This study was designed to improve blood glucose level predictability and future hypoglycemic and hyperglycemic event alerts through a novel patient‐specific supervised‐machine‐learning (SML) ...analysis of glucose level based on a continuous‐glucose‐monitoring system (CGM) that needs no human intervention, and minimises false‐positive alerts. The CGM data over 7 to 50 non‐consecutive days from 11 type‐1 diabetic patients aged 18 to 39 with a mean HbA1C of 7.5% ± 1.2% were analysed using four SML models. The algorithm was constructed to choose the best‐fit model for each patient. Several statistical parameters were calculated to aggregate the magnitudes of the prediction errors. The personalised solutions provided by the algorithm were effective in predicting glucose levels 30 minutes after the last measurement. The average root‐mean‐square‐error was 20.48 mg/dL and the average absolute‐mean‐error was 15.36 mg/dL when the best‐fit model was selected for each patient. Using the best‐fit‐model, the true‐positive‐hypoglycemia‐prediction‐rate was 64%, whereas the false‐positive‐ rate was 4.0%, and the false‐negative‐rate was 0.015%. Similar results were found even when only CGM samples below 70 were considered. The true‐positive‐hyperglycemia‐prediction‐rate was 61%. State‐of‐the‐art SML tools are effective in predicting the glucose level values of patients with type‐1diabetes and notifying these patients of future hypoglycemic and hyperglycemic events, thus improving glycemic control. The algorithm can be used to improve the calculation of the basal insulin rate and bolus insulin, and suitable for a closed loop “artificial pancreas” system. The algorithm provides a personalised medical solution that can successfully identify the best‐fit method for each patient.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Summary
background Ghrelin is a potent GH secretagogue that also plays an important role in appetite and weight regulation. Ghrelin increases hunger and food intake, and its levels decrease after a ...standard meal or glucose.
objective To examine the effects of standard oral glucose, lipid and protein loads on ghrelin levels, investigating the possibility that these responses may be modulated by several anthropometric and metabolic factors.
subjects and methods There were 24 adult nondiabetic subjects (13 men/11 women; mean age 55·3 ± 2·9 years, range 26–74 years). Each participant underwent one or more of the following nutrient loads: (i) a standard oral glucose (75 g) load (n = 18); (ii) an oral lipid load (40 g, with 24 g saturated fat; n = 13); (iii) an oral protein load (40 g; n = 11).
results Fasting ghrelin levels were negatively related to body mass index (BMI; r =−0·47; P = 0·02), waist circumference (r = −0·58; P = 0·0028), waist/hip ratio (r = −0·56; P = 0·0046), fasting insulin (r = −0·44, P = 0·03), and homeostasis model assessment insulin resistance index (HOMA‐R; r = −0·43, P = 0·034). Glucose load induced a decrease in ghrelin levels (P < 0·0001), and this response was modulated by sex (P < 0·0001), in that levels were significantly higher in females. The presence of obesity affected ghrelin response to glucose (< 0·0217), in that log‐transformed ghrelin levels started to increase back to baseline after its initial decline earlier in obese than in lean subjects. Ghrelin levels after a glucose load were lower over time in subjects with more pronounced insulin resistance (P < 0·0001). Similarly, ghrelin levels decreased significantly following the lipid meal (P = 0·035), and were modulated by HOMA‐R (P = 0·027) and gender (P = 0·029). Protein did not affect ghrelin levels.
conclusions This study demonstrates that ghrelin levels respond in a different manner to glucose, lipid and protein loads, and are subject to modulation according to gender, obesity and insulin sensitivity.
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Measuring resting metabolic rate (RMR) is time-consuming and expensive, and thus various equations for estimating RMR have been developed. This study's objective was to compare five equations in ...elderly people with type 2 diabetes (T2DM). RMR was measured in 90 older adults (≥65 years) with T2DM (mean body mass index (BMI) of 31.5 kg/m
), using indirect calorimetry. Results were compared to four frequently used equations (those of Cunningham, Harris and Benedict, and Gougeon developed for young adults with T2DM, and that of Lührmann, which was developed for the elderly), in addition to a new equation developed recently at the Academic College at Wingate (Nachmani) for overweight individuals. Estimation accuracy was defined as the percentage of subjects with calculated RMR within ±10% of measured RMR. Measured RMR was significantly underestimated by all equations. The equations of Nachmani and Lührmann had the best estimation accuracy: 71.4% in males and 50.9% in females. Skeletal muscle mass, fat mass, hemoglobin A1c (HbA1c), and the use of insulin explained 70.6% of the variability in measured RMR. RMR in elderly participants with T2DM was higher than that calculated using existing equations. The most accurate equations for this specific population were those developed for obesity or the elderly. Unbalanced T2DM may increase caloric demands in the elderly. It is recommended to adjust the RMR equations used for the target population.
Background: Obesity can resemble Cushing's syndrome not only with respect to some clinical and biochemical features such as visceral adiposity, hypertension and metabolic abnormalities but also in ...terms of increased urinary excretion of cortisol and cortisol metabolites. This has subsequently led to some confusion regarding activity level of the hypothalamic-pituitary axis in obesity. Here we re-examined this question using several tools developed after the evolution of the concept of "pseudo-Cushing in obesity," namely, the measurement of serum free cortisol, salivary cortisol and the dynamic changes of these measures in response to the low dose lug ACTH test. Methods: Total, free and salivary cortisol were tested at the basal state and after a standard challenge with 1 ug ACTH in 60 healthy obese subjects (mean BMI = 39) and 54 healthy lean controls (mean BMI = 23). Results: Mean (+/-SD) basal state total cortisol was significantly lower in obese than in lean subjects (13.1 ± 4.8 vs. 15 ± 4.4 ug/dl, p = 0.019) as was also basal state salivary cortisol (0.27 ± 0.03 vs. 0.39 ± 0.07 ug/dl, p = 0.003), but not basal state serum free cortisol (0.61 ± 0.14 vs 0.67+/-0.1 ug/dL, ns). Additionally, baseline total cortisol was inversely related to BMI (r = -0.23; p = 0.01), to waist circumference (r = -0.26; p < 0.01) and to triglycerides (r = -0.23; p < 0.05). When exposed to a lug ACTH challenge, the area under the response curve indicated a tendency for a lower total cortisol response in obese individuals compared to lean subjects. Concordant with these findings peak post-lug ACTH total serum and salivary cortisol levels were lower in the obese relative to the lean subjects (24.1 ± 5.5 vs. 26.4 ± 4.5 ug/dl, p < 0.05; 1.09 ± 0.38 vs. 1.27 ± 0.61 ug/dl, p < 0.05, respectively). Conclusions: Basal state as well as peak stimulated cortisol and integrated post-lug ACTH-stimulated total serum and salivary cortisol levels, while within the test-defined normal range, were significantly lower in obese subjects. Obesity is not associated with higher basal cortisol or ACTH-stimulated cortisol reserve and indeed is linked to diminished circulating cortisol which is negatively related to body mass index and waist circumference. In fact, increased serum or salivary cortisol is atypical for obesity and should not be viewed as probable "pseudo-Cushing syndrome."
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Background & Aims We investigated the effects of the fatty acid–bile acid conjugate 3β-arachidyl-amido, 7α-12α-dihydroxy, 5β-cholan-24-oic acid (Aramchol; Trima Israel Pharmaceutical Products Ltd, ...Maabarot, Israel) in a phase 2 trial of patients with nonalcoholic fatty liver disease (NAFLD). Methods We performed a randomized, double-blind, placebo-controlled trial of 60 patients with biopsy-confirmed NAFLD (6 with nonalcoholic steatohepatitis) at 10 centers in Israel. Patients were given Aramchol (100 or 300 mg) or placebo once daily for 3 months (n = 20/group). The main end point was the difference between groups in the change in liver fat content according to magnetic resonance spectroscopy. The secondary end points focused on the differences between groups in alterations of liver enzyme levels, levels of adiponectin, homeostasis model assessment scores, and endothelial function. Results No serious or drug-related adverse events were observed in the 58 patients who completed the study. Over 3 months, liver fat content decreased by 12.57% ± 22.14% in patients given 300 mg/day Aramchol, but increased by 6.39% ± 36.27% in the placebo group ( P = .02 for the difference between groups, adjusted for age, sex, and body mass index). Liver fat content decreased in the 100-mg Aramchol group, by 2.89% ± 28.22%, but this change was nonsignificant ( P = .35), indicating a dose–response relationship ( P for trend = .01). Groups given Aramchol had nonsignificant improvements over time in endothelial function and levels of alanine aminotransferase and adiponectin, but homeostasis model assessment scores did not change. The appropriateness of a single daily dose was confirmed by pharmacokinetic analysis. Conclusions Three months' administration of the fatty acid–bile acid conjugate Aramchol is safe, tolerable, and significantly reduces liver fat content in patients with NAFLD. The reduction in liver fat content occurred in a dose-dependent manner and was associated with a trend of metabolic improvements, indicating that Aramchol might be used for the treatment of fatty liver disease. ClinicalTrials.gov number: NCT01094158.
Weigh More, Lose Less Bone Tai, Brurya; Shefer, Gabi; Sack, Jessica ...
Obesity (Silver Spring, Md.),
11/2023, Volume:
31
Journal Article
Peer reviewed
Background: Several reports indicated that intentional weight loss can result in reduction in bone mineral density (BMD), particularly in postmenopausal women, and older individuals. This is a ...post-hoc analysis of a prospective multidisciplinary weight loss trial, in search of predictors of bone loss in the Metabolic Syndrome (MS). Methods: 73 MS subjects (ATPIII criteria; F/M = 34/39) participated in a 1-year intensive multidisciplinary treatment, based on personalized physical training and a low calorie/high protein Mediterranean diet. Baseline (±SD): age 53.3 ± 11.2 years; weight 98.6 kg ± 16.8; BMI 34.4 ± 3.8 kg/m2; lean body mass (LBM) 55.48 kg ± 11.66 kg; Spine BMD 1.21 ± 016 g/cm2, femur neck BMD 0.99 ± 0.13 g/cm2. Results: By the end of 1-year BMI declined by 9.1% (p < 0.001); LBM declined by 2.68% (p < 0.001). There were no significant overall changes in spine or femur BMD; no difference in the change in BMD between participants under the age of 50 years or above 51 years, and between male and female subjects. Despite the lack of overall change in BMD during weight loss, when individual changes in spinal BMD were analyzed, participants who clustered above the median post-treatment versus pre-treatment BMD level, showed a higher initial BMI compared to participants whose change in spinal BMD was below the median level (BMI 35.6 ± 3.6 vs. 32.5 ± 3.52 kg/m2, respectively (p < 0.0001). Conclusions: In subjects with MS undergoing intensive and closely supervised multidisciplinary intentional 1 year weight loss program, higher initial weight is associated with lesser spine bone loss.
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A series of new hybrid structures containing fluoroquinolone (ciprofloxacin) and aminoglycoside (neomycin) antibiotics linked via 1,2,3-triazole moiety were designed and synthesized, and their ...antibacterial activities were determined against both Gram-negative and Gram-positive bacteria, including resistant strains. The nature of spacers in both the ciprofloxacin and neomycin parts greatly influenced the antibacterial activity. The majority of hybrids was significantly more potent than the parent neomycin and overcame most prevalent types of resistance associated with aminoglycosides. Selected hybrids inhibited bacterial protein synthesis with the potencies similar to or better than that of neomycin and were up to 32-fold more potent inhibitors than ciprofloxacin for the fluoroquinolone targets, DNA gyrase and toposiomerase IV, indicating a balanced dual mode of action. Significant delay of resistance formation was observed in both E. coli and B. subtilis to the treatment with ciprofloxacin−neomycin hybrid in comparison to that of each drug separately or their 1:1 mixture.
Sea turtles represent an ancient lineage of marine vertebrates that evolved from terrestrial ancestors over 100 Mya. The genomic basis of the unique physiological and ecological traits enabling these ...species to thrive in diverse marine habitats remains largely unknown. Additionally, many populations have drastically declined due to anthropogenic activities over the past two centuries, and their recovery is a high global conservation priority. We generated and analyzed high-quality reference genomes for the leatherback (
) and green (
) turtles, representing the two extant sea turtle families. These genomes are highly syntenic and homologous, but localized regions of noncollinearity were associated with higher copy numbers of immune, zinc-finger, and olfactory receptor (OR) genes in green turtles, with ORs related to waterborne odorants greatly expanded in green turtles. Our findings suggest that divergent evolution of these key gene families may underlie immunological and sensory adaptations assisting navigation, occupancy of neritic versus pelagic environments, and diet specialization. Reduced collinearity was especially prevalent in microchromosomes, with greater gene content, heterozygosity, and genetic distances between species, supporting their critical role in vertebrate evolutionary adaptation. Finally, diversity and demographic histories starkly contrasted between species, indicating that leatherback turtles have had a low yet stable effective population size, exhibit extremely low diversity compared with other reptiles, and harbor a higher genetic load compared with green turtles, reinforcing concern over their persistence under future climate scenarios. These genomes provide invaluable resources for advancing our understanding of evolution and conservation best practices in an imperiled vertebrate lineage.
Background
Solid‐organ transplant recipients are at increased risk of developing human papillomavirus‐related diseases.
Methods
To evaluate the immunogenicity of a quadrivalent vaccine, a prospective ...observational study included females aged 12–19 years who had received kidney or liver transplants, or were otherwise healthy volunteers. With the three‐dose vaccination, serum antibodies were measured.
Results
The study included 17 transplant recipients (seven kidney and 10 liver) and 16 healthy participants. Six of seven kidney transplant recipients were on three immunosuppressive medications, whereas 9 of the 10 liver transplant recipients were on one. For the serology within 6 months from the last vaccine dose, the geometric mean titers of human papillomavirus types 6, 11, 16, and 18 were 26.7, 8.6, 35.7, and 42.4 (kidney transplant); 579.2, 569.3, 3097.3, and 835.7 (liver transplant); and 860.5, 638.8, 4391.6, and 902.6 milli‐Merck Units/ml (healthy). The seropositivity rates of kidney transplant recipients for the four serotypes ranged from 50% to 75%, while all liver transplant recipients and healthy participants had 100% seropositivity rates for all four types. While there were no statistical differences of titers between liver transplant recipients and healthy participants, the titers of kidney transplant recipients were lower than those of healthy participants for type 6 (p = .034), type 11 (p = .032), and type 16 (p = .032).
Conclusions
The results support the recommendation of human papillomavirus vaccination in pediatric transplant recipients given the significant risk of human papillomavirus‐related diseases in this population, though immunogenicity was lower in kidney transplant recipients on multiple immunosuppressive medications.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
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