Search results for: Raphael Zanella

Authors: Aderet M. Pantierer, Shmuel Pantierer, Raphael Cordina, Yougashwar Budhoo

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Stress concentration occurs when there is an abrupt change in geometry, a mechanical part under loading. These changes in geometry can include holes, notches, or cracks within the component. The modifications create larger stress within the part. This maximum stress is difficult to determine, as it is directly at the point of the minimum area. Strain gauges have yet to be developed to analyze stresses at such minute areas. Therefore, a stress concentration factor must be utilized. The stress concentration factor is a dimensionless parameter calculated solely on the geometry of a part. The factor is multiplied by the nominal, or average, stress of the component, which can be found analytically or experimentally. Stress concentration graphs exist for common loading conditions and geometrical configurations to aid in the determination of the maximum stress a part can withstand. These graphs were developed from historical data yielded from experimentation. This project seeks to verify a stress concentration graph for combined loading conditions. The aforementioned graph was developed using CATIA Finite Element Analysis software. The results of this analysis will be validated through further testing. The 3D modeled parts will be subjected to further finite element analysis using Patran-Nastran software. The finite element models will then be verified by testing physical specimen using a tensile testing machine. Once the data is validated, the unique stress concentration graph will be submitted for publication so it can aid engineers in future projects.

Keywords: stress concentration, finite element analysis, finite element models, combined loading

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Authors: T. Botelho de Sousa, F. Raphael Cabral Furtado, O. Eduardo da Silva Ferri, A. Batista, W. Augusto Varella, C. Eduardo Pinto, J. Mimar Santa Cruz Yabarrena, S. Gibran Ruwer, F. Müller Guerrini, L. Adalberto Philippsen Júnior

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Lean Supply Chain Management (LSCM) is an emerging research field in Operations Management (OM). As a strategic model that focuses on reduced cost and waste with fulfilling the needs of customers, LSCM attracts great interest among researchers and practitioners. The purpose of this paper is to present an overview of Lean Supply Chains literature, based on bibliometric analysis through 57 papers published in indexed journals by SCOPUS and/or Web of Science databases. The results indicate that the last three years (2015, 2016, and 2017) were the most productive on LSCM discussion, especially in Supply Chain Management and International Journal of Lean Six Sigma journals. India, USA, and UK are the most productive countries; nevertheless, cross-country studies by collaboration among researchers were detected, by social network analysis, as a research practice, appearing to play a more important role on LSCM studies. Despite existing limitation, such as limited indexed journal database, bibliometric analysis helps to enlighten ongoing efforts on LSCM researches, including most used technical procedures and collaboration network, showing important research gaps, especially, for development countries researchers.

Keywords: Lean Supply Chains, Bibliometric Study, SCOPUS, Web of Science

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Authors: Raphael de Oliveira Garcia, Samuel Rocha de Oliveira

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We have developed a new computer program in Fortran 90, in order to obtain numerical solutions of a system of Relativistic Magnetohydrodynamics partial differential equations with predetermined gravitation (GRMHD), capable of simulating the formation of relativistic jets from the accretion disk of matter up to his ejection. Initially we carried out a study on numerical methods of unidimensional Finite Volume, namely Lax-Friedrichs, Lax-Wendroff, Nessyahu-Tadmor method and Godunov methods dependent on Riemann problems, applied to equations Euler in order to verify their main features and make comparisons among those methods. It was then implemented the method of Finite Volume Centered of Nessyahu-Tadmor, a numerical schemes that has a formulation free and without dimensional separation of Riemann problem solvers, even in two or more spatial dimensions, at this point, already applied in equations GRMHD. Finally, the Nessyahu-Tadmor method was possible to obtain stable numerical solutions - without spurious oscillations or excessive dissipation - from the magnetized accretion disk process in rotation with respect to a central black hole (BH) Schwarzschild and immersed in a magnetosphere, for the ejection of matter in the form of jet over a distance of fourteen times the radius of the BH, a record in terms of astrophysical simulation of this kind. Also in our simulations, we managed to get substructures jets. A great advantage obtained was that, with the our code, we got simulate GRMHD equations in a simple personal computer.

Keywords: finite volume methods, central schemes, fortran 90, relativistic astrophysics, jet

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Authors: Raphael M. Ritti-Dias, Marilia A. Correia, Wagner J. R. Domingues, Aline C. Palmeira, Paulo Longano, Nelson Wolosker, Lauro C. Vianna, Gabriel G. Cucato

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Patients with peripheral arterial disease (PAD) have a high prevalence of hypertension, which contributes to a high risk of acute cardiovascular events and cardiovascular mortality. Strategies to reduce cardiovascular risk of these patients are needed. Meta-analysis studies have shown that isometric handgrip training promotes reductions in clinical blood pressure in normotensive, pre-hypertensive and hypertensive individuals. However, the effect of this exercise training on other cardiovascular function indicators in PAD patients remains unknown. Thus, the aim of this study was to analyze the effects of isometric handgrip training on blood pressure in patients with PAD. In this clinical trial, 28 patients were randomly allocated into two groups: isometric handgrip training (HG) and control (CG). The HG conducted the unilateral handgrip training three days per week (four sets of two minutes, with 30% of maximum voluntary contraction with an interval of four minutes between sets). CG was encouraged to increase their physical activity levels. At baseline and after eight weeks blood pressure and heart rate were obtained. ANOVA two-way for repeated measures with the group (GH and GC) and time (pre- and post-intervention) as factors was performed. After 8 weeks of training there were no significant changes in systolic blood pressure (HG pre 141 ± 24.0 mmHg vs. HG post 142 ± 22.0 mmHg; CG pre 140 ± 22.1 mmHg vs. CG post 146 ± 16.2 mmHg; P=0.18), diastolic blood pressure (HG pre 74 ± 10.4 mmHg vs. HG post 74 ± 11.9 mmHg; CG pre 72 ± 6.9 mmHg vs. CG post 74 ± 8.0 mmHg; P=0.22) and heart rate (HG pre 61 ± 10.5 bpm vs. HG post 62 ± 8.0 bpm; CG pre 64 ± 11.8 bpm vs. CG post 65 ± 13.6 bpm; P=0.81). In conclusion, our preliminary data indicate that isometric handgrip training did not modify blood pressure and heart rate in patients with PAD.

Keywords: blood pressure, exercise, isometric, peripheral artery disease

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Authors: Nathalie Baeza-Kallee, Raphaël Bergès, Victoria Hein, Stéphanie Cabaret, Jeremy Garcia, Abigaëlle Gros, Emeline Tabouret, Aurélie Tchoghandjian, Carole Colin, Dominique Figarella-Branger

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Glioblastoma (GBM) contains cancer stem cells that are resistant to treatment. GBM cancer stem cell expresses glycolipids recognized by the A2B5 antibody. A2B5, induced by the enzyme ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyl transferase 3 (ST8Sia3), plays a crucial role in the proliferation, migration, clonogenicity, and tumorigenesis of GBM cancer stem cells. Our aim was to characterize the resulting effects of neuraminidase that remove A2B5 in order to target GBM cancer stem cells. To this end, we set up a GBM organotypic slice model; quantified A2B5 expression by flow cytometry in U87-MG, U87-ST8Sia3, and GBM cancer stem cell lines, treated or not by neuraminidase; performed RNAseq and DNA methylation profiling; and analyzed the ganglioside expression by liquid chromatography-mass spectrometry in these cell lines, treated or not with neuraminidase. Results demonstrated that neuraminidase decreased A2B5 expression, tumor size, and regrowth after surgical removal in the organotypic slice model but did not induce a distinct transcriptomic or epigenetic signature in GBM CSC lines. RNAseq analysis revealed that OLIG2, CHI3L1, TIMP3, TNFAIP2, and TNFAIP6 transcripts were significantly overexpressed in U87-ST8Sia3 compared to U87-MG. RT-qPCR confirmed these results and demonstrated that neuraminidase decreased gene expression in GBM cancer stem cell lines. Moreover, neuraminidase drastically reduced ganglioside expression in GBM cancer stem cell lines. Neuraminidase, by its pleiotropic action, is an attractive local treatment against GBM.

Keywords: cancer stem cell, ganglioside, glioblastoma, targeted treatment

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Authors: João Pedro Zanella, Michel J. O. Fagundes

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Introduction: Drug use has been practised by humans universally for millennia, not excluding any population from these habits, however, the rampant drug use is a global concern due to the harm that affects the health of the world population. In this sense, it is observed the reduction of lasting and effective public policies for the resolution, increasing the demand for treatment services. With this comes ibogaine, an alkaloid derived from the root of an African bush (Tabernanthe Iboga), found mostly in Gabon and used widely by the native Bwiti population in rituals, and also other social groups, which demonstrates efficacy against chemical dependence, psychic and emotional disorders, opioid withdrawal was first confirmed by a study in rats done by Michailo Dzoljic and associates in 1988 and again in 1994. Methods: A brief description of the plant, its neurohumoral potential and the effects caused by ingested doses, in a simplified and objective way, will be discussed in the course of this abstract. Results: Ibogaine is not registered or passed by Anvisa, regarding safety and efficacy, and cannot be sold in Brazil. Its illegal trade reaches R$ 5 thousand for a session with the proceeds of the root, and its effect can last up to 72 hours, attributing Iboga's psychoactive effects to the alkaloid called ibogaine. The shrub where Ibogaine is located has pink and yellow flowers, and its fruit produced does not have psychoactive substances, but its root bark contains 6 to 7% indolic alkaloids. Besides extraction from the iboga plant, ibogaine hydrochloride can be semisynthesized from voacangine, another plant alkaloid that acts as a precursor. Its potential has the ability to perform multiple interactions with the neurotransmitter system, which are closely associated with addiction, including nicotinic, opioid and serotoninergic systems. Studies carried out by Edwards found that the doses administered of Iboga should be determined by a health professional when its purpose is to treat individuals for dependence on other drugs. Its use in small doses may cause an increase in sensibility, impaired vision and motor alterations; in moderate quantities, hallucinations, motor and neurological alterations and impaired vision; in high quantities it may cause hallucinations with personal events at a deeper level lasting up to 24 hours or more, followed by motor and visual alterations. Conclusion: The product extracted from the Iboga plant is of great importance in controlling addiction, reducing the need for the use of narcotics by patients, thus gaining a space of extreme importance in the treatment of users of psychoactive substances. It is remarkable the progress of the latest’s research about the usefulness of Ibogaine, and its benefits for certain treatments, even with the restriction of its sale in Brazil. Besides this, Ibogaine has an additional benefit of helping the patient to gain self-control over their destructive behaviours.

Keywords: alkaloids, dependence, Gabon, ibogaine

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Authors: Bambang Novianto, Rizal Aditya Herdianto, Raphael Bianco Huwae, Afifah, Alfonso Brolin Sihite, Rudi Lumanto

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The mobile banking application is a type of mobile application that is growing rapidly. This is caused by the ease of service and time savings in making transactions. On the other hand, this certainly provides a challenge in security issues. The use of mobile banking can not be separated from cyberattacks that may occur which can result the theft of sensitive information or financial loss. The financial loss and the theft of sensitive information is the most avoided thing because besides harming the user, it can also cause a loss of customer trust in a bank. Cyberattacks that are often carried out against mobile applications are phishing, hacking, theft, misuse of data, etc. Cyberattack can occur when a vulnerability is successfully exploited. OWASP mobile Top 10 has recorded as many as 10 vulnerabilities that are most commonly found in mobile applications. In the others, android permissions also have the potential to cause vulnerabilities. Therefore, an overview of the profile of the mobile banking application becomes an urgency that needs to be known. So that it is expected to be a consideration of the parties involved for improving security. In this study, an experiment has been conducted to capture the profile of the mobile banking applications in Indonesia based on android permission and OWASP mobile top 10 2016. The results show that there are six basic vulnerabilities based on OWASP Mobile Top 10 that are most commonly found in mobile banking applications in Indonesia, i.e. M1:Improper Platform Usage, M2:Insecure Data Storage, M3:Insecure Communication, M5:Insufficient Cryptography, M7:Client Code Quality, and M9:Reverse Engineering. The most permitted android permissions are the internet, status network access, and telephone read status.

Keywords: mobile banking application, OWASP mobile top 10 2016, android permission, sensitive information, financial loss

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Authors: Kechnit Djamel, Ammarri Abdelhadi, Raphael Tshimang, Mark Trrig

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One of the most important aspects of monitoring rivers is navigation. The variation of discharge in the river generally produces a change in available draft for a vessel, particularly in the low flow season, which can impact the navigable water path, especially when the water depth is less than the normal one, which allows safe navigation for boats. The water depth is related to the bathymetry of the channel as well as the discharge. For a seasonal update of the navigation maps, a daily discharge value is required. Many novel approaches based on earth observation and remote sensing have been investigated for large rivers. However, it should be noted that most of these approaches are not currently able to directly estimate river discharge. This paper discusses the application of remote sensing tools using the analysis of the reflectance value of MODIS imagery and is combined with field measurements for the estimation of discharge. This approach is applied in the lower reach of the Congo River (Pool Malebo) for the period between 2019 and 2021. The correlation obtained between the observed discharge observed in the gauging station and the reflectance ratio time series is 0.81. In this context, a Discharge Reflectance Model (DRM) was developed to express discharge as a function of reflectance. This model introduces a non-contact method that allows discharge monitoring using earth observation. DRM was validated by field measurements using ADCP, in different sections on the Pool Malebo, over two different periods (dry and wet seasons), as well as by the observed discharge in the gauging station. The observed error between the estimated and measured discharge values ranges from 1 to 8% for the ADCP and from (1% to 11%) for the gauging station. The study of the uncertainties will give us the possibility to judge the robustness of the DRM.

Keywords: discharge monitoring, navigation, MODIS, empiric, ADCP, Congo River

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Authors: Ismaila Oladunni Muhammed, Adegbenga Raphael Ashiru

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Construction industry has been attributed to be the engine growth of Nigerian economic and infrastructural development. It promotes infrastructural development and grows an average output of Nigerian Gross Domestic Profit. However, from this great prospect, yearly reports show that consistent accidents on construction sites in Zamfara State has affected a substantial number of workers as they become temporarily or permanently disabled, thereby making many construction sites a death trap. This posed a great threat to the industry’s sustainability, de- motivate workers from working in the industry, and further have negative impact on the economy as well. It is as a result of high construction site accident currently experiencing in Zamfara state that this research was carried out to appraise the sustainability of health and safety of construction workers on sites. The proper practice and compliance to Construction Health and safety laws are very vital to the output and growth of Zamfara State construction sector. However, a quantitative approach was adopted to justify the aforesaid statement which will provide a broader understanding of the study. Descriptive statistical analysis was obtained through Statistical Package for the Social Sciences (SPSS Version 20). Furthermore, the findings from the research highlighted that the performance and output of construction workers on construction sites depends on the proper practice of health and safety. The research findings also recommended ways to enhance employers and employee’s compliance with existing laws guiding health and safety on Zamfara State construction sites. Nevertheless, the purpose of the paper is to appraise the sustainability of Health and Safety on Zamfara State construction sites. This study further provided thorough information for resolving challenges of construction sites accidents to improve construction firm productivity and also ensured construction worker’s safety on site.

Keywords: construction industry, health and safety regulations, causes of accident, construction safety practices

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Authors: Sarah Gaßmeyer, Nadine Hülsemann, Raphael Stoll, Kenji Miyamoto, Robert Kourist

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Enzymatic racemization allows the smooth interconversion of stereocenters under very mild reaction conditions. Racemases find frequent applications in deracemization and dynamic kinetic resolutions. Arylmalonate decarboxylase (AMDase) from Bordetella Bronchiseptica has high structural similarity to amino acid racemases. These cofactor-free racemases are able to break chemically strong CH-bonds under mild conditions. The racemase-like catalytic machinery of mutant G74C conveys it a unique activity in the racemisation of pharmacologically relevant derivates of 2-phenylpropionic acid (profenes), which makes AMDase G74C an interesting object for the mechanistic investigation of cofactor-independent racemases. Structure-guided protein engineering achieved a variant of this unique racemase with 40-fold increased activity in the racemisation of several arylaliphatic carboxylic acids. By saturation–transfer–difference NMR spectroscopy (STD-NMR), substrate binding during catalysis was investigated. All atoms of the substrate showed interactions with the enzyme. STD-NMR measurements revealed distinct nuclear Overhauser effects in experiments with and without molecular conversion. The spectroscopic analysis led to the identification of several amino acid residues whose variation increased the activity of G74C. While single-amino acid exchanges increased the activity moderately, structure-guided saturation mutagenesis yielded a quadruple mutant with a 40 times higher reaction rate. This study presents STD-NMR as versatile tool for the analysis of enzyme-substrate interactions in catalytically competent systems and for the guidance of protein engineering.

Keywords: racemase, rational protein design, STD-NMR, structure guided saturation mutagenesis

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Authors: Adeyi Akindele Oluwatosin, Mustapha Kaosarat Keji, Ajisebiola Babafemi Siji, Adeyi Olubisi Esther, Damilohun Samuel Metibemu, Raphael Emuebie Okonji

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Envenoming by Echis ocellatus is potentially life-threatening due to severe hemorrhage, renal failure, and capillary leakage. These effects are attributed to snake venom metalloproteinases (SVMPs). Due to drawbacks in the use of antivenom, natural inhibitors from plants are of interest in studies of new antivenom treatment. Antagonizing effects of bioactive compounds of Moringa oleifera, a known antisnake plant, are yet to be tested against SVMPs of E. ocellatus (SVMP-EO). Ethanol crude extract of M. oleifera was partitioned using n-hexane and ethyl acetate. Each partition was fractionated using column chromatography and tested against SVMP-EO purified through ion-exchange chromatography with EchiTab-PLUS polyvalent anti-venom as control. Phytoconstituents of ethyl acetate fraction were screened against the catalytic site of crystal of BaP1-SVMP, while drug-likeness and ADMET toxicity of compound were equally determined. The molecular weight of isolated SVMP-EO was 43.28 kDa, with a specific activity of 245 U/ml, a percentage yield of 62.83 %, and a purification fold of 0.920. The Vmax and Km values are 2 mg/ml and 38.095 μmol/ml/min, respectively, while the optimal pH and temperature are 6.0 and 40°C, respectively. Polyvalent anti-venom, crude extract, and ethyl acetate fraction of M. oleifera exhibited a complete inhibitory effect against SVMP-EO activity. The inhibitions of the P-1 and P-II metalloprotease’s enzymes by the ethyl acetate fraction are largely due to methanol, 6, 8, 9-trimethyl-4-(2-phenylethyl)-3-oxabicyclo[3.3.1]non-6-en-1-yl)- and paroxypropione, respectively. Both compounds are potential drug candidates with little or no concern of toxicity, as revealed from the in-silico predictions. The inhibitory effects suggest that this compound might be a therapeutic candidate for further exploration for treatment of Ocellatus’ envenoming.

Keywords: Echis ocellatus, Moringa oleifera, anti-venom, metalloproteases, snakebite, molecular docking

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Authors: Tim Giesen, Raphael Adamietz, Pablo Mayer, Philipp Stiefel, Patrick Alle, Dirk Schlenker

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The competitiveness and success of new electrical energy storages such as battery cells are significantly dependent on a short time-to-market. Producers who decide to supply new battery cells to the market need to be easily adaptable in manufacturing with respect to the early customers’ needs in terms of cell size, materials, delivery time and quantity. In the initial state, the required output rates do not yet allow the producers to have a fully automated manufacturing line nor to supply handmade battery cells. Yet there was no solution for manufacturing battery cells in low to medium volumes in a reproducible way. Thus, in terms of cell format and output quantity, a concept for the flexible assembly of battery cells was developed by the Fraunhofer-Institute for Manufacturing Engineering and Automation. Based on clustered processes, the modular system platform can be modified, enlarged or retrofitted in a short time frame according to the ordered product. The paper shows the analysis of the production steps from a conventional battery cell assembly line. Process solutions were found by using I/O-analysis, functional structures, and morphological boxes. The identified elementary functions were subsequently clustered by functional coherences for automation solutions and thus the single process cluster was generated. The result presented in this paper enables to manufacture different cell products on the same production system using seven process clusters. The paper shows the solution for a batch-wise flexible battery cell production using advanced process control. Further, the performed tests and benefits by using the process clusters as cyber-physical systems for an integrated production and value chain are discussed. The solution lowers the hurdles for SMEs to launch innovative cell products on the global market.

Keywords: automation, battery production, carrier, advanced process control, cyber-physical system

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Authors: Matthew F. Gibson, Narasimha D. Rao, Raphael B. Slade, Joana Portugal Pereira, Joeri Rogelj

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Globally, India’s population is among the most severely impacted by nutrient deficiency, yet millions of tonnes of food are lost before reaching consumers. Across food groups, grains represent the largest share of daily calories and overall losses by mass in India. If current losses remain unresolved and follow projected population rates, we estimate, by 2030, losses from grains for human consumption could increase by 1.3-1.8 million tonnes (Mt) per year against current levels of ~10 Mt per year. This study quantifies energy input to minimise storage losses across India, responsible for a quarter of grain supply chain losses. In doing so, we identify and explore a Sustainable Development Goal (SDG) triplet between SDG₂, SDG₇, and SDG₁₂ and provide insight for development of joined up agriculture and health policy in the country. Analyzing rice, wheat, maize, bajra, and sorghum, we quantify one route to reduce losses in supply chains, by modelling the energy input to maintain favorable climatic conditions in modern silo storage. We quantify key nutrients (calories, protein, zinc, iron, vitamin A) contained within these losses and calculate roughly how much deficiency in these dietary components could be reduced if grain losses were eliminated. Our modelling indicates, with appropriate uncertainty, maize has the highest energy input intensity for storage, at 110 kWh per tonne of grain (kWh/t), and wheat the lowest (72 kWh/t). This energy trade-off represents 8%-16% of the energy input required in grain production. We estimate if grain losses across the supply chain were saved and targeted to India’s nutritionally deficient population, average protein deficiency could reduce by 46%, calorie by 27%, zinc by 26%, and iron by 11%. This study offers insight for development of Indian agriculture, food, and health policy by first quantifying and then presenting benefits and trade-offs of tackling food grain losses.

Keywords: energy, food loss, grain storage, hunger, India, sustainable development goal, SDG

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Authors: Raphael C. Zero, Thiago A. S. S. Rocha, Marita V. Cardozo, Caio C. C. Santos, Alisson D. S. Fechis, Antonio C. Shimano, FabríCio S. Oliveira

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Biomechanical analysis is an important factor in tissue studies. The objective of this study was to determine the feasibility of a new anatomical technique and quantify the changes in skin and the jejunum resistance of cats’ corpses throughout the process. Eight adult cat cadavers were used. For every kilogram of weight, 120ml of fixative solution (95% 96GL ethyl alcohol and 5% pure glycerin) was applied via the external common carotid artery. Next, the carcasses were placed in a container with 96 GL ethyl alcohol for 60 days. After fixing, all carcasses were preserved in a 30% sodium chloride solution for 60 days. Before fixation, control samples were collected from fresh cadavers and after fixation, three skin and jejunum fragments from each cadaver were tested monthly for strength and displacement until complete rupture in a universal testing machine. All results were analyzed by F-test (P <0.05). In the jejunum, the force required to rupture the fresh samples and the samples fixed in alcohol for 60 days was 31.27±19.14N and 29.25±11.69N, respectively. For the samples preserved in the sodium chloride solution for 30 and 60 days, the strength was 26.17±16.18N and 30.57±13.77N, respectively. In relation to the displacement required for the rupture of the samples, the values of fresh specimens and those fixed in alcohol for 60 days was 2.79±0.73mm and 2.80±1.13mm, respectively. For the samples preserved for 30 and 60 days with sodium chloride solution, the displacement was 2.53±1.03mm and 2.83±1.27mm, respectively. There was no statistical difference between the samples (P=0.68 with respect to strength, and P=0.75 with respect to displacement). In the skin, the force needed to rupture the fresh samples and the samples fixed for 60 days in alcohol was 223.86±131.5N and 211.86±137.53N respectively. For the samples preserved in sodium chloride solution for 30 and 60 days, the force was 227.73±129.06 and 224.78±143.83N, respectively. In relation to the displacement required for the rupture of the samples, the values of fresh specimens and those fixed in alcohol for 60 days were 3.67±1.03mm and 4.11±0.87mm, respectively. For the samples preserved for 30 and 60 days with sodium chloride solution, the displacement was 4.21±0.93mm and 3.93±0.71mm, respectively. There was no statistical difference between the samples (P=0.65 with respect to strength, and P=0.98 with respect to displacement). The resistance of the skin and intestines of the cat carcasses suffered little change when subjected to alcohol fixation and preservation in sodium chloride solution, each for 60 days, which is promising for use in surgery training. All experimental procedures were approved by the Municipal Legal Department (protocol 02.2014.000027-1). The project was funded by FAPESP (protocol 2015-08259-9).

Keywords: anatomy, conservation, fixation, small animal

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Authors: Raphael Udeh, Luis García De Guadiana Romualdo, Xenia Dolje-Gore

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Background: Quite disturbing is the huge public health impact of COVID-19: As at today [25th March 2021, the COVID-19 global burden shows over 123 million cases and over 2.7 million deaths worldwide. Rationale: Recent evidence shows calprotectin’s potential as a therapeutic target, stating that tasquinimod, from the Quinoline-3-Carboxamide family is capable of blocking the interaction between calprotectin and TLR4. Hence preventing the cytokine release syndrome, that heralds the functional exhaustion in COVID-19. Early preclinical studies showed that tasquinimod inhibit tumor growth and prevent angiogenesis/cytokine storm. Phase I – III clinical studies in prostate cancer showed it has a good safety profile with good radiologic progression free survival but no effect on overall survival. Rationale/hypothesis: Strategic endeavors have been amplified globally to assess new therapeutic interventions for COVID-19 management – thus the clinical and antiviral efficacy of tasquinimod in COVID-19 remains to be explored. Hence the primary objective of this trial will be to evaluate the efficacy of tasquinimod in the treatment of adult patients with severe COVID-19 infections. Therefore, I hypothesise that among adults with COVID19 infection, tasquinimod will reduce the severe respiratory distress associated with COVID-19 compared to placebo, over a 28-day study period. Method: The setting is in Europe. Design – a randomized, placebo-controlled, phase II double-blinded trial. Trial lasts for 28 days from randomization, Tasquinimod capsule given as 0.5mg daily 1st fortnight, then 1mg daily 2nd fortnight. I0 outcome - assessed using six-point ordinal scale alongside eight 20 outcomes. 125 participants to be enrolled, data collection at baseline and subsequent data points, and safety reporting monitored via serological profile. Significance: This work could potentially establish tasquinimod as an effective and safe therapeutic agent for COVID-19 by reducing the severe respiratory distress, related time to recovery, time on oxygen/admission. It will also drive future research – as in larger multi-centre RCT.

Keywords: Calprotectin, COVID-19, Phase II Trial, Tasquinimod

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Authors: Reinaldo Biscaro, Luciano R. Ferreira, Leonardo C. Biscaro, Raphael C. Biscaro, Isabela S. Vasconcelos, Laura C. R. Ferreira, Cristiano M. Galhardi, Erica P. Baciuk

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Introduction: The present study had the objective to present the profile of workers with shoulder disorders related to labor lawsuits in Brazil. The study analyzed the association between the worker’s health and the actions performed by the companies related to injured professional. The research method performed a retrospective, cross-sectional and quantitative database analysis. The documents of labor lawsuits with shoulder injury registered at the Regional Labor Court in the 15^th region (Campinas - São Paulo) were submitted to the medical examination and evaluated during the period from 2012 until 2015. The data collected were age, gender, onset of symptoms, length of service, current occupation, type of shoulder injury, referred complaints, type of acromion, associated or related diseases, company actions as CAT (workplace accident communication), compliance of NR7 by the organization (Environmental Risk Prevention Program - PPRA and Medical Coordination Program in Occupational Health - PCMSO). Results: From the 93 workers evaluated, there was a prevalence of men (58.1%), with a mean age of 42.6 y-o, and 54.8% were included in the age group 35-49 years. Regarding the length of work time in the company, 66.7% have worked for more than 5 years. There was an association between gender and current occupational status (p < 0.005), with predominance of women in household occupation (13 vs. 2) and predominance of unemployed men in job search situation (24 vs. 10) and reintegrated to work by judicial decision (8 vs. 2). There was also a correlation between pain and functional limitation (p < 0.01). There was a positive association of PPRA with the complaint of functional limitation and negative association with pain (p < 0.04). There was also a correlation between the sedentary lifestyle and the presence of PCMSO and PPRA (p < 0.04), and the absence of CAT in the companies (p < 0.001). It was concluded that the appearance or aggravation of osseous and articular shoulder pathologies in workers who have undertaken labor law suits seem to be associated with individual habits or inadequate labor practices. These data can help preventing the occurrence of these lesions by implementing local health promotion policies at work.

Keywords: work-related accidents, cross-sectional study, shoulder lesions, labor lawsuits

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Authors: Raphael M. Rettig, Tessa C. Flatten

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This empirical study answer calls for research on Absorptive Capacity and Process Innovation. Due to the fourth industrial revolution, manufacturing companies face the biggest disruption of their production processes since the rise of advanced manufacturing technologies in the last century. Therefore, process innovation will become a critical task to master in the future for many manufacturing firms around the world. The general ability of organizations to acquire, assimilate, transform, and exploit external knowledge, known as Absorptive Capacity, was proven to positively influence product innovation and is already conceptually associated with process innovation. The presented research provides empirical evidence for this influence. The findings are based on an empirical analysis of 732 companies from seven leading and emerging countries: Brazil, China, France, Germany, India, Japan, and the United States of America. The answers to the survey were collected in February and March 2018 and addressed senior- and top-level management with a focus on operations departments. The statistical analysis reveals the positive influence of potential and Realized Absorptive Capacity on successful process innovation taking the implementation of new digital manufacturing processes as an example. Potential Absorptive Capacity covering the acquisition and assimilation capabilities of an organization showed a significant positive influence (β = .304, p < .05) on digital manufacturing implementation success and therefore on process innovation. Realized Absorptive Capacity proved to have significant positive influence on process innovation as well (β = .461, p < .01). The presented study builds on prior conceptual work in the field of Absorptive Capacity and process innovation and contributes theoretically to ongoing research in two dimensions. First, the already conceptually associated influence of Absorptive Capacity on process innovation is backed by empirical evidence in a broad international context. Second, since Absorptive Capacity was measured with a focus on new product development, prior empirical research on Absorptive Capacity was tailored to the research and development departments of organizations. The results of this study highlight the importance of Absorptive Capacity as a capability in mechanical engineering and operations departments of organizations. The findings give managers an indication of the importance of implementing new innovative processes into their production system and fostering the right mindset of employees to identify new external knowledge. Through the ability to transform and exploit external knowledge, own production processes can be innovated successfully and therefore have a positive influence on firm performance and the competitive position of their organizations.

Keywords: absorptive capacity, digital manufacturing, dynamic capabilities, process innovation

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Authors: Raphael C. Zero, Marita V. Cardozo, Thiago A. S. S. Rocha, Mariana T. Kihara, Fernando A. Ávila, Fabrício S. Oliveira

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There are several fixative and preservative solutions for use on cadavers, many of them using formaldehyde as the fixative or anatomical part preservative. In some countries, such as Brazil, this toxic agent has been increasingly restricted. The objective of this study was to microbiologically identify and quantify the key agents in tanks containing 96GL ethanol or sodium chloride solutions, used respectively as fixatives and preservatives of cat cadavers. Eight adult cat corpses, three females and five males, with an average weight of 4.3 kg, were used. After injection via the external common carotid artery (120 ml/kg, 95% 96GL ethyl alcohol and 5% pure glycerin), the cadavers were fixed in a plastic tank with 96GL ethanol for 60 days. After fixing, they were stored in a 30% sodium chloride aqueous solution for 120 days in a similar tank. Samples were collected at the start of the experiment - before the animals were placed in the ethanol tanks, and monthly thereafter. The bacterial count was performed by Pour Plate Method in BHI agar (Brain Heart Infusion) and the plates were incubated aerobically and anaerobically for 24h at 37ºC. MacConkey agar, SPS agar (Sulfite Polymyxin Sulfadizine) and MYP Agar Base were used to isolate the microorganisms. There was no microbial growth in the samples prior to alcohol fixation. After 30 days of fixation in the alcohol solution, total aerobic and anaerobic (<1.0 x 10 CFU/ml) were found and Pseudomonas sp., Staphylococcus sp., Clostridium sp. were the identified agents. After 60 days in the alcohol fixation solution, total aerobes (<1.0 x 10 CFU/ml) and total anaerobes (<2.2 x 10 CFU/mL) were found, and the identified agents were the same. After 30 days of storage in the aqueous solution of 30% sodium chloride, total aerobic (<5.2 x 10 CFU/ml) and total anaerobes (<3.7 x 10 CFU/mL) were found and the agents identified were Staphylococcus sp., Clostridium sp., and fungi. After 60 days of sodium chloride storage, total aerobic (<3.0 x 10 CFU / ml) and total anaerobes (<7.0 x 10 CFU/mL) were found and the identified agents remained the same: Staphylococcus sp., Clostridium sp., and fungi. The microbiological count was low and visual inspection did not reveal signs of contamination in the tanks. There was no strong odor or purification, which proved the technique to be microbiologically effective in fixing and preserving the cat cadavers for the four-month period in which they are provided to undergraduate students of University of Veterinary Medicine for surgery practice. All experimental procedures were approved by the Municipal Legal Department (protocol 02.2014.000027-1). The project was funded by FAPESP (protocol 2015-08259-9).

Keywords: anatomy, fixation, microbiology, small animal, surgery

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Authors: Fahad Ibrahim, Raphaël Akamavi

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Bangladesh has encountered several industrial disasters (e.g. fire and building collapse tragedies) leading to the loss of valuable human lives. Irrespective of various institutions’ making effort to improve the safety situation, industry compliance and safety behaviour have not yet been improved. Hence, one question remains, to what extent does the institutional elements efficient enough to make any difference in improving safety behaviours? Thus, this study explores the relationship between institutional perspective and safety performance. Structural equation modelling results, using survey data from 256 RMG workers’ of 128 garments manufacturing factories in Bangladesh, show that institutional facets strongly influence management safety commitment to induce workers participation in safety activities and reduce workplace accident rates. The study also found that by upholding industrial standards and inspecting the safety situations, institutions facets significantly and directly affect workers involvement in safety participations and rate of workplace accidents. Additionally, workers involvement to safety practices significantly predicts the safety environment of the workplace. Subsequently, our findings demonstrate that institutional culture, norms, and regulations enact play an important role in altering management commitment to set-up a safer workplace environment. As a result, when workers’ perceive their management having high level of commitment to safety, they are inspired to be involved more in the safety practices, which significantly alter the workplace safety situation and lessen injury experiences. Due to the fact that institutions have strong influence on management commitment, legislative members should endorse, regulate, and strictly monitor workplace safety laws to be exercised by the factory owners. Further, management should take initiatives for adopting OHS features and conceive strategic directions (i.e., set up safety committees, risk assessments, innovative training) for promoting a positive safety climate to provide a safe workplace environment. Arguably, an inclusive public-private partnership is recommended for ensuring better and safer workplace for RMG workers. However, as our data were under a cross-sectional design; the respondents’ perceptions might get changed over a period of time and hence, a longitudinal study is recommended. Finally, further research is needed to determine the impact of improvement mechanisms on workplace safety performance, such as how workplace design, safety training programs, and institutional enforcement policies protect the well-being of workers.

Keywords: institutional perspective, management commitment, safety participation, work injury, safety performance, occupational health and safety

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Authors: Raphael Palucci Rosa, Giuseppe Rosace

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Stereolithography (SLA) is one of the 3D-printing technologies that has been steadily growing in popularity for both industrial and personal applications due to its versatility, high accuracy, and low cost. Its printing process consists of using a light emitter to solidify photosensitive liquid resins layer-by-layer to produce solid objects. However, the majority of the resins used in SLA are derived from petroleum and characterized by toxicity, stability, and recalcitrance to degradation in natural environments. Aiming to develop an eco-friendly resin, in this work, different combinations of a standard commercial SLA resin (Peopoly UV professional) with a vegetable-based resin were investigated. To reach this goal, different mass concentrations (varying from 10 to 50 wt%) of acrylated epoxidized soybean oil (AESO), a vegetable resin produced from soyabean oil, were mixed with a commercial acrylate-based resin. 1.0 wt% of Diphenyl(2,4,6-trimethylbenzoyl) phosphine oxide (TPO) was used as photo-initiator, and the samples were printed using a Peopoly moai 130. The machine was set to operate at standard configurations when printing commercial resins. After the print was finished, the excess resin was drained off, and the samples were washed in isopropanol and water to remove any non-reacted resin. Finally, the samples were post-cured for 30 min in a UV chamber. FT-IR analysis was used to confirm the UV polymerization of the formulated resin with different AESO/Peopoly ratios. The signals from 1643.7 to 1616, which corresponds to the C=C stretching of the AESO acrylic acids and Peopoly acrylic groups, significantly decreases after the reaction. The signal decrease indicates the consumption of the double bonds during the radical polymerization. Furthermore, the slight change of the C-O-C signal from 1186.1 to 1159.9 decrease of the signals at 809.5 and 983.1, which corresponds to unsaturated double bonds, are both proofs of the successful polymerization. Mechanical analyses showed a decrease of 50.44% on tensile strength when adding 10 wt% of AESO, but it was still in the same range as other commercial resins. The elongation of break increased by 24% with 10 wt% of AESO and swelling analysis showed that samples with a higher concentration of AESO mixed absorbed less water than their counterparts. Furthermore, high-resolution prototypes were printed using both resins, and visual analysis did not show any significant difference between both products. In conclusion, the AESO resin was successful incorporated into a commercial resin without affecting its printability. The bio-based resin showed lower tensile strength than the Peopoly resin due to network loosening, but it was still in the range of other commercial resins. The hybrid resin also showed better flexibility and water resistance than Peopoly resin without affecting its resolution. Finally, the development of new types of SLA resins is essential to provide new sustainable alternatives to the commercial petroleum-based ones.

Keywords: 3D-printing, bio-based, resin, soybean, stereolithography

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Authors: Trina Isabel D. Santiago, Juan Raphael M. Perez, Maria Angelica O. Soriano, Teresita B. Suing, Jumee F. Tayaban

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To achieve universal healthcare for everyone, the World Health Organization has emphasized the importance of National Medicines Policies for increased accessibility and utilization of high-quality and affordable medications. In the Philippines, significant challenges have been identified surrounding the sustainability of essential medicines, resulting in limited access such as high cost and dominance and market dominance and monopoly of multinational companies (MNCs) in the Philippine pharmaceutical industry. These identified challenges have been addressed by several initiatives, such as the Philippine National Drug Policy and Generics Act of 1988 (Republic Act 6675), to attempt to reduce drug prices. Despite these efforts, the concerns with drug accessibility and affordability continue to persist; hence, Republic Act 9502 was enacted. This paper attempts to review RA 9502 in the pursuit of making medicines more affordable for Filipinos, analyze and critique the problems and challenges associated with the law, and provide recommendations to address identified problems and challenges. A literature search and review, as well as an analysis of the law, has been done to evaluate the policy. RA 9502 recognizes the importance of market competition in drug price reduction and quality medicine accessibility. Contentious issues prior to enactment of the law include 1) parallel importation, pointing out that the drug price will depend on the global market price, 2) contrasting approaches in the drafting of the law as the House version focused on medicine price control while the Senate version prioritized market competition, and 3) MNCs opposing the amendments with concerns on discrimination, constitutional violations, and noncompliance with international treaty obligations. There are also criticisms and challenges with the implementation of the law in terms of content or modeling, interpretation and implementation, and other external factors or hindrances. The law has been criticized for its narrow scope as it only covers specific essential medicines with no cooperation with the national health insurance program. Moreover, the law has sections taking advantage of the TRIPS flexibilities, which disallow smaller countries to reap the benefits of flexibilities. The sanctions and penalties have an insignificant role in implementation as they only ask for a small portion of the income of MNCs. Proposed recommendations for policy improvement include aligning existing legislation through strengthened price regulation and expanded law coverage, strengthening penalties to promote law adherence, and promoting research and development to encourage and support local initiatives. Through these comprehensive recommendations, the issues surrounding the policy can be addressed, and the goal of enhancing the affordability and accessibility of medicines in the country can be achieved.

Keywords: drug accessibility, drug affordability, price regulation, Republic Act 9502

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Authors: Leslie Raphael de M. Ferraz, Salvana Priscylla M. Costa, Tarcyla de A. Gomes, Giovanna Christinne R. M. Schver, Cristóvão R. da Silva, Magaly Andreza M. de Lyra, Danilo Augusto F. Fontes, Larissa A. Rolim, Amanda Carla Q. M. Vieira, Miracy M. de Albuquerque, Pedro J. Rolim-Neto

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Efavirenz (EFV) is a drug used as first-line treatment of AIDS. However, it has poor aqueous solubility and wettability, presenting problems in the gastrointestinal tract absorption and bioavailability. One of the most promising strategies to improve the solubility is the use of solid dispersions (SD). Therefore, this study aimed to characterize SD EFZ with the polymers: PVP-K30, PVPVA 64 and SOLUPLUS in order to find an optimal formulation to compose a future pharmaceutical product for AIDS therapy. Initially, Physical Mixtures (PM) and SD with the polymers were obtained containing 10, 20, 50 and 80% of drug (w/w) by the solvent method. The best formulation obtained between the SD was selected by in vitro dissolution test. Finally, the drug-carrier system chosen, in all ratios obtained, were analyzed by the following techniques: Differential Scanning Calorimetry (DSC), polarization microscopy, Scanning Electron Microscopy (SEM) and spectrophotometry of absorption in the region of infrared (IR). From the dissolution profiles of EFV, PM and SD, the values of area Under The Curve (AUC) were calculated. The data showed that the AUC of all PM is greater than the isolated EFV, this result is derived from the hydrophilic properties of the polymers thus favoring a decrease in surface tension between the drug and the dissolution medium. In adittion, this ensures an increasing of wettability of the drug. In parallel, it was found that SD whom had higher AUC values, were those who have the greatest amount of polymer (with only 10% drug). As the amount of drug increases, it was noticed that these results either decrease or are statistically similar. The AUC values of the SD using the three different polymers, followed this decreasing order: SD PVPVA 64-EFV 10% > SD PVP-K30-EFV 10% > SD Soluplus®-EFV 10%. The DSC curves of SD’s did not show the characteristic endothermic event of drug melt process, suggesting that the EFV was converted to its amorphous state. The analysis of polarized light microscopy showed significant birefringence of the PM’s, but this was not observed in films of SD’s, thus suggesting the conversion of the drug from the crystalline to the amorphous state. In electron micrographs of all PM, independently of the percentage of the drug, the crystal structure of EFV was clearly detectable. Moreover, electron micrographs of the SD with the two polymers in different ratios investigated, we observed the presence of particles with irregular size and morphology, also occurring an extensive change in the appearance of the polymer, not being possible to differentiate the two components. IR spectra of PM corresponds to the overlapping of polymer and EFV bands indicating thereby that there is no interaction between them, unlike the spectra of all SD that showed complete disappearance of the band related to the axial deformation of the NH group of EFV. Therefore, this study was able to obtain a suitable formulation to overcome the solubility limitations of the EFV, since SD PVPVA 64-EFZ 10% was chosen as the best system in delay crystallization of the prototype, reaching higher levels of super saturation.

Keywords: characterization, dissolution, Efavirenz, solid dispersions

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Authors: Majed Al Otaibi, Melissa Lessard-Beaudoin, Amel Loudghi, Raphael Chouinard-Watkins, Melanie Plourde, Frederic Calon, C. Alexandre Castellano, Stephen Cunnane, Helene Payette, Pierrette Gaudreau, Denis Gris, Rona K. Graham

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Introduction: Alzheimer disease (AD) is a chronic disorder that affects millions of individuals worldwide. Symptoms include memory dysfunction, and also alterations in attention, planning, language and overall cognitive function. Olfactory dysfunction is a common symptom of several neurological disorders including AD. Studying the mechanisms underlying the olfactory dysfunction may therefore lead to the discovery of potential biomarkers and/or treatments for neurodegenerative diseases. Objectives: To determine if olfactory dysfunction predicts future cognitive impairment in the aging population and to characterize the olfactory system in a murine model expressing a genetic factor of AD. Method: For the human study, quantitative olfactory tests (UPSIT and OMT) have been done on 93 subjects (aged 80 to 94 years) from the Quebec Longitudinal Study on Nutrition and Successful Aging (NuAge) cohort accepting to participate in the ORCA secondary study. The telephone Modified Mini Mental State examination (t-MMSE) was used to assess cognition levels, and an olfactory self-report was also collected. In a separate cohort, olfactory cortical volume was calculated using MRI results from healthy old adults (n=25) and patients with AD (n=18) using the AAL single-subject atlas and performed with the PNEURO tool (PMOD 3.7). For the murine study, we are using Western blotting, RT-PCR and immunohistochemistry. Result: Human Study: Based on the self-report, 81% of the participants claimed to not suffer from any problem with olfaction. However, based on the UPSIT, 94% of those subjects showed a poor olfactory performance and different forms of microsmia. Moreover, the results confirm that olfactory function declines with age. We also detected a significant decrease in olfactory cortical volume in AD individuals compared to controls. Murine study: Preliminary data demonstrate there is a significant decrease in expression levels of the proform of caspase-3 and the caspase substrate STK3, in the olfactory bulb of mice expressing human APOE4 compared with controls. In addition, there is a significant decrease in the expression level of the caspase-9 proform and caspase-8 active fragment. Analysis of the mature neuron marker, NeuN, shows decreased expression levels of both isoforms. The data also suggest that Iba-1 immunostaining is increased in the olfactory bulb of APOE4 mice compared to wild type mice. Conclusions: The activation of caspase-3 may be the cause of the decreased levels of STK3 through caspase cleavage and may play role in the inflammation observed. In the clinical study, our results suggest that seniors are unaware of their olfactory function status and therefore it is not sufficient to measure olfaction using the self-report in the elderly. Studying olfactory function and cognitive performance in the aging population will help to discover biomarkers in the early stage of the AD.

Keywords: Alzheimer's disease, APOE4, cognition, caspase, brain atrophy, neurodegenerative, olfactory dysfunction

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