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Background: The increasing prevalence of multimorbidity among older people in Lithuania and other Central-Eastern European countries leads to a greater patient treatment burden and puts additional pressure on healthcare services., Objectives: This study aimed to validate the Lithuanian version of the Multimorbidity Treatment Burden Questionnaire (MTBQ)., Methods: The Lithuanian version of the MTBQ was tested (2021-2022) with 789 patients from seven Lithuanian primary care centres who had two or more long-term conditions. The questionnaire translation's reliability, validity and dimensionality of the were assessed with Spearman's rank correlation, Cronbach's alpha, and factor reduction analysis. Treatment burden and its associations with sociodemographic and other indicators were analysed., Results: Lithuanian version of MTBQ had good internal reliability (Cronbach's alpha 0.711), validity, factor reduction applicability, and interpretability. The MTBQ scores of the questionnaire had a negative association with the quality-of-life scale (r=-0.327, 95% CI [-0.389, -0.264]) and positive associations with the self-rated health scores ( r  = 0.230, 95% CI [0.163, 0.297]) and with the number of comorbidities ( r  = 0.164, 95% CI [0.097, 0.233]). Distribution of treatment burden was identified (none (19,4%), low (46,6%), medium (25%), high (9%)). High treatment burden was found to be associated with having five or more long-term diseases, taking five or more medications, having anxiety or depression and living in a rural area., Conclusion: The study's findings show that the MTBQ is applicable in assessing the treatment burden of multimorbid patients in Lithuania. Furthermore, the study demonstrates that Lithuanian patients with multimorbidity have average treatment burden scores similar to or higher than participants in previous MTBQ validation studies.

The electronic structures and contrasting reactivity of [Cu(CF 3 ) 4 ] - and [Cu(CF 3 ) 3 (CH 3 )] - were probed using coupled cluster and ab initio valence bond calculations. The Cu-C bonds in these complexes were found to be charge shift bonds. A key finding is that electrostatics likely prevent [Cu(CF 3 ) 4 ] - from accessing a productive transition state for C-C bond formation while promote one for [Cu(CF 3 ) 3 (CH 3 )] - . These results therefore highlight essential design criteria for Cu-mediated C-C/C-heteroatom bond formation.

High-valent first-row transition-metal-oxo complexes are important intermediates in biologically and chemically relevant oxidative transformations of organic molecules and in the water splitting reaction in (artificial) photosynthesis. While high-valent Fe- and Mn-oxo complexes have been characterized in detail, much less is known about their analogues with late transition metals. In this study, we present the synthesis and detailed characterization of a unique mononuclear terminal Ni-O complex. This compound, [Ni(TAML)(O)(OH)] 3- , is characterized by an intense charge-transfer (CT) band around 730 nm and has an S t = 1 ground state, as determined by magnetic circular dichroism spectroscopy. From extended X-ray absorption fine structure (EXAFS), the Ni-O bond distance is 1.84 Å. Ni K edge XAS data indicate that the complex contains a Ni(III) center, which results from an unusually large degree of Ni-O π-bond inversion, with one hole located on the oxo ligand. The complex is therefore best described as a low-spin Ni(III) complex ( S = 1/2) with a bound oxyl (O •- ) ligand ( S = 1/2), where the spins of Ni and oxyl are ferromagnetically coupled, giving rise to the observed S t = 1 ground state. This bonding description is roughly equivalent to the presence of a Ni-O single (σ) bond. Reactivity studies show that [Ni(TAML)(O)(OH)] 3- is a strong oxidant capable of oxidizing thioanisole and styrene derivatives with large negative ρ values in the Hammett plot, indicating its electrophilic nature. The intermediate also shows high reactivity in C-H bond activation of hydrocarbons with a kinetic isotope effect of 7.0(3) in xanthene oxidation.

Current fructose consumption levels often overwhelm the intestinal capacity to absorb fructose. We investigated the impact of fructose malabsorption on intestinal endocrine function and addressed the role of the microbiota in this process. To answer this question, a mouse model of moderate fructose malabsorption [ketohexokinase mutant (KHK) -/- ] and wild-type (WT) littermate mice were used and received a 20%-fructose (KHK-F and WT-F) or 20%-glucose diet. Cholecystokinin ( Cck ) mRNA and protein expression in the ileum and cecum, as well as preproglucagon ( Gcg ) and neurotensin ( Nts ) mRNA expression in the cecum, increased in KHK-F mice. In KHK-F mice, triple-label immunohistochemistry showed major up-regulation of CCK in enteroendocrine cells (EECs) that were glucagon-like peptide-1 (GLP-1) + /Peptide YY (PYY - ) in the ileum and colon and GLP-1 - /PYY - in the cecum. The cecal microbiota composition was drastically modified in the KHK-F in association with an increase in glucose, propionate, succinate, and lactate concentrations. Antibiotic treatment abolished fructose malabsorption-dependent induction of cecal Cck mRNA expression and, in mouse GLUTag and human NCI-H716 cells, Cck mRNA expression levels increased in response to propionate, both suggesting a microbiota-dependent process. Fructose reaching the lower intestine can modify the composition and metabolism of the microbiota, thereby stimulating the production of CCK from the EECs possibly in response to propionate.-Zhang, X., Grosfeld, A., Williams, E., Vasiliauskas, D., Barretto, S., Smith, L., Mariadassou, M., Philippe, C., Devime, F., Melchior, C., Gourcerol, G., Dourmap, N., Lapaque, N., Larraufie, P., Blottière, H. M., Herberden, C., Gerard, P., Rehfeld, J. F., Ferraris, R. P., Fritton, J. C., Ellero-Simatos, S., Douard, V. Fructose malabsorption induces cholecystokinin expression in the ileum and cecum by changing microbiota composition and metabolism.

In Drosophila, the clock that controls rest-activity rhythms synchronizes with light-dark cycles through either the blue-light sensitive cryptochrome (Cry) located in most clock neurons, or rhodopsin-expressing histaminergic photoreceptors. Here we show that, in the absence of Cry, each of the two histamine receptors Ort and HisCl1 contribute to entrain the clock whereas no entrainment occurs in the absence of the two receptors. In contrast to Ort, HisCl1 does not restore entrainment when expressed in the optic lobe interneurons. Indeed, HisCl1 is expressed in wild-type photoreceptors and entrainment is strongly impaired in flies with photoreceptors mutant for HisCl1. Rescuing HisCl1 expression in the Rh6-expressing photoreceptors restores entrainment but it does not in other photoreceptors, which send histaminergic inputs to Rh6-expressing photoreceptors. Our results thus show that Rh6-expressing neurons contribute to circadian entrainment as both photoreceptors and interneurons, recalling the dual function of melanopsin-expressing ganglion cells in the mammalian retina.

Each individual perceives the world in a unique way, but little is known about the genetic basis of variation in sensory perception. In the fly eye, the random mosaic of color-detecting R7 photoreceptor subtypes is determined by stochastic on/off expression of the transcription factor Spineless (Ss). In a genome-wide association study, we identified a naturally occurring insertion in a regulatory DNA element in ss that lowers the ratio of Ss ON to Ss OFF cells. This change in photoreceptor fates shifts the innate color preference of flies from green to blue. The genetic variant increases the binding affinity for Klumpfuss (Klu), a zinc finger transcriptional repressor that regulates ss expression. Klu is expressed at intermediate levels to determine the normal ratio of Ss ON to Ss OFF cells. Thus, binding site affinity and transcription factor levels are finely tuned to regulate stochastic expression, setting the ratio of alternative fates and ultimately determining color preference.

Objective: The aim of this study was to investigate the impact of admission systolic blood pressure (ASBP) and left ventricular (LV) mass on the postreperfusion LV recovery in patients with ST-segment elevation myocardial infarction (STEMI) and concomitant coronary multivessel disease (MVD)., Materials and Methods: A retrospective analysis of 12-month postreperfusion LV recovery was performed in 104 patients after primary percutaneous coronary intervention (PPCI). Patients with elevated ASBP (>140mmHg) were assigned to the first group (n=58); with normal ASBP (<140mmHg), to the second group (n=46); with increased myocardial mass index (MMI) (>100g/m(2)), to the third group (n=70); and with normal MMI (<100g/m(2)), to the fourth group (n=34). Severity of MVD was evaluated by the Syntax score. The LV recovery was assessed by evolution of quantitative characteristics of electrocardiography (QRS score, ST score, ECG STEMI stage) and echocardiography (LV ejection fraction, volume and mass indices) registered before and after PPCI, at discharge, and after 1, 6, and 12 months., Results: There were no significant differences in the baseline QRS and ST scores, ECG STEMI stage, LVEF, MMI, and Syntax score comparing all the patients' groups. The serial ECG criteria showed only a very small impact of ASBP on postreperfusion LV recovery. Only ECG STEMI stage progression was slower in the patients with elevated ASBP. In patients with different MMI, the QRS and ST scores were higher and ECG STEMI stage was lower in patients with increased MMI. LVEF after 1 year was significantly lower in the third group as compared to the fourth group (42.58%±8.25% vs. 46.8%±7.13%, P=0.018)., Conclusion: Postreperfusion LV recovery was more related not to ASBP but to the increased LV mass assessed by echocardiography in patients with STEMI and MVD., (Copyright © 2015 Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Objective: The aim of this study was to evaluate the effectiveness of a supervised exercise program (SEP) plus at home nonsupervised exercise therapy (non-SET) on functional status, quality of life (QoL) and hemodynamic response in post-lower-limb bypass surgery patients., Results: One hundred and seventeen patients were randomized to an intervention (n = 57) or a control group (n = 60). A new individual SEP was designed for patients with peripheral arterial disease (PAD) and applied to the studied subjects of the intervention group who also continued non-SET at home, whereas those assigned to the control group received just usual SEP according to a common cardiovascular program. The participants of the study were assessed by a 6-min walking test (6 MWT), an ankle-brachial index (ABI), and the Medical Outcomes Study Short Form-36 (SF-36) of QoL at baseline, at 1 and 6 months after surgery. A significant improvement was observed in the walked distance in the intervention group after 6 months compared with the control group (p < 0.001). The intervention group had significantly higher QoL score in the physical and mental component of SF-36 (p < 0.05)., Conclusions: A 6-month application of the new SEP and non-SET at home has yielded significantly better results in walking distance and QoL in the intervention group than in the controls.

In visual and olfactory sensory systems with high discriminatory power, each sensory neuron typically expresses one, or very few, sensory receptor genes, excluding all others. Recent studies have provided insights into the mechanisms that generate and maintain sensory receptor expression patterns. Here, we review how this is achieved in the fly retina and compare it with the mechanisms controlling sensory receptor expression patterns in the mouse retina and in the mouse and fly olfactory systems.

The compound eye of Drosophila melanogaster consists of about 750 ommatidia (unit eyes). Each ommatidium is composed of about 20 cells, including lens-secreting cone cells, pigment cells, a bristle cell and eight photoreceptors (PRs) R1-R8. The PRs have specialized microvillar structures, the rhabdomeres, which contain light-sensitive pigments, the Rhodopsins (Rhs). The rhabdomeres of six PRs (R1-R6) form a trapezoid and contain Rh1. The rhabdomeres of R7 and R8 are positioned in tandem in the center of the trapezoid and share the same path of light. R7 and R8 PRs stochastically express different combinations of Rhs in two main subtypes: In the 'p' subtype, Rh3 in pR7s is coupled with Rh5 in pR8s, whereas in the 'y' subtype, Rh4 in yR7s is associated with Rh6 in yR8s. Early specification of PRs and development of ommatidia begins in the larval eye-antennal imaginal disc, a monolayer of epithelial cells. A wave of differentiation sweeps across the disc and initiates the assembly of undifferentiated cells into ommatidia. The 'founder cell' R8 is specified first and recruits R1-6 and then R7. Subsequently, during pupal development, PR differentiation leads to extensive morphological changes, including rhabdomere formation, synaptogenesis and eventually rh expression. In this protocol, we describe methods for retinal dissections and immunohistochemistry at three defined periods of retina development, which can be applied to address a variety of questions concerning retinal formation and developmental pathways. Here, we use these methods to visualize the stepwise PR differentiation at the single-cell level in whole mount larval, midpupal and adult retinas (Figure 1).

Background: Each year more than 4.3 million people in Europe will die of cardiovascular disease. Therefore, the implementation of simple interventions such as smoking cessation, weight loss, improved diets, and increased exercise is the top priority in prevention and rehabilitation programs. The aim of this study was to evaluate the impact of complex rehabilitation on the manifestation of risk factors and cardiac events in patients with coronary heart disease., Material and Methods: A total of 140 patients with coronary heart disease and NYHA functional class II-IV ischemic heart failure were recruited to the study. The patients were divided into 2 groups: 70 patients who underwent a 6-month complex rehabilitation course (rehabilitation group) and 70 patients who received drug treatment only (control group). Smoking, dietary, and physical activity habits were documented using the questionnaires. Blood pressure (BP), body weight and height, and total serum cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride (Tg), and blood glucose levels were measured. Measurements were repeated after 3 and 6 months., Results: After 6 months, significantly reduced systolic BP was observed in both the groups as compared with the baseline values (P<0.05). A significant decrease in the diastolic BP; total cholesterol, LDL-cholesterol, triglyceride and blood glucose levels; body mass index, and percentage of patients with the metabolic syndrome as compared with the baseline data was documented only in the rehabilitation group (P<0.05). All the patients quitted smoking as well as all the patients in the rehabilitation group changed their dietary habits (P<0.05). Fewer patients were excluded from the rehabilitation group because of cardiac events as compared with the control group (7.1% vs. 11.4%, P<0.05)., Conclusions: Complex long-term rehabilitation of cardiovascular patients significantly reduced the manifestation of major cardiovascular risk factors and the rate of cardiac events. Aerobic exercise must be the most important part of training but well-done resistance training must also be encouraged.

Sensory systems with high discriminatory power use neurons that express only one of several alternative sensory receptor proteins. This exclusive receptor gene expression restricts the sensitivity spectrum of neurons and is coordinated with the choice of their synaptic targets. However, little is known about how it is maintained throughout the life of a neuron. Here we show that the green-light sensing receptor rhodopsin 6 (Rh6) acts to exclude an alternative blue-sensitive rhodopsin 5 (Rh5) from a subset of Drosophila R8 photoreceptor neurons. Loss of Rh6 leads to a gradual expansion of Rh5 expression into all R8 photoreceptors of the ageing adult retina. The Rh6 feedback signal results in repression of the rh5 promoter and can be mimicked by other Drosophila rhodopsins; it is partly dependent on activation of rhodopsin by light, and relies on G(αq) activity, but not on the subsequent steps of the phototransduction cascade. Our observations reveal a thus far unappreciated spectral plasticity of R8 photoreceptors, and identify rhodopsin feedback as an exclusion mechanism.

This study was carried out to compare cardiac structure and function and blood lipids among Strongmen, sedentary controls, and marathoners. Echocardiography was performed, and endothelial function, blood lipids and maximal oxygen uptake were measured in 27 Caucasian adult men (8 Strongmen, 10 marathoners, 9 controls). Absolute cardiac size parameters such as left ventricular (LV) diameter and wall thickness of Strongmen were higher (p < 0.05), but relative (body surface area indexed) parameters were not different between controls and Strongmen. In Strongmen, the relative LV diameter (p < 0.05), wall thickness (p < 0.001), and LV mass index (p < 0.01) were lower than in marathoners. The absolute but not relative right ventricular diameter was larger in Strongmen as compared with controls, whereas all of the measured relative cardiac size parameters were higher in marathoners as opposed to in controls. The endothelial function and the ratio of wall thickness to chamber diameter were similar among the groups (p > 0.05). Maximal oxygen uptake of Strongmen was lower than in controls (p < 0.05) and marathoners (p < 0.001). Global diastolic LV function of Strongmen was impaired in comparison to controls (p < 0.05) and marathoners (p < 0.05). Plasma lipids were not different between Strongmen and sedentary controls, but in comparison to runners, Strongmen had higher low-density lipoprotein-cholesterol (p < 0.05) and lower high-density lipoprotein cholesterol (p < 0.01). Participation in Strongmen sport is associated with higher absolute but not relative cardiac size parameters, impaired myocardial relaxation, and low cardiorespiratory fitness. Therefore, Strongmen may demand greater attention as an extreme group of athletes with regard to cardiovascular risk.

How complex networks of activators and repressors lead to exquisitely specific cell-type determination during development is poorly understood. In the Drosophila eye, expression patterns of Rhodopsins define at least eight functionally distinct though related subtypes of photoreceptors. Here, we describe a role for the transcription factor gene defective proventriculus (dve) as a critical node in the network regulating Rhodopsin expression. dve is a shared component of two opposing, interlocked feedforward loops (FFLs). Orthodenticle and Dve interact in an incoherent FFL to repress Rhodopsin expression throughout the eye. In R7 and R8 photoreceptors, a coherent FFL relieves repression by Dve while activating Rhodopsin expression. Therefore, this network uses repression to restrict and combinatorial activation to induce cell-type-specific expression. Furthermore, Dve levels are finely tuned to yield cell-type- and region-specific repression or activation outcomes. This interlocked FFL motif may be a general mechanism to control terminal cell-fate specification., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Sensory systems generally contain a number of neuronal subtypes that express distinct sensory receptor proteins. This diversity is generated through deterministic and stochastic cell fate choices, while maintaining the subtype often requires a distinct mechanism. In a study published in the February 1, 2009, issue of Genes & Development, Lesch and colleagues (pp. 345-358) describe a new transcription factor, NSY-7, that acts to stabilize a stochastic subtype choice in AWC chemosensory neurons in Caenorhabditis elegans.

Background: Screening results of EuroAspire III study have revealed the failure of effective correction of cardiovascular risk factors in all 22 participating EU countries. How long should cardiac rehabilitation programs last to impact motivation for lifestyle change?, Aim and Objectives: To compare the impact of long-term (6 months) rehabilitation versus short-term (4 weeks) rehabilitation on the reduction of risk factors and cardiac events, as well as on the use of cardioprotective drugs., Methods: Study contingent of 150 patients, suffering from functional class III-IV (NYHA) chronic heart failure caused by ischemic and hypertensive cardiomyopathy, was subjected to complex rehabilitation: exercise training, dietary corrections, and smoking cessation. The patients were divided into two groups: long-term rehabilitation group (n=80) and short-term rehabilitation group (n=70). Blood pressure, body mass index, dietary habits, dyslipidemia, sedentary lifestyle, smoking, chronic fatigue, and use of cardioprotective drugs were evaluated in all patients at the onset of study, after 4 weeks, and 6 months. Cardiovascular events were estimated throughout the whole 6-month period., Results: In the long-term rehabilitation group, there was a significant reduction (P<0.05) in systolic blood pressure (151+/-9.2 vs. 135+/-9.7 mm Hg), diastolic blood pressure (92.3+/-6.5 vs. 75.4+/-3.8 mm Hg,) body mass index (35.4+/-3.5 vs. 27.2+/-4.8 kg/m(2)), dyslipidemia (56.3 vs. 23.4%), sedentary lifestyle (31.3 vs. 4.7%), and smoking (10.0 vs. 0%). The impact of a short-term rehabilitation was not significant. Because of cardiac events, 13 patients (16.3%) in the long-term rehabilitation group and 26 (16.3%) in the short-term rehabilitation group failed to complete the 6-month study (P<0.05). The following change in drug use pattern was noted in the long-term rehabilitation group: nitrates, 74 vs. 65%; digitalis, 42 vs. 32%; antiarrhythmic agents, 15 vs. 10%; statins, 36 vs. 20% (P<0.05). During 6 months, in both groups, because of better physician monitoring, there was no decrease in the use of major cardioprotective drugs, such as antiaggregants, beta-blockers, and ACE inhibitors., Conclusions: Long-term (6 months) versus short-term (4 weeks) rehabilitation of cardiovascular patients significantly reduces manifestation of major cardiovascular risk factors, the rate of cardiac events, chronic fatigue and improves the use of cardioprotective drugs.

The Drosophila eye is a mosaic that results from the stochastic distribution of two ommatidial subtypes. Pale and yellow ommatidia can be distinguished by the expression of distinct rhodopsins and other pigments in their inner photoreceptors (R7 and R8), which are implicated in color vision. The pale subtype contains ultraviolet (UV)-absorbing Rh3 in R7 and blue-absorbing Rh5 in R8. The yellow subtype contains UV-absorbing Rh4 in R7 and green-absorbing Rh6 in R8. The exclusive expression of one rhodopsin per photoreceptor is a widespread phenomenon, although exceptions exist. The mechanisms leading to the exclusive expression or to co-expression of sensory receptors are currently not known. We describe a new class of ommatidia that co-express rh3 and rh4 in R7, but maintain normal exclusion between rh5 and rh6 in R8. These ommatidia, which are localized in the dorsal eye, result from the expansion of rh3 into the yellow-R7 subtype. Genes from the Iroquois Complex (Iro-C) are necessary and sufficient to induce co-expression in yR7. Iro-C genes allow photoreceptors to break the "one receptor-one neuron" rule, leading to a novel subtype of broad-spectrum UV- and green-sensitive ommatidia.

Unlabelled: The aim of the study was to evaluate the impact of a long-term rehabilitation on chronic fatigue and cardiorespiratory parameters in patients with chronic heart failure., Material and Methods: One hundred seventy patients with class III-IV (NYHA) chronic heart failure were examined. The study population was divided into two groups: long-term rehabilitation group and control group. They underwent cardiopulmonary exercise test and completed questionnaires on chronic fatigue (MFI-20L, DUFS, and DEFS). Measurements were repeated 3 and 6 months after long-term complex rehabilitation., Results: According to the data of MFI-20L, DUFS, and DEFS questionnaires, 170 patients (100%) with class III-IV (NYHA) chronic heart failure complained of fatigue. Overall daily fatigue was 56.8+/-28.5 points on a 100-point scale, and after 6-month rehabilitation, this parameter was statistically significantly reduced on all scales (P<0.05). Physical fatigue and self-care improved in controls. Cardiopulmonary exercise test showed that parameters of hyperventilation, ventilatory equivalents, and pCO2 were significantly improved in rehabilitation group after 6 months as compared to baseline data (P<0.05), but not in the control group., Conclusion: Patients with class III-IV (NYHA) chronic heart failure experience chronic fatigue, which reduces their motivation and self-care abilities. Long-term complex rehabilitation programs improve all parameters of chronic fatigue, respiratory efficiency, and prognostic indicator of chronic heart failure--ventilatory equivalent for carbon dioxide.

The aim of this study was to assess the possible reasons for not returning to work after coronary artery bypass surgery. A total of 134 patients (aged 65 years and younger) who underwent coronary bypass surgery in 2003 were examined. The analysis was performed in three groups of the patients: Group I, patients who were employed before surgery and returned to work after it (n=51); Group II, patients who were employed before surgery but did not return to work after surgery (n=55); and Group III, patients who were unemployed before and remained unemployed after surgery due to health problems (n=28). Number of injured coronary arteries, the extent of operation, postoperative complications, risk factors for ischemic heart disease, clinical status of patients (angina pain and heart failure), physical tolerance, and return to work within one year after coronary bypass surgery were analyzed. It was found that 48.1% of patients who were employed before surgery returned to work after myocardial revascularization. About 30% of patients experienced recurrent symptoms of angina after 12 months. Logistic regression analysis revealed that return to work was significantly influenced by female gender, physical pattern of work, age, and severity of heart failure.

The Aim of the Study: To evaluate the chronic fatigue and its relation to the function of hypothalamus-pituitary-adrenal axis in patients with New York Heart Association (NYHA) functional class III-IV chronic heart failure., Material and Methods: A total of 170 patients with NYHA functional class III-IV chronic heart failure completed MFI-20L, DUFS, and DEFS questionnaires assessing chronic fatigue and underwent echocardiography. Blood cortisol concentration was assessed at 8:00 am and 3:00 pm, and plasma N-terminal brain natriuretic pro-peptide (NT-proBNP) concentration was measured at 8:00 am. Neurohumoral investigations were repeated before cardiopulmonary exercise test and after it., Results: The results of all questionnaires showed that 100% of patients with NYHA functional class III-IV heart failure complained of chronic fatigue. The level of overall fatigue was 54.5+/-31.5 points; physical fatigue - 56.8+/-24.6 points. Blood cortisol concentration at 8:00 am was normal (410.1+/-175.1 mmol/L) in majority of patients. Decreased concentration was only in four patients (122.4+/-15.5 mmol/L); one of these patients underwent heart transplantation. In the afternoon, blood cortisol concentration was insufficiently decreased (355.6+/-160.3 mmol/L); reaction to a physical stress was attenuated (Delta 92.9 mmol/L). Plasma NT-proBNP concentration was 2188.9+/-1852.2 pg/L; reaction to a physical stress was diminished (Delta 490.3 pg/L)., Conclusion: All patients with NYHA class III-IV heart failure complained of daily chronic fatigue. Insufficiently decreased blood cortisol concentration in the afternoon showed that in the presence of chronic fatigue in long-term cardiovascular organic disease, disorder of a hypothalamus-pituitary-adrenal axis is involved.

Aim: The aim of this prospective randomized study was to evaluate the impact of long-term aerobic exercise training on respiratory function, left ventricular systolic function and remodeling in patients with coronary heart disease and ischemic heart failure after successful angioplasty., Design: Patients (n=185) have undergone Doppler echocardiography and ergospirometry. Ninety-five patients practiced 6 month-term aerobic exercise training, less by 10% to their anaerobic threshold. Ninety patients were studied as controls. They were given only drug treatment without training. Measurements were repeated after 6 and 12 months., Results: Training group patients after 6 months showed significant (p<0.05) improvement in exercise capacity, oxygen consumption and ventilating equivalents. The Doppler echocardiographic findings revealed significant (p<0.05) improvement in ejection fraction, left ventricular and atria morphometric data. Improved ergospirometric and echocardiographic data were established after 12 months, too., Conclusions: Long-term aerobic exercise training is an effective and workable measure improving respiratory efficiency, left ventricular systolic function, attenuating negative remodeling and stopping further progression in patients with coronary heart disease and chronic heart failure after successful angioplasty.

Background: As specific features of the basketball player's myocardial structure and function are still rather poorly investigated, we aimed at comparing left ventricular (LV) echocardiographic indices in players of different age groups., Methods: Male basketball players aged 8-13 years (n=31), 14-17 years (n=31) and 18-28 years (n=31) were examined using standard echocardiography. End-diastolic LV posterior wall thickness and internal diameter, as well as interventricular septum thickness, were measured by M-mode. Relative wall thickness was calculated by dividing the sum of the thicknesses of the interventricular septum and LV posterior wall by LV internal diameter. LV mass and ejection fraction were also calculated. The morphological LV parameters were corrected for body surface area. The peak early (E) and peak late (A) transmitral flow velocities were measured using pulsed Doppler, and the ratio (E/A) was calculated., Results: Significant differences in the absolute internal LV diameter among the age groups disappeared after allometric scaling. However, relative wall thickness as well as body size indexed LV posterior wall thickness and LV mass were significantly greater in the adolescents and adults than in the children. Players of different age groups did not differ in the E/A ratio, while ejection fraction was elevated in adolescents., Conclusions: Regular basketball training results in moderate cardiac hypertrophy in adolescents and adult athletes due to thickening of myocardial walls.

Chronic fatigue markedly worsens quality of life of cardiological patients. Chronic fatigue and chronic fatigue syndrome are neuro-immuno-endocrine disorders which manifest as moderate and severe even invalidizing fatigue with psychosomatic symptoms. External and internal stress such as psychological stress, stress after major surgery and trauma, depressive states, inadequate physical exercise, chronic heart failure, chronic viral infection, oncologic diseases, -- can promote development of chronic fatigue. Immune and hypothalamic-pituitary-adrenal (HPA) axis abnormalities were found to be associated with this condition. Measurement of plasma cortisol concentration is used as basic characteristic of HPA axis function. Measures aimed at detection of chronic fatigue in cardiological patients and its appropriate management should supplement programs of integrated rehabilitation in order to improve quality of life and facilitate return to work.

Our study aimed at determining the effects of long-term exercise training on cardiorespiratory function and left ventricular remodeling in ischemic heart disease patients with the evidence of chronic heart failure, who had undergone a successful coronary angioplasty. One hundred thirty-five patients were entered into one-year study: 70 patients were assigned to the long-term exercise training group, and the remaining 65 persons--to the control group. All the patients were subjected to ergospirometry and echocardiography at study entry and at 6 and 12 months. At the outset, both groups showed no significant difference (P>0.05) in terms of ergospirometry findings. However, after 6 months, the rehabilitation group demonstrated significant changes (P<0.05) in exercise time, double product, RQ, AT VO2, VE/VO2, while the control group displayed no significant changes. After 12 months, the patients of rehabilitation group showed further increase in exercise time (from 5.6+/-1.9 min to 6.5+/-2.1 min) and AT VO2 (from 17.3+/-7.2 ml/kg/min to 20.8+/-5.4 ml/kg/min) indices (P<0.05). Those of double product and VE/VO2 decreased slightly when compared with findings at 6 months. RQ remained virtually at the same level, but significantly differed from the corresponding indices at the outset. Echocardiography performed at the entry and at 6 and 12 months revealed significant changes in systolic left ventricular function among the patients of rehabilitation group: wall movement index, ejection fraction as well as the left atrial long axis and left ventricular wall thickness. Echocardiographic changes indicate a positive impact of complex rehabilitative measures on systolic left ventricular function as evidenced by the ejection fraction and wall movement index values, as well as by regression of left ventricular wall thickness and left atrial long axis. Ergospirometry findings allow us to propose that the adequate choice of rehabilitative tools favorably affects the cardiovascular system, and this is reflected in exercise time and AT VO2 indices.

Study Objective: The aim of the study was to evaluate the impact of a long-term (6-month) correct breathing stereotype on minute ventilation, capillary blood gases and acid-base balance in post-myocardial infarction patients., Methods: Fifty-five men (age 57.2 +/- 12.5) were examined 2 months later after myocardial infarction. Spirometry and assessment of acid-base balance and capillary blood gases were performed at rest and repeated after 10 days and 6 months. Breathing correction was taught over 5 days. A session for the control and maintenance of the correct breathing skills was hosted once a month (during the 6-month period)., Results: Changes of minute ventilation, capillary blood gases and acid-base balance were revealed in 55% of patients 2 months later after myocardial infarction. Twenty patients (group I) were randomly selected for breathing correction while 10 patients made up the control group (group II). After breathing correction minute ventilation significantly decreased (18.5 +/- 5.5 versus 9.8 +/- 2.5 l/min), oxygen ventilatory equivalent decreased (39.8 +/- 5.2 versus 22.5 +/- 3.8), partial pressure of blood carbon dioxide increased (33.2 +/- 1.7 versus 44.2 +/- 2.5 mmHg), plasma bicarbonate concentration augmented (19.1 +/- 2.2 versus 24.5 +/- 1.8 mmol/l), base excess normalized (-2.90 +/- 2.5 versus +1.3 +/- 2.1 mmol/l), and pH shifted to more alkaline value (7.36 +/- 0.01 versus 7.43 +/- 0.02)., Conclusions: A long-term correct breathing stereotype improved respiratory function and could be an additional measure in rehabilitation programmes for post-myocardial infarction patients.

Limb growth in higher vertebrate embryos is initially due to the outgrowth of limb buds and later continues as a result of elongation of the skeletal elements. The distal limb mesenchyme is crucial for limb bud outgrowth. Members of the Hairy/Enhancer of Split family of DNA binding transcriptional repressors can be effectors of Notch signaling and often act to maintain cell populations in an undifferentiated, proliferating state, properties predicted for the distal limb mesenchyme. We find that a member of this family, c-hairy1, is expressed in this region and that two alternatively spliced isoforms, c-hairy1A and c-hairy1B, of this gene are produced, predicting proteins that differ in their basic, DNA binding, domains. Viral misexpression of c-hairy1A causes a reduction in size of the limb and shortened skeletal elements, without affecting the chondrocyte differentiation program. Misexpression of c-hairy1B leads to a significantly lesser shortening of the bones, implying functional differences between the two isoforms. We conclude that c-hairy1 regulates the size of the limb, suggesting a role for Notch signaling in the distal mesenchyme.

Unlabelled: The aim of the study was to evaluate spiroveloergometric and blood gases data and compare them among swimmers and basketball players. Examinations were performed for swimmers and basketball players (n=85). Spirometry at rest and spiroveloergometry, analysis of blood gases and acid-base equilibrium at rest and during exercise were performed. Minute ventiliation of swimmers at rest was statistically significantly (p<0.001) lower than of basketball players: 11.0 l/min and 22.1 l/min correspondingly. Partial pressure of blood carbon dioxide for swimmers was larger, than of basketball players (41.5 and 35.9 mm Hg correspondingly, p<0.001), plasma bicarbonates as well (25.2 and 22.5 mmol/l, p<0.01) and there was no bases excess (BE -0.22 and -2.95, p<0.001). Spiroveloergometry showed, that at the same minute ventiliation and the same work level oxygen metabolic units (MET) were significantly (p<0.001) larger for swimmers: 21.2 and 14.9 correspondingly. Decompensated metabolic acidosis during maximal exercise for swimmers was not determined., Conclusions: swimmers' ventilation was more economic than of basketball players, oxygen consumption and aerobic capacity were statistically significantly better.

Characterization of Anopheles gambiae genomic clones containing Ikirara inverted repeats revealed five novel sequences related to known transposable elements (TEs). One TE is related to the mariner/Tc1 superfamily of class II (DNA-to-DNA) transposons, while four are related to class I (RNA-mediated transposition) elements. Crusoe, the class II element; is most similar to the Caenorhabditis elegans transposon Tc1-like TEs. Vash elements, represented twice in our clones, are related to the Q/T1 family of A. gambiae non-LTR retrotransposable elements. Guildenstern is a member of the RT1 and RT2 non-LTR retrotransposon family. Although RT1 and RT2 elements normally have a highly stereotyped insertion preference for sequences within ribosomal genes, Guildenstern is not located in ribosomal sequence. JuanAg is the first anopheline member of the mosquito non-LTR retrotransposon family of Juan elements that previously had included just the culicine elements JuanA and JuanC. Approximately 753 bp is missing from the central portion of the JuanAg reverse transcriptase gene, where an Ikirara inverted repeat is found in its stead. Ozymandias, the only LTR retrotransposon found in the clones, is most similar to the Drosophila melanogaster 412 element. Single Ikirara inverted repeats were also found adjacent to nontransposable element repetitious sequences. Our analysis suggests that the A. gambiae genome organization could best be described as islands of short-period interspersion repetitious DNA in a sea of long-period interspersion, mostly unique sequence DNA.

We studied the expression of mouse HES-6, a new member of the Hairy/Enhancer of split family of basic helix-loop-helix transcription factors. HES-6 is expressed in all neurogenic placodes and their derivatives and in the brain, where it is patterned along both the anteroposterior and dorsoventral axes. HES-6 is also expressed in the trunk, in the dorsal root ganglia and in the myotomes. In the limb buds HES-6 is expressed in skeletal muscle and presumptive tendons.

Segmentation, or metamerism, consists of the subdivision of the body into discrete units that subsequently acquire regional specializations. In vertebrates, the most obvious manifestation of this phenomenon is seen during the formation of the mesodermal somites and their derivatives. This review surveys three different models for how somites form, and how they relate to recent molecular data suggesting the involvement of transcription factors and cell surface molecules. A new model (the "Morse code" model) is proposed to convey positional information to somitogenic cells. Finally, the molecular events of boundary formation (during the initial epithelialization of somites) and boundary maintenance (between adjacent somite halves as well as in resegmentation) are discussed.

We describe a novel chick WD-protein, cSWiP-1, expressed in somitic mesoderm and developing limb buds as well as in other embryonic structures where Hedgehog signalling has been shown to play a role. Using embryonic manipulations we show that in somites cSWiP-1 expression integrates two signals originating from structures adjacent to the segmental mesoderm: a positive signal from the notochord and a negative signal from intermediate and/or lateral mesoderm. In explant cultures of somitic mesoderm, Shh protein induces cSWiP-1, while a blocking antibody to Shh inhibits the induction of cSWiP-1 by the notochord. These results show that the positive signal from the notochord is mediated by Shh. We also show that in limb buds cSWiP-1 is upregulated by ectopic Shh. This occurs in about the same time period as upregulation of BMP2, placing cSWiP-1 among the earliest markers for the change of limb pattern caused by ectopic Shh. We also describe a human homologue of cSWiP-1 and a mouse gene, mSWiP-2, that is more distantly related to SWiP-1, suggesting that SWiP-1 belongs to a novel subfamily of WD-proteins.

A recent paper describes a striking expression pattern during somite formation for a chick ortholog of the fly hairy gene. Before segmentation, c-hairy1 mRNA oscillates in the presomitic mesoderm such that three distinct spatial patterns are seen. The authors use a series of ingenious manipulations to show that these phases follow each other in time, adding up to a 90-minute periodicity in c-hairy1 expression. The discovery of this clock of gene expression emphasizes the importance of temporally regulated events in the establishment of spatial patterns.