Delaying aging in Caenorhabditis elegans with protein aggregation inhibitors.

Recent evidence suggests that during aging there is widespread accumulation of aggregated insoluble proteins, even in the absence of pathological conditions. Pharmacological manipulation of protein aggregation might be helpful to unveil the involvement of protein aggregates during aging, as well as to develop novel strategies to delay aging. Here we investigated the effect of known protein aggregation inhibitors on the lifespan and health-span of Caenorhabditis elegans.

Comparison of SemiQuantitative Cotinine Values Obtained by the DRI Immunoassay and Values Obtained by a Liquid Chromatography-Tandem Mass Spectrometry-Based Method: The DRI Immunoassay is Suitable for Screening Purposes Only Because Semiquantitative Values May Be Unreliable.

Background: DRI cotinine assay is suitable only for screening for cotinine in urine specimens. We studied the reliability of DRI cotinine semiquantitative values by comparing them with the cotinine concentration obtained with a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method.

Methods: Semiquantitative cotinine concentrations in 39 urine specimens obtained by the DRI immunoassay were compared with cotinine concentrations obtained by LC-MS/MS.

External Mechanical Devices and Vascular Surgery for Erectile Dysfunction.

Introduction: The field of sexual medicine is continuously advancing, with novel outcomes reported on a regular basis. Given the rapid evolution, updated guidelines are essential to inform practicing clinicians on best practices.

Aim: To summarize the current literature and provide clinical guidelines on penile traction therapy, vacuum erection devices, and penile revascularization.

Cryo-EM Structure of Caspase-8 Tandem DED Filament Reveals Assembly and Regulation Mechanisms of the Death-Inducing Signaling Complex.

Caspase-8 activation can be triggered by death receptor-mediated formation of the death-inducing signaling complex (DISC) and by the inflammasome adaptor ASC. Caspase-8 assembles with FADD at the DISC and with ASC at the inflammasome through its tandem death effector domain (tDED), which is regulated by the tDED-containing cellular inhibitor cFLIP and the viral inhibitor MC159. Here we present the caspase-8 tDED filament structure determined by cryoelectron microscopy.

Suitability of the DRI Hydrocodone/Hydromorphone Immunoassay in the Clinical Environment at a Lower Cutoff: Validation With LC-MS/MS Analysis.

Background: We evaluated the analytical performance of the DRI hydrocodone/hydromorphone assay by comparing semiquantitative values obtained by this assay with values obtained by a liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) method. We also evaluated the possibility of lowering the cutoff of the DRI assay from 300 to 100 ng/mL.

Methods: We compared semiquantitative values obtained by the DRI assay in 97 specimens with values obtained by the LC-MS/MS method including 10 specimens containing hydrocodone and/or hydromorphone concentrations between 105.

Therapeutic Drug Monitoring of Mycophenolic Acid.

Mycophenolic acid (MPA) is an immunosuppressant requiring therapeutic drug monitoring. Although immunoassays are commercially available, there is significant positive bias using this approach when compared to high-performance liquid chromatography or LC combined with mass spectrometry (LC/MS) or tandem mass spectrometry (LC/MS/MS). Positive bias is due to variable cross-reactivity of MPA acyl glucuronide with antibodies traditionally used in immunoassay formats.

Management of Head Louse Infestations in the United States-A Literature Review.

Unlabelled: Head lice are a source of scalp irritation, social disruption, and loss of school time. Health care providers need authoritative information to help avoid the costs and risks of ineffective treatment. A review was completed to provide relevant information on infestation treatments available in the United States.

Variation in high-priority drug-drug interaction alerts across institutions and electronic health records.

Objective: The United States Office of the National Coordinator for Health Information Technology sponsored the development of a "high-priority" list of drug-drug interactions (DDIs) to be used for clinical decision support. We assessed current adoption of this list and current alerting practice for these DDIs with regard to alert implementation (presence or absence of an alert) and display (alert appearance as interruptive or passive).

Materials And Methods: We conducted evaluations of electronic health records (EHRs) at a convenience sample of health care organizations across the United States using a standardized testing protocol with simulated orders.

Erythrocytes do not activate purified and platelet soluble guanylate cyclases even in conditions favourable for NO synthesis.

Background: Direct interaction between Red blood cells (RBCs) and platelets is known for a long time. The bleeding time is prolonged in anemic patients independent of their platelet count and could be corrected by transfusion of RBCs, which indicates that RBCs play an important role in hemostasis and platelet activation. However, in the last few years, opposing mechanisms of platelet inhibition by RBCs derived nitric oxide (NO) were proposed.

Extended Use of Hypothermia in Elderly Patients with Malignant Cerebral Edema as an Alternative to Hemicraniectomy.

Background And Purpose: The use of decompressive hemicraniectomy (DHC) for the treatment of malignant cerebral edema can decrease mortality rates. However, this benefit is not sufficient to justify its use in elderly patients. We investigated the effects of therapeutic hypothermia (TH) on safety, feasibility, and functional outcomes in elderly patients with malignant middle cerebral artery (MCA) infarcts.

Structural Insight into Substrate Selection and Catalysis of Lipid Phosphate Phosphatase PgpB in the Cell Membrane.

PgpB belongs to the lipid phosphate phosphatase protein family and is one of three bacterial integral membrane phosphatases catalyzing dephosphorylation of phosphatidylglycerol phosphate (PGP) to generate phosphatidylglycerol. Although the structure of its apo form became recently available, the mechanisms of PgpB substrate binding and catalysis are still unclear. We found that PgpB was inhibited by phosphatidylethanolamine (PE) in a competitive mode in vitro Here we report the crystal structure of the lipid-bound form of PgpB.

Novel use of non-ablative fractional photothermolysis for café-au-lait macules in darker skin types.

Importance: The removal of café-au-lait macules (CALMs) in patients with darker skin phototypes poses a significant challenge due to limited available therapeutic options and increased risk of adverse effects, including permanent scarring and further dyspigmentation. Herein, we demonstrate the novel use of non-ablative fractional photothermolysis for the safe removal of CALMs in individuals with Fitzpatrick skin type (FST) IV-V.

Observations: Retrospective analysis of four patients (FST IV-V) with CALMs revealed that three of these patients had greater than 50% clearance after multiple treatment sessions with the non-ablative fractional 1,550-nm erbium-doped fiber laser.

Effect of Carbamazepine 10, 11-Epoxide on Serum Carbamazepine Measurement Using a New CMIA Assay: Comparison of Values Obtained by Using PETINIA, CEDIA and Liquid Chromatography Combined with Tandem Mass Spectrometry.

Background: Carbamazepine is a classical anticonvulsant that requires therapeutic drug monitoring. We evaluated the effect of carbamazepine 10, 11 epoxide on a new chemiluminescent immunoassay (CMIA) for application on the Architect i1000SR analyzer.

Materials And Methods: Carbamazepine concentrations were measured in 40 specimens collected from patients taking carbamazepine using a PETINIA assay (Vista 1500 analyzer), a CEDIA assay (Cobas c501 analyzer) and the new CMIA assay (Architect i1000 analyzer).

Systematic review of published trials: long-term safety of topical corticosteroids and topical calcineurin inhibitors in pediatric patients with atopic dermatitis.

Background: Many clinicians have concerns about the safety of atopic dermatitis (AD) treatments, particularly in children requiring long-term daily maintenance therapy. Topical corticosteroids (TCS) have been widely used for >5 decades. Long-term TCS monotherapy has been associated with adverse cutaneous effects including atrophy, rebound flares, and increased percutaneous absorption with potential for adverse systemic effects.

Mechanistic Study of the Conversion of Superoxide to Oxygen and Hydrogen Peroxide in Carbon Nanoparticles.

Hydrophilic carbon clusters (HCCs) are oxidized carbon nanoparticles with a high affinity for electrons. The electron accepting strength of HCCs, employing the efficient conversion of superoxide (O2(•-)) to molecular oxygen (O2) via single-electron oxidation, was monitored using cyclic voltammetry and electron paramagnetic resonance spectroscopy. We found that HCCs possess O2 reduction reaction (ORR) capabilities through a two-electron process with the formation of H2O2.

Activation of the pluripotency factor OCT4 in smooth muscle cells is atheroprotective.

Although somatic cell activation of the embryonic stem cell (ESC) pluripotency factor OCT4 has been reported, this previous work has been controversial and has not demonstrated a functional role for OCT4 in somatic cells. Here we demonstrate that smooth muscle cell (SMC)-specific conditional knockout of Oct4 in Apoe(-/-) mice resulted in increased lesion size and changes in lesion composition that are consistent with decreased plaque stability, including a thinner fibrous cap, increased necrotic core area, and increased intraplaque hemorrhage. Results of SMC-lineage-tracing studies showed that these effects were probably the result of marked reductions in SMC numbers within lesions and SMC investment within the fibrous cap, which may result from impaired SMC migration.

A review on the role of moisturizers for atopic dermatitis.

Effective management of atopic dermatitis (AD) involves the treatment of a defective skin barrier. Patients with AD are therefore advised to use moisturizers regularly. To date, there are few comparative studies involving moisturizers in patients with AD, and no classification system exists to objectively determine which types of moisturizers are best suited to specific AD phenotypes.

Analytical Performance Evaluation of a New Cobas Tacrolimus Assay on Cobas e411 Analyzer: Comparison of Values Obtained by the CMIA Tacrolimus Assay and a Liquid Chromatography Combined with Tandem Mass Spectrometric Method.

Background: Recently Roche Diagnostics (Indianapolis, IN) developed Cobas tacrolimus assay (currently for investigational use only in U.S) for application on multiple platforms including Cobas e 411 analyzer. We evaluated analytic performance of this new assay.

The stress of prion disease.

Prion diseases are fatal neurodegenerative disorders that include scrapie of sheep, bovine spongiform encephalopathy of cattle, chronic wasting disease of cervids, and Creutzfeldt-Jakob disease (CJD) of humans. The etiology for prion diseases can be infectious, sporadic, or hereditary. However, the common denominator for all types is the formation of a transmissible agent composed of a β-sheet-rich, misfolded version of the host-encoded prion protein (PrP), known as PrP.

Role of Prion Replication in the Strain-dependent Brain Regional Distribution of Prions.

One intriguing feature of prion diseases is their strain variation. Prion strains are differentiated by the clinical consequences they generate in the host, their biochemical properties, and their potential to infect other animal species. The selective targeting of these agents to specific brain structures have been extensively used to characterize prion strains.

Hypertrichotic Becker's nevi treated with combination 1,550 nm non-ablative fractional photothermolysis and laser hair removal.

Background: The removal of Becker's nevi poses a significant challenge due to limited available therapeutic options and increased risk of adverse effects, including scarring and dyspigmentation. Herein, we present the use of the non-ablative fractional photothermolysis in combination with laser hair removal for the treatment of hypertrichotic Becker's nevi.

Method: Retrospective analysis of three patients with Becker's nevi revealed that two patients with hypertrichotic Becker's nevi had greater than 75% clearance with combination therapy, and one patient with atrichotic Becker's nevus had a similar result with monotherapy non-ablative fractional photothermolysis.

An injectable nanoparticle generator enhances delivery of cancer therapeutics.

The efficacy of cancer drugs is often limited because only a small fraction of the administered dose accumulates in tumors. Here we report an injectable nanoparticle generator (iNPG) that overcomes multiple biological barriers to cancer drug delivery. The iNPG is a discoidal micrometer-sized particle that can be loaded with chemotherapeutics.

CnaA domains in bacterial pili are efficient dissipaters of large mechanical shocks.

Pathogenic bacteria adhere despite severe mechanical perturbations induced by the host, such as coughing. In Gram-positive bacteria, extracellular protein appendages termed pili are necessary for adherence under mechanical stress. However, little is known about the behavior of Gram-positive pili under force.