Do COX-2 inhibitors worsen renal function?

No, COX-2 inhibitors, as a class, do not worsen renal function for those without renal disease. Celecoxib is the only COX-2 inhibitor available, and it is associated with a lower risk of renal dysfunction and hypertension when compared with controls. Available data do not allow for adjusted risk assessment for patients with preexisting renal disease on COX-2 inhibitors (strength of recommendation [SOR]: A, based on meta-analysis)

Toward a Model for Fisheries Social Impact Assessment

This paper presents a model for Fisheries Social Impact Assessment (SIA) that lays the groundwork for development of fisheries-focused, quantitative social assessments with a clear conceptual model. The usefulness of current fisheries SIA’s has been called into question by some as incompatible with approaches taken by fisheries biologists and economists when assessing potential effects of management actions. Our model’s approach is closer to the economists’ and biologists’ assessments and is therefore more useful for Fishery Management Council members. The paper was developed by anthropologists initially brought together in 2004 for an SIA Modeling Workshop by the National Marine Fisheries Service, NOAA. Opinions and conclusions expressed or implied are solely those of the authors and do not necessarily reflect the views or policy of the National Marine Fisheries Service, NOAA

What is the best test to detect herpes in skin lesions?

Polymerase chain reaction (PCR) techniques appear to be more sensitive and specific in detecting herpes simplex virus (HSV) in genital lesions (strength of recommendation [SOR]: A, based on 2 diagnostic cohort studies); however, viral culture remains the gold standard (SOR: C, based on expert opinion). Studies of serologic and antibody detection tests report higher sensitivities than viral culture (SOR: C, based on consensus guidelines). Cytologic tests such as the Tzanck smear and Papanicolaou (Pap) smear have poor sensitivities and specificities and should not be relied upon for a diagnosis of genital herpes (SOR: C, based on expert opinion)

How should we manage a patient with a positive PPD and prior BCG vaccination?

Prior bacille Calmette-Guérin (BCG) vaccination increases the likelihood of a positive tuberculosis (TB) 5TU purified protein derivative (PPD) skin test. The PPD response following BCG vaccine varies with age at vaccination, number of years since the BCG vaccination, number of times vaccinated, and number of PPDs performed. An induration of greater than 14 mm is unlikely to be due to prior BCG vaccination (strength of recommendation [SOR]: A, based on meta-analysis of validation cohort studies)

Treatment of Hyperhidrosis

OnabotulinumtoxinA injections (Botox; formerly botulinum toxin type A) are effective for the treatment of primary axillary and palmar hyperhidrosis. (Strength of Recommendation [SOR]: A, based on a systematic review of randomized controlled trials). Topical aluminum chloride (Drysol) is effective for the treatment of palmar hyperhidrosis. (SOR: B, based on one small controlled study). Iontophoresis is effective for treating palmar, plantar, and axillary hyperhidrosis. (SOR: C, based on one unblinded, randomized controlled trial). There are no identified randomized, placebo-controlled trials of thoracoscopic sympathectomy or systemic medical therapy for the treatment of hyperhidrosis

A TPX2 Proteomimetic Has Enhanced Affinity for Aurora-A Due to Hydrocarbon Stapling of a Helix

Inhibition of protein kinases using ATP-competitive compounds is an important strategy in drug discovery. In contrast, the allosteric regulation of kinases through the disruption of protein-protein interactions has not been widely adopted, despite the potential for selective targeting. Aurora-A kinase regulates mitotic entry and mitotic spindle assembly and is a promising target for anticancer therapy. The microtubule-associated protein TPX2 activates Aurora-A through binding to two sites. Aurora-A recognition is mediated by two motifs within the first 43 residues of TPX2, connected by a flexible linker. To characterize the contributions of these three structural elements, we prepared a series of TPX2 proteomimetics and investigated their binding affinity for Aurora-A using isothermal titration calorimetry. A novel stapled TPX2 peptide was developed that has improved binding affinity for Aurora-A and mimics the function of TPX2 in activating Aurora-A's autophosphorylation. We conclude that the helical region of TPX2 folds upon binding Aurora-A, and that stabilization of this helix does not compromise Aurora-A activation. This study demonstrates that the preparation of these proteomimetics using modern synthesis methods is feasible and their biochemical evaluation demonstrates the power of proteomimetics as tool compounds for investigating PPIs involving intrinsically disordered regions of proteins

Water quality impacts and river system recovery following the 2014 Mount Polley mine tailings dam spill, British Columbia, Canada

The Mount Polley mine tailings embankment breach on August 4th 2014, in British Columbia, Canada, is the second largest mine waste spill on record. The mine operator responded swiftly by removing significant quantities of tailings from the primary receiving watercourse, stabilizing the river corridor and beginning construction of a new river channel. This presented a unique opportunity to study spatial patterns of element cycling in a partially-restored and alkaline river system. Overall, water quality impacts are considered low with Cu, and to a lesser extent V, being the only elements of concern. However, the spatial pattern of stream Cu loading suggested chemical (dominant at low flow) and physical (dominant at high flow) mobilization processes operating in different parts of the watershed. Chemical mobilization was hypothesized to be due to Cu sulfide (chalcopyrite) oxidation in riparian tailings and reductive dissolution of Cu-bearing Fe oxides in tailings and streambed sediments whereas physical mobilization was due to erosion and suspension of Cu-rich stream sediments further downstream. Although elevated aqueous Cu was evident in Hazeltine Creek, this is considered a relatively minor perturbation to a watershed with naturally elevated stream Cu concentrations. The alkaline nature of the tailings and the receiving watercourse ensures most aqueous Cu is rapidly complexed with dissolved organic matter or precipitates as secondary mineral phases. Our data highlights how swift removal of spilled tailings and river corridor stabilization can limit chemical impacts in affected watersheds but also how chemical mobilization (of Cu) can still occur when the spilled tailings and the receiving environment are alkaline. We present a conceptual model of Cu cycling in the Hazeltine Creek watershed.publishersversionPeer reviewe

Limited historical admixture between European wildcats and domestic cats

Domestic cats were derived from the Near Eastern wildcat (Felis lybica), after which they dispersed with people into Europe. As they did so, it is possible that they interbred with the indigenous population of European wildcats (Felis silvestris). Gene flow between incoming domestic animals and closely related indigenous wild species has been previously demonstrated in other taxa, including pigs, sheep, goats, bees, chickens, and cattle. In the case of cats, a lack of nuclear, genome-wide data, particularly from Near Eastern wildcats, has made it difficult to either detect or quantify this possibility. To address these issues, we generated 75 ancient mitochondrial genomes, 14 ancient nuclear genomes, and 31 modern nuclear genomes from European and Near Eastern wildcats. Our results demonstrate that despite cohabitating for at least 2,000 years on the European mainland and in Britain, most modern domestic cats possessed less than 10% of their ancestry from European wildcats, and ancient European wildcats possessed little to no ancestry from domestic cats. The antiquity and strength of this reproductive isolation between introduced domestic cats and local wildcats was likely the result of behavioral and ecological differences. Intriguingly, this long-lasting reproductive isolation is currently being eroded in parts of the species’ distribution as a result of anthropogenic activities