Generalizable Deep Learning-based Sleep Staging Approach for Ambulatory Textile Electrode Headband Recordings.

Reliable, automated, and user-friendly solutions for the identification of sleep stages in home environment are needed in various clinical and scientific research settings. Previously we have shown that signals recorded with an easily applicable textile electrode headband (FocusBand, T 2 Green Pty Ltd) contain characteristics similar to the standard electrooculography (EOG, E1-M2). We hypothesize that the electroencephalographic (EEG) signals recorded using the textile electrode headband are similar enough with standard EOG in order to develop an automatic neural network-based sleep staging method that generalizes from diagnostic polysomnographic (PSG) data to ambulatory sleep recordings of textile electrode-based forehead EEG. Standard EOG signals together with manually annotated sleep stages from clinical PSG dataset (n = 876) were used to train, validate, and test a fully convolutional neural network (CNN). Furthermore, ambulatory sleep recordings including a standard set of gel-based electrodes and the textile electrode headband were conducted for 10 healthy volunteers at their homes to test the generalizability of the model. In the test set (n = 88) of the clinical dataset, the model's accuracy for 5-stage sleep stage classification was 80% (κ = 0.73) using only the single-channel EOG. The model generalized well for the headband-data, reaching 82% (κ = 0.75) overall sleep staging accuracy. In comparison, accuracy of the model was 87% (κ = 0.82) in home recordings using the standard EOG. In conclusion, the CNN model shows potential on automatic sleep staging of healthy individuals using a reusable electrode headband in a home environment.

Secondary squamous cell prostate cancer after prostate brachytherapy treatment.

This report describes the case of a patient with prostate cancerat the age of 59 years, who was treated by interstitial prostate brachytherapy with iodine-125 seeds. Ten years later, he developed a probable secondary squamous cell cancer in his prostate.

Effect of diet-induced weight loss on plasma apelin and cytokine levels in individuals with the metabolic syndrome.

BACKGROUND AND AIMS: Adipose tissue is an active endocrine organ that secretes signaling molecules involved in the regulation of insulin sensitivity, food intake and inflammation. Apelin is a peptide secreted by adipose tissue that has been shown to modulate cardiovascular tone in animals. The aim of this study was to measure abdominal fat, blood pressure and circulating apelin, adiponectin, leptin, ghrelin, TNF-alpha and IL-6 levels in patients with the metabolic syndrome after a diet-induced weight loss. METHODS AND RESULTS: 35 obese individuals with the metabolic syndrome underwent an 8-week very-low-calorie diet (VLCD) and a 6-month weight maintenance period (WM) with 120mg orlistat or placebo administered 3 times daily. VLCD and WM (-15.1+/-1.0kg) decreased mean arterial pressure (MAP), insulin, leptin, triglycerides and visceral and subcutaneous adipose tissue. Moreover, adiponectin increased in response to the weight loss. However, the overall changes in plasma apelin, TNF-alpha and IL-6 were non-significant. A correlation between plasma apelin and TNF-alpha was observed at baseline (0.41, p<0.05), and the minor changes in plasma apelin levels were associated with changes in BMI during VLCD and MAP and TNF-alpha during VLCD and WM periods. CONCLUSION: Despite reductions in BMI, body adiposity, MAP and enhancement of glucose metabolism and adiponectin in response to weight loss, no significant changes in plasma apelin, TNF-alpha and IL-6 were observed. However, apelin significantly correlated with TNF-alpha and MAP. These results suggest that apelin may not be that strongly correlated with the fat mass as an adipokine like the more abundant adipokines adiponectin or leptin and it might be involved in the regulation of inflammation and cardiovascular tone.

High circulating levels of RBP4 and mRNA levels of aP2, PGC-1alpha and UCP-2 predict improvement in insulin sensitivity following pioglitazone treatment of drug-naïve type 2 diabetic subjects.

CONTEXT: High levels of circulating retinol-binding protein 4 (RBP4) and baseline expression of adipogenic genes correlate with subsequent improvement in insulin sensitivity following Thiazolidinedione (TZD) treatment. OBJECTIVE: The aim was to identify baseline characteristics and early changes related to TZD treatment that could predict a good treatment response. DESIGN: Subjects were examined with oral glucose tolerance test, intravenous glucose tolerance test, hyperinsulinaemic euglycaemic clamp, body composition and standard blood sampling at baseline and after 4 and 12 weeks treatment. Subcutaneous adipose tissue biopsies were taken from the abdominal region at baseline, after 3 days and 4 weeks treatment to examine the gene expression profile. SETTING: Research laboratory in a University hospital. PARTICIPANTS: Ten newly diagnosed and previously untreated type 2 diabetic subjects were treated with pioglitazone for 3 months. MAIN OUTCOME MEASURES: Baseline characteristics and early changes related to TZD treatment that could predict the response after 3 months. RESULTS: Pioglitazone improved insulin sensitivity after 4 weeks combined with lower glucose and insulin levels without any change in BMI. It was accompanied by lower circulating resistin and plasminogen activator inhibitor-1 levels rapidly increased levels of circulating total and high molecular weight adiponectin as well as adiponectin and adipocyte fatty acid-binding protein (aP2) mRNA expression in the adipose tissue. High levels of circulating RBP4 at baseline and adipose tissue expression of aP2, proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1alpha) and uncoupling protein 2 (UCP-2) predicted a good treatment response measured as improvement in insulin-stimulated whole-body glucose uptake after 3 months. CONCLUSIONS: Circulating levels of RBP4 as an index of insulin sensitivity and mRNA levels of adipogenic genes correlate with the subsequent improvement in insulin sensitivity following TZD treatment.

Defects in insulin secretion and insulin action in non-insulin-dependent diabetes mellitus are inherited. Metabolic studies on offspring of diabetic probands.

No studies are available that have compared early defects in glucose metabolism in the offspring of insulin-deficient and insulin-resistant probands with non-insulin-dependent diabetes mellitus (NIDDM). To investigate this issue, we evaluated insulin secretion capacity with oral and intravenous glucose tolerance tests and with the hyperglycemic clamp, and insulin action with the euglycemic insulin clamp in 20 offspring of NIDDM patients with low fasting C-peptide (+/-450 pmol/liter), reflecting deficient insulin secretion (IS-group), 18 offspring of NIDDM patients with high fasting C-peptide (>/= 880 pmol/liter), reflecting insulin resistance (IR-group), and 14 healthy control subjects without a family history of NIDDM. The frequency of impaired glucose tolerance was 45.0% in the IS-group and 50% in the IR-group. The IS-group had lower insulin-glucose response at 30 min in the oral glucose tolerance test (85.2+/-10.0 pmol insulin per mmol glucose) than the control group (136.4+/-23.1 pmol insulin per mmol glucose; P < 0.05) and the IR-group (115.6+/-11.8 pmol insulin per mmol glucose; P = 0.05). Furthermore, the acute insulin response during the first 10 min of an intravenous glucose tolerance test was lower in the IS-group than in the IR-group. Maximal insulin secretion capacity evaluated by C-peptide levels during the hyperglycemic clamp did not differ between the groups. The IR-group had lower rates of whole body glucose uptake (60.1+/-4.6 micromol per lean body mass per minute) than did the control group (84.2+/-5.0 micromol per lean body mass per minute; P < 0.001) or the IS-group (82.6+/-5.9 micromol per lean body mass per minute; P < 0.01) and this was due to reduced glucose nonoxidation. To conclude, both impaired insulin secretion and insulin action seem to be inherited and could represent the primary defects in glucose metabolism in the offspring of NIDDM probands.

Dexamethasone in head and neck cancer patients with microvascular reconstruction: No benefit, more complications.

OBJECTIVES: Glucocorticoids are widely used in association with major surgery of the head and neck to improve postoperative rehabilitation, shorten intensive care unit and hospital stay, and reduce neck swelling. This study aimed to clarify whether peri- and postoperative use of dexamethasone in reconstructive head and neck cancer surgery is associated with any advantages or disadvantages. MATERIALS AND METHODS: This prospective double-blind randomized controlled trial comprised 93 patients. A total dose of 60mg of dexamethasone was administered to 51 patients over three days peri- and postoperatively. The remaining 42 patients served as controls. The main primary outcome variables were neck swelling, length of intensive care unit and hospital stay, duration of intubation or tracheostomy, and delay to start of possible radiotherapy. Complications were also recorded. RESULTS: No statistical differences emerged between the two groups in any of the main primary outcome variables. However, there were more major complications, especially infections, needing secondary surgery within three weeks of the operation in patients receiving dexamethasone than in control patients (27% vs. 7%, p=0.012). CONCLUSIONS: The use of dexamethasone in oral cancer patients with microvascular reconstruction did not provide a benefit. More major complications, especially infections, occurred in patients receiving dexamethasone. Our data thus do not support the use of peri- and postoperative dexamethasone in oropharyngeal cancer patients undergoing microvascular reconstruction.

Insulin resistant phenotype is associated with high serum leptin levels in offspring of patients with non-insulin-dependent diabetes mellitus.

OBJECTIVE: To investigate whether there are differences in serum leptin levels between the offspring of non-insulin-dependent diabetes mellitus (NIDDM) patients representing different phenotypes of NIDDM, and furthermore to investigate the role of different fat tissue (subcutaneous fat area (SCFAT) and intra-abdominal fat area (IAFAT)) and insulin sensitivity on serum leptin levels. DESIGN: Twenty non-diabetic offspring of NIDDM patients with insulin secretion deficient phenotype (IS-group), 18 non-diabetic offspring of NIDDM patients with insulin resistant phenotype (IR-group) and 14 healthy control subjects without a family history of diabetes were studied. METHODS: Serum leptin levels were measured by RIA. SCFAT and IAFAT were measured by computed tomography. the total fat mass (TFM) by bioelectrical impedance and the whole body glucose uptake (WBGU) by the euglycemic hyperinsulinemic clamp technique. RESULTS: Subjects of the control group (P = 0.003) and the IS-group (P<0.001) had lower serum leptin levels than subjects of the IR-group even after adjustment for gender (P<0.001). TFM (P = 0.009), fasting plasma insulin (P = 0.003) and for IAFAT (P<0.001). The differences weakened after adjustments for SCFAT (P = 0.028) or WBGU (P = 0.040) and disappeared after adjustment for both SCFAT and WBGU (P = 0.058). In the stepwise multiple regression analyses SCFAT. WBGU and gender explained 58% of the variation of serum leptin levels whereas IAFAT failed to be a significant determinant of serum leptin levels. CONCLUSIONS: The higher serum leptin levels in the IR-group was markedly, but not solely, explained by lower rates of WBGU and higher SCFAT. SCFAT was shown to be a more important determinant of serum leptin levels than IAFAT among these study groups.

Common polymorphisms of calpain-10 are associated with abdominal obesity in subjects at high risk of type 2 diabetes.

AIMS/HYPOTHESIS: The mechanisms by which the calpain-10 gene (CAPN10) affects the risk of type 2 diabetes are unclear. Therefore, we investigated the effects of four polymorphisms in CAPN10 (single nucleotide polymorphism [SNP]-43, SNP-44, Insertion/Deletion [Indel]-19 and SNP-63) on insulin secretion, insulin action and abdominal fat distribution in offspring of patients with type 2 diabetes. SUBJECTS AND METHODS: Insulin secretion was determined by an IVGTT, insulin action by the hyperinsulinaemic-euglycaemic clamp and abdominal fat distribution by computed tomography in 158 non-diabetic offspring (age 34.9+/-6.3 years [mean+/-SD], BMI 26.2+/-4.9 kg/m(2)) of type 2 diabetic patients. RESULTS: SNP-43 (p=0.009 over the three genotypes, adjusted for age, sex, BMI and family relationship) and haplotypes carrying the A allele of SNP-43 were associated with intra-abdominal fat area. The A allele of SNP-43 was associated with intra-abdominal fat area in men (p=0.014) but not in women. SNP-44, InDel-19 and SNP-63 were not associated with intra-abdominal fat area or insulin action. Furthermore, we demonstrated in a separate sample of middle-aged men (n=234) who had a history of type 2 diabetes in first-degree relatives that the A allele of SNP-43 was associated with a large waist circumference, and high insulin levels in an OGTT. CONCLUSIONS/INTERPRETATION: SNP-43 of CAPN10 may contribute to the risk of diabetes by regulating abdominal obesity in subjects with high risk of type 2 diabetes.

Haplotypes of PPARGC1A are associated with glucose tolerance, body mass index and insulin sensitivity in offspring of patients with type 2 diabetes.

AIMS/HYPOTHESIS: Decreased expression of the peroxisomal proliferator activated receptor gamma coactivator 1 alpha gene (PPARGC1A) is found in patients with type 2 diabetes, and variants in this gene have been linked with type 2 diabetes. Therefore, we investigated the effects of single nucleotide polymorphisms in PPARGC1A on body composition and glucose tolerance and on insulin sensitivity and secretion. METHODS: Non-diabetic offspring (n=156, age 34.9+/-0.5 years [mean+/-SEM], BMI 26.2+/-0.4 kg/m2) underwent an OGTT and an IVGTT and the hyperinsulinaemic-euglycaemic clamp. The promoter and coding regions of PPARGC1A were sequenced. RESULTS: Two haplotype blocks in PPARGC1A were observed, one in the promoter region (G-1774A, A-1679G, T-1422C, A-1278G, C-543A) and one in the coding region and 3' regions (Thr394Thr, Asp475Asp, Gly482Ser, Thr528Thr, Thr612Met, G+2381A). The coding region haplotype carrying the rare allele in codons 482 and 528 was associated with elevated glucose levels in an OGTT (p=0.024, adjusted for age, sex and BMI) and a haplotype carrying the rare alleles in codons 394 and 475 was associated with low BMI (p=0.033), high rates of whole-body glucose uptake (p=0.045) and low glucose levels in the OGTT (p=0.037). CONCLUSIONS/INTERPRETATION: We conclude that PPARGC1A is likely to contribute to the risk of diabetes in offspring of patients with type 2 diabetes.

High amount of visceral fat mass is associated with multiple metabolic changes in offspring of type 2 diabetic patients.

OBJECTIVE: To investigate the relative contribution of total body fat mass (TFM) and intra-abdominal fat mass (IAFM) to metabolic consequences of obesity in offspring of type 2 diabetic parents. DESIGN: Cross-sectional study of 129 nondiabetic offspring of diabetic parents (59 men, 70 women, age 35.7 +/- 6.3 y, body mass index 26.2 +/- 4.6 kg/m2). Study subjects were grouped according to TFM (assessed with bioelectrical impedance) and IAFM (assessed with CT). Insulin sensitivity was assessed with the euglycemic hyperinsulinemic clamp, insulin secretion with the intravenous glucose tolerance test and energy expenditure with indirect calorimetry. Furthermore, C-reactive protein (CRP) and adiponectin levels were measured. RESULTS: Insulin resistance, low rates of oxidative and nonoxidative glucose disposal, high rates of lipid oxidation and reduced energy expenditure during hyperinsulinemia were associated with high IAFM, independently of TFM. Adiponectin level was reduced and CRP level increased in subjects with high IAFM. CONCLUSIONS: The metabolic changes relating to obesity are largely attributable to high IAFM, and are present even in normal weight subjects with high IAFM.

Relationships between changes in abdominal fat distribution and insulin sensitivity during a very low calorie diet in abdominally obese men and women.

BACKGROUND AND AIM: Little is known about the association between abdominal obesity and insulin sensitivity during rapid weight loss. We assessed the role of visceral and subcutaneous fat as determinants of insulin sensitivity during rapid weight loss in obese persons with the metabolic syndrome. METHODS AND RESULTS: Twenty abdominally obese individuals [11 women and 9 men, body mass index (BMI) 35.8+/-3.5 kg/m2] with the metabolic syndrome underwent a very-low-calorie diet (VLCD) for nine weeks. At baseline, the computed tomography (CT) measured area of total (r=-0.50, p=0.033) and visceral fat tissue (r=-0.48, p=0.043), but not that of subcutaneous fat tissue (r=-0.34, p=0.17), correlated with insulin sensitivity as assessed by the quantitative insulin sensitivity check index after adjusting for sex and age. The 18 subjects who completed the study lost 14.8 kg during the VLCD. Total, visceral and subcutaneous abdominal fat tissue decreased by 22%, 29% and 17%, respectively. The decrease in total (r=-0.51, p=0.035) and subcutaneous abdominal fat (r=-0.57, p=0.017), but not visceral fat (r=0.11, p=0.68), correlated with the increase in insulin sensitivity. Waist circumference did not offer any additional information concerning abdominal fat distribution or insulin sensitivity compared with that provided by BMI at baseline or after weight loss. The waist/hip ratio was not associated with the CT measures of abdominal fat distribution or insulin sensitivity. CONCLUSIONS: Total abdominal fat may be more important than its compartmentalisation in abdominally obese individuals with the metabolic syndrome. In this subgroup of individuals with obesity, the measurement of waist circumference and the waist/hip ratio offered little additional information over that provided by BMI at baseline or after weight loss.

Interobserver variability in measuring the dimensions of the abdominal aorta: comparison of ultrasound and computed tomography.

OBJECTIVES: To examine the interobserver variability in measuring the abdominal aorta by ultrasound (US) and computed tomography (CT). DESIGN: A prospective clinical study in a university hospital. MATERIALS: Thirty-three patients whose abdominal aortas were scanned both with CT and US as a part of aneurysm investigation or for a variety of other reasons. METHODS: Three radiologists measured abdominal aortic diameters by US and CT. The interobserver differences (IOD) in US and CT and intraobserver differences for CT-US-pairs were analysed by various statistical methods. A new concept of "clinically acceptable difference" (CAD) was adopted denoting differences of less than 5mm. RESULTS: The IOD in US was 2mm or less in 65% of the anteroposterior and 61% of the transverse measurements and 5mm or more in 11% of the anteroposterior and 14% in the transverse measurements in 102 observer pairs for all aortas. The IODs were significantly larger in measuring the aneurysmal aortas compared with normal aortas (p < 0.001). The CAD-value for the aneurysmal aortas was 84% in the anteroposterior and 82% in the transverse directions. In CT the IODs were 2mm or less in 62% of the anteroposterior and 66% of the transverse measurements and 5mm or more in 12% of both anteroposterior and transverse measurements in 94 observer pairs for all aortas. The CAD-value in the aneurysmal aortas was 91% in the anteroposterior and 85% in the transverse directions. There was no significant difference between the US and CT CAD-levels. The absolute CT-US difference of an individual observer was 2mm or less in 54%, 5mm or more in 17% and 10mm or more in 2% of the anteroposterior measurements in the 95 CT-US pairs. In the transverse direction the corresponding figures were: 2mm or less in 63%, 5mm or more 13% and 10mm or more in 2% of the pairs. The diameters obtained by US were smaller in 84% of the cases compared with those of CT in measuring the maximum aortic diameter in anteroposterior direction, whereas the same figure for the transverse measurements was 59%. CONCLUSIONS: Both US and CT measurements are subject to significant interobserver variability that must be taken into account in the clinical follow-up of small abdominal aortic aneurysms and in screening studies. Neither of these methods can be considered as a 'gold standard'.

Impaired insulin secretion in non-diabetic offspring of probands with latent autoimmune diabetes mellitus in adults.

AIMS/HYPOTHESIS: This study was undertaken to investigate metabolic and genetic characteristics of latent autoimmune diabetes in adults (LADA). METHODS: We evaluated insulin secretory capacity with oral and intravenous glucose tolerance tests (early insulin response) and hyperglycaemic clamp (insulin secretory capacity) and the rates of whole body glucose uptake with the euglycaemic clamp, HLA-DQB1 genotypes (time-resolved fluorescence) and islet cell antibodies (ICA) (immunofluorescence) and antibodies to glutamic acid decarboxylase (GAD) (radio-immunoprecipitation) in 36 non-diabetic offspring (LADA-offspring) of patients with Type II (non-insulin-dependent) diabetes mellitus who tested positive for ICA and/or GAD antibodies during the 10-year follow-up from the diagnosis and in 19 healthy control subjects without a family history of diabetes. RESULTS: The early insulin response during the first 10 min of an intravenous glucose tolerance test was about 40% lower in the LADA-offspring than in the control group (p = 0.008). Insulin secretory capacity in the hyperglycaemic clamp was also about 30% lower in the LADA-offspring (p = 0.048). The rates of whole body glucose uptake were similar in both groups. The frequency of low risk HLA-DQB1 genotypes was higher in the LADA-offspring than among Finnish healthy blood donors (p = 0.033). The risk conferring genotypes were associated with the lowest tertile of insulin secretory capacity in the LADA-offspring (p = 0.032). There were no associations between the autoantibodies and early insulin response or insulin secretory capacity within the study groups. CONCLUSION/INTERPRETATION: We conclude that LADA is a familial disease involving most likely gene defects leading to a slow progressive beta-cell destruction and insulin deficiency.