Search results for: end-stage renal disease (ESRD)

Authors: L. Szymanski, S. Wiak, Z. Kolacinski, G. Raniszewski, L. Pietrzak, Z. Staniszewska

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There exist more than one hundred different types of cancer, and therefore no particular treatment is offered to people struggling with this disease. The character of treatment proposed to a patient will depend on a variety of factors such as type of the cancer diagnosed, advancement of the disease, its location in the body, as well as personal preferences of a patient. None of the commonly known methods of cancer-fighting is recognised as a perfect cure, however great advances in this field have been made over last few decades. Once a patient is diagnosed with cancer, he is in need of medical care and professional treatment for upcoming months, and in most cases even for years. Among the principal modes of treatment offered by medical centres, one can find radiotherapy, chemotherapy, and surgery. All of them can be applied separately or in combination, and the relative contribution of each is usually determined by medical specialist in agreement with a patient. In addition to the conventional treatment option, every day more complementary and alternative therapies are integrated into mainstream care. There is one promising cancer modality - hyperthermia therapy which is based on exposing body tissues to high temperatures. This treatment is still being investigated and is not widely available in hospitals and oncological centres. There are two kinds of hyperthermia therapies with direct and indirect heating. The first is not commonly used due to low efficiency and invasiveness, while the second is deeply investigated and a variety of methods have been developed, including ultrasounds, infrared sauna, induction heating and magnetic hyperthermia. The aim of this work was to examine possibilities of heating magnetic nanoparticles under the influence of electromagnetic field for cancer treatment. For this purpose, multiwalled carbon nanotubes used as nanocarriers for iron particles were investigated for its heating properties. The samples were subjected to an alternating electromagnetic field with frequency range between 110-619 kHz. Moreover, samples with various concentrations of carbon nanotubes were examined. The lowest frequency of 110 kHz and sample containing 10 wt% of carbon nanotubes occurred to influence the most effective heating process. Description of hyperthermia therapy aiming at enhancing currently available cancer treatment was also presented in this paper. Most widely applied conventional cancer modalities such as radiation or chemotherapy were also described. Methods for overcoming the most common obstacles in conventional cancer modalities, such as invasiveness and lack of selectivity, has been presented in magnetic hyperthermia characteristics, which explained the increasing interest of the treatment.

Keywords: hyperthermia, carbon nanotubes, cancer colon cells, ligands

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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: Folorunsho J. O., Umar M. A.

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Access to potable water supply in both the rural and urban regions of the world has been neglected, and this has severely affected man and the aesthetics of the natural environment of man. This has further worsened the issue of diseases prevalence. This study considered the effects of inadequate domestic water supply on human health in selected neighbourhoods of Lokoja. The study used descriptive statistics such as relative frequencies, percentages and inferential statistics to analyse the data obtained through the use of structured questionnaire. The results revealed that the females and male constituted 56% and 44% of the respondents respectively; 62% of the respondents married and 32% are unmarried; respondents between ages 31 and 40 years constitute majority of the study population, while respondents with tertiary education constituted 35%, and those with secondary education were 32% of the total respondents. Furthermore, civil servants constituted 40% and unemployed 16% of the total respondents. In terms of monthly income, 40% of the respondents was found to earn between ₦31,000 - 40,000 monthly. On the perception of households on the availability and adequacy of domestic water supply, the study revealed that 64.7% of the respondents have pipe-borne water as their main source of water supply, with only 28.5% out of the 64.7% have pipe-borne water supply daily. On the relationship between water supply characteristics and health status among households, the result shows that 76% of the respondents perceived a strong relationship between water supply and health status. Cumulatively, 67% of the respondents confirm that both the quality and quantity of water supplied play a critical role in determining health status of residents of the study area. The respondents also reported skin diseases (96%), diarrhoea (96%), malaria (91%), cholera (67%), dysentery (67%), and respiratory diseases (67%) as the most perceived and experienced in the area, the disease rate in the prevalence order of malaria (81%), diarrhoea (61%), skin diseases (58%), cholera (34%), dysentery (31%) and respiratory disease (14%) respectively. Finally, the results further showed how households cope with inadequate water supply with 52% of the respondents confirm that they regularly treat their water before it was deployed for domestic uses, while 35%, 26%, 25%, 10% and 4% of the 52% respectively, adopted boiling, addition of alums, filtering with fabrics, chlorination and bleaching as the preferred treatment methods. The study thus recommended policy options that will aggressively launch adequate potable water supply infrastructure in the study area.Keywords: Potable Water, Supply, Human Health, Perception, Chlorination

Keywords: potable water, human health, perception, chlorination

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Authors: Rashid Azeem

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Introduction: Eosinophilia, which can be categorized as mild, moderate, and severe form on the basis of increasing eosinophil counts, might be responsible for a wide range of cardiac manifestations, varying from a simple myocarditis to a severe state like endomyocardial fibrosis. Eosinophils are involved in the pathogenesis of a variety of cardiovascular disorder like Loffler endocarditis, eosinophilic granulomatosis with polyangitis (EGPH), and hyper eosinophilic (HES). Among them HES carries and incidence rate b/w 48% and 75% and is the main causes of cardiac motility and mobility due to eosinophilia involvement. Aims and objectives: The aim of this study is to determine the frequency of eosinophilia in cardiac patients and to ascertain the evidence of endomyocardial diseases in eosinophilic patients in a cardiology institution Material and Methods: This cross sectional analytical study was conducted in hematology Department of Peshawar institute of Cardiology after approval from hospital ethical and research committee. All 70 patients were subjected to detailed history and clinical examination. Investigation like CBC, Chest X-ray, ECG, Echo, Angiography findings were used to monitor patient’s clinical status. Data is analyzed using SPSS version 25 and MS Excel. Results: Out of 70 patients in our study, a total of 66 patients(94 %) shows evidence of cardiac manifestations. In our study, we have observed a number of abnormal ECG patterns in cardiac patients presenting with eosinophilia, like T wave changes, loss of R wave, sinus bradycardia with LVH strain, and ST wave abnormality. abnormal echocardiographic findings were observed in our patients, like valvular abnormalities (in 45.7%), RWMA abnormalities (in 2.8%), isolated ventricular dysfunction (in 21.4%), and in 10% patients, normal echocardiography. We further noted abnormal coronary angiography findings in cardiac patients with eosinophilia ranging from single vessel to multi vessel occlusions. Conclusions: Eosinophils are involved in the pathogenesis of a variety of cardiovascular disorders which can be detected by various diagnostic means, and the severity of the disease increases with time and with increasing eosinophil count ranging from simple myocarditis to a fatal condition like endomyocardial fibrosis. Thus, increased eosinophilic count as a laboratory parameter in cardiac patients may be a sign of endomyocardial damage which will further help cardiologist to intervene more aggressively then routine approach to a cardiac patient.

Keywords: eosinophilia, endomyocardial fibrosis, cardiac, hypereosinophilic syndrome

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Authors: Syed Asif Hassan, Tabrej Khan

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Multiple sclerosis (MS) is a chronic demyelinating autoimmune disorder, of the central nervous system (CNS). In the present scenario, the current therapies either do not halt the progression of the disease or have side effects which limit the usage of current Disease Modifying Therapies (DMTs) for a longer period of time. Therefore, keeping the current treatment failure schema, we are focusing on screening novel analogues of the available DMTs that specifically bind and inhibit the Sphingosine1-phosphate receptor1 (S1PR1) thereby hindering the lymphocyte propagation toward CNS. The novel drug-like analogs molecule will decrease the frequency of relapses (recurrence of the symptoms associated with MS) with higher efficacy and lower toxicity to human system. In this study, an integrated approach involving ligand-based virtual screening protocol (Ultrafast Shape Recognition with CREDO Atom Types (USRCAT)) to identify the non-toxic drug like analogs of the approved DMTs were employed. The potency of the drug-like analog molecules to cross the Blood Brain Barrier (BBB) was estimated. Besides, molecular docking and simulation using Auto Dock Vina 1.1.2 and GOLD 3.01 were performed using the X-ray crystal structure of Mtb LprG protein to calculate the affinity and specificity of the analogs with the given LprG protein. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has a higher hypothetical affinity, also has greater negative value. Further, the non-specific ligands were screened out using the structural filter proposed by Baell and Holloway. Based on the USRCAT, Lipinski’s values, toxicity and BBB analysis, the drug-like analogs of fingolimod and BG-12 showed that RTL and CHEMBL1771640, respectively are non-toxic and permeable to BBB. The successful docking and DSX analysis showed that RTL and CHEMBL1771640 could bind to the binding pocket of S1PR1 receptor protein of human with greater affinity than as compared to their parent compound (Fingolimod). In this study, we also found that all the drug-like analogs of the standard MS drugs passed the Bell and Holloway filter.

Keywords: antagonist, binding affinity, chemotherapeutics, drug-like, multiple sclerosis, S1PR1 receptor protein

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Authors: E. Njuguna, S. Ilovi, P. Muiruri, K. Mutai, J. Kinuthia, P. Njoroge

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Introduction: Cervical cancer is the commonest cause of cancer-related morbidity and mortality among women in developing countries in Sub Saharan Africa. Screening for cervical cancer in all women regardless of HIV status is crucial for the early detection of cancer of the cervix when treatment is most effective in curing the disease. It is particularly more important to screen HIV infected women as they are more at risk of developing the disease and progressing faster once infected with HPV (Human Papilloma Virus). We aimed to determine the factors affecting the utilization of cervical cancer screenings among HIV infected women above 18 years of age at Kenyatta National Hospital (KNH) Comprehensive Care Center (CCC). Materials and Methods: A cross-sectional mixed quantitative and qualitative study involving randomly and purposefully selected HIV positive female respectively was conducted. Qualitative data collection involved 4 focus group discussions of eligible female participants while quantitative data were acquired by one to one interviewer administered structured questionnaires. The outcome variable was the utilization of cervical cancer screening. Data were entered into Access data base and analyzed using Stata version 11.1. Qualitative data were analyzed after coding for significant clauses and transcribing to determine themes arising. Results: We enrolled a total of 387 patients, mean age (IQ range) 40 years (36-44). Cervical cancer screening utilization was 46% despite a health care provider recommendation of 85%. The screening results were reported as normal in 72 of 81 (88.9%) and abnormal 7 of 81(8.6%) of the cases. Those who did not know their result were 2 of 81(2.5%). Patients were less likely to utilize the service with increasing number of years attending the clinic (OR 0.9, 95% CI 0.86-0.99, p-value 0.02), but more likely to utilize the service if recommendation by a staff was made (OR 10, 95% CI 4.2-23.9, p<0.001), and if cervical screening had been done before joining KNH CCC (OR 2.9, 95% CI 1.7-4.9, p < 0.001). Similarly, they were more likely to rate the services on cervical cancer screening as good (OR 5.0, 95% CI 1.7-3.4, p <0.001) and very good (OR 8.1, 95% CI 2.5-6.1, p<0.001) if they had utilized the service. The main barrier themes emerging from qualitative data included fear of screening due to excessive pain or bleeding, lack of proper communication on screening procedures and increased waiting time. Conclusions: Utilization of cervical cancer screening services was low despite health care recommendation. Patient socio-demographic characteristics did not influence whether or not they utilized the services, indicating the important role of the health care provider in the referral and provision of the service.

Keywords: cervical, cancer, HIV, women, comprehensive care center

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Authors: Yong H Sheng, Beatriz Garcillán, Eden Whitlock, Yukli Freedman, SiLing Yang, M Arifur Rahman, Nicholas Weber, Fabienne Mackay

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Chronic lymphocytic leukemia (CLL) is closely associated with immune dysfunction, yet the mechanisms underlying this immune deficiency remain poorly understood. Transmembrane Activator and CAML Interactor (TACI), a receptor known for its role in IL-10 regulation and autoimmunity, to the best of our knowledge has not been investigated in the context of anti-tumor immunity or its impact on CLL progression. This study addresses the gap by exploring the role of TACI in regulating CLL cells within the tumor microenvironment and its broader effects on disease progression and immune competence. We utilized the Eµ-TCL1 mouse model to generate CLL mice deficient in TACI and examined the consequences of TACI loss in adoptive transfer models over a five-week period. Comprehensive transcriptomic analysis, including RNA sequencing and microarray, was employed to determine TACI’s influence on the CLL gene expression profile. Additionally, we studied TACI’s direct role in CLL cell migration and immune modulation using patient-derived CLL cells in culture and Patient-Derived Xenograph (PDX) models. Our findings demonstrate that TACI signaling plays a pivotal role in promoting CLL progression and immune suppression. Loss of TACI signaling significantly inhibited CLL development and enhanced immune functionality. When TACI+/+ or TACI-/- TCL1 CLL cells were transferred into wild-type recipient mice, those receiving TACI-deficient cells showed reduced disease progression and lower incidence of CLL. Mice with TACI-/- CLL cells exhibited normalized serum levels of pro-inflammatory cytokines IL-6 and IL-10, restored proportions of T-cell subsets, and improved immune compartment function compared to counterparts with TACI+/+ CLL cells. Mechanistically, TACI-deficient CLL cells expressed significantly lower levels of IL-10, TNF, and inhibitory receptors such as PD-L1 and PD-L2. These cells also display restored circulating immunoglobulin levels and responses to T cell-dependent antigens, highlighting a recovery of immune competence. Further mechanistic studies revealed that TACI signaling drives CLL cell migration and homing to the spleen, where these cells actively establish an immunosuppressive microenvironment that supports immune evasion and tumor growth. Patient-derived CLL cells and PDX models confirmed TACI’s direct role in enhancing CLL cell migration and fostering immune suppression, emphasizing its critical function in the tumor microenvironment. By disrupting TACI signaling, we observed a reduction in CLL-associated immune suppression and tumor progression, offering a promising therapeutic avenue. This study establishes, for the first time, that targeting TACI disrupts key mechanisms underlying CLL progression while preserving vital immune functions. Unlike existing treatments that often impair immunity and lead to infection-related complications, TACI inhibition offers the dual benefit of controlling disease and maintaining immune homeostasis. These findings provide a strong rationale for developing therapeutic strategies that inhibit TACI as a means to improve outcomes in CLL patients. Beyond its implications for CLL, this research underscores the broader importance of TACI in regulating immune-tumor interactions, paving the way for future studies into its role in other malignancies.

Keywords: chronic lymphocytic leukemia, TACI, IL-10, immune suppression

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Authors: Eva de Mingo-Fernández, Lourdes Rubio Rico, Carmen Ortega-Segura, Montserrat Querol-García, Raúl González-Jauregui

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Today, one of the great challenges that the university faces is to get closer to society and transfer knowledge. The competency-based training approach favours a continuous interaction between practice and theory, which is why it is essential to establish real experiences with reflection and debate and to contrast them with personal and professional knowledge. Service-learning (SL) consists of an integration of academic learning with service in the community, which enables teachers to transfer knowledge with social value and students to be trained on the basis of experience of real needs and problems with the aim of solving them. SLE combines research, teaching, and social value knowledge transfer with the real social needs and problems of a community. Goal: The objective of this study was to design, implement, and evaluate a service-learning program in the subject of adult nursing for second-year nursing students. Methodology: After establishing collaboration with eight associations of people with different pathologies, the students were divided into eight groups, and each group was assigned an association. The groups were made up of 10-12 students. The associations willing to participate were for the following conditions: diabetes, multiple sclerosis, cancer, inflammatory bowel disease, fibromyalgia, heart, lung, and kidney diseases. The methodological design consisting of 5 activities was then applied. Three activities address personal and individual reflections, where the student initially describes what they think it is like to live with a certain disease. They then express their reflections resulting from an interview conducted by peers, in person or online, with a person living with this particular condition, and after sharing the results of their reflections with the rest of the group, they make an oral presentation in which they present their findings to the other students. This is followed by a service task in which the students collaborate in different activities of the association, and finally, a third individual reflection is carried out in which the students express their experience of collaboration. The evaluation of this activity is carried out by means of a rubric for both the reflections and the presentation. It should be noted that the oral presentation is evaluated both by the rest of the classmates and by the teachers. Results: The evaluation of the activity, given by the students, is 7.80/10, commenting that the experience is positive and brings them closer to the reality of the people and the area.

Keywords: academic learning integration, knowledge transfer, service-learning, teaching methodology

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Authors: Lalita Subedi, Jae Kyoung Chae, Yong Un Park, Cho Kyo Hee, Lee Jae Hyuk, Kang Min Cheol, Sun Yeou Kim

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Neuroinflammation may mediate the relationship between low levels of estrogens and neurodegenerative disease. Estrogens are neuroprotective and anti-inflammatory in neurodegenerative disease models. Due to the long term side effects of estrogens, researches have been focused on finding an effective phytoestrogens for biological activities. Daidzein present in soybeans and its active metabolite equol (7-hydroxy-3-(4'-hydroxyphenyl)-chroman) bears strong antioxidant and anticancer showed more potent anti-inflammatory and neuroprotective role in neuroinflammatory model confirmed its in vitro activity with molecular mechanism through NF-κB pathway. Three major CNS cells Microglia (BV-2), Astrocyte (C6), Neuron (N2a) were used to find the effect of equol in inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), MAPKs signaling proteins, apoptosis related proteins by western blot analysis. Nitric oxide (NO) and prostaglandin E2 (PGE2) was measured by the Gries method and ELISA, respectively. Cytokines like tumor necrosis factor-α (TNF-α) and IL-6 were also measured in the conditioned medium of LPS activated cells with or without equol. Equol inhibited the NO production, PGE-2 production and expression of COX-2 and iNOS in LPS-stimulated microglial cells at a dose dependent without any cellular toxicity. At the same time Equol also showed promising effect in modulation of MAPK’s and nuclear factor kappa B (NF-κB) expression with significant inhibition of the production of proinflammatory cytokine like interleukin -6 (IL-6), and tumor necrosis factor -α (TNF-α). Additionally, it inhibited the LPS activated microglia-induced neuronal cell death by downregulating the apoptotic phenomenon in neuronal cells. Furthermore, equol increases the production of neurotrophins like NGF and increase the neurite outgrowth as well. In conclusion the natural daidzein metabolite equol are more active than daidzein, which showed a promising effectiveness as an anti-neuroinflammatory and neuroprotective agent via downregulating the LPS stimulated microglial activation and neuronal apoptosis. This work was supported by Brain Korea 21 Plus project and High Value-added Food Technology Development Program 114006-4, Ministry of Agriculture, Food and Rural Affairs.

Keywords: apoptosis, equol, neuroinflammation, phytoestrogen

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Authors: Felicia N. Obialo, Aliza Wingo, Thomas Wingo

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Psychosocial factors such as personality traits and social networks influence cognitive aging and dementia outcomes both positively and negatively. The inherent complexity of these factors makes defining the underlying mechanisms of their influence difficult; however, exploring their interactions affords promise in the field of cognitive aging. The objective of this study was to elucidate some of these interactions by determining the relationship between social network size and dementia outcomes and by determining whether personality traits mediate this relationship. The longitudinal Alzheimer’s Disease (AD) database provided by Rush University’s Religious Orders Study/Memory and Aging Project was utilized to perform retrospective regression and mediation analyses on 3,591 participants. Participants who were cognitively impaired at baseline were excluded, and analyses were adjusted for age, sex, common chronic diseases, and vascular risk factors. Dementia outcome measures included cognitive trajectory, clinical dementia diagnosis, and postmortem beta-amyloid plaque (AB), and neurofibrillary tangle (NT) accumulation. Personality traits included agreeableness (A), conscientiousness (C), extraversion (E), neuroticism (N), and openness (O). The results show a positive correlation between social network size and cognitive trajectory (p-value = 0.004) and a negative relationship between social network size and odds of dementia diagnosis (p = 0.024/ Odds Ratio (OR) = 0.974). Only neuroticism mediates the positive relationship between social network size and cognitive trajectory (p < 2e-16). Agreeableness, extraversion, and neuroticism all mediate the negative relationship between social network size and dementia diagnosis (p=0.098, p=0.054, and p < 2e-16, respectively). All personality traits are independently associated with dementia diagnosis (A: p = 0.016/ OR = 0.959; C: p = 0.000007/ OR = 0.945; E: p = 0.028/ OR = 0.961; N: p = 0.000019/ OR = 1.036; O: p = 0.027/ OR = 0.972). Only conscientiousness and neuroticism are associated with postmortem AD pathologies; specifically, conscientiousness is negatively associated (AB: p = 0.001, NT: p = 0.025) and neuroticism is positively associated with pathologies (AB: p = 0.002, NT: p = 0.002). These results support the study’s objectives, demonstrating that social network size and personality traits are strongly associated with dementia outcomes, particularly the odds of receiving a clinical diagnosis of dementia. Personality traits interact significantly and beneficially with social network size to influence the cognitive trajectory and future dementia diagnosis. These results reinforce previous literature linking social network size to dementia risk and provide novel insight into the differential roles of individual personality traits in cognitive protection.

Keywords: Alzheimer’s disease, cognitive trajectory, personality traits, social network size

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Authors: Mengnan Sun

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It is unclear about the association between air pollution and Tourette Syndrome (TS), although people have suspected that air pollution might trigger TS. TS is a type of neural system disease usually found among children. The number of TS patients has significantly increased in recent decades, suggesting an importance and urgency to examine the possible triggers or conditions that are associated with TS. In this study, the correlation between air pollution and three allergic diseases---asthma, allergic conjunctivitis (AC), and allergic rhinitis (AR)---is examined. Then, a correlation between these allergic diseases and TS is proved. In this way, this study establishes a positive correlation between air pollution and TS. Measures the public can take to help TS patients are also analyzed at the end of this article. The article hopes to raise people’s awareness to reduce air pollution for the good of TS patients or people with other disorders that are associated with air pollution.

Keywords: air pollution, allergic diseases, climate change, Tourette Syndrome

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Authors: Y. S. Yusoff, G. Streftaris, H. R Waters

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Death within 30 days is an important factor to be looked into, as there is a significant risk of deaths immediately following or soon after, Myocardial Infarction (MI) or stroke. In this paper, we will model the deaths within 30 days following a Myocardial Infarction (MI) or stroke in the UK. We will see how the probabilities of sudden deaths from MI or stroke have changed over the period 1981-2000. We will model the sudden deaths using a Generalized Linear Model (GLM), fitted using the R statistical package, under a Binomial distribution for the number of sudden deaths. We parameterize our model using the extensive and detailed data from the Framingham Heart Study, adjusted to match UK rates. The results show that there is a reduction for the sudden deaths following a MI over time but no significant improvement for sudden deaths following a stroke.

Keywords: sudden deaths, myocardial infarction, stroke, ischemic heart disease

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Authors: Philippa Saunders, Claire Fletcher

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INTRODUCTION: Prostate cancer is the most prevalent malignancy affecting Western males. It is initially an androgen-dependent disease: androgens bind to the androgen receptor and drive the expression of genes that promote proliferation and evasion of apoptosis. Despite reduced androgen dependence in advanced prostate cancer, androgen receptor signaling remains a key driver of growth. Androgen deprivation therapy (ADT) is, therefore, a first-line treatment approach and works well initially, but resistance inevitably develops. Abiraterone and Enzalutamide are drugs widely used in ADT and are androgen synthesis and androgen receptor signaling inhibitors, respectively. The shortage of other treatment options means acquired resistance to these drugs is a major clinical problem. MicroRNAs (miRs) are important mediators of post-transcriptional gene regulation and show altered expression in cancer. Several have been linked to the development of resistance to ADT. Manipulation of such miRs may be a pathway to breakthrough treatments for advanced prostate cancer. This study aimed to validate ADT resistance-implicated miRs and their clinically relevant targets. MATERIAL AND METHOD: Small RNA-sequencing of Abiraterone- and Enzalutamide-resistant C42 prostate cancer cells identified subsets of miRs dysregulated as compared to parental cells. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was used to validate altered expression of candidate ADT resistance-implicated miRs 195-5p, 497-5p and 29a-5p in ADT-resistant and -responsive prostate cancer cell lines, patient-derived xenografts (PDXs) and primary prostate cancer explants. RESULTS AND DISCUSSION: This study suggests a possible role for miR-497-5p in the development of ADT resistance in prostate cancer. MiR-497-5p expression was increased in ADT-resistant versus ADT-responsive prostate cancer cells. Importantly, miR-497-5p expression was also increased in Enzalutamide-treated, castrated (ADT-mimicking) PDXs versus intact PDXs. MiR-195-5p was also elevated in ADT-resistant versus -responsive prostate cancer cells, while there was a drop in miR-29a-5p expression. Candidate clinically relevant targets of miR-497-5p in prostate cancer were identified by mining AGO-PAR-CLIP-seq data sets and may include AVL9 and FZD6. CONCLUSION: In summary, this study identified microRNAs that are implicated in prostate cancer resistance to androgen deprivation therapy and could represent novel therapeutic targets for advanced disease.

Keywords: microRNA, androgen deprivation therapy, Enzalutamide, abiraterone, patient-derived xenograft

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Authors: Sang-Hoon Park, Yeji Ho, Gwang-Moon Eom

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Fast and accurate detection of Freezing of Gait (FOG) is desirable for appropriate application of cueing which has been shown to ameliorate FOG. Utilization of frequency spectrum of leg acceleration to derive the freeze index requires much calculation and it would lead to delayed cueing. We hypothesized that FOG can be reasonably detected from the time domain amplitude of foot acceleration. A time instant was recognized as FOG if the mean amplitude of the acceleration in the time window surrounding the time instant was in the specific FOG range. Parameters required in the FOG detection was optimized by simulated annealing. The suggested time domain methods showed performances comparable to those of frequency domain methods.

Keywords: freezing of gait, detection, Parkinson's disease, time-domain method

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Authors: Hafid Nadia, Meziane Toufik

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The aim of this study was the characterization of the goat meat by the determination of quantity and the quality in Batna region. The first part was the evaluation of production and consumption. The investigations show that the goat meat third after mutton and beef, it’s especially consumed by the indigenous population located in the Mountain and steep area. The second part of this review treats nutritional quality of this meat by the quantification of the chemical composition, including fat profile, and establishes a link between animal age and the values of these parameters. Moisture, fat contents, and cholesterol levels varied with age. Because of the decreasing level of cholesterol in the Chevon meat, it is more recommended for consumption to prevent or reduce the incidence of coronary disease and heart attack.

Keywords: biochemical composition, cholesterol, goat meat, heart attack

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Authors: Mengistu G. Woldu, Hani Y. Zaki, Areeg Faggad, Badreldin E. Abdalla

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Background: Type 2 diabetes mellitus (T2DM) is a complex, degenerative, and multi-factorial disease, which is culpable for huge mortality and morbidity worldwide. Even though relatively significant numbers of studies are conducted on the genetics domain of this disease in the developed world, there is huge information gap in the sub-Saharan Africa region in general and in Eritrea in particular. Objective: The principal aim of this study was to investigate the association of common variants of the Insulin Receptor Substrate 1 (IRS1) and Transcription Factor 7-Like 2 (TCF7L2) genes with T2DM in the Eritrean population. Method: In this cross-sectional case control study 200 T2DM patients and 112 non-diabetes subjects were participated and genotyping of the IRS1 (rs13431179, rs16822615, 16822644rs, rs1801123) and TCF7L2 (rs7092484) tag SNPs were carries out using PCR-RFLP method of analysis. Haplotype analyses were carried out using Plink version 1.07, and Haploview 4.2 software. Linkage disequilibrium (LD), and Hardy-Weinberg equilibrium (HWE) analyses were performed using the Plink software. All descriptive statistical data analyses were carried out using SPSS (Version-20) software. Throughout the analysis p-value ≤0.05 was considered statistically significant. Result: Significant association was found between rs13431179 SNP of the IRS1 gene and T2DM under the recessive model of inheritance (OR=9.00, 95%CI=1.17-69.07, p=0.035), and marginally significant association found in the genotypic model (OR=7.50, 95%CI=0.94-60.06, p=0.058). The rs7092484 SNP of the TCF7L2 gene also showed markedly significant association with T2DM in the recessive (OR=3.61, 95%CI=1.70-7.67, p=0.001); and allelic (OR=1.80, 95%CI=1.23-2.62, p=0.002) models. Moreover, eight haplotypes of the IRS1 gene found to have significant association withT2DM (p=0.013 to 0.049). Assessments made on the interactions of genotypes of the rs13431179 and rs7092484 SNPs with various parameters demonstrated that high density lipoprotein (HDL), low density lipoprotein (LDL), waist circumference (WC), and systolic blood pressure (SBP) are the best T2DM onset predicting models. Furthermore, genotypes of the rs7092484 SNP showed significant association with various atherogenic indexes (Atherogenic index of plasma, LDL/HDL, and CHLO/HDL); and Eritreans carrying the GG or GA genotypes were predicted to be more susceptible to cardiovascular diseases onset. Conclusions: Results of this study suggest that IRS1 (rs13431179) and TCF7L2 (rs7092484) gene polymorphisms are associated with increased risk of T2DM in Eritreans.

Keywords: IRS1, SNP, TCF7L2, type 2 diabetes

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Authors: Haris Setiawan, Phongsakorn Chuammitri, Korawan Sringarm, Montira Intanon, Anucha Sathanawongs

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Capacitation is a prerequisite to achieving sperm competency to penetrate the oocyte naturally occurring in vivo throughout the female reproductive tract and entangling secretory fluid and epithelial cells. One of the crucial compounds in the oviductal fluid which promotes capacitation is albumin, secreted in major concentrations. However, the difficulties in the collection and the inconsistency of the oviductal fluid composition throughout the estrous cycle have replaced its function with serum-based albumins such as bovine serum albumin (BSA). BSA has been primarily involved and evidenced for their stabilizing effect to maintain the acrosome intact during the capacitation process, modulate hyperactivation, and elevate the number of sperm bound to zona pellucida. Contrary to its benefits, the use of blood-derived products in the culture system is not sustainable and increases the risk of disease transmissions, such as Creutzfeldt-Jakob disease (CJD) and bovine spongiform encephalopathy (BSE). Moreover, it has been asserted that this substance is an aeroallergen that produces allergies and respiratory problems. In an effort to identify an alternative sustainable and non-toxic albumin source, the present work evaluated sperm reactions to a capacitation medium containing albumin derived from the flesh of the snakehead fish (Channa striata). Before examining the ability of this non-serum albumin to promote capacitation in bovine sperm, the presence of albumin was detected using bromocresol purple (BCP) at the level of 25% from snakehead fish extract. Following the SDS-PAGE and densitometric analysis, two major bands at 40 kDa and 47 kDa consisting of 57% and 16% of total protein loaded were detected as the potential albumin-related bands. Significant differences were observed in all kinematic parameters upon incubation in the capacitation medium. Moreover, consistently higher values were shown for the kinematic parameters related to hyperactivation, such as amplitude lateral head (ALH), velocity curve linear (VCL), and linearity (LIN) when sperm were treated with 3 mg/mL of snakehead fish albumin among other treatments. Likewise, substantial differences of higher acrosome intact presented in sperm upon incubation with various concentrations of snakehead fish albumin for 90 minutes, indicating that this level of snakehead fish albumin can be used to replace the bovine serum albumin. However, further study is highly required to purify the albumin from snakehead fish extract for more reliable findings.

Keywords: capacitation promoter, snakehead fish, non-serum albumin, bovine sperm

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Authors: Imran Muhammad

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The main cause of infectious disease in the modern world is Mycobacterium Tuberculosis (MT). To combat tuberculosis, new and efficient drugs are an urgent need in the modern world. Schif bases are potent for their biological pharmacophore activity. Thus we selected different Vanillin-based Schiff bases for their binding activity against target enzymes of Mycobacterium tuberculosis that is (DprE1 (decaprenyl phosphoryl-β-D-ribose 2′-epimerase), and DNA gyrase subunit-A), using molecular docking. We evaluate the inhibition potential, interaction, and binding mode of these compounds with the target enzymes.

Keywords: schiff bases, tuberculosis, DNA gyrase, DprE1, docking

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Authors: Kotomi Yamashita, Hiromi Kawasaki, Satoko Yamasaki, Susumu Fukita, Risako Sakai

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Lifestyle-related diseases develop from the long-term accumulation of health consequences from a poor lifestyle. Thus, schoolchildren, who have not accumulated long-term lifestyle habits, are believed to be at a lower risk for lifestyle-related diseases. However, schoolchildren rarely receive blood tests unless they are under treatment for a serious disease; without such data on their blood, the impacts of their young lifestyle could not be known. Blood data from physical measurements can help in the implementation of more effective health education. Therefore, we examined the correlation between body mass index (BMI) and blood sugar/serum lipid (BS/SL) levels. From 2014 to 2016, we measured the blood data of fourth-grade students living in a city in Japan. The present study reported on the results of 281 fourth-grade boys only (80.3% of total). We analyzed their BS/SL levels by comparing the blood data against the criteria of the National Center for Child Health and Development in Japan. Next, we examined the correlation between BMI and BS/SL levels. IBM SPSS Statistics for Windows, Version 25 was used for analysis. A total of 69 boys (24.6%) were within the normal range for BMI (18.5–24), whereas 193 (71.5%) and 8 boys (2.8%) had lower and higher BMI, respectively. Regarding BS levels, 280 boys were within the normal range (70–90 mg/dl); 1 boy reported a higher value. All the boys were within the normal range for glycated Hemoglobin (HbA1c) (4.6–6.2%). Regarding SL levels, 271 boys were within the normal range (125–230 mg/dl) for total cholesterol (TC), whereas 5 boys (1.8%) had lower and 5 boys (1.8%) had higher levels. A total of 243 boys (92.7%) were within the normal range (36-138mg/dL) for triglycerides (TG), whereas 19 boys (7.3%) had lower and 19 boys (7.3%) had higher levels. Regarding high-density lipoprotein cholesterol (HDL-C), 276 boys (98.2%) were within the normal range (40-mg/dl), whereas 5 boys (1.8%) reported lower values. All but one boy (280, 99.6%) were within the normal range (-170 mg/dl) for low-density lipoprotein cholesterol (LDL-C); the exception (0.4%) had a higher level. BMI and BS didn’t show a correlation. BMI and HbA1c were moderately positively correlated (r = 0.139, ｐ＝0.019). We also observed moderate positive correlations between BMI and TG (r = 0.328, p < 0.01), TC (r=0.239, p< 0.01), LDL-C (r = 0.324, p < 0.01), respectively. BMI and HDL-C were low correlated (r = -0.185, p = 0.002). Most of the boys were within the normal range for BS/SL levels. However, some boys exceeded the normal TG range. Fourth graders with a high TG may develop a lifestyle-related disease in the future. Given its relation to TG, food habits should be improved in this group. Our findings suggested a positive correlation between BMI and BS/SL levels. Fourth-grade schoolboys with a high BMI may be at high risk for developing lifestyle-related diseases. Lifestyle improvement may be recommended to lower the BS/SL levels in this group.

Keywords: blood sugar level, lifestyle-related diseases, school students, serum lipid level

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Authors: Madeleine Elder, Aye Htun

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Background: Myiasis is the parasitic infestation of body tissues by fly larvae. It predominantly occurs in poor socioeconomic regions of tropical and subtropical countries where it is associated with poor hygiene and sanitation. Cutaneous and wound myiasis are the most common presentations whereas urogenital myiasis is rare, with few reported cases. Case: a 26-year-old primiparous woman with a low-risk pregnancy presented to the emergency department at 37+3-weeks’ gestation after passing a 2cm black larva during micturition, with 2 weeks of mild vulvar pruritus and dysuria. She had travelled to India 9-months prior. Examination of the external genitalia showed small white larvae over the vulva and anus and a mildly inflamed introitus. Speculum examination showed infiltration into the vagina and heavy white discharge. High vaginal swab reported Candida albicans. Urine microscopy reported bacteriuria with Enterobacter cloacae. Urine parasite examination showed myiasis caused by Clogmia albipunctata species of fly larvae from the family Psychodidae. Renal tract ultrasound and inflammatory markers were normal. Infectious diseases, urology and paediatric teams were consulted. The woman received treatment for her urinary tract infection (which was likely precipitated by bladder irritation from local parasite infestation) and vaginal candidiasis. She underwent daily physical removal of parasites with cleaning, speculum examination and removal, and hydration to promote bladder emptying. Due to the risk of neonatal exposure, aspiration pneumonitis and facial infestation, the woman was steroid covered and proceeded to have an elective caesarean section at 38+3-weeks’ gestation, with delivery of a healthy infant. She then proceeded to have a rigid cystoscopy and washout, which was unremarkable. Placenta histopathology revealed focal eosinophilia in keeping with the history of maternal parasites. Conclusion: Urogenital myiasis is very rare, especially in the developed world where it is seen in returned travellers. Treatment may include systemic therapy with ivermectin and physical removal of parasites. During pregnancy, physical removal is considered the safest treatment option, and discussion around the timing and mode of delivery should consider the risk of harm to the foetus.

Keywords: urogenital myiasis, parasitic infection, infection in pregnancy, returned traveller

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Authors: Teklay Gebrecherkos, Mahmud Abdulkadir

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Abstract: The emergence and subsequent rapid worldwide spread of the COVID-19 pandemic have posed a global crisis, with a tremendously increasing burden of infection, morbidity, and mortality risks. Recent studies have suggested that severe cases of COVID-19 are characterized by massive biochemical, hematological, and inflammatory alterations whose synergistic effect is estimated to progress to multiple organ damage and failure. In this regard, biochemical monitoring of COVID-19 patients, based on comprehensive laboratory assessments and findings, is expected to play a crucial role in effective clinical management and improving the survival rates of patients. However, biochemical markers that can be informative of COVID-19 patient risk stratification and predictor of clinical outcomes are currently scarcely available. The study aims to investigate the profiles of common biochemical markers and their influence on the severity of the COVID-19 infection in Tigray, Ethiopia. Methods: A laboratory-based cross-sectional study was conducted from July to August 2020 at Quiha College of Engineering, Mekelle University COVID-19 isolation and treatment center. Sociodemographic and clinical data were collected using a structured questionnaire. Whole blood was collected from each study participant, and serum samples were separated after being delivered to the laboratory. Hematological biomarkers were analyzed using FACS count, while organ tests and serum electrolytes were analyzed using ion-selective electrode methods using a Cobas-6000 series machine. Data was analyzed using SPSS Vs 20. Results: A total of 120 SARS-CoV-2 patients were enrolled during the study. The participants ranged between 18 and 91 years, with a mean age of 52 (±108.8). The majority (40%) of participants were between the ages of 60 and above. Patients with multiple comorbidities developed severe COVID-19, though not statistically significant (p=0.34). Mann-Whitney U test analysis showed that biochemical tests such as neuropile count (p=0.003), AST levels (p=0.050), serum creatinine (p=0.000), and serum sodium (p=0.015) were significantly correlated with severe COVID-19 disease as compared to non-severe disease. Conclusion: The severity of COVID-19 was associated with higher age, organ tests AST and creatinine, serum Na+, and elevated total neutrophile count. Thus, further study needs to be conducted to evaluate the alterations of biochemical biomarkers and their impact on COVID-19.

Keywords: COVID-19, biomarkers, mortality, Tigray, Ethiopia

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Authors: Temitayo Abayomi Ewemoje, Isaac Olugbemiga Afolayan, Badmus Alao Tayo

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Researchers in developing countries have worked on improving cassava resistance to diseases and pests, high yielding and early maturity However, water management has received little or no attention as cassava cultivation in Sub-Saharan Africa depended on available precipitation (rain-fed condition). Therefore the need for water management in Agricultural crop production cannot be overemphasized. As other sectors compete with agricultural sector for fresh water (which is not readily available), there is need to increase water productivity in agricultural production. Experimentation was conducted to examine water use, growth and yield of improved cassava varieties under rain fed condition using Latin- square design with four replications. Four improved disease free stem cassava varieties TMS (30572, 980505, 920326 and 090581) were planted and growth parameters of the varieties were monitored for 90 and 120 days after planting (DAP). Effective rainfall useful for the plant growth was calculated using CROPWAT8 for Windows. Results indicated TMS090581 was having the highest tuber yield and plant height while TMS30572 had highest number of nodes. Tuber stem and leaf water productivities at 90 and 120 DAP of TMS (30572, 980505, 920326 and 090581) are (1.27 and 3.58, 1.44 and 2.35, 0.89 and 1.86, 1.64 and 3.77) kg/m3 (1.56 and 2.59, 1.95 and 2.02, 1.98 and 2.05, 1.95 and 2.18) kg/m3, and (1.34 and 2.32, 1.94 and 2.16, 1.57 and 1.40, 1.27 and 1.80) kg/m3 respectively. Based on tuber water productivity TMS090581 are recommended while TMS30572 are recommended based on leaf and stem productivity in water scarce regions.Experimentation was conducted to examine water use, growth and yield of improved cassava varieties under rain fed condition using Latin- square design with four replications. Four improved disease free stem cassava varieties TMS (30572, 980505, 920326 and 090581) were planted and growth parameters of the varieties were monitored for 90 and 120 days after planting (DAP). Effective rainfall useful for the plant growth was calculated using CROPWAT8 for Windows. Results indicated TMS090581 was having the highest tuber yield and plant height while TMS30572 had the highest number of nodes. Tuber, stem and leaf water productivities at 90 and 120 DAP of TMS (30572, 980505, 920326 and 090581) are (1.27 and 3.58, 1.44 and 2.35, 0.89 and 1.86, 1.64 and 3.77) kg/m3 (1.56 and 2.59, 1.95 and 2.02, 1.98 and 2.05, 1.95 and 2.18) kg/m3, and (1.34 and 2.32, 1.94 and 2.16, 1.57 and 1.40, 1.27 and 1.80) kg/m3 respectively. Based on tuber water productivity TMS090581 are recommended while TMS30572 are recommended based on leaf and stem productivity in water scarce regions

Keywords: improved TMS varieties, leaf productivity, rain-fed cassava production, stem productivity, tuber productivity

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Authors: Somayeh Khanjani, Samaneh Nabavi, Shirin Jalili

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Aluminum phosphide (ALP) is an inorganic phosphide used to control insects and is a highly effective insecticide and rodenticide used frequently to protect stored grain. Acute poisoning with this compound is common in some countries including India and Iran, and is a serious health problem. In Iran it was known as "rice tablet", for its use to preserve rice. Two kinds of rice tablets one being herbal while other containing 3g aluminum phosphide (AlP) are available for use in Iranian households to protect stored food grains from pests and rodents. The toxicity of Aluminum phosphide is attributed to the liberation of phosphine gas in contact with water or weak acid and is the major cause of poisoning and deaths. Rice tablet (Aluminum Phosphid) poisoning may be associated with serious and sometimes incurable complications. In 61.3% of patients were shown uniform ingestion. Vomiting was the most common symptoms reported by 96.4% patients. Agitation was reported in 36.9% and felling of thirsty in 27.9 %. Although many complications such as Hypotension, Adult Respiratory Distress Syndrome (ARDS), Acute Renal Failure (ARF) AND Multi Organ Failure (MOF) were the common complications observed in these patients, but the most lethal complication was Cardiac Arrhythmias occurred in 36.9% of cases. Abdominal pain in 31.4% of the patients, nausea in 79.4% of the patients and 41.1% of the patients showed metabolic acidosis. Suicidal intention was the most common cause of poisoning leading to deaths in 18.6% of the patients. Aluminum phosphide can cause either elevation, decrease or no change in electrolytes, bicarbonate and blood glucose level. The possible mechanism for changes in blood glucose levels are complex and depend on the balance of factors which increase its concentration and those which reduce it. AlP poisoning has been postulated to stimulate cortisol which leads to increasing blood level of cortisol, also it may cause stimulation of glucagon, and Adrenaline secretion; in addition, it can inhibit insulin synthesis which may lead to hyperglycemia. Another suggested mechanism of hyperglycemia is rennin activity in some cases, an increase in magnesium level of plasma and that of tissues, and high phosphate level. Although hyperglycemia is most frequent in this poisoning and also is known as a marker of poor prognostic, hypoglycemia in aluminum phosphide poisoning is a rare finding which may be so dangerous. Patients showed sever hypotension and sever acidosis in addition to sever hypoglycemia. The presenting features of AlP intoxication are rapid onset of shock, severe metabolic acidosis, cardiac dysrhythmias and adult respiratory distress syndrome (ARDS).

Keywords: aluminum phosphide (ALP), rice tablet, poisoning, phosphine gas

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Authors: J. H. Bang, H. J. Baek, K. I. Kim, B. J. Lee, H. J. Jung, H. J. Jang, S. K. Jung

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Asthma is a chronic inflammatory lung disease characterized by airway hyper responsiveness (AHR), airway obstruction and airway wall remodeling responsible for significant morbidity and mortality worldwide. Genetic and environment factors may result in asthma, but there are no the exact causes of asthma. Chungpye-tang (CPT) has been prescribed as a representative aerosol agent for patients with dyspnea, cough and phlegm in the respiratory clinic at Kyung Hee Korean Medicine Hospital. This Korean herbal medicines have the effect of dispelling external pathogen and dampness pattern. CPT is composed of 4 species of herbal medicines. The 4 species of herbal medicines are Ephedrae herba, Pogostemonis(Agatachis) herba, Caryophylli flos and Zingiberis rhizoma crudus. CPT suppresses neutrophil infiltration and the production of pro-inflammatory cytokines in lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. Moreover, the anti-inflammatory effects of CPT on a mouse model of Chronic Obstructive Pulmonary Disease (COPD) was proved. Activation of the NF-κB has been proven that it plays an important role in inflammation via inducing transcription of pro-inflammatory genes. Over-expression of NF-κB has been believed be related to many inflammatory diseases such as arthritis, gastritis, asthma and COPD. So we firstly hypothesize whether CPT has an anti-inflammatory effect on asthmatic human airway epithelial tissue via inhibiting NF-κB pathway. In this study, CPT was extracted with distilled water for 3 hours at 100°C. After process of filtration and evaporation, it was freeze dried. And asthmatic human lung tissues were provided by MatTek Corp. We investigated the precise mechanism of the anti-inflammatory effect of CPT by western blotting analysis. We observed whether the decoction extracts could reduce NF-κB activation, COX-2 protein expression and NF-κB-mediated pro-inflammatory cytokines such as TNF-α, eotaxin, IL-4, IL-9 and IL-13 in asthmatic human lung tissue. As results of this study, there was a trend toward decreased NF-κB expression in asthmatic human airway epithelial tissue. We found that the inhibition effects of CPT on COX-2 expression was not determined. IL-9 and IL-13 secretion was significantly reduced in the asthmatic human lung tissue treated with CPT. Overall, our results indicate that CPT has an anti-inflammatory effect through blocking the signaling pathway of NF-κB, thereby CPT may be a potential remedial agent for allergic asthma.

Keywords: Chungpye-tang, allergic asthma, asthmatic human airway epithelial tissue, nuclear factor kappa B (NF-κB) pathway, COX-2

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Authors: Sean Sloan

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Probability Risk Assessments (PRA) can be a difficult concept for students to grasp. So in searching for different ways to describe PRA to relate it to their lives; COVID-19 came up. The parallels are amazing. Soon students began analyzing acceptable risk with the virus. This helped them to quantify just how dangerous is dangerous. The original lesson was dismissed and for the remainder of the period, the probability of risk, and the lethality of risk became the topic. Spreading events such as a COVID carrier on an airline became analogous to single fault casualties such as a Tsunami. Odds of spreading became odds of backup-diesel-generator failure – like with Fukashima Daiichi. Fatalities of the disease became expected fatalities due to radiation spread. Quantification from this discussion took it from hyperbole and emotion into one where we could rationally base guidelines. It has been one of the most effective educational devices observed.

Keywords: COVID, education, probability, risk

Procedia PDF Downloads 152

Authors: Danyi Wang, Andrew Schriefer, Dennis O'Rourke, Brajendra Kumar, Yang Liu, Fei Zhong, Juergen Scheuenpflug, Zheng Feng

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Purpose: It has been recognized that the microbiome plays critical roles in disease pathogenesis, including cancer, autoimmune disease, and multiple sclerosis. To develop a clinical-grade assay for exploring microbiome-derived clinical biomarkers across disease areas, a two-phase approach is implemented. 1) Identification of the optimal sample preparation reagents using pre-mixed bacteria and healthy donor stool samples coupled with proprietary Sigma-Aldrich® bioinformatics solution. 2) Exploratory analysis of patient samples for enabling precision medicine. Study Procedure: In phase 1 study, we first compared the 16S sequencing results of two ATCC® microbiome standards (MSA 2002 and MSA 2003) across five different extraction kits (Kit A, B, C, D & E). Both microbiome standards samples were extracted in triplicate across all extraction kits. Following isolation, DNA quantity was determined by Qubit assay. DNA quality was assessed to determine purity and to confirm extracted DNA is of high molecular weight. Bacterial 16S ribosomal ribonucleic acid (rRNA) amplicons were generated via amplification of the V3/V4 hypervariable region of the 16S rRNA. Sequencing was performed using a 2x300 bp paired-end configuration on the Illumina MiSeq. Fastq files were analyzed using the Sigma-Aldrich® Microbiome Platform. The Microbiome Platform is a cloud-based service that offers best-in-class 16S-seq and WGS analysis pipelines and databases. The Platform and its methods have been extensively benchmarked using microbiome standards generated internally by MilliporeSigma and other external providers. Data Summary: The DNA yield using the extraction kit D and E is below the limit of detection (100 pg/µl) of Qubit assay as both extraction kits are intended for samples with low bacterial counts. The pre-mixed bacterial pellets at high concentrations with an input of 2 x106 cells for MSA-2002 and 1 x106 cells from MSA-2003 were not compatible with the kits. Among the remaining 3 extraction kits, kit A produced the greatest yield whereas kit B provided the least yield (Kit-A/MSA-2002: 174.25 ± 34.98; Kit-A/MSA-2003: 179.89 ± 30.18; Kit-B/MSA-2002: 27.86 ± 9.35; Kit-B/MSA-2003: 23.14 ± 6.39; Kit-C/MSA-2002: 55.19 ± 10.18; Kit-C/MSA-2003: 35.80 ± 11.41 (Mean ± SD)). Also, kit A produced the greatest yield, whereas kit B provided the least yield. The PCoA 3D visualization of the Weighted Unifrac beta diversity shows that kits A and C cluster closely together while kit B appears as an outlier. The kit A sequencing samples cluster more closely together than both the other kits. The taxonomic profiles of kit B have lower recall when compared to the known mixture profiles indicating that kit B was inefficient at detecting some of the bacteria. Conclusion: Our data demonstrated that the DNA extraction method impacts DNA concentration, purity, and microbial communities detected by next-generation sequencing analysis. Further microbiome analysis performance comparison of using healthy stool samples is underway; also, colorectal cancer patients' samples will be acquired for further explore the clinical utilities. Collectively, our comprehensive qualification approach, including the evaluation of optimal DNA extraction conditions, the inclusion of positive controls, and the implementation of a robust qualified bioinformatics pipeline, assures accurate characterization of the microbiota in a complex matrix for deciphering the deep biology and enabling precision medicine.

Keywords: 16S rRNA sequencing, analytical validation, bioinformatics pipeline, metagenomics

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Authors: Shikha Rani, Neeta Sehgal, Vipin Kumar Verma, Om Prakash

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Introduction: Fish is an important protein source for humans and has great economic value. Fish cultures are affected due to various anthropogenic activities that lead to bacterial and viral infections. Aeromonas hydrophila is a fish pathogenic bacterium that causes several aquaculture outbreaks throughout the world and leads to huge mortalities. In this study, plants of no commercial value were used to investigate their immunostimulatory, antioxidant, anti-inflammatory, anti-bacterial, and disease resistance potential in fish against Aeromonas hydrophila, through fish feed fortification. Methods: The plant was dried at room temperature in the shade, dissolved in methanol, and analysed for biological compounds through GC-MS/MS. DPPH, FRAP, Phenolic, and flavonoids were estimated following standardized protocols. In silico molecular docking was also performed to validate its broad-spectrum activities based on binding affinity with specific proteins. Fish were divided into four groups (n=6; total 30 in a group): Group 1, non-challenged fish (fed on a non-supplemented diet); Group 2, fish challenged with bacteria (fed on a non-supplemented diet); Group 3 and 4, fish challenged with bacteria (A. hydrophila) and fed on plant supplemented feed at 2.5% and 5%. Blood was collected from the fish on 0, 7th, 14th, 21st, and 28th days. Serum was separated for glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase assay (ALP), lysozyme activity assay, superoxide dismutase assay (SOD), lipid peroxidation assay (LPO) and molecular parameters (including cytokine levels) were estimated through ELISA. The phagocytic activity of macrophages from the spleen and head kidney, along with quantitative analysis of immune-related genes, were analysed in different tissue samples. The digestive enzymes (Pepsin, Trypsin, and Chymotrypsin) were also measured to evaluate the effect of plant-supplemented feed on freshwater fish. Results and Discussion: GC-MS/MS analysis of a methanolic extract of plant validated the presence of key compounds having antioxidant, anti-inflammatory, anti-bacterial, anti-inflammatory, and immunomodulatory activities along with disease resistance properties. From biochemical investigations like ABTS, DPPH, and FRAP, the amount of total flavonoids, phenols, and promising binding affinities towards different proteins in molecular docking analysis helped us to realize the potential of this plant that can be used for investigation in the supplemented feed of fish. Measurement liver function tests, ALPs, oxidation-antioxidant enzyme concentrations, and immunoglobulin concentrations in the experimental groups (3 and 4) showed significant improvement as compared to the positive control group. The histopathological evaluation of the liver, spleen, and head kidney supports the biochemical findings. The isolated macrophages from the group fed on supplemented feed showed a higher percentage of phagocytosis and a phagocytic index, indicating an enhanced cell-mediated immune response. Significant improvements in digestive enzymes were also observed in fish fed on supplemented feed, even after weekly challenges with bacteria. Hence, the plant-fortified feed can be recommended as a regular feed to enhance fish immunity and disease resistance against the Aeromonas hydrophila infection after confirmation from the field trial.

Keywords: immunostimulation, antipathogen, plant fortified feed, macrophages, GC-MS/MS, in silico molecular docking

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Authors: Liping Qiu, Xiaofeng Zhang

Abstract:

In its long history, precious tomb murals suffered from various diseases due to natural and man-made destruction. The key to how to protect tomb murals is how to strengthen and protect the tomb murals. In order to maximize the life of the tomb murals, the artistic, historic, and scientific values of the tomb murals can be continued. In this paper, four kinds of traditional reinforcement materials (silicone acrylic lotion, pure acrylic lotion, polyvinyl acetate lotion, and B72) are selected to reinforce the ground support layer of tomb murals, and the reinforcement effect of each reinforcement material on the ground support layer of murals is compared and analyzed, and the best protection material is obtained.

Keywords: mural, destruction cycle, reinforcement material, disease

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Authors: Tais Basaco, Stefanie Pektor, Josue A. Moreno, Matthias Miederer, Andreas Türler

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Radiopharmaceuticals based in monoclonal anti-body (mAb) via chemical linkers have become a potential tool in nuclear medicine because of their specificity and the large variability and availability of therapeutic radiometals. It is important to identify the conjugation sites and number of attached chelator to mAb to obtain radioimmunoconjugates with required immunoreactivity and radiostability. Girentuximab antibody (G250) is a potential candidate for radioimmunotherapy of clear cell carcinomas (RCCs) because it is reactive with CAIX antigen, a transmembrane glycoprotein overexpressed on the cell surface of most ( > 90%) (RCCs). G250 was conjugated with the bifunctional chelating agent DOTA (1,4,7,10-Tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid) via a benzyl-thiocyano group as a linker (p-SCN-Bn-DOTA). DOTA-G250 conjugates were analyzed by size exclusion chromatography (SE-HPLC) and by electrophoresis (SDS-PAGE). The potential site-specific conjugation was identified by liquid chromatography–mass spectrometry (LC/MS-MS) and the number of linkers per molecule of mAb was calculated using the molecular weight (MW) measured by matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The average number obtained in the conjugates in non-reduced conditions was between 8-10 molecules of DOTA per molecule of mAb. The average number obtained in the conjugates in reduced conditions was between 1-2 and 3-4 molecules of DOTA per molecule of mAb in the light chain (LC) and heavy chain (HC) respectively. Potential DOTA modification sites of the chelator were identified in lysine residues. The biological activity of the conjugates was evaluated by flow cytometry (FACS) using CAIX negative (SKRC-18) and CAIX positive (SKRC-52). The DOTA-G250 conjugates were labelled with 177Lu with a radiochemical yield > 95% reaching specific activities of 12 MBq/µg. The stability in vitro of different types of radioconstructs was analyzed in human serum albumin (HSA). The radiostability of 177Lu-DOTA-G250 at high specific activity was increased by addition of sodium ascorbate after the labelling. The immunoreactivity was evaluated in vitro and in vivo. Binding to CAIX positive cells (SK-RC-52) at different specific activities was higher for conjugates with less DOTA content. Protein dose was optimized in mice with subcutaneously growing SK-RC-52 tumors using different amounts of 177Lu- DOTA-G250.

Keywords: mass spectrometry, monoclonal antibody, radiopharmaceuticals, radioimmunotheray, renal cancer

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Authors: Wissam Saliba, Mandy Nicholson

Abstract:

Secretory carcinoma (SC) is a rare type of salivary gland cancer. It was first realized as a distinct type of malignancy in 2010and wasinitially termed “mammary analogue secretory carcinoma” because of similarities with secretory breast cancer. The name was later changed to SC. Most SCs originate in parotid glands, and most harbour a rare gene mutation: ETV6-NTRK3. This mutation is rare in common cancers and common in rare cancers; it is present in most secretory carcinomas. Disease outcomes for SC are usually described as favourable as many cases of SC are lowgrade (LG), and cancer growth is slow. In early stages, localized therapy is usually indicated (surgery and/or radiation). Despitea favourable prognosis, a sub-set of casescan be much more aggressive.These cases tend to be of high-grade(HG).HG casesare associated with a poorer prognosis.Management of such cases can be challenging due to limited evidence for effective systemic therapy options. This case report describes the clinical management of a 46-year-oldmale patient with a unique case of SC. He was initially diagnosed with a low/intermediate grade carcinoma of the left parotid gland in 2009; he was treated with surgery and adjuvant radiation. Surgical pathology favoured primary salivary adenocarcinoma, and 2 lymph nodes were positive for malignancy. SC was not yet realized as a distinct type of cancerat the time of diagnosis, and the pathology reportvalidated this gap by stating that the specimen lacked features of the defined types of salivary carcinoma.Slow-growing pulmonary nodules were identified in 2017. In 2020, approximately 11 years after the initial diagnosis, the patient presented with malignant pleural effusion. Pathology from a pleural biopsy was consistent with metastatic poorly differentiated cancer of likely parotid origin, likely mammary analogue secretory carcinoma. The specimen was sent for Next Generation Sequencing (NGS); ETV6-NTRK3 gene fusion was confirmed, and systemic therapy was initiated.One cycle ofcarboplatin/paclitaxel was given in June 2020. He was switched to Larotrectinib (NTRK inhibitor (NTRKi)) later that month. Larotrectinib continued for approximately 9 months, with discontinuation in March 2021 due to disease progression. A second-generation NTRKi (Selitrectinib) was accessed and prescribedthrough a single patient study. Selitrectinib was well tolerated. The patient experienced a complete radiological response within~4 months. Disease progression occurred once again in October 2021. Progression was slow, and Selitrectinib continuedwhile the medical team performed a thorough search for additional treatment options. In January 2022, a liver lesion biopsy was performed, and NGS showed an NTRKG623R solvent-front resistance mutation. Various treatment pathways were considered. The patient pursuedanother investigational NTRKi through a clinical trial, and Selitrectinib was discontinued in July 2022. Excellent performance status was maintained throughout the entire course of treatment.It can be concluded that NTRK inhibitors provided satisfactory treatment efficacy and tolerance for this patient with high-grade transformation and NTRK gene fusion cancer. In the future, more clinical research is needed on systemic treatment options for high-grade transformations in NTRK gene fusion SCs.

Keywords: secretory carcinoma, high-grade transformations, NTRK gene fusion, NTRK inhibitor

Procedia PDF Downloads 108