Accurate whole human genome sequencing using reversible terminator chemistry.

DNA sequence information underpins genetic research, enabling discoveries of important biological or medical benefit. Sequencing projects have traditionally used long (400-800 base pair) reads, but the existence of reference sequences for the human and many other genomes makes it possible to develop new, fast approaches to re-sequencing, whereby shorter reads are compared to a reference to identify intraspecies genetic variation. Here we report an approach that generates several billion bases of accurate nucleotide sequence per experiment at low cost.

Parallel confocal detection of single molecules in real time.

The confocal detection principle is extended to a highly parallel optical system that continuously analyzes thousands of concurrent sample locations. This is achieved through the use of a holographic laser illumination multiplexer combined with a confocal pinhole array before a prism dispersive element used to provide spectroscopic information from each confocal volume. The system is demonstrated to detect and identify single fluorescent molecules from each of several thousand independent confocal volumes in real time.

Chronic exercise is associated with enhanced cutaneous blood flow in type 2 diabetes.

Impaired blood flow to skin contributes to foot ulceration and amputation. The overall objective of this cross-sectional study was to examine the relationship between chronic physical activity and skin blood flow in Type 2 diabetes. To do so, diabetic and control subjects were separated into four groups based on a physical activity questionnaire: control exerciser (CE), control sedentary (CS), diabetic exerciser (DE), and diabetic sedentary (DS) subjects.

Primary nociceptive afferents mediate the blood flow dysfunction in non-glabrous (hairy) skin of type 2 diabetes: a new model for the pathogenesis of microvascular dysfunction.

Objective: To test the independent contributions of vascular endothelium, sympathetic activation and inhibition, vessel distensibility, and nociceptor-mediated vasodilation in both glabrous and hairy skin circulations.

Research Design And Methods: We measured blood flow using laser Doppler techniques in 10 people with type 2 diabetes and 10 age- and BMI-matched healthy control subjects at the pulp of the index finger (glabrous skin) and the dorsum of the hand (hairy skin). A 5-min ischemic block of the arm was used to test vascular endothelium.

Normal blood flow response and vasomotion in the diabetic Charcot foot.

Vasomotion, the spontaneous rhythmic contraction exhibited by small arteries and arterioles is dysregulated in patients with diabetic neuropathy. We examined the relationship between Charcot arthropathy and vasomotion at the dorsum of the foot. We studied nine diabetic patients with clinically diagnosed neuropathy and Charcot arthropathy in 13 feet (n=13), twelve subjects with diabetic neuropathy and no Charcot deformity (n=12), and 11 healthy controls (n=11).

Impairment of peripheral blood flow responses in diabetes resembles an enhanced aging effect.

Objective: To test the hypothesis that skin blood flow responses in the fingertip of diabetic patients are impaired and to examine the role of aging in both healthy control subjects and diabetic patients.

Research Design And Methods: We measured cutaneous blood flow using laser Doppler techniques in 40 people with diabetes and in 20 age- and sex-matched healthy control subjects. To induce vasoconstriction, subjects were asked to perform three 1-min stressor tasks: mental arithmetic, contralateral hand grip, and immersion of the contralateral hand in ice water.

Impaired peripheral vasomotion in diabetes.

Objective: To test the hypothesis that vasomotion, the rhythmic contraction exhibited by small arteries and arterioles, is impaired in diabetic subjects compared with healthy control subjects.

Research Design And Methods: We mathematically modeled the oscillations in laser Doppler microvascular measurements taken from the pulpar surface of the index finger in 20 healthy control subjects and 20 age-matched diabetic subjects (8 with type I and 12 with type II diabetes). The mean duration of diabetes was 17.

Quantitative measurement of cutaneous perception in diabetic neuropathy.

To determine the diagnostic value of various cutaneous sensory modalities in diabetic neuropathy, we studied cutaneous perception at the dominant hallux of 113 subjects (32 normal healthy controls and 81 diabetic subjects). The cutaneous sensory perception tests included warm and cold thermal perception, vibration, touch-pressure sensation, and current perception testing (CPT). The sensitivity of each modality when specificity is held greater than 90% was as follows: warm = 78%, cold = 77%, vibration = 88%, tactile-pressure = 77%, 5-Hz CPT = 52%, 250-Hz CPT = 48%, and 2000-Hz CPT = 56%.