Nighttime Hypoglycemia in Children with Type 1 Diabetes after one Day of Football Tournament.

The aim of the study was to investigate factors related to the occurrence of nighttime hypoglycemia after a football tournament in children with type 1 diabetes mellitus. The multicenter study (GoalDiab study) included 189 children and adolescents with type 1 diabetes mellitus, from 11 diabetes care centers in Poland. Hypoglycemia was defined according to the International Hypoglycemia Study Group Statement. We analyzed the data of 95 participants with completed protocols with regards to nighttime hypoglycemia (82% male), aged 11.6 (9.8-14.2) years, diabetes duration 5.0 (2.0-8.0) years. There were 47 episodes of nighttime Level 1 hypoglycemia (≤3.9 mmol/L). Occurrence of clinically important Level 2 hypoglycemia (<3.0 mmol/L) during a game period was positively associated with nighttime hypoglycemia (≤3.9 mmol/L) incident (Odds Ratio=10.7; 95% Confidence Interval: 1.1-100.2; p=0.04). Using Continuous Glucose Monitoring was negatively associated with the occurrence of nighttime hypoglycemia (≤3.9 mmol/L) compared with using glucose meters or Flash Glucose Monitoring (Odds Ratio=0.31; 95% Confidence Interval: 0.12-0.83; p=0.02). The occurrence of clinically important hypoglycemia related to physical activity is associated with the occurrence of hypoglycemia during the night. Continuous Glucose Monitoring is negatively associated with nighttime hypoglycemia after a day of competition.

Dermal microvessel density and maturity is closely associated with atherogenic dyslipidemia and accumulation of advanced glycation end products in adult patients with type 1 diabetes.

In patients with diabetes, functional changes in microcirculation and subclinical vascular pathology precede clinical manifestation of microangiopathic complications. The objective of this study was to evaluate the association between established vascular risk factors and density, maturity, and reactivity of dermal blood vessels in adults with type 1 diabetes (DM1). We included 148 DM1 patients (87 men) with a median (IQR) age of 40.5 (30.5-49) years and a median diabetes duration of 21 (17-29.5) years. The control group consisted of 13 healthy volunteers (6 men) with a median (IQR) age of 36 (31-43). Accumulation of advanced glycation end products (AGEs) was assessed using the AGE-Reader device. In the immunohistochemical (IHC) analyses, anti-CD133, anti-CD34, anti-CD31, and anti-vWF autoantibodies were used. Microvessel density (MVD) in the skin was calculated using the "hot spots technique". Microvascular function was examined by single-point laser-Doppler flowmetry (LDF). Median MVD, calculated for both papillary and reticular dermis, for CD31 antigen expression was 38 (19-56) per 1 mm2. The median CD34+ blood vessel density was 121 (100-155) per 1 mm2, CD133+ was 79 (63-92) per 1 mm2, and vWF+ was 50 (40-69) per 1 mm2. The average CD34/CD31 index was 2.78, the vWF/CD31 ratio was 1.32 and the CD133/CD31 ratio was 1.75. The CD34/CD31 index was positively associated with serum triglyceride concentration (Beta: 0.26, p = 0.012) and negatively associated with serum HDL cholesterol concentration (Beta: -0.22, p = 0.027), both independently from age, sex, diabetes duration, BMI, HbA1c value, presence of hypertension, and eGFR. We found a negative correlation between MVD assessed by CD31 and skin AF (r = -0.21, p = 0.016). In LDF, the area under the blood flow/time curve (AUC) correlated positively with CD31+ MVD (r = 0.21, p = 0.011) and negatively with CD34+ MVD (r = -0.20, p = 0.017). The MVD did not differ between participants with diabetes and healthy controls, and it did not differ according to the presence of retinopathy among the participants with diabetes. Atherogenic dyslipidemia is associated with increased formation of new blood vessels, characterized by high expression of CD34 and low reactivity in LDF. Conversely, chronic hyperglycemia and excessive formation of AGEs may result in decreased vascularity.

Assessment of Safety and Glycemic Control During Football Tournament in Children and Adolescents With Type 1 Diabetes-Results of GoalDiab Study.

PURPOSE: To assess glycemic control and safety of children and adolescents with type 1 diabetes participating in a 2-day football tournament. METHODS: In total, 189 children with type 1 diabetes from 11 diabetes care centers, in Poland, participated in a football tournament in 3 age categories: 7-9 (21.2%), 10-13 (42.9%), and 14-17 (36%) years. Participants were qualified and organized in 23 football teams, played 4 to 6 matches of 30 minutes, and were supervised by a medical team. Data on insulin dose and glycemia were downloaded from personal pumps, glucose meters, continuous glucose monitoring, and flash glucose monitoring systems. RESULTS: The median level of blood glucose before the matches was 6.78 (4.89-9.39) mmol/L, and after the matches, it was 7.39 (5.5-9.87) mmol/L (P = .001). There were no episodes of severe hypoglycemia or ketoacidosis. The number of episodes of low glucose value (blood glucose ≤3.9 mmol/L) was higher during the tournament versus 30 days before: 1.2 (0-1.5) versus 0.7 (0.3-1.1) event/person/day, P < .001. Lactate levels increased during the matches (2.2 [1.6-4.0] mmol/L to 4.4 [2.6-8.5] mmol/L after the matches, P < .001). CONCLUSIONS: Large football tournaments can be organized safely for children with type 1 diabetes. For the majority of children, moderate mixed aerobic-anaerobic effort did not adversely affect glycemic results and metabolic safety.

Alpha-Hederin, the Active Saponin of Nigella sativa, as an Anticancer Agent Inducing Apoptosis in the SKOV-3 Cell Line.

Alpha-hederin (α-HN), a pentacyclic triterpene saponin, has recently been identified as one of the active compounds of Nigella sativa, as a potential anticancer agent. However, no extensive studies on α-HN have been done as yet, as it was in the case of thymoquinone-the main ingredient of the N. sativa essential oil. To our knowledge, there are also no data available on how α-HN acts on the human cancer ovarian cell line SKOV-3. In this study we attempt to present the cytotoxic influence of α-HN on the SKOV-3 cell line by means of two methods: Real-Time xCELLigence and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The obtained IC50 values are 2.62 ± 0.04 µg/mL and 2.48 ± 0.32 µg/mL, respectively. An induction of apoptosis in SKOV-3 cells was confirmed by staining cellular nuclei with Hoechst 33342 dye and by flow cytometry analysis by binding annexin V to the cell membranes. We found that α-HN induces apoptosis in a dose-dependent manner. In the first stages of apoptosis, the mitochondrial membrane potential was found to decrease. Also, inactivation of anti-apoptotic protein Bcl-2 was observed, as well as the caspase-9 and then caspase-3/7 activation. In addition, the treatment of SKOV-3 cells with α-HN induced the cell cycle arrest of cancer cells in G0/G1 phase. The results of our investigations indicate that α-HN induces apoptosis in the SKOV-3 cell line and that the intrinsic mitochondrial pathway is involved in the programmed cancer cell death.

Markers of Glomerular and Tubular Damage in the Early Stage of Kidney Disease in Type 2 Diabetic Patients.

Diabetic kidney disease develops in half of genetically predisposed patients with type 2 diabetes (T2DM). Early diagnosis of kidney damage and nephroprotective treatment are the ways of preventing the disease progression. Our aim was to evaluate selected laboratory markers of glomerular and tubular damage in T2DM patients with early stages of chronic kidney disease (G1/G2, A1/A2) for their associations with A2 albuminuria and early decline in the estimated glomerular filtration rate (eGFR). Among 80 T2DM patients with median eGFR of 92.4 ml/min/1.73 m2 and median urinary albumin to creatinine ratio (uACR) of 4.69 mg/g, 19 had uACR > 30 mg/g (A2). Higher serum cystatin C, serum and urine neutrophil gelatinase associated lipocalin (NGAL), urine kidney injury molecule 1 (KIM-1), detectable urine transferrin and IgG, and lower serum uromodulin significantly predicted A2 albuminuria, urine KIM-1/creatinine ratio, and IgG being the best predictors. Albuminuria, urine NGAL/creatinine, and IgG correlated with diabetes duration. Albuminuria, urine NGAL, transferrin, IgG, and uromodulin correlated with diabetes control. In a subgroup of 29 patients, retrospective data were available on changes in eGFR and uACR over one year. Decline in eGFR was observed in 17 patients and increase in uACR in 10 patients. Serum and urine NGAL correlated with eGFR changes. Higher urine NGAL, KIM-1/creatinine ratio, and detectable IgG were significantly associated with the increase in uACR. Widely available markers, serum cystatin C, urine IgG, transferrin, and NGAL, may help in early assessment of kidney disease in T2DM patients; however, large prospective studies are needed to confirm the conclusion.

Synthesis, biological evaluation and structural analysis of novel peripherally active morphiceptin analogs.

Morphiceptin (Tyr-Pro-Phe-Pro-NH2), a tetrapeptide amide, is a selective ligand of the µ-opioid receptor (MOR). This study reports the synthesis and biological evaluation of a series of novel morphiceptin analogs modified in positions 2 or/and 4 by introduction of 4,4-difluoroproline (F2Pro) in l or d configuration. Depending on the fluorinated amino acid configuration and its position in the sequence, new analogs behaved as selective full MOR agonists showing high, moderate, or relatively low potency. The most potent analog, Tyr-F2Pro-Phe-D-F2Pro-NH2, was also able to activate the κ-opioid receptor (KOR), although with low potency. Docking studies and the comparison of results with the high resolution crystallographic structure of a MOR-agonist complex revealed possible structure-activity relationships of this compound family.

Synthesis of linear and cyclic opioid-based peptide analogs containing multiple N-methylated amino acid residues.

A series of six novel opioid peptide analogs containing one to three N-methylamino acid residues, and six cyclic counterparts of these peptides were prepared by the solid-phase method. Introduction of two consecutive N-methylated amino acids, as well as cyclization of such conformationally constrained sequences, turned out to be challenging. The use of a recently reported triazine-based coupling reagent, 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium toluene-4-sulfonate, enabled the synthesis and cyclization of the designed analogs in acceptable yields and with a lesser amount of by-products than observed with the standard coupling reagents such as TBTU or HATU.

Serum pregnancy-associated plasma protein A correlates with inflammation and malnutrition in patients treated with maintenance hemodialysis.

Advanced chronic kidney disease (CKD) leads to complications such as anemia, electrolyte abnormalities, bone and mineral disorder, and malnutrition-inflammation-atherosclerosis (MIA) syndrome, that result in high cardiovascu- lar mortality. One of the biomarkers associated with inflammation and cardiovascular events is pregnancy-associated plasma protein A (PAPP-A). The aim of the study was to measure serum PAPP-A in hemodialyzed CKD patients, and to investigate its correlations with the laboratory markers of the complications. We enrolled 78 consecutive stable adult CKD patients treated with maintenance hemodialysis for median period of 60 months. PAPP-A concentrations were measured with by electrochemiluminescence immunoassay. Average serum PAPP-A in hemodialyzed patients was almost two times higher than the upper reference limit. It positively correlated with N-terminal pro-brain natriuretic peptide (NT-proBNP), serum sodium, and the markers of inflammation and malnutrition. In conclusion, serum PAPP-A seems a useful biomarker associated with cardiovascular dysfunction, inflammatory state and malnutrition in hemodialysis patients.

Cyclic side-chain-linked opioid analogs utilizing cis- and trans-4-aminocyclohexyl-D-alanine.

Cyclization of linear sequences is a well recognized tool in opioid peptide chemistry for generating analogs with improved bioactivities. Cyclization can be achieved through various bridging bonds between peptide ends or side-chains. In our earlier paper we have reported the synthesis and biological activity of a cyclic peptide, Tyr-c[D-Lys-Phe-Phe-Asp]NH2 (1), which can be viewed as an analog of endomorphin-2 (EM-2, Tyr-Pro-Phe-Phe-NH2). Cyclization was achieved through an amide bond between side-chains of D-Lys and Asp residues. Here, to increase rigidity of the cyclic structure, we replaced d-Lys with cis- or trans-4-aminocyclohexyl-D-alanine (D-ACAla). Two sets of analogs incorporating either Tyr or Dmt (2',6'-dimethyltyrosine) residues in position 1 were synthesized. In the binding studies the analog incorporating Dmt and trans-D-ACAla showed high affinity for both, µ- and δ-opioid receptors (MOR and DOR, respectively) and moderate affinity for the κ-opioid receptor (KOR), while analog with Dmt and cis-D-ACAla was exceptionally MOR-selective. Conformational analyses by NMR and molecular docking studies have been performed to investigate the molecular structural features responsible for the noteworthy MOR selectivity.

Modification of selected anti-HCMV drugs with lipophilic boron cluster modulator.

Methods for the modification of ganciclovir (GCV), acyclovir (ACV), cidofovir (CDV) and valganciclovir (VCDV) with boron cluster have been developed. Toxicity of the new derivatives was evaluated in adherent cells; no cytotoxicity was observed in five different cell lines up to 1000 microM with the exception of modified valganciclovir which was cytotoxic above 300 microM. The compounds were active against HCMV or HSV-1 by cytopathic effect or plaque reduction assays. None of the tested compounds had activity against HPIV-3 or VSV.

Large Prostate Volume Does Not Negatively Impact Health-Related Quality of Life in Patients with Prostate Cancer Treated with Ultrahypofractionated Stereotactic Body Radiotherapy.

BACKGROUND: Survival outcomes after primary radiotherapy for localized prostate cancer (PCa) are excellent, regardless of the specific treatment modality. For this reason, health-related quality of life (HRQOL) has come to play an ever more important role in treatment selection. Stereotactic body radiation therapy (SBRT) is increasingly used to treat patients with PCa. However, the impact of prostate volume on HRQOL is not clear. In this study, we aimed to determine whether a large prostate volume negatively influences HRQOL outcomes in patients undergoing ultrahypofractionated SBRT. MATERIAL AND METHODS: We conducted a prospective study of 530 men with low- and intermediate-risk localized PCa. All patients were treated from 2013 to 2017 with SBRT (Cyberknife system). HRQOL data were collected at baseline (pre-treatment), immediately after treatment, and at 12 and 24 months. QOL variables were assessed with the European Organization for Research and Treatment of Cancer QLQ-C30 and PR-25 module. Differences in the QLQ-C30 scales were considered clinically relevant when the change was >10 points. For the analysis, patients were classified into two groups according to prostate volume (≤60 vs. >60 cm3). RESULTS: The prostate volume was ≤60 cm3 in 415 patients (78.3%) and >60 cm3 in 115 (21.7%). No between-group differences were observed at baseline for any of the following variables: clinical stage; hormonal therapy; marital status; educational level; or employment status. No clinically-significant deterioration (functional and symptom scales) was observed in either group between the baseline and 24-month assessment. There were no clinically-relevant differences between the groups on any of the HRQOL variables, regardless of the prostate volume. CONCLUSIONS: This study shows that a large prostate volume (>60 cm3) does not appear to negatively impact HRQOL outcomes at two years in patients with localized prostate cancer treated with ultrahypofractionated SBRT administered with the CyberKnife system.

Helicobacter pylori infection is associated with increased accumulation of advanced glycation end products in the skin in patients with type 1 diabetes: A preliminary study.

BACKGROUND: Helicobacter pylori infection (HPI) is more frequently diagnosed in patients with diabetes. Insulin resistance in patients with type 1 diabetes (DMT1) is associated with the accumulation of advanced glycation end products (AGEs) in the skin and progression of chronic complications. OBJECTIVES: Assessment of the relationship between the incidence of HPI and skin AGEs in patients with DMT1. MATERIAL AND METHODS: The study included 103 Caucasian patients with a DMT1 duration >5 years. A fast qualitative test was performed to detect the HP antigen in fecal samples (Hedrex). The content of AGEs in the skin was estimated using an AGE Reader device (DiagnOptics). RESULTS: The HP-positive (n = 31) and HP-negative (n = 72) groups did not differ in terms of age, gender, duration of diabetes, fat content, body mass index (BMI) and lipid profile, metabolic control, and inflammatory response markers. The studied groups differed in the amount of AGEs in the skin. The relationship between HPI and increased AGEs in the skin was confirmed in a multifactor regression model taking into account age, gender, DMT1 duration, glycated hemoglobin A1c (HbA1c), BMI, low-density lipoprotein cholesterol (LDL-C) and the presence of hypertension, and tobacco use. The studied groups also differed in serum levels of vitamin D. CONCLUSIONS: Increased accumulation of AGEs in the skin of patients with DMT1 with coexisting HPI suggests that eradication of HP may significantly improve DMT1 outcomes.

SDS Electrophoresis on Gradient Polyacrylamide Gels as a Semiquantitative Tool for the Evaluation of Proteinuria.

Proteinuria is an important sign of kidney diseases. Different protein patterns in urine associated with glomerular, tubular and overload proteinuria may be differentiated using the immunochemical detection of indicator proteins or via urinary proteins electrophoresis. Our aim was to characterize sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) using commercially available 4-20% gradient gels as a method to detect and differentiate proteinuria. Our laboratory-based study used excess urine samples collected for routine diagnostic purposes from adult patients of a tertiary-care hospital, including patients with albumin/creatinine < 30 mg/g and patients with dipstick proteinuria. The limit of albumin detection was estimated to be 3 mg/L. In 93 samples with albumin/creatinine < 30 mg/g, an albumin fraction was detected in 87% of samples with a minimum albumin concentration of 2.11 mg/L. The separation of 300 urine samples of patients with proteinuria revealed distinct protein patterns differentiated using the molecular weights of the detected proteins: glomerular (albumin and higher molecular weights) and two types of tubular proteinuria ("upper" ≥20 kDa and "lower" with lower molecular weights). These patterns were associated with different values of the glomerular filtration rate (median 66, 71 and 31 mL/min/1.72 m2, respectively, p = 0.004) and different proportions of multiple myeloma and nephrological diagnoses. As confirmed using tandem mass spectrometry and western blot, the SDS-PAGE protein fractions contained indicator proteins including immunoglobulin G, transferrin (glomerular proteinuria), α1-microglobulin, retinol-binding protein, neutrophil gelatinase-associated lipocalin, cystatin C, and ß2-microglobulin (tubular), immunoglobulin light chain, myoglobin, and lysozyme (overflow). SDS-PAGE separation of urine proteins on commercially available 4-20% gradient gels is a reliable technique to diagnose proteinuria and differentiate between its main clinically relevant types.

Oseltamivir analog with boron cluster modulator.

Synthesis of novel neuraminidase inhibitor -- carborane ester of oseltamivir carboxylic acid is described, and its physicochemical and spectral characteristics is provided. Surprisingly, carborane analog of oseltamivir is of an order of magnitude less active than its precursor, the corresponding ethyl ester, which is the active principle of pharmaceutical preparations used in influenza prophylactics and therapy.

Criteria for Verification and Replanning Based on the Adaptive Radiotherapy Protocol "Best for Adaptive Radiotherapy" in Head and Neck Cancer.

No clear criteria have yet been established to guide decision-making for patient selection and the optimal timing of adaptive radiotherapy (ART) based on image-guided radiotherapy (IGRT). We have developed a novel protocol­the Best for Adaptive Radiotherapy (B-ART) protocol­to guide patient selection for ART. The aim of the present study is to describe this protocol, to evaluate its validity in patients with head and neck (HN) cancer, and to identify the anatomical and clinical predictors of the need for replanning. We retrospectively evaluated 82 patients with HN cancer who underwent helical tomotherapy (HT) and subsequently required replanning due to soft tissue changes upon daily MVCT. Under the proposed criteria, patients with anatomical changes >3 mm on three to four consecutive scans are candidates for ART. We compared the volumes on the initial CT scan (iCT) and the replanning CT (rCT) scan for the clinical target volumes (CTV1, referring to primary tumor or tumor bed and CTV2, metastatic lymph nodes) and for the parotid glands (PG) and body contour (B-body). The patients were stratified by primary tumor localization, clinical stage, and treatment scheme. The main reasons for replanning were: (1) a planning target volume (PTV) outside the body contour (n = 70; 85.4%), (2) PG shrinkage (n = 69; 84.1%), (3) B-body deviations (n = 69; 84.1%), and (4) setup deviations (n = 40; 48.8%). The replanning decision was made, on average, during the fourth week of treatment (n = 47; 57.3%). The mean reductions in the size of the right and left PG volumes were 6.31 cc (20.9%) and 5.98 cc (20.5%), respectively (p < 0.001). The reduction in PG volume was ≥30% in 30 patients (36.6%). The volume reduction in all of the anatomical structures was statistically significant. Four variables­advanced stage disease (T3−T4), chemoradiation, increased weight loss, and oropharyngeal localization­were significantly associated with the need for ART. The B-ART protocol provides clear criteria to eliminate random errors, and to allow for an early response to relevant changes in target volumes.

Fluoride enhances polystyrene nanoparticles cytotoxicity in colonocytes in vitro model.

Human gastrointestinal cells can be exposed to different xenobiotics present in food or drinking water. In this work, we assessed the cytotoxicity of polystyrene nanoparticles (PS-NPs) and how it is impacted by fluoride (F-) presence. We decided to examine PS-NPs and F- which can be easily found in drinking water and food. Commercially available amine-modified 100 nm PS-NPs were used in the study. Scanning Electron Microscopy with Electron Dispersive Spectroscopy (SEM-EDS) and Dynamic Light Scattering (DLS) were used to characterize PS-NPs. The colon cell lines (HT-29, Caco-2, CCD 841 CoN) were used. Cytotoxicity of PS-NPs and F- alone or in co-exposition were assessed with MTT assay in a time- and concentration-dependent manner. Flow cytometry was used to measure reactive oxygen species (ROS) production, cell cycle distribution, and apoptosis analysis. Transmission electron microscopy (TEM) was used to determine whether PS-NPs and/or F- can cause ultrastructure changes in the cells. We have shown that PS-NPs are cytotoxic to human colon cells in a time- and concentration-dependent manner. PS-NPs did not impact neither intracellular ROS production nor the cells cell cycle distribution. However, if HT-29 cells were co-exposed to PS-NPs and F-, an increased number of cells in G0/G1 phase and decreased number of cells in G2/M were observed. PS-NPs can cause apoptosis in HT-29 cells, this effect was enhanced if cells were co-exposed to PS-NP and F-. PS-NPs were internalised by the cells and caused ultrastructure changes. Fluoride itself (1 mM) was not cytotoxic to the cells and did not cause any changes in the ultrastructure of the cells. We have proven that polystyrene nanoparticles can be cytotoxic to human gastrointestinal cells and this effect is enhanced by fluoride.

Safety and glycemic outcomes of do-it-yourself AndroidAPS hybrid closed-loop system in adults with type 1 diabetes.

BACKGROUND: The aim of the study was to assess the safety and glycemic outcomes with the use of a Do-It-Yourself (DIY) Hybrid Closed-Loop (HCL) system based on the AndroidAPS application in type 1 diabetes (T1D). METHODS: Single-center clinical trial, with 3-week run-in and 12-week study period. DIY HCL system consisted of the Dana Diabecare RS insulin pump, Dexcom G5 continuous glucose monitoring system and AndroidAPS application. Primary outcome was safety: incidences of severe hypoglycemia, diabetic ketoacidosis, time spent in glycemia <54 mg/dl. Secondary endpoints included percentage of time in range (TIR) 70-180 mg/dl, time below 70 mg/dl, HbA1c, insulin requirements, and body weight. RESULTS: In total 12 subjects (5 men, 7 women) were enrolled, mean age 31.3±6.7, 95%CI(27.7-34.9) years, mean diabetes duration 16.1±5.7, 95%CI(13.0-19.2) years. No episodes of severe hypoglycemia or ketoacidosis were observed. Percentage of time spent in glycemia below 54mg/dl was not increased. Average sensor glycemia was lower in the study period than baseline (141.1 ± 8.4, 95%CI(136.3-145.9) vs. 153.3 ± 17.9, 95%CI(143.2-163.4), mg/dl p<0.001). TIR 70-180 mg/dl was improved by 11.3%, 95%CI(2.8%-19.8%) (from 68.0 ± 12.7 to 79.3 ± 6.4%, p<0.001), without increasing hypoglycemia time. The HbA1c level decreased by -0.5%, 95%CI(-0.9%--0.1%) (from 6.8 ± 0.5 to 6.3 ± 0.4%, p<0.001). Additionally, in the last 4 weeks of the study period participants significantly improved and showed TIR 70-180 mg/dl 82.1 ± 5.6%, 95%CI(78.9-85.3), time <54 mg/dl 0.30 (0.20-0.55)%, median 95%CI(0.1-0.7) and <70 mg/dl 1.90 (1.10-3.05)%, median 95%CI(0.7-3.2). The insulin requirement and body weight did not change in the study. CONCLUSIONS: The study revealed safety of the Do-It-Yourself HCL system AndroidAPS in adults with T1D, limited to well-controlled, highly selected and closely monitored patients. The use of AndroidAPS significantly improved HbA1c, time in range and average sensor glycemia without increasing hypoglycemia. As both patients and their medical team are gaining experience using the system over time, they improve glycemic control. TRIAL REGISTRATION: German Clinical Trials Register: no. DRKS00015439; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00015439.

Acute Phase Proteins and Vitamin D Seasonal Variation in End-Stage Renal Disease Patients.

End-stage renal disease (ESRD) patients are vulnerable to vitamin D deficiency due to impaired renal hydroxylation, low dietary intake and inadequate sun exposure. Vitamin D plays a role in innate and adaptive immunity and its seasonal variation has been linked to mortality. ESRD is associated with inadequate removal of pro-inflammatory cytokines regulating acute phase protein (APP) synthesis. Our aim was to look for associations between lifestyle factors, diet, and vitamin D seasonal variation and their relationship with selected APPs and calcium-phosphate metabolism. The study included 59 ESRD patients treated with maintenance hemodialysis. A 24-hour dietary recall was conducted in the post-summer (November 2018, PS) and post-winter (February/March 2019, PW) period, and blood was collected for the measurements of serum total vitamin D, α1-acid glycoprotein (AGP), C-reactive protein (CRP), albumin, prealbumin (PRE), parathormone, calcium and phosphate. A self-constructed questionnaire gathered information on vitamin D supplementation, sun exposure and physical activity. Higher caloric intake was observed PW compared PS. Less than 15% of participants met the dietary recommendations for energy, protein, fiber, vitamin D and magnesium intake. Vitamin D supplementation was associated with higher serum vitamin D regardless of season. AGP, PRE, albumin, and vitamin D presented seasonal changes (higher values PS). In patients with serum vitamin D below 25 ng/mL, vitamin D seasonal change correlated with CRP and prealbumin change. Phosphate and Ca × P correlated positively with AGP. A low vitamin D serum level could impact the inflammatory process; however, more studies are needed to confirm the relationship.

Does Beta-Trace Protein (BTP) Outperform Cystatin C as a Diagnostic Marker of Acute Kidney Injury Complicating the Early Phase of Acute Pancreatitis?

Acute pancreatitis (AP) belongs to the commonest acute gastrointestinal conditions requiring hospitalization. Acute kidney injury (AKI) often complicates moderately severe and severe AP, leading to increased mortality. Among the laboratory markers proposed for early diagnosis of AKI, few have been studied in AP, including cystatin C and neutrophil gelatinase-associated lipocalin (NGAL). Beta-trace protein (BTP), a low-molecular-weight glycoprotein proposed as an early marker of decreased glomerular filtration, has never been studied in AP. We investigated the diagnostic usefulness of serum BTP for early diagnosis of AKI complicating AP in comparison to previously studied markers. BTP was measured in serum samples collected over the first three days of hospital stay from 73 adult patients admitted within 24 h of mild to severe AP. Thirteen patients (18%) developed AKI in the early phase of AP. Serum BTP was higher in patients who developed AKI, starting from the first day of hospitalization. Strong correlations were observed between BTP and serum cystatin C but not serum or urine NGAL. On admission, BTP positively correlated with endothelial dysfunction. The diagnostic usefulness of BTP for AKI was similar to cystatin C and lower than NGAL. Increased BTP is an early predictor of AKI complicating AP. However, it does not outperform cystatin C or NGAL.

An increased skin microvessel density is associated with neurovascular complications in type 1 diabetes mellitus.

The aim of this study was to assess the blood vessel density and maturity in the skin of adults with type 1 diabetes in relation to the presence of late neurovascular complications. We included 148 patients (87 men) with a median (interquartile range) age of 41 (31-49) and median diabetes duration of 21 (17-30) years. Microvessel (CD133, CD34, CD31 and von Willebrand factor) markers were evaluated by indirect immunohistochemistry assay in material from a skin biopsy. Diabetic retinopathy was diagnosed using direct ophthalmoscopy, and diabetic kidney disease was estimated in people with increased albuminuria and a 10-year duration of diabetes or evidence of diabetic retinopathy . Diabetic peripheral neuropathy diagnosis was based on Toronto definition, cardiac autonomic neuropathy on validated ProSciCard III program. Microvessel density, assessed by CD34 and CD133, was significantly higher in patients with cardiac autonomic neuropathy [160 (125-175) vs 121 (100-154)/1 mm2, p = 0.001 and 92 (83-104) vs 79 (63-92)/1 mm2, p = 0.007, respectively] and CD34 in patients with diabetic peripheral neuropathy [135 (106-168) vs 121 (95-145)/1 mm2, p = 0.018], as compared with subjects without complications. In multivariate logistic regression, density of CD34 and CD133 positive vessels was associated with presence of cardiac autonomic neuropathy [odds ratio 1.016 (95% confidence interval: 1.002-1.029), p = 0.019 and odds ratio 1.037 (95% confidence interval: 1.008-1.067), p = 0.011, respectively]. It was independent from age, sex, diabetes duration, smoking status, body mass index and HbA1c value. Density of CD34 positive vessels was also associated with diabetic peripheral neuropathy, independently from sex and diabetes duration [odds ratio 1.009 (95% confidence interval: 1.001-1.020), p = 0.037]. Skin microvessel density is increased in adults with clinical evidence of neurovascular complications of type 1 diabetes. This is associated with predominance of the vessels of low maturity.