Search results for: moisture related issues
Commenced in January 2007
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Paper Count: 13874

Search results for: moisture related issues

44 Young People and Their Parents Accessing Their Digital Health Data via a Patient Portal: The Ethical and Legal Implications

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

Abstract:

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

Procedia PDF Downloads 89
43 Linking the Genetic Signature of Free-Living Soil Diazotrophs with Process Rates under Land Use Conversion in the Amazon Rainforest

Authors: Rachel Danielson, Brendan Bohannan, S.M. Tsai, Kyle Meyer, Jorge L.M. Rodrigues

Abstract:

The Amazon Rainforest is a global diversity hotspot and crucial carbon sink, but approximately 20% of its total extent has been deforested- primarily for the establishment of cattle pasture. Understanding the impact of this large-scale disturbance on soil microbial community composition and activity is crucial in understanding potentially consequential shifts in nutrient or greenhouse gas cycling, as well as adding to the body of knowledge concerning how these complex communities respond to human disturbance. In this study, surface soils (0-10cm) were collected from three forests and three 45-year-old pastures in Rondonia, Brazil (the Amazon state with the greatest rate of forest destruction) in order to determine the impact of forest conversion on microbial communities involved in nitrogen fixation. Soil chemical and physical parameters were paired with measurements of microbial activity and genetic profiles to determine how community composition and process rates relate to environmental conditions. Measuring both the natural abundance of 15N in total soil N, as well as incorporation of enriched 15N2 under incubation has revealed that conversion of primary forest to cattle pasture results in a significant increase in the rate of nitrogen fixation by free-living diazotrophs. Quantification of nifH gene copy numbers (an essential subunit encoding the nitrogenase enzyme) correspondingly reveals a significant increase of genes in pasture compared to forest soils. Additionally, genetic sequencing of both nifH genes and transcripts shows a significant increase in the diversity of the present and metabolically active diazotrophs within the soil community. Levels of both organic and inorganic nitrogen tend to be lower in pastures compared to forests, with ammonium rather than nitrate as the dominant inorganic form. However, no significant or consistent differences in total, extractable, permanganate-oxidizable, or loss-on-ignition carbon are present between the two land-use types. Forest conversion is associated with a 0.5- 1.0 unit pH increase, but concentrations of many biologically relevant nutrients such as phosphorus do not increase consistently. Increases in free-living diazotrophic community abundance and activity appear to be related to shifts in carbon to nitrogen pool ratios. Furthermore, there may be an important impact of transient, low molecular weight plant-root-derived organic carbon on free-living diazotroph communities not captured in this study. Preliminary analysis of nitrogenase gene variant composition using NovoSeq metagenomic sequencing indicates that conversion of forest to pasture may significantly enrich vanadium-based nitrogenases. This indication is complemented by a significant decrease in available soil molybdenum. Very little is known about the ecology of diazotrophs utilizing vanadium-based nitrogenases, so further analysis may reveal important environmental conditions favoring their abundance and diversity in soil systems. Taken together, the results of this study indicate a significant change in nitrogen cycling and diazotroph community composition with the conversion of the Amazon Rainforest. This may have important implications for the sustainability of cattle pastures once established since nitrogen is a crucial nutrient for forage grass productivity.

Keywords: free-living diazotrophs, land use change, metagenomic sequencing, nitrogen fixation

Procedia PDF Downloads 163
42 Uterine Leiomyomas and Urological Complications

Authors: Dharshini Selvarajah, Nicula Lui, Karen Kong

Abstract:

Background: Uterine fibroids are a common benign gynaecologic neoplasm in reproductive-aged women. Fibroids may become symptomatic in a vast majority of nulliparous women. Their diagnosis and management is often coordinated between gyneacologists, radiologists and urologists depending on the anatomical location, growth, size and the fibroids sarcomatous evolvement. Some patients may develop obstructive uropathy symptoms, either uni or bilateral secondary urethral obstruction causing hydronephrosis. Uterine artery emoblisation (UAE) has previously shown to effectively resolve symptoms as well as relieve urethral obstruction and resolve the hydronephrosis. UAE has now established itself as an organ preserving and minimally invasive procedure in the management of symptomatic uterine fibroids. It is a safe and effective alternative to hysterectomy for resolving fibroid related pressure symptoms. The case presented examines the clinical manifestations and impact of uterine fibroids on the urinary tract system. The therapeutic options to relieve the urological symptoms as well as preserve fertility are explored and presented. Case: The case is a 29-year-old Nepalese female admitted to hospital with recurrent urosepsis with multiresistant organisms. This was on a background of an enlarged uterus (measuring 17cm x11cm) with multiple subserosal, intramural and exophytic fibroids- causing external ureteric compression. She had bilateral ureteric stents insitu and required bilateral right and left nephrostomies during repeated episodes of urosepsis and bilateral ureteric obstruction. The left nephrostomy was removed a month prior to admission and her most recent CT KUB demonstrated hypofunctioning ureteric stents with bilateral hydronephrosis. Options of hysterectomy versus uterine artery emoblisation (UAE) were extensively explored. The patient was keen to preserve fertility. Risks associated with UAE such as expulsion of the submucosal component of the fibroids and the possibilities of sepsis in the setting of ongoing ureteric colonisation were particularly high. The patient opted to trial UAE even though the risks of recurrent hospital admissions with urosepsis were going to be particularly high. In the event, the uterus fails to shrink adequately enough to relieve the obstructed ureters a hysterectomy would inevitably be required in future. Day 3 post UAE the patient developed fevers, was hypotensive and tachycardic post-receiving prophylactic meropenem and fluconazole pre emoblisation. She was noted to have a CRP of 293 with the most recent urine culture during this time growing Candida albicans. The patient was recommenced on oral fluconazole and IV meropenem, with good effect. Her repeat renal tract ultrasound post-UAE showed ongoing marked left hydronephrosis relatively unchanged from the scan one month prior to the procedure, however the right-sided hydronephrosis had resolved. The patient was discharged on a 2-week course of antibiotics. The patient will have a repeat renal tract ultrasound and MRI of the ureters to re-evaluate the degree of hydronephrosis and progress- this was unavailable at the time of abstract submission and will be presented at the conference. Conclusion: Fibroids are a common benign tumour of the uterus and can frequently impact the lower urinary system resulting in significant uropathy. They often enlarge and compress the urinary bladder, urethra and lower end of the ureters. The effectiveness of UAE as a fertility preserving option is described.

Keywords: Uterine leiomyomas and urological complications, uterine artery embolisation for fibroids, Uterine fibroids and complications, Management of uterine fibroids

Procedia PDF Downloads 193
41 Impact of Elevated Temperature on Spot Blotch Development in Wheat and Induction of Resistance by Plant Growth Promoting Rhizobacteria

Authors: Jayanwita Sarkar, Usha Chakraborty, Bishwanath Chakraborty

Abstract:

Plants are constantly interacting with various abiotic and biotic stresses. In changing climate scenario plants are continuously modifying physiological processes to adapt to changing environmental conditions which profoundly affect plant-pathogen interactions. Spot blotch in wheat is a fast-rising disease in the warmer plains of South Asia where the rise in minimum average temperature over most of the year already affecting wheat production. Hence, the study was undertaken to explore the role of elevated temperature in spot blotch disease development and modulation of antioxidative responses by plant growth promoting rhizobacteria (PGPR) for biocontrol of spot blotch at high temperature. Elevated temperature significantly increases the susceptibility of wheat plants to spot blotch causing pathogen Bipolaris sorokiniana. Two PGPR Bacillus safensis (W10) and Ochrobactrum pseudogrignonense (IP8) isolated from wheat (Triticum aestivum L.) and blady grass (Imperata cylindrical L.) rhizophere respectively, showing in vitro antagonistic activity against Bipolaris sorokiniana were tested for growth promotion and induction of resistance against spot blotch in wheat. GC-MS analysis showed that Bacillus safensis (W10) and Ochrobactrum pseudogrignonense (IP8) produced antifungal and antimicrobial compounds in culture. Seed priming with these two bacteria significantly increase growth, modulate antioxidative signaling and induce resistance and eventually reduce disease incidence in wheat plants at optimum as well as elevated temperature which was further confirmed by indirect immunofluorescence assay using polyclonal antibody raised against Bipolaris sorokiniana. Application of the PGPR led to enhancement in activities of plant defense enzymes- phenylalanine ammonia lyase, peroxidase, chitinase and β-1,3 glucanase in infected leaves. Immunolocalization of chitinase and β-1,3 glucanase in PGPR primed and pathogen inoculated leaf tissue was further confirmed by transmission electron microscopy using PAb of chitinase, β-1,3 glucanase and gold labelled conjugates. Activity of ascorbate-glutathione redox cycle related enzymes such as ascorbate peroxidase, superoxide dismutase and glutathione reductase along with antioxidants such as carotenoids, glutathione and ascorbate and osmolytes like proline and glycine betain accumulation were also increased during disease development in PGPR primed plant in comparison to unprimed plants at high temperature. Real-time PCR analysis revealed enhanced expression of defense genes- chalcone synthase and phenyl alanineammonia lyase. Over expression of heat shock proteins like HSP 70, small HSP 26.3 and heat shock factor HsfA3 in PGPR primed plants effectively protect plants against spot blotch infection at elevated temperature as compared with control plants. Our results revealed dynamic biochemical cross talk between elevated temperature and spot blotch disease development and furthermore highlight PGPR mediated array of antioxidative and molecular alterations responsible for induction of resistance against spot blotch disease at elevated temperature which seems to be associated with up-regulation of defense genes, heat shock proteins and heat shock factors, less ROS production, membrane damage, increased expression of redox enzymes and accumulation of osmolytes and antioxidants.

Keywords: antioxidative enzymes, defense enzymes, elevated temperature, heat shock proteins, PGPR, Real-Time PCR, spot blotch, wheat

Procedia PDF Downloads 140
40 Implementation of Green Deal Policies and Targets in Energy System Optimization Models: The TEMOA-Europe Case

Authors: Daniele Lerede, Gianvito Colucci, Matteo Nicoli, Laura Savoldi

Abstract:

The European Green Deal is the first internationally agreed set of measures to contrast climate change and environmental degradation. Besides the main target of reducing emissions by at least 55% by 2030, it sets the target of accompanying European countries through an energy transition to make the European Union into a modern, resource-efficient, and competitive net-zero emissions economy by 2050, decoupling growth from the use of resources and ensuring a fair adaptation of all social categories to the transformation process. While the general purpose to allow the realization of the purposes of the Green Deal already dates back to 2019, strategies and policies keep being developed coping with recent circumstances and achievements. However, general long-term measures like the Circular Economy Action Plan, the proposals to shift from fossil natural gas to renewable and low-carbon gases, in particular biomethane and hydrogen, and to end the sale of gasoline and diesel cars by 2035, will all have significant effects on energy supply and demand evolution across the next decades. The interactions between energy supply and demand over long-term time frames are usually assessed via energy system models to derive useful insights for policymaking and to address technological choices and research and development. TEMOA-Europe is a newly developed energy system optimization model instance based on the minimization of the total cost of the system under analysis, adopting a technologically integrated, detailed, and explicit formulation and considering the evolution of the system in partial equilibrium in competitive markets with perfect foresight. TEMOA-Europe is developed on the TEMOA platform, an open-source modeling framework totally implemented in Python, therefore ensuring third-party verification even on large and complex models. TEMOA-Europe is based on a single-region representation of the European Union and EFTA countries on a time scale between 2005 and 2100, relying on a set of assumptions for socio-economic developments based on projections by the International Energy Outlook and a large technological dataset including 7 sectors: the upstream and power sectors for the production of all energy commodities and the end-use sectors, including industry, transport, residential, commercial and agriculture. TEMOA-Europe also includes an updated hydrogen module considering its production, storage, transportation, and utilization. Besides, it can rely on a wide set of innovative technologies, ranging from nuclear fusion and electricity plants equipped with CCS in the power sector to electrolysis-based steel production processes and steel in the industrial sector – with a techno-economic characterization based on public literature – to produce insightful energy scenarios and especially to cope with the very long analyzed time scale. The aim of this work is to examine in detail the scheme of measures and policies for the realization of the purposes of the Green Deal and to transform them into a set of constraints and new socio-economic development pathways. Based on them, TEMOA-Europe will be used to produce and comparatively analyze scenarios to assess the consequences of Green Deal-related measures on the future evolution of the energy mix over the whole energy system in an economic optimization environment.

Keywords: European Green Deal, energy system optimization modeling, scenario analysis, TEMOA-Europe

Procedia PDF Downloads 81
39 Management of Urological Complications Secondary to Uterine Fibroids

Authors: Dharshini Selvarajah, Karen Kong

Abstract:

Background: Uterine fibroids are a common benign gynaecologic neoplasm in reproductive-aged women. Fibroids may become symptomatic in a vast majority of nulliparous women. Their diagnosis and management are often coordinated between gyneacologists, radiologists and urologists depending on the anatomical location, growth, size and the fibroids' sarcomatous evolvement. Some patients may develop obstructive uropathy symptoms, either uni or bilateral secondary urethral obstruction causing hydronephrosis. Uterine artery embolization (UAE) has previously been shown to effectively resolve symptoms as well as relieve urethral obstruction and resolve hydronephrosis. UAE has now established itself as an organ-preserving and minimally invasive procedure in the management of symptomatic uterine fibroids. It is a safe and effective alternative to hysterectomy for resolving fibroid-related pressure symptoms. The case presented examines the clinical manifestations and impact of uterine fibroids on the urinary tract system. The therapeutic options to relieve the urological symptoms as well as preserve fertility are explored and presented. Case: The case is a 29-year-old Nepalese female admitted to the hospital with recurrent urosepsis with multiresistant organisms. This was on a background of an enlarged uterus (measuring 17cm x11cm) with multiple subserosal, intramural and exophytic fibroids- causing external ureteric compression. She had bilateral ureteric stents in situ and required bilateral right and left nephrostomies during repeated episodes of urosepsis and bilateral ureteric obstruction. The left nephrostomy was removed a month prior to admission, and her most recent CT KUB demonstrated hypofunctioning ureteric stents with bilateral hydronephrosis. Options of hysterectomy versus uterine artery embolization (UAE) were extensively explored. The patient was keen to preserve fertility. Risks associated with UAE, such as the expulsion of the submucosal component of the fibroids and the possibilities of sepsis in the setting of ongoing ureteric colonisation were particularly high. The patient opted to trial UAE even though the risks of recurrent hospital admissions with urosepsis were going to be particularly high. In the event, the uterus fails to shrink adequately enough to relieve the obstructed ureters, a hysterectomy would inevitably be required in the future. Day 3 post-UAE the patient developed fevers, was hypotensive and tachycardic post-receiving prophylactic meropenem and fluconazole pre emoblisation. She was noted to have a CRP of 293 with the most recent urine culture during this time growing Candida albicans. The patient was recommenced on oral fluconazole and IV meropenum, with good effect. Her repeat renal tract ultrasound post-UAE showed ongoing marked left hydronephrosis relatively unchanged from the scan one month prior to the procedure; however, the right-sided hydronephrosis had resolved. The patient was discharged on a 2-week course of antibiotics. The patient will have a repeat renal tract ultrasound and MRI of the ureters to re-evaluate the degree of hydronephrosis and progress- this was unavailable at the time of abstract submission and will be presented at the conference. Conclusion: Fibroids are a common benign tumor of the uterus and can frequently impact the lower urinary system resulting in significant uropathy. They often enlarge and compress the urinary bladder, urethra and lower end of the ureters. The effectiveness of the UAE as a fertility-preserving option is described.

Keywords: uterine artery embolisation for fibroids, urological complications from fibroids, uropathy of fibroids, obstructive fibroid management

Procedia PDF Downloads 183
38 Interpretable Deep Learning Models for Medical Condition Identification

Authors: Dongping Fang, Lian Duan, Xiaojing Yuan, Mike Xu, Allyn Klunder, Kevin Tan, Suiting Cao, Yeqing Ji

Abstract:

Accurate prediction of a medical condition with straight clinical evidence is a long-sought topic in the medical management and health insurance field. Although great progress has been made with machine learning algorithms, the medical community is still, to a certain degree, suspicious about the model's accuracy and interpretability. This paper presents an innovative hierarchical attention deep learning model to achieve good prediction and clear interpretability that can be easily understood by medical professionals. This deep learning model uses a hierarchical attention structure that matches naturally with the medical history data structure and reflects the member’s encounter (date of service) sequence. The model attention structure consists of 3 levels: (1) attention on the medical code types (diagnosis codes, procedure codes, lab test results, and prescription drugs), (2) attention on the sequential medical encounters within a type, (3) attention on the medical codes within an encounter and type. This model is applied to predict the occurrence of stage 3 chronic kidney disease (CKD3), using three years’ medical history of Medicare Advantage (MA) members from a top health insurance company. The model takes members’ medical events, both claims and electronic medical record (EMR) data, as input, makes a prediction of CKD3 and calculates the contribution from individual events to the predicted outcome. The model outcome can be easily explained with the clinical evidence identified by the model algorithm. Here are examples: Member A had 36 medical encounters in the past three years: multiple office visits, lab tests and medications. The model predicts member A has a high risk of CKD3 with the following well-contributed clinical events - multiple high ‘Creatinine in Serum or Plasma’ tests and multiple low kidneys functioning ‘Glomerular filtration rate’ tests. Among the abnormal lab tests, more recent results contributed more to the prediction. The model also indicates regular office visits, no abnormal findings of medical examinations, and taking proper medications decreased the CKD3 risk. Member B had 104 medical encounters in the past 3 years and was predicted to have a low risk of CKD3, because the model didn’t identify diagnoses, procedures, or medications related to kidney disease, and many lab test results, including ‘Glomerular filtration rate’ were within the normal range. The model accurately predicts members A and B and provides interpretable clinical evidence that is validated by clinicians. Without extra effort, the interpretation is generated directly from the model and presented together with the occurrence date. Our model uses the medical data in its most raw format without any further data aggregation, transformation, or mapping. This greatly simplifies the data preparation process, mitigates the chance for error and eliminates post-modeling work needed for traditional model explanation. To our knowledge, this is the first paper on an interpretable deep-learning model using a 3-level attention structure, sourcing both EMR and claim data, including all 4 types of medical data, on the entire Medicare population of a big insurance company, and more importantly, directly generating model interpretation to support user decision. In the future, we plan to enrich the model input by adding patients’ demographics and information from free-texted physician notes.

Keywords: deep learning, interpretability, attention, big data, medical conditions

Procedia PDF Downloads 63
37 Nanocarriers Made of Amino Acid Based Biodegradable Polymers: Poly(Ester Amide) and Related Cationic and PEGylating Polymers

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

Abstract:

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

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36 The Impact of Efflux Pump Inhibitor on the Activity of Benzosiloxaboroles and Benzoxadiboroles against Gram-Negative Rods

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

Abstract:

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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35 Understanding Systemic Barriers (and Opportunities) to Increasing Uptake of Subcutaneous Medroxy Progesterone Acetate Self-Injection in Health Facilities in Nigeria

Authors: Oluwaseun Adeleke, Samuel O. Ikani, Fidelis Edet, Anthony Nwala, Mopelola Raji, Simeon Christian Chukwu

Abstract:

Background: The DISC project collaborated with partners to implement demand creation and service delivery interventions, including the MoT (Moment of Truth) innovation, in over 500 health facilities across 15 states. This has increased the voluntary conversion rate to self-injection among women who opt for injectable contraception. While some facilities recorded an increasing trend in key performance indicators, few others persistently performed sub-optimally due to provider and system-related barriers. Methodology: Twenty-two facilities performing sub-optimally were selected purposively from three Nigerian states. Low productivity was appraised using low reporting rates and poor SI conversion rates as indicators. Interviews were conducted with health providers across these health facilities using a rapid diagnosis tool. The project also conducted a data quality assessment that evaluated the veracity of data elements reported across the three major sources of family planning data in the facility. Findings: The inability and sometimes refusal of providers to support clients to self-inject effectively was associated with the misunderstanding of its value to their work experience. It was also observed that providers still held a strong influence over clients’ method choices. Furthermore, providers held biases and misconceptions about DMPA-SC that restricted the access of obese clients and new acceptors to services – a clear departure from the recommendations of the national guidelines. Additionally, quality of care standards was compromised because job aids were not used to inform service delivery. Facilities performing sub-optimally often under-reported DMPA-SC utilization data, and there were multiple uncoordinated responsibilities for recording and reporting. Additionally, data validation meetings were not regularly convened, and these meetings were ineffective in authenticating data received from health facilities. Other reasons for sub-optimal performance included poor documentation and tracking of stock inventory resulting in commodity stockouts, low client flow because of poor positioning of health facilities, and ineffective messaging. Some facilities lacked adequate human and material resources to provide services effectively and received very few supportive supervision visits. Supportive supervision visits and Data Quality Audits have been useful to address the aforementioned performance barriers. The project has deployed digital DMPA-SC self-injection checklists that have been aligned with nationally approved templates. During visits, each provider and community mobilizer is accorded special attention by the supervisor until he/she can perform procedures in line with best practice (protocol). Conclusion: This narrative provides a summary of a range of factors that identify health facilities performing sub-optimally in their provision of DMPA-SC services. Findings from this assessment will be useful during project design to inform effective strategies. As the project enters its final stages of implementation, it is transitioning high-impact activities to state institutions in the quest to sustain the quality of service beyond the tenure of the project. The project has flagged activities, as well as created protocols and tools aimed at placing state-level stakeholders at the forefront of improving productivity in health facilities.

Keywords: family planning, contraception, DMPA-SC, self-care, self-injection, barriers, opportunities, performance

Procedia PDF Downloads 50
34 Stabilizing Additively Manufactured Superalloys at High Temperatures

Authors: Keivan Davami, Michael Munther, Lloyd Hackel

Abstract:

The control of properties and material behavior by implementing thermal-mechanical processes is based on mechanical deformation and annealing according to a precise schedule that will produce a unique and stable combination of grain structure, dislocation substructure, texture, and dispersion of precipitated phases. The authors recently developed a thermal-mechanical technique to stabilize the microstructure of additively manufactured nickel-based superalloys even after exposure to high temperatures. However, the mechanism(s) that controls this stability is still under investigation. Laser peening (LP), also called laser shock peening (LSP), is a shock based (50 ns duration) post-processing technique used for extending performance levels and improving service life of critical components by developing deep levels of plastic deformation, thereby generating high density of dislocations and inducing compressive residual stresses in the surface and deep subsurface of components. These compressive residual stresses are usually accompanied with an increase in hardness and enhance the material’s resistance to surface-related failures such as creep, fatigue, contact damage, and stress corrosion cracking. While the LP process enhances the life span and durability of the material, the induced compressive residual stresses relax at high temperatures (>0.5Tm, where Tm is the absolute melting temperature), limiting the applicability of the technology. At temperatures above 0.5Tm, the compressive residual stresses relax, and yield strength begins to drop dramatically. The principal reason is the increasing rate of solid-state diffusion, which affects both the dislocations and the microstructural barriers. Dislocation configurations commonly recover by mechanisms such as climbing and recombining rapidly at high temperatures. Furthermore, precipitates coarsen, and grains grow; virtually all of the available microstructural barriers become ineffective.Our results indicate that by using “cyclic” treatments with sequential LP and annealing steps, the compressive stresses survive, and the microstructure is stable after exposure to temperatures exceeding 0.5Tm for a long period of time. When the laser peening process is combined with annealing, dislocations formed as a result of LPand precipitates formed during annealing have a complex interaction that provides further stability at high temperatures. From a scientific point of view, this research lays the groundwork for studying a variety of physical, materials science, and mechanical engineering concepts. This research could lead to metals operating at higher sustained temperatures enabling improved system efficiencies. The strengthening of metals by a variety of means (alloying, work hardening, and other processes) has been of interest for a wide range of applications. However, the mechanistic understanding of the often complex processes of interactionsbetween dislocations with solute atoms and with precipitates during plastic deformation have largely remained scattered in the literature. In this research, the elucidation of the actual mechanisms involved in the novel cyclic LP/annealing processes as a scientific pursuit is investigated through parallel studies of dislocation theory and the implementation of advanced experimental tools. The results of this research help with the validation of a novel laser processing technique for high temperature applications. This will greatly expand the applications of the laser peening technology originally devised only for temperatures lower than half of the melting temperature.

Keywords: laser shock peening, mechanical properties, indentation, high temperature stability

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33 Drug Reaction with Eosinophilia and Systemic Symptoms (Dress) Syndrome Presenting as Multi-Organ Failure

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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32 Biotech Processes to Recover Valuable Fraction from Buffalo Whey Usable in Probiotic Growth, Cosmeceutical, Nutraceutical and Food Industries

Authors: Alberto Alfano, Sergio D’ambrosio, Darshankumar Parecha, Donatella Cimini, Chiara Schiraldi.

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The main objective of this study regards the setup of an efficient small-scale platform for the conversion of local renewable waste materials, such as whey, into added-value products, thereby reducing environmental impact and costs deriving from the disposal of processing waste products. The buffalo milk whey derived from the cheese-making process, called second cheese whey, is the main by-product of the dairy industry. Whey is the main and most polluting by-product obtained from cheese manufacturing consisting of lactose, lactic acid, proteins, and salts, making whey an added-value product. In Italy, and in particular, in the Campania region, soft cheese production needs a large volume of liquid waste, especially during late spring and summer. This project is part of a circular economy perspective focused on the conversion of potentially polluting and difficult to purify waste into a resource to be exploited, and it embodies the concept of the three “R”: reduce, recycle, and reuse. Special focus was paid to the production of health-promoting biomolecules and biopolymers, which may be exploited in different segments of the food and pharmaceutical industries. These biomolecules may be recovered through appropriate processes and reused in an attempt to obtain added value products. So, ultrafiltration and nanofiltration processes were performed to fractionate bioactive components starting from buffalo milk whey. In this direction, the present study focused on the implementation of a downstream process that converts waste generated from food and food processing industries into added value products with potential applications. Owing to innovative downstream and biotechnological processes, rather than a waste product may be considered a resource to obtain high added value products, such as food supplements (probiotics), cosmeceuticals, biopolymers, and recyclable purified water. Besides targeting gastrointestinal disorders, probiotics such as Lactobacilli have been reported to improve immunomodulation and protection of the host against infections caused by viral and bacterial pathogens. Interestingly, also inactivated microbial (probiotic) cells and their metabolic products, indicated as parabiotic and postbiotics, respectively, have a crucial role and act as mediators in the modulation of the host’s immune function. To boost the production of biomass (both viable and/or heat inactivated cells) and/or the synthesis of growth-related postbiotics, such as EPS, efficient and sustainable fermentation processes are necessary. Based on a “zero-waste” approach, wastes generated from local industries can be recovered and recycled to develop sustainable biotechnological processes to obtain probiotics as well as post and parabiotic, to be tested as bioactive compounds against gastrointestinal disorders. The results have shown it was possible to recover an ultrafiltration retentate with suitable characteristics to be used in skin dehydration, to perform films (i.e., packaging for food industries), or as a wound repair agent and a nanofiltration retentate to recover lactic acid and carbon sources (e.g., lactose, glucose..) used for microbial cultivation. On the side, the last goal is to obtain purified water that can be reused throughout the process. In fact, water reclamation and reuse provide a unique and viable opportunity to augment traditional water supplies, a key issue nowadays.

Keywords: biotech process, downstream process, probiotic growth, from waste to product, buffalo whey

Procedia PDF Downloads 43
31 Optical Coherence Tomography in Differentiation of Acute and Non-Healing Wounds

Authors: Ananya Barui, Provas Banerjee, Jyotirmoy Chatterjee

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Application of optical technology in medicine and biology has a long track-record. In this endeavor, OCT is able to attract both engineers and biologists to work together in the field of photonics for establishing a striking non-invasive imaging technology. In contrast to other in vivo imaging modalities like Raman imaging, confocal imaging, two-photon microscopy etc. which can perform in vivo imaging upto 100-200 micron depth due to limitation in numerical aperture or scattering, however, OCT can achieve high-resolution imaging upto few millimeters of tissue structures depending on their refractive index in different anatomical location. This tomographic system depends on interference of two light waves in an interferometer to produce a depth profile of specimen. In wound healing, frequent collection of biopsies for follow-up of repair process could be avoided by such imaging technique. Real time skin OCT (the optical biopsy) has efficacy in deeper and faster illumination of cutaneou tissue to acquire high resolution cross sectional images of their internal micro-structure. Swept Source-OCT (SS-OCT), a novel imaging technique, can generate high-speed depth profile (~ 2 mm) of wound at a sweeping rate of laser with micron level resolution and optimum coherent length of 5-6 mm. Normally multi-layered skin tissue depicts different optical properties along with variation in thickness, refractive index and composition (i.e. keratine layer, water, fat etc.) according to their anatomical location. For instance, stratum corneum, the upper-most and relatively dehydrated layer of epidermis reflects more light and produces more lucid and a sharp demarcation line with rest of the hydrated epidermal region. During wound healing or regeneration, optical properties of cutaneous tissue continuously altered with maturation of wound bed. More mature and less hydrated tissue component reflects more light and becomes visible as a brighter area in comparison to immature region which content higher amount water or fat that depicts as a darker area in OCT image. Non-healing wound possess prolonged inflammation and inhibits nascent proliferative stage. Accumulation of necrotic tissues also prevents the repair of non-healing wounds. Due to high resolution and potentiality to reflect the compositional aspects of tissues in terms of their optical properties, this tomographic method may facilitate in differentiating non-healing and acute wounds in addition to clinical observations. Non-invasive OCT offers better insight regarding specific biological status of tissue in health and pathological conditions, OCT images could be associated with histo-pathological ‘gold standard’. This correlated SS-OCT and microscopic evaluation of the wound edges can provide information regarding progressive healing and maturation of the epithelial components. In the context of searching analogy between two different imaging modalities, their relative performances in imaging of healing bed were estimated for probing an alternative approach. Present study validated utility of SS-OCT in revealing micro-anatomic structure in the healing bed with newer information. Exploring precise correspondence of OCT images features with histo-chemical findings related to epithelial integrity of the regenerated tissue could have great implication. It could establish the ‘optical biopsy’ as a potent non-invasive diagnostic tool for cutaneous pathology.

Keywords: histo-pathology, non invasive imaging, OCT, wound healing

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30 A Generative Pretrained Transformer-Based Question-Answer Chatbot and Phantom-Less Quantitative Computed Tomography Bone Mineral Density Measurement System for Osteoporosis

Authors: Mian Huang, Chi Ma, Junyu Lin, William Lu

Abstract:

Introduction: Bone health attracts more attention recently and an intelligent question and answer (QA) chatbot for osteoporosis is helpful for science popularization. With Generative Pretrained Transformer (GPT) technology developing, we build an osteoporosis corpus dataset and then fine-tune LLaMA, a famous open-source GPT foundation large language model(LLM), on our self-constructed osteoporosis corpus. Evaluated by clinical orthopedic experts, our fine-tuned model outperforms vanilla LLaMA on osteoporosis QA task in Chinese. Three-dimensional quantitative computed tomography (QCT) measured bone mineral density (BMD) is considered as more accurate than DXA for BMD measurement in recent years. We develop an automatic Phantom-less QCT(PL-QCT) that is more efficient for BMD measurement since no need of an external phantom for calibration. Combined with LLM on osteoporosis, our PL-QCT provides efficient and accurate BMD measurement for our chatbot users. Material and Methods: We build an osteoporosis corpus containing about 30,000 Chinese literatures whose titles are related to osteoporosis. The whole process is done automatically, including crawling literatures in .pdf format, localizing text/figure/table region by layout segmentation algorithm and recognizing text by OCR algorithm. We train our model by continuous pre-training with Low-rank Adaptation (LoRA, rank=10) technology to adapt LLaMA-7B model to osteoporosis domain, whose basic principle is to mask the next word in the text and make the model predict that word. The loss function is defined as cross-entropy between the predicted and ground-truth word. Experiment is implemented on single NVIDIA A800 GPU for 15 days. Our automatic PL-QCT BMD measurement adopt AI-associated region-of-interest (ROI) generation algorithm for localizing vertebrae-parallel cylinder in cancellous bone. Due to no phantom for BMD calibration, we calculate ROI BMD by CT-BMD of personal muscle and fat. Results & Discussion: Clinical orthopaedic experts are invited to design 5 osteoporosis questions in Chinese, evaluating performance of vanilla LLaMA and our fine-tuned model. Our model outperforms LLaMA on over 80% of these questions, understanding ‘Expert Consensus on Osteoporosis’, ‘QCT for osteoporosis diagnosis’ and ‘Effect of age on osteoporosis’. Detailed results are shown in appendix. Future work may be done by training a larger LLM on the whole orthopaedics with more high-quality domain data, or a multi-modal GPT combining and understanding X-ray and medical text for orthopaedic computer-aided-diagnosis. However, GPT model gives unexpected outputs sometimes, such as repetitive text or seemingly normal but wrong answer (called ‘hallucination’). Even though GPT give correct answers, it cannot be considered as valid clinical diagnoses instead of clinical doctors. The PL-QCT BMD system provided by Bone’s QCT(Bone’s Technology(Shenzhen) Limited) achieves 0.1448mg/cm2(spine) and 0.0002 mg/cm2(hip) mean absolute error(MAE) and linear correlation coefficient R2=0.9970(spine) and R2=0.9991(hip)(compared to QCT-Pro(Mindways)) on 155 patients in three-center clinical trial in Guangzhou, China. Conclusion: This study builds a Chinese osteoporosis corpus and develops a fine-tuned and domain-adapted LLM as well as a PL-QCT BMD measurement system. Our fine-tuned GPT model shows better capability than LLaMA model on most testing questions on osteoporosis. Combined with our PL-QCT BMD system, we are looking forward to providing science popularization and early morning screening for potential osteoporotic patients.

Keywords: GPT, phantom-less QCT, large language model, osteoporosis

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29 Cardiac Hypertrophy in Diabetes; The Role of Factor Forkhead Box Class O-Regulation by O-GlcNAcylation

Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian

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Cardiac hypertrophy arises in response to persistent increases in hemodynamic loads. In comparison, diabetic cardiomyopathy is defined by an abnormal myocardial changes without other cardiac-related risk factors. Pathological cardiac hypertrophy and myocardial remodeling are hallmarks of cardiovascular diseases and are risk factors for heart failure. The transcription factor forkhead box class O (FOXOs) can protect heart tissue by hostile oxidative stress and stimulating apoptosis and autophagy. FOXO proteins, as sensitive elements and mediators in response to environmental changes, have been revealed to prevent and inverse cardiac hypertrophy. FOXOs are inhibited by insulin and are critical mediators of insulin action. Insulin deficiency and uncontrolled diabetes lead to a catabolic state. FOXO1 acts downstream of the insulin-dependent pathways, which are dysregulated in diabetes. It regulates cardiomyocyte hypertrophy downstream of IGF1R/PI3K/Akt activation, which are critical regulators of cardiac hypertrophy. The complex network of signaling pathways comprising insulin/IGF-1 signaling, AMPK, JNK, and Sirtuins regulate the development of cardiovascular dysfunction by modulating the activity of FOXOs. Insulin receptors and IGF1R act via the PI3k/Akt and the MAPK/ERK pathways. Activation of Akt in response to insulin or IGF-1 induces phosphorylation of FOXOs. Increased protein synthesis induced by activation of the IGF-I/Akt/mTOR signaling pathway leads to hypertrophy. This pathway and the myostatin/Smad pathway are potent negative muscle development regulators. In cardiac muscle, insulin receptor substrates (IRS)-1 or IRS-2 activates the Akt signaling pathway and inactivate FOXO1. Under metabolic stress, p38 MAPK promotes degradation of IRS-1 and IRS-2 in cardiac myocytes and activates FOXO1, leading to cardiomyopathy. Sirt1 and FOXO1 interaction play an essential role in starvation-induced autophagy in cardiac metabolism. Inhibition of Angiotensin-II induced cardiomyocyte hypertrophy is associated with reduced FOXO1 acetylation and activation of Sirt1. The NF-κB, ERK, and FOXOs are de-acetylated by SIRT1. De-acetylation of FOXO1 induces the expression of genes involved in autophagy and stimulates autophagy flux. Therefore, under metabolic stress, FOXO1 can cause diabetic cardiomyopathy. The overexpression of FOXO1 leads to decreased cardiomyocyte size and suppresses cardiac hypertrophy through inhibition of the calcineurin–NFAT pathway. Diabetes mellitus is associated with elevation of O-GlcNAcylation. Some of its binding partners regulate the substrate selectivity of O-GlcNAc transferase (OGT). O-GlcNAcylation of essential contractile proteins may inhibit protein-protein interactions, reduce calcium sensitivity, and modulate contractile function. Uridine diphosphate (UDP)-GlcNAc is the obligatory substrate of OGT, which catalyzes a reversible post-translational protein modification. The increase of O-GlcNAcylation is accompanied by impaired cardiac hypertrophy in diabetic hearts. Inhibition of O-GlcNAcylation blocks activation of ERK1/2 and hypertrophic growth. O-GlcNAc modification on NFAT is required for its translocation from the cytosol to the nucleus, where NFAT stimulates the transcription of various hypertrophic genes. Inhibition of O-GlcNAcylation dampens NFAT-induced cardiac hypertrophic growth. Transcriptional activity of FOXO1 is enriched by improved O-GlcNAcylation upon high glucose stimulation or OGT overexpression. In diabetic conditions, the modification of FOXO1 by O-GlcNAc is promoted in cardiac troponin I and myosin light chain 2. Therefore targeting O-GlcNAcylation represents a potential therapeutic option to prevent hypertrophy in the diabetic heart.

Keywords: diabetes, cardiac hypertrophy, O-GlcNAcylation, FOXO1, Akt, PI3K, AMPK, insulin

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28 Preparedness and Control of Mosquito-Borne Diseases: Experiences from Northwestern Italy

Authors: Federica Verna, Alessandra Pautasso, Maria Caramelli, Cristiana Maurella, Walter Mignone, Cristina Casalone

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Mosquito-Borne Diseases (MBDs) are dangerously increasing in prevalence, geographical distribution and severity, representing an emerging threat for both humans and animals. Interaction between multiple disciplines is needed for an effective early warning, surveillance and control of MBDs, according to the One Health concept. This work reports the integrated surveillance system enforced by IZSPLV in Piedmont, Liguria and Valle d’Aosta regions (Northwestern Italy) in order to control MDBs spread. Veterinary services and local human health authority are involved in an information network, to connect the surveillance of human clinical cases with entomological surveillance and veterinary monitoring in order to implement control measures in case of outbreak. A systematic entomological surveillance is carried out during the vector season using mosquitoes traps located in sites selected according to risk factors. Collected mosquitoes are counted, identified to species level by morphological standard classification keys and pooled by collection site, date and species with a maximum of 100 individuals. Pools are analyzed, after RNA extraction, by Real Time RT-PCR distinctive for West Nile Virus (WNV) Lineage 1 and Lineage 2, Real Time RT-PCR USUTU virus (USUV) and a traditional flavivirus End-point RT-PCR. Positive pools are sequenced and the related sequences employed to perform a basic local alignment search tool (BLAST) in the GenBank library. Positive samples are sent to the National Reference Centre for Animal Exotic Diseases (CESME, Teramo) for confirmation. With particular reference to WNV, after the confirmation, as provided by national legislation, control measures involving both local veterinary and human health services are activated: equine sera are randomly sampled within a 4 km radius from the positive collection sites and tested with ELISA kit and WNV NAT screening of blood donors is introduced. This surveillance network allowed to detect since 2011 USUV circulation in this area of Italy. WNV was detected in Piedmont and Liguria for the first time in 2014 in mosquitoes. During the 2015 vector season, we observed the expansion of its activity in Piedmont. The virus was detected in almost all Provinces both in mosquitoes (6 pools) and animals (19 equine sera, 4 birds). No blood bag tested resulted infected. The first neuroinvasive human case occurred too. Competent authorities should be aware of a potentially increased risk of MBDs activity during the 2016 vector season. This work shows that this surveillance network allowed to early detect the presence of MBDs in humans and animals, and provided useful information to public authorities, in order to apply control measures. Finally, an additional value of our diagnostic protocol is the ability to detect all viruses belonging to the Flaviviridae family, considering the emergence caused by other Flaviviruses in humans such as the recent Zika virus infection in South America. Italy has climatic and environmental features conducive to Zika virus transmission, the competent vector and many travellers from Brazil reported every year.

Keywords: integrated surveillance, mosquito borne disease, West Nile virus, Zika virus

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27 Mobi-DiQ: A Pervasive Sensing System for Delirium Risk Assessment in Intensive Care Unit

Authors: Subhash Nerella, Ziyuan Guan, Azra Bihorac, Parisa Rashidi

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Intensive care units (ICUs) provide care to critically ill patients in severe and life-threatening conditions. However, patient monitoring in the ICU is limited by the time and resource constraints imposed on healthcare providers. Many critical care indices such as mobility are still manually assessed, which can be subjective, prone to human errors, and lack granularity. Other important aspects, such as environmental factors, are not monitored at all. For example, critically ill patients often experience circadian disruptions due to the absence of effective environmental “timekeepers” such as the light/dark cycle and the systemic effect of acute illness on chronobiologic markers. Although the occurrence of delirium is associated with circadian disruption risk factors, these factors are not routinely monitored in the ICU. Hence, there is a critical unmet need to develop systems for precise and real-time assessment through novel enabling technologies. We have developed the mobility and circadian disruption quantification system (Mobi-DiQ) by augmenting biomarker and clinical data with pervasive sensing data to generate mobility and circadian cues related to mobility, nightly disruptions, and light and noise exposure. We hypothesize that Mobi-DiQ can provide accurate mobility and circadian cues that correlate with bedside clinical mobility assessments and circadian biomarkers, ultimately important for delirium risk assessment and prevention. The collected multimodal dataset consists of depth images, Electromyography (EMG) data, patient extremity movement captured by accelerometers, ambient light levels, Sound Pressure Level (SPL), and indoor air quality measured by volatile organic compounds, and the equivalent CO₂ concentration. For delirium risk assessment, the system recognizes mobility cues (axial body movement features and body key points) and circadian cues, including nightly disruptions, ambient SPL, and light intensity, as well as other environmental factors such as indoor air quality. The Mobi-DiQ system consists of three major components: the pervasive sensing system, a data storage and analysis server, and a data annotation system. For data collection, six local pervasive sensing systems were deployed, including a local computer and sensors. A video recording tool with graphical user interface (GUI) developed in python was used to capture depth image frames for analyzing patient mobility. All sensor data is encrypted, then automatically uploaded to the Mobi-DiQ server through a secured VPN connection. Several data pipelines are developed to automate the data transfer, curation, and data preparation for annotation and model training. The data curation and post-processing are performed on the server. A custom secure annotation tool with GUI was developed to annotate depth activity data. The annotation tool is linked to the MongoDB database to record the data annotation and to provide summarization. Docker containers are also utilized to manage services and pipelines running on the server in an isolated manner. The processed clinical data and annotations are used to train and develop real-time pervasive sensing systems to augment clinical decision-making and promote targeted interventions. In the future, we intend to evaluate our system as a clinical implementation trial, as well as to refine and validate it by using other data sources, including neurological data obtained through continuous electroencephalography (EEG).

Keywords: deep learning, delirium, healthcare, pervasive sensing

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26 Comparative Analysis of Pet-parent Reported Pruritic Symptoms in Cats: Data from Social Media Listening and Surveys Similar

Authors: Georgina Cherry, Taranpreet Rai, Luke Boyden, Sitira Williams, Andrea Wright, Richard Brown, Viva Chu, Alasdair Cook, Kevin Wells

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Estimating population-level burden, abilities of pet-parents to identify disease and demand for veterinary services worldwide is challenging. The purpose of this study is to compare a feline pruritus survey with social media listening (SML) data discussing this condition. Surveys are expensive and labour intensive to analyse, but SML data is freeform and requires careful filtering for relevancy. This study considers data from a survey of owner-observed symptoms of 156 pruritic cats conducted using Pet Parade® and SML posts collected through web-scraping to gain insights into the characterisation and management of feline pruritus. SML posts meeting a feline body area, behaviour and symptom were captured and reviewed for relevance representing 1299 public posts collected from 2021 to 2023. The survey involved 1067 pet-parents who reported on pruritic symptoms in their cats. Among the observed cats, approximately 18.37% (n=196) exhibited at least one symptom. The most frequently reported symptoms were hair loss (9.2%), bald spots (7.3%) and infection, crusting, scaling, redness, scabbing, scaling, or bumpy skin (8.2%). Notably, bald spots were the primary symptom reported for short-haired cats, while other symptoms were more prevalent in medium and long-haired cats. Affected body areas, according to pet-parents, were primarily the head, face, chin, neck (27%), and the top of the body, along the spine (22%). 35% of all cats displayed excessive behaviours consistent with pruritic skin disease. Interestingly, 27% of these cats were perceived as non-symptomatic by their owners, suggesting an under-identification of itch-related signs. Furthermore, a significant proportion of symptomatic cats did not receive any skin disease medication, whether prescribed or over the counter (n=41). These findings indicate a higher incidence of pruritic skin disease in cats than recognized by pet owners, potentially leading to a lack of medical intervention for clinically symptomatic cases. The comparison between the survey and social media listening data revealed bald spots were reported in similar proportions in both datasets (25% in the survey and 28% in SML). Infection, crusting, scaling, redness, scabbing, scaling, or bumpy skin accounted for 31% of symptoms in the survey, whereas it represented 53% of relevant SML posts (excluding bumpy skin). Abnormal licking or chewing behaviours were mentioned by pet-parents in 40% of SML posts compared to 38% in the survey. The consistency in the findings of these two disparate data sources, including a complete overlap in affected body areas for the top 80% of social media listening posts, indicates minimal biases in each method, as significant biases would likely yield divergent results. Therefore, the strong agreement across pruritic symptoms, affected body areas, and reported behaviours enhances our confidence in the reliability of the findings. Moreover, the small differences identified between the datasets underscore the valuable insights that arise from utilising multiple data sources. These variations provide additional depth in characterising and managing feline pruritus, allowing for more comprehensive understanding of the condition. By combining survey data and social media listening, researchers can obtain a nuanced perspective and capture a wider range of experiences and perspectives, supporting informed decision-making in veterinary practice.

Keywords: social media listening, feline pruritus, surveys, felines, cats, pet owners

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25 Settings of Conditions Leading to Reproducible and Robust Biofilm Formation in vitro in Evaluation of Drug Activity against Staphylococcal Biofilms

Authors: Adela Diepoltova, Klara Konecna, Ondrej Jandourek, Petr Nachtigal

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A loss of control over antibiotic-resistant pathogens has become a global issue due to severe and often untreatable infections. This state is reflected in complicated treatment, health costs, and higher mortality. All these factors emphasize the urgent need for the discovery and development of new anti-infectives. One of the most common pathogens mentioned in the phenomenon of antibiotic resistance are bacteria of the genus Staphylococcus. These bacterial agents have developed several mechanisms against the effect of antibiotics. One of them is biofilm formation. In staphylococci, biofilms are associated with infections such as endocarditis, osteomyelitis, catheter-related bloodstream infections, etc. To author's best knowledge, no validated and standardized methodology evaluating candidate compound activity against staphylococcal biofilms exists. However, a variety of protocols for in vitro drug activity testing has been suggested, yet there are often fundamental differences. Based on our experience, a key methodological step that leads to credible results is to form a robust biofilm with appropriate attributes such as firm adherence to the substrate, a complex arrangement in layers, and the presence of extracellular polysaccharide matrix. At first, for the purpose of drug antibiofilm activity evaluation, the focus was put on various conditions (supplementation of cultivation media by human plasma/fetal bovine serum, shaking mode, the density of initial inoculum) that should lead to reproducible and robust in vitro staphylococcal biofilm formation in microtiter plate model. Three model staphylococcal reference strains were included in the study: Staphylococcus aureus (ATCC 29213), methicillin-resistant Staphylococcus aureus (ATCC 43300), and Staphylococcus epidermidis (ATCC 35983). The total biofilm biomass was quantified using the Christensen method with crystal violet, and results obtained from at least three independent experiments were statistically processed. Attention was also paid to the viability of the biofilm-forming staphylococcal cells and the presence of extracellular polysaccharide matrix. The conditions that led to robust biofilm biomass formation with attributes for biofilms mentioned above were then applied by introducing an alternative method analogous to the commercially available test system, the Calgary Biofilm Device. In this test system, biofilms are formed on pegs that are incorporated into the lid of the microtiter plate. This system provides several advantages (in situ detection and quantification of biofilm microbial cells that have retained their viability after drug exposure). Based on our preliminary studies, it was found that the attention to the peg surface and substrate on which the bacterial biofilms are formed should also be paid to. Therefore, further steps leading to the optimization were introduced. The surface of pegs was coated by human plasma, fetal bovine serum, and L-polylysine. Subsequently, the willingness of bacteria to adhere and form biofilm was monitored. In conclusion, suitable conditions were revealed, leading to the formation of reproducible, robust staphylococcal biofilms in vitro for the microtiter model and the system analogous to the Calgary biofilm device, as well. The robustness and typical slime texture could be detected visually. Likewise, an analysis by confocal laser scanning microscopy revealed a complex three-dimensional arrangement of biofilm forming organisms surrounded by an extracellular polysaccharide matrix.

Keywords: anti-biofilm drug activity screening, in vitro biofilm formation, microtiter plate model, the Calgary biofilm device, staphylococcal infections, substrate modification, surface coating

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24 Enhanced Bioproduction of Moscatilin in Dendrobium ovatum through Hairy Root Culture

Authors: Ipsita Pujari, Abitha Thomas, Vidhu S. Babu, K. Satyamoorthy

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Orchids are esteemed as celebrities in cut flower industry globally, due to their long-lasting fragrance and freshness. Apart from splendor, the unique metabolites endowed with pharmaceutical potency have made them one of the most hunted in plant kingdom. This had led to their trafficking, resulting in habitat loss, subsequently making them occupiers of IUCN red list as RET species. Many of the orchids especially wild varieties still remain undiscovered. In view to protect and conserve the wild germplasm, researchers have been inventing novel micropropagation protocols; thereby conserving Orchids. India is overflowing with exclusive wild cultivars of Orchids, whose pharmaceutical properties remain untapped and are not marketed owing to relatively small flowers. However, their germplasm is quite pertinent to be preserved for making unusual hybrids. Dendrobium genus is the second largest among Orchids exists in India and has highest demand attributable to enduring cut flowers and significant therapeutic uses in traditional medicinal system. Though the genus is quite endemic in Western Ghat regions of the country, many species are still anonymous with their unknown curative properties. A standard breeding cycle in Orchids usually takes five to seven years (Dendrobium hybrids taking a long juvenile phase of two to five years reaching maturity and flowering stage) and this extensive life cycle has always hindered the development of Dendrobium breeding. Dendrobium is reported with essential therapeutic plant bio-chemicals and ‘Moscatilin’ is one, found exclusive to this famous Dendrobium genus. Moscatilin is reported to have anti-mutagenic and anti-cancer properties, whose positive action has very recently been demonstrated against a range of cancers. Our preliminary study here established a simple and economic small-scale propagation protocol of Dendrobium ovatum describing in vitro production of Moscatilin. Subsequently for enhancing the content of Moscatilin, an efficient experimental related to the organization of transgenic (hairy) D. ovatum root cultures through infection of Agrobacterium rhizogenes 2364 strain on MS basal medium is being reported in the present study. Hairy roots generated on almost half of the explants used (spherules, in vitro plantlets and calli) maintained through suspension cultures, after 8 weeks of co-cultivation with Agrobacterium rhizogenes. GFP assay performed with isolated hairy roots has confirmed the integrative transformation which was further positively confirmed by PCR using rolB gene specific primers. Reverse phase-high performance liquid chromatography and mass spectrometry techniques were used for quantification and accurate identification of Moscatilin respectively from transgenic systems. A noticeable ~3 fold increase in contents were observed in transformed D. ovatum root cultures as compared to the simple in vitro culture, callus culture and callus regeneration plantlets. Role of elicitors e.g., Methyl jasmonate, Salicylic acid, Yeast extract and Chitosan were tested for elevating the Moscatilin content to obtain a comprehensive optimized protocol facilitating the in vitro production of valuable Moscatilin with larger yield. This study would provide evidence towards the in vitro assembly of Moscatilin within a short time-period through not a so-expensive technology for the first time. It also serves as an appropriate basis for bioreactor scale-up resulting in commercial bioproduction of Moscatilin.

Keywords: bioproduction, Dendrobium ovatum, hairy root culture, moscatilin

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23 Measuring the Biomechanical Effects of Worker Skill Level and Joystick Crane Speed on Forestry Harvesting Performance Using a Simulator

Authors: Victoria L. Chester, Usha Kuruganti

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The forest industry is a major economic sector of Canada and also one of the most dangerous industries for workers. The use of mechanized mobile forestry harvesting machines has successfully reduced the incidence of injuries in forest workers related to manual labor. However, these machines have also created additional concerns, including a high machine operation learning curve, increased the length of the workday, repetitive strain injury, cognitive load, physical and mental fatigue, and increased postural loads due to sitting in a confined space. It is critical to obtain objective performance data for employers to develop appropriate work practices for this industry, however ergonomic field studies of this industry are lacking mainly due to the difficulties in obtaining comprehensive data while operators are cutting trees in the woods. The purpose of this study was to establish a measurement and experimental protocol to examine the effects of worker skill level and movement training speed (joystick crane speed) on harvesting performance using a forestry simulator. A custom wrist angle measurement device was developed as part of the study to monitor Euler angles during operation of the simulator. The device of the system consisted of two accelerometers, a Bluetooth module, three 3V coin cells, a microcontroller, a voltage regulator and an application software. Harvesting performance and crane data was provided by the simulator software and included tree to frame collisions, crane to tree collisions, boom tip distance, number of trees cut, etc. A pilot study of 3 operators with various skill levels was tested to identify factors that distinguish highly skilled operators from novice or intermediate operators. Dependent variables such as reaction time, math skill, past work experience, training movement speed (e.g. joystick control speeds), harvesting experience level, muscle activity, and wrist biomechanics were measured and analyzed. A 10-channel wireless surface EMG system was used to monitor the amplitude and mean frequency of 10 upper extremity muscles during pre and postperformance on the forestry harvest stimulator. The results of the pilot study showed inconsistent changes in median frequency pre-and postoperation, but there was the increase in the activity of the flexor carpi radialis, anterior deltoid and upper trapezius of both arms. The wrist sensor results indicated that wrist supination and pronation occurred more than flexion and extension with radial-ulnar rotation demonstrating the least movement. Overall, wrist angular motion increased as the crane speed increased from slow to fast. Further data collection is needed and will help industry partners determine those factors that separate skill levels of operators, identify optimal training speeds, and determine the length of training required to bring new operators to an efficient skill level effectively. In addition to effective and employment training programs, results of this work will be used for selective employee recruitment strategies to improve employee retention after training. Further, improved training procedures and knowledge of the physical and mental demands on workers will lead to highly trained and efficient personnel, reduced risk of injury, and optimal work protocols.

Keywords: EMG, forestry, human factors, wrist biomechanics

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22 Establishment of a Classifier Model for Early Prediction of Acute Delirium in Adult Intensive Care Unit Using Machine Learning

Authors: Pei Yi Lin

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Objective: The objective of this study is to use machine learning methods to build an early prediction classifier model for acute delirium to improve the quality of medical care for intensive care patients. Background: Delirium is a common acute and sudden disturbance of consciousness in critically ill patients. After the occurrence, it is easy to prolong the length of hospital stay and increase medical costs and mortality. In 2021, the incidence of delirium in the intensive care unit of internal medicine was as high as 59.78%, which indirectly prolonged the average length of hospital stay by 8.28 days, and the mortality rate is about 2.22% in the past three years. Therefore, it is expected to build a delirium prediction classifier through big data analysis and machine learning methods to detect delirium early. Method: This study is a retrospective study, using the artificial intelligence big data database to extract the characteristic factors related to delirium in intensive care unit patients and let the machine learn. The study included patients aged over 20 years old who were admitted to the intensive care unit between May 1, 2022, and December 31, 2022, excluding GCS assessment <4 points, admission to ICU for less than 24 hours, and CAM-ICU evaluation. The CAMICU delirium assessment results every 8 hours within 30 days of hospitalization are regarded as an event, and the cumulative data from ICU admission to the prediction time point are extracted to predict the possibility of delirium occurring in the next 8 hours, and collect a total of 63,754 research case data, extract 12 feature selections to train the model, including age, sex, average ICU stay hours, visual and auditory abnormalities, RASS assessment score, APACHE-II Score score, number of invasive catheters indwelling, restraint and sedative and hypnotic drugs. Through feature data cleaning, processing and KNN interpolation method supplementation, a total of 54595 research case events were extracted to provide machine learning model analysis, using the research events from May 01 to November 30, 2022, as the model training data, 80% of which is the training set for model training, and 20% for the internal verification of the verification set, and then from December 01 to December 2022 The CU research event on the 31st is an external verification set data, and finally the model inference and performance evaluation are performed, and then the model has trained again by adjusting the model parameters. Results: In this study, XG Boost, Random Forest, Logistic Regression, and Decision Tree were used to analyze and compare four machine learning models. The average accuracy rate of internal verification was highest in Random Forest (AUC=0.86), and the average accuracy rate of external verification was in Random Forest and XG Boost was the highest, AUC was 0.86, and the average accuracy of cross-validation was the highest in Random Forest (ACC=0.77). Conclusion: Clinically, medical staff usually conduct CAM-ICU assessments at the bedside of critically ill patients in clinical practice, but there is a lack of machine learning classification methods to assist ICU patients in real-time assessment, resulting in the inability to provide more objective and continuous monitoring data to assist Clinical staff can more accurately identify and predict the occurrence of delirium in patients. It is hoped that the development and construction of predictive models through machine learning can predict delirium early and immediately, make clinical decisions at the best time, and cooperate with PADIS delirium care measures to provide individualized non-drug interventional care measures to maintain patient safety, and then Improve the quality of care.

Keywords: critically ill patients, machine learning methods, delirium prediction, classifier model

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21 Exploratory Characterization of Antibacterial Efficacy of Synthesized Nanoparticles on Staphylococcus Isolates from Hospital Specimens in Saudi Arabia

Authors: Reham K. Sebaih, Afaf I. Shehata , Awatif A. Hindi, Tarek Gheith, Amal A. Hazzani Anas Al-Orjan

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Staphylococci spp are ubiquitous gram-positive bacteria is often associated with infections, especially nosocomial infections, and antibiotic resistanceStudy pathogenic bacteria and its use as a tool in the technology of Nano biology and molecular genetics research of the latest research trends of modern characterization and definition of different multiresistant of bacteria including Staphylococci. The Staphylococci are widespread all over the world and particularly in Saudi Arabia The present work study was conducted to evaluate the effect of five different types of nanoparticles (biosynthesized zinc oxide, Spherical and rod of each silver and gold nanoparticles) and their antibacterial impact on the Staphylococcus species. Ninety-six isolates of Staphylococcus species. Staphylococcus aureus, Staphylococcus epidermidis, MRSA were collected from different sources during the period between March 2011G to June 2011G. All isolates were isolated from inpatients and outpatients departments at Royal Commission Hospital in Yanbu Industrial, Saudi Arabia. High percentage isolation from males(55%) than females (45%). Staphylococcus epidermidis from males was (47%), (28%), and(25%). For Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus (MRSA. Isolates from females were Staphylococcus aureus with higher percent of (47%), (30%), and (23%) for MRSA, Staphylococcus epidermidis. Staphylococcus aureus from wound swab were the highest percent (51.42%) followed by vaginal swab (25.71%). Staphylococcus epidermidis were founded with higher percentage in blood (37.14%) and wound swab (34.21%) respectively related to other. The highest percentage of methicillin-resistant Staphylococcus aureus (MRSA)(80.77%) were isolated from wound swab, while those from nostrils were (19.23%). Staphylococcus species were isolates in highest percentage from hospital Emergency department with Staphylococcus aureus (59.37%), Methicillin-resistant Staphylococcus aureus (MRSA) (28.13%)and Staphylococcus epidermidis (12.5%) respectively. Evaluate the antibacterial property of Zinc oxide, Silver, and Gold nanoparticles as an alternative to conventional antibacterial agents Staphylococci isolates from hospital sources we screened them. Gold and Silver rods Nanoparticles to be sensitive to all isolates of Staphylococcus species. Zinc oxide Nanoparticles gave sensitivity impact range(52%) and (48%). The Gold and Silver spherical nanoparticles did not showed any effect on Staphylococci species. Zinc Oxide Nanoparticles gave bactericidal impact (25%) and bacteriostatic impact (75%) for of Staphylococci species. Detecting the association of nanoparticles with Staphylococci isolates imaging by scanning electron microscope (SEM) of some bacteriostatic isolates for Zinc Oxide nanoparticles on Staphylococcus aureus, Staphylococcus epidermidis and Methicillin resistant Staphylococcus aureus(MRSA), showed some Overlapping Bacterial cells with lower their number and appearing some appendages with deformities in external shape. Molecular analysis was applied by Multiplex polymerase chain reaction (PCR) used for the identification of genes within Staphylococcal pathogens. A multiplex polymerase chain reaction (PCR) method has been developed using six primer pairs to detect different genes using 50bp and 100bp DNA ladder marker. The range of Molecular gene typing ranging between 93 bp to 326 bp for Staphylococcus aureus and Methicillin resistant Staphylococcus aureus by TSST-1,mecA,femA and eta, while the bands border were from 546 bp to 682 bp for Staphylococcus epidermidis using icaAB and atlE. Sixteen isolation of Staphylococcus aureus and Methicillin resistant Staphylococcus aureus were positive for the femA gene at 132bp,this allowed the using of this gene as an internal positive control, fifteen isolates of Staphylococcus aureus and Methicillin resistant Staphylococcus aureus were positive for mecA gene at163bp.This gene was responsible for antibiotic resistant Methicillin, Two isolates of Staphylococcus aureus and Methicillin resistant Staphylococcus aureus were positive for the TSST-1 gene at326bp which is responsible for toxic shock syndrome in some Staphylococcus species, None were positive for eta gene at 102bpto that was responsible for Exfoliative toxins. Six isolates of Staphylococcus epidermidis were positive for atlE gene at 682 bp which is responsible for the initial adherence, three isolates of Staphylococcus epidermidis were positive for icaAB gene at 546bp that are responsible for mediates the formation of the biofilm. In conclusion, this study demonstrates the ability of the detection of the genes to discriminate between infecting Staphylococcus strains and considered biological tests, they may potentiate the clinical criteria used for the diagnosis of septicemia or catheter-related infections.

Keywords: multiplex polymerase chain reaction, toxic shock syndrome, Staphylococcus aureus, nosocomial infections

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20 White-Rot Fungi Phellinus as a Source of Antioxidant and Antitumor Agents

Authors: Yogesh Dalvi, Ruby Varghese, Nibu Varghese, C. K. Krishnan Nair

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Introduction: The Genus Phellinus, locally known as Phansomba is a well-known traditional folk medicine. Especially, in Western Ghats of India, many tribes use several species of Phellinus for various ailments related to teeth, throat, tongue, stomach and even wound healing. It is one of the few mushrooms which play a pivotal role in Ayurvedic Dravyaguna. Aim: The present study focuses on to investigate phytochemical analysis, antioxidant, and antitumor (in vitro and in vivo) potential of Phellinus robinae from South India, Kerala Material and Methods: The present study explores the following: 1. Phellinus samples were collected from Ranni, Pathanamthitta district of Kerala state, India from Artocarpus heterophyllus Lam. and species were identified using rDNA region. 2. The fruiting body was shadow dried, powdered and extracted with 50% alcohol using water bath at 60°C which was further condensed by rotary evaporator and lyophilized at minus 40°C temperature. 3. Secondary metabolites were analyzed by using various phytochemical screening assay (Hager’s Test, Wagner’s Test, Sodium hydroxide Test, Lead acetate Test, Ferric chloride Test, Folin-ciocalteu Test, Foaming Test, Benedict’s test, Fehling’s Test and Lowry’s Test). 4. Antioxidant and free radical scavenging activity were analyzed by DPPH, FRAP and Iron chelating assay. 5. The antitumor potential of Water alcohol extract of Phellinus (PAWE) is evaluated through In vitro condition by Trypan blue dye exclusion method in DLA cell line and In vivo by murine model. Result and Discussion: Preliminary phytochemical screening by various biochemical tests revealed presence of a variety of active secondary molecules like alkaloids, flavanoids, saponins, carbohydrate, protein and phenol. In DPPH and FRAP assay PAWE showed significantly higher antioxidant activity as compared to standard Ascorbic acid. While, in Iron chelating assay, PAWE exhibits similar antioxidant activity that of Butylated Hydroxytoluene (BHT) as standard. Further, in the in vitro study, PAWE showed significant inhibition on DLA cell proliferation in dose dependent manner and showed no toxicity on mice splenocytes, when compared to standard chemotherapy drug doxorubicin. In vivo study, oral administration of PAWE showed dose dependent tumor regression in mice and also raised the immunogenicity by restoring levels of antioxidant enzymes in liver and kidney tissue. In both in vitro and in vivo gene expression studies PAWE up-regulates pro-apoptotic genes (Bax, Caspases 3, 8 and 9) and down- regulates anti-apoptotic genes (Bcl2). PAWE also down regulates inflammatory gene (Cox-2) and angiogenic gene (VEGF). Conclusion: Preliminary phytochemical screening revealed that PAWE contains various secondary metabolites which contribute to its antioxidant and free radical scavenging property as evaluated by DPPH, FRAP and Iron chelating assay. PAWE exhibits anti-proliferative activity by the induction of apoptosis through a signaling cascade of death receptor-mediated extrinsic (Caspase8 and Tnf-α), as well as mitochondria-mediated intrinsic (caspase9) and caspase pathways (Caspase3, 8 and 9) and also by regressing angiogenic factor (VEGF) without any inflammation or adverse side effects. Hence, PAWE serve as a potential antioxidant and antitumor agent.

Keywords: antioxidant, antitumor, Dalton lymphoma ascites (DLA), fungi, Phellinus robinae

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19 An Exploration of Health Promotion Approach to Increase Optimal Complementary Feeding among Pastoral Mothers Having Children between 6 and 23 Months in Dikhil, Djibouti

Authors: Haruka Ando

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Undernutrition of children is a critical issue, especially for people in the remote areas of the Republic of Djibouti, since household food insecurity, inadequate child caring and feeding, unhealthy environment and lack of clean water, as well as insufficient maternal and child healthcare, are underlying causes which affect. Nomadic pastoralists living in the Dikhil region (Dikhil) are socio-economically and geographically more vulnerable due to displacement, which in turn worsens the situation of child stunting. A high prevalence of inappropriate complementary feeding among pastoral mothers might be a significant barrier to child growth. This study aims to identify health promotion intervention strategies that would support an increase in optimal complementary feeding among pastoral mothers of children aged 6-23 months in Dikhil. There are four objectives; to explore and to understand the existing practice of complementary feeding among pastoral mothers in Dikhil; to identify the barriers in appropriate complementary feeding among the mothers; to critically explore and analyse the strategies for an increase in complementary feeding among the mothers; to make pragmatic recommendations to address the barriers in Djibouti. This is an in-depth study utilizing a conceptual framework, the behaviour change wheel, to analyse the determinants of complementary feeding and categorize health promotion interventions for increasing optimal complementary feeding among pastoral mothers living in Dikhil. The analytical tool was utilized to appraise the strategies to mitigate the selected barriers against optimal complementary feeding. The data sources were secondary literature from both published and unpublished sources. The literature was systematically collected. The findings of the determinants including the barriers of optimal complementary feeding were identified: heavy household workload, caring for multiple children under five, lack of education, cultural norms and traditional eating habits, lack of husbands' support, poverty and food insecurity, lack of clean water, low media coverage, insufficient health services on complementary feeding, fear, poor personal hygiene, and mothers' low decision-making ability and lack of motivation for food choice. To mitigate selected barriers of optimal complementary feeding, four intervention strategies based on interpersonal communication at the community-level were chosen: scaling up mothers' support groups, nutrition education, grandmother-inclusive approach, and training for complementary feeding counseling. The strategies were appraised through the criteria of effectiveness and feasibility. Scaling up mothers' support groups could be the best approach. Mid-term and long-term recommendations are suggested based on the situation analysis and appraisal of intervention strategies. Mid-term recommendations include complementary feeding promotion interventions are integrated into the healthcare service providing system in Dikhil, and donor agencies advocate and lobby the Ministry of Health Djibouti (MoHD) to increase budgetary allocation on complementary feeding promotion to implement interventions at a community level. Moreover, the recommendations include a community health management team in Dikhil training healthcare workers and mother support groups by using complementary feeding communication guidelines and monitors behaviour change of pastoral mothers and health outcome of their children. Long-term recommendations are the MoHD develops complementary feeding guidelines to cover sector-wide collaboration for multi-sectoral related barriers.

Keywords: Afar, child food, child nutrition, complementary feeding, complementary food, developing countries, Djibouti, East Africa, hard-to-reach areas, Horn of Africa, nomad, pastoral, rural area, Somali, Sub-Saharan Africa

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18 Synthesis of Chitosan/Silver Nanocomposites: Antibacterial Properties and Tissue Regeneration for Thermal Burn Injury

Authors: B.L. España-Sánchez, E. Luna-Hernández, R.A. Mauricio-Sánchez, M.E. Cruz-Soto, F. Padilla-Vaca, R. Muñoz, L. Granados-López, L.R. Ovalle-Flores, J.L. Menchaca-Arredondo, G. Luna-Bárcenas

Abstract:

Treatment of burn injured has been considered an important clinical problem due to the fluid control and the presence of microorganisms during the healing process. Conventional treatment includes antiseptic techniques, topical medication and surgical removal of damaged skin, to avoid bacterial growth. In order to accelerate this process, different alternatives for tissue regeneration have been explored, including artificial skin, polymers, hydrogels and hybrid materials. Some requirements consider a nonreactive organic polymer with high biocompatibility and skin adherence, avoiding bacterial infections. Chitin-derivative biopolymer such as chitosan (CS) has been used in skin regeneration following third-degree burns. The biological interest of CS is associated with the improvement of tissue cell stimulation, biocompatibility and antibacterial properties. In particular, antimicrobial properties of CS can be significantly increased when is blended with nanostructured materials. Silver-based nanocomposites have gained attention in medicine due to their high antibacterial properties against pathogens, related to their high surface area/volume ratio at nanomolar concentrations. Silver nanocomposites can be blended or synthesized with chitin-derivative biopolymers in order to obtain a biodegradable/antimicrobial hybrid with improved physic-mechanical properties. In this study, nanocomposites based on chitosan/silver nanoparticles (CS/nAg) were synthesized by the in situ chemical reduction method, improving their antibacterial properties against pathogenic bacteria and enhancing the healing process in thermal burn injuries produced in an animal model. CS/nAg was prepared in solution by the chemical reduction method, using AgNO₃ as precursor. CS was dissolved in acetic acid and mixed with different molar concentrations of AgNO₃: 0.01, 0.025, 0.05 and 0.1 M. Solutions were stirred at 95°C during 20 hours, in order to promote the nAg formation. CS/nAg solutions were placed in Petri dishes and dried, to obtain films. Structural analyses confirm the synthesis of silver nanoparticles (nAg) by means of UV-Vis and TEM, with an average size of 7.5 nm and spherical morphology. FTIR analyses showed the complex formation by the interaction of hydroxyl and amine groups with metallic nanoparticles, and surface chemical analysis (XPS) shows low concentration of Ag⁰/Ag⁺ species. Topography surface analyses by means of AFM shown that hydrated CS form a mesh with an average diameter of 10 µm. Antibacterial activity against S. aureus and P. aeruginosa was improved in all evaluated conditions, such as nAg loading and interaction time. CS/nAg nanocomposites films did not show Ag⁰/Ag⁺ release in saline buffer and rat serum after exposition during 7 days. Healing process was significantly enhanced by the presence of CS/nAg nanocomposites, inducing the production of myofibloblasts, collagen remodelation, blood vessels neoformation and epidermis regeneration after 7 days of injury treatment, by means of histological and immunohistochemistry assays. The present work suggests that hydrated CS/nAg nanocomposites can be formed a mesh, improving the bacterial penetration and the contact with embedded nAg, producing complete growth inhibition after 1.5 hours. Furthermore, CS/nAg nanocomposites improve the cell tissue regeneration in thermal burn injuries induced in rats. Synthesis of antibacterial, non-toxic, and biocompatible nanocomposites can be an important issue in tissue engineering and health care applications.

Keywords: antibacterial, chitosan, healing process, nanocomposites, silver

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17 Modelling Farmer’s Perception and Intention to Join Cashew Marketing Cooperatives: An Expanded Version of the Theory of Planned Behaviour

Authors: Gospel Iyioku, Jana Mazancova, Jiri Hejkrlik

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The “Agricultural Promotion Policy (2016–2020)” represents a strategic initiative by the Nigerian government to address domestic food shortages and the challenges in exporting products at the required quality standards. Hindered by an inefficient system for setting and enforcing food quality standards, coupled with a lack of market knowledge, the Federal Ministry of Agriculture and Rural Development (FMARD) aims to enhance support for the production and activities of key crops like cashew. By collaborating with farmers, processors, investors, and stakeholders in the cashew sector, the policy seeks to define and uphold high-quality standards across the cashew value chain. Given the challenges and opportunities faced by Nigerian cashew farmers, active participation in cashew marketing groups becomes imperative. These groups serve as essential platforms for farmers to collectively navigate market intricacies, access resources, share knowledge, improve output quality, and bolster their overall bargaining power. Through engagement in these cooperative initiatives, farmers not only boost their economic prospects but can also contribute significantly to the sustainable growth of the cashew industry, fostering resilience and community development. This study explores the perceptions and intentions of farmers regarding their involvement in cashew marketing cooperatives, utilizing an expanded version of the Theory of Planned Behaviour. Drawing insights from a diverse sample of 321 cashew farmers in Southwest Nigeria, the research sheds light on the factors influencing decision-making in cooperative participation. The demographic analysis reveals a diverse landscape, with a substantial presence of middle-aged individuals contributing significantly to the agricultural sector and cashew-related activities emerging as a primary income source for a substantial proportion (23.99%). Employing Structural Equation Modelling (SEM) with Maximum Likelihood Robust (MLR) estimation in R, the research elucidates the associations among latent variables. Despite the model’s complexity, the goodness-of-fit indices attest to the validity of the structural model, explaining approximately 40% of the variance in the intention to join cooperatives. Moral norms emerge as a pivotal construct, highlighting the profound influence of ethical considerations in decision-making processes, while perceived behavioural control presents potential challenges in active participation. Attitudes toward joining cooperatives reveal nuanced perspectives, with strong beliefs in enhanced connections with other farmers but varying perceptions on improved access to essential information. The SEM analysis establishes positive and significant effects of moral norms, perceived behavioural control, subjective norms, and attitudes on farmers’ intention to join cooperatives. The knowledge construct positively affects key factors influencing intention, emphasizing the importance of informed decision-making. A supplementary analysis using partial least squares (PLS) SEM corroborates the robustness of our findings, aligning with covariance-based SEM results. This research unveils the determinants of cooperative participation and provides valuable insights for policymakers and practitioners aiming to empower and support this vital demographic in the cashew industry.

Keywords: marketing cooperatives, theory of planned behaviour, structural equation modelling, cashew farmers

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16 Interference of Polymers Addition in Wastewaters Microbial Survey: Case Study of Viral Retention in Sludges

Authors: Doriane Delafosse, Dominique Fontvieille

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Background: Wastewater treatment plants (WWTPs) generally display significant efficacy in virus retention yet, are sometimes highly variable, partly in relation to large fluctuating loads at the head of the plant and partly because of episodic dysfunctions in some treatment processes. The problem is especially sensitive when human enteric viruses, such as human Noroviruses Genogroup I or Adenoviruses, are in concern: their release downstream WWTP, in environments often interconnected to recreational areas, may be very harmful to human communities even at low concentrations. It points out the importance of WWTP permanent monitoring from which their internal treatment processes could be adjusted. One way to adjust primary treatments is to add coagulants and flocculants to sewage ahead settling tanks to improve decantation. In this work, sludge produced by three coagulants (two organics, one mineral), four flocculants (three cationic, one anionic), and their combinations were studied for their efficacy in human enteric virus retention. Sewage samples were coming from a WWTP in the vicinity of the laboratory. All experiments were performed three times and in triplicates in laboratory pilots, using Murine Norovirus (MNV-1), a surrogate of human Norovirus, as an internal control (spiking). Viruses were quantified by (RT-)qPCR after nucleic acid extraction from both treated water and sediment. Results: Low values of sludge virus retention (from 4 to 8% of the initial sewage concentration) were observed with each cationic organic flocculant added to wastewater and no coagulant. The largest part of the virus load was detected in the treated water (48 to 90%). However, it was not counterbalancing the amount of the introduced virus (MNV-1). The results pertained to two types of cationic flocculants, branched and linear, and in the last case, to two percentages of cations. Results were quite similar to the association of a linear cationic organic coagulant and an anionic flocculant, though suggesting that differences between water and sludges would sometimes be related to virus size or virus origins (autochthonous/allochthonous). FeCl₃, as a mineral coagulant associated with an anionic flocculant, significantly increased both auto- and allochthonous virus retention in the sediments (15 to 34%). Accordingly, virus load in treated water was lower (14 to 48%) but with a total that still does not reach the amount of the introduced virus (MNV-1). It also appeared that the virus retrieval in a bare 0.1M NaCl suspension varied rather strongly according to the FeCl₃ concentration, suggesting an inhibiting effect on the molecular analysis used to detect the virus. Finally, no viruses were detected in both phases (sediment and water) with the combination branched cationic coagulant-linear anionic flocculant, which was later demonstrated as an effect, here also, of polymers on the virus detection-molecular analysis. Conclusions: The combination of FeCl₃-anionic flocculant gave its highest performance to the decantation-based virus removal process. However, large unbalanced values in spiking experiments were observed, suggesting that polymers cast additional obstacles to both elution buffer and lysis buffer on their way to reach the virus. The situation was probably even worse with autochthonous viruses already embedded into sewage's particulate matter. Polymers and FeCl₃ also appeared to interfere in some steps of molecular analyses. More attention should be paid to such impediments wherever chemical additives are considered to be used to enhance WWTP processes. Acknowledgments: This research was supported by the ABIOLAB laboratory (Montbonnot Saint-Martin, France) and by the ASPOSAN association. Field experiments were possible thanks to the Grand Chambéry WWTP authorities (Chambéry, France).

Keywords: flocculants-coagulants, polymers, enteric viruses, wastewater sedimentation treatment plant

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15 Machine Learning Based Digitalization of Validated Traditional Cognitive Tests and Their Integration to Multi-User Digital Support System for Alzheimer’s Patients

Authors: Ramazan Bakir, Gizem Kayar

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It is known that Alzheimer and Dementia are the two most common types of Neurodegenerative diseases and their visibility is getting accelerated for the last couple of years. As the population sees older ages all over the world, researchers expect to see the rate of this acceleration much higher. However, unfortunately, there is no known pharmacological cure for both, although some help to reduce the rate of cognitive decline speed. This is why we encounter with non-pharmacological treatment and tracking methods more for the last five years. Many researchers, including well-known associations and hospitals, lean towards using non-pharmacological methods to support cognitive function and improve the patient’s life quality. As the dementia symptoms related to mind, learning, memory, speaking, problem-solving, social abilities and daily activities gradually worsen over the years, many researchers know that cognitive support should start from the very beginning of the symptoms in order to slow down the decline. At this point, life of a patient and caregiver can be improved with some daily activities and applications. These activities include but not limited to basic word puzzles, daily cleaning activities, taking notes. Later, these activities and their results should be observed carefully and it is only possible during patient/caregiver and M.D. in-person meetings in hospitals. These meetings can be quite time-consuming, exhausting and financially ineffective for hospitals, medical doctors, caregivers and especially for patients. On the other hand, digital support systems are showing positive results for all stakeholders of healthcare systems. This can be observed in countries that started Telemedicine systems. The biggest potential of our system is setting the inter-user communication up in the best possible way. In our project, we propose Machine Learning based digitalization of validated traditional cognitive tests (e.g. MOCA, Afazi, left-right hemisphere), their analyses for high-quality follow-up and communication systems for all stakeholders. R. Bakir and G. Kayar are with Gefeasoft, Inc, R&D – Software Development and Health Technologies company. Emails: ramazan, gizem @ gefeasoft.com This platform has a high potential not only for patient tracking but also for making all stakeholders feel safe through all stages. As the registered hospitals assign corresponding medical doctors to the system, these MDs are able to register their own patients and assign special tasks for each patient. With our integrated machine learning support, MDs are able to track the failure and success rates of each patient and also see general averages among similarly progressed patients. In addition, our platform also supports multi-player technology which helps patients play with their caregivers so that they feel much safer at any point they are uncomfortable. By also gamifying the daily household activities, the patients will be able to repeat their social tasks and we will provide non-pharmacological reminiscence therapy (RT – life review therapy). All collected data will be mined by our data scientists and analyzed meaningfully. In addition, we will also add gamification modules for caregivers based on Naomi Feil’s Validation Therapy. Both are behaving positively to the patient and keeping yourself mentally healthy is important for caregivers. We aim to provide a therapy system based on gamification for them, too. When this project accomplishes all the above-written tasks, patients will have the chance to do many tasks at home remotely and MDs will be able to follow them up very effectively. We propose a complete platform and the whole project is both time and cost-effective for supporting all stakeholders.

Keywords: alzheimer’s, dementia, cognitive functionality, cognitive tests, serious games, machine learning, artificial intelligence, digitalization, non-pharmacological, data analysis, telemedicine, e-health, health-tech, gamification

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