Search results for: chronic hepatitis C screening

Authors: Azizollah Khodakaram- Tafti, Ali Mohammadi, Ghasem Farjanikish

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Bovine viral diarrhea virus (BVDV) is one of the most important viral pathogens of cattle worldwide caused by Pestivirus genus, Flaviviridae family.The aim of the present study was to comparison several diagnostic methods and determine the prevalence of BVDV infection for the first time in dairy herds of Fars province, Iran. For initial screening, a total of 400 blood samples were randomly collected from 12 industrial dairy herds and analyzed using reverse transcription (RT)-PCR on the buffy coat. In the second step, blood samples and also ear notch biopsies were collected from 100 cattle of infected farms and tested by antigen capture ELISA (ACE), RT-PCR and immunohistochemistry (IHC). The results of nested RT-PCR (outer primers 0I100/1400R and inner primers BD1/BD2) was successful in 16 out of 400 buffy coat samples (4%) as acute infection in initial screening. Also, 8 out of 100 samples (2%) were positive as persistent infection (PI) by all of the diagnostic tests similarly including RT-PCR, ACE and IHC on buffy coat, serum and skin samples, respectively. Immunoreactivity for bovine BVDV antigen as brown, coarsely to finely granular was observed within the cytoplasm of epithelial cells of epidermis and hair follicles and also subcutaneous stromal cells. These findings confirm the importance of monitoring BVDV infection in cattle of this region and suggest detection and elimination of PI calves for controlling and eradication of this disease.

Keywords: antigen capture ELISA, bovine viral diarrhea virus, immunohistochemistry, RT-PCR, cattle

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Authors: Amal Saafan, Kareem Al Sofy, Sameh AbdelGhani, Magdy Amin

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Background: Acinetobacter spp. resistance towards β-lactam antibiotics is mediated mainly by different classes of β-lactamases production; detection of some genes responsible for production of β-lactamases is the objective of the study. Methods: One hundred fifty bacterial isolates were recovered from blood, sputum, and urine specimens from different hospitals in Egypt. Sixty-nine isolate were identified as Acinetobacter baumannii using traditional biochemical tests, CHROM agar, MicroScan and PCR amplification of blaoxa-51like gene. Acinetobacterbaumannii isolates were grouped into carbapenem resistant group (GP1), cefotaxime, ceftazidime and cefoxitin resistant group (GP2) and carbapenem and cephalosporin non-resistant group (GP3). Carbapenemase activity was screened using modified Hodge test (MHT) for GP1.Metallo-β-lactamases screening was performed for MHT positive isolates using double disk synergy test (DDST) and combined disk test (CDT). Amp C activity was screened using Amp C disk test with Tris-EDTA, DDST, and CDT for GP2. Finally, PCR amplification of blaoxa-51like, blaoxa-23like, blaIMP-like, blaVIM-like, and blaADC-like genes was performed for isolates that showed, at least, two positive results of three for both AmpC and carbapenemases phenotypic screening tests (obvious activity), in addition to GP3 (for comparison). Detection of blaoxa-51like and blaADC-like genes preceded by ISAba1 was also performed. Results: Antibiogram of 69 pure Acinetobacter baumannii isolates resulted in 57, 64, and 2 isolates enrolled into GP1, GP2, and GP3, respectively. Carbapenemase activity was shown by 49(85.9%) isolate using MHT. Metallo-β-lactamases screening revealed 32(65.3%) and 35(71.4%) using DDST and CDT, respectively.AmpC activity was shown by 43(67.2%) and 50 (78.1%) isolates using AmpC disk test with Tris-EDTA, and both DDST and CDT, respectively. Twenty-seven isolates showed obvious activity, all of them (100%) were harboring blaoxa-51like and blaADC-like genes, while blaoxa-23like, blaIMP-like andblaVIM-like genes were harbored by 23(85.2%), 9 (33.%) and no isolate respectively. Only 12 (44.4%) isolates harbored blaoxa-51like and blaADC-like genes preceded by ISAba1. GP3 isolates showed only positive blaoxa-51like and blaADC-like genes. Conclusion: It is not possible to correlate resistance with presence of blaoxa-51like and blaADC-like genes and presence of ISAba1 was immediate as transcriptional promoter. A blaoxa-23like gene played an important role in carbapenem resistance when compared with blaIMP-like and blaVIM-like gene.

Keywords: acinetobacter, beta-lactams, resistance, antimicrobial agents

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Authors: Adekunle O. Afolabi, Pekka Toivanen

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The world is expected to experience growth in the number of ageing population, and this will bring about high cost of providing care for these valuable citizens. In addition, many of these live with chronic diseases that come with old age. Providing adequate care in the face of rising costs and dwindling personnel can be challenging. However, advances in technologies and emergence of the Internet of Things are providing a way to address these challenges while improving care giving. This study proposes the integration of recommendation systems into homecare to provide real-time recommendations for effective management of people receiving care at home and those living with chronic diseases. Using the simplified Training Logic Concept, stakeholders and requirements were identified. Specific requirements were gathered from people living with cancer. The solution designed has two components namely home and community, to enhance recommendations sharing for effective care giving. The community component of the design was implemented with the development of a mobile app called Recommendations Sharing Community for Aged and Chronically Ill People (ReSCAP). This component has illustrated the possibility of real-time recommendations, improved recommendations sharing among care receivers and between a physician and care receivers. Full implementation will increase access to health data for better care decision making.

Keywords: recommendation systems, Internet of Things, healthcare, homecare, real-time

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Authors: Amer A. Hasan, Mehri Igci, Ersin Borazan, Rozhgar A. Khailany, Emine Bayraktar, Ahmet Arslan

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Gastric cancer (GC) has high morbidity and fatality rate in various countries and is still one of the most frequent and deadly diseases. Novel mitogenic and motogenic Gastrokine1 (GKN1) and Gastrokine 2 (GKN2) genes that are highly expressed in the normal stomach epithelium and plays an important role in maintaining the integrity and homeostasis of stomach mucosal epithelial cells. Significant loss of copy number and mRNA transcript of GKN1 and GKN2 gene expression were frequently observed in all types of gastric cancer. In this study, 47 paired samples that were grouped according to the types of gastric cancer and the clinical characteristics of the patients, including gender and average of age were investigated with gene expression analysis and mutation screening by monetering RT-PCR, SSCP and nucleotide sequencing techniques. Both GKN1 and GKN2 genes were observed significantly reduced found by (Wilcoxon signed rank test; p<0.05). As a result of gene screening, no mutation (no different genotype) was detected. It is considered that gene mutations are not the cause of inactivation of gastrokines. In conclusion, the mRNA expression level of GKN1 and GKN2 genes statistically was decreased regardless the gender, age or cancer type of patients. Reduced of gastrokine genes seems to occur at the initial steps of cancer development. In order to understand the investigation between gastric cancer and diagnostic biomarker; further analysis is necessary.

Keywords: gastric cancer, diagnostic biomarker, nucleotide sequencing, semi-quantitative RT-PCR

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Authors: Alireza Javed, Keivan Jamshidi

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Reactive amyloidosis is a condition that complicates a long list of chronic inflammation, chronic infectious, malignant, and hereditary disorders. In the present study the potential effects of two amyloidogenic substances: ie. AgNO3 and Freund's Adjuvant (AF) with that of vitamin free casein, on spatio-temporal pattern of experimental amyloidosis in mice, were compared. For this purpose, a total of 40 male Swees mice, obtained from Pasteur Institute Tehran, after being weighted were randomly divided into 4 groups including 2 treatments, 1 control (vitamin free casein) and 1 positive control (normal saline). At the end of 3rd, 5th and 7th weeks of experiment 3 mice were randomly selected and euthnised. Spleen sample of each animal obtained and preserved in 10% neutral buffer formalin. Sample were then processed through different stages of dehydration, clearing and impregnation and finally embedded in paraffin blocks. Sections of 5µm thickness then cut and stained by alkaline Congo red techniques. Spleen weights and the data obtained from the microscopic quantitative analysis did show no significant differences between groups A and B, A and C, and B and C. However, significant differences were observed between groups A and D, B and D, and C and D respectively. It is concluded that two compounds ie; AgNO3 and Freund's Adjuvant have the same potential, as does vitamin free casein have, in spatio – temporal pattern of experimental amyloidosis in mice.

Keywords: amyloidosis, mice, AgNO3, Freund's Adjuvant

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Authors: Allyson Augusta Shrikhande, Alexa Rains, Tayyaba Ahmed, Marjorie Mamsaang, Rakhi Vyas, Janaki Natarajan, Erika Moody, Christian Reutter, Kimberlee Leishear, Yogita Tailor, Sandra Sandhu-Restaino, Lora Liu, Neha James, Rosemarie Filart

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Characterized by consistent difficulty getting and keeping an erection firm enough for intercourse, Erectile Dysfunction may affect up to 15% of adult men. Although awareness and access to treatment have improved in recent years, many patients do not actively seek diagnosis or treatment due to the stigma surrounding this condition. Patients who do seek treatment are often dissatisfied by the efficacy of the medication. The condition inhibits patients’ quality of life by worsening mental health and relationships. The purpose of this study was to test the effectiveness of an outpatient neuromuscular treatment protocol in treating the symptoms of Chronic Pelvic Pain and Erectile Dysfunction, improving pain and function. 56 patients ages 20-79 presented to an outpatient clinic for treatment of pelvic pain and Erectile Dysfunction symptoms. These symptoms had persisted for an average of 4 years. All patients underwent external ultrasound-guided hydro-dissection technique targeted at pelvic peripheral nerves in combination with pelvic floor musculature trigger-point injections. To measure the effects of this treatment, a five question Erectile Dysfunction questionnaire was completed by each patient at their first visit to a clinic and three months after treatment began. Answers were summed for a total score of 5-25, with a higher score indicating optimal function. The average score before treatment was 14.125 (SD 5.411) (a=0.05; CI 12.708-15.542), which increased by 18% to an average of 16.625 (SD 6.423) (a=0.05; CI 14.943-18.307) after treatment (P=0.0004). Secondary outcome variables included a Visual Analogue Scale (VAS) to measure pelvic pain intensity and the Functional Pelvic Pain Scale (FPPS) to measure function across multiple areas. VAS scores reduced by 51% after three months. Before treatment, the mean VAS score was 5.87, and the posttreatment mean VAS score was 2.89. Pelvic pain functionality improved by 34% after three months. Pretreatment FPPS scores averaged at 7.48, decreasing to 4.91 after treatment. These results indicate that this unique treatment was very effective at relieving pain and increasing function for patients with Erectile Dysfunction.

Keywords: chronic pelvic pain, erectile dysfunction, nonsurgical, outpatient, trigger point injections

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Authors: Chia-Pei Chen, Yu-Ju Chen, Yu-Juei Hsu

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The prevalence and incidence of end-stage renal disease in Taiwan ranks the highest in the world. According to the statistical survey of the Ministry of Health and Welfare in 2019, kidney disease is the ninth leading cause of death in Taiwan. It leads to autonomic dysfunction, inflammatory response and symptom distress, and further increases the damage to the structure and function of the kidneys, leading to increased demand for renal replacement therapy and risks of cardiovascular disease, which also has medical costs for the society. If we can intervene in a feasible manual to effectively regulate the autonomic nerve function of CKD patients, reduce the inflammatory response and symptom distress. To prolong the progression of the disease, it will be the main goal of caring for CKD patients. This study aims to test the effect of heart rate variability biofeedback (HRVBF) on improving autonomic nerve function (Heart Rate Variability, HRV), inflammatory response (Interleukin-6 [IL-6], C reaction protein [CRP] ), symptom distress (Piper fatigue scale, Pittsburgh Sleep Quality Index [PSQI], and Beck Depression Inventory-II [BDI-II] ) in patients with chronic kidney disease. This study was experimental research, with a convenience sampling. Participants were recruited from the nephrology clinic at a medical center in northern Taiwan. With signed informed consent, participants were randomly assigned to the HRVBF or control group by using the Excel BINOMDIST function. The HRVBF group received four weekly hospital-based HRVBF training, and 8 weeks of home-based self-practice was done with StressEraser. The control group received usual care. We followed all participants for 3 months, in which we repeatedly measured their autonomic nerve function (HRV), inflammatory response (IL-6, CRP), and symptom distress (Piper fatigue scale, PSQI, and BDI-II) on their first day of study participation (baselines), 1 month, and 3 months after the intervention to test the effects of HRVBF. The results were analyzed by SPSS version 23.0 statistical software. The data of demographics, HRV, IL-6, CRP, Piper fatigue scale, PSQI, and BDI-II were analyzed by descriptive statistics. To test for differences between and within groups in all outcome variables, it was used by paired sample t-test, independent sample t-test, Wilcoxon Signed-Rank test and Mann-Whitney U test. Results: Thirty-four patients with chronic kidney disease were enrolled, but three of them were lost to follow-up. The remaining 31 patients completed the study, including 15 in the HRVBF group and 16 in the control group. The characteristics of the two groups were not significantly different. The four-week hospital-based HRVBF training combined with eight-week home-based self-practice can effectively enhance the parasympathetic nerve performance for patients with chronic kidney disease, which may against the disease-related parasympathetic nerve inhibition. In the inflammatory response, IL-6 and CRP in the HRVBF group could not achieve significant improvement when compared with the control group. Self-reported fatigue and depression significantly decreased in the HRVBF group, but they still failed to achieve a significant difference between the two groups. HRVBF has no significant effect on improving the sleep quality for CKD patients.

Keywords: heart rate variability biofeedback, autonomic nerve function, inflammatory response, symptom distress, chronic kidney disease

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Authors: Lindsay Fink, Sarha Smith-Moyo, Leanne W. Charlesworth

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In recent years, the number of individuals experiencing homelessness has increased in the United States. This paper analyzes 2019 data from 16 different emergency shelters in Monroe County, located in Upstate New York. The data were collected through the County’s Homeless Management Information System (HMIS), and individuals were de-identified and de-duplicated for analysis. The purpose of this study is to explore the basic characteristics of the homeless population in Monroe County, and the dynamics of shelter use. The results of this study showed gender as a significant factor when analyzing the relationship between demographic variables and recorded reasons for shelter entry. Results also indicated that age and ethnicity did not significantly influence odds of re-entering a shelter, but did significantly influence reasons for shelter entry. Overall, the most common recorded cause of shelter entry in 2019 in the examined county was eviction by primary tenant. Recommendations to better address recurrent shelter entry and potential chronic homelessness include more consideration for the diversity existing within the homeless population, and the dynamics leading to shelter stays, including enhanced funding and training for shelter staff, as well as expanded access to permanent supportive housing programs.

Keywords: chronic homelessness, homeless shelter stays, permanent supportive housing, shelter population dynamics

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Authors: Robert E. Kenney, Richard B. Aguilar, Efrain Antunez, Gregory Schor-Haskin, Rafael Rey, Catie Falcon, Luis Arce

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This study sought to explore the effect of Sarapin injections on chronic knee pain (CKP). Many adults suffer from CKP which is most often attributed to osteoarthritis. Current treatment regimens for CKP involve the use NSAIDS medications, injections with steroids/analgesic, platelet rich plasma injections, or orthopedic surgical interventions. Sarapin is a commercially available homeopathic aqueous extract from the pitcher plant. Studies on the use of Sarapin as a treatment for cervical, thoracic, and lumbosacral facet joint nerve blocks have been performed with mixed results. There is little available evidence on the use of Sarapin in CKP. This study examines the effect of a series of 3 weekly injections of aqueous Sarapin in 95 elderly patients with CKP in a primary care setting. Cano Health, a primary care group, identified 95 successive patients with CKP from its multimodal physiotherapy program for chronic pain. Patients underwent evaluation by a clinician, underwent diagnostic Xrays of the knees, and the treatment plan with three weekly Sarapin injections was discussed. A pain and functional limitation survey (a modified Lower Extremity Functional Scale (mLEFS)) was administered prior to initiating treatment (Entry Survey (ES)). Each patient received an intraarticular injection of 2 cc of aqueous Sarapin with 1cc 1% lidocaine during weeks 1, 2 and 3. The mLEFS was administered again at week 4, one week after the third Sarapin injection (Exit Survey (ExS)). Demographics: Mean Age 62 +/- 9.8; 73% female; 89% Hispanic/Latino; mean time between ES and ExS was 27.5 +/-8.2 days. Survey: The mLEFS was based on a published Lower Extremity Functional Scale and each patient rated their pain or functional limitation from 0 (no difficulty) to 5 (severe difficulty) for 10 questions. Answers were summed and compared. Maximum score for severe difficulty would be 50 points. Results: Mean pain/functional scores: ES was 30.3 +/-12.1 and ExS was 19.5 +/- 12.5. This represents a relative improvement of 35.7% (P<0.00001). A total of 81% (77/95) of the patients showed improvement in symptoms at week four as assessed by the mLEFS. There were 11 patients who reported an increase in their survey scores while 7 patients reported no change. When evaluating the cohort that reported improvement, the ES was 30.9 +/-11.4 and ExS was 16.3 +/-9.8 yielding a 47.2% relative improvement (P<0.00001). Injections were well tolerated, and no adverse events were reported. Conclusions: In this cohort of 95 elderly patients with CKP, treatment with 3 weekly injections of Sarapin significantly improved pain and function as assessed by a mLEFS survey. The majority (81%) of patients responded positively to therapy, 12% had worsening symptoms and 7% reported no change. The use of intraarticular injections of Sarapin for CKP was shown to be an effective modality of treatment. Sarapin’s low cost, tolerability, and ease of use make it an attractive alternative to NSAIDS, steroids, PRP or surgical intervention for this common debilitating condition.

Keywords: Sarapin, intraarticular, chronic knee pain, osteoarthritis

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Authors: Anjani Kumar Tiwari, Neelam Kumari, Anil Mishra

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The 18-kDa translocator protein (TSPO) previously called as peripheral benzodiazepine receptor, is proven biomarker for variety of neuroinflammation. TSPO is tryptophane rich five transmembranal protein found on outer mitochondrial membrane of steroid synthesising and immunomodulatory cells. In case of neuronal damage or inflammation the expression level of TSPO get upregulated as an immunomodulatory response. By utilizing Benzoxazolone as a basic scaffold, series of TSPO ligands have been designed followed by their screening through in silico studies. Synthesis has been planned by employing convergent methodology in six high yielding steps. For the synthesized ligands the ‘in vitro’ assay was performed to determine the binding affinity in term of Ki. On ischemic rat brain, autoradiography studies were also carried to check the specificity and affinity of the designed radiolabelled ligand for TSPO.Screening was performed on the basis of GScore of CADD based schrodinger software. All the modified and better prospective compound were successfully carried out and characterized by spectroscopic techniques (FTIR, NMR and HRMS). In vitro binding assay showed best binding affinity Ki = 6.1+ 0.3 for TSPO over central benzodiazepine receptor (CBR) Ki > 200. ARG studies indicated higher uptake of two analogues on the lesion side compared with that on the non-lesion side of ischemic rat brains. Displacement experiments with unlabelled ligand had minimized the difference in uptake between the two sides which indicates the specificity of the ligand towards TSPO receptor.

Keywords: TSPO, PET, imaging, Acetamidobenzoxazolone

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Authors: Angelis P. Barlampas

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PURPOSE: The purpose of this paper is to demonstrate the important role of taking an appropriate and detailed history, in order to reach the best possible diagnostic conclusion. MATERIAL: A patient presented to the emergency department due to the sudden onset of continuous abdominal pain, during the last hour and with the clinical symptoms of an acute abdomen. During the clinical examination, signs of peritoneal irritation and diffuse abdominal tenderness were found. The rest of the clinical and laboratory tests did not reveal anything important. From the reported medical history, nothing of note was found, except for the report of a large liver cyst, for which he was advised not to take any further action, except from regular ultrasound examination . METHOD: A computed tomography examination was performed after per os administration of gastrografin, which revealed a hyperdense ascitic effusion, similar in density to that of gastrografin within the intestinal tract. The presence of a large cyst of the left hepatic lobe was confirmed, contacting and pushing against the stomach. In the area of the contact between the liver cyst and the pylorus, there were extraluminal air bubbles and local opacity of the peritoneal fat, with a small hyperdense effusion. Result : The above, as well as the absence of a history of stomach ulcer or recent trauma, or other pathology, argue in favor of acute pyloric perforation, due to mural necrosis, in response to chronic external pressure from the pre-existing large liver cyst.

Keywords: perforation, stomach, large liver cyst, CT abdomen, acute abdominal pain, intraperitoneal leakage, constrast leakage

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Authors: J. K. D. M. P. Madara, R. B. L. Dharmawickreme, Linu John, Ivee Boiss

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Flemingia vestita, commonly known as ‘Sohphlang’ is an important medicinal plant found in the North-Eastern region of India, which is traditionally recognized for its anthelmintic properties. This study was aimed to evaluate the phytochemical constituents and antibacterial activity of the tuber skin extracts of the plant species. Methanol, acetone, and water were used to obtain the solvent extractions of the skin peel extracts. Concentrated extracts of skin peel were tested using previously established qualitative phytochemical assays. The antibacterial efficacy of methanol tuber skin extract was tested against Gram-negative and positive microorganisms, namely, Klebsiella pneumonia, Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, and Mycobacterium tuberculosis strains. Agar well diffusion method was employed to determine the zone of inhibition of the plant extracts. Obtained data were statistically analyzed. Methanol extracts of Flemingia vestita were found to be effective against Bacillus subtilis and Mycobacterium tuberculosis at concentrations of 0.5 mg/ml. The reported zone of inhibition for the two strains was 13.3mm ± 0.57 and 16.3mm ± 4.9, respectively. However Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli were resistant to the plant extracts with no zone of inhibition. Alkaloids, glycosides, and phenols were found to be present in aqueous, methanol, and acetone extracts of the plant in qualitative phytochemical analysis.

Keywords: flemingia vestita, antibacterial activity, phytochemical screening, well diffusion method

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Authors: Gabriel S. De Oliveira, Patricia P. Adriani, Christophe Moriseau, Bruce D. Hammock, Felipe S. Chambergo

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Epoxide hydrolases (EHs) are enzymes that are present in all living organisms and catalyze the hydrolysis of epoxides to the corresponding vicinal diols. EHs have high biotechnological interest for the drug design and chemistry transformation for industries. In this study, we describe the identification of substrates and inhibitors of epoxide hydrolase enzyme from the filamentous fungus Trichoderma reesei (TrEH), and these inhibitors showed the fungal growth inhibitory activity. We have used the cloned enzyme and expressed in E. coli to develop the screening in the library of fluorescent substrates with the objective of finding the best substrate to be used in the identification of good inhibitors for the enzyme TrEH. The substrate (3-phenyloxiranyl)-acetic acid cyano-(6-methoxy-naphthalen-2-yl)-methyl ester showed the highest specific activity and was chosen for the next steps of the study. The inhibitors screening was performed in the library with more than three thousand molecules and we could identify the 6 best inhibitors. The IC50 of these molecules were determined in nM and all the best inhibitors have urea or amide in their structure, because It has been recognized that these groups fit well in the hydrolase catalytic pocket of the epoxide hydrolases. Then the growth of T. reesei in PDA medium containing these TrEH inhibitors was tested, and fungal growth inhibition activity was demonstrated with more than 60% of inhibition of fungus growth in the assay with the TrEH inhibitor with the lowest IC50. Understanding how this EH enzyme from T. reesei responds to inhibitors may contribute for the study of fungal metabolism and drug design against pathogenic fungi.

Keywords: epoxide hydrolases, fungal growth inhibition, inhibitor, Trichoderma reesei

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Authors: Aisling Eves, Andrew Pieri, Ross McLean, Nerys Forester

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Background: The breast unit local guideline recommends that 12 cores should be used in a stereotactic-guided biopsy to diagnose DCIS. Twelve cores are regarded to provide good diagnostic value without removing more breast tissue than necessary. This study aimed to determine compliance with guidelines and investigated how the number of cores impacted upon the re-excision rate and size discrepancies. Methods: This single-centre retrospective cohort study of 72 consecutive breast screened patients with <15mm DCIS on radiological report underwent stereotactic-guided core biopsy and subsequent surgical excision. Clinical, radiological, and histological data were collected over 5 years, and ASCO guidelines for margin involvement of <2mm was used to guide the need for re-excision. Results: Forty-six (63.9%) patients had <12 cores taken, and 26 (36.1%) patients had ≥12 cores taken. Only six (8.3%) patients had 12 cores taken in their stereotactic biopsy. Incomplete surgical excision was seen in 17 patients overall (23.6%), and of these patients, twelve (70.6%) had fewer than 12 cores taken (p=0.55 for the difference between groups). Mammogram and biopsy underestimated the size of the DCIS in this subgroup by a median of 15mm (range: 6-135mm). Re-excision was required in 9 patients (12.5%), and five patients (6.9%) were found to have invasive ductal carcinoma on excision (80% had <12 cores, p=0.43). Discussion: There is poor compliance with the breast unit local guidelines and higher rates of re-excision in patients who did not have ≥12 cores taken. Taking ≥12 cores resulted in fewer missed invasive cancers lower incomplete excision and re-excision rates.

Keywords: stereotactic core biopsy, DCIS, breast screening, Re-excision rates, core biopsy

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Authors: Rana Praween Kumar

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Preterm-low birth weight delivery is a major cause of infant morbidity and mortality in developing countries and has been linked to poor periodontal health during pregnancy. Gingivitis and chronic periodontitis are highly prevalent chronic inflammatory oral diseases. The detection and diagnosis of these common diseases is a fundamentally important component of oral health care. This study is intended to investigate predisposing and enabling factors as determinants of oral health indicators in pregnancy as well as the association between periodontal problems during pregnancy with age and socio economic status of the individual. A community –based prospective cohort study will be conducted in Jamshedpur, Jharkhand, India among pregnant women using completed interviews and a full mouth oral clinical examination using the CPITN (Community Periodontal Index of Treatment Need) and OHI-S (Simplified Oral Hygiene) indices with adequate sample size and informed consent to the patient following proper inclusion and exclusion criteria. Multiple logistic regression analyses will be used to identify independent determinants of periodontal problems and use of dental services during pregnancy. Analysis of covariance (ANCOVA) will be used to investigate the relationship between periodontal problems with the age and socioeconomic status. The result will help in proper monitoring of periodontal health during pregnancy encouraging the delivery of healthy child and the maintenance of proper health of the mother.

Keywords: infant, periodontal problems, pregnancy, pre-term-low birth weight delivery

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Authors: Restuning Widiasih, Katherine Nelson, Joan Skinner

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Muslim husbands have significant roles in the family including their roles in women’s health and illness. However, studies that explore Muslim husbands’ participation in women’s health is limited. The objective of this study was to uncover Muslim husbands’ participation in women’ health and illness including cancer prevention and screening. A descriptive exploratory approach was used involving 20 Muslim women from urban and rural areas of West Java Province, Indonesia. Muslim women shared experience related to their husbands support and activities in women’s health and illness. The data from the interviews were analyzed using the Comparative Analysis for Interview (CAI). Women perceived that husbands fully supported their health by providing opportunities for activities, and reminding them about healthy food, their workloads, and family planning. Husbands actively involved when women faced health issues including sharing knowledge and experience, discussing any health problems, advising for medical check-ups, and accompanying them for treatments. The analysis also found that husbands were less active and offered less advice regarding prevention and early detection of cancer. This study highlights the significant involvement of Muslim husbands in women’s health and illness, yet a lack of support from husbands related to screening and cancer prevention. This condition could be a burden for Muslim women to participate in health programs related to cancer prevention and early detection. Health education programs to improve Muslim husbands’ understanding of women’s health is needed.

Keywords: descriptive exploratory study, Muslim husbands, Muslim women, women's health and illness

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Authors: Devender Mandala, Paul Watts

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Cis-Nucleosides mainly lamivudine (3TC) and emtricitabine (FTC) are an important tool in the treatment of Human immune deficiency virus (HIV), Hepatitis B virus (HBV) and Human T-Lymotropoic virus (HTLV). Lamivudine and emtricitabine are potent nucleoside analog reverse transcriptase inhibitors (nRTI). These two drugs are synthesized by a four-stage process from the starting materials: menthyl glyoxylate hydrate and 1,4-dithane-2,5-diol to produce the 5-hydroxy oxathiolane which upon acetylation with acetic anhydride to yield 5-acetoxy oxathiolane. Then glycosylation of this acetyl product with silyl protected nucleoside to produce the intermediate. The reduction of this intermediates can provide the final targets. Although there are several different methods reported for the synthesis of lamivudine and emtricitabine as a single enantiomer, we required an efficient route, which was suitable for large-scale synthesis to support the development of these compounds. In this process, we successfully prepared the intermediates of lamivudine and emtricitabine without using any solvents and catalyst, thus promoting the green synthesis. All the synthesized compound were confirmed by TLC, GC, Mass, NMR and 13C NMR spectroscopy.

Keywords: emtricitabine, green synthesis, lamivudine, nucleoside

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Authors: Prof. Ammal Mokhtar Metwally, Samia M. Sami, Nihad A. Ibrahim, Fatma A. Shaaban, Iman I. Salama

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Objectives: Reducing neonatal mortality by 2030 is still a challenging goal in developing countries. low birth weight (LBW) is a significant contributor to this, especially where weighing newborns is not possible routinely. The present study aimed to determine a simple, easy, reliable anthropometric measure(s) that can predict LBW) and neonatal mortality. Methods: A prospective cohort study of 570 babies born in districts of El Menia governorate, Egypt (where most deliveries occurred at home) was examined at birth. Newborn weight, length, head, chest, mid-arm, and thigh circumferences were measured. Follow up of the examined neonates took place during their first four weeks of life to report any mortalities. The most predictable anthropometric measures were determined using the statistical package of SPSS, and multiple Logistic regression analysis was performed.: Results: Head and chest circumferences with cut-off points < 33 cm and ≤ 31.5 cm, respectively, were the significant predictors for LBW. They carried the best combination of having the highest sensitivity (89.8 % & 86.4 %) and least false negative predictive value (1.4 % & 1.7 %). Chest circumference with a cut-off point ≤ 31.5 cm was the significant predictor for neonatal mortality with 83.3 % sensitivity and 0.43 % false negative predictive value. Conclusion: Using chest circumference with a cut-off point ≤ 31.5 cm is recommended as a single simple anthropometric measurement for the prediction of both LBW and neonatal mortality. The predicted measure could act as a substitute for weighting newborns in communities where scales to weigh them are not routinely available.

Keywords: low birth weight, neonatal mortality, anthropometric measures, practical screening

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Authors: Xin Qi Dong, Melissa Simon

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Aims: Elder mistreatment and suicidal ideation are important public health concerns among aging populations. This study will examine the association between elder mistreatment and suicidal ideation among Chinese older adults in the USA. Methods: Guided by a community-based participatory research approach, in this study we conducted in-person interviews with Chinese older adults aged 60 years and older in the Greater Chicago area from 2011 to 2013. Elder mistreatment was assessed by a 10-item instrument derived from the Hwalek-Sengstock Elder Abuse Screening Test (H-S/EAST) and the Vulnerability to Abuse Screening Scale (VASS). Suicidal ideation was assessed by the ninth item of the Patient Health Questionnaire-9 (PHQ-9) and the Geriatric Mental State Examination-Version A (GMS-A). Results: Overall, 3,159 Chinese older adults participated in this study, and their mean age was 72.8 years. After controlling for age, gender, education, income, medical comorbidities, depressive symptoms, and social support, elder mistreatment was significantly associated with 2-week suicidal ideation (OR 2.46, 95% CI 1.52--4.01) and 12-month suicidal ideation (OR 2.46, 95% CI 1.62--3.73). With respect to gender differences, the study found that the association remained significant for older women but not for older men after adjusting for all confounding factors. Conclusion: As the largest epidemiology study conducted among Chinese older adults in the USA, this study suggests that elder mistreatment is significantly associated with 2-week and 12-month suicidal ideation in older women but not in older men. Longitudinal studies should be conducted to explore the mechanisms through which elder mistreatment links with suicidal ideation.

Keywords: suicidal ideation, elder abuse, family violence, Asian health equity

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Authors: Haoyu Zhao, Qianshu Ma, Min Xie, Yunqi Huang, Yunjia Liu, Huan Song, Hongsheng Gui, Mingli Li, Qiang Wang

Abstract:

Rationale: Bipolar disorder (BD) and major depressive disorder (MDD), as severe chronic illnesses that restrict patients’ psychosocial functioning and reduce their quality of life, are both categorized into mood disorders. Emerging evidence has suggested that the reliability of self-rated health (SRH) was wellvalidated and that the risk of various health outcomes, including mortality and health care costs, could be predicted by SRH. Compared with other lengthy multi-item patient-reported outcomes (PRO) measures, SRH was proven to have a comparable predictive ability to predict mortality and healthcare utilization. However, to our knowledge, no study has been conducted to assess the association between SRH and hospitalization among people with mental disorders. Therefore, our study aims to determine the association between SRH and subsequent all-cause hospitalizations in patients with BD and MDD. Methods: We conducted a prospective cohort study on people with BD or MDD in the UK from 2006 to 2010 using UK Biobank touchscreen questionnaire data and linked administrative health databases. The association between SRH and 2-year all-cause hospitalizations was assessed using proportional hazard regression after adjustment for sociodemographics, lifestyle behaviors, previous hospitalization use, the Elixhauser comorbidity index, and environmental factors. Results: A total of 29,966 participants were identified, experiencing 10,279 hospitalization events. Among the cohort, the average age was 55.88 (SD 8.01) years, 64.02% were female, and 3,029 (10.11%), 15,972 (53.30%), 8,313 (27.74%), and 2,652 (8.85%) reported excellent, good, fair, and poor SRH, respectively. Among patients reporting poor SRH, 54.19% had a hospitalization event within 2 years compared with 22.65% for those having excellent SRH. In the adjusted analysis, patients with good, fair, and poor SRH had 1.31 (95% CI 1.21-1.42), 1.82 (95% CI 1.68-1.98), and 2.45 (95% CI 2.22, 2.70) higher hazards of hospitalization, respectively, than those with excellent SRH. Conclusion: SRH was independently associated with subsequent all-cause hospitalizations in patients with BD or MDD. This large study facilitates rapid interpretation of SRH values and underscores the need for proactive SRH screening in this population, which might inform resource allocation and enhance high-risk population detection.

Keywords: severe mental illnesses, hospitalization, risk prediction, patient-reported outcomes

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Authors: Huajuan Shi

Abstract:

Background: The biopsy of the preimplantation embryo may increase the potential risk and concern of embryo viability. Clinically discarded spent embryo medium (SEM) has entered the view of researchers, sparking an interest in noninvasive embryo screening. However, one of the major restrictions is the extremelty low quantity of cf-RNA, which is difficult to efficiently and unbiased amplify cf-RNA using traditional methods. Hence, there is urgently need to an efficient and low bias amplification method which can comprehensively and accurately obtain cf-RNA information to truly reveal the state of SEM cf-RNA. Result: In this present study, we established an agarose PCR amplification system, and has significantly improved the amplification sensitivity and efficiency by ~90 fold and 9.29 %, respectively. We applied agarose to sequencing library preparation (named AG-seq) to quantify and characterize cf-RNA in SEM. The number of detected cf-RNAs (3533 vs 598) and coverage of 3' end were significantly increased, and the noise of low abundance gene detection was reduced. The increasing percentage 5' end adenine and alternative splicing (AS) events of short fragments (< 400 bp) were discovered by AG-seq. Further, the profiles and characterizations of cf-RNA in spent cleavage medium (SCM) and spent blastocyst medium (SBM) indicated that 4‐mer end motifs of cf-RNA fragments could remarkably differentiate different embryo development stages. Significance: This study established an efficient and low-cost SEM amplification and library preparation method. Not only that, we successfully described the characterizations of SEM cf-RNA of preimplantation embryo by using AG-seq, including abundance features fragment lengths. AG-seq facilitates the study of cf-RNA as a noninvasive embryo screening biomarker and opens up potential clinical utilities of trace samples.

Keywords: cell-free RNA, agarose, spent embryo medium, RNA sequencing, non-invasive detection

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Authors: Rachel Thomas Tharmabalan

Abstract:

The growing unease over the matter of food security in the world is the result of a maturing realization that the genetic base of most human caloric intake from plants is dangerously narrow. Malaysia’s tropical rainforests have the potential to contribute to diet diversification and provide a source of nutrient-rich food as the Orang Asli communities in Malaysia have relied almost entirely on the jungle for food, fodder, medicine and fuel antithetical to what is happening today. This segregation of the Orang Asli from traditional lands and resources leads to severe loss of knowledge of biodiversity. In order to preserve these wild edibles, four different types of vegetables that are frequently consumed by the Orang Asli which consists of Rebu, Meranti, Saya and Pama were selected. These vegetables were then analysed to determine its proximate and mineral content to help ascertain claims and reaffirm the impact it can play in ensuring food and nutrition security, in addition to combating chronic diseases. From the results obtained, the Meranti had the highest crude fiber, iron and calcium content. Other minerals such as potassium, magnesium and copper were also found in varying content. These wild edibles could also contribute to education and bring awareness to younger generations as well as urban populations to start consuming more of these in their daily life as it could prevent various chronic diseases in Malaysia.

Keywords: food and nutrition security, Orang Asli, underutilized plants, wild edible food systems

Procedia PDF Downloads 157

Authors: Hansraj Riteesh Bookun, Cassandra Monique Hidajat

Abstract:

This pilot study investigated the efficacy of a newly designed shoe which will act as an intermittent pneumatic compression device to augment venous flow in the lower limb. The aim was to assess the degree with which a wearable intermittent compression device can increase the venous flow in the popliteal vein. Background: Deep venous thrombosis and chronic venous insufficiency are relatively common problems with significant morbidity and mortality. While mechanical and chemical thromboprophylaxis measures are in place in hospital environments (in the form of TED stockings, intermittent pneumatic compression devices, analgesia, antiplatelet and anticoagulant agents), there are limited options in a community setting. Additionally, many individuals are poorly tolerant of graduated compression stockings due to the difficulty in putting them on, their constant tightness and increased associated discomfort in warm weather. These factors may hinder the management of their chronic venous insufficiency. Method: The device is lightweight, easy to wear and comfortable, with a self-contained power source. It features a Bluetooth transmitter and can be controlled with a smartphone. It is externally almost indistinguishable from a normal shoe. During activation, two bladders are inflated -one overlying the metatarsal heads and the second at the pedal arch. The resulting cyclical increase in pressure squeezes blood into the deep venous system. This will decrease periods of stasis and potentially reduce the risk of deep venous thrombosis. The shoe was fitted to 2 healthy participants and the peak systolic velocity of flow in the popliteal vein was measured during and prior to intermittent compression phases. Assessments of total flow volume were also performed. All haemodynamic assessments were performed with ultrasound by a licensed sonographer. Results: Mean peak systolic velocity of 3.5 cm/s with standard deviation of 1.3 cm/s were obtained. There was a three fold increase in mean peak systolic velocity and five fold increase in total flow volume. Conclusion: The device augments venous flow in the leg significantly. This may contribute to lowered thromboembolic risk during periods of prolonged travel or immobility. This device may also serve as an adjunct in the treatment of chronic venous insufficiency. The study will be replicated on a larger scale in a multi—centre trial.

Keywords: venous, intermittent compression, shoe, wearable device

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Authors: Julia R. Beulig, Stefan Ohla, Detlev Belder

Abstract:

In contrast to off-line analytical methods, lab-on-a-chip technology delivers direct information about the observed reaction. Therefore, microfluidic devices make an important scientific contribution, e.g. in the field of synthetic chemistry. Herein, the rapid generation of analytical data can be applied for the optimization of chemical reactions. These microfluidic devices enable a fast change of reaction conditions as well as a resource saving method of operation. In the presented work, we focus on the investigation of multiphase regimes, more specifically on a biphasic microfluidic droplet systems. Here, every single droplet is a reaction container with customized conditions. The biggest challenge is the rapid qualitative and quantitative readout of information as most detection techniques for droplet systems are non-specific, time-consuming or too slow. An exception is the electrospray mass spectrometry (ESI-MS). The combination of a reaction screening platform with a rapid and specific detection method is an important step in droplet-based microfluidics. In this work, we present a novel approach for synthesis optimization on the nanoliter scale with direct ESI-MS detection. The development of a droplet-based microfluidic device, which enables the modification of different parameters while simultaneously monitoring the effect on the reaction within a single run, is shown. By common soft- and photolithographic techniques a polydimethylsiloxane (PDMS) microfluidic chip with different functionalities is developed. As an interface for the MS detection, we use a steel capillary for ESI and improve the spray stability with a Teflon siphon tubing, which is inserted underneath the steel capillary. By optimizing the flow rates, it is possible to screen parameters of various reactions, this is exemplarity shown by a Domino Knoevenagel Hetero-Diels-Alder reaction. Different starting materials, catalyst concentrations and solvent compositions are investigated. Due to the high repetition rate of the droplet production, each set of reaction condition is examined hundreds of times. As a result, of the investigation, we receive possible reagents, the ideal water-methanol ratio of the solvent and the most effective catalyst concentration. The developed system can help to determine important information about the optimal parameters of a reaction within a short time. With this novel tool, we make an important step on the field of combining droplet-based microfluidics with organic reaction screening.

Keywords: droplet, mass spectrometry, microfluidics, organic reaction, screening

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Authors: Luiz Carlos Wrobel, Matjaz Hribersek, Jure Marn, Jurij Iljaz

Abstract:

Dynamic thermography has been clinically proven to be a valuable diagnostic technique for skin tumor detection as well as for other medical applications such as breast cancer diagnostics, diagnostics of vascular diseases, fever screening, dermatological and other applications. Thermography for medical screening can be done in two different ways, observing the temperature response under steady-state conditions (passive or static thermography), and by inducing thermal stresses by cooling or heating the observed tissue and measuring the thermal response during the recovery phase (active or dynamic thermography). The numerical modelling of heat transfer phenomena in biological tissue during dynamic thermography can aid the technique by improving process parameters or by estimating unknown tissue parameters based on measured data. This paper presents a nonlinear numerical model of multilayer skin tissue containing a skin tumor, together with the thermoregulation response of the tissue during the cooling-rewarming processes of dynamic thermography. The model is based on the Pennes bioheat equation and solved numerically by using a subdomain boundary element method which treats the problem as axisymmetric. The paper includes computational tests and numerical results for Clark II and Clark IV tumors, comparing the models using constant and temperature-dependent thermophysical properties, which showed noticeable differences and highlighted the importance of using a local thermoregulation model.

Keywords: boundary element method, dynamic thermography, static thermography, skin tumor diagnostic

Procedia PDF Downloads 107

Authors: Huajuan Shi

Abstract:

Background: The biopsy of the preimplantation embryo may increase the potential risk and concern of embryo viability. Clinically discarded spent embryo medium (SEM) has entered the view of researchers, sparking an interest in noninvasive embryo screening. However, one of the major restrictions is the extremelty low quantity of cf-RNA, which is difficult to efficiently and unbiased amplify cf-RNA using traditional methods. Hence, there is urgently need to an efficient and low bias amplification method which can comprehensively and accurately obtain cf-RNA information to truly reveal the state of SEM cf-RNA. Result: In this present study, we established an agarose PCR amplification system, and has significantly improved the amplification sensitivity and efficiency by ~90 fold and 9.29 %, respectively. We applied agarose to sequencing library preparation (named AG-seq) to quantify and characterize cf-RNA in SEM. The number of detected cf-RNAs (3533 vs 598) and coverage of 3' end were significantly increased, and the noise of low abundance gene detection was reduced. The increasing percentage 5' end adenine and alternative splicing (AS) events of short fragments (< 400 bp) were discovered by AG-seq. Further, the profiles and characterizations of cf-RNA in spent cleavage medium (SCM) and spent blastocyst medium (SBM) indicated that 4‐mer end motifs of cf-RNA fragments could remarkably differentiate different embryo development stages. Significance: This study established an efficient and low-cost SEM amplification and library preparation method. Not only that, we successfully described the characterizations of SEM cf-RNA of preimplantation embryo by using AG-seq, including abundance features fragment lengths. AG-seq facilitates the study of cf-RNA as a noninvasive embryo screening biomarker and opens up potential clinical utilities of trace samples.

Keywords: cell-free RNA, agarose, spent embryo medium, RNA sequencing, non-invasive detection

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Authors: Lian Wu, Mervyn Merrilees

Abstract:

Chronic Obstructive Pulmonary Disease (COPD) is a worldwide problem, characterized by irreversible and progressive airflow obstruction. In New Zealand, it is currently the 4th commonest cause of death and exacerbations of COPD are a frequent cause of admission to hospital. Serum levels of Clara cell secretory protein-16 (CC-16) are believed to represent Clara cell toxicity. More recently, CC-16 has been found to be associated with smoker COPD. It is produced almost exclusively by non-ciliated Clara cells in the airways, and its primary function is to protect the lungs against oxidative stress and carcinogenesis. After acute exposure to cigarette smoke, serum levels of CC-16 become elevated. CC16 is a potent natural immune-suppressor and anti-inflammatory agent. In vitro, CC16 inhibits both monocyte and polymorphonuclear neutrophils chemotaxis and phagocytosis. CC16 also inhibits fibroblast chemotaxis. However, the role of CC-16 in non-smoking related COPD is still not clear. In this study, we investigated serum CC-16 levels in non-smoking related COPD. Methods: We compared non-smoker patients with COPD (FEV1<60% of predicted, FEV1/FVC <0.7, n=100) and individuals with normal lung function FEV1≥ 80% of predicted and FEV1/FVC≥ 0.7, n=80). All subjects had no smoking history. CC-16 was measured by ELISA. Results and conclusion: Serum CC-16 levels are reduced in individuals with non-smoking related COPD, and there is a weak correlation with disease severity in non-smoking related COPD group compared to non-smoker controls.

Keywords: COPD, CC-16, ELISA, non-smoking-related COPD

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Authors: Vichayada Laohapiboolkul

Abstract:

Introduction: As the legal use of cannabis is being widely accepted throughout the world, medical cannabis has been explored in order to become an alternative cure for patients. Tetrahydrocannabinol (THC) and Cannabidiol (CBD) are natural cannabinoids found in the Cannabis plant which is proved to have positive treatment for various diseases and symptoms such as chronic pain, neuropathic pain, spasticity resulting from multiple sclerosis, reduce cancer-associated pain, autism spectrum disorders (ASD), dementia, cannabis and opioid dependence, psychoses/schizophrenia, general social anxiety, posttraumatic stress disorder, anorexia nervosa, attention-deficit hyperactivity disorder, and Tourette's disorder. Regardless of all the medical benefits, THC, if not metabolized, can lead to mild up to severe adverse drug reactions (ADR). The enzyme CYP2C19 was found to be one of the metabolizers of THC. However, the suballele CYP2C19*2 manifests as a poor metabolizer which could lead to higher levels of THC than usual, possibly leading to various ADRs. Objective: The aim of this study was to investigate the distribution of CYP2C19, specifically CYP2C19*2, genes in Thai patients treated with medical cannabis along with adverse drug reactions. Materials and Methods: Clinical data and EDTA whole blood for DNA extraction and genotyping were collected from patients for this study. CYP2C19*2 (681G>A, rs4244285) genotyping was conducted using the Real-time PCR (ABI, Foster City, CA, USA). Results: There were 42 medical cannabis-induced ADRs cases and 18 medical cannabis tolerance controls who were included in this study. A total of 60 patients were observed where 38 (63.3%) patients were female and 22 (36.7%) were male, with a range of age approximately 19 - 87 years. The most apparent ADRs for medical cannabis treatment were dry mouth/dry throat (76.7%), followed by tachycardia (70%), nausea (30%) and a few arrhythmias (10%). In the total of 27 cases, we found a frequency of 18 CYP2C19*1/*1 alleles (normal metabolizers, 66.7%), 8 CYP2C19*1/*2 alleles (intermediate metabolizers, 29.6%) and 1 CYP2C19*2/*2 alleles (poor metabolizers, 3.7%). Meanwhile, 63.6% of CYP2C19*1/*1, 36.3% and 0% of CYP2C19*1/*2 and *2/*2 in the tolerance controls group, respectively. Conclusions: This is the first study to confirm the distribution of CYP2C19*2 allele and the prevalence of poor metabolizer genes in Thai patients who received medical cannabis for treatment. Thus, CYP2C19 allele might serve as a pharmacogenetics marker for screening before initiating treatment.

Keywords: medical cannabis, adverse drug reactions, CYP2C19, tetrahydrocannabinol, poor metabolizer

Procedia PDF Downloads 103

Authors: Md. Fazlul Karim, Ashik Sharfaraz, Aysha Ferdoushi

Abstract:

Background: Computational medicinal chemistry approaches are used for designing and identifying new drug-like molecules, predicting properties and pharmacological activities, and optimizing lead compounds in drug development. SIRT7, a nicotinamide adenine dinucleotide (NAD+)-dependent deacylase which regulates aging, is an emerging target for cancer therapy with mounting evidence that SIRT7 downregulation plays important roles in reversing cancer phenotypes and suppressing tumor growth. Activation or altered expression of SIRT7 is associated with the progression and invasion of various cancers, including liver, breast, gastric, prostate, and non-small cell lung cancer. Objectives: The goal of this work was to identify potent and selective bioactive candidate inhibitors of SIRT7 by in silico screening of small molecule compounds obtained from Nigella sativa (N. sativa). Methods: SIRT7 structure was retrieved from The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), and its active site was identified using CASTp and metaPocket. Molecular docking simulation was performed with PyRx 0.8 virtual screening software. Drug-likeness properties were tested using SwissADME and pkCSM. In silico toxicity was evaluated by Osiris Property Explorer. Bioactivity was predicted by Molinspiration software. Antitumor activity was screened for Prediction of Activity Spectra for Substances (PASS) using Way2Drug web server. Molecular dynamics (MD) simulation was carried out by Desmond v3.6 package. Results: A total of 159 bioactive compounds from the N. Sativa were screened against the SIRT7 enzyme. Five bioactive compounds: chrysin (CID:5281607), pinocembrin (CID:68071), nigellidine (CID:136828302), nigellicine (CID:11402337), and epicatechin (CID:72276) were identified as potent SIRT7 anti-cancer candidates after docking score evaluation and applying Lipinski's Rule of Five. Finally, MD simulation identified Chrysin as the top SIRT7 anti-cancer candidate molecule. Conclusion: Chrysin, which shows a potential inhibitory effect against SIRT7, can act as a possible anti-cancer drug candidate. This inhibitor warrants further evaluation to check its pharmacokinetics and pharmacodynamics properties both in vitro and in vivo.

Keywords: SIRT7, antitumor, molecular docking, molecular dynamics simulation

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Authors: D. S. Mohale, A. P. Dewani, A. S.tripathi, A. V. Chandewar

Abstract:

Present work demonstrates the applicability of high-performance liquid chromatography (HPLC) with UV-Vis detection for the quantification of malondialdehyde as malondialdehyde-thiobarbituric acid complex (MDA-TBA) in-vivo in rats. The HPLC method for MDA-TBA was achieved by isocratic mode on a reverse-phase C18 column (250mm×4.6mm) at a flow rate of 1.0mLmin−1 followed by detection at 532 nm. The chromatographic conditions were optimized by varying the concentration and pH of water followed by changes in percentage of organic phase optimal mobile phase consisted of mixture of water (0.2% triethylamine pH adjusted to 2.3 by ortho-phosphoric acid) and acetonitrile in ratio (80:20v/v). The retention time of MDA-TBA complex was 3.7 min. The developed method was sensitive as limit of detection and quantification (LOD and LOQ) for MDA-TBA complex were (standard deviation and slope of calibration curve) 110 ng/ml and 363 ng/ml respectively. Calibration studies were done by spiking MDA into rat plasma at concentrations ranging from 500 to 1000 ng/ml. The precision of developed method measured in terms of relative standard deviations for intra-day and inter-day studies was 1.6–5.0% and 1.9–3.6% respectively. The HPLC method was applied for monitoring MDA levels in rats subjected to chronic treatment of levofloxacin (LEV) (5mg/kg/day) for 21 days. Results were compared by findings in control group rats. Mean peak areas of both study groups was subjected for statistical treatment to unpaired student t-test to find p-values. The p value was <0.001 indicating significant results and suggesting increased MDA levels in rats subjected to chronic treatment of LEV of 21 days.

Keywords: malondialdehyde-thiobarbituric acid complex, levofloxacin, HPLC, oxidative stress

Procedia PDF Downloads 334