Search results for: dry eye disease

Authors: Yuvarani Naidu, Yasmeen Siddiqui, Mohd Yusof Rafii , Abu Seman Idris

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Sustainability of oil palm production in Southeast Asia, especially in Indonesia and Malaysia, is jeopardized by Ganoderma boninense, the fungus which causes basal stem rot (BSR) in oil palm. The root contact with unattended infected debris left in the plantations during replanting is known to be the primary source of inoculum. Abiding by the law, potentially effective technique of managing Ganoderma infected oil palm debris is deemed necessary because of the zero-burning policy in Malaysian oil palm plantations. White-rot hymenomycetes antagonistic to Ganoderma sp were selected to test their efficacy as log treatments in degrading Ganoderma infected oil palm logs and to minimize the survival of Ganoderma inoculum. Decay rate in terms of mass loss was significantly higher after the application of solid-state cultivation (SSC) of Trametes lactinea FBW (64% ±1.2), followed by Pycnoporus sanguineus FBR (55% ±1.7) in infected log block tissues, after 10 months of treatments. The degradation pattern was clearly distinguished between the treated and non-treated log blocks with the developed SSC formulations. The control infected log blocks showed the highest, whereas infected log blocks treated with either P. sanguineus FBR or T. lactinea FBW SSC formulations exhibited statistically lowest number of Ganoderma spp. recovery on Ganoderma Selective Medium (GSM), after 8 months of treatment. Out of that, the lowest recovery of Ganoderma spp. was reported in infected log blocks inoculated with the strain T. lactinea FBW (21% ± 0.9) followed by P. sanguineus FBR (33% ± 2.2), after 8 months, Further, no recovery of Ganoderma was noticeable, 10 months after treatment applications in log blocks treated with both of the formulations. This is the first nursery-base study to substantiate the initial colonization of white-rot hymenomycetes on oil palm log blocks previously infected with BSR pathogen, G. boninense. The present study has indicated that log blocks treatment with white-rot hymenomycetes significantly affected the mass loss of diseased and healthy log block tissues. This study provides a basis of biotechnological approaches inefficient degradation of oil palm-generated crop debris, under natural conditions with an ultimate aim of reducing the Ganoderma inoculum under heavy BSR infection pressure in eco-friendly manner.

Keywords: basal stem rot disease, ganoderma boninense, oil palm, white-rot fungi

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Authors: J. Adeppa, S. Samanta, O. K. Raina

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Fasciolosis is a widespread economically important parasitic infection throughout the world caused by Fasciola hepatica and F. gigantica. In order to identify novel immunogen conferring significant protection against fasciolosis, currently, research has been focused on the defined antigens viz. glutathione S-transferase, fatty acid binding protein, cathepsin-L, fluke hemoglobin, paramyosin, myosin and F. hepatica- Kunitz Type Molecule. Among various antigens, GST which plays a crucial role in detoxification processes, i.e. phase II defense mechanism of this parasite, has a unique position as a novel vaccine candidate and a drug target in the control of this disease. For producing the antigens in large quantities and their purification to complete homogeneity, the recombinant DNA technology has become an important tool to achieve this milestone. RT- PCR was carried out using F. gigantica total RNA as template, and an amplicon of 657 bp GST gene was obtained. TA cloning vector was used for cloning of this gene, and the presence of insert was confirmed by blue-white selection for recombinant colonies. Sequence analysis of the present isolate showed 99.1% sequence homology with the published sequence of the F. gigantica GST gene of cattle origin (accession no. AF112657), with six nucleotide changes at 72, 74, 423, 513, 549 and 627th bp found in the present isolate, causing an overall change of 4 amino acids. The 657 bp GST gene was cloned at BamH1 and HindIII restriction sites of the prokaryotic expression vector pPROEXHTb in frame with six histidine residues and expressed in E. coli DH5α. Recombinant protein was purified from the bacterial lysate under non-denaturing conditions by the process of sonication after lysozyme treatment and subjecting the soluble fraction of the bacterial lysate to Ni-NTA affinity chromatography. Western blotting with rabbit hyper-immune serum showed immuno-reactivity with 25 kDa recombinant GST. Recombinant protein detected F. gigantica experimental as well as field infection in buffaloes by dot-ELISA. However, cross-reactivity studies on Fasciola gigantica GST antigen are needed to evaluate the utility of this protein in the serodiagnosis of fasciolosis.

Keywords: fasciola gigantic, fasciola hepatica, GST, RT- PCR

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Authors: Cemile Kütmeç Yilmaz, Güler Duru Asiret, Gulcan Bagcivan

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The aim of this study was to evaluate the reliability and validity of the Turkish version of the Carer’s Assessment of Satisfaction Index (CASI-TR). The study was conducted between the dates of June 2016 and September 2017 at the Training and Research Hospital of Aksaray University with the caregiving family members of the inpatients with chronic diseases. For this study, the sample size was calculated as at least 10 individuals for each item (item number (30)X10=300). The study sample included 300 caregiving family members, who provided primer care for at least three months for a patient (who had at least one chronic disease and received inpatient treatment in general internal medicine and palliative care units). Data were collected by using a demographic questionnaire and CASI-TR. Descriptive statistics, and psychometric tests were used for the data analysis. Of those caregivers, 76.7% were female, 86.3% were 65 years old and below, 43.7% were primary school graduates, 87% were married, 86% were not working, 66.3% were housewives, and 60.3% defined their income status as having an income covering one’s expenses. Care recipients often had problems in terms of walking, sleep, balance, feeding and urinary incontinence. The Cronbach Alpha value calculated for the CASI-TR (30 items) was 0,949. Internal consistency coefficients calculated for subscales were: 0.922 for the subscale of ‘caregiver satisfaction related to care recipient’, 0.875 for the subscale of ‘caregiver satisfaction related to themselves’, and 0.723 for the subscale of ‘dynamics of interpersonal relations’. Factor analysis revealed that three factors accounted for 57.67% of the total variance, with an eigenvalue of >1. assessed in terms of significance, we saw that the items came together in a significant manner. The factor load of the items were between 0.311 and 0.874. These results show that the CASI-TR is a valid and reliable scale. The adoption of the translated CASI in Turkey is found reliable and valid to assessing the satisfaction of caregivers. CASI-TR can be used easily in clinics or house visits by nurses and other health professionals for assessing caregiver satisfaction from caregiving.

Keywords: carer’s assessment of satisfaction index, caregiver, validity, reliability

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Authors: Kristian Bugeja, Upeshala A. Jayawardena, Clarissa Fenech, Mark Zammit Vincenti

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Introduction: Biliary colic, acute cholecystitis, and gallstone pancreatitis are some of the most common surgical presentations at Gozo General Hospital (GGH). National Institute for Health and Care Excellence (NICE) guidelines advise that suitable patients with acute biliary problems should be offered a laparoscopic cholecystectomy within one week of diagnosis. There has traditionally been difficulty in achieving this mainly due to the reluctance of some surgeons to operate in the acute setting, limited, timely access to MRCP and ERCP, and organizational issues. Methodology: A retrospective study was performed involving all biliary pathology-related admissions to GGH during the two-year period of 2019 and 2020. Patients’ files and electronic case summary (ECS) were used for data collection, which included demographic data, primary diagnosis, co-morbidities, management, waiting time to surgery, length of stay, readmissions, and reason for readmissions. NICE clinical guidance 188 – Gallstone disease were used as the standard. Results: 51 patients were included in the study. The mean age was 58 years, and 35 (68.6%) were female. The main diagnoses on admission were biliary colic in 31 (60.8%), acute cholecystitis in 10 (19.6%). Others included gallstone pancreatitis in 3 (5.89%), chronic cholecystitis in 2 (3.92%), gall bladder malignancy in 4 (7.84%), and ascending cholangitis in 1 (1.97%). Management included laparoscopic cholecystectomy in 34 (66.7%); conservative in 8 (15.7%) and ERCP in 6 (11.7%). The mean waiting time for laparoscopic cholecystectomy for patients with acute cholecystitis was 74 days – range being between 3 and 146 days since the date of diagnosis. Only one patient who was diagnosed with acute cholecystitis and managed with laparoscopic cholecystectomy was done so within the 7-day time frame. Hospital re-admissions were reported in 5 patients (9.8%) due to vomiting (1), ascending cholangitis (1), and gallstone pancreatitis (3). Discussion: Guidelines were not met for patients presenting to Gozo General Hospital with acute biliary pathology. This resulted in 5 patients being re-admitted to hospital while waiting for definitive surgery. The local issues resulting in the delay to surgery need to be identified and steps are taken to facilitate the provision of urgent cholecystectomy for suitable patients.

Keywords: biliary colic, acute cholecystits, laparoscopic cholecystectomy, conservative management

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Authors: Rayhana Begum, Manju Sharma

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Careya arborea Roxb. belongs to the Lecythidaceae family, is traditionally used in tumors, anthelmintic, bronchitis, epileptic fits, astringents, inflammation, an antidote to snake-venom, skin disease, diarrhea, dysentery with bloody stools, dyspepsia, ulcer, toothache, and ear pain. The present study was focused on investigating the anti-arthritic effect of coumaroyl lupendioic acid, a new lupane-type triterpene from Careya arborea stem bark in the chronic inflammatory model and further assessing its possible mechanism on the modulation of inflammatory biomarkers. Arthritis was induced by injecting 0.1 ml of Complete Freund’s Adjuvant (5 mg/ml of heat killed Mycobacterium tuberculosis) into the subplantar region of the left hind paw. Treatment with coumaroyl lupendioic acid (10 and 20 mg/kg, p.o.) and reference drugs (indomethacin and dexamethasone at the dose of 5 mg/kg, p.o.) were started on the day of induction and continued up to 28 days. The progression of arthritis was evaluated by measuring paw volume, tibio tarsal joint diameters, and arthritic index. The effect of coumaroyl lupendioic acid (CLA) on the production PGE₂, NO, MPO, NF-κB, TNF-α, IL-1β, and IL-6 on serum level as well as inflamed paw tissue were also assessed. In addition, ankle joints and spleen were collected and prepared for histological examination. CLA in inflamed rats resulted in significant amelioration of paw edema, tibio-tarsal joint swelling and arthritic score as compared to CFA control group. The results indicated that CLA treated groups markedly decreased the levels of inflammatory mediators (PGE₂, NO, MPO and NF-κB levels) and down-regulated the production of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in paw tissue homogenates as well as in serum. However, the more pronounced effect was observed in the inflamed paw tissue homogenates. CLA also revealed a protective effect to the tibio-tarsal joint cartilage and spleen. These results suggest that coumaroyl lupendioic acid inhibits inflammation may be through the suppression of the cascade of proinflammatory mediators via the down-regulation of NF-ҡB.

Keywords: complete Freund’s adjuvant , Coumaroyl lupendioic acid, pro-inflammatory cytokines, prostaglandin E2

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Authors: Sunil Kumar, Uday C. Ghoshal

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Background and aims: Serotonin (5-hydroxtryptamine, 5-HT) is an important factor in gut function, playing key roles in intestinal peristalsis and secretion, and in sensory signaling in the brain-gut axis. Removal from its sites of action is mediated by a specific protein called the serotonin reuptake transporter (SERT). Polymorphisms in the promoter region of the SERT gene have effects on transcriptional activity, resulting in altered 5-HT reuptake efficiency. Functional polymorphisms may underlie disturbance in gut function in individuals suffering with disorders such as irritable bowel syndrome (IBS). The aim of this study was to assess the potential association between SERT polymorphisms and the diarrhea predominant IBS (D-IBS) phenotype Subjects: A total of 36 northern Indian female patients and 55 female northern Indian healthy controls (HC) were subjected to genotyping. Methods: Leucocyte DNA of all subjects was analyzed by polymerase chain reaction based technologies for SERT polymorphisms, specifically the insertion/deletion polymorphism in the promoter (SERT-P). Statistical analysis was performed to assess association of SERT polymorphism allele with the D-IBS phenotype. Results: The frequency of distribution of SERT-P gene was comparable between female patients with IBS and HC (p = 0.086). However, frequency of SERT-P deletion/deletion genotype was significantly higher in female patients with D-IBS compared to C-IBS and A-IBS [17/19 (89.5%) vs. 4/12 (33.3%) vs. 1/5 (20%), p=0.001, respectively]. The mucosal level of serotonin was higher in D-IBS compared to C-IBS and A-IBS [Median, range (159.26, 98.78–212.1) vs. 110.4, 67.87–143.53 vs. 92.34, 78.8–166.3 pmol/mL, p=0.001, respectively]. The mucosal level of serotonin was higher in female patients with IBS with SERT-P deletion/deletion genotype compared deletion/insertion and insertion/insertion [157.65, 67.87–212.1 vs. 110.4, 78.1–143.32 vs. 100.5, 69.1–132.03 pmol/mL, p=0.001, respectively]. Patients with D-IBS with deletion/deletion genotype more often reported symptoms of abdominal pain, discomfort (p=0.025) and bloating (p=0.039). Symptoms development following lactose ingestion was strongly associated with D-IBS and SERT-P deletion/deletion genotype (p=0.004). Conclusions: Significant association was observed between D-IBS and the SERT-P deletion/deletion genotype, suggesting that the serotonin transporter is a potential candidate gene for D-IBS in women.

Keywords: serotonin, SERT, inflammatory bowel disease, genetic polymorphism

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Authors: Salima Taleb, Kafila Boulaba, Ahlem Yousfi, Nada Taleb, Difallah Basma

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Introduction: Obesity is recognized as a cardiovascular risk factor. It is associated with cardio-metabolic diseases. Its prevalence is increasing significantly in both rich and poor countries. However, there are obese people who have no metabolic disturbance. So we think obesity is not always a risk factor for an abnormal metabolic profile that increases the risk of cardiometabolic problems. However, there is no definition that allows us to identify the individual group Metabolically Healthy but Obese (MHO). Objective: The objective of this study is to evaluate the relationship between MHO and some factors associated with it. Methods: A longitudinal study is a prospective cohort study of 600 participants aged ≥18 years. Metabolic status was assessed by the following parameters: blood pressure, fasting glucose, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides. Body Mass Index (BMI) was calculated as weight (in kg) divided by height (m2), BMI = Weight/(Height)². According to the BMI value, our population was divided into four groups: underweight subjects with BMI <18.5 kg/m2, normal weight subjects with BMI = 18.5–24.9 kg/m², overweight subjects with BMI=25–29.9 kg/m², and obese subjects who have (BMI ≥ 30 kg/m²). A value of P < 0.05 was considered significant. Statistical processing was done using the SPSS 25 software. Results: During this study, 194 (32.33%) were identified as MHO among 416 (37%) obese individuals. The prevalence of the metabolically unhealthy phenotype among normal-weight individuals was (13.83%) vs. (37%) in obese individuals. Compared with metabolically healthy normal-weight individuals (10.93%), the prevalence of diabetes was (30.60%) in MHO, (20.59%) in metabolically unhealthy normal weight, and (52.29%) for metabolically unhealthy obese (p = 0.032). Blood pressure was significantly higher in MHO individuals than in metabolically healthy normal-weight individuals and in metabolically unhealthy obese than in metabolically unhealthy normal weight (P < 0.0001). Familial coronary artery disease does not appear to have an effect on the metabolic status of obese and normal-weight patients (P = 0.544). However, waist circumference appears to have an effect on the metabolic status of individuals (P < 0.0001). Conclusion: This study showed a high prevalence of metabolic profile disruption in normal-weight subjects and a high rate of overweight and/or obese people who are metabolically healthy. To understand the physiological mechanism related to these metabolic statuses, a thorough study is needed.

Keywords: metabolically health, obesity, factors associated, cardiovascular diseases

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Authors: Diya Kohli, Amalia Ardeljan, Lexi Frankel, Jose Garcia, Lokesh Manjani, Omar Rashid

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Gonorrhea is the second most common sexually transmitted disease (STDs) in the United States of America. Gonorrhea affects the urethra, rectum, or throat and the cervix in females. Lymphoma is a cancer of the immune network called the lymphatic system that includes the lymph nodes/glands, spleen, thymus gland, and bone marrow. Lymphoma can affect many organs in the body. When a lymphocyte develops a genetic mutation, it signals other cells into rapid proliferation that causes many mutated lymphocytes. Multiple studies have explored the incidence of cancer in people infected with STDs such as Gonorrhea. For instance, the studies conducted by Wang Y-C and Co., as well as Caini, S and Co. established a direct co-relationship between Gonorrhea infection and incidence of prostate cancer. We hypothesize that Gonorrhea infection also increases the incidence of Lymphoma in patients. This research study aimed to evaluate the correlation between Gonorrhea infection and the incidence of Lymphoma. The data for the research was provided by a Health Insurance Portability and Accountability Act (HIPAA) compliant national database. This database was utilized to evaluate patients infected with Gonorrhea versus the ones who were not infected to establish a correlation with the prevalence of Lymphoma using ICD-10 and ICD-9 codes. Access to the database was granted by the Holy Cross Health, Fort Lauderdale for academic research. Standard statistical methods were applied throughout. Between January 2010 and December 2019, the query was analyzed and resulted in 254 and 808 patients in both the infected and control group, respectively. The two groups were matched by Age Range and CCI score. The incidence of Lymphoma was 0.998% (254 patients out of 25455) in the Gonorrhea group (patients infected with Gonorrhea that was Lymphoma Positive) compared to 3.174% and 808 patients in the control group (Patients negative for Gonorrhea but with Lymphoma). This was statistically significant by a p-value < 2.210-16 with an OR= 0.431 (95% CI 0.381-0.487). The patients were then matched by antibiotic treatment to avoid treatment bias. The incidence of Lymphoma was 1.215% (82 patients out of 6,748) in the Gonorrhea group compared to 2.949% (199 patients out of 6748) in the control group. This was statistically significant by a p-value <5.410-10 with an OR= 0.468 (95% CI 0.367-0.596). The study shows a statistically significant correlation between Gonorrhea and a reduced incidence of Lymphoma. Further evaluation is recommended to assess the potential of Gonorrhea in reducing Lymphoma.

Keywords: gonorrhea, lymphoma, STDs, cancer, ICD

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Authors: Erna Judith Roach, Nalini Bhaskaranand

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Background & Significance: Asthma is the most common chronic disease among children. Education is the cornerstone of management of asthma to help the affected children. In India there are about 1.5- 3.0 million asthmatic children in the age group of 5-11 years. Many parents face management dilemmas in administration of medications to their children. Mothers being primary caregivers of children are often responsible for administering medications to them. The purpose of the study was to develop an educational package on techniques of drug administration for mothers of asthmatic children and determine its effectiveness in terms of improvement in skill in drug administration. Methodology: A quasi- experimental time series pre-test post -test control group design was used. Mothers of asthmatic children attending paediatric outpatient departments of selected hospitals along with their children between 5 and 12 years were included. Sample size consisted of 40 mothers in the experimental and 40 mothers in the control groups. Block randomization was used to assign samples to both the groups. The data collection instruments used were Baseline Proforma, Clinical Proforma, Daily asthma drug intake and symptoms diary and Observation Rating Scales on technique of using a metered dose inhaler with spacer; metered dose inhaler with facemask; metered dose inhaler alone and dry powder inhaler. The educational package consisted of a video and booklet on techniques of drug administration. Data were collected at baseline, 1, 3 and 6 months. Findings: The mean post-test scores in techniques of drug administration were higher than the mean pre-test scores in the experimental group in all techniques. The Friedman test (p < 0.01), Wilcoxon Signed Rank test (p < 0.008) and Mann Whitney U (p < 0.01) showed statistically significant difference in the experimental group than the control group. There was significant decrease in the average number of symptom days (11 Vs. 4 days/ month) and hospital visits (5 to 1 per month) in the experimental group when compared to the control group. Conclusion: The educational package was found to be effective in improving the skill of mothers in drug administration in all the techniques, especially with using the metered dose inhaler with spacer.

Keywords: childhood asthma, drug administration, mothers of children, inhaler

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Authors: Hossein Rassi, Marjan Moradi Fard, Masoud Houshmand

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Background: Cervical cancer is multistep disease that is thought to result from an interaction between genetic background and environmental factors. Human papillomavirus (HPV) infection is the leading risk factor for cervical intraepithelial neoplasia (CIN) and cervical cancer. In other hand, some of p53 and miRNA polymorphism may plays an important role in carcinogenesis. This study attempts to clarify the relation of p53 genotypes and miR-146a rs2910164 polymorphism in cervical lesions. Method: Forty two archival samples with cervical lesion retired from Khatam hospital and 40 sample from healthy persons used as control group. A simple and rapid method was used to detect the simultaneous amplification of the HPV consensus L1 region and HPV-16,-18, -11, -31, 33 and -35 along with the b-globin gene as an internal control. We use Multiplex PCR for detection of P53 and miR-146a rs2910164 genotypes in our lab. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Results: Cervix lesions were collected from 42 patients with Squamous metaplasia, cervical intraepithelial neoplasia, and cervical carcinoma. Successful DNA extraction was assessed by PCR amplification of b-actin gene (99bp). According to the results, p53 GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of cervical lesions in the study population. In this study, we detected 13 HPV 18 from 42 cervical cancer. Conclusion: The connection between several SNP polymorphism and human virus papilloma in rare researches were seen. The reason of these differences in researches' findings can result in different kinds of races and geographic situations and also differences in life grooves in every region. The present study provided preliminary evidence that a p53 GG genotype and miR-146a rs2910164 CC genotype may effect cervical cancer risk in the study population, interacting synergistically with HPV 18 genotype. Our results demonstrate that the testing of p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes in combination with HPV18 can serve as major risk factors in the early identification of cervical cancers. Furthermore, the results indicate the possibility of primary prevention of cervical cancer by vaccination against HPV18 in Iran.

Keywords: cervical cancer, HPV18, p53 codon 72 polymorphism, miR-146a rs2910164 polymorphism

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Authors: M. Osibemhe, I. O. Onoagbe

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Diabetes mellitus is a common disease that has no known cure. The available orthodox drugs used for its management have one or more disadvantages. This study investigated the potency of aqueous and ethanol extracts of Strophanthus hispidus (SH) stem bark in the management of diabetes mellitus. Glucose concentration and lipid profile parameters of normal and streptozotocin-induced diabetic rats were monitored for 12weeks. Diabetes mellitus was induced by intraperitoneal injection of streptozotocin (55 mg/kg). Male rats (wistar strain) numbering 30 were randomly selected into six groups of five rats each. Groups 1 and 6 served as normal and diabetic control respectively and received distilled water for 12weeks. Groups 2 and 3 were normal rats treated orally with the aid of a gavage, 250 mg/kg of aqueous and ethanol extracts respectively for 12weeks. Groups 4 and 5 were diabetic rats and were treated with the respective dose of aqueous and ethanol extracts for the same period. A significant (P˂0.05) progressive decrease in blood glucose concentrations of both normal and diabetic rats treated with the extracts were observed from the 2nd to 12th weeks when compared with the respective controls. No significant (P˃0.05) effects were observed in the basal values of both normal and diabetic rats. Administration of both extracts of SH to diabetic rats significantly (P˂0.05) lowered the concentrations of Total cholesterol, TG, and LDL, whereas it increases the concentration of HDL when compared with diabetic control. The concentrations of total cholesterol and LDL in normal rats treated with SH were also reduced when compared with normal control whereas SH had no significant (P˃0.05) effect on HDL. However, TG level of normal control was significantly (P˂0.05) lower than normal rats treated with both extracts. A progressive increase in weight of normal and diabetic rats treated with the extracts was observed on the 2nd – 12th weeks of administration, whereas diabetic control showed a progressive decrease in weight. The findings from this study indicated that SH has hypoglycemic and anti-lipidemic properties as well as anti-diabetic potentials. It also showed that ethanol extract had greater glucose lowering effect. Hence, SH may be considered as a potent anti-diabetic plant and could be used as alternative drug for the management of diabetes mellitus.

Keywords: concentration, ethanol extract, hypoglycemic, total cholesterol

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Authors: Mei-Ling Chan, Jin-Ming Wu, Konstantin V. Kudryavtsev, Jih-Hwa Guh

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Prostate cancer is one of the most common malignant disease in men. KUD983 is an enantiomerically pure β-dipeptide derivative, which may have anti-cancer effects. In the present study, KUD983 exhibits powerful activity against hormone-refractory prostate cancer (HRPC) PC-3 and DU145 cells. The IC50 values of KUD983 in PC-3 and DU145 cells are 0.56±0.07M and 0.50±0.04 M respectively. KUD983 induced G1 arrest of the cell cycle and subsequent apoptosis associated with the down-regulation of several related proteins including cyclin D1, cyclin E and Cdk4, and the de-phosphorylation of RB. The protein expressions of nuclear and total c-Myc protein, which was able to regulate the expression of both cyclin D1 and cyclin E, were significantly suppressed by KUD983. Phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) is an important signaling pathway that influences the energy metabolism, cell cycle, proliferation, survival and apoptosis of cells, and is associated with numerous other signaling pathways. The Western Blot data revealed that KUD983 inhibited PI3K/Akt and mTOR/p70S6K/4E-BP1 pathways. The transient transfection of constitutively active myristylated Akt (myr-Akt) cDNA significantly reversed KUD983-induced caspase activation but did not abolish the suppression of mTOR/p70S6K/4E-BP1 signaling cascade indicating the presence of both Akt-dependent and -independent pathways. Moreover, KUD983-induced effect was collaborated with the down-regulation of anti-apoptotic Bcl-2 members (e.g., Bcl-2, and Mcl-1) and IAP family members (e.g., survivin). Furthermore, KUD983 induced autophagic cell death using confocal microscopic examination, investigating the level of conversion of LC3-I to LC3-II and flow cytometric detection of AVO-positive cells. Taken together, the data suggest that KUD983 is an anticancer β-dipeptide against HRPCs through the inhibition of cell proliferation and induction of apoptotic and autophagic cell death. The suppression of signaling pathways mediated by c-Myc, PI3K/Akt and mTOR/p70S6K/4E-BP1 and the collaboration with down-regulation of Mcl-1 and survivin may indicate the mechanism of KUD983 against HRPC.

Keywords: β-dipeptide, hormone-refractory prostate cancer, mTOR, PI3K/Akt

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Authors: Ruqayya Naheed Khan, Awais Amjad Malik, Awais Naeem, Amina Khan, Asad Parvaiz

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Introduction: Axillary nodal status in breast cancer patients is a paramount prognosticator, next to primary tumor size and grade. It has been well established that patients with negative sentinel lymph node biopsy can safely avoid axillary lymph node dissection. A positive sentinel lymph node has traditionally required subsequent axillary dissection. According to ACOSOG Z11 trial, patients who underwent axillary dissection with 3 or more positive sentinel nodes or opted for observation in case of negative sentinel lymph node, did not find any difference in Overall Survival (OS) and Disease Free Survival (DFS). The Z11 trial included patients who underwent breast conserving surgery and excluded patients with mastectomies. The purpose of this study is to determine whether Z0011 can be applied to mastectomy patients as well in 1-3 positive sentinel lymph nodes and avoid unnecessary ALND. Methods: A retrospective review was conducted at Shaukat Khanam Memorial Cancer Hospital Pakistan from Jan 2015 to Dec 2017 including patients who were treated for invasive breast cancer and required upfront mastectomy. They were clinically node negative, so sentinel lymph node biopsy was performed. Patients underwent ALND with positive sentinel lymph node. A total of 156 breast cancer patients with mastectomies were reviewed. Results: 95% of the patients were female while 3% were male. Average age was 44 years. There was no difference in race, comorbidities, histology, T stage, N stage, and overall stage, use of adjuvant chemotherapy and radiation therapy. 64 patients underwent ALND for positive lymph node while 92 patients were spared of axillary dissection due to negative sentinel lymph node biopsy. Out of 64 patients, 38 patients (59%) had only 1 lymph node positive which was the sentinel node. 18 patients (28%) had 2 lymph nodes positive including the sentinel node while only 8 patients (13%) had 3 or more positive nodes. Conclusion: Keeping in mind the complications related to ALND, above results clearly show that ALND could have been avoided in 87% of patients in the setting of adjuvant radiation, possibly avoiding the morbidity associated with axillary lymphadenectomy although a prospective randomized trial needs to confirm these results.

Keywords: mastectomy, sentinel lymph node biopsy, axillary lymph node dissection, breast cancer

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Authors: Gal Zagron, Nitza Abramson, Deena R. Zimmerman, Chen Stein-Zamir

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Background: Salmonella enteritidis is a common cause of foodborne outbreaks, primarily associated with poultry eggs. S. enteritidis This is the only Salmonella type that is found inside the eggshell. A rise in Salmonella enteritidis notifications was noted in spring 2017. Aims: The aim of this study is to describe the epidemiological investigation of the outbreak in the Jerusalem district, along with the containment measures taken. Methods: This study is a population-based epidemiological study with a description of environmental control activities. Results: During the months May - July, 2017 848 salmonellosis cases were reported to the Jerusalem district health office compared to 294 cases May - July 2016. Salmonella enteritidis was isolated in 58% of reported cases. Clusters and outbreaks ( > 2 cases) were reported among nursery schools, nursing homes, persons residing in one kibbutz and several cases in different food service establishments in the Jerusalem district. Epidemiological investigations revealed eggs consumption as a common feature among the cases (uncooked or undercooked eggs in most cases). A national investigation among egg suppliers revealed that most cases consumed eggs provided by a single provider with isolation of Salmonella enteritidis at the source as well. Containment measures were taken to control the epidemic including distributing information via electronic and written media to the public, searching for all egg distribution centers, informing local authorities, the poultry council and food stores. The eggs originating from the provider were recalled and extinguished. Written instructions to all food preparation facilities in the district were distributed regarding the proper storage and preparation of eggs. The number of reported cases declined and the outbreak vanished during correlating months of 2018. Conclusions: The investigation of Salmonella enteritidis outbreaks should include epidemiological and laboratory investigations, tracing the source of the eggs and testing the eggs and the source of eggs. Health education activities are essential as to the proper handling of eggs and egg products aiming to minimize susceptibility to Salmonella infection.

Keywords: epidemiological investigation, food-borne disease, food safety, Salmonella enteritidis

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Authors: Kremena Ivanona, Bistra Kunovska, Jana Djunova, Desislava Djunakova, Zdenka Stojanovska

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In recent decades, the general public has become increasingly interested in the impact of air pollutions on their health. Currently, numerous studies are aimed at identifying pollutants in the indoor environment where they carry out daily activities. Internal pollutants can be of both natural and artificial origin. With regard to natural pollutants, special attention is paid to natural radioactivity. In recent years, radon has been one of the most studied indoor pollutants because it has the greatest contribution to human exposure to natural radionuclides. It is a known fact that lung cancer can be caused by radon radiation and it is the second risk factor after smoking for the onset of the disease. The main objective of the study under the National Science Fund of Bulgaria, in the framework of grant No КП-06-Н23/1/07.12.2018 is to evaluate the indoor radon as an important air pollutant in school buildings in order to reduce the exposure to children. The measurements were performed in 48 schools located in 55 buildings in one Bulgarian administrative district (Kardjaly). The nuclear track detectors (CR-39) were used for measurements. The arithmetic and geometric means of radon concentrations are AM = 140 Bq/m3, and GM = 117 Bq/m3 respectively. In 51 school rooms, the radon levels were greater than 200 Bq/m3, and in 28 rooms, located in 17 school buildings, it exceeded the national reference level of 300 Bq/m3, defined in the Bulgarian ordinance on radiation protection (or 30% of the investigated buildings). The statistically significant difference in the values of radon concentration by municipalities (KW, р < 0.001) obtained showed that the most likely reason for the differences between the groups is the geographical location of the buildings and the possible influence of the geological composition. The combined effect of the year of construction (technical condition of the buildings) and the energy efficiency measures was considered. The values of the radon concentration in the buildings where energy efficiency measures have been implemented are higher than those in buildings where they have not been performed. This result confirms the need for investigation of radon levels before conducting the energy efficiency measures in buildings. Corrective measures for reducing the radon levels have been recommended in school buildings with high radon levels in order to decrease the children's exposure.

Keywords: air pollution, indoor radon, children exposure, schools

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Authors: Ammar Amsyar Abdul Haddi, Mohd Hasni Jaafar

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Heavy metals are elements naturally presented in the environment that can cause adverse effect to health. But not much literature was found on effects toward lung function, where impairment of lung function may lead to various lung diseases. The objective of the study is to explore the lung function impairment, urinary heavy metal level, and its associated factors among the community in Klang valley, Malaysia. Sampling was done in Kuala Lumpur suburb public and housing areas during community events throughout March 2019 till October 2019. respondents who gave the consent were given a questionnaire to answer and was proceeded with a lung function test. Urine samples were obtained at the end of the session and sent for Inductively coupled plasma mass spectrometry (ICP-MS) analysis for heavy metal cadmium (Cd) and lead (Pb) concentration. A total of 200 samples were analysed, and of all, 52% of respondents were male, Age ranging from 18 years old to 74 years old with a mean age of 38.44. Urinary samples show that 12% of the respondent (n=22) has Cd level above than average, and 1.5 % of the respondent (n=3) has urinary Pb at an above normal level. Bivariate analysis show that there was a positive correlation between urinary Cd and urinary Pb (r= 0.309; p<0.001). Furthermore, there was a negative correlation between urinary Cd level and full vital capacity (FVC) (r=-0.202, p=0.004), Force expiratory volume at 1 second (FEV1) (r = -0.225, p=0.001), and also with Force expiratory flow between 25-75% FVC (FEF25%-75%) (r= -0.187, p=0.008). however, urinary Pb did not show any association with FVC, FEV1, FEV1/FVC, or FEF25%-75%. Multiple linear regression analysis shows that urinary Cd remained significant and negatively affect FVC% (p=0.025) and FEV1% (p=0.004) achieved from the predicted value. On top of that, other factors such as education level (p=0.013) and duration of smoking(p=0.003) may influencing both urinary Cd and performance in lung function as well, suggesting Cd as a potential mediating factor between smoking and impairment of lung function. however, there was no interaction detected between heavy metal or other influencing factor in this study. In short, there is a negative linear relationship detected between urinary Cd and lung function, and urinary Cd is likely to affects lung function in a restrictive pattern. Since smoking is also an influencing factor for urinary Cd and lung function impairment, it is highly suggested that smokers should be screened for lung function and urinary Cd level in the future for early disease prevention.

Keywords: lung function, heavy metals, community

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Authors: Timmis W., Simms M., Thomas C.

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This case discusses the management of two floors of mouth (FOM) Squamous Cell Carcinomas (SCC) not identified upon initial biopsy. A 51 year-old male presented with right FOM erythroleukoplakia. Relevant medical history included alcoholic dependence syndrome and alcoholic liver disease. Relevant drug therapy encompassed acamprosate, folic acid, hydroxocobalamin and thiamine. The patient had a 55.5 pack-year smoking history and alcohol dependence from age 14, drinking 16 units/day. FOM incisional biopsy and histopathological analysis diagnosed Carcinoma in situ. Treatment involved wide local excision. Specimen analysis revealed two separate foci of pT1 moderately differentiated SCCs. Carcinoma staging scans revealed no pathological lymphadenopathy, no local invasion or metastasis. SCCs had been excised in completion with narrow margins. MDT discussion concluded that in view of the field changes it would be difficult to identify specific areas needing further excision, although techniques such as Lugol’s Iodine were considered. Further surgical resection, surgical neck management and sentinel lymph node biopsy was offered. The patient declined intervention, primary management involved close monitoring alongside alcohol and smoking cessation referral. Narrow excisional margins can increase carcinoma recurrence risk. Biopsy failed to identify SCCs, despite sampling an area of clinical concern. For gross field change multiple incisional biopsies should be considered to increase chance of accurate diagnosis and appropriate treatment. Coupling of tobacco and alcohol has a synergistic effect, exponentially increasing the relative risk of oral carcinoma development. Tobacco and alcoholic control is fundamental in reducing treatment‑related side effects, recurrence risk and second primary cancer development.

Keywords: alcohol dependence, biopsy, oral carcinoma, tobacco

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Authors: Eisha Vienna M. Fernandez, Cristan Q. Cabanilla, Hiyasmin Lim, John Donnie A. Ramos

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Allergy is a multifactorial disease affecting a significant proportion of the population. It is developed through the interaction of allergens and the presence of certain polymorphisms in various susceptibility genes. In this study, the correlation of the 105A/C single nucleotide polymorphism (SNP) of the IL-18 gene and house dust mite-specific IgE among Filipino allergic and non-allergic population was investigated. Atopic status was defined by serum total IgE concentration of ≥100 IU/mL, while house dust mite allergy was defined by specific IgE value ≥ +1SD of IgE of nonatopic participants. Two hundred twenty match-paired Filipino cases and controls aged 6-60 were the subjects of this investigation. The level of total IgE and Specific IgE were measured using Enzyme-Linked Immunosorbent Assay (ELISA) while Polymerase Chain Reaction – Restriction Fragment Length Polymorphism (PCR-RFLP) analysis was used in the SNP detection. Sensitization profiles of the allergic patients revealed that 97.3% were sensitized to Blomia tropicalis, 40.0% to Dermatophagoides farinae, and 29.1% to Dermatophagoides pteronyssinus. Multiple sensitization to HDMs was also observed among the 47.27% of the atopic participants. Any of the allergy classes of the atopic triad were exhibited by the cases (allergic asthma: 48.18%; allergic rhinitis: 62.73%; atopic dermatitis: 19.09%), and two or all of these atopic states are concurrently occurring in 26.36% of the cases. A greater proportion of the atopic participants with allergic asthma and allergic rhinitis were sensitized to D. farinae, and D. pteronyssinus, while more of those with atopic dermatitis were sensitized to D. pteronyssinus than D. farinae. Results show that there is overrepresentation of the allele “A” of the 105A/C IL-18 gene SNP in both cases and control groups of the population. The genotype that predominate the population is the heterozygous “AC”, followed by the homozygous wild “AA”, and the homozygous variant “CC” being the least. The study confirmed a positive association between serum specific IgE against B. tropicalis and D. pteronyssinus and the allele “C” (Bt P=0.021, Dp P=0.027) and “AC” (Bt P=0.003, Dp P=0.026) genotype. Findings also revealed that the genotypes “AA” (OR:1.217; 95% CI: 0.701-2.113) and “CC” (OR, 3.5; 95% CI: 0.727-16.849) increase the risk of developing allergy. This indicates that the 105A/C IL-18 gene SNP is a candidate genetic marker for HDM allergy among Filipino patients.

Keywords: house dust mite allergy, interleukin-18 (IL-18), single nucleotide polymorphism,

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Authors: Ari Prasetyo, Taufik Faturohman

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The COVID-19 pandemic in Indonesia is part of the ongoing worldwide pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was confirmed to have spread to Indonesia on 2 March 2020. Moreover, the government of Indonesia has been conducting a local lockdown to limit people's movement from one city to another city. Therefore, this situation has impact on business operation, especially on highway companies listed on the Indonesia stock exchange. This study evaluates and measures three companies’ financial performance and health conditions before and during the COVID-19 pandemic from 2016 – 2020. The measurement is conducted by using financial ratio analysis and the Altman Z-score method. The ratio used to measure the financial ratio analysis is taken from the decree of the Ministry of SOE’s KEP-100/MBU/2002 about the company’s health level condition. From the decree, there are eight financial ratios used such as return on equity (ROE), return on investment (ROI), current ratio, cash ratio, collection period, inventory turnover, total asset turnover, and total equity to total asset. Altman Z-score is used to calculate the financial distress condition. The result shows that the highway companies for the period 2016 – 2020 are as follows: PT Jasa Marga (Persero) Tbk (AA, BB, BB, BB, C), PT Citra Marga Nusaphala Persada Tbk (BB, AA, BB, BBB, C), and PT Nusantara Infrastructure Tbk (BB, BB, AA, BBB, C). In addition, the Altman Z-score assessment performed in 2016-2020 shows that PT Jasa Marga (Persero) Tbk was in the grey zone area for 2015-2018 and in the distress zone for 2019-2020. PT Citra Marga Nusaphala Persada Tbk was in the grey zone area for 2015-2019 and in the distress zone for 2020. PT Nusantara Infrastructure Tbk was in the grey zone area for 2015-2018 and in the distress zone for 2019-2020.

Keywords: financial performance, financial ratio, Altman Z-score, financial distress, highway company

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Authors: Sungpil Ha, Ju Yong Kang, Sangbaek Park, Seung-Ju Lee, Soo-Won Chae

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The growing number of obese patients in aging societies has led to an increase in the number of patients with knee medial osteoarthritis (OA). Artificial joint insertion is the most common treatment for knee medial OA. Surgery is effective for patients with serious arthritic symptoms, but it is costly and dangerous. It is also inappropriate way to prevent a disease as an early stage. Therefore Non-operative treatments such as toe-in gait are proposed recently. Toe-in gait is one of non-surgical interventions, which restrain the progression of arthritis and relieves pain by reducing knee adduction moment (KAM) to facilitate lateral distribution of load on to knee medial cartilage. Numerous studies have measured KAM in various foot progression angle (FPA), and KAM data could be obtained by motion analysis. However, variations in stress at knee cartilage could not be directly observed or evaluated by these experiments of measuring KAM. Therefore, this study applied motion analysis to major gait points (1st peak, mid –stance, 2nd peak) with regard to FPA, and to evaluate the effects of FPA on the human lower extremity, the finite element (FE) method was employed. Three types of gait analysis (toe-in, toe-out, baseline gait) were performed with markers placed at the lower extremity. Ground reaction forces (GRF) were obtained by the force plates. The forces associated with the major muscles were computed using GRF and marker trajectory data. MRI data provided by the Visible Human Project were used to develop a human lower extremity FE model. FE analyses for three types of gait simulations were performed based on the calculated muscle force and GRF. We observed the maximum stress point during toe-in gait was lower than the other types, by comparing the results of FE analyses at the 1st peak across gait types. This is the same as the trend exhibited by KAM, measured through motion analysis in other papers. This indicates that the progression of knee medial OA could be suppressed by adopting toe-in gait. This study integrated motion analysis with FE analysis. One advantage of this method is that re-modeling is not required even with changes in posture. Therefore another type of gait simulation or various motions of lower extremity can be easily analyzed using this method.

Keywords: finite element analysis, gait analysis, human model, motion capture

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Authors: Cha-ah C. N., Awah N. J., Mouiche M. M. M.

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Brucellosis is a neglected zoonotic disease of animals and man caused by bacteria of genus Brucella. Though eradicated in some parts of the world, it remains endemic in sub-Saharan Africa including Cameroon. The aim of this study was to contribute to the epidemiology of brucellosis in the North-West region of Cameroon by detecting the presence of anti-Brucella antibodies in bovine bulk milk as this serves as a route of transmission from animals to man. A cross sectional study was conducted to determine the prevalence of Brucella abortus antibodies in bovine bulk milk in the peri-urban zones of Bamenda. One hundred bulk milk samples were collected from 100 herds and tested by milk I-ELISA test. The conducted study revealed the presence of anti-Brucella abortus antibodies in bovine bulk milk. The study revealed that bovine brucellosis is widespread in animal production systems in this area. The animal infection pressure in these systems has remained strong due to movement of livestock in search of pasture, co-existence of animal husbandry, communal sharing of grazing land, concentration of animals around water points, abortions in production systems, locality of production systems and failure to quarantine upon introduction of new animals. The circulation of Brucella abortus antibodies in cattle farms recorded in the study revealed potential public health implication and suggest economic importance of brucellosis to the cattle industry in the Northwest region of Cameroon. The risk for re-emergence and transmission of brucellosis is evident as a result of the co-existence of animal husbandry activities and social-cultural activities that promote brucellosis transmission. Well-designed countrywide, evidence-based studies of brucellosis are needed. These could help to generate reliable frequency and potential impact estimates, to identify Brucella reservoirs, and to propose control strategies of proven efficacy.

Keywords: brucellosis, bulk milk, northwest region Cameroon, prevalence

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Authors: A. O. Omonona, T. A. Jarikre

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Increase specialization in agriculture and use of pesticides may inadvertently cause ecosystem degradation and eventually loss of biodiversity. The populations of numerous wildlife species have undergone a precipitous decline. Many of these problems have been attributed directly to habitat loss and over exploitation resulting from unregulated pesticide uses. Carbendazim a broad spectrum benzimidazole fungicide and a metabolite of benomyl, is used to control plant disease in cereals and fruit. The effect of carbendazim exposure and the ameliorative effect of tocopherol (vitamin E) were assessed on African giant rat AGR. Hematological, biochemical and histological changes were used to determine the health condition of the animals exposed to pesticide. Sixteen AGR were stabilized, weighed and then divided into four experimental groups (A to D). Two groups were pretreated with vitamin. Group A was exposed to carbendazim only, B- carbendazim + vitamin, C- vitamin only, and D- blank (control). Packed cell volume PCV was estimated by the microhematocrit method, Leucocyte and Platelet counts were determined using the hemocytometric method. Cholinesterase (AchE) and markers of oxidative stress were quantified, and tissue changes examined microscopically. There were no behavioral changes observed in the animals, but there was a decrease in body weight and abortion after 23 days of exposure to carbendazim. There was significant differences in the packed cell volume, the hemoglobin concentration and the red blood cell counts (p < 0.05). The increases in malonyl aldehyde MDA was significant (p < 0.05) in the pesticide intoxicated rats compared to control. Vitamin E supplementation reduced MDA level significantly (p < 0.05). There was a sharp remarkable decrease in acetylcholinesterase levels in the pesticide intoxicated rats (p < 0.05). Vitamin E supplementation normalise the AchE levels comparable to that in control. Grossly, the vital organs appeared normal in the pesticide exposed and control groups except moderate pulmonary congestion. Microscopically, there was severe diffuse hepatocellular swelling in carbendazim exposed group. The severity of hepatocellular injury was reduced in the rats with vitamin E. This study ascertained the toxic effect of carbendazim and antioxidative properties of vitamins in the Africa giant rat.

Keywords: African giant rat, antioxidant, carbendazim, pesticides, toxicity

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Authors: Manjusha R. Vagal, Shyam K. Shrivastava, Umesh Mahantshetty, Sudeep Gupta, Supriya Chopra, Reena Engineer, Amita Maheshwari, Atul Buduk

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Vaginal stenosis is a common side effect associated with pelvic radiotherapy in cervical cancer patients which contributes negatively to woman’s health and prevents adequate vaginal/cervical examination. Vaginal dilation with a dilator is routine practice and is internationally advocated as a prophylactic measure to preserve vaginal patency. This retrospective study was carried out with the aim to know the usefulness of vaginal dilation following pelvic radiation therapy in cervical cancer patients in India. Data from medical records of 183 cervical cancer patients, which met the study criteria, were collected related to the stage of the disease, treatment received, commencement period of dilation post radiation therapy, sexual status and side effects associated to dilation practice. Data related to vaginal dimensions as per the length of insertion of a small, medium and large dilator were collected on regular follow-ups until 36 months and/or more. Vaginal dimensions as measured with the length of medium dilator insertion were used for analysis of dilation therapy results using paired t-test. Patients who underwent vaginal dilation with dilator maintained vaginal patency, also the mean vaginal length significantly increased, from 8.02 cm ± 2.69 to 9.96 ± 2.89 cm with a p value <0.001. There was no significant difference found on vaginal patency with different intervals of initiation of dilation therapy. At the third year and more following dilation therapy, significant increase in vaginal length observed with a p value of 0.0001 in both sexually active and inactive patients. Compilation of vaginal dosage during brachytherapy was inadequate, and hence, the secondary objective of the study to determine the effect of radiotherapy on the outcome of rehabilitation intervention was not studied in detail. This retrospective study has found that dilation therapy with vaginal dilators post pelvic radiotherapy is effective in preventing vaginal stenosis and improving vaginal patency and cannot be substituted with vaginal intercourse. Sexual quality of life assessment in the Indian population needs much attention.

Keywords: dilator, sexually active, vaginal dilation, vaginal stenosis

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Authors: Laura Amato, Paolo Mulatti, Fabrizio Montarsi, Matteo Mazzucato, Laura Gagliazzo, Michele Brichese, Manlio Palei, Gioia Capelli, Lebana Bonfanti

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West Nile virus (WNV) re-emerged in north-eastern Italy in 2008, after ten years from its first appearance in Tuscany. In 2009, a national surveillance programme was implemented, and re-modulated in north-eastern Italy in 2011. Hereby, we present the results of surveillance activities in 2008-2016 in the north-eastern Italian regions, with inferences on WNV epidemiological trend in the area. The re-modulated surveillance programmes aimed at early detecting WNV seasonal reactivation by searching IgM antibodies in horses. In 2013, the surveillance plans were further modified including a risk-based approach. Spatial analysis techniques, including Bernoulli space-time scan-statistics, were applied to the results of 2010–2012 surveillance on mosquitoes, equines, and humans to identify areas where WNV reactivation was more likely to occur. From 2008 to 2016, residential horses tested positive for anti-WNV antibodies on a yearly basis (503 cases), also in areas where WNV circulation was not detected in mosquito populations. Surveillance activities detected 26 syndromic cases in horses, 102 infected mosquito pools and WNV in 18 dead wild birds. Human cases were also recurrently detected in the study area during the surveillance period (68 cases of West Nile neuroinvasive disease). The recurrent identification of WNV in animals, mosquitoes, and humans indicates the virus has likely become endemic in the area. In 2016, findings of WNV positives in horses or mosquitoes were included as triggers for enhancing screening activities in humans. The evolution of the epidemiological situation prompts for continuous and accurate surveillance measures. The results of the 2013-2016 surveillance indicate that the risk-based approach was effective in early detecting seasonal reactivation of WNV, key factor of the integrated surveillance strategy in endemic areas.

Keywords: arboviruses, horses, Italy, surveillance, west nile virus, zoonoses

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Authors: Mohamed Moussaoui, Mouna Baassi, Soukayna Baammi, Hatim Soufi, Mohammed Salah, Rachid Daoud, Achraf EL Allali, Mohammed Elalaoui Belghiti, Said Belaaouad

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The present study aims to investigate the quantitative structure-activity relationship (QSAR) of a series of Thiazole derivatives reported as anticancer agents (hepatocellular carcinoma), using principally the electronic descriptors calculated by the density functional theory (DFT) method and by applying the multiple linear regression method. The developed model showed good statistical parameters (R²= 0.725, R²ₐ𝒹ⱼ= 0.653, MSE = 0.060, R²ₜₑₛₜ= 0.827, Q²𝒸ᵥ = 0.536). The energy of the highest occupied molecular orbital (EHOMO) orbital, electronic energy (TE), shape coefficient (I), number of rotatable bonds (NROT), and index of refraction (n) were revealed to be the main descriptors influencing the anti-cancer activity. Additional Thiazole derivatives were then designed and their activities and pharmacokinetic properties were predicted using the validated QSAR model. These designed molecules underwent evaluation through molecular docking (MD) and molecular dynamic (MD) simulations, with binding affinity calculated using the MMPBSA script according to a 100 ns simulation trajectory. This process aimed to study both their affinity and stability towards Cyclin-Dependent Kinase 2 (CDK2), a target protein for cancer disease treatment. The research concluded by identifying four CDK2 inhibitors - A1, A3, A5, and A6 - displaying satisfactory pharmacokinetic properties. MDs results indicated that the designed compound A5 remained stable in the active center of the CDK2 protein, suggesting its potential as an effective inhibitor for the treatment of hepatocellular carcinoma. The findings of this study could contribute significantly to the development of effective CDK2 inhibitors.

Keywords: QSAR, ADMET, Thiazole, anticancer, molecular docking, molecular dynamic simulations, MMPBSA calculation

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Authors: Owonikoko Abayomi Dele

Abstract:

Epilepsy is an unresolved disease that needs urgent attention. It is a brain disorder that affects over sixty-five (65) million people around the globe. Despite the availability of commercial anti-epileptic drugs, the war against this unmet condition is yet to be resolved. Most epilepsy patients are resistant to available anti-epileptic medications thus the need for affordable novel therapy against epilepsy is a necessity. Numerous phytochemicals have been reported for their potency, efficacy and safety as therapeutic agents against many diseases. This study investigated 99 isolated phytochemicals from Chasmanthera dependens and Carissa edulis against carbonic anhydrase (ii) drug target. The absorption, distribution, metabolism, excretion and toxicity (ADMET) of the isolated compounds were examined using admet SAR-2 web server while Swiss ADME was used to analyze the oral bioavailability, drug-likeness and lead-likeness properties of the selected leads. PASS web server was used to predict the biological activities of selected leads while other important physicochemical properties and interactions of the selected leads with the active site of the target after successful molecular docking simulation with the pyrx virtual screening tool were also examined. The results of these study identified seven lead compounds; C49- alpha-carissanol (-7.6 kcal/mol), C13- Catechin (-7.4 kcal/mol), C45- Salicin (-7.4 kcal/mol), C6- Bisnorargemonine (-7.3 kcal/mol), C36- Pallidine (-7.1 kcal/mol), S4- Lacosamide (-7.1 kcal/mol), and S7- Acetazolamide (-6.4 kcal/mol) for CA II (3HS4 receptor). These leads compounds are probable inhibitors of this drug target due to the observed good binding affinities and favourable interactions with the active site of the drug target, excellent ADMET profiles, PASS Properties, drug-likeness, lead-likeness and oral bioavailability properties. The identified leads have better binding energies as compared to the binding energies of the two standards. Thus, seven identified lead compounds can be developed further towards the development of new anti-epileptic medications.

Keywords: drug-likeness, phytochemicals, carbonic anhydrases, metalloeazymes, active site, ADMET

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Authors: Valeria Arcucci, Musarat Ishaq, Steven A. Stacker, Greg J. Goodall, Marc G. Achen

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Metastasis is the lethal aspect of cancer for most patients. Remodelling of lymphatic vessels associated with a tumour is a key initial step in metastasis because it facilitates the entry of cancer cells into the lymphatic vasculature and their spread to lymph nodes and distant organs. Although it is clear that vascular endothelial growth factors (VEGFs), such as VEGF-C and VEGF-D, are key drivers of lymphatic remodelling, the means by which many signaling pathways in endothelial cells are coordinately regulated to drive growth and remodelling of lymphatics in cancer is not understood. We seek to understand the broader molecular mechanisms that control cancer metastasis, and are focusing on microRNAs, which coordinately regulate signaling pathways involved in complex biological responses in health and disease. Here, using small RNA sequencing, we found that a specific microRNA, miR-132, is upregulated in expression in lymphatic endothelial cells (LECs) in response to the lymphangiogenic growth factors. Interestingly, ectopic expression of miR-132 in LECs in vitro stimulated proliferation and tube formation of these cells. Moreover, miR-132 is expressed in lymphatic vessels of a subset of human breast tumours which were previously found to express high levels of VEGF-D by immunohistochemical analysis on tumour tissue microarrays. In order to dissect the complexity of regulation by miR-132 in lymphatic biology, we performed Argonaute HITS-CLIP, which led us to identify the miR-132-mRNA interactome in LECs. We found that this microRNA in LECs is involved in the control of many different pathways mainly involved in cell proliferation and regulation of the extracellular matrix and cell-cell junctions. We are now exploring the functional significance of miR-132 targets in the biology of LECs using biochemical techniques, functional in vitro cell assays and in vivo lymphangiogenesis assays. This project will ultimately define the molecular regulation of lymphatic remodelling by miR-132, and thereby identify potential therapeutic targets for drugs designed to restrict the growth and remodelling of tumour lymphatics resulting in metastatic spread.

Keywords: argonaute HITS-CLIP, cancer, lymphatic remodelling, miR-132, VEGF

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Authors: Les Moncrieff

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

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

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Authors: Raviv Harris, Maggie Levy

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Natural product-based pesticides may serve as an alternative to the traditional synthetic pesticides, which have a potentially damaging effect, both to human health and for the environment. Along with plants, microorganisms are a prospective source of such biological pesticides. A unique and active strain of P. aphidis (designated isolate L12, Israel 2004), an epiphytic and non-pathogenic basidiomycete yeast, was isolated in our lab from strawberry leaves. P. aphidis L12 secretions were found to inhibit broad range of plant pathogens. This work demonstrates that metabolites isolated from the biocontrol agent P. aphidis (isolate L12) can inhibit varied fungal and bacterial phytopathogens. Biologically active metabolites were extracted from P. aphidis biomass, using the organic solvent ethyl acetate. The antimicrobial activity of the extract was demonstrated, both in vitro and in planta. Using disk diffusion assays, the following inhibition zones were obtained: 43cm² for Pseudomonas syringae pv. tomato, 28.5cm² for Xanthomonas campestris pv. vesicatoria, 59cm² for Clavibacter michiganensis subsp. michiganensis, 34cm² for Erwinia amylovora and 34cm² for Agrobacterium tumefaciens. Additionally, strong inhibitory activity of the extract against fungi mycelial growth was established, with IC₅₀ values of 606µg ml⁻¹ for Botrytis cinerea, 221µg ml⁻¹ for Pythium spp., 519µg ml⁻¹ for Rhizoctonia solani, 455µg ml⁻¹ for Sclerotinia sclerotiorum, 2270µg ml⁻¹ for Fusarium oxysporum f. sp. lycopersici, and 2038µg ml⁻¹ for Alternaria alternata. The results of the in planta experiments demonstrated a dose-dependent reduction in disease infection. Significant inhibition of B. cinerea lesions on tomato plants was obtained when a spore suspension of this pathogen was treated with extract concentrations higher than 4.2mg ml⁻¹. Concentration of 7mg ml⁻¹ caused a reduction of over 95% in the lesion size of B. cinerea on tomato plants. The strong antimicrobial activity demonstrated both in vitro and in planta against varied phytopathogens, may indicate that the extracted antimicrobial metabolites have potential to serve as natural pesticides in the field.

Keywords: antimicrobial, B. cinerea, metabolites, natural pesticides, P. aphidis

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Authors: Kathleen Cravero, Amanda Nace, Samantha Ski

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The Violence Against Children Surveys (VACS) is nationally representative surveys of male and female youth ages 13-24, designed to measure the burden of sexual, physical, and emotional violence experienced in childhood and adolescence. As of 2019, 24 countries implemented or are in the process of implementing a VACS, covering over ten percent of the world’s child population. Since the first article using VACS data from Swaziland was published in 2009, several peer-reviewed articles have been published on the VACS. However, no publications to date have analyzed the breadth of the work and analyzed how the data are represented in the peer-reviewed literature. In this study, we conducted a literature review of all peer-reviewed research that used VACS data or discussed the implementation and methodology of the VACS. The literature review revealed several important findings. Between 2009 and July 2019, thirty-five peer-reviewed articles using VACS data from 12 countries have been published. Twenty of the studies focus on one country, while 15 of the studies focus on two or more countries. Some countries are featured in the literature more than others, for example Kenya (N=14), Malawi (N=12), and Tanzania (N=12). A review of the research by gender demonstrates that research on violence against boys is under-represented. Only two studies specifically focused on boys/young men, while 11 studies focused only on violence against girls. This is despite research which suggests boys and girls experience similar rates of violence. A review of the publications by type of violence revealed significant differences in the types of violence being featured in the literature. Thirteen publications specifically focused on sexual violence, while three studies focused on physical violence, and only one study focused on emotional violence. Almost 70% of the peer-reviewed articles (24 of the 35) were first-authored by someone at the U.S. Centers for Disease Control and Prevention. There were very few first authors from VACS countries, which raises questions about who is leveraging the data and the extent to which capacities for data liberation are being developed within VACS countries. The VACS provide an unprecedented amount of information on the prevalence and past-year incidence of violence against children. Through a review of the peer-reviewed literature on the VACS we can begin to identify trends and gaps in how the data is being used as well as identify areas for further research.

Keywords: data to action, global health, implementation science, violence against children surveys

Procedia PDF Downloads 133