OBJECTIVE -Foot ulceration is a serious complication of diabetes, and new techniques that can predict wound healing may prove very helpful. We tested the ability of medical hyperspectral technology (HT), a novel diagnostic scanning technique that can quantify tissue oxy-and deoxyhemoglobin to predict diabetic foot ulcer healing.RESEARCH DESIGN AND METHODS -Ten type 1 diabetic patients with 21 foot ulcer sites, 13 type 1 diabetic patients without ulcers, and 14 nondiabetic control subjects were seen up to 4 times over a 6-month period. HT measurements of oxyhemoglobin (HT-oxy) and deoxyhemoglobin (HT-deoxy) were performed at or near the ulcer area and on the upper and lower extremity distant from the ulcer. An HT healing index for each site was calculated from the HT-oxy and -deoxy values.RESULTS -Hyperspectral tissue oxygenation measurements observed changes in tissue immediately surrounding the ulcer when comparing ulcers that heal and ulcers that do not heal (P Ͻ 0.001). The sensitivity, specificity, and positive and negative predictive values of the HT index for predicting healing were 93, 86, 93, and 86%, respectively, when evaluated on images taken at the first visit. Changes in HT-oxy among the three risk groups were noted for the metatarsal area of the foot (P Ͻ 0.05) and the palm (P Ͻ 0.01). Changes in HT-deoxy and the HT healing index were noted for the palm only (P Ͻ 0.05 and P Ͻ 0.01, respectively).CONCLUSIONS -HT has the capability to identify microvascular abnormalities and tissue oxygenation in the diabetic foot and predict ulcer healing. HT can assist in the management of foot ulceration. Diabetes Care 30:903-910, 2007D iabetic foot ulceration (DFU) remains a serious problem, as 15% of all diabetic patients are expected to be affected with the complication during their lifespan (1). Infected and/or ischemic DFU accounts for ϳ25% of all hospital stays among diabetic patients, while foot ulceration precedes 85% of lowerextremity amputations (2). Currently, large multicenter studies (3-5) have reported that the healing rate of DFU over a 12-to 20-week period lies between 30 and 60%. Early identification of patients who will go on to fail to heal an ulcer can be of particular help, as it can allow the physician to make the right choice of treatment between a conservative and aggressive path. Pathways can be developed to streamline patient care and to apply new, expensive therapies only in patients who need them.The evaluation of neuropathy, peripheral vascular disease, presence of infection, and the depth of the ulcer are standard procedures for the management of DFU (6). However, none of the above measurements can predict wound healing. The only method that has previously been shown to predict wound healing is the measurement of changes in the ulcer area over a 4-week period of intensive care (7). However, the positive predictive value of this technique is only 58%, while the negative predictive value is 91%. Additionally, using the measurement-of-change method requires sequential patient examination...

OBJECTIVE -Localized low-level mechanical or electrical noise can significantly enhance tactile sensitivity in healthy young subjects and older adults. This phenomenon is termed stochastic resonance (SR). In this study, we examined the effect of SR on vibratory and tactile sensation in patients with moderate to severe diabetic peripheral neuropathy. RESEARCH DESIGN AND METHODS-A total of 20 subjects were included in the study. The vibration perception threshold (VPT) test and the Semmes-Weinstein filament (SWF) threshold at the plantar surface of the left foot and the big toe were determined under two mechanical noise stimulus conditions: null (no noise) condition and at 10% lower than each subject's mechanical noise threshold of perception. RESULTS -The baseline values (mean Ϯ SD) were as follows: Neuropathy Symptom Score (NSS) 5.2 Ϯ 2.5, Neuropathy Disability Score (NDS) 5.0 Ϯ 2.1, VPT 24 Ϯ 11 V, and SWF threshold 5.6 Ϯ 0.8 at the plantar surface of the foot and 5.3 Ϯ 0.9 at the big toe. The VPT improved significantly from 24 Ϯ 11 under null condition to 19 Ϯ 10 V with mechanical noise (P Ͻ 0.0001). Mechanical noise also significantly increased the number of detections of the SWF at the plantar surface of the foot (detection rate 66 Ϯ 11 vs. 59 Ϯ 15%, P Ͻ 0.02) but not at the big toe (63 Ϯ 10 vs. 61 Ϯ 16%, P ϭ NS).CONCLUSIONS -Mechanical noise stimulation improves vibration and tactile perception in diabetic patients with moderate to severe neuropathy. Additional studies are required to examine the effect of long-term noise stimulation on parameters of nerve function. Diabetes Care 26:3280 -3283, 2003D iabetic neuropathy is the most common neuropathy in western countries. This condition is estimated to occur in 20 -50% of diabetic patients, depending on the patient population studied and the criteria used for diagnosis (1-5). When compounded by peripheral vascular disease and impaired wound healing, the result is a classic cascade of skin and other medical problems in the affected areas (6). Seemingly innocuous circumstances such as ill-fitting shoes and minor skin lacerations progress into serious medical problems such as slowh e a l i n g s k i n u l c e r s . P e r i p h e r a l neuropathy can also lead to deformity of the foot and Charcot arthropathy (7,8). In severe cases, which are all too common, amputation of the affected extremity becomes necessary. In the U.S., Ͼ50,000 amputations are performed annually for these reasons (9). The cost to the U.S. health care system for diabetic foot problems exceeds $3,000,000,000 annually.Recently, a wide range of studies from computer models to human experiments have shown conclusively that low-level mechanical or electrical noise presented directly to sensory neurons can significantly enhance their ability to detect weak stimuli. This phenomenon of noise improving system performance is termed stochastic resonance (SR) and has been seen to occur in a variety of physical and biological systems. From a clinical perspective, one particularly important finding is that ...

OBJECTIVE -To characterize structural changes and the metabolic profile of foot muscles and correlate them with diabetic neuropathy measurements using phosphorus-31 ( 31 P) rapid acquisition with relaxation enhancement (RARE) magnetic resonance imaging (MRI).RESEARCH DESIGN AND METHODS -We studied 12 control subjects, 9 nonneuropathic diabetic patients, and 12 neuropathic diabetic patients using 31 P RARE and proton ( 1 H) MRI at 3 Tesla. The ratio of the total cross-sectional area of the foot to that of the muscle tissue was calculated from transaxial 1 H and 31 P images. The average 31 P concentration across the metatarsal head region was measured from the 31 P images.RESULTS -The muscle areaϪtoϪtotal area ratio differed among all three groups (means Ϯ SD): 0.55 Ϯ 0.04 vs. 0.44 Ϯ 0.05 vs. 0.06 Ϯ 0.06 for control, nonneuropathic, and neuropathic subjects, respectively (P Ͻ 0.0001). The average 31 P concentration also differed among all groups: 27.7 Ϯ 3.8 vs. 21.7 Ϯ 4.8 vs. 7.9 Ϯ 8.8 mmol/l for control, nonneuropathic, and neuropathic subjects (P Ͻ 0.0001). The muscle areaϪtoϪtotal area ratio strongly correlated with clinical measurements: Neuropathy Disability Score, r ϭ Ϫ0.83, P Ͻ 0.0001; vibration perception threshold, r ϭ Ϫ0.79, P Ͻ 0.0001; and Semmes-Weinstein monofilaments, r ϭ Ϫ0.87, P Ͻ 0.0001.CONCLUSIONS -Small muscle atrophy is present in diabetes before clinical peripheral neuropathy can be detected using standard clinical techniques. The 31 P RARE MRI method evaluates the severity of muscle atrophy, even in the early stages when neuropathy is absent. This technique may prove to be a useful diagnostic tool in identifying early-stage diabetic foot problems. Diabetes Care 28:1425-1430, 2005A trophy of the small muscles of the foot is common in diabetes and is related to peripheral motor neuropathy (1). The atrophy is believed to be the main factor responsible for the development of an imbalance between the flexor and extensor muscles, which results in clawing of the toes, prominent metatarsal heads, and the development of high foot pressures that play a direct role in the development of foot ulceration (2). Currently, there are no established methods to evaluate and follow the progress of small muscle atrophy in diabetic patients. As a result, little information is available regarding the onset of muscle changes and the natural history of their progression in diabetes.Concentrations of phosphorus-31 ( 31 P) cellular metabolites in skeletal muscle change immediately with the onset of ischemia and return quickly to normal levels in viable muscle tissue after reperfusion (3,4). Thus a method that accurately quantifies 31 P metabolite concentrations in foot muscles in vivo and spatially maps the resulting values to an anatomic, radiological image of the foot would be a sensitive, direct indicator of the health of muscle tissue in the diabetic foot. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) provide data for the noninvasive assessment of deep-lying soft tissue anatomy (5-7). R...

Acute application of stochastic resonance (SR), defined as a subsensory level of mechanical noise presented directly to sensory neurons, improves the vibration and tactile perception in diabetic patients with mild to moderate neuropathy. This study examined the effect of 1 hour of continuous SR stimulation on sensory nerve function. Twenty diabetic patients were studied. The effect of stimulation was measured at 2 time points, at the beginning and after 60 minutes of continual SR stimulation. This effect was measured using the vibration perception threshold (VPT) at the big toe under 2 conditions: a null (no SR) condition and active SR, defined as mechanical noise below the subject's own threshold of perception. The measurements under null and active conditions were done randomly and the examiner was blinded regarding the type of condition. Immediately after SR application, the VPT with SR in null condition was similar to baseline (32.2 +/- 13.1, P = nonsignificant) but was significantly lower during active SR (27.4 +/- 11.9) compared with both baseline (P = .018) and off position (P = .045). The 60 minutes VPT with active SR (28.7 +/- 11.1) reached significance comparing the baseline when one outlier was removed from the analysis (P = .031). It may be concluded that SR for a continuous 60-minute period can sustain the VPT improvement in diabetic patients with moderate to severe neuropathy. These results permit the conclusion that there is no short-term adaptation to the stimulation signal. Long-term application of this technique, perhaps in the form of a continually vibrating shoe insert, or insole, may result in sustained improvement of nerve function.

Cry1Ab and Cry1Fa toxins are environmentally safe insecticides that control important insect pests. is an important maize pest that shows low susceptibility to Cry1A toxins, in contrast to Cry1Fa, which is highly active against this pest and is used in transgenic maize for control. The β16 region from domain III of Cry1Ab has been shown to be involved in interactions with receptors such as alkaline phosphatase (ALP) or aminopeptidase (APN) in different lepidopteran insects. Alanine-scanning mutagenesis of amino acids of Cry1Ab β16 (STLRVN) revealed that certain β16 mutations, such as N514A, resulted in increased toxicity of Cry1Ab for without affecting the toxicity for other lepidopteran larvae, such as larvae. Exhaustive mutagenesis of N514 was performed, showing that the Cry1Ab N514F, N514H, N514K, N514L, N514Q, and N514S mutations increased the toxicity toward A corresponding mutation was constructed in Cry1Fa (N507A). Toxicity assays of wild-type and mutant toxins (Cry1Ab, Cry1AbN514A, Cry1AbN514F, Cry1Fa, and Cry1FaN507A) against four populations from Mexico and one from Brazil revealed that Cry1AbN514A and Cry1FaN507A consistently showed 3- to 18-fold increased toxicity against four of five populations. In contrast, Cry1AbN514F showed increased toxicity in only two of the populations analyzed. The mutants Cry1AbN514A and Cry1AbN514F showed greater stability to midgut protease treatment. In addition, binding analysis of the Cry1Ab mutants showed that the increased toxicity correlated with increased binding to brush border membrane vesicles and increased binding affinity for ALP, APN, and cadherin receptors. is the main maize pest in South and North America and also is an invasive pest in different African countries. However, it is poorly controlled by Cry1A toxins expressed in transgenic crops, which effectively control other lepidopteran pests. In contrast, maize expressing Cry1Fa is effective in the control of , although its effectiveness is being lost due to resistance evolution. Some of the Cry1Ab domain III mutants characterized here show enhanced toxicity for without loss of toxicity to Thus, these Cry1Ab mutants could provide useful engineered toxins that, along with other Cry toxins, would be useful for developing transgenic maize expressing stacked proteins for the effective control of and other lepidopteran pests in the field.