Thermal Waves and Heat Transfer Efficiency Enhancement in Harmonically Modulated Turbulent Thermal Convection.

We study turbulent Rayleigh-Bénard convection over four decades of Rayleigh numbers 4×10^{8}

The fox tapeworm, Echinococcus multilocularis, in grey wolves and dogs in Slovakia: epidemiology and genetic analysis.

Echinococcus multilocularis, the causative agent of human alveolar echinococcosis, is an important emerging parasite in the northern hemisphere. In epidemiological studies, the highest attention is being paid to foxes as the main reservoir hosts responsible for geographic expansion from multiple focal populations and the invasion of urban habitats, but little information is available on the parasite distribution in other carnivores. Hence, the study was designed to obtain updated information about the occurrence and genetic diversity of E. multilocularis in grey wolves and dogs in Slovakia. Faecal samples of wolves were collected from three locations under a certain level of environmental protection in the central and eastern parts of the country, and the presence of the parasite DNA was detected in 35.7% of 112 samples, with the highest rate (51.2%) recorded in the Poloniny National Park in north-eastern Slovakia. Among 110 faecal dog samples, E. multilocularis was detected in three faeces from segregated Roma settlements in the eastern part of the country, which accounted for an overall positivity of 2.7%. Sequence analysis of two mitochondrial genes, 12S rRNA and NADH dehydrogenase subunit 1, revealed four haplotypes in 13 isolates from wolves and dogs originating from four sites in eastern and central Slovakia, with all samples bearing a European-type pattern of E. multilocularis. The more than one-third positivity rate of E. multilocularis in wolf faecal samples dispersed over a large part of the country has corroborated the extensive circulation of the parasite in wildlife and confirmed the need to improve intervention control strategies.

Polypharmacy in Parkinson's disease: risks and benefits with little evidence.

Polypharmacy is common practice in Parkinson's disease. Medical treatment targeting the dopaminergic system alone may include up to five different compounds: L-DOPA (in combination with a DOPA decarboxylase inhibitor), a catechol-O-methyltransferase (COMT) and a monoamine oxidase (MAO-B) inhibitor and a dopamine agonist. Particular motor and non-motor symptoms may require additional specific therapeutics, such as drugs aimed at tremor control and to treat depression, dementia and orthostatic and autonomic dysfunction. No prospective studies have yet been performed with regard to the efficacy or the long-term benefit of combining such different treatments in Parkinson's disease and retrospective analyses are sparse. We thus tried to compile the available evidence for polypharmacy strategies in Parkinson's disease and devised an expert opinion statement.

Phase II study of buparlisib (BKM120) and trastuzumab in patients with HER2+ locally advanced or metastatic breast cancer resistant to trastuzumab-based therapy.

PURPOSE: A Phase Ib study in patients with trastuzumab-resistant, human epidermal growth factor receptor-2- (HER2)-positive advanced breast cancer defined the recommended Phase II dose of buparlisib as 100 mg/day in combination with 2 mg/kg weekly trastuzumab, and reported preliminary signs of clinical activity. Here we present results from the Phase II portion. METHODS: Patients with trastuzumab-resistant, HER2-positive advanced breast cancer received buparlisib plus trastuzumab. Study endpoints included safety/tolerability and antitumour activity. The study was extended to include a Phase Ib dose-escalation phase, in which patients with progressive brain metastases also received capecitabine. RESULTS: In the Phase II portion, of 50 patients treated with buparlisib and trastuzumab, the most common (≥ 30%) all-grade adverse events (AEs) were diarrhoea (54%), nausea (48%), decreased appetite, increased alanine aminotransferase (36% each), increased aspartate aminotransferase (34%), fatigue, rash (32% each), cough and hyperglycemia (30% each). One (2%) patient achieved complete response and four (8%) patients had confirmed partial responses [PR; including two patients with phosphatidylinositol 3-kinase (PI3 K) pathway-activated tumours]. Overall response rate (ORR) was 10%: the primary endpoint (ORR ≥ 25%) was therefore not met. In the Phase Ib portion, all patients with measurable brain lesions at baseline showed tumour shrinkage to some degree; due to low enrollment, maximum tolerated dose of buparlisib in combination with trastuzumab and capecitabine was not determined. CONCLUSION: Buparlisib plus trastuzumab, as a chemotherapy-free regimen, demonstrated an acceptable safety profile but limited efficacy in patients with heavily pretreated, trastuzumab-resistant HER2-positive breast cancer, and in patients with progressive brain metastases also receiving capecitabine.

Demonstration of a 120° hybrid based simplified coherent receiver on SOI for high speed PON applications.

We demonstrate the first simplified coherent receiver using a 120° hybrid on silicon-on-insulator (SOI) for high speed PON applications. This coherent receiver integrates an inverse taper edge coupler for the received signal, a vertical grating coupler for the local oscillator input, a polarization splitter and rotator (PSR), a 120° hybrid based on a 3×3 multimode interference (MMI) coupler, and three germanium photodetectors. We achieved 25 Gbit/s two-level pulse amplitude modulation (PAM-2) transmission over 30 km standard single mode fiber (SMF) in the C-band without any digital signal processing (DSP) (e.g., pre-emphasis, pulse shaping, equalization, nonlinearity compensation) and dispersion compensation (e.g., optical or digital) either at the transmitter or at the receiver. The requirements for frequency and phase locking of the local oscillator (LO) were avoided due to the use of intensity modulated signals. Receiver sensitivities of -23.70 dBm, -20.30 dBm, and -15.10 dBm are achieved at a bit error rate (BER) below the hard-decision forward error correction (HD-FEC) threshold (i.e., 3.8 × 10-3) in back-to-back (B2B), after 21 km and 30 km, respectively. We also demonstrate 25 Gbit/s PAM-4 transmission achieving receiver sensitivities of -15.30 dBm, -13.90 dBm, and -9.50 dBm below the HD-FEC threshold in B2B, after 10.5 km and 21 km, respectively.

Recurrent stenosis following carotid artery stenting treated with a drug-eluting balloon: a single-center retrospective analysis.

PURPOSE: Early in-stent restenosis after stent-protected angioplasty of the carotid artery (SPAC) is an infrequent, but potentially harmful condition for patients with carotid artery disease. METHODS: In our retrospective single-center analysis of 176 patients with carotid artery stenting between 2009 and 2015, using duplex ultrasound, we detected 9 patients with high-grade carotid artery in-stent restenosis. All restenosis patients were treated with a drug-eluting balloon (DEB) to prevent recurrent neointimal hyperplasia. One patient had bilateral carotid artery disease with bilateral in-stent restenosis, and 1 patient needed repeated DEB treatment 19 months after the first DEB intervention, so 11 DEB procedures, in total, were performed. RESULTS: The median time-interval between primary carotid artery stenting and first DEB-treatment was 9 months. In 3 of the 11 interventions, the DEB treatment was assisted by an additional stent. One repeat DEB treatment was necessary, and three DEB treatments were followed by a secondary stent. No peri-interventional complications (TIA, stroke, or death) were observed during or after DEB intervention. Therefore, in the entire group, the 1y event-free survival (EFS) was 100%, and the 2y/3y/5y EFS was 83%. CONCLUSION: DEB intervention seems to be an effective and safe treatment for patients with high-grade in-stent restenosis after SPAC.

[Myasthenia gravis should be considered in cases of Parkinson's disease and progressive dysphagia]. / Bei Morbus Parkinson und progredienter Dysphagie an Myasthenia gravis denken.

We report on four consecutive patients with Parkinson's disease, in whom anti-acetylcholine receptor (AChR) antibody positive bulbar myasthenia gravis (MG) turned out to be responsible for progressive dysphagia.

A randomized adaptive phase II/III study of buparlisib, a pan-class I PI3K inhibitor, combined with paclitaxel for the treatment of HER2- advanced breast cancer (BELLE-4).

Background: Phosphatidylinositol 3-kinase (PI3K) pathway activation in preclinical models of breast cancer is associated with tumor growth and resistance to anticancer therapies, including paclitaxel. Effects of the pan-Class I PI3K inhibitor buparlisib (BKM120) appear synergistic with paclitaxel in preclinical and clinical models. Patients and methods: BELLE-4 was a 1:1 randomized, double-blind, placebo-controlled, adaptive phase II/III study investigating the combination of buparlisib or placebo with paclitaxel in women with human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer with no prior chemotherapy for advanced disease. Patients were stratified by PI3K pathway activation and hormone receptor status. The primary endpoint was progression-free survival (PFS) in the full and PI3K pathway-activated populations. An adaptive interim analysis was planned following the phase II part of the study, after ≥125 PFS events had occurred in the full population, to decide whether the study would enter phase III (in the full or PI3K pathway-activated population) or be stopped for futility. Results: As of August 2014, 416 patients were randomized to receive buparlisib (207) or placebo (209) with paclitaxel. At adaptive interim analysis, there was no improvement in PFS with buparlisib versus placebo in the full (median PFS 8.0 versus 9.2 months, hazard ratio [HR] 1.18), or PI3K pathway-activated population (median PFS 9.1 versus 9.2 months, HR 1.17). The study met protocol-specified criteria for futility in both populations, and phase III was not initiated. Median duration of study treatment exposure was 3.5 months in the buparlisib arm versus 4.6 months in the placebo arm. The most frequent adverse events with buparlisib plus paclitaxel (≥40% of patients) were diarrhea, alopecia, rash, nausea, and hyperglycemia. Conclusions: Addition of buparlisib to paclitaxel did not improve PFS in the full or PI3K pathway-activated study population. Consequently, the trial was stopped for futility at the end of phase II.

[Idiopathic cranial nerve failure]. / Idiopathische Hirnnervenausfälle.

Cranial nerve lesions require a thorough diagnostic work-up and known etiologies have to be excluded before the term idiopathic can be considered. The focus of the present review is on idiopathic peripheral facial nerve paralysis (Bell's palsy) for which this terminology has been established. For all other cranial nerve lesions the typical clinical signs, established etiologies and possible diagnostic pitfalls are discussed.

[Wearable Technique for the Assessment of Parkinson Symptoms: What's the Future?]. / Tragbare und aktiv vom Parkinson-Patienten genutzte Technologie im häuslichen Umfeld: Was bringt die Zukunft?

Parkinson's disease (PD) is a multisystem disorder with a plethora of symptoms affecting the quality of life of patients in the home environment. Due to the rapid development of wearable technique in the health and fitness sector, an increasing number of such wearable devices are available to complement diagnostic strategies of PD symptoms not only in the clinical but also in the home environment. This development has clear advantages over clinical evaluation, as the latter is relatively subjective, time-consuming and costly, and provides only a snapshot of the condition. First results about the use of such technology for the assessment of PD symptoms (including bradykinesia, dyskinesia, tremor, daily activity and sleep behavior) in the home environment are promising. They suggest that these techniques can provide complementary information about the symptoms of PD patients, and have the potential to be included in future diagnostic workup concepts of routine care in PD. The use of such technique provides also the opportunity to more actively include patients into medical decision-making processes.

[The Importance of MITF Signaling Pathway in the Regulation of Proliferation and Invasiveness of Malignant Melanoma]. / Význam signálnej dráhy MITF pri regulácii proliferácie a invazivity malígneho melanómu.

BACKGROUND: Malignant melanoma is one of the most aggressive types of cancers. Melanoma is derived from pigment-producing cells, melanocytes, which are characterized by a specific survival mechanism. Microphthalmia-associated transcription factor (MITF-M) plays a role in the metabolism of melanoma and is involved in the regulation of the expression of multiple genes mediating processes such as melanogenesis, proliferation, differentiation, and melanocyte survival. The expression of this transcription factor in melanocytes is activated by several signaling pathways, and reduced expression or function of MITF-M can cause the dysregulation of anti-apoptotic mechanisms. MITF-M is also involved in matrix metalloproteinase 14 (MMP14) activity, which is responsible for shape changes in melanocytes and increases in their motility and invasiveness. Very low levels of expression of MITF-M are found in human melanocytes with an invasive phenotype, indicating that this transcription factor acts as a suppressor of the metastatic process. Cancer cells with low expression of cytosolic/nuclear ß-catenin have a small amount of MITF-M 14 that is insufficient to inhibit MMP transcription. The enzyme catalyzes the degradation of laminin and fibronectin, thereby changing the shape of melanocytes, which leads to their increased mobility and invasiveness. AIMS: This review describes the regulatory pathway of MITF-M activation, its involvement in the proliferation of transformed melanocytes, and its role in increasing the invasiveness of malignant melanoma. A detailed understanding of the MITF-M signaling pathway is highly topical and could help to develop new diagnostic and therapeutic applications for patients with malignant melanoma.Key words: neoplastic cell transformation - melanoma - MITF transcription factorThis work was supported by grant projects VEGA 1/0115/14 and VEGA 1/0873/16.The authors declare they have no potential confl icts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 4. 12. 2015Accepted: 14. 6. 2016.

Fusion of microlitre water-in-oil droplets for simple, fast and green chemical assays.

A simple format for microscale chemical assays is proposed. It does not require the use of test tubes, microchips or microtiter plates. Microlitre-range (ca. 0.7-5.0 µL) aqueous droplets are generated by a commercial micropipette in a non-polar matrix inside a Petri dish. When two droplets are pipetted nearby, they spontaneously coalesce within seconds, priming a chemical reaction. Detection of the reaction product is accomplished by colorimetry, spectrophotometry, or fluorimetry using simple light-emitting diode (LED) arrays as the sources of monochromatic light, while chemiluminescence detection of the analytes present in single droplets is conducted in the dark. A smartphone camera is used as the detector. The limits of detection obtained for the developed in-droplet assays are estimated to be: 1.4 nmol (potassium permanganate by colorimetry), 1.4 pmol (fluorescein by fluorimetry), and 580 fmol (sodium hypochlorite by chemiluminescence detection). The format has successfully been used to monitor the progress of chemical and biochemical reactions over time with sub-second resolution. A semi-quantitative analysis of ascorbic acid using Tillman's reagent is presented. A few tens of individual droplets can be scanned in parallel. Rapid switching of the LED light sources with different wavelengths enables a spectral analysis of multiple droplets. Very little solid waste is produced. The assay matrix is readily recycled, thus the volume of liquid waste produced each time is also very small (typically, 1-10 µL per analysis). Various water-immiscible translucent liquids can be used as the reaction matrix: including silicone oil, 1-octanol as well as soybean cooking oil.

Essential Hypertension: Cardiovascular Response to Breath Hold Combined with Exercise.

Essential hypertension (EH) is a widespread disease and might be prevalent in apnea divers and master athletes. Little is known about the influence of EH and the antihypertensive drugs (AHD) on cardiovascular reactions to combined breath hold (BH) and exercise. In this pilot study, healthy divers (HCON) were compared with treated hypertensive divers with regard to heart rate (HR) and mean blood-pressure (MAP) responses to BH, exercise and the combination of both. Ten subjects with EH and ten healthy divers were tested. 3 different 20 s stimuli were applied: BH combined with 30 W or 150 W and 150 W without BH. The time-charts during the stress intervals and during recovery were compared. Subjects treated with an angiotensin-converting enzyme (ACE) inhibitor showed higher changes for MAP values if breath hold was performed. HR responses were obviously changed if a ß-blocker was part of the medication. One subject showed extreme MAP responses to all stimuli and conspicuous HR if BH was involved. The modulation of HR-/MAP-response in EH subjects depends on the mechanisms of antihypertensive agents. The combination of an ACE inhibitor and a ß-blocker may give the best protection. It is recommended to include short apnea tests in the fitness-to-dive examination to individually predict potential endangerment.

[Occupational tuberculosis in Slovakia and in the Czech Republic]. / Profesionálna TBC na Slovensku a v Ceskej republike.

STUDY OBJECTIVE: To conduct a retrospective 15-year study to monitor trends in the number of employees at risk for occupational tuberculosis (TB) (levels III and IV) in the Slovak Republic, and in particular in the sector of economic activities Q (health care and social assistance). Furthermore, to analyze reported cases of occupational TB and to compare the incidence and sex-specific and age-specific prevalence with the data reported in the Czech Republic. MATERIAL AND METHODS: Data on the number of employees at risk of exposure to occupational TB were derived from the Automated Risk Classification System of the Slovak Republic. Data on cases of occupational TB were taken from health statistics (Institute of Health Information and Statistics/National Health Information Center in the Slovak Republic and the National Institute of Public Health in the Czech Republic). A retrospective analysis was conducted (for 1998-2012) of reported cases of occupational TB, selected from Article 24 of the List of occupational diseases (infectious and parasitic diseases except tropical infectious and parasitic diseases and diseases transmissible from animals to humans). The selection criterion was a TB diagnosis according to ICD-10. In the Czech Republic, the data were derived from Article 5.1.02 (tuberculosis), Chapter V. of the List of Occupational Diseases. The data obtained were analyzed by methods of descriptive statistics. RESULTS: The numbers of employees with a level III risk of exposure to occupational TB in the Slovak Republic declined by 30% over the 15 years of study and by 40% in category Q. In 2012, 2027 employees were classified in category III and 1442 of them belonged to group Q. Females accounted for 81-84% of employees at risk of exposure to occupational TB. Eighty-six and 181 cases of occupational TB were reported in the Slovak Republic and in the Czech Republic, respectively, in 1998-2012, with the incidence showing a downward trend in both countries. TB of the respiratory tract was reported most often (83.7% of the total of reported cases of occupational TB). As expected, more cases occurred in females than in males (1.9 times as many cases in females as in males in the Slovak Republic and three times as many cases in females as in males in the Czech Republic). The incidence of occupational TB was the highest in sector Q, with the highest absolute numbers reported in nurses. In 2012, the incidence rates of occupational TB were 0.22 cases per 100,000 sick benefit policy holders in the Slovak Republic and 0.13 cases per 100,000 sick benefit policy holders in the Czech Republic. CONCLUSION: The incidence of occupational TB has a downward trend in both countries, similarly to TB incidence in the general population. A negative aspect in both countries is the incidence of occupational TB at the middle productive age, in contrast to the population occupationally non-exposed to TB. Slovakia is surrounded by higher prevalence countries, with the exception of the Czech Republic. It cannot be ruled out that, in addition to the known factors influencing the prevalence of TB, including occupational TB, migration from eastern countries, including job search migration, can also play a role in increase in TB cases. It is vital to continue epidemiological surveillance and to reduce the risk of TB as much as possible also in healthcare settings by adhering to barrier nursing practices. Cases of active TB need early and adequately long, controlled treatment in order to reduce, among others, the incidence of multi-drug resistant TB.

[Effect of vitamin d receptor polymorphisms on the development and progression of malignant melanoma]. / Prehlad vplyvu polymorfizmov receptora vitamínu D na vznik a progresiu malígneho melanómu.

BACKGROUND: Malignant melanoma is one of the most aggressive cutaneous tumors in men and women. The risk of developing a malignant melanoma depends on several external factors along with deregulation of mutual interaction of genotype and phenotype. Nowadays, growing attention is focused on the study of the interactions of the active form of vitamin D3 with its receptor and inhibitory effect of vitamin D3 receptor polymorphisms on multiple signaling pathways involved in proliferative and metastatic processes. OBJECTIVES: This review article addresses the relationship between factors involved in the development of malignant melanoma through Hedgehog signaling pathway (HH). It summarizes current knowledge of malignant melanoma in regard to the role of the active form of vitamin D3 binding to vitamin D3 receptor (VDR), as well as it describes the influence of polymorphisms of VDR on the inhibition of HH. Understanding of these mechanisms and critical assessment of available data is beneficial to both primary and secondary prevention of malignant melanoma particularly by means of chemo -preventive substances.

[Cardiovascular cooperation with the BPKIHS Hospital, in Dharan Bazar, Nepal]. / Coopération cardiovasculaire avec l'Hôpital BPKIHS, à Dharan Bazar, Népal.

Thanks to a collaboration project that was developed by Swiss cardiologists, the Coeur de la Tour Foundation, and BPKIHS, a teaching hospital in Dharan, it has been possible, within two years and using a "hybrid approach", to set up the first independent invasive and interventional program in East Nepal. 496 patients have been investigated and/or treated since January 2011, during an initial period of 23 months (coronary angiographies, coronary angioplasties, temporary and permanent pacemaker implantations, pericardiocenteses, etc.). In parallel with this, our Foundation, in the same area of the country, has also supported a pre-existing cardiovascular prevention program and has helped start a population-based study of rheumatic heart disease prevalence and treatment outcome among school children.

Effect of boundary layers asymmetry on heat transfer efficiency in turbulent Rayleigh-Bénard convection at very high Rayleigh numbers [corrected].

The heat transfer efficiency in turbulent Rayleigh-Bénard convection is investigated experimentally, in a cylindrical cell of height 0.3 m, diameter 0.3 m. We show that for Rayleigh numbers 10(12) < or approximately equal to Ra < or approximately equal to 10(15) the Nusselt number closely follows Nu is proportional to Ra(1/3 if the mean temperature of the working fluid-cryogenic helium gas-is measured by small sensors directly inside the cell at about half of its height. In contrast, if the mean temperature is determined in a conventional way, as an arithmetic mean of the bottom and top plate temperatures, the Nu(Ra) is proportional to Ra(γ) displays spurious crossover to higher γ that might be misinterpreted as a transition to the ultimate Kraichnan regime.

Progression of apoptic signaling from mesenteric ischemia-reperfusion injury to lungs: correlation in the level of ER chaperones expression.

Multiple organ dysfunction syndrome (MODS) is characterized by the development of probably reversible, progressive dysfunction of vital systems in two or more organs, directly undamaged by surgery or other trauma. The organs which have the most common potential dysfunction are lungs, liver, kidneys, heart and gastrointestinal tract. The small intestine is the source of production of proinflammatory mediators leading and contributing to multiorgan failure. The endoplasmic reticulum (ER), after ischemia and post-ischemic reperfusion, is significantly involved in the activation of enterocyte apoptosis. The purpose of this study was to determine the stage of apoptosis in the lungs, initiated through inflammatory response from the small intestine. We analyzed changes in mRNA levels of pro-apoptotic genes Gadd153 (Chop) and anti-apoptotic genes Grp78 (Bip) in the small intestine wall and lung parenchyma. During experimental procedure the rats underwent 60 min of ischemia, caused by complete occlusion of the mesenteric arteria cranialis, with subsequent reperfusion and evaluation after 1 h, 24 h and 30 days (from R1, R24 to R30, respectively, each group n = 8). The gene expression levels were measured using RT-PCR followed by electrophoresis and visualization under UV. In the lungs we detected significantly lower level of expression Grp78 by 45 ± 6.9%. This suggests that ischemic attack and subsequent reperfusion did not promote ER stress in the lungs through induction of Gadd153 expression in the small intestine. There is still no effective approach to the treatment of affected ischemic intestine tissue, to stop the processes with could eventually lead to MODS. Therefore it is necessary to study changes in the damaged tissue at the molecular level and try to suggest possible therapeutic defined routes to the protection of tissue.