Search results for: soft tissues

Authors: Ana L. M. Pavan, Guilherme Giacomini, Allan F. F. Alves, Marcela De Oliveira, Fernando A. B. Neto, Maria E. D. Rosa, Andre P. Trindade, Diana R. De Pina

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Mammography is a worldwide image modality used to diagnose breast cancer, even in asymptomatic women. Due to its large availability, mammograms can be used to measure breast density and to predict cancer development. Women with increased mammographic density have a four- to sixfold increase in their risk of developing breast cancer. Therefore, studies have been made to accurately quantify mammographic breast density. In clinical routine, radiologists perform image evaluations through BIRADS (Breast Imaging Reporting and Data System) assessment. However, this method has inter and intraindividual variability. An automatic objective method to measure breast density could relieve radiologist’s workload by providing a first aid opinion. However, pectoral muscle is a high density tissue, with similar characteristics of fibroglandular tissues. It is consequently hard to automatically quantify mammographic breast density. Therefore, a pre-processing is needed to segment the pectoral muscle which may erroneously be quantified as fibroglandular tissue. The aim of this work was to develop an automatic algorithm to segment and extract pectoral muscle in digital mammograms. The database consisted of thirty medio-lateral oblique incidence digital mammography from São Paulo Medical School. This study was developed with ethical approval from the authors’ institutions and national review panels under protocol number 3720-2010. An algorithm was developed, in Matlab® platform, for the pre-processing of images. The algorithm uses image processing tools to automatically segment and extract the pectoral muscle of mammograms. Firstly, it was applied thresholding technique to remove non-biological information from image. Then, the Hough transform is applied, to find the limit of the pectoral muscle, followed by active contour method. Seed of active contour is applied in the limit of pectoral muscle found by Hough transform. An experienced radiologist also manually performed the pectoral muscle segmentation. Both methods, manual and automatic, were compared using the Jaccard index and Bland-Altman statistics. The comparison between manual and the developed automatic method presented a Jaccard similarity coefficient greater than 90% for all analyzed images, showing the efficiency and accuracy of segmentation of the proposed method. The Bland-Altman statistics compared both methods in relation to area (mm²) of segmented pectoral muscle. The statistic showed data within the 95% confidence interval, enhancing the accuracy of segmentation compared to the manual method. Thus, the method proved to be accurate and robust, segmenting rapidly and freely from intra and inter-observer variability. It is concluded that the proposed method may be used reliably to segment pectoral muscle in digital mammography in clinical routine. The segmentation of the pectoral muscle is very important for further quantifications of fibroglandular tissue volume present in the breast.

Keywords: active contour, fibroglandular tissue, hough transform, pectoral muscle

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Authors: Wang Heng, Zhong Zhaoping, Guo Feihong, Wang Jia, Wang Xiaoyi

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Flow of gas and particles in fluidized beds is complex and chaotic, which is difficult to measure and analyze by experiments. Some bed materials with bad fluidized performance always fluidize with fluidized medium. The material and the fluidized medium are different in many properties such as density, size and shape. These factors make the dynamic process more complex and the experiment research more limited. Numerical simulation is an efficient way to describe the process of gas-solid flow in fluidized bed. One of the most popular numerical simulation methods is CFD-DEM, i.e., computational fluid dynamics-discrete element method. The shapes of particles are always simplified as sphere in most researches. Although sphere-shaped particles make the calculation of particle uncomplicated, the effects of different shapes are disregarded. However, in practical applications, the two-component systems in fluidized bed also contain sphere particles and non-sphere particles. Therefore, it is needed to study the two component flow of sphere particles and non-sphere particles. In this paper, the flows of mixing were simulated as the flow of molding biomass particles and quartz in fluidized bad. The integrated model was built on an Eulerian–Lagrangian approach which was improved to suit the non-sphere particles. The constructed methods of cylinder-shaped particles were different when it came to different numerical methods. Each cylinder-shaped particle was constructed as an agglomerate of fictitious small particles in CFD part, which means the small fictitious particles gathered but not combined with each other. The diameter of a fictitious particle d_fic and its solid volume fraction inside a cylinder-shaped particle α_fic, which is called the fictitious volume fraction, are introduced to modify the drag coefficient β by introducing the volume fraction of the cylinder-shaped particles α_cld and sphere-shaped particles α_sph. In a computational cell, the void ε, can be expressed as ε=1-〖α_cld α〗_fic-α_sph. The Ergun equation and the Wen and Yu equation were used to calculate β. While in DEM method, cylinder-shaped particles were built by multi-sphere method, in which small sphere element merged with each other. Soft sphere model was using to get the connect force between particles. The total connect force of cylinder-shaped particle was calculated as the sum of the small sphere particles’ forces. The model (size=1×0.15×0.032 mm3) contained 420000 sphere-shaped particles (diameter=0.8 mm, density=1350 kg/m3) and 60 cylinder-shaped particles (diameter=10 mm, length=10 mm, density=2650 kg/m3). Each cylinder-shaped particle was constructed by 2072 small sphere-shaped particles (d=0.8 mm) in CFD mesh and 768 sphere-shaped particles (d=3 mm) in DEM mesh. The length of CFD and DEM cells are 1 mm and 2 mm. Superficial gas velocity was changed in different models as 1.0 m/s, 1.5 m/s, 2.0m/s. The results of simulation were compared with the experimental results. The movements of particles were regularly as fountain. The effect of superficial gas velocity on cylinder-shaped particles was stronger than that of sphere-shaped particles. The result proved this present work provided a effective approach to simulation the flow of two component particles.

Keywords: computational fluid dynamics, discrete element method, fluidized bed, multiphase flow

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Authors: Inas Raafat, Azza El Bassiouny, Waldemar L. Olszewsky, Nagui E. Mikhail, Mona Nossier, Nora E. I. El-Bassiouni, Mona Zoheiry, Houda Abou Taleb, Noha Abd El-Aal, Ali Baioumy, Shimaa Attia

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Background: Orthotopic liver transplantation is an established treatment for patients with severe acute and end-stage chronic liver disease. The shortage of donor organs continues to be the rate-limiting factor for liver transplantation throughout the world. Hepatocyte transplantation is a promising treatment for several liver diseases and can, also, be used as a "bridge" to liver transplantation in cases of liver failure. Aim of the work: This study was designed to develop a highly efficient protocol for isolation and transplantation of hepatocytes in experimental Lewis rat model to provide satisfactory guidelines for future application on humans.Materials and Methods: Hepatocytes were isolated from the liver by double perfusion technique and bone marrow cells were isolated by centrifugation of shafts of tibia and femur of donor Lewis rats. Recipient rats were subjected to sub-lethal dose of irradiation 2 days before transplantation. In a laparotomy operation the spleen was injected by freshly isolated hepatocytes and bone marrow cells were injected intravenously. The animals were sacrificed 45 day latter and splenic sections were prepared and stained with H & E, PAS AFP and Prox1. Results: The data obtained from this study showed that the double perfusion technique is successful in separation of hepatocytes regarding cell number and viability. Also the method used for bone marrow cells separation gave excellent results regarding cell number and viability. Intrasplenic engraftment of hepatocytes and live tissue formation within the splenic tissue were found in 70% of cases. Hematoxylin and eosin stained splenic sections from 7 rats showed sheets and clusters of cells among the splenic tissues. Periodic Acid Schiff stained splenic sections from 7 rats showed clusters of hepatocytes with intensely stained pink cytoplasmic granules denoting the presence of glycogen. Splenic sections from 7 rats stained with anti-α-fetoprotein antibody showed brownish cytoplasmic staining of the hepatocytes denoting positive expression of AFP. Splenic sections from 7 rats stained with anti-Prox1 showed brownish nuclear staining of the hepatocytes denoting positive expression of Prox1 gene on these cells. Also, positive expression of Prox1 gene was detected on lymphocytes aggregations in the spleens. Conclusions: Isolation of liver cells by double perfusion technique using collagenase buffer is a reliable method that has a very satisfactory yield regarding cell number and viability. The intrasplenic route of transplantation of the freshly isolated liver cells in an immunocompromised model was found to give good results regarding cell engraftment and tissue formation. Further studies are needed to assess function of engrafted hepatocytes by measuring prothrombin time, serum albumin and bilirubin levels.

Keywords: Lewis rats, hepatocytes, BMCs, transplantation, AFP, Prox1

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Authors: Ayalew Yimam Ali

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The Y-shaped microchannel is used to mix both miscible or immiscible fluids with different viscosities. However, mixing at the entrance of the Y-junction microchannel can be a difficult mixing phenomena due to micro-scale laminar flow aspects with the two miscible high-viscosity water-glycerol fluids. One of the most promising methods to improve mixing performance and diffusion mass transfer in laminar flow phenomena is acoustic streaming (AS), which is a time-averaged, second-order steady streaming that can produce rolling motion in the microchannel by oscillating a low-frequency range acoustic transducer and inducing an acoustic wave in the flow field. The developed 3D trapezoidal, triangular structure spine used in this study was created using sophisticated CNC machine cutting tools used to create microchannel mold with a 3D trapezoidal triangular structure spine alone the Y-junction longitudinal mixing region. In order to create the molds for the 3D trapezoidal structure with the 3D sharp edge tip angles of 30° and 0.3mm trapezoidal triangular sharp edge tip depth from PMMA glass (Polymethylmethacrylate) with advanced CNC machine and the channel manufactured using PDMS (Polydimethylsiloxane) which is grown up longitudinally on top surface of the Y-junction microchannel using soft lithography nanofabrication strategies. Flow visualization of 3D rolling steady acoustic streaming and mixing enhancement with high-viscosity miscible fluids with different trapezoidal, triangular structure longitudinal length, channel width, high volume flow rate, oscillation frequency, and amplitude using micro-particle image velocimetry (μPIV) techniques were used to study the 3D acoustic streaming flow patterns and mixing enhancement. The streaming velocity fields and vorticity flow fields show 16 times more high vorticity maps than in the absence of acoustic streaming, and mixing performance has been evaluated at various amplitudes, flow rates, and frequencies using the grayscale value of pixel intensity with MATLAB software. Mixing experiments were performed using fluorescent green dye solution with de-ionized water in one inlet side of the channel, and the de-ionized water-glycerol mixture on the other inlet side of the Y-channel and degree of mixing was found to have greatly improved from 67.42% without acoustic streaming to 0.96.83% with acoustic streaming. The results show that the creation of a new 3D steady streaming rolling motion with a high volume flowrate around the entrance was enhanced by the formation of a new, three-dimensional, intense streaming rolling motion with a high-volume flowrate around the entrance junction mixing zone with the two miscible high-viscous fluids which are influenced by laminar flow fluid transport phenomena.

Keywords: micro fabrication, 3d acoustic streaming flow visualization, micro-particle image velocimetry, mixing enhancement

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Authors: Lesly Y Carmona-Sarabia, Luisa Barraza-Vergara, Vilmalí López-Mejías, Wandaliz Torres-García, Maribella Domenech-Garcia, Madeline Torres-Lugo

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Biosensors are used in many applications providing real-time monitoring to treat long-term conditions. Thus, understanding the physicochemical properties and biological side effects on the skin of polymers (e. g., poly(methyl methacrylate), PMMA) employed in the fabrication of wearable biosensors is crucial for the selection of manufacturing materials within this field. The PMMA (hydrophobic and thermoplastic polymer) is commonly employed as a coating material or substrate in the fabrication of wearable devices. The cytotoxicityof PMMA (including residual monomers or degradation products) on the skin, in terms of cells and tissue, is required to prevent possible adverse effects (cell death, skin reactions, sensitization) on human health. Within this work, accelerated aging of PMMA (Mw ~ 15000) through thermal and photochemical degradation was under-taken. The accelerated aging of PMMA was carried out by thermal (200°C, 1h) and photochemical degradation (UV-Vis, 8-15d) adapted employing ISO protocols (ISO-10993-12, ISO-4892-1:2016, ISO-877-1:2009, ISO-188: 2011). In addition, in vitro cytotoxicity evaluation of PMMA degradation products was performed using NIH3T3 fibroblast cells to assess the response of skin tissues (in terms of cell viability) exposed with polymers utilized to manufacture wearable biosensors, such as PMMA. The PMMA (Mw ~ 15000) before and after accelerated aging experiments was characterized by thermal gravimetric analysis (TGA), differential scanning calorimetric (DSC), powder X-ray diffractogram (PXRD), and scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) to determine and verify the successful degradation of this polymer under the specific conditions previously mention. The degradation products were characterized through nuclear magnetic resonance (NMR) to identify possible byproducts generated after the accelerated aging. Results demonstrated a percentage (%) weight loss between 1.5-2.2% (TGA thermographs) for PMMA after accelerated aging. The EDS elemental analysis reveals a 1.32 wt.% loss of carbon for PMMA after thermal degradation. These results might be associated with the amount (%) of PMMA degrade after the accelerated aging experiments. Furthermore, from the thermal degradation products was detected the presence of the monomer and methyl formate (low concentrations) and a low molecular weight radical (·COOCH3) in higher concentrations by NMR. In the photodegradation products, methyl formate was detected in higher concentrations. These results agree with the proposed thermal or photochemical degradation mechanisms found in the literature.1,2 Finally, significant cytotoxicity on the NIH3T3 cells was obtained for the thermal and photochemical degradation products. A decrease in cell viability by > 90% (stock solutions) was observed. It is proposed that the presence of byproducts (e.g. methyl formate or radicals such as ·COOCH₃) from the PMMA degradation might be responsible for the cytotoxicity observed in the NIH3T3 fibroblast cells. Additionally, experiments using skin models will be employed to compare with the NIH3T3 fibroblast cells model.

Keywords: biosensors, polymer, skin irritation, degradation products, cell viability

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Authors: Soumava Boral, Sanjay K. Chaturvedi, Ian Howard, Kristoffer McKee, V. N. A. Naikan

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Due to strict regulations from government to enhance the possibilities of sustainability practices in industries, and noting the advances in sustainable manufacturing practices, it is necessary that the associated processes are also sustainable. Maintenance of large scale and complex machines is a pivotal task to maintain the uninterrupted flow of manufacturing processes. Appropriate maintenance practices can prolong the lifetime of machines, and prevent associated breakdowns, which subsequently reduces different cost heads. Selection of the best maintenance strategies for such machines are considered as a burdensome task, as they require the consideration of multiple technical criteria, complex mathematical calculations, previous fault data, maintenance records, etc. In the era of the fourth industrial revolution, organizations are rapidly changing their way of business, and they are giving their utmost importance to sensor technologies, artificial intelligence, data analytics, automations, etc. In this work, the effectiveness of several maintenance strategies (e.g., preventive, failure-based, reliability centered, condition based, total productive maintenance, etc.) related to a large scale and complex gearbox, operating in a steel processing plant is evaluated in terms of economic, social, environmental and technical criteria. As it is not possible to obtain/describe some criteria by exact numerical values, these criteria are evaluated linguistically by cross-functional experts. Fuzzy sets are potential soft-computing technique, which has been useful to deal with linguistic data and to provide inferences in many complex situations. To prioritize different maintenance practices based on the identified sustainable criteria, multi-criteria decision making (MCDM) approaches can be considered as potential tools. Multi-Attributive Ideal Real Comparative Analysis (MAIRCA) is a recent addition in the MCDM family and has proven its superiority over some well-known MCDM approaches, like TOPSIS (Technique for Order Preference by Similarity to Ideal Solution) and ELECTRE (ELimination Et Choix Traduisant la REalité). It has a simple but robust mathematical approach, which is easy to comprehend. On the other side, due to some inherent drawbacks of Intuitionistic Fuzzy Sets (IFS) and Pythagorean Fuzzy Sets (PFS), recently, the use of Fermatean Fuzzy Sets (FFSs) has been proposed. In this work, we propose the novel concept of FF-MAIRCA. We obtain the weights of the criteria by experts’ evaluation and use them to prioritize the different maintenance practices according to their suitability by FF-MAIRCA approach. Finally, a sensitivity analysis is carried out to highlight the robustness of the approach.

Keywords: Fermatean fuzzy sets, Fermatean fuzzy MAIRCA, maintenance strategy selection, sustainable manufacturing, MCDM

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Authors: Sajmina Khatun, Monika Pebam, Aravind Kumar Rengan

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Photothermal therapy, a subset of nanomedicine, takes advantage of light-absorbing agents to generate localized heat, selectively eradicating cancer cells. This innovative approach minimizes damage to healthy tissues and offers a promising avenue for targeted cancer treatment. Unlike conventional therapies, photothermal therapy harnesses the power of light to combat malignancies precisely and effectively, showcasing its potential to revolutionize cancer treatment paradigms. The combined strengths of nanomedicine and photothermal therapy signify a transformative shift toward more effective, targeted, and tolerable cancer treatments in the medical landscape. Utilizing natural products becomes instrumental in formulating diverse bioactive medications owing to their various pharmacological properties attributed to the existence of phenolic structures, triterpenoids, and similar compounds. Hyptis suaveolens, commonly known as pignut, stands as an aromatic herb within the Lamiaceae family and represents a valuable therapeutic plant. Flourishing in swamps and alongside tropical and subtropical roadsides, these noxious weeds impede the development of adjacent plants. Hyptis suaveolens ranks among the most globally distributed alien invasive species. The present investigation revealed that a versatile, biodegradable liposome nanosystem (HIL NPs), incorporating bioactive molecules from Hyptis suaveolens, exhibits effective bioavailability to cancer cells, enabling tumor ablation upon near-infrared (NIR) laser exposure. The components within the nanosystem, specifically the bioactive molecules from Hyptis, function as anticancer agents, aiding in the photothermal ablation of highly metastatic lung cancer cells. Despite being a prolific weed impeding neighboring plant growth, Hyptis suaveolens showcases therapeutic benefits through its bioactive compounds. The obtained HIL NPs, characterized as a photothermally active liposome nanosystem, demonstrate a pronounced fluorescence absorption peak in the NIR range and achieve a high photothermal conversion efficiency under NIR laser irradiation. Transmission electron microscopy (TEM) and particle size analysis reveal that HIL NPs possess a spherical shape with a size of 141 ± 30 nm. Moreover, in vitro assessments of HIL NPs against lung cancer cell lines (A549) indicate effective anticancer activity through a combined cytotoxic effect and hyperthermia. Tumor ablation is facilitated by apoptosis induced by the overexpression of ɣ-H2AX, arresting cancer cell proliferation. Consequently, the multifunctional and biodegradable nanosystem (HIL NPs), incorporating bioactive compounds from Hyptis, provides valuable perspectives for developing an innovative therapeutic strategy originating from a challenging weed. This approach holds promise for potential applications in both bioimaging and the combined use of phyto-photothermal therapy for cancer treatment.

Keywords: bioactive liposome, hyptis suaveolens, photothermal therapy, lung cancer

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Authors: Kseniya Gladun

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Tactile stimulation of a dorsal side of the wrist can have a strong impact on our attitude toward physical objects such as pleasant and unpleasant impact. This study explored different aspects of tactile perception to investigate atypical touch sensitivity in children with autism spectrum disorder (ASD). This study included 40 children with ASD and 40 healthy children aged 5 to 9 years. We recorded rsEEG (sampling rate of 250 Hz) during 20 min using EEG amplifier “Encephalan” (Medicom MTD, Taganrog, Russian Federation) with 19 AgCl electrodes placed according to the International 10–20 System. The electrodes placed on the left, and right mastoids served as joint references under unipolar montage. The registration of EEG v19 assignments was carried out: frontal (Fp1-Fp2; F3-F4), temporal anterior (T3-T4), temporal posterior (T5-T6), parietal (P3-P4), occipital (O1-O2). Subjects were passively touched by 4 types of tactile stimuli on the left wrist. Our stimuli were presented with a velocity of about 3–5 cm per sec. The stimuli materials and procedure were chosen for being the most "pleasant," "rough," "prickly" and "recognizable". Type of tactile stimulation: Soft cosmetic brush - "pleasant" , Rough shoe brush - "rough", Wartenberg pin wheel roller - "prickly", and the cognitive tactile stimulation included letters by finger (most of the patient’s name ) "recognizable". To designate the moments of the stimuli onset-offset, we marked the moment when the moment of the touch began and ended; the stimulation was manual, and synchronization was not precise enough for event-related measures. EEG epochs were cleaned from eye movements by ICA-based algorithm in EEGLAB plugin for MatLab 7.11.0 (Mathwork Inc.). Muscle artifacts were cut out by manual data inspection. The response to tactile stimuli was significantly different in the group of children with ASD and healthy children, which was also depended on type of tactile stimuli and the severity of ASD. Amplitude of Alpha rhythm increased in parietal region to response for only pleasant stimulus, for another type of stimulus ("rough," "thorny", "recognizable") distinction of amplitude was not observed. Correlation dimension D2 was higher in healthy children compared to children with ASD (main effect ANOVA). In ASD group D2 was lower for pleasant and unpleasant compared to the background in the right parietal area. Hilbert transform changes in the frequency of the theta rhythm found only for a rough tactile stimulation compared with healthy participants only in the right parietal area. Children with autism spectrum disorders and healthy children were responded to tactile stimulation differently with specific frequency distribution alpha and theta band in the right parietal area. Thus, our data supports the hypothesis that rsEEG may serve as a sensitive index of altered neural activity caused by ASD. Children with autism have difficulty in distinguishing the emotional stimuli ("pleasant," "rough," "prickly" and "recognizable").

Keywords: autism, tactile stimulation, Hilbert transform, pediatric electroencephalography

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Authors: Maksim Barsakov

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Introduction. In modern plastic surgery, there are a large number of breast lift techniques.Due to the spreading information about the "side effects" of silicone implants, interest in implant-free mastopexy is increasing year after year. However, despite the variety of techniques, patients sometimes do not get full satisfaction from the results of mastopexy because of the unexpressed filling of the upper pole, extended anchoring postoperative scars and sometimes because of obtaining an aesthetically unattractive breast shape. The stability of the result after mastopexy depends on many factors, including postoperative rehabilitation. Stability of weight and hormonal background, stretchability of tissues. The high recurrence rate of ptosis and short-term aesthetic effect of mastopexy indicate the urgency of improving surgical techniques and increasing the stabilization of breast tissue. Purpose of the study. To develop and introduce into practice a technique of mastopexy based on the use of a modified Ribeiro flap, as well as elements of tissue movement and fixation designed to increase the stability of postoperative mastopexy. In addition, to give indications for the application of this surgical technique. Materials and Methods. it operated on 103 patients aged 18 to 53 years from 2019 to 2023 according to the reported method. These were patients with primary mastopexy, secondary mastopexy, and also patient with implant removal and one-stage mastopexy. The patients were followed up for 12 months to assess the stability of the result. Results and their discussion. Observing the patients, we noted greater stability of the breast shape and upper pole filling compared to the conventional classical methods. We did not have to resort to anchoring scars. In 90 percent of cases, a inverted T-shape scar was used. In 10 percent, the J-scar was used. The quantitative distribution of complications identified among the operated patients is as follows: worsened healing of the junction of vertical and horizontal sutures at the period of 1-1.5 months after surgery - 15 patients; at treatment with ointment method healing was observed in 7-30 days; permanent loss of NAC sensitivity - 0 patients; vascular disorders in the area of NAC/areola necrosis - 0 patients; marginal necrosis of the areola-2 patients. independent healing within 3-4 weeks without aesthetic defects. Aesthetically unacceptable mature scars-3 patients; partial liponecrosis of the autoflap unilaterally - 1 patient. recurrence of ptosis - 1 patient (after weight loss of 12 kg). In the late postoperative period, 2 patients became pregnant, gave birth, and no lactation problems were observed. Conclusion. Thus, in the world of plastic surgery methods of breast lift continue to improve, which is especially relevant in modern times, due to the increased attention to this operation. The author's proposed method of mastopexy with glandular autoflap allows obtaining in most cases a stable result, a fuller breast shape, avoiding the presence of extended anchoring scars, and also preserves the possibility of lactation. The author of this article has obtained a patent for invention for this method of mastopexy.

Keywords: mastopexy, mammoplasty, autoflap, personal technique

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Authors: José Manuel Palma, Paula Pereira, Margarida Tomás

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Foreseen the future: Human factors integration in European Horizon Projects The development of new technology as artificial intelligence, smart sensing, robotics, cobotics or intelligent machinery must integrate human factors to address the need to optimize systems and processes, thereby contributing to the creation of a safe and accident-free work environment. Human Factors Integration (HFI) consistently pose a challenge for organizations when applied to daily operations. AGILEHAND and FORTIS projects are grounded in the development of cutting-edge technology - industry 4.0 and 5.0. AGILEHAND aims to create advanced technologies for autonomously sort, handle, and package soft and deformable products, whereas FORTIS focuses on developing a comprehensive Human-Robot Interaction (HRI) solution. Both projects employ different approaches to explore HFI. AGILEHAND is mainly empirical, involving a comparison between the current and future work conditions reality, coupled with an understanding of best practices and the enhancement of safety aspects, primarily through management. FORTIS applies HFI throughout the project, developing a human-centric approach that includes understanding human behavior, perceiving activities, and facilitating contextual human-robot information exchange. it intervention is holistic, merging technology with the physical and social contexts, based on a total safety culture model. In AGILEHAND we will identify safety emergent risks, challenges, their causes and how to overcome them by resorting to interviews, questionnaires, literature review and case studies. Findings and results will be presented in “Strategies for Workers’ Skills Development, Health and Safety, Communication and Engagement” Handbook. The FORTIS project will implement continuous monitoring and guidance of activities, with a critical focus on early detection and elimination (or mitigation) of risks associated with the new technology, as well as guidance to adhere correctly with European Union safety and privacy regulations, ensuring HFI, thereby contributing to an optimized safe work environment. To achieve this, we will embed safety by design, and apply questionnaires, perform site visits, provide risk assessments, and closely track progress while suggesting and recommending best practices. The outcomes of these measures will be compiled in the project deliverable titled “Human Safety and Privacy Measures”. These projects received funding from European Union’s Horizon 2020/Horizon Europe research and innovation program under grant agreement No101092043 (AGILEHAND) and No 101135707 (FORTIS).

Keywords: human factors integration, automation, digitalization, human robot interaction, industry 4.0 and 5.0

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Authors: Iman Farasat, Howard M. Salis

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Engineered genetic circuits reprogram cellular behavior to act as living computers with applications in detecting cancer, creating self-controlling artificial tissues, and dynamically regulating metabolic pathways. Phenemenological models are often used to simulate and design genetic circuit behavior towards a desired behavior. While such models assume that each circuit component’s function is modular and independent, even small changes in a circuit (e.g. a new promoter, a change in transcription factor expression level, or even a new media) can have significant effects on the circuit’s function. Here, we use statistical thermodynamics to account for the several factors that control transcriptional regulation in bacteria, and experimentally demonstrate the model’s accuracy across 825 measurements in several genetic contexts and hosts. We then employ our first principles model to design, experimentally construct, and characterize a family of signal amplifying genetic circuits (genetic OpAmps) that expand the dynamic range of cell sensors. To develop these models, we needed a new approach to measuring the in vivo binding free energies of transcription factors (TFs), a key ingredient of statistical thermodynamic models of gene regulation. We developed a new high-throughput assay to measure RNA polymerase and TF binding free energies, requiring the construction and characterization of only a few constructs and data analysis (Figure 1A). We experimentally verified the assay on 6 TetR-homolog repressors and a CRISPR/dCas9 guide RNA. We found that our binding free energy measurements quantitatively explains why changing TF expression levels alters circuit function. Altogether, by combining these measurements with our biophysical model of translation (the RBS Calculator) as well as other measurements (Figure 1B), our model can account for changes in TF binding sites, TF expression levels, circuit copy number, host genome size, and host growth rate (Figure 1C). Model predictions correctly accounted for how these 8 factors control a promoter’s transcription rate (Figure 1D). Using the model, we developed a design framework for engineering multi-promoter genetic circuits that greatly reduces the number of degrees of freedom (8 factors per promoter) to a single dimensionless unit. We propose the Ptashne (Pt) number to encapsulate the 8 co-dependent factors that control transcriptional regulation into a single number. Therefore, a single number controls a promoter’s output rather than these 8 co-dependent factors, and designing a genetic circuit with N promoters requires specification of only N Pt numbers. We demonstrate how to design genetic circuits in Pt number space by constructing and characterizing 15 2-repressor OpAmp circuits that act as signal amplifiers when within an optimal Pt region. We experimentally show that OpAmp circuits using different TFs and TF expression levels will only amplify the dynamic range of input signals when their corresponding Pt numbers are within the optimal region. Thus, the use of the Pt number greatly simplifies the genetic circuit design, particularly important as circuits employ more TFs to perform increasingly complex functions.

Keywords: transcription factor, synthetic biology, genetic circuit, biophysical model, binding energy measurement

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Authors: Theophilus Asante, Comfort Nyarko, Daniel Antwi

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Drug-resistant tuberculosis, together with the associated comorbidities like pulmonary fibrosis and silicosis, has been one of the most serious global public health threats that requires immediate action to curb or mitigate it. This prolongs hospital stays, increases the cost of medication, and increases the death toll recorded annually. Crinum asiaticum bulb (CAE) and betulin (BET) are known for their biological and pharmacological effects. Pharmacological effects reported on CAE include antimicrobial, anti-inflammatory, anti-pyretic, anti-analgesic, and anti-cancer effects. Betulin has exhibited a multitude of powerful pharmacological properties ranging from antitumor, anti-inflammatory, anti-parasitic, anti-microbial, and anti-viral activities. This work sought to investigate the anti-tuberculosis and resistant modulatory effects and also assess their effects on mitigating pulmonary fibrosis and silicosis. In the anti-tuberculosis and resistant modulatory effects, both CAE and BET showed strong antimicrobial activities (31.25 ≤ MIC ≤ 500) µg/ml against the studied microorganisms and also produced significant anti-efflux pump and biofilm inhibitory effects (ρ < 0.0001) as well as exhibiting resistance modulatory and synergistic effects when combined with standard antibiotics. Crinum asiaticum bulbs extract and betulin were shown to possess anti-pulmonary fibrosis effects. There was an increased survival rate in the CAE and BET treatment groups compared to the BLM-induced group. There was a marked decrease in the levels of hydroxyproline and collagen I and III in the CAE and BET treatment groups compared to the BLM-treated group. The treatment groups of CAE and BET significantly downregulated the levels of pro-fibrotic and pro-inflammatory cytokine concentrations such as TGF-β1, MMP9, IL-6, IL-1β and TNF-alpha compared to an increase in the BLM-treated groups. The histological findings of the lungs suggested the curative effects of CAE and BET following BLM-induced pulmonary fibrosis in mice. The study showed improved lung functions with a wide focal area of viable alveolar spaces and few collagen fibers deposition on the lungs of the treatment groups. In the anti-silicosis and pulmonoprotective effects of CAE and BET, the levels of NF-κB, TNF-α, IL-1β, IL-6 and hydroxyproline, collagen types I and III were significantly reduced by CAE and BET (ρ < 0.0001). Both CAE and BET significantly (ρ < 0.0001) inhibited the levels of hydroxyproline, collagen I and III when compared with the negative control group. On BALF biomarkers such as macrophages, lymphocytes, monocytes, and neutrophils, CAE and BET were able to reduce their levels significantly (ρ < 0.0001). The CAE and BET were examined for anti-oxidant activity and shown to raise the levels of catalase (CAT) and superoxide dismutase (SOD) while lowering the level of malondialdehyde (MDA). There was an improvement in lung function when lung tissues were examined histologically. Crinum asiaticum bulbs extract and betulin were discovered to exhibit anti-tubercular and resistance-modulatory properties, as well as the capacity to minimize TB comorbidities such as pulmonary fibrosis and silicosis. In addition, CAE and BET may act as protective mechanisms, facilitating the preservation of the lung's physiological integrity. The outcomes of this study might pave the way for the development of leads for producing single medications for the management of drug-resistant tuberculosis and its accompanying comorbidities.

Keywords: fibrosis, crinum, tuberculosis, antiinflammation, drug resistant

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Authors: Maria Thaemar Tana

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The paper examines the policy and practice of Japan’s human security. Specifically, it asks the question: How does Japan’s shift towards a more proactive defence posture affect the place of human security in its foreign policy agenda? Corollary to this, how is Japan sustaining its human security policy? The objective of this research is to understand how Japan, chiefly through the Ministry of Foreign Affairs (MOFA) and JICA (Japan International Cooperation Agency), sustains the concept of human security as a policy framework. In addition, the paper also aims to show how and why Japan continues to include the concept in its overall foreign policy agenda. In light of the recent developments in Japan’s security policy, which essentially result from the changing security environment, human security appears to be gradually losing relevance. The paper, however, argues that despite the strategic challenges Japan faced and is facing, as well as the apparent decline of its economic diplomacy, human security remains to be an area of critical importance for Japanese foreign policy. In fact, as Japan becomes more proactive in its international affairs, the strategic value of human security also increases. Human security was initially envisioned to help Japan compensate for its weaknesses in the areas of traditional security, but as Japan moves closer to a more activist foreign policy, the soft policy of human security complements its hard security policies. Using the framework of neoclassical realism (NCR), the paper recognizes that policy-making is essentially a convergence of incentives and constraints at the international and domestic levels. The theory posits that there is no perfect 'transmission belt' linking material power on the one hand, and actual foreign policy on the other. State behavior is influenced by both international- and domestic-level variables, but while systemic pressures and incentives determine the general direction of foreign policy, they are not strong enough to affect the exact details of state conduct. Internal factors such as leaders’ perceptions, domestic institutions, and domestic norms, serve as intervening variables between the international system and foreign policy. Thus, applied to this study, Japan’s sustained utilization of human security as a foreign policy instrument (dependent variable) is essentially a result of systemic pressures (indirectly) (independent variables) and domestic processes (directly) (intervening variables). Two cases of Japan’s human security practice in two regions are examined in two time periods: Iraq in the Middle East (2001-2010) and South Sudan in Africa (2011-2017). The cases show that despite the different motives behind Japan’s decision to participate in these international peacekeepings ad peace-building operations, human security continues to be incorporated in both rhetoric and practice, thus demonstrating that it was and remains to be an important diplomatic tool. Different variables at the international and domestic levels will be examined to understand how the interaction among them results in changes and continuities in Japan’s human security policy.

Keywords: human security, foreign policy, neoclassical realism, peace-building

Procedia PDF Downloads 133

Authors: Marcin Zieliński, Marcin Dębowski, Mirosław Krzemieniewski

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The anaerobic degradation of substrates is limited especially by the rate and effectiveness of the first (hydrolytic) stage of fermentation. This stage may be intensified through pre-treatment of substrate aimed at disintegration of the solid phase and destruction of substrate tissues and cells. The most frequently applied criterion of disintegration outcomes evaluation is the increase in biogas recovery owing to the possibility of its use for energetic purposes and, simultaneously, recovery of input energy consumed for the pre-treatment of substrate before fermentation. Hydrodynamic cavitation is one of the methods for organic substrate disintegration that has a high implementation potential. Cavitation is explained as the phenomenon of the formation of discontinuity cavities filled with vapor or gas in a liquid induced by pressure drop to the critical value. It is induced by a varying field of pressures. A void needs to occur in the flow in which the pressure first drops to the value close to the pressure of saturated vapor and then increases. The process of cavitation conducted under controlled conditions was found to significantly improve the effectiveness of anaerobic conversion of organic substrates having various characteristics. This phenomenon allows effective damage and disintegration of cellular and tissue structures. Disintegration of structures and release of organic compounds to the dissolved phase has a direct effect on the intensification of biogas production in the process of anaerobic fermentation, on reduced dry matter content in the post-fermentation sludge as well as a high degree of its hygienization and its increased susceptibility to dehydration. A device the efficiency of which was confirmed both in laboratory conditions and in systems operating in the technical scale is a hydrodynamic generator of cavitation. Cavitators, agitators and emulsifiers constructed and tested worldwide so far have been characterized by low efficiency and high energy demand. Many of them proved effective under laboratory conditions but failed under industrial ones. The only task successfully realized by these appliances and utilized on a wider scale is the heating of liquids. For this reason, their usability was limited to the function of heating installations. Design of the presented cavitation generator allows achieving satisfactory energy efficiency and enables its use under industrial conditions in depolymerization processes of biomass with various characteristics. Investigations conducted on the laboratory and industrial scale confirmed the effectiveness of applying cavitation in the process of biomass destruction. The use of the cavitation generator in laboratory studies for disintegration of sewage sludge allowed increasing biogas production by ca. 30% and shortening the treatment process by ca. 20 - 25%. The shortening of the technological process and increase of wastewater treatment plant effectiveness may delay investments aimed at increasing system output. The use of a mechanical cavitator and application of repeated cavitation process (4-6 times) enables significant acceleration of the biogassing process. In addition, mechanical cavitation accelerates increases in COD and VFA levels.

Keywords: hydrodynamic cavitation, pretreatment, biomass, methane fermentation, Virginia fanpetals

Procedia PDF Downloads 435

Authors: Natalia C. E. S. Nascimento, Mercia L. Oliveira, Fernando R. A. Lima, Leonardo T. C. do Nascimento, Marina B. Silveira, Brigida G. A. Schirmer, Andrea V. Ferreira, Carlos Malamut, Juliana B. da Silva

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Tissue hypoxia is a common characteristic of solid tumors leading to decreased sensitivity to radiotherapy and chemotherapy. In the clinical context, tumor hypoxia assessment employing the positron emission tomography (PET) tracer ¹⁸F-fluoromisonidazole ([¹⁸F]FMISO) is helpful for physicians for planning and therapy adjusting. The aim of this work was to implement the synthesis of 18F-FMISO in a TRACERlab® MXFDG module and also to establish the quality control procedure. [¹⁸F]FMISO was synthesized at Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN/Brazil) using an automated synthesizer (TRACERlab® MXFDG, GE) adapted for the production of [¹⁸F]FMISO. The FMISO chemical standard was purchased from ABX. 18O- enriched water was acquired from Center of Molecular Research. Reagent kits containing eluent solution, acetonitrile, ethanol, 2.0 M HCl solution, buffer solution, water for injections and [¹⁸F]FMISO precursor (dissolved in 2 ml acetonitrile) were purchased from ABX. The [¹⁸F]FMISO samples were purified by Solid Phase Extraction method. The quality requirements of [¹⁸F]FMISO are established in the European Pharmacopeia. According to that reference, quality control of [¹⁸F]FMISO should include appearance, pH, radionuclidic identity and purity, radiochemical identity and purity, chemical purity, residual solvents, bacterial endotoxins, and sterility. The duration of the synthesis process was 53 min, with radiochemical yield of (37.00 ± 0.01) % and the specific activity was more than 70 GBq/µmol. The syntheses were reproducible and showed satisfactory results. In relation to the quality control analysis, the samples were clear and colorless at pH 6.0. The spectrum emission, measured by using a High-Purity Germanium Detector (HPGe), presented a single peak at 511 keV and the half-life, determined by the decay method in an activimeter, was (111.0 ± 0.5) min, indicating no presence of radioactive contaminants, besides the desirable radionuclide (¹⁸F). The samples showed concentration of tetrabutylammonium (TBA) < 50μg/mL, assessed by visual comparison to TBA standard applied in the same thin layer chromatographic plate. Radiochemical purity was determined by high performance liquid chromatography (HPLC) and the results were 100%. Regarding the residual solvents tested, ethanol and acetonitrile presented concentration lower than 10% and 0.04%, respectively. Healthy female mice were injected via lateral tail vein with [¹⁸F]FMISO, microPET imaging studies (15 min) were performed after 2 h post injection (p.i), and the biodistribution was analyzed in five-time points (30, 60, 90, 120 and 180 min) after injection. Subsequently, organs/tissues were assayed for radioactivity with a gamma counter. All parameters of quality control test were in agreement to quality criteria confirming that [¹⁸F]FMISO was suitable for use in non-clinical and clinical trials, following the legal requirements for the production of new radiopharmaceuticals in Brazil.

Keywords: automatic radiosynthesis, hypoxic tumors, pharmacopeia, positron emitters, quality requirements

Procedia PDF Downloads 193

Authors: Husham Bayazed

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Purpose of Presentation: Obesity and overweight are among the biggest health challenges of the 21st century, according to the WHO. Obviously, obese individuals suffer different courses of disease – from infections and allergies to cancer- and even respond differently to some treatment options. Of note, obesity often seems to predispose and triggers several secondary diseases such as diabetes, arteriosclerosis, or heart attacks. Since decades it seems that immunological signals gear inflammatory processes among obese individuals with the aforementioned conditions. This review aims to shed light how obesity sparks or rewire the immune system and predisposes to such unpleasant health outcomes. Moreover, lessons from the Covid-19 pandemic ascertain that people living with pre-existing conditions such as obesity can develop severe acute respiratory syndrome (SARS), which needs to be elucidated how obesity and its adjuvant inflammatory process distortion contribute to enhancing severe COVID-19 consequences. Recent Findings: In recent clinical studies, obesity was linked to alter and sparks the immune system in different ways. Adipose tissue (AT) is considered as a secondary immune organ, which is a reservoir of tissue-resident of different immune cells with mediator release, making it a secondary immune organ. Adipocytes per se secrete several pro-inflammatory cytokines (IL-6, IL-4, MCP-1, and TNF-α ) involved in activation of macrophages resulting in chronic low-grade inflammation. The correlation between obesity and T cells dysregulation is pivotal in rewiring the immune system. Of note, autophagy occurrence in adipose tissues further rewire the immune system due to flush and outburst of leptin and adiponectin, which are cytokines and influencing pro-inflammatory immune functions. These immune alterations among obese individuals are collectively incriminated in triggering several metabolic disorders and playing role in increasing cancers incidence and susceptibility to different infections. During COVID-19 pandemic, it was verified that patients with pre-existing obesity being at greater risk of suffering severe and fatal clinical outcomes. Beside obese people suffer from increased airway resistance and reduced lung volume, ACE2 expression in adipose tissue seems to be high and even higher than that in lungs, which spike infection incidence. In essence, obesity with pre-existence of pro-inflammatory cytokines such as LI-6 is a risk factor for cytokine storm and coagulopathy among COVID-19 patients. Summary: It is well documented that obesity is associated with chronic systemic low-grade inflammation, which sparks and alter different pillars of the immune system and triggers different metabolic disorders, and increases susceptibility of infections and cancer incidence. The pre-existing chronic inflammation in obese patients with the augmented inflammatory response against the viral infection seems to increase the susceptibility of these patients to developing severe COVID-19. Although the new weight loss drugs and bariatric surgery are considered as breakthrough news for obesity treatment, but preventing is easier than treating it once it has taken hold. However, obesity and immune system link new insights dispute the role of immunotherapy and regulating immune cells treating diet-induced obesity.

Keywords: immunity, metabolic disorders, cancer, COVID-19

Procedia PDF Downloads 74

Authors: Maria Elisabete da Costa Ferreira

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Violent crimes, such as terrorism, organized crime and homicides, are increasing all around the World. This fact calls for the necessity to reflect upon the effectiveness of the deterrence offered by the criminal sanctions set today. The severity of the penalties depends on the social, cultural and even religious background of the State in question. In some States, such as Portugal, the common citizen finds the sentences too soft on the perpetrator and too long to be obtained. On the other hand, in 2023, several States still apply the death penalty, among which the USA, China, and most Middle Eastern countries. As for life in prison without the possibility of parole, the number of countries accepting this possibility in their criminal law is much higher, including England and Wales, the Netherlands, Moldova, Bulgaria, Italy, Ukraine, Poland, Turkey, Russia, and Serbia. This research aims to demonstrate that both the death penalty and life in prison penalty violate the principles of human dignity and social rehabilitation of the perpetrator and propose alternative penalties that can effectively protect society from crime. The research utilizes three main methodologies: the historical method, the comparative method, and the critical method. The historical method is employed to investigate the evolution of criminal penalties over time. The comparative method is used to compare the practices of different states regarding the death penalty and life in prison penalty. Finally, the critical method is applied to analyze and evaluate the shortcomings of these penalties. From a theoretical point of view, there have been drawn several theories throughout the years to support the idea that perpetrators of crimes should be punished. Today, one of the most commonly accepted theories sustains that the penalty will only be legitimate when necessary to protect society from the perpetrator and to rehabilitate him into society. Foremost, the choice of the penalty and the form of its execution should be guided by the principle of human dignity. The death penalty and life in prison penalty fail to achieve the goal of rehabilitation and disregard the human dignity principle. The right to life is a fundamental right declared in the Universal Declaration of Human Rights and stated in most Constitutions in the World. In conclusion, the research demonstrates that the death penalty and life in prison penalty are in violation of the principles of human dignity and social rehabilitation. These penalties fail to achieve their intended goals and disregard fundamental human rights. Although it may sound tempting to some States to rethink the current system of instated penalties to the admission of these penalties, it is imperative to take the inverse road because the protection of society must be achieved with respect to the perpetrator's fundamental rights, so, alternative penalties must be enforced. Society's belief in its citizen's ability to change must be reinforced, and, ultimately, the belief in Humankind. The findings of this research contribute to the discussion on the use of these penalties and aim to contribute to their decreasing usage in society.

Keywords: death penalty, life in prison penalty, human dignity, rehabilitation

Procedia PDF Downloads 66

Authors: Hilal Turkoglu Sasmazel, Ozan Ozkan, Seda Surucu

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Tissue engineering is the field of treating defects caused by injuries, trauma or acute/chronic diseases by using artificial scaffolds that mimic the extracellular matrix (ECM), the natural biological support for the tissues and cells within the body. The main aspects of a successful artificial scaffold are (i) large surface area in order to provide multiple anchorage points for cells to attach, (ii) suitable porosity in order to achieve 3 dimensional growth of the cells within the scaffold as well as proper transport of nutrition, biosignals and waste and (iii) physical, chemical and biological compatibility of the material in order to obtain viability throughout the healing process. By hybrid scaffolds where two or more different materials were combined with advanced fabrication techniques into complex structures, it is possible to combine the advantages of individual materials into one single structure while eliminating the disadvantages of each. Adding this to the complex structure provided by advanced fabrication techniques enables obtaining the desired aspects of a successful artificial tissue scaffold. In this study, fibroblast compatibility of poly(ε-caprolactone) (PCL)/chitosan core-shell electrospun hybrid scaffolds with proper mechanical, chemical and physical properties successfully developed in our previous study was investigated. Standard 7-day cell culture was carried out with L929 fibroblast cell line. The viability of the cells cultured with the scaffolds was monitored with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) viability assay for every 48 h starting with 24 h after the initial seeding. In this assay, blank commercial tissue culture polystyrene (TCPS) Petri dishes, single electrospun PCL and single electrospun chitosan mats were used as control in order to compare and contrast the performance of the hybrid scaffolds. The adhesion, proliferation, spread and growth of the cells on/within the scaffolds were observed visually on the 3rd and the 7th days of the culture period with confocal laser scanning microscopy (CSLM) and scanning electron microscopy (SEM). The viability assay showed that the hybrid scaffolds caused no toxicity for fibroblast cells and provided a steady increase in cell viability, effectively doubling the cell density for every 48 h for the course of 7 days, as compared to TCPS, single electrospun PCL or chitosan mats. The cell viability on the hybrid scaffold was ~2 fold better compared to TCPS because of its 3D ECM-like structure compared to 2D flat surface of commercially cell compatible TCPS, and the performance was ~2 fold and ~10 fold better compared to single PCL and single chitosan mats, respectively, even though both fabricated similarly with electrospinning as non-woven fibrous structures, because single PCL and chitosan mats were either too hydrophobic or too hydrophilic to maintain cell attachment points. The viability results were verified with visual images obtained with CSLM and SEM, in which cells found to achieve characteristic spindle-like fibroblast shape and spread on the surface as well within the pores successfully at high densities.

Keywords: chitosan, core-shell, fibroblast, electrospinning, PCL

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Authors: Lachin Mikjtarnejad, Mohsen Farzaneh

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Various microbes, such as fungi and bacteria species, are naturally found in the fruit microbiota, and some of them act as a pathogen and result in fruit rot. Among non-pathogenic microbes, yeasts (single-celled microorganisms belonging to the fungi kingdom) can colonize fruit tissues and interact with them without causing any damage to them. Although yeasts are part of the plant microbiota, there is little information about their interactions with plants in comparison with bacteria and filamentous fungi. According to several existing studies, some yeasts can colonize different plant species and have the biological control ability to suppress some of the plant pathogens. It means those specific yeast-colonized plants are more resistant to some plant pathogens. The major objective of the present investigation is to isolate yeast strains from apple fruit and screen their ability to control Penicillium expansum, the causal agent of blue mold of fruits. In the present study, psychrotrophic and epiphytic yeasts were isolated from apple fruits that were stored at low temperatures (0–1°C). Totally, 42 yeast isolates were obtained and identified by molecular analysis based on genomic sequences of the D1/D2 and ITS1/ITS4 regions of their rDNA. All isolated yeasts were primarily screened by' in vitro dual culture assay against P. expansum by measuring the fungus' relative growth inhibition after 10 days of incubation. The results showed that the mycelial growth of P. expansum was reduced between 41–53% when challenged by promising yeast strains. The isolates with the strongest antagonistic activity belonged to Metschnikowia pulcherrima A13, Rhodotorula mucilaginosa A41, Leucosporidium Scottii A26, Aureobasidium pullulans A19, Pichia guilliermondii A32, Cryptococcus flavescents A25, and Pichia kluyveri A40. The results of seven superior isolates to inhibit blue mold decay on fruit showed that isolates A. pullulans A19, L. scottii A26, and Pi. guilliermondii A32 could significantly reduce the fruit rot and decay with 26 mm, 22 mm and 20 mm zone diameter, respectively, compared to the control sample with 43 mm. Our results show Pi. guilliermondii strain A13 was the most effective yeast isolates in inhibiting P. expansum on apple fruits. In addition, various biological control mechanisms of promising biological isolates against blue mold have been evaluated to date, including competition for nutrients and space, production of volatile metabolites, reduction of spore germination, production of siderophores and production of extracellular lytic enzymes such as chitinase and β-1,3-glucanase. However, the competition for nutrients and the ability to inhibit P. expansum spore growth have been introduced as the prevailing mechanisms among them. Accordingly, in our study, isolates A13, A41, A40, A25, A32, A19 and A26 inhibited the germination of P. expansum, whereas isolates A13 and A19 were the strongest inhibitors of P. expansum mycelia growth, causing 89.13% and 81.75 % reduction in the mycelial surface, respectively. All the promising isolates produced chitinase and β-1,3-glucanase after 3, 5 and 7 days of cultivation. Finally, based on our findings, we are proposing that, Pi. guilliermondiias as an effective biocontrol agent and alternative to chemical fungicides to control the blue mold of apple fruit.

Keywords: yeast, yeast enzymes, biocontrol, post harvest diseases

Procedia PDF Downloads 127

Authors: Hilal T. Sasmazel, Seda Surucu

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Skin tissue engineering is a promising field for the treatment of skin defects using scaffolds. This approach involves the use of living cells and biomaterials to restore, maintain, or regenerate tissues and organs in the body by providing; (i) larger surface area for cell attachment, (ii) proper porosity for cell colonization and cell to cell interaction, and (iii) 3-dimensionality at macroscopic scale. Recent studies on this area mainly focus on fabrication of scaffolds that can closely mimic the natural extracellular matrix (ECM) for creation of tissue specific niche-like environment at the subcellular scale. Scaffolds designed as ECM-like architectures incorporating into the host with minimal scarring/pain and facilitate angiogenesis. This study is related to combining of synthetic PCL and natural chitosan polymers to form 3D PCL/Chitosan core-shell structures for skin tissue engineering applications. Amongst the polymers used in tissue engineering, natural polymer chitosan and synthetic polymer poly(ε-caprolactone) (PCL) are widely preferred in the literature. Chitosan has been among researchers for a very long time because of its superior biocompatibility and structural resemblance to the glycosaminoglycan of bone tissue. However, the low mechanical flexibility and limited biodegradability properties reveals the necessity of using this polymer in a composite structure. On the other hand, PCL is a versatile polymer due to its low melting point (60°C), ease of processability, degradability with non-enzymatic processes (hydrolysis) and good mechanical properties. Nevertheless, there are also several disadvantages of PCL such as its hydrophobic structure, limited bio-interaction and susceptibility to bacterial biodegradation. Therefore, it became crucial to use both of these polymers together as a hybrid material in order to overcome the disadvantages of both polymers and combine advantages of those. The scaffolds here were fabricated by using electrospinning technique and the characterizations of the samples were done by contact angle (CA) measurements, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-Ray Photoelectron spectroscopy (XPS). Additionally, gas permeability test, mechanical test, thickness measurement and PBS absorption and shrinkage tests were performed for all type of scaffolds (PCL, chitosan and PCL/chitosan core-shell). By using ImageJ launcher software program (USA) from SEM photographs the average inter-fiber diameter values were calculated as 0.717±0.198 µm for PCL, 0.660±0.070 µm for chitosan and 0.412±0.339 µm for PCL/chitosan core-shell structures. Additionally, the average inter-fiber pore size values exhibited decrease of 66.91% and 61.90% for the PCL and chitosan structures respectively, compare to PCL/chitosan core-shell structures. TEM images proved that homogenous and continuous bead free core-shell fibers were obtained. XPS analysis of the PCL/chitosan core-shell structures exhibited the characteristic peaks of PCL and chitosan polymers. Measured average gas permeability value of produced PCL/chitosan core-shell structure was determined 2315±3.4 g.m-2.day-1. In the future, cell-material interactions of those developed PCL/chitosan core-shell structures will be carried out with L929 ATCC CCL-1 mouse fibroblast cell line. Standard MTT assay and microscopic imaging methods will be used for the investigation of the cell attachment, proliferation and growth capacities of the developed materials.

Keywords: chitosan, coaxial electrospinning, core-shell, PCL, tissue scaffold

Procedia PDF Downloads 481

Authors: G. Kontochristopoulos, T. Spiliopoulos, V. Markantoni, E. Platsidaki, A. Kouris, E. Balamoti, C. Bokotas, G. Haidemenos

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Introduction: There is a high patient demand for periorbital rejuvenation since the facial area is often the first to show visible signs of aging. With advancing age, there are sometimes marked changes that occur in the skin, fat, muscle and bone of the periorbital region, resulting to wrinkles and skin laxity. These changes are among the easiest areas to correct using several minimally invasive techniques, which have become increasingly popular over the last decade. Lasers, radiofrequency, botulinum toxin, fat grafting and fillers are available treatments sometimes in combination to traditional blepharoplasty. This study attempts to show the benefits of a minimally invasive approach to periorbital wrinkles and skin laxity that combine microneedling and 10% trichloroacetic acid (TCA) peels. Method: Eleven female patients aged 34-72 enrolled in the study. They all gave informed consent after receiving detailed information regarding the treatment procedure. Exclusion criteria in the study were previous treatment for the same condition in the past six months, pregnancy, allergy or hypersensitivity to the components, infection, inflammation and photosensitivity on the affected region. All patients had diffuse periorbital wrinkles and mild to moderate upper or lower eyelid skin laxity. They were treated with Automatic Microneedle Therapy System-Handhold and topical application of 10% trichloroacetic acid solution to each periorbital area for five minutes. Needling at a 0,25 mm depth was performed in both latelar (x-y) directions. Subsequently, the peeling agent was applied to each periorbital area for five minutes. Patients were subjected to the above combination every two weeks for a series of four treatments. Subsequently they were followed up regularly every month for two months. The effect was photo-documented. A Physician's and a Patient's Global Assessment Scale was used to evaluate the efficacy of the treatment (0-25% indicated poor response, 25%-50% fair, 50%-75% good and 75%-100% excellent response). Safety was assessed by monitoring early and delayed adverse events. Results: At the end of the study, almost all patients demonstrated significant aesthetic improvement. Physicians assessed a fair and a good improvement in 9(81.8% of patients) and 2(18.1% of patients) participants respectively. Patients Global Assessment rated a fair and a good response in 6 (54.5%) and 5 (45.4%) participants respectively. The procedure was well tolerated and all patients were satisfied. Mild discomfort and transient erythema were quite common during or immediately after the procedure, however only temporary. During the monthly follow up, no complications or scars were observed. Conclusions: Microneedling is known as a simple, office–based collagen induction therapy. Low concentration TCA solution applied to the epidermis that has been more permeable by microneedling, can reach the dermis more effectively. In the present study, chemical peels with 10% TCA acted as an adjuvant to microneedling, as it causes controlled skin damage, promoting regeneration and rejuvenation of tissues. This combined therapy improved periorbital fine lines, wrinkles, and overall appearance of the skin. Thus it constitutes an alternative treatment of periorbital skin aging, with encouraging results and minor side-effects.

Keywords: chemical peels, microneedling, periorbital wrinkles, skin laxity

Procedia PDF Downloads 354

Authors: Aurora Sheehy, Caitlin Prince

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Within current orthodox medical protocols, trauma and mental health issues are deemed to reside within the realm of cognitive or psychological therapists and are marginalised in these areas, in part due to limited drugs option available, mostly manipulating neurotransmitters or sedating patients to reduce symptoms. By contrast, this research presents examples from the clinical practice of how trauma can be assessed and treated physiologically. Adverse Childhood Experiences (ACEs) are a tally of different types of abuse and neglect. It has been used as a measurable and reliable predictor of the likelihood of the development of autoimmune disease. It is a direct way to demonstrate reliably the health impact of traumatic life experiences. A second assessment tool is Allostatic Load, which refers to the cumulative effects that chronic stress has on mental and physical health. It records the decline of an individual’s physiological capacity to cope with their experience. It uses a specific grouping of serum testing and physical measures. It includes an assessment of neuroendocrine, cardiovascular, immune and metabolic systems. Allostatic load demonstrates the health impact that trauma has throughout the body. It forms part of an initial intake assessment in clinical practice and could also be used in research to evaluate treatment. Examining medicinal plants for their physiological, neurological and somatic effects through the lens of Polyvagal theory offers new opportunities for trauma treatments. In situations where Polyvagal theory recommends activities and exercises to enable parasympathetic activation, many herbs that affect Effector Memory T (TEM) cells also enact these responses. Traditional or Indigenous European herbs show the potential to support the polyvagal tone, through multiple mechanisms. As the ventral vagal nerve reaches almost every major organ, plants that have actions on these tissues can be understood via their polyvagal actions, such as monoterpenes as agents to improve respiratory vagal tone, cyanogenic glycosides to reset polyvagal tone, volatile oils rich in phenyl methyl esters improve both sympathetic and parasympathetic tone, bitters activate gut function and can strongly promote parasympathetic regulation. Auricular Acupuncture uses a system of somatotopic mapping of the auricular surface overlaid with an image of an inverted foetus with each body organ and system featured. Given that the concha of the auricle is the only place on the body where the Vagus Nerve neurons reach the surface of the skin, several investigators have evaluated non-invasive, transcutaneous electrical nerve stimulation (TENS) at auricular points. Drawn from an interdisciplinary evidence base and developed through clinical practice, these assessment and treatment tools are examples of practitioners in the field innovating out of necessity for the best outcomes for patients. This paper draws on case studies to direct future research.

Keywords: polyvagal, auricular acupuncture, trauma, herbs

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Authors: Nabil Omar, Farah Jibril, Oraib Amjad

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Purpose: Trabecatine is a is a potent marine-derived antineoplastic drug which binds to the minor groove of the DNA, bending DNA towards the major groove resulting in a changed conformation that interferes with several DNA transcription factors, repair pathways and cell proliferation. Trabectedin was approved by the European Medicines Agency (EMA; London, UK) for the treatment of adult patients with advanced stage soft tissue sarcomas in whom treatment with anthracyclines and ifosfamide has failed, or for those who are not candidates for these therapies. The recommended dosing regimen is 1.5 mg/m2 IV over 24 hours every 3 weeks. The purpose of this study was to comprehensively review available data on the safety and efficacy of trabectedin used as indicated for patients at a Tertiary Cancer Center at Qatar. Methods: A medication administration report generated in the electronic health record identified all patients who received trabectedin between November 1, 2015 and November 1, 2017. This retrospective chart review evaluated the indication of trabectedin use, compliance to administration protocol and the recommended monitoring parameters, number of patients improved on the drug and continued treatment, number of patients discontinued treatment due to side-effects and the reported side effects. Progress and discharged notes were utilized to report experienced side effects during trabectedin therapy. A total of 3 patients were reviewed. Results: Total of 2 out of 3 patients who received trabectedin were receiving it for non-FDA and non-EMA, approved indications; metastatic rhabdomyosarcoma and ovarian cancer stage IV with poor prognosis. And only one patient received it as indicated for leiomyosarcoma of left ureter with metastases to liver, lungs and bone. None of the patients has continued the therapy due to development of serious side effects. One patient had stopped the medication after one cycle due to disease progression and transient hepatic toxicity, the other one had disease progression and developed 12 % reduction in LVEF after 12 cycles of trabectedin, and the third patient deceased, had disease progression on trabectedin after the 10th cycle that was received through peripheral line which resulted in developing extravasation and left arm cellulitis requiring debridement. Regarding monitoring parameters, at baseline the three patients had ECHO, and Creatine Phosphokinase (CPK) but it was not monitored during treatment as recommended. Conclusion: Utilizing this medication as indicated with performing the appropriate monitoring parameters as recommended can benefit patients who are receiving it. It is important to reinforce the intravenous administration via central intravenous line, the re-assessment of left ventricular ejection fraction (LVEF) by echocardiogram or multigated acquisition (MUGA) scan at 2- to 3-month intervals thereafter until therapy is discontinued, and CPK and LFTs levels prior to each administration of trabectedin.

Keywords: trabectedin, drug-use evaluation, safety, effectiveness, adverse drug reaction, monitoring

Procedia PDF Downloads 143

Authors: Saheli Mitra, Ramesh Karri, Praveen K. Mylapalli, Arka. B. Dey, Gourav Bhattacharya, Gouriprasanna Roy, Syed M. Kamil, Surajit Dhara, Sunil K. Sinha, Sajal K. Ghosh

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The most well-known structures of lyotropic liquid crystalline systems are the two dimensional hexagonal phase of cylindrical micelles with a positive interfacial curvature and the lamellar phase of flat bilayers with zero interfacial curvature. In aqueous solution of surfactants, the concentration dependent phase transitions have been investigated extensively. However, instead of changing the surfactant concentrations, the local curvature of an aggregate can be altered by tuning the electrostatic interactions among the constituent molecules. Intermediate phases with non-uniform interfacial curvature are still unexplored steps to understand the route of phase transition from hexagonal to lamellar. Understanding such structural evolution in lyotropic liquid crystalline systems is important as it decides the complex rheological behavior of the system, which is one of the main interests of the soft matter industry. Sodium dodecyl sulfate (SDS) is an anionic surfactant and can be considered as a unique system to tune the electrostatics by cationic additives. In present study, imidazolium-based ionic liquids (ILs) with different number of carbon atoms in their single hydrocarbon chain were used as the additive in the aqueous solution of SDS. At a fixed concentration of total non-aqueous components (SDS and IL), the molar ratio of these components was changed, which effectively altered the electrostatic interactions between the SDS molecules. As a result, the local curvature is observed to modify, and correspondingly, the structure of the hexagonal liquid crystalline phases are transformed into other phases. Polarizing optical microscopy of SDS and imidazole-based-IL systems have exhibited different textures of the liquid crystalline phases as a function of increasing concentration of the ILs. The small angle synchrotron x-ray diffraction (SAXD) study has indicated the hexagonal phase of direct cylindrical micelles to transform to a rectangular phase at the presence of short (two hydrocarbons) chain IL. However, the hexagonal phase is transformed to a lamellar phase at the presence of long (ten hydrocarbons) chain IL. Interestingly, at the presence of a medium (four hydrocarbons) chain IL, the hexagonal phase is transformed to another hexagonal phase of direct cylindrical micelles through the lamellar phase. To the best of our knowledge, such a phase sequence has not been reported earlier. Even though the small angle x-ray diffraction study has revealed the lattice parameters of these phases to be similar to each other, their rheological behavior has been distinctly different. These rheological studies have shed lights on how these phases differ in their viscoelastic behavior. Finally, the packing parameters, calculated for these phases based on the geometry of the aggregates, have explained the formation of the self-assembled aggregates.

Keywords: lyotropic liquid crystals, polarizing optical microscopy, rheology, surfactants, small angle x-ray diffraction

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Authors: Fernanda Piculo, Giovana Vesentini, Gabriela Marini, Debora Cristina Damasceno, Angelica Mercia Pascon Barbosa, Marilza Vieira Cunha Rudge

Abstract:

Introduction: Women with previous gestational diabetes mellitus (GDM) were significantly more likely to have urinary incontinence (UI) and pelvic floor muscle dysfunction compared to non-diabetic women two years after a cesarean section. Additional results demonstrated that induced diabetes causes detrimental effects on pregnant rat urethral muscle. These results indicate the need for exploration of the mechanistic role of a recovery factor in female UI. Chemokine ligand 7 (CCL7) was significantly over expressed in rat serum, urethral and vaginal tissues immediately following induction of stress UI in a rat model simulating birth trauma. CCL7 over expression has shown potency for stimulating targeted stem cell migration and provide a translational link (clinical measurement) which further provide opportunities for treatment. The aim of this study was to investigate the CCL7 levels profile in diabetic pregnant women with urinary incontinence during pregnancy over the first year postpartum. Methods: This study was conducted in the Perinatal Diabetes Research Center of the Botucatu Medical School/UNESP, and was approved by the Research Ethics Committee of the Institution (CAAE: 20639813.0.0000.5411). The diagnosis of GDM was established between 24th and 28th gestational weeks, by the 75 g-OGTT test according to ADA’s criteria. Urinary incontinence was defined according to the International Continence Society and the CCL7 levels was measured by ELISA (R&D Systems, Catalog Number DCC700). Two hundred twelve women were classified into four study groups: normoglycemic continent (NC), normoglycemic incontinent (NI), diabetic continent (DC) and diabetic incontinent (DI). They were evaluated at six-time-points: 12-18, 24-28 and 34-38 gestational weeks, 24-48 hours, 6 weeks and 6-12 months postpartum. Results: At 12-18 weeks, it was possible to consider only two groups, continent and incontinent, because at this early gestational period has not yet been the diagnosis of GDM. The group with GDM and UI (DI group) showed lower levels of CCL7 in all time points during pregnancy and postpartum, compared to normoglycemic groups (NC and NI), indicating that these women have not recovered from child birth induced UI during the 6-12 months postpartum compared to their controls, and that the progression of UI and/or lack of recovery throughout the first postpartum year can be related with lower levels of CCL7. Instead, serum CCL7 was significantly increased in the NC group. Taken together, these findings of overexpression of CCL7 in the NC group and decreased levels in the DI group, could confirm that diabetes delays the recovery from child birth induced UI, and that CCL7 could potentially be used as a serum marker of injury. Conclusion: This study demonstrates lower levels of CCL7 in the DI group during pregnancy and postpartum and suggests that the progression of UI in diabetic women and/or lack of recovery throughout the first postpartum year can be related with low levels of CCL7. This provides a translational potential where CCL7 measurement could be used as a surrogate for injury after delivery. Successful controlled CCL7 mediated stem cell homing to the lower urinary tract could one day introduce the potential for non-operative treatment or prevention of stress urinary incontinence.

Keywords: CCL7, gestational diabetes, pregnancy, urinary incontinence

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Authors: J. Chamorro-Servent, S. Tassani, M. A. Gonzalez-Ballester, L. J. Roca, J. Romeu, O. Camara

Abstract:

Electromagnetic and microwave imaging (MWI) have been used in medical imaging in the last years, being the most common applications of breast cancer and stroke detection or monitoring. In those applications, the subject or zone to observe is surrounded by a number of antennas, and the Nyquist criterium can be satisfied. Additionally, the space between the antennas (transmitting and receiving the electromagnetic fields) and the zone to study can be prepared in a homogeneous scenario. However, this may differ in other cases as could be intracardiac catheters, stomach monitoring devices, pelvic organ systems, liver ablation monitoring devices, or uterine fibroids’ ablation systems. In this work, we analyzed different MWI algorithms to find the most suitable method for dealing with an intrabody scenario. Due to the space limitations usually confronted on those applications, the device would have a cylindrical configuration of a maximum of eight transmitters and eight receiver antennas. This together with the positioning of the supposed device inside a body tract impose additional constraints in order to choose a reconstruction method; for instance, it inhabitants the use of well-known algorithms such as filtered backpropagation for diffraction tomography (due to the unusual configuration with probes enclosed by the imaging region). Finally, the difficulty of simulating a realistic non-homogeneous background inside the body (due to the incomplete knowledge of the dielectric properties of other tissues between the antennas’ position and the zone to observe), also prevents the use of Born and Rytov algorithms due to their limitations with a heterogeneous background. Instead, we decided to use a time-reversed algorithm (mostly used in geophysics) due to its characteristics of ignoring heterogeneities in the background medium, and of focusing its generated field onto the scatters. Therefore, a 2D time-reversed finite difference time domain was developed based on the time-reversed approach for microwave breast cancer detection. Simultaneously an in-silico testbed was also developed to compare ground-truth dielectric properties with corresponding microwave imaging reconstruction. Forward and inverse problems were computed varying: the frequency used related to a small zone to observe (7, 7.5 and 8 GHz); a small polyp diameter (5, 7 and 10 mm); two polyp positions with respect to the closest antenna (aligned or disaligned); and the (transmitters-to-receivers) antenna combination used for the reconstruction (1-1, 8-1, 8-8 or 8-3). Results indicate that when using the existent time-reversed method for breast cancer here for the different combinations of transmitters and receivers, we found false positives due to the high degrees of freedom and unusual configuration (and the possible violation of Nyquist criterium). Those false positives founded in 8-1 and 8-8 combinations, highly reduced with the 1-1 and 8-3 combination, being the 8-3 configuration de most suitable (three neighboring receivers at each time). The 8-3 configuration creates a region-of-interest reduced problem, decreasing the ill-posedness of the inverse problem. To conclude, the proposed algorithm solves the main limitations of the described intrabody application, successfully detecting the angular position of targets inside the body tract.

Keywords: FDTD, time-reversed, medical imaging, microwave imaging

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Authors: Zahirah Dhurmeea, Iker Zudaire, Heidi Pethybridge, Emmanuel Chassot, Maria Cedras, Natacha Nikolic, Jerome Bourjea, Wendy West, Chandani Appadoo, Nathalie Bodin

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Scientific advice on the status of fish stocks relies on indicators that are based on strong assumptions on biological parameters such as condition, maturity and fecundity. Currently, information on the biology of albacore tuna, Thunnus alalunga, in the Indian Ocean is scarce. Consequently, many parameters used in stock assessment models for Indian Ocean albacore originate largely from other studied stocks or species of tuna. Inclusion of incorrect biological data in stock assessment models would lead to inappropriate estimates of stock status used by fisheries manager’s to establish future catch allowances. The reproductive biology of albacore tuna in the western Indian Ocean was examined through analysis of the sex ratio, spawning season, length-at-maturity (L50), spawning frequency, fecundity and fish condition. In addition, the total lipid content (TL) and lipid class composition in the gonads, liver and muscle tissues of female albacore during the reproductive cycle was investigated. A total of 923 female and 867 male albacore were sampled from 2013 to 2015. A bias in sex-ratio was found in favour of females with fork length (LF) <100 cm. Using histological analyses and gonadosomatic index, spawning was found to occur between 10°S and 30°S, mainly to the east of Madagascar from October to January. Large females contributed more to reproduction through their longer spawning period compared to small individuals. The L50 (mean ± standard error) of female albacore was estimated at 85.3 ± 0.7 cm LF at the vitellogenic 3 oocyte stage maturity threshold. Albacore spawn on average every 2.2 days within the spawning region and spawning months from November to January. Batch fecundity varied between 0.26 and 2.09 million eggs and the relative batch fecundity (mean  standard deviation) was estimated at 53.4 ± 23.2 oocytes g-1 of somatic-gutted weight. Depending on the maturity stage, TL in ovaries ranged from 7.5 to 577.8 mg g-1 of wet weight (ww) with different proportions of phospholipids (PL), wax esters (WE), triacylglycerol (TAG) and sterol (ST). The highest TL were observed in immature (mostly TAG and PL) and spawning capable ovaries (mostly PL, WE and TAG). Liver TL varied from 21.1 to 294.8 mg g-1 (ww) and acted as an energy (mainly TAG and PL) storage prior to reproduction when the lowest TL was observed. Muscle TL varied from 2.0 to 71.7 g-1 (ww) in mature females without a clear pattern between maturity stages, although higher values of up to 117.3 g-1 (ww) was found in immature females. TL results suggest that albacore could be viewed predominantly as a capital breeder relying mostly on lipids stored before the onset of reproduction and with little additional energy derived from feeding. This study is the first one to provide new information on the reproductive development and classification of albacore in the western Indian Ocean. The reproductive parameters will reduce uncertainty in current stock assessment models which will eventually promote sustainability of the fishery.

Keywords: condition, size-at-maturity, spawning behaviour, temperate tuna, total lipid content

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Authors: Huan Peng, Chenye Zeng, Zhao Wang

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Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is a leading cause of dementia syndromes and has become a huge burden on society and families. The main pathological features of AD involve excessive deposition of β-amyloid (Aβ) and Tau proteins in the brain, resulting in loss of neurons, expansion of neuroinflammation, and cognitive dysfunction in patients. Researchers have found effective drugs to clear the brain of error-accumulating proteins or to slow the loss of neurons, but their direct administration has key bottlenecks such as single-drug limitation, rapid blood clearance rate, impenetrable blood-brain barrier (BBB), and poor ability to target tissues and cells. Therefore, we are committed to seeking a suitable and efficient delivery system. Inspired by the possibility that exosomes may be involved in the secretion and transport mechanism of many signaling molecules or proteins in the brain, exosomes have attracted extensive attention as natural nanoscale drug carriers. We selected exosomes derived from bone marrow mesenchymal stem cells (MSC-EXO) with low immunogenicity and exosomes derived from hippocampal neurons (HT22-EXO) that may have excellent homing ability to overcome the deficiencies of oral or injectable pathways and bypass the BBB through nasal administration and evaluated their delivery ability and effect on AD. First, MSC-EXO and HT22 cells were isolated and cultured, and MSCs were identified by microimaging and flow cytometry. Then MSC-EXO and HT22-EXO were obtained by gradient centrifugation and qEV SEC separation column, and a series of physicochemical characterization were performed by transmission electron microscope, western blot, nanoparticle tracking analysis and dynamic light scattering. Next, exosomes labeled with lipophilic fluorescent dye were administered to WT mice and APP/PS1 mice to obtain fluorescence images of various organs at different times. Finally, APP/PS1 mice were administered intranasally with two exosomes 20 times over 40 days and 20 μL each time. Behavioral analysis and pathological section analysis of the hippocampus were performed after the experiment. The results showed that MSC-EXO and HT22-EXO were successfully isolated and characterized, and they had good biocompatibility. MSC-EXO showed excellent brain enrichment in APP/PS1 mice after intranasal administration, could improve the neuronal damage and reduce inflammation levels in the hippocampus of APP/PS1 mice, and the improvement effect was significantly better than HT22-EXO. However, intranasal administration of the two exosomes did not cause depression and anxious-like phenotypes in APP/PS1 mice, nor significantly improved the short-term or spatial learning and memory ability of APP/PS1 mice, and had no significant effect on the content of Aβ plaques in the hippocampus, which also meant that MSC-EXO could use their own advantages in combination with other drugs to clear Aβ plaques. The possibility of realizing highly effective non-invasive synergistic treatment for AD provides new strategies and ideas for clinical research.

Keywords: Alzheimer’s disease, exosomes derived from mesenchymal stem cell, intranasal administration, therapy-carrier dual roles

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Authors: Anatoliy A. Alabugin, Nikolay K. Topuzov, Sergei V. Aliukov

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It is well known, that while we do a quantitative evaluation of the quality control of some economic processes (in particular, resource saving) with help innovation factors, there are three groups of problems: high uncertainty of indicators of the quality management, their considerable ambiguity, and high costs to provide a large-scale research. These problems are defined by the use of contradictory objectives of enhancing of the quality control in accordance with innovation factors and preservation of economic stability of the enterprise. The most acutely, such factors are felt in the countries lagging behind developed economies of the world according to criteria of innovativeness and effectiveness of management of the resource saving. In our opinion, the following two methods for reconciling of the above-mentioned objectives and reducing of conflictness of the problems are to solve this task most effectively: 1) the use of paradigms and concepts of evolutionary improvement of quality of resource-saving management in the cycle "from the project of an innovative product (technology) - to its commercialization and update parameters of customer value"; 2) the application of the so-called integrative-cyclical approach which consistent with complexity and type of the concept, to studies allowing to get quantitative assessment of the stages of achieving of the consistency of these objectives (from baseline of imbalance, their compromise to achievement of positive synergies). For implementation, the following mathematical tools are included in the integrative-cyclical approach: index-factor analysis (to identify the most relevant factors); regression analysis of relationship between the quality control and the factors; the use of results of the analysis in the model of fuzzy sets (to adjust the feature space); method of non-parametric statistics (for a decision on the completion or repetition of the cycle in the approach in depending on the focus and the closeness of the connection of indicator ranks of disbalance of purposes). The repetition is performed after partial substitution of technical and technological factors ("hard") by management factors ("soft") in accordance with our proposed methodology. Testing of the proposed approach has shown that in comparison with the world practice there are opportunities to improve the quality of resource-saving management using innovation factors. We believe that the implementation of this promising research, to provide consistent management decisions for reducing the severity of the above-mentioned contradictions and increasing the validity of the choice of resource-development strategies in terms of parameters of quality management and sustainability of enterprise, is perspective. Our existing experience in the field of quality resource-saving management and the achieved level of scientific competence of the authors allow us to hope that the use of the integrative-cyclical approach to the study and evaluation of the resulting and factor indicators will help raise the level of resource-saving characteristics up to the value existing in the developed economies of post-industrial type.

Keywords: integrative-cyclical approach, quality control, evaluation, innovation factors. economic sustainability, innovation cycle of management, disbalance of goals of development

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Authors: Audrey Ngambia, Ondrej Masek, Valentina Erastova

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Biochar is an amorphous carbon-rich material generated from the pyrolysis of biomass with multifarious properties and functionality. Biochar has shown proven applications in the treatment of flue gas and organic and inorganic pollutants in soil and water/wastewater as a result of its multiple surface functional groups and porous structures. These properties have also shown potential in energy storage and carbon capture. The availability of diverse sources of biomass to produce biochar has increased interest in it as a sustainable and environmentally friendly material. The properties and porous structures of biochar vary depending on the type of biomass and high heat treatment temperature (HHT). Biochars produced at HHT between 400°C – 800°C generally have lower H/C and O/C ratios, higher porosities, larger pore sizes and higher surface areas with temperature. While all is known experimentally, there is little knowledge on the porous role structure and functional groups play on processes occurring at the atomistic scale, which are extremely important for the optimization of biochar for application, especially in the adsorption of gases. Atomistic simulations methods have shown the potential to generate such amorphous materials; however, most of the models available are composed of only carbon atoms or graphitic sheets, which are very dense or with simple slit pores, all of which ignore the important role of heteroatoms such as O, N, S and pore morphologies. Hence, developing realistic models that integrate these parameters are important to understand their role in governing adsorption mechanisms that will aid in guiding the design and optimization of biochar materials for target applications. In this work, molecular dynamics simulations in the isobaric ensemble are used to generate realistic biochar models taking into account experimentally determined H/C, O/C, N/C, aromaticity, micropore size range, micropore volumes and true densities of biochars. A pore generation approach was developed using virtual atoms, which is a Lennard-Jones sphere of varying van der Waals radius and softness. Its interaction via a soft-core potential with the biochar matrix allows the creation of pores with rough surfaces while varying the van der Waals radius parameters gives control to the pore-size distribution. We focused on microporosity, creating average pore sizes of 0.5 - 2 nm in diameter and pore volumes in the range of 0.05 – 1 cm3/g, which corresponds to experimental gas adsorption micropore sizes of amorphous porous biochars. Realistic biochar models with surface functionalities, micropore size distribution and pore morphologies were developed, and they could aid in the study of adsorption processes in confined micropores.

Keywords: biochar, heteroatoms, micropore size, molecular dynamics simulations, surface functional groups, virtual atoms

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