Search results for: synovial arthritis

Authors: Obinna Benedict Duru

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This study focuses on the elderly and the challenges that confront them. The elderly are that particular segment of our population who by virtue of the aging process have attained the stage in most cases where they are confronted with the challenges of economic dependency and social marginality. These challenges are as a result of the physical and biological decline occasioned by social myths and realities which portray the elderly as a dependent population whose members could not and should not work and who need social assistance that the younger population is obliged to provide. From the moment of birth to the moment of death, our bodies are constantly changing. We are all enmeshed in the process of growing old, a transition from youthfulness to elderliness. In youth-oriented modern societies like ours, we tend to attach positive importance and significance to the biological changes that occur early in life and define later physical changes in negative terms. Children growing up and young adults receive more attention, greater responsibilities and more legal rights to reward them on their way. But few people are congratulated on getting old. We commiserate with people who are getting old and make jokes about their supposedly physical, mental and biological decline. Wrinkles, loss of weight and vitality are all parts of the aging process. In almost all parts of the world, earlier researches have shown that about fifty percent of the elderly who suffer from stroke, arthritis, senility and other age related diseases are the disengaged and neglected elderly. Rapid technological changes render the knowledge and skills of the elderly obsolete; education is geared toward the young and the generational competition for jobs leads to pressures on the elderly to retire. Control of initial resources are shifted to the middle-aged and older workers are pushed into positions of economic dependency. This study therefore, among other things tend to discover how some government policies have affected the elderly particularly in Africa. To discover the prospects and possibilities of the elderly for a better living. To make a comparison of the advances in healthcare giving made in the advanced western societies to the practice in Sub Saharan Africa etc. The hypotheses of this study include: that the elderly in Sub Saharan Africa are more vulnerable than their counterparts in Europe and America. The elderly are more prone to social isolation, and that the elderly are mostly affected by age-related sickness etc. With a survey method as the research design, and sample size of about 500 respondents,probability sampling technique was used. Data which were analyzed using chi-square and tables were collected through primary and secondary sources. The findings made include: that the elderly suffer pains of old age especially when disengaged from work or social activity. That loss of income condemn the elderly to a life of vegetable existence, and that those who do not have other means of re-integration usually see old age with regret and despair. It is therefore, recommended among other things that social welfare scheme and the process of re-integration at old age be introduced for the non pensionable elderly in Africa.

Keywords: elderly, social isolation, dependency, re-integration

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Authors: Ladda Thiamwong, Renata Komalasari

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Falls are the leading cause of disability and hospitalization in low-income older adults. Fear of falling is present in 20% to 85 % of older adults and has been identified as an independent risk factor of fall risk, activity restriction, and loss of independence. About 12% of American older adults have subjective cognitive decline. Cognitive impairment is also an established factor of fall risk. However, it is unclear whether measures of fear of falling and subjective cognitive decline have the greatest association with fall risk in low-income older adults. The aim of this study was to evaluate the association between fear of falling, subjective cognitive decline-functional performance (SCD-FP), and fall risk using simple screening tools. In this cross-section study, we collected data from community-dwelling older adults 60 years or older in low-income settings in Central Florida, and 86 participants were included in the data analysis. Fear of falling was assessed by the Short Fall Efficacy Scale- International (Short FES-I) with seven items. Subjective cognitive decline-functional performance (SCD-FP) was assessed by a self-reported experience of worsening or more frequent confusion or memory loss in the past 12 months and its functional implications. Fall risk was evaluated by the Centers for Disease Control and Prevention (CDC)'s Stay Independent checklist with 12 items. The majority of participants were female, and more than half of the participants were African American. More than half of the participants had a higher school degree or higher, and less than 20% had no financial problems. Less than 30% of the participants perceived their general health as very good- excellent. More than half of the participants lived alone, and less than 15% lived with a partner or spouse. About 60% of the participants had hypertension, 40% had diabetes, 16% had cancer, and 50% had arthritis. About 30% of the participants had difficulty walking up ten steps without resting, more than 40% felt unsteady when walking, and 30% had been advised to use a cane or walker to get around safely. Regression analysis showed that fall risk was associated with fear of falling ( = .524, p <.001) and subjective cognitive decline-functional performance ( = .465, p =.027). The structure coefficient showed that fear of falling (rs2 = .922) was a stronger predictor of fall risk than subjective cognitive decline-functional performance (rs2= .200). Fear of falling and subjective cognitive decline-functional performance are growing public health issues, and addressing those issues is a public priority. Proactive screening for fear of falling and subjective cognitive decline-functional performance is critical in fall prevention. A combination of all three self-reported tools (Short FES-I, SCD-FP, and CDC's Stay Independent checklist) takes less than 5 minutes to complete. Primary care providers or public health professionals should consider including these tools to screen fear of falling and subjective cognitive decline-functional performance as part of fall risk assessment, especially in low-income settings. Thus, encouraging older adults and healthcare professionals to discuss fear of falling, subjective cognitive decline, and fall risk during routine medical office visits.

Keywords: falls, fall risk, fear of falling, cognition, subjective cognitive decline, low-income, older adults, community, screening, nursing, primary care

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Authors: Maryam Tabrizi, Shahrzad Aarup

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Objectives- Understanding the close association between oral health and overall health for older adults at the right time and right place, a person, focus treatment through Project ECHO telementoring. Methodology- Data from monthly ECHO telementoring sessions were provided for three years. Sessions including case presentations, overall health conditions, considering medications, organ functions limitations, including the level of cognition. Contributions- Providing the specialist level of providing care to all elderly regardless of their location and other health conditions and decreasing oral health inequity by increasing workforce via Project ECHO telementoring program worldwide. By 2030, the number of adults in the USA over the age of 65 will increase more than 60% (approx.46 million) and over 22 million (30%) of 74 million older Americans will need specialized geriatrician care. In 2025, a national shortage of medical geriatricians will be close to 27,000. Most individuals 65 and older do not receive oral health care due to lack of access, availability, or affordability. One of the main reasons is a significant shortage of Oral Health (OH) education and resources for the elderly, particularly in rural areas. Poor OH is a social stigma, a thread to quality and safety of overall health of the elderly with physical and cognitive decline. Poor OH conditions may be costly and sometimes life-threatening. Non-traumatic dental-related emergency department use in Texas alone was over $250 M in 2016. Most elderly over the age of 65 present with at least one or multiple chronic diseases such as arthritis, diabetes, heart diseases, and chronic obstructive pulmonary disease (COPD) are at higher risk to develop gum (periodontal) disease, yet they are less likely to get dental care. In addition, most older adults take both prescription and over-the-counter drugs; according to scientific studies, many of these medications cause dry mouth. Reduced saliva flow due to aging and medications may increase the risk of cavities and other oral conditions. Most dental schools have already increased geriatrics OH in their educational curriculums, but the aging population growth worldwide is faster than growing geriatrics dentists. However, without the use of advanced technology and creating a network between specialists and primary care providers, it is impossible to increase the workforce, provide equitable oral health to the elderly. Project ECHO is a guided practice model that revolutionizes health education and increases the workforce to provide best-practice specialty care and reduce health disparities. Training oral health providers for utilizing the Project ECHO model is a logical response to the shortage and increases oral health access to the elderly. Project ECHO trains general dentists & hygienists to provide specialty care services. This means more elderly can get the care they need, in the right place, at the right time, with better treatment outcomes and reduces costs.

Keywords: geriatric, oral health, project echo, chronic disease, oral health

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Authors: Tauseef Ahmad, Muhammad Ishaq, Mathew Eapen, Ahyoung Park, Sam Karpiniec, Vanni Caruso, Rajaraman Eri

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Fucoidans are complex, fucose-rich sulfated polymers discovered in brown seaweeds. Fucoidans are popular around the world, particularly in the nutraceutical and pharmaceutical industries, due to their promising medicinal properties. Fucoidans have been shown to have a variety of biological activities, including anti-inflammatory effects. They are known to inhibit inflammatory processes through a variety of mechanisms, including enzyme inhibition and selectin blockade. Inflammation is a part of the complicated biological response of living systems to damaging stimuli, and it plays a role in the pathogenesis of a variety of disorders, including arthritis, inflammatory bowel disease, cancer, and allergies. In the current investigation, various fucoidan extracts from Undaria pinnatifida, Fucus vesiculosus, Macrocystis pyrifera, Ascophyllum nodosum, and Laminaria japonica were assessed for inhibition of pro-inflammatory cytokine production (TNF-α, IL-1β, and IL-6) in LPS induced human macrophage cell line (THP-1) and human peripheral blood mononuclear cells (PBMCs). Furthermore, we also sought to catalogue these extracts based on their anti-inflammatory effects in the current in-vitro cell model. Materials and Methods: To assess the cytotoxicity of fucoidan extracts, MTT (3-[4,5-dimethylthiazol-2-yl]-2,5, -diphenyltetrazolium bromide) cell viability assay was performed. Furthermore, a dose-response for fucoidan extracts was performed in LPS induced THP-1 cells and PBMCs after pre-treatment for 24 hours, and levels of TNF-α, IL-1β, and IL-6 cytokines were measured using Enzyme-Linked Immunosorbent Assay (ELISA). Results: The MTT cell viability assay demonstrated that fucoidan extracts exhibited no evidence of cytotoxicity in THP-1 cells or PBMCs after 48 hours of incubation. The results of the sandwich ELISA revealed that all fucoidan extracts suppressed cytokine production in LPS-stimulated PBMCs and human THP-1 cells in a dose-dependent manner. Notably, at lower concentrations, the lower molecular fucoidan (5-30 kDa) extract from Macrocystis pyrifera was a highly efficient inhibitor of pro-inflammatory cytokines. Fucoidan extracts from all species including Undaria pinnatifida, Fucus vesiculosus, Macrocystis pyrifera, Ascophyllum nodosum, and Laminaria japonica exhibited significant anti-inflammatory effects. These findings on several fucoidan extracts provide insight into strategies for improving their efficacy against inflammation-related diseases. Conclusion: In the current research, we have successfully catalogued several fucoidan extracts based on their efficiency in LPS-induced macrophages and PBMCs in downregulating the key pro-inflammatory cytokines (TNF-, IL-1 and IL-6), which are prospective targets in human inflammatory illnesses. Further research would provide more information on the mechanism of action, allowing it to be tested for therapeutic purposes as an anti-inflammatory medication.

Keywords: fucoidan, PBMCs, THP-1, TNF-α, IL-1β, IL-6, inflammation

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Authors: L. Bidyalakshmi, R. Ananthan, T. Longvah

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Antioxidants are substances that can prevent or delay oxidative damage of lipids, proteins and nucleic acids by reactive oxygen species. These help in lowering incidence of degenerative diseases such as cancer, arthritis, atherosclerosis, heart disease, inflammation, brain dysfunction and acceleration of the ageing process. The north eastern part of India falls among the global hotspots of biodiversity. Over the years, the local communities in the region have developed ingenious uses of many wild plants within their environment as food sources. Many of these less familiar foods form an integral part of the diet of these communities, and some are traditionally valued for its therapeutic effects. So the study was carried to estimate the antioxidant activity of some of these indigenous foods. Twenty-eight indigenous plant foods were studied for their antioxidant activity. Antioxidant activities were determined by using DPPH (2, 2-diphenyl-1-picrylhydrazyl) assay, FRAP (Ferric Reducing Antioxidant Power) assay and SOSA (Super Oxide Scavenging Assay). Out of the twenty-eight plant foods, there were thirteen leafy vegetables, four fruits, five roots and tubers, four spices and two mushrooms. Water extract and methanol extract of the samples were used for the analysis. The leafy vegetable samples exhibited antioxidant capacity with IC50 ranging from 8-1414 mg/ml for lipid extract and 34-37878 mg/ml for aqueous extract in DPPH assay. Total FRAP value ranging from 58-1005 mmol FeSO4 Eq/100g of the sample, which is comparatively higher than the antioxidant capacity of some commonly consumed leafy vegetables. In SOSA, water extract of leafy vegetables show a range of 0.05-193.68 µmol ascorbic acid equivalent/g of the samples. While the methanol extract of the samples show 0.20-21.94 µmol Trolox equivalent/g of the samples. Polygonum barbatum, Wendlandia glabrata and Polygonum posumbu have higher antioxidant activity among the leafy vegetables analysed. Among the fruits, Rhus hookerii showed the highest antioxidant activities in both FRAP and SOSA methods while Spondias magnifera exhibited higher antioxidant activity in DPPH method. Alocasia cucullata exhibited higher antioxidant activity in DPPH and FRAP assays while Alpinia galanga showed higher antioxidant activity in SOSA assay when compared to the other samples of roots and tubers. Elsholtzia communis showed high antioxidant activity in all the three parameters among the spices. For the mushrooms, Pleurotus ostreatus exhibited higher antioxidant activity than Auricularia delicate in DPPH and SOSA. The samples analysed exhibited antioxidant activity at varying levels and some exhibited higher antioxidant activity than the commonly consumed foods. So consumption of these less familiar foods may play a role in preventing human disease in which free radicals are involved. Further studies on these food samples on phytonutrients and its contribution to the antioxidant activities are required.

Keywords: antioxidant activity, DPPH, FRAP, SOSA

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Authors: Vanessa G. P. Severino, Eliangela Cristina Candida Costa, Nubia Alves Mariano Teixeira Pires Gomides, Lucilia Kato, Afif Felix Monteiro, Maria Anita Lemos Vasconcelos Ambrosio, Carlos Henrique Gomes Martins

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One of the biomes present in Brazil is known as Cerrado, which is a vast tropical savanna ecoregion, particularly in the states of Goiás, Mato Grosso do Sul, Mato Grosso, Tocantins and Minas Gerais. Many species of plants are characterized as endemic and they have therapeutic value for a large part of the population, especially to the rural communities. Given that, the southeastern region of the state of Goiás contains about 21 rural communities, which present a form of organization based on the use of natural resources available. One of these rural communities is named of Coqueiros, where the knowledge about the medicinal plants was very important to this research. Thus, this study focuses on the ethnobotanical survey of this community on the use of Kielmeyera coriacea to treat diseases. From the 37 members interviewed, 76% indicated this species for the treatment of intestinal infection, leukemia, anemia, gastritis, gum pain, toothache, cavity, arthritis, arthrosis, healing, vermifuge, rheumatism, antibiotic, skin problems, mycoses and all kinds of infections. The medicinal properties attributed during the interviews were framed in the body system (disease categories), adapted from ICD 10; thus, 20 indications of use were obtained, among five body systems. Therefore, the root of this species was select to chemical and biological (antioxidant and antimicrobial) studies. From the liquid-liquid extraction of ethanolic extract of root (EER), the hexane (FH), ethyl acetate (FAE), and hydro alcoholic (FHA) fractions were obtained. The chemical profile study of these fractions was performed by LC-MS, identifying major compounds such as δ-tocotrienol, prenylated acylphoroglucinol, 2-hydroxy-1-methoxyxanthone and quercitrin. EER, FH, FAE and FHA were submitted to biological tests. FHA presented the best antioxidant action (EC50 201.53 μg mL-1). EER inhibited the bacterial growth of Streptococcus pyogenes and Pseudomonas aeruginosa, microorganisms associated with rheumatism, at Minimum Inhibitory Concentration (MIC) of 6.25 μg mL-1. In addition, the FH-10 subfraction, obtained from FH fractionation, presented MIC of 1.56 μg mL-1 against S. pneumoniae; EER also inhibited the fungus Candida glabrata (MIC 7.81 μg mL- 1). The FAE-4.7.3 fraction, from the fractionation of FAE, presented MIC of 200 μg mL-1 against Lactobacillus casei, which is one of the causes of caries and oral infections. By the correlation of the chemical and biological data, it is possible to note that the FAE-4.7.3 and FH-10 are constituted 4-hydroxy-2,3-methylenedioxy xanthone, 3-hydroxy-1,2-dimethoxy xanthone, lupeol, prenylated acylphoroglucinol and quercitrin, which could be associated with the biological potential found. Therefore, this study provides an important basis for further investigations regarding the compounds present in the active fractions of K. coriacea, which will permit the establishment of a correlation between ethnobotanical survey and bioactivity.

Keywords: biological activity, ethnobotanical survey, Kielmeyera coriacea Mart., LC-MS profile

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Authors: Ved Vrat Verma, Rani Gupta, Manisha Goel

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γ-glutamyltranspeptidase (GGT: EC 2.3.2.2) is an N-terminal nucleophile hydrolase conserved in all three domains of life. GGT plays a key role in glutathione metabolism where it catalyzes the breakage of the γ-glutamyl bonds and transfer of γ-glutamyl group to water (hydrolytic activity) or amino acids or short peptides (transpeptidase activity). GGTs from bacteria, archaea, and eukaryotes (human, rat and mouse) are homologous proteins sharing >50% sequence similarity and conserved four layered αββα sandwich like three dimensional structural fold. These proteins though similar in their structure to each other, are quite diverse in their enzyme activity: some GGTs are better at hydrolysis reactions but poor in transpeptidase activity, whereas many others may show opposite behaviour. GGT is known to be involved in various diseases like asthma, parkinson, arthritis, and gastric cancer. Its inhibition prior to chemotherapy treatments has been shown to sensitize tumours to the treatment. Microbial GGT is known to be a virulence factor too, important for the colonization of bacteria in host. However, all known inhibitors (mimics of its native substrate, glutamate) are highly toxic because they interfere with other enzyme pathways. However, a few successful efforts have been reported previously in designing species specific inhibitors. We aim to leverage the diversity seen in GGT family (pathogen vs. eukaryotes) for designing specific inhibitors. Thus, in the present study, we have used DIVERGE software to identify sites in GGT proteins, which are crucial for the functional and structural divergence of these proteins. Since, type II divergence sites vary in clade specific manner, so type II divergent sites were our focus of interest throughout the study. Type II divergent sites were identified for pathogen vs. eukaryotes clusters and sites were marked on clade specific representative structures HpGGT (2QM6) and HmGGT (4ZCG) of pathogen and eukaryotes clade respectively. The crucial divergent sites within 15 A radii of the binding cavity were highlighted, and in-silico mutations were performed on these sites to delineate the role of these sites on the mechanism of catalysis and protein folding. Further, the amino acid network (AAN) analysis was also performed by Cytoscape to delineate assortative mixing for cavity divergent sites which could strengthen our hypothesis. Additionally, molecular dynamics simulations were performed for wild complexes and mutant complexes close to physiological conditions (pH 7.0, 0.1 M ionic strength and 1 atm pressure) and the role of putative divergence sites and structural integrities of the homologous proteins have been analysed. The dynamics data were scrutinized in terms of RMSD, RMSF, non-native H-bonds and salt bridges. The RMSD, RMSF fluctuations of proteins complexes are compared, and the changes at protein ligand binding sites were highlighted. The outcomes of our study highlighted some crucial divergent sites which could be used for novel inhibitors designing in a species-specific manner. Since, for drug development, it is challenging to design novel drug by targeting similar protein which exists in eukaryotes, so this study could set up an initial platform to overcome this challenge and help to deduce the more effective targets for novel drug discovery.

Keywords: γ-glutamyltranspeptidase, divergence, species-specific, drug design

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Authors: Maria Zulema Morquecho Vega, Fabiola CarolinaMiranda Castro, Rafael Verdugo Miranda, Ignacio Yocupicio Villegas, Ana lidia Barron Raygoza, Martin enrique MArquez Cordova, Jose Alberto Duarte Moller

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Background: Anemopsis californica, also called (tame grass) belongs to the Saururaceae family small, green plant. The blade is long and wide. Gives a white flower. The plant population is only found in humid, swampy habitats, it grows where there is water, along the banks of streams and water holes. In the winter, it dries up. The leaves, rhizomes, or roots of this plant have been used to treat a range of diseases. Some of its healing properties are used to treat wounds, cold and flu symptoms, spasmodic cough, infection, pain and inflammation, burns, swollen feet, as well as lung ailments, asthma, circulatory problems (varicose veins), rheumatoid arthritis, purifies blood, helps in urinary and digestive tract diseases, sores and healing, for headache, sore throat, diarrhea, kidney pain. The tea made from the leaves and roots is used to treat uterine cancer, womb cancer, relieves menstrual pain and stops excessive bleeding after childbirth. It is also used as a gynecological treatment for infections, hemorrhoids, candidiasis and vaginitis. Objective: To study the cytotoxicity of gels prepared with silver nanoparticles in AC extract combined with chitosan, collagen and hyaluronic acid as an alternative therapy for skin conditions. Methods: The Ag NPs were synthesized according to the following method. A 0.3 mg/mL solution is prepared in 10 ml of deionized water, adjust to pH 12 with NaOH, stirring is maintained constant magnetic and a temperature of 80 °C. Subsequently, 100 ul of a 0.1 M AgNO3 solution and kept stirring constantly for 15 min. Once the reaction is complete, measurements are performed by UV-Vis. A gel was prepared in a 5% solution of acetic acid with the respective nanoparticles and AC extract of silver in the extract of AC. Chitosan is added until the process begins to occur gel. At that time, collagen will be added in a ratio of 3 to 5 drops, and later, hyaluronic acid in 2% of the total compound formed. Finally, after resting for 24 hours, the cytotoxic effect of the gels was studied. in the presence of highly positive bacteria Staphylococcus aureus and highly negative for Escherichia coli. Cultures will be incubated for 24 hours in the presence of the compound and compared with the reference. Results: Silver nanoparticles obtained had a spherical shape and sizes among 20 and 30 nm. UV-Vis spectra confirm the presence of silver nanoparticles showing a surface plasmon around 420 nm. Finally, the test in presence of bacteria yield a good antibacterial property of this nanocompound and tests in people were successful. Conclusion: Gel prepared by biogenic synthesis shown beneficious effects in severe acne, acne vulgaris and wound healing with diabetic patients.

Keywords: anemopsis californica, nanomedicina, biotechnology, biomedicine

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Authors: Daniel Puciato, Piotr Oleśniewicz, Julita Markiewicz-Patkowska, Krzysztof Widawski, Michał Rozpara, Władysław Mynarski, Agnieszka Gawlik, Małgorzata Dębska, Soňa Jandová

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Physical activity as a part of people’s everyday life reduces the risk of many diseases, including those induced by lifestyle, e.g. obesity, type 2 diabetes, osteoporosis, coronary heart disease, degenerative arthritis, and certain types of cancer. That refers particularly to professionally active people, including the early senior group working on non-manual positions. The aim of the study is to evaluate the relationship between physical activity and the socio-economic status of non-manual workers from Wroclaw—one of the biggest cities in Poland, a model setting for such investigations in this part of Europe. The crucial problem in the research is to find out the percentage of respondents who meet the health-related recommendations of the World Health Organization (WHO) concerning the volume, frequency, and intensity of physical activity, as well as to establish if the most important socio-economic factors, such as gender, age, education, marital status, per capita income, savings and debt, determine the compliance with the WHO physical activity recommendations. During the research, conducted in 2013, 1,170 people (611 women and 559 men) aged 21–60 years were examined. A diagnostic poll method was applied to collect the data. Physical activity was measured with the use of the short form of the International Physical Activity Questionnaire with extended socio-demographic questions, i.e. concerning gender, age, education, marital status, income, savings or debts. To evaluate the relationship between physical activity and selected socio-economic factors, logistic regression was used (odds ratio statistics). Statistical inference was conducted on the adopted ex ante probability level of p<0.05. The majority of respondents met the volume of physical effort recommended for health benefits. It was particularly noticeable in the case of the examined men. The probability of compliance with the WHO physical activity recommendations was highest for workers aged 21–30 years with secondary or higher education who were single, received highest incomes and had savings. The results indicate the relations between physical activity and socio-economic status in the examined women and men. People with lower socio-economic status (e.g. manual workers) are physically active primarily at work, whereas those better educated and wealthier implement physical effort primarily in their leisure time. Among the investigated subjects, the youngest group of non-manual workers have the best chances to meet the WHO standards of physical activity. The study also confirms that secondary education has a positive effect on the public awareness on the role of physical activity in human life. In general, the analysis of the research indicates that there is a relationship between physical activity and some socio-economic factors of the respondents, such as gender, age, education, marital status, income per capita, and the possession of savings. Although the obtained results cannot be applied for the general population, they show some important trends that will be verified in subsequent studies conducted by the authors of the paper.

Keywords: IPAQ, nonmanual workers, physical activity, socioeconomic factors, WHO

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Authors: Charalabos Antonatos, Mariza Panoutsopoulou, Georgios K. Georgakilas, Evangelos Evangelou, Yiannis Vasilopoulos

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The extended tissue damage and severe clinical outcomes of autoimmune diseases, accompanied by the high annual costs to the overall health care system, highlight the need for an efficient therapy. Increasing knowledge over the pathophysiology of specific chronic inflammatory diseases, namely Psoriasis (PsO), Inflammatory Bowel Diseases (IBD) consisting of Crohn’s disease (CD) and Ulcerative colitis (UC), and Rheumatoid Arthritis (RA), has provided insights into the underlying mechanisms that lead to the maintenance of the inflammation, such as Tumor Necrosis Factor alpha (TNF-α). Hence, the anti-TNFα biological agents pose as an ideal therapeutic approach. Despite the efficacy of anti-TNFα agents, several clinical trials have shown that 20-40% of patients do not respond to treatment. Nowadays, high-throughput technologies have been recruited in order to elucidate the complex interactions in multifactorial phenotypes, with the most ubiquitous ones referring to transcriptome quantification analyses. In this context, a random effects meta-analysis of available gene expression cDNA microarray datasets was performed between responders and non-responders to anti-TNFα therapy in patients with IBD, PsO, and RA. Publicly available datasets were systematically searched from inception to 10th of November 2020 and selected for further analysis if they assessed the response to anti-TNFα therapy with clinical score indexes from inflamed biopsies. Specifically, 4 IBD (79 responders/72 non-responders), 3 PsO (40 responders/11 non-responders) and 2 RA (16 responders/6 non-responders) datasetswere selected. After the separate pre-processing of each dataset, 4 separate meta-analyses were conducted; three disease-specific and a single combined meta-analysis on the disease-specific results. The MetaVolcano R package (v.1.8.0) was utilized for a random-effects meta-analysis through theRestricted Maximum Likelihood (RELM) method. The top 1% of the most consistently perturbed genes in the included datasets was highlighted through the TopConfects approach while maintaining a 5% False Discovery Rate (FDR). Genes were considered as Differentialy Expressed (DEGs) as those with P ≤ 0.05, |log2(FC)| ≥ log2(1.25) and perturbed in at least 75% of the included datasets. Over-representation analysis was performed using Gene Ontology and Reactome Pathways for both up- and down-regulated genes in all 4 performed meta-analyses. Protein-Protein interaction networks were also incorporated in the subsequentanalyses with STRING v11.5 and Cytoscape v3.9. Disease-specific meta-analyses detected multiple distinct pro-inflammatory and immune-related down-regulated genes for each disease, such asNFKBIA, IL36, and IRAK1, respectively. Pathway analyses revealed unique and shared pathways between each disease, such as Neutrophil Degranulation and Signaling by Interleukins. The combined meta-analysis unveiled 436 DEGs, 86 out of which were up- and 350 down-regulated, confirming the aforementioned shared pathways and genes, as well as uncovering genes that participate in anti-inflammatory pathways, namely IL-10 signaling. The identification of key biological pathways and regulatory elements is imperative for the accurate prediction of the patient’s response to biological drugs. Meta-analysis of such gene expression data could aid the challenging approach to unravel the complex interactions implicated in the response to anti-TNFα therapy in patients with PsO, IBD, and RA, as well as distinguish gene clusters and pathways that are altered through this heterogeneous phenotype.

Keywords: anti-TNFα, autoimmune, meta-analysis, microarrays

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Authors: Pauline Nyssen, Ange Mouithys-Mickalad, Maryse Hoebeke

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Inflammation is a complex physiological phenomenon involving chemical and enzymatic mechanisms. Polymorphonuclear neutrophil leukocytes (PMNs) play an important role by producing reactive oxygen species (ROS) and releasing myeloperoxidase (MPO), a pro-oxidant enzyme. Released both in the phagolysosome and the extracellular medium, MPO produces during its peroxidase and halogenation cycles oxidant species, including hypochlorous acid, involved in the destruction of pathogen agents, like bacteria or viruses. Inflammatory pathologies, like rheumatoid arthritis, atherosclerosis induce an excessive stimulation of the PMNs and, therefore, an uncontrolled release of ROS and MPO in the extracellular medium, causing severe damages to the surrounding tissues and biomolecules such as proteins, lipids, and DNA. The treatment of chronic inflammatory pathologies remains a challenge. For many years, MPO has been used as a target for the development of effective treatments. Numerous studies have been focused on the design of new drugs presenting more efficient MPO inhibitory properties. However, some designed inhibitors can be toxic. An alternative consists of assessing the potential inhibitory action of clinically-known molecules, having antioxidant activity. Propofol, 2,6-diisopropyl phenol, which is used as an intravenous anesthetic agent, meets these requirements. Besides its anesthetic action employed to induce a sedative state during surgery or in intensive care units, propofol and its injectable form Diprivan indeed present antioxidant properties and act as ROS and free radical scavengers. A study has also evidenced the ability of propofol to inhibit the formation of the neutrophil extracellular traps fibers, which are important to trap pathogen microorganisms during the inflammation process. The aim of this study was to investigate the potential inhibitory action mechanism of propofol and Diprivan on MPO activity. To go into the anti-inflammatory action of propofol in-depth, two of its oxidative derivatives, 2,6-diisopropyl-1,4-p-benzoquinone (PPFQ) and 3,5,3’,5’-tetra isopropyl-(4,4’)-diphenoquinone (PPFDQ), were studied regarding their inhibitory action. Specific immunological extraction followed by enzyme detection (SIEFED) and molecular modeling have evidenced the low anti-catalytic action of propofol. Stopped-flow absorption spectroscopy and direct MPO activity analysis have proved that propofol acts as a reversible MPO inhibitor by interacting as a reductive substrate in the peroxidase cycle and promoting the accumulation of redox compound II. Overall, Diprivan exhibited a weaker inhibitory action than the active molecule propofol. In contrast, PPFQ seemed to bind and obstruct the enzyme active site, preventing the trigger of the MPO oxidant cycles. PPFQ induced a better chlorination cycle inhibition at basic and neutral pH in comparison to propofol. PPFDQ did not show any MPO inhibition activity. The three interest molecules have also demonstrated their inhibition ability on an important step of the inflammation pathway, the PMNs superoxide anions production, thanks to EPR spectroscopy and chemiluminescence. In conclusion, propofol presents an interesting immunomodulatory activity by acting as a reductive substrate in the peroxidase cycle of MPO, slowing down its activity, whereas PPFQ acts more as an anti-catalytic substrate. Although PPFDQ has no impact on MPO, it can act on the inflammation process by inhibiting the superoxide anions production by PMNs.

Keywords: Diprivan, inhibitor, myeloperoxidase, propofol, spectroscopy

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Authors: Siti Rahayu, Khairulniza Mohd Puat, Kesavan R., Mohammad Harris A., Jalila, Kunalan G., Fazir Mohamad

Abstract:

The greatest challenge has been in establishing and maintaining the dedicated nursing team. Continuity is served when nurses are assigned exclusively for managing wound, where they can continue to build expertise and skills. In addition, there is a growing incidence of chronic wounds and recognition of the complexity involved in caring for these patients. We would like to share 4 cases with different techniques of wound management. 1st case, 39 years old gentleman with underlying rheumatoid arthritis with chronic periprosthetic joint infection of right total knee replacement presented with persistent drainage over right knee. Patient was consulted for two stage revision total knee replacement. However, patient only agreed for debridement and retention of implant. After debridement, large medial and lateral wound was treated with Instillation Negative Pressure Wound Therapy Dressings. After several cycle, the wound size reduced, and conventional dressing was applied. 2nd case, 58 years old gentleman with underlying diabetes presented with right foot necrotizing fasciitis with gangrene of 5th toe. He underwent extensive debridement of foot with rays’ amputation of 5th toe. Post debridement patient was started on Instillation Negative Pressure Wound Therapy Dressings. After several cycle of VAC, the wound bed was prepared, and he underwent split skin graft over right foot. 3 rd case, 60 years old gentleman with underlying diabetes mellitus presented with right foot necrotizing soft tissue infection. He underwent rays’ amputation and extensive wound debridement. Upon stabilization of general condition, patient was discharge with regular wound dressing by same nurse and doctor during each visit to clinic follow up. After 6 months of follow up, the wound healed well. 4th case, 38-year-old gentleman had alleged motor vehicle accident and sustained closed fracture right tibial plateau. Open reduction and proximal tibial locking plate were done. At 2 weeks post-surgery, the patient presented with warm, erythematous leg and pus discharge from the surgical site. Empirical antibiotic was started, and wound debridement was done. Intraoperatively, 50cc pus was evacuated, unhealthy muscle and tissue debrided. No loosening of the implant. Patient underwent multiple wound debridement. At 2 weeks post debridement wound healed well, but the proximal aspect was unable to close immediately. This left the proximal part of the implant to be exposed. Patient was then put on VAC dressing for 3 weeks until healthy granulation tissue closes the implant. Meanwhile, antibiotic was change according to culture and sensitivity. At 6 weeks post the first debridement, the wound was completely close, and patient was discharge home well. At 3 months post operatively, patient wound and fracture healed uneventfully and able to ambulate independently. Complex wounds are too serious to be dealt with. Team managing complex wound need continuous support through the provision of educational tools to support their professional development, engagement with local and international expert, as well as highquality products that increase efficiencies in services

Keywords: VAC (Vacuum Assisted Closure), empirical- initial antibiotics, NPWT- negative pressure wound therapy, NF- necrotizing fasciitis, gangrene- blackish discoloration due to poor blood supply

Procedia PDF Downloads 105

Authors: Patricia Shirley Almeida Prado, Selma Paixão Argollo, Maria De Fátima Teixeira Guimarães, Leticia Matos Sobrinho

Abstract:

Skeletal differential diagnosis is essential in forensic anthropology in order to differentiate skeletal trauma from normal osseous variation and pathological processes. Thus, part of forensic anthropological field is differentiate skeletal criminal injuries from the normal skeletal variation (bone fusion or nonunion, transitional vertebrae and other non-metric traits), non-traumatic skeletal pathology (myositis ossificans, arthritis, bone metastasis, osteomyelitis) from traumatic skeletal pathology (myositis ossificans traumatic) avoiding misdiagnosis. This case shows the importance of effective pathological diagnosis in order to accelerate the identification process of skeletonized human remains. THE CASE: An unidentified skeletal remains at the medico legal institute Nina Rodrigues-Salvador, of a male young adult (29 to 40 years estimated) showing a massive heterotopic ossification on its right tibia at upper epiphysis and adjacent articular femur surface; an extensive ossification on the right clavicle (at the sternal extremity) also presenting an heterotopic ossification at right scapulae (upper third of scapulae lateral margin and infraglenoid tubercule) and at the head of right humerus at the shoulder joint area. Curiously, this case also shows an unusual porosity in certain vertebrae´s body and in some tarsal and carpal bones. Likewise, his left fifth metacarpal bones (right and left) showed a healed fracture which led both bones distorted. Based on identification, of pathological conditions in human skeletal remains literature and protocols these alterations can be misdiagnosed and this skeleton may present more than one pathological process. The anthropological forensic lab at Medico-legal Institute Nina Rodrigues in Salvador (Brazil) adopts international protocols to ancestry, sex, age and stature estimations, also implemented well-established conventions to identify pathological disease and skeletal alterations. The most compatible diagnosis for this case is hematogenous osteomyelitis due to following findings: 1: the healed fracture pattern at the clavicle showing a cloaca which is a pathognomonic for osteomyelitis; 2: the metacarpals healed fracture does not present cloaca although they developed a periosteal formation. 3: the superior articular surface of the right tibia shows an extensive inflammatory healing process that extends to adjacent femur articular surface showing some cloaca at tibia bone disease. 4: the uncommon porosities may result from hematogenous infectious process. The fractures probably have occurred in a different moments based on the healing process; the tibia injury is more extensive and has not been reorganized, while metacarpals and clavicle fracture is properly healed. We suggest that the clavicle and tibia´s fractures were infected by an existing infectious disease (syphilis, tuberculosis, brucellosis) or an existing syndrome (Gorham’s disease), which led to the development of osteomyelitis. This hypothesis is supported by the fact that different bones are affected in diverse levels. Like the metacarpals that do not show the cloaca, but then a periosteal new bone formation; then the unusual porosities do not show a classical osteoarthritic processes findings as the marginal osteophyte, pitting and new bone formation, they just show an erosive process without bone formation or osteophyte. To confirm and prove our hypothesis we are working on different clinical approaches like DNA, histopathology and other image exams to find the correct diagnostic.

Keywords: bone disease, forensic anthropology, hematogenous osteomyelitis, human identification, human remains

Procedia PDF Downloads 325