULTS: In intestinal smooth muscle cells TRPC4 forms a 55 pS cation channel and underlies more than 80% of the muscarinic receptor-induced cation current (mI(CAT)). The residual mI(CAT) depends on the expression of TRPC6, indicating that TRPC6 and TRPC4 determine mI(CAT) channel activity independent of other channel subunits. In TRPC4-deficient ileal myocytes the carbachol-induced membrane depolarizations are diminished greatly and the atropine-sensitive contraction elicited by acetylcholine release from excitatory motor neurons is reduced greatly. Additional deletion of TRPC6 aggravates these effects. Intestinal transit is slowed down in mice lacking TRPC4 and TRPC6. CONCLUSIONS: In intestinal smooth muscle cells TRPC4 and TRPC6 channels are gated by muscarinic receptors and are responsible for mI(CAT). They couple muscarinic receptors to depolarization of intestinal smooth muscle cells and voltage-activated Ca(2+)-influx and contraction, and thereby accelerate small intestinal motility in vivo.

Chromium, iron, ruthenium and gold complexes of 3,3-(biphenyl-2,2 '-diyl)-1-diphenylphosphino-1-phenylallene: A versatile ligand

Successive treatment of 9-(phenylethynyl)fluoren-9-ol (1a), with HBr, butyllithium and chlorodiphenylphosphine furnishes 3,3-(biphenyl-2,2'-diyl)-1-diphenylphosphino-1-phenylallene (5). Moreover, reaction of 1a directly with chlorodiphenylphosphine yields the corresponding allenylphosphine oxide (6). The allenylphosphine (5), and Fe-2(CO)(9) initially form the phosphine-Fe(CO)(4) complex, 11, which is very thermally sensitive and readily loses a carbonyl ligand. In the resulting phosphine-Fe(CO)(3) system, 12, the additional site at iron is coordinated by the allene double bond adjacent to phosphorus; the Fe(CO) 3 tripod in 12 exhibits restricted rotation on the NMR time-scale even at room temperature. The corresponding chromium complex, (5)-Cr(CO)5 (9), has also been prepared. The gold complexes (5)AuCl (13), and [(5)-Au(THT)](+) X-, where (THT) is tetrahydrothiophene, and X = PF6 (14a), or ClO4 (14b), are analogous to the known triphenylphosphine-gold complexes. In contrast, in the (arene)(allenylphosphine) RuCl2 system the allene double bond adjacent to phosphorus displaces a chloride, and the resulting cationic species undergoes nucleophilic attack by water yielding ultimately a five-membered Ru-P-C=C-O ruthenacycle (17). Thus, the allenylphosphine (5), reacts initially as a conventional mono-phosphine but, when the metal centre has a readily displaceable ligand such as a carbonyl or halide, the allene double bond adjacent to the phosphorus can also function as a donor. X- ray crystal structures are reported for 5, 6, 11, 12, 13, 14a, 14b and 17.

Relations between premise similarity and inductive strength

According to the diversity principle, diverse evidence is strong evidence. There has been considerable evidence that people respect this principle in inductive reasoning. However, exceptions may be particularly informative. Medin, Coley, Storms, and Hayes (2003) introduced a relevance theory of inductive reasoning and used this theory to predict exceptions, including the nondiversity-by-property-reinforcement effect. A new experiment in which this phenomenon was investigated is reported here. Subjects made inductive strength judgments and similarity judgments for stimuli from Medin et al. (2003). The inductive strength judgments showed the same pattern as that in Medin et al. (2003); however, the similarity judgments suggested that the pattern should be interpreted as a diversity effect, rather than as a nondiversity effect. It is concluded that the evidence regarding the predicted nondiversity-by-property-reinforcement effect does not give distinctive support for relevance theory, although this theory does address other results.

Wasp-7: A Bright Transiting-Exoplanet System in the Southern Hemisphere

We report that a Jupiter-mass planet, WASP-7b, transits the V = 9.5 star HD 197286 every 4.95 d. This is the brightest discovery from the WASP-South transit survey so far and is currently the brightest transiting-exoplanet system in the southern hemisphere. WASP-7b is among the densest of the known Jupiter-mass planets, suggesting that it has a massive core. The planet mass is 0.96+0.12 -0.18 M Jup, the radius is 0.915+0.046 -0.040 R Jup, and the density is 1.26+0.25 -0.21 ?Jup (1.67+0.33 -0.28 g cm-3).

STAT3, p38 MAP Kinase and NF-{kappa}B Drive Unopposed Monocyte-dependent Fibroblast MMP-1 Secretion in Tuberculosis.

Tissue destruction characterizes infection with Mycobacterium tuberculosis (Mtb). Type I collagen provides the lung's tensile strength, is extremely resistant to degradation, but is cleaved by matrix metalloproteinase (MMP)-1. Fibroblasts potentially secrete quantitatively more MMP-1 than other lung cells. We investigated mechanisms regulating Mtb-induced collagenolytic activity in fibroblasts in vitro and in patients. Lung fibroblasts were stimulated with conditioned media from Mtb-infected monocytes (CoMTb). CoMTb induced sustained increased MMP-1 (74 versus 16 ng/ml) and decreased tissue inhibitor of metalloproteinase (TIMP)-1 (8.6 versus 22.3 ng/ml) protein secretion. CoMTb induced a 2.7-fold increase in MMP-1 promoter activation and a 2.5-fold reduction in TIMP-1 promoter activation at 24 hours (P = 0.01). Consistent with this, TIMP-1 did not co-localize with fibroblasts in patient granulomas. MMP-1 up-regulation and TIMP-1 down-regulation were p38 (but not extracellular signal–regulated kinase or c-Jun N-terminal kinase) mitogen-activated protein kinase–dependent. STAT3 phosphorylation was detected in fibroblasts in vitro and in tuberculous granulomas.STAT3 inhibition reduced fibroblast MMP-1 secretion by 60% (P = 0.046). Deletion of the MMP-1 promoter NF-B–binding site abrogated promoter induction in response to CoMTb. TNF-, IL-1ß, or Oncostatin M inhibition in CoMTb decreased MMP-1 secretion by 65, 63, and 25%, respectively. This cytokine cocktail activated the same signaling pathways in fibroblasts and induced MMP-1 secretion similar to that induced by CoMTb. This study demonstrates in a cellular model and in patients with tuberculosis that in addition to p38 and NF-B, STAT3 has a key role in driving fibroblast-dependent unopposed MMP-1 production that may be key in tissue destruction in patients.

Comparison of weight in middle age, weight at 18 years, and weight change between, in predicting subsequent 14 year mortality and coronary events: Caerphilly Prospective Study

Objective-The prevalence of obesity is increasing in many European countries and in the United States. This report examines the mortality and morbidity associated with being overweight and obese in the Caerphilly Prospective Study and the relative effects of weight in middle age and self reported weight at 18 years.

Deforestation and apparent extinctions of endemic forest beetles in Madagascar

Madagascar has lost about half of its forest cover since 1953 with much regional variation, for instance most of the coastal lowland forests have been cleared. We sampled the endemic forest dwelling Helictopleurini dung beetles across Madagascar during 2002–2006. Our samples include 29 of the 51 previously known species for which locality information is available. The most significant factor explaining apparent extinctions (species not collected by us) is forest loss within the historical range of the focal species, suggesting that deforestation has already caused the extinction, or effective extinction, of a large number of insect species with small geographical ranges, typical for many endemic taxa in Madagascar. Currently, roughly 10% of the original forest cover remains. Species–area considerations suggest that this will allow roughly half of the species to persist. Our results are consistent with this prediction.

Variation in RTN3 and PPIL2 Genes Does not Influence Platelet Membrane β-Secretase Activity or Susceptibility to Alzheimer’s Disease in the Northern Irish Population

beta-site amyloid precursor protein cleaving enzyme (BACE1) is the rate-limiting enzyme for production of beta-amyloid peptides (A beta), which are proposed to drive the pathological changes found in Alzheimer's disease (AD). Reticulon 3 (RTN3) is a negative modulator of BACE1 (beta-secretase) proteolytic activity, while peptidylprolyl isomerase (cyclophilin)-like 2 (PPIL2) positively regulates BACE1 expression. The present study investigated whether there was any association between genetic variation in RTN3 and PPIL2, and either risk for AD, or levels of platelet beta-secretase activity, in a large Northern Irish case-control sample. Four hundred and sixty-nine patients with a diagnosis of probable AD (NINCDS-ADRDA criteria) and 347 control individuals (MMSE > 28/30) were genotyped. SNPs in both genes were selected by downloading genotype data from the International HapMap Project (Phase II) and tags selected using multimarker approach in Haploview, where r (2) > 0.8 and LOD > 3.0. Non-synonymous SNPs of interest were also included. Genotyping was performed by Sequenom iPLEX and TaqMan technologies. Alleles, genotypes and multi-marker haplotypes were tested for association with AD, and platelet beta-secretase activities were measured for a subset of individuals (n = 231). Eight SNPs in RTN3 and 7 in PPIL2 were genotyped. We found no significant associations between allele, genotype or haplotype frequencies and risk of AD. Further, there was no effect of genotype on platelet membrane beta-secretase activity. We conclude that common or potentially functional genetic variation in these BACE1 interacting proteins does not affect platelet membrane beta-secretase activity or contribute to risk of AD in this population.