Search results for: chronic liver disease

Authors: Katarzyna Lubecka, Kirsty Flower, Megan Beetch, Lucinda Kurzava, Hannah Buvala, Samer Gawrieh, Suthat Liangpunsakul, Tracy Gonzalez, George McCabe, Naga Chalasani, James M. Flanagan, Barbara Stefanska

Abstract:

Hepatocellular carcinoma (HCC), the most prevalent type of primary liver cancer, is the second leading cause of cancer death worldwide. Late onset of clinical symptoms in HCC results in late diagnosis and poor disease outcome. Approximately 85% of individuals with HCC have underlying liver cirrhosis. However, not all cirrhotic patients develop cancer. Reliable early detection biomarkers that can distinguish cirrhotic patients who will develop cancer from those who will not are urgently needed and could increase the cure rate from 5% to 80%. We used Illumina-450K microarray to test whether blood DNA, an easily accessible source of DNA, bear site-specific changes in DNA methylation in response to HCC before diagnosis with conventional tools (pre-diagnostic). Top 11 differentially methylated sites were selected for validation by pyrosequencing. The diagnostic potential of the 11 pyrosequenced probes was tested in blood samples from a prospective cohort of cirrhotic patients. We identified 971 differentially methylated CpG sites in pre-diagnostic HCC cases as compared with healthy controls (P < 0.05, paired Wilcoxon test, ICC ≥ 0.5). Nearly 76% of differentially methylated CpG sites showed lower levels of methylation in cases vs. controls (P = 2.973E-11, Wilcoxon test). Classification of the CpG sites according to their location relative to CpG islands and transcription start site revealed that those hypomethylated loci are located in regulatory regions important for gene transcription such as CpG island shores, promoters, and 5’UTR at higher frequency than hypermethylated sites. Among 735 CpG sites hypomethylated in cases vs. controls, 482 sites were assigned to gene coding regions whereas 236 hypermethylated sites corresponded to 160 genes. Bioinformatics analysis using GO, KEGG and DAVID knowledgebase indicate that differentially methylated CpG sites are located in genes associated with functions that are essential for gene transcription, cell adhesion, cell migration, and regulation of signal transduction pathways. Taking into account the magnitude of the difference, statistical significance, location, and consistency across the majority of matched pairs case-control, we selected 11 CpG loci corresponding to 10 genes for further validation by pyrosequencing. We established that methylation of CpG sites within 5 out of those 10 genes distinguish cirrhotic patients who subsequently developed HCC from those who stayed cancer free (cirrhotic controls), demonstrating potential as biomarkers of early detection in populations at risk. The best predictive value was detected for CpGs located within BARD1 (AUC=0.70, asymptotic significance ˂0.01). Using an additive logistic regression model, we further showed that 9 CpG loci within those 5 genes, that were covered in pyrosequenced probes, constitute a panel with high diagnostic accuracy (AUC=0.887; 95% CI:0.80-0.98). The panel was able to distinguish pre-diagnostic cases from cirrhotic controls free of cancer with 88% sensitivity at 70% specificity. Using blood as a minimally invasive material and pyrosequencing as a straightforward quantitative method, the established biomarker panel has high potential to be developed into a routine clinical test after validation in larger cohorts. This study was supported by Showalter Trust, American Cancer Society (IRG#14-190-56), and Purdue Center for Cancer Research (P30 CA023168) granted to BS.

Keywords: biomarker, DNA methylation, early detection, hepatocellular carcinoma

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Authors: N. N. Pilau, M. S. Abubakar, A. Danmaigoro, P. C. Mshelia, Y. Sani

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A severely debilitated 4months old Caucasian male dog presented dehydration, emaciation, vomiting, icteric ocular and oral mucous membranes, generalized lymphadenopathy, hematuria, anorexia and prolonged recumbency. Clinical workup was done in established protocols for diagnosis based on history, clinical signs and selected laboratory tests. Treatment course were administered over 48hours during which the patient died of overwhelming hepatopathy, nephropathy and pneumonia. Postmortem findings supported by ante mortem laboratory test results tentatively diagnosed leptospirosis, a disease endemic and presenting potentially fatal epidemics and zoonoses in some countries amongst the developing regions of the world. This disease is reviewed and a call for attention on the public health significance of the disease is hereby presented through this case report.

Keywords: canine, endemic, leptospirosis, prevalence

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Authors: Mustafa M. Donma, Ayşen Haksayar, Bahadır Batar, Buse Tepe, Birol Topçu, Orkide Donma

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Childhood obesity is an ever-increasing health problem. The Association of obesity with severe chronic diseases such as diabetes and cardiovascular diseases makes the problem life-threatening. Aside from psychological, societal and metabolic factors, genetic polymorphisms have gained importance concerning etiology in recent years. The aim of this study was to evaluate the relationship between rs10455872 gene polymorphism in the Lipoprotein (a) locus and the development of childhood obesity. This was a prospective study carried out according to the Helsinki Declarations. The study protocol was approved by the Institutional Ethics Committee. This study was supported by Tekirdag Namik Kemal University Rectorate, Scientific Research Projects Coordination Unit. Project No: NKUBAP.02.TU.20.278. A total of 180 children (103 obese (OB) and 77 healthy), aged 6-18 years, without any acute or chronic disease, participated in the study. Two different groups were created: OB and healthy control. Each group was divided into two further groups depending on the nature of the polymorphism. Anthropometric measurements were taken during the detailed physical examination. Laboratory tests and TANITA measurements were performed. For the statistical evaluations, SPSS version 28.0 was used. A P-value smaller than 0.05 was the statistical significance degree. The distribution of lipoprotein (a) rs10455872 gene polymorphism did not differ between OB and healthy children. Children with AG genotype in both OB and control groups had lower body mass index (BMI), diagnostic obesity notation model assessment index (DONMA II), body fat ratio (BFR), C-reactive protein (CRP), and metabolic syndrome index (MetS index) values compared to children with normal AA genotype. In the OB group, serum iron, vitamin B12, hemoglobin, MCV, and MCH values were found to be higher in the AG genotype group than those of children with the normal AA genotype. A significant correlation was found between the MetS index and BFR among OB children with normal homozygous genotype. MetS index increased as BFR increased in this group. However, such a correlation was not observed in the OB group with heterozygous AG genotype. To the best of our knowledge, the association of lipoprotein (a) rs10455872 gene polymorphism with the etiology of childhood obesity has not been studied yet. Therefore, this study was the first report suggesting polymorphism with AG genotype as a good risk factor for obesity.

Keywords: child, gene polymorphism, lipoprotein (a), obesity, rs10455872

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Authors: Sirilak Kongkaew, Pathumwadee Yodmanee, Nopporn Kaiyawet, Arthitaya Meeprasert, Thanyada Rungrotmongkol, Toshikatsu Kaburaki, Hiroshi Noguchi, Fujio Takeuch, Nawee Kungwan, Supot Hannongbua

Abstract:

Behçet’s disease (BD) is a genetic autoimmune expressed by multisystemic inflammatory disorder mostly occurred at the skin, joints, gastrointestinal tract, and genitalia, including ocular, oral, genital, and central nervous systems. Most BD patients in Japan and Korea were strongly indicated by the genetic factor namely HLA-B*51 (especially, HLA-B*51:01) marker in HMC class I, while HLA-A*26:01 allele has been detected from the BD patients in Greek, Japan, and Taiwan. To understand the selective binding of the MICA-TM peptide towards the HLAs associated with BD, the molecular dynamics simulations were applied on the four HLA alleles (B*51:01, B*35:01, A*26:01, and A*11:01) in complex with such peptide. As a result, the key residues in the binding groove of HLA protein which play an important role in the MICA-TM peptide binding and stabilization were revealed. The Van der Waals force was found to be the main protein-protein interaction. Based on the binding free energy prediction by MM/PBSA method, the MICA-TM peptide interacted stronger to the HLA alleles associated to BD in the identical class by 7-12 kcal/mol. The obtained results from the present study could help to differentiate the HLA alleles and explain a source of Behçet’s disease.

Keywords: Behçet’s disease, MD simulations, HMC class I, autoimmune

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Authors: Mostafa Elbaba

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Because childhood renal diseases are grossly different compared to adult diseases, pediatric nephrology was founded as a specialty in 1965. Renal pathology specialty was introduced at the London Ciba Symposium in 1961. The history of renal pathology can be divided into two eras: one starting in the 1650s with the invention of the microscope, the second in the 1950s with the implementation of renal biopsy, and the presence of electron microscopy and immunofluorescence study. Prior to the 1950s, the study of diseased human kidneys was restricted to postmortem examination by gross pathology. In 1827, Richard Bright first described his triad of kidney disease, which was confirmed by morbid kidney changes at autopsy. In 1905 Friedrich Mueller coined the term “nephrosis” describing the inflammatory form of “degenerative” diseases, and later F. Munk added the term “lipoid nephrosis”. The most profound influence on renal diseases’ classification came from the publication of Volhard and Fahr in 1914. In 1899, Carl Max Wilhelm Wilms described Wilms' tumor of the kidneys in children. Chronic pyelonephritis was a popular renal diagnosis and the most common cause of uremia until the 1960s. Although kidney biopsy had been used early in the 1930s for renal tumors, the earliest reports of its use in the diagnosis of medical kidney disease were by Iversen and Brun in 1951, followed by Alwall in 1952, then by Pardo in 1953. The earliest intentional renal biopsies were done in 1944 by Nils Alwall, while the procedure was abandoned after the death of one of his 13 patients who biopsied. In 1950, Antonino Perez-Ara attempted renal biopsies, but his results were missed because of an unpopular journal publication. In the year 1951, Claus Brun and Poul Iverson developed the biopsy procedure using an aspiration technique. Popularizing renal biopsy practice is accredited to Robert Kark, who published his distinct work in 1954. He perfected the technique of renal biopsy in the prone position using the Vim-Silverman needle and used intravenous pyelography to improve the localization of the kidney.

Keywords: history, medicine, nephrology, pediatrics, pathology

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Authors: Myoungsoon You, Heejung Son

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Background: In the current study, we investigated the effects of emotions induced by an infectious disease outbreak on the various protective behaviors taken during the crisis and on the perception after the crisis. The investigation was based on two psychological theories of appraisal tendency and action tendency. Methods: A total of 900 participants in South Korea who experienced the 2015 Middle East Respiratory Syndrome outbreak were sampled by a professional survey agency. To assess the influence of the emotions fear and anger, a regression approach was used. The effect of emotions on various protective behaviors and perceptions was observed using a hierarchical regression method. Results: Fear and anger induced by the infectious disease outbreak were both associated with increased protective behaviors during the crisis. However, the differences between the emotions were observed. While protective behaviors with avoidance tendency (adherence to recommendations, self-mitigation), were raised by both fear and anger, protective behaviors with approach tendency (information-seeking) were increased by anger, but not fear. Regarding the effect of emotion on the risk perception after the crisis, only fear was associated with a higher level of risk perception. Conclusions: This study confirmed the role of emotions in crisis protective behaviors and post-crisis perceptions regarding an infectious disease outbreak. These findings could enhance understanding of the public’s protective behaviors during infectious disease outbreaks and afterward risk perception corresponding to emotions. The results also suggested strategies for communicating with the public that takes into account emotions that are prominently induced by crises associated with disease outbreaks.

Keywords: crisis communication, emotion, infectious disease outbreak, protective behavior, risk perception

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Authors: Emily Hickmann, Peggy Richter, Maren Kaehlig, Hannes Schlieter

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Patient engagement is a cornerstone of high-quality care and essential for patients with chronic diseases to achieve improved health outcomes. Through digital transformation, possibilities to engage patients in their personal healthcare have multiplied. However, the exploitation of this potential is still lagging. To support the transmission of patient engagement theory into practice, this paper’s objective is to give a state-of-the-art overview of patient engagement tools and methods. A systematic literature review was conducted. Overall, 56 tools and methods were extracted and synthesized according to the four attributes of patient engagement, i.e., personalization, access, commitment, and therapeutic alliance. The results are discussed in terms of their potential to be implemented in digital health solutions under consideration of the “computers are social actors” (CASA) paradigm. It is concluded that digital health can catalyze patient engagement in practice, and a broad future research agenda is formulated.

Keywords: chronic diseases, digitalization, patient-centeredness, patient empowerment, patient engagement

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Authors: Magda Milleyde de Sousa Lima, Letícia Lima Aguiar, Marina Guerra Martins, Erika Veríssimo Dias Sousa, Lizandra Sampaio de Oliveira, Lívia Moreira Barros, Joselany Áfio Caetano

Abstract:

Patients with chronic kidney disease are vulnerable to episodes which make the safety of their health vulnerable, mainly due to the treatment process that exposes them to high rates of interventions during hemodialysis sessions. Some factors associated with health care contribute to the risk of death and complications. However, there are a small number of scientific studies evaluating the level of safety of hemodialysis clinics, and the sociodemographic characteristics of patients and professionals associated with this safety. Therefore, the present study aims to examine the level of patient safety in hemodialysis clinics in the Brazilian capital, to identify the sociodemographic and clinical factors of patients and nursing staff associated with the level of safety. This is an observational, descriptive and quantitative research conducted in three hemodialysis clinics placed in the city of Fortaleza-CE, Brazil, from September to November 2019. The sample was formed after a sample calculation for finite inhabitants of correlation with 200 chronic renal patients, 30 nursing technicians and seven nurses. Conventional sampling was used based on the inclusion criteria: being present at the hemodialysis session on the day the researcher performed the data collection and being 18 years of age or older. Participants who presented communication difficulties to listen to and/or answer the sociodemographic and clinical questionnaire were excluded. Two instruments were applied: sociodemographic and clinical characterization form and Chronic Renal Patient Safety Assessment Scale on Hemodialysis (EASPRCH). The data were analyzed using the Kruskal Walls Test for categorical variables and Spearman correlation coefficient for non-categorical variables, using the Statistical Package SPSS version 20.0. The present study respected the ethical and legal principles determined by resolution 466/2012 of the National Health Council, under the approval of the Ethics and Research Committee with an opinion number: 3,255,635. The results showed that a hemodialysis clinic presented unsafe care practices of 32 points in the EASPRCH (p=0.001). A statistical association was identified between the level of safety and the variables of the patients: level of education (p=0.018), family income (p=0.049), type of employment (p=0.012), venous access site (p=0.009), use of medication during the session (p=0.008) and time of hemodialysis (p=0.002). When evaluating the profile of nurses, a statistical association was evidenced between the level of safety with the variables: marital status (p=0.000), race (p=0.017), schooling (p= 0.000), income (p=0.013), age (p=0.000), clinic workload (p=0.000), time working with hemodialysis (p=0.000), time working in the clinic (p= 0.007) and clinic sizing (p=0.000). In order, the sociodemographic factors of nursing technicians associated with the level of patient safety were: race (p= 0.001) and weekly workload at (p=0.010). Therefore, it is concluded that there is a non-conformity in the level of patient safety in one of the clinics studied and, that sociodemographic and clinical factors of patients and health professionals corroborate the level of safety of the health unit.

Keywords: hemodialysis, nursing, patient safety, quality improvement

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Authors: Recep Keşli, Onur Türkyılmaz, Hayriye Tokay, Kasım Demir

Abstract:

Objective: Coeliac disease (CD) is a primary small intestine disorder caused by high sensitivity to gluten which is present in the crops, characterized by inflammation in the small intestine mucosa. The goal of this study was to determine and to compare the sensitivity and specificity values of anti-endomysial IgA (EMA IgA) (IFA) and anti-tissue transglutaminase IgA (anti-tTG IgA) (ELISA) antibodies in the diagnosis of patients suspected with the CD. Methods: One thousand two hundred seventy three patients, who have applied to gastroenterology and pediatric disease polyclinics of Afyon Kocatepe University ANS Research and Practice Hospital were included into the study between 23.09.2010 and 30.05.2016. Sera samples were investigated by immunofluorescence method for EMA positiveness (Euroimmun, Luebeck, Germany). In order to determine quantitative value of Anti-tTG IgA (EIA) (Orgentec Mainz, Germany) fully automated ELISA device (Alisei, Seac, Firenze, Italy) were used. Results: Out of 1273 patients, 160 were diagnosed with coeliac disease according to ESPGHAN 2012 diagnosis criteria. Out of 160 CD patients, 120 were female, 40 were male. The EMA specificity and sensitivity were calculated as 98% and 80% respectively. Specificity and sensitivity of Anti-tTG IgA were determined as 99% and 96% respectively. Conclusion: The specificity of EMA for CD was excellent because all EMA-positive patients (n = 144) were diagnosed with CD. The presence of human anti-tTG IgA was found as a reliable marker for diagnosis and follow-up the CD. Diagnosis of CD should be established on both the clinical and serologic profiles together.

Keywords: anti-endomysial antibody, anti-tTG IgA, coeliac disease, immunofluorescence assay (IFA)

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Authors: Nabil Omar, Farah Jibril, Oraib Amjad

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Purpose: Trabecatine is a is a potent marine-derived antineoplastic drug which binds to the minor groove of the DNA, bending DNA towards the major groove resulting in a changed conformation that interferes with several DNA transcription factors, repair pathways and cell proliferation. Trabectedin was approved by the European Medicines Agency (EMA; London, UK) for the treatment of adult patients with advanced stage soft tissue sarcomas in whom treatment with anthracyclines and ifosfamide has failed, or for those who are not candidates for these therapies. The recommended dosing regimen is 1.5 mg/m2 IV over 24 hours every 3 weeks. The purpose of this study was to comprehensively review available data on the safety and efficacy of trabectedin used as indicated for patients at a Tertiary Cancer Center at Qatar. Methods: A medication administration report generated in the electronic health record identified all patients who received trabectedin between November 1, 2015 and November 1, 2017. This retrospective chart review evaluated the indication of trabectedin use, compliance to administration protocol and the recommended monitoring parameters, number of patients improved on the drug and continued treatment, number of patients discontinued treatment due to side-effects and the reported side effects. Progress and discharged notes were utilized to report experienced side effects during trabectedin therapy. A total of 3 patients were reviewed. Results: Total of 2 out of 3 patients who received trabectedin were receiving it for non-FDA and non-EMA, approved indications; metastatic rhabdomyosarcoma and ovarian cancer stage IV with poor prognosis. And only one patient received it as indicated for leiomyosarcoma of left ureter with metastases to liver, lungs and bone. None of the patients has continued the therapy due to development of serious side effects. One patient had stopped the medication after one cycle due to disease progression and transient hepatic toxicity, the other one had disease progression and developed 12 % reduction in LVEF after 12 cycles of trabectedin, and the third patient deceased, had disease progression on trabectedin after the 10th cycle that was received through peripheral line which resulted in developing extravasation and left arm cellulitis requiring debridement. Regarding monitoring parameters, at baseline the three patients had ECHO, and Creatine Phosphokinase (CPK) but it was not monitored during treatment as recommended. Conclusion: Utilizing this medication as indicated with performing the appropriate monitoring parameters as recommended can benefit patients who are receiving it. It is important to reinforce the intravenous administration via central intravenous line, the re-assessment of left ventricular ejection fraction (LVEF) by echocardiogram or multigated acquisition (MUGA) scan at 2- to 3-month intervals thereafter until therapy is discontinued, and CPK and LFTs levels prior to each administration of trabectedin.

Keywords: trabectedin, drug-use evaluation, safety, effectiveness, adverse drug reaction, monitoring

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Authors: Laura Gleason, Sahithi Talasila, Lauren Banner, Ladan Afifi, Neda Nikbakht

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Primary cutaneous anaplastic large cell lymphoma (pcALCL) accounts for 9% of all cutaneous T-cell lymphomas. pcALCL is classically characterized as a solitary papulonodule that often enlarges, ulcerates, and can be locally destructive, but overall exhibits an indolent course with overall 5-year survival estimated to be 90%. Distinguishing pcALCL from systemic ALCL (sALCL) is essential as sALCL confers a poorer prognosis with average 5-year survival being 40-50%. Although extremely rare, there have been several cases of ALK-positive ALCL diagnosed on skin biopsy without evidence of systemic involvement, which poses several challenges in the classification, prognostication, treatment, and follow-up of these patients. Objectives: We present a case of cutaneous ALK-positive ALCL without evidence of systemic involvement, and a narrative review of the literature to further characterize that ALK-positive ALCL limited to the skin is a distinct variant with a unique presentation, history, and prognosis. A 30-year-old woman presented for evaluation of an erythematous-violaceous papule present on her right chest for two months. With the development of multifocal disease and persistent lymphadenopathy, a bone marrow biopsy and lymph node excisional biopsy were performed to assess for systemic disease. Both biopsies were unrevealing. The patient was counseled on pursuing systemic therapy consisting of Brentuximab, Cyclophosphamide, Doxorubicin, and Prednisone given the concern for sALCL. Apropos of the patient we searched for clinically evident, cutaneous ALK-positive ALCL cases, with and without systemic involvement, in the English literature. Risk factors, such as tumor location, number, size, ALK localization, ALK translocations, and recurrence, were evaluated in cases of cutaneous ALK-positive ALCL. The majority of patients with cutaneous ALK-positive ALCL did not progress to systemic disease. The majority of cases that progressed to systemic disease in adults had recurring skin lesions and cytoplasmic localization of ALK. ALK translocations did not influence disease progression. Mean time to disease progression was 16.7 months, and significant mortality (50%) was observed in those cases that progressed to systemic disease. Pediatric cases did not exhibit a trend similar to adult cases. In both the adult and pediatric cases, a subset of cutaneous-limited ALK-positive ALCL were treated with chemotherapy. All cases treated with chemotherapy did not progress to systemic disease. Apropos of an ALK-positive ALCL patient with clinical cutaneous limited disease in the histologic presence of systemic markers, we discussed the literature data, highlighting the crucial issues related to developing a clinical strategy to approach this rare subtype of ALCL. Physicians need to be aware of the overall spectrum of ALCL, including cutaneous limited disease, systemic disease, disease with NPM-ALK translocation, disease with ALK and EMA positivity, and disease with skin recurrence.

Keywords: anaplastic large cell lymphoma, systemic, cutaneous, anaplastic lymphoma kinase, ALK, ALCL, sALCL, pcALCL, cALCL

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Authors: Madihah Shukri

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Research examining whether eating behaviour is related to unhealthy or healthy eating pattern is required to explain the mechanisms underlying obesity, and to inform health intervention aim to prevent and treat obesity. The purpose of this study was to investigate the relationship between eating behaviours and nature of food consumption. Methods: This was a cross-sectional study of 588 adults (males = 231 and females = 357). The Dutch Eating Behaviour Questionnaire (DEBQ) was used to measure restrained, emotional and external eating. Nature of food consumption was assessed by self-reported consumption of fruit and vegetables, sweet food, junk food and snacking. Results: Results revealed that emotional eating was found to be the principal predictor of the consumption of less healthy food (sweet food, junk food and snacking), while external eating predicted sweet food intake. Intake of fruit and vegetable was associated with restrained eating. In light of the significant associations between eating behaviour and nature of food consumption, acknowledging individuals eating styles can have implications for tailoring effective nutritional programs in the context of obesity and chronic disease epidemic.

Keywords: eating behaviour, food consumption, adult, Malaysia

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Authors: Kathryn Nderitu, Atunga Nyachieo, Ezekiel Mecha

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Introduction: Solanum nigrum , also known as black nightshade, biosynthesizes various phytochemical compounds with various pharmacological activities, including treating cardiovascular diseases and type 2 diabetes, among others. Materials and Methods: To assess the anti-obesity effects of Solanum nigrum using high-fat-fed diet rats, Sprague Dawley male rats (n = 35) of weights 160–180 g were assigned randomly into seven groups comprising n = 5 rats each. Each group was fed for 11 weeks as follows: normal group (normal chow rat feed); high-fat diet control (HFD); HFD and standard drug (Orlistat 30 mg/kg bw); HFD and methanolic extract 150 mg/kgbw; HFD and methanolic extract 300 mg/kgbw; HFD and dichloromethane extract 150 mg/kgbw; HFD and dichloromethane extract 300 mg/kgbw. Body mass index and food intake were monitored per week, and an oral glucose tolerance test was measured in weeks 5 and 10. Lipid profiles, liver function tests, adipose tissue, liver weights, and phytochemical analysis of Solanum nigrum were later carried out. Results: High-fat diet control group rats exhibited a significant increase in body mass index (BMI), while rats administered with leaf extracts of Solanum nigrum showed a reduction in BMI. Both low doses of dichloromethane (150 mg/kgbw) and high doses of methanol extracts (300 mg/kgbw) showed a better reduction in BMI than the other treatment groups. A significant decrease (p <0.05) in low-density lipoprotein-cholesterol, triglycerides, and cholesterol was observed among the rats administered with Solanum nigrum extracts compared to those of HFD control. Moreover, the HFD control group significantly increased liver and adipose tissue weights compared to other treatment groups (p<0.05). Solanum nigrum also decreased glycemic levels and normalized the hepatic enzymes of HFD control. However, food intake among the groups showed no significant difference (p>0.05). Qualitative analysis of Solanum nigrum leaf extracts indicated the presence of various bioactive compounds associated with anti-obesity. Conclusion: These results validate the use of Solanum nigrum in controlling obesity.

Keywords: solanum nigrum, High fat diet, phytocompounds, obesity

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Authors: Shreya Ghosh, Akansha Garg, Chayanika Kala, Ashwani Kumar Thakur

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Background: Granuloma formation is one of the characteristic features of tuberculosis. Besides, chronic inflammation underlying tuberculosis is often indicated by an increase in the concentration of serum amyloid A (SAA) protein. The connection between tuberculosis and SAA-driven secondary amyloidosis is well documented. However, SAA-derived amyloid deposition start sites are not well understood in tuberculosis and other chronic inflammatory conditions. It was hypothesized that granuloma could be a potential site for an amyloid deposition because both SAA protein and proteases that cleave SAA into aggregation-prone fragments are reported to be present in the granuloma. Here the authors have shown the presence of SAA-derived amyloid deposits in the granuloma of tuberculosis patients. Methodology: Over a period of two years, tuberculosis patients were screened, and biopsies were collected from the affected organs of the patients. The gold standard, Congo red dye staining, was used to identify amyloid deposits in the tissue sections of tuberculosis patients containing granulomatous structure. Results: 11 out of 150 FFPE biopsy specimens of tuberculosis patients showed eosinophilic hyaline-rich deposits surrounding granuloma. Upon Congo red staining, these deposits exhibited characteristic apple-green birefringence under polarized light, confirming amyloid deposits. Further, upon immunohistochemical staining with anti-SAA, the amyloid enriched areas showed positive immunoreactivity. Conclusion: In this pilot study, we have shown that granuloma can be a potential site for serum amyloid A-derived amyloid formation in tuberculosis patients. Moreover, the presence of amyloid gave significant cues that granuloma might be a probable amyloid deposition start in tuberculosis patients. This study will set a stage to expand the clinical and fundamental research in the understanding of amyloid formation in granuloma underlying tuberculosis and chronic inflammatory conditions.

Keywords: amyloid, granuloma, periphery, serum amyloid A, tuberculosis

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Authors: Maryam Amiri Resketi, Sakineh Yeganeh, Khosro Jani Khalili

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The aim of this study was to investigate the effect of dietary lemon peel essential oil (Citrus limon) on serum parameters and liver enzyme activity of rainbow trout (Oncorhynchus mykiss) was exposed to deltamethrin. The 96-hour lethal concentrations of the toxin on rainbow trout (Oncorhynchus mykiss), was determined according to standard procedures O.E.C.D in static (Static). 96-hour LC50 was obtained 0.0082 mg/l by using statistical methods Probit program version. The maximum allowable concentration of deltamethrin was calculated 0.00082 mg/l in natural environment and was used for this experiment. Eight treatments were designed based on 3 levels of lemon essential oil 200, 400 and 600 mg/kg and 2 levels of deltamethrin 0 and 0.00082. Rainbow trout with an average weight of 95.14 ± 3.8 g were distributed in 300-liter tanks and cultured for eight weeks. Fish were fed in an amount of 2% of body weight. Water changes were done on a daily basis (90 percent of the tank). About the tanks containing 10 % deltamethrin, after dewatering, suitable concentration of toxin was added to water. At the end of the test, serum biochemical parameters (total protein, albumin, glucose, cholesterol, and triglycerides) and liver enzymes (ALP, AST, ALT and LDH) were evaluated. In treatments without and with toxin, increasing 400 mg/kg oil increased total protein and albumin levels and lower cholesterol and triglycerides were observed (p < 0.05). Rise to the level of 400 mg/kg of lemon peel essential oil treatments contain pesticides, reduced the amount of enzymes ALP, ALT and LDH compared to treatment of toxin-free lemon peel essential oil (p < 0.05). The results showed that usage of lemon peel essential oil in fish diet can increase the immune system parameters and strengthen it with strong antioxidant activity followed by reducing the effect of deltamethrin on the immune system of fish and effective dose can prevent the adverse effects of toxin due to the weakening of the fish immune system at the time of toxic pollutant entrance in fish farms.

Keywords: deltamethrin, Oncorhynchus mykiss, LC5096h, lemon peel (citrus limon) essential oil, serum parameters, liver enzymes

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Authors: H. Shola Adeosun, F. Ajoke Adebiyi

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This study appraises the impact of television on the coverage of Lassa Fever disease. The objectives of the study are to find out whether television is an effective tool for raising awareness about Lassa fever shapes the perception of members of the public. The research work was based on the theoretical foundation of Agenda – setting and reinforcement theory. Survey research method was adopted in the study to elicit data from the residents of Obafemi Owode Local Government, area of Ogun state. Questionnaire and oral interview were adopted as a tool for data gathering. Simple random sampling techniques were used to draw a sample for this study. Out of filled 400 questionnaires distributed to the respondents. 37 of them were incorrectly filled and returned at the stipulated time. This is about (92.5% Tables, percentages, and figures were used to analyse and interpret the data and hypothesis formulation for this study revealed that Lassa fever diseases with higher media coverage were considered more serious and more representative of a disease and estimated to have lower incidents, than diseases less frequently found in the media. Thus, 92% of the respondents agree that they have access to television coverage of Lassa fever disease led to exaggerated perceptions of personal vulnerability. It, therefore, concludes that there is a need for relevant stakeholders to ensure better community health education and improved housing conditions in southwestern Nigeria, with an emphasis on slum areas and that Nigeria need to focus on the immediate response, while preparing for the future because a society or community is all about the people who inhabit. Therefore every effort must be geared towards their society and survival.

Keywords: impact, television, coverage, Lassa fever disease

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Authors: Gehan Hussein, Hala Agha, Rasha Abdelraof, Marina George, Antoine Fakhri

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Background: β-Thalassemia major (TM) and sickle cell disease (SCD) are inherited hemoglobin disorders resulting in chronic hemolytic anemia. Cardiovascular involvement is an important cause of morbidity and mortality in these groups of patients. The narrow border is between overt myocardial dysfunction and clinically silent left ventricular (LV) and / or right ventricular (RV) dysfunction in those patients. 3 D Speckle tracking echocardiography (3D STE) is a novel method for the detection of subclinical myocardial involvement. We aimed to study myocardial affection in SCD and TM using 3D STE, comparing it with conventional echocardiography, correlate it with serum ferritin level and lactate dehydrogenase (LDH). Methodology: Thirty SCD and thirty β TM patients, age range 4-18 years, were compared to 30 healthy age and sex matched control group. Cases were subjected to clinical examination, laboratory measurement of hemoglobin level, serum ferritin, and LDH. Transthoracic color Doppler echocardiography, 3D STE, tissue Doppler echocardiography, and aortic speckle tracking were performed. Results: significant reduction in global longitudinal strain (GLS), global circumferential strain (GCS), and global area strain (GAS) in SCD and TM than control (P value <0.001) there was significantly lower aortic speckle tracking in patients with TM and SCD than control (P value< 0.001). LDH was significantly higher in SCD than both TM and control and it correlated significantly positive mitral inflow E, (p value:0.022 and 0.072. r: 0.416 and -0.333 respectively) lateral E/E’ (p value.<0.001and 0.818. r. 0.618 and -0. 044.respectively) and septal E/E’ (p value 0.007 and 0.753& r value 0.485 and -0.060 respectively) in SCD but not TM and significant negative correlation between LDH and aortic root speckle tracking (value 0.681& r. -0.078.). The potential diagnostic accuracy of LDH in predicting vascular dysfunction as represented by aortic root GCS with a sensitivity 74% and aortic root GCS was predictive of LV dysfunction in SCD patients with sensitivity 100% Conclusion: 3D STE LV and RV systolic dysfunction in spite of their normal values by conventional echocardiography. SCD showed significantly lower right ventricular dysfunction and aortic root GCS than TM and control. LDH can be used to screen patients for cardiac dysfunction in SCD, not in TM

Keywords: thalassemia major, sickle cell disease, 3d speckle tracking echocardiography, LDH

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Authors: Ghada Esheba, Bayan Hafiz, Ashwaq Al-Qarni, Abdulelah AlMalki, Esraa Kaheel

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Hydatid disease is caused by genus Echinococcus, it is transmitted to human through sheep and cattle. People who lived in an endemic area should be suspected to have the disease. Pulmonary hydatid disease can be presented by respiratory manifestations as in our case. We report a case of child, 13 years old, who was presented by shortness of breath and non-productive cough 2 months ago. The patient had an attack of hemoptysis 3 months ago but there is no history of fever, other constitutional symptoms or any medical illness. The patient has had a close contact with a horse. On examination, the patient was oriented and vitally stable. Both side of chest were moving equally with decrease air entry on the left side of the chest. Cervical lymph node enlargement was also detected. The case was provisionally diagnosed as tuberculosis. The x-ray was normal, while CT scan showed two cysts in the left side. The patient was treated surgically with resection of both cysts without lobectomy. Broncho-alveolar lavage was done and together with plural effusion and both cysts were sent for histopathology. The patient received the following medication: albendazole 200MG/BID/Orally for 30 days and Cefuroxime 250MG/Q12H/Orally for 10 days.

Keywords: Echinococcus granulosus, hydatid disease, pediatrics, pulmonary hydatid cyst

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Authors: Yongrong Liu, Xin Tang

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Background: Persistent atrial fibrillation is a common arrhythmia closely related to heart failure. Heart rate control is an essential strategy for treating persistent atrial fibrillation. Still, the understanding of the relationship between different heart rate control levels and the risk of heart failure rehospitalization is limited. Objective: The objective of the study is to determine the relationship between different levels of heart rate control in patients with persistent atrial fibrillation and the risk of readmission for heart failure. Methods: We conducted a retrospective dual-centre cohort study, collecting data from patients with persistent atrial fibrillation who received outpatient treatment at two tertiary hospitals in central and western China from March 2019 to March 2020. The collected data included age, gender, body mass index (BMI), medical history, and hospitalization frequency due to heart failure. Patients were divided into three groups based on their heart rate control levels: Group I with a resting heart rate of less than 80 beats per minute, Group II with a resting heart rate between 80 and 100 beats per minute, and Group III with a resting heart rate greater than 100 beats per minute. The readmission rates due to heart failure within one year after discharge were statistically analyzed using propensity score matching in a 1:1 ratio. Differences in readmission rates among the different groups were compared using one-way ANOVA. The impact of varying levels of heart rate control on the risk of readmission for heart failure was assessed using the Cox proportional hazards model. Binary logistic regression analysis was employed to control for potential confounding factors. Results: We enrolled a total of 1136 patients with persistent atrial fibrillation. The results of the one-way ANOVA showed that there were differences in readmission rates among groups exposed to different levels of heart rate control. The readmission rates due to heart failure for each group were as follows: Group I (n=432): 31 (7.17%); Group II (n=387): 11.11%; Group III (n=317): 90 (28.50%) (F=54.3, P<0.001). After performing 1:1 propensity score matching for the different groups, 223 pairs were obtained. Analysis using the Cox proportional hazards model showed that compared to Group I, the risk of readmission for Group II was 1.372 (95% CI: 1.125-1.682, P<0.001), and for Group III was 2.053 (95% CI: 1.006-5.437, P<0.001). Furthermore, binary logistic regression analysis, including variables such as digoxin, hypertension, smoking, coronary heart disease, and chronic obstructive pulmonary disease as independent variables, revealed that coronary heart disease and COPD also had a significant impact on readmission due to heart failure (p<0.001). Conclusion: The correlation between the heart rate control level of patients with persistent atrial fibrillation and the risk of heart failure rehospitalization is positive. Reasonable heart rate control may significantly reduce the risk of heart failure rehospitalization.

Keywords: heart rate control levels, heart failure rehospitalization, persistent atrial fibrillation, retrospective cohort study

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Authors: Hong Su, Qiuju Yan, Wei Du, En Hu, Zhaoyu Yang, Wei Zhang, Yusheng Li, Tao Tang, Wang yang, Shushan Zhao

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Osteoarthritis (OA) is a severe chronic inflammatory disease. As the main active component of Astragalus mongholicus Bunge, a classic traditional ethnic herb, calycosin exhibits anti-inflammatory action and its mechanism of exact targets for OA have yet to be determined. In this study, we established an anterior cruciate ligament transection (ACLT) mouse model. Mice were randomized to sham, OA, and calycosin groups. Cartilage synthesis markers type II collagen (Col-2) and SRY-Box Transcription Factor 9 (Sox-9) increased significantly after calycosin gavage. While cartilage matrix degradation index cyclooxygenase-2 (COX-2), phosphor-epidermal growth factor receptor (p-EGFR), and matrix metalloproteinase-9 (MMP9) expression were decreased. With the help of network pharmacology and molecular docking, these results were confirmed in chondrocyte ATDC5 cells. Our results indicated that the calycosin treatment significantly improved cartilage damage, this was probably attributed to reversing the imbalance between chondrocyte synthesis and catabolism.

Keywords: calycosin, osteoarthritis, network pharmacology, molecular docking, inflammatory, cyclooxygenase 2

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Authors: Sanjay Shukla, A. Nayak, R. K. Sharma, A. P. Singh, S. P. Tiwari

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Excessive use of antibiotics is a major problem in the treatment of wounds and other chronic infections, and antibiotic treatment is frequently non-curative, thus alternative treatment is necessary. Phage therapy is considered one of the most promising approaches to treat multi-drug resistant bacterial pathogens. Infections caused by Staphylococcus aureus are very efficiently controlled with phage cocktails, containing a different individual phages lysate infecting a majority of known pathogenic S. aureus strains. The aim of the present study was to evaluate the efficacy of a purified phage cocktail for prophylactic as well as therapeutic application in mouse model and in large animals with chronic septic infection of wounds. A total of 150 sewage samples were collected from various livestock farms. These samples were subjected for the isolation of bacteriophage by the double agar layer method. A total of 27 sewage samples showed plaque formation by producing lytic activity against S. aureus in the double agar overlay method out of 150 sewage samples. In TEM, recovered isolates of bacteriophages showed hexagonal structure with tail fiber. In the bacteriophage (ØVS) had an icosahedral symmetry with the head size 52.20 nm in diameter and long tail of 109 nm. Head and tail were held together by connector and can be classified as a member of the Myoviridae family under the order of Caudovirale. Recovered bacteriophage had shown the antibacterial activity against the S. aureus in vitro. Cocktail (ØVS1, ØVS5, ØVS9, and ØVS 27) of phage lysate were tested to know in vivo antibacterial activity as well as the safety profile. Result of mice experiment indicated that the bacteriophage lysate were very safe, did not show any appearance of abscess formation, which indicates its safety in living system. The mice were also prophylactically protected against S. aureus when administered with cocktail of bacteriophage lysate just before the administration of S. aureuswhich indicates that they are good prophylactic agent. The S. aureusinoculated mice were completely recovered by bacteriophage administration with 100% recovery, which was very good as compere to conventional therapy. In the present study, ten chronic cases of the wound were treated with phage lysate, and follow up of these cases was done regularly up to ten days (at 0, 5, and 10 d). The result indicated that the six cases out of ten showed complete recovery of wounds within 10 d. The efficacy of bacteriophage therapy was found to be 60% which was very good as compared to the conventional antibiotic therapy in chronic septic wounds infections. Thus, the application of lytic phage in single dose proved to be innovative and effective therapy for the treatment of septic chronic wounds.

Keywords: phage therapy, S aureus, antimicrobial resistance, lytic phage, and bacteriophage

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Authors: Ashit Syngle, Inderjit Verma, Pawan Krishan

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Therapeutic approaches used previously relied on disease-modifying antirheumatic drugs (DMARDs) that had only partial clinical benefit and were associated with significant toxicity. Spironolactone, an oral aldosterone antagonist, suppresses inflammatory mediators. Clinical efficacy of spironolactone compared with placebo in patients with active psoriatic arthritis despite treatment with prior traditional DMARDs. In the 24-week, placebo-controlled study patients (n=31) were randomized to placebo and spironolactone (2 m/kg/day). Patients on background concurrent DMARDs continued stable doses (methotrexate, leflunomide, and/or sulfasalazine). Primary outcome measures were the assessment of disease activity measures i.e. 28-joint disease activity score (DAS28) and diseases activity in psoriatic arthritis (DAPSA) at week 24. The key secondary endpoint was change from baseline in Health Assessment Questionnaire–Disability Index (HAQ-DI) at week 24. Additional efficacy outcome measures at week 24 included improvements in the markers of inflammation (ESR and CRP) and pro-inflammatory cytokines TNF-α, IL-6 and IL-1. At week 24, spironolactone significantly reduced disease activity measure DAS-28 (p<0.001) and DAPSA (p=0.001) compared with placebo. Significant improvements in key secondary measures HAQ-DI (disability index) were evident with spironolactone (p=0.02) versus placebo. After week 24, there was significant reduction in pro-inflammatory cytokines level TNF-α, IL-6 (p<0.01) as compared with placebo group. However, there was no significant improvement in IL-1 in both treatment and placebo groups. There were minor side effects which did not mandate stopping of spironolactone. No change in any biochemical profile was noted after spironolactone treatment. Spironolactone was effective in the treatment of PsA, improving disease activity, physical function and suppressing the level of pro-inflammatory cytokines. Spironolactone demonstrated an acceptable safety profile and was well tolerated.

Keywords: spironolactone, inflammation, inflammatory cytokine, psoriatic arthritis

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Authors: Ghoul Rachid Brahim

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Introduction: Back pain is a real public health problem with a significant socio-economic impact. It is the consequence of a degeneration of the lumbar intervertebral disc (IVD). This often asymptomatic pathology is compatible with an active life. As soon as it becomes symptomatic, conservative treatment is recommended in the majority of cases. The physical or functional disability is resistant to well-monitored conservative treatment, which justifies a surgical alternative which imposes a well-studied reflection on the objectives to be achieved. Objective: Evaluate the indication and short and medium term contribution of surgery in the management of painful degenerative lumbar disc disease. To prove the effectiveness of surgical treatment in the management of painful lumbar degenerative disc disease. Materials and methods: This is a prospective descriptive mono-centric study without comparison group, comprising a series of 104 patients suffering from lumbar painful degenerative disc disease treated surgically. Retrospective analysis of data collected prospectively. Comparison between pre and postoperative clinical status, by pain self-assessment scores and on the impact on pre and postoperative quality of life (3, 6 to 12 months). Results: This study showed that patients who received surgical treatment had great improvements in symptoms, function and several health-related quality of life in the first year after surgery. Conclusions: The surgery had a significantly positive impact on patients' pain, disability and quality of life. Overall, 97% of the patients were satisfied.

Keywords: degenerative disc disease, intervertebral disc, several health-related quality, lumbar painful

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Authors: Ali Kassem, Yaser Kamal, Mohamed Abdel Wahab, Mohamed Hussen

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Introduction: Atherosclerosis is one of the leading causes of death all over the world. Recently, there is an increasing interest in Carotid Intima-Medial Thickness (CIMT) and Ankle Brachial Index (ABI) as non-invasive tools for identifying subclinical atherosclerosis. We aim to examine the role of CIMT and ABI as predictors of the severity of angiographically documented coronary artery disease (CAD). Methods: A cross-sectional study conducted on 60 patients who were investigated by coronary angiography at Sohag University Hospital, Egypt. CIMT: After the carotid arteries were located by transverse scans, the probe was rotated 90 ° to obtain and record longitudinal images of bilateral carotid arteries ABI: Each patient was evaluated in the supine position after resting for 5 min. ABI was measured in each leg using a Doppler Ultrasound while the patient remained in the same position. The lowest ABI obtained for either leg was taken as the ABI measurement for the patient. Results: Patients with carotid mean IMT ≥ 0.9 mm had significantly more severe coronary artery disease than patients without thickening (mean IMT > 0.9 mm). Similarly, patients with low ABI (< 0.9) had significantly more severe coronary artery disease than patients with ABI ≥ 0.9. When the patients were divided into 4 groups (group A, n = 15, mean IMT < 0.9 mm, ABI ≥ 0.9; group B, n = 25, mean IMT < 0.9 mm, low ABI; group C, n = 5, mean IMT ≥ 0.9 mm, ABI ≥ 0.9; group D, n = 19, mean IMT ≤ 0.9 mm, low ABI), the presence of significant coronary stenosis (> 50%) of the groups were significantly different (group A, n = 5: (33.3%); group B, n = 11: (52.4%); group C, n = 4: (60%); group D, n=15, (78.9%), P = 0.001). Conclusion: CIMT and ABI provide useful information on the severity of CAD. Early and aggressive intervention should be considered in patients with CAD and abnormalities in one or both of these non-invasive modalities.

Keywords: ankle brachial index, carotid intima media thickness, coronary artery disease, predictors of severity

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Authors: G. E. Forcados, M. L. Shu, C. N. Chinyere

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Acalypha wilkesiana is a medicinal plant commonly used in most parts of West Africa as a decoction in treating several human diseases. Existing literature on its toxicity is predominantly on the organic extracts in contrast to the routine use of hot aqueous extracts as decoction. The aim of this study was to examine the phytochemical profile and sub-acute toxicity of A. wilkesiana leaf extracts in albino rats. Three groups of 8 experimental rats each were administered 300 mg/kg, 600 mg/kg and 1200 mg/kg body weight per day for 14 days while a fourth (control) group took tap-water. On day 15, the rats were sacrificed, and blood collected. Biochemical and hematological parameters were analysed and histopathological examination of liver and kidney were performed. There was significant increase (p<0.05) in the levels of some biochemical parameters (AST, ALT, creatinine, urea) in all the test groups compared to control. Histopathological examination of the liver revealed centrilobular degeneration and necrosis with sinusoidal dilatation as well as polymorphonuclear and mononuclear infiltration, likewise severe glomerular and tubular degeneration and necrosis with hemorrhage in the kidney at all dose levels. The results from this study suggest that aqueous leaf extract of A. wilkesiana is hepatotoxic and nephrotoxic at dose levels of 300 mg/kg and above. Therefore, precautionary measures are necessary for home use of the leaf extract of A. wilkesiana.

Keywords: acute toxicity, A. wilkesiana, aqeous extract, albino rats, biochemical and haematological parameters, histopathological examination

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Authors: Laura Bellassen, Idit Shachar

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Multiple sclerosis (MS) is a chronic neurological disorder characterized by demyelination of the central nervous system (CNS), leading to a wide range of physical and cognitive impairments. Myeloid cells in the CNS, such microglia and border associated macrophage cells, participate in the neuroinflammation in MS. Activation of those cells in MS contributes to the inflammatory response in the CNS and recruitment of immune cells in the this compartment. SLAMF5 is a cell surface receptor that functions as a homophilic adhesion molecule, whose signaling can activate or inhibit leukocyte function. In the current study we followed the expression and function of SLAMF5 in myeloid cells in the CNS and in the periphery in the murine model for MS, the experimental autoimmune encephalomyelitis model (EAE). Our results show that SLAMF5 deficiency or blocking decreases the expression of activation molecules and costimulatory molecules such as MHCII and CD80, resulting in delayed onset and reduced progression of the disease. Moreover, blocking SLAMF5 in peripheral monocytes derived from MS patients and iPSC-derived microglia cells, controls the expression of HLA-DR and CD80. Thus, SLAMF5 is a regulator of myeloid cells function and can serve as a therapeutic target in autoimmune disorders as Multiple Sclerosis.

Keywords: multiple sclerosis, EAE model, myeloid cells, new antibody, neuroimmunology

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Authors: Asmaa M. Hussein, Amr Wassal, Ahmed Farouk Al-Sadek, A. F. Abd El-Rahman

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In this study, a multivariate analysis of potato spectroscopic data was presented to detect the presence of brown rot disease or not. Near-Infrared (NIR) spectroscopy (1,350-2,500 nm) combined with multivariate analysis was used as a rapid, non-destructive technique for the detection of brown rot disease in potatoes. Spectral measurements were performed in 565 samples, which were chosen randomly at the infection place in the potato slice. In this study, 254 infected and 311 uninfected (brown rot-free) samples were analyzed using different advanced statistical analysis techniques. The discrimination performance of different multivariate analysis techniques, including classification, pre-processing, and dimension reduction, were compared. Applying a random forest algorithm classifier with different pre-processing techniques to raw spectra had the best performance as the total classification accuracy of 98.7% was achieved in discriminating infected potatoes from control.

Keywords: Brown rot disease, NIR spectroscopy, potato, random forest

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Authors: Hanan Begali, Shahi Dost, Annett Ziegler, Markus Cornberg, Maria-Esther Vidal, Anke R. M. Kraft

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Chronic hepatitis B virus (HBV) infection can be treated with nucleot(s)ide analog (NA), for example, which inhibits HBV replication. However, they have hardly any influence on the functional cure of HBV, which is defined by hepatitis B surface antigen (HBsAg) loss. NA needs to be taken life-long, which is not available for all patients worldwide. Additionally, NA-treated patients are still at risk of developing cirrhosis, liver failure, or hepatocellular carcinoma (HCC). Although each patient has the same components of the immune system, immune responses vary between patients. Therefore, a deeper understanding of the immune response against HBV in different patients is necessary to understand the parameters leading to HBV cure and to use this knowledge to optimize HBV therapies. This requires seamless integration of an enormous amount of diverse and fine-grained data from viral markers, e.g., hepatitis B core-related antigen (HBcrAg) and hepatitis B surface antigen (HBsAg). The data integration system relies on the assumption that profiling human immune systems requires the analysis of various variables (e.g., demographic data, treatments, pre-existing conditions, immune cell response, or HLA-typing) rather than only one. However, the values of these variables are collected independently. They are presented in a myriad of formats, e.g., excel files, textual descriptions, lab book notes, and images of flow cytometry dot plots. Additionally, patients can be identified differently in these analyses. This heterogeneity complicates the integration of variables, as data management techniques are needed to create a unified view in which individual formats and identifiers are transparent when profiling the human immune systems. The proposed study (HBsRE) aims at integrating heterogeneous data sets of 87 chronically HBV-infected patients, e.g., clinical data, immune cell response, and HLA-typing, with knowledge encoded in biomedical ontologies and open-source databases into a knowledge-driven framework. This new technique enables us to harmonize and standardize heterogeneous datasets in the defined modeling of the data integration system, which will be evaluated in the knowledge graph (KG). KGs are data structures that represent the knowledge and data as factual statements using a graph data model. Finally, the analytic data model will be applied on top of KG in order to develop a deeper understanding of the immune profiles among various patients and to evaluate factors playing a role in a holistic profile of patients with HBsAg level loss. Additionally, our objective is to utilize this unified approach to stratify patients for new effective treatments. This study is developed in the context of the project “Transforming big data into knowledge: for deep immune profiling in vaccination, infectious diseases, and transplantation (ImProVIT)”, which is a multidisciplinary team composed of computer scientists, infection biologists, and immunologists.

Keywords: chronic hepatitis B infection, immune response, knowledge graphs, ontology

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Authors: Soumaya Mrabet, Taieb Ach, Imen Akkari, Amira Atig, Neirouz Ghannouchi, Koussay Ach, Elhem Ben Jazia

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Introduction: Celiac disease (CD) is an immune-mediated small intestinal disorder that occurs in genetically susceptible people. It is significantly associated with other autoimmune disorders represented mainly by type 1 diabetes and autoimmune dysthyroidism. The aim of our study is to determine the prevalence and the type of the various autoimmune diseases associated with CD in adult patients. Material and methods: This is a retrospective study including patients diagnosed with CD, explored in Internal Medicine, Gastroenterology and Endocrinology and Diabetology Departments of the Farhat Hached University Hospital, between January 2005 and January 2016. The diagnosis of CD was confirmed by serological tests and duodenal biopsy. The screening of autoimmune diseases was based on physical examination, biological and serological tests. Results: Sixty five patients with a female predominance were included, 48women (73.8%) and 17 men (26.2%). The mean age was 31.8 years (17-75). A family history of CD or other autoimmune diseases was present in 5 and 10 patients respectively. Clinical presentation of CD was made by recurrent abdominal pain in 49 cases, diarrhea in 29 cases, bloating in 17 cases, constipation in 25 cases and vomiting in 8 cases. Autoimmune diseases associated with CD were found in 30 cases (46.1%): type 1 diabetes in 15 patients attested by the positivity of anti-GAD antibodies in 11 cases and anti-IA2 in 4 cases, Hashimoto thyroiditis in 8 cases confirmed by the positivity of anti-TPO antibodies, Addison's disease in 2 patients, Anemia of Biermer in 2 patients, autoimmune hepatitis, Systemic erythematosus lupus, Gougerot Sjögren syndrome, rheumatoid arthritis, Vitiligo and antiphospholipid syndrome in one patient each. CD was associated with more than one autoimmune disease defining multiple autoimmune syndrome in 2 female patients. The first patient had Basedow disease, Addison disease and type 1 diabetes. The second patient had systemic erythematosus lupus and Gougerot Sjögren syndrome. Conclusion: In our study autoimmune diseases were associated with CD in 46.1% of cases and were dominated by diabetes and dysthroidism. After establishing the diagnosis of CD the search of associated autoimmune diseases is necessary in order to avoid any therapeutic delay which can alter the prognosis of the patient.

Keywords: association, autoimmune thyroiditis, celiac disease, diabetes

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Authors: A. K. Faizah, G. Vadamalai, S. K. Balasundram, W. L. Lim

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Pineapple (Ananas comosus) is a common crop in tropical and subtropical areas of the world. Malaysia once ranked as one of the top 3 pineapple producers in the world in the 60's and early 70's, after Hawaii and Brazil. Moreover, government’s recognition of the pineapple crop as one of priority commodities to be developed for the domestics and international markets in the National Agriculture Policy. However, pineapple industry in Malaysia still faces numerous challenges, one of which is the management of disease and pest. Red tip disease on pineapple was first recognized about 20 years ago in a commercial pineapple stand located in Simpang Renggam, Johor, Peninsular Malaysia. Since its discovery, there has been no confirmation on its causal agent of this disease. The epidemiology of red tip disease is still not fully understood. Nevertheless, the disease symptoms and the spread within the field seem to point toward viral infection. Bioassay test on nucleic acid extracted from the red tip-affected pineapple was done on Nicotiana tabacum cv. Coker by rubbing the extracted sap. Localised lesions were observed 3 weeks after inoculation. Negative staining of the fresh inoculated Nicotiana tabacum cv. Coker showed the presence of membrane-bound spherical particles with an average diameter of 94.25nm under transmission electron microscope. The shape and size of the particles were similar to tospovirus. SDS-PAGE analysis of partial purified virions from inoculated N. tabacum produced a strong and a faint protein bands with molecular mass of approximately 29 kDa and 55 kDa. Partial purified virions of symptomatic pineapple leaves from field showed bands with molecular mass of approximately 29 kDa, 39 kDa and 55kDa. These bands may indicate the nucleocapsid protein identity of tospovirus. Furthermore, a handheld sensor, Greenseeker, was used to detect red tip symptoms on pineapple non-destructively based on spectral reflectance, measured as Normalized Difference Vegetation Index (NDVI). Red tip severity was estimated and correlated with NDVI. Linear regression models were calibrated and tested developed in order to estimate red tip disease severity based on NDVI. Results showed a strong positive relationship between red tip disease severity and NDVI (r= 0.84).

Keywords: pineapple, diagnosis, virus, NDVI

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