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The effects of 25 mg propiomazine were examined in ten healthy volunteers in a sleep laboratory setting. A significant decrease in sleep latency and a corresponding decrement in subjectively assessed sleep latency was found during drug treatment. The distribution of the different sleep stages was affected to a relatively small extent. Some evidence for a suppression of REM-sleep in the early part of the treatment period was found. Based on subjective assessment, the subjects rated their sleep quality as significantly improved during treatment. Ratings of 'drowsiness in the morning' were not different during baseline and drug treatment, but there was a significant decrease at withdrawal. [ABSTRACT FROM AUTHOR]

Myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS) are two common and aggressive subtypes of soft tissue sarcoma. The aim of this study was to assess potential transcriptomic differences between MFS and UPS tumours and to evaluate the extent to which differences in gene expression profiles were associated with genomic and clinical features. The study included 162 patients with tumours diagnosed as MFS (N = 62) or UPS (N = 100). The patients had been diagnosed and treated at two Swedish sarcoma centres during a 30-year period. For gene expression profiling and gene fusion detection all tumours were analysed using RNA-sequencing and could be compared with data on clinical outcome (N = 155), global copy number profiles (N = 145), and gene mutations (N = 128). Gene expression profiling revealed three transcriptomic clusters (TCs) without any clear separation of MFS and UPS. One TC was associated with longer metastasis-free survival. These tumours had lower tumour mutation burden (TMB), were enriched for a copy number signature representative of focal LOH and chromosomal instability on a diploid background, and were relatively immune-depleted. MFS and UPS showed extensive genomic overlap, with whole genome doubling occurring more frequently among the latter. The results support the idea that MFS and UPS tumours have largely overlapping genomic and transcriptomic features, with UPS tumours showing more aggressive behaviour and more complex genomes. Independently of the tumour type, clinically relevant subgroups were revealed by gene expression analysis, and the finding of multiple genomic subgroups strongly suggest the existence of subgroups of relevance to treatment stratification. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland., (© 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)

Red hair has been linked to altered sensitivity to pain, analgesics, and hypnotics. This alteration may be impacted by variants in the melanocortin-1 receptor ( MC1R ) gene, which are mainly found in redheads. The aim of this narrative review was to explore and present the current state of knowledge on red hair and its plausible associations with altered responsiveness to pain, analgesics, and hypnotics. Structured searches in the PubMed, CINAHL Complete, and Scopus electronic databases were conducted. Evidence suggests that women with red hair have an increased sensitivity to pain. Conversely, data also indicate a higher pain tolerance in homozygous carriers of MC1R variant alleles. Varied responses to analgesia have been reported, with both increased analgesic responsiveness in homozygous carriers of MC1R variant alleles and less analgesia in redheads. Data indicate an increased need for hypnotics in redheads. However, failed attempts to find statistical associations between red hair and altered responsiveness to hypnotics are also evident. Even though there seems to be an association between red hair and an altered responsiveness to pain, analgesics, and/or hypnotics, the results of this narrative review are inconclusive. Further research studies with larger populations and MC1R testing are needed.

Atrial high rate episodes (AHRE) are frequently detected in patients with pacemakers or implantable cardioverter defibrillators. AHRE episodes ≥5 minutes are associated with increased risk of ischemic stroke. There is no clear temporal relationship between AHRE and ischemic stroke, therefore atrial arrhythmia could be suspected to at least in part be a risk marker and not solely a direct cause of stroke. No results have been published on the effect of anticoagulation in patients with AHRE, but several studies are in progress. The European Heart Rhythm Association (EHRA) recommends anticoagulation for patients with AHRE ≥5.5 hours per day and a CHA2DS2-VASc score of ≥2 (≥3 in females). Anticoagulation may be considered for CHA2DS2-VASc scores of 1 (2 in females). In patients with several risk factors anticoagulation should be considered also in cases with shorter duration of AHRE.

Ventricular tachycardia or ventricular fibrillation can be terminated by defibrillation and implantable cardioverter defibrillators (ICDs) prevent sudden cardiac death. Since 2001 the wearable cardioverter defibrillator (WCD) has been available to provide temporary protection; it safely and effectively detects and terminates ventricular tachyarrhythmias. VEST (published in 2018) compared the effect of WCD in patients with ejection fraction ≤35 percent following myocardial infarction. Total mortality was reduced but sudden cardiac death did not reach statistical significance. According to European guidelines a WCD could be used to protect patients during the time they are evaluated for ICD; for example, during the three-month period with optimal medical therapy awaiting recovery of a low ejection fraction. It could also be considered during the period following extraction due to endocarditis before reimplantation of ICD or during the waiting period for heart transplant.

An acoustic trap with miniaturized integrated transducers (MITs) for applications in non-contact trapping of cells or particles in a microfluidic channel was characterized by measuring the temperature increase and trapping strength. The fluid temperature was measured by the fluorescent response of Rhodamine B in the microchannel. The trapping strength was measured by the area of a trapped particle cluster counter-balanced by the hydrodynamic force. One of the main objectives was to obtain quantitative values of the temperature in the fluidic channel to ensure safe handling of cells and proteins. Another objective was to evaluate the trapping-to-temperature efficiency for the trap as a function of drive frequency. Thirdly, trapping-to-temperature efficiency data enables identifying frequencies and voltage values to use for in-trap temperature regulation. It is envisioned that operation with only in-trap temperature regulation enables the realization of small, simple and fast temperature-controlled trap systems. The significance of potential gradients at the trap edges due to the finite size of the miniaturized transducers for the operation was emphasized and expressed analytically. The influence of the acoustic near field was evaluated in FEM-simulation and compared with a more ideal 1D standing wave. The working principle of the trap was examined by comparing measurements of impedance, temperature increase and trapping strength with impedance transfer calculations of fluid-reflector resonances and frequencies of high reflectance at the fluid-reflector boundary. The temperature increase was found to be moderate, 7°C for a high trapping strength, at a fluid flow of 0.5mms(-1) for the optimal driving frequency. A fast temperature response with a fall time of 8s and a rise time of 11s was observed. The results emphasize the importance of selecting the proper drive frequency for long term handling of cells, as opposed to the more pragmatic way of selecting the frequency of the highest acoustic output. Trapping was demonstrated in a large interval between 9 and 11.5MHz, while the main trapping peak displayed FWHM of 0.5MHz. A large bandwidth enables a more robust manufacturing and operation while allowing the trapping platform to be used in applications where the fluid wavelength varies due to external variations in fluid temperature, density and pressure., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Previous studies have shown that obesity and hypertension are associated with increased risk of renal cell carcinoma (RCC), but less is known about the association to other metabolic factors. In the Metabolic Syndrome and Cancer project (Me-Can) data on body mass index (BMI, kg/m2), blood pressure, and circulating levels of glucose, cholesterol, and triglycerides were collected from 560,388 men and women in cohorts from Norway, Austria, and Sweden. By use of Cox proportional hazard models, hazard ratios (HR) were calculated for separate and composite metabolic exposures. During a median follow-up of 10 years, 592 men and 263 women were diagnosed with RCC. Among men, we found an increased risk of RCC for BMI, highest vs. lowest quintile, (HR = 1.51, 95% CI 1.13-2.03), systolic blood pressure, (HR = 3.40, 95% CI 1.91-6.06), diastolic blood pressure, (HR = 3.33, 95% CI 1.85-5.99), glucose, (HR = 3.75, 95% CI 1.46-9.68), triglycerides, (HR = 1.79, 95% CI 1.00-3.21) and a composite score of these metabolic factors, (HR = 2.68, 95% CI 1.75-4.11). Among women we found an increased risk of RCC for BMI, highest vs. lowest quintile, (HR = 2.21, 95% CI 1.32-3.70) and the composite score, (HR = 2.29, 95% CI 1.12-4.68). High levels of the composite score were also associated with risk of death from RCC among both men and women. No multiplicative statistical or biological interactions between metabolic factors on risk of RCC were found. High levels of BMI, blood pressure, glucose and triglycerides among men and high BMI among women were associated with increased risk of RCC.

Background: There are inconsistent data regarding the association between metabolic factors, separately and combined, and the risk of prostate cancer and death from prostate cancer., Methods: In the Metabolic Syndrome and Cancer Project (Me-Can), data on body mass index (BMI); blood pressure; and blood levels of glucose, cholesterol, and triglycerides were collected for 289,866 men. Cox proportional hazard models were used to calculate relative risks (RRs) by exposures in quintiles as well as for z scores (with a mean of 0 and a standard deviation of 1) together with a composite sum of scores to assess the combined effect of metabolic factors. RRs were corrected for random errors in measurement., Results: During a mean follow-up of 12 years, 6673 men were diagnosed with prostate cancer and 961 died of the disease. Men with high levels of glucose and triglycerides were found to have a decreased risk of prostate cancer: top versus bottom quintile of glucose: RR, 0.82 (95% confidence interval [95% CI], 0.62-1.08; P value for trend = .03) and top versus bottom quintile of triglycerides: RR, 0.88 (95% CI, 0.74-1.04; P value for trend = .001). High BMI, elevated blood pressure, and a high composite z score were found to be associated with an increased risk of death from prostate cancer: top versus bottom quintile of BMI: RR, 1.36 (95% CI, 1.08-1.71); systolic blood pressure: RR, 1.62 (95% CI, 1.07-2.45); and per 1-unit increase of the composite z score: RR, 1.13 (95% CI, 1.03-1.25)., Conclusions: The authors found no evidence of an association between high levels of metabolic factors and the risk of prostate cancer, but high BMI, elevated blood pressure, and a composite score of all metabolic factors were associated with an increased risk of death from prostate cancer., (Copyright © 2012 American Cancer Society.)

Recordings of the acoustic activity of free-swimming groups of echolocating dolphins increase the likelihood of collecting overlapping click trains, originating from multiple individuals, in the same set of data. In order to evaluate the click properties of each individual based on such recordings it is necessary to identify which clicks originate from which animal. This paper suggests a computationally efficient strategy to separate overlapping click trains originating from multiple free-swimming bottlenose dolphins, enabling echolocation analysis at an individual level on several animals. This technique is based on sequential matching of the frequency spectra of successive clicks. The clicks are grouped together as individual click trains if the correlation coefficients between clicks are higher than a pre-set threshold level. The robustness of the algorithm is tested by adding artificially generated white Gaussian noise and comparing the results with other comparable commonly used methods based on inter-click intervals, centroid frequencies, and amplitude levels. The described method is applicable to a variety of experimental and observational contexts, e.g., those regarding echolocation development of calves, the hypothesized acoustic "etiquette" among dolphins when investigating the same object, and the possible occurrence of eavesdropping in large dolphin pods.

Detailed echolocation behavior studies on free-swimming dolphins require a measurement system that incorporates multiple hydrophones (often >16). However, the high data flow rate of previous systems has limited their usefulness since only minute long recordings have been manageable. To address this problem, this report describes a 47-channel burst-mode recording hydrophone system that enables highly resolved full beamwidth measurements on multiple free-swimming dolphins during prolonged recording periods. The system facilitates a wide range of biosonar studies since it eliminates the need to restrict the movement of animals in order to study the fine details of their sonar beams.

The present study describes the development and testing of a tool for dolphin research. This tool was able to visualize the dolphin echolocation signals as well as function as an acoustically operated "touch screen." The system consisted of a matrix of hydrophones attached to a semitransparent screen, which was lowered in front of an underwater acrylic panel in a dolphin pool. When a dolphin aimed its sonar beam at the screen, the hydrophones measured the received sound pressure levels. These hydrophone signals were then transferred to a computer where they were translated into a video image that corresponds to the dynamic sound pressure variations in the sonar beam and the location of the beam axis. There was a continuous projection of the image back onto the hydrophone matrix screen, giving the dolphin an immediate visual feedback to its sonar output. The system offers a whole new experimental methodology in dolphin research and since it is software-based, many different kinds of scientific questions can be addressed. The results were promising and motivate further development of the system and studies of sonar and cognitive abilities of dolphins.

Techniques for manipulating, separating, and trapping particles and cells are highly desired in today's bioanalytical and biomedical field. The microfluidic chip-based acoustic noncontact trapping method earlier developed within the group now provides a flexible platform for performing cell- and particle-based assays in continuous flow microsystems. An acoustic standing wave is generated in etched glass channels (600x61 microm2) by miniature ultrasonic transducers (550x550x200 microm3). Particles or cells passing the transducer will be retained and levitated in the center of the channel without any contact with the channel walls. The maximum trapping force was calculated to be 430+/-135 pN by measuring the drag force exerted on a single particle levitated in the standing wave. The temperature increase in the channel was characterized by fluorescence measurements using rhodamine B, and levels of moderate temperature increase were noted. Neural stem cells were acoustically trapped and shown to be viable after 15 min. Further evidence of the mild cell handling conditions was demonstrated as yeast cells were successfully cultured for 6 h in the acoustic trap while being perfused by the cell medium at a flowrate of 1 microL/min. The acoustic microchip method facilitates trapping of single cells as well as larger cell clusters. The noncontact mode of cell handling is especially important when studies on nonadherent cells are performed, e.g., stem cells, yeast cells, or blood cells, as mechanical stress and surface interaction are minimized. The demonstrated acoustic trapping of cells and particles enables cell- or particle-based bioassays to be performed in a continuous flow format.

This paper demonstrates that light diffraction tomography can be used to measure the acoustic field of micromachined ultrasonic transducers (MUT) in cases in which standard methods like hydrophone and microphone measurements fail. Two types of MUTs have been characterized with the method, one air-coupled capacitive MUT (cMUT) and one waterloaded continuous wave (CW) miniature multilayer lead zirconate titanate (PZT) transducer. Light diffraction tomography is an ultrasound measurement method with some special characteristics. Based on the interaction of light and ultrasound, it combines light intensity measurements with tomography algorithms to produce a measurement system. The method offers nonperturbing pressure measurements with high spatial resolution. It has been shown that, under certain circumstances, light diffraction tomography can be used as an absolute pressure measurement method with accuracy in the order of 10% in water and 13% in air. The results show that air-coupled cMUTs in the frequency range of about 1 MHz as well as the extreme near field of a miniaturized CW 10 MHz water-loaded transducer were successfully characterized with light diffraction tomography.

We are investigating means of handling microparticles in microfluidic systems, in particular localized acoustic trapping of microparticles in a flow-through device. Standing ultrasonic waves were generated across a microfluidic channel by ultrasonic microtransducers integrated in one of the channel walls. Particles in a fluid passing a transducer were drawn to pressure minima in the acoustic field, thereby being trapped and confined at the lateral position of the transducer. The spatial distribution of trapped particles was evaluated and compared with calculated acoustic intensity distributions. The particle trapping was found to be strongly affected by near field pressure variations due to diffraction effects associated with the finite sized transducer element. Since laterally confining radiation forces are proportional to gradients in the acoustic energy density, these near field pressure variations may be used to get strong trapping forces, thus increasing the lateral trapping efficiency of the device. In the experiments, particles were successfully trapped in linear fluid flow rates up to 1mm/s. It is anticipated that acoustic trapping using integrated transducers can be exploited in miniaturised total chemical analysis systems (microTAS), where e.g. microbeads with immobilised antibodies can be trapped in arrays and subjected to minute amounts of sample followed by a reaction, detected using fluorescence.

Nitric oxide (NO) is an important signal molecule. In blood vessels, nitric oxide produced by the endothelium modulates vascular tone by inducing cGMP formation in smooth muscle cells. The latter cell type does not express NO synthase normally but expression is induced by the cytokines, interferon-gamma, tumor necrosis factor, and interleukin-1. We have constructed a cDNA library from cytokine-stimulated rat aortic smooth muscle cells and isolated a cDNA clone that contains the full-length sequence of inducible NO synthase. It is 4119 bp and confers NO synthesizing activity when transfected into COS-7 cells. The nucleotide sequence is 92% identical with inducible NO synthase of murine macrophages and contains a 497 bp untranslated 3' sequence with five conserved A(U)nA motifs that may be important in the regulation of mRNA turnover. This is supported by the short half-life (2.6 h) of smooth muscle NO synthase mRNA, which contrasts with brain and endothelial NO synthase.

An experimental, in vivo study was performed to measure height changes in subjects exposed to whole body vibrations while seated. Twelve women, with an average age of 22 years, were exposed to sinusoidal vibrations for 5 mins. The vibration frequency was 5 Hz, and the acceleration was 0.1 g Rms. The height loss stemming from vibration exposure was compared with that experienced while sitting without being subjected to vibrations. The height losses that always occurred from the two exposures were corrected for the effect of posture change. The height loss from vibration was significantly greater than when no vibration was present. Height loss due to posture change was responsible for approximately 50% of the total height loss. From this study it was concluded that whole body vibrations cause increased height loss.