Search results for: perceptual present

Authors: Annis Lai Chu Fung

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While aggression had high stability throughout developmental stages and across generations, it should be the top priority of researchers and frontline helping professionals to develop prevention and intervention programme for aggressive children and children at risk of developing aggressive behaviours. Although there is a substantial amount of anti-bullying programmes, they gave disappointingly small effect sizes. The neglectful practical significance could be attributed to the overly simplistic categorisation of individuals involved as bullies or victims. In the past three decades, the distinction between reactive and proactive aggression has been well-proved. As children displaying reactively aggressive behaviours have distinct social-information processing pattern with those showing proactively aggressive behaviours, it is critical to identify the unique needs of the two subtypes accordingly when designing an intervention. The onset of reactive aggression and proactive aggression was observed at earliest in 4.4 and 6.8 years old respectively. Such findings called for a differential early intervention targeting these high-risk children. However, to the best of the author’s knowledge, the author was the first to establish an evidence-based intervention programme against reactive and proactive aggression. With the largest samples in the world, the author, in the past 10 years, explored three different approaches and their effectiveness against aggression quantitatively and qualitatively with longitudinal design. The three approaches presented are (a) cognitive-behavioral approach, (b) moral education, with Chinese marital arts and ethics as the medium, and (c) bioneurological measures (omega-3 supplementation). The studies adopted a multi-informant approach with repeated measures before and after the intervention, and follow-up assessment. Participants were recruited from primary and secondary schools in Hong Kong. In the cognitive-behavioral approach, 66 reactive aggressors and 63 proactive aggressors, aged from 11 to 17, were identified from 10,096 secondary-school children with questionnaire and subsequent structured interview. Participants underwent 10 group sessions specifically designed for each subtype of aggressor. Results revealed significant declines in aggression levels from the baseline to the follow-up assessment after 1 year. In moral education through the Chinese martial arts, 315 high-risk aggressive children, aged 6 to 12 years, were selected from 3,511 primary-school children and randomly assigned into four types of 10-session intervention group, namely martial-skills-only, martial-ethics-only, both martial-skills-and-ethics, and physical fitness (placebo). Results showed only the martial-skills-and-ethics group had a significant reduction in aggression after treatment and 6 months after treatment comparing with the placebo group. In the bioneurological approach, 218 children, aged from 8 to 17, were randomly assigned to the omega-3 supplement group and the placebo group. Results revealed that compared with the placebo group, the omega-3 supplement group had significant declines in aggression levels at the 6-month follow-up assessment. All three approaches were effective in reducing proactive and reactive aggression. Traditionally, intervention programmes against aggressive behaviour often adapted the cognitive and/or behavioural approach. However, cognitive-behavioural approach for children was recently challenged by its demanding requirement of cognitive ability. Traditional cognitive interventions may not be as beneficial to an older population as in young children. The present study offered an insightful perspective in aggression reduction measures.

Keywords: intervention, outcome effectiveness, proactive aggression, reactive aggression

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Authors: Tatiana Rizova

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The migrant crisis, which peaked in 2015-2016, posed an unprecedented challenge to the European Union’s (EU) newest member states, including Bulgaria and Hungary. Their governments had to formulate sound migration policies with expediency and sensitivity to the needs of millions of people fleeing violent conflicts in the Middle East and failed states in North Africa. Political leaders in post-communist countries had to carefully coordinate with other EU member states on joint policies and solutions while minimizing the risk of alienating their increasingly anti-migrant domestic constituents. Post-communist member states’ governments chose distinct policy responses to the crisis, which were dictated by factors such as their governments’ partisan stances on migration, their views of the European Union, and the decision to frame the crisis as a security or a humanitarian issue. This paper explores how two Bulgarian governments (Boyko Borisov’s second and third government formed during the 43rd and 44th Bulgarian National Assembly, respectively) navigated the processes of EU migration policy making and managing the expectations of their electorates. Based on a comparative analysis of refugee policies in Bulgaria and Hungary during the height of the crisis (2015-2016) and a temporal analysis of refugee policies in Bulgaria (2015-2018), the paper advances the following conclusions. Drawing on insights of the Copenhagen school of security studies, the paper argues that cultural concerns dominated domestic debates in both Bulgaria and Hungary; both governments framed the issue predominantly as a matter of security rather than humanitarian disaster. Regardless of the similarities in issue framing, however, the two governments sought different paths of tackling the crisis. While the Bulgarian government demonstrated its willingness to comply with EU decisions (such as the proposal for mandatory quotas for refugee relocation), the Hungarian government defied EU directives and became a leading voice of dissent inside the EU. The current Bulgarian government (April 2017 - present) appears to be committed to complying with EU decisions and accepts the strategy of EU burden-sharing, while the Hungarian government has continually snubbed the EU’s appeals for cooperation despite the risk of hefty financial penalties. Hungary’s refugee policies have been influenced by the parliamentary representation of the far right-wing party Movement for a Better Hungary (Jobbik), which has encouraged the majority party (FIDESZ) to adopt harsher anti-migrant rhetoric and more hostile policies toward refugees. Bulgaria’s current government is a coalition of the center-right Citizens for a European Development of Bulgaria (GERB) and its far right-wing junior partners – the United Patriots (comprised of three nationalist political parties). The parliamentary presence of Jobbik in Hungary’s parliament has magnified the anti-migrant stance, rhetoric, and policies of Mr. Orbán’s Civic Alliance; we have yet to observe a substantial increase in the anti-migrant rhetoric and policies in Bulgaria’s case. Analyzing responses to the migrant/refugee crisis is a critical opportunity to understand how issues of cultural identity and belonging, inclusion and exclusion, regional integration and disintegration are debated and molded into policy in Europe’s youngest member states in the broader EU context.

Keywords: Copenhagen School, migrant crisis, refugees, security

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Authors: F. Madani, M. Doudi, L. Rahimzadeh Torabi

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The irregular consumption of current antibiotics contributes to an escalation in antibiotic resistance among urinary pathogens on a global scale. The objective of this research was to investigate the process of biologically synthesized silver nanoparticles through the utilization of Zataria multiflora extract. Additionally, the study aimed to evaluate the efficacy of these synthesized nanoparticles in inhibiting the growth of multi-drug resistant negative bacillus bacteria, which commonly contribute to urinary tract infections. The botanical specimen utilized in the current research investigation was Z. multiflora, and its extract was produced employing the Soxhlet extraction technique. The study examined the green synthesis conditions of silver nanoparticles by considering three key parameters: the quantity of extract used, the concentration of silver nitrate salt, and the temperature. The particle dimensions were ascertained using the Zetasizer technique. In order to identify synthesized Silver nanoparticles TEM, XRD, and FTIR methods were used. For evaluating the antibacterial effects of nanoparticles synthesized through a biological method, different concentrations of silver nanoparticles were studied on 140 cases of Multiple drug resistance (MDR) bacteria strains Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes, Proteus vulgaris,Citrobacter freundii, Acinetobacter bumanii and Pseudomonas aeruginosa, (each genus of bacteria, 20 samples), which all were MDR and cause urinary tract infections, for identification of bacteria were used of PCR test and laboratory methods (Agar well diffusion and Microdilution methods) to assess their sensitivity to Nanoparticles. The data were subjected to analysis using the statistical software SPSS, specifically employing nonparametric Kruskal-Wallis and Mann-Whitney tests. This study yielded noteworthy findings regarding the impacts of varying concentrations of silver nitrate, different quantities of Z. multiflora extract, and levels of temperature on nanoparticles. Specifically, it was observed that an increase in the concentration of silver nitrate, extract amount, and temperature resulted in a reduction in the size of the nanoparticles synthesized. However, the impact of the aforementioned factors on the index of particle diffusion was found to be statistically non-significant. According to the transmission electron microscopy (TEM) findings, the particles exhibited predominantly spherical morphology, with a diameter spanning from 25 to 50 nanometers. Nanoparticles in the examined sample. Nanocrystals of silver. FTIR method illustrated that the spectrums of Z. multiflora and synthesized nanoparticles had clear peaks in the ranges of 1500-2000, and 3500 - 4000. The obtained results of antibacterial effects of different concentrations of silver nanoparticles on according to agar well diffusion and microdilution method, biologically synthesized nanoparticles showed 1000 mg /ml highest and lowest mean inhibition zone diameter in E. coli, A. bumanii 23 and 15mm, respectively. MIC was observed for all of bacteria 125 mg/ml and for A. bumanii 250 mg/ml. Comparing the growth inhibitory effect of chemically synthesized the results obtained from the experiment indicated that both nanoparticles and biologically synthesized nanoparticles exhibit a notable growth inhibition effect. Specifically, the chemical method of synthesizing nanoparticles demonstrated the highest level of growth inhibition at a concentration of 62.5 mg/mL The present study demonstrated an inhibitory effect on bacterial growth, facilitating the causative factors of urine infection and multidrug resistance (MDR).

Keywords: multiple drug resistance, negative bacillus bacteria, urine infection, Zataria multiflora

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Authors: George Charkoftakis, Panagiotis Liosatos, Nicolas-Alexander Tatlas, Dimitrios Goustouridis, Stelios M. Potirakis

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E-maintenance is a relatively new concept, generally referring to maintenance management by monitoring assets over the Internet. One of the key links in the chain of an e-maintenance system is data acquisition and transmission. Specifically for the case of a fleet of heavy-duty vehicles, where the main challenge is the diversity of the vehicles and vehicle-embedded self-diagnostic/reporting technologies, the design of the data acquisition and transmission unit is a demanding task. This clear if one takes into account that a heavy-vehicles fleet assortment may range from vehicles with only a limited number of analog sensors monitored by dashboard light indicators and gauges to vehicles with plethora of sensors monitored by a vehicle computer producing digital reporting. The present work proposes an adaptable internet of things (IoT) sensor node that is capable of addressing this challenge. The proposed sensor node architecture is based on the increasingly popular single-board computer – expansion boards approach. In the proposed solution, the expansion boards undertake the tasks of position identification by means of a global navigation satellite system (GNSS), cellular connectivity by means of 3G/long-term evolution (LTE) modem, connectivity to on-board diagnostics (OBD), and connectivity to analog and digital sensors by means of a novel design of expansion board. Specifically, the later provides eight analog plus three digital sensor channels, as well as one on-board temperature / relative humidity sensor. The specific device offers a number of adaptability features based on appropriate zero-ohm resistor placement and appropriate value selection for limited number of passive components. For example, although in the standard configuration four voltage analog channels with constant voltage sources for the power supply of the corresponding sensors are available, up to two of these voltage channels can be converted to provide power to the connected sensors by means of corresponding constant current source circuits, whereas all parameters of analog sensor power supply and matching circuits are fully configurable offering the advantage of covering a wide variety of industrial sensors. Note that a key feature of the proposed sensor node, ensuring the reliable operation of the connected sensors, is the appropriate supply of external power to the connected sensors and their proper matching to the IoT sensor node. In standard mode, the IoT sensor node communicates to the data center through 3G/LTE, transmitting all digital/digitized sensor data, IoT device identity, and position. Moreover, the proposed IoT sensor node offers WiFi connectivity to mobile devices (smartphones, tablets) equipped with an appropriate application for the manual registration of vehicle- and driver-specific information, and these data are also forwarded to the data center. All control and communication tasks of the IoT sensor node are performed by dedicated firmware. It is programmed with a high-level language (Python) on top of a modern operating system (Linux). Acknowledgment: This research has been co-financed by the European Union and Greek national funds through the Operational Program Competitiveness, Entrepreneurship, and Innovation, under the call RESEARCH—CREATE—INNOVATE (project code: T1EDK- 01359, IntelligentLogger).

Keywords: IoT sensor nodes, e-maintenance, single-board computers, sensor expansion boards, on-board diagnostics

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Authors: Abouchouaib Belahmira, Joerg W. Schneider, Hafid Saber, Sara Akboub

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The lithofacies analyzed herein were reported from the interbedded fluvial and lacustrine deposits of the Oued Issene and El Menizla formations. These formations are part of the sedimentary fill of the Carboniferous (Stephanian) submontaneous Souss basin. The latter is situated in the western High Atlas Mountains, south-central Morocco, about 50km east of Agadir. The Souss basin started as a single basin but was separated into sub-basins called Ida Ou Zal and Ida Ou Ziki by sinistral displacement along the west branch of the Tizi N'Test Fault during the end of the Mauritanid phase of the Variscan orogeny in Morocco, after the early Stephanian (Kasimovian) and before the late middle Permian (Capitanian). The studied succession is a monotonous finning-upward sequence of 1800 m thick. It consists of fine-grained sandstone, finely bedded siltstone and thinly laminated claystone, and black shale. Herein we provide a detailed characterization of lithofacies of the upper El Menizla and Oued Issène formations, with a focus on the prevailing overbank to flood plain fine-grained lithofacies. The studied facies are capping the Stephanian alluvial fan basal clast-supported conglomerates that are intercalated bedded coarse-grained sandstones of Ikhourba Formation in the Ou Zal subbasin and Tajgaline Formation in the Ida Ou Ziki subbasin, respectively. Within the fluvial elements, only two main facies have been observed. It comprises channel-fill and channel-bar deposits, mostly occur as lenticular –shape sand bodies or sheet-like sand greenish to gray fine-to medium (Fm), massive internally structureless, or very locally exhibits a medium to large scale trough-cross bedding medium to coarse sandstone (St), observable in relatively thicker bed. These facies are laterally extensive, with a thickness varying from a few to several meters. Finer-grained sediments such as mud can be present as drapes over bedforms. Whilst the fluvial association FA1, the overbank elements are represented by a relatively wide range of 5 facies. This exhibit mostly a cm scale horizontally bedded greenish fine- to medium sand and silt, and mm scale fossiliferous thinly laminated dark gray- black Corganic-rich clays to siltstone associated with black shale. Thus, FA2 includes flood plain fines (Fh, R) associated with the paleosols and back swamp coaly clay facies (C). The floodplain lake element comprises only laminated organic-rich dark gray facies of claystone, black shale, and graded siltstone. Bedsets are dm to several meters thick (typically < 1 m thick). They are intercalated between several m-thick fluvial sandstone, extend over a few meters, and are poorly bioturbated. The lacustrine facies described in this study have been divided into two sub-facies (Fl, B) based on field observations that indicate differing environmental conditions of formation. Thus, the thorough analysis of the lithofacies of the Souss basin units allows us to reconstruct the original environment that was interpreted as a typical fluvial-dominated braided to anastomosing wide distributary channel system and surrounding deep to shallow freshwater floodplain lakes and back swamps.

Keywords: Souss, carboniferous, facies, depositional setting

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Authors: Jonas Volungevicius, Kristina Amaleviciute, Rimantas Vaisvalavicius, Alvyra Slepetiene, Darijus Veteikis

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Lithuanian territory is characterized by landscape with prevailing morain hills and clayey lowlands. The largest part of it has endured agrogenization of various degrees which was the cause of changes both in the structure of landscape and soil cover, transformations of soil profile and degradation of natural background soils. These changes influence negatively geoecological potential of landscape and soil and contribute to the weakening of the sustainability of agroecosystems. Research objective: to reveal the landscape agrogenization induced alterations of catenae and their appendant soil profiles in Lithuanian morain hills and clayey lowlands. Methods: Soil cover analysis and catenae charting was conducted using landscape profiling; soil morphology detected and soil type identified following WRB 2014. Granulometric composition of soil profiles was obtained by laser diffraction method (lazer diffractometer Mastersizer 2000). pH was measured in H2O extraction using potentiometric titration; SOC was determined by the Tyurin method modified by Nikitin, measuring with spectrometer Cary 50 (VARIAN) in 590 nm wavelength using glucose standards. Results: analysis showed that the decrease of forest vegetation and the other natural landscape components following the agrogenization of the research area influenced differently but significantly the structural alterations in soil cover and vertical soil profile. The research detected that due to landscape agrogenization, the suppression of zone-specific processes and the intensification of inter-zone processes determined by agrogenic factors take place in Lithuanian agroecosystems. In forested hills historically prevailing Retisols and Histosols territorial complex is transforming into the territorial complex of Regosols, Deluvial soils and drained Histosols. Processes taking place are simplification of vertical profile structure, intensive rejuvenation of profile, disappearance of the features of zone-specific soil-forming processes (podzolization, lessivage, gley formation). Erosion and deluvial processes manifest more intensively and weakly accumulating organic material more intensively spread in a vertical soil profile. The territorial soil complex of Gleyic Luvisols and Gleysols dominating in forested clayey lowlands subjected to agrogenization is transformed into the catena of drained Luvisols and pseudo Cambisols. The best expressed are their changes in moisture regime (morphological features of gley and stagnic properties are on decline) together with alterations of pH and distribution and intensity of accumulation of organic matter in profile. A specific horizon, antraquic, uncharacteristic to natural soil formation is appearing. Important to note that due to deep ploughing and other agrotechnical measures, the natural vertical differentiation of clay particles in a soil profile is destroyed which leads not only to alterations of physical qualities of soil, but also encumbers the identification of Luvisols by creating presumptions to misidentify them as Cambisols. The latter have never developed in these ecosystems under the present climatic conditions. Acknowledgements: This work was supported by the National Science Program: The effect of long-term, different-intensity management of resources on the soils of different genesis and on other components of the agro-ecosystems [grant number SIT-9/2015] funded by the Research Council of Lithuania.

Keywords: agroecosystems, landscape agrogenization, luvisols, retisols, transformation of soil profile

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

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

Keywords: autism, epigenetics, LSD1, personalized medicine

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Authors: M. Doudi, M. H. Pazandeh, L. Rahimzadeh Torabi

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Bedsores are pressure ulcers that occur on the skin or tissue due to being immobile and lying in bed for extended periods. Bedsores have the potential to progress into open ulcers, increasing the possibility of variety of bacterial infection. Acinetobacter baumannii, a pathogen of considerable clinical importance, exhibited a significant correlation with Bedsores (pressure ulcers) infections, thereby manifesting a wide spectrum of antibiotic resistance. The emergence of drug resistance has led researchers to focus on alternative methods, particularly phage therapy, for tackling bacterial infections. Phage therapy has emerged as a novel therapeutic approach to regulate the activity of these agents. The management of bacterial infections greatly benefits from the clinical utilization of bacteriophages as a valuable antimicrobial intervention. The primary objective of this investigation consisted of isolating and discerning potent bacteriophage capable of targeting multi drug-resistant (MDR) and extensively drug-resistant (XDR) bacteria obtained from pressure ulcers. In present study, analyzed and isolated A. baumannii strains obtained from a cohort of patients suffering from pressure ulcers at Taleghani Hospital in Ahvaz, Iran. An approach that included biochemical and molecular identification techniques was used to determine the taxonomic classification of bacterial isolates at the genus and species levels. The molecular identification process was facilitated by using the 16S rRNA gene in combination with universal primers 27 F, and 1492 R. Bacteriophage was obtained through the isolation process conducted on treatment plant sewage located in Isfahan, Iran. The main goal of this study was to evaluate different characteristics of phage, such as their appearance, range of hosts they can infect, how quickly they can enter a host, their stability at varying temperatures and pH levels, their effectiveness in killing bacteria, the growth pattern of a single phage stage, mapping of enzymatic digestion, and identification of proteomics patterns. The findings demonstrated that an examination was conducted on a sample of 50 specimens, wherein 15 instances of A. baumannii were identified. These microorganisms are the predominant Gram-negative agents known to cause wound infections in individuals suffering from bedsores. The study's findings indicated a high prevalence of antibiotic resistance in the strains isolated from pressure ulcers, excluding the clinical strains that exhibited responsiveness to colistin.According to the findings obtained from assessments of host range and morphological characteristics of bacteriophage VbɸAB-1, it can be concluded that this phage possesses specificity towards A. Baumannii BAH_Glau1001 was classified as a member of the Plasmaviridae family. The bacteriophage mentioned earlier showed the strongest antibacterial effect at a temperature of 18 °C and a pH of 6.5. Through the utilization of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis on protein fragments, it was established that the bacteriophage VbɸAB-1 exhibited a size range between 50 and 75 kilodaltons (KDa). The numerous research findings on the effectiveness of phages and the safety studies conducted suggest that the phages studied in this research can be considered as a practical solution and recommended approach for controlling and treating stubborn pathogens in burn wounds among hospitalized patients.

Keywords: acinetobacter baumannii, extremely drug- resistant, phage therapy, surgery wound

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Authors: Wissam Saliba, Mandy Nicholson

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Secretory carcinoma (SC) is a rare type of salivary gland cancer. It was first realized as a distinct type of malignancy in 2010and wasinitially termed “mammary analogue secretory carcinoma” because of similarities with secretory breast cancer. The name was later changed to SC. Most SCs originate in parotid glands, and most harbour a rare gene mutation: ETV6-NTRK3. This mutation is rare in common cancers and common in rare cancers; it is present in most secretory carcinomas. Disease outcomes for SC are usually described as favourable as many cases of SC are lowgrade (LG), and cancer growth is slow. In early stages, localized therapy is usually indicated (surgery and/or radiation). Despitea favourable prognosis, a sub-set of casescan be much more aggressive.These cases tend to be of high-grade(HG).HG casesare associated with a poorer prognosis.Management of such cases can be challenging due to limited evidence for effective systemic therapy options. This case report describes the clinical management of a 46-year-oldmale patient with a unique case of SC. He was initially diagnosed with a low/intermediate grade carcinoma of the left parotid gland in 2009; he was treated with surgery and adjuvant radiation. Surgical pathology favoured primary salivary adenocarcinoma, and 2 lymph nodes were positive for malignancy. SC was not yet realized as a distinct type of cancerat the time of diagnosis, and the pathology reportvalidated this gap by stating that the specimen lacked features of the defined types of salivary carcinoma.Slow-growing pulmonary nodules were identified in 2017. In 2020, approximately 11 years after the initial diagnosis, the patient presented with malignant pleural effusion. Pathology from a pleural biopsy was consistent with metastatic poorly differentiated cancer of likely parotid origin, likely mammary analogue secretory carcinoma. The specimen was sent for Next Generation Sequencing (NGS); ETV6-NTRK3 gene fusion was confirmed, and systemic therapy was initiated.One cycle ofcarboplatin/paclitaxel was given in June 2020. He was switched to Larotrectinib (NTRK inhibitor (NTRKi)) later that month. Larotrectinib continued for approximately 9 months, with discontinuation in March 2021 due to disease progression. A second-generation NTRKi (Selitrectinib) was accessed and prescribedthrough a single patient study. Selitrectinib was well tolerated. The patient experienced a complete radiological response within~4 months. Disease progression occurred once again in October 2021. Progression was slow, and Selitrectinib continuedwhile the medical team performed a thorough search for additional treatment options. In January 2022, a liver lesion biopsy was performed, and NGS showed an NTRKG623R solvent-front resistance mutation. Various treatment pathways were considered. The patient pursuedanother investigational NTRKi through a clinical trial, and Selitrectinib was discontinued in July 2022. Excellent performance status was maintained throughout the entire course of treatment.It can be concluded that NTRK inhibitors provided satisfactory treatment efficacy and tolerance for this patient with high-grade transformation and NTRK gene fusion cancer. In the future, more clinical research is needed on systemic treatment options for high-grade transformations in NTRK gene fusion SCs.

Keywords: secretory carcinoma, high-grade transformations, NTRK gene fusion, NTRK inhibitor

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Authors: Meron Zenaselase Rata, Euridice Leyequien Abarca

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The production of major crops in Northern Ethiopia, especially the Tigray Region, is at subsistence level due to drought, erratic rainfall, and poor soil fertility. Since cactus pear is a drought-resistant plant, it is considered as a lifesaver fruit and a strategy for poverty reduction in a drought-affected area of the region. Despite its contribution to household income and food security in the area, the cactus pear sub-sector is experiencing many constraints with limited attention given to its post-harvest loss management. Therefore, this research was carried out to identify opportunities for reducing post-harvest losses and recommend possible strategies to reduce post-harvest losses, thereby improving production and smallholder’s income. Both probability and non-probability sampling techniques were employed to collect the data. Ganta Afeshum district was selected from Eastern Tigray, and two peasant associations (Buket and Golea) were also selected from the district purposively for being potential in cactus pear production. Simple random sampling techniques were employed to survey 30 households from each of the two peasant associations, and a semi-structured questionnaire was used as a tool for data collection. Moreover, in this research 2 collectors, 2 wholesalers, 1 processor, 3 retailers, 2 consumers were interviewed; and two focus group discussion was also done with 14 key farmers using semi-structured checklist; and key informant interview with governmental and non-governmental organizations were interviewed to gather more information about the cactus pear production, post-harvest losses, the strategies used to reduce the post-harvest losses and suggestions to improve the post-harvest management. To enter and analyze the quantitative data, SPSS version 20 was used, whereas MS-word were used to transcribe the qualitative data. The data were presented using frequency and descriptive tables and graphs. The data analysis was also done using a chain map, correlations, stakeholder matrix, and gross margin. Mean comparisons like ANOVA and t-test between variables were used. The analysis result shows that the present cactus pear value chain involves main actors and supporters. However, there is inadequate information flow and informal market linkages among actors in the cactus pear value chain. The farmer's gross margin is higher when they sell to the processor than sell to collectors. The significant postharvest loss in the cactus pear value chain is at the producer level, followed by wholesalers and retailers. The maximum and minimum volume of post-harvest losses at the producer level is 4212 and 240 kgs per season. The post-harvest loss was caused by limited farmers skill on-farm management and harvesting, low market price, limited market information, absence of producer organization, poor post-harvest handling, absence of cold storage, absence of collection centers, poor infrastructure, inadequate credit access, using traditional transportation system, absence of quality control, illegal traders, inadequate research and extension services and using inappropriate packaging material. Therefore, some of the recommendations were providing adequate practical training, forming producer organizations, and constructing collection centers.

Keywords: cactus pear, post-harvest losses, profit margin, value-chain

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Authors: Pippa Sipanoun, Jo Wray, Kate Oulton, Faith Gibson

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Background: With rapidly evolving digital health innovation, there is a need for digital health transformation that is accessible and sustainable, that demonstrates utility for all stakeholders while maintaining data safety. Great Ormond Street Hospital for Children aimed to future-proof the hospital by transitioning to an electronic patient record (EPR) system with a tethered patient portal (MyGOSH) in April 2019. MyGOSH patient portal enables patients 12 years or older (with their parent's consent) to access their digital health data. This includes access to results, documentation, and appointments that facilitate communication with their care team. As part of the Going Digital Study conducted between 2018-2021, data were collected from a sample of all relevant stakeholders before and after EPR and MyGOSH implementation. Data collection reach was wide and included the hospital legal and ethics teams. Aims: This study aims to understand the ethical and legal implications of young people and their parents accessing their digital health data. Methods: A focus group was conducted. Recruited participants were members of the Great Ormond Street Hospital Paediatric Bioethics Centre. Participants included expert and lay members from the Committee from a variety of professional or academic disciplines. Written informed consent was provided by all participants (n=7). The focus group was recorded, transcribed verbatim, and analyzed using thematic analysis. Results: Six themes were identified: access, competence and capacity - granting access to the system; inequalities in access resulting in inequities; burden, uncertainty and responding to change - managing expectations; documenting, risks and data safety; engagement, empowerment and understanding – how to use and manage personal information; legal considerations and obligations. Discussion: If healthcare professionals are to empower young people to be more engaged in their care, the importance of including them in decisions about their health is paramount, especially when they are approaching the age of becoming the consenter for treatment. Complexities exist in assessing competence or capacity when granting system access, when disclosing sensitive information, and maintaining confidentiality. Difficulties are also present in managing clinician burden, managing user expectations whilst providing an equitable service, and data management that meets professional and legal requirements. Conclusion: EPR and tethered-portal implementation at Great Ormond Street Hospital for Children was not only timely, due to the need for a rapid transition to remote consultations during the COVID-19 pandemic, which would not have been possible had EPR/MyGOSH not been implemented, but also integral to the digital health revolution required in healthcare today. This study is highly relevant in understanding the complexities around young people and their parents accessing their digital health data and, although the focus of this research related to portal use and access, the findings translate to young people in the wider digital health context. Ongoing support is required for all relevant stakeholders following MyGOSH patient portal implementation to navigate the ethical and legal complexities. Continued commitment is needed to balance the benefits and burdens, promote inclusion and equity, and ensure portal utility for patient benefit, whilst maintaining an individualized approach to care.

Keywords: patient portal, young people and their parents, ethical, legal

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Authors: Victor Kang, Sirene Bellahnid, Amy Al-Simaani

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Efficient documentation and completion of clerical tasks are pillars of efficient patient-centered care in acute settings such as the emergency department (ED). Medical scribes aid physicians with documentation, navigation of electronic health records, results gathering, and communication coordination with other healthcare teams. However, the use of medical scribes is not widespread, with some hospitals even continuing to discontinue their programs. One reason for this could be the lack of studies that have outlined concrete improvements in efficiency and patient and provider satisfaction in emergency departments before and after incorporating scribes. Methods: We conducted a review of the literature concerning the implementation of a medical scribe program and emergency department performance. For this review, a narrative synthesis accompanied by textual commentaries was chosen to present the selected papers. PubMed was searched exclusively. Initially, no date limits were set, but seeing as the electronic medical record was officially implemented in Canada in 2013, studies published after this date were preferred as they provided insight into the interplay between its implementation and scribes on quality improvement. Results: Throughput, efficiency, and cost-effectiveness were the most commonly used parameters in evaluating scribes in the Emergency Department. Important throughput metrics, specifically door-to-doctor and disposition time, were significantly decreased in emergency departments that utilized scribes. Of note, this was shown to be the case in community hospitals, where the burden of documentation and clerical tasks would fall directly upon the attending physician. Academic centers differ in that they rely heavily on residents and students; so the implementation of scribes has been shown to have limited effect on these metrics. However, unique to academic centers was the provider’s perception of incrased time for teaching was unique to academic centers. Consequently, providers express increased work satisfaction in relation to time spent with patients and in teaching. Patients, on the other hand, did not demonstrate a decrease in satisfaction in regards to the care that was provided, but there was no significant increase observed either. Of the studies we reviewed, one of the biggest limitations was the lack of significance in the data. While many individual studies reported that medical scribes in emergency rooms improved relative value units, patient satisfaction, provider satisfaction, and increased number of patients seen, there was no statistically significant improvement in the above criteria when compiled in a systematic review. There is also a clear publication bias; very few studies with negative results were published. To prove significance, data from more emergency rooms with scribe programs would need to be compiled which also includes emergency rooms who did not report noticeable benefits. Furthermore, most data sets focused only on scribes in academic centers. Conclusion: Ultimately, the literature suggests that while emergency room physicians who have access to medical scribes report higher satisfaction due to lower clerical burdens and can see more patients per shift, there is still variability in terms of patient and provider satisfaction. Whether or not this variability exists due to differences in training (in-house trainees versus contractors), population profile (adult versus pediatric), setting (academic versus community), or which shifts scribe work cannot be determined based on the studies that exist. Ultimately, more scribe programs need to be evaluated to determine whether these variables affect outcomes and prove whether scribes significantly improve emergency room efficiency.

Keywords: emergency medicine, medical scribe, scribe, documentation

Procedia PDF Downloads 90

Authors: Wellemans Isabelle, Remmelink Myriam, Foucart Annick, Rusu Stefan, Compère Christophe

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Primary pulmonary meningioma (PPM) is a very rare tumor, and its occurrence has been reported only sporadically. Multiple PPMs are even more exceptional, and herein, we report, to the best of our knowledge, the fourth case, focusing on the clinicopathological features of the tumor. Moreover, the possible relationship between the use of progesterone–only contraceptives and the development of these neoplasms will be discussed. Case Report: We report a case of a 51-year-old female presenting three solid pulmonary nodules, with the following localizations: right upper lobe, middle lobe, and left lower lobe, described as incidental findings on computed tomography (CT) during a pre-bariatric surgery check-up. The patient revealed no drinking or smoking history. The physical exam was unremarkable except for the obesity. The lesions ranged in size between 6 and 24 mm and presented as solid nodules with lobulated contours. The largest lesion situated in the middle lobe had mild fluorodeoxyglucose (FDG) uptake on F-18 FDG positron emission tomography (PET)/CT, highly suggestive of primary lung neoplasm. For pathological assessment, video-assisted thoracoscopic middle lobectomy and wedge resection of the right upper nodule was performed. Histological examination revealed relatively well-circumscribed solid proliferation of bland meningothelial cells growing in whorls and lobular nests, presenting intranuclear pseudo-inclusions and psammoma bodies. No signs of anaplasia were observed. The meningothelial cells expressed diffusely Vimentin, focally Progesterone receptors and were negative for epithelial (cytokeratin (CK) AE1/AE3, CK7, CK20, Epithelial Membrane Antigen (EMA)), neuroendocrine markers (Synaptophysin, Chromogranin, CD56) and Estrogenic receptors. The proliferation labelling index Ki-67 was low (<5%). Metastatic meningioma was ruled out by brain and spine magnetic resonance imaging (MRI) scans. The third lesion localized in the left lower lobe was followed-up and resected three years later because of its slow but significant growth (14 mm to 16 mm), alongside two new infra centimetric lesions. Those three lesions showed a morphological and immunohistochemical profile similar to previously resected lesions. The patient was disease-free one year post-last surgery. Discussion: Although PPMs are mostly benign and slow-growing tumors with an excellent prognosis, they do not present specific radiological characteristics, and it is difficult to differentiate it from other lung tumors, histopathologic examination being essential. Aggressive behavior is associated with atypical or anaplastic features (WHO grades II–III) The etiology is still uncertain and different mechanisms have been proposed. A causal connection between sexual hormones and meningothelial proliferation has long been suspected and few studies examining progesterone only contraception and meningioma risk have all suggested an association. In line with this, our patient was treated with Levonorgestrel, a progesterone agonist, intra-uterine device (IUD). Conclusions: PPM, defined by the typical histological and immunohistochemical features of meningioma in the lungs and the absence of central nervous system lesions, is an extremely rare neoplasm, mainly solitary and associating, and indolent growth. Because of the unspecific radiologic findings, it should always be considered in the differential diagnosis of lung neoplasms. Regarding multiple PPM, only three cases are reported in the literature, and this is the first described in a woman treated by a progesterone-only IUD to the best of our knowledge.

Keywords: pulmonary meningioma, multiple meningioma, meningioma, pulmonary nodules

Procedia PDF Downloads 114

Authors: Jan F. Talts, Amit Saxena, Kåre Engkilde

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Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent side effects caused by anti-neoplastic agents, with a prevalence from 19 % to 85 %. Clinically, CIPN is a mostly sensory neuropathy leading to pain and to motor and autonomic changes. Due to its high prevalence among cancer patients, CIPN constitutes a major problem for both cancer patients and survivors, especially because currently, there is no single effective method of preventing CIPN. Hearing loss is the most common form of sensory impairment in humans and can be caused by ototoxic chemical compounds such as chemotherapy (platinum-based antineoplastic agents).In rodents, single or repeated cisplatin injections induce peripheral neuropathy and hearing impairment mimicking human disorder, allowing studying the efficacy of new pharmacological candidates in chemotherapy-induced hearing loss and peripheral neuropathy. RNA sequencing data from full term amniotic fluid (TAF) mesenchymal stemcell (MSC) clones was used to identify neural-specific markers present on TAF-MSC. Several prospective neural markers were tested by flow cytometry on cultured TAF-MSC. One of these markers was used for cell-sorting using Tyto MACSQuant cell sorter, and the neural marker positive cell population was expanded for several passages to the final therapeutic product stage. Peripheral neuropathy and hearing loss was induced in mice by administration of cisplatin in three week-long cycles. The efficacy of neural-specific TAF-MSC in treating hearing loss and pain perception was evaluated by administration of three injections of 3 million cells/kg by intravenous route or three injections of 3 million cells/kg by intra-arterial route after each cisplatin cycle treatment. Auditory brainstem responses (ABR) are electric potentials recorded from scalp electrodes, and the first ABR wave represents the summed activity of the auditory nerve fibers contacting the inner hair cells. For ABR studies, mice were anesthetized, then earphones were placed in the left ear of each mouse, an active electrode was placed in the vertex of the skull, a reference electrode under the skin of the mastoid bone, and a ground electrode in the neck skin. The stimuli consisted of tone pips of five frequencies (2, 4, 6, 12, 16, and 24 kHz) at various sound levels (from 0 to 90 dB) ranging to cover the mouse auditory frequency range. The von Frey test was used to assess the onset and maintenance of mechanical allodynia over time. Mice were placed in clear plexiglass cages on an elevated mesh floor and tested after 30 min of habituation. Mechanical paw withdrawal threshold was examined using an electronic von Frey anesthesiometer. Cisplatin groups treated with three injections of 3 million cells/kg by intravenous route and three injections of 3 million cells/kg by intra-arterial route after each cisplatin cycle treatment presented, a significant increase of hearing acuity characterized by a decrease of ABR threshold and a decrease of neuropathic pain characterized by an increase of von Frey paw withdrawal threshold compared to controls only receiving cisplatin. This study shows that treatment with MSCselected for neural specificity presents significant positive efficacy on the chemotherapy-induced neuropathic pain and the chemotherapy-induced hearing loss.

Keywords: mesenchymal stem cell, peripheral neuropathy, amniotic fluid, regenerative medicine

Procedia PDF Downloads 166

Authors: Marija Mihajlovic Pereira

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Teaching and learning a musical instrument is challenging for both teachers and students. Teachers generally use diverse strategies to resolve students' particular issues in a one-to-one context. Considering individual sessions as a supportive educational context, the teacher can play a decisive role in stimulating and promoting self-regulated learning strategies, especially with beginning learners. The teachers who promote self-controlling behaviors, strategic monitoring, and regulation of actions toward goals could expect their students to practice more qualitatively and consciously. When encouraged to adopt self-regulation habits, students' could benefit from greater productivity on a longer path. Founded on Bary Zimmerman's cyclical model that comprehends three phases - forethought, performance, and self-reflection, this work aims to articulate self-regulated and music learning. Self-regulated learning appeals to the individual's attitude in planning, controlling, and reflecting on their performance. Furthermore, this study aimed to present an observation grid for perceiving teaching instructions that encourage students' controlling cognitive behaviors in light of the belief that conscious promotion of self-regulation may motivate strategic actions toward goals in musical performance. The participants, two teachers, and two students have been involved in the social inclusion project in Lisbon (Portugal). The author and one independent inter-observer analyzed six video-recorded string instrument lessons. The data correspond to three sessions per teacher lectured to one (different) student. Violin (f) and violoncello (m) teachers hold a Master's degree in music education and approximately five years of experience. In their second year of learning an instrument, students have acquired reasonable skills in musical reading, posture, and sound quality until then. The students also manifest positive learning behaviors, interest in learning a musical instrument, although their study habits are still inconsistent. According to the grid's four categories (parent codes), in-class rehearsal frames were coded using MaxQda software, version 20, according to the grid's four categories (parent codes): self-regulated learning, teaching verbalizations, teaching strategies, and students' in-class performance. As a result, selected rehearsal frames qualitatively describe teaching instructions that might promote students' body and hearing awareness, such as "close the eyes while playing" or "sing to internalize the pitch." Another analysis type, coding the short video events according to the observation grid's subcategories (child codes), made it possible to perceive the time teachers dedicate to specific verbal or non-verbal strategies. Furthermore, a coding overlay analysis indicated that teachers tend to stimulate. (i) Forethought – explain tasks, offer feedback and ensure that students identify a goal, (ii) Performance – teach study strategies and encourage students to sing and use vocal abilities to ensure inner audition, (iii) Self-reflection – frequent inquiring and encouraging the student to verbalize their perception of performance. Although developed in the context of individual string instrument lessons, this classroom observation grid brings together essential variables in a one-to-one lesson. It may find utility in a broader context of music education due to the possibility to organize, observe and evaluate teaching practices. Besides that, this study contributes to cognitive development by suggesting a practical approach to fostering self-regulated learning.

Keywords: music education, observation grid, self-regulated learning, string instruments, teaching practices

Procedia PDF Downloads 98

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

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

Keywords: cancer, microtubule dynamics, radiation therapy, radiosensitization

Procedia PDF Downloads 207

Authors: Vipin Bhandari, Anupama Singh, Kopal Gupta

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Solid state fermentation, an eminent bioconversion technique for converting many biological substrates into a value-added product, has proven its role in the biotransformation of crops by nutritionally enriching them. Hence, an effort was made for nutritional enhancement of underutilized crops viz. barnyard millet, amaranthus and horse gram based composite flour using SSF. The grains were given pre-treatments before fermentation and these pre-treatments proved quite effective in diminishing the level of antinutrients in grains and in improving their nutritional characteristics. The present study deals with the enhancement of nutritional characteristics of underutilized crops viz. barnyard millet, amaranthus and horsegram based composite flour using solid state fermentation (SSF) as the principle bioconversion technique to convert the composite flour substrate into a nutritionally enriched value added product. Response surface methodology was used to design the experiments. The variables selected for the fermentation experiments were substrate particle size, substrate blend ratio, fermentation time, fermentation temperature and moisture content having three levels of each. Seventeen designed experiments were conducted randomly to find the effect of these variables on microbial count, reducing sugar, pH, total sugar, phytic acid and water absorption index. The data from all experiments were analyzed using Design Expert 8.0.6 and the response functions were developed using multiple regression analysis and second order models were fitted for each response. Results revealed that pretreatments proved quite handful in diminishing the level of antinutrients and thus enhancing the nutritional value of the grains appreciably, for instance, there was about 23% reduction in phytic acid levels after decortication of barnyard millet. The carbohydrate content of the decorticated barnyard millet increased to 81.5% from initial value of 65.2%. Similarly popping and puffing of horsegram and amaranthus respectively greatly reduced the trypsin inhibitor activity. Puffing of amaranthus also reduced the tannin content appreciably. Bacillus subtilis was used as the inoculating specie since it is known to produce phytases in solid state fermentation systems. These phytases remarkably reduce the phytic acid content which acts as a major antinutritional factor in food grains. Results of solid state fermentation experiments revealed that phytic acid levels reduced appreciably when fermentation was allowed to continue for 72 hours at a temperature of 35°C. Particle size and substrate blend ratio also affected the responses positively. All the parameters viz. substrate particle size, substrate blend ratio, fermentation time, fermentation temperature and moisture content affected the responses namely microbial count, reducing sugar, pH, total sugar, phytic acid and water absorption index but the effect of fermentation time was found to be most significant on all the responses. Statistical analysis resulted in the optimum conditions (particle size 355µ, substrate blend ratio 50:20:30 of barnyard millet, amaranthus and horsegram respectively, fermentation time 68 hrs, fermentation temperature 35°C and moisture content 47%) for maximum reduction in phytic acid. The model F- value was found to be highly significant at 1% level of significance in case of all the responses. Hence, second order model could be fitted to predict all the dependent parameters. The effect of fermentation time was found to be most significant as compared to other variables.

Keywords: composite flour, solid state fermentation, underutilized crops, cereals, fermentation technology, food processing

Procedia PDF Downloads 327

Authors: Gousilin Leandra Rocha Da Silva, Stéfani T. A. Dantas, Bruna F. Rossi, Erika R. Bonsaglia, Ivana G. Castilho, Terue Sadatsune, Ary Fernandes Júnior, Vera l. M. Rall

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Kidney failure causes decreased diuresis and accumulation of nitrogenous substances in the body. To increase patient survival, hemodialysis is used as a partial substitute for renal function. However, contamination of the water used in this treatment, causing bacteremia in patients, is a worldwide concern. The Burkholderia cepacia complex (Bcc), a group of bacteria with more than 20 species, is frequently isolated from hemodialysis water samples and comprises opportunistic bacteria, affecting immunosuppressed patients, due to its wide variety of virulence factors, in addition to innate resistance to several antimicrobial agents, contributing to the permanence in the hospital environment and to the pathogenesis in the host. The objective of the present work was to characterize molecularly and phenotypically Bcc isolates collected from the water and dialysate of the Hemodialysis Unit and from the blood of patients at a Public Hospital in Botucatu, São Paulo, Brazil, between 2019 and 2021. We used 33 Bcc isolates, previously obtained from blood cultures from patients with bacteremia undergoing hemodialysis treatment (2019-2021) and 24 isolates obtained from water and dialysate samples in a Hemodialysis Unit (same period). The recA gene was sequenced to identify the specific species among the Bcc group. All isolates were tested for the presence of some genes that encode virulence factors such as cblA, esmR, zmpA and zmpB. Considering the epidemiology of the outbreak, the Bcc isolates were molecularly characterized by Multi Locus Sequence Type (MLST) and by pulsed-field gel electrophoresis (PFGE). The verification and quantification of biofilm in a polystyrene microplate were performed by submitting the isolates to different incubation temperatures (20°C, average water temperature and 35°C, optimal temperature for group growth). The antibiogram was performed with disc diffusion tests on agar, using discs impregnated with cefepime (30µg), ceftazidime (30µg), ciprofloxacin (5µg), gentamicin (10µg), imipenem (10µg), amikacin 30µg), sulfametazol/trimethoprim (23.75/1.25µg) and ampicillin/sulbactam (10/10µg). The presence of ZmpB was identified in all isolates, while ZmpA was observed in 96.5% of the isolates, while none of them presented the cblA and esmR genes. The antibiogram of the 33 human isolates indicated that all were resistant to gentamicin, colistin, ampicillin/sulbactam and imipenem. 16 (48.5%) isolates were resistant to amikacin and lower rates of resistance were observed for meropenem, ceftazidime, cefepime, ciprofloxacin and piperacycline/tazobactam (6.1%). All isolates were sensitive to sulfametazol/trimethoprim, levofloxacin and tigecycline. As for the water isolates, resistance was observed only to gentamicin (34.8%) and imipenem (17.4%). According to PFGE results, all isolates obtained from humans and water belonged to the same pulsotype (1), which was identified by recA sequencing as B. cepacia¸, belonging to sequence type ST-767. By observing a single pulse type over three years, one can observe the persistence of this isolate in the pipeline, contaminating patients undergoing hemodialysis, despite the routine disinfection of water with peracetic acid. This persistence is probably due to the production of biofilm, which protects bacteria from disinfectants and, making this scenario more critical, several isolates proved to be multidrug-resistant (resistance to at least three groups of antimicrobials), turning the patient care even more difficult.

Keywords: hemodialysis, burkholderia cepacia, PFGE, MLST, multi drug resistance

Procedia PDF Downloads 99

Authors: Sophio Kobauri, Temur Kantaria, Nina Kulikova, David Tugushi, Ramaz Katsarava

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Polymeric nanoparticles-based drug delivery systems and therapeutics have a great potential in the treatment of a numerous diseases, due to they are characterizing the flexible properties which is giving possibility to modify their structures with a complex definition over their structures, compositions and properties. Important characteristics of the polymeric nanoparticles (PNPs) used as drug carriers are high particle’s stability, high carrier capacity, feasibility of encapsulation of both hydrophilic and hydrophobic drugs, and feasibility of variable routes of administration, including oral application and inhalation; NPs are especially effective for intracellular drug delivery since they penetrate into the cells’ interior though endocytosis. A variety of PNPs based drug delivery systems including charged and neutral, degradable and non-degradable polymers of both natural and synthetic origin have been developed. Among these huge varieties the biodegradable PNPs which can be cleared from the body after the fulfillment of their function could be considered as one of the most promising. For intracellular uptake it is highly desirable to have positively charged PNPs since they can penetrate deep into cell membranes. For long-lasting circulation of PNPs in the body it is important they have so called “stealth coatings” to protect them from the attack of immune system of the organism. One of the effective ways to render the PNPs “invisible” for immune system is their PEGylation which represent the process of pretreatment of polyethylene glycol (PEG) on the surface of PNPs. The present work deals with constructing PNPs from amino acid based biodegradable polymers – regular poly(ester amide) (PEA) composed of sebacic acid, leucine and 1,6-hexandiol (labeled as 8L6), cationic PEA composed of sebacic acid, arginine and 1,6-hexandiol (labeled as 8R6), and comb-like co-PEA composed of sebacic acid, malic acid, leucine and 1,6-hexandiol (labeled as PEG-PEA). The PNPs were fabricated using the polymer deposition/solvent displacement (nanoprecipitation) method. The regular PEA 8L6 form stable negatively charged (zeta-potential within 2-12 mV) PNPs of desired size (within 150-200 nm) in the presence of various surfactants (Tween 20, Tween 80, Brij 010, etc.). Blending the PEAs 8L6 and 8R6 gave the 130-140 nm sized positively charged PNPs having zeta-potential within +20 ÷ +28 mV depending 8L6/8R6 ratio. The PEGylating PEA PEG-PEA was synthesized by interaction of epoxy-co-PEA [8L6]0,5-[tES-L6]0,5 with mPEG-amine-2000 The stable and positively charged PNPs were fabricated using pure PEG-PEA as a surfactant. A firm anchoring of the PEG-PEA with 8L6/8R6 based PNPs (owing to a high afinity of the backbones of all three PEAs) provided good stabilization of the NPs. In vitro biocompatibility study of the new PNPs with four different stable cell lines: A549 (human), U-937 (human), RAW264.7 (murine), Hepa 1-6 (murine) showed they are biocompatible. Considering high stability and cell compatibility of the elaborated PNPs one can conclude that they are promising for subsequent therapeutic applications. This work was supported by the joint grant from the Science and Technology Center in Ukraine and Shota Rustaveli National Science Foundation of Georgia #6298 “New biodegradable cationic polymers composed of arginine and spermine-versatile biomaterials for various biomedical applications”.

Keywords: biodegradable poly(ester amide)s, cationic poly(ester amide), pegylating poly(ester amide), nanoparticles

Procedia PDF Downloads 121

Authors: Abbas Ahmadi, Nasser Aliasgharzad, Ali Asghar Jafarzadeh

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Nowadays, drying of the Urmia Lake as a largest saline lake in the world and emerging its saline bed from water has caused the risk of salty dune storms, which threats the health of human society and also plants and animal communities living in the region. Biological soil crusts (BSCs) as a dust stabilizer attracted the attention of Soil conservation experts in recent years. Although the presence of water by the impenetrable lake bed and endorheic basin can be an advantage to create BSCs, but the extraordinary of the lake bed salinity is a factor for prevention of its establishment in the region. Therefore, the present research work has been carried out to investigate the effects of inoculating the Cyanobacteria, algae and their combination to create BSCs for dust control. In this study, an algae attributed to Chlamydomonas sp and a cyanobacteria attributed to Anabaena sp isolated from the soils of Urmia Lake margin were used to create BSC in four soil samples which collected from 0-10 cm of the current margin (A), the previous bed (B), affected lands by lake (C) and Quomtappe sand dune (D). The main characteristics of the A, B and C soil samples are their highly salinity (their ECe are 108, 140 and 118 dS/m, respectively) and sodicity. Also, texture class of the soil A was loamy sand, and other two soils had clay textures. Soil D was Non-saline, but it was sodic with a sandy texture class. This study was conducted separately in each soil in a completely randomized design under four inoculation treatments of non-inoculated (T0), Algae (T1), cyanobacteria (T2) and equal mixture of algae and cyanobacteria (T3) with three replications. In the experiment, the soil was placed into wind tunnel trays, and a suspension containing microorganisms mixed with the trays surface soil. During the experiment, water was sprayed to the trays at the morning and evening of every day. After passing the incubation period (30 days), some characteristics of samples such as pH, EC, cold water extractable carbohydrate (CWEC), hot water extractable carbohydrate (HWEC), sulfuric acid extractable carbohydrate (SAEC), organic matter, crust thickness, penetration resistance, wind erosion threshold velocity and soil loss in the wind tunnel were measured, and Correlation between the measured characteristics was obtained through the SPSS software. Analysis of variance and so comparison between the means of treatments were analyzed with MSTATC software. In this research, Chlorophyll, an amount, was used as an indicator of the microorganism's population in the samples. Based on obtained results, the amount of Chlorophyll a in the T2 treatment of soil A and all treatments of soil D was significantly increased in comparison to the control and crust thickness showed increase in all treatments by microorganism’s inoculation. But effect of the treatments was significant in soils A and D. At all treatment’s inoculation of microorganisms in soil A caused to increase %46, %34 and %55 of the wind erosion threshold velocity in T1, T2 and T3 treatments in comparison to the control, respectively, and in soil D all treatments caused wind erosion threshold velocity became two times more than control. However, soil loss in the wind tunnel experiments was significant in T2 and T3 treatments of these soils and T1 treatment had no effect in reducing soil loss. Correlation between Chlorophyll a and salinity shows the important role of salinity in microbial growth prevention and formation of BSCs in the studied samples. In general, according to the obtained results, it can be concluded that salinity reduces the growth of microorganisms in saline soils of the region, and in soils with fine textures, salinity role in prevention of the microbial growth is clear. Also, using the mix of algae and cyanobacteria together caused the synergistic growth of them and consequently, better protection of the soil against wind erosion was provided.

Keywords: wind erosion, algae, cyanobacteria, carbohydrate

Procedia PDF Downloads 63

Authors: Patrizia Firmani, Sara Perucchini, Irene Rapone, Raffella Borrelli, Stefano Chiaberge, Manuela Grande, Rosamaria Marrazzo, Alberto Savoini, Andrea Siviero, Silvia Spera, Fabio Vago, Davide Deriu, Sergio Fanutti, Alessandro Oldani

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According to the Renewable Energy Directive II, the use of palm oil in diesel will be gradually reduced from 2023 and should reach zero in 2030 due to the deforestation caused by its production. Eni aims at finding alternative feedstocks for its biorefineries to eliminate the use of palm oil by 2023. Therefore, the ideal vegetable oils to be used in bio-refineries are those obtainable from plants that grow in marginal lands and with low impact on food-and-feed chain; hence, Eni research is studying the possibility of using oleaginous seeds, such as castor, croton, and cotton, to extract the oils to be exploited as feedstock in bio-refineries. To verify their suitability for the upgrading processes, an analytical protocol for their characterization has been drawn up and applied. The analytical characterizations include a step of water and ashes content determination, elemental analysis (CHNS analysis, X-Ray Fluorescence, Inductively Coupled Plasma - Optical Emission Spectroscopy, ICP– Mass Spectrometry), and total acid number determination. Gas chromatography coupled to flame ionization detector (GC-FID) is used to quantify the lipid content in terms of free fatty acids, mono-, di- and triacylglycerols, and fatty acids composition. Eventually, Nuclear Magnetic Resonance and Fourier Transform-Infrared spectroscopies are exploited with GC-MS and Fourier Transform-Ion Cyclotron Resonance to study the composition of the oils. This work focuses on the GC-FID analysis of the lipid fraction of these oils, as the main constituent and of greatest interest for bio-refinery processes. Specifically, the lipid component of the extracted oil was quantified after sample silanization and transmethylation: silanization allows the elution of high-boiling compounds and is useful for determining the quantity of free acids and glycerides in oils, while transmethylation leads to a mixture of fatty acid esters and glycerol, thus allowing to evaluate the composition of glycerides in terms of Fatty Acids Methyl Esters (FAME). Cotton oil was extracted from cotton oilcake, croton oil was obtained by seeds pressing and seeds and oilcake ASE extraction, while castor oil comes from seed pressing (not performed in Eni laboratories). GC-FID analyses reported that the cotton oil is 90% constituted of triglycerides and about 6% diglycerides, while free fatty acids are about 2%. In terms of FAME, C18 acids make up 70% of the total and linoleic acid is the major constituent. Palmitic acid is present at 17.5%, while the other acids are in low concentration (<1%). Both analyzes show the presence of non-gas chromatographable compounds. Croton oils from seed pressing and extraction mainly contain triglycerides (98%). Concerning FAME, the main component is linoleic acid (approx. 80%). Oilcake croton oil shows higher abundance of diglycerides (6% vs ca 2%) and a lower content of triglycerides (38% vs 98%) compared to the previous oils. Eventually, castor oil is mostly constituted of triacylglycerols (about 69%), followed by diglycerides (about 10%). About 85.2% of total FAME is ricinoleic acid, as a constituent of triricinolein, the most abundant triglyceride of castor oil. Based on the analytical results, these oils represent feedstocks of interest for possible exploitation as advanced biofuels.

Keywords: analytical protocol, biofuels, biorefinery, gas chromatography, vegetable oil

Procedia PDF Downloads 144

Authors: Agnieszka E. Laudy, Karolina Stępien, Sergiusz Lulinski, Krzysztof Durka, Stefan Tyski

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1,3-dihydro-1-hydroxy-2,1-benzoxaborole and its derivatives are a particularly interesting group of synthetic agents and were successfully employed in supramolecular chemistry medicine. The first important compounds, 5-fluoro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole and 5-chloro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole were identified as potent antifungal agents. In contrast, (S)-3-(aminomethyl)-7-(3-hydroxypropoxy)-1-hydroxy-1,3-dihydro-2,1-benzoxaborole hydrochloride is in the second phase of clinical trials as a drug for the treatment of Gram-negative bacterial infections of the Enterobacteriaceae family and Pseudomonas aeruginosa. Equally important and difficult task is to search for compounds active against Gram-negative bacilli, which have multi-drug-resistance efflux pumps actively removing many of the antibiotics from bacterial cells. We have examined whether halogen-substituted benzoxaborole-based derivatives and their analogues possess antibacterial activity and are substrates for multi-drug-resistance efflux pumps. The antibacterial activity of 1,3-dihydro-3-hydroxy-1,1-dimethyl-1,2,3-benzosiloxaborole and 10 halogen-substituted its derivatives, as well as 1,2-phenylenediboronic acid and 3 synthesised fluoro-substituted its analogs, were evaluated. The activity against the reference strains of Gram-positive (n=5) and Gram-negative bacteria (n=10) was screened by the disc-diffusion test (0.4 mg of tested compounds was applied onto paper disc). The minimal inhibitory concentration values and the minimal bactericidal concentration values were estimated according to The Clinical and Laboratory Standards Institute and The European Committee on Antimicrobial Susceptibility Testing recommendations. During the minimal inhibitory concentration values determination with or without phenylalanine-arginine beta-naphthylamide (50 mg/L) efflux pump inhibitor, the concentrations of tested compounds ranged 0.39-400 mg/L in the broth medium supplemented with 1 mM magnesium sulfate. Generally, the studied benzosiloxaboroles and benzoxadiboroles showed a higher activity against Gram-positive cocci than against Gram-negative rods. Moreover, benzosiloxaboroles have the higher activity than benzoxadiboroles compounds. In this study, we demonstrated that substitution (mono-, di- or tetra-) of 1,3-dihydro-3-hydroxy-1,1-dimethyl-1,2,3-benzosiloxaborole with halogen groups resulted in an increase in antimicrobial activity as compared to the parent substance. Interestingly, the 6,7-dichloro-substituted parent substance was found to be the most potent against Gram-positive cocci: Staphylococcus sp. (minimal inhibitory concentration 6.25 mg/L) and Enterococcus sp. (minimal inhibitory concentration 25 mg/L). On the other hand, mono- and dichloro-substituted compounds were the most actively removed by efflux pumps present in Gram-negative bacteria mainly from Enterobacteriaceae family. In the presence of efflux pump inhibitor the minimal inhibitory concentration values of chloro-substituted benzosiloxaboroles decreased from 400 mg/L to 3.12 mg/L. Of note, the highest increase in bacterial susceptibility to tested compounds in the presence of phenylalanine-arginine beta-naphthylamide was observed for 6-chloro-, 6,7-dichloro- and 6,7-difluoro-substituted benzosiloxaboroles. In the case of Escherichia coli, Enterobacter cloacae and P. aeruginosa strains at least a 32-fold decrease in the minimal inhibitory concentration values of these agents were observed. These data demonstrate structure-activity relationships of the tested derivatives and highlight the need for further search for benzoxaboroles and related compounds with significant antimicrobial properties. Moreover, the influence of phenylalanine-arginine beta-naphthylamide on the susceptibility of Gram-negative rods to studied benzosiloxaboroles indicate that some tested agents are substrates for efflux pumps in Gram-negative rods.

Keywords: antibacterial activity, benzosiloxaboroles, efflux pumps, phenylalanine-arginine beta-naphthylamide

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Authors: Łukasz Mazur, Kamil Domaradzki, Bartosz Kamecki, Justyna Ignaczak, Sebastian Molin, Aleksander Gil, Tomasz Brylewski

Abstract:

The rising global power consumption necessitates the development of new energy storage solutions. Prospective technologies include solid oxide electrolyzer cells (SOECs), which convert surplus electrical energy into hydrogen. An electrolyzer cell consists of a porous anode, and cathode, and a dense electrolyte. Power output is increased by connecting cells into stacks using interconnects. Interconnects are currently made from high-chromium ferritic steels – for example, Crofer 22 APU – which exhibit high oxidation resistance and a thermal expansion coefficient that is similar to that of electrode materials. These materials have one disadvantage – their area-specific resistance (ASR) gradually increases due to the formation of a Cr₂O₃ scale on their surface as a result of oxidation. The chromia in the scale also reacts with the water vapor present in the reaction media, forming volatile chromium oxyhydroxides, which in turn react with electrode materials and cause their deterioration. The electrochemical efficiency of SOECs thus decreases. To mitigate this, the interconnect surface can be modified with protective-conducting coatings of spinel or other materials. The high prices of SOEC components -especially the Crofer 22 APU- have prevented their widespread adoption. More inexpensive counterparts, therefore, need to be found, and their properties need to be enhanced to make them viable. Candidates include the Nirosta 4016/1,4016 low-chromium ferritic steel with a chromium content of just 16.3 wt%. This steel's resistance to high-temperature oxidation was improved by depositing Gd₂O₃ nanoparticles on its surface via either dip coating or electrolysis. Modification with CeO₂ or Ce₀.₉Y₀.₁O₂ nanoparticles deposited by means of spray pyrolysis was also tested. These methods were selected because of their low cost and simplicity of application. The aim of this study was to investigate the oxidation kinetics of Nirosta 4016/1,4016 modified using the afore-mentioned methods and to subsequently measure the obtained samples' ASR. The samples were oxidized for 100 h in the air as well as air/H₂O and Ar/H₂/H₂O mixtures at 1073 K. Such conditions reflect those found in the anode and cathode operating space during real-life use of SOECs. Phase and chemical composition and the microstructure of oxidation products were determined using XRD and SEM-EDS. ASR was measured over the range of 623-1073 K using a four-point, two-probe DC technique. The results indicate that the applied nanoparticles improve the oxidation resistance and electrical properties of the studied layered systems. The properties of individual systems varied significantly depending on the applied reaction medium. Gd₂O₃ nanoparticles improved oxidation resistance to a greater degree than either CeO₂ or Ce₀.₉Y₀.₁O₂ nanoparticles. On the other hand, the cerium-containing nanoparticles improved electrical properties regardless of the reaction medium. The ASR values of all surface-modified steel samples were below the 0.1 Ω.cm² threshold set for interconnect materials, which was exceeded in the case of the unmodified reference sample. It can be concluded that the applied modifications increased the oxidation resistance of Nirosta 4016/1.4016 to a level that allows its use as SOEC interconnect material. Acknowledgments: Funding of Research project supported by program "Excellence initiative – research university" for the AGH University of Krakow" is gratefully acknowledged (TB).

Keywords: cerium oxide, ferritic stainless steel, gadolinium oxide, interconnect, SOEC

Procedia PDF Downloads 87

Authors: Mary-Ann N. Jallad, Dalal F. Jaber, Alexander M. Abdelnoor

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Introduction: Current evidence confirms that both innate and adaptive immune systems are capable of recognizing and abolishing malignant cells. The emergence of cancerous tumors in patients is, therefore, an indication that certain cancer cells can resist elimination by the immune system through a process known as “immune evasion”. In fact, cancer cells often exploit regulatory mechanisms to escape immunity. Such mechanisms normally exist to control the immune responses and prohibit exaggerated or autoimmune reactions. Recently, immunotherapies have shown promising yet limited results. Therefore this study investigates several immunotherapeutic combinations and devises a triple immunotherapy which harnesses the innate and acquired immune responses towards the annihilation of malignant cells through overcoming their ability of immune evasion, consequently hampering malignant progression and eliminating established tumors. The aims of the study are to rule out acute/chronic toxic effects of the proposed treatment combinations, to assess the effect of these combinations on tumor growth and survival rates, and to investigate potential mechanisms underlying the phenotypic results through analyzing serum levels of anti-tumor cytokines, angiogenic factors and tumor progression indicator, and the tumor-infiltrating immune-cells populations. Methodology: For toxicity analysis, cancer-free C57BL/6 mice are randomized into 9 groups: Group 1 untreated, group 2 treated with sterile saline (solvent of used treatments), group 3 treated with Monophosphoryl-lipid-A, group 4 with anti-CTLA4-antibodies, group 5 with 1-Methyl-Tryptophan (Indolamine-Dioxygenase-1 inhibitor), group 6 with both MPLA and anti-CTLA4-antibodies, group 7 with both MPLA and 1-MT, group 8 with both anti-CTLA4-antibodies and 1-MT, and group 9 with all three: MPLA, anti-CTLA4-antibodies and 1-MT. Mice are monitored throughout the treatment period and for three following months. At that point, histological sections from their main organs are assessed. For tumor progression and survival analysis, a murine melanoma model is generated by injecting analogous mice with B16F10 melanoma cells. These mice are segregated into the listed nine groups. Their tumor size and survival are monitored. For a depiction of underlying mechanisms, melanoma-bearing mice from each group are sacrificed at several time-points. Sera are tested to assess the levels of Interleukin-12 (IL-12), Vascular-Endothelial-Growth Factor (VEGF), and S100B. Furthermore, tumors are excised for analysis of infiltrated immune cell populations including T-cells, macrophages, natural killer cells and immune-regulatory cells. Results: Toxicity analysis shows that all treated groups present no signs of neither acute nor chronic toxicity. Their appearance and weights were comparable to those of control groups throughout the treatment period and for the following 3 months. Moreover, histological sections from their hearts, kidneys, lungs, and livers were normal. Work is ongoing for completion of the remaining study aims. Conclusion: Toxicity was the major concern for the success of the proposed comprehensive combinational therapy. Data generated so far ruled out any acute or chronic toxic effects. Consequently, ongoing work is quite promising and may significantly contribute to the development of more effective immunotherapeutic strategies for the treatment of cancer patients.

Keywords: cancer immunotherapy, check-point blockade, combination therapy, melanoma

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Authors: Boris Nemzer, Nebiyu Abshiru, Z. B. Pietrzkowski

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Coffee cherry is one of the most ubiquitous agricultural commodities which possess nutritional and human health beneficial properties. Between the two most widely used coffee cherries Coffea arabica (Arabica) and Coffea canephora (Robusta), Coffea arabica remains superior due to its sensory properties and, therefore, remains in great demand in the global coffee market. In this study, the phytochemical contents and pharmacokinetics of Coffeeberry® Energy (CBE), a commercially available Arabica whole coffee fruit caffeine extract, are investigated. For phytochemical screening, 20 mg of CBE was dissolved in an aqueous methanol solution for analysis by mass spectrometry (MS). Quantification of caffeine and chlorogenic acids (CGAs) contents of CBE was performed using HPLC. For the bioavailability study, serum samples were collected from human subjects before and after 1, 2 and 3 h post-ingestion of 150mg CBE extract. Protein precipitation and extraction were carried out using methanol. Identification of compounds was performed using an untargeted metabolomic approach on Q-Exactive Orbitrap MS coupled to reversed-phase chromatography. Data processing was performed using Thermo Scientific Compound Discover 3.3 software. Phytochemical screening identified a total of 170 compounds, including organic acids, phenolic acids, CGAs, diterpenoids and hydroxytryptamine. Caffeine & CGAs make up more than, respectively, 70% & 9% of the total CBE composition. For serum samples, a total of 82 metabolites representing 32 caffeine- and 50 phenolic-derived metabolites were identified. Volcano plot analysis revealed 32 differential metabolites (24 caffeine- and 8 phenolic-derived) that showed an increase in serum level post-CBE dosing. Caffeine, uric acid, and trimethyluric acid isomers exhibited 4- to 10-fold increase in serum abundance post-dosing. 7-Methyluric acid, 1,7-dimethyluric acid, paraxanthine and theophylline exhibited a minimum of 1.5-fold increase in serum level. Among the phenolic-derived metabolites, iso-feruloyl quinic acid isomers (3-, 4- and 5-iFQA) showed the highest increase in serum level. These compounds were essentially absent in serum collected before dosage. More interestingly, the iFQA isomers were not originally present in the CBE extract, as our phytochemical screen did not identify these compounds. This suggests the potential formation of the isomers during the digestion and absorption processes. Pharmacokinetics parameters (Cmax, Tmax and AUC0-3h) of caffeine- and phenolic-derived metabolites were also investigated. Caffeine was rapidly absorbed, reaching a maximum concentration (Cmax) of 10.95 µg/ml in just 1 hour. Thereafter, caffeine level steadily dropped from the peak level, although it did not return to baseline within the 3-hour dosing period. The disappearance of caffeine from circulation was mirrored by the rise in the concentration of its methylxanthine metabolites. Similarly, serum concentration of iFQA isomers steadily increased, reaching maximum (Cmax: 3-iFQA, 1.54 ng/ml; 4-iFQA, 2.47 ng/ml; 5-iFQA, 2.91 ng/ml) at tmax of 1.5 hours. The isomers remained well above the baseline during the 3-hour dosing period, allowing them to remain in circulation long enough for absorption into the body. Overall, the current study provides evidence of the potential health benefits of a uniquely formulated whole coffee fruit product. Consumption of this product resulted in a distinct serum profile of bioactive compounds, as demonstrated by the more than 32 metabolites that exhibited a significant change in systemic exposure.

Keywords: phytochemicals, mass spectrometry, pharmacokinetics, differential metabolites, chlorogenic acids

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Authors: Aidan Ryan, Nahima Miah, Sahaj Kaur, Imogen Sutherland, Mohamed Saleh

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Pulmonary symptoms are a common presentation to the emergency department. Due to a lack of understanding of the underlying pathophysiology, chronic liver disease is not often considered a cause of dyspnea. We present three patients who were admitted with significant respiratory distress secondary to hepatopulmonary syndrome, portopulmonary hypertension, and hepatic hydrothorax. The first is a 27-year-old male with a 6-month history of progressive dyspnea. The patient developed a severe type 1 respiratory failure with a PaO₂ of 6.3kPa and was escalated to critical care, where he was managed with non-invasive ventilation to maintain oxygen saturation. He had an agitated saline contrast echocardiogram, which showed the presence of a possible shunt. A CT angiogram revealed significant liver cirrhosis, portal hypertension, and large para esophageal varices. Ultrasound of the abdomen showed coarse liver echo patter and enlarged spleen. Along with these imaging findings, his biochemistry demonstrated impaired synthetic liver function with an elevated international normalized ratio (INR) of 1.4 and hypoalbuminaemia of 28g/L. The patient was then transferred to a tertiary center for further management. Further investigations confirmed a shunt of 56%, and liver biopsy confirmed cirrhosis suggestive of alpha-1-antitripsyin deficiency. The findings were consistent with a diagnosis of hepatopulmonary syndrome, and the patient is awaiting a liver transplant. The second patient is a 56-year-old male with a 12-month history of worsening dyspnoea, jaundice, confusion. His medical history included liver cirrhosis, portal hypertension, and grade 1 oesophageal varices secondary to significant alcohol excess. On admission, he developed a type 1 respiratory failure with PaO₂ of 6.8kPa requiring 10L of oxygen. CT pulmonary angiogram was negative for pulmonary embolism but showed evidence of chronic pulmonary hypertension, liver cirrhosis, and portal hypertension. An echocardiogram revealed a grossly dilated right heart with reduced function, pulmonary and tricuspid regurgitation, and pulmonary artery pressures estimated at 78mmHg. His biochemical markers showed impaired synthetic liver function with an INR of 3.2, albumin of 29g/L, along with raised bilirubin of 148mg/dL. During his long admission, he was managed with diuretics with little improvement. After three weeks, he was diagnosed with portopulmonary hypertension and was commenced on terlipressin. This resulted in successfully weaning off oxygen, and he was discharged home. The third patient is a 61-year-old male who presented to the local ambulatory care unit for therapeutic paracentesis on a background of decompensated liver cirrhosis. On presenting, he complained of a 2-day history of worsening dyspnoea and a productive cough. Chest x-ray showed a large pleural effusion, increasing in size over the previous eight months, and his abdomen was visibly distended with ascitic fluid. Unfortunately, the patient deteriorated, developing a larger effusion along with an increase in oxygen demand, and passed away. Without underlying cardiorespiratory disease, in the presence of a persistent pleural effusion with underlying decompensated cirrhosis, he was diagnosed with hepatic hydrothorax. While each presented with dyspnoea, the cause and underlying pathophysiology differ significantly from case to case. By describing these complications, we hope to improve awareness and aid prompt and accurate diagnosis, vital for improving outcomes.

Keywords: dyspnea, hepatic hydrothorax, hepatopulmonary syndrome, portopulmonary syndrome

Procedia PDF Downloads 121

Authors: M. Doudi, M. H. Pazandeh, L. Rahimzadeh Torabi

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Bedsores are pressure ulcers that occur on the skin or tissue due to being immobile and lying in bed for extended periods. Bedsores have the potential to progress into open ulcers, increasing the possibility of a variety of bacterial infections. Acinetobacter baumannii, a pathogen of considerable clinical importance, exhibited a significant correlation with Bedsores (pressure ulcers) infections, thereby manifesting a wide spectrum of antibiotic resistance. The emergence of drug resistance has led researchers to focus on alternative methods, particularly phage therapy, for tackling bacterial infections. Phage therapy has emerged as a novel therapeutic approach to regulate the activity of these agents. The management of bacterial infections greatly benefits from the clinical utilization of bacteriophages as a valuable antimicrobial intervention. The primary objective of this investigation consisted of isolating and discerning potent bacteriophage capable of targeting multi-drug-resistant (MDR) and extensively drug-resistant (XDR) bacteria obtained from pressure ulcers. The present study analyzed and isolated A. baumannii strains obtained from a cohort of patients suffering from pressure ulcers at Taleghani Hospital in Ahvaz, Iran. An approach that included biochemical and molecular identification techniques was used to determine the taxonomic classification of bacterial isolates at the genus and species levels. The molecular identification process was facilitated by using the 16S rRNA gene in combination with universal primers 27 F and 1492 R. Bacteriophage was obtained through the isolation process conducted on treatment plant sewage located in Isfahan, Iran. The main goal of this study was to evaluate different characteristics of phage, such as their appearance, the range of hosts they can infect, how quickly they can enter a host, their stability at varying temperatures and pH levels, their effectiveness in killing bacteria, the growth pattern of a single phage stage, mapping of enzymatic digestion, and identification of proteomics patterns. The findings demonstrated that an examination was conducted on a sample of 50 specimens, wherein 15 instances of A. baumannii were identified. These microorganisms are the predominant Gram-negative agents known to cause wound infections in individuals suffering from bedsores. The study's findings indicated a high prevalence of antibiotic resistance in the strains isolated from pressure ulcers, excluding the clinical strains that exhibited responsiveness to colistin. According to the findings obtained from assessments of host range and morphological characteristics of bacteriophage VbɸAB-1, it can be concluded that this phage possesses specificity towards A. Baumannii BAH_Glau1001 was classified as a member of the Podoviridae family. The bacteriophage mentioned earlier showed the strongest antibacterial effect at a temperature of 18 °C and a pH of 6.5. Through the utilization of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis on protein fragments, it was established that the bacteriophage VbɸAB-1 exhibited a size range between 50 and 75 kilodaltons (KDa). The numerous research findings on the effectiveness of phages and the safety studies conducted suggest that the phages studied in this research can be considered as a practical solution and recommended approach for controlling and treating stubborn pathogens in burn wounds among hospitalized patients. The findings of our research indicated that isolated phages could be an effective antimicrobial and an appreciate candidate for prophylaxis against pressure ulcers.

Keywords: acinetobacter baumannii, extremely drug-resistant, phage therapy, surgery wound

Procedia PDF Downloads 90

Authors: Ayla Hoeta

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In a post-colonial Aotearoa New Zealand, solutions by rangatahi (youth) for rangatahi are essential as is civic participation and building economic agency in an increasingly tough economic climate. Upsouth was an online community crowdsourcing platform developed by The Southern Initiative, in collaboration with Itsnoon that provides rangatahi and whānau (family) a safe space to share lived experience, thoughts and ideas about local kaupapa (issues/topics) of importance to them. The target participants were Māori indigenous peoples and Pacifica groups, aged 14 - 21 years. In the Aotearoa New Zealand context, this participant group is not likely to engage in traditional consultation processes despite being an essential constituent in helping shape better local communities, whānau and futures. The Upsouth platform was active for two years from 2018-2019 where it completed 42 callups with 4300+ participants. The web platform collates the ideas, voices, feedback, and content of users around a callup that has been commissioned by a sponsor, such as Auckland Council, Z Energy or Auckland Transport. A callup may be about a pressing challenge in a community such as climate change, a new housing development, homelessness etc. Each callup was funded by the sponsor with Upsouths main point of difference being that participants are given koha (money donation) through digital wallets for their ideas. Depending on the quality of what participants upload, the koha varies between small micropayments and larger payments. This encouraged participants to develop creative and critical thinking - upskilling for future focussed jobs, enterprise and democratic skills while earning pocket money at the same time. Upsouth enables youth-led action and voice, and empowers them to be a part of a reciprocal and creative economy. Rangatahi are encouraged to express themselves culturally, creatively, freely and in a way they are free to choose - for example, spoken word, song, dance, video, drawings, and/or poems. This challenges and changes what is considered acceptable as community engagement feedback by the local government. Many traditional engagement platforms are not as consultative, do not accept diverse types of feedback, nor incentivise this valuable expression of feedback. Upsouth is also empowering for rangatahi, since it allows them the opportunity to express their opinions directly to the government. Upsouth gained national and international recognition for the way it engages with youth: winning the Supreme Award and the Accessibility and Transparency Award at Auckland Council’s 2018 Engagement Awards, becoming a finalist in the 2018 Digital Equity and Accessibility category of International Data Corporation’s Smart City Asia and Pacific Awards. This paper will fully contextualize the challenges of rangatahi and whānau civic engagement in Aotearoa New Zealand and then present a reflective case study of the Upsouth project, with examples from some of the callups. This is intended to form part of the Divided Cities 22 conference New Ground sub-theme as a critical reflection on a design intervention, which was conceived and implemented by the lead author to overcome the post-colonial divisions of Māori, Pacifica and minority ethnic rangatahi in Aotearoa New Zealand.

Keywords: rangatahi, youth empowerment, civic engagement, enabling, relating, digital platform, participation

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Authors: Keshari Shrestha, Philip Vatterott

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Introduction: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially fatal drug-related syndrome. DRESS classically presents with a diffuse maculopapular rash, fevers, and eosinophilia more than three weeks after drug exposure. DRESS can present with multi-organ involvement, with liver damage being the most common and severe. Pulmonary involvement is a less common manifestation and is associated with poor clinical outcomes. Chest imaging is often nonspecific, and symptoms can range from mild cough to acute respiratory distress syndrome (ARDS) . This is a case of a 49-year-old female with a history of recent clostridium difficile colitis status post treatment with oral vancomycin who presented with rash, acute liver and kidney failure, as well as diffuse nodular alveolar lung opacities concerning for DRESS syndrome with multi-organ involvement. Clinical Course: This patient initially presented to an outside hospital with clostridium difficile colitis, acute liver injury, and acute kidney injury. She developed a desquamating maculopapular rash in the setting of recent oral vancomycin, meloxicam, and furosemide initiation. She was hospitalized on two additional occasions with worsening altered mental status, liver injury, and acute kidney injury and was initiated on intermittent hemodialysis. Notably, she was found to have systemic eosinophilia (4100 cells/microliter) several weeks prior. She was transferred to this institution for further management where she was found to have encephalopathy, jaundice, lower extremity edema, and diffuse bilateral rhonchorous breath sounds on pulmonary examination. The patient was started on methylprednisolone for suspected DRESS syndrome. She underwent an evaluation for alternative causes of her organ failure. Her workup included a negative infectious, autoimmune, metabolic, toxic, and malignant work-up. Abdominal computed tomography (CT) and ultrasound were remarkable for evidence of hepatic steatosis and possible cirrhotic morphology. Additionally, a chest CT demonstrated diffuse and symmetric nodular alveolar lung opacities with peripheral sparing not consistent with acute respiratory distress syndrome or edema. Ultimately, her condition continued to decline, and she required intubation on several occasions. On hospital day 25 she succumbed to distributive shock in the setting of probable sepsis and multi-organ failure. Discussion: DRESS syndrome occurs in 1 in 1,000 to 10,000 patients with a mortality rate of around 10%. Anti-convulsant, anti-bacterial, anti-viral, and sulfonamide drugs are the most common drugs implicated in the development of DRESS syndrome; however, the list of offending agents is extensive . The diagnosis of DRESS syndrome is made after excluding other causes of disease such as infectious and autoimmune etiologies. The RegiSCAR scoring system is used to diagnose DRESS syndrome with 2-3 points indicating possible disease, 4-5 probable disease, and >5 definite disease. This patient scored a 7 on the RegiSCAR scale for eosinophilia, rash, organ involvement, and exclusion of other causes (infectious and autoimmune). While the pharmacologic trigger in this case is unknown, it is speculated to be caused by vancomycin, meloxicam, or furosemide due to the favorable timeline of initiation. Despite aggressive treatment, DRESS syndrome can often be fatal. Because of this, early diagnosis and treatment of patients with suspected DRESS syndrome is imperative.

Keywords: drug reaction with eosinophilia and systemic symptoms, multi-organ failure, pulmonary involvement, renal failure

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Authors: Denis V. Axenov-Gribanov, Irina V. Voytsekhovskaya, Evgenii S. Protasov, Maxim A. Timofeyev

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Isolated ecosystems existing under specific environmental conditions have been shown to be promising sources of new strains of actinobacteria. The taiga forest of Baikal Siberia has not been well studied, and its actinobacterial population remains uncharacterized. The proximity between the huge water mass of Lake Baikal and high mountain ranges influences the structure and diversity of the plant world in Siberia. Here, we report the isolation of eighteen actinobacterial strains from male cones of Pinus sylvestris trees growing on the shore of the ancient Lake Baikal in Siberia. The actinobacterial strains were isolated on solid nutrient MS media and Czapek agar supplemented with cycloheximide and phosphomycin. Identification of actinobacteria was carried out by 16S rRNA gene sequencing and further analysis of the evolutionary history. Four different liquid and solid media (NL19, DNPM, SG and ISP) were tested for metabolite production. The metabolite extracts produced by the isolated strains were tested for antibacterial and antifungal activities. Also, antiradical activity of crude extracts was carried out. Strain Streptomyces sp. IB 2014 I 74-3 that active against Gram-negative bacteria was selected for dereplication analysis with using the high-yield liquid chromatography with mass-spectrometry. Mass detection was performed in both positive and negative modes, with the detection range set to 160–2500 m/z. Data were collected and analyzed using Bruker Compass Data Analysis software, version 4.1. Dereplication was performed using the Dictionary of Natural Products (DNP) database version 6.1 with the following search parameters: accurate molecular mass, absorption spectra and source of compound isolation. Thus, in addition to more common representative strains of Streptomyces, several species belonging to the genera Rhodococcus, Amycolatopsis, and Micromonospora were isolated. Several of the selected strains were deposited in the Russian Collection of Agricultural Microorganisms (RCAM), St. Petersburg, Russia. All isolated strains exhibited antibacterial and antifungal activities. We identified several strains that inhibited the growth of the pathogen Candida albicans but did not hinder the growth of Saccharomyces cerevisiae. Several isolates were active against Gram-positive and Gram-negative bacteria. Moreover, extracts of several strains demonstrated high antioxidant activity. The high proportion of biologically active strains producing antibacterial and specific antifungal compounds may reflect their role in protecting pollen against phytopathogens. Dereplication of the secondary metabolites of the strain Streptomyces sp. IB 2014 I 74-3 was resulted in the fact that a total of 59 major compounds were detected in the culture liquid extract of strain cultivated in ISP medium. Eight compounds were preliminarily identified based on characteristics described in the Dictionary of Natural Products database, using the search parameters Streptomyces sp. IB 2014 I 74-3 was found to produce saframycin A, Y3 and S; 2-amino-3-oxo-3H-phenoxazine-1,8-dicarboxylic acid; galtamycinone; platencin A4-13R and A4-4S; ganefromycin d1; the antibiotic SS 8201B; and streptothricin D, 40-decarbamoyl, 60-carbamoyl. Moreover, forty-nine of the 59 compounds detected in the extract examined in the present study did not result in any positive hits when searching within the DNP database and could not be identified based on available mass-spec data. Thus, these compounds might represent new findings.

Keywords: actinobacteria, Baikal Lake, biodiversity, male cones, Pinus sylvestris

Procedia PDF Downloads 232