Which combined nerve conduction study scores are best suited for polyneuropathy in diabetic patients?

INTRODUCTION/AIMS: Nerve conduction studies (NCS) are widely used in diagnosing diabetic polyneuropathy. Combining the Z scores of several measures (Z-compounds) may improve diagnostics by grading abnormality. We aimed to determine which combination of nerves and measures is best suited for studies of diabetic polyneuropathy. METHODS: Sixty-eight patients with type 1 diabetes and 35 controls were included in this study. NCS measurements were taken from commonly investigated nerves in one arm and both legs. Different Z-compounds were calculated and compared with reference material to assess abnormality. A sensitivity proxy, the accuracy index (AI), and Cohen's d were calculated. RESULTS: Z-compounds with the highest AI consisted of the tibial and peroneal motor, and the sural, superficial peroneal, and tibial medial plantar sensory nerves in one or two legs. All Z-compounds were able to discriminate between diabetic subjects and nondiabetic controls (mean Cohen's d = 1.42 [range, 1.03-1.63]). The association between AI and number of measures was best explained logarithmically (R2  = 0.401), with diminishing returns above approximately 14 or 15 measures. F-wave inclusion may increase the AI of the Z compounds. Although often clinically useful among the non-elderly, the additional inclusion of medial plantar NCS into Z-compounds in general did not improve AI. DISCUSSION: Performing unilateral NCS in several motor and sensory lower extremity nerves is suited for the evaluation of polyneuropathy in diabetic patients. The use of Z-compounds may improve diagnostic accuracy in diabetic polyneuropathy and may be particularly useful for follow-up research studies as single summary measures of NCS abnormality development over time.

Ancient genomes revisit the ancestry of domestic and Przewalski's horses.

The Eneolithic Botai culture of the Central Asian steppes provides the earliest archaeological evidence for horse husbandry, ~5500 years ago, but the exact nature of early horse domestication remains controversial. We generated 42 ancient-horse genomes, including 20 from Botai. Compared to 46 published ancient- and modern-horse genomes, our data indicate that Przewalski's horses are the feral descendants of horses herded at Botai and not truly wild horses. All domestic horses dated from ~4000 years ago to present only show ~2.7% of Botai-related ancestry. This indicates that a massive genomic turnover underpins the expansion of the horse stock that gave rise to modern domesticates, which coincides with large-scale human population expansions during the Early Bronze Age.

Cognitive deficits associated with impaired awareness of hypoglycaemia in type 1 diabetes.

AIMS/HYPOTHESIS: The aim of this study was to compare cognitive function in adults with type 1 diabetes who have impaired awareness of hypoglycaemia with those who have normal awareness of hypoglycaemia. A putative association was sought between cognitive test scores and a history of severe hypoglycaemia. METHODS: A total of 68 adults with type 1 diabetes were included: 33 had impaired and 35 had normal awareness of hypoglycaemia, as confirmed by formal testing. The groups were matched for age, sex and diabetes duration. Cognitive tests of verbal memory, object-location memory, pattern separation, executive function, working memory and processing speed were administered. RESULTS: Participants with impaired awareness of hypoglycaemia scored significantly lower on the verbal and object-location memory tests and on the pattern separation test (Cohen's d -0.86 to -0.55 [95% CI -1.39, -0.05]). Participants with impaired awareness of hypoglycaemia had reduced planning ability task scores, although the difference was not statistically significant (Cohen's d 0.57 [95% CI 0, 1.14]). Frequency of exposure to severe hypoglycaemia correlated with the number of cognitive tests that had not been performed according to instructions. CONCLUSIONS/INTERPRETATION: Impaired awareness of hypoglycaemia was associated with diminished learning, memory and pattern separation. These cognitive tasks all depend on the hippocampus, which is vulnerable to neuroglycopenia. The findings suggest that hypoglycaemia contributes to the observed correlation between impaired awareness of hypoglycaemia and impaired cognition.

Impaired Awareness of Hypoglycemia in Adults With Type 1 Diabetes Is Not Associated With Autonomic Dysfunction or Peripheral Neuropathy.

OBJECTIVE: Impaired awareness of hypoglycemia (IAH) is a risk factor for severe hypoglycemia in people with insulin-treated diabetes; autonomic neuropathy has been suggested to underlie its development. The aim was to evaluate a putative association between IAH and autonomic dysfunction using novel and sensitive measures of autonomic neural function. RESEARCH DESIGN AND METHODS: Sixty-six adults with type 1 diabetes were studied, 33 with IAH and 33 with normal awareness of hypoglycemia (NAH), confirmed by formal testing. Participants were matched for age, sex, and diabetes duration. Clinical and laboratory evaluations included extensive autonomic function testing, peripheral nerve conduction studies, and quantitative sensory testing. Composite abnormality Z scores were used for group comparisons. RESULTS: The IAH and NAH group had similar median (interquartile range) age of 48 (14.5) vs. 47 (14.5) years, diabetes duration of 30 (13.5) vs. 31 (13.5) years, and mean ± SD HbA1c 7.8 ± 2.2% vs. 8.1 ± 1.9%, respectively. The autonomic composite Z score did not differ between the two groups (mean difference -0.15, 95% CI -0.46, 0.16; P = 0.33), nor did the thermal detection (mean difference 0.15, 95% CI -0.31, 0.61; P = 0.51) or nerve conduction scores (mean difference 0.03, 95% CI -0.43, 0.49; P = 0.89). CONCLUSIONS: In adults with type 1 diabetes, IAH was not associated with autonomic dysfunction or peripheral neuropathy.

Fear of hypoglycemia in women and men with type 1 diabetes.

BACKGROUND: Severe hypoglycemia is a serious complication of type1 diabetes feared by many who have the disease. OBJECTIVES: The aim of this study was to investigate specific fears related to hypoglycemia in adults with type 1 diabetes and to investigate how aspects of fear of hypoglycemia may differ between genders. METHODS: A cross-sectional study with questionnaires sent to 636 patients with type 1 diabetes, aged 18-75 years, who attended the outpatient clinic at St. Olavs Hospital, Trondheim, Norway. Fears related to hypoglycemia were assessed using the Hypoglycemia Fear Survey II Worry subscale (HFS-II-Worry). RESULTS: The response rate was 70% (N = 445, 216 women and 229 men). The mean HFS-II-Worry score was higher in women than in men (2.46 [SD = 0.80] vs. 2.22 [SD = 0.74], respectively; p < .001). Women scored higher than men in all items in the HFS-II-Worry, and women's average scores were statistically significantly higher in 5 of the 18 items after correction for multiple comparisons. The largest gender differences in mean scores occurred in the items "low blood glucose interfering with important things," "becoming upset and difficult," "difficulty thinking clearly," and "feeling lightheaded or dizzy." In both women and men, the highest mean scores appeared in the worry items "become hypoglycemic while sleeping" and "not having food available." DISCUSSION: In this sample of Norwegian adults with type 1 diabetes, women expressed more concerns about hypoglycemia than men. The highest HFS-II-Worry scores occurred in the same items in women and men, but the largest gender differences in mean scores appeared across a variety of other items, some of which were related to social esteem.

Leveraging EMR functionality to improve patient care.

Querying patient electronic medical records to improve patient care and process outcomes can seem overwhelming. Our quality improvement model is a simple, user-friendly approach to make quality improvement tasks less daunting. We have successfully used the quality improvement model, written meaningful reports, and given provider feedback that has led to measurable improvements in our clinical and operational performance.

The earliest horse harnessing and milking.

Horse domestication revolutionized transport, communications, and warfare in prehistory, yet the identification of early domestication processes has been problematic. Here, we present three independent lines of evidence demonstrating domestication in the Eneolithic Botai Culture of Kazakhstan, dating to about 3500 B.C.E. Metrical analysis of horse metacarpals shows that Botai horses resemble Bronze Age domestic horses rather than Paleolithic wild horses from the same region. Pathological characteristics indicate that some Botai horses were bridled, perhaps ridden. Organic residue analysis, using delta13C and deltaD values of fatty acids, reveals processing of mare's milk and carcass products in ceramics, indicating a developed domestic economy encompassing secondary products.

Mercapturate metabolism of 4-hydroxy-2-nonenal in rat and human cerebrum.

4-Hydroxy-2-nonenal (HNE), a potent toxin formed in the brain from oxidation of polyunsaturated fatty acids, is increased in Alzheimer disease (AD), where it is a proposed effector of amyloid beta peptide-mediated neurotoxicity. Detoxification of HNE via the mercapturic acid pathway (MAP) is the primary means by which other organs, such as liver, limit its toxic effects. Here we examined the distribution and activity of MAP detoxification for HNE in cerebrum. Our results showed that rat cerebral cortex and especially synaptosomes were less well equipped to detoxify HNE via the MAP than liver. Glutathione transferases (GSTs) catalyze the committed step in the MAP; GST-mu and GST-pi, but not OST-alpha, were detected in neurons and astrocytes in cerebrum from AD patients and controls. MAP activity in frontal cortex of AD patients was modestly but significantly increased compared to controls. These data suggest that lipid peroxidation may present a greater toxic burden to cerebrum than to other organs, and that a component of response to injury in late stage AD is a slight increase in MAP activity.

Importance of epidermal growth factor receptor signaling in establishment of adenomas and maintenance of carcinomas during intestinal tumorigenesis.

We used the hypomorphic Egfr(wa2) allele to genetically examine the impact of impaired epidermal growth factor receptor (Egfr) signaling on the Apc(Min) mouse model of familial adenomatous polyposis. Transfer of the Apc(Min) allele onto a homozygous Egfr(wa2) background results in a 90% reduction in intestinal polyp number relative to Apc(Min) mice carrying a wild-type Egfr allele. This Egfr effect is potentially synergistic with the actions of the modifier-of-min (Mom1) locus. Surprisingly, the size, expansion, and pathological progression of the polyps appear Egfr-independent. Histological examination of the ilea of younger animals revealed no differences in the number of microadenomas, the presumptive precursor lesions to gross intestinal polyps. Pharmacological inhibition with EKI-785, an Egfr tyrosine kinase inhibitor, produced similar results in the Apc(Min) model. These data suggest that normal Egfr activity is required for establishment of intestinal tumors in the Apc(Min) model between initiation and subsequent expansion of initiated tumors. The role of Egfr signaling during later stages of tumorigenesis was examined by using nude mice xenografts of two human colorectal cancer cell lines. Treatment with EKI-785 produced a dose-dependent reduction in tumor growth, suggesting that Egfr inhibitors may be useful for advanced colorectal cancer treatment.