Search results for: peripheral nerve regeneration

Authors: Liza Ireni-Saban

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The 6.6 magnitude quake event that occurred in 2003 (Bam, Iran) made it impossible for the Iranian government to handle disaster relief efforts domestically. In this extreme event, the Iranian government reached out to the international community, and this created a momentum that had to be carried out by trust-building efforts on all sides, often termed ‘Disaster Diplomacy’. Indeed, the circumstances were even more critical when one considers the increasing political and economic isolation of Iran within the international community. The potential for transformative political space to be opened by disaster has been recognized by dominant international political actors. Despite the fact that Bam 2003 post-disaster relief efforts did not catalyze any diplomatic activities on all sides, it is suggested that few international aid agencies have successfully used disaster recovery to enhance their popular legitimacy and reputation among the international community. In terms of disaster diplomacy, an actor’s reputational capital may affect his ability to build coalitions and alliances to achieve international political ends, to negotiate and build understanding and trust with foreign publics. This study suggests that the post-disaster setting may benefit from using the ecology of games framework to evaluate the role of bridging actors and mediators in facilitating collaborative governance networks. Recent developments in network theory and analysis provide means of structural embeddedness to explore how reputational capital can be built through brokerage roles of actors engaged in a disaster management network. This paper then aims to structure the relations among actors that participated in the post-disaster relief efforts in the 2003 Bam earthquake (Iran) in order to assess under which conditions actors may be strategically utilized to serve as mediating organizations for future disaster events experienced by isolated nations or nations in conflict. The results indicate the strategic use of reputational capital by the Iranian Ministry of Foreign Affairs as key broker to build a successful coordinative system for reducing disaster vulnerabilities. International aid agencies rarely played brokerage roles to coordinate peripheral actors. U.S. foreign assistance (USAID), despite coordination capacities, was prevented from serving brokerage roles in the system.

Keywords: coordination, disaster diplomacy, international aid organizations, Iran

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Authors: Tianyue Wan

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Lost space is the space that has not been used for a long time and is in decline, proposed by Roger Trancik. And in his book Finding Lost Space: Theories of Urban Design, the concept of lost space is defined as those anti-traditional spaces that are unpleasant, need to be redesigned, and have no benefit to the environment and users. They have no defined boundaries and do not connect the various landscape elements in a coherent way. With the rapid development of urbanization in China, the blind areas of urban renewal have become a chaotic lost space that is incompatible with the rapid development of urbanization. Therefore, lost space needs to be reconstructed urgently under the background of infill development and reduction planning in China. The formation of lost space is also an invisible division of social hierarchy. This paper tries to break down the social class division and the estrangement between people through the regeneration of lost space. Ultimately, it will enhance vitality, rebuild a sense of belonging, and create a continuous open public space for local people. Based on the concept of lost space and energy field, this paper clarifies the significance of the energy field in the lost space renovation. Then it introduces the energy field into lost space by using the magnetic field in physics as a prototype. The construction of the energy field is support by space theory, spatial morphology analysis theory, public communication theory, urban diversity theory and city image theory. Taking Wuhan’s Lingjiao Park of China as an example, this paper chooses the lost space on the west side of the park as the research object. According to the current situation of this site, the energy intervention strategies are proposed from four aspects: natural ecology, space rights, intangible cultural heritage and infrastructure configuration. And six specific lost space renewal methods are used in this work, including “riveting”, “breakthrough”, “radiation”, “inheritance”, “connection” and “intersection”. After the renovation, space will be re-introduced into the active crow. The integration of activities and space creates a sense of place, improve the walking experience, restores the vitality of the space, and provides a reference for the reconstruction of lost space in the city.

Keywords: dynamic vitality intervention, lost space, space vitality, sense of place

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Authors: Edward A. Osifodunrin, Jose Manuel Dias Lopes

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In Nigeria, enormous efforts/resources had, over the years, been expended on promoting financial inclusion (FI); however, it is seemingly discouraging that many of its self-declared targets on FI remained unachieved, especially amongst the Rural Dwellers and Actors in the Informal Sectors (RDAIS). Expectedly, many reasons had been earmarked for these failures: low literacy level, huge informal/rural sectors, etc. This study posits that in spite of these truly-debilitating factors, these FI policy failures could have been avoided or mitigated if the principles of active and better-managed citizens’ participation had been strictly followed in the (re)design/implementation of its FI policies. In other words, in a bid to mitigate the prevalent FE in Nigeria, this study hypothesizes the positive impact of increased/active citizens’ participation on FI outcome(s), backed by a preliminary empirical validation. Also, the study introduces the RDAIS-focused participatory financial inclusion policy (PFIP) as a major FI policy regeneration/improvement tool. The three categories of respondents that served as research subjects are FI experts in Nigeria (n = 72), RDAIS from the very rural/remote village of Unguwar Dogo in Northern Nigeria (n = 43), and RDAIS from another rural village of Sekere (n = 56) in the Southern region of Nigeria. Using survey design (5-point Likert scale questionnaires), random/stratified sampling, and descriptive/inferential statistics, the study often recorded independent consensus (amongst these three categories of respondents) that RDAIS’s active participation in iterative FI policy initiation, (re)design, implementation, (re)evaluation could indeed give improved FI outcomes. However, some questionnaire items also recorded divergent opinions and various statistically significant differences in the mean scores of these three categories. The PFIP (or any customized version of it) should then be carefully integrated into the NFIS of Nigeria (and possibly in the NFIS of other developing countries) to truly/fully provide FI policy integration for these excluded RDAIS and arrest the prevalence of FE.

Keywords: citizens’ participation, development, financial inclusion, formal financial services, national financial inclusion strategy, participatory financial inclusion policy, rural dwellers and actors in the informal sectors

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Authors: Hager E. Amer, Hany El Saftawy, Laila Rashed, Ahmed M. Ata, Fatma Metwally, Hesham Mettawei, Hossam E. Sayed, Tamer Adel, Kareem M. El Sawah

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Aim: The purpose of this study is to regenerate the damaged photoreceptor cells as a result of argon laser as a model of Retinitis Pigmentosa in rabbits' retina by using adult stem cells from rabbits' bone marrow. Background: Retinitis pigmentosa (RP) is a group of inherited disorders that primarily affect photoreceptor and pigment epithelium function. RP leads to loss of the rod outer segment and shorten the photoreceptor layer and expose the photoreceptor cell body to high-pressure levels in oxygen (oxidative stress) leads to apoptosis to the rod and cone cells. In particular, there is no specific treatment for retinitis pigmentosa. Materials and Methods: Forty Two Giant (Rex) rabbits were used in this experiment divided into 3 groups: Group 1: Control (6 rabbits), Group 2: Argon laser radiated as a model of retinitis pigmentosa (12 rabbits), Group 3: Laser radiated and treated by 6 million stem cells (12 rabbits). The last two groups are divided each into two subgroups each subgroup contains 6 rabbits, the ophthalmological examination was performed on rabbits, blood samples and retina samples were taken after 25 days and after 36 days from the laser radiation (10 days and 21 days after stem cells insertion in group 3) to perform the biochemical analysis. Results: Compared to control Group, a decrease of ERG wave amplitude and antioxidant substances (Glutathione) in blood and retina in group 2, and an increase of oxidative stress substances (Nitric oxide, Malonaldehyde, and carponyl protein) and apoptotic substances (Advanced glycation end product and M-metalloproteinase) in blood and retina. Compared to group 2, mostly increases of antioxidant substances and ERG wave amplitude in group 3, and mostly decreases in oxidative stress substances and apoptotic substances. Conclusion: Insertion of 6 million stem cells intravitreous gives good results in regeneration of the damaged photoreceptor cells after 21 days.

Keywords: retinitis pigmentosa, stem cells, argon laser, oxidative stress, apoptosis

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Authors: Hiba Naccache, Rima Hleiss

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Additive manufacturing AM or 3D printing is one of the pillars of Industry 4.0. Compared to traditional manufacturing, AM provides a prototype before production in order to optimize the design and avoid the stock market and uses strictly necessary material which can be recyclable, for the benefit of leaning towards local production, saving money, time and resources. Different types of AM exist and it has a broad range of applications across several industries like aerospace, automotive, medicine, education and else. The Laser Powder Bed Fusion (LPBF) is a metal AM technique that uses a laser to liquefy metal powder, layer by layer, to build a three-dimensional (3D) object. In industry 4.0 and aligned with the numbers 9 (Industry, Innovation and Infrastructure) and 12 (Responsible Production and Consumption) of the Sustainable Development Goals of the UNESCO 2030 Agenda, the AM’s manufacturers committed to minimizing the environmental impact by being sustainable in every production. The LPBF has several environmental advantages, like reduced waste production, lower energy consumption, and greater flexibility in creating components with lightweight and complex geometries. However, LPBF also have environmental drawbacks, like energy consumption, gas consumption and emissions. It is critical to recognize the environmental impacts of LPBF in order to mitigate them. To increase awareness and promote sustainable practices regarding LPBF, the researchers use the Elaboration Likelihood Model (ELM) theory where people from multiple universities in France and Qatar process information in two ways: peripherally and centrally. The peripheral campaigns use superficial cues to get attention, and the central campaigns provide clear and concise information. The authors created a seminar including a video showing LPBF production and a website with educational resources. The data is collected using questionnaire to test attitude about the public awareness before and after the seminar. The results reflected a great shift on the awareness toward LPBF and its impact on the environment. With no presence of similar research, to our best knowledge, this study will add to the literature on the sustainability of the LPBF production technique.

Keywords: additive manufacturing, laser powder bed fusion, elaboration likelihood model theory, sustainable development goals, education-awareness, France, Qatar, specific energy consumption, environmental impact, lightweight components

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Authors: Mohammad Arifur Rahman

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The research study aims to bring to light the contribution of sir Sayeed Ahmed in the realm of education and literature. Sir Sayeed Ahmed Khan (1817 –1898), commonly known as Sir Sayeed, was an Indian Muslim leader, Islamic modernist, philosopher and social reformer of the nineteenth century. He earned a reputation as a distinguished scholar while working as a jurist for British India. During the Indian Rebellion of 1857, he remained loyal to the British Empire and was noted for his actions in saving European lives. Believing that the future of Muslims was threatened by the rigidity of their orthodox outlook, Sir Sayeed began promoting Western–style scientific education by founding modern schools and journals and organizing Muslim entrepreneurs. He was one of the founders of the Aligarh Movement and Aligarh Muslim University. He began focusing on writing, from his early life, on various subjects, mainly educational issues. He launched his attempts to revive the spirit of progress within the Muslim community of India. Therefore, modern education became the pivot of his movement for the regeneration of the Indian Muslims. Sayeed Ahmed Khan found time for literary and scholarly pursuits. The range of his literary and scholarly interests was very wide, comprising all the major areas: education, law, philosophy, history, politics, archeology, journalism, Muslim modernism, literature, science and culture, mainly based on his comprehensive religious ideas should be well measured in view to making out him and his contribution to the context. The books written by himself and the books composed by him by some of the great writers like Altaf Hussein Hali, Hafee z Malick, Nasim Rashid, and Christian W. Troll were studied to understand him and his contribution. The readers of this paper would benefit from dispelling the hazy ideas about this great man of India who made an immense contribution. Further research should be undertaken to know more about the different sides of his thought and personality. The qualitative and the historical methods are adopted for the accomplishment of the work.

Keywords: thinker, reformer, educator and Philosopher, modernist

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Authors: Komal Vig, Syamala Soumyakrishnan, Yadav Baral

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Bypass surgery, using the autologous vein has been one of the most effective treatments for cardiovascular diseases (CVD). More recently tissue engineering including engineered vascular grafts to synthesize blood vessels is gaining usage. Dacron and ePTFE has been employed for vascular grafts, however, these does not work well for small diameter grafts (<6 mm) due to intimal hyperplasia and thrombosis. In the present study PTFE was treated with LTP to improve the endothelialization of intimal surface of graft. Scaffolds were also modified with polyvinylpyrrolidone coated silver nanoparticles (Ag-PVP) and the antimicrobial peptides, p753 and p359. Human umbilical vein endothelial cells (HUVEC) were plated on the developed scaffolds and cell proliferation was determined by the MTT assay. Cells attachment on scaffolds was visualized by microscopy. mRNA expressions levels of different cell markers were investigated using quantitative real-time PCR (qPCR). X ray photoelectron spectroscopic confirmed the introduction of oxygenated functionalities from LTP air plasma. Microscopic and MTT assays indicated increase in cell viability in LTP treated scaffolds. Gene expression studies shows enhanced expression of cell adhesion marker Integrin- α 5 gene after LTP treatment. The KB test displayed a zone of inhibition for Ag-PVP, p753 and p359 of 19mm, 14mm, and 12mm respectively. To determine toxicity of antimicrobial agents to cells, MTT Assay was performed using HEK293 cells. MTT Assay exhibited that Ag-PVP and the peptides were non-toxic to cells at 100μg/mL and 50μg/mL, respectively. Live/dead analysis and plate count of treated bacteria exhibited bacterial inhibition on develop scaffold compared to non-treated scaffold. SEM was performed to analyze the structural changes of bacteria after treatment with antimicrobial agents. Gene expression studies were conducted on RNA from bacteria treated with Ag-PVP and peptides using qRT-PCR. Based on our initial results, more scaffolds alternatives will be developed and investigated for cell growth and vascularization studies.

Keywords: low temperature plasma, vascular graft, HUVEC cells, antimicrobial

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Authors: Keith T. S. Tung, H. W. Tsang, Rosa S. Wong, Frederick K. Ho, Patrick Ip

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Objectives: Atopic diseases are increasingly prevalent among children and adolescents, both locally and internationally. One of the possible contributing factors could be the hypercholesterolemia which leads to cholesterol accumulation in macrophages and other immune cells that would eventually promote inflammatory responses, including augmentation of toll-like receptor (TLR). Meanwhile, physical activity is well known for its beneficial effects against the condition of hypercholesterolemia and incidence of atopic diseases. This study, therefore, explored whether atopic diseases were associated with increased cholesterol levels and whether physical activity habit influenced this association. Methods: This is a sub-study derived from the longitudinal cohort study which recruited a group of children at five years of age in Kindergarten 3 (K3) to investigate the long-term impact of family socioeconomic status on child development. In 2018/19, adolescents (average age: 13 years old) were asked to report their physical activity habit and history of any atopic diseases. During health assessment, peripheral blood samples were collected from the adolescents to study their lipid profile [total cholesterol, high-density lipoprotein (HDL)-cholesterol, and low-density lipoprotein (LDL)-cholesterol]. Regression analyses were performed to test the relationships between variables of interest. Results: Among the 315 adolescents, 99 (31.4%) reported to have allergic rhinitis. There were 45 (14.3%) with eczema, 17 (5.4%) with a food allergy, and 12 (3.8%) with asthma. Regression analyses showed that adolescents with a history of any type of atopic diseases had significantly higher total cholesterol (B=13.3, p < 0.01) and LDL cholesterol (B=7.9, p < 0.05) levels. Further subgroup analyses were conducted to examine the effect of physical activity level on the association between atopic diseases and cholesterol levels. We found stronger associations among those who did not meet the World Health Organization recommendation of at least 60 minutes of moderate-to-vigorous activities each day (total cholesterol: B=15.5, p < 0.01; LDL cholesterol: B=10.4, p < 0.05). For those who met this recommendation, the associations between atopic diseases and cholesterol levels became insignificant. Conclusion: Our study results support the current research evidence on the relationship between an elevated level of cholesterol and atopic diseases. More importantly, our results provide preliminary support for the protective effect of regular exercises against elevated cholesterol level due to atopic diseases. The findings highlight the importance of a healthy lifestyle for keeping cholesterol levels in the normal range, which can bring benefits to both physical and mental health.

Keywords: atopic diseases, Chinese adolescents, cholesterol level, physical activity

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Authors: Les Moncrieff

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In a world awash with potent opioids flaming an international crisis, the need to explore safe alternatives has never been more urgent. Bio-electrode Therapy is a novel adjunctive treatment method for relieving acute opioid withdrawal symptoms and many types of complex acute and chronic pain (often the underlying cause of opioid dependence). By combining the science of developmental bioelectricity with Traditional Chinese Medicine’s theory of meridians, rapid relief from pain is routinely being achieved in the clinical setting. Human body functions are dependent on electrical factors, and acupuncture points on the body are known to have higher electrical conductivity than surrounding skin tissue. When tiny gold- and silver-plated electrodes are secured to the skin at specific acupuncture points using established Chinese Medicine principles and protocols, an enhanced microcurrent and electrical field are created between the electrodes, influencing the entire meridian and connecting meridians. No external power source or electrical devices are required. Endogenous DC electric fields are an essential fundamental component for development, regeneration, and wound healing. Disruptions in the normal ion-charge in the meridians and circulation of blood will manifest as pain and development of disease. With the application of these simple electrodes (gold acting as cathode and silver as anode) according to protocols, the resulting microcurrent is directed along the selected meridians to target injured or diseased organs and tissues. When injured or diseased cells have been stimulated by the microcurrent and electrical fields, the permeability of the cell membrane is affected, resulting in an immediate relief of pain, a rapid balancing of positive and negative ions (sodium, potassium, etc.) in the cells, the restoration of intracellular fluid levels, replenishment of electrolyte levels, pH balance, removal of toxins, and a re-establishment of homeostasis.

Keywords: bioelectricity, electrodes, electrical fields, acupuncture meridians, complex pain, opioid withdrawal management

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Authors: Prince Vivek, Vijay K. Bharti, Manishi Mukesh, Ankita Sharma, Om Prakash Chaurasia, Bhuvnesh Kumar

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High performance of endurance in equid requires adaptive changes involving physio-biochemical, and molecular responses in an attempt to regain homeostasis. We hypothesized that the identification of the suitable reference genes might be considered for assessing of endurance related traits in pony at high altitude and may ensure for individuals struggling to potent endurance trait in ponies at high altitude. A total of 12 mares of ponies, Zanskar breed, were divided into three groups, group-A (without load), group-B, (60 Kg) and group-C (80 Kg) on backpack loads were subjected to a load carry protocol, on a steep climb of 4 km uphill, and of gravel, uneven rocky surface track at an altitude of 3292 m to 3500 m (endpoint). Blood was collected before and immediately after the load carry on sodium heparin anticoagulant, and the peripheral blood mononuclear cell was separated for total RNA isolation and thereafter cDNA synthesis. Real time-PCR reactions were carried out to evaluate the mRNAs expression profile of a panel of putative internal control genes (ICGs), related to different functional classes, namely glyceraldehyde 3-phosphate dehydrogenase (GAPDH), β₂ microglobulin (β₂M), β-actin (ACTB), ribosomal protein 18 (RS18), hypoxanthine-guanine phosophoribosyltransferase (HPRT), ubiquitin B (UBB), ribosomal protein L32 (RPL32), transferrin receptor protein (TFRC), succinate dehydrogenase complex subunit A (SDHA) for normalizing the real-time quantitative polymerase chain reaction (qPCR) data of native pony’s. Three different algorithms, geNorm, NormFinder, and BestKeeper software, were used to evaluate the stability of reference genes. The result showed that GAPDH was best stable gene and stability value for the best combination of two genes was observed TFRC and β₂M. In conclusion, the geometric mean of GAPDH, TFRC and β₂M might be used for accurate normalization of transcriptional data for assessing endurance related traits in Zanskar ponies during load carrying.

Keywords: endurance exercise, ubiquitin B (UBB), β₂ microglobulin (β₂M), high altitude, Zanskar ponies, reference gene

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Authors: Jienny Lee, In-Soo Cho, Sang-Ho Cha

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Adult mesenchymal stem cells (MSCs) have been investigated using preclinical approaches for tissue regeneration. Porcine MSCs (pMSCs) are capable of growing and attaching to plastic with a fibroblast-like morphology and then differentiating into bone, adipose, and cartilage tissues in vitro. This study was conducted to investigate the proliferating abilities, differentiation potentials, and multipotency of miniature pig adipose tissue-derived MSCs (mpAD-MSCs) with or without long-term cryopreservation, considering that cryostorage has the potential for use in clinical applications. After confirming the characteristics of the mpAD-MSCs, we examined the effect of long-term cryopreservation (> 2 years) on expression of cell surface markers (CD34, CD90 and CD105), proliferating abilities (cumulative population doubling level, doubling time, colony-forming unit, and MTT assay) and differentiation potentials into mesodermal cell lineages. As a result, the expression of cell surface markers is similar between thawed and fresh mpAD-MSCs. However, long-term cryopreservation significantly lowered the differentiation potentials (adipogenic, chondrogenic, and osteogenic) of mpAD-MSCs. When compared with fresh mpAD-MSCs, thawed mpAD-MSCs exhibited lower expression of mesodermal cell lineage-related genes such as peroxisome proliferator-activated receptor-g2, lipoprotein lipase, collagen Type II alpha 1, osteonectin, and osteocalcin. Interestingly, long-term cryostoraged mpAD-MSCs exhibited significantly higher cell viability than the fresh mpAD-MSCs. Long-term cryopreservation induced a 30% increase in the cell viability of mpAD-MSCs when compared with the fresh mpAD-MSCs at 5 days after thawing. However, long-term cryopreservation significantly lowered expression of stemness markers such as Oct3/4, Sox2, and Nanog. Furthermore, long-term cryopreservation negatively affected expression of senescence-associated genes such as telomerase reverse transcriptase and heat shock protein 90 of mpAD-MSCs when compared with the fresh mpAD-MSCs. The results from this study might be important for the successful application of MSCs in clinical trials after long-term cryopreservation.

Keywords: mesenchymal stem cells, cryopreservation, stemness, senescence

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Authors: Clara Luwe, Oliver Harness, Helena Meally, Kim Martin, Alexandra Harrington

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Background: The role of ‘Renal Specialist Podiatrist’ originated in 2022 due to prevailing evidence of patients with diabetes and end-stage renal disease (ESRD) on haemodialysis (HD) and active ulcerations that were at higher risk of rapid deterioration, foot-related hospital admissions, and lower limb amputations. This role started in April 2022 with the aim of screening all patients on haemodialysis and instigating preventative measures to reduce serious foot related complications. Methods: A comprehensive neurovascular foot assessment was completed to establish baseline vascular status and identify those with peripheral arterial disease (PAD) for all patients on HD. Individual’s foot risk was stratified, advice and education tailored and issued. Identifying all diabetes patients on HD as high-risk for diabetic foot complications. Major Findings: All patients screened revealed over half of the caseload had diabetes, and more than half had a clinical presentation of PAD. All those presenting with ulcerations had a diagnosis of diabetes. Of the presenting ulcerations, the majority of these ulcers predated the renal specialist post and were classified as severe >3 SINBAD Score. Since April’22, complications have been identified quicker, reducing the severity (SINBAD<3 or below), and have improved healing times, in line with the national average. During the eight months of the role being in place, we have seen a reduction in minor amputations and no major amputations. Conclusion: By screening all patients on haemodialysis and focusing on education, early recognition of complications, appropriate treatment, and timely onward referral, we can reduce the risk of foot Diabetic foot ulcerations and lower limb amputations. Having regular podiatry input to stratify and facilitate high-risk, active wound patients across different services has helped to keep these patients stable, prevent amputations, and reduce foot-related hospital admissions and mortality from foot-related disease. By improving the accessibility to a specialist podiatrist, patients felt able to raise concerns sooner. This has helped to implement treatment at the earliest possible opportunity, enabling the identification and healing of ulcers at an earlier and less complex stage (SINBAD <3), thus, preventing potential limb-threatening complications.

Keywords: renal, podiatry, haemodialysis, prevention, early detection

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Authors: Samantha A. Cintron, Janet Pierce, Mihaela E. Sardiu, Diane Mahoney, Jill Peltzer, Bhanu Gupta, Qiuhua Shen

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High output heart failure (HOHF) is characterized a high output state resulting from an underlying disease process and is commonly caused by obesity. As obesity levels increase, more individuals will be at risk for obesity-related HOHF. However, the underlying pathophysiologic mechanisms of obesity-related HOHF are not well understood and need further research. The aim of the study was to describe the differences in leukocyte transcriptomes of morbidly obese patients with HOHF and those with non-HOHF. In this cross-sectional study, the study team collected blood samples, demographics, and clinical data of six patients with morbid obesity and HOHF and six patients with morbid obesity and non-HOHF. The study team isolated the peripheral blood leukocyte RNA and applied stranded total RNA sequencing. Differential gene expression was calculated, and Ingenuity Pathway Analysis software was used to interpret the canonical pathways, functional changes, upstream regulators, and mechanistic and causal networks that were associated with the significantly different leukocyte transcriptomes. The study team identified 116 differentially expressed genes; 114 were upregulated, and 2 were downregulated in the HOHF group (Benjamini-Hochberg adjusted p-value ≤ 0.05 and log2(fold-change) of ±1). The differentially expressed genes were involved with cell proliferation, mitochondrial function, erythropoiesis, erythrocyte stability, and apoptosis. The top upregulated canonical pathways associated with differentially expressed genes were autophagy, adenosine monophosphate-activated protein kinase signaling, and senescence pathways. Upstream regulator GATA Binding Protein 1 (GATA1) and a network associated with nuclear factor kappa-light chain-enhancer of activated B cells (NF-kB) were also identified based on the different leukocyte transcriptomes of morbidly obese patients with HOHF and non-HOHF. To the author’s best knowledge, this is the first study that reported the differential gene expression in patients with obesity-related HOHF and demonstrated the unique pathophysiologic mechanisms underlying the disease. Further research is needed to determine the role of cellular function and maintenance, inflammation, and iron homeostasis in obesity-related HOHF.

Keywords: cardiac output, heart failure, obesity, transcriptomics

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Authors: Sadie Namani, Lindita Ajazaj, Arjeta Zogaj, Vera Berisha, Bahrije Halili, Luljeta Hasani, Ajete Aliu

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Background: The outcome of bacterial meningitis is strongly related to the resistance of bacterial pathogens to the initial antimicrobial therapy. The objective of the study was to analyze the initial antimicrobial therapy, the resistance of meningeal pathogens and the outcome of adults bacterial meningitis cases. Materials/methods: This prospective study enrolled 46 adults older than 16 years of age, treated for bacterial meningitis during the years 2009 and 2010 at the infectious diseases clinic in Prishtinë. Patients are categorized into specific age groups: > 16-26 years of age (10 patients), > 26-60 years of age (25 patients) and > 60 years of age (11 patients). All p-values < 0.05 were considered statistically significant. Data were analyzed using Stata 7.1 and SPSS 13. Results: During the two year study period 46 patients (28 males) were treated for bacterial meningitis. 33 patients (72%) had a confirmed bacterial etiology; 13 meningococci, 11 pneumococci, 7 gram-negative bacilli (Ps. aeruginosa 2, Proteus sp. 2, Acinetobacter sp. 2 and Klebsiella sp. 1 case) and 2 staphylococci isolates were found. Neurological complications developed in 17 patients (37%) and the overall mortality rate was 13% (6 deaths). Neurological complications observed were: cerebral abscess (7/46; 15.2%), cerebral edema (4/46; 8.7%); haemiparesis (3/46; 6.5%); recurrent seizures (2/46; 4.3%), and single cases of thrombosis sinus cavernosus, facial nerve palsy and decerebration (1/46; 2.1%). The most common meningeal pathogens were meningococcus in the youngest age group, gram negative-bacilli in second age group and pneumococcus in eldery age group. Initial single-agent antibiotic therapy (ceftriaxone) was used in 17 patients (37%): in 60% of patients in the youngest age group and in 44% of cases in the second age group. 29 patients (63%) were treated with initial dual-agent antibiotic therapy; ceftriaxone in combination with vancomycin or ampicillin. Ceftriaxone and ampicillin were the most commonly used antibiotics for the initial empirical therapy in adults > 50 years of age. All adults > 60 years of age were treated with the initial dual-agent antibiotic therapy as in this age group was recorded the highest mortality rate (M=27%) and adverse outcome (64%). Resistance of pathogens to antimicrobics was recorded in cases caused by gram-negative bacilli and was associated with greater risk for developing neurological complications (p=0.09). None of the gram-negative bacilli were resistant to carbapenems; all were resistant to ampicillin while 5/7 isolates were resistant to cefalosporins. Resistance of meningococci and pneumococci to beta-lactams was not recorded. There were no statistical differences in the occurrence of neurological complications (p > 0.05), resistance of meningeal pathogens to antimicrobics (p > 0.05) and the inital antimicrobial therapy (one vs. two antibiotics) concerning group-ages in adults. Conclusions: The initial antibiotic therapy with ceftriaxone alone or in combination with vancomycin or ampicillin did not cover cases caused by gram-negative bacilli.

Keywords: adults, bacterial meningitis, outcomes, therapy

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Authors: Vincenzo Piemonte

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The liver is a complex, large-scale biochemical reactor which plays a unique role in the human physiology. When liver ceases to perform its physiological activity, a functional replacement is required. Actually, liver transplantation is the only clinically effective method of treating severe liver disease. Anyway, the aforementioned therapeutic approach is hampered by the disparity between organ availability and the number of patients on the waiting list. In order to overcome this critical issue, research activities focused on liver support device systems (LSDs) designed to bridging patients to transplantation or to keep them alive until the recovery of native liver function. In recirculating albumin dialysis devices, such as MARS (Molecular Adsorbed Recirculating System), adsorption is one of the fundamental steps in albumin-dialysate regeneration. Among the albumin-bound toxins that must be removed from blood during liver-failure therapy, bilirubin and tryptophan can be considered as representative of two different toxin classes. The first one, not water soluble at physiological blood pH and strongly bounded to albumin, the second one, loosely albumin bound and partially water soluble at pH 7.4. Fixed bed units are normally used for this task, and the design of such units requires information both on toxin adsorption equilibrium and kinetics. The most common adsorptive media used in LSDs are activated carbon, non-ionic polymeric resins and anionic resins. In this paper, bilirubin adsorption isotherms on different adsorptive media, such as polymeric resin, albumin-coated resin, anionic resin, activated carbon and alginate beads with entrapped albumin are presented. By comparing all the results, it can be stated that the adsorption capacity for bilirubin of the five different media increases in the following order: Alginate beads < Polymeric resin < Albumin-coated resin < Activated carbon < Anionic resin. The main focus of this paper is to provide useful guidelines for the optimization of liver support devices which implement adsorption columns to remove albumin-bound toxins from albumin dialysate solutions.

Keywords: adsorptive media, adsorption equilibrium, artificial liver devices, bilirubin, mathematical modelling

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Authors: C. Busuioc, I. Stancu, A. Nicoara, A. Zamfirescu, A. Evanghelidis

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The field of tissue engineering has expanded its potential due to the use of composite biomaterials belonging to increasingly complex systems, leading to bone substitutes with properties that are continuously improving to meet the patient's specific needs. Furthermore, the development of biomaterials based on ceramic and polymeric phases is an unlimited resource for future scientific research, with the final aim of restoring the original tissue functionality. Thus, in the first stage, composite scaffolds based on polycaprolactone (PCL) or polylactic acid (PLA) and inorganic powders were prepared by employing the electrospinning technique. The targeted powders were: commercial and laboratory synthesized hydroxyapatite (HAp), as well as barium titanate (BT). By controlling the concentration of the powder within the precursor solution, together with the processing parameters, different types of three-dimensional architectures were achieved. In the second stage, both the mineral powders and hybrid composites were investigated in terms of composition, crystalline structure, and microstructure so that to demonstrate their suitability for tissue engineering applications. Regarding the scaffolds, these were proven to be homogeneous on large areas and loaded with mineral particles in different proportions. The biological assays demonstrated that the addition of inorganic powders leads to modified responses in the presence of simulated body fluid (SBF) or cell cultures. Through SBF immersion, the biodegradability coupled with bioactivity were highlighted, with fiber fragmentation and surface degradation, as well as apatite layer formation within the testing period. Moreover, the final composites represent supports accepted by the cells, favoring implant integration. Concluding, the purposed fibrous materials based on bioresorbable polymers and mineral powders, produced by the electrospinning technique, represent candidates with considerable potential in the field of tissue engineering. Future improvements can be attained by optimizing the synthesis process or by simultaneous incorporation of multiple inorganic phases with well-defined biological action in order to fabricate multifunctional composites.

Keywords: barium titanate, electrospinning, fibre networks, hydroxyapatite, smart scaffolds

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Authors: Gabriela C. Caldas, Fernanda C. Jacome, Arthur da C. Rasinhas, Ortrud M. Barth, Flavia B. dos Santos, Priscila C. G. Nunes, Yuli R. M. de Souza, Pedro Paulo de A. Manso, Marcelo P. Machado, Debora F. Barreto-Vieira

Abstract:

The establishment of animal models for studies of DENV infections has been challenging, since circulating epidemic viruses do not naturally infect nonhuman species. Such studies are of great relevance to the various areas of dengue research, including immunopathogenesis, drug development and vaccines. In this scenario, the main objective of this study is to verify possible morphological changes, as well as the presence of antigens and viral RNA in lung samples from BALB/c mice experimentally infected with an epidemic and non-neuroadapted DENV-3 strain. Male BALB/c mice, 2 months old, were inoculated with DENV-3 by intravenous route. After 72 hours of infection, the animals were euthanized and the lungs were collected. Part of the samples was processed by standard technique for analysis by light and transmission electronic microscopies and another part was processed for real-time PCR analysis. Morphological analyzes of lungs from uninfected mice showed preserved tissue areas. In mice infected with DENV-3, the analyzes revealed interalveolar septum thickening with presence of inflammatory infiltrate, foci of alveolar atelectasis and hyperventilation, bleeding foci in the interalveolar septum and bronchioles, peripheral capillary congestion, accumulation of fluid in the blood capillary, signs of interstitial cell necrosis presence of platelets and mononuclear inflammatory cells circulating in the capillaries and/or adhered to the endothelium. In addition, activation of endothelial cells, platelets, mononuclear inflammatory cell and neutrophil-type polymorphonuclear inflammatory cell evidenced by the emission of cytoplasmic membrane prolongation was observed. DEN-like particles were seen in the cytoplasm of endothelial cells. The viral genome was recovered from 3 in 12 lung samples. These results demonstrate that the BALB / c mouse represents a suitable model for the study of the histopathological changes induced by DENV infection in the lung, with tissue alterations similar to those observed in human cases of DEN.

Keywords: BALB/c mice, dengue, histopathology, lung, ultrastructure

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Authors: Nataliya L. Ogurechnikova

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The paper aims to clarify the function of articles in the English speech and specify their place and role in the English language, taking into account the use of articles for delimitation of speech. A focus of the paper is the use of the definite and the indefinite articles with different types of noun phrases which comprise either one noun with or without attributes, such as the King, the Queen, the Lion, the Unicorn, a dimple, a smile, a new language, an unknown dialect, or several nouns with or without attributes, such as the King and Queen of Hearts, the Lion and Unicorn, a dimple or smile, a completely isolated language or dialect. It is stated that the function of delimitation is related to perception: the number of speech units in a text correlates with the way the speaker perceives and segments the denotation. The two following combinations of words the house and garden and the house and the garden contain different numbers of speech units, one and two respectively, and reveal two different perception modes which correspond to the use of the definite article in the examples given. Thus, the function of delimitation is twofold, it is related to perception and cognition, on the one hand, and, on the other hand, to grammar, if the subject of grammar is the structure of speech. Analysis of speech units in the paper is not limited by noun phrases and is amplified by discussion of peripheral phenomena which are nevertheless important because they enable to qualify articles as a syntactic phenomenon whereas they are not infrequently described in terms of noun morphology. With this regard attention is given to the history of linguistic studies, specifically to the description of English articles by Niels Haislund, a disciple of Otto Jespersen. A discrepancy is noted between the initial plan of Jespersen who intended to describe articles as a syntactic phenomenon in ‘A Modern English Grammar on Historical Principles’ and the interpretation of articles in terms of noun morphology, finally given by Haislund. Another issue of the paper is correlation between description and denotation, being a traditional aspect of linguistic studies focused on articles. An overview of relevant studies, given in the paper, goes back to the works of G. Frege, which gave rise to a series of scientific works where the meaning of articles was described within the scope of logical semantics. Correlation between denotation and description is treated in the paper as the meaning of article, i.e. a component in its semantic structure, which differs from the function of delimitation and is similar to the meaning of other quantifiers. The paper further explains why the relation between description and denotation, i.e. the meaning of English article, is irrelevant for noun morphology and has nothing to do with nominal categories of the English language.

Keywords: delimitation of speech, denotation, description, perception, speech units, syntax

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Authors: Madeleine Cox

Abstract:

Objective: Discussion of diagnosis and management options for myometrial ectopic pregnancy Case: A 30 yo G1P0 presented to the emergency department with vaginal bleeding for the last 4 days. She had a positive home urine pregnancy test, confirmed with a serum HCG. When she presented for an ultrasound, there was no intrauterine pregnancy, no evidence of adnexal pregnancy, however, the anterior myometrium of the uterus was noted to be markedly abnormal. When she presented to the emergency department of a busy tertiary hospital in Queensland, she had a small amount of vaginal bleeding, was anxious but well, observations normal. Repeat blood testes demonstrated a serum HCG of 9246 IU/L, haemoglobin of 143g/L. The patient had an interesting history of a right oophorectomy and open myomectomy in another country. A repeat ultrasound again showed an abnormality within the myometrium of the uterus, which was initially reported as concerning for an AVM, or potentially invasive gestational trophoblastic disease. An MRI was organised 2 days later, which demonstrated a intramural/subserosal irregularity in the right lateral body measuring 35x38x42mm with peripheral enhancement and central cystic components, favouring a myometrial ectopic most likely at the site of previous myomectomy. Alternative diagnosis of AVM, GTD were considered less likely. After discussion with the patient, IV methotrexate was administered as an in patient 4 days after her initial presentation to emergency. After this, her HCG fell to 1236 IU/L on day 6 post treatment. Weekly reviews showed stable ultrasound appearances with a steadily dropping HCG level. A repeat MRI was performed 3 weeks after methotrexate administration which confirmed involution of the myometrial ectopic, however, showed ongoing progression of vascularity surrounding the site. Despite resolution of HCG, the patient persisted to have ongoing bleeding associated with this and went to have uterine artery embolisation. Follow up ultrasound showed resolution of abnormal vascularity and negative HCG levels. Conclusion: Myometrial ectopic pregnancies are a rare occurrence and require a multidisciplinary approach to achieve timely management for these patients. This patient was in a very well resourced setting with excellent access to Interventional Radiology and specialist Radiologists who could work together with the Obstetrics, Gynaecology, and Maternal Fetal Medicine team to provide multiple options of management which preserved her fertility. This case has a very good outcome, with the patient being referred back to our service 12 months later with an early intrauterine pregnancy.

Keywords: ectopic, pregnancy, miscarriage, gynaecology

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Authors: Jean De Dieu Ayabagabo, Paul A.Onjoro, Karubiu P. Migwi, Marie C. Dusingize

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This study investigated the effects of feed on milk yield and quality through feed monitoring and quality assessment, and the consequent enteric methane gas emissions from smallholder dairy farms in drier areas of Rwanda, using the Tier II approach for four seasons in three zones, namely; Mayaga and peripheral Bugesera (MPB), Eastern Savanna and Central Bugesera (ESCB), and Eastern plateau (EP). The study was carried out using 186 dairy cows with a mean live weight of 292 Kg in three communal cowsheds. The milk quality analysis was carried out on 418 samples. Methane emission was estimated using prediction equations. Data collected were subjected to ANOVA. The dry matter intake was lower (p<0.05) in the long dry season (7.24 Kg), with the ESCB zone having the highest value of 9.10 Kg, explained by the practice of crop-livestock integration agriculture in that zone. The Dry matter digestibility varied between seasons and zones, ranging from 52.5 to 56.4% for seasons and from 51.9 to 57.5% for zones. The daily protein supply was higher (p<0.05) in the long rain season with 969 g. The mean daily milk production of lactating cows was 5.6 L with a lower value (p<0.05) during the long dry season (4.76 L), and the MPB zone having the lowest value of 4.65 L. The yearly milk production per cow was 1179 L. The milk fat varied from 3.79 to 5.49% with a seasonal and zone variation. No variation was observed with milk protein. The seasonal daily methane emission varied from 150 g for the long dry season to 174 g for the long rain season (p<0.05). The rain season had the highest methane emission as it is associated with high forage intake. The mean emission factor was 59.4 Kg of methane/year. The present EFs were higher than the default IPPC value of 41 Kg from developing countries in African, the Middle East, and other tropical regions livestock EFs using Tier I approach due to the higher live weight in the current study. The methane emission per unit of milk production was lower in the EP zone (46.8 g/L) due to the feed efficiency observed in that zone. Farmers should use high-quality feeds to increase the milk yield and reduce the methane gas produced per unit of milk. For an accurate assessment of the methane produced from dairy farms, there is a need for the use of the Life Cycle Assessment approach that considers all the sources of emissions.

Keywords: footprint, forage, girinka, tier

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Authors: P. R. Chauhan, S. K. Tyagi

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Adsorption refrigeration technology offers a sustainable and energy-efficient cooling alternative over traditional refrigeration technologies for meeting the fast-growing cooling demands. With its ability to utilize natural refrigerants, low-grade heat sources, and modular configurations, it has the potential to revolutionize the cooling industry. Despite these benefits, the commercial viability of this technology is hampered by several fundamental limiting constraints, including its large size, low uptake capacity, and poor performance as a result of deficient heat and mass transfer characteristics. The primary cause of adequate heat and mass transfer characteristics and magnitude of exergy loss in various real processes of adsorption cooling system can be assessed by the entropy generation rate analysis, i. e. Second law of Thermodynamics. Therefore, this article presents the second law of thermodynamic-based investigation in terms of entropy generation rate (EGR) to identify the energy losses in various processes of the HPCC-based adsorption system using MATLAB R2021b software. The adsorption technology-based cooling system consists of two beds made up of silica gel and arranged in a single stage, while the water is employed as a refrigerant, coolant, and hot fluid. The variation in process-wise EGR is examined corresponding to cycle time, and a comparative analysis is also presented. Moreover, the EGR is also evaluated in the external units, such as the heat source and heat sink unit used for regeneration and heat dump, respectively. The research findings revealed that the combination of adsorber and desorber, which operates across heat reservoirs with a higher temperature gradient, shares more than half of the total amount of EGR. Moreover, the EGR caused by the heat transfer process is determined to be the highest, followed by a heat sink, heat source, and mass transfer, respectively. in case of heat transfer process, the operation of the valve is determined to be responsible for more than half (54.9%) of the overall EGR during the heat transfer. However, the combined contribution of the external units, such as the source (18.03%) and sink (21.55%), to the total EGR, is 35.59%. The analysis and findings of the present research are expected to pinpoint the source of the energy waste in HPCC based adsorption cooling systems.

Keywords: adsorption cooling cycle, heat transfer, mass transfer, entropy generation, silica gel-water

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Authors: Po-Ching Wang

Abstract:

Public art may be regarded as a social agenda. It is assumed that public art acts as an intermediate form that contributes significantly to community resurgence. That is, public art may be regarded as a verb/process or social intervention. It functions as a vanguard form, attacking boundaries and providing a sensibility for social strategy. Public art in tradition is generally expected to bring aesthetic pleasure to public. Contemporary public art, however, not only focuses on art installation, but it also often offers a process that aims to comment on, question, and challenge the socio-cultural status quo. During the last few decades, accelerated changes in the values and expectations brought to bear on varied urban issues, together with the destruction of the hegemony of traditional art and of museum authorities, has begun to contribute to freer and more democratic representations of public art. It is said that part of a public artwork’s role is to ruffle sacred feathers. In many cases, public art is created to address the dynamic social contradictions and mutability of public life; and artists and community participants approach public art from a variety of social critical perspectives and methodologies. Urban issues, such as social and environmental justice, health problems, violence, and political statements, provide plentiful source materials that fuel the performance of public art in many different settings. Further, public artworks have been extensively adopted to express social identity, make political statements, and/or to remedy social and environmental crises. Many murals on urban walls, for instance, reflect social conflicts and address civic rights, and these projects are usually the work of artists who though denied access to traditional gallery and museum channels are supported by community engagement and involvement. Public art as a social practice challenges the traditional western view of artistic practice. Art in the public realm creates a new media that provides a platform for a dialogical exchange between diverse social groups. It seems that public art has evolved as an arena for activism that addresses wide-ranging and highly controversial social issues and civilian concerns. The findings of this study indicate that public artworks are capable of playing a role of activist in facilitating community evolution via social progress.

Keywords: aesthetics, community regeneration, city development, publicness, public participation, social progress

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Authors: Raheel Shakoor Siddiqui, Shahbaz Malik, Manikandar Srinivas Cheruvu, Sanjay Narayana Murthy, Livio DiMascio

Abstract:

Background: elderly traumatic hip fracture patients frequently present to trauma services globally. Rising low energy falls amongst an osteoporotic aging population is the commonest cause for injury. Hip fractures in this population are a major cause for severe pain, morbidity and mortality. The term hip fracture is interchangeable with neck of femur fracture, fractured neck of femur or proximal femur fracture. Hip fracture pain management protocols and guidelines suggest conventional analgesia, nerve block and opioid based treatment as rescue analgesia. There is a current global opioid crisis with overuse, abuse and dependence. Adverse opioid related complications in vulnerable elderly patients further adds to morbidity and mortality. Systematic reviews in literature have evidenced superiority of multimodal analgesia in osteoarthritic primary joint replacements compared to opioids however, this has not yet been conducted for elderly traumatic hip fracture patients. Aims: The primary aim of this systematic review is to provide standardised evidence following Cochrane and PRISMA guidance in determining advantages of perioperative multimodal analgesia over conventional opioid based treatments in elderly traumatic hip fractures. Methods: 5 databases were searched from January 2000-2023 which identified 8 randomised controlled trials and 446 total participants. These trials met defined PICOS eligibility criteria of patient mean age ≥ 65 years presenting with a unilateral traumatic fractured neck of femur for operative intervention. Analgesic intervention with perioperative multimodal analgesia has been compared to conventional opioid based analgesia. Outcomes of interest include, primarily, the change in postoperative opioid consumption within a 0-30 postoperative period and secondarily, the change in postoperative adverse events and complications. A qualitative synthesis has been performed due to clinical heterogenicity and variance amongst trials. Results: GRADE evidence of moderate quality supports perioperative multimodal analgesia leads to a reduction in postoperative opioid consumption however, low quality evidence supports a reduction of adverse effects and complications. Conclusion: Perioperative multimodal analgesia whether used preoperative, intraoperative and/or postoperative leads to a reduction in postoperative opioid consumption for elderly traumatic hip fracture patients. This review recommends the use of perioperative multimodal analgesia as part of hip fracture pain protocols however, caution and clinical judgement should be used as the risk of adverse effects may not be lower.

Keywords: trauma, orthopaedics, hip, fracture, neck of femur fracture, analgesia, multimodal analgesia, opioid

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Authors: Krytskyy T.

Abstract:

Introduction: The role of androgen deficiency in men as a factor in the pathogenesis of many somatic diseases is unmistakable. The interaction of thyroid and sex hormones with hypothyroidism in men is still the subject of discussions. The purpose of the study is to assess the androgen status of men with primary hypothyroidism, depending on its duration and the state of compensation. Materials and methods: 45 men with primary hypothyroidism aged 35 to 60 years, as well as 25 healthy men, who formed a control group, were under supervision. A selection of men for examination was conducted in the process of outpatient and in-patient treatment at the endocrinology department of the University Hospital in Ternopil. The functional state of the pituitary-gonadal system was evaluated in order to characterize the androgen status of patients. The concentration of follicle stimulating hormone, luteinizing hormone, prolactin, thyroid-stimulating hormone was determined in blood with the help of enzyme-linked method. Also, the content of hormones: total testosterone, linking sex hormones globulin were determined. Results: Reduced total testosterone (TT) content was found in 42.2% of patients with hypothyroidism. Herewith in 17.8% of patients, blood TT levels were lower than 8.0 nmol / L, and in 11 (24.4%) men, the rate was in the range of 8.0 to 12.0 nmol / L. Based on the results of the determination of the content of free testosterone (FT), the frequency of laboratory hypogonadism in men with hypothyroidism was higher than the results of the determination of TT. The degree of compensation of hypothyroidism probably did not affect the average levels of gonadotropic and sex hormones. Conclusions: Reduced total testosterone content was found in 42.2% of patients with primary hypothyroidism. Herewith, in 17.8% of patients blood TT levels were lower than 8.0 nmol / L, which is a sign of absolute deficiency of testosterone, and in 24.4% of men the rate ranged from 8.0 to 12.0 nmol / l , indicating partial androgen deficiency. Linking sex hormones globulin levels were believed to be lower in 46.7% of patients with hypothyroidism compared to control group. The average levels of E2 in the examined patients did not significantly differ from the mean of control group. FSH, LH, and prolactin levels in men with hypothyroidism were within the normal age limits and probably did not differ from those of control group. The degree of compensation of hypothyroidism probably did not affect the average levels of gonadotropic and sex hormones. The mean LH content in the blood was significantly increased in men with a duration of hypothyroidism up to 5 years and did not differ from that of the control group and in men with a duration of hypothyroidism over 5 years. In men with hypothyroidism, a probable reduction in T / LH coefficient is found. The obtained data may indicate a combined lesion of the central and peripheral parts of the pituitary-gonadal system in men with hypothyroidism.

Keywords: androgenic status, hypothyroidism, testosterone, linking sex hormones globulin

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Authors: Sharat Chandra, Zilong Wang, Ru-Rong Ji, Andrey Bortsov

Abstract:

Chronic pain (CP) therapeutic approaches have limited efficacy. As a result, doctors are prescribing opioids for chronic pain, leading to opioid overuse, abuse, and addiction epidemic. Therefore, the development of effective and safe CP drugs remains an unmet medical need. Voltage-gated sodium (Nav) channels act as cardiovascular and neurological disorder’s molecular targets. Nav channels selective inhibitors are hard to design because there are nine closely-related isoforms (Nav1.1-1.9) that share the protein sequence segments. We are targeting the Nav1.7 found in the peripheral nervous system and engaged in the perception of pain. The objective of this project was to screen a 1.5 million compound library for identification of inhibitors for Nav1.7 with analgesic effect. In this study, we designed a protocol for identification of isoform-selective inhibitors of Nav1.7, by utilizing the prior information on isoform-selective antagonists. First, a similarity search was performed; then the identified hits were docked into a binding site on the fourth voltage-sensor domain (VSD4) of Nav1.7. We used the FTrees tool for similarity searching and library generation; the generated library was docked in the VSD4 domain binding site using FlexX and compounds were shortlisted using a FlexX score and SeeSAR hyde scoring. Finally, the top 25 compounds were tested with molecular dynamics simulation (MDS). We reduced our list to 9 compounds based on the MDS root mean square deviation plot and obtained them from a vendor for in vitro and in vivo validation. Whole-cell patch-clamp recordings in HEK-293 cells and dorsal root ganglion neurons were conducted. We used patch pipettes to record transient Na⁺ currents. One of the compounds reduced the peak sodium currents in Nav1.7-HEK-293 stable cell line in a dose-dependent manner, with IC50 values at 0.74 µM. In summary, our computer-aided analgesic discovery approach allowed us to develop pre-clinical analgesic candidate with significant reduction of time and cost.

Keywords: chronic pain, voltage-gated sodium channel, isoform-selective antagonist, similarity search, virtual screening, analgesics development

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Authors: Lukas J. Evans, Danilo D. Fernando

Abstract:

Shrub willows (Salix spp.) have many characteristics which make them suitable for a variety of applications such as riparian zone buffers, environmental contaminant sequestration, living snow fences, and biofuel production. In some cases, these functions are limited due to physical or financial obstacles associated with the number of individuals needed to reasonably satisfy that purpose. One way to increase the efficiency of willows is to bioengineer them with the genetic improvements suitable for the desired use. To accomplish this goal, an optimized in vitro transformation protocol via Agrobacterium tumefaciens is necessary to reliably express genes of interest. Therefore, the aim of this study is to observe the influence of tissue culture with different willow cultivars, hormones, and explants on the percentage of calli expressing reporter gene green florescent protein (GFP) to find ideal transformation conditions. Each callus was produced from 1 month old open-pollinated seedlings of three Salix miyabeana cultivars (‘SX61’, ‘WT1’, and ‘WT2’) from three different explants (lamina, petiole, and internodes). Explants were cultured for 1 month on an MS media with different concentrations of 6-Benzylaminopurine (BAP) and 1-Naphthaleneacetic acid (NAA) (No hormones, 1 mg⁻¹L BAP only, 3 mg⁻¹L NAA only, 1 mg⁻¹L BAP and 3 mg⁻¹L NAA, and 3 mg⁻¹L BAP and 1 mg⁻¹L NAA) to produce a callus. Samples were then treated with Agrobacterium tumefaciens at an OD600 of 0.6-0.8 to insert the transgene GFP for 30 minutes, co-cultivated for 72 hours, and selected on the same media type they were cultured on with added 7.5 mg⁻¹L of Hygromycin for 1 week before GFP visualization under a UV dissecting scope. Percentage of GFP expressing calli as well as the average number of fluorescing GFP units per callus were recorded and results were evaluated through an ANOVA test (α = 0.05). The WT1 internode-derived calli on media with 3 mg-1L NAA+1 mg⁻¹L BAP and mg⁻¹L BAP alone produced a significantly higher percentage of GFP expressing calli than each other group (19.1% and 19.4%, respectively). Additionally, The WT1 internode group cultured with 3 mg⁻¹L NAA+1 mg⁻¹L BAP produced an average of 2.89 GFP units per callus while the group cultivated with 1 mg⁻¹L BAP produced an average of 0.84 GFP units per callus. In conclusion, genotype, explant choice, and hormones all play a significant role in increasing successful transformation in willows. Future studies to produce whole callus GFP expression and subsequent plantlet regeneration are necessary for a complete willow transformation protocol.

Keywords: agrobacterium, callus, Salix, tissue culture

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Authors: Julius Niba Fon, Jean Hude E. Moudingo

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Mangrove ecosystems in Cameroon are valuable both in services and functions as they play host to carbon sinks, fishery breeding grounds and natural coastal barriers against storms. In addition to the globally important biodiversity that they contain, they also contribute to local livelihoods. Despite these appraisals, a reduction of about 30 % over a 25 years period due to anthropogenic and natural actions has been recorded. The key drivers influencing mangrove change include population growth, climate change, economic and political trends and upstream habitat use. Reversing the trend of mangrove loss and growing vulnerability of coastal peoples requires a real commitment by the government to develop and implement robust level policies. It has been observed in Cameroon that special ecosystems like mangroves are insufficiently addressed by forestry and/or environment programs. Given these facts, the Food Agriculture Organization (FAO) in partnership with the Government of Cameroon and other development actors have put in place the project for sustainable community-based management and conservation of mangrove ecosystems in Cameroon. The aim is to address two issues notably the present weak institutional and legal framework for mangrove management, and the unrestricted and unsustainable harvesting of mangrove resources. Civil society organizations like the Cameroon Wildlife Conservation Society, Cameroon Ecology and Organization for the Environment and Development have been working to reduce the deforestation and degradation trend of Cameroon mangroves and also bringing the mangrove agenda to the fore in national and international arenas. Following a desktop approach, we found out that in situ and ex situ initiatives on mangrove management and conservation exist on propagation of improved fish smoke ovens to reduce fuel wood consumption, mangrove forest regeneration, shrimps farming and mangrove protected areas management. The evidence generated from the field experiences are inputs for processes of improving the legal and institutional framework for mangrove management in Cameroon, such as the elaboration of norms for mangroves management engaged by the government.

Keywords: mangrove ecosystem, legal and institutional framework, climate change, civil society organizations

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Authors: Bianca Maria Rulli, Lenny Valentino Schiaretti

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The considerable recent urbanization has increasingly sharpened environmental and social problems all over the world. During the recent years, many answers to the alarming attitudes in modern cities have emerged: a drastic reduction in the rate of growth is becoming essential for future generations and small scale economies are considered more adaptive and sustainable. According to the concept of degrowth, cities should consider surpassing the centralization of urban living by redefining the relationship between rural and urban knowledge; growing food in cities fundamentally contributes to the increase of social and ecological resilience. Through an innovative approach, this research combines the benefits of urban agriculture (increase of biological diversity, shorter and thus more efficient supply chains, food security) and temporary land use. They stimulate collaborative practices to satisfy the changing needs of communities and stakeholders. The concept proposes a coherent strategy to create a sustainable development of urban spaces, introducing a productive green-network to link specific areas in the city. By shifting the current relationship between architecture and landscape, the former process of ground consumption is deeply revised. Temporary modules can be used as concrete tools to create temporal areas of innovation, transforming vacant or marginal spaces into potential laboratories for the development of the city. The only permanent ground traces, such as foundations, are minimized in order to allow future land re-use. The aim is to describe a new mindset regarding the quality of space in the metropolis which allows, in a completely flexible way, to bring back the green and the urban farming into the cities. The wide possibilities of the research are analyzed in two different case-studies. The first is a regeneration/connection project designated for social housing, the second concerns the use of temporary modules to answer to the potential needs of social structures. The intention of the productive green-network is to link the different vacant spaces to each other as well as to the entire urban fabric. This also generates a potential improvement of the current situation of underprivileged and disadvantaged persons.

Keywords: degrowth, green network, land use, temporary building, urban farming

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Authors: Ben Cheikh Asma, Bouafia Nabiha, Ammar Asma, Ezzi Olfa, Meddeb Khaoula, Chouchène Imed, Boussarsar Hamadi, Njah Mansour

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Background: Hospital Acquired Infection (HAI) constitutes an important worldwide health problem. It was associated with high mortality rate in intensive care units (ICU). This study aimed to determine HAI mortality rate in Tunisian intensive care units and identify its risk factors. Methods: We conducted a prospective observational cohort study over a 12 months period (September 15th 2015 to September 15 th 2016) in the adult medical ICU of University Hospital-Farhat Hached (Sousse-Tunisia). All patients admitted in the ICU for more than 48 hours were included in the study. We used an anonymous standardized survey record form to collect data by a medical hygienist assisted by an intensivist. We adopted definitions of Center for Diseases Control and prevention of Atlanta to detect HAI, Kaplan Meier survival analysis and Cox proportional hazard regression to identify independent risk factor of HAI mortality. Results: Of 171 patients, 67 developed ICU-acquired infection (global incidence rate=39.2%). The mean age of patients was 59 ± 21.2 years and 60.8% were male. The most frequently identified infections were pulmonary acquired infection (ventilator associated pneumonia (VAP) and infected atelectasis with density rates 21.4 VAP/1000 days of mechanical ventilation and 9.4 infected atelectasis /1000 days of mechanical ventilation; respectively) and central venous catheter associated infection (CVC - AI) with density rate 28.4 CVC-AI / 1000 CVC-days). HAI mortality rate was 66.7% (n=44). The median survival was 20 days 3.36, 95% Confidential Interval [13.39 – 26.60]. Specific mortality rates according to infectious site were 65.5%, 36.4% and 4.5% respectively for VAP, CVC associated infection and infected atelectasis. In univariate analysis, a significant associations between mortality and cardiovascular history (p=0.04) tracheotomy (p=0.00), peripheral venous catheterization (p=0.04), VAP (p=0.04) and infected atelectasis (p=0.04) were detected. Independent risk factors for HAI mortality were VAP with Hazard Ratio = 3.14, 95% Confidential Interval [1.63 – 6.05] (p=0.001) and tracheotomy (Hazard Ratio=0.22, 95% Confidential Interval [0.10 – 0.44], p=0.000). Conclusions: In the present study, hospital acquired infection mortality rate was relatively high. We need to intensify the fight against these infections especially ventilator-associated pneumonia that is associated with higher risk of mortality in many studies. Thus, more effective infection control interventions were necessary in our hospital.

Keywords: hospital acquired infection, intensive care unit, mortality, risk factors

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Authors: Drago Bratkovic, Curtis Gravance, David Ketteridge, Ravi Krishnan, Michael Imperiale

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The mucopolysaccharidoses (MPSs) are a group of lysosomal storage diseases that have a common defect in the catabolism of glycosaminoglycans (GAGs). MPS I is the most common of the MPS diseases. Manifestations of MPS I include coarsening of facial features, corneal clouding, developmental delay, short stature, skeletal manifestations, hearing loss, cardiac valve disease, hepatosplenomegaly, and umbilical and inguinal hernias. Treatments for MPS I restore or activate the missing or deficient enzyme in the case of enzyme replacement therapy (ERT) and haematopoietic stem cell transplantation (HSCT). Pentosan polysulfate sodium (PPS) is a potential treatment to improve bone and joint manifestations of MPS I. The mechanisms of action of PPS that are relevant to the treatment of MPS I are the ability to: (i) Reduce systemic and accumulated GAG, (ii) Reduce inflammatory effects via the inhibition of NF-kB, resulting in the reduction in pro-inflammatory mediators. (iii) Reduce the expression of the pain mediator nerve growth factor in osteocytes from degenerating joints. (iv) Inhibit the cartilage degrading enzymes related to joint dysfunction in MPS I. PPS is being evaluated as an adjunctive therapy to ERT and/or HSCT in an open-label, single-centre, phase 2 study. Patients are ≥ 5 years of age with a diagnosis of MPS I and previously received HSCT and/or ERT. Three white, female, patients with MPS I-Hurler, ages 14, 15, and 19 years, and one, white male patient aged 15 years are enrolled. All were diagnosed at ≤2 years of age. All patients received HSCT ≤ 6 months after diagnosis. Two of the patients were treated with ERT prior to HSCT, and 1 patient received ERT commencing 3 months prior to HSCT. Two patients received 0.75mg/kg and 2 patients received 1.5mg/kg of PPS. PPS was well tolerated at doses of 0.75 and 1.5 mg/kg to 47 weeks of continuous dosing. Of the 19 adverse events (AEs), 2 were related to PPS. One AE was moderate (pre-syncope) and 1 was mild (injection site bruising), experienced in the same patient. All AEs were reported as mild or moderate. There have been no SAEs. One subject experienced a COVID-19 infection and PPS was interrupted. The MPS I signature GAG fragments, sulfated disaccharide and UA-HNAc S, tended to decrease in 3 patients from baseline through Week 25. Week 25 GAG data are pending for the 4th patient. Overall, most biomarkers (inflammatory, cartilage degeneration, and bone turnover) evaluated in the 3 patients with 25-week assessments have indicated either no change or a reduction in levels compared to baseline. In 3 patients, there was a trend toward improvement in the 2MWT from baseline to Week 48 with > 100% increase in 1 patient (01-201). In the 3 patients that had Week 48 assessments, patients and proxies reported improvement in PGIC, including “worthwhile difference” (n=1), or “made all the difference” (n=2).

Keywords: MPS I, pentosan polysulfate sodium, clinical study, 2MWT, QoL

Procedia PDF Downloads 111