Development of a Highly Multiplexed RT-LAMP Assay for Coverage of Genetic Sequence Diversity.

Nucleic acid amplification tests (NAATs) can achieve high accuracy for diagnosing infectious diseases by targeting conserved genetic sequences specific to the target organism. Isothermal NAATs, such as reverse-transcription loop mediated isothermal amplification (RT-LAMP), simplify instrumentation requirements, facilitating point-of-care testing. However, sequence variation due to genetic variability can cause false negative results.

Within-Host Rhinovirus Evolution in Upper and Lower Respiratory Tract Highlights Capsid Variability and Mutation-Independent Compartmentalization.

Background: Rhinovirus (RV) infections can progress from the upper (URT) to lower (LRT) respiratory tract in immunocompromised individuals, causing high rates of fatal pneumonia. Little is known about how RV evolves within hosts during infection.

Methods: We sequenced RV complete genomes from 12 hematopoietic cell transplant patients with infection for up to 190 days from both URT (nasal wash, NW) and LRT (bronchoalveolar lavage, BAL).

Determining mushroom tyrosinase inhibition by imidazolium ionic liquids: A spectroscopic and molecular docking study.

The inhibition effects of imidazolium ionic liquids (ILs) on the enzyme kinetics of mushroom tyrosinase is reported. A simple UV-VIS spectrophotometric assay was used to measure the reaction kinetics of the reaction between mushroom tyrosinase and L-dopa. Seven different imidazolium ILs, comprised of 1-alkyl-3-methylimidazolium ([Im], n=2, 4, 6) cations paired with several anions that included Cl, [NO], methanesulfonate ([MeSO]), trifluoromethanesulfonate (or triflate, [TFMS]), and bis(trifluoromethylsulfonyl)imide ([TfN]).

Retaining clinician-scientists: nature versus nurture.

In their IOVS article "Rejuvenating Clinician-Scientist Training" (published March 28, 2014), Balamurali Ambati and Judd Cahoon rightly point out the dearth of new clinician-scientists in ophthalmology. Within the context of their suggestions for increasing the number of successful clinician-scientists, they claim that the traditional MD-PhD training programs and K awards have failed to produce individuals who will carry on the important work of clinically relevant research that will improve patients' lives and sight. In this response we present data, including information on the career paths of graduates of the Washington University ophthalmology residency, that call into question the presumed failure of MD-PhD and K award programs and show that, in fact, graduates of these programs are more likely to succeed as clinician-scientists than are their peers who have not trained in such scientifically rigorous environments.

Comparison of vertical and horizontal saccade measures and their relation to gray matter changes in premanifest and manifest Huntington disease.

Saccades are a potentially important biomarker of Huntington disease (HD) progression, as saccadic abnormalities can be detected both cross-sectionally and longitudinally. Although vertical saccadic impairment was reported decades ago, recent studies have focused on horizontal saccades. This study investigated antisaccade (AS) and memory guided saccade (MG) impairment in both the horizontal and vertical directions in individuals with the disease-causing CAG expansion (CAG+; n = 74), using those without the expansion (CAG-; n = 47) as controls.

Progression in prediagnostic Huntington disease.

Objective: To examine rates of decline in individuals at risk for Huntington disease (HD).

Methods: 106 individuals at risk for HD completed a battery of neurocognitive, psychomotor and oculomotor tasks at two visits, approximately 2.5 years apart.

Multiple step pattern as a biomarker in Parkinson disease.

Objective: To evaluate quantitative measures of saccades as possible biomarkers in early stages of Parkinson disease (PD) and in a population at-risk for PD.

Methods: The study sample (n=68) included mildly to moderately affected PD patients, their unaffected siblings, and control individuals. All participants completed a clinical evaluation by a movement disorder neurologist.

The molecular basis of chloroquine block of the inward rectifier Kir2.1 channel.

Although chloroquine remains an important therapeutic agent for treatment of malaria in many parts of the world, its safety margin is very narrow. Chloroquine inhibits the cardiac inward rectifier K(+) current I(K1) and can induce lethal ventricular arrhythmias. In this study, we characterized the biophysical and molecular basis of chloroquine block of Kir2.

Cooperative interactions between R531 and acidic residues in the voltage sensing module of hERG1 channels.

HERG1 K(+) channels are critical for modulating the duration of the cardiac action potential. The role of hERG1 channels in maintaining electrical stability in the heart derives from their unusual gating properties: slow activation and fast inactivation. HERG1 channel inactivation is intrinsically voltage sensitive and is not coupled to activation in the same way as in the Shaker family of K(+) channels.

The S4-S5 linker directly couples voltage sensor movement to the activation gate in the human ether-a'-go-go-related gene (hERG) K+ channel.

A key unresolved question regarding the basic function of voltage-gated ion channels is how movement of the voltage sensor is coupled to channel opening. We previously proposed that the S4-S5 linker couples voltage sensor movement to the S6 domain in the human ether-a'-go-go-related gene (hERG) K+ channel. The recently solved crystal structure of the voltage-gated Kv1.

A comparison of Thermo Electron RSV OIA to viral culture and direct fluorescent assay testing for respiratory syncytial virus.

Background: Rapid diagnostic methods for respiratory syncytial virus are useful tools available for the clinician.

Objectives: The Thermo Electron RSV OIA (optical immunoassay kit) was prospectively compared with direct immunofluorescent assay and viral culture at Primary Children's Medical Center, Salt Lake City, Utah.

Study Design: Specimens from three hundred and thirty patients exhibiting respiratory symptoms were collected for testing by the three methods above.