Search results for: Chronic heart disease

Authors: Cecília M. Antão, Paulo Jorge Nogueira

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Breast cancer (BC) is the first cause of cancer mortality among Portuguese women. This retrospective observational study aimed at identifying comorbidities associated with BC female patients admitted to Portuguese public hospitals (2010-2018), investigating the effect of comorbidities on BC mortality rate, and building a predictive model using logistic regression. Results showed that the BC mortality in Portugal decreased in this period and reached 4.37% in 2018. Adjusted odds ratio indicated that secondary malignant neoplasms of liver, of bone and bone marrow, congestive heart failure, and diabetes were associated with an increased chance of dying from breast cancer. Although the Lisbon district (the most populated area) accounted for the largest percentage of BC patients, the logistic regression model showed that, besides patient’s age, being resident in Bragança, Castelo Branco, or Porto districts was directly associated with an increase of the mortality rate.

Keywords: breast cancer, comorbidities, logistic regression, adjusted odds ratio

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Authors: Wondale Getinet Alemu, Lillian Mwanri, Clemence Due, Telake Azale, Anna Ziersch

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Background: Mental illness is one of the most severe, chronic, and disabling public health problems that affect patients' Quality of life (QoL). Improving the QoL for people with mental illness is one of the most critical steps in stopping disease progression and avoiding complications of mental illness. Therefore, we aimed to assess the QoL and its determinants in patients with mental illness in outpatient clinics in Northwest Ethiopia in 2023. Methods: A facility-based cross-sectional study was conducted among people with mental illness in an outpatient clinic in Ethiopia. The sampling interval was decided by dividing the total number of study participants who had a follow-up appointment during the data collection period (2400) by the total sample size of 638, with the starting point selected by lottery method. The interviewer-administered WHOQOL BREF-26 tool was used to measure the QoL of people with mental illness. The domains and Health-Related Quality of Life (HRQoL) were identified. The indirect and direct effects of variables were calculated using structural equation modeling with SPSS-28 and Amos-28 software. A p-value of < 0.05 and a 95% CI were used to evaluate statistical significance. Results: A total of 636 (99.7%) participants responded and completed the WHOQOL-BREF questionnaire. The mean score of overall HRQoL of people with mental illness in the outpatient clinic was (49.6 ± 10 Sd). The highest QoL was found in the physical health domain (50.67 ±9.5 Sd), and the lowest mean QoL was found in the psychological health domain (48.41±10 Sd). Rural residents, drug nonadherence, suicidal ideation, not getting counseling, moderate or severe subjective severity, the family does not participate in patient care, and a family history of mental illness had an indirect negative effect on HRQoL. Alcohol use and psychological health domain had a direct positive effect on QoL. Furthermore, objective severity of illness, having low self-esteem, and having a history of mental illness in the family had both direct and indirect effects on QoL. Furthermore, sociodemographic factors (residence, educational status, marital status), social support-related factors (self-esteem, family not participating in patient care), substance use factors (alcohol use, tobacco use,) and clinical factors (objective and subjective severity of illness, not getting counseling, suicidal ideation, number of episodes, comorbid illness, family history of mental illness, poor drug adherence) directly and indirectly affected QoL. Conclusions: In this study, the QoL of people with mental illness was poor, with the psychological health domain being the most affected. Sociodemographic factors, social support-related factors, drug use factors, and clinical factors directly and indirectly, affect QoL through the mediator variables of physical health domains, psychological health domains, social relation health domains, and environmental health domains. In order to improve the QoL of people with mental illnesses, we recommend that emphasis be given to addressing the scourge of mental health, including the development of policy and practice drivers that address the above-identified factors.

Keywords: quality of life, mental wellbeing, mental illness, mental disorder, Ethiopia

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Authors: Garima Anand, Rupam Kapoor

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Alternaria leaf spot caused by Alternaria carthami is one of the most devastating diseases of safflower. It has resulted in huge losses in crop production and cultivation leading to a fall out of India’s rank as the leading producer of safflower in the world. Understanding the diversity of any pathogen is essential for its management and for the development of disease control strategies. The diversity of A. carthami was therefore analysed on the basis of biochemical, pathogenicity and genetic lines using ISSR markers. Collections and isolations of 95 isolates of A. carthami were made from major safflower producing states of India. Virulence was analysed to evaluate the pathogenic potential of these isolates. The isolates from Bijapur, Dharwad districts (Karnataka), and Parbhani and Solapur districts (Maharashtra) were found to be highly virulent. The virulence assays showed low virulence levels (42%) for the largest part of the population. Biochemical characterization to assess aggressiveness of these isolates was done by estimating the activity of cell wall degrading enzymes where isolates from districts Dharwad, Bijapur of Karnataka and districts Parbhani and Latur of Maharashtra were found to be most aggressive. Genetic diversity among isolates of A. carthami was determined using eighteen ISSR markers. Distance analysis using neighbour joining method and PCoA analysis of the ISSR profiles divided the isolates into three sub-populations. The most virulent isolates clustered in one group in the dendrogram. The study provided no evidence for geographical clustering indicating that isolates are randomly spread across the states, signifying the high potential of the fungus to adapt to diverse regions. The study can, therefore, aid in the breeding and deployment of A. carthami resistant safflower varieties and in the management of Alternaria leaf spot disease.

Keywords: alternaria leaf spot, genetic diversity, pathogenic potential, virulence

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Authors: Chandu Rathnayake, Isuri Anuradha

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Early detection and accurate diagnosis of lung diseases play a crucial role in improving patient prognosis. However, conventional diagnostic methods heavily rely on subjective symptom assessments and medical imaging, often causing delays in diagnosis and treatment. To overcome this challenge, we propose a novel lung disease prediction system that integrates patient symptoms and X-ray images to provide a comprehensive and reliable diagnosis.In this project, develop a mobile application specifically designed for detecting lung diseases. Our application leverages both patient symptoms and X-ray images to facilitate diagnosis. By combining these two sources of information, our application delivers a more accurate and comprehensive assessment of the patient's condition, minimizing the risk of misdiagnosis. Our primary aim is to create a user-friendly and accessible tool, particularly important given the current circumstances where many patients face limitations in visiting healthcare facilities. To achieve this, we employ several state-of-the-art algorithms. Firstly, the Decision Tree algorithm is utilized for efficient symptom-based classification. It analyzes patient symptoms and creates a tree-like model to predict the presence of specific lung diseases. Secondly, we employ the Random Forest algorithm, which enhances predictive power by aggregating multiple decision trees. This ensemble technique improves the accuracy and robustness of the diagnosis. Furthermore, we incorporate a deep learning model using Convolutional Neural Network (CNN) with the RestNet50 pre-trained model. CNNs are well-suited for image analysis and feature extraction. By training CNN on a large dataset of X-ray images, it learns to identify patterns and features indicative of lung diseases. The RestNet50 architecture, known for its excellent performance in image recognition tasks, enhances the efficiency and accuracy of our deep learning model. By combining the outputs of the decision tree-based algorithms and the deep learning model, our mobile application generates a comprehensive lung disease prediction. The application provides users with an intuitive interface to input their symptoms and upload X-ray images for analysis. The prediction generated by the system offers valuable insights into the likelihood of various lung diseases, enabling individuals to take appropriate actions and seek timely medical attention. Our proposed mobile application has significant potential to address the rising prevalence of lung diseases, particularly among young individuals with smoking addictions. By providing a quick and user-friendly approach to assessing lung health, our application empowers individuals to monitor their well-being conveniently. This solution also offers immense value in the context of limited access to healthcare facilities, enabling timely detection and intervention. In conclusion, our research presents a comprehensive lung disease prediction system that combines patient symptoms and X-ray images using advanced algorithms. By developing a mobile application, we provide an accessible tool for individuals to assess their lung health conveniently. This solution has the potential to make a significant impact on the early detection and management of lung diseases, benefiting both patients and healthcare providers.

Keywords: CNN, random forest, decision tree, machine learning, deep learning

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Authors: Ryotaro Ishikawa

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Obsessive-Compulsive Disorder (OCD) is a common, chronic and long-lasting disorder in which a person has uncontrollable, reoccurring thoughts (obsessions) and behaviors (compulsions) that he or she feels the urge to repeat over and over. Inflated responsibility attitude and interpretation are central beliefs in a cognitive model of OCD. This study aimed to develop a Japanese version of the Responsibility Attitude Scale (RAS-J) and Responsibility Interpretation Questionnaire (RIQ-J). 98 participants (OCD group = 37; anxiety control group = 24; healthy control group = 37) completed the RAS-J, RIQ-J and other measures to assess the validity of the RAS-J and RIQ-J. As a result of analysis, both scales had adequate concurrent validity, demonstrated by significant correlations with other measures of OCD, anxiety, and depression. Group comparison data using ANOVA with Bonferroni method indicated that RAS-J and RIQ-J scores for the OCD group not only differed from the nonclinical group, but also from the clinically anxious comparison group. In conclusion, this study indicated that the developed RAS-J and RIQ-J effectively measure responsibility attitude and responsibility interpretation in the Japanese population.

Keywords: obsessive-compulsive disorder, responsibility, cognitive theory, anxiety disorder

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Authors: Arezoo Fallahi

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Background and purpose: Non-alcoholic fatty liver is one of the most common liver disorders, which, as the most important cause of death from liver disease, has unpleasant consequences and complications. The aim of this study was to investigate the effect of an educational intervention based on a health belief model to prevent non-alcoholic fatty liver among women. Materials and Methods: This experimental study was performed among 110 women referring to comprehensive health service centers in Malayer City, west of Iran, in 2023. Using the available sampling method, 110 Participants were divided into experimental and control groups. The data collection tool included demographic characteristics and a questionnaire based on the health belief model. In The experimental group, three one-hour training sessions were conducted in the form of pamphlets, lectures and group discussions. Data were analyzed using SPSS software version 21, by correlation tests, paired t-tests independent t-tests. Results: The mean age of participants was 38.07±6.28 years, and Most of the participants were middle-aged, married, housewives with academic education, middle-income and overweight. After the educational intervention, the mean scores of the constructs include perceived sensitivity (p=0.01), perceived severity (p=0.01), perceived benefits (p=0.01), guidance for internal (p=0.01) and external action (p=0.01), and perceived self-efficacy (p=0.01) in the experimental group were significantly higher than the control group. The score of perceived barriers in the experimental group decreased after training. The perceived obstacles score in the test group decreased after the training (15.2 ± 3.9 v.s 11.2 ± 3.3, (p<0.01). Conclusion: The findings of the study showed that the design and implementation of educational programs based on the constructs of the health belief model can be effective in preventing women from developing higher levels of non-alcoholic fatty liver.

Keywords: health, education, believe, behaviour

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Authors: Fadime Eroglu

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Acanthamoeba genus belongs to kingdom protozoa, and it is known as free-living amoebae. Acanthamoeba genus has been isolated from human bodies, swimming pools, bottled mineral water, contact lens solutions, dust, and soil. The members of the genus Acanthamoeba causes Acanthamoeba Keratitis which is a painful sight-threatening disease of the eyes. In recent years, the prevalence of Acanthamoeba keratitis has been high rate reported. The eight different Acanthamoeba species are known to be effective in Acanthamoeba keratitis. These species are Acanthamoeba castellanii, Acanthamoeba polyphaga, Acanthamoeba griffini, Acanthamoeba hatchetti, Acanthamoeba culbertsoni and Acanhtamoeba rhysodes. The conventional diagnosis of Acanthamoeba Keratitis has relied on cytological preparations and growth of Acanthamoeba in culture. However molecular methods such as real-time PCR has been found to be more sensitive. The real-time PCR has now emerged as an effective method for more rapid testing for the diagnosis of infectious disease in decade. Therefore, a real-time PCR assay for the detection of Acanthamoeba keratitis and Acanthamoeba species have been developed in this study. The 18S rRNA sequences from Acanthamoeba species were obtained from National Center for Biotechnology Information and sequences were aligned with MEGA 6 programme. Primers and probe were designed using Custom Primers-OligoPerfectTMDesigner (ThermoFisherScientific, Waltham, MA, USA). They were also assayed for hairpin formation and degree of primer-dimer formation with Multiple Primer Analyzer ( ThermoFisherScientific, Watham, MA, USA). The eight different ATCC Acanthamoeba species were obtained, and DNA was extracted using the Qiagen Mini DNA extraction kit (Qiagen, Hilden, Germany). The DNA of Acanthamoeba species were analyzed using newly designed primer and probe set in real-time PCR assay. The early definitive laboratory diagnosis of Acanthamoeba Keratitis and the rapid initiation of suitable therapy is necessary for clinical prognosis. The results of the study have been showed that new primer and probes could be used for detection and distinguish for Acanthamoeba species. These new developing methods are helpful for diagnosis of Acanthamoeba Keratitis.

Keywords: Acathamoeba Keratitis, Acanthamoeba species, fast diagnosis, Real-Time PCR

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Authors: Jade Edey, Andrew Bennett, Gareth Hathway

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Nuclear receptor-related 1 protein (also known as Nurr1 or NR4A2) is an orphan nuclear receptor which plays a vital role in the development, survival and maintenance of dopaminergic (DA) neurons particularly in the substantia nigra (SN). Increasing research has investigated Nurr1’s additional role within microglia and astrocytes where it has been suggested to act as a negative regulator of inflammation; potentially offering neuroprotection. Considering both DA neurodegeneration and neuroinflammation are commonly accepted constituents of Parkinson’s Disease (PD), understanding the mechanisms by which Nurr1 regulates inflammatory processes could provide an attractive therapeutic target. Nurr1 regulates inflammation via a transrepressive mechanism possibly dependent upon SUMOylation. In addition, Nurr1 can transactivate numerous genes involved in DA synthesis, such as Tyrosine Hydroxylase (TH). A C-terminal splice variant of Nurr1, Nurr-1a, has been reported in both neuronal and glial cells. However, research into its transcriptional activity is minimal. We employed in vitro methods such as SUMO-Pulldown experiments alongside Luciferase reporter assays to investigate the SUMOylation status and transactivation capabilities of Nurr1 and Nurr-1a respectively. The SUMO-Pulldown assay demonstrated Nurr-1a undergoes significantly more SUMO modification than its full-length variant. Consequently, despite having less transcriptional activation than Nurr1, Nurr1a may play a more prominent role in repression of microglial inflammation. Contrary to published literature we also identified that SUMOylation enhances transcriptional activation by Nurr1 and Nurr1a. SUMOylation-dependent increases in Nurr1 and Nurr1a transcriptional activation were only evident in neuronal SHSY5Y cells but not in HEK293 cells. This research provides novel insight into the regulation of Nurr-1a and indicates differential effects of SUMOylation dependent regulation in neuronal and inflammatory cells.

Keywords: nuclear receptors, Parkinson’s disease, inflammation, transcriptional regulation

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Authors: Tengku Farah Petri Tengku Mahmood, Shameem Rafik-Galea, Zalina Mohd Kasim, Norlijah Othman

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Childhood vaccination programme is mandatory in Malaysia. However, the decision to vaccinate or not vaccinate children is still left to the parents. Presently, there are parents who are opting out of vaccination claiming that it causes autism and other chronic disorders despite inconclusive evidence. There appears to be a dangerous trend among some Malaysian parents to not vaccinate their children and to not participate in the childhood vaccination programme. This study presents preliminary findings of parental discourse on childhood vaccination programme through the perspective of the Integrated Threat Theory. An in-depth interview was carried out to investigate a parent’s concern of the effects of childhood vaccination on children. A thematic discourse analysis was used to analyse the transcribed data. The emerging themes based on the analysis and their relevance to our understanding of a parent’s concerns of the effects of childhood vaccination on children are discussed.

Keywords: case study, parental discourse, thematic discourse analysis, childhood vaccination

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Authors: Ateeqa Aslam, Hans J. Nauwynck

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Porcine hemagglutinating encephalomyelitis virus (PHEV) is a betacoronavirus that has been studied in the past as a cause of vomiting and wasting disease (VWD) in young piglets (<3 weeks). Nowadays, the virus is still circulating on most farms in Belgium, but there are no descriptions anymore of VWD. Therefore, we are interested in differences between the old and new strains. We compared the replication kinetics of the old well-studied strain VW572 (1972) and the recent isolate P412 (2020) in a susceptible continuous cell line (RPD cells) and in primary porcine respiratory epithelial cells (PoRECs). The RPD cell line was inoculated with each PHEV strain at an m.o.i. of 1 the supernatant was collected, and the cells were fixed at different time points post-inoculation. The supernatant was titrated (extracellular virus titer), and the infected cells were revealed by immunofluorescence staining and quantitated by fluorescence microscopy. We found that VW572 replicated better in the RPD cell line at earlier time points when compared to P412. Porcine respiratory epithelial cells (PoREC) were isolated, grown at air-liquid interphase in transwells and inoculated with both strains of PHEV at a virus titer of 106.6TCID50 per 200 µl either at the apical side or at the basal side of the cells. At different time points after inoculation, the transwells were fixed and stained for infected cells. VW572 preferentially infected the epithelial cells via the basolateral side of porcine nasal epithelial cells, whereas P412 preferred the apical side. These findings suggest that there has been an evolution of PHEV in its interaction with the respiratory epithelial cells. In the future, more virus strains will be enclosed and the tropism of the strains for different neuronal cell types will be examined for the change in virus neurotropism.

Keywords: porcine hemagglutinating encephalomyelitis virus (PHEV), primary porcine respiratory epithelial cells (PoRECs), virus tropism, vomiting and wasting disease (VWD)

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Authors: Narottam Puri, Bishnu Panigrahi, Narayan Pendse

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Background: Clinical Outcomes are the globally agreed upon, evidence-based measurable changes in health or quality of life resulting from the patient care. Reporting of outcomes and its continuous monitoring provides an opportunity for both assessing and improving the quality of patient care. In 2012, International Consortium Of HealthCare Outcome Measurement (ICHOM) was founded which has defined global Standard Sets for measuring the outcome of various treatments. Method: Monitoring of Clinical Outcomes was identified as a pillar of Fortis’ core value of Patient Centricity. The project was started as an in-house developed Clinical Outcomes Reporting Portal by the Fortis Medical IT team. Standard sets of Outcome measurement developed by ICHOM were used. A pilot was run at Fortis Escorts Heart Institute from Aug’13 – Dec’13.Starting Jan’14, it was implemented across 11 hospitals of the group. The scope was hospital-wide and major clinical specialties: Cardiac Sciences, Orthopedics & Joint Replacement were covered. The internally developed portal had its limitations of report generation and also capturing of Patient related outcomes was restricted. A year later, the company provisioned for an ICHOM Certified Software product which could provide a platform for data capturing and reporting to ensure compliance with all ICHOM requirements. Post a year of the launch of the software; Fortis Healthcare has become the 1st Healthcare Provider in Asia to publish Clinical Outcomes data for the Coronary Artery Disease Standard Set comprising of Coronary Artery Bypass Graft and Percutaneous Coronary Interventions) in the public domain. (Jan 2016). Results: This project has helped in firmly establishing a culture of monitoring and reporting Clinical Outcomes across Fortis Hospitals. Given the diverse nature of the healthcare delivery model at Fortis Network, which comprises of hospitals of varying size and specialty-mix and practically covering the entire span of the country, standardization of data collection and reporting methodology is a huge achievement in itself. 95% case reporting was achieved with more than 90% data completion at the end of Phase 1 (March 2016). Post implementation the group now has one year of data from its own hospitals. This has helped identify the gaps and plan towards ways to bridge them and also establish internal benchmarks for continual improvement. Besides the value created for the group includes: 1. Entire Fortis community has been sensitized on the importance of Clinical Outcomes monitoring for patient centric care. Initial skepticism and cynicism has been countered by effective stakeholder engagement and automation of processes. 2. Measuring quality is the first step in improving quality. Data analysis has helped compare clinical results with best-in-class hospitals and identify improvement opportunities. 3. Clinical fraternity is extremely pleased to be part of this initiative and has taken ownership of the project. Conclusion: Fortis Healthcare is the pioneer in the monitoring of Clinical Outcomes. Implementation of ICHOM standards has helped Fortis Clinical Excellence Program in improving patient engagement and strengthening its commitment to its core value of Patient Centricity. Validation and certification of the Clinical Outcomes data by an ICHOM Certified Supplier adds confidence to its claim of being leaders in this space.

Keywords: clinical outcomes, healthcare delivery, patient centricity, ICHOM

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Authors: Naveen Kumar B. T., Anuj Tyagi, Niraj Kumar Singh, Visanu Boonyawiwat, Shanthanagouda A. H., Orawan Boodde, Shankar K. M., Prakash Patil, Shubhkaramjeet Kaur

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Since 2009, Acute Hepatopancreatic Necrosis Disease (AHPND) outbreaks have increased rapidly, and these have led to the major economic losses to the global shrimp industry. In comparison to other treatments, passive immunity and monoclonal antibody (MAb) based farmer level kit have proved their importance in controlling and treating the diseases in the shrimp industry. In the present study, MAbs were produced against the recombinant PirB protein Vibrio parahaemolyticus strain causing AHPND. Briefly, Balb/C mice were immunized with rPirB at 15 days interval, and antibody titer was determined by ELISA. Spleen cells from mice showing high antibody titer were fused with SP2O myeloma cells for hybridoma production. Among 130 hybridomas, four showed high antibody titer and positive reactivity in an immunoblot assay. In Western blot assay, three out of four MAbs (4C4, 2C2 and 4G3) showed reactivity to rPirB protein. However, in the natural host, only Mab clone 4G3 show strong reactivity (with a strain of V. parahemolyticus causing EMS/AHPND). These clones also showed reactivity with less than 20 kDa proteins in AHPND free V. parahaemolyticus (Thailand stain). Further, on from MAb 4G3 clone, four panels of single cell MAbs clones (G3F5, G3B8, G3H2, and G3D6) were produced of which three showed strong positive reactivity to rPirB protein in the Western blot. These MAbs have potential for controlling and prevention of the AHPND through passive immunity and development of filed level rapid diagnostic kits.

Keywords: shrimp, economic loss, AHPND, MAb

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Authors: Shalu Jain, Anju Bansal, Anup Kumar, Sunita Saxena

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Objectives: The novel TMPRSS2:ERG gene fusion is a common somatic event in prostate cancer that in some studies is linked with a more aggressive disease phenotype. Thus, this study aims to determine whether clinical variables are associated with the presence of TMPRSS2:ERG-fusion gene transcript in Indian patients of prostate cancer. Methods: We evaluated the clinical variables with presence and absence of TMPRSS2:ERG gene fusion in prostate cancer and BPH association of clinical patients. Patients referred for prostate biopsy because of abnormal DRE or/and elevated sPSA were enrolled for this prospective clinical study. TMPRSS2:ERG mRNA copies in samples were quantified using a Taqman chemistry by real time PCR assay in prostate biopsy samples (N=42). The T2:ERG assay detects the gene fusion mRNA isoform TMPRSS2 exon1 to ERG exon4. Results: Histopathology report has confirmed 25 cases as prostate cancer adenocarcinoma (PCa) and 17 patients as benign prostate hyperplasia (BPH). Out of 25 PCa cases, 16 (64%) were T2: ERG fusion positive. All 17 BPH controls were fusion negative. The T2:ERG fusion transcript was exclusively specific for prostate cancer as no case of BPH was detected having T2:ERG fusion, showing 100% specificity. The positive predictive value of fusion marker for prostate cancer is thus 100% and the negative predictive value is 65.3%. The T2:ERG fusion marker is significantly associated with clinical variables like no. of positive cores in prostate biopsy, Gleason score, serum PSA, perineural invasion, perivascular invasion and periprostatic fat involvement. Conclusions: Prostate cancer is a heterogeneous disease that may be defined by molecular subtypes such as the TMPRSS2:ERG fusion. In the present prospective study, the T2:ERG quantitative assay demonstrated high specificity for predicting biopsy outcome; sensitivity was similar to the prevalence of T2:ERG gene fusions in prostate tumors. These data suggest that further improvement in diagnostic accuracy could be achieved using a nomogram that combines T2:ERG with other markers and risk factors for prostate cancer.

Keywords: prostate cancer, genetic rearrangement, TMPRSS2:ERG fusion, clinical variables

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Authors: Sayyed Mostafa Ahmadi, Neda Raeesi

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Background and Objectives: Cervical spondylosis is a common problem that affects the adult spine and is the most common cause of radiculopathy and myelopathy in older patients. Anterior discectomy and fusion is a well-known technique in degenerative cervical disc disease. However, one of the late undesirable complications is adjacent disc degeneration, which affects about 91% of patients in ten years. Many factors can be effective in causing this complication, but some are still debatable. Discovering these risk factors and eliminating them can improve the quality of life. Methods: This is a retrospective cohort study. All patients who underwent anterior discectomy and fusion surgery in the neurosurgery ward of Imam Khomeini Hospital between 2013 and 2016 were evaluated. Their demographic information was collected. All patients were visited and examined for radiculopathy, myelopathy, and muscular force. At the same visit, all patients were asked to have a facelift, and neck profile, as well as a neck MRI(General Tesla 3). Preoperative graphs were used to measure the diameter of the cervical canal(Pavlov ratio) and to evaluate sagittal alignment(Cobb Angle). Preoperative MRI of patients was reviewed for anterior and posterior longitudinal ligament calcification. Result: In this study, 57 patients were studied. The mean age of patients was 50.63 years, and 49.1% were male. Only 3.5% of patients had anterior and posterior longitudinal ligament calcification. Symptomatic ASD was observed in 26.6%. The X-rays and MRIs showed evidence of 80.7% radiological ASD. Among patients who underwent one-level surgery, 20% had symptomatic ASD, but among patients who underwent two-level surgery, the rate of ASD was 50%.In other words, the higher the number of surfaces that are operated and fused, the higher the probability of symptomatic ASD(P-value <0.05). The X-rays and MRIs showed 80.7% of radiological ASD. Among patients who underwent surgery at one level, 78% had radiological ASD, and this number was 92% among patients who underwent two-level surgery(P-value> 0.05). Demographic variables such as age, sex, height, weight, and BMI did not have a significant effect on the incidence of radiological ASD(P-value> 0.05), but sex and height were two influential factors on symptomatic ASD(P-value <0.05). Other related variables such as family history, smoking and exercise also have no significant effect(P-value> 0.05). Radiographic variables such as Pavlov ratio and sagittal alignment were also unaffected by the incidence of radiological and symptomatic ASD(P-value> 0.05). The number of surgical surfaces and the incidence of anterior and posterior longitudinal ligament calcification before surgery also had no statistically significant effect(P-value> 0.05). In the study of the ability of the neck to move in different directions, none of these variables are statistically significant in the two groups with radiological and symptomatic ASD and the non-affected group(P-value> 0.05). Conclusion: According to the findings of this study, this disease is considered to be a multifactorial disease. The incidence of radiological ASD is much higher than symptomatic ASD (80.7% vs. 26.3%) and sex, height and number of fused surfaces are the only factors influencing the incidence of symptomatic ASD and no variable influences radiological ASD.

Keywords: risk factors, anterior neck disectomy and fusion, adjucent segment degeneration, complication

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Authors: Joanna Gerszon, Aleksandra Rodacka

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In the pathogenesis of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, protein and peptide aggregation processes play a vital role in contributing to the formation of intracellular and extracellular protein deposits. One of the major components of these deposits is the oxidatively modified glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Therefore, the purpose of this research was to answer the question whether piceatannol, a stilbene derivative, counteracts and/or slows down oxidative stress-induced GAPDH aggregation. The study also aimed to determine if this natural occurring compound prevents unfavorable nuclear translocation of GAPDH in hippocampal cells. The isothermal titration calorimetry (ITC) analysis indicated that one molecule of GAPDH can bind up to 8 molecules of piceatannol (7.3 ± 0.9). As a consequence of piceatannol binding to the enzyme, the loss of activity was observed. Parallel with GAPDH inactivation the changes in zeta potential, and loss of free thiol groups were noted. Nevertheless, the ligand-protein binding does not influence the secondary structure of the GAPDH. Precise molecular docking analysis of the interactions inside the active center allowed to presume that these effects are due to piceatannol ability to assemble a covalent binding with nucleophilic cysteine residue (Cys149) which is directly involved in the catalytic reaction. Molecular docking also showed that simultaneously 11 molecules of ligand can be bound to dehydrogenase. Taking into consideration obtained data, the influence of piceatannol on level of GAPDH aggregation induced by excessive oxidative stress was examined. The applied methods (thioflavin-T binding-dependent fluorescence as well as microscopy methods - transmission electron microscopy, Congo Red staining) revealed that piceatannol significantly diminishes level of GAPDH aggregation. Finally, studies involving cellular model (Western blot analyses of nuclear and cytosolic fractions and confocal microscopy) indicated that piceatannol-GAPDH binding prevents GAPDH from nuclear translocation induced by excessive oxidative stress in hippocampal cells. In consequence, it counteracts cell apoptosis. These studies demonstrate that by binding with GAPDH, piceatannol blocks cysteine residue and counteracts its oxidative modifications, that induce oligomerization and GAPDH aggregation as well as it prevents hippocampal cells from apoptosis by retaining GAPDH in the cytoplasm. All these findings provide a new insight into the role of piceatannol interaction with GAPDH and present a potential therapeutic strategy for some neurological disorders related to GAPDH aggregation. This work was supported by the by National Science Centre, Poland (grant number 2017/25/N/NZ1/02849).

Keywords: glyceraldehyde-3-phosphate dehydrogenase, neurodegenerative disease, neuroprotection, piceatannol, protein aggregation

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Authors: Mark Berry

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A number of studies have identified several factors involved in the malignant progression of cancer cells. The Primary modulator in driving inflammation to these transformed cells has been identified as the transcription factor known as nuclear factor-κB. This essential regulator of inflammation and the development of cancer, combined with a microenvironment of inflammation and signaling molecules, plays a major role in the malignant progression of cancer, and this progression is the result of the mutagenic predisposition of persistent substances that combat infection at tumor sites and other areas of chronic inflammation. Inflammation-induced tumors, and their inflammatory cells and regulators may be the primary source of metastasis of tumor cells through angiogenesis. Previous research on cytokines and chemokines, including their downstream targets, has been the focus of the cancer/inflammation connection. The identification of the biological mechanisms of other proteins vital to the inflammation cascade and their interactions are crucial to novel and effective therapeutic protocols for the treatment of inflammation-induced cancers. The Ancelim HSRP Protocol is just such a therapeutic intervention.

Keywords: ancelim, cancer, inflammation, tumor

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Authors: Makkhan Lal Meena, R. C. Bairwa, G. S. Dangayach, Rahul Jain

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The current study looked at the frequency of chronic illness conditions, accidents, health complaints, and ergonomic issues among 100 conventional and 100 greenhouse farmers. Data related to the health symptoms and ergonomic problems were collected through questionnaires by conducting direct interviews of farmers. According to the findings, symptoms of heat exposure (skin rashes, headache, dizziness, and lack of appetite) were substantially higher among conventional farmers than greenhouse farmers. The greenhouse farmers reported much more pain, numbness, or weakness in wrists/hands, fingers, upper back, hips, and ankles/feet than conventional farmers. The findings of the study suggest that suitable ergonomic knowledge and awareness campaign programs concentrating on safety at work, particularly low back pain, should be implemented in workplaces to allow for earlier detection of symptoms among the greenhouse farmers.

Keywords: accident, conventional farmer, ergonomics, health symptoms, greenhouse farmers, pesticide

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Authors: Ioannis Panagiotopoulos, Aristidis Anastasakis, Konstantinos Toutouzas, Ioannis Iakovou, Charalampos Vlachopoulos, Vasilis Voudris, Georgios Tziomalos, Konstantinos Tsioufis, Efstathios Kastritis, Alexandros Briassoulis, Kimon Stamatelopoulos, Alexios Antonopoulos, Paraskevi Exadaktylou, Evanthia Giannoula, Anastasia Katinioti, Maria Kalantzi, Evangelos Leontiadis, Eftychia Smparouni, Ioannis Malakos, Nikolaos Aravanis, Argyrios Doumas, Maria Koutelou

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Introduction: Cardiac amyloidosis from Transthyretin (ATTR-CA) is an infiltrative disease characterized by the deposition of pathological transthyretin complexes in the myocardium. This study describes the characteristics of patients diagnosed with ATTR-CA from 2019 until present at the Nuclear Medicine Department of Onassis Cardiac Surgery Center and AHEPA Hospital. These centers have extensive experience in amyloidosis and modern technological equipment for its diagnosis. Materials and Methods: Records of consecutive patients (N=73) diagnosed with any type of amyloidosis were collected, analyzed, and prospectively followed. The diagnosis of amyloidosis was made using specific myocardial scintigraphy with Tc-99m DPD. Demographic characteristics, including age, gender, marital status, height, and weight, were collected in a database. Clinical characteristics, such as amyloidosis type (ATTR and AL), serum biomarkers (BNP, troponin), electrocardiographic findings, ultrasound findings, NYHA class, aortic valve replacement, device implants, and medication history, were also collected. Some of the most significant results are presented. Results: A total of 73 cases (86% male) were diagnosed with amyloidosis over four years. The mean age at diagnosis was 82 years, and the main symptom was dyspnea. Most patients suffered from ATTR-CA (65 vs. 8 with AL). Out of all the ATTR-CA patients, 61 were diagnosed with wild-type and 2 with two rare mutations. Twenty-eight patients had systemic amyloidosis with extracardiac involvement, and 32 patients had a history of bilateral carpal tunnel syndrome. Four patients had already developed polyneuropathy, and the diagnosis was confirmed by DPD scintigraphy, which is known for its high sensitivity. Among patients with isolated cardiac involvement, only 6 had left ventricular ejection fraction below 40%. The majority of ATTR patients underwent tafamidis treatment immediately after diagnosis. Conclusion: In conclusion, the experiences shared by the two centers and the continuous exchange of information provide valuable insights into the diagnosis and management of cardiac amyloidosis. Clinical suspicion of amyloidosis and early diagnostic approach are crucial, given the availability of non-invasive techniques. Cardiac scintigraphy with DPD can confirm the presence of the disease without the need for a biopsy. The ultimate goal still remains continuous education and awareness of clinical cardiologists so that this systemic and treatable disease can be diagnosed and certified promptly and treatment can begin as soon as possible.

Keywords: amyloidosis, diagnosis, myocardial scintigraphy, Tc-99m DPD, transthyretin

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Authors: J. Al-Dmour, A. Sagahyroon, A. Al-Ali, S. Abusnana

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Radio Frequency Based Identification Systems have emerged as one of the possible valuable solutions that can be utilized in healthcare systems. Nowadays, RFID tags are available with built-in human vital signs sensors such as Body Temperature, Blood Pressure, Heart Rate, Blood Sugar level and Oxygen Saturation in Blood. This work proposes the design, implementation, and testing of an integrated mobile RFID-based health care system. The system consists of a wireless mobile vital signs data acquisition unit (RFID-DAQ) integrated with a fuzzy-logic–based software algorithm to monitor and assess patients conditions. The system is implemented and tested in ‘Rashid Center for Diabetes and Research’, Ajman, UAE. System testing results are compared with the Modified Early Warning System (MEWS) that is currently used in practice. We demonstrate that the proposed and implemented system exhibits an accuracy level that is comparable and sometimes better than the widely adopted MEWS system.

Keywords: healthcare, fuzzy logic, MEWS, RFID

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Authors: Warda Jabeen, Romaisa Shamim Khan, Osama Shakeel, Ahmed Faraz Bhatti, Raza Hussain

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Background: The worldwide incidence of cutaneous melanoma (CM) has been on the rise over the past few decades. Primary prevention and early treatment remain the focus of management to reduce the burden of disease. This entails identification of risk factors to prompt early diagnosis. In Pakistan, there is a scarcity of clinico-pathological data relating to cutaneous malignant melanoma. Objective: The purpose of this study was to analyze the epidemiological and clinical characteristics of patients presenting with cutaneous malignant melanoma in Pakistan, and to compare the results with other studies. Method: Shaukat Khanum Memorial Cancer Hospital and Research Centre is currently the only dedicated cancer hospital in the country, accepting patients from all over Pakistan. Majority of the patients, however, belong to the northern half of the country. From the recorded data of the hospital, all cutaneous melanoma cases were identified and evaluated. Results: Between 1997 and 2017, a total of 169 cutaneous melanoma patients were registered at Shaukat Khanum. Mean age was 47.5 years. The highest incidence of melanoma was seen in the age group 40-59 years (n=69, 40.8%). Most commonly reported clinical subtype was unspecified melanoma (n=154, 91%). Amongst those in which T stage was reported, the most frequently observed T-stage at presentation was T4 (n=23, 13.6%). With regards to body distribution, in our study CM was seen most commonly in the lower limb including the hip. The yearly incidence of melanoma has increased/remained stable from 2007 to 2017. Conclusion: cutaneous malignant melanoma is a fairly common disease in Pakistan. Patients tend to present at a more advanced stage as compared to patients in developed countries. Identification of risk factors and tumor characteristics is therefore of paramount importance to deal with these patients.

Keywords: epidemiology of cutaneous malignant melanoma, cutaneous malignant melanoma, Pakistan, skin cancer

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Authors: Muchiri Josephine, Qdero Agnes

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The current study was conducted during the coronavirus pandemic (COVID-19) period, soon after the lifting of the lockdown measures and schools had just re-opened. It investigated the sociodemographic correlates of Post-Traumatic Stress Disorder (PTSD) among adolescents (13-18 years) who had undergone domestic violence (DV) in Kajiado County, Kenya. The adolescents were administered a sociodemographic questionnaire to ascertain the forms of domestic violence experienced, and those who met the criteria were assessed for the presence of PTSD using the Harvard Trauma Questionnaire (HTQ). Overall, 93(90.3%) had experienced domestic violence, and 57(61.3%) had PTSD; where the severity and prevalence of PTSD increased with increased age, and it also increased significantly among those in higher academic levels, indicating that PTSD prevalence was chronic and additionally influenced by increased academic pressure. Social connections seemed to mitigate PTSD prevalence, whereas, regarding the family background, those living with guardians seemed to have more severe PTSD.

Keywords: age, education level, gender, post-traumatic stress disorder

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Authors: Abdorrasoul Malekpour, Mohammad Ghorbani Mojtaba Mortazavi, Mohammadreza Fattahi, Mohammad Hassan Meshkibaf, Ali Fakhrzad, Saeid Salehi, Saeideh Zahedi, Amir Ahmadimoghaddam, Parviz Farzadnia Dr., Mohammadreza Hajyani Asl Bs

Abstract:

Hepatitis B as an infectious disease has eight main genotypes (A–H). The aim of this study is to Bioinformatically identify Rare Codon Clusters (RCC) in proteins structure of HBV. For detection of protein family accession numbers (Pfam) of HBV proteins; used of uni-prot database and Pfam search tool were used. Obtained Pfam IDs were analyzed in Sherlocc program and RCCs in HBV proteins were detected. In further, the structures of TrEMBL entries proteins studied in PDB database and 3D structures of the HBV proteins and locations of RCCs were visualized and studied using Swiss PDB Viewer software. Pfam search tool have found nine significant hits and 0 insignificant hits in 3 frames. Results of Pfams studied in the Sherlocc program show this program not identified RCCs in the external core antigen (PF08290) and truncated HBeAg protein (PF08290). By contrast the RCCs become identified in Hepatitis core antigen (PF00906) Large envelope protein S (PF00695), X protein (PF00739), DNA polymerase (viral) N-terminal domain (PF00242) and Protein P (Pf00336). In HBV genome, seven RCC identified that found in hepatitis core antigen, large envelope protein S and DNA polymerase proteins and proteins structures of TrEMBL entries sequences that reported in Sherlocc program outputs are not complete. Based on situation of RCC in structure of HBV proteins, it suggested those RCCs are important in HBV life cycle. We hoped that this study provide a new and deep perspective in protein research and drug design for treatment of HBV.

Keywords: rare codon clusters, hepatitis B virus, bioinformatic study, infectious disease

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Authors: Francesca Nardi, Kashish Aneja, Katherine Ginsbach

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The COVID-19 pandemic has demonstrated both a need for evidence-based and rights-based public health policy and how challenging it can be to make effective decisions with limited information, evidence, and data. The O’Neill Institute, in conjunction with several partners, has been working since the beginning of the pandemic to collect, analyze, and distribute critical data on public health policies enacted in response to COVID-19 around the world in the COVID-19 Law Lab. Well-designed laws and policies can help build strong health systems, implement necessary measures to combat viral transmission, enforce actions that promote public health and safety for everyone, and on the individual level have a direct impact on health outcomes. Poorly designed laws and policies, on the other hand, can fail to achieve the intended results and/or obstruct the realization of fundamental human rights, further disease spread, or cause unintended collateral harms. When done properly, laws can provide the foundation that brings clarity to complexity, embrace nuance, and identifies gaps of uncertainty. However, laws can also shape the societal factors that make disease possible. Law is inseparable from the rest of society, and COVID-19 has exposed just how much laws and policies intersects all facets of society. In the COVID-19 context, evidence-based and well-informed law and policy decisions—made at the right time and in the right place—can and have meant the difference between life or death for many. Having a solid evidentiary base of legal information can promote the understanding of what works well and where, and it can drive resources and action to where they are needed most. We know that legal mechanisms can enable nations to reduce inequities and prepare for emerging threats, like novel pathogens that result in deadly disease outbreaks or antibiotic resistance. The collection and analysis of data on these legal mechanisms is a critical step towards ensuring that legal interventions and legal landscapes are effectively incorporated into more traditional kinds of health science data analyses. The COVID-19 Law Labs see a unique opportunity to collect and analyze this kind of non-traditional data to inform policy using laws and policies from across the globe and across diseases. This global view is critical to assessing the efficacy of policies in a wide range of cultural, economic, and demographic circumstances. The COVID-19 Law Lab is not just a collection of legal texts relating to COVID-19; it is a dataset of concise and actionable legal information that can be used by health researchers, social scientists, academics, human rights advocates, law and policymakers, government decision-makers, and others for cross-disciplinary quantitative and qualitative analysis to identify best practices from this outbreak, and previous ones, to be better prepared for potential future public health events.

Keywords: public health law, surveillance, policy, legal, data

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Authors: Mariam Aref Mahmoud

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After centuries of historical development, Egypt is no stranger to national identity frustrations. What may or may not be counted as this “national identity” becomes a source of contention. Today, after decades of neoliberal reform, Cairo has become the center of Egypt’s cultural debacle. At its heart, the Egyptian capital serves as Egypt’s extension into global capitalism, its flailing hope to become part of the modernized, cosmopolitan world. Yet, to converge into this image of cosmopolitanism, Cairo must silence the perceived un-modernized sounds, cultures, and spaces that arise from within its alleyways. Currently, the agitation surrounding shaabi music, particularly, that of mahraganat, places these contentions to the center of the modernization debates. This paper will discuss the process through which the conversations between modernization, space, and culture have taken place through a historical analysis of national identity formation under Egypt’s neoliberal regimes. Through this, the paper concludes that music becomes a spatial force through which public space, identity, and globalization must be contested. From these findings researchers can then analyze Cairo through not only its physical landscapes, but also its metaphysical features – such as the soundscape.

Keywords: music, space, globalization, Cairo

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Authors: Felix Gbenoba, Opeyemi Dahunsi

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Customised, self-instructional materials are at the heart of instructional delivery in Open and Distance Learning (ODL). The success of any ODL institution depends on the availability of learning materials in quality and quantity. An ODL study material is expected to imitate what the teacher does in the face-to-face learning environment. This paper evaluates these expectation based on existing data and evidence. It concludes that the reality has not matched the expectation so far in terms of pedagogic aspect of instructional delivery especially in West Africa. This does not mean that instructional materials development has not produced any significant positive results in improving the overall learning (and teaching) experience in these institutions; it implies what will help further to identify the new challenges. Obstacles and problems of instructional materials development that could have affected the open educational resource initiatives are well established. The first section of this paper recalls some of the proposed values of instructional materials. The second section compares achievements so far and suggests that instructional materials development should be consider first at an early stage to realise the aspirations of instructional delivery. The third section highlights the challenges of instructional materials development in the future.

Keywords: face-to-face learning, instructional delivery, open and distance education, self-instructional materials

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Authors: Marco Frieslaar, Bing Chu, Eric Rogers

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Stroke is a devastating illness that is the second biggest cause of death in the world (after heart disease). Where it does not kill, it leaves survivors with debilitating sensory and physical impairments that not only seriously harm their quality of life, but also cause a high incidence of severe depression. It is widely accepted that early intervention is essential for recovery, but current rehabilitation techniques largely favor hospital-based therapies which have restricted access, expensive and specialist equipment and tend to side-step the emotional challenges. In addition, there is insufficient funding available to provide the long-term assistance that is required. As a consequence, recovery rates are poor. The relatively unexplored solution is to develop therapies that can be harnessed in the home and are formulated from technologies that already exist in everyday life. This would empower individuals to take control of their own improvement and provide choice in terms of when and where they feel best able to undertake their own healing. This research seeks to identify how effective post-stroke, rehabilitation therapy can be applied to upper limb mobility, within the physical context of a home rather than a hospital. This is being achieved through the design and construction of an automation scheme, based on iterative learning control and the Riener muscle model, that has the ability to adapt to the user and react to their level of fatigue and provide tangible physical recovery. It utilizes a SMART Phone and laptop to construct an iterative learning control (ILC) system, that monitors upper arm movement in three dimensions, as a series of exercises are undertaken. The equipment generates functional electrical stimulation to assist in muscle activation and thus improve directional accuracy. In addition, it monitors speed, accuracy, areas of motion weakness and similar parameters to create a performance index that can be compared over time and extrapolated to establish an independent and objective assessment scheme, plus an approximate estimation of predicted final outcome. To further extend its assessment capabilities, nerve conduction velocity readings are taken by the software, between the shoulder and hand muscles. This is utilized to measure the speed of response of neuron signal transfer along the arm and over time, an online indication of regeneration levels can be obtained. This will prove whether or not sufficient training intensity is being achieved even before perceivable movement dexterity is observed. The device also provides the option to connect to other users, via the internet, so that the patient can avoid feelings of isolation and can undertake movement exercises together with others in a similar position. This should create benefits not only for the encouragement of rehabilitation participation, but also an emotional support network potential. It is intended that this approach will extend the availability of stroke recovery options, enable ease of access at a low cost, reduce susceptibility to depression and through these endeavors, enhance the overall recovery success rate.

Keywords: home-based therapy, iterative learning control, Riener muscle model, SMART phone, stroke rehabilitation

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Authors: Daniel C. S. Lim, W. Y. Tan

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The world is facing a growing food crisis. The concerns of food nutritional value, food safety and food security are becoming increasingly real. There is also a direct relationship to the risk of diseases, particularly chronic diseases, to the food we consume. So, there are increasing concerns about the modern day food ecosystem creating foods that can provide the nutritional components for organ function sustenance, as well as, taking a serious view on diet-related diseases. This paper addresses some of the above concerns and gives an overview of the current global situation relating to food nutrition and safety. The paper reviews nutritional aspects of food today compared to those of the last century, compares whole foods found in supermarkets versus those organically grown, as well as population behaviour towards food choices. It provides scientific insights into the effects of some of the global trends such as climate change and other changes environmental changes, and presents what individuals and corporations are doing to use the latest nutritional technologies as strategic assets. Finally, it briefly highlights some of the innovative solutions that are being applied to address several of the above concerns.

Keywords: food crisis, food safety, global trends, nutritional aspects

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Authors: Babak Nemat

Abstract:

Background and Purpose: Non-alcoholic fatty liver is one of the most common liver disorders, which, as the most important cause of death from liver disease, has unpleasant consequences and complications. The aim of this study was to investigate the effect of an educational intervention based on a health belief model to prevent non-alcoholic fatty liver among women. Materials and Methods: This experimental study was performed among 110 women referring to comprehensive health service centers in Malayer City, west of Iran, in 2023. Using the available sampling method, 110 participants were divided into experimental and control groups. The data collection tool included demographic characteristics and a questionnaire based on the health belief model. In the experimental group, three one-hour training sessions were conducted in the form of pamphlets, lectures, and group discussions. Data were analyzed using SPSS software version 21, by correlation tests, paired t-tests, and independent t-tests. Results: The mean age of participants was 38.07±6.28 years, and most of the participants were middle-aged, married, housewives with academic education, middle-income, and overweight. After the educational intervention, the mean scores of the constructs include perceived sensitivity (p=0.01), perceived severity (p=0.01), perceived benefits (p=0.01), guidance for internal (p=0.01), and external action (p=0.01), and perceived self-efficacy (p=0.01) in the experimental group were significantly higher than the control group. The score of perceived barriers in the experimental group decreased after training. The perceived obstacles score in the test group decreased after the training (15.2 ± 3.9 v.s 11.2 ± 3.3, (p<0.01). Conclusion: The findings of the study showed that the design and implementation of educational programs based on the constructs of the health belief model can be effective in preventing women from developing higher levels of non-alcoholic fatty liver.

Keywords: non-alcoholic fatty liver, health belief model, education, women

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Authors: Zinhle Cindi, Collet Dandara, Mpiko Ntsekhe, Edson Makambwa, Miguel Larceda

Abstract:

Background: Warfarin is the most commonly used drug in the management of thromboembolic disease. However, there is a huge variability in the time, number of doses or starting doses for patients to achieve the required international normalised ratio (INR) which is compounded by a narrow therapeutic index. Many genetic-association studies have reported on European and Asian populations which have led to the designing of specific algorithms that are now being used to assist in warfarin dosing. However, very few or no studies have looked at the pharmacogenetics of warfarin in African populations, yet, huge differences in dosage requirements to reach the same INR have been observed. Objective: We set out to investigate the distribution of 3 SNPs CYP4F2 c.1347C > T, VKORC1 g.-1639G > A and VKORC1 c.1173C > T among South African Mixed Ancestry (MA) and Black African patients. Methods: DNA was extracted from 383 participants and subsequently genotyped using PCR/RFLP for the CYP4F2 c.1347 (V433M) (rs2108622), VKORC1 g.-1639 (rs9923231) and VKORC1 c.1173 (rs9934438) SNPs. Results: Comparing the Black and MA groups, significant differences were observed in the distribution of the following genotypes; CYP4F2 c.1347C/T (23% vs. 39% p=0.03). All VKORC1 g.-1639G > A genotypes (p < 0.006) and all VKORC1 c.1173C > T genotypes (p < 0.007). Conclusion: CYP4F2 c.1347T (V433M) reduces CYP4F2 protein levels and therefore expected to affect the amount of warfarin needed to block vitamin k recycling. The VKORC1 g-1639A variant alters transcriptional regulation therefore affecting the function of vitamin k epoxide reductase in vitamin k production. The VKORC1 c.1173T variant reduces the enzyme activity of VKORC1 consequently enhancing the effectiveness of warfarin. These are preliminary results; more genetic characterization is required to understand all the genetic determinants affecting how patients respond to warfarin.

Keywords: algorithms, pharmacogenetics, thromboembolic disease, warfarin

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Authors: V. T. Gerov, D. I. Gerova, I. D. Micheva, N. F. Nazifova-Tasinova, M. N. Nikolova, M. G. Pasheva, B. T. Galunska

Abstract:

Multiple myeloma (MM) is the most frequent plasma cell (PC) dyscrasia that involves the skeleton. Myeloma bone disease (MBD) is characterized by osteolytic bone lesions as a result of increased osteoclasts activity not followed by reactive bone formation due to osteoblasts suppression. Skeletal complications cause significant adverse effects on quality of life and lead to increased morbidity and mortality. Last decade studies revealed the implication of different proteins in osteoclast activation and osteoblast inhibition. The aim of the present study was to determine serum levels of periostin, sRANKL and osteopontin and to evaluate their role as bone markers in MBD. Materials and methods. Thirty-two newly diagnosed MM patients (mean age: 62.2 ± 10.7 years) and 33 healthy controls (mean age: 58.9 ± 7.5 years) were enrolled in the study. According to IMWG criteria 28 patients were with symptomatic MM and 4 with monoclonal gammopathy of undetermined significance (MGUS). In respect to their bone involvement all symptomatic patients were divided into two groups (G): 9 patients with 0-3 osteolytic lesions (G1) and 19 patients with >3 osteolytic lesions and/or pathologic fractures (G2). Blood samples were drawn for routine laboratory analysis and for measurement of periostin, sRANKL and osteopontin serum levels by ELISA kits (Shanghai Sunred Biological Technology, China). Descriptive analysis, Mann-Whitney test for assessment the differences between groups and non-parametric correlation analysis were performed using GraphPad Prism v8.01. Results. The median serum levels of periostin, sRANKL and osteopontin of ММ patients were significantly higher compared to controls (554.7pg/ml (IQR=424.0-720.6) vs 396.9pg/ml (IQR=308.6-471.9), p=0.0001; 8.9pg/ml (IQR=7.1-10.5) vs 5.6pg/ml (IQR=5.1-6.4, p<0.0001 and 514.0ng/ml (IQR=469.3-754.0) vs 387.0ng/ml (IQR=335.9-441.9), p<0.0001, respectively). for assessment of differences between groups and non-parametric correlation analysis were performed using GraphPad Prism v8.01. Statistical significance was found for all tested bone markers between symptomatic MM patients and controls: G1 vs controls (p<0.03), G2 vs controls (p<0.0001) for periostin; G1 vs controls (p<0.0001), G2 vs controls (p<0.0001) for sRANKL; G1 vs controls (p=0.002), G2 vs controls (p<0.0001) for osteopontin, as well between symptomatic MM patients and MGUS patients: G1 vs MGUS (p<0.003), G2 vs MGUS (p=0.003) for periostin; G1 vs MGUS (p<0.05), G2 vs MGUS (p<0.001) for sRANKL; G1 vs MGUS (p=0.011), G2 vs MGUS (p=0.0001) for osteopontin. No differences were detected between MGUS and controls and between patients in G1 and G2 groups. Spearman correlation analysis revealed moderate positive correlation between periostin and beta-2-microglobulin (r=0.416, p=0.018), percentage bone marrow myeloma PC (r=0.432, p=0.014), and serum total protein (r=0.427, p=0.015). Osteopontin levels were also positively related to beta-2-microglobulin (r=0.540, p=0.0014), percentage bone marrow myeloma PC (r=0.423, p=0.016), and serum total protein (r=0.413, p=0.019). Serum sRANKL was only related to beta-2-microglobulin levels (r=0.398, p=0.024). Conclusion: In the present study, serum levels of periostin, sRANKL and osteopontin in newly diagnosed MM patients were evaluated. They gradually increased from MGUS to more advanced stages of MM reflecting the severity of bone destruction. These results support the idea that some new protein markers could be used in monitoring the MBD as a most severe complication of MM.

Keywords: myeloma bone disease, periostin, sRANKL, osteopontin

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