Melatonin inhibits apoptosis and oxidative tissue damage in cisplatin-induced pulmonary toxicity in rats.

Introduction: Cisplatin is one of the most frequently used chemotherapeutics, which is known to cause both tumor and normal lung tissue damage through the generation of free radicals and cells apoptosis/necrosis. Melatonin is a neurohormone that regulates numerous physiological processes in the body both through receptor pathways and by maintaining tissue redox homeostasis. Material and methods: The extent of rat lung damage induced by cisplatin and the effects of melatonin on this process was determined based on the pathohistological changes and biochemical disturbances in tissue lipid peroxidation, protein carbonyl modification and in the activity of xanthine oxidase (XO), caspase-3 and DNases. Results: Histopathological analysis of rat lung tissue obtained from animals that received cisplatin found them to be edematous, with significant deterioration of alveolar epithelium. These morphological changes are accompanied by a significant increase in all studied oxidative stress-related parameters, as well as with the activity of apoptosis-related enzymes. A five-day treatment with melatonin completely prevented a cisplatin-induced increase in oxidative stress-related parameters and in the activity of XO, caspase-3 and alkaline DNase. Also, the histopathological changes observed during microscopic analysis were much less pronounced than in the group that received cisplatin only. Conclusions: These results can potentially be connected with the ability of melatonin to inhibit the activity of XO, caspase-3 and alkaline DNase and/or its ability to scavenge free radicals, thus preventing lung damage induced by cisplatin.

Parametric Amplification of Acoustically Actuated Micro Beams Using Fringing Electrostatic Fields.

We report on theoretical and experimental investigation of parametric amplification of acoustically excited vibrations in micromachined single-crystal silicon cantilevers electrostatically actuated by fringing fields. The device dynamics are analyzed using the Mathieu-Duffing equation, obtained using the Galerkin order reduction technique. Our experimental results show that omnidirectional acoustic pressure used as a noncontact source for linear harmonic driving is a convenient and versatile tool for the mechanical dynamic characterization of unpackaged, nonintegrated microstructures. The fringing field's electrostatic actuation allows for efficient parametric amplification of an acoustic signal. The suggested amplification approach may have applications in a wide variety of micromechanical devices, including resonant sensors, microphones and microphone arrays, and hearing aids. It can be used also for upward frequency tuning.

Presence of morphological integration and modularity of the forcipular apparatus in Lithobius melanops (Chilopoda: Lithobiomorpha: Lithobiidae).

The presence of morphological integration and modularity of the forcipular apparatus, despite its evolutionary significance, has not been analyzed in centipedes. This morphological structure has a crucial role in feeding and defense, thanks to its poisonous part (forcipules), which is important for catching the prey. The aims of our study were: i) to test the hypothesis of modularity of the forcipular apparatus in centipede Lithobius melanops; and ii) to investigate the influence of allometry on overall morphological integration in the aforementioned species using a geometric morphometric approach. The presence of fluctuating asymmetry was obtained by Procrustes ANOVA. Allometry was significant only for the symmetric component of the forcipular apparatus. The modularity hypothesis was not accepted, because the covariance coefficients for symmetric and asymmetric components were lower than 89.5% and 72.1% (respectively) of other RV coefficients obtained by a random contiguous partition of the forcipular apparatus. Results of the present study indicate that allometry does increase the level of morphological integration in the forcipular apparatus. According to our results, the forcipular coxosternite and forcipules could not be considered as separate modules; namely, they probably share similar developmental pathways and function in different forms of behavior and survival in L. melanops.

Morphological integration of the head capsule in the millipede Megaphyllum unilineatum (C. L. Koch, 1838) (Diplopoda: Julida): can different modules be recognized?

Covariation of multiple morphological traits and modularity have been widely studied in the field of evolutionary developmental biology. Subunits of a morphological structure can evolve separately from each other in a modular fashion. The aims of our study therefore were: i) to test the hypothesis of modularity in the dorsal part of the head capsule and the gnathochilarium separately during late postembryogenesis in the julidan millipede Megaphyllum unilineatum (C. L. Koch, 1838) using geometric morphometrics; and ii) to investigate the influence of allometry on overall morphological integration in the dorsal part of the head capsule and the gnathochilarium in the mentioned species. Individuals from different ontogenetic stadia (stadium VI - stadium XI) were included in the analyses. Significant influence of fluctuating asymmetry on the dorsal part of the head capsule shape was detected by Procrustes ANOVA. Regressions were significant for the symmetric component of both analysed morphological traits, while non-significant regression was detected for the asymmetric component of the head capsule's dorsal part. Hypotheses of modularity for the dorsal part of the head capsule and the gnathochilarium are rejected because our results indicate that a small proportion of alternate partitions has higher covariation between subsets of structure than between the hypothesized modules. Contrary to our expectations, results of the present study show that allometry does not increase the level of morphological integration in the dorsal part of the head capsule and the gnathochilarium in M. unilineatum. Based on the obtained results, we conclude that the dorsal part of the head capsule and the gnathochilarium are not composed of independent modules and that in the case of the capsule's dorsal part, developmental processes affect morphological integration in different ways at different levels of shape variation.

Lycopene and Caffeic Acid Phenethyl Ester Affect Caspase-3 Activity, but Do Not Alter the NO Pathway in Lung Tissue Damage Induced by Cisplatin.

INTRODUCTION: Antioxidants such as lycopene (LCP) and caffeic acid phenethyl ester (CAPE) represent ideal molecules for the treatment of different reactive oxygen species (ROS) associated disorders. Cisplatin is a chemotherapeutic agent, causing an increase in ROS and DNA damage, with numerous side effects, which include lung toxicity. In the presents study, we evaluated and mutually compared the potential of LCP and CAPE in preventing cisplatin-induced rat lung damage. METHODS: The study was done using pathohistological analysis and a panel of biochemical parameters that reflect lung oxidative tissue damage, inflammation, and apoptosis. RESULTS: The obtained results suggest that cisplatin (10 mg/kg) causes significant disturbances in the lung tissue morphology, followed by an increase in lipid peroxidization and protein modification. Also, a pronounced inflammatory response and cell apoptosis cascade activation was noted. Both LCP and CAPE were able to mitigate the changes, to a different extent, in oxidative damage and apoptosis progression induced by cisplatin. However, they both had limited effect on inflammation since they only prevented an increase in myeloperoxidase activity but had not been able to prevent the NO generation. CONCLUSION: It is hard to be exact in saying whether LCP or CAPE is better in preventing cis-platin-induced lung damage since they obviously possess different mechanisms of action.

Does HAS-BLED risk score underestimate the risk of bleeding in patients with triple antithrombotic therapy?

stroke or other thromboembolic complications in patients with atrial fibrillation (AF). On the other hand, dual antiplatelet therapy (aspirin plus P2Y12 inhibitor) represents a cornerstone in the treatment of acute coronary syndrome. Atrial fibrillation is relatively common in patients with coronary artery disease and patients who undergo primary percutaneous coronary interventions (PCI) with stent implantation. They should be on triple antithrombotic therapy (TAT): preferably direct oral anticoagulants (DOAC) plus aspirin plus clopidogrel as it prevents ischemic as well as thromboembolic events. Before introducing OAT in patients with AF we must assess the risk of future bleeding episodes as OAT can lead to some life-threatening bleeding events. The most common risk score used for that purpose is HASBLED score. HAS-BLED score is valuable, proven tool in assessing future bleeding events in patients with AF. Nevertheless, it does not make the difference between dual and triple antithrombotic therapy which can be of great importance in preventing bleeding events.

Depicting the RNA Virome of Hematophagous Arthropods from Belgrade, Serbia.

Hematophagous arthropods are important vectors for zoonotic pathogens. To date, a huge number of viruses have been identified in these arthropods, with a considerable proportion of them being human pathogens. However, the viromes of hematophagous arthropods are still largely unresearched. In this study, a number of arthropods were collected from Belgrade, Serbia including mosquitoes, ticks and bedbugs. The viromes of these arthropods were identified and characterized using Illumina MiSeq sequencing. In total, 21 viruses belonging to 11 families were characterized, with 11 of them representing novel species. These results may contribute to our knowledge of RNA viruses in arthropods and the discovery of novel human pathogens.

Sexual size and shape dimorphism in Brachydesmus troglobius Daday, 1889 (Diplopoda, Polydesmida).

Until now, morphological trait variation has been investigated in several millipede species using geometric morphometrics. The present study is the first attempt to explore sexual shape and size dimorphism (SShD and SSD) of morphological structures in Polydesmida. We here analyse antennal, head, and leg SShD and SSD in Brachydesmus troglobius Daday, 1889. Our results show that SSD exists in all of the analysed structures, while SShD is present only in the legs. In comparison with females, males possess longer and wider legs, as well as longer antennae and a shorter head. Contrary to previous findings in some Julida, in B. troglobiusSSD of the antennae and legs varies more than SShD in these morphological structures.

Insight into diversity of bacteria belonging to the order Rickettsiales in 9 arthropods species collected in Serbia.

Rickettsiales bacteria in arthropods play a significant role in both public health and arthropod ecology. However, the extensive genetic diversity of Rickettsiales endosymbionts of arthropods is still to be discovered. In 2016, 515 arthropods belonging to 9 species of four classes (Insecta, Chilopoda, Diplopoda and Arachnida) were collected in Serbia. The presence and genetic diversity of Rickettsiales bacteria were evaluated by characterizing the 16S rRNA (rrs), citrate synthase (gltA) and heat shock protein (groEL) genes. The presence of various Rickettsiales bacteria was identified in the majority of tested arthropod species. The results revealed co-circulation of five recognized Rickettsiales species including Rickettsia, Ehrlichia and Wolbachia, as well as four tentative novel species, including one tentative novel genus named Neowolbachia. These results suggest the remarkable genetic diversity of Rickettsiales bacteria in certain arthropod species in this region. Furthermore, the high prevalence of spotted fever group Rickettsia in Ixodes ricinus ticks highlights the potential public health risk of human Rickettsia infection.

Revisiting the Photon-Drag Effect in Metal Films.

The photon-drag effect, the rectified current in a medium induced by conservation of momentum of absorbed or redirected light, is a unique probe of the detailed mechanisms underlying radiation pressure. We revisit this effect in gold, a canonical Drude metal. We discover that the signal for p-polarized illumination in ambient air is affected in both sign and magnitude by adsorbed molecules, opening previous measurements for reinterpretation. Further, we show that the intrinsic sign of the photon-drag effect is contrary to the prevailing intuitive model of direct momentum transfer to free electrons.

Phenol-based millipede defence: antimicrobial activity of secretions from the Balkan endemic millipede Apfelbeckia insculpta (L. Koch, 1867) (Diplopoda: Callipodida).

Millipedes use an array of chemical compounds to defend themselves from predator attack. These chemical substances can have additional roles, i.e. defence against various pathogens. We evaluated the efficacy of the defensive secretion of Apfelbeckia insculpta (L. Koch, 1867) against bacteria, yeasts, and filamentous fungi. The tested secretion consisted of two compounds, p-cresol and phenol, and showed antibacterial, antibiofilm, and antifungal potential against all selected microorganisms. The most sensitive bacterium in our study was Pseudomonas aeruginosa, while the tested defensive secretion manifested the lowest activity against Escherichia coli. The defensive secretion of A. insculpta also showed an ability, albeit mild, to suppress biofilm formation by P. aeruginosa. Among the tested yeasts, Candida albicans and C. krusei were the most susceptible and most resistant species, respectively. Finally, the concentration of extracts obtained from the tested defensive secretion needed to achieve an antifungal effect was lowest in the case of Cladosporium cladosporioides. Fusarium verticillioides and Penicillium rubens were the micromycetes most resistant to the tested secretion. Our results indicate that antibacterial activity of the defensive secretion of A. insculpta is similar to or slightly weaker than that of streptomycin, while comparison with antimycotics showed that the tested millipede secretion has stronger activity than fluconazole, but weaker activity than nystatin and ketoconazole. The present study corroborates previous findings indicating that the defensive secretions of millipedes can have different roles apart from antipredator protection and are effective against pathogenic microorganisms.

Multifaceted activity of millipede secretions: Antioxidant, antineurodegenerative, and anti-Fusarium effects of the defensive secretions of Pachyiulus hungaricus (Karsch, 1881) and Megaphyllum unilineatum (C. L. Koch, 1838) (Diplopoda: Julida).

Members of the millipede order Julida rely on dominantly quinonic defensive secretions with several minor, non-quinonic components. The free radical-scavenging activities of ethanol, methanol, hexane, and dichloromethane extracts of defensive secretions emitted by Pachyiulus hungaricus (Karsch, 1881) and Megaphyllum unilineatum (C. L. Koch, 1838) were investigated using the ABTS, DPPH, and total reducing power (TRP) tests. The obtained extracts were also tested for inhibition of acetylcholinesterase and tyrosinase activity. Finally, the antifungal potential of both julid extracts was evaluated against seven Fusarium species. Secretions of both species showed activity against free radicals, acetylcholinesterase, tyrosinase, and all of the selected fungal species. The secretions of P. hungaricus exhibited a more potent antioxidative effect than did those of M. unilineatum, while there were no significant differences of antiacetylcholinesterase activity between the tested extracts. Only the hexane extract of M. unilineatum showed an effect on tyrosinase activity stronger than that of P. hungaricus. Fusarium sporotrichioides, F. graminearum, and F. verticillioides were the fungi most resistant to secretions of both julids. The Fusarium species most susceptible to the secretion of P. hungaricus was F. avenaceum, while the concentrations of M. unilienatum extracts needed to inhibit and completely suppress fungal growth were lowest in the case of their action on F. lateritium. Our data support previous findings that julid defensive secretions possess an antimicrobial potential and reveal their antioxidative and antineurodegenrative properties. Bearing in mind the chemical complexity of the tested defensive secretions, we presume that they can also exhibit other biological activities.

Two-Directional Operation of Bistable Latchable Micro Switch Actuated by a Single Electrode.

Curved micromechanical beams are a versatile platform for exploring multistable behavior, with potential applications in mechanical based logic elements and electrical and optical switches. Here we demonstrate bidirectional electrostatic actuation of a bistable, latched, micromechanical beam by the same electrode, which was used for the snap-through switching of the device. The release of the mechanically-latched beam is achieved by pre-loading the structure using a rising voltage applied to the electrode, followed by a sudden decrease of the voltage. This abrupt removal of the loading results in a transient response and dynamic snap-back of the beam.

Handheld real-time PCR device.

Here we report one of the smallest real-time polymerase chain reaction (PCR) systems to date with an approximate size of 100 mm × 60 mm × 33 mm. The system is an autonomous unit requiring an external 12 V power supply. Four simultaneous reactions are performed in the form of virtual reaction chambers (VRCs) where a ≈200 nL sample is covered with mineral oil and placed on a glass cover slip. Fast, 40 cycle amplification of an amplicon from the H7N9 gene was used to demonstrate the PCR performance. The standard curve slope was -3.02 ± 0.16 cycles at threshold per decade (mean ± standard deviation) corresponding to an amplification efficiency of 0.91 ± 0.05 per cycle (mean ± standard deviation). The PCR device was capable of detecting a single deoxyribonucleic acid (DNA) copy. These results further suggest that our handheld PCR device may have broad, technologically-relevant applications extending to rapid detection of infectious diseases in small clinics.

AN INCIDENTAL FINDING OF THYMIC CARCINOMA DURING ELECTIVE CORONARY ARTERY BYPASS GRAFTING.

INTRODUCTION: Thymoma is a rare malignant tumor of the anterior mediastinum. Thymic squamous cell carcinoma has been recognized as an aggressive form of thymoma with different behavior. It is associated with paraneoplastic syndromes, variety of clinical presentations, different way of treatment and complex prognosis. Improved imaging techniques show that an early diagnosis of thymoma is possible, which makes thymoma a potentially dangerous but preventable disease. CASE REPORT: In this report. we describe the clinical and histological findings of a patient with incidental finding of squamouscell thymic carcinoma presented during elcc tive coronary artery bypass grafting surgery.

Chemistry of the sternal gland secretion of the Mediterranean centipede Himantarium gabrielis (Linnaeus, 1767) (Chilopoda: Geophilomorpha: Himantariidae).

The geophilomorph centipede, Himantarium gabrielis, when disturbed, discharges a viscous and proteinaceous secretion from the sternal glands. This exudate was found by gas chromatography-mass spectrometry, liquid chromatography-high resolution mass spectrometry, liquid chromatography-mass spectrometry-mass spectrometry and NMR analyses to be composed of hydrogen cyanide, benzaldehyde, benzoyl nitrile, benzyl nitrile, mandelonitrile, mandelonitrile benzoate, 3,7,6O-trimethylguanine (himantarine), farnesyl 2,3-dihydrofarnesoate and farnesyl farnesoate. This is the first report on the presence of benzyl nitrile and mandelonitrile benzoate in secreted substances from centipedes. Farnesyl 2,3-dihydrofarnesoate is a new compound, while himantarine and farnesyl farnesoate were not known as natural products. A post-secretion release of hydrogen cyanide by reaction of mandelonitrile and benzoyl nitrile was observed by NMR, and hydrogen cyanide signals were completely assigned. In addition, a protein component of the secretion was analysed by electrophoresis which revealed the presence of a major 55 kDa protein. Analyses of the defensive exudates of other geophilomorph families should produce further chemical surprises.

Composition of the defensive secretion in three species of European millipedes.

Three European julid species, Cylindroiulus boleti, Leptoiulus trilineatus, and Megaphyllum bosniense, secrete mixtures of up to 12 different quinones. The major components in these species are 2-methoxy-3-methyl-1,4-benzoquinone and 2-methyl-1,4-benzoquinone. 2-Methoxy-5-methylhydroquinone is detected for the first time in the Class Diplopoda. 2-Hydroxy-3-methyl-1,4-benzoquinone, 2,3-dimethoxyhydroquinone, 2-methyl-3,4-methylendioxyphenol, and 2,3-dimethoxy-5-methylhydroquinone are registered for the first time in representatives of the family Julidae. The similar chemical composition of defense secretions in all analyzed European julids and Pacific spirobolids supports the idea of the chemical consistency of defensive compounds in juliform millipedes.

Label-free biomarker detection from whole blood.

Label-free nanosensors can detect disease markers to provide point-of-care diagnosis that is low-cost, rapid, specific and sensitive. However, detecting these biomarkers in physiological fluid samples is difficult because of problems such as biofouling and non-specific binding, and the resulting need to use purified buffers greatly reduces the clinical relevance of these sensors. Here, we overcome this limitation by using distinct components within the sensor to perform purification and detection. A microfluidic purification chip simultaneously captures multiple biomarkers from blood samples and releases them, after washing, into purified buffer for sensing by a silicon nanoribbon detector. This two-stage approach isolates the detector from the complex environment of whole blood, and reduces its minimum required sensitivity by effectively pre-concentrating the biomarkers. We show specific and quantitative detection of two model cancer antigens from a 10 microl sample of whole blood in less than 20 min. This study marks the first use of label-free nanosensors with physiological solutions, positioning this technology for rapid translation to clinical settings.