Search

Abstract A new series of substituted benzo[h]chromene, benzochromenopyrimidine, and benzochromenotriazolopyrimidine derivatives were synthesized via chemical transformations of iminonitrile, ethoxymethylene amino, and cyanomethylene functionalities. The chemical structures of the synthesized compounds were assured by spectroscopic data and elemental analysis. The larvicidal efficacy of these compounds against Culex pipiens L. larvae was investigated, revealing potent insecticidal activity, particularly for compounds 6, 10, and 16, exceeding that of the standard insecticide chlorpyrifos. The mode of action of these compounds was explored through molecular docking studies, indicating their potential as acetylcholine esterase (AChE) inhibitors and nicotinic acetylcholine receptors (nAChR) blockers. The structure–activity relationship analysis highlighted the influence of substituents and fused heterocyclic rings on larvicidal potency. These findings suggest that the synthesized compounds hold promise as potential candidates for developing novel and effective mosquito control agents.

Abstract Accurate intraoperative assessment of organ perfusion is a pivotal determinant in preserving organ function e.g. during kidney surgery including partial nephrectomy or kidney transplantation. Hyperspectral imaging (HSI) has great potential to objectively describe and quantify this perfusion as opposed to conventional surrogate techniques such as ultrasound flowmeter, indocyanine green or the subjective eye of the surgeon. An established live porcine model under general anesthesia received median laparotomy and renal mobilization. Different scenarios that were measured using HSI were (1) complete, (2) gradual and (3) partial malperfusion. The differences in spectral reflectance as well as HSI oxygenation (StO2) between different perfusion states were compelling and as high as 56.9% with 70.3% (± 11.0%) for “physiological” vs. 13.4% (± 3.1%) for “venous congestion”. A machine learning (ML) algorithm was able to distinguish between these perfusion states with a balanced prediction accuracy of 97.8%. Data from this porcine study including 1300 recordings across 57 individuals was compared to a human dataset of 104 recordings across 17 individuals suggesting clinical transferability. Therefore, HSI is a highly promising tool for intraoperative microvascular evaluation of perfusion states with great advantages over existing surrogate techniques. Clinical trials are required to prove patient benefit.

Abstract The symbiosis between corals and dinoflagellates of the family Symbiodiniaceae is sensitive to environmental stress. The oxidative bleaching hypothesis posits that extreme temperatures lead to accumulation of photobiont-derived reactive oxygen species ROS, which exacerbates the coral environmental stress response (ESR). To understand how photosymbiosis modulates coral ESRs, these responses must be explored in hosts in and out of symbiosis. We leveraged the facultatively symbiotic coral Astrangia poculata, which offers an opportunity to uncouple the ESR across its two symbiotic phenotypes (brown, white). Colonies of both symbiotic phenotypes were exposed to three temperature treatments for 15 days: (i) control (static 18 °C), (ii) heat challenge (increasing from 18 to 30 °C), and (iii) cold challenge (decreasing from 18 to 4 °C) after which host gene expression was profiled. Cold challenged corals elicited widespread differential expression, however, there were no differences between symbiotic phenotypes. In contrast, brown colonies exhibited greater gene expression plasticity under heat challenge, including enrichment of cell cycle pathways involved in controlling photobiont growth. While this plasticity was greater, the genes driving this plasticity were not associated with an amplified environmental stress response (ESR) and instead showed patterns of a dampened ESR under heat challenge. This provides nuance to the oxidative bleaching hypothesis and suggests that, at least during the early onset of bleaching, photobionts reduce the host’s ESR under elevated temperatures in A. poculata.

Abstract The areal extent of seagrass meadows is in rapid global decline, yet they provide highly valuable societal benefits. However, their conservation is hindered by data gaps on current and historic spatial extents. Here, we outline an approach for national-scale seagrass mapping and monitoring using an open-source platform (Google Earth Engine) and freely available satellite data (Landsat, Sentinel-2) that can be readily applied in other countries globally. Specifically, we map contemporary (2021) and historical (2000–2021; n = 10 maps) shallow water seagrass extent across the Maldives. We found contemporary Maldivian seagrass extent was ~ 105 km2 (overall accuracy = 82.04%) and, notably, that seagrass area increased threefold between 2000 and 2021 (linear model, + 4.6 km2 year−1, r2 = 0.93, p

Abstract Background In vitro data suggested reduced neutralizing capacity of sotrovimab, a monoclonal antibody, against Omicron BA.2 subvariant. However, limited in vivo data exist regarding clinical effectiveness of sotrovimab for coronavirus disease 2019 (COVID-19) due to Omicron BA.2. Methods A multicentre, retrospective cohort study was conducted at three Canadian academic tertiary centres. Electronic medical records were reviewed for patients ≥ 18 years with mild COVID-19 (sequencing-confirmed Omicron BA.1 or BA.2) treated with sotrovimab between February 1 to April 1, 2022. Thirty-day co-primary outcomes included hospitalization due to moderate or severe COVID-19; all-cause intensive care unit (ICU) admission, and all-cause mortality. Risk differences (BA.2 minus BA.1 group) for co-primary outcomes were adjusted with propensity score matching (e.g., age, sex, vaccination, immunocompromised status). Results Eighty-five patients were included (15 BA.2, 70 BA.1) with similar baseline characteristics between groups. Adjusted risk differences were non-statistically significant between groups for 30-day hospitalization (− 14.3%; 95% confidence interval (CI): − 32.6 to 4.0%), ICU admission (− 7.1%; 95%CI: − 20.6 to 6.3%), and mortality (− 7.1%; 95%CI: − 20.6 to 6.3%). Conclusions No differences were demonstrated in hospitalization, ICU admission, or mortality rates within 30 days between sotrovimab-treated patients with BA.1 versus BA.2 infection. More real-world data may be helpful to properly assess sotrovimab’s effectiveness against infections due to specific emerging COVID-19 variants.

Abstract Habitat selection studies facilitate assessing and predicting species distributions and habitat connectivity, but habitat selection can vary temporally and among individuals, which is often ignored. We used GPS telemetry data from 96 Gray wolves (Canis lupus) in the western Great Lakes region of the USA to assess differences in habitat selection while wolves exhibited resident (territorial) or non-resident (dispersing or floating) movements and discuss implications for habitat connectivity. We used a step-selection function (SSF) to assess habitat selection by wolves exhibiting resident or non-resident movements, and modeled circuit connectivity throughout the western Great Lakes region. Wolves selected for natural land cover and against areas with high road densities, with no differences in selection among wolves when resident, dispersing, or floating. Similar habitat selection between resident and non-resident wolves may be due to similarity in environmental conditions, when non-resident movements occur largely within established wolf range rather than near the periphery or beyond the species range. Alternatively, non-resident wolves may travel through occupied territories because higher food availability or lower human disturbance outweighs risks posed by conspecifics. Finally, an absence of differences in habitat selection between resident and non-resident wolf movements may be due to other unknown reasons. We recommend considering context-dependency when evaluating differences in movements and habitat use between resident and non-resident individuals. Our results also provide independent validation of a previous species distribution model and connectivity analysis suggesting most potential wolf habitat in the western Great Lakes region is occupied, with limited connectivity to unoccupied habitat.

Rats are an important issue in cities globally. Despite their ubiquity, perceptions and concerns about rats vary with circumstance and the context in which a person interacts with them. Municipal rat management programs are a service to communities and therefore must be responsive to the varied concerns of their residents. Understanding why communities are concerned about rats can help inform rat management programs to meet the specific needs of their residents. The objective of this study was to identify why the residents of Vancouver, Canada care about rats and what they want done to address them. To do this, we qualitatively analyzed 6,158 resident complaints about rats made to the city's municipal government between January 2014 and May 2020. Using a qualitative descriptive coding process, we found that rats were a priority in a minority of cases. In general, people were more concerned about broader community issues, such as neighborhood disorder, of which rats were one part. Complaints tended to be made when problems were highly visible, nearby, and when the complainant wanted the city to take action to alleviate this issue, particularly when they were in and around their living spaces. The rates of complaints were highest in the most economically and socially deprived neighborhoods and lowest in the most privileged neighbourhoods. We synthesize this information with a view towards understanding how to develop objectives and actions for municipal management strategies that are grounded in community concerns.

Abstract Background and Aims This study aims to describe inequalities in health indicators according to gender, area of residence, and socioeconomic position among Brazilian adolescents. Methods Cross‐sectional study using data from a school‐based survey carried out in Brazil in 2019. Twelve health outcomes were evaluated. Dimensions of inequality assessed were gender, area of residence, wealth and subnational region. Results This study comprises a sample of 124,898 adolescents. The most prevalent outcome was physical inactivity (71.9%) followed by thinking life is worthless (52.6%) and bullying (51.8%). Gender inequalities were more marked for physical inactivity and thinking life is worthless with girls presenting a prevalence more than 20 p.p. higher than boys. In zero‐dose HPV, however, the prevalence in girls was 17.7 p.p. lower than in boys. Area of residence and wealth inequalities were smaller than gender disparities. Context presented a relevant role in inequality with analysis stratified by states of the country, revealing high variability in estimates. Conclusions We highlight the need for attention to disparities between subgroups of the adolescent population, especially for gender inequalities that were the most marked for this age group.

Abstract It is important to decipher the diversity and distribution of benthic dinoflagellates, as there are many morphologically indistinct taxa that differ from one another in production of potent toxins. To date, the genus Ostreopsis comprises twelve described species, of which seven are potentially toxic and produce compounds presenting a threat to human and environmental health. In this study, isolates previously identified as “Ostreopsis sp. 3” were sampled from the area where it was first reported, Rarotonga, Cook Islands, and have been taxonomically and phylogenetically characterised as Ostreopsis tairoto sp. nov. Phylogenetically, the species is closely related to “Ostreopsis sp. 8”, O. mascarenensis, “O. sp. 4”, O. fattorussoi, O. rhodesiae and O. cf. siamensis. Previously, it was considered a part of the O. cf. ovata complex but can be distinguished from O. cf. ovata based on the small pores identified on this study, and from O. fattorussoi and O. rhodesiae based on relative lengths of the 2′ plates. No known palytoxin -like compounds were detected in strains investigated in this study. Strains of O. lenticularis, Coolia malayensis and C. tropicalis were also identified and described. This study advances our knowledge of biogeography, distribution, and toxins of Ostreopsis and Coolia species.

Abstract Background An increase in the demand for general practitioners is expected in many countries, but only a minority of medical students consider a career in general practice. More detailed and up-to-date knowledge about medical student’s perception of general practice would be helpful for efforts to encourage medical students to consider a career in general practice. Methods We performed a cross-sectional single center survey among Dutch medical students to evaluate their perception of general practice at three different stages in their study: Ba1: first-year bachelor students; Ba3: third-year bachelor students; Ma3: third-year master students. The impact of different factors on their attitudes and perceptions was quantified. A multivariate logistic regression was performed with ‘interest in general practice’ as the outcome variable. Results The median age for Ba1 was 18 (IQR: 18–19) and 71.5% were female, for Ba3 the median age was 20 (IQR: 20–21) and 70.6% were female and for Ma3 the median age was 25 years (IQR: 24–26) and 73.3% were female. On average, 31.2% of the respondents had a migration background. The mean response rate for this study was 77.1%. Of the participating Ba1 students (n = 340) only 22.4% considered working as a GP after medical school; for Ba3 students (n = 231) this percentage was 33.8%, and for Ma3 students (n = 210) it was significantly higher at 70.5%; in the final multivariate model this corresponded to an odds ratio (OR) of 4.3 (95%-CI:2.6–6.9) compared to Ba1 students. The strongest predictor in the final model was the opinion that general practice provides a pleasant working environment (OR 9.5; 95%-CI: 6.2–14.5). Conclusion This study showed that multiple factors are significantly related to medical students’ interest in general practice. Although students believed that general practice does not have a high status within the medical profession, they acknowledged the social importance and the pleasant working environment of general practice. Knowledge obtained in this study can be used when designing a medical curriculum or a general practice course.

Abstract Mandibular distraction osteogenesis (DO) is mediated by skeletal stem cells (SSCs) in mice, which enact bone regeneration via neural crest re-activation. As peripheral nerves are essential to progenitor function during development and in response to injury, we questioned if denervation impairs mandibular DO. C57Bl6 mice were divided into two groups: DO with a segmental defect in the inferior alveolar nerve (IAN) at the time of mandibular osteotomy (“DO Den”) and DO with IAN intact (“DO Inn”). DO Den demonstrated significantly reduced histological and radiological osteogenesis relative to DO Inn. Denervation preceding DO results in reduced SSC amplification and osteogenic potential in mice. Single cell RNA sequencing analysis revealed that there was a predominance of innervated SSCs in clusters dominated by pathways related to bone formation. A rare human patient specimen was also analyzed and suggested that histological, radiological, and transcriptional alterations seen in mouse DO may be conserved in the setting of denervated human mandible distraction. Fibromodulin (FMOD) transcriptional and protein expression were reduced in denervated relative to innervated mouse and human mandible regenerate. Finally, when exogenous FMOD was added to DO-Den and DO-Inn SSCs undergoing in vitro osteogenic differentiation, the osteogenic potential of DO-Den SSCs was increased in comparison to control untreated DO-Den SSCs, modeling the superior osteogenic potential of DO-Inn SSCs.

Abstract An accurate estimator of the real-time fatality rate is warranted to monitor the progress of ongoing epidemics, hence facilitating the policy-making process. However, most of the existing estimators fail to capture the time-varying nature of the fatality rate and are often biased in practice. A simple real-time fatality rate estimator with adjustment for reporting delays is proposed in this paper using the fused lasso technique. This approach is easy to use and can be broadly applied to public health practice as only basic epidemiological data are required. A large-scale simulation study suggests that the proposed estimator is a reliable benchmark for formulating public health policies during an epidemic with high accuracy and sensitivity in capturing the changes in the fatality rate over time, while the other two commonly-used case fatality rate estimators may convey delayed or even misleading signals of the true situation. The application to the COVID-19 data in Germany between January 2020 and January 2022 demonstrates the importance of the social restrictions in the early phase of the pandemic when vaccines were not available, and the beneficial effects of vaccination in suppressing the fatality rate to a low level since August 2021 irrespective of the rebound in infections driven by the more infectious Delta and Omicron variants during the fourth wave.

Abstract We present observations of the high momentum tail in expanding Bose–Einstein condensates of metastable Helium atoms released from a harmonic trap. The far-field density profile exhibits features that support identification of the tails of the momentum distribution as originating in the in-situ quantum depletion prior to release. Thus, we corroborate recent observations of slowly-decaying tails in the far-field beyond the thermal component. This observation is in conflict with the hydrodynamic theory, which predicts that the in-situ depletion does not survive when atoms are released from a trap. Indeed, the depleted tails even appear stronger in the far-field than expected before release, and we discuss the challenges of interpreting this in terms of the Tan contact in the trapped gas. In complement to these observations, full quantum simulations of the experiment show that, under the right conditions, the depletion can persist into the far field after expansion. Moreover, the simulations provide mechanisms for survival and for the the large-momentum tails to appear stronger after expansion due to an acceleration of the depleted atoms by the mean-field potential. However, while in qualitative agreement, the final depletion observed in the experiment is much larger than in the simulation.

Abstract Optical generation of kilo-tesla scale magnetic fields enables prospective technologies and fundamental studies with unprecedentedly high magnetic field energy density. A question is the optimal configuration of proposed setups, where plenty of physical phenomena accompany the generation and complicate both theoretical studies and experimental realizations. Short laser drivers seem more suitable in many applications, though the process is tangled by an intrinsic transient nature. In this work, an artificial neural network is engaged for unravelling main features of the magnetic field excited with a picosecond laser pulse. The trained neural network acquires an ability to read the magnetic field values from experimental data, extremely facilitating interpretation of the experimental results. The conclusion is that the short sub-picosecond laser pulse may generate a quasi-stationary magnetic field structure living on a hundred picosecond time scale, when the induced current forms a closed circuit.

Abstract Background African ancestry is a significant risk factor for advanced prostate cancer (PCa). Mortality rates in sub-Saharan Africa are 2.5-fold greater than global averages. However, the region has largely been excluded from the benefits of whole genome interrogation studies. Additionally, while structural variation (SV) is highly prevalent, PCa genomic studies are still biased towards small variant interrogation. Methods Using whole genome sequencing and best practice workflows, we performed a comprehensive analysis of SVs for 180 (predominantly Gleason score ≥ 8) prostate tumours derived from 115 African, 61 European and four ancestrally admixed patients. We investigated the landscape and relationship of somatic SVs in driving ethnic disparity (African versus European), with a focus on African men from southern Africa. Results Duplication events showed the greatest ethnic disparity, with a 1.6- (relative frequency) to 2.5-fold (count) increase in African-derived tumours. Furthermore, we found duplication events to be associated with CDK12 inactivation and MYC copy number gain, and deletion events associated with SPOP mutation. Overall, African-derived tumours were 2-fold more likely to present with a hyper-SV subtype. In addition to hyper-duplication and deletion subtypes, we describe a new hyper-translocation subtype. While we confirm a lower TMPRSS2-ERG fusion-positive rate in tumours from African cases (10% versus 33%), novel African-specific PCa ETS family member and TMPRSS2 fusion partners were identified, including LINC01525, FBXO7, GTF3C2, NTNG1 and YPEL5. Notably, we found 74 somatic SV hotspots impacting 18 new candidate driver genes, with CADM2, LSAMP, PTPRD, PDE4D and PACRG having therapeutic implications for African patients. Conclusions In this first African-inclusive SV study for high-risk PCa, we demonstrate the power of SV interrogation for the identification of novel subtypes, oncogenic drivers and therapeutic targets. Identifying a novel spectrum of SVs in tumours derived from African patients provides a mechanism that may contribute, at least in part, to the observed ethnic disparity in advanced PCa presentation in men of African ancestry.

Abstract Worker reproduction in social insects is often regulated by the queen, but can be regulated by the brood and nestmates, who may use different mechanisms to induce the same outcomes in subordinates. Analysis of brain gene expression patterns in bumble bee workers (Bombus impatiens) in response to the presence of the queen, the brood, both or neither, identified 18 differentially expressed genes, 17 of them are regulated by the queen and none are regulated by the brood. Overall, brain gene expression differences in workers were driven by the queen’s presence, despite recent studies showing that brood reduces worker egg laying and provides context to the queen pheromones. The queen affected important regulators of reproduction and brood care across insects, such as neuroparsin and vitellogenin, and a comparison with similar datasets in the honey bee and the clonal raider ant revealed that neuroparsin is differentially expressed in all species. These data emphasize the prominent role of the queen in regulating worker physiology and behavior. Genes that serve as key regulators of workers’ reproduction are likely to play an important role in the evolution of sociality.

The review summarizes and analyzes the results of domestic and major foreign studies of recent years concerning gender characteristics of the epidemiology and development mechanisms of metabolic syndrome and urolithiasis as an associated disease. A deep understanding of gender aspects in the pathogenesis of these pathologies can form the basis for development of high-quality diagnostic algorithms and pathogenetically grounded approaches to treatment.

BackgroundProviding high-quality early childhood care and education is understood as key to maximizing children's potential to succeed later in life, as it stimulates young children's development of skills and competencies needed to promote optimal outcomes and success later in life. Despite the government's efforts to support the early childhood sector, educators in Singapore continue to report difficulties in implementing practices in classrooms that promote children's social, emotional, and cognitive development. To enhance educators' skills in these domains, we developed the Enhancing And Supporting Early development to better children's Lives (EASEL) Approach, a set of universal, educator-delivered practices for use with 3-6-year-old children in early childhood settings to improve social, emotional, behavioral, and executive functioning (SEB+EF) outcomes.MethodsThis study will evaluate the effectiveness and implementation of the EASEL Approach in improving early childhood educators' teaching practices and, in turn, children's SEB+EF outcomes. We will conduct a cluster randomized controlled trial with a type 2 hybrid effectiveness-implementation study in 16 childcare centers. The EPIS (Explore, Prepare, Implement, Sustain) Framework will be used to inform the implementation of the EASEL Approach. Implementation strategies include training, educator self-assessments, practice-based coaching, and data monitoring. Our primary outcome is educators' teaching practices. Secondary outcomes include educators' adoption of the EASEL Approach in everyday practice, the acceptability and feasibility of the EASEL Approach, and children's SEB+EF outcomes. Quantitative and qualitative data will be collected at baseline, six months, and after implementation.ConclusionFindings from this study will provide significant evidence on the effectiveness of the EASEL Approach in improving educators' teaching practices and its impact on children's SEB+EF outcomes and the implementation of the EASEL Approach in early childhood classrooms in Singapore.Trial registrationThis study was prospectively registered on ClinicalTrials.gov, Identifier: NCT05445947 on 6th July 2022.

Background and Objectives: Antimicrobial Resistance (AMR) is considered an imminent “silent” pandemic of current times. Therefore, understanding the level of knowledge and prevalent practices of antibiotic misuse are important to establish targeted educational and other interventional programmes. Methods: This was a cross sectional descriptive study conducted among 450 patients who attended the Outpatient Department of Teaching Hospital, Peradeniya, Sri Lanka. An interviewer administered type questionnaire was used to evaluate knowledge of the patients regarding the drivers of AMR, and to assess the prevalence of common malpractices regarding the usage of antibiotics. For the knowledge section, marks were given out of 10. Results: Out of 450, 92 (20.4%) scored 5 or over 5 while 358 (79.6%) scored below 5. Seventy-two (16%) failed to score any marks. The mean score was 2.87 (SD 2.1) and median was 3. The obtained scores ranged from 0 to 9. Common misconceptions identified were that antibiotics were active against the common cold and antibiotics are effective against viruses. Conclusion: Awareness and knowledge regarding antibiotics and antibiotic resistance was poor within our study population. Hence, there is a need of immediate correction through a collaborative effort of healthcare practitioners and national policymakers.

Abstract An approximate 1:1 sex ratio of American lobsters can be skewed due to environmental factors or fisheries management. Substantial skewness can impact mating behaviour and lower reproduction which could have far-reaching ecological and economic consequences. The aim was to investigate the sex ratio patterns of lobsters in two lobster fishing areas (LFAs) in southwestern Nova Scotia, Canada and identify factors associated with skewed sex ratios. This study analyzed biological data from more than 270,000 lobsters sampled over ten years (2010–2019) by the Fishermen and Scientists Research Society. A mixed effect logistic regression model evaluated the effect of spatial, temporal and environmental factors as well as size on the sex ratio of lobsters. There were significant temporal patterns in sex ratios that differed by LFA. After the effects of sampling month, year and LFA were accounted for, lower bottom temperature and deeper water depth were associated with a higher prevalence of females, especially in larger lobsters. We present the first long term analyses of sex ratio patterns in H. americanus in Atlantic Canada’s most commercially important region for this species and provide evidence that these patterns are influenced by environmental factors and fisheries. In view of future climate change scenarios, monitoring the population dynamics of this iconic fishery species is crucial to ensure sustainable fisheries and healthy lobster stocks.

Abstract As one of the leading causes of elderly patients’ hospitalisation, proximal femur fractures (PFFs) will present an increasing socioeconomic problem in the near future. This is a result of the demographic change that is expressed by the increasing proportion of elderly people in society. Peri-operative management must be handled attentively to avoid complications and decrease mortality rates. To deal with the exceptional needs of the elderly, the development of orthogeriatric centres to support orthogeriatric co-management is mandatory. Adequate pain medication, balanced fluid management, delirium prevention and the operative treatment choice based on comorbidities, individual demands and biological rather than chronological age, all deserve particular attention to improve patients’ outcomes. The operative management of intertrochanteric and subtrochanteric fractures favours intramedullary nailing. For femoral neck fractures, the Garden classification is used to differentiate between non-displaced and displaced fractures. Osteosynthesis is suitable for biologically young patients with non-dislocated fractures, whereas total hip arthroplasty and hemiarthroplasty are the main options for biologically old patients and displaced fractures. In bedridden patients, osteosynthesis might be an option to establish transferability from bed to chair and the restroom. Postoperatively, the patients benefit from early mobilisation and early geriatric care. During the COVID-19 pandemic, prolonged time until surgery and thus an increased rate of complications took a toll on frail patients with PFFs. This review aims to offer surgical guidelines for the treatment of PFFs in the elderly with a focus on pitfalls and challenges particularly relevant to frail patients.

Abstract Misokinesia––or the ‘hatred of movements’––is a psychological phenomenon that is defined by a strong negative affective or emotional response to the sight of someone else’s small and repetitive movements, such as seeing someone fidget with a hand or foot. Among those who regularly experience misokinesia sensitivity, there is a growing grass-roots recognition of the challenges that it presents as evidenced by on-line support groups. Yet surprisingly, scientific research on the topic is lacking. This article is novel in systematically examining whether misokinesia sensitivity actually exists in the general population, and if so, whether there is individual variability in the intensity or extent of what sensitivities are reported. Across three studies that included 4100 participants, we confirmed the existence of misokinesia sensitivity in both student and non-student populations, with approximately one-third of our participants self-reporting some degree of sensitivity to seeing the repetitive, fidgeting behaviors of others as encountered in their daily lives. Moreover, individual variability in the range and intensity of sensitivities reported suggest that the negative social-affective impacts associated with misokinesia sensitivities may grow with age. Our findings thus confirm that a large segment of the general population may have a visual-social sensitivity that has received little formal recognition.

Neutrophils are multifaceted cells that, upon activation, release meshes of chromatin associated with different proteins, known as neutrophil extracellular traps (NETs). Leishmania amazonensis promastigotes and amastigotes induce NET release, and we have identified the signaling pathways involved in NET extrusion activated by promastigotes. Amastigotes maintain the infection in vertebrate hosts, and we have shown the association of NETs with amastigotes in human biopsies of cutaneous leishmaniasis. However, the interaction of amastigotes and neutrophils remains poorly understood. Our study aimed to characterize the pathways involved in the formation of NETs induced by axenic amastigotes from L. infantum, the causal agent of visceral leishmaniasis. Human neutrophils pretreated with signaling pathway inhibitors were incubated with amastigotes, and NET release was quantified in the culture supernatant. Amastigote viability was checked after incubation with NETs. We found that the release of NETs by neutrophils stimulated with these amastigotes requires the participation of elastase and peptidyl arginine deaminase and the involvement of PI3K, ROS, and calcium. Moreover, amastigotes are not susceptible to NET-mediated killing. Altogether, these findings improve our comprehension of the signaling pathways implicated in the interaction between amastigotes and human neutrophils.

Abstract A growing body of evidence indicates that information can be stored even in the absence of conscious awareness. Despite these findings, unconscious memory is still poorly understood with limited evidence for unconscious iconic memory storage. Here we show that strongly masked visual data can be stored and accumulate to elicit clear perception. We used a repetition method across a wide range of conditions (Experiment 1) and a more focused follow-up experiment with enhanced masking conditions (Experiment 2). Information was stored despite being masked, demonstrating that masking did not erase or overwrite memory traces but limited perception. We examined the temporal properties and found that stored information followed a gradual but rapid decay. Extraction of meaningful information was severely impaired after 300 ms, and most data was lost after 700 ms. Our findings are congruent with theories of consciousness that are based on an integration of subliminal information and support theoretical predictions based on the global workspace theory of consciousness, especially the existence of an implicit iconic memory buffer store.

Abstract Nucleation is generally viewed as a structural fluctuation that passes a critical size to eventually become a stable emerging new phase. However, this concept leaves out many details, such as changes in cluster composition and competing pathways to the new phase. In this work, both experimental and computer modeling studies are used to understand the cluster composition and pathways. Monte Carlo and molecular dynamics approaches are used to analyze the thermodynamic and kinetic contributions to the nucleation landscape in barium silicate glasses. Experimental techniques examine the resulting polycrystals that form. Both the modeling and experimental data indicate that a silica rich core plays a dominant role in the nucleation process.

Huntington’s disease (HD) is an autosomal dominant progressive neurodegenerative disease. Its molecular cause is a cytosine-adenine-guanine (CAG) trinucleotide repeat dynamic expansion in the huntingtin (HTT) gene. Alleles with 36–39 CAG-repeats are incompletely penetrant, as individuals might develop symptoms but typically with a later age of onset. When repeats are equal or greater than 40, the symptoms of the disease occur. It is considered that CAG-repeats in the “intermediate” alleles (27–35 repeats) also cause the symptoms of the HD.We present here the case of a patient who has clinical phenotype and family history of Parkinson’s disease (PD), but 27 CAG-repeats. The feature of this patient is early development of non-motor manifestations such as cognitive impairment, psychotic disorders, early dystonia in a hand, camptocormia and poor response to levodopa. It is believed that the intermediate allele of HTT gene might modify the clinical phenotype of PD in this patient.

Abstract Androgen deprivation therapy (ADT) is the standard treatment for advanced prostate cancer, but its effect on cardiovascular and metabolic function in Asian patients is still inconclusive. We prospectively assess the effects of ADT on 36 patients with advanced prostate cancer, with reference to another 24 prostate cancer patients not requiring ADT, for 2 years. Patients’ anthropometric, metabolic and vascular parameters were assessed every six-monthly. The baseline parameters of the two groups were comparable. There was a significant negative effect of the usage of ADT on the changes in BMI (p = 0.020), waist to hip ratio (p = 0.005), body fat percentage (p = 0.012), and high-density-lipoprotein (p = 0.012). ADT-patients were 4.9 times more likely to have metabolic syndrome at 24 months. (CI 0.889–27.193, p = 0.068). The Framingham risk score (p = 0.018) and pulse-wave-velocity (p = 0.024) for ADT-group were also significantly higher than controls, which signified increase in cardiovascular risk. Although there was no statistically significant difference in ischemic cardiovascular events between two groups, a trend for more events in ADT-group was observed. Therefore, Asian patients have increased cardiovascular and metabolic risks after being treated with ADT for two years. Appropriate counselling and monitoring of associated complications with ADT are essential.

Preterm labour (PL) is a relevant problem in maternal and child healthcare displaying a persistent trend. The risk of death is 25–35 times higher in premature infants than in normal children, whilst PL-associated stillbirth is 8–13 times more frequent over term labours. Severity of complications with prematurity is inversely proportional to the term of gestation. In general, PLs account for up to 70% of perinatal mortality. At the last FIGO Congress in 2018, PL was identified as an unsolved problem with no current treatment. Lack of scientific grounds for the PL aetiology and pathogenesis precludes practical success alike in prevention and treatment of this complication of pregnancy. In the bottom line, the past 60 years have not witnessed a global decline in the PL rate, it reaches to 9.5% of total births (with a slight variation depending on national commonwealth), and 15m premature infants are born annually. Two challenges currently face improvement of the PL perinatal outcomes: understanding the mechanism of PL and developing a strategy to render support at each stage of medical care to postpone, prevent the distress syndrome and sustain the foetus. The article tackles major issues in the diagnosis, treatment and prevention of preterm labour, aside with its impact on neonatal morbidity and mortality.

With approximately 95 million Americans diagnosed with high cholesterol, and many searching for a nonmedicinal treatment, intermittent fasting as a method to improve health has become increasingly popular in the lay public. We conducted a clinical inquiry to determine whether intermittent fasting is superior to a low-calorie diet in improving lipids, searching the Cochrane, EBSCOhost, Embase, MEDLINE, and Scopus databases using the terms intermittent fasting, lipids, and calorie-restricted diet. Studies that included surgical weight loss or medicine-assisted weight loss were excluded. We identified 6 published studies, 5 of which were randomized controlled trials. In reviewing the selected studies, there did not appear to be a consistent difference in lipid change between restricted-calorie diet and intermittent fasting. Because of differences in study methods and in how intermittent fasting was defined, additional studies are needed.

Abstract Background Aim of the present study is the evaluation of ultrasound as a physical method for virus inactivation in human plasma products prior to transfusion. Our study is focused on achieving a high level of virus inactivation simultaneously leaving blood products unaltered, measured by the level of degradation of coagulation factors, especially in third world countries where virus contamination of blood products poses a major problem. Virus inactivation plays an important role, especially in the light of newly discovered or unknown viruses, which cannot be safely excluded via prior testing. Methods Taking into account the necessary protection of the relevant coagulation activity for plasma, the basis for a sterile virus inactivation under shielding gas insufflation was developed for future practical use. Influence of frequency and power density in the range of soft and hard cavitation on the inactivation of transfusion-relevant model viruses for Hepatitis-(BVDV = bovine diarrhea virus), for Herpes-(SFV = Semliki Forest virus, PRV = pseudorabies virus) and Parvovirus B19 (PPV = porcine parvovirus) were examined. Coagulation activity was examined via standard time parameters to minimize reduction of functionality of coagulation proteins. A fragmentation of coagulation proteins via ultrasound was ruled out via gel electrophoresis. The resulting virus titer was examined using end point titration. Results Through CO2 shielding gas insufflation—to avoid radical emergence effects—the coagulation activity was less affected and the time window for virus inactivation substantially widened. In case of the non-lipidated model virus (AdV-luc = luciferase expressing adenoviral vector), the complete destruction of the virus capsid through hard cavitation was proven via scanning electron microscopy (SEM). This can be traced back to microjets and shockwaves occurring in hard cavitation. The degree of inactivation seems to depend on size and compactness of the type of viruses. Using our pre-tested and subsequently chosen process parameters with the exception of the small PPV, all model viruses were successfully inactivated and reduced by up to log 3 factor. For a broad clinical usage, protection of the coagulation activities may require further optimization. Conclusions Building upon the information gained, an optimum inactivation can be reached via raising of power density up to 1200 W and simultaneous lowering of frequency down to 27 kHz. In addition, the combination of the two physical methods UV treatment and ultrasound may yield optimum results without the need of substance removal after the procedure.

As people, animals and materials are transported across increasingly large distances in a globalized world, threats to our biosecurity and food security are rising. Aotearoa New Zealand is an island nation with many endemic species, a strong local agricultural industry, and a need to protect these from pest threats, as well as the economy from fraudulent commodities. Mitigation of such threats is much more effective if their origins and pathways for entry are understood. We propose that this may be addressed in Aotearoa using strontium isotope analysis of both pests and products. Bioavailable radiogenic isotopes of strontium are ubiquitous markers of provenance that are increasingly used to trace the origin of animals and plants as well as products, but currently a baseline map across Aotearoa is lacking, preventing use of this technique. Here, we have improved an existing methodology to develop a regional bioavailable strontium isoscape using the best available geospatial datasets for Aotearoa. The isoscape explains 53% of the variation (R2 = 0.53 and RMSE = 0.00098) across the region, for which the primary drivers are the underlying geology, soil pH, and aerosol deposition (dust and sea salt). We tested the potential of this model to determine the origin of cow milk produced across Aotearoa. Predictions for cow milk (n = 33) highlighted all potential origin locations that share similar 87Sr/86Sr values, with the closest predictions averaging 7.05 km away from their true place of origin. These results demonstrate that this bioavailable strontium isoscape is effective for tracing locally produced agricultural products in Aotearoa. Accordingly, it could be used to certify the origin of Aotearoa’s products, while also helping to determine if new pest detections were of locally breeding populations or not, or to raise awareness of imported illegal agricultural products.

Objective Intensive ambulatory assessment, such as ecological momentary assessment (EMA), is increasingly used to capture naturalistic patient-reported outcomes. EMA design features (eg, study duration, prompt frequency) vary widely between studies, but it is not known if such design decisions influence potential subjects’ willingness to participate in a study. We hypothesise that intentions to participate will be higher in studies that are less burdensome and have higher reward (eg, compensation).Design This experimental study examined if four EMA study design features (study duration, prompt frequency, prompt length, compensation) affected intentions to participate in a hypothetical EMA study and participation appraisals (eg, participation effort). Participants were randomly assigned to conditions (reflecting a fully crossed design of the four features, each with two levels). Each condition presented a vignette describing a study (each a unique combination of design features) and asked them to report on likelihood of participating and study appraisals.Participants A convenience sample of participants (n=600; 46% female, Mage=40.39) were recruited using an online service.Primary and secondary outcome measures Primary outcomes were willingness to participate (No/Yes) and reported participation likelihood (0–100 scale). Secondary outcomes included appraisals of interest, enjoyment, effort, and if the study makes a valuable contribution to science.Results We examined main effects, and two-way interactions for participation likelihood, across study design features. Overall, reported willingness to participate and participation likelihood were high (89%, M=83.90, respectively). Shorter study duration, fewer prompts, shorter prompts and higher compensation increased willingness to participate and elicited higher participation likelihood (each associated with ~6%–8% increases). Findings suggested that more intensive studies were judged as somewhat less interesting and enjoyable, and requiring more effort.Conclusion Hypotheses were generally supported. Design features influence behavioural intentions to participate in, and appraisals of, EMA studies. Implications for participant recruitment and generalisability, and remaining research questions, are discussed.

Abstract Background In colorectal cancer surgery there is a delicate balance between complete removal of the tumor and sparing as much healthy tissue as possible. Especially in rectal cancer, intraoperative tissue recognition could be of great benefit in preventing positive resection margins and sparing as much healthy tissue as possible. To better guide the surgeon, we evaluated the accuracy of diffuse reflectance spectroscopy (DRS) for tissue characterization during colorectal cancer surgery and determined the added value of DRS when compared to clinical judgement. Methods DRS spectra were obtained from fat, healthy colorectal wall and tumor tissue during colorectal cancer surgery and results were compared to histopathology examination of the measurement locations. All spectra were first normalized at 800 nm, thereafter two support vector machines (SVM) were trained using a tenfold cross-validation. With the first SVM fat was separated from healthy colorectal wall and tumor tissue, the second SVM distinguished healthy colorectal wall from tumor tissue. Results Patients were included based on preoperative imaging, indicating advanced local stage colorectal cancer. Based on the measurement results of 32 patients, the classification resulted in a mean accuracy for fat, healthy colorectal wall and tumor of 0.92, 0.89 and 0.95 respectively. If the classification threshold was adjusted such that no false negatives were allowed, the percentage of false positive measurement locations by DRS was 25% compared to 69% by clinical judgement. Conclusion This study shows the potential of DRS for the use of tissue classification during colorectal cancer surgery. Especially the low false positive rate obtained for a false negative rate of zero shows the added value for the surgeons. Trail registration This trail was performed under approval from the internal review board committee (Dutch Trail Register NTR5315), registered on 04/13/2015, https://www.trialregister.nl/trial/5175.

Abstract Background Phenylketonuria (PKU) is an inherited deficiency in the enzyme phenylalanine hydroxylase (PAH), which, when poorly-managed, is associated with clinical features including deficient growth, microcephaly, seizures, and intellectual impairment. The management of PKU should start as soon as possible after diagnosis to prevent irreversible damage and be maintained throughout life. The aim of this study was to assess the burden of illness in PKU patients in general and in PKU patients born before and after the introduction of newborn screening in Germany. Methods This retrospective matched cohort analysis used the Institut für angewandte Gesundheitsforschung Berlin (InGef) research database containing anonymized healthcare claims of approximately 4 million covered lives. PKU patients were compared with matched controls from the general population within the same database (1:10 ratio via direct, exact matching on age and gender without replacement). PKU patients were included if they were aged ≥18 years on 01/01/15 and were continuously enrolled from 01/01/10 to 31/12/15. The 50 most commonly reported comorbidities and 50 most commonly prescribed medications in the PKU population were analyzed. Differences between groups were tested using 95% confidence interval (CI) of prevalence ratio (PR) values. Results The analysis included 377 adult PKU patients ( 1.5 vs controls included major depressive disorders (PR = 2.3), chronic ischemic heart disease (PR = 1.7), asthma (PR = 1.7), dizziness and giddiness (PR = 1.8), unspecified diabetes mellitus (PR = 1.7), infectious gastroenteritis and colitis (PR = 1.7), and reaction to severe stress and adjustment disorders (PR = 1.6). The most commonly prescribed Anatomical Therapeutic Chemical (ATC) subcodes among PKU patients (vs the control population) are for systemic antibacterials (34.7% vs 32.8%), anti-inflammatory and antirheumatic (29.4% vs 27.5%), renin-angiotensin agents (30.0% vs 27.0%), acid-related disorders (29.4% vs 20.2%), and beta-blockers (24.9% vs 19.9%). Conclusion The overall clinical burden on patients with PKU is exacerbated by a significantly higher risk of numerous comorbidities and hence, prescribing of the requisite medication, both for recognized (e.g. major depressive disorders) and more unexpected comorbidities (e.g. ischemic heart disease).

Introduction Dementia is a group of disabling disorders that can be devastating for persons living with it and for their families. Data-informed decision-making strategies to identify individuals at high risk of dementia are essential to facilitate large-scale prevention and early intervention. This population-based case–control study aims to develop and validate a clinical algorithm for predicting dementia diagnosis, based on the cognitive footprint in personal and medical history.Methods and analysis We will use territory-wide electronic health records from the Clinical Data Analysis and Reporting System (CDARS) in Hong Kong between 1 January 2001 and 31 December 2018. All individuals who were at least 65 years old by the end of 2018 will be identified from CDARS. A random sample of control individuals who did not receive any diagnosis of dementia will be matched with those who did receive such a diagnosis by age, gender and index date with 1:1 ratio. Exposure to potential protective/risk factors will be included in both conventional logistic regression and machine-learning models. Established risk factors of interest will include diabetes mellitus, midlife hypertension, midlife obesity, depression, head injuries and low education. Exploratory risk factors will include vascular disease, infectious disease and medication. The prediction accuracy of several state-of-the-art machine-learning algorithms will be compared.Ethics and dissemination This study was approved by Institutional Review Board of The University of Hong Kong/Hospital Authority Hong Kong West Cluster (UW 18-225). Patients’ records are anonymised to protect privacy. Study results will be disseminated through peer-reviewed publications. Codes of the resulted dementia risk prediction algorithm will be made publicly available at the website of the Tools to Inform Policy: Chinese Communities’ Action in Response to Dementia project (https://www.tip-card.hku.hk/).

The inability of beef cattle to maintain full term pregnancies has become an economic concern for the beef industry. Herd management and nutritional improvements have alleviated environmental impacts on embryonic and fetal loss, yet additional gains can be made through genomic selection. The objectives of this study were to identify loci and gene-sets in crossbred beef heifers associated with the number of services required to become pregnant (TBRD) and heifer conception rate at first service (HCR1). Heifers (n = 709) from a commercial beef operation underwent one round of artificial insemination, before exposure to bulls for natural service for 50 days. Pregnancy and time of conception was determined by ultrasound 35 days after the breeding season. Heifers were genotyped using the GeneSeek (Lincoln, NE) Bovine GGP50K BeadChip prior to genome-wide association analyses (GWAA) conducted using an EIGENSTRAT-like model to identify loci associated (P < 1 × 10-5) with TBRD and HCR1. One locus was associated (P = 8.97 × 10-6) with TBRD on BTA19 and included the positional candidate gene ASIC2, which is differentially expressed in the endometrium of fertility classified heifers, and the positional candidate gene, SPACA3. Gene-set enrichment analyses using SNP (GSEA-SNP) data, was performed and identified one gene-set, oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen as enriched (NES = 3.15) with TBRD and contained nine leading edge genes that contributed to the enrichment of the gene set. The enriched gene-set is involved in catalyzing oxidation-reduction reactions, which have been associated with oxidative stressors impacting pregnancy success. No loci were associated nor gene-sets enriched with HCR1. Identification of loci, positional candidate genes, gene-sets and leading edge genes enriched for fertility facilitate genomic selection that allows producers to select for reproductively superior cattle, reduce costs associated with infertility, and increase percent calf crop.

Somatic structural variants are an important contributor to cancer development and evolution. Accurate detection of these complex variants from whole genome sequencing data is influenced by a multitude of parameters. However, there are currently no tools for guiding study design nor are there applications that could predict the performance of somatic structural variant detection. To address this gap, we developed Shiny-SoSV, a user-friendly web-based calculator for determining the impact of common variables on the sensitivity, precision and F1 score of somatic structural variant detection, including choice of variant detection tool, sequencing depth of coverage, variant allele fraction, and variant breakpoint resolution. Using simulation studies, we determined singular and combinatoric effects of these variables, modelled the results using a generalised additive model, allowing structural variant detection performance to be predicted for any combination of predictors. Shiny-SoSV provides an interactive and visual platform for users to easily compare individual and combined impact of different parameters. It predicts the performance of a proposed study design, on somatic structural variant detection, prior to the commencement of benchwork. Shiny-SoSV is freely available at https://hcpcg.shinyapps.io/Shiny-SoSV with accompanying user's guide and example use-cases.

A 58-year-old male with a one-year history of lower medial eyelid swelling and no other ocular and systemic abnormalities was examined. The examination revealed a medial bluish firm left lower eyelid mass. Subsequently, he had an in toto excisional biopsy of a cystic mass, which was confirmed histopathologically to be syringocystadenoma papilliferum. A higher level of suspicion by the ophthalmologist and the histopathologist plays a vital role in the management of this tumour.

Abstract Different cerebral small vessel disease (SVD) lesion types have been shown to disrupt structural brain network individually. Considering that they often coexist, we investigated the relation between their collective effect using the recently proposed total SVD score and structural brain network on MRI in 95 patients with first transient ischemic attack (TIA) or ischemic stroke. Fifty-nine patients with and 36 without any SVD lesions were included. The total SVD score was recorded. Diffusion tensor imaging was performed to estimate structural brain connections for subsequent brain connectivity analysis. The global efficiency and characteristic path length of the structural brain network are respectively lower and higher due to SVD. Lower nodal efficiency is also found in the insular, precuneus, supplementary motor area, paracentral lobule, putamen and hippocampus. The total SVD score is correlated with global network measures, the local clustering coefficient and nodal efficiency of hippocampus, and the nodal efficiency of paracentral lobule. We have successfully demonstrated that the disruption of global and local structural brain networks are associated with the increase in the overall SVD severity or burden of patients with TIA or first-time stroke.

Cervical cancer is one of the most common localized tumours of the female genital sphere. According to WHO, 16 710 new cases of cervical cancer were registered in Russia in 2015. 6,628 patients died of the progression of the malignant process of this localization in 2015. The standardized morbidity rate in 2015 was 15.1 per 100 thousand of population [1, 2].

Aim. Study of SS-68 impact on primary generalized convulsions in basic estimation tests of anticonvulsant action of agents.Material and methods. Study of the SS-68 impact on primary generalized convulsions included an estimation of anticonvulsant action with maximal electric shock, thiosemicarbazide and pilocarpine antagonism tests performed on white outbred male mice and rats.Results. SS-68 compound possesses dosage dependent anticonvulsant action in maximal electric shock test indicating its ability to prevent death of 100% animals and its activity in thiosemicarbazide and pilocarpine antagonism tests as well. In the maximal electric shock test SS-68 surpassed sodium valproate in its anticolvulsant activity.Conclusion. Neurotransmitter systems of the brain such as GABA, cholinergic and amino acid stimulant system as well as K+, Na+ and Ca2+ channels of neurons shall be the most possible molecular targets of SS-68 anticonvulsant action. Higher activity of SS-68 comparing with sodium valproate in the maximal electric shock test (increasing GABA content in central nervous system) can be related with its wide range of neurotropic action.

Abstract Lignin’s aromatic building blocks provide a chemical resource that is, in theory, ideal for substitution of aromatic petrochemicals. Moreover, degradation and valorization of lignin has the potential to generate many high-value chemicals for technical applications. In this study, electrochemical degradation of alkali and Organosolv lignin was performed using the ionic liquids 1-ethyl-3-methylimidazolium trifluoromethanesulfonate and triethylammonium methanesulfonate. The extensive degradation of the investigated lignins with simultaneous almost full recovery of the electrolyte materials provided a sustainable alternative to more common lignin degradation processes. We demonstrate here that both the presence (and the absence) of water during electrolysis and proton transport reactions had significant impact on the degradation efficiency. Hydrogen peroxide radical formation promoted certain electrochemical mechanisms in electrolyte systems “contaminated” with water and increased yields of low molecular weight products significantly. The proposed mechanisms were tentatively confirmed by determining product distributions using a combination of liquid chromatography-mass spectrometry and gas-chromatography-mass spectrometry, allowing measurement of both polar versus non-polar as well as volatile versus non-volatile components in the mixtures.

The article presents advantages of usе the diffusion-weighted magnetic resonance imaging (DW MRI) for revealing of hypoxic-ischemic brain lesions in neonates. The trial included 105 neonates with perinatal brain lesions who had been undergoing treatment at a resuscitation department or neonatel pathology department in the first month of life. The article shows high information value of diffusion-weighted imagings (DWI) for diagnostics of hypoxic-ischemic lesions. In the event of no structural brain lesions of neonates, pronounced increase in signal characteristics revealed by DWI indicated considerable pathophysiological alterations. Subsequently, children developed structural alterations in the form of cystic encephalomalacia with the expansion of cerebrospinal fluid spaces manifested with pronounced neurological deficit.

The influence of compound SS-68, known for its marked antiarrhythmic properties, on the intension of electrophysiological effects of α1- и β- adrenoreceptors stimulation was studied in right atrial preparations from rat. Activation of α1-adrenoreceptors by methoxamine (3×10-5М) led to prominent prolongation of action potentials without significant changes in their rhythm. SS-68 attenuated this effect with IC50 = 5,27×10-6М. The standard α1-blocker prazosine appeared to be more effective (IC50 = 2×10-7М). The activation of β-adrenoreceptors by isoproterenol (3×10-7М) led to drastic acceleration of sinus rhythm. However, only the highest tested concentration of SS-68 (3×10-5М) reduced this effect, while the conventional β-blocker atenolol effectively inhibited it with IC50 = 3,95×10-6М.

Abstract We present the characteristics of track formation on the front and rear surfaces of CR-39 produced by laser-driven protons and carbon ions. A methodological approach, based on bulk etch length, is proposed to uniquely characterize the particle tracks in CR-39, enabling comparative description of the track characteristics in different experiments. The response of CR-39 to ions is studied based on the energy dependent growth rate of the track diameter to understand the intrinsic particle stopping process within the material. A large non-uniformity in the track diameter is observed for CR-39 with thickness matching with the stopping range of particles. Simulation and experimental results show the imprint of longitudinal range straggling for energetic protons. Moreover, by exploiting the energy dependence of the track diameter, the energy resolution (δE/E) of CR-39 for few MeV protons and Carbon ion is found to be about 3%.

In the experiments on isolated circular segments of the thoracic aorta of a rat it has been proved that indole SS-66 derivative in 10-5 and 10-4 М concentrations can relax smooth muscle cells (SMS) due to its impact on the SMS potassium conduction thus facilitating their hyperpolarization. It results in the block of voltage-sensitive calcium channels, the decrease in calcium input and the SMS relaxing. Lack of the NO-synthase Nω-nitro-L-arginine blocker impact on this process indicates of the lack of the SS-68 impact on the processes connected with the endothelium-dependant SMS relaxation.

In experiments on anaesthetized cats in the sinoatrial node (SAN), located in induced high-frequency electric field, focus glow (FG) is visualized, which upon stimulation of the vagus nerve (VN) by periodic electrical impulses undergoes significant changes, characterized by FG weakening and its migration, the emergence of pacemaker cells odd pools (PCP); bradycardia and sinus arrhythmia are also observed. Intravenous indole SS-68 derivative (50 mkg/kg) injection which is included in III antiarrhythmic class and is M2 holinoblocator, causes the increase in the FG intensity, its returning to the original location, PCP combination, bradycardia relief and sinus arrhythmia arrest. Under vagal-cardiac synchronization (VCS), caused by VN volleys of electrical impulses stimulation, FG in SAN is intensified and increases its square. PCP are combining thus causing bradycardia. SS-68 (50 mkg/kg) intravenous injection does not cause visible changes in the SAN functional state. It is suggested that the lack of SS-68 activity under the experimental conditions is masked by the processes that occur in the SAN under VCS, that requires additional specific investigations.