Impact of Nutrient Intake on Body Composition in Very Low-Birth Weight Infants Following Early Progressive Enteral Feeding.

Preterm infants have increased body adiposity at term-equivalent age and risk of adverse metabolic outcomes. The aim of the study was to define how nutrient intake may impact body composition (BC) of very low-birth weight infants fed with early progressive enteral feeding and standard fortification. Eighty-six infants with <1500 g birth weight were included in the BC study and stratified into extremely preterm (EP) and very preterm (VP) groups. Nutrient intake was calculated during the first 28 days and BC assessed by dual X-ray absorptiometry at discharge and by skinfold thickness at 12 months of corrected age (CA). Total nutrient intake did not differ between the groups. EP infants had a higher fat mass percentage at discharge than VP infants (24.8% vs. 19.4%, p < 0.001); lean mass did not differ. None of the nutrients had any impact on BC of EP infants. Protein intake did not result in a higher lean mass in either group; fat intake was a significant predictor of increased fat mass percentage in VP infants at discharge (p = 0.007) and body adiposity at 12 months of CA (p = 0.021). Nutritional needs may depend on gestational age and routine fortification should be used with caution in more mature infants.

A pilot cost-analysis study comparing AI-based EyeArt® and ophthalmologist assessment of diabetic retinopathy in minority women in Oslo, Norway.

BACKGROUND: Diabetic retinopathy (DR) is the leading cause of adult blindness in the working age population worldwide, which can be prevented by early detection. Regular eye examinations are recommended and crucial for detecting sight-threatening DR. Use of artificial intelligence (AI) to lessen the burden on the healthcare system is needed. PURPOSE: To perform a pilot cost-analysis study for detecting DR in a cohort of minority women with DM in Oslo, Norway, that have the highest prevalence of diabetes mellitus (DM) in the country, using both manual (ophthalmologist) and autonomous (AI) grading. This is the first study in Norway, as far as we know, that uses AI in DR- grading of retinal images. METHODS: On Minority Women's Day, November 1, 2017, in Oslo, Norway, 33 patients (66 eyes) over 18 years of age diagnosed with DM (T1D and T2D) were screened. The Eidon - True Color Confocal Scanner (CenterVue, United States) was used for retinal imaging and graded for DR after screening had been completed, by an ophthalmologist and automatically, using EyeArt Automated DR Detection System, version 2.1.0 (EyeArt, EyeNuk, CA, USA). The gradings were based on the International Clinical Diabetic Retinopathy (ICDR) severity scale [1] detecting the presence or absence of referable DR. Cost-minimization analyses were performed for both grading methods. RESULTS: 33 women (64 eyes) were eligible for the analysis. A very good inter-rater agreement was found: 0.98 (P < 0.01), between the human and AI-based EyeArt grading system for detecting DR. The prevalence of DR was 18.6% (95% CI: 11.4-25.8%), and the sensitivity and specificity were 100% (95% CI: 100-100% and 95% CI: 100-100%), respectively. The cost difference for AI screening compared to human screening was $143 lower per patient (cost-saving) in favour of AI. CONCLUSION: Our results indicate that The EyeArt AI system is both a reliable, cost-saving, and useful tool for DR grading in clinical practice.

Automatic Detection of Microaneurysms in Fundus Images Using an Ensemble-Based Segmentation Method.

In this study, a novel method for automatic microaneurysm detection in color fundus images is presented. The proposed method is based on three main steps: (1) image breakdown to smaller image patches, (2) inference to segmentation models, and (3) reconstruction of the predicted segmentation map from output patches. The proposed segmentation method is based on an ensemble of three individual deep networks, such as U-Net, ResNet34-UNet and UNet++. The performance evaluation is based on the calculation of the Dice score and IoU values. The ensemble-based model achieved higher Dice score (0.95) and IoU (0.91) values compared to other network architectures. The proposed ensemble-based model demonstrates the high practical application potential for detection of early-stage diabetic retinopathy in color fundus images.

Co-segregation analysis and functional trial in vivo of candidate genes for monogenic diabetes.

INTRODUCTION: The aim of this study was to perform familial co-segregation analysis and functional trial in vivo during mixed meal tolerance test (MMTT) of novel variants in diabetes candidate genes. RESEARCH DESIGN AND METHODS: It is a continuation of the project "Genetic diabetes in Lithuania" with the cohort of 1209 patients with diabetes. Prior screening for autoimmune markers confirmed type 1 diabetes (T1D) diagnosis in 88.1% (n=1065) of patients, and targeted next-generation sequencing identified 3.5% (n=42) pathogenic variants in MODY genes. Subsequently, 102 patients were classified as having diabetes of unknown etiology. 12/102 were found to have novel variants in potential diabetes genes (RFX2, RREB1, SLC5A1 (3 patients with variants in this gene), GCKR, MC4R, CASP10, TMPRSS6, HGFAC, DACH1, ZBED3). Co-segregation analysis and MMTT were carried out in order to study beta-cell function in subjects with specific variants. RESULTS: MMTT analysis showed that probands with variants in MC4R, CASP10, TMPRSS6, HGFAC, and SLC5A1 (c.1415T>C) had sufficient residual beta-cell function with stimulated C-peptide (CP) >200 pmol/L. Seven individuals with variants in RFX2, RREB1, GCKR, DACH1, ZBED3 and SLC5A1 (c.1415T>C, and c.932A>T) presented with complete beta-cell failure. No statistical differences were found between patients with sufficient CP production and those with complete beta-cell failure when comparing age at the onset and duration of diabetes. Nineteen family members were included in co-segregation analysis; no diabetes cases were reported among them. Only in patient with the variant c.1894G>A in RFX2 gene, none of the family members were affected by proband's variant. CONCLUSIONS: Functional beta-cell study in vivo allowed to select five most probable genes for monogenic diabetes. Familial co-segregation analysis showed that novel variant in RFX2 gene could be a possible cause of diabetes. Future functional analysis in vitro is necessary to support or rule out the genetic background as a cause of diabetes.

Pancreatic beta-cell function dynamics in youth with GCK, HNF1A, and KCNJ11 genes mutations during mixed meal tolerance test.

OBJECTIVE: The aims were (1) to assess beta-cell function in GCK diabetes patients over 2-year period; (2) to evaluate the dynamics of beta-cell function in HNF1A and KCNJ11 patients after treatment optimization; using mixed meal tolerance test (MMTT) as a gold standard for non-invasive beta-cell function assessment. RESEARCH DESIGN AND METHODS: Twenty-two GCK diabetes patients, 22 healthy subjects, 4 patients with HNF1A and 2 with KCNJ11 were recruited. Firstly, beta-cell function was compared between GCK patients versus controls; the dynamics of beta-cell function were assessed in GCK patients with two MMTTs in 2-year period. Secondly, the change of beta-cell function was evaluated in HNF1A and KCNJ11 patients after successful treatment optimization in 2-year period. RESULTS: GCK diabetes patients had lower area under the curve (AUC) of C-peptide (CP), average CP and peak CP compared to controls. Also, higher levels of fasting, average, peak and AUC of glycemia during MMTT were found in GCK patients compared to healthy controls. No significant changes in either CP or glycemia dynamics were observed in GCK diabetes group comparing 1st and 2nd MMTTs. Patients with HNF1A and KCNJ11 diabetes had significantly improved diabetes control 2 years after the treatment was optimized (HbA1c 7.1% vs. 5.9% [54 mmol/mol vs. 41 mmol/mol], respectively, p = 0.028). Higher peak CP and lower HbA1c were found during 2nd MMTT in patients with targeted treatment compared to the 1st MMTT before the treatment change. CONCLUSION: In short-term perspective, GCK diabetes group revealed no deterioration of beta-cell function. Individualized treatment in monogenic diabetes showed improved beta-cell function.

Impact of Early Nutrient Intake and First Year Growth on Neurodevelopment of Very Low Birth Weight Newborns.

Optimal nutrient intake ensuring better neurodevelopment for very low birth weight (VLBW) infants remains unknown. The aim of this study was to assess the relationship between early (first 28 days) nutritional intake, first year growth, and neurodevelopment. In total, 120 VLBW infants were included into the study. A group of 95 infants completed follow-up to 12 months of corrected gestational age (CGA). Nutrient intake was assessed, and weight, length, and head circumference (HC) were measured weekly until discharge and at 3, 6, 9, and 12 months of CGA. Neurodevelopment was assessed at 12 months of CGA. Two groups-extremely preterm (EP) and very/moderately preterm (VP)-were compared. Growth before discharge was slower in the EP group than the VP group. At 12 months, there was no difference in anthropometric characteristics or neurodevelopmental scores between the groups. Higher carbohydrate intake during the first 28 days was the single significant predictor for better cognitive scores only in the EP group (ßs = 0.60, p = 0.017). Other nutrients and growth before discharge were not significant for cognitive and motor scores in either group in multivariable models, whereas post-discharge HC growth was associated with both cognitive and motor scores in the VP group. Monitoring intake of all nutrients and both pre-discharge and post-discharge growth is essential for gaining knowledge about individualized nutrition for optimal neurodevelopment.

Ubiquitin-proteasome system in diabetic retinopathy.

Diabetic retinopathy (DR) is the most common complication of diabetes, being the most prevalent reason for blindness among the working-age population in the developed world. Despite constant improvement of understanding of the pathogenesis of DR, identification of novel biomarkers of DR is needed for improvement of patient risk stratification and development of novel prevention and therapeutic approaches. The ubiquitin-proteasome system (UPS) is the primary protein quality control system responsible for recognizing and degrading of damaged proteins. This review aims to summarize literature data on modifications of UPS in diabetes and DR. First, we briefly review the structure and functions of UPS in physiological conditions. We then describe how UPS is involved in the development and progression of diabetes and touch upon the association of UPS genetic factors with diabetes and its complications. Further, we focused on the effect of diabetes-induced hyperglycemia, oxidative stress and hypoxia on UPS functioning, with examples of studies on DR. In other sections, we discussed the association of several other mechanisms of DR (endoplasmic reticulum stress, neurodegeneration etc) with UPS modifications. Finally, UPS-affecting drugs and remedies are reviewed. This review highlights UPS as a promising target for the development of therapies for DR prevention and treatment and identifies gaps in existing knowledge and possible future study directions.

Reply to Manzar, S. Comment on "Brinkis et al. Nutrient Intake with Early Progressive Enteral Feeding and Growth of Very Low-Birth-Weight Newborns. Nutrients 2022, 14, 1181".

We appreciate Dr. Shabih Manzar's interest [...].

Telomere Lengths and Serum Proteasome Concentrations in Patients with Type 1 Diabetes and Different Severities of Diabetic Retinopathy in Latvia and Lithuania.

The aim of the study was to compare telomere lengths and circulating proteasome concentrations in patients with different stages of diabetic retinopathy and type 1 diabetes in Latvia and Lithuania. Methods. Patients with no diabetic retinopathy and with non-proliferative diabetic retinopathy were included in the NDR/NPDR group (n = 187). Patients with proliferative diabetic retinopathy and status post laser-photocoagulation were included int the PDR/LPC group (n = 119). Telomeres were evaluated by real-time quantitative polymerase chain reaction. Proteasome concentration was measured by ELISA. Results. Telomeres were longer in PDR/LPC (ΔCT 0.21 (0.12−0.28)) vs. NDR/NPDR (ΔCT 0.18 (0.1−0.28)), p = 0.036. In NDR/NPDR, telomeres were correlated negatively with age (R = −0.17, p = 0.019), BMI (R = −0.21, p = 0.004), waist/hip ratio (R = −0.21, p = 0.005), total cholesterol (R = −0.18, p = 0.021), and low-density cholesterol (R = −0.20, p = 0.010), and positively with estimated glomerular filtration rate (eGFR) (R = 0.28, p < 0.001). None of the above correlations were observed in PRD/LPC. Proteasome concentrations were lower in PDR/LPC (130 (90−210) ng/mL) vs. NDR/NPDR (150 (100−240) ng/mL), p = 0.024. This correlated negatively with eGFR (R = −0.17, p = 0.025) in the NDR/NPDR group and positively with age (R = 0.23, p = 0.014) and systolic blood pressure (R = 0.20, p = 0.032) in the PRD/LPC group. Telomere lengths did not correlate with proteasome concentrations. Conclusion. Longer telomeres and lower circulating proteasome concentrations are observed in patients with type 1 diabetes and advanced diabetic retinopathy.

Diagnostic Value of Circulating Cell-free DNA in Patients With Papillary Thyroid Cancer.

AIM: We investigated whether the occurrence and development of papillary thyroid cancer (PTC) might be predicted using levels of circulating cell-free DNA (cfDNA). MATERIALS AND METHODS: The peripheral blood samples were collected from 68 patients with PTC, 31 patients with nodular goiter (NG), and 86 healthy controls (HC). The concentration of cfDNA was measured by qPCR using three primer sets: ß-actin99, ß-actin394 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in plasma samples. RESULTS: It was demonstrated that plasma ß-actin99 and ß-actin394 in the PTC group were significantly higher compared to HC (p<0.05 and p<0.001, respectively). The cfDNA integrity index was significantly higher in the PTC patients compared to HC and NG (p<0.001, p<0.05, respectively). The cfDNA concentration in the NG group was significantly higher than in the PTC (p<0.05 and p<0.001, respectively). Moreover, in most PTC patients with suppressed thyroglobulin, the ß-actin394 and cfDNA integrity index was significantly decreased after surgery (p<0.05 and p<0.001, respectively). ROC analysis revealed that cfDNA integrity index can be used as a potential marker in distinguishing PTC from HC (AUC 0.901, p<0.001) and NG (AUC 0.629, p<0.05). CONCLUSION: Increased concentration of cfDNA ß-actin99 and ß-actin394 may be a valuable biomarker that differentiates PTC patients from HC. Also, an increased cfDNA integrity index may be a suitable parameter which differentiates PTC patients from NG and HC.

Cardiometabolic Health in Adolescents and Young Adults with Congenital Adrenal Hyperplasia.

Background and objectives: Data on long-term cardiometabolic consequences in patients with congenital adrenal hyperplasia (CAH) are controversial. The aim of our study was to evaluate body mass index (BMI), body composition, blood pressure (BP) and insulin sensitivity in adolescents and young adults with CAH in comparison with healthy controls. Methods: Thirty-two patients with classical CAH (13 males; mean of age 26.0 ± 7.1, years (14.0−37.3) were compared to 32 healthy sex and age-matched controls (13 males; mean of age 28.7 ± 4.6 years (14.1−37.2), p = 0.13). Body composition was evaluated in all subjects with DXA (Hologic Inc., Bedford, MA, USA). Elevated BP was defined as BP > 95th percentile in adolescents, and >140/90 mmHg in adults. Comparisons between the two groups were adjusted for age, gender, pubertal stage and height. An oral glucose tolerance test was performed, and fasting insulin levels were evaluated. Insulin sensitivity was determined using a homeostasis model assessment of insulin resistance index (HOMA-IR). Results: The median BMI was significantly higher in subjects with CAH (1.63 (0.3−2.4) SDS and 0.41 (−0.63−1.19) SDS, respectively, p < 0.001). Visceral adipose tissue (VAT) in grams was significantly higher in CAH females versus control females (467 (231−561) vs. 226 (164−295), p = 0.002). Elevated BP was identified in 34% of CAH patients (nine SW and two SV) and 12.5% (n = 4) of controls (p = 0.038). Impaired fasting glycemia was detected in one SW CAH patient and impaired glucose tolerance in three SV CAH patients; normal glucose tolerance was found in all controls. A strong positive correlation was found between median cumulative hydrocortisone (HC) dose equivalents and LDL-cholesterol and a negative association with lean body mass (r = −0.79, p = 0.036) in females with CAH. BMI, VAT, BP and HOMA-IR were not related to median cumulative HC dose equivalents. Conclusions: CAH patients had higher BMI, VAT and frequency of elevated BP compared to controls. Doses of glucocorticoids were related directly to LDL-cholesterol and inversely to lean body mass in CAH females, but not associated with body composition, insulin sensitivity and BP in the whole cohort of CAH patients.

Nutrient Intake with Early Progressive Enteral Feeding and Growth of Very Low-Birth-Weight Newborns.

Early nutrition is one of the most modifiable factors influencing postnatal growth. Optimal nutrient intakes for very preterm infants remain unknown, and poor postnatal growth is common in this population. The aim of this study was to assess nutrient intake during the first 4 weeks of life with early progressive enteral feeding and its impact on the in-hospital growth of very low-birth-weight (VLBW) infants. In total, 120 infants with birth weights below 1500 g and gestational ages below 35 weeks were included in the study. Nutrient intakes were assessed daily for the first 28 days. Growth was measured weekly until discharge. Median time of parenteral nutrition support was 6 days. Target enteral nutrient and energy intake were reached at day 10 of life, and remained stable until day 28, with slowly declining protein intake. Median z-scores at discharge were -0.73, -0.49, and -0.31 for weight, length, and head circumference, respectively. Extrauterine growth restriction was observed in 30.3% of the whole cohort. Protein, carbohydrates, and energy intakes correlated positively with weight gain and head circumference growth. Early progressive enteral feeding with human milk is well tolerated in VLBW infants. Target enteral nutrient intake may be reached early and improve in-hospital growth.

Serum Cystatin C as a Biomarker for Early Diabetic Kidney Disease and Dyslipidemia in Young Type 1 Diabetes Patients.

Background and objectives: This study aimed to assess the clinical significance of serum cystatin C in the early diagnosis of renal injury and its association with dyslipidemia in young T1D patients. Materials and Methods: A total of 779 subjects were evaluated for kidney function by estimating glomerular filtration rate (eGFR) based on serum creatinine (eGFRcreat) and cystatin C (eGFRcys). Results: The median age of study subjects was 16.2 years (2.1;26.4), diabetes duration-5.3 years (0.51;24.0). The median of HbA1c was 8% (5.2;19.9) (64 mmol/mol (33.3;194)); 24.2% of participants had HbA1c < 7% (53 mmol/mol). Elevated albumin excretion rate was found in 13.5% of subjects. The median of cystatin C was 0.8 mg/L (0.33;1.71), the median of creatinine-63 µmol/L (6;126). The median of eGFRcys was lower than eGFRcreat (92 mL/min/1.73 m2 vs. 101 mL/min/1.73 m2, p < 0.001). A total of 30.2% of all patients were classified as having worse kidney function when using cystatin C vs. creatinine for eGFR calculation. Linear correlations were found between cystatin C and HbA1c, r = -0.088, p < 0.05, as well as cystatin C and HDL, r = -0.097, p < 0.01. Conclusions: This study showed that cystatin C might be used as an additional biomarker of early kidney injury in young patients with T1D.

Colorimetric and Electrochemical Screening for Early Detection of Diabetes Mellitus and Diabetic Retinopathy-Application of Sensor Arrays and Machine Learning.

In this review, a selection of works on the sensing of biomarkers related to diabetes mellitus (DM) and diabetic retinopathy (DR) are presented, with the scope of helping and encouraging researchers to design sensor-array machine-learning (ML)-supported devices for robust, fast, and cost-effective early detection of these devastating diseases. First, we highlight the social relevance of developing systematic screening programs for such diseases and how sensor-arrays and ML approaches could ease their early diagnosis. Then, we present diverse works related to the colorimetric and electrochemical sensing of biomarkers related to DM and DR with non-invasive sampling (e.g., urine, saliva, breath, tears, and sweat samples), with a special mention to some already-existing sensor arrays and ML approaches. We finally highlight the great potential of the latter approaches for the fast and reliable early diagnosis of DM and DR.

Impact of Newborn Screening on Clinical Presentation of Congenital Adrenal Hyperplasia.

Background and Objectives: The main reason for Newborn screening (NBS) for congenital adrenal hyperplasia (CAH) is to prevent adrenal insufficiency that can lead to life-threatening conditions. On the other hand, screening programs are not always sensitive and effective enough to detect the disease. We aimed to evaluate impact of the national NBS on the clinical presentation of patients with CAH in Lithuania. Materials and Methods: A retrospective study was performed on data of 88 patients with CAH from 1989 to 2020. Patients with confirmed CAH were divided into two groups: (1) 75 patients diagnosed before NBS: 52 cases with salt-wasting (SW), 21 with simple virilising (SV) and two with non-classical (NC) form; (2) 13 patients diagnosed with NBS: 12 cases with SW and 1 case with SV form. For the evaluation of NBS effectiveness, data of only male infants with salt-wasting CAH were analysed (n = 36, 25 unscreened and nine screened). Data on gestational age, birth weight, weight, symptoms, and laboratory tests (serum potassium and sodium levels) on the day of diagnosis, were analysed. Results: A total of 158,486 neonates were screened for CAH from 2015 to 2020 in Lithuania and CAH was confirmed in 13 patients (12 SW, one-SV form), no false negative cases were found. The sensitivity and specificity of NBS program for classical CAH forms were 100%; however, positive predictive value was only 4%. There were no significant differences between unscreened and screened male infant groups in terms of age at diagnosis, serum potassium, and serum sodium levels. Significant differences were found in weight at diagnosis between the groups (-1.67 ± 1.12 SDS versus 0.046 ± 1.01 SDS of unscreened and screened patients respectively, p = 0.001). Conclusions: The sensitivity and specificity of NBS for CAH program were 100%, but positive predictive value-only 4%. Weight loss was significantly lower and the weight SDS at diagnosis was significantly higher in the group of screened patients.

Kinetics of C-peptide during mixed meal test and its value for treatment optimization in monogenic diabetes patients.

AIM: The mixed meal tolerance test (MMTT) is a gold standard for evaluating beta-cell function. There is limited data on MMTT in monogenic diabetes (MD). Therefore, we aimed to analyze plasma C-peptide (CP) kinetics during MMTT in young MODY and neonatal diabetes patients as a biomarker for beta-cell function. METHODS: We included 41 patients with MD diagnosis (22 GCK, 8 HNF1A, 3 HNF4A, 4 KCNJ11, 2 ABCC8, 1 INS, 1 KLF11). Standardized 3-hour MMTT with glycemia and plasma CP measurements were performed for all individuals. Pancreatic beta-cell response was assessed by the area under the curve CP (AUCCP), the baseline CP (CPBase) and the peak CP (CPmax). Threshold points of CPBase, CP90, CPmax and CPAUC were determined from analysis of ROC curves. RESULTS: GCK diabetes patients had significantly higher AUCCP, CPBase and CPmax compared to HNF4A and KCNJ11 patients. In HNF4A, KCNJ11 and ABCC8 patients with all CP levels < 200 pmol/L, the treatment change attempt to sulfonylurea agent was unsuccessful. The ROC analysis showed that CP baseline threshold equal or higher to 133.5 pmol/L could be used to predict successful switch to oral agents. CONCLUSION: A pretreatment challenge with MMTT might be used to guide the optimal treatment after molecular diagnosis of MD.

Prevalence of Metabolic Syndrome and Impaired Glucose Metabolism among 10- to 17-Year-Old Overweight and Obese Lithuanian Children and Adolescents.

BACKGROUND: Overweight (Ow) and obesity among adults and children increases the risk of metabolic consequences. Metabolic syndrome (MS) and impaired glucose metabolism are well-known risk factors for cardiovascular diseases and type 2 diabetes. The aim of this study was to evaluate the prevalence of MS and impaired glucose metabolism among Ow and obese (Ob) children and adolescents (aged 10-17 years) in Lithuania, and to evaluate the associations between insulin resistance (IR) indices and anthropometric parameters as well as metabolic disturbances. METHODS: The study population consisted of 344 OwOb children and adolescents of all pubertal stages. Oral glucose tolerance tests (OGTTs), IR and ß cell function indices, lipid profile, and anthropometric parameters of all subjects were analyzed. MS was defined according to the International Diabetes Federation consensus guidelines. RESULTS: MS was found in 21.3% of the OwOb children and adolescents, and 12.1% had impaired glucose metabolism (6.9% with impaired fasting glucose, 4.5% with impaired glucose tolerance, and 0.6% with type 2 diabetes). IR was directly related to body mass index and waist circumference, waist-to-height and waist-to-hip ratios, and sum of skin-fold thicknesses. Children with MS were more insulin-resistant, had higher odds ratio for prediabetes and had a more disturbed lipid profile than subjects without MS. Moreover, total cholesterol and low-density lipoprotein cholesterol levels were significantly lower in the more mature OwOb adolescents. CONCLUSION: MS and lipid profile disturbances are common in OwOb children and adolescents. MS is directly associated with IR. Therefore, OwOb children and adolescents should be carefully followed up for metabolic abnormalities during late childhood as these can persist into adulthood.

Papillary Thyroid Carcinoma Tissue miR-146b, -21, -221, -222, -181b Expression in Relation with Clinicopathological Features.

We analyzed miR-146b, miR-21, miR-221, miR-21, and miR-181b in formalin fixed paraffin-embedded papillary thyroid carcinoma (PTC) tissue samples of 312 individuals and evaluated their expression relationship with clinicopathological parameters. A higher expression of miR-21 was related to unifocal lesions (p < 0.011) and autoimmune thyroiditis (0.007). miR-221, miR-222 expression was higher in the PTC tissue samples with extrathyroidal extension (p = 0.049, 0.003, respectively). In a group of PTC patients with pT1a and pT1b sized tumors, the expression of miR-146b, miR-21, miR-221, and miR-222 in PTC tissue samples was lower than in patients with pT2, pT3, and pT4 (p = 0.032; 0.0044; 0.003; 0.001; 0.001, respectively). Patients with lymph node metastases had higher expression of miR-21, -221, -222, and -181b (p < 0.05). A high expression of miR-146b, miR-21, miR-221 panel was associated with decreased overall survival (OS) (Log rank p = 0.019). Univariate analysis revealed that presence of metastatic lymph nodes and high expression of miR-146b, miR-21, and miR-221 panels were associated with increased hazard of shorter OS. After multivariate analysis, only sex (male) and age (≥55 years) emerged as independent prognostic factors associated with shorter OS (HR 0.28 (95% CI 0.09-0.86) and HR 0.05 (95% CI 0.01-0.22), respectively). In conclusion, 5 analyzed miRs expression have significant relations to clinicopathologic parameters so further investigations of these molecules are expedient while searching for prognostic PTC biomarkers.

Association between symptoms of depression, diabetes complications and vascular risk factors in four European cohorts of individuals with type 1 diabetes - InterDiane Consortium.

AIMS: To investigate the association between depressive symptomatology and health markers in type 1 diabetes. METHODS: Four countries from the InterDiane Consortium had adopted the Finnish Diabetic Nephropathy Study protocol, including the Beck Depression Inventory (BDI). Associations between depression symptomatology, diabetes complications (diabetic nephropathy, proliferative retinopathy, major adverse cardiovascular events [MACE]) and vascular risk factors (metabolic syndrome, body mass index, glycaemic control) were investigated. RESULTS: In a sample of 1046 participants (Croatia n = 99; Finland n = 314; Latvia n = 315; Lithuania n = 318), 13.4% displayed symptoms of depression (BDI score ≥ 16) with no statistically significant difference in the prevalence of depression among the cohorts. The highest rates of diabetic nephropathy (37.1%) and proliferative retinopathy (36.3%) were observed in Lithuania. The rates of MACE and metabolic syndrome were highest in Finland. In joint analyses, individuals exhibiting depression symptomatology had higher HbA1c (79 vs. 72 mmol/mol, p < 0.001) and higher triglyceride concentration (1.67 vs. 1.28 mmol/l, p < 0.001), than those without. In the multivariable model, BDI score was positively associated with the presence of diabetic nephropathy, proliferative retinopathy, MACE, and metabolic syndrome and its triglyceride component. Moreover, BDI score was positively associated with the number of metabolic syndrome components, triglyceride concentration, and HbA1c. CONCLUSIONS: Comorbid depression should be considered a relevant factor explaining metabolic problems and vascular outcomes. Causality cannot be inferred from this cross-sectional study.

Plasma-Derived miRNA-222 as a Candidate Marker for Papillary Thyroid Cancer.

We analyzed five miRNA molecules (miR-221; miR-222; miR-146b; miR-21; miR-181b) in the plasma of patients with papillary thyroid cancer (PTC), nodular goiter (NG) and healthy controls (HC) and evaluated their diagnostic value for differentiation of PTC from NG and HC. Preoperative PTC plasma miRNA expression (n = 49) was compared with plasma miRNA in the HC group (n = 57) and patients with NG (n = 23). It was demonstrated that miR-221; miR-222; miR-146b; miR-21 and miR-181b were overexpressed in preoperative PTC plasma samples compared to HC (p < 0.0001; p < 0.0001; p < 0.0001; p < 0.0001; p < 0.002; respectively). The upregulation in tumor tissue of these miRNAs was consistent with The Cancer Genome Atlas Thyroid Carcinoma dataset. A significant decrease in miR-21; miR-221; miR-146b and miR-181b expression was observed in the plasma of PTC patients after total thyroidectomy (p = 0.004; p = 0.001; p = 0.03; p = 0.036; respectively). The levels of miR-222 were significantly higher in the preoperative PTC compared to the NG group (p = 0.004). ROC curve (receiver operating characteristic curve) analysis revealed miR-222 as a potential marker in distinguishing PTC from NG (AUC 0.711; p = 0.004). In conclusion; circulating miR-222 profiles might be useful in discriminating PTC from NG.