•We reconstructed cubic centimeters of human cerebellar samples at micrometer resolution in five subjects.•Thickness of the granular layer varies greater than that of the molecular ...layer.•Cross-subject variability is higher in optical property than cortical morphology.•Our results suggest homogenous cell and myelin density in the cortical layers of human cerebellum despite the highly convoluted folding patterns.
The surface of the human cerebellar cortex is much more tightly folded than the cerebral cortex. Volumetric analysis of cerebellar morphometry in magnetic resonance imaging studies suffers from insufficient resolution, and therefore has had limited impact on disease assessment. Automatic serial polarization-sensitive optical coherence tomography (as-PSOCT) is an emerging technique that offers the advantages of microscopic resolution and volumetric reconstruction of large-scale samples. In this study, we reconstructed multiple cubic centimeters of ex vivo human cerebellum tissue using as-PSOCT. The morphometric and optical properties of the cerebellar cortex across five subjects were quantified. While the molecular and granular layers exhibited similar mean thickness in the five subjects, the thickness varied greatly in the granular layer within subjects. Layer-specific optical property remained homogenous within individual subjects but showed higher cross-subject variability than layer thickness. High-resolution volumetric morphometry and optical property maps of human cerebellar cortex revealed by as-PSOCT have great potential to advance our understanding of cerebellar function and diseases.
The importance of polarization-sensitive optical coherence tomography (PS-OCT) has been increasingly recognized in human brain imaging. Despite the recent progress of PS-OCT in revealing white matter ...architecture and orientation, quantification of fine-scale fiber tracts in the human brain cortex has been a challenging problem, due to a low birefringence in the gray matter. In this study, we investigated the effect of refractive index matching by 2,2'-thiodiethanol (TDE) immersion on the improvement of PS-OCT measurements in
human brain tissue. We show that we can obtain fiber orientation maps of U-fibers that underlie sulci, as well as cortical fibers in the gray matter, including radial fibers in gyri and distinct layers of fibers exhibiting laminar organization. Further analysis shows that index matching reduces the noise in axis orientation measurements by 56% and 39%, in white and gray matter, respectively. Index matching also enables precise measurements of apparent birefringence, which was underestimated in the white matter by 82% but overestimated in the gray matter by 16% prior to TDE immersion. Mathematical simulations show that the improvements are primarily attributed to the reduction in the tissue scattering coefficient, leading to an enhanced signal-to-noise ratio in deeper tissue regions, which could not be achieved by conventional noise reduction methods.
Chronic heart failure remains a major cause of mortality and morbidity. The role of antithrombotic therapy in patients with chronic heart failure has long been debated. The objective of this study ...was to determine the optimal antithrombotic agent for heart failure patients with reduced ejection fractions who are in sinus rhythm.
This prospective, randomized clinical trial of open-label warfarin (target international normalized ratio of 2.5 to 3.0) and double-blind treatment with either aspirin (162 mg once daily) or clopidogrel (75 mg once daily) had a 30-month enrollment period and a minimum of 12 months of treatment. We enrolled 1587 men and women >/=18 years of age with symptomatic heart failure for at least 3 months who were in sinus rhythm and had left ventricular ejection fraction of </=35%. The primary outcome was the time to first occurrence of death, nonfatal myocardial infarction, or nonfatal stroke. For the primary composite end point, the hazard ratios were as follows: for warfarin versus aspirin, 0.98 (95% CI, 0.86 to 1.12; P=0.77); for clopidogrel versus aspirin, 1.08 (95% CI, 0.83 to 1.40; P=0.57); and for warfarin versus clopidogrel, 0.89 (95% CI, 0.68 to 1.16; P=0.39). Warfarin was associated with fewer nonfatal strokes than aspirin or clopidogrel. Hospitalization for worsening heart failure occurred in 116 (22.2%), 97 (18.5%), and 89 (16.5%) patients treated with aspirin, clopidogrel, and warfarin, respectively (P=0.02 for warfarin versus aspirin).
The primary outcome measure and the mortality data do not support the primary hypotheses that warfarin is superior to aspirin and that clopidogrel is superior to aspirin.
To assess the influence of contemporary physical therapy clinical practice guidelines (CPG) on concussion evaluation practice patterns and barriers/facilitators for CPG adherence.
Electronic ...cross-sectional survey.
Online survey platform.
US licensed physical therapists that manage concussion.
1) practice patterns 2) knowledge/use of CPG 3) barriers/facilitations to CPG adherence.
Knowledge/use of CPG categories significantly predicted the model (χ2(1) = 10.966, p < .001) of total vignette scores/practice patterns with a statistically significant effect. A Kruskal-Wallis test indicated significant differences in total vignette score means based on knowledge/use between “not aware of the concussion CPG” and “integrated concussion CPG into practice” groups (p < .001, ES = .21). Knowledge/use of the CPG predicted the perceived barriers/facilitators model for three questions: investment in specialized concussion training (χ2(1) = 39.52, p < .001), necessary equipment to complete concussion evaluation (χ2(1) = 16.01, p < .001), and confidence around concussion evaluation knowledge (χ2(1) = 27.46, p < .001) with a significant effect.
The results of this study provide support for guiding documents like the CPG to positively influence concussion practice patterns and insight into facilitators for guideline adherence.
•Reading and integrated the concussion CPG enhanced practice pattern performance.•Volume of patients with concussion being treated weekly predicted performance.•Knowledge/use of the CPG predicted several perceived facilitators to CPG adherence.
Indoor hockey officials might be at high risk of hearing loss at an earlier age because their noise exposures have not been evaluated and officiating can begin as early as 10 years of age. Officials ...of junior and collegiate hockey leagues in northern Colorado participated in noise dosimetry and pre and postgame pure-tone audiometry to determine if a ≥10 decibels (dB) decrease in hearing sensitivity resulted from noise exposures during the game. All of the officials (N = 23) were exposed to equivalent sound pressure levels ≥85 A-weighted decibels (dBA) and 65% were overexposed based on noise criteria set by the American Conference of Governmental Industrial Hygienists. Of the sampled officials, 10 of 18 demonstrated a ≥10 dB increase in hearing threshold, seven of whom included shifts in more than one ear and/or frequency and two of whom demonstrated a 15 dB shift. The results of this study suggest exposure to hazardous levels of noise and a possible increased risk for hearing loss among hockey officials.
The role of anticoagulation in patients with chronic heart failure has long been an area of interest and controversy. Traditionally the goal of anticoagulation has been to prevent embolic events, but ...recent trials also demonstrated that oral anticoagulation also prevents vascular events in patients with prior myocardial infarction, who constitute the majority of heart failure patients. Although antiplatelet agents also reduce postinfarction vascular events, few data are available in heart failure patients, and some evidence suggests that aspirin may also have the potential to worsen heart failure morbidity and mortality, possibly by interfering with the effects of angiotensin-converting enzyme inhibitors.
The Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial was undertaken to determine the optimal antithrombotic agent for heart failure patients. WATCH was a prospective-randomized trial in which symptomatic heart failure patients in sinus rhythm with ejection fractions ≤35% taking angiotensin-converting enzyme inhibitors (unless not tolerated) and diuretics were randomized to open-label warfarin (target International Normalized Ratio 2.5-3.0) or double-blind antiplatelet therapy with aspirin 162 mg or clopidogrel 75 mg. Two primary comparisons were specified: anticoagulation with warfarin versus antiplatelet therapy with aspirin and antiplatelet therapy with clopidogrel versus antiplatelet therapy with aspirin. The primary outcome is the composite of death from all causes, nonfatal myocardial infarction, and nonfatal stroke analyzed as time to first event using the intent-to-treat approach. The secondary endpoint was the broader composite of death from all causes, nonfatal myocardial infarction, non-fatal stroke, and hospitalizations for worsening heart failure, unstable angina pectoris, and systemic or pulmonary artery embolic events. Additional prespecified analyses include heart failure events, coronary events, and resource utilization.
Although the trial was designed to enter 4500 patients, it was terminated 18 months prematurely in June 2003 by the VA Cooperative Study Program because of poor enrollment with a resulting reduction of its power to achieve its original objective. This manuscript describes the study rationale, protocol design, and the baseline characteristics of the 1587 patients who were entered into the study. The WATCH trial will help define the optimal approach to antithrombotic therapy in the contemporary management of patients with chronic heart failure resulting from left ventricular systolic dysfunction.
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