Homotypic antibodies target novel E glycoprotein domains after natural DENV 3 infection/vaccination.

The envelope (E) glycoprotein is the primary target of type-specific (TS) neutralizing antibodies (nAbs) after infection with any of the four distinct dengue virus serotypes (DENV1-4). nAbs can be elicited to distinct structural E domains (EDs) I, II, or III. However, the relative contribution of these domain-specific antibodies is unclear.

Dengue virus 4/2 envelope domain chimeric virus panel maps type-specific responses against dengue serotype 2.

The four dengue virus (DENV) serotypes infect several hundred million people each year. Although primary infection is generally mild, subsequent infection by differing serotypes increases the risk for symptomatic disease ranging from fever to life-threatening shock. Despite the availability of licensed vaccines, a comprehensive understanding of antibodies that target the viral envelope protein and protect from infection remains incomplete.

A live dengue virus vaccine carrying a chimeric envelope glycoprotein elicits dual DENV2-DENV4 serotype-specific immunity.

The four dengue virus serotypes co-circulate globally and cause significant human disease. Dengue vaccine development is challenging because some virus-specific antibodies are protective, while others are implicated in enhanced viral replication and more severe disease. Current dengue tetravalent vaccines contain four live attenuated serotypes formulated to theoretically induce balanced protective immunity.

Vaccine-induced antibodies to contemporary strains of dengue virus type 4 show a mechanistic correlate of protective immunity.

The four dengue virus serotypes (DENV1-4) are mosquito-borne flaviviruses of humans. Several live-attenuated tetravalent DENV vaccines are at different stages of clinical development and approval. In children with no baseline immunity to DENVs, a leading vaccine (Dengvaxia) is efficacious against vaccine-matched DENV4 genotype II (GII) strains but not vaccine-mismatched DENV4 GI viruses.

Dengue vaccine breakthrough infections reveal properties of neutralizing antibodies linked to protection.

The 4 serotypes of dengue virus (DENV1-4) are mosquito-borne flaviviruses that infect humans. Live attenuated tetravalent DENV vaccines are at different phases of clinical testing. DENV vaccine developers have relied on neutralizing antibodies (NAbs) as a correlate of protection.

Defining levels of dengue virus serotype-specific neutralizing antibodies induced by a live attenuated tetravalent dengue vaccine (TAK-003).

The four dengue virus serotypes (DENV1-4) infect several hundred million people each year living in tropical and sub-tropical regions. Clinical development of DENV vaccines is difficult because immunity to a single serotype increases risk of severe disease during a second infection with a new serotype. Leading vaccines are based on tetravalent formulations to induce simultaneous and balanced protective immunity to all 4 serotypes.

Screening for Atrial Fibrillation in the Older Population: A Randomized Clinical Trial.

Importance: Atrial fibrillation (AF) is a major cause of preventable strokes. Screening asymptomatic individuals for AF may increase anticoagulant use for stroke prevention.

Objective: To evaluate 2 home-based AF screening interventions.

Foucault pendulum properties of spherical oscillators.

The Foucault pendulum provides a demonstration of the turning of the Earth. The principle at work is that linear oscillations of a two-degree-of-freedom isotropic harmonic oscillator remain unchanged in an inertial frame of reference, so appear to precess in a rotating frame of reference. In recent work, we applied two-degree-of-freedom isotropic oscillators to mechanical timekeeping.

Prevalence of undiagnosed atrial fibrillation in elderly individuals and potential cost-effectiveness of non-invasive ambulatory electrocardiographic screening: The ASSERT-III study.

Background: In approximately 10% of patients with implanted pacemakers or defibrillators, previously unrecognized atrial fibrillation (AF) is detected within 3 months. It is unknown whether elderly patients without implanted devices have a similar prevalence of undiagnosed AF using non-invasive ECG monitoring, and if this approach to screening in this population is cost-effective.

Methods: Individuals ≥80 years old attending outpatient clinics without a history of AF and with hypertension and one additional risk factor underwent 30 days of continuous ECG monitoring with an option for an additional 30 days of monitoring if no AF was detected.

Antibody persistence and booster response in adolescents and young adults 4 and 7.5 years after immunization with 4CMenB vaccine.

Background: Data on duration of protection against invasive meningococcal disease post-vaccination with the recombinant, 4-component, meningococcal serogroup B vaccine (4CMenB) are limited. We evaluated bactericidal activity persistence in adolescents/young adults up to 7.5 years post-primary vaccination with 4CMenB, and response to a booster dose compared with vaccine-naïve controls.

Is Screening for Atrial Fibrillation in Canadian Family Practices Cost-Effective in Patients 65 Years and Older?

We present an economic evaluation of a recently completed cohort study in which 2054 seniors were screened for atrial fibrillation (AF) in 22 Canadian family practices. Using a Markov model, trial and literature data were used to project long-term outcomes and costs associated with 4 AF screening strategies for individuals aged 65 years or older: no screening, screen with 30-second radial manual pulse check (pulse check), screen with a blood pressure machine with AF detection (BP-AF), and screen with a single-lead electrocardiogram (SL-ECG). Costs and outcomes were discounted at 1.

Diagnostic accuracy and yield of screening tests for atrial fibrillation in the family practice setting: a multicentre cohort study.

Background: Detection of undiagnosed or undertreated ("actionable") atrial fibrillation could increase the use of appropriate oral anticoagulant therapy and reduce the risk of stroke. We sought to compare newer screening technologies with a pulse-check for the detection of atrial fibrillation and to determine whether the detection of actionable atrial fibrillation increases the use of oral anticoagulant agents.

Methods: This prospective multicentre cohort study involved 22 primary care clinics.

Analyzing the Human Serum Antibody Responses to a Live Attenuated Tetravalent Dengue Vaccine Candidate.

Background: Dengue virus serotypes 1-4 (DENV-1-4) are the most common vector-borne viral pathogens of humans and the etiological agents of dengue fever and dengue hemorrhagic syndrome. A live-attenuated tetravalent dengue vaccine (TDV) developed by Takeda Vaccines has recently progressed to phase 3 safety and efficacy evaluation.

Methods: We analyzed the qualitative features of the neutralizing antibody (nAb) response induced in naive and DENV-immune individuals after TDV administration.

Delineating the serotype-specific neutralizing antibody response to a live attenuated tetravalent dengue vaccine.

The dengue virus (DENV) vaccines that are licensed or in clinical development consist of DENV serotype 1-4 tetravalent formulations given simultaneously and are not acquired sequentially like natural infections. It is unclear what effect this has on development of protective levels of immunity to all four serotypes. Serotype-specific neutralizing antibody (NAb) is considered the most relevant correlate of protection from dengue disease.

Dissecting Antibodies Induced by a Chimeric Yellow Fever-Dengue, Live-Attenuated, Tetravalent Dengue Vaccine (CYD-TDV) in Naive and Dengue-Exposed Individuals.

Sanofi Pasteur has developed a chimeric yellow fever-dengue, live-attenuated, tetravalent dengue vaccine (CYD-TDV) that is currently approved for use in several countries. In clinical trials, CYD-TDV was efficacious at reducing laboratory-confirmed cases of dengue disease. Efficacy varied by dengue virus (DENV) serotype and prevaccination dengue immune status.

Surgical Anatomy of the Human Round Window Region: Implication for Cochlear Endoscopy Through the External Auditory Canal.

Objective: To enable development of an endoscope for cellular-level optical imaging of the inner ear.

Study Design: A prospective study of 50 cadaveric human temporal bones to define detailed surgical anatomy of the round window (RW) region and the range of angles necessary to reach the RW membrane perpendicularly via the external ear canal.

Main Outcome Measure: The transcanal angle to the RW membrane was surgically measured in 3D intact specimens, and correlated with the angle calculated from temporal bone computed tomography (CT) scans of the same specimens obtained before and after measurements in situ.

Controlled-release oxycodone and naloxone in the treatment of chronic low back pain: a placebo-controlled, randomized study.

Background: For Canadian regulatory purposes, an analgesic study was required to complement previously completed, pivotal studies on bowel effects and analgesia associated with controlled-release (CR) oxycodone⁄CR naloxone.

Objectives: To compare the analgesic efficacy and safety of CR oxycodone⁄CR naloxone versus placebo in patients with chronic low back pain.

Methods: Patients requiring opioid therapy underwent a two- to seven-day opioid washout before being randomly assigned to receive either 10 mg⁄5 mg CR oxycodone⁄CR naloxone or placebo every 12 h, titrated weekly according to efficacy and tolerability to 20 mg⁄10 mg, 30 mg⁄15 mg or 40 mg⁄20 mg every 12 h.

Fiberoptic bronchoscopy in the presence of space-occupying intracranial lesions.

The performance of flexible fiberoptic bronchoscopy (FFB) has anecdotally been considered to carry a high risk of neurologic complications in patients with raised intracranial pressure (ICP). There is no evidence in the literature to support this concern. We evaluated this risk by reviewing hospital records of 132 patients who underwent FFB and computer tomography of the central nervous system (CNS-CT) during the same hospitalization.

Nontuberculous mycobacterial infection of the central nervous system in patients with AIDS.

Infections due to nontuberculous mycobacteria (NTM) are especially common in patients with AIDS. Meningitis due to NTM, however, is rare. A search for CSF cultures positive for NTM over the past 11 years at our hospital yielded 16 cases.