The making and breaking of tRNAs by ribonucleases.

Ribonucleases (RNases) play important roles in supporting canonical and non-canonical roles of tRNAs by catalyzing the cleavage of the tRNA phosphodiester backbone. Here, we highlight how recent advances in cryo-electron microscopy (cryo-EM), protein structure prediction, reconstitution experiments, tRNA sequencing, and other studies have revealed new insight into the nucleases that process tRNA. This represents a very diverse group of nucleases that utilize distinct mechanisms to recognize and cleave tRNA during different stages of a tRNA's life cycle including biogenesis, fragmentation, surveillance, and decay.

Domain acquisition by class I aminoacyl-tRNA synthetase urzymes coordinated the catalytic functions of HVGH and KMSKS motifs.

Leucyl-tRNA synthetase (LeuRS) is a Class I aminoacyl-tRNA synthetase (aaRS) that synthesizes leucyl-tRNAleu for codon-directed protein synthesis. Two signature sequences, HxGH and KMSKS help stabilize transition-states for amino acid activation and tRNA aminoacylation by all Class I aaRS. Separate alanine mutants of each signature, together with the double mutant, behave in opposite ways in Pyrococcus horikoshii LeuRS and the 129-residue urzyme ancestral model generated from it (LeuAC).

High Prevalence of Suboptimal Peak Inspiratory Flow in Hospitalized Patients With COPD: A Real-world Study.

For optimal drug delivery, dry powder inhalers (DPIs) depend on the patient's peak inspiratory flow (PIF) and the internal resistance of the device to create turbulent energy and disaggregate the powder. A suboptimal PIF may lead to ineffective drug inhalation into the lungs. Our objective was to report the prevalence of suboptimal PIF in patients with COPD hospitalized for any reason using 1 or more DPIs.

Clinical improvement with intensive robot-assisted arm training in chronic stroke is unchanged by supplementary tDCS.

Background: Intensive robot-assisted arm training in the chronic phase of stroke recovery can lead to clinical improvement. Combinatorial therapeutic approaches are sought to further optimize stroke recovery. Transcranial direct current stimulation (tDCS) is one candidate to combine with robotic training, as transient increases in excitability and improvements in motor behavior have separately been reported.

Health Care Resource Utilization and Costs Among Newly Diagnosed and Oral Anticoagulant-Naive Nonvalvular Atrial Fibrillation Patients Treated with Dabigatran or Warfarin in the United States.

Background: Warfarin has a long history of use to reduce the risk of stroke in patients with atrial fibrillation (AF), but it requires frequent laboratory monitoring to maintain international normalized ratio levels in the therapeutic range. Dabigatran, a novel oral anticoagulant (OAC), has demonstrated efficacy in reducing the risk of stroke and systemic embolism and does not require laboratory monitoring.

Objective: To compare health care resource utilization (HCRU) and costs of OAC-naive patients newly diagnosed with nonvalvular atrial fibrillation (NVAF), using dabigatran or warfarin.

tDCS does not enhance the effects of robot-assisted gait training in patients with subacute stroke.

Background: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique, which can modulate cortical excitability and combined with rehabilitation therapies may improve motor recovery after stroke.

Objective: Our aim was to study the feasibility of a 4-week robotic gait training protocol combined with tDCS, and to study tDCS to the leg versus hand motor cortex or sham to improve walking ability in patients after a subacute stroke.

Methods: Forty-nine subacute stroke patients underwent 20 daily sessions (5 days a week for 4 weeks) of robotic gait training combined with tDCS.

Treatment patterns and health care resource utilization associated with dalfampridine extended release in multiple sclerosis: a retrospective claims database analysis.

Background: Although previous studies have demonstrated the clinical benefits of dalfampridine extended release (D-ER) tablets in patients with multiple sclerosis (MS), there are limited real-world data on D-ER utilization and associated outcomes in patients with MS.

Purpose: The objective of this study was to evaluate treatment patterns, budget impact, and health care resource utilization (HRU) associated with D-ER use in a real-world setting.

Methods: A retrospective claims database analysis was conducted using the HealthCore Integrated Research Database(SM).

Vitamin B1 (thiamine) and dementia.

The earliest and perhaps best example of an interaction between nutrition and dementia is related to thiamine (vitamin B1). Throughout the last century, research showed that thiamine deficiency is associated with neurological problems, including cognitive deficits and encephalopathy. Multiple similarities exist between classical thiamine deficiency and Alzheimer's disease (AD) in that both are associated with cognitive deficits and reductions in brain glucose metabolism.

Post-stroke apathy and hypersomnia lead to worse outcomes from acute rehabilitation.

Apathy and hypersomnia occur after stroke and, by definition, reduce participation in rehabilitation, but their effect on outcome from acute rehabilitation is not known. We performed a retrospective review of 213 patients admitted to a stroke-specialized acute rehabilitation unit in the United States. All patients had ischemic or hemorrhagic stroke, and no dementia or dependence on others pre-stroke.

The epigenetics of stroke recovery and rehabilitation: from polycomb to histone deacetylases.

Classical de-afferentation studies, as well as experience-dependent visual plasticity paradigms, have confirmed that both the developing and adult nervous system are capable of unexpected levels of plasticity. This capacity is underscored by the significant spontaneous recovery that can occur in patients with mild-to-moderate impairment following stroke. An evolving model is that an interaction of biological and environmental factors during all epochs post-stroke influences the extent and quality of this plasticity.

Improved motor performance in chronic spinal cord injury following upper-limb robotic training.

Background: Recovering upper-limb motor function has important implications for improving independence of patients with tetraplegia after traumatic spinal cord injury (SCI).

Objective: To evaluate the feasibility, safety and effectiveness of robotic-assisted training of upper limb in a chronic SCI population.

Methods: A total of 10 chronic tetraplegic SCI patients (C4 to C6 level of injury, American Spinal Injury Association Impairment Scale, A to D) participated in a 6-week wrist-robot training protocol (1 hour/day 3 times/week).

Abnormal thiamine-dependent processes in Alzheimer's Disease. Lessons from diabetes.

Reduced glucose metabolism is an invariant feature of Alzheimer's Disease (AD) and an outstanding biomarker of disease progression. Glucose metabolism may be an attractive therapeutic target, whether the decline initiates AD pathophysiology or is a critical component of a cascade. The cause of cerebral regional glucose hypometabolism remains unclear.

Effect of gender on cardiovascular risk stratification with ECG gated SPECT left ventricular volume indices and ejection fraction.

Background: Optimal gender-specific risk prediction using ECG-gated SPECT left ventricular (LV) volumes and ejection fraction (EF) remains undefined despite reported gender differences in baseline LV function.

Methods: ECG-gated SPECT studies of 891 consecutively referred patients (43% women) were evaluated for LV end-systolic and diastolic volume indices (ESVI, EDVI) and EF. Effects of gender on prediction of hard cardiac events (HCE) and the combined endpoint of all-cause mortality or non-fatal infarction (ACMMI) were evaluated.

Increased cardiovascular risk associated with reduced kidney function.

Background: Individuals with chronic kidney disease (CKD) are at substantial risk for cardiovascular mortality, but the risk associated with specific glomerular filtration rates (GFRs) is unknown. The objective of this study was to investigate the relationship between level of kidney function and the risk of cardiovascular mortality in a diverse population.

Methods And Results: This was a nonconcurrent cohort study of 34,982 ambulatory patients.