MyomiRs in cultured muscle cells from patients with idiopathic inflammatory myopathy are modulated by disease but not by 6-month exercise training.

OBJECTIVES: Idiopathic inflammatory myopathies/IIM are associated with changes in muscle-specific microRNA/miR. Exercise improves muscle function and metabolism in parallel with changes in miR expression. We investigated the effects of disease and exercise on miRs in differentiated muscle cells/myotubes from IIM patients and controls. METHODS: Samples of m. vastus lateralis were obtained by needle biopsy from IIM patients before/after 6-month training and from matched sedentary healthy controls. Muscle cell cultures were established and exposed to saturated fatty acid during differentiation. MiR-133a,-133b,-206,-1 and their target genes (qPCR), fat oxidation (FOx), lipids (chromatography) and mitochondrial oxidative phosphorylation (OxPHOS) complexes (immunoblotting) were measured. Interrelations between in vitro miRs and metabolism of myotubes as well as clinical parameters and disease activity/MITAX were explored. RESULTS: Levels of miRs were higher in myotubes derived from IIM patients compared to healthy controls (up to 3.5-fold, p<0.05). Neither 6-month training (IIM patients) nor in vitro palmitate treatment modulated myomiRs in myotubes. However, miR-133a,-133b, and miR-1 correlated negatively with FOx (p<0.01), triacylglycerols (p<0.05) and OxPHOS complex-V (p<0.05) and positively with OxPHOS complex-I (p<0.05) in myotubes. MiR-133a and miR-133b in myotubes were related to disease activity and fasting glycaemia in vivo (both p<0.05). CONCLUSIONS: Upregulation of microRNAs involved in myogenesis and regeneration in muscle cells derived from IIM patients indicates activation of compensatory epigenetic mechanisms, potentially aimed to counteract disease progression. Relationships of microRNAs with in vitro metabolic profile of muscle cells as well as with clinical parameters support the role of muscle-specific microRNAs in modulating muscle metabolism and clinical state of patients.

Effects of Short- and Long-Term Aerobic-Strength Training and Determinants of Walking Speed in the Elderly.

BACKGROUND/AIMS: Walking speed (WS) is an objective measure of physical capacity and a modifiable risk factor of morbidity and mortality in the elderly. In this study, we (i) determined effects of 3-month supervised aerobic-strength training on WS, muscle strength, and habitual physical activity; (ii) evaluated capacity of long-term (21 months) training to sustain higher WS; and (iii) identified determinants of WS in the elderly. METHODS: Volunteers (F 48/M 14, 68.4 ± 7.1 years) completed either 3-month aerobic-strength (3 × 1 h/week, n = 48) or stretching (active control, n = 14) intervention (study A). Thirty-one individuals (F 24/M 7) from study A continued in supervised aerobic-strength training (2 × 1 h/week, 21 months) and 6 (F 5/M 1) became nonexercising controls. RESULTS: Three-month aerobic-strength training increased preferred and maximal WS (10-m walk test, p < 0.01), muscle strength (p < 0.01) and torque (p < 0.01) at knee extension, and 24-h habitual physical activity (p < 0.001), while stretching increased only preferred WS (p < 0.03). Effect of training on maximal WS was most prominent in individuals with baseline WS between 1.85 and 2.30 m·s-1. Maximal WS measured before intervention correlated negatively with age (r = -0.339, p = 0.007), but this correlation was weakened by the intervention (r = -0.238, p = 0.06). WS progressively increased within the first 9 months of aerobic-strength training (p < 0.001) and remained elevated during 21-month intervention (p < 0.01). Cerebellar gray matter volume (MRI) was positively associated with maximal (r = 0.54; p < 0.0001) but not preferred WS and explained >26% of its variability, while age had only minor effect. CONCLUSIONS: Supervised aerobic-strength training increased WS, strength, and dynamics of voluntary knee extension as well as habitual physical activity in older individuals. Favorable changes in WS were sustainable over the 21-month period by a lower dose of aerobic-strength training. Training effects on WS were not limited by age, and cerebellar cortex volume was the key determinant of WS.

A kestrel without hooked beak and talons is not a kestrel for the red-backed shrike (Lanius collurio).

Birds are strongly motivated to recognize various predators to secure survival and reproductive success. Thus, predator recognition provides a useful tool for the investigation of the process of discrimination and categorization in non-trained animals. The most important role in this process is usually attributed to the prominent unique features shared by all members within the wider category of predators (sharp teeth or beaks, claws, talons and conspicuous eyes). However, birds are also able to discriminate between particular predator species according to their species-specific features (based mainly on colouration). We manipulated general raptor salient features (hooked beak, talons with claws and eyes with supraorbital ridges) and/or species-specific plumage colouration on the dummy of a Eurasian kestrel (Falco tinnunculus) to investigate their importance in the recognition process of the red-backed shrikes (Lanius collurio) during nest defence. We showed that the presence of general raptor salient features is necessary for the recognition of a predator. The kestrel dummy with natural species-specific colouration with altered raptor salient features was treated by shrikes as a harmless bird. Nevertheless, pronounced changes in colouration also prevented successful recognition of the dummy as a kestrel, even when raptor salient features of a raptor were present.

Platelets mitochondrial function depends on CoQ10 concentration in winter, not in spring season.

Seasonal variations in temperature may influence the physiological and pathological metabolic pathways, concentrations of antioxidants, degree of oxidative stress and mitochondrial function. The aim of this study was to evaluate platelet mitochondrial function in human subjects during seasonal variations in temperature. Two groups of healthy young subjects were enroled in the study. Winter group, mean outside temperature was 4.77°C and Spring group, mean outside temperature was 24.32°C. High-resolution respirometry method was used for determination of mitochondrial respiration and oxidative phosphorylation in platelets. Concentrations of coenzyme Q10 (CoQ10) and tocopherols were determined in platelets, blood and plasma. Our data showed slightly (not significantly) reduced respiration in intact platelets, basal and ADP-stimulated mitochondrial respiration at Complex I, as well as CoQ10-TOTAL and α-tocopherol concentrations in winter. The concentration of γ-tocopherol was higher in winter. Platelet mitochondrial ATP production depended on platelet CoQ10-TOTAL concentration in winter, not in spring. We conclude that seasonal temperature participates in the mechanism of platelet mitochondrial respiratory chain function and oxidative phosphorylation that depends on their CoQ10-TOTAL concentration at lower winter outside temperature. CoQ10 supplementation may improve platelets mitochondrial ATP production at winter season. High-resolution respirometry offers sensitive method for detection of changes of platelets mitochondrial respiratory function.

Line-tunable Er:GGAG laser.

In this Letter, for the first time, to the best of our knowledge, a pulse and CW laser based on an Er-doped Gd3Ga2.7Al2.3O12 (Er:GGAG) active medium emitting laser radiation at 2.8 µm are presented. With the longitudinal diode pumping, the maximal output energy of 4.9 mJ and slope efficiency of 13.5% in the pulse regime were reached. Using the birefringent MgF2 plate, the line tunability of Er:GGAG at several spectral bands of 2800-2822 nm, 2829-2891 nm, and 2917-2942 nm were obtained.

Thulium fiber pumped tunable Ho:CaF2 laser.

The paper reports the first room-temperature operation of the in-band pumped Ho:CaF2 laser. A set of Ho:CaF2 crystals varying in holmium concentrations (from 0.1 up to 2.5 mol. % of HoF2), synthesized using the Bridgeman technique, was used for lasing and related spectroscopy investigation. A pulsed 1.94 µm thulium fiber laser system was used for Ho:CaF2 longitudinal pumping. For 1.5 mol. % of Ho:CaF2, the maximal wavelength tunability (from 2073 to 2114 nm) and output energy (1.6 mJ at 2113 nm) were obtained for absorbed pumping energy 34 mJ. Without the tuning element, the slope efficiency up to 30% in respect to absorbed power was obtained using this sample.

Surface texture and priming play important roles in predator recognition by the red-backed shrike in field experiments.

We compared the responses of the nesting red-backed shrikes (Lanius collurio) to three dummies of a common nest predator, the Eurasian jay (Garrulus glandarius), each made from a different material (stuffed, plush, and silicone). The shrikes performed defensive behaviour including attacks on all three dummies. Nevertheless, the number of attacks significantly decreased from the stuffed dummy through the plush dummy and finally to the silicone dummy. Our results show that wild birds use not only colours but also other surface features as important cues for recognition and categorization of other bird species. Moreover, the silicone dummy was attacked only when presented after the stuffed or plush dummy. Thus, we concluded that the shrikes recognized the jay only the stuffed (with feathered surface) and plush (with hairy surface) dummies during the first encounter. Recognition of the silicon dummy (with glossy surface) was facilitated by previous encounters with the more accurate model. This process resembles the effect of perceptual priming, which is widely described in the literature on humans.

Diode-pumped Er:CaF2 ceramic 2.7 µm tunable laser.

Spectroscopic and laser properties of a newly developed high optical quality Er:CaF2 hot-formed ceramic were investigated. Under pulsed 968 nm laser diode pumping, the mid-infrared (2.7 µm) radiation was obtained with a slope efficiency of 3%. Laser tunability was reached using a birefringent filter and the laser tuning range of 118 nm, from 2687 up to 2805 nm, was demonstrated. The maximal output energy reached was 0.48 mJ at 2730 nm for the absorbed pumping energy 34 mJ.

Acute endurance exercise modulates growth differentiation factor 11 in cerebrospinal fluid of healthy young adults.

Objective: Strong evidence supports the benefits of exercise for healthy ageing, including reduced risk of neurodegenerative diseases. Recent studies suggested interorgan crosstalk as a key element of systemic adaptive response, however, the role of specific molecules in mediating exercise effects on the human brain are not fully understood. In the present study, we explored the exercise-related regulation of Growth Differentiation Factor 11 (GDF11) in cerebrospinal fluid (CSF) and blood. Methods: The samples of serum, plasma and CSF were obtained before and 60min after acute exercise (90min run) from twenty healthy young individuals. Additional serum and plasma samples were collected immediately after run. GDF11 protein content (immunoblotting), body composition (bioelectrical impedance), physical fitness (VO2max, cycle spiroergometry) and cognitive functions (standardized computerized tests, Cogstate) were evaluated. Results: Running decreased GDF11 protein content in CSF (-20.6%. p=0.046), while GDF11 in plasma and serum were not regulated. Two GDF11-specific antibodies of different origin were used to corroborate this result. Individuals with higher physical fitness displayed greater exercise-induced decrease of GDF11 in CSF than those with lower physical fitness (p=0.025). VO2max correlated positively with GDF11 in serum (r=0.63, p=0.020) as well as with the exercise-induced change in GDF11 levels in CSF (r=0.59, p=0.042). Indirect measure of blood-brain barrier permeability (i.e. CSF/serum albumin ratio) tended to positively correlate with CSF/serum GDF11 ratio (p=0.060). CSF levels of GDF11 correlated positively with cognitive functions, including working memory, both before and after run (p<0.05). Conclusion: Running-induced down-regulation of the GDF11 protein in the cerebrospinal fluid of healthy young individuals indicates the potential role of GDF11 in the exercise-induced cross-talk between periphery and the brain.

Mid-Infrared Laser Generation of Zn1-xMnxSe and Zn1-xMgxSe (x ≈ 0.3) Single Crystals Co-Doped by Cr2+ and Fe2+ Ions-Comparison of Different Excitation Wavelengths.

Two different mid-infrared (mid-IR) solid-state crystalline laser active media of Cr2+, Fe2+:Zn1-xMnxSe and Cr2+, Fe2+:Zn1-xMgxSe with similar amounts of manganese or magnesium ions of x ≈ 0.3 were investigated at cryogenic temperatures for three different excitation wavelengths: Q-switched Er:YLF laser at the wavelength of 1.73 µm, Q-switched Er:YAG laser at 2.94 µm, and the gain-switched Fe:ZnSe laser operated at a liquid nitrogen temperature of 78 K at ∼4.05 µm. The temperature dependence of spectral and laser characteristics was measured. Depending on the excitation wavelength and the selected output coupler, both laser systems were able to generate radiation by Cr2+ or by Fe2+ ions under direct excitation or indirectly by the Cr2+→ Fe2+ energy transfer mechanism. Laser generation of Fe2+ ions in Cr2+, Fe2+:Zn1-xMnxSe and Cr2+, Fe2+:Zn1-xMgxSe (x ≈ 0.3) crystals at the wavelengths of ∼4.4 and ∼4.8 µm at a temperature of 78 K was achieved, respectively. The excitation of Fe2+ ions in both samples by direct 2.94 µm as well as ∼4.05 µm radiation or indirectly via the Cr2+→ Fe2+ ions' energy transfer-based mechanism by 1.73 µm radiation was demonstrated. Based on the obtained results, the possibility of developing novel coherent laser systems in mid-IR regions (∼2.3-2.5 and ∼4.4-4.9 µm) based on AIIBVI matrices was presented.

The Use of the Er:YAG Laser for Bracket Debonding and Its Effect on Enamel Damage.

OBJECTIVE: The aim of the study was to evaluate the influence of Er:YAG laser irradiation on the debonding of metal and ceramic brackets and enamel damage ex vivo. BACKGROUND DATA: The principle of safe bracket debonding is to degrade the adhesive resin strength connecting the tooth and bracket. Removal of adhesive resin from tooth surfaces without iatrogenic damage (enamel loss) is generally the main problem of the otherwise very successful method of aesthetic straightening of teeth. METHODS: Forty ceramic and metal brackets (Clarity™ Advanced and Victory Series™; 3M Unitek, Monrovia, CA) were standardly bonded to buccal polished enamel surfaces of 30 caries-free human third molars. Two types of adhesive resins (Transbond™ XT Light Cure Adhesive; 3M Unitek, and Variolink II Professional Set; Ivoclar Vivadent AG) were used. Before debonding, the brackets in the laser group were irradiated with the Er:YAG laser (FJFI CVUT) 280 mJ, 250 µs long, repetition rate 6 Hz, spot focus 1 mm, and 140 sec. The control group was debonded without the laser irradiation. During the bracket irradiation, temperature changes inside the tooth were monitored using a thermal image infrared camera. The enamel surface was investigated by SEM. RESULTS: It has been observed that bracket removal was easier after the Er:YAG laser irradiation, and temperature rise was limited (from 2.0°C to 3.2°C) also for metal brackets. As against the nonirradiated samples, SEM investigation has confirmed no damage to enamel. CONCLUSIONS: Irradiation with Er:YAG laser radiation before debonding of ceramic brackets significantly decreases the bonding failure and amount of remaining adhesive.

Facing a Clever Predator Demands Clever Responses - Red-Backed Shrikes (Lanius collurio) vs. Eurasian Magpies (Pica pica).

Red-backed shrikes (Lanius collurio) behave quite differently towards two common nest predators. While the European jay (Garrulus glandarius) is commonly attacked, in the presence of the Eurasian magpie (Pica pica), shrikes stay fully passive. We tested the hypotheses that this passive response to the magpie is an alternative defense strategy. Nesting shrikes were exposed to the commonly attacked European kestrel (Falco tinnunculus) in a situation in which i) a harmless domestic pigeon, ii) a commonly attacked European jay, and iii) a non-attacked black-billed magpie are (separately) presented nearby. The kestrel dummy presented together with the magpie dummy was attacked with a significantly lower intensity than when it was presented with the other intruders (pigeon, jay) or alone. This means that the presence of the magpie inhibited the shrike's defense response towards the other intruder. These results support our previous hypotheses that shrikes use an alternative defense strategy in the magpie's presence. We hypothesize that the magpie is able to associate the active defense of the shrikes with the close proximity of a nest and that shrikes try not to draw the magpie's attention to the nest. The reason why this strategy is not used against the jay remains unanswered as jays as well as magpies show very similar cognitive and foraging skills enabling them to individuate the nest presence according to active parental defense.

X-ray opaque waveguide for dentistry.

OBJECTIVE: The aim of this study is the design, realization, and examination of a new x-ray contrast hollow waveguide which will be suitable for x-ray diagnostics or treatment required in medicine, as dentistry, maxiollofacial surgery or oncology. BACKGROUND DATA: With the growing usefulness of laser radiation therapeutic interventions, a strong demand for radiation delivery from the laser source to the interaction place has appeared. For more complicated surgery, especially for internal intervention, an x-ray is necessary. In such cases, as a minimum, the end of the delivery system must be x-ray contrasted to distinguish where the interaction of radiation with tissue would take place. Up to now, neither fiber, hollow waveguide, nor other delivery system have been x-ray opaque. MATERIALS AND METHODS: A new type of hollow glass waveguide was designed, fabricated, and examined as a delivery system for an endodontic treatment. The system is composed from the cyclic olefin polymer coated silver hollow glass waveguide with special covering for x-ray visibility. The inner diameter of the waveguide was 320 microm, the outer diameter was 630 microm, and its length was 100 mm. After the delivery system was created, the hollow waveguide was checked under an x-ray machine and its opacity was measured. For actual treatment, an Er:YAG laser system generating a mid-infrared radiation was used. The root canals of 10 molars were treated endodontically, and the result of that treatment was compared with the common cleaning methods. During treatment, digital x-ray images were taken with conventional files, using this new designed hollow waveguide. RESULTS: The position of a metal instrument demonstrates the quality of opacity after conventional step-back technique. The hollow waveguide is visible in the left tooth canal. A bone density analysis shows no differences between a left (waveguide) and right (tooth) canal. CONCLUSION: It was demonstrated that no differences exist between x-ray opacity of the metal instrument used for endodontic treatment and a special hollow waveguide. The digitalized, three-dimensional image helps to detect a precise position of customary instrument or waveguide in root canal.

Diode laser-activated bleaching.

This study describes a preclinical investigation with laser-activated bleaching agent for discolored teeth. Bleaching techniques involve a broad-spectrum approach utilizing hydrogen peroxide (3-38%) with or without heat or laser, carbamide peroxide (10-30%), or a mixture of sodium perborate and hydrogen peroxide. Extracted human maxillary central incisors were selected. In the bleaching experiment, 38% hydrogen peroxide was used. Two different laser systems and light emission diodes for activation of the bleaching agent were used: diode laser, wavelength 970 nm, and infra-red diode laser, wavelength 790 nm, with eight blue light emission diodes, wavelength 467 nm. The enamel surface was evaluated with the scanning electron microscope. The method of chemical oxidation resulted in a 2-3 shade change in one treatment (15 min). Shorter time (5 min) was not effective. The diode laser, wavelength 970 nm, and the bleaching agent produced the same effect but with a shorter time of bleaching process (5 min - 1 W, 2.5 min - 2 W). Infra-red diode laser, wavelength 790 nm with eight blue light emission diodes, wavelength 467 nm, and the bleaching agent reached the desired color shade also after a shorter time (5 min - 40 mW). Slight surface modification after the bleaching process was detected with scanning electron microscopy. Currently, the laser has been proven the most valuable energy source for power bleaching with simple and short application in the dental office.

Ceramic bracket debonding by Tm:YAP laser irradiation.

OBJECTIVE: The aim of this study was to prepare a simple and reliable method for ceramic bracket debonding, ensuring minimal changes in the enamel structure and an acceptable temperature rise in the pulp. BACKGROUND DATA: Ceramic bracket debonding is based on the principle of degrading the strength of adhesive resin between the tooth and ceramic bracket. The search for a safe and efficient method of adhesive resin removal following debonding has resulted in the introduction of a wide range of instruments and procedures, among which proper use of laser irradiation can be promising. METHODS: The debonding of two types of ceramic brackets utilized a diode-pumped Thulium:Ytterbium-Aluminium-Perovskite (Tm:YAP) microchip laser generating irradiation at a wavelength of 1998 nm (spot size 3 mm; focused by lens), with two power settings (1-2 W). Loss of enamel and residual resin on teeth, as well as rise in temperature inside the tooth were subsequently investigated in detail. RESULTS: A 1W power of irradiation during a 60-sec period resulted in a temperature rise from 3 to 4°C in the approximate root location. This power is also suitable for debracketing from the point of view of damage to enamel lying below the bracket. Only a slight damage to the enamel was registered by SEM compared to conventional bracket removal. CONCLUSIONS: Use of a Tm:YAP laser (wavelength 1998 nm, power 1 W, irradiance 14 W/cm(2), interacting time 60 sec) which is at the same time compact and small enough to be used in the dental practice, together with moderate cooling, could be an efficient tool for debracketing.

Liquid chromatographic-electrospray mass spectrometric determination (LC-ESI-MS) of phase II metabolites of flobufen in rat liver microsomes-Chiral discrimination.

Glucuronidation of the non-steroidal anti-inflammatory chiral drug flobufen and its major metabolite M17203 has been implicated as an important mechanism of flobufen elimination. To characterize flobufen metabolism by O-glucuronidation, new liquid chromatographic method (LC) coupled with ESI-MS was developed to detect the conjugates of flobufen and its metabolites formed in vitro in rat liver microsomes. Discovery DSC-18 LT cartridge columns were utilized for solid phase extraction (SPE) and Discovery C18 column (150 mm x 2.1 mm, 5 microm particle size) was used for LC separation. Chiral inversion of flobufen and its metabolites enantiomers was checked by special 1-allyl-(5R,8S,10R)-terguride column (150 mm x 4.6 mm). O-Glucuronidation of the S-enantiomer displayed a typical Michaelis-Menten kinetics, whereas the R-enantiomer exhibited a substrate inhibition type of kinetics. The study of glucuronidation of M17203 led to kinetics with sigmoidal characteristics.

Endodontic treatment with application of Er:YAG laser waveguide radiation disinfection.

OBJECTIVE: The objective of this study is to examine the ability of Er:YAG laser radiation. Using a movable waveguide helps to obtain an antibacterial effect, not only in root canal walls but also in the surrounding tissues. BACKGROUND DATA: Conventional endodontic treatment is not fully effective due to microbial colonization of root canal walls dentin in premolars and molars. Various laser systems seem to be effective to kill the remaining microbial content in the root canal. The problem is in the flexibility of laser system tips. MATERIALS AND METHODS: The Er:YAG laser system was designed with a fluorocarbon polymer-coated silver hollow glass waveguide. Root canal systems of 44 premolars and molars were treated endodontically, using a step-back technique; 10 teeth were then treated with calcium hydroxide paste, and 22 teeth were irradiated by a movable waveguide. Before and after treatment, the colony-forming units were counted to determine 21 various microorganisms. RESULTS: Classical enlargement and shaping of the root canal is effective in 60%. Application of calcium hydroxide prepares sterile root canal in 80%. Er:YAG laser irradiation via movable waveguide (energy of 100 mJ, 30 pulses, repetition rate 4 Hz) can ensure residual disinfection of the root canal. CONCLUSION: Application of Er:YAG laser radiation through a flexible waveguide helps to attain antibacterial effect, not only in the root canal walls, but also in the surrounding tissues. Therapeutic doses of laser radiation guarantee one-step disinfection, including of anaerobic microorganisms.

Erbium:YAG laser lithotripsy by use of a flexible hollow waveguide with an end-scaling cap.

An Er:YAG laser light delivery system composed of a polymer-coated silver hollow waveguide and a quartz sealing cap has been developed for calculus fragmentation. Sealing caps with various distal-end geometries were fabricated, and the focusing effects of these caps for Er:YAG laser light were measured both in air and in water. Owing to the high power capability of the quartz a beam of sealing caps, Er:YAG laser light with an output energy of 200 mJ and a repetition rate of 10 Hz was successfully transmitted in saline solution by use of the system. Calculus fragmentation experiments conducted in vitro showed that the delivery system is suitable for medical applications in lithotripsy. We also found that the cap with a focusing effect is more effective in cutting calculi. The deterioration of the sealing caps after calculus fragmentation is also discussed.