Search results for: treatment strategy

Authors: Achraf Al Faraj, Asma Sultana Shaik, Baraa Al Sayed

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Specific and effective targeting of drug delivery systems (DDS) to cancerous sites remains a major challenge for a better diagnostic and therapy. Recently, SWCNTs with their unique physicochemical properties and the ability to cross the cell membrane show promising in the biomedical field. The purpose of this study was first to develop a biocompatible iron oxide tagged SWCNTs as diagnostic nanoprobes to allow their noninvasive detection using MRI and their preferential targeting in a breast cancer murine model by placing an optimized flexible magnet over the tumor site. Magnetic targeting was associated to specific antibody-conjugated SWCNTs active targeting. The therapeutic efficacy of doxorubicin-conjugated SWCNTs was assessed, and the superiority of diffusion-weighted (DW-) MRI as sensitive imaging biomarker was investigated. Short Polyvinylpyrrolidone (PVP) stabilized water soluble SWCNTs were first developed, tagged with iron oxide nanoparticles and conjugated with Endoglin/CD105 monoclonal antibodies. They were then conjugated with doxorubicin drugs. SWCNTs conjugates were extensively characterized using TEM, UV-Vis spectrophotometer, dynamic light scattering (DLS) zeta potential analysis and electron spin resonance (ESR) spectroscopy. Their MR relaxivities (i.e. r1 and r2*) were measured at 4.7T and their iron content and metal impurities quantified using ICP-MS. SWCNTs biocompatibility and drug efficacy were then evaluated both in vitro and in vivo using a set of immunological assays. Luciferase enhanced bioluminescence 4T1 mouse mammary tumor cells (4T1-Luc2) were injected into the right inguinal mammary fat pad of Balb/c mice. Tumor bearing mice received either free doxorubicin (DOX) drug or SWCNTs with or without either DOX or iron oxide nanoparticles. A multi-pole 10x10mm high-energy flexible magnet was maintained over the tumor site during 2 hours post-injections and their properties and polarity were optimized to allow enhanced magnetic targeting of SWCNTs toward the primary tumor site. Tumor volume was quantified during the follow-up investigation study using a fast spin echo MRI sequence. In order to detect the homing of SWCNTs to the main tumor site, susceptibility-weighted multi-gradient echo (MGE) sequence was used to generate T2* maps. Apparent diffusion coefficient (ADC) measurements were also performed as a sensitive imaging biomarker providing early and better assessment of disease treatment. At several times post-SWCNT injection, histological analysis were performed on tumor extracts and iron-loaded SWCNT were quantified using ICP-MS in tumor sites, liver, spleen, kidneys, and lung. The optimized multi-poles magnet revealed an enhanced targeting of magnetic SWCNTs to the primary tumor site, which was found to be much higher than the active targeting achieved using antibody-conjugated SWCNTs. Iron-loading allowed their sensitive noninvasive tracking after intravenous administration using MRI. The active targeting of doxorubicin through magnetic antibody-conjugated SWCNTs nanoprobes was found to considerably decrease the primary tumor site and may have inhibited the development of metastasis in the tumor-bearing mice lung. ADC measurements in DW-MRI were found to significantly increase in a time-dependent manner after the injection of DOX-conjugated SWCNTs complexes.

Keywords: single-walled carbon nanotubes, nanomedicine, magnetic resonance imaging, cancer diagnosis and therapy

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Authors: Men An Pan, Ho Hsiung Huang, Jui Chuan Lin, Tsui Hsun Wu, Hsing Yuan Yen

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Pingtung County, located in the southernmost region of Taiwan, has the largest number of pig farms in the country. In the past, livestock operators in Dongpian Village discharged their wastewater into the nearby water bodies, causing water pollution in the local rivers and polluting the air with the stench of the pig excrement. These resulted in many complaints from the local residents. In response to a long time fighting back of the community against the livestock farms due to the confrict, the County Government's Environmental Protection Bureau (PTEPB) examined potential wayouts in addition to heavy fines to the perpetrators. Through helping the livestock farms to upgrade their pollution prevention equipment, promoting the reuse of biogas residue and slurry from the pig excrement, and environmental education, the confrict was successfully resolved. The properly treated wastewater from the livestock farms has been freely provided to the neighboring farmlands via pipelines and tankers. Thus, extensive cultivation of bananas, papaya, red dragon fruit, Inca nut, and cocoa has resulted in 34% resource utilization of biogas residue as a fertilizer. This has encouraged farmers to reduce chemical fertilizers and use microbial materials like photosynthetic bacteria after banning herbicides while lowering the cost of wastewater treatment in livestock farms and alleviating environmental pollution simultaneously. That is, the livestock farms fully demonstrate the determination to fulfill their corporate social responsibility (CSR). Due to the success, Eight farms jointly established a social enterprise - "Dongpian Gemstone Village Co., Ltd." to promote organic farming through a "shared farm." The company appropriates 5% of its total revenue back to the community through caregiving services for the elderly and a fund for young local farmers. The community adopted the Satoyama Initiative in accordance with the Conference of the CBD COP10. Through the positive impact of environmental education, the community seeks to realize the coexistence between society and nature while maintaining and developing socio-economic activities (including agriculture) with respect for nature and building a harmonic relationship between humans and nature. By way of sustainable management of resources and ensuring biodiversity, the community is transforming into a socio-ecological production landscape. Apart from nature conservation and watercourse ecology, preserving local culture is also a key focus of the environmental education. To mitigate the impact of global warming and climate change, the community and the government have worked together to develop a disaster prevention and relief system, strive to establish a low-carbon emitting homeland, and become a model for resilient communities. By the power of environmental education, this community has turned its residents’ hearts and minds into concrete action, fulfilled social responsibility, and moved towards realizing the UN SDGs. Even though it is not the only community to integrate government agencies, research institutions, and NGOs for environmental education, it is a prime example of a low-carbon sustainable community that achieves more than 9 SDGs, including responsible consumption and production, climate change action, and diverse partnerships. The community is also leveraging environmental education to become a net-zero carbon community targeted by COP26.

Keywords: environmental education, biogas residue, biogas slurry, CSR, SDGs, climate change, net-zero carbon emissions

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Authors: Ching-Sung Lee, Wei-Chou Hsu, Han-Yin Liu, Hung-Hsi Huang, Si-Fu Chen, Yun-Jung Yang, Bo-Chun Chiang, Yu-Chuang Chen, Shen-Tin Yang

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AlGaN/GaN high electron mobility transistors (HEMTs) have been intensively studied due to their intrinsic advantages of high breakdown electric field, high electron saturation velocity, and excellent chemical stability. They are also suitable for ultra-violet (UV) photodetection due to the corresponding wavelengths of GaN bandgap. To improve the optical responsivity by decreasing the dark current due to gate leakage problems and limited Schottky barrier heights in GaN-based HEMT devices, various metal-oxide-semiconductor HEMTs (MOS-HEMTs) have been devised by using atomic layer deposition (ALD), molecular beam epitaxy (MBE), metal-organic chemical vapor deposition (MOCVD), liquid phase deposition (LPD), and RF sputtering. The gate dielectrics include MgO, HfO2, Al2O3, La2O3, and TiO2. In order to provide complementary circuit operation, enhancement-mode (E-mode) devices have been lately studied using techniques of fluorine treatment, p-type capper, piezoneutralization layer, and MOS-gate structure. This work reports an Al2O3-dielectric Al0.25Ga0.75N/GaN E-mode MOS-HEMT design by using a cost-effective ozone water oxidization technique. The present ozone oxidization method advantages of low cost processing facility, processing simplicity, compatibility to device fabrication, and room-temperature operation under atmospheric pressure. It can further reduce the gate-to-channel distance and improve the transocnductance (gm) gain for a specific oxide thickness, since the formation of the Al2O3 will consume part of the AlGaN barrier at the same time. The epitaxial structure of the studied devices was grown by using the MOCVD technique. On a Si substrate, the layer structures include a 3.9 m C-doped GaN buffer, a 300 nm GaN channel layer, and a 5 nm Al0.25Ga0.75N barrier layer. Mesa etching was performed to provide electrical isolation by using an inductively coupled-plasma reactive ion etcher (ICP-RIE). Ti/Al/Au were thermally evaporated and annealed to form the source and drain ohmic contacts. The device was immersed into the H2O2 solution pumped with ozone gas generated by using an OW-K2 ozone generator. Ni/Au were deposited as the gate electrode to complete device fabrication of MOS-HEMT. The formed Al2O3 oxide thickness 7 nm and the remained AlGaN barrier thickness is 2 nm. A reference HEMT device has also been fabricated in comparison on the same epitaxial structure. The gate dimensions are 1.2 × 100 µm 2 with a source-to-drain spacing of 5 μm for both devices. The dielectric constant (k) of Al2O3 was characterized to be 9.2 by using C-V measurement. Reduced interface state density after oxidization has been verified by the low-frequency noise spectra, Hooge coefficients, and pulse I-V measurement. Improved device characteristics at temperatures of 300 K-450 K have been achieved for the present MOS-HEMT design. Consequently, Al2O3-dielectric Al0.25Ga0.75N/GaN E-mode MOS-HEMTs by using the ozone water oxidization method are reported. In comparison with a conventional Schottky-gate HEMT, the MOS-HEMT design has demonstrated excellent enhancements of 138% (176%) in gm, max, 118% (139%) in IDS, max, 53% (62%) in BVGD, 3 (2)-order reduction in IG leakage at VGD = -60 V at 300 (450) K. This work is promising for millimeter-wave integrated circuit (MMIC) and three-terminal active UV photodetector applications.

Keywords: MOS-HEMT, enhancement mode, AlGaN/GaN, passivation, ozone water oxidation, gate leakage

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Authors: Siddhant Yadav, Rylea Ranum, Hannah Alberts, Abdul Kalaiger, Brent Bauer, Ryan Hurt, Ann Vincent, Loren Toussaint, Sanjeev Nanda

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Background and significance: Fibromyalgia (FM) is a chronic pain disorder also characterized by chronic fatigue, morning stiffness, sleep, and cognitive symptoms, psychological disturbances (anxiety, depression), and is comorbid with multiple medical and psychiatric conditions. It has an incidence of 2-4% in the general population and is reported more commonly in women. Oxidative stress and inflammation are thought to contribute to pain in patients with FM, and the adoption of an antioxidant/anti-inflammatory diet has been suggested as a modality to alleviate symptoms. The aim of this systematic review was to evaluate the efficacy of specialized diets (ketogenic, gluten free, Mediterranean, and low carbohydrate) in improving FM symptoms. Methodology: A comprehensive search of the following databases from inception to July 15th, 2021, was conducted: Ovid MEDLINE and Epub ahead of print, in-process and other non-indexed citations and daily, Ovid Embase, Ovid EBM reviews, Cochrane central register of controlled trials, EBSCO host CINAHL with full text, Elsevier Scopus, website and citation index, web of science emerging sources citation and clinicaltrials.gov. We included randomized controlled trials, non-randomized experimental studies, cross-sectional studies, cohort studies, case series, and case reports in adults with fibromyalgia. The risk of bias was assessed with the Agency for Health Care Research and Quality designed, specific recommended criteria (AHRQ). Results: Thirteen studies were eligible for inclusion. This included a total of 761 participants. Twelve out of the 13 studies reported improvement in widespread body pain, joint stiffness, sleeping pattern, mood, and gastrointestinal symptoms, and one study reported no changes in symptomatology in patients with FM on specialized diets. None of the studies showed the worsening of symptoms associated with a specific diet. Most of the patient population was female, with the mean age at which fibromyalgia was diagnosed being 48.12 years. Improvement in symptoms was reported by the patient's adhering to a gluten-free diet, raw vegan diet, tryptophan- and magnesium-enriched Mediterranean diet, aspartame- and msg- elimination diet, and specifically a Khorasan wheat diet. Risk of bias assessment noted that 6 studies had a low risk of bias (5 clinical trials and 1 case series), four studies had a moderate risk of bias, and 3 had a high risk of bias. In many of the studies, the allocation of treatment (diets) was not adequately concealed, and the researchers did not rule out any potential impact from a concurrent intervention or an unintended exposure that might have biased the results. On the other hand, there was a low risk of attrition bias in all the trials; all were conducted with an intention-to-treat, and the inclusion/exclusion criteria, exposures/interventions, and primary outcomes were valid, reliable, and implemented consistently across all study participants. Concluding statement: Patients with fibromyalgia who followed specialized diets experienced a variable degree of improvement in their widespread body pain. Improvement was also seen in stiffness, fatigue, moods, sleeping patterns, and gastrointestinal symptoms. Additionally, the majority of the patients also reported improvement in overall quality of life.

Keywords: fibromyalgia, specialized diet, vegan, gluten free, Mediterranean, systematic review

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Authors: Sadaf Abbas, HimGauri Sabnis

Abstract:

Introduction: Peripartum cardiomyopathy is a rare but potentially life-threatening condition that presents as heart failure during the last month of pregnancy or within five months postpartum. The incidence of postpartum cardiomyopathy ranges from 1 in 1300 to 1 in 15,000 pregnancies. Risk factors include multiparty, advanced maternal age, multiple pregnancies, pre-eclampsia, and chronic hypertension. Study: A 30-year-old Para3+0 presented to the Emergency Department of St’Marry Hospital, Isle of Wight, on the seventh day postpartum, with acute shortness of breath (SOB), chest pain, cough, and a temperature of 38 degrees. The risk factors were smoking and class II obesity (BMI of 40.62). The patient had mild pre-eclampsia in the last pregnancy and was on labetalol and aspirin during an antenatal period, which was stopped postnatally. There was also a history of pre-eclampsia and haemolysis, elevated liver enzymes, low platelets (HELLP syndrome) in previous pregnancies, which led to preterm delivery at 35 weeks in the second pregnancy, and the first baby was stillborn at 24 weeks. On assessment, there was a national early warning score (NEWS score) of 3, persistent tachycardia, and mild crepitation in the lungs. Initial investigations revealed an enlarged heart on chest X-ray, and a CT pulmonary angiogram indicated bilateral basal pulmonary congestion without pulmonary embolism, suggesting fluid overload. Laboratory results showed elevated CRP and normal troponin levels initially, which later increased, indicating myocardial involvement. Echocardiography revealed a severely dilated left ventricle with an ejection fraction (EF) of 31%, consistent with severely impaired systolic function. The cardiology team reviewed the patient and admitted to the Coronary Care Unit. As sign and symptoms were suggestive of fluid overload and congestive cardiac failure, management was done with diuretics, beta-blockers, angiotensin-converting enzyme inhibitors (ACE inhibitors), proton pump inhibitors, and supportive care. During admission, there was complications such as acute kidney injury, but then recovered well. Chest pain had resolved following the treatment. After being admitted for eight days, there was an improvement in the symptoms, and the patient was discharged home with a further plan of cardiac MRI and genetic testing due to a family history of sudden cardiac death. Regular appointment has been made with the Cardiology team to follow-up on the symptoms. Since discharge, the patient made a good recovery. A cardiac MRI was done, which showed severely impaired left ventricular function, ejection fraction (EF) of 38% with mild left ventricular dilatation, and no evidence of previous infarction. Overall appearance is of non-ischemic dilated cardiomyopathy. The main challenge at the time of admission was the non-availability of a cardiac radiology team, so the definitive diagnosis was delayed. The long-term implications include risk of recurrence, chronic heart failure, and, consequently, an effect on quality of life. Therefore, regular follow-up is critical in patient’s management. Conclusions: Peripartum cardiomyopathy is one of the cardiovascular diseases whose causes are still unknown yet and, in some cases, are uncontrolled. By raising awareness about the symptoms and management of this complication it will reduce morbidity and mortality rates and also the length of stay in the hospital.

Keywords: cardiomyopathy, cardiomegaly, pregnancy, puerperium

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

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

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

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

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

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

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Authors: Farideh Namvar, Rosfarizan Mohamed

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In the field of nanotechnology, the use of various biological units instead of toxic chemicals for the reduction and stabilization of nanoparticles, has received extensive attention. This use of biological entities to create nanoparticles has designated as “Green” synthesis and it is considered to be far more beneficial due to being economical, eco-friendly and applicable for large-scale synthesis as it operates on low pressure, less input of energy and low temperatures. The lack of toxic byproducts and consequent decrease in degradation of the product renders this technique more preferable over physical and classical chemical methods. The variety of biomass having reduction properties to produce nanoparticles makes them an ideal candidate for fabrication. Metal oxide nanoparticles have been said to represent a "fundamental cornerstone of nanoscience and nanotechnology" due to their variety of properties and potential applications. However, this also provides evidence of the fact that metal oxides include many diverse types of nanoparticles with large differences in chemical composition and behaviour. In this study, iron oxide nanoparticles (Fe3O4-NPs) were synthesized using a rapid, single step and completely green biosynthetic method by reduction of ferric chloride solution with brown seaweed (Sargassum muticum) water extract containing polysaccharides as a main factor which acts as reducing agent and efficient stabilizer. Antimicrobial activity against six microorganisms was tested using well diffusion method. The resulting S-IONPs are crystalline in nature, with a cubic shape. The average particle diameter, as determined by TEM, was found to be 18.01 nm. The S-IONPs were efficiently inhibited the growth of Listeria monocytogenes, Escherichia coli and Candida species. Our favorable results suggest that S-IONPs could be a promising candidate for development of future antimicrobial therapies. The nature of biosynthesis and the therapeutic potential by S-IONPs could pave the way for further research on design of green synthesis therapeutic agents, particularly nanomedicine, to deal with treatment of infections. Further studies are needed to fully characterize the toxicity and the mechanisms involved with the antimicrobial activity of these particles. Antioxidant activity of S-IONPs synthesized by green method was measured by ABTS (2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (IC50= 1000µg) radical scavenging activity. Also, with the increasing concentration of S-IONPs, catalase gene expression compared to control gene GAPDH increased. For anti-angiogenesis study the Ross fertilized eggs were divided into four groups; the control and three experimental groups. The gelatin sponges containing albumin were placed on the chorioalantoic membrane and soaked with different concentrations of S-IONPs. All the cases were photographed using a photo stereomicroscope. The number and the lengths of the vessels were measured using Image J software. The crown rump (CR) and weight of the embryo were also recorded. According to the data analysis, the number and length of the blood vessels, as well as the CR and weight of the embryos reduced significantly compared to the control (p < 0.05), dose dependently. The total hemoglobin was quantified as an indicator of the blood vessel formation, and in the treated samples decreased, which showed its inhibitory effect on angiogenesis.

Keywords: anti-angiogenesis, antimicrobial, antioxidant, biosynthesis, iron oxide (fe3o4) nanoparticles, sargassum muticum, seaweed

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Authors: Yung-Chih Kuo, Che-Yu Lin, Jay-Shake Li, Yung-I Lou

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Curcumin (CRM) and nerve growth factor (NGF) were entrapped in liposomes (LIP) with cardiolipin (CL) to downregulate the phosphorylation of mitogen-activated protein kinases for Alzheimer’s disease (AD) management. AD belongs to neurodegenerative disorder with a gradual loss of memory, yielding irreversible dementia. CL-conjugated LIP loaded with CRM (CRM-CL/LIP) and that with NGF (NGF-CL/LIP) were applied to AD models of SK-N-MC cells and Wistar rats with an insult of β-amyloid peptide (Aβ). Lipids comprising 1,2-dipalmitoyl-sn-glycero-3- phosphocholine (Avanti Polar Lipids, Alabaster, AL), 1',3'-bis[1,2- dimyristoyl-sn-glycero-3-phospho]-sn-glycerol (CL; Avanti Polar Lipids), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N- [methoxy(polyethylene glycol)-2000] (Avanti Polar Lipids), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethylene glycol)-2000] (Avanti Polar Lipids) and CRM (Sigma–Aldrich, St. Louis, MO) were dissolved in chloroform (J. T. Baker, Phillipsburg, NJ) and condensed using a rotary evaporator (Panchum, Kaohsiung, Taiwan). Human β-NGF (Alomone Lab, Jerusalem, Israel) was added in the aqueous phase. Wheat germ agglutinin (WGA; Medicago AB, Uppsala, Sweden) was grafted on LIP loaded with CRM for (WGA-CRM-LIP) and CL-conjugated LIP loaded with CRM (WGA-CRM-CL/LIP) using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (Sigma–Aldrich) and N-hydroxysuccinimide (Alfa Aesar, Ward Hill, MA). The protein samples of SK-N-MC cells (American Type Tissue Collection, Rockville, MD) were used for sodium dodecyl sulfate (Sigma–Aldrich) polyacrylamide gel (Sigma–Aldrich) electrophoresis. In animal study, the LIP formulations were administered by intravenous injection via a tail vein of male Wistar rats (250–280 g, 8 weeks, BioLasco, Taipei, Taiwan), which were housed in the Animal Laboratory of National Chung Cheng University in accordance with the institutional guidelines and the guidelines of Animal Protection Committee under the Council of Agriculture of the Republic of China. We found that CRM-CL/LIP could inhibit the expressions of phosphorylated p38 (p-p38), p-Jun N-terminal kinase (p-JNK), and p-tau protein at serine 202 (p-Ser202) to retard the neuronal apoptosis. Free CRM and released CRM from CRM-LIP and CRM-CL/LIP were not in a straightforward manner to effectively inhibit the expression of p-p38 and p-JNK in the cytoplasm. In addition, NGF-CL/LIP enhanced the quantities of p-neurotrophic tyrosine kinase receptor type 1 (p-TrkA) and p-extracellular-signal-regulated kinase 5 (p-ERK5), preventing the Aβ-induced degeneration of neurons. The membrane fusion of NGF-LIP activated the ERK5 pathway and the targeting capacity of NGF-CL/LIP enhanced the possibility of released NGF to affect the TrkA level. Moreover, WGA-CRM-LIP improved the permeation of CRM across the blood–brain barrier (BBB) and significantly reduced the Aβ plaque deposition and malondialdehyde level and increased the percentage of normal neurons and cholinergic function in the hippocampus of AD rats. This was mainly because the encapsulated CRM was protected by LIP against a rapid degradation in the blood. Furthermore, WGA on LIP could target N-acetylglucosamine on endothelia and increased the quantity of CRM transported across the BBB. In addition, WGA-CRM-CL/LIP could be effective in suppressing the synthesis of acetylcholinesterase and reduced the decomposition of acetylcholine for better neurotransmission. Based on the in vitro and in vivo evidences, WGA-CRM-CL/LIP can rescue neurons from apoptosis in the brain and can be a promising drug delivery system for clinical AD therapy.

Keywords: Alzheimer’s disease, β-amyloid, liposome, mitogen-activated protein kinase

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Authors: Wiseman Emmanuel Nkhomah, Chiyembekezo Kachimanga, Moses Banda Aron, Julia Higgins, Manuel Mulwafu, Kondwani Mpinga, Mwayi Chunga, Grace Momba, Enock Ndarama, Dickson Sumphi, Atupere Phiri, Fabien Munyaneza

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Background: Data is key to supporting health service delivery as stakeholders, including NGOs rely on it for effective service delivery, decision-making, and system strengthening. Several studies generated debate on data quality from national health management information systems (HMIS) in sub-Saharan Africa. This limits the utilization of data in resource-limited settings, which already struggle to meet standards set by the World Health Organization (WHO). We aimed to evaluate data quality improvement of Neno district HMIS over a 4-year period (2018 – 2021) following quarterly data reviews introduced in January 2020 by the district health management team and Partners In Health. Methods: Exploratory Mixed Research was used to examine report rates, followed by in-depth interviews using Key Informant Interviews (KIIs) and Focus Group Discussions (FGDs). We used the WHO module desk review to assess the quality of HMIS data in the Neno district captured from 2018 to 2021. The metrics assessed included the completeness and timeliness of 34 reports. Completeness was measured as a percentage of non-missing reports. Timeliness was measured as the span between data inputs and expected outputs meeting needs. We computed T-Test and recorded P-values, summaries, and percentage changes using R and Excel 2016. We analyzed demographics for key informant interviews in Power BI. We developed themes from 7 FGDs and 11 KIIs using Dedoose software, from which we picked perceptions of healthcare workers, interventions implemented, and improvement suggestions. The study was reviewed and approved by Malawi National Health Science Research Committee (IRB: 22/02/2866). Results: Overall, the average reporting completeness rate was 83.4% (before) and 98.1% (after), while timeliness was 68.1% and 76.4 respectively. Completeness of reports increased over time: 2018, 78.8%; 2019, 88%; 2020, 96.3% and 2021, 99.9% (p< 0.004). The trend for timeliness has been declining except in 2021, where it improved: 2018, 68.4%; 2019, 68.3%; 2020, 67.1% and 2021, 81% (p< 0.279). Comparing 2021 reporting rates to the mean of three preceding years, both completeness increased from 88% to 99% (in 2021), while timeliness increased from 68% to 81%. Sixty-five percent of reports have maintained meeting a national standard of 90%+ in completeness while only 24% in timeliness. Thirty-two percent of reports met the national standard. Only 9% improved on both completeness and timeliness, and these are; cervical cancer, nutrition care support and treatment, and youth-friendly health services reports. 50% of reports did not improve to standard in timeliness, and only one did not in completeness. On the other hand, factors associated with improvement included improved communications and reminders using internal communication, data quality assessments, checks, and reviews. Decentralizing data entry at the facility level was suggested to improve timeliness. Conclusion: Findings suggest that data quality in HMIS for the district has improved following collaborative efforts. We recommend maintaining such initiatives to identify remaining quality gaps and that results be shared publicly to support increased use of data. These results can inform Ministry of Health and its partners on some interventions and advise initiatives for improving its quality.

Keywords: data quality, data utilization, HMIS, collaboration, completeness, timeliness, decision-making

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

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

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

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Authors: Fahimeh Palizban, Farshad Noravesh, Amir Hossein Saeidian, Mahya Mehrmohamadi

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In the recent decade, the emergence of liquid biopsy has significantly improved cancer monitoring and detection. Dying cells, including those originating from tumors, shed their DNA into the blood and contribute to a pool of circulating fragments called cell-free DNA. Accordingly, identifying the tissue origin of these DNA fragments from the plasma can result in more accurate and fast disease diagnosis and precise treatment protocols. Open chromatin regions are important epigenetic features of DNA that reflect cell types of origin. Profiling these features by DNase-seq, ATAC-seq, and histone ChIP-seq provides insights into tissue-specific and disease-specific regulatory mechanisms. There have been several studies in the area of cancer liquid biopsy that integrate distinct genomic and epigenomic features for early cancer detection along with tissue of origin detection. However, multimodal analysis requires several types of experiments to cover the genomic and epigenomic aspects of a single sample, which will lead to a huge amount of cost and time. To overcome these limitations, the idea of predicting OCRs from WGS is of particular importance. In this regard, we proposed a computational approach to target the prediction of open chromatin regions as an important epigenetic feature from cell-free DNA whole genome sequence data. To fulfill this objective, local sequencing depth will be fed to our proposed algorithm and the prediction of the most probable open chromatin regions from whole genome sequencing data can be carried out. Our method integrates the signal processing method with sequencing depth data and includes count normalization, Discrete Fourie Transform conversion, graph construction, graph cut optimization by linear programming, and clustering. To validate the proposed method, we compared the output of the clustering (open chromatin region+, open chromatin region-) with previously validated open chromatin regions related to human blood samples of the ATAC-DB database. The percentage of overlap between predicted open chromatin regions and the experimentally validated regions obtained by ATAC-seq in ATAC-DB is greater than 67%, which indicates meaningful prediction. As it is evident, OCRs are mostly located in the transcription start sites (TSS) of the genes. In this regard, we compared the concordance between the predicted OCRs and the human genes TSS regions obtained from refTSS and it showed proper accordance around 52.04% and ~78% with all and the housekeeping genes, respectively. Accurately detecting open chromatin regions from plasma cell-free DNA-seq data is a very challenging computational problem due to the existence of several confounding factors, such as technical and biological variations. Although this approach is in its infancy, there has already been an attempt to apply it, which leads to a tool named OCRDetector with some restrictions like the need for highly depth cfDNA WGS data, prior information about OCRs distribution, and considering multiple features. However, we implemented a graph signal clustering based on a single depth feature in an unsupervised learning manner that resulted in faster performance and decent accuracy. Overall, we tried to investigate the epigenomic pattern of a cell-free DNA sample from a new computational perspective that can be used along with other tools to investigate genetic and epigenetic aspects of a single whole genome sequencing data for efficient liquid biopsy-related analysis.

Keywords: open chromatin regions, cancer, cell-free DNA, epigenomics, graph signal processing, correlation clustering

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Authors: Chandra Shekhar Majumder, Md. Shamsul Haque, Khondaker Anower Hossain, Md. Rafiqul Islam

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Introduction: Ocular helminths are parasites that infect the eye or its adnexa. They can be either motile worms or sessile worms that form cysts. These parasites require two hosts for their life cycle, a definite host (usually a human) and an intermediate host (usually an insect). While there have been reports of ocular helminths infecting various structures of the eye, including the anterior chamber and subconjunctival space, there is no previous record of such a case involving the lens. Research Aim: The aim of this case report is to present a rare case of ocular helminth infection in the lens and to contribute to the understanding of this unusual site of infection. Methodology: This study is a case report, presenting the details and findings of an 80-year-old retired policeman who presented with severe pain, redness, and vision loss in the left eye. The patient had a history of diabetes mellitus and hypertension. The examination revealed the presence of a thread-like helminth in the lens. The patient underwent treatment and follow-up, and the helminth specimen was sent for identification to the department of Parasitology. Case report: An 80-year-old retired policeman attended the OPD, Faridpur Medical College Hospital with the complaints of severe pain, redness and gross dimness of vision of the left eye for 5 days. He had a history of diabetes mellitus and hypertension for 3 years. On examination, L/E visual acuity was PL only, moderate ciliary congestion, KP 2+, cells 2+ and posterior synechia from 5 to 7 O’clock position was found. Lens was opaque. A thread like helminth was found under the anterior of the lens. The worm was moving and changing its position during examination. On examination of R/E, visual acuity was 6/36 unaided, 6/18 with pinhole. There was lental opacity. Slit-lamp and fundus examination were within normal limit. Patient was admitted in Faridpur Medical College Hospital. Diabetes mellitus was controlled with insulin. ICCE with PI was done on the same day of admission under depomedrol coverage. The helminth was recovered from the lens. It was thread like, about 5 to 6 mm in length, 1 mm in width and pinkish in colour. The patient followed up after 7 days, VA was HM, mild ciliary congestion, few KPs and cells were present. Media was hazy due to vitreous opacity. The worm was sent to the department of Parasitology, NIPSOM, Dhaka for identification. Findings: The findings of this case report highlight the presence of a helminth in the lens, which has not been previously reported. The helminth was successfully removed from the lens, but the patient experienced complications such as anterior uveitis and vitreous opacity. The exact mechanism by which the helminth enters the lens remains unclear. Theoretical Importance: This case report contributes to the existing literature on ocular helminth infections by reporting a unique case involving the lens. It highlights the need for further research to understand the pathogenesis and mechanism of entry of helminths in the lens. Data Collection and Analysis Procedures: The data for this case report were collected through clinical examination and medical records of the patient. The findings were described and presented in a descriptive manner. No statistical analysis was conducted. Question Addressed: This case report addresses the question of whether ocular helminth infections can occur in the lens, which has not been previously reported. Conclusion: To the best of our knowledge, this is the first reported case of ocular helminth infection in the lens. The presence of the helminth in the lens raises interesting questions regarding its pathogenesis and entry mechanism. Further study and research are needed to explore these aspects. Ophthalmologists and parasitologists should be aware of the possibility of ocular helminth infections in unusual sites like the lens.

Keywords: ocular, helminth, unsual site, lens

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Authors: Faranak Felfeliyan, Parvaneh Shokrani, Maryam Atarod

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Introduction Using electron beam is widespread in radiotherapy. The main criteria in radiation therapy is to irradiate the tumor volume with maximum prescribed dose and minimum dose to vital organs around it. Using abutting fields is common in radiotherapy. The main problem in using abutting fields is dose inhomogeneity in the junction region. Electron beam divergence and lateral scattering may lead to hot and cold spots in the junction region. One solution for this problem is using of a spoiler to broaden the penumbra and uniform dose in the junction region. The goal of this research was to compare titanium and aluminum effects as a spoiler for dose uniformity achievement in the junction region of oblique electron fields with Monte Carlo simulation. Dose uniformity in the junction region depends on density, scattering power, thickness of the spoiler and the angle between two fields. Materials and Methods In this study, Monte Carlo model of Siemens Primus linear accelerator was simulated for a 5 MeV nominal energy electron beam using manufacture provided specifications. BEAMnrc and EGSnrc user code were used to simulate the treatment head in electron mode (simulation of beam model). The resulting phase space file was used as a source for dose calculations for 10×10 cm2 field size at SSD=100 cm in a 30×30×45 cm3 water phantom using DOSXYZnrc user code (dose calculations). An automatic MP3-M water phantom tank, MEPHYSTO mc2 software platform and a Semi-Flex Chamber-31010 with sensitive vol­ume of 0.125 cm3 (PTW, Freiburg, Germany) were used for dose distribution measurements. Moreover, the electron field size was 10×10 cm2 and SSD=100 cm. Validation of devel­oped beam model was done by comparing the measured and calculated depth and lateral dose distributions (verification of electron beam model). Simulation of spoilers (using SLAB compo­nent module) placed at the end of the electron applicator, was done using previously vali­dated phase space file for a 5 MeV nominal energy and 10×10 cm2 field size (simulation of spoiler). An in-house routine was developed in order to calculate the combined isodose curves re­sulting from the two simulated abutting fields (calculation of dose distribution in abutting electron fields). Results Verification of the developed 5.9 MeV elec­tron beam model was done by comparing the calculated and measured dose distributions. The maximum percentage difference between calculated and measured PDD was 1%, except for the build-up region in which the difference was 2%. The difference between calculated and measured profile was 2% at the edges of the field and less than 1% in other regions. The effect of PMMA, aluminum, titanium and chromium in dose uniformity achievement in abutting normal electron fields with equivalent thicknesses to 5mm PMMA was evaluated. Comparing R90 and uniformity index of different materials, aluminum was chosen as the optimum spoiler. Titanium has the maximum surface dose. Thus, aluminum and titanium had been chosen to use for dose uniformity achievement in oblique electron fields. Using the optimum beam spoiler, junction dose decreased from 160% to 110% for 15 degrees, from 180% to 120% for 30 degrees, from 160% to 120% for 45 degrees and from 180% to 100% for 60 degrees oblique abutting fields. Using Titanium spoiler, junction dose decreased from 160% to 120% for 15 degrees, 180% to 120% for 30 degrees, 160% to 120% for 45 degrees and 180% to 110% for 60 degrees. In addition, penumbra width for 15 degrees, without spoiler in the surface was 10 mm and was increased to 15.5 mm with titanium spoiler. For 30 degrees, from 9 mm to 15 mm, for 45 degrees from 4 mm to 6 mm and for 60 degrees, from 5 mm to 8 mm. Conclusion Using spoilers, penumbra width at the surface increased, size and depth of hot spots was decreased and dose homogeneity improved at the junc­tion of abutting electron fields. Dose at the junction region of abutting oblique fields was improved significantly by using spoiler. Maximum dose at the junction region for 15⁰, 30⁰, 45⁰ and 60⁰ was decreased about 40%, 60%, 40% and 70% respectively for Titanium and about 50%, 60%, 40% and 80% for Aluminum. Considering significantly decrease in maximum dose using titanium spoiler, unfortunately, dose distribution in the junction region was not decreased less than 110%.

Keywords: abutting fields, electron beam, radiation therapy, spoilers

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Authors: Ling Ai, Ziyu Zhao, Zeyu Zhou, Xiaochen Yang, Heng Zhai, Stuart Holmes

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Optimizing the catalyst layer structure is crucial for enhancing the performance of proton exchange membrane fuel cells (PEMFCs) with low Platinum (Pt) loading. Current works focused on the utilization, durability, and site activity of Pt particles on support, and performance enhancement has been achieved by loading Pt onto porous support with different morphology, such as graphene, carbon fiber, and carbon black. Some schemes have also incorporated cost considerations to achieve lower Pt loading. However, the design of the catalyst layer (CL) structure in the membrane electrode assembly (MEA) must consider the interactions between the layers. Addressing the crucial aspects of water management, low contact resistance, and the establishment of effective three-phase boundary for MEA, multi-walled carbon nanotubes (MWCNTs) are promising CL support due to their intrinsically high hydrophobicity, high axial electrical conductivity, and potential for ordered alignment. However, the drawbacks of MWCNTs, such as strong agglomeration, wall surface chemical inertness, and unopened ends, are unfavorable for Pt nanoparticle loading, which is detrimental to MEA processing and leads to inhomogeneous CL surfaces. This further deteriorates the utilization of Pt and increases the contact resistance. Robust chemical oxidation or nitrogen doping can introduce polar functional groups onto the surface of MWCNTs, facilitating the creation of open tube ends and inducing defects in tube walls. This improves dispersibility and load capacity but reduces length and conductivity. Consequently, a trade-off exists between maintaining the intrinsic properties and the degree of functionalization of MWCNTs. In this work, MWCNTs were modified based on the operational requirements of the MEA from the viewpoint of interlayer interactions, including the search for the optimal degree of oxidation, N-doping, and micro-arrangement. MWCNT were functionalized by oxidizing, N-doping, as well as micro-alignment to achieve lower contact resistance between CL and proton exchange membrane (PEM), better hydrophobicity, and enhanced performance. Furthermore, this work expects to construct a more continuously distributed three-phase boundary by aligning MWCNT to form a locally ordered structure, which is essential for the efficient utilization of Pt active sites. Different from other chemical oxidation schemes that used HNO3:H2SO4 (1:3) mixed acid to strongly oxidize MWCNT, this scheme adopted pure HNO3 to partially oxidize MWCNT at a lower reflux temperature (80 ℃) and a shorter treatment time (0 to 10 h) to preserve the morphology and intrinsic conductivity of MWCNT. The maximum power density of 979.81 mw cm-2 was achieved by Pt loading on 6h MWCNT oxidation time (Pt-MWCNT6h). This represented a 59.53% improvement over the commercial Pt/C catalyst of 614.17 (mw cm-2). In addition, due to the stronger electrical conductivity, the charge transfer resistance of Pt-MWCNT6h in the electrochemical impedance spectroscopy (EIS) test was 0.09 Ohm cm-2, which was 48.86% lower than that of Pt/C. This study will discuss the developed catalysts and their efficacy in a working fuel cell system. This research will validate the impact of low-functionalization modification of MWCNTs on the performance of PEMFC, which simplifies the preparation challenges of CL and contributing for the widespread commercial application of PEMFCs on a larger scale.

Keywords: carbon nanotubes, electrocatalyst, membrane electrode assembly, proton exchange membrane fuel cell

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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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Authors: Zeynep Busra Velioglu, Deniz Pulat, Beril Demirbakan, Burak Ozcan, Ece Bayrak, Cevat Erisken

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Bone tissue has the ability to perform a wide array of functions including providing posture, load-bearing capacity, protection for the internal organs, initiating hematopoiesis, and maintaining the homeostasis of key electrolytes via calcium/phosphate ion storage. The most common cause for bone defects is extensive trauma and subsequent infection. Bone tissue has the self-healing capability without a scar tissue formation for the majority of the injuries. However, some may result with delayed union or fracture non-union. Such cases include reconstruction of large bone defects or cases of compromised regenerative process as a result of avascular necrosis and osteoporosis. Several surgical methods exist to treat bone defects, including Ilizarov method, Masquelete technique, growth factor stimulation, and bone replacement. Unfortunately, these are technically demanding and come with noteworthy disadvantages such as lengthy treatment duration, adverse effects on the patient’s psychology, repeated surgical procedures, and often long hospitalization times. These limitations associated with surgical techniques make bone substitutes an attractive alternative. Here, it was hypothesized that a 3D printed scaffold will mimic trabecular bone in terms of biomechanical properties and that such scaffolds will support cell attachment and survival. To test this hypothesis, this study aimed at fabricating poly(lactic acid), PLA, structures using 3D printing technology for trabecular bone defects, characterizing the scaffolds and comparing with bovine trabecular bone. Capacity of scaffolds on human bone marrow stem cell (hBMSC) attachment and survival was also evaluated. Cubes with a volume of 1 cm³ having pore sizes of 0.50, 1.00 and 1.25 mm were printed. The scaffolds/grafts were characterized in terms of porosity, contact angle, compressive mechanical properties as well cell response. Porosities of the 3D printed scaffolds were calculated based on apparent densities. For contact angles, 50 µl distilled water was dropped over the surface of scaffolds, and contact angles were measured using ‘Image J’ software. Mechanical characterization under compression was performed on scaffolds and native trabecular bone (bovine, 15 months) specimens using a universal testing machine at a rate of 0.5mm/min. hBMSCs were seeded onto the 3D printed scaffolds. After 3 days of incubation with fully supplemented Dulbecco’s modified Eagle’s medium, the cells were fixed using 2% formaldehyde and glutaraldehyde mixture. The specimens were then imaged under scanning electron microscopy. Cell proliferation was determined by using EZQuant dsDNA Quantitation kit. Fluorescence was measured using microplate reader Spectramax M2 at the excitation and emission wavelengths of 485nm and 535nm, respectively. Findings suggested that porosity of scaffolds with pore dimensions of 0.5mm, 1.0mm and 1.25mm were not affected by pore size, while contact angle and compressive modulus decreased with increasing pore size. Biomechanical characterization of trabecular bone yielded higher modulus values as compared to scaffolds with all pore sizes studied. Cells attached and survived in all surfaces, demonstrating higher proliferation on scaffolds with 1.25mm pores as compared with those of 1mm. Collectively, given lower mechanical properties of scaffolds as compared to native bone, and biocompatibility of the scaffolds, the 3D printed PLA scaffolds of this study appear as candidate substitutes for bone repair and regeneration.

Keywords: 3D printing, biomechanics, bone repair, stem cell

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Authors: Jonathan Adeyemi

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Context: This study focuses on El Anatsui and his global acclaim in the art world despite his origins from the global artworld’s margins. It addresses the disparities in the treatment between Western and non-Western artists and questions whether Anatsui’s consecration is a result of exoticism or the growing consensus on decolonization. Research Aim: The aim of this study is to investigate how El Anatsui achieved global acclaim from the margins of the art world and determine if his consecration represents a mark of decolonization or the typical Western desire for exoticism. Methodology: The study utilizes a case study approach, literature analysis, and in-depth interviews. The artist, the organizers of the Venice Biennale, the relevant curators at Tate Modern London, and the October Gallery in London, and other galleries in Nigeria, which represent the artist were interviewed for data collection. Findings: The study seeks to determine the authenticity of the growing consensus on decolonization, inclusion, and diversity in the global artistic field. Preliminary findings show that domestic socio-economic and political factors debilitated the mechanisms for local validation in Nigeria, weakening the domestic foundation for international engagement. However, alternative systems of exhibition, especially in London and the USA contributed critically to providing the initial international visibility, which formed the foundation for his global acclaim. Out of the 21 winners of the Golden Lion for Lifetime Achievement since its inception at the 47th Venice Biennale in 1997, American artists have dominated with 10 recipients, 8 recipients from Europe, 2 recipients from Africa (2007 and 2015) and 1 from Asia. This aligns with Bourdieu’s concept of cultural and economic capital, which prevented Africa countries from participation until recently. Moreover, while the average age of recipients is 76 years, Anatsui received the award at the age of 71, while Malick Sidibé (Mali) was awarded at 72. Thus, the Venice Biennale award for El Anatsui incline more towards a commitment to decolonisation than exoticism. Theoretical Importance: This study contributes to the field by examining the dynamics of the art world's monopoly of legitimation and the role of national, ethnicity and cultural differences in the promotion of artists. It aims to challenge the Westernized hierarchy of valorization and consecration in the art world. The research supports Bourdieu’s artistic field theory, which emphasises the importance of cultural, economic and social capital in determining agents’ position and access to the field resources (symbolic capital). Bourdieu also established that dominated agents can change their position in the field’s hierarchy either by establishing or navigating alternative systems. Data Collection and Analysis Procedures: The opacity of art world’s operations places the required information within the purview of the insiders (agents). Thus, the study collects data through in-depth interviews with relevant and purposively selected individuals and organizations. The data was/will be analyzed using qualitative methods, such as thematic analysis and content analysis. The interpretive analytical approach adopted facilitated the construction of meanings that may not be apparent in the data or responses. Questions Addressed: The study addresses how El Anatsui achieved global acclaim despite being from the margins, whether his consecration represents decolonization or exoticism, and the extent to which the global artistic field embraces decolonization, inclusion, and diversity. Conclusion: The study will contribute to knowledge by providing insights into the extent of commitment to decolonization, inclusion, and diversity in the global artistic field. It also shed light on the mechanisms behind El Anatsui's rise to global acclaim and challenge Western-dominated artistic hierarchies.

Keywords: decolonisation, exorticism, artistic field, culture game

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Authors: Robert E. Kenney, Efrain Antunez, Samuel Nodal, Ameer Malik, Richard B. Aguilar

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Physician burnout has gained much attention during the COVID pandemic. After-hours workload, HCC coding, HEDIS metrics, and clinical documentation negatively impact career satisfaction. These and other influences have increased the rate of physicians leaving the workforce. In addition, roughly 1% of the entire physician workforce will be retiring earlier than expected based on pre-pandemic trends. The two Medical Specialties with the highest rates of burnout are Family Medicine and Primary Care. With a predicted shortage of primary care physicians looming, the need to address physician burnout is crucial. Commonly reported issues leading to clinician burnout are clerical documentation requirements, increased time working on Electronic Health Records (EHR) after hours, and a decrease in work-life balance. Clinicians experiencing burnout with physical and emotional exhaustion are at an increased likelihood of providing lower quality and less efficient patient care. This may include a lack of suitable clinical documentation, medication reconciliation, clinical assessment, and treatment plans. While the annual baseline turnover rates of physicians hover around 6-7%, the COVID pandemic profoundly disrupted the delivery of healthcare. A report found that 43% of physicians switched jobs during the initial two years of the COVID pandemic (2020 and 2021), tripling the expected average annual rate to 21.5 %/yr. During this same time, an average of 4% and 1.5% of physicians retired or left the workforce for a non-clinical career, respectively. The report notes that 35.2% made career changes for a better work-life balance and another 35% reported the reason as being unhappy with their administration’s response to the pandemic. A physician-led primary care-focused health organization, Cano Health (CH), based out of Florida, sought to preemptively address this problem by implementing several supportive measures. Working with >120 clinics and >280 PCPs from Miami to Tampa and Orlando, managing nearly 120,000 Medicare Advantage lives, CH implemented a number of changes to assist with the clinician’s workload. Supportive services such as after hour and home visits by APRNs, in-clinic care managers, and patient educators were implemented. In 2021, assistive Artificial Intelligence Software (AIS) was integrated into the EHR platform. This AIS converts free text within PDF files into a usable (copy-paste) format facilitating documentation. The software also systematically and chronologically organizes clinical data, including labs, medical records, consultations, diagnostic images, medications, etc., into an easy-to-use organ system or chronic disease state format. This reduced the excess time and documentation burden required to meet payor and CMS guidelines. A clinician Documentation Support team was employed to improve the billing/coding performance. The effects of these newly designed workflow interventions were measured via analysis of clinician turnover from CH’s hiring and termination reporting software. CH’s annualized average clinician turnover rate in 2020 and 2021 were 17.7% and 12.6%, respectively. This represents a 30% relative reduction in turnover rate compared to the reported national average of 21.5%. Retirement rates during both years were 0.1%, demonstrating a relative reduction of >95% compared to the national average (4%). This model successfully promoted the retention of clinicians in a Value-Based Care setting.

Keywords: clinician burnout, COVID-19, value-based care, burnout, clinician retirement

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Authors: Jennifer Wheeldon, Nick de Viggiani, Nikki Cotterill

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Background: Urinary and fecal incontinence affect a significant proportion of older adults aged 65 and over who permanently reside in residential and nursing home facilities. Incontinence symptoms have been linked to comorbidities, an increased risk of infection and reduced quality of life and mental wellbeing of residents. However, continence care provision can often be poor, further compromising the health and wellbeing of this vulnerable population. Objectives: To identify experiences and perceptions of continence care provision in older adult residential care settings and to identify factors that help or hinder good continence care provision. Settings included both residential care homes and nursing homes for older adults. Methods: A qualitative evidence synthesis using systematic review methodology established the current evidence-base. Data from 20 qualitative and mixed-method studies was appraised and synthesized. Following the review process, 10* qualitative interviews with staff working in older adult residential care settings were conducted across six* sites, which included registered managers, registered nurses and nursing/care assistants/aides. Purposive sampling recruited individuals from across England. Both evidence synthesis and interview data was analyzed thematically, both manually and with NVivo software. Results: The evidence synthesis revealed complex barriers and facilitators for continence care provision at three influencing levels: macro (structural and societal external influences), meso (organizational and institutional influences) and micro (day-to-day actions of individuals impacting service delivery). Macro-level barriers included negative stigmas relating to incontinence, aging and working in the older adult social care sector, restriction of continence care resources such as containment products (i.e. pads), short staffing in care facilities, shortfalls in the professional education and training of care home staff and the complex health and social care needs of older adult residents. Meso-level barriers included task-centered organizational cultures, ageist institutional perspectives regarding old age and incontinence symptoms, inadequate care home management and poor communication and teamwork among care staff. Micro-level barriers included poor knowledge and negative attitudes of care home staff and residents regarding incontinence symptoms and symptom management and treatment. Facilitators at the micro-level included proactive and inclusive leadership skills of individuals in management roles. Conclusions: The findings of the evidence synthesis study help to outline the complexities of continence care provision in older adult care homes facilities. Macro, meso and micro level influences demonstrate problematic and interrelated barriers across international contexts, indicating that improving continence care in this setting is extremely challenging due to the multiple levels at which care provision and services are impacted. Both international and national older adult social care policy-makers, researchers and service providers must recognize this complexity, and any intervention seeking to improve continence care in older adult care home settings must be planned accordingly and appreciatively of the complex and interrelated influences. It is anticipated that the findings of the qualitative interviews will shed further light on the national context of continence care provision specific to England; data collection is ongoing*. * Sample size is envisaged to be between 20-30 participants from multiple sites by Spring 2023.

Keywords: continence care, residential and nursing homes, evidence synthesis, qualitative

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Authors: Farid Risheq, M. Zaid Alrisheq, Shuaa Al-Sadoon, Karim Al-Faqih, Mays Abdulazeez

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Breast cancer is the most frequently diagnosed cancer worldwide, and a common cause of death among women. Various conventional anatomical imaging tools are utilized for diagnosis, histological assessment and TNM (Tumor, Node, Metastases) staging of breast cancer. Biopsy of sentinel lymph node is becoming an alternative to the axillary lymph node dissection. Advances in 18-Fluoro-Deoxi-Glucose Positron Emission Tomography/Computed Tomography (18FDG-PET/CT) imaging have facilitated breast cancer diagnosis utilizing biological trapping of 18FDG inside lesion cells, expressed as Standardized Uptake Value (SUVmax). Objective: To present the utility of 18FDG uptake PET/CT scans in detecting active extra lymph nodes and distant occult metastases for breast cancer staging. Subjects and Methods: Four female patients were presented with initially classified TNM stages of breast cancer based on conventional anatomical diagnostic techniques. 18FDG-PET/CT scans were performed one hour post 18FDG intra-venous injection of (300-370) MBq, and (7-8) bed/130sec. Transverse, sagittal, and coronal views; fused PET/CT and MIP modality were reconstructed for each patient. Results: A total of twenty four lesions in breast, extended lesions to lung, liver, bone and active extra lymph nodes were detected among patients. The initial TNM stage was significantly changed post 18FDG-PET/CT scan for each patient, as follows: Patient-1: Initial TNM-stage: T1N1M0-(stage I). Finding: Two lesions in right breast (3.2cm2, SUVmax=10.2), (1.8cm2, SUVmax=6.7), associated with metastases to two right axillary lymph nodes. Final TNM-stage: T1N2M0-(stage II). Patient-2: Initial TNM-stage: T2N2M0-(stage III). Finding: Right breast lesion (6.1cm2, SUVmax=15.2), associated with metastases to right internal mammary lymph node, two right axillary lymph nodes, and sclerotic lesions in right scapula. Final TNM-stage: T2N3M1-(stage IV). Patient-3: Initial TNM-stage: T2N0M1-(stage III). Finding: Left breast lesion (11.1cm2, SUVmax=18.8), associated with metastases to two lymph nodes in left hilum, and three lesions in both lungs. Final TNM-stage: T2N2M1-(stage IV). Patient-4: Initial TNM-stage: T4N1M1-(stage III). Finding: Four lesions in upper outer quadrant area of right breast (largest: 12.7cm2, SUVmax=18.6), in addition to one lesion in left breast (4.8cm2, SUVmax=7.1), associated with metastases to multiple lesions in liver (largest: 11.4cm2, SUV=8.0), and two bony-lytic lesions in left scapula and cervicle-1. No evidence of regional or distant lymph node involvement. Final TNM-stage: T4N0M2-(stage IV). Conclusions: Our results demonstrated that 18FDG-PET/CT scans had significantly changed the TNM stages of breast cancer patients. While the T factor was unchanged, N and M factors showed significant variations. A single session of PET/CT scan was effective in detecting active extra lymph nodes and distant occult metastases, which were not identified by conventional diagnostic techniques, and might advantageously replace bone scan, and contrast enhanced CT of chest, abdomen and pelvis. Applying 18FDG-PET/CT scan early in the investigation, might shorten diagnosis time, helps deciding adequate treatment protocol, and could improve patients’ quality of life and survival. Trapping of 18FDG in malignant lesion cells, after a PET/CT scan, increases the retention index (RI%) for a considerable time, which might help localize sentinel lymph node for biopsy using a hand held gamma probe detector. Future work is required to demonstrate its utility.

Keywords: axillary lymph nodes, breast cancer staging, fluorodeoxyglucose positron emission tomography/computed tomography, lymph nodes

Procedia PDF Downloads 311

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

Procedia PDF Downloads 135

Authors: Alexandria Carey, Angela Starkweather, Ann Horgas, Hwayoung Cho, Jason Beneciuk

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Background/Significance: Over 3.4 million acute axial low back pain (aLBP) cases are treated annually in the United States (US) emergency departments (ED). ED patients with aLBP receive varying verbal and written discharge routine care (RC), leading to ineffective patient self-management. Ineffective self-management increase chronic low back pain (cLPB) transition risks, a chief cause of worldwide disability, with associated costs >$60 million annually. This research addresses this significant problem by evaluating an ED digital pain self-management intervention (EDPSI) focused on improving self-management through improved knowledge retainment, skills, and self-efficacy (confidence) (KSC) thus reducing aLBP to cLBP transition in ED patients discharged with aLBP. The research has significant potential to increase self-efficacy, one of the most potent mechanisms of behavior change and improve health outcomes. Focusing on accessibility and usability, the intervention may reduce discharge disparities in aLBP self-management, especially with low health literacy. Study Questions: This research will answer the following questions: 1) Will an EDPSI focused on improving KSC progress patient self-management behaviors and health status?; 2) Is the EDPSI sustainable to improve pain severity, interference, and pain recurrence?; 3) Will an EDPSI reduce aLBP to cLBP transition in patients discharged with aLBP? Aims: The pilot randomized-controlled trial (RCT) study’s objectives assess the effects of a 12-week digital self-management discharge tool in patients with aLBP. We aim to 1) Primarily assess the feasibility [recruitment, enrollment, and retention], and [intervention] acceptability, and sustainability of EDPSI on participant’s pain self-management; 2) Determine the effectiveness and sustainability of EDPSI on pain severity/interference among participants. 3) Explore patient preferences, health literacy, and changes among participants experiencing the transition to cLBP. We anticipate that EDPSI intervention will increase likelihood of achieving self-management milestones and significantly improve pain-related symptoms in aLBP. Methods: The study uses a two-group pilot RCT to enroll 30 individuals who have been seen in the ED with aLBP. Participants are randomized into RC (n=15) or RC + EDPSI (n=15) and receive follow-up surveys for 12-weeks post-intervention. EDPSI innovative content focuses on 1) highlighting discharge education; 2) provides self-management treatment options; 3) actor demonstration of ergonomics, range of motion movements, safety, and sleep; 4) complementary alternative medicine (CAM) options including acupuncture, yoga, and Pilates; 5) combination therapies including thermal application, spinal manipulation, and PT treatments. The intervention group receives Booster sessions via Zoom to assess and reinforce their knowledge retention of techniques and provide return demonstration reinforcing ergonomics, in weeks two and eight. Outcome Measures: All participants are followed for 12-weeks, assessing pain severity/ interference using the Brief Pain Inventory short-form (BPI-sf) survey, self-management (measuring KSC) using the short 13-item Patient Activation Measure (PAM), and self-efficacy using the Pain Self-Efficacy Questionnaire (PSEQ) weeks 1, 6, and 12. Feasibility is measured by recruitment, enrollment, and retention percentages. Acceptability and education satisfaction are measured using the Education-Preference and Satisfaction Questionnaire (EPSQ) post-intervention. Self-management sustainment is measured including PSEQ, PAM, and patient satisfaction and healthcare utilization (PSHU) requesting patient overall satisfaction, additional healthcare utilization, and pain management related to continued back pain or complications post-injury.

Keywords: digital, pain self-management, education, tool

Procedia PDF Downloads 48

Authors: Piotr K. Szewczyk, Arkadiusz Gradys, Sungkyun Kim, Luana Persano, Mateusz M. Marzec, Oleksander Kryshtal, Andrzej Bernasik, Sohini Kar-Narayan, Pawel Sajkiewicz, Urszula Stachewicz

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Piezoelectric polymers have received great attention in smart textiles, wearables, and flexible electronics. Their potential applications range from devices that could operate without traditional power sources, through self-powering sensors, up to implantable biosensors. Semi-crystalline PVDF is often proposed as the main candidate for industrial-scale applications as it exhibits exceptional energy harvesting efficiency compared to other polymers combined with high mechanical strength and thermal stability. Plenty of approaches have been proposed for obtaining PVDF rich in the desired β-phase with electric polling, thermal annealing, and mechanical stretching being the most prevalent. Electrospinning is a highly tunable technique that provides a one-step process of obtaining highly piezoelectric PVDF fibers without the need for post-treatment. In this study, voltage polarity and relative humidity influence on electrospun PVDF, fibers were investigated with the main focus on piezoelectric β-phase contents and piezoelectric performance. Morphology and internal structure of fibers were investigated using scanning (SEM) and transmission electron microscopy techniques (TEM). Fourier Transform Infrared Spectroscopy (FITR), wide-angle X-ray scattering (WAXS) and differential scanning calorimetry (DSC) were used to characterize the phase composition of electrospun PVDF. Additionally, surface chemistry was verified with X-ray photoelectron spectroscopy (XPS). Piezoelectric performance of individual electrospun PVDF fibers was measured using piezoresponse force microscopy (PFM), and the power output from meshes was analyzed via custom-built equipment. To prepare the solution for electrospinning, PVDF pellets were dissolved in dimethylacetamide and acetone solution in a 1:1 ratio to achieve a 24% solution. Fibers were electrospun with a constant voltage of +/-15kV applied to the stainless steel nozzle with the inner diameter of 0.8mm. The flow rate was kept constant at 6mlh⁻¹. The electrospinning of PVDF was performed at T = 25°C and relative humidity of 30 and 60% for PVDF30+/- and PVDF60+/- samples respectively in the environmental chamber. The SEM and TEM analysis of fibers produced at a lower relative humidity of 30% (PVDF30+/-) showed a smooth surface in opposition to fibers obtained at 60% relative humidity (PVDF60+/-), which had wrinkled surface and additionally internal voids. XPS results confirmed lower fluorine content at the surface of PVDF- fibers obtained by electrospinning with negative voltage polarity comparing to the PVDF+ obtained with positive voltage polarity. Changes in surface composition measured with XPS were found to influence the piezoelectric performance of obtained fibers what was further confirmed by PFM as well as by custom-built fiber-based piezoelectric generator. For PVDF60+/- samples humidity led to an increase of β-phase contents in PVDF fibers as confirmed by FTIR, WAXS, and DSC measurements, which showed almost two times higher concentrations of β-phase. A combination of negative voltage polarity with high relative humidity led to fibers with the highest β-phase contents and the best piezoelectric performance of all investigated samples. This study outlines the possibility to produce electrospun PVDF fibers with tunable piezoelectric performance in a one-step electrospinning process by controlling relative humidity and voltage polarity conditions. Acknowledgment: This research was conducted within the funding from m the Sonata Bis 5 project granted by National Science Centre, No 2015/18/E/ST5/00230, and supported by the infrastructure at International Centre of Electron Microscopy for Materials Science (IC-EM) at AGH University of Science and Technology. The PFM measurements were supported by an STSM Grant from COST Action CA17107.

Keywords: crystallinity, electrospinning, PVDF, voltage polarity

Procedia PDF Downloads 130

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

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

Keywords: crocetin, crocin, medulloblastoma, saffron

Procedia PDF Downloads 215

Authors: L. Ereku, R. E. Mackay, A. Naveenathayalan, K. Ajayi, W. Balachandran

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Over the past decade the increase of sexually transmitted infections (STIs) especially in the developing world due to high cost and lack of sufficient medical testing have given rise to the need for a rapid, low cost point of care medical diagnostic that is disposable and most significantly reproduces equivocal results achieved within centralised laboratories. This paper present the development of a disposable PDMS microfluidic cartridge incorporating blisters filled with reagents required for isothermal DNA amplification in clinical diagnostics and point-of-care testing. In view of circumventing the necessity for external complex microfluidic pumps, designing on-chip pressurised fluid reservoirs is embraced using finger actuation and blister storage. The fabrication of the blisters takes into consideration three proponents that include: material characteristics, fluid volume and structural design. Silicone rubber is the chosen material due to its good chemical stability, considerable tear resistance and moderate tension/compression strength. The case of fluid capacity and structural form go hand in hand as the reagent need for the experimental analysis determines the volume size of the blisters, whereas the structural form has to be designed to provide low compression stress when deformed for fluid expulsion. Furthermore, the top and bottom section of the blisters are embedded with miniature polar opposite magnets at a defined parallel distance. These magnets are needed to lock or restrain the blisters when fully compressed so as to prevent unneeded backflow as a result of elasticity. The integrated chip is bonded onto a large microscope glass slide (50mm x 75mm). Each part is manufactured using a 3D printed mould designed using Solidworks software. Die-casting is employed, using 3D printed moulds, to form the deformable blisters by forcing a proprietary liquid silicone rubber through the positive mould cavity. The set silicone rubber is removed from the cast and prefilled with liquid reagent and then sealed with a thin (0.3mm) burstable layer of recast silicone rubber. The main microfluidic cartridge is fabricated using classical soft lithographic techniques. The cartridge incorporates microchannel circuitry, mixing chamber, inlet port, outlet port, reaction chamber and waste chamber. Polydimethylsiloxane (PDMS, QSil 216) is mixed and degassed using a centrifuge (ratio 10:1) is then poured after the prefilled blisters are correctly positioned on the negative mould. Heat treatment of about 50C to 60C in the oven for about 3hours is needed to achieve curing. The latter chip production stage involves bonding the cured PDMS to the glass slide. A plasma coroner treater device BD20-AC (Electro-Technic Products Inc., US) is used to activate the PDMS and glass slide before they are both joined and adequately compressed together, then left in the oven over the night to ensure bonding. There are two blisters in total needed for experimentation; the first will be used as a wash buffer to remove any remaining cell debris and unbound DNA while the second will contain 100uL amplification reagents. This paper will present results of chemical cell lysis, extraction using a biopolymer paper membrane and isothermal amplification on a low-cost platform using the finger actuated blisters for reagent storage. The platform has been shown to detect 1x105 copies of Chlamydia trachomatis using Recombinase Polymerase Amplification (RPA).

Keywords: finger actuation, point of care, reagent storage, silicone blisters

Procedia PDF Downloads 367

Authors: Kelsi Hagerty, Ami Rosen, Aaliyah Heyward, Nadia Ali, Emily Brown, Erin Demo, Yue Guan, Modele Ogunniyi, Brianna McDaniels, Alanna Morris, Kunal Bhatt

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Hereditary transthyretin amyloidosis (hATTR) is a progressive, multi-systemic, and life-threatening disease caused by a disruption in the TTR protein that delivers thyroxine and retinol to the liver. This disruption causes the protein to misfold into amyloid fibrils, leading to the accumulation of the amyloid fibrils in the heart, nerves, and GI tract. Over 130 variants in the TTR gene are known to cause hATTR. The Val122Ile variant is the most common in the United States and is seen almost exclusively in people of African descent. TTR variants are inherited in an autosomal dominant fashion and have incomplete penetrance and variable expressivity. Individuals with hATTR may exhibit symptoms from as early as 30 years to as late as 80 years of age. hATTR is characterized by a wide range of clinical symptoms such as cardiomyopathy, neuropathy, carpal tunnel syndrome, and GI complications. Without treatment, hATTR leads to progressive disease and can ultimately lead to heart failure. hATTR disproportionately affects individuals of African descent; the estimated prevalence of hATTR among Black individuals in the US is 3.4%. Unfortunately, hATTR is often underdiagnosed and misdiagnosed because many symptoms of the disease overlap with other cardiac conditions. Due to the progressive nature of the disease, multi-systemic manifestations that can lead to a shortened lifespan, and the availability of free genetic testing and promising FDA-approved therapies that enhance treatability, early identification of individuals with a pathogenic hATTR variant is important, as this can significantly impact medical management for patients and their relatives. Furthermore, recent literature suggests that TTR genetic testing should be performed in all patients with suspicion of TTR-related cardiomyopathy, regardless of age, and that follow-up with genetic counseling services is recommended. Relatives of patients with hATTR benefit from genetic testing because testing can identify carriers early and allow relatives to receive regular screening and management. Despite the striking prevalence of hATTR among Black individuals, hATTR remains underdiagnosed in this patient population, and germline genetic testing for hATTR in Black individuals seems to be underrepresented, though the reasons for this have not yet been brought to light. Historically, Black patients experience a number of barriers to seeking healthcare that has been hypothesized to perpetuate the underdiagnosis of hATTR, such as lack of access and mistrust of healthcare professionals. Prior research has described a myriad of factors that shape an individual’s decision about whether to pursue presymptomatic genetic testing for a familial pathogenic variant, such as family closeness and communication, family dynamics, and a desire to inform other family members about potential health risks. This study explores these factors through 10 in-depth interviews with patients with hATTR about what factors may be contributing to the underdiagnosis of hATTR in the Black population. Participants were selected from the Emory University Amyloidosis clinic based on having a molecular diagnosis of hATTR. Interviews were recorded and transcribed verbatim, then coded using MAXQDA software. Thematic analysis was completed to draw commonalities between participants. Upon preliminary analysis, several themes have emerged. Barriers identified include i) Misdiagnosis and a prolonged diagnostic odyssey, ii) Family communication and dynamics surrounding health issues, iii) Perceptions of healthcare and one’s own health risks, and iv) The need for more intimate provider-patient relationships and communication. Overall, this study gleaned valuable insight from members of the Black community about possible factors contributing to the underdiagnosis of hATTR, as well as potential solutions to go about resolving this issue.

Keywords: cardiac amyloidosis, heart failure, TTR, genetic testing

Procedia PDF Downloads 96

Authors: P. J. Sweeney, T. Ahtoniemi, J. Puoliväli, T. Laitinen, K.Lehtimäki, A. Nurmi, D. Wells

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Duchenne muscular dystrophy (DMD) is an X-linked, lethal muscle wasting disease for which there are currently no treatment that effectively prevents the muscle necrosis and progressive muscle loss. DMD is among the most common of inherited diseases affecting around 1/3500 live male births. MDX (X-linked muscular dystrophy) mice only partially encapsulate the disease in humans and display weakness in muscles, muscle damage and edema during a period deemed the “critical period” when these mice go through cycles of muscular degeneration and regeneration. Although the MDX mutant mouse model has been extensively studied as a model for DMD, to-date an extensive temporal, non-invasive imaging profile that utilizes magnetic resonance imaging (MRI) and 1H-magnetic resonance spectroscopy (1H-MRS) has not been performed.. In addition, longitudinal imaging characterization has not coincided with attempts to exacerbate the progressive muscle damage by exercise. In this study we employed an 11.7 T small animal MRI in order to characterize the MRI and MRS profile of MDX mice longitudinally during a 12 month period during which MDX mice were subjected to exercise. Male mutant MDX mice (n=15) and male wild-type mice (n=15) were subjected to a chronic exercise regime of treadmill walking (30 min/ session) bi-weekly over the whole 12 month follow-up period. Mouse gastrocnemius and tibialis anterior muscles were profiled with baseline T2-MRI and 1H-MRS at 6 weeks of age. Imaging and spectroscopy was repeated again at 3 months, 6 months, 9 months and 12 months of age. Plasma creatine kinase (CK) level measurements were coincided with time-points for T2-MRI and 1H-MRS, but also after the “critical period” at 10 weeks of age. The results obtained from this study indicate that chronic exercise extends dystrophic phenotype of MDX mice as evidenced by T2-MRI and1H-MRS. T2-MRI revealed extent and location of the muscle damage in gastrocnemius and tibialis anterior muscles as hyperintensities (lesions and edema) in exercised MDX mice over follow-up period.. The magnitude of the muscle damage remained stable over time in exercised mice. No evident fat infiltration or cumulation to the muscle tissues was seen at any time-point in exercised MDX mice. Creatine, choline and taurine levels evaluated by 1H-MRS from the same muscles were found significantly decreased in each time-point, Extramyocellular (EMCL) and intramyocellular lipids (IMCL) did not change in exercised mice supporting the findings from anatomical T2-MRI scans for fat content. Creatine kinase levels were found to be significantly higher in exercised MDX mice during the follow-up period and importantly CK levels remained stable over the whole follow-up period. Taken together, we have described here longitudinal prophile for muscle damage and muscle metabolic changes in MDX mice subjected to chronic exercised. The extent of the muscle damage by T2-MRI was found to be stable through the follow-up period in muscles examined. In addition, metabolic profile, especially creatine, choline and taurine levels in muscles, was found to be sustained between time-points. The anatomical muscle damage evaluated by T2-MRI was supported by plasma CK levels which remained stable over the follow-up period. These findings show that non-invasive imaging and spectroscopy can be used effectively to evaluate chronic muscle pathology. These techniques can be also used to evaluate the effect of various manipulations, like here exercise, on the phenotype of the mice. Many of the findings we present here are translatable to clinical disease, such as decreased creatine, choline and taurine levels in muscles. Imaging by T2-MRI and 1H-MRS also revealed that fat content or extramyocellar and intramyocellular lipids, respectively, are not changed in MDX mice, which is in contrast to clinical manifestation of the Duchenne’s muscle dystrophy. Findings show that non-invasive imaging can be used to characterize the phenotype of a MDX model and its translatability to clinical disease, and to study events that have traditionally been not examined, like here rigorous exercise related sustained muscle damage after the “critical period”. The ability for this model to display sustained damage beyond the spontaneous “critical period“ and in turn to study drug effects on this extended phenotype will increase the value of the MDX mouse model as a tool to study therapies and treatments aimed at DMD and associated diseases.

Keywords: 1H-MRS, MRI, muscular dystrophy, mouse model

Procedia PDF Downloads 356

Authors: Z. S. Haidar

Abstract:

Millions of teeth are removed annually, and dental extraction is one of the most commonly performed surgical procedures globally. Whether due to caries, periodontal disease, or trauma, exodontia and the ensuing wound healing and bone remodeling processes of the resultant socket (hole in the jaw bone) usually result in serious deformities of the residual alveolar osseous ridge and surrounding soft tissues (reduced height/width). Such voluminous changes render the placement of a proper conventional bridge, denture, or even an implant-supported prosthesis extremely challenging. Further, most extractions continue to be performed with no regard for preventing the onset of alveolar osteitis (also known as dry socket, a painful and difficult-to-treat/-manage condition post-exodontia). Hence, such serious resorptive morphological changes often result in significant facial deformities and a negative impact on the overall Quality of Life (QoL) of patients (and oral health-related QoL); alarming, particularly for the geriatric with compromised healing and in light of the thriving longevity statistics. Despite advances in tissue/wound grafting, serious limitations continue to exist, including efficacy and clinical outcome predictability, cost, treatment time, expertise, and risk of immune reactions. For cases of dry socket, specifically, the commercially available and often-prescribed home remedies are highly-lacking. Indeed, most are not recommended for use anymore. Alveogyl is a fine example. Hence, there is a great market demand and need for alternative solutions. Herein, SockGEL/PLUG (patent pending), an innovative, all-natural, drug-free, and injectable thermo-responsive hydrogel, was designed, formulated, characterized, and evaluated as an osteogenic, angiogenic, anti-microbial, and pain-soothing suture-free intra-alveolar dressing, safe and efficacious for use in fresh extraction sockets, immediately post-exodontia. It is composed of FDA-approved, biocompatible and biodegradable polymers, self-assembled electro-statically to formulate a scaffolding matrix to (1) prevent the on-set of alveolar osteitis via securing the fibrin-clot in situ and protecting/sealing the socket from contamination/infection; and (2) endogenously promote/accelerate wound healing and bone remodeling to preserve the volume of the alveolus. The intrinsic properties of the SockGEL/PLUG hydrogel were evaluated physical-chemical-mechanically for safety (cell viability), viscosity, rheology, bio-distribution, and essentially, capacity to induce wound healing and osteogenesis (small defect, in vivo) without any signaling cues from exogenous cells, growth factors or drugs. The proposed animal model of cranial critical-sized and non-vascularized bone defects shall provide new and critical insights into the role and mechanism of the employed natural bio-polymer blend and gel product in endogenous reparative regeneration of soft tissues and bone morphogenesis. Alongside, the fine-tuning of our modified formulation method will further tackle appropriateness, reproducibility, scalability, ease, and speed in producing stable, biodegradable, and sterilizable thermo-sensitive matrices (3-dimensional interpenetrating yet porous polymeric network) suitable for the intra-socket application. Findings are anticipated to provide sufficient evidence to translate into pilot clinical trials and validate the innovation before engaging the market for feasibility, acceptance, and cost-effectiveness studies.

Keywords: hydrogel, nanotechnology, bioengineering, bone regeneration, nanogel, drug delivery

Procedia PDF Downloads 109

Authors: Katie M. Clark, Adriana A. Tienda, Krista C. Paffenroth, Lindsey N. Brigante, Daniel C. Colvin, Jose Maldonado, Erin S. Calipari, Fiona E. Harrison

Abstract:

Manganese (Mn) is an essential trace element required for human health and is important in antioxidant defenses, as well as in the development and function of dopaminergic neurons. However, chronic low-level Mn exposure, such as through contaminated drinking water, poses risks that may contribute to neurodevelopmental and neurodegenerative conditions, including attention deficit hyperactivity disorder (ADHD). Pharmacological inhibition of the dopamine transporter (DAT) blocks reuptake, elevates synaptic dopamine, and alleviates ADHD symptoms. This study aimed to determine whether Mn exposure in juvenile mice modifies their response to DAT blockers, amphetamine, and methylphenidate and utilize neuroimaging methods to visualize and quantify Mn distribution across dopaminergic brain regions. Male and female heterozygous DATᵀ³⁵⁶ᴹ and wild-type littermates were randomly assigned to receive control (2.5% Stevia) or high Manganese (2.5 mg/ml Mn + 2.5% Stevia) via water ad libitum from weaning (21-28 days) for 4-5 weeks. Mice underwent repeated testing in locomotor activity chambers for three consecutive days (60 mins.) to ensure that they were fully habituated to the environments. On the fourth day, a 3-hour activity session was conducted following treatment with amphetamine (3 mg/kg) or methylphenidate (5 mg/kg). The second drug was administered in a second 3-hour activity session following a 1-week washout period. Following the washout, the mice were given one last injection of amphetamine and euthanized one hour later. Using the ex-vivo brains, magnetic resonance relaxometry (MRR) was performed on a 7Telsa imaging system to map T1- and T2-weighted (T1W, T2W) relaxation times. Mn inherent paramagnetic properties shorten both T1W and T2W times, which enhances the signal intensity and contrast, enabling effective visualization of Mn accumulation in the entire brain. A subset of mice was treated with amphetamine 1 hour before euthanasia. SmartSPIM light sheet microscopy with cleared whole brains and cFos and tyrosine hydroxylase (TH) labeling enabled an unbiased automated counting and densitometric analysis of TH and cFos positive cells. Immunohistochemistry was conducted to measure synaptic protein markers and quantify changes in neurotransmitter regulation. Mn exposure elevated Mn brain levels and potentiated stimulant effects in males. The globus pallidus, substantia nigra, thalamus, and striatum exhibited more pronounced T1W shortening, indicating regional susceptibility to Mn accumulation (p<0.0001, 2-Way ANOVA). In the cleared whole brains, initial analyses suggest that TH and c-Fos co-staining mirrors behavioral data with decreased co-staining in DATT356M+/- mice. Ongoing studies will identify the molecular basis of the effect of Mn, including changes to DAergic metabolism and transport and post-translational modification to the DAT. These findings demonstrate that alterations in T1W relaxation times, as measured by MRR, may serve as an early biomarker for Mn neurotoxicity. This neuroimaging approach exhibits remarkable accuracy in identifying Mn-susceptible brain regions, with a spatial resolution and sensitivity that surpasses current conventional dissection and mass spectrometry approaches. The capability to label and map TH and cFos expression across the entire brain provides insights into whole-brain neuronal activation and its connections to functional neural circuits and behavior following amphetamine and methylphenidate administration.

Keywords: manganese, environmental toxicology, dopamine dysfunction, biomarkers, drinking water, light sheet microscopy, magnetic resonance relaxometry (MRR)

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