Search results for: biographical disruption

Authors: Kusno Kamil, Andi Asni, Sungkono

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According to a report of the World Food and Agriculture Agency (FAO): the post-harvest fish losses in Indonesia reaches 30 percent from 170 trillion rupiahs of marine fisheries reserves, then the potential loss reaches 51 trillion rupiahs (end of 2016 data). This condition is caused by traditionally vulnerable fish catches damaged due to disruption of the cold chain of preservation. The physical and chemical changes in fish flesh increase rapidly, especially if exposed to the scorching heat in the middle of the sea, exacerbated by the low awareness of catch hygiene; many unclean catches which contain blood are often treated without special attention and mixed with freshly caught fish, thereby increasing the potential for faster fish spoilage. This background encourages research on traditional fisherman catch preservation methods that aim to find the best and most affordable methods and/or combinations of fish preservation methods so that they can help fishermen increase their fishing duration without worrying that their catch will be damaged, thereby reducing their economic value when returning to the beach to sell their catches. This goal is expected to be achieved through experimental methods of treatment of fresh fish catches in containers with the addition of anti-bacterial copper, liquid smoke solution, and the use of vacuum containers. The other three treatments combined the three previous treatment variables with an electrically powered cooler (temperature 0~4 ᵒC). As a control specimen, the untreated fresh fish (placed in the open air and in the refrigerator) were also prepared for comparison for 1, 3, and 6 days. To test the level of freshness of fish for each treatment, physical observations were used, which were complemented by tests for bacterial content in a trusted laboratory. The content of copper (Cu) in fish meat (which is suspected of having a negative impact on consumers) was also part of the examination on the 6th day of experimentation. The results of physical observations on the test specimens (organoleptic method) showed that preservation assisted by the use of coolers was still better for all treatment variables. The specimens, without cooling, sequentially showed that the best preservation effectiveness was the addition of copper plates, the use of vacuum containers, and then liquid smoke immersion. Especially for liquid smoke, soaking for 6 days of preservation makes the fish meat soft and easy to crumble, even though it doesn't have a bad odor. The visual observation was then complemented by the results of testing the amount of growth (or retardation) of putrefactive bacteria in each treatment of test specimens within similar observation periods. Laboratory measurements report that the minimum amount of putrefactive bacteria achieved by preservation treatment combining cooler with liquid smoke (sample A+), then cooler only (D+), copper layer inside cooler (B+), vacuum container inside cooler (C+), respectively. Other treatments in open air produced a hundred times more putrefactive bacteria. In addition, treatment of the copper layer contaminated the preserved fresh fish more than a thousand times bigger compared to the initial amount, from 0.69 to 1241.68 µg/g.

Keywords: fish, preservation, traditional, fishermen, boat

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Authors: D. Norton

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This qualitative study focuses on the lived experience and displacement of young white-collar masculinities in Japan. In recent years, the salaryman lifestyle has undergone significant disruption - increased competition for regular employment, rise in non-regular structurings of labour across public/private sectors, and shifting role expectations within the home. Despite this, related scholarship hints at a continued reinforcement of the traditional male gender role - that the salaryman remains a key benchmark of Japanese masculine identity. For those in structural proximity to these more ‘normative’ performativities, interest lies their engagement with such narratives - how they make sense of their masculinity in response to stated changes. In light of the historical emphasis on labour and breadwinning logics, notions of respective security or precarity generated as a result remain unclear. Similarly, concern extends to developments within the private sphere - by what means young white-collar men construct ideas of singlehood and companionship according to traditional gender ideologies or more contemporary, flexible readings. The influence of these still-emergent status distinctions on the logics of the social group in question is yet to be explored in depth by gender scholars. This project, therefore, focuses on a salaryman archetype as hegemonic - its transformation amidst these changes and socialising mechanisms that continue to legitimate unequal gender hierarchies. For data collection, a series of ethnographic interviews were held over a period of 12 months with university-educated, white-collar male employees from both Osaka and the Greater Tokyo Area. Findings suggest a modern salaryman ideal reflecting both continuities and shifts within white-collar employment. Whilst receptive to more contemporary workplace practices, the narratives of those interviewed remain imbued with logics supporting patterns of internal hegemony. Regular/non-regular distinction emerged as the foremost variable for both material and discursive patterns of white-collar stratification, with variants of displacement for each social group. Despite the heightened valorisation of stable employment, regular workers articulated various concerns over a model of corporate masculinity seen to be incompatible with recent socioeconomic developments. Likewise, non-regular employees face detachment owing to a still-inflexible perception of their working masculinity as marginalized amidst economic precarity. In seeking to negotiate respective challenges, those interviewed demonstrated an engagement with various concurrent social changes that would often either accommodate, reinforce, or expand upon traditional role behaviours. Few of these narratives offered any notable transgression of said ideal, however, suggesting that within the spectre of white-collar employment in Japan for the near future, any substantive transformation of corporate masculinity remains dependant upon economic developments, less so the agency of those involved.

Keywords: gender ideologies, hegemonic masculinity, Japan, white-collar employment

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Authors: Ricardo Godoy, Herbert Venthur, Hector Jimenez, Andres Quiroz, Ana Mutis

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In agriculture, grape production has great economic importance at global level, considering that in 2013 it reached 7.4 million hectares (ha) covered by plantations of this fruit worldwide. Chile is the number one exporter in the world with 800,000 tons. However, these values have been threatened by the attack of the grapevine moth, Lobesia botrana (Denis & Schiffermuller) (Lepidoptera: Tortricidae), since its detection in 2008. Nowadays, the use of semiochemicals, in particular the major component of the sex pheromone, (E,Z)-7.9-dodecadienil acetate, are part of mating disruption methods to control L. botrana. How insect pests can recognize these molecules, is being part of huge efforts to deorphanize their olfactory mechanism at molecular level. Thus, an interesting group of proteins has been identified in the antennae of insects, where odorant-binding proteins (OBPs) are known by transporting molecules to odorant receptors (ORs) and a co-receptor (ORCO) causing a behavioral change in the insect. Other proteins such as chemosensory proteins (CSPs), ionotropic receptors (IRs), odorant degrading enzymes (ODEs) and sensory neuron membrane proteins (SNMPs) seem to be involved, but few studies have been performed so far. The above has led to an increasing interest in insect communication at a molecular level, which has contributed to both a better understanding of the olfaction process and the design of new pest management strategies. To date, it has been reported that the ORs can detect one or a small group of odorants in a specific way. Therefore, the objective of this study is the identification of genes that encode these ORs using the antennal transcriptome of L. botrana. Total RNA was extracted for females and males of L. botrana, and the antennal transcriptome sequenced by Next Generation Sequencing service using an Illumina HiSeq2500 platform with 50 million reads per sample. Unigenes were assembled using Trinity v2.4.0 package and transcript abundance was obtained using edgeR. Genes were identified using BLASTN and BLASTX locally installed in a Unix system and based on our own Tortricidae database. Those Unigenes related to ORs were characterized using ORFfinder and protein Blastp server. Finally, a phylogenetic analysis was performed with the candidate amino acid sequences for LbotORs including amino acid sequences of other moths ORs, such as Bombyx mori, Cydia pomonella, among others. Our findings suggest 61 genes encoding ORs and one gene encoding an ORCO in both sexes, where the greatest difference was found in the OR6 because of the transcript abundance according to the value of FPKM in females and males was 1.48 versus 324.00. In addition, according to phylogenetic analysis OR6 is closely related to OR1 in Cydia pomonella and OR6, OR7 in Epiphyas postvittana, which have been described as pheromonal receptors (PRs). These results represent the first evidence of ORs present in the antennae of L. botrana and a suitable starting point for further functional studies with selected ORs, such as OR6, which is potentially related to pheromonal recognition.

Keywords: antennal transcriptome, lobesia botrana, odorant receptors (ORs), phylogenetic analysis

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Authors: Serena Salvi

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Ageistic stereotypes and practices have become a normal and therefore pervasive phenomenon in various aspects of everyday life. Over the past years, renewed awareness towards self-directed age stereotyping in older adults has given rise to a line of research focused on the potential role of attitudes towards ageing on seniors’ health and functioning. This set of studies has showed how a negative internalisation of ageistic stereotypes would discourage older adults in seeking medical advice, in addition to be associated to negative subjective health evaluation. An important dimension of mental health that is often affected in older adults is represented by sleep quality. Self-reported sleep quality among older adults has shown to be often unreliable when compared to their objective sleep measures. Investigations focused on self-reported sleep quality among older adults have suggested how this portion of the population would tend to accept disrupted sleep if believed to be up to standard for their age. On the other hand, unrealistic expectations, and dysfunctional beliefs towards sleep in ageing, might prompt older adults to report sleep disruption even in the absence of objective disrupted sleep. Objective of this study is to examine an association between personal attitudes towards ageing in adults aged 60+ and dysfunctional sleep related cognition. More in detail, this study aims to investigate a potential association between personal attitudes towards ageing, sleep locus of control and dysfunctional beliefs towards sleep among this portion of the population. Data in this study were statistically analysed in SPSS software. Participants were recruited through the online participants recruitment system Prolific. Inclusion of attention check questions throughout the questionnaire and consistency of responses were looked at. Prior to the commencement of this study, Ethical Approval was granted (ref. 39396). Descriptive statistics were used to determine the frequency, mean, and SDs of the variables. Pearson coefficient was used for interval variables, independent T-test for comparing means between two independent groups, analysis of variance (ANOVA) test for comparing the means in several independent groups, and hierarchical linear regression models for predicting criterion variables based on predictor variables. In this study self-perceptions of ageing were assessed using APQ-B’s subscales, while dysfunctional sleep related cognition was operationalised using the SLOC and the DBAS16 scales. Of the final subscales taken in consideration in the brief version of the APQ questionnaire, Emotional Representations (ER), Control Positive (PC) and Control and Consequences Negative (NC) have shown to be of particularly relevance for the remits of this study. Regression analysis show how an increase in the APQ-B subscale Emotional Representations (ER) predicts an increase in dysfunctional beliefs and attitudes towards sleep in this sample, after controlling for subjective sleep quality, level of depression and chronological age. A second regression analysis showed that APQ-B subscales Control Positive (PC) and Control and Consequences Negative (NC) were significant predictors in the change of variance of SLOC, after controlling for subjective sleep quality, level of depression and dysfunctional beliefs about sleep.

Keywords: sleep-related cognition, perceptions of aging, older adults, sleep quality

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Authors: D. Mokatsanyane, J. Jansen Van Rensburg

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This paper analyses the influence and impact of COVID-19 on major agricultural commodity prices in South Africa. According to a World Bank report, the agricultural sector in South Africa has been unable to reduce the domestic food crisis that has been occurring over the past years, hence the increased rate of poverty, which is currently at 55.5 percent as of April 2020. Despite the significance of this sector, empirical findings concluded that the agricultural sector now accounts for 1.88 percent of South Africa's gross domestic product (GDP). Suggesting that the agricultural sector's contribution to the economy has diminished. Despite the low contribution to GDP, this primary sector continues to play an essential role in the economy. Over the past years, multiple factors have contributed to the soaring commodities prices, namely, climate shocks, biofuel demand, demand and supply shocks, the exchange rate, speculation in commodity derivative markets, trade restrictions, and economic growth. The COVID-19 outbursts have currently disturbed the supply and demand of staple crops. To address the disruption, the government has exempted the agricultural sector from closure and restrictions on movement. The spread of COVID-19 has caused turmoil all around the world, but mostly in developing countries. According to Statistic South Africa, South Africa's economy decreased by seven percent in 2020. Consequently, this has arguably made the agricultural sector the most affected sector since slumped economic growth negatively impacts food security, trade, farm livelihood, and greenhouse gas emissions. South Africa is sensitive to the fruitfulness of global food chains. Restrictions in trade, reinforced sanitary control systems, and border controls have influenced food availability and prices internationally. The main objective of this study is to evaluate the behavior of agricultural commodity prices pre-and during-COVID to determine the impact of volatility drivers on these crops. Historical secondary data of spot prices for the top five major commodities, namely white maize, yellow maize, wheat, soybeans, and sunflower seeds, are analysed from 01 January 2017 to 1 September 2021. The timeframe was chosen to capture price fluctuations between pre-COVID-19 (01 January 2017 to 23 March 2020) and during-COVID-19 (24 March 2020 to 01 September 2021). The Generalised Autoregressive Conditional Heteroscedasticity (GARCH) statistical model will be used to measure the influence of price fluctuations. The results reveal that the commodity market has been experiencing volatility at different points. Extremely high volatility is represented during the first quarter of 2020. During this period, there was high uncertainty, and grain prices were very volatile. Despite the influence of COVID-19 on agricultural prices, the demand for these commodities is still existing and decent. During COVID-19, analysis indicates that prices were low and less volatile during the pandemic. The prices and returns of these commodities were low during COVID-19 because of the government's actions to respond to the virus's spread, which collapsed the market demand for food commodities.

Keywords: commodities market, commodity prices, generalised autoregressive conditional heteroscedasticity (GARCH), Price volatility, SAFEX

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Authors: Caridad Maylin-Aguilar, Beatriz Duarte-Monedero

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Problem-based learning (PBL) is a useful tool for adult and practice oriented audiences, as University students. As a consequence of the huge disruption caused by the COVID pandemic in the hospitality industry, hotels of all categories closed down in Spain from March 2020. Since that moment, the luxury segment was blooming with optimistic prospects for new openings. Hence, Hospitality students were expecting a positive situation in terms of employment and career development. By the beginning of the 2020-21 academic year, these expectations were seriously harmed. By October 2020, only 9 of the 32 hotels in the luxury segment were opened with an occupation rate of 9%. Shortly after, the evidence of a second wave affecting especially Spain and the homelands of incoming visitors bitterly smashed all forecasts. In accordance with the situation, a team of four professors and practitioners, from four different subject areas, developed a real case, inspired in one of these hotels, the 5-stars Emperatriz by Barceló. Students in their 2nd course were provided with real information as marketing plans, profit and losses and operational accounts, employees profiles and employment costs. The challenge for them was to act as consultants, identifying potential courses of action, related to best, base and worst case. In order to do that, they were organized in teams and supported by 4th course students. Each professor deployed the problem in their subject; thus, research on the customers behavior and feelings were necessary to review, as part of the marketing plan, if the current offering of the hotel was clear enough to guarantee and to communicate a safe environment, as well as the ranking of other basic, supporting and facilitating services. Also, continuous monitoring of competitors’ activity was necessary to understand what was the behavior of the open outlets. The actions designed after the diagnose were ranked in accordance with their impact and feasibility in terms of time and resources. Also they must be actionable by the current staff of the hotel and their managers and a vision of internal marketing was appreciated. After a process of refinement, seven teams presented their conclusions to Emperatriz general manager and the rest of professors. Four main ideas were chosen, and all the teams, irrespectively of authorship, were asked to develop them to the state of a minimum viable product, with estimations of impacts and costs. As the process continues, students are nowadays accompanying the hotel and their staff in the prudent reopening of facilities, almost one year after the closure. From a professor’s point of view, key learnings were 1.- When facing a real problem, a holistic view is needed. Therefore, the vision of subjects as silos collapses, 2- When educating new professionals, providing them with the resilience and resistance necessaries to deal with a problem is always mandatory, but now seems more relevant and 3.- collaborative work and contact with real practitioners in such an uncertain and changing environment is a challenge, but it is worth when considering the learning result and its potential.

Keywords: problem-based learning, hospitality recovery, collaborative learning, resilience

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Authors: T. Ul Rehman, S. Agnello, F. M. Gelardi, M. M. Calvino, G. Lazzara, G. Buscarino, M. Cannas

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Metal-Organic Frameworks (MOFs) have emerged as promising candidates for detecting metal ions owing to their large surface area, customizable porosity, and diverse functionalities. In recent years, there has been a surge in research focused on MOFs with luminescent properties. These frameworks are constructed through coordinated bonding between metal ions and multi-dentate ligands, resulting in inherent fluorescent structures. Their luminescent behavior is influenced by factors like structural composition, surface morphology, pore volume, and interactions with target analytes, particularly metal ions. MOFs exhibit various sensing mechanisms, including photo-induced electron transfer (PET) and charge transfer processes such as ligand-to-metal (LMCT) and metal-to-ligand (MLCT) transitions. Among these, MIL-53(Al) stands out due to its flexibility, stability, and specific affinity towards certain metal ions, making it a promising platform for selective metal ion sensing. This study investigates the structural, thermal, and luminescent properties of MIL-53(Al) metal-organic framework (MOF) upon Fe3+ cation exchange. Two separate sets of samples were prepared to activate the MOF powder at different temperatures. The first set of samples, referred to as MIL-53(Al), activated (120°C), was prepared by activating the raw powder in a glass tube at 120°C for 12 hours and then sealing it. The second set of samples, referred to as MIL-53(Al), activated (300°C), was prepared by activating the MIL-53(Al) powder in a glass tube at 300°C for 70 hours. Additionally, 25 mg of MIL-53(Al) powder was dispersed in 5 mL of Fe3+ solution at various concentrations (0.1-100 mM) for the cation exchange experiment. The suspension was centrifuged for five minutes at 10,000 rpm to extract MIL-53(Al) powder. After three rounds of washing with ultrapure water, MIL-53(Al) powder was heated at 120°C for 12 hours. For PXRD and TGA analyses, a sample of the obtained MIL-53(Al) was used. We also activated the cation-exchanged samples for time-resolved photoluminescence (TRPL) measurements at two distinct temperatures (120 and 300°C) for comparative analysis. Powder X-ray diffraction patterns reveal amorphization in samples with higher Fe3+ concentrations, attributed to alterations in coordination environments and ion exchange dynamics. Thermal decomposition analysis shows reduced weight loss in Fe3+-exchanged MOFs, indicating enhanced stability due to stronger metal-ligand bonds and altered decomposition pathways. Raman spectroscopy demonstrates intensity decrease, shape disruption, and frequency shifts, indicative of structural perturbations induced by cation exchange. Photoluminescence spectra exhibit ligand-based emission (π-π* or n-π*) and ligand-to-metal charge transfer (LMCT), influenced by activation temperature and Fe3+ incorporation. Quenching of luminescence intensity and shorter lifetimes upon Fe3+ exchange result from structural distortions and Fe3+ binding to organic linkers. In a nutshell, this research underscores the complex interplay between composition, structure, and properties in MOFs, offering insights into their potential for diverse applications in catalysis, gas storage, and luminescent devices.

Keywords: Fe³⁺ cation exchange, luminescent metal-organic frameworks (LMOFs), MIL-53(Al), solid-state analysis

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Authors: Helen S. Joyner (Melito), Mohammad Anvari

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Concentrated emulsions stabilized by proteins are systems of great importance in food, pharmaceutical and cosmetic products. Controlling emulsion rheology is critical for ensuring desired properties during formation, storage, and consumption of emulsion-based products. Studies on concentrated emulsions have focused on rheology of monodispersed systems. However, emulsions used for industrial applications are polydispersed in nature, and this polydispersity is regarded as an important parameter that also governs the rheology of the concentrated emulsions. Therefore, the objective of this study was to characterize rheological (small and large deformation behaviors) and microstructural properties of concentrated emulsions which were not truly monodispersed as usually encountered in food products such as margarines, mayonnaise, creams, spreads, and etc. The concentrated emulsions were prepared at different concentrations of fish gelatin (0.2, 0.4, 0.8% w/v in the whole emulsion system), oil-water ratio 80-20 (w/w), homogenization speed 10000 rpm, and 25oC. Confocal laser scanning microscopy (CLSM) was used to determine the microstructure of the emulsions. To prepare samples for CLSM analysis, FG solutions were stained by Fluorescein isothiocyanate dye. Emulsion viscosity profiles were determined using shear rate sweeps (0.01 to 100 1/s). The linear viscoelastic regions (LVRs) of the emulsions were determined using strain sweeps (0.01 to 100% strain) for each sample. Frequency sweeps were performed in the LVR (0.1% strain) from 0.6 to 100 rad/s. Large amplitude oscillatory shear (LAOS) testing was conducted by collecting raw waveform data at 0.05, 1, 10, and 100% strain at 4 different frequencies (0.5, 1, 10, and 100 rad/s). All measurements were performed in triplicate at 25oC. The CLSM results revealed that increased fish gelatin concentration resulted in more stable oil-in-water emulsions with homogeneous, finely dispersed oil droplets. Furthermore, the protein concentration had a significant effect on emulsion rheological properties. Apparent viscosity and dynamic moduli at small deformations increased with increasing fish gelatin concentration. These results were related to increased inter-droplet network connections caused by increased fish gelatin adsorption at the surface of oil droplets. Nevertheless, all samples showed shear-thinning and weak gel behaviors over shear rate and frequency sweeps, respectively. Lissajous plots, or plots of stress versus strain, and phase lag values were used to determine nonlinear behavior of the emulsions in LAOS testing. Greater distortion in the elliptical shape of the plots followed by higher phase lag values was observed at large strains and frequencies in all samples, indicating increased nonlinear behavior. Shifts from elastic-dominated to viscous dominated behavior were also observed. These shifts were attributed to damage to the sample microstructure (e.g. gel network disruption), which would lead to viscous-type behaviors such as permanent deformation and flow. Unlike the small deformation results, the LAOS behavior of the concentrated emulsions was not dependent on fish gelatin concentration. Systems with different microstructures showed similar nonlinear viscoelastic behaviors. The results of this study provided valuable information that can be used to incorporate concentrated emulsions in emulsion-based food formulations.

Keywords: concentrated emulsion, fish gelatin, microstructure, rheology

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Authors: Ekaterina Zvorykina

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Nowadays, Arctic and Antarctic regions are distinguished to be one of the most important strategic resources for global development. Nonetheless, living conditions in Arctic regions still demand certain improvements. As soon as the region is rarely populated, one of the main points of interest is health accommodation of the people, who migrate to Arctic region for permanent and shift work. At Arctic and Antarctic latitudes, personnel face polar day and polar night conditions during the time of the year. It means that they are deprived of natural sunlight in winter season and have continuous daylight in summer. Firstly, the change in light intensity during 24-hours period due to migration affects circadian rhythms. Moreover, the controlled artificial light in winter is also an issue. The results of the recent studies on night shift medical professionals, who were exposed to permanent artificial light, have already demonstrated higher risks in cancer, depression, Alzheimer disease. Moreover, people exposed to frequent time zones change are also subjected to higher risks of heart attack and cancer. Thus, our main goals are to understand how high latitude work and living conditions can affect human health and how it can be prevented. In our study, we analyze molecular and cellular factors, which play important role in circadian rhythm change and distinguish main risk groups in people, migrating to high latitudes. The main well-studied index of circadian timing is melatonin or its metabolite 6-sulfatoxymelatonin. In low light intensity melatonin synthesis is disturbed and as a result human organism requires more time for sleep, which is still disregarded when it comes to working time organization. Lack of melatonin also causes shortage in serotonin production, which leads to higher depression risk. Melatonin is also known to inhibit oncogenes and increase apoptosis level in cells, the main factors for tumor growth, as well as circadian clock genes (for example Per2). Thus, people who work in high latitudes can be distinguished as a risk group for cancer diseases and demand more attention. Clock/Clock genes, known to be one of the main circadian clock regulators, decrease sensitivity of hypothalamus to estrogen and decrease glucose sensibility, which leads to premature aging and oestrous cycle disruption. Permanent light exposure also leads to accumulation superoxide dismutase and oxidative stress, which is one of the main factors for early dementia and Alzheimer disease. We propose a new screening system adjusted for people, migrating from middle to high latitudes and accommodation therapy. Screening is focused on melatonin and estrogen levels, sleep deprivation and neural disorders, depression level, cancer risks and heart and vascular disorders. Accommodation therapy includes different types artificial light exposure, additional melatonin and neuroprotectors. Preventive procedures can lead to increase of migration intensity to high latitudes and, as a result, the prosperity of Arctic region.

Keywords: circadian rhythm, high latitudes, melatonin, neuroprotectors

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Authors: M. Trousselard, D. Steiler, C. Drogou, P. van-Beers, G. Lamour, S. N. Crosnier, O. Bouilland, P. Dubost, M. Chennaoui, D. Léger

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According to published data, undersea navigation for long periods (nuclear-powered ballistic missile submarine, SSBN) constitutes an extreme environment in which crews are subjected to multiple stresses, including the absence of natural light, illuminance below 1,000 lux, and watch schedules that do not respect natural chronobiological rhythms, for a period of 60-80 days. These stresses seem clearly detrimental to the submariners’ sleep, with consequences for their affective (seasonal affective disorder-like) and cognitive functioning. In the long term, there are abundant publications regarding the consequences of sleep disruption for the occurrence of organic cardiovascular, metabolic, immunological or malignant diseases. It seems essential to propose countermeasures for the duration of the patrol in order to reduce the negative physiological effects on the sleep and mood of submariners. Light therapy, the preferred treatment for dysfunctions of the internal biological clock and the resulting seasonal depression, cannot be used without data to assist knowledge of submariners’ chronobiology (melatonin secretion curve) during patrols, given the unusual characteristics of their working environment. These data are not available in the literature. The aim of this project was to assess, in the course of two studies, the benefits of two environmental techniques for managing chronobiological stress: techniques for optimizing potential (TOP; study 1)3, an existing programme to help in the psychophysiological regulation of stress and sleep in the armed forces, and dawn and dusk simulators (DDS, study 2). For each experiment, psychological, physiological (sleep) or biological (melatonin secretion) data were collected on D20 and D50 of patrol. In the first experiment, we studied sleep and depressive distress in 19 submariners in an operational setting on board an SSBM during a first patrol, and assessed the impact of TOP on the quality of sleep and depressive distress in these same submariners over the course of a second patrol. The submariners were trained in TOP between the two patrols for a 2-month period, at a rate of 1 h of training per week, and assigned daily informal exercises. Results show moderate disruptions in sleep pattern and duration associated with the intensity of depressive distress. The use of TOP during the following patrol improved sleep and depressive mood only in submariners who regularly practiced the techniques. In light of these limited benefits, we assessed, in a second experiment, the benefits of DDS on chronobiology (daily secretion of melatonin) and depressive distress. Ninety submariners were randomly allocated to two groups, group 1 using DDS daily, and group 2 constituting the control group. Although the placebo effect was not controlled, results showed a beneficial effect on chronobiology and depressive mood for submariners with a morning chronotype. Conclusions: These findings demonstrate the difficulty of practicing the tools of psychophysiological management in real life. They raise the question of the subjects’ autonomy with respect to using aids that involve regular practice. It seems important to study autonomy in future studies, as a cognitive resource resulting from the interaction between internal positive resources and “coping” resources, to gain a better understanding of compliance problems.

Keywords: chronobiology, light therapy, seasonal affective disorder, sleep, stress, stress management, submarine

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Authors: Tamar Lin, Nufar Buchshtab, Yifat Elharar, Julian Nicenboim, Rotem Edgar, Iddo Weiner, Lior Zelcbuch, Ariel Cohen, Sharon Kredo-Russo, Inbar Gahali-Sass, Naomi Zak, Sailaja Puttagunta, Merav Bassan

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Background: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder that is characterized by dry skin and flares of eczematous lesions and intense pruritus. Multiple lines of evidence suggest that AD is associated with increased colonization by Staphylococcus aureus, which contributes to disease pathogenesis through the release of virulence factors that affect both keratinocytes and immune cells, leading to disruption of the skin barrier and immune cell dysfunction. The aim of the current study is to develop a bacteriophage-based product that specifically targets S. aureus. Methods: For the discovery of phage, environmental samples were screened on 118 S. aureus strains isolated from skin samples, followed by multiple enrichment steps. Natural phages were isolated, subjected to Next-generation Sequencing (NGS), and analyzed using proprietary bioinformatics tools for undesirable genes (toxins, antibiotic resistance genes, lysogeny potential), taxonomic classification, and purity. Phage host range was determined by an efficiency of plating (EOP) value above 0.1 and the ability of the cocktail to completely lyse liquid bacterial culture under different growth conditions (e.g., temperature, bacterial stage). Results: Sequencing analysis demonstrated that the 118 S. aureus clinical strains were distributed across the phylogenetic tree of all available Refseq S. aureus (~10,750 strains). Screening environmental samples on the S. aureus isolates resulted in the isolation of 50 lytic phages from different genera, including Silviavirus, Kayvirus, Podoviridae, and a novel unidentified phage. NGS sequencing confirmed the absence of toxic elements in the phages’ genomes. The host range of the individual phages, as measured by the efficiency of plating (EOP), ranged between 41% (48/118) to 79% (93/118). Host range studies in liquid culture revealed that a subset of the phages can infect a broad range of S. aureus strains in different metabolic states, including stationary state. Combining the single-phage EOP results of selected phages resulted in a broad host range cocktail which infected 92% (109/118) of the strains. When tested in vitro in a liquid infection assay, clearance was achieved in 87% (103/118) of the strains, with no evidence of phage resistance throughout the study (24 hours). A S. aureus host was identified that can be used for the production of all the phages in the cocktail at high titers suitable for large-scale manufacturing. This host was validated for the absence of contaminating prophages using advanced NGS methods combined with multiple production cycles. The phages are produced under optimized scale-up conditions and are being used for the development of a topical formulation (BX005) that may be administered to subjects with atopic dermatitis. Conclusions: A cocktail of natural phages targeting S. aureus was effective in reducing bacterial burden across multiple assays. Phage products may offer safe and effective steroid-sparing options for atopic dermatitis.

Keywords: atopic dermatitis, bacteriophage cocktail, host range, Staphylococcus aureus

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Authors: Rocio Murad, Marcela Sanchez, Mariana Calderon Jaramillo, Danny Rivera, Angela Cifuentes, Daniela Roldán, Juan Carlos Rivillas

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Women and girls have specific health needs, but during health pandemics such as COVID19 they are less likely to have access to quality essential health information, commodities and services, or insurance coverage for routine and catastrophic health expenses, especially in rural and marginalized communities. This is compounded by multiple or intersecting inequalities, such as ethnicity, socioeconomic status, disability, age, geographic location, and sexual orientation, among others. Despite concerted collective action, there is a lack of information on the situation of women, adolescents and youth, including gender inequalities exacerbated by the pandemic. Much more needs to be done to amplify the lived realities of women and adolescents in global and national advocacy and policy responses. The COVID 19 pandemic reflects the need for systematic advocacy policies based on the lived experiences of women and adolescents, underpinned by human rights. This research is part of the initiative of Profamilia Association (Solidarity Study), and its objective is twofold: i) to analyze the behavioral changes and immediate expectations of Colombians during the stage of relaxation of the confinement measures decreed by the national government; and ii) to identify the needs, experiences and resilient practices of adolescents and young women during the COVID-19 crisis in Colombia. Descriptive analysis of data collected by Profamilia through the Solidaridad study, an exploratory cross-sectional descriptive study that used subnational level data from a nonprobabilistic sample survey conducted to 1735 adults, between September 01 and 11, 2020. Interviews were conducted with key stakeholders about their experiences during COVID19, under three key axes: i) main challenges for adolescents and young women; ii) examples of what has worked well in responding to the challenge; and iii) how/what services are/should be provided during COVID-19 (and beyond) to address the challenge. Interviewees were selected based on prior mapping of social groups of interest. In total, 23 adolescents and young women participated in the interviews. The results show that people adopted behavioral changes such as wearing masks, avoiding people with symptoms, and reducing mobility, but there was also a doubling of concerns for many reasons, from effects on mental health, sexual health, and unattended reproductive health to the burden of care and working at home. The favorable perception that people had at the beginning of the quarantine about the response and actions of the national and local government to control Covid-19 decreased over the course of the quarantine. The challenges and needs of adolescents and young women were highlighted during the most restrictive measures to contain the COVID-19 pandemic, which resulted in disruptions to daily activities, education and work, as well as restrictions to mobility and social interaction. Concerns raised by participants included: impact on mental health and wellbeing due to disruption of daily life; limitations in access to formal and informal education; food insecurity; migration; loss of livelihoods; lack of access to health information and services; limitations to sexual and reproductive health and rights; insecurity problems; and problems in communication and treatment among household members.

Keywords: COVID-19, changes in behavior, adolescents, women

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Authors: Aussara Panya, Nunghathai Sawasdee, Mutita Junking, Chatchawan Srisawat, Kiattawee Choowongkomon, Pa-Thai Yenchitsomanus

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Dengue virus (DENV) infection is a global public health problem with approximately 100 million infected cases a year. Presently, there is no approved vaccine or effective drug available; therefore, the development of anti-DENV drug is urgently needed. The clinical reports revealing the positive association between the disease severity and viral titer has been reported previously suggesting that the anti-DENV drug therapy can possibly ameliorate the disease severity. Although several anti-DENV agents showed inhibitory activities against DENV infection, to date none of them accomplishes clinical use in the patients. The surface envelope (E) protein of DENV is critical for the viral entry step, which includes attachment and membrane fusion; thus, the blocking of envelope protein is an attractive strategy for anti-DENV drug development. To search the safe anti-DENV agent, this study aimed to search for novel peptide inhibitors to counter DENV infection through the targeting of E protein using a structure-based in silico design. Two selected strategies has been used including to identify the peptide inhibitor which interfere the membrane fusion process whereby the hydrophobic pocket on the E protein was the target, the destabilization of virion structure organization through the disruption of the interaction between the envelope and membrane proteins, respectively. The molecular docking technique has been used in the first strategy to search for the peptide inhibitors that specifically bind to the hydrophobic pocket. The second strategy, the peptide inhibitor has been designed to mimic the ectodomain portion of membrane protein to disrupt the protein-protein interaction. The designed peptides were tested for the effects on cell viability to measure the toxic to peptide to the cells and their inhibitory assay to inhibit the DENV infection in Vero cells. Furthermore, their antiviral effects on viral replication, intracellular protein level and viral production have been observed by using the qPCR, cell-based flavivirus immunodetection and immunofluorescence assay. None of tested peptides showed the significant effect on cell viability. The small peptide inhibitors achieved from molecular docking, Glu-Phe (EF), effectively inhibited DENV infection in cell culture system. Its most potential effect was observed for DENV2 with a half maximal inhibition concentration (IC50) of 96 μM, but it partially inhibited other serotypes. Treatment of EF at 200 µM on infected cells also significantly reduced the viral genome and protein to 83.47% and 84.15%, respectively, corresponding to the reduction of infected cell numbers. An additional approach was carried out by using peptide mimicking membrane (M) protein, namely MLH40. Treatment of MLH40 caused the reduction of foci formation in four individual DENV serotype (DENV1-4) with IC50 of 24-31 μM. Further characterization suggested that the MLH40 specifically blocked viral attachment to host membrane, and treatment with 100 μM could diminish 80% of viral attachment. In summary, targeting the hydrophobic pocket and M-binding site on the E protein by using the peptide inhibitors could inhibit DENV infection. The results provide proof of-concept for the development of antiviral therapeutic peptide inhibitors to counter DENV infection through the use of a structure-based design targeting conserved viral protein.

Keywords: dengue virus, dengue virus infection, drug design, peptide inhibitor

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Authors: Rob Schindler

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Industry-standard methods of mitigating erosion of seabed sediments rely on ‘hard engineering’ approaches which have numerous environmental shortcomings: (1) direct loss of habitat by smothering of benthic species, (2) disruption of sediment transport processes, damaging geomorphic and ecosystem functionality (3) generation of secondary erosion problems, (4) introduction of material that may propagate non-local species, and (5) provision of pathways for the spread of invasive species. Recent studies have also revealed the importance of biological cohesion, the result of naturally occurring extra-cellular polymeric substances (EPS), in stabilizing natural sediments. Mimicking the strong bonding kinetics through the deliberate addition of EPS to sediments – henceforth termed ‘biostabilisation’ - offers a means in which to mitigate against erosion induced by structures or episodic increases in hydrodynamic forcing (e.g. storms and floods) whilst avoiding, or reducing, hard engineering. Here we present unique experiments that systematically examine how biostabilisation reduces scour around a monopile in a current, a first step to realizing the potential of this new method of scouring reduction for a wide range of engineering purposes in aquatic substrates. Experiments were performed in Plymouth University’s recirculating sediment flume which includes a recessed scour pit. The model monopile was 0.048 m in diameter, D. Assuming a prototype monopile diameter of 2.0 m yields a geometric ratio of 41.67. When applied to a 10 m prototype water depth this yields a model depth, d, of 0.24 m. The sediment pit containing the monopile was filled with different biostabilised substrata prepared using a mixture of fine sand (D50 = 230 μm) and EPS (Xanthan gum). Nine sand-EPS mixtures were examined spanning EPS contents of 0.0% < b0 < 0.50%. Scour development was measured using a laser point gauge along a 530 mm centreline at 10 mm increments at regular periods over 5 h. Maximum scour depth and excavated area were determined at different time steps and plotted against time to yield equilibrium values. After 5 hours the current was stopped and a detailed scan of the final scour morphology was taken. Results show that increasing EPS content causes a progressive reduction in the equilibrium depth and lateral extent of scour, and hence excavated material. Very small amounts equating to natural communities (< 0.1% by mass) reduce scour rate, depth and extent of scour around monopiles. Furthermore, the strong linear relationships between EPS content, equilibrium scour depth, excavation area and timescales of scouring offer a simple index on which to modify existing scour prediction methods. We conclude that the biostabilisation of sediments with EPS may offer a simple, cost-effective and ecologically sensitive means of reducing scour in a range of contexts including OWFs, bridge piers, pipeline installation, and void filling in rock armour. Biostabilisation may also reduce economic costs through (1) Use of existing site sediments, or waste dredged sediments (2) Reduced fabrication of materials, (3) Lower transport costs, (4) Less dependence on specialist vessels and precise sub-sea assembly. Further, its potential environmental credentials may allow sensitive use of the seabed in marine protection zones across the globe.

Keywords: biostabilisation, EPS, marine, scour

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Authors: Ekta Yadav, Sukanta Bhattacharya, Brijesh Yadav, Ariel Hus, Jagjit Yadav

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Background and Significance: Respiratory exposure to toxicants (chemicals or particulates) causes disruption of lung homeostasis leading to lung toxicity/injury manifested as pulmonary inflammation, edema, and/or other effects depending on the type and extent of exposure. This emphasizes the need for investigating toxicant type-specific mechanisms to understand therapeutic targets. Aquaporins, aka water channels, are known to play a role in lung homeostasis. Particularly, the two major lung aquaporins AQP5 and AQP1 expressed in alveolar epithelial and vasculature endothelia respectively allow for movement of the fluid between the alveolar air space and the associated vasculature. In view of this, the current study is focused on understanding the regulation of lung aquaporins and other targets during inhalation exposure to toxic chemicals (Cigarette smoke chemicals) versus toxic particles (Carbon nanoparticles) or co-exposures to understand their relevance as markers of injury and intervention. Methodologies: C57BL/6 mice (5-7 weeks old) were used in this study following an approved protocol by the University of Cincinnati Institutional Animal Care and Use Committee (IACUC). The mice were exposed via oropharyngeal aspiration to multiwall carbon nanotube (MWCNT) particles suspension once (33 ugs/mouse) followed by housing for four weeks or to Cigarette smoke Extract (CSE) using a daily dose of 30µl/mouse for four weeks, or to co-exposure using the combined regime. Control groups received vehicles following the same dosing schedule. Lung toxicity/injury was assessed in terms of homeostasis changes in the lung tissue and lumen. Exposed lungs were analyzed for transcriptional expression of specific targets (AQPs, surfactant protein A, Mucin 5b) in relation to tissue homeostasis. Total RNA from lungs extracted using TRIreagent kit was analyzed using qRT-PCR based on gene-specific primers. Total protein in bronchoalveolar lavage (BAL) fluid was determined by the DC protein estimation kit (BioRad). GraphPad Prism 5.0 (La Jolla, CA, USA) was used for all analyses. Major findings: CNT exposure alone or as co-exposure with CSE increased the total protein content in the BAL fluid (lung lumen rinse), implying compromised membrane integrity and cellular infiltration in the lung alveoli. In contrast, CSE showed no significant effect. AQP1, required for water transport across membranes of endothelial cells in lungs, was significantly upregulated in CNT exposure but downregulated in CSE exposure and showed an intermediate level of expression for the co-exposure group. Both CNT and CSE exposures had significant downregulating effects on Muc5b, and SP-A expression and the co-exposure showed either no significant effect (Muc5b) or significant downregulating effect (SP-A), suggesting an increased propensity for infection in the exposed lungs. Conclusions: The current study based on the lung toxicity mouse model showed that both toxicant types, particles (CNT) versus chemicals (CSE), cause similar downregulation of lung innate defense targets (SP-A, Muc5b) and mostly a summative effect when presented as co-exposure. However, the two toxicant types show differential induction of aquaporin-1 coinciding with the corresponding differential damage to alveolar integrity (vascular permeability). Interestingly, this implies the potential of AQP1 as a differential marker of toxicant type-specific lung injury.

Keywords: aquaporin, gene expression, lung injury, toxicant exposure

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Authors: Michelle Maurer, Antonia Last, Mark S. Gresnigt, Bernhard Hube, Alexander S. Mosig

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The intestinal epithelium forms an essential barrier to prevent translocation of microorganisms, toxins or other potentially harmful molecules into the bloodstream. In particular, dendritic cells of the intestinal epithelium orchestrate an adapted response of immune tolerance to commensals and immune defense against invading pathogens. Systemic inflammation is typically associated with a dysregulation of this adapted immune response and is accompanied by a disruption of the epithelial and endothelial gut barrier which enables dissemination of pathogens within the human body. To understand the pathophysiological mechanisms underlying the inflammation-associated gut barrier breakdown, it is crucial to elucidate the complex interplay of the host and the intestinal microbiome. A microfluidically perfused three-dimensional intestine-on-chip model was established to emulate these processes in the presence of immune cells, commensal bacteria, and facultative pathogens. Multi-organ tissue flow (MOTiF) biochips made from polystyrene were used for microfluidic perfusion of the intestinal tissue model. The biochips are composed of two chambers separated by a microporous membrane. Each chamber is connected to inlet and outlet channels allowing independent perfusion of the individual channels and application of microfluidic shear stress. Human umbilical vein endothelial cells (HUVECs), monocyte-derived macrophages and intestinal epithelial cells (Caco-2) were assembled on the biochip membrane. Following 7 – 14 days of growth in the presence of physiological flow conditions, the epithelium was colonized with the commensal bacterium Lactobacillus rhamnosus, while the endothelium was perfused with peripheral blood mononuclear cells (PBMCs). Additionally, L. rhamnosus was co-cultivated with the opportunistic fungal pathogen Candida albicans. Within one week of perfusion, the epithelial cells formed self-organized and well-polarized villus- and crypt-like structures that resemble essential morphological characteristics of the human intestine. Dendritic cells were differentiated in the epithelial tissue that specifically responds to bacterial lipopolysaccharide (LPS) challenge. LPS is well-tolerated at the luminal epithelial side of the intestinal model without signs of tissue damage or induction of an inflammatory response, even in the presence of circulating PBMC at the endothelial lining. In contrast, LPS stimulation at the endothelial side of the intestinal model triggered the release of pro-inflammatory cytokines such as TNF, IL-1β, IL-6, and IL-8 via activation of macrophages residing in the endothelium. Perfusion of the endothelium with PBMCs led to an enhanced cytokine release. L. rhamnosus colonization of the model was tolerated in the immune competent tissue model and was demonstrated to reduce damage induced by C. albicans infection. A microfluidic intestine-on-chip model was developed to mimic a systemic infection with a dysregulated immune response under physiological conditions. The model facilitates the colonization of commensal bacteria and co-cultivation with facultative pathogenic microorganisms. Both, commensal bacteria alone and facultative pathogens controlled by commensals, are tolerated by the host and contribute to cell signaling. The human intestine-on-chip model represents a promising tool to mimic microphysiological conditions of the human intestine and paves the way for more detailed in vitro studies of host-microbiota interactions under physiologically relevant conditions.

Keywords: host-microbiota interaction, immune tolerance, microfluidics, organ-on-chip

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Authors: C. Bel, J. Nevado, F. Ciceri, M. Ropacki, T. Hoffmann, P. Lapunzina, C. Buesa

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Background: The Phelan-McDermid syndrome (PMS) is a genetic disorder caused by the deletion of the terminal region of chromosome 22 or mutation of the SHANK3 gene. Shank3 disruption in mice leads to dysfunction of synaptic transmission, which can be restored by epigenetic regulation with both Lysine Specific Demethylase 1 (LSD1) inhibitors. PMS subjects result in a variable degree of intellectual disability, delay or absence of speech, autistic spectrum disorders symptoms, low muscle tone, motor delays and epilepsy. Vafidemstat is an LSD1 inhibitor in Phase II clinical development with a well-established and favorable safety profile, and data supporting the restoration of memory and cognition defects as well as reduction of agitation and aggression in several animal models and clinical studies. Therefore, vafidemstat has the potential to become a first-in-class precision medicine approach to treat PMS patients. Aims: The goal of this research is to perform an observational trial to psychometrically characterize individuals carrying deletions in SHANK3 and build a foundation for subsequent precision psychiatry clinical trials with vafidemstat. Methodology: This study is characterizing the clinical profile of 20 to 40 subjects, > 16-year-old, with genotypically confirmed PMS diagnosis. Subjects will complete a battery of neuropsychological scales, including the Repetitive Behavior Questionnaire (RBQ), Vineland Adaptive Behavior Scales, Escala de Observación para el Diagnostico del Autismo (Autism Diagnostic Observational Scale) (ADOS)-2, the Battelle Developmental Inventory and the Behavior Problems Inventory (BPI). Results: By March 2021, 19 patients have been enrolled. Unsupervised hierarchical clustering of the results obtained so far identifies 3 groups of patients, characterized by different profiles of cognitive and behavioral scores. The first cluster is characterized by low Battelle age, high ADOS and low Vineland, RBQ and BPI scores. Low Vineland, RBQ and BPI scores are also detected in the second cluster, which in contrast has high Battelle age and low ADOS scores. The third cluster is somewhat in the middle for the Battelle, Vineland and ADOS scores while displaying the highest levels of aggression (high BPI) and repeated behaviors (high RBQ). In line with the observation that female patients are generally affected by milder forms of autistic symptoms, no male patients are present in the second cluster. Dividing the results by gender highlights that male patients in the third cluster are characterized by a higher frequency of aggression, whereas female patients from the same cluster display a tendency toward higher repetitive behavior. Finally, statistically significant differences in deletion sizes are detected comparing the three clusters (also after correcting for gender), and deletion size appears to be positively correlated with ADOS and negatively correlated with Vineland A and C scores. No correlation is detected between deletion size and the BPI and RBQ scores. Conclusions: Precision medicine may open a new way to understand and treat Central Nervous System disorders. Epigenetic dysregulation has been proposed to be an important mechanism in the pathogenesis of schizophrenia and autism. Vafidemstat holds exciting therapeutic potential in PMS, and this study will provide data regarding the optimal endpoints for a future clinical study to explore vafidemstat ability to treat shank3-associated psychiatric disorders.

Keywords: autism, epigenetics, LSD1, personalized medicine

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Authors: Elsie M. Nolte, Annie M. Joubert, Roy Lakier, Maryke Etsebeth, Jolene M. Helena, Marcel Verwey, Laurence Lafanechere, Anne E. Theron

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Treatment regimens for breast- and lung cancers may include both radiation- and chemotherapy. Ideally, a pharmaceutical agent which selectively sensitizes cancer cells to gamma (γ)-radiation would allow administration of lower doses of each modality, yielding synergistic anti-cancer benefits and lower metastasis occurrence, in addition to decreasing the side-effect profiles. A range of 2-methoxyestradiol (2-ME) analogues, namely 2-ethyl-3-O-sulphamoyl-estra-1,3,5 (10) 15-tetraene-3-ol-17one (ESE-15-one), 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10),15-tetraen-17-ol (ESE-15-ol) and 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16) were in silico-designed by our laboratory, with the aim of improving the parent compound’s bioavailability in vivo. The main effect of these compounds is the disruption of microtubule dynamics with a resultant mitotic accumulation and induction of programmed cell death in various cancer cell lines. This in vitro study aimed to determine the cellular responses involved in the radiation sensitization effects of these analogues at low doses in breast- and lung cancer cell lines. The oestrogen receptor positive MCF-7-, oestrogen receptor negative MDA-MB-231- and triple negative BT-20 breast cancer cell lines as well as the A549 lung cancer cell line were used. The minimal compound- and radiation doses able to induce apoptosis were determined using annexin-V and cell cycle progression markers. These doses (cell line dependent) were used to pre-sensitize the cancer cells 24 hours prior to 6 gray (Gy) radiation. Experiments were conducted on samples exposed to the individual- as well as the combination treatment conditions in order to determine whether the combination treatment yielded an additive cell death response. Morphological studies included light-, fluorescence- and transmission electron microscopy. Apoptosis induction was determined by flow cytometry employing annexin V, cell cycle analysis, B-cell lymphoma 2 (Bcl-2) signalling, as well as reactive oxygen species (ROS) production. Clonogenic studies were performed by allowing colony formation for 10 days post radiation. Deoxyribonucleic acid (DNA) damage was quantified via γ-H2AX foci and micronuclei quantification. Amplification of the p53 signalling pathway was determined by western blot. Results indicated that exposing breast- and lung cancer cells to nanomolar concentrations of these analogues 24 hours prior to γ-radiation induced more cell death than the compound- and radiation treatments alone. Hypercondensed chromatin, decreased cell density, a damaged cytoskeleton and an increase in apoptotic body formation were observed in cells exposed to the combination treatment condition. An increased number of cells present in the sub-G1 phase as well as increased annexin-V staining, elevation of ROS formation and decreased Bcl-2 signalling confirmed the additive effect of the combination treatment. In addition, colony formation decreased significantly. p53 signalling pathways were significantly amplified in cells exposed to the analogues 24 hours prior to radiation, as was the amount of DNA damage. In conclusion, our results indicated that pre-treatment of breast- and lung cancer cells with low doses of 2-ME analogues sensitized breast- and lung cancer cells to γ-radiation and induced apoptosis more so than the individual treatments alone. Future studies will focus on the effect of the combination treatment on non-malignant cellular counterparts.

Keywords: cancer, microtubule dynamics, radiation therapy, radiosensitization

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Authors: Kyriaki Hatziagapiou, Eleni Kakouri, Konstantinos Bethanis, Alexandra Nikola, Eleni Koniari, Charalabos Kanakis, Elias Christoforides, George Lambrou, Petros Tarantilis

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Medulloblastoma is a highly invasive tumour, as it tends to disseminate throughout the central nervous system early in its course. Despite the high 5-year-survival rate, a significant number of patients demonstrate serious long- or short-term sequelae (e.g., myelosuppression, endocrine dysfunction, cardiotoxicity, neurological deficits and cognitive impairment) and higher mortality rates, unrelated to the initial malignancy itself but rather to the aggressive treatment. A strong rationale exists for the use of Crocus sativus L (saffron) and its bioactive constituents (crocin, crocetin, safranal) as pharmaceutical agents, as they exert significant health-promoting properties. Crocins are water soluble carotenoids. Unlike other carotenoids, crocins are highly water-soluble compounds, with relatively low toxicity as they are not stored in adipose and liver tissues. Crocins have attracted wide attention as promising anti-cancer agents, due to their antioxidant, anti-inflammatory, and immunomodulatory effects, interference with transduction pathways implicated in tumorigenesis, angiogenesis, and metastasis (disruption of mitotic spindle assembly, inhibition of DNA topoisomerases, cell-cycle arrest, apoptosis or cell differentiation) and sensitization of cancer cells to radiotherapy and chemotherapy. The current research aimed to study the potential cytotoxic effect of crocins on TE671 medulloblastoma cell line, which may be useful in the optimization of existing and development of new therapeutic strategies. Crocins were extracted from stigmas of saffron in ultrasonic bath, using petroleum-ether, diethylether and methanol 70%v/v as solvents and the final extract was lyophilized. Identification of crocins according to high-performance liquid chromatography (HPLC) analysis was determined comparing the UV-vis spectra and the retention time (tR) of the peaks with literature data. For the biological assays crocin was diluted to nuclease and protease free water. TE671 cells were incubated with a range of concentrations of crocins (16, 8, 4, 2, 1, 0.5 and 0.25 mg/ml) for 24, 48, 72 and 96 hours. Analysis of cell viability after incubation with crocins was performed with Alamar Blue viability assay. The active ingredient of Alamar Blue, resazurin, is a blue, nontoxic, cell permeable compound virtually nonfluorescent. Upon entering cells, resazurin is reduced to a pink and fluorescent molecule, resorufin. Viable cells continuously convert resazurin to resorufin, generating a quantitative measure of viability. The colour of resorufin was quantified by measuring the absorbance of the solution at 600 nm with a spectrophotometer. HPLC analysis indicated that the most abundant crocins in our extract were trans-crocin-4 and trans-crocin-3. Crocins exerted significant cytotoxicity in a dose and time-dependent manner (p < 0.005 for exposed cells to any concentration at 48, 72 and 96 hours versus cells not exposed); as their concentration and time of exposure increased, the reduction of resazurin to resofurin decreased, indicating reduction in cell viability. IC50 values for each time point were calculated ~3.738, 1.725, 0.878 and 0.7566 mg/ml at 24, 48, 72 and 96 hours, respectively. The results of our study could afford the basis of research regarding the use of natural carotenoids as anticancer agents and the shift to targeted therapy with higher efficacy and limited toxicity. Acknowledgements: The research was funded by Fellowships of Excellence for Postgraduate Studies IKY-Siemens Programme.

Keywords: crocetin, crocin, medulloblastoma, saffron

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Authors: Stephen Verderber

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The World Health Organization (WHO) calls for research and development on ecologically sustainable, resilient structures capable of effectively responding to disaster events globally, in response to climate change, politically based diasporas, earthquakes, and other adverse events upending the rhythms of everyday life globally. By 2050, nearly 80% of the world’s population will reside in coastal zones, and this, coupled with the increasingly dire impacts of climate change, constitute a recipe for further chaos and disruption, and in light of these events, architects have yet to rise up to meet the challenge. In the arena of healthcare, rapidly deployable clinics and field hospitals can provide immediate assistance in medically underserved disaster strike zones. Transportable facilities offer multiple advantages over conventional, fixed-site hospitals, as lightweight, comparatively unencumbered alternatives. These attributes have been proven repeatedly in 20th century vehicular and tent-based structures deployed in frontline combat theaters and in prior natural disasters. Prefab transportable clinics and trauma centers recently responded adroitly to medical emergencies in the aftermath of the Haitian (2010) and Ecuadorian (2016) earthquakes, and in North American post-hurricane relief efforts (2017) while architects continue to be castigated by their engineer colleagues as chronically poor first responders. Architecturally based portable structures for healthcare currently include Redeployable Health Centers (RHCs), Redeployable Trauma Centers (RTCs), and Permanent Modular Installations (PMIs). Five tectonic variants within this typology have recently been operationalized in the field: 1. Vehicular-based Nomadics: Prefab modules installed on a truck chassis with interior compartments dropped in prior to final assembly. Alternately, a two-component apparatus is preferred, with a truck cab pulling a modular medical unit, with independent transiting component; 2. Tent and Pneumatic Systems: Tent/yurt precursors and inflatable systems lightweight and responsive to topographically challenging terrain and diverse climates; 3. Containerized Systems: The standard modular intermodal-shipping container affords structural strength, resiliency in difficult transiting conditions, and can be densely close-packed and these can be custom-built or hold flat-pack systems; 4. Flat-Packs and Pop-Up Systems: These kit-of-part assemblies are shipped in standardized or specially-designed ISO containers; and 5. Hybrid Systems: These consist of composite facilities representing a synthesis of mobile vehicular components and/or tent or shipping containers, fused with conventional or pneumatically activated tent systems. Hybrids are advantageous in many installation contexts from an aesthetic, fabrication, and transiting perspective. Advantages/disadvantages of various modular systems are comparatively examined, followed by presentation of a compendium of 80 evidence (research)-based planning and design considerations addressing site/context, transiting and commissioning, triage, decontamination/intake, diagnostic and treatment, facility tectonics, and administration/total environment. The benefits of offsite pre-manufactured fabrication are examined, as is anticipated growth in international demand for transportable healthcare facilities to meet the challenges posed by accelerating global climate change and global conflicts. This investigation into rapid response facilities for pre and post-disaster zones is drawn from a recent book by the author, the first on architecture on this topic (Innovations in Transportable Healthcare Architecture).

Keywords: disaster mitigation, rapid response healthcare architecture, offsite prefabrication

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