Search results for: high-throughput drug screening

Authors: Tsu-Yin Wu, Jenni Hoffman, Lydia McMurrows, Sarah Lally

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Recent events of the Flint Water Crisis and elevated lead levels in Detroit public school water have highlighted a specific public health disparity and shown the need for better education of healthcare providers on lead education. Identifying children and pregnant women with a high risk for lead poisoning and ensuring lead testing is completed is critical. The purpose of this study is to explore the impact of an educational intervention on knowledge and confidence levels among nursing students enrolled in the prelicensure Bachelor of Science in Nursing (BSN) and Registered Nurse to BSN program (R2B). The study used both quantitative and qualitative research methods to assess the impact of multi-modal pedagogy on knowledge and confidence of lead screening and prevention among prelicensure and R2B nursing students. The students received lead poisoning and prevention content in addition to completing an e-learning module developed by the Pediatric Environmental Health Specialty Units. A total of 115 students completed the pre-and post-test instrument that consisted of demographic, lead knowledge, and confidence items. Despite the increase of total knowledge, three dimensions of lead poisoning, and confidence from pre- to post-test scores for both groups, there was no statistical significance on the increase between prelicensure and R2B students. Thematic analysis of qualitative data showed five themes from participants' learning experiences: lead exposure, signs and symptoms of lead poisoning, screening and diagnosis, prevention, and policy and statewide issues. The study is limited by a small sample and participants recalling some correct answers from the pretest, thus, scoring higher on the post-test. The results contribute to the minimally existent literature examining a critical public health concern regarding lead health exposure and prevention education of nursing students. Incorporating such content area into the nursing curriculum is essential in ensuring that such public health disparities are mitigated.

Keywords: lead poisoning, emerging public health issue, community health, nursing edducation

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Authors: V. Bezverbny

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The actuality of the project deals with stable growing of deviant behavior’ statistics among Moscow citizens. During the recent years the socioeconomic health, wealth and life expectation of Moscow residents is regularly growing up, but the limits of crime and drug addiction have grown up seriously. Another serious Moscow problem has been economical stratification of population. The cost of identical residential areas differs at 2.5 times. The project is aimed at complex research and the development of methodology for main factors and reasons evaluation of deviant behavior growing in Moscow. The main project objective is finding out the links between the urban environment quality and dynamics of citizens’ deviant behavior in regional and municipal aspect using the statistical research methods and GIS modeling. The conducted research allowed: 1) to evaluate the dynamics of deviant behavior in Moscow different administrative districts; 2) to describe the reasons of crime increasing, drugs addiction, alcoholism, suicides tendencies among the city population; 3) to develop the city districts classification based on the level of the crime rate; 4) to create the statistical database containing the main indicators of Moscow population deviant behavior in 2010-2015 including information regarding crime level, alcoholism, drug addiction, suicides; 5) to present statistical indicators that characterize the dynamics of Moscow population deviant behavior in condition of expanding the city territory; 6) to analyze the main sociological theories and factors of deviant behavior for concretization the deviation types; 7) to consider the main theoretical statements of the city sociology devoted to the reasons for deviant behavior in megalopolis conditions. To explore the level of deviant behavior’ factors differentiation, the questionnaire was worked out, and sociological survey involved more than 1000 people from different districts of the city was conducted. Sociological survey allowed to study the socio-economical and psychological factors of deviant behavior. It also included the Moscow residents’ open-ended answers regarding the most actual problems in their districts and reasons of wish to leave their place. The results of sociological survey lead to the conclusion that the main factors of deviant behavior in Moscow are high level of social inequality, large number of illegal migrants and bums, nearness of large transport hubs and stations on the territory, ineffective work of police, alcohol availability and drug accessibility, low level of psychological comfort for Moscow citizens, large number of building projects.

Keywords: deviant behavior, megapolis, Moscow, urban environment, social stratification

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Authors: Li Shihao, Dieter Trau

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Bilirubin is a yellow substance that is made when the body breaks down old red blood cells. High levels of bilirubin can cause jaundice, a condition that makes the newborn's skin and the white part of the eyes look yellow. Jaundice is a serial-killer in developing countries in Southeast Asia such as Myanmar and most parts of Africa where jaundice screening is largely unavailable. Worldwide, 60% of newborns experience infant jaundice. One in ten will require therapy to prevent serious complications and lifelong neurologic sequelae. Limitations of current solutions: - Blood test: Blood tests are painful may largely unavailable in poor areas of developing countries, and also can be costly and unsafe due to the insufficient investment and lack of access to health care systems. - Transcutaneous jaundice-meter: 1) can only provide reliable results to caucasian newborns, due to skin pigmentations since current technologies measure bilirubin by the color of the skin. Basically, the darker the skin is, the harder to measure, 2) current jaundice meters are not affordable for most underdeveloped areas in Africa like Kenya and Togo, 3) fat tissue under the skin also influences the accuracy, which will give overestimated results, 4) current jaundice meters are not reliable after treatment (phototherapy) because bilirubin levels underneath the skin will be reduced first, while overall levels may be quite high. Thus, there is an urgent need for a low-cost non-invasive device, which can be effective not only for caucasian babies but also Asian and African newborns, to save lives at the most vulnerable time and prevent any complications like brain damage. Instead of measuring bilirubin on skin, we proposed a new method to do the measurement on the sclera, which can avoid the difference of skin pigmentations and ethnicities, due to the necessity for the sclera to be white regardless of racial background. This is a novel approach for measuring bilirubin by an optical method of light reflection off the white part of the eye. Moreover, the device is connected to a smart device, which can provide a user-friendly interface and the ability to record the clinical data continuously A disposable eye cap will be provided avoiding contamination and fixing the distance to the eye.

Keywords: Jaundice, bilirubin, non-invasive, sclera

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Authors: Mohsen Shati, Seyede Salehe Mortazavi, Seyed Kazem Malakouti, Hamidreza Khanke Fazlollah Ahmadi

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Taking unnecessary or excessive medication or using drugs with no indication (polypharmacy) by people of all ages, especially the elderly, is associated with increased adverse drug reactions (ADR), medical errors, hospitalization and escalating the costs. It may be facilitated or impeded by the healthcare system. In this study, we are going to describe the role of the health system in the practice of polypharmacy in Iranian elderly. In this Inductive qualitative content analysis using Graneheim and Lundman methods, purposeful sample selection until saturation has been made. Participants have been selected from doctors, pharmacists, policy-makers and the elderly. A total of 25 persons (9 men and 16 women) have participated in this study. Data analysis after incorporating codes with similar characteristics revealed 14 subcategories and six main categories of the referral system, physicians’ accessibility, health data management, drug market, laws enforcement, and social protection. Some of the conditions of the healthcare system have given rise to polypharmacy in the elderly. In the absence of a comprehensive specialty and subspecialty referral system, patients may go to any physician office so may well be confused about numerous doctors' prescriptions. Electronic records not being prepared for the patients, failure to comply with laws, lack of robust enforcement for the existing laws and close surveillance are among the contributing factors. Inadequate insurance and supportive services are also evident. Age-specific care providing has not yet been institutionalized, while, inadequate specialist workforce playing a major role. So, one may not ignore the health system as contributing factor in designing effective interventions to fix the problem.

Keywords: elderly, polypharmacy, health system, qualitative study

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Authors: Omoruyi Gold Idemudia, Alexander P. Sadimenko

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The synthesis of N-heterocycles with novel properties, having broad spectrum biological activities that may become alternative medicinal drugs, have been attracting a lot of research attention due to the emergence of medicinal drug’s limitations such as disease resistance and their toxicity effects among others. Acylpyrazolones have been employed as pharmaceuticals as well as analytical reagent and their application as coordination complexes with transition metal ions have been well established. By way of a condensation reaction with amines acylpyrazolone ketones form a more chelating and superior group of compounds known as azomethines. 4-propyl-3-methyl-1-phenyl-2-pyrazolin-5-one was reacted with phenylhydrazine to get a new phenylhydrazone which was further reacted with aqueous solutions of palladium and platinum salts, in an effort towards the discovery of transition metal based synthetic drugs. The compounds were characterized by means of analytical, spectroscopic, thermogravimetric analysis TGA, as well as x-ray crystallography. 4-propyl-3-methyl-1-phenyl-2-pyrazolin-5-one phenylhydrazone crystallizes in a triclinic crystal system with a P-1 (No. 2) space group based on x-ray crystallography. The bidentate ON ligand formed a square planar geometry on coordinating with metal ions based on FTIR, electronic and NMR spectra as well as magnetic moments. Reported compounds showed antibacterial activities against the nominated bacterial isolates using the disc diffusion technique at 20 mg/ml in triplicates. The metal complexes exhibited a better antibacterial activity with platinum complex having an MIC value of 0.63 mg/ml. Similarly, ligand and complexes also showed antioxidant scavenging properties against 2, 2-diphenyl-1-picrylhydrazyl DPPH radical at 0.5mg/ml relative to ascorbic acid (standard drug).

Keywords: acylpyrazolone, antibacterial studies, metal complexes, phenylhydrazone, spectroscopy

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Authors: Nisa Mohan

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Adverse drug event (ADE) related hospital admissions are common among older people. The first step in prevention is accurately estimating the prevalence of ADE admissions. Clinical coding is an efficient method to estimate the prevalence of ADE admissions. The objective of the study is to estimate the rate of under-coding of ADE admissions in older people in New Zealand and to explore how clinical coders decide whether or not to code an admission as an ADE. There has not been any research in New Zealand to explore these areas. This study is done using a mixed-methods approach. Two common and serious ADEs in older people, namely bleeding and hypoglycaemia were selected for the study. In study 1, eight hundred medical records of people aged 65 years and above who are admitted to hospital due to bleeding and hypoglycemia during the years 2015 – 2016 were selected for quantitative retrospective medical records review. This selection was made to estimate the proportion of ADE-related bleeding and hypoglycemia admissions that are not coded as ADEs. These files were reviewed and recorded as to whether the admission was caused by an ADE. The hospital discharge data were reviewed to check whether all the ADE admissions identified in the records review were coded as ADEs, and the proportion of under-coding of ADE admissions was estimated. In study 2, thirteen clinical coders were selected to conduct qualitative semi-structured interviews using a general inductive approach. Participants were selected purposively based on their experience in clinical coding. Interview questions were designed in a way to investigate the reasons for the under-coding of ADE admissions. The records review study showed that 35% (Cl 28% - 44%) of the ADE-related bleeding admissions and 22% of the ADE-related hypoglycemia admissions were not coded as ADEs. Although the quality of clinical coding is high across New Zealand, a substantial proportion of ADE admissions were under-coded. This shows that clinical coding might under-estimate the actual prevalence of ADE related hospital admissions in New Zealand. The interviews with the clinical coders added that lack of time for searching for information to confirm an ADE admission, inadequate communication with clinicians, along with coders’ belief that an ADE is a small thing might be the potential reasons for the under-coding of the ADE admissions. This study urges the coding policymakers, auditors, and trainers to engage with the unconscious cognitive biases and short-cuts of the clinical coders. These results highlight that further work is needed on interventions to improve the clinical coding of ADE admissions, such as providing education to coders about the importance of ADEs, education to clinicians about the importance of clear and confirmed medical records entries, availing pharmacist service to improve the detection and clear documentation of ADE admissions and including a mandatory field in the discharge summary about external causes of diseases.

Keywords: adverse drug events, bleeding, clinical coders, clinical coding, hypoglycemia

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Authors: Haykal. Kay-Anne

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The health and well-being of students is a priority for the Faculty of Medicine at the University of Ottawa. The demands of medical studies are extreme, and many studies confirm that the prevalence of psychological distress is very high among medical students and that it is higher than that of the general population of the same age. The main goal is to identify risk factors for mental health among medical students at the University of Ottawa. The secondary objectives are to determine the variation of these risk factors according to demographic variables, as well as to determine if there is a change in the mental health of students during the 1st and 3rd years of their study. Medical students have a mandatory first and third-year wellness check meeting. This assessment includes a questionnaire on demographic information, mental health, and risk factors such as physical health, sleep, social support, financial stress, education and career, stress and drug use and/or alcohol. Student responses were converted to numerical values and analyzed statistically. The results show that 61% of the variation in the mean of the mental health score is explained by the following risk factors (R2 = 0.61, F (9.396) = 67.197, p < 0.01): lack of sleep and fatigue (β = 0.281, p < 0.001), lack of social support (β = 0.217, p <0.001), poor study or career development (β = 0.195, p < 0.001) and an increase stress and drug and alcohol use (β = -0.239, p < 0.001). No demographic variable has a significant effect on the presence of risk factors. In addition, fixed-effects regression demonstrated significantly lower mental health (p < 0.1) among first-year students (M = 0.587, SD = 0.072) than among third-year students (M = 0.719, SD = 0.071). This preliminary study indicates the need to continue data collection and analysis to increase the significance of the study results. As risk factors are present at the beginning of medical studies, it is important to offer resources to students very early in their medical studies and to have close monitoring and supervision.

Keywords: assessment of mental health, medical students, risk factors for mental health, wellness assessment

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Authors: Cornelia-Eugenia Munteanu

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The goal of this paper is to present the diagnostic contribution that the screening instrument, Mini-Mental State Examination-2: Expanded Version (MMSE-2:EV), brings in detecting the cognitive impairment or in monitoring the progress of degenerative disorders. The diagnostic signification is underlined by the interpretation of the MMSE-2:EV scores, resulted from the test application to patients with mild and major neurocognitive disorders. The original MMSE is one of the most widely used screening tools for detecting the cognitive impairment, in clinical settings, but also in the field of neurocognitive research. Now, the practitioners and researchers are turning their attention to the MMSE-2. To enhance its clinical utility, the new instrument was enriched and reorganized in three versions (MMSE-2:BV, MMSE-2:SV and MMSE-2:EV), each with two forms: blue and red. The MMSE-2 was adapted and used successfully in Romania since 2013. The cases were selected from current practice, in order to cover vast and significant neurocognitive pathology: mild cognitive impairment, Alzheimer’s disease, vascular dementia, mixed dementia, Parkinson’s disease, conversion of the mild cognitive impairment into Alzheimer’s disease. The MMSE-2:EV version was used: it was applied one month after the initial assessment, three months after the first reevaluation and then every six months, alternating the blue and red forms. Correlated with age and educational level, the raw scores were converted in T scores and then, with the mean and the standard deviation, the z scores were calculated. The differences of raw scores between the evaluations were analyzed from the point of view of statistic signification, in order to establish the progression in time of the disease. The results indicated that the psycho-diagnostic approach for the evaluation of the cognitive impairment with MMSE-2:EV is safe and the application interval is optimal. The alternation of the forms prevents the learning phenomenon. The diagnostic accuracy and efficient therapeutic conduct derive from the usage of the national test norms. In clinical settings with a large flux of patients, the application of the MMSE-2:EV is a safe and fast psycho-diagnostic solution. The clinicians can draw objective decisions and for the patients: it doesn’t take too much time and energy, it doesn’t bother them and it doesn’t force them to travel frequently.

Keywords: MMSE-2, dementia, cognitive impairment, neuropsychology

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Authors: Saravanan Govindaraju, Kyusik Yun

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The purpose of this study is to develop the chitosan doped curcumin gold cluster nanofiber for wound healing and skin cancer drug delivery applications. Chitosan is a typical marine polysaccharide composed of glucosamine and n-acetyl glucosamine biodegradable and biocompatible polymer. Curcumin is a natural bioactive molecule obtained from Curcuma longo, it mostly occurs in some Asian countries like India and China. It has naturally antioxidant, antimicrobial, wound healing and anticancer property. Due to this advantage, we prepared a combination of natural polymer chitosan with Curcumin and gold nanocluster nanofiber (CH-CUR-AuNCs nanofibers). The prepared nanofiber was characterized by using Fourier transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM). Antibacterial studies were performed with E.coli and S.aureus. Antioxidant assay, drug release test, and cytotoxicity will be evaluated. Prepared nanofiber emits low intensity of red fluorescent. The FTIR confirm the presence of chitosan and Curcumin in the nanofiber. In vitro study clearly shows the antibacterial activity against the gram negative and gram positive bacteria. Particularly, synthesised nanofibers provide better antibacterial activity against gram negative than gram positive. Cytotoxicity study also provides better killing rate in cancer cell, biocompatible with normal cell. Prepared CH-CUR-AuNCs nanofibers provide the better killing rate to bacterial strains and cancer cells. Finally, prepared nanofiber can be possible to use for wound healing dressing, patch for skin cancer and other biomedical applications.

Keywords: curcumin, chitosan, gold clusters, nanofibers

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Authors: Rachmat Mauludin, Dita Sasri Primaviri, Irda Fidrianny

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Propolis contains several antioxidant compounds which can be used in topical application to protect skin against free radical, prevent skin cancer and skin aging. Previous study showed that 70% ethanolic extract of propolis (EEP) provided the greatest antioxidant activity. Since EEP has very small solubility in water, the extract was prepared in nanoemulsion (NE). Nanoemulsion is chosen as cosmetic dosage forms according to its properties namely to decrease the risk of skin’s irritation, increase penetration, prolong its time to remain in our skin, and improve stability. Propolis was extracted using reflux methods and concentrated using rotavapor. EEP was characterized with several tests such as phytochemical screening, density, and antioxidant activity using DPPH method. Optimation of total surfactant, co-surfactant, oil, and amount of EEP that can be included in NE were required to get the best NE formulation. The evaluations included to organoleptic observation, globul size, polydispersity index, morphology using TEM, viscosity, pH, centrifuge, stability, Freeze and Thaw test, radical scavenging activity using DPPH method, and primary irritation test. The yield extracts was 11.12% from raw propolis contained of steroid/triterpenoid, flavonoid, and saponin based on phytochemical screening. EEP had the value of DPPH scavenging activity 61.14% and IC50 0.41629 ppm. The best NE formulation consisted of 26.25% Kolliphor RH40; 8.75% glycerine; 5% rice bran oil; and 3% EEP. NE was transparant, had globul size of 21.9 nm; polydispersity index of 0.338; and pH of 5.67. Based on TEM morphology, NE was almost spherical and has particle size below 50 nm. NE propolis revealed to be physically stable after stability test within 63 days at 25oC, centrifuged for 30 mins at 13.000 rpm, and passed 6 cycles of Freeze and Thaw test without separated. NE propolis reduced 58% of free radical DPPH similar to antioxidant activity of the original extracts. Antioxidant activity of NE propolis is relatively stable after stored for 6 weeks. NE Propolis was proven to be safe by primary irritation test with the value of primary irritation index (OECD) was 0. The best formulation for NE propolis contained of 26.25% Kolliphor RH40; 8.75% glycerine; 5% rice bran oil; and 3% EEP with globul size of 21.9 nm and polydispersity index of 0.338. NE propolis was stable and had antioxidant activity similar to EEP.

Keywords: propolis, antioxidant, nanoemulsion, irritation test

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Authors: Y. Mohammed, A. I. Kabuga

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Sexually transmitted infections (STIs) have continued to be a major public health problem in sub-Saharan Africa especially with the recent resurgence of syphilis. Syphilis is a systemic disease caused by the bacterium, spirochete Treponema pallidum and has been reported as one of the common sexually transmitted infections (STIs) in Nigeria. Presence of genital ulcer disease from syphilis facilitates human immunodeficiency virus (HIV) transmission and their ¬diagnosis is essential for the proper management. Venereal Disease Research Laboratory (VDRL) test is used as a screening test for the diagnosis of syphilis. However, unusual VDRL test results have been reported in HIV-infected persons with syphilis. There are reports showing higher than expected VDRL titers as well as biological false positive in most of the studies. A negative Rapid Plasma Reagin (RPR) test or VDRL test result may not rule out syphilis in patients with HIV infection. For laboratory confirmation of syphilis, one specific Treponemal test, namely, Fluroscent Treponemal Antibody Absorption (FTA-ABS) test or Treponema Pallidum Haemagglutination Assay (TPHA) should be done along with VDRL. A prospective cross sectional study was conducted for 2 years from Jun, 2012 to Jun 2014 to determine the prevalence of syphilis in HIV-seroreactive patients at 5 selected HIV/AIDS treatment and counseling centers in Kano State, North Western, Nigeria. New HIV-Seroreactive patients who gave informed consent to participate in the study were recruited. Venereal Diseases Research Laboratory (VDRL) test for Syphilis screening was performed on the same sera samples which were collected for HIV testing. A total of 238 patients, 113 (47%) males and 125 (53%) females, were enrolled. In the present study, 238 HIV-seropositive patients were screened for syphilis by VDRL test. Out of these 238 cases, 72 (32%) patients were positive for TPHA and 8 (3.4%) patients were reactive for VDRL in various titers with an overall prevalence of 3.4%. All the eight patients who were reactive for VDRL test were also positive for TPHA test. In Conclusions, with high prevalence of syphilis among HIV-infected people from this study, it is recommended that serological testing for syphilis should be carried out in all patients with newly diagnosed HIV infection. Detection and treatment of STI should have a central role in HIV prevention and control. This will help in proper management of patients having STIs and HIV co infection.

Keywords: HIV, infections, STIs, syphilis

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Authors: Alex Kiselyov, Suehyun Cho, Darrell Harrington; Florent Cros, Olin Palmer, John Caputo, Michael Kardosh, Eran Oren, William Loudon, Michael Shpigelmacher

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Despite the most aggressive surgical and adjuvant therapeutic strategies, treatment of both pediatric and adult brainstem tumors remains problematic. Novel strategies, including targeted biologics, immunotherapy, and specialized delivery systems such as convection-enhanced delivery (CED), have been proposed. While some of these novel treatments are entering phase I trials, the field is still in need of treatment(s) that exhibits dramatically enhanced potency with optimal therapeutic ratio. Bionaut Labs has developed a modular microrobotic platform for performing localized delivery of diverse therapeutics in vivo. Our biocompatible particles (Bionauts™) are externally propelled and visualized in real-time. Bionauts™ are specifically designed to enhance the effect of radiation therapy via anatomically precise delivery of a radiosensitizing agent, as exemplified by temozolomide (TMZ) and Avastin™ to the brainstem gliomas of diverse origin. The treatment protocol is designed to furnish a better therapeutic outcome due to the localized (vs systemic) delivery of the drug to the neoplastic lesion(s) for use as a synergistic combination of radiation and radiosensitizing agent. In addition, the procedure is minimally invasive and is expected to be appropriate for both adult and pediatric patients. Current progress, including platform optimization, selection of the lead radiosensitizer as well as in vivo safety studies of the Bionauts™ in large animals, specifically the spine and the brain of porcine and ovine models, will be discussed.

Keywords: Bionaut, brainstem, glioma, local delivery, micro-robot, radiosensitizer

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Authors: Mouna Baassi, Mohamed Moussaoui, Hatim Soufi, Sanchaita RajkhowaI, Ashwani Sharma, Subrata Sinha, Said Belaaouad

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Human Immunodeficiency Virus type 1 protease (HIV-1 PR) is one of the most challenging targets of antiretroviral therapy used in the treatment of AIDS-infected people. The performance of protease inhibitors (PIs) is limited by the development of protease mutations that can promote resistance to the treatment. The current study was carried out using statistics and bioinformatics tools. A series of thirty-three compounds with known enzymatic inhibitory activities against HIV-1 protease was used in this paper to build a mathematical model relating the structure to the biological activity. These compounds were designed by software; their descriptors were computed using various tools, such as Gaussian, Chem3D, ChemSketch and MarvinSketch. Computational methods generated the best model based on its statistical parameters. The model’s applicability domain (AD) was elaborated. Furthermore, one compound has been proposed as efficient against HIV-1 protease with comparable biological activity to the existing ones; this drug candidate was evaluated using ADMET properties and Lipinski’s rule. Molecular Docking performed on Wild Type and Mutant Type HIV-1 proteases allowed the investigation of the interaction types displayed between the proteases and the ligands, Darunavir (DRV) and the new drug (ND). Molecular dynamics simulation was also used in order to investigate the complexes’ stability, allowing a comparative study of the performance of both ligands (DRV & ND). Our study suggested that the new molecule showed comparable results to that of Darunavir and may be used for further experimental studies. Our study may also be used as a pipeline to search and design new potential inhibitors of HIV-1 proteases.

Keywords: QSAR, ADMET properties, molecular docking, molecular dynamics simulation.

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Authors: Priyanka Sharma, Ranjita Das, Mohan C. Kalita, Debajit Thakur

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Background: Actinomycetes are the richest source of novel bioactive secondary metabolites such as antibiotics, enzymes and other therapeutically useful metabolites with diverse biological activities. The present study aims at the antimicrobial potential and genetic diversity of culturable Actinomycetes isolated from protected forest ecosystems of Assam which includes Kaziranga National Park (26°30˝-26°45˝N and 93°08˝-93°36˝E), Pobitora Wildlife Sanctuary (26º12˝-26º16˝N and 91º58˝-92º05˝E) and Gibbon Wildlife Sanctuary (26˚40˝-26˚45˝N and 94˚20˝-94˚25˝E) which are located in the North-eastern part of India. Northeast India is a part of the Indo-Burma mega biodiversity hotspot and most of the protected forests of this region are still unexplored for the isolation of effective antibiotic-producing Actinomycetes. Thus, there is tremendous possibility that these virgin forests could be a potential storehouse of novel microorganisms, particularly Actinomycetes, exhibiting diverse biological properties. Methodology: Soil samples were collected from different ecological niches of the protected forest ecosystems of Assam and Actinomycetes were isolated by serial dilution spread plate technique using five selective isolation media. Preliminary screening of Actinomycetes for an antimicrobial activity was done by spot inoculation method and the secondary screening by disc diffusion method against several test pathogens, including multidrug resistant Staphylococcus aureus (MRSA). The strains were further screened for the presence of antibiotic synthetic genes such as type I polyketide synthases (PKS-I), type II polyketide synthases (PKS-II) and non-ribosomal peptide synthetases (NRPS) genes. Genetic diversity of the Actinomycetes producing antimicrobial metabolites was analyzed through 16S rDNA-RFLP using Hinf1 restriction endonuclease. Results: Based on the phenotypic characterization, a total of 172 morphologically distinct Actinomycetes were isolated and screened for antimicrobial activity by spot inoculation method on agar medium. Among the strains tested, 102 (59.3%) strains showed activity against Gram-positive bacteria, 98 (56.97%) against Gram-negative bacteria, 92 (53.48%) against Candida albicans MTCC 227 and 130 (75.58%) strains showed activity against at least one of the test pathogens. Twelve Actinomycetes exhibited broad spectrum antimicrobial activity in the secondary screening. The taxonomic identification of these twelve strains by 16S rDNA sequencing revealed that Streptomyces was found to be the predominant genus. The PKS-I, PKS-II and NRPS genes detection indicated diverse bioactive products of these twelve Actinomycetes. Genetic diversity by 16S rDNA-RFLP indicated that Streptomyces was the dominant genus amongst the antimicrobial metabolite producing Actinomycetes. Conclusion: These findings imply that Actinomycetes from the protected forest ecosystems of Assam, India, are a potential source of bioactive secondary metabolites. These areas are as yet poorly studied and represent diverse and largely unscreened ecosystem for the isolation of potent Actinomycetes producing antimicrobial secondary metabolites. Detailed characterization of the bioactive Actinomycetes as well as purification and structure elucidation of the bioactive compounds from the potent Actinomycetes is the subject of ongoing investigation. Thus, to exploit Actinomycetes from such unexplored forest ecosystems is a way to develop bioactive products.

Keywords: Actinomycetes, antimicrobial activity, forest ecosystems, RFLP

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Authors: Akane Uda, Ami Tabata, Mi An, Misa Komaki, Ryotaro Ito, Mayumi Inoue, Takehiro Sasai, Yusuke Kusano, Toshihiro Kato

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Early intervention is recommended for children with autism spectrum disorder (ASD), and an increasing number of children have received support and intervention before school age in recent years. In this study, we systematically reviewed preschool interventions focused on repetitive behaviors observed in children with ASD, which are often observed at younger ages. Inclusion criteria were as follows : (1) Child of preschool status (age ≤ 7 years) with a diagnosis of ASD (including autism, Asperger's, and pervasive developmental disorder) or a parent (caregiver) with a preschool child with ASD, (2) Physician-confirmed diagnosis of ASD (autism, Asperger's, and pervasive developmental disorder), (3) Interventional studies for repetitive behaviors, (4) Original articles published within the past 10 years (2012 or later), (5) Written in English and Japanese. Exclusion criteria were as follows: (1) Systematic reviews or meta-analyses, (2) Conference reports or books. We carefully scrutinized databases to remove duplicate references and used a two-step screening process to select papers. The primary screening included close scrutiny of titles and abstracts to exclude articles that did not meet the eligibility criteria. During the secondary screening, we carefully read the complete text to assess eligibility, which was double-checked by six members at the laboratory. Disagreements were resolved through consensus-based discussion. Our search yielded 304 papers, of which nine were included in the study. The level of evidence was as follows: three randomized controlled trials (level 2), four pre-post studies (level 4b), and two case reports (level 5). Seven articles selected for this study described the effectiveness of interventions. Interventions for repetitive behaviors in preschool children with ASD were categorized as five interventions that directly involved the child and four educational programs for caregivers and parents. Studies that directly intervened with children used early intensive intervention based on applied behavior analysis (Early Start Denver Model, Early Intensive Behavioral Intervention, and the Picture Exchange Communication System) and individualized education based on sensory integration. Educational interventions for caregivers included two methods; (a) education regarding combined methods and practices of applied behavior analysis in addition to classification and coping methods for repetitive behaviors, and (b) education regarding evaluation methods and practices based on children’s developmental milestones in play. With regard to the neurophysiological basis of repetitive behaviors, environmental factors are implicated as possible contributors. We assumed that applied behavior analysis was shown to be effective in reducing repetitive behaviors because analysis focused on the interaction between the individual and the environment. Additionally, with regard to educational interventions for caregivers, the intervention was shown to promote behavioral change in children based on the caregivers' understanding of the classification of repetitive behaviors and the children’s developmental milestones in play and adjustment of the person-environment context led to a reduction in repetitive behaviors.

Keywords: autism spectrum disorder, early intervention, repetitive behaviors, systematic review

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Authors: B. Sadek, N. Khan, Shreesh K. Ojha, Adel Sadeq, D. Lazewska, K. Kiec-Kononowicz

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The involvement of Histamine H3 receptors (H3Rs) in memory and the potential role of H3R antagonists in pharmacological control of neurodegenerative disorders, e.g., Alzheimer disease (AD) is well established. Therefore, the memory-enhancing effects of the H3R antagonist DL77 on MK801-induced cognitive deficits were evaluated in passive avoidance paradigm (PAP) and novel object recognition (NOR) tasks in adult male rats, applying donepezil (DOZ) as a reference drug. Animals pretreated with acute systemic administration of DL77 (2.5, 5, and 10 mg/kg, i.p.) were significantly ameliorated in regard to MK801-induced memory deficits in PAP. The ameliorative effect of most effective dose of DL77 (5 mg/kg, i.p.) was abrogated when animals were pretreated with a co-injection with the H3R agonist R-(α)-methylhistamine (RAMH, 10 mg/kg, i.p.). Moreover, and in the NOR paradigm, DL77 (5 mg/kg, i.p.) reversed MK801-induced deficits long-term memory (LTM), and the DL77-provided procognitive effect was comparable to that of reference drug DOZ, and was reversed when animals were co-injected with RAMH (10 mg/kg, i.p.). However, DL77(5 mg/kg, i.p.) failed to alter short-term memory (STM) impairment in NOR test. Furthermore, DL77 (5 mg/kg) failed to induce any alterations of anxiety and locomotor behaviors of animals naive to elevated-plus maze (EPM), indicating that the ameliorative effects observed in PAP or NOR tests were not associated to alterations in emotions or in natural locomotion of tested animals. These results reveal the potential contribution of H3Rs in modulating CNS neurotransmission systems associated with neurodegenerative disorders, e.g., AD.

Keywords: histamine H3 receptor, antagonist, learning and memory, Alzheimer's disease, neurodegeneration, passive avoidance paradigm, novel object recognition, behavioral research

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Authors: Anindita Sen

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Oral fluid is a promising diagnostic matrix for drugs of abuse compared to urine and serum. Detection of methamphetamine in oral fluid would pave way for the easy evaluation of impairment in drivers during roadside drug testing as well as ensure safe working environments by facilitating evaluation of impairment in employees at workplaces. A membrane-based point-of-care (POC) friendly pre-treatment technique has been developed which aided elimination of interferences caused by salivary proteins and facilitated the demonstration of methamphetamine detection in saliva using a gold nanoparticle based colorimetric aptasensor platform. It was found that the colorimetric response in saliva was always suppressed owing to the matrix effects. By navigating the challenging interfering issues in saliva, we were successfully able to detect methamphetamine at nanomolar levels in saliva offering immense promise for the translation of these platforms for on-site diagnostic systems. This subsequently motivated the development of a handheld portable light meter device that can reliably transduce the aptasensors colorimetric response into absorbance, facilitating quantitative detection of analyte concentrations on-site. This is crucial due to the prevalent unreliability and sensitivity problems of the conventional drug testing kits. The fabricated light meter device response was validated against a standard UV-Vis spectrometer to confirm reliability. The portable and cost-effective handheld detector device features sensitivity comparable to the well-established UV-Vis benchtop instrument and the easy-to-use device could potentially serve as a prototype for a commercial device in the future.

Keywords: aptasensors, colorimetric gold nanoparticle assay, point-of-care, oral fluid

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Authors: Nunila Ferreira de Oliveira, Silvana Martins Mishima

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Diabetes mellitus type 2 (DM2) prevalence, is increasing on the world, in Brazil is considered a public health problem. Treatment focuses on glycemic control depending primarily of lifestyle changes - not drug treatment (NDT), may involve drug therapy (DT) and requires continuous health monitoring. In Brazil this monitoring is performed by the Unified Health System (SUS) through Primary Health Care (PHC), which stimulate people with DM2 empowerment for care management. SUS was approved in 1988 and the PHC operationalization was strengthened with the creation of the Family Health Strategy (FHS) in 1994. Our aim was to analyze the people with DM2 participation in front of the care management health monitoring in the FHS. Qualitative research was carried out through non-participant observation of attendance of 25 people with DM2 in the FHS and interviewed at home. Ethical guidelines were followed. It was found that people with DM2 only follow professionals’ recommendations that make sense according to their own conceptions of health/disease; most of them emphasize the importance of (DT) with little emphasis on the NDT, was found great difficulty in the NDT and lack of knowledge about the disease and care. As regards monitoring the FHS, were observed therapeutic practices based on the bio medical model, although the APS search for another care perspective; NDT is not systematically accompanied by the health team and takes place a few educational activities on the DM2 in the FHS, with low user adoption. The work of the FHS is done by multidisciplinary teams, but we see the need for greater participation of nurses in clinical-care follow-up of this population and may also act in adapting to the NDT. Finally we emphasize the need for professional practices that consider the difficulties to care management by people with DM2, especially because of the NDT. It is noticed that the measures recommended by the FHS professionals are not always developed by people with DM2. We must seek the empowerment of people with DM2 to manage the form of care associated with the FHS team, seeking to reduce the incidence of complications and higher quality of life.

Keywords: diabetes mellitus, primary health care, nursing, management of care

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Authors: Mukul Sharma, Madhusmita Das, Sundeep Chaitanya Vedithi

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Leprosy is a chronic human disease caused by Mycobacterium leprae, that cannot be cultured in vitro. Though treatable with multidrug therapy (MDT), recently, bacteria reported resistance to multiple antibiotics. Targeting DNA replication and repair pathways can serve as the foundation of developing new anti-leprosy drugs. Due to the absence of an axenic culture medium for the propagation of M. leprae, studying cellular processes, especially those belonging to DNA repair pathways, is challenging. Genomic understanding of M. Leprae harbors several protein-coding genes with no previously assigned function known as 'hypothetical proteins'. Here, we report identification and expression of known and hypothetical DNA repair genes from a human skin biopsy and mouse footpads that are involved in base excision repair, direct reversal repair, and SOS response. Initially, a bioinformatics approach was employed based on sequence similarity, identification of known protein domains to screen the hypothetical proteins in the genome of M. leprae, that are potentially related to DNA repair mechanisms. Before testing on clinical samples, pure stocks of bacterial reference DNA of M. leprae (NHDP63 strain) was used to construct standard graphs to validate and identify lower detection limit in the qPCR experiments. Primers were designed to amplify the respective transcripts, and PCR products of the predicted size were obtained. Later, excisional skin biopsies of newly diagnosed untreated, treated, and drug resistance leprosy cases from SIHR & LC hospital, Vellore, India were taken for the extraction of RNA. To determine the presence of the predicted transcripts, cDNA was generated from M. leprae mRNA isolated from clinically confirmed leprosy skin biopsy specimen across all the study groups. Melting curve analysis was performed to determine the integrity of the amplification and to rule out primer‑dimer formation. The Ct values obtained from qPCR were fitted to standard curve to determine transcript copy number. Same procedure was applied for M. leprae extracted after processing a footpad of nude mice of drug sensitive and drug resistant strains. 16S rRNA was used as positive control. Of all the 16 genes involved in BER, DR, and SOS, differential expression pattern of the genes was observed in terms of Ct values when compared to human samples; this was because of the different host and its immune response. However, no drastic variation in gene expression levels was observed in human samples except the nth gene. The higher expression of nth gene could be because of the mutations that may be associated with sequence diversity and drug resistance which suggests an important role in the repair mechanism and remains to be explored. In both human and mouse samples, SOS system – lexA and RecA, and BER genes AlkB and Ogt were expressing efficiently to deal with possible DNA damage. Together, the results of the present study suggest that DNA repair genes are constitutively expressed and may provide a reference for molecular diagnosis, therapeutic target selection, determination of treatment and prognostic judgment in M. leprae pathogenesis.

Keywords: DNA repair, human biopsy, hypothetical proteins, mouse footpads, Mycobacterium leprae, qPCR

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Authors: Rania Hanafi Said, Rasha Mohamed Taha

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Background: By using nanoparticles as drug delivery, it may be possible to avoid the drawbacks of systemic antibiotic dosing, including bacterial antibiotic resistance. The goal of this study was to see how well tetracycline loaded on nanochitosan worked to treat gingival inflammation in albino rats caused by Porphyromonas gingivalis. The study analyzed immunohistochemically the localization of the pro-inflammatory cytokine Interleukin-1beta (IL-1β). Material and methods: In this study, fifty mature male albino rats weighing 150 to 180 grams each were used. They were randomly divided into five groups. We checked for weight changes in rats. Ten male albino rats were included in Group I, which served as a negative control group. Ten rats were included in Group II, where they were exposed once to Porphyromonas. Group III contained ten rats, which were treated the same as Group II plus daily injections of diluted tetracycline powder at the infection sites. Ten rats in Group IV received the same procedure as those in Group II before receiving daily injections of nanochitosan at the injection sites. Finally, Group V, which had ten rats. Following the same protocol as Group II, they received localized injections of tetracycline loaded on nanochitosan once daily. Rats' gingivae were extracted and prepared after they were anesthetized. The biopsies were examined histologically and immunohistochemically by light microscopy. Results: Groups I and V had a nearly normal histological appearance of gingival tissue. In Groups II, III, and IV, degeneration was seen because the epithelial cells were bigger, collagen fibers were pulling away from the lamina propria connective tissue, and the basement membranes had come to an end. There was no discernible difference between groups V and I when they were examined immunohistochemically. Conclusion: The use of nano chitosan as a tetracycline carrier is a novel technique to overcome the drug's rising level of resistance.

Keywords: Immunohistochemistry, Nanochitosan, porphyromonas gingivitis, Tetracycline

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Authors: Mercy Marimirofa, Farai Machinga, Alfred Zvoushe, Tsitsidzaishe Musvosvi

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The Government of Zimbabwe embarked on integrating family planning with Sexually Transmitted Infection (STI) and Human Immunodeficiency Virus (HIV) services in May 2020 with support from the World Health Organization (WHO). There was high HIV prevalence, incidence rates and STI infections among women attending FP clinics. Spilhaus is a specialized center of excellence clinic which offers a range of sexual reproductive health services. HIV services were limited to testing only, and clients were referred to other facilities for further management. Integration of services requires that all the services be available at one point so that clients will access them during their visit to the facility. Objectives: The study was conducted to assess the impact the one-stop-shop model has made in accessing integrated Family Planning services and sexual reproductive health services compared to the supermarket approach. It also assessed the relationship family planning services have with other sexual reproductive health services. Methods: A secondary data analysis was conducted at Spilhaus clinic in Harare using family planning registers and HIV services registers comparing years 2019 and 2021. A 2 sample t-test was used to determine the difference in clients accessing the services under the two models. A Spearman’s rank correlation was used to determine if accessing family planning services has a relationship with other sexual reproductive health services. Results: In 2019, 7,548 clients visited the Spilhaus clinic compared to 8,265 during the period January to December 2021. The median age for all clients accessing services was 32 years. An increase of 69% in the number of services accessed was recorded from 2019 to 2021. More services were accessed in 2021. There was no difference in the number of clients accessing family planning services cervical cancer, and HIV services. A difference was found in the number of clients who were offered STI screening services. There was also a relationship between accessing family planning services and STI screening services (ρ = 0.729, p-value=0.006). Conclusion: Programming towards SRH services was a great achievement, the use of an integrated approach proved to be cost-effective as it minimised the required resources for separate programs. Clients accessed important health needs at once. The integration of these services provided an opportunity to offer comprehensive information which addressed an individual’s sexual reproductive health needs.

Keywords: intergration, one stop shop, family planning, reproductive health

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Authors: Umme Hani, H. G. Shivakumar, M. D. Younus Pasha

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The purpose of this work was to design and optimize a novel vaginal drug delivery system for more effective treatment against vaginal candidiasis. To achieve a better therapeutic efficacy and patient compliance in the treatment for vaginal candidiasis, herbal antifungal agent Curcumin which is 2.5 fold more potent than fluconazole at inhibiting the adhesion of candida albicans has been formulated in a bio-adhesive vaginal film. Curcumin was formulated in bio-adhesive film formulations that could be retained in the vagina for prolonged intervals. The polymeric films were prepared by solvent evaporation and optimized for various physicodynamic and aesthetic properties. Curcumin HPβCD (Hydroxypropyl β Cyclodextrin) was first developed to increase the solubility of curcumin. The formation of the Curcumin HPβCD complex was characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and FT-IR and evaluated for its solubility. Curcumin HPβCD complex was formulated in a bio-adhesive film using hydroxypropyl methyl cellulose (HPMC) and Carbopol 934P and characterized. DSC and FT-IR data of Curcumin HPβCD indicate there was complex formation between the drug and HPβCD. The little moisture content (8.02±0.34% w/w) was present in the film, which helps them to remain stable and kept them from being completely dry and brittle. The mechanical properties, tensile strength, and percentage elongation at break reveal that the formulations were found to be soft and tough. The films showed good peelability, relatively good swelling index, and moderate tensile strength and retained vaginal mucosa up to 8 h. The developed Curcumin vaginal film could be a promising safe herbal medication and can ensure longer residence at the vagina and provide an efficient therapy for vaginal candidiasis.

Keywords: curcumin, curcumin-HPβCD complex, bio-adhesive vaginal film, vaginal candidiasis, 23 factorial design

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Authors: Jungkyun Im

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Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective for relieving pain and reducing inflammation. They are nonselective inhibitors of two isoforms of COX, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), and thereby inhibiting the production of hormone-like lipid compounds such as, prostaglandins and thromboxanes which cause inflammation, pain, fever, platelet aggregation, etc. In addition, recently there are many research articles reporting the neuroprotective effect of NSAIDs in neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). However, the clinical use of NSAIDs in these diseases is limited by low brain distribution. Therefore, in order to assist the in-depth investigation on the pharmaceutical mechanism of flurbiprofen in neuroprotection and to make flurbiprofen a more potent drug to prevent or alleviate neurodegenerative diseases, delivery of flurbiprofen to brain should be effective and sufficient amount of flurbiprofen must penetrate the BBB thus gaining access into the patient’s brain. We have recently developed several types of guanidine-rich molecular carriers with high molecular weights and good water solubility that readily cross the blood-brain barrier (BBB) and display efficient distributions in the mouse brain. The G8 (having eight guanidine groups) molecular carrier based on D-sorbitol was found to be very effective in delivering anticancer drugs to a mouse brain. In the present study, employing the same molecular carrier, we prepared the flurbiprofen conjugate and studied its BBB permeation by mouse tissue distribution study. Flurbiprofen was attached to a molecular carrier with a fluorescein probe and multiple terminal guanidiniums. The conjugate was found to internalize into live cells and readily cross the BBB to enter the mouse brain. Our novel synthetic flurbiprofen conjugate will hopefully delivery NSAIDs into brain, and is therefore applicable to the neurodegenerative diseases treatment or prevention.

Keywords: flurbiprofen, drug delivery, molecular carrier, organic synthesis

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Authors: Angalabiri-Owei E. Bekekeme, Brambaifa Nelson

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In view of the peculiar environment of the Niger Delta, access to modern health care is limited, hence the inhabitants especially those in the swampy areas resorts to sourcing for alternatives cure for their ailments using plants commonly found in this area without scientific evaluation. Rhizophora racemosa, G. F. Meyer (Rhizophoraceae) is the most abundant mangrove plant in the Niger Delta Area of Nigeria. The plant has been observed to be used for relief of a toothache and dysmenorrhoea among some Ijaw communities in the region. This work has revealed the likely potential of the plant in drug discovery and development. The crude methanol extract at doses of 300 mg/kg and 600 mg/kg (intraperitoneal) were tested for analgesic effect using fresh egg albumin induced inflammatory pain and Randall–Sellito method to assess the pain threshold. The anti-inflammatory effect was also evaluated with the extract at doses of 300 mg/kg and 600 mg/kg (intraperitoneal) using acute inflammatory model; fresh egg albumin induced paw oedema and assessed using Plethysmometer in rats. The methanol extracts 300 mg/kg and 600 mg/kg exhibited a significant (P < 0.001) and dose-dependent analgesic activity compared with the negative control and a standard drug diclofenac using ANOVA with Least Significant Difference post hoc test as evidenced by increased pain threshold. Also, the extract significantly (P < 0.001) reduced the rat paw oedema induced by the sub plantar injection of fresh egg albumin when compared with the negative control and a standard diclofenac using above statistical methods. This study revealed that the plant possesses analgesic and anti-inflammatory activities hence provide scientific bases for use as medicine.

Keywords: analgesic, anti-inflammatory, plethysmometer, Rhizophora racemosa

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Authors: Amanda J. Burridge, Keith J. Edwards, Paul A. Wilkinson, Tom Batstone, Erik H. Murchie, Lorna McAusland, Ana Elizabete Carmo-Silva, Ivan Jauregui, Tracy Lawson, Silvere R. M. Vialet-Chabrand

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The rate of genetic progress in wheat production must be improved to meet global food security targets. However, past selection for domestication traits has reduced the genetic variation in modern wheat cultivars, a fact that could severely limit the future rate of genetic gain. The genetic variation in agronomically important traits for the wild relatives and progenitors of wheat is far greater than that of the current domesticated cultivars, but transferring these traits into modern cultivars is not straightforward. Between the elite cultivars of wheat, photosynthetic capacity is a key trait for which there is limited variation. Early screening of wheat wild relative and progenitors has shown differences in photosynthetic capacity and efficiency not only between wild relative species but marked differences between the accessions of each species. By identifying wild relative accessions with improved photosynthetic traits and characterising the genetic variation responsible, it is possible to incorporate these traits into advanced breeding programmes by wide crossing and introgression programmes. To identify the potential variety of photosynthetic capacity and efficiency available in the secondary and tertiary genepool, a wide scale survey was carried out for over 600 accessions from 80 species including those from the genus Aegilops, Triticum, Thinopyrum, Elymus, and Secale. Genotype data were generated for each accession using a ‘Wheat Wild Relative’ Single Nucleotide Polymorphism (SNP) genotyping array composed of 35,000 SNP markers polymorphic between wild relatives and elite hexaploid wheat. This genotype data was combined with phenotypic measurements such as gas exchange (CO₂, H₂O), chlorophyll fluorescence, growth, morphology, and RuBisCO activity to identify potential breeding material with enhanced photosynthetic capacity and efficiency. The data and associated analysis tools presented here will prove useful to anyone interested in increasing the genetic diversity in hexaploid wheat or the application of complex genotyping data to plant breeding.

Keywords: wheat, wild relatives, pre-breeding, genomics, photosynthesis

Procedia PDF Downloads 215

Authors: Petcharat  Kerdonfag, Surasak Taneepanichskul, Winai Wadwongtham

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Industrial noise is usually considered as the main impact of the environmental health and safety because its exposure can cause permanently serious hearing damage. Despite providing strictly hearing protection standards and campaigning extensively encouraging public health awareness among industrial workers in Thailand, hazard noise-induced hearing loss has dramatically been massive obstacles for workers’ health. The aims of the study were to explore and specify the hearing threshold levels among steel industrial workers responsible in which higher noise levels of work zone and to examine the relationships of hearing loss and workers’ age and the length of employment in Samut Prakan province, Thailand. Cross-sectional study design was done. Ninety-three steel industrial workers in the designated zone of higher noise (> 85dBA) with more than 1 year of employment from two factories by simple random sampling and available to participate in were assessed by the audiometric screening at regional Samut Prakan hospital. Data of doing screening were collected from October to December, 2016 by the occupational medicine physician and a qualified occupational nurse. All participants were examined by the same examiners for the validity. An Audiometric testing was performed at least 14 hours after the last noise exposure from the workplace. Workers’ age and the length of employment were gathered by the developed occupational record form. Results: The range of workers’ age was from 23 to 59 years, (Mean = 41.67, SD = 9.69) and the length of employment was from 1 to 39 years, (Mean = 13.99, SD = 9.88). Fifty three (60.0%) out of all participants have been exposing to the hazard of noise in the workplace for more than 10 years. Twenty-three (24.7%) of them have been exposing to the hazard of noise less than or equal to 5 years. Seventeen (18.3%) of them have been exposing to the hazard of noise for 5 to 10 years. Using the cut point of less than or equal to 25 dBA of hearing thresholds, the average means of hearing thresholds for participants at 4, 6, and 8 kHz were 31.34, 29.62, and 25.64 dB, respectively for the right ear and 40.15, 32.20, and 25.48 dB for the left ear, respectively. The more developing age of workers in the work zone with hazard of noise, the more the hearing thresholds would be increasing at frequencies of 4, 6, and 8 kHz (p =.012, p =.026, p =.024) for the right ear, respectively and for the left ear only at the frequency 4 kHz (p =.009). Conclusion: The participants’ age in the hazard of noise work zone was significantly associated with the hearing loss in different levels while the length of participants’ employment was not significantly associated with the hearing loss. Thus hearing threshold levels among industrial workers would be regularly assessed and needed to be protected at the beginning of working.

Keywords: hearing threshold levels, hazard of noise, hearing loss, audiometric testing

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Authors: Jose D. Zapata-Torres, Esteban Naranjo-Gutiérrez, Angela M. Martínez-Valencia, Jenny J. Chaparro-Gutiérrez, David Villar-Argaiz

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Reports of drug resistance have been made in every livestock host and to every anthelmintic class. In some regions of world, the extremely high prevalence of multi-drug resistance in nematodes of sheep and goats threatens the viability of small-ruminant industries. In the region of Antioquia, Colombia, no reports of nematode resistance have been documented due to a lack of veterinary diagnostic laboratories. The objective of this study was to evaluate the efficacy of albendazole, fenbendazole, and levamisole to control gastrointestinal nematodes in goat farms of Antioquia by doing fecal egg count reduction tests. A total of 139 crossbreed goats from four separate farms were sampled for feces prior to, and 14 days following anthelmintc treatments. Individual fecal egg counts were performed using the modified three chamber McMaster technique. The anthelmintics administered at day 0 were albendazole (farm 1, n=63), fenbendazole (farm 2, n=20), and levamisole (farm 3 and 4, n= 37, and 19). Larval cultures were used to identify the genus of nematodes using Baermann`s technique and the morphological keys for identification of L3 in small ruminants. There was no difference in fecal egg counts between 0 and 14, with means (±SD) of 1681,5 ± 2121,5 and 1715,12 ± 1895,4 epg (eggs per gram), respectively. The egg count reductions for each anthelmintic and farm were 25,86% for albendazole (farm 1), 0% for fenbendazole (farm 2), 0% (farm 3), and 5,5% (farm 4) for levamisole. The genus of nematodes identified was predominantly Haemonchus spp., with 70,27% and 82,81% for samples from day 0 and 14, respectively. These results provide evidence of a total state of resistance to 3 common anthelmintics. Further research is needed to design integrate management programs to control nematodes in small ruminants in Colombia.

Keywords: anthelmintics, goat, haemonchus, resistance

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Authors: Dong Tran, Thanh Dac Van, Ly Le

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Hemagglutinin (HA) and Neuraminidase (NA) play an important role in host immune evasion across influenza virus evolution process. The correlation between HA and NA evolution in respect to epitopic evolution and drug interaction has yet to be investigated. In this study, combining of sequence to structure evolution and statistical analysis on epitopic/binding site specificity, we identified potential therapeutic features of HA and NA that show specific antibody binding site of HA and specific binding distribution within NA active site of current inhibitors. Our approach introduces the use of sequence variation and molecular interaction to provide an effective strategy in establishing experimental based distributed representations of protein-protein/ligand complexes. The most important advantage of our method is that it does not require complete dataset of complexes but rather directly inferring feature interaction from sequence variation and molecular interaction. Using correlated sequence analysis, we additionally identified co-evolved mutations associated with maintaining HA/NA structural and functional variability toward immunity and therapeutic treatment. Our investigation on the HA binding specificity revealed unique conserved stalk domain interacts with unique loop domain of universal antibodies (CR9114, CT149, CR8043, CR8020, F16v3, CR6261, F10). On the other hand, NA inhibitors (Oseltamivir, Zaninamivir, Laninamivir) showed specific conserved residue contribution and similar to that of NA substrate (sialic acid) which can be exploited for drug design. Our study provides an important insight into rational design and identification of novel therapeutics targeting universally recognized feature of influenza HA/NA.

Keywords: influenza virus, hemagglutinin (HA), neuraminidase (NA), sequence evolution

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Authors: Priya Patel, Paresh Patel, Mihir Raval

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Silibinin, a flavanone as an antimicrotubular agent used in the treatment of cancer, was encapsulated in nanoparticles (NPs) of poly (lactide-co-glycolide) (PLGA) polymer using the spray-drying technique. The effects of various experimental parameters were optimized by box-behnken experimental design. Production yield, encapsulation efficiency and dissolution study along with characterization by scanning electron microscopy, DSC, FTIR followed by bioavailability study. Particle size and zeta potential were evaluated by using zetatrac particle size analyzer. Experimental design it was evaluated that inlet temperature and polymer concentration influence on the drug release. Feed flow rate impact on particle size. Results showed that spray drying technique yield 149 nm indicate nanosize range. The small size of the nanoparticle resulted in an enhanced cellular entry and greater bioavailability. Entrapment efficiency was found between 89.35% and 98.36%. Zeta potential shows good stability index of nanoparticle formulation. The in vitro release studies indicated the silibinin loaded PLGA nanoparticles provide controlled drug release over a period of 32 h. Pharmacokinetic studies demonstrated that after oral administration of silibinin-loaded PLGA nanoparticles to rats at a dose of 10 mg/kg, relative bioavailability was enhanced about 8.85-fold, compared to silibinin suspension as control hence, this investigation demonstrated the potential of the experimental design in understanding the effect of the formulation variables on the quality of silibinin loaded PLGA nanoparticles. These results describe an effective strategy of silibinin loaded PLGA nanoparticles and might provide a promising approach against the cancer.

Keywords: silibinin, cancer, nanoparticles, PLGA, bioavailability

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Authors: Salwa M. Almomen, Mona A. Almaghrabi, Saja M. Alhabardi, Adel A. Alrwisan

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Background: Hepatotoxicity is a major reason for medication withdrawal from the markets. Unfortunately, serious adverse hepatic effects can occur after marketing with limited indicators during clinical development. Therefore, finding possible predictors for hepatotoxicity might guide the monitoring program of various stakeholders. Methods: We examined the clinical review documents for drugs approved in the US from 2011 to 2016 to evaluate their hepatic safety profile. Predictors: we assessed whether these medications meet Hy’s Law with hepatotoxicity grade ≥ 3, labeled hepatic adverse effects at approval, or accelerated approval status. Outcome: post-marketing regulatory action related to hepatotoxicity, including product withdrawal or updates to warning, precaution, or adverse effects sections. Statistical analysis: drugs were included in the analysis from the time of approval until the end of 2019 or the first post-marketing regulatory action related to hepatotoxicity, whichever occurred first. The hazard ratio (HR) was estimated using Cox-regression analysis. Results: We included 192 medications in the study. We classified 48 drugs as having grade ≥ 3 hepatotoxicities, 43 had accelerated approval status, and 74 had labeled information about hepatotoxicity prior to marketing. The adjusted HRs for post-marketing regulatory action for products with grade ≥ 3 hepatotoxicity was 0.61 (95% confidence interval [CI], 0.17-2.23), 0.92 (95%CI, 0.29-2.93) for a drug approved via accelerated approval program, and was 0.91 (95%CI, 0.33-2.56) for drugs with labeled hepatotoxicity information at approval time. Conclusion: This study does not provide conclusive evidence on the association between post-marketing regulatory action and grade ≥ 3 hepatotoxicity, accelerated approval status, or availability of labeled information at approval due to sampling size and channeling bias.

Keywords: accelerated approvals, hepatic adverse effects, drug-induced liver injury, hepatotoxicity predictors, post-marketing withdrawal

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