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Background: Neurocysticercosis (NCC), and cystic echinococcosis (CE) are two neglected diseases caused by cestodes, co-endemic in many areas of the world. Imaging studies and serological tests are used in the diagnosis of both parasitic diseases, but cross-reactions may confound the results of the latter. The novel multiplex bead-based assay with recombinant antigens has been reported to increases the diagnostic accuracy of serological techniques., Methodology: We set-up an immunoassay based on the multiplex bead-based platform (MBA), using the rT24H (against Cysticercus cellulosae, causing cysticercosis) and r2B2t (against Echinococcus granulosus sensu lato, causing CE) recombinant antigens, for simultaneous and differential diagnosis of these infections. The antigens were tested on 356 sera from 151 patients with CE, 126 patients with NCC, and 79 individuals negative for both diseases. Specificity was calculated including sera from healthy donors, other neurological diseases and the respective NCC or CE sera counterpart. The diagnostic accuracy of this assay was compared with two commercial ELISA tests, Novalisa and Ridascreen, widely used in the routine diagnosis of cysticercosis and CE, respectively., Main Findings: For the diagnosis of NCC, sensitivity ranged from 57.94-63.49% for the rT24H-MBA, and 40.48-46.03% for Novalisa ELISA depending on exclusion or inclusion of sera having equivocal results on ELISA from the analysis; specificities ranged from 90.87-91.30% and 70.43-76.96%, respectively. AUC values of the ROC curve were 0.783 (rT24H) and 0.619 (Novalisa) (p-value < 0.001). For the diagnosis of CE, the sensitivity of the r2B2t-MBA ranged from 68.87-69.77% and of Ridascreen ELISA from 50.00-57.62%; specificities from 92.47-92.68% and from 74.15-80.98%, respectively. AUC values were 0.717 and 0.760, respectively., Conclusions/significance: Overall, the recombinant antigens tested with the bead-based technology showed better diagnostic accuracy than the commercial assays, particularly for the diagnosis of NCC. The possibility of testing the same serum sample simultaneously for the presence of antibodies against both antigens is an added value particularly in seroprevalence studies for cysticercosis linked to control programs in endemic areas where these two parasites coexist., Competing Interests: The authors have declared that no competing interests exist.

Neutral arenes such as benzene have never been considered suitable ligands for electropositive actinide cations, yet we find that even simple U III UX 3 aryloxide complexes such as U(ODipp) 3 bind and reduce arenes spontaneously at room temperature, forming inverse arene sandwich (IAS) complexes X n U(μ-C 6 D 6 )UX m (X = ODipp, n =2, m =3; X = OBMes 2 n=m=2 or 3) (ODipp = OC 6 H 3 i Pr 2 -2,6; Mes = 2,4,6-Me 3 -C 6 H 2 ). In some of these cases, further arene reduction has occured as a result of X ligand redistribution. These unexpected spontaneous reactions explain the anomalous spectra and reported lack of further reactivity of strongly reducing U III centers of U(ODipp) 3 . Phosphines that are not considered suitable ligands for actinides can catalyze the formation of the IAS complexes. This enables otherwise inaccessible asymmetric and less congested IAS complexes to be isolated and the bonding in this series compared.

Reelin is an extracellular glycoprotein that modulates neuronal function and synaptic plasticity in the adult brain. Decreased levels of Reelin activity have been postulated as a key factor during neurodegeneration in Alzheimer´s disease (AD) and in aging. Thus, changes in levels of full-length Reelin and Reelin fragments have been revealed in cerebrospinal fluid (CSF) and in post-mortem brains samples of AD patients with respect to non-AD patients. However, conflicting studies have reported decreased or unchanged levels of full-length Reelin in AD patients compared to control (nND) cases in post-mortem brains and CSF samples. In addition, a compelling analysis of Reelin levels in neurodegenerative diseases other than AD is missing. In this study, we analyzed brain levels of RELN mRNA and Reelin protein in post-mortem frontal cortex samples from different sporadic AD stages, Parkinson's disease with dementia (PDD), and Creutzfeldt-Jakob disease (sCJD), obtained from five different Biobanks. In addition, we measured Reelin protein levels in CSF samples of patients with mild cognitive impairment (MCI), dementia, or sCJD diagnosis and a group of neurologically healthy cases. The results indicate an increase in RELN mRNA in the frontal cortex of advanced stages of AD and in sCJD(I) compared to controls. This was not observed in PDD and early AD stages. However, Reelin protein levels in frontal cortex samples were unchanged between nND and advanced AD stages and PDD. Nevertheless, they decreased in the CSF of patients with dementia in comparison to those not suffering with dementia and patients with MCI. With respect to sCJD, there was a tendency to increase in brain samples in comparison to nND and to decrease in the CSF with respect to nND. In conclusion, Reelin levels in CSF cannot be considered as a diagnostic biomarker for AD or PDD. However, we feel that the CSF Reelin changes observed between MCI, patients with dementia, and sCJD might be helpful in generating a biomarker signature in prodromal studies of unidentified dementia and sCJD.

The boroxide ligand [OBAr2]- (Ar = Mes, Trip) is shown to be able to support both UIII and UIV centres for the first time. The synthesis and structures of homoleptic and heteroleptic UIII and UIV complexes are reported. The UX3 complex with larger substituents, [U(OBTrip2)3]2, exhibits greater thermal stability compared to less encumbered [U(OBMes2)3]2 but reacts with a smaller range of the small molecules tested to date. Initial studies on their capacity to participate in small molecule chemistry show that dark purple [U(OBMes2)3]2 binds and/or reductively activates a variety of small molecules such as pyridine-oxide, triphenylphosphineoxide, sulfur, and dicyclohexylcarbodiimide. While [U(OBMes2)3]2 shows no reaction with CO or CO2, [U(OBTrip2)3]2 is oxidised by both, in the former case forming [U(OBTrip2)4], and in the latter case forming a small quantity of the structurally characterised μ-carbonate product [(μ-CO3){U(OBTrip2)3}2].

The cellular prion protein, encoded by the gene Prnp, has been reported to be a receptor of β-amyloid. Their interaction is mandatory for neurotoxic effects of β-amyloid oligomers. In this study, we aimed to explore whether the cellular prion protein participates in the spreading of α-synuclein. Results demonstrate that Prnp expression is not mandatory for α-synuclein spreading. However, although the pathological spreading of α-synuclein can take place in the absence of Prnp, α-synuclein expanded faster in PrP C -overexpressing mice. In addition, α-synuclein binds strongly on PrP C -expressing cells, suggesting a role in modulating the effect of α-synuclein fibrils.

Reelin is an extracellular glycoprotein involved in key cellular processes in developing and adult nervous system, including regulation of neuronal migration, synapse formation, and plasticity. Most of these roles are mediated by the intracellular phosphorylation of disabled-1 (Dab1), an intracellular adaptor molecule, in turn mediated by binding Reelin to its receptors. Altered expression and glycosylation patterns of Reelin in cerebrospinal and cortical extracts have been reported in Alzheimer's disease. However, putative changes in Reelin are not described in natural prionopathies or experimental models of prion infection or toxicity. With this is mind, in the present study, we determined that Reelin protein and mRNA levels increased in CJD human samples and in mouse models of human prion disease in contrast to murine models of prion infection. However, changes in Reelin expression appeared only at late terminal stages of the disease, which prevent their use as an efficient diagnostic biomarker. In addition, increased Reelin in CJD and in in vitro models does not correlate with Dab1 phosphorylation, indicating failure in its intracellular signaling. Overall, these findings widen our understanding of the putative changes of Reelin in neurodegeneration.

The term 'prion-like' is used to define some misfolded protein species that propagate intercellularly, triggering protein aggregation in recipient cells. For cell binding, both direct plasma membrane interaction and membrane receptors have been described for particular amyloids. In this respect, emerging evidence demonstrates that several β-sheet enriched proteins can bind to the cellular prion protein (PrP C ). Among other interactions, the physiological relevance of the binding between β-amyloid and PrP C has been a relevant focus of numerous studies. At the molecular level, published data point to the second charged cluster domain of the PrP C molecule as the relevant binding domain of the β-amyloid/PrP C interaction. In addition to β-amyloid, participation of PrP C in binding α-synuclein, responsible for neurodegenerative synucleopathies, has been reported. Although results indicate relevant participation of PrP C in the spreading of α-synuclein in living mice, the physiological relevance of the interaction remains elusive. In this comment, we focus our attention on summarizing current knowledge of PrP C as a receptor for amyloid proteins and its physiological significance, with particular focus on α-synuclein.

Background: Total shoulder arthroplasty (TSA) is an effective treatment for painful glenohumeral arthritis, but its morbidity has not been thoroughly documented., Methods: The National Surgical Quality Improvement Program database was queried to identify all patients undergoing primary TSA between 2006 and 2011, with extraction of selected patient-based or surgical variables and 30-day clinical course. Postoperative complications were stratified as major systemic, minor systemic, major local, and minor local, and mortality was recorded. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were derived from bivariate and multivariable analysis to express the association between risk factors and clinical outcomes., Results: Among the 2004 patients identified, the average age was 69 years, and 57% were women. Obesity was present in 46%, and 48% had an American Society of Anesthesiologists classification of ≥3. The 30-day mortality and total complication rates were 0.25% and 3.64%, respectively. Comorbid cardiac disease (OR, 85.31; 95% CI, 8.15, 892.84) and increasing chronologic age (OR, 1.19; 95% CI, 1.06, 1.33) were independent predictors of mortality, whereas peripheral vascular disease was associated with statistically significant increase in any complication (OR, 6.25; 95% CI, 1.24, 31.40). Operative time >174 minutes was an independent predictor for development of a major local complication (OR, 4.05; 95% CI, 1.45, 11.30). Obesity was not associated with any specified complication after controlling for other variables., Conclusions: Whereas TSA has low short-term rates of perioperative complications and mortality, careful perioperative medical optimization and efficient surgical technique should be emphasized to decrease morbidity and mortality., (Published by Elsevier Inc.)

Eight normal cadaveric knee specimens were used to evaluate the effects of femoral and tibial tunnel positions on length excursions of a single wire and bone-patellar tendon-bone graft as measured by an isometer. Femoral attachment sites were varied by using a commercially available femoral pin guide with either a 5.5- or 7.0-mm offset and by aiming with the guide oriented vertically (12:00 notch position) or rotating 45 degrees toward the lateral condyle (1:30 or 10:30 notch position depending on right or left knee). Tibial isometry was altered by testing the wire against the posterior tunnel wall or 5-mm anterior using a custom centering device. Isometry was measured from 0 degrees to 120 degrees for each position tested. A 7-mm offset guide rotated to the 12:00 position yielded the best single fiber and graft excursion patterns (P < .05). A 5.5-mm offset guide yielded inferior single fiber and graft excursion patterns. Single fiber and graft isometry were found to be similar, but not identical in endoscopic anterior cruciate ligament reconstruction. Centering the single fiber in the tibial tunnel had little effect on excursion patterns, showing that the more posterior tibial positions needed for endoscopic reconstruction are acceptable from an isometry standpoint.

The effect of femoral guide rotation in endoscopic anterior cruciate ligament (ACL) reconstruction is reviewed based on a previous report. The effect of varied offsets of the femoral guide (5.5 and 7.0 mm) are described. This is one of the few isometry studies to evaluate the knee through a practically full range of motion (0 degree-120 degrees). A 7-mm offset guide rotated to the 12:00 position yields the best single fiber and graft excursion patterns (P < 0.05). A 5.5-mm offset guide yields inferior single fiber and graft excursion patterns. Single fiber and graft isometry are similar but not identical in endoscopic ACL reconstruction. Centering the single fiber in the tibial tunnel has little effect on isometry patterns, demonstrating that the more posterior tibial positions needed for endoscopic reconstruction are acceptable from an isometry standpoint.