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.

Prognostic Value of Cortisol Index of Endobiogeny in Acute Myocardial Infarction Patients.

Background and Objectives: Serum cortisol has been extensively studied for its role during acute myocardial infarction (AMI). Reports have been inconsistent, with high and low serum cortisol associated with various clinical outcomes. Several publications claim to have developed methods to evaluate cortisol activity by using elements of complete blood count with its differential. This study aims to compare the prognostic value of the cortisol index of Endobiogeny with serum cortisol in AMI patients, and to identify if the risk of mortality in AMI patients can be more precisely assessed by using both troponin I and cortisol index than troponin I alone. Materials and methods: This prospective study included 123 consecutive patients diagnosed with AMI. Diagnostic coronary angiography and revascularization was performed for all patients. Cortisol index was measured on admission, on discharge, and after 6 months. Two year follow-up for all patients was obtained. Results: Our study shows cortisol index peaks at 7-12 h after the onset of AMI, while serum cortisol peaked within 3 h from the onset of AMI. The cortisol index is elevated at admission, then significantly decreases at discharge; furthermore, the decline to its bottom most at 6 months is observed with mean values being constantly elevated. The cortisol index on admission correlated with 24-month mortality. We established combined cut-off values of cortisol index on admission > 100 and troponin I > 1.56 µg/las a prognosticator of poor outcomes for the 24-month period. Conclusions: The cortisol index derived from the global living systems theory of Endobiogeny is more predictive of mortality than serum cortisol. Moreover, a combined assessment of cortisol index and Troponin I during AMI offers more accurate risk stratification of mortality risk than troponin alone.

Risk Factors for Delayed Neurocognitive Recovery According to Brain Biomarkers and Cerebral Blood Flow Velocity.

Background and Objectives: The aim of this study is to identify risk factors for the development of delayed neurocognitive recovery (dNCR). Methods: 140 patients underwent neurocognitive evaluations (Adenbrooke, MoCa, trial making, and CAM test) and middle cerebral artery (MCA) blood flow velocity (BFV) measurements, one day before cardiac surgery. BFV was re-evaluated after anesthesia induction, before the beginning, middle, end, and after cardiopulmonary bypass (CPB) and postsurgery. To measure glial fibrillary acidic protein (GFAP) and neurofilament heavy chain (Nf-H), blood samples were collected after anesthesia induction, 24 and 48 h after the surgery. Neurocognitive evaluation was repeated 7-10 days after surgery. According to the results, patients were divided into two groups: with dNCR (dNCR group) and without dNCR (non-dNCR group). Results: 101 patients completed participation in this research. GFAP increased in both the non-dNCR group (p < 0.01) and in the dNCR group (p < 0.01), but there was no difference between the groups (after 24 h, p 0.342; after 48 h, p 0.273). Nf-H increased in both groups (p < 0.01), but there was no difference between them (after 24 h, p = 0.240; after 48 h, p = 0.597). MCA BFV was significantly lower in the dNCR group during the bypass (37.13 cm/s SD 7.70 versus 43.40 cm/s SD 9.56; p = 0.001) and after surgery (40.54 cm/s SD 11.21 versus 47.6 cm/s SD 12.01; p = 0.003). Results of neurocognitive tests correlated with CO2 concentration (Pearson's r 0.40, p < 0.01), hematocrit (r 0.42, p < 0.01), MCA BFV during bypass (r 0.41, p < 0.01), and age (r -0.533, p < 0.01). The probability of developing dNCR increases 1.21 times with every one year of increased age (p < 0.01). The probability of developing dNCR increases 1.07 times with a decrease of BFV within 1 cm/s during bypass (p = 0.02). Conclusion: Risk factors contributing to dNCR among the tested patients were older age and middle cerebral artery blood flow velocity decrease during bypass.

The influence of blood flow velocity changes to postoperative cognitive dysfunction development in patients undergoing heart surgery with cardiopulmonary bypass.

BACKGROUND: The aim of this study was to compare blood flow velocity changes in the middle cerebral artery before, during and after heart surgery with cardiopulmonary bypass for patients with and without postoperative cognitive dysfunction. MATERIALS AND METHODS: A total of 100 patients, undergoing elective coronary artery bypass grafting or/and valve surgery enrolled in the study. A neurocognitive test evaluation included Adenbrooke, Mini-Mental State Examination and Trial Making test before and 7-10 days after surgery. Middle cerebral artery mean blood flow velocity was evaluated 1 day before the surgery, after anaesthesia induction, before cardiopulmonary bypass, at the beginning, ending and after cardiopulmonary bypass, and post surgery in intensive care unit. Blood samples for glial fibrillary acidic protein were measured after anaesthesia induction, 24 hours and 48 hours after surgery. According to neurocognitive tests results patients were divided in to two groups: patients with and without postoperative cognitive dysfunction. RESULTS: Of the 100, 86 patients completed investigation. After induction, blood flow velocity of the middle cerebral artery was lower in postoperative cognitive dysfunction group (41.2; min 27.91, max 49.47) than in the H group (41.2, min 21.9, max 84.3) p = 0.034, and during cardiopulmonary bypass, blood flow velocity of the middle cerebral artery was lower in the postoperative cognitive dysfunction group (37.35, min 26.6, max 44.02) than the H group (42.3, min 20.1, max 86.5), p = 0.001. After the surgery, blood flow velocity of the middle cerebral artery was lower in the postoperative cognitive dysfunction group (40.7, min 29.7, max 50.4) than in the H group (45.3, min 34.12, max 59.88), p = 0.05. Results of cognitive tests had weak correlation (rho, 0.391) with middle cerebral artery's blood flow velocity after anaesthesia induction (p = 0.001) and during bypass (p = 0.018). The receiver operating characteristic analysis showed that the blood flow velocity of the middle cerebral artery during bypass (area under the curve = 0.735) was a fair predictor for postoperative cognitive dysfunction (p = 0.001). No significant correlations were found among glial fibrillary acidic protein, middle cerebral artery blood flow velocity, and cognitive tests results. CONCLUSION: Middle cerebral artery's blood flow velocity was decreased after anaesthesia induction and during cardiopulmonary bypass for patients with postoperative cognitive dysfunction comparing with their blood flow velocity preoperatively. Blood flow velocity during bypass has diagnostic value for postoperative cognitive dysfunction. Brain biomarker glial fibrillary acidic protein is not helpful in diagnosing postoperative cognitive dysfunction.

The association of matrix metalloproteinases polymorphisms and interleukins in advanced age-related macular degeneration.

PURPOSE: To assess the impact of matrix metalloproteinase (MMP)1-1607 1G/2G (rs1799750), MMP7-181 A/G (rs11568818) single-nucleotide polymorphism and systemic cytokins interleukin-1 beta (IL-1ß), IL-6 levels on the development of exudative age-related macular degeneration (eAMD) Methodology: The study group comprised 282 patients with eAMD, and the control group enrolled 379 randomly selected persons. The genotyping of MMP1-1607 (rs1799750) and MMP7-181 (rs11568818) was performed by using the polymerase chain reaction-based restriction fragment length polymorphism method. To determine IL-1ß and IL-6 serum levels, the immunoenzymatic method with monoclonal antibodies coated plates was performed. RESULTS: MMP1 rs1799750 1G/2G genotype was more frequently found in the development of eAMD. It was associated with a 4.3-fold increased risk for eAMD under the codominant model and a 4.9-fold increased risk for eAMD under the overdominant model. The effect was more pronounced at the age of less than 65 years. IL-1ß concentration was significantly higher for MMP1 rs1799750 1G/1G genotype and MMP7 rs11568818 A/G genotype in eAMD patients compared with control group subjects. CONCLUSIONS: MMP1 rs1799750 1G/2G genotype was found to play a significant role in the development of eAMD at the age of less than 65 years. IL-1ß concentration was significantly higher in eAMD patients for MMP1 rs1799750 1G/1G genotype and MMP7 rs11568818 A/G genotype compared with control group subjects.

Three different motor task strategies to assess neuromuscular adjustments during fatiguing muscle contractions in young and older men.

Healthy aging is associated with a marked decline in motor performance. The functional consequences of applying varying novel or unexpected motor stimuli during intermittent isometric prolonged (fatiguing) motor tasks for lower limb neuromuscular fatigability and steadiness, perception of effort, and blood markers of stress in healthy aged men compared with young men have not been investigated. The participants in this study were 15 young men (aged 22 ± 4 years) and 10 older men (aged 67 ± 6 years). They performed 100 intermittent isometric knee extensions under three experimental conditions involving intermittent isometric contraction tasks according to constant, predictable, and unpredictable torque target sequences. The variability in maximal voluntary contraction averaged 50%, and was 25, 50, and 75% for the three strategies. All included a 5-s contraction and 20-s rest. The main variables were measured before exercise, after 100 repetitions, and 1 h after exercise. In all experimental trials, the decreases in the maximal voluntary contraction and central activation ratio, and the increases in effort sensation and muscle temperature, were smaller in older men than in younger men. The coefficient of variation during the motor performance did not differ between age groups. However, in all three strategies, the dopamine concentration was significantly higher in older than in younger men. The prolactin concentration did not differ significantly between age groups or conditions, although its decrease during loading correlated negatively with the central activation ratio.

Tracking Restoration of Park and Urban Street Settings in Coronary Artery Disease Patients.

UNLABELLED: The physiological effects of natural and urban environments on the cardiovascular system of coronary artery disease (CAD) patients are not fully understood. This controlled field study examines the effects of restorative walking in a park vs. in an urban street environment on CAD patients' stress parameters and cardiac function. METHODS: Twenty stable CAD patients were randomly allocated to 7 days controlled walking in a city park or in an urban street environment group. The relationship between different environmental exposures and health effects was analyzed using Wilcoxon signed-rank test and exact Mann-Whitney U test. RESULTS: The mean reduction in cortisol levels and negative effects after the walk on the first day was greater in the city park than in the urban street exposed group, while a reduction in negative effects in the urban group were greater after seven days. The reduction in diastolic blood pressure (DBP) in the park group was evident on the seventh day before the walk (-4 mm Hg, p = 0.031) and 60 min after the walk (-6.00 mm Hg, p = 0.002). The cortisol slope was negatively associated with the DBP changes (r = -0.514, p < 0.05). CONCLUSIONS: Physical activity in a green environment with noise and air pollution levels lower than in an urban environment has a greater positive effect on CAD patients' stress level and hemodynamic parameters. Mitigating green environmental influences may allow urban residents to maintain health and reduce disability.

N-carboxymethyllysine as a biomarker for coronary artery disease and age-related macular degeneration.

BACKGROUND AND OBJECTIVE: An association between coronary artery disease (CAD) and age-related macular degeneration (ARMD) has long been postulated, but exact mechanisms remain unclear. The global prevalence of CAD and ARMD increases and early biomarkers for early diagnosis of these diseases are necessary. The aim of this study was to investigate the plasma level of oxidative stress biomarker CML in patients with and without angiographic findings of atherosclerosis in the coronary arteries (CADath+ and CADath-, respectively) and to assess if there was an association of CAD with ARMD. MATERIALS AND METHODS: The study enrolled 233 subjects. Based on cardiologic and ophthalmologic examinations, the patients were divided into four subgroups: CADath+ARMD+, CADath+ARMD-, CADath-ARMD+, and CADath-ARMD-. The enzyme-linked immunosorbent assay was used for the measurement of plasma CML levels. Serum lipid levels were determined by an automatic analyzer using conventional enzymatic methods. RESULTS: CADath+ patients had higher CML concentration compared to CADath- subjects (1.04±0.6 vs. 0.83±0.4ng/mL, P<0.001). The highest mean CML level (1.12±0.7ng/mL) was found in CADath+ARMD+ patients. The mean plasma CML concentration was higher in subjects with any of the analyzed diseases compared to CADath-ARMD- subjects. A significant positive association of CADath+ (OR=2.50, 95% CI 1.60-3.90, P=0.0001), ARMD (OR=2.08, 95% CI 1.40-3.11, P=0.0001) and both analyzed diseases (OR=4.67, 95% CI 2.29-9.53, P=0.0001) with an increased level of plasma CML in a logistic regression model adjusting by age was identified. CONCLUSIONS: The level of CML, an oxidative stress biomarker, reflects the presence of atherosclerosis in coronary arteries and shows a possible link between ARMD and CADath+ via oxidative status.

Changes in Indirect Markers of Muscle Damage and Tendons After Daily Drop Jumping Exercise with Rapid Load Increase.

The aim of this study was to assess changes in indirect markers of muscle damage and type I collagen degradation, as well as, patellar and Achilles tendon morphological differences during nine daily drop-jumps sessions with constant load alternated with rapid increases in load to test the hypothesis that frequent drop-jump training results in negative muscular and tendon adaptation. Young men (n = 9) performed daily drop jump workouts with progression every 3 days in terms of number of jumps, platform height and squat amplitude. Voluntary and electrically evoked knee extensor torque, muscle soreness, blood plasma creatine kinase (CK) activity and carboxyterminal cross-linked telopeptide (ICTP), patellar and Achilles tendon thickness and cross-sectional area (CSA) were assessed at different time points during the training period and again on days 1, 3, 10 and 17 after the training. The findings were as follows: (1) steady decline in maximal muscle strength with major recovery within 24 hours after the first six daily training sessions; (2) larger decline in electrically induced muscle torque and prolonged recovery during last three training sessions; (3) increase in patellar and Achilles tendons CSA without change in thickness towards the end of training period; (4) increase in jump height but not in muscle strength after whole training period. Our findings suggest that frequent drop-jump sessions with constant load alternated with rapid increases in load do not induce severe muscle damage or major changes in tendons, nonetheless, this type of loading is not advisable for muscle strength improvement. Key pointsFrequent drop jump training induces activation mode dependent muscle torque depression late in the training period.No significant changes in the thickness of patellar and Achilles tendons are observed during frequent training, while CSA increases towards the end of training period.Longitudinal effect for jump height but not for muscle strength is evident after the whole training period.

Left ventricular function by speckle-tracking echocardiography in patients with low-T3 syndrome and acute myocardial infarction.

BACKGROUND AND OBJECTIVE: Low-T3 syndrome is common in patients with acute myocardial infarction (AMI). Recent experimental and clinical data have suggested a potential negative impact of low-T3 syndrome on myocardial function in patients with AMI. The aim of this study was to assess left ventricular (LV) myocardial function in patients with low-T3 syndrome and to investigate the association between hormonal profile and the severity of LV dysfunction using speckle-tracking echocardiography (STE). MATERIALS AND METHODS: In 130 patients with first-onset ST-segment elevation acute myocardial infarction (STEMI), conventional 2D and speckle-tracking echocardiography within 48-72h after the hospitalization was performed, and blood samples for TSH, fT4, fT3, and anti-TPO levels were obtained to investigate thyroid hormone production within 24h and on the fourth day after the onset of STEMI symptoms. RESULTS: The patients were divided into two groups according to their serum level of fT3: group 1 with fT3 concentration below 3.2pmol/L (n=34) and group 2 with normal fT3 (>3.2pmol/L) level (n=96). LV ejection fraction (EF) tended to be lower in the low fT3 group. The systolic longitudinal strain did not differ between the groups, but the late diastolic longitudinal strain rate was lower in group 1 (P=0.011). The systolic basal LV rotation positively correlated with the level of fT3 (r=0.4; P<0.001), while a negative correlation was detected between myocardial rotational parameters - systolic apical rotation (r=-0.2; P<0.05), torsion (r=-0.3; P<0.001), and diastolic apical rotation rate (r=-0.3; P<0.01) - and fT3 levels. CONCLUSIONS: The late diastolic longitudinal LV strain rate and LV rotation evaluated by speckle-tracking echocardiography were impaired in patients with low-T3 syndrome after AMI.

Two strategies for response to 14 °C cold-water immersion: is there a difference in the response of motor, cognitive, immune and stress markers?

Here, we address the question of why some people have a greater chance of surviving and/or better resistance to cold-related-injuries in prolonged exposure to acute cold environments than do others, despite similar physical characteristics. The main aim of this study was to compare physiological and psychological reactions between people who exhibited fast cooling (FC; n = 20) or slow cooling (SC; n = 20) responses to cold water immersion. Individuals in whom the T(re) decreased to a set point of 35.5 °C before the end of the 170-min cooling time were indicated as the FC group; individuals in whom the T(re) did not decrease to the set point of 35.5 °C before the end of the 170-min cooling time were classified as the SC group. Cold stress was induced using intermittent immersion in bath water at 14 °C. Motor (spinal and supraspinal reflexes, voluntary and electrically induced skeletal muscle contraction force) and cognitive (executive function, short term memory, short term spatial recognition) performance, immune variables (neutrophils, leucocytes, lymphocytes, monocytes, IL-6, TNF-α), markers of hypothalamic-pituitary-adrenal axis activity (cortisol, corticosterone) and autonomic nervous system activity (epinephrine, norepinephrine) were monitored. The data obtained in this study suggest that the response of the FC group to cooling vs the SC group response was more likely an insulative-hypothermic response and that the SC vs the FC group displayed a metabolic-insulative response. The observations that an exposure time to 14 °C cold water--which was nearly twice as short (96-min vs 170-min) with a greater rectal temperature decrease (35.5 °C vs 36.2 °C) in the FC group compared with the SC group--induces similar responses of motor, cognitive, and blood stress markers were novel. The most important finding is that subjects with a lower cold-strain-index (SC group) showed stimulation of some markers of innate immunity and suppression of markers of specific immunity.

Optically controlled molecular switching of an indolobenzoxazine-type photochromic compound.

Photochromic forward (oxazine ring-opening) and backward (oxazine ring-closing) switching dynamics of an indolobenzoxazine compound were studied by femtosecond pump-repump-probe technique. A UV pulse was used to excite the ring-closed form of the photochromic compound, causing a C-O bond cleavage and the formation of a spectrally red-shifted isomer within a time scale of ca. 100 ps. A successive, temporally delayed near-IR pulse, resonant to the red-most absorption maximum of the ring-opened form, was used to reexcite the molecular system, causing a fast photoinduced oxazine ring closure, thereby "short-circuiting" the normally nanosecond lasting photocycle and returning ∼6% of the molecules to the main molecular ground state. Two possible models, involving the S1 excited state of the terminal photoproduct and its hot ground state, are introduced to explain the pre- and post-reexcitation spectral development and the photoinduced switching back mechanics.