Search results for: in silico screening

Authors: Rashini Maduka, C. R. Wijesinghe, A. R. Weerasinghe

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Drug-drug interactions (DDIs) can happen when two or more drugs are taken together. Today DDIs have become a serious health issue due to adverse drug effects. In vivo and in vitro methods for identifying DDIs are time-consuming and costly. Therefore, in-silico-based approaches are preferred in DDI identification. Most machine learning models for DDI prediction are used chemical and biological drug properties as features. However, some drug features are not available and costly to extract. Therefore, it is better to make automatic feature engineering. Furthermore, people who have diabetes already suffer from other diseases and take more than one medicine together. Then adverse drug effects may happen to diabetic patients and cause unpleasant reactions in the body. In this study, we present a model with a graph convolutional autoencoder and a graph decoder using a dataset from DrugBank version 5.1.3. The main objective of the model is to identify unknown interactions between antidiabetic drugs and the drugs taken by diabetic patients for other diseases. We considered automatic feature engineering and used Known DDIs only as the input for the model. Our model has achieved 0.86 in AUC and 0.86 in AP.

Keywords: drug-drug interaction prediction, graph embedding, graph convolutional networks, adverse drug effects

Procedia PDF Downloads 79

Authors: Vagolu S. Krishna, Shan Zheng, Estharla M. Rekha, Luke W. Guddat, Dharmarajan Sriram

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Tuberculosis (TB) remains a major threat to human health. This due to the fact that current drug treatments are less than optimal as well as the rising occurrence of multi drug-resistant and extensively drug-resistant strains of the etiological agent, Mycobacterium tuberculosis (Mt). Given the wide-spread significance of this disease, we have undertaken a design and evaluation program to discover new anti-TB drug leads. Here, our attention is focused on ketol-acid reductoisomerase (KARI), the second enzyme in the branched-chain amino acid biosynthesis pathway. Importantly, this enzyme is present in bacteria but not in humans, making it an attractive proposition for drug discovery. In the present work, we used high-throughput virtual screening to identify seventeen potential inhibitors of KARI using the Birla Institute of Technology and Science in-house database. Compounds were selected based on high docking scores, which were assigned as the result of favourable interactions between the compound and the active site of KARI. The Ki values for two leads, compounds 14 and 16 are 3.71 and 3.06 µM, respectively for Mt KARI. To assess the mode of binding, 100 ns molecular dynamics simulations for these two compounds in association with Mt KARI were performed and showed that the complex was stable with an average RMSD of less than 2.5 Å for all atoms. Compound 16 showed an MIC of 2.06 ± 0.91 µM and a 1.9 fold logarithmic reduction in the growth of Mt in an infected macrophage model. The two compounds exhibited low toxicity against murine macrophage RAW 264.7 cell lines. Thus, both compounds are promising candidates for development as an anti-TB drug leads.

Keywords: ketol-acid reductoisomerase, macrophage, molecular docking and dynamics, tuberculosis

Procedia PDF Downloads 103

Authors: Nargiza Nuralieva

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The study delves into assessing the influence of mindfulness and mental resilience training on the cognitive performance and stress management of pilots. Employing a meticulous literature search across databases such as Medline and Google Scholar, the study used specific keywords to target a wide array of studies. Inclusion criteria were stringent, focusing on peer-reviewed studies in English that utilized designs like randomized controlled trials, with a specific interest in interventions related to mindfulness or mental resilience training for pilots and measured outcomes pertaining to cognitive performance and stress management. The initial literature search identified a pool of 123 articles, with subsequent screening resulting in the exclusion of 77 based on title and abstract. The remaining 54 articles underwent a more rigorous full-text screening, leading to the exclusion of 41. Additionally, five studies were selected from the World Health Organization's clinical trials database. A total of 11 articles from meta-analyses were retained for examination, underscoring the study's dedication to a meticulous and robust inclusion process. The interventions varied widely, incorporating mixed approaches, Cognitive behavioral Therapy (CBT)-based, and mindfulness-based techniques. The analysis uncovered positive effects across these interventions. Specifically, mixed interventions demonstrated a Standardized Mean Difference (SMD) of 0.54, CBT-based interventions showed an SMD of 0.29, and mindfulness-based interventions exhibited an SMD of 0.43. Long-term effects at a 6-month follow-up suggested sustained impacts for both mindfulness-based (SMD: 0.63) and CBT-based interventions (SMD: 0.73), albeit with notable heterogeneity.

Keywords: mindfulness, mental resilience, pilots, cognitive performance, stress management

Procedia PDF Downloads 34

Authors: Kai-Jui Kou, Tzu-Ling Shen, Ying-Fang Wang

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The objectives of the present study are to characterize nanoparticles generated from the different working type in 3D printing room and the stack flue during 3D printing process. The studied laboratory (10.5 m× 7.2 m × 3.2 m) with a ventilation rate of 500 m³/H is installed a 3D metal printing machine. Direct-reading instrument of a scanning mobility particle sizer (SMPS, Model 3082, TSI Inc., St. Paul, MN, USA) was used to conduct static sampling for nanoparticle number concentration and particle size distribution measurements. The SMPS obtained particle number concentration at every 3 minutes, the diameter of the SMPS ranged from 11~372 nm when the aerosol and sheath flow rates were set at 0.6 and 6 L/min, respectively. The concentrations of background, printing process, clearing operation, and screening operation were performed in the laboratory. On the other hand, we also conducted nanoparticle measurement on the 3D printing machine's stack flue to understand its emission characteristics. Results show that the nanoparticles emitted from the different operation process were the same distribution in the form of the uni-modal with number median diameter (NMD) as approximately 28.3 nm to 29.6 nm. The number concentrations of nanoparticles were 2.55×10³ count/cm³ in laboratory background, 2.19×10³ count/cm³ during printing process, 2.29×10³ count/cm³ during clearing process, 3.05×10³ count/cm³ during screening process, 2.69×10³ count/cm³ in laboratory background after printing process, and 6.75×10³ outside laboratory, respectively. We found that there are no emission nanoparticles during the printing process. However, the number concentration of stack flue nanoparticles in the ongoing print is 1.13×10⁶ count/cm³, and that of the non-printing is 1.63×10⁴ count/cm³, with a NMD of 458 nm and 29.4 nm, respectively. It can be confirmed that the measured particle size belongs to easily penetrate the filter in theory during the printing process, even though the 3D printer has a high-efficiency filtration device. Therefore, it is recommended that the stack flue of the 3D printer would be equipped with an appropriate dust collection device to prevent the operators from exposing these hazardous particles.

Keywords: nanoparticle, particle emission, 3D printing, number concentration

Procedia PDF Downloads 156

Authors: Matei Tudor Berceanu, Hema Viswambharan, Kirti Kain, Chew Weng Cheng

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Background - Obesity parameters, particularly visceral obesity as measured by the waist-to-height ratio (WHtR), correlate with insulin resistance. The metabolic microvascular changes associated with insulin resistance causes increased peripheral arteriolar resistance primarily to the lower limb vessels. We hypothesize that ankle systolic blood pressures (SBPs) are more significantly associated with visceral obesity than brachial SBPs. Methods - 1098 adults enriched in south Asians or Europeans with diabetes (T2DM) were recruited from a primary care practice in West Yorkshire. Their medical histories, including T2DM and cardiovascular disease (CVD) status, were gathered from an electronic database. The brachial, dorsalis pedis, and posterior tibial SBPs were measured using a Doppler machine. Their body mass index (BMI) and WHtR were calculated after measuring their weight, height, and waist circumference. Linear regressions were performed between the 6 SBPs and both obesity parameters, after adjusting for covariates. Results - Generally, the left posterior tibial SBP (P=4.559*10⁻¹⁵) and right posterior tibial SBP (P=1.114* 10⁻¹³ ) are the pressures most significantly associated with the BMI, as well as in south Asians (P < 0.001) and Europeans (P < 0.001) specifically. In South Asians, although the left (P=0.032) and right brachial SBP (P=0.045) were associated to the WHtR, the left posterior tibial SBP (P=0.023) showed the strongest association. Conclusion - Regardless of ethnicity, ankle SBPs are more significantly associated with generalized obesity than brachial SBPs, suggesting their screening potential for screening for early detection of T2DM and CVD. A combination of ankle SBPs with WHtR is proposed in south Asians.

Keywords: ankle blood pressures, body mass index, insulin resistance, waist-to-height-ratio

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Authors: Ahmed Samy Elnoby

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Ailanthus altissima native to Asia which belongs to the family Simaroubaceae was subjected to phytochemical screening and biological investigations. Phytochemical screening revealed the presence of carbohydrates, tannins, sterols, flavonoids and traces of saponins. In addition, quantitative determination of phenolics and flavonoid content were performed. The antimicrobial activity of methanolic extract of the leaves was determined against gram-positive, gram-negative bacteria in addition to fungi using a modified Kirby-Bauer disc diffusion method that was compared with standard discs ampicillin which acts as an antibacterial agent and amphotericin B which acts as an antifungal agent. A high potency was observed against gram-positive bacteria mainly staphylococcus aureus, gram-negative bacteria mainly Escherichia coli and showed no potency against fungi mainly Aspergillus flavus and candida albicans. On the other hand, the antioxidant activity of the extract was determined by 1, 1-diphenyl-2- diphenyl-2-picryl-hydrazil (DPPH). A very low potency was shown by using DPPH for the antioxidant effect so IC50 = 0 ug/ml, IC90 =0 ug /ml and remark gave 47.2 % at 100 ug/ml which is very weak. Cytotoxic activity was determined by using MTT assay (3-4, 5-Dimethylthiazol-2-yl)-2, 5-Diphenyltetrazolium Bromide) against MCF7 (Human Caucasian breast adenocarcinoma) cell line. A moderate potency was shown by using MCF7 cell line for cytotoxic effect so LC50= 90.2 ug/ml, LC90=139.9 ug/ml and the remark gave 55.2% at 100 ug/ml which is of moderate activity so, Ailanthus altissima can be considered to be a promising antimicrobial agent from natural origin.

Keywords: Ailanthus altissima, TLC, HPLC, anti-microbial activity, antifungal activity, antioxidant, cytotoxic activity

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Authors: Ashwinder K. Dhaliwal, G. P. S. Dhillon

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Eucalyptus is one of the most important forest tree species that can tolerate and grow well on degraded and unfertile soils which are not suitable for other tree species. Besides this, these trees have a short rotation and good economic value. However, the gall inducing wasp Leptocybe invasa Fisher and La Salle has been reported from many countries throughout the world. The spread of L. invasa is of huge economic concern as more than 20,000 ha of young Eucalyptus trees have already been affected in southern states of India. The host plant resistance being the first line of defense against insect pests demands the screening of different germplasm source against L. invasa. Keeping this in view, fourteen different clones of Eucalyptus spp. were evaluated for their susceptibility to L. invasa from a replicated clonal trial planted at Punjab Agricultural University, Ludhiana. The degree of gall infestation was recorded from three plants of each clone in each replication. Three branches selected from the lower, middle and upper canopy of the trees were selected for recording the total number of galls induced by L. invasa. The statistical analysis was done as per the procedure laid down for completely randomised block design (CRBD), analysis of variance (ANOVA), critical difference (CD) and variance components using Proc GLM (SAS software 9.3, SAS Institute Ltd. U.S.A). All possible treatment means were compared with Duncan’s multiple range test (DMRT) at 1 % probability level. The results showed that the clones C-9, C-45 and C-42 were completely free from the infestation of L. invasa. However, there was minor infestation of L. invasa on C-2135, C-413, C-407, C-35, C-72 and C-37 clones. The clone C-6 was severely infested by L. invasa followed by C-11, C-12, F-316 and C-25 clones. The information generated by this study will be helpful for future breeding and use in afforestation programmes.

Keywords: eucalyptus clones, gall wasp, Leptocybe invasa, screening, susceptibility

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Authors: Hiba T. Allah ALtieb Gusm ALsied, Amna Beshir Medani Ahmed, Ikram Mohamed ELtayeb, Saad Mohamed Hussein Ayoub

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This study was carried out to determine the hepatoactivity and the antioxidant activity of Coiradrum sativum L. aerial part and fruit extracts against CCL4 induced acute liver damages in Wistar rats. The aerial parts and fruits part of the plant were extracted 96% ethanol with soxhlet apparatus. Hepatic injury was achieved by subcutaneous injection of 3 ml/kg of CCL4 diluted with olive oil with ratio 1:1. The extracts were mixed together 1:1 ratio and given in different doses 100,200,400 mg/kg/day for 5 days under CCL4 induction at 3rd day. The significance of differences between means by using T-test was compared among the groups. The mixture of the two extracts didn’t show any significant result in protecting liver injury (antagonistic effects), it shows high level of liver enzyme like alkaline phosphatase (ALP), glutamate oxaloacetate transaminase (SGOT) and glutamate pyruvate transaminase (SGPT). Serological studies further confirmed the results. The results obtained were compared with silymarin (70 mg/kg/day) orally, the standard drug for hepatoprotection which show recovery close to normalization almost like that of silymarin; therefore, further studies on this plant with different ratios especially in isolated tissue to spot more light on antagonistic effects of the two extracts. Antioxidant activity of the extracts was determined by the DPPH method. The results obtained show high anti-oxidant activity for fruits extract while slight or moderate antioxidant activity to aerial extracts.

Keywords: antioxidant, aerial part, Coriadrum sativum L., fruity, hepatoprotection, Silymarin, phytochemical screening

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Authors: Muhammad Solikhudin Nafi, Wahyu Afif Mufida, Mita Erna Wati, Fitri Setyani Rokim, M. Al-Rizqi Dharma Fauzi

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High dose activity without any pre-exercise will impact Delayed Onset Muscle Soreness (DOMS). DOMS known as delayed pain post-exercise and induce skeletal injury which will decrease athletes’ performances. From now on, post-exercise muscle damage can be detected by measuring skeletal troponin I (sTnI) concentration in serum using ELISA but this method needs more time and cost. To prevent decreased athletes performances, screening need to be done rapidly. We want to introduce our new prototype to detect DOMS acutely. Rapid detection tests are based on immunological reaction between skeletal troponin I antibodies and sTnI in human serum or whole blood. Chemical methods that are used in the manufacture of diagnostic test is lateral flow immunoassay. The material used is rat monoclonal antibody sTnI, colloidal gold, anti-mouse IgG, nitrocellulose membrane, conjugate pad, sample pad, wick and backing card. The procedure are made conjugate (colloidal gold and mAb sTnI) and insert into the conjugate pad, gives spray sTnI mAb and anti-mouse IgG into nitrocellulose membrane, and assemble RDT. RDT had been evaluated by measuring the sensitivity of positive human serum (n = 30) and negative human serum (n = 30). Overall sensitivity value was 93% and specificity value was 90%. ADCOR as the first rapid detection test qualitatively showed antigen-antibody reaction and showed good overall performances for screening of muscle damage. Furthermore, these finding still need more improvements to get best results.

Keywords: DOMS, sTnI, rapid detection test, ELISA

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Authors: Nisha Harry, Keshia Sing

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Orientation: The Multifactor Leadership Questionnaire (MLF) and the sense of coherence-29 (SCS) is an effective tools to assess the prevalence and underlying structures of empirically based taxonomies related to leadership and wellbeing. Research purpose: The purpose of the study was to test the psychometric properties of the SCS and Multifactor Leadership Questionnaire (MLQ) to screen for psychological wellness indices within the banking industry in South Africa. Motivation for the study: The contribution of these two instruments for the purpose of determining psychological wellness in a banking work environment is unique. Research design, approach, or method: The sample consisted of (N = 150) financial staff employed in a South African banking organisation. The age of the sample was: 37% (30 -40 yrs), 31% (20-30 yrs), 26% (40- 50 yrs), and 6% (50+yrs), of which 52% were males, 48% were females. The white race group was the majority at 29%, African at 26%, Coloured at 23%, and Indian was 22%. Main findings: Results from the exploratory factor analysis revealed a two-factor structure as the most satisfactory. Confirmatory factor analyses revealed the two-factor model displayed better good of-fit indices. Practical implications: The factor structure of the Sense of Coherence-29 scale (SCS), and the Multifactor Leadership Questionnaire (MLQ), have a value-added focus to determine psychological wellness within banking staff. It is essential to take into account these constructs when developing employee wellness interventions. Contribution/value add: Understanding the psychometric properties of the SCS, the self-reported form, and the MLQ questionnaire contributes to screening psychological wellness indices such as coping within the banking industry in a developing country like South Africa. Leaders are an important part of the implementation process of organisational employee wellness practices.

Keywords: factorial structure, leadership, measurement invariance, psychological wellness, sense of coherence

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Authors: Andrew Read, Alice Parry, Kate Woods

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Since the advent of the SARS-CoV-2 pandemic, the search for medications that can reduce mortality and morbidity has been a global research priority. Several multi-center trials have recently demonstrated improved mortality associated with the use of Tocilizumab, an interleukin-6 receptor antagonist, in patients with severe SARS-CoV-2 pneumonia. Initial data supported the administration in patients requiring respiratory support (non-invasive or invasive ventilation), but more recent data has shown benefit in all hypoxic patients. At the height of the second wave of COVID-19 infections in London, our hospital introduced the use of Tocilizumab for patients with severe COVID-19. Tocilizumab is licensed for use in chronic inflammatory conditions and has been associated with an increased risk of severe bacterial and fungal infections, as well as reactivation of chronic viral infections (e.g., hepatitis B). It is a specialist drug that suppresses the formation of C-reactive protein (CRP) for 6 – 12 weeks. It is not widely used by the general medical community. We aimed to assess Tocilizumab use in our hospital and to implement changes to the protocol as required to ensure administration was safe and appropriate. A retrospective study design was used to assess prescriptions over an initial 3-week period in both intensive care and on the medical wards. This amounted to a total of 13 patients. The initial data collection identified four key areas of concern: adherence to national and local inclusion & exclusion criteria; a collection of appropriate screening blood prior to administration; documentation of informed consent or best interest decision and documentation of Tocilizumab administration on patient discharge information, to alert future healthcare providers that typical measures of inflammation and infection, such as CRP, are unreliable for up to 3-months. Data were collected from electronic notes, blood results and observation charts, and cross referenced with pharmacy data. Initial results showed that all four key areas were completed in approximately 50% of cases. Of particular concern was adherence to exclusion criteria, such as current evidence of bacterial infection, and ensuring the correct screening blood was sent to exclude infections such as hepatitis. To remedy this and improve patient safety, the initial data was presented to relevant healthcare professionals. Subsequently, three interventions were introduced and education on each provided to hospital staff. An electronic ‘order set’ collating the appropriate screening blood was created simplifying the screening process. Pre-formed electronic documentation which can be inserted into the notes was created to provide a framework for consent discussions and reduce the time needed for junior doctors to complete this task. Additionally, a ‘Tocilizumab’ administration card was created and administered via pharmacy. This was distributed to each patient on discharge to ensure future healthcare professionals were aware of the potential effects of Tocilizumab administration, including suppression of CRP. Following these changes, repeat data collection over two months illustrated that each of the 4 safety aspects was met with a 100% success rate in every patient. Although this demonstrates good progress and effective interventions the challenge will be to maintain this progress. The audit data collection is ongoing

Keywords: education, patient safety , SARS-CoV-2, Tocilizumab

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Authors: Muhammad Asif ShakoorI, Maogang He, Aamir Shahzad

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Dusty (complex) plasmas contained micro-sized charged dust particles in addition to ions, electrons, and neutrals. It is typically low-temperature plasma and exists in a wide variety of physical systems. In this work, the effects of an external electric field on the diffusion coefficient and share viscosity are investigated through equilibrium molecular dynamics (EMD) simulations in three-dimensional (3D) strongly coupled (SC) dusty plasmas (DPs). The effects of constant and varying normalized electric field strength (E*) have been computed along with different combinations of plasma states on the diffusion of dust particles using EMD simulations. Diffusion coefficient (D) and share viscosity (η) along with varied system sizes, in the limit of varying E* values, is accounted for an appropriate range of plasma coupling (Γ) and screening strength (κ) parameters. At varying E* values, it is revealed that the 3D diffusion coefficient increases with increasing E* and κ; however, it decreases with an increase of Γ but within statistical limits. The share viscosity increases with increasing E*and Γ and decreases with increasing κ. New simulation results are outstanding that the combined effects of electric field and screening strengths give well-matched values of Dandη at low-intermediate to large Γ with varying small-intermediate to large N. The current EMD simulation outcomes under varying electric field strengths are in satisfactory well-matched with previous known simulation data of EMD simulations of the SC-DPs. It has been shown that the present EMD simulation data enlarged the range of E* strength up to 0.1 ≤ E*≤ 1.0 in order to find the linear range of the DPs system and to demonstrate the fundamental nature of electric field linearity of 3D SC-DPs.

Keywords: strongly coupled dusty plasma, diffusion coefficient, share viscosity, molecular dynamics simulation, electric field strength

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Authors: Osman Turkoglu, Alvin Estilo, Ritu Gupta, Liliam Pineda-Salgado, Rajesh Pandey

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Background: Hepatotoxicity can be linked to a variety of clinical symptoms and histopathological signs, posing a great challenge in the surveillance of suspected drug-induced liver injury (DILI) cases in the safety database. Additionally, the majority of such cases are rare, idiosyncratic, highly unpredictable, and tend to demonstrate unique individual susceptibility; these qualities, in turn, lend to a pharmacovigilance monitoring process that is often tedious and time-consuming. Objective: Develop a multifactorial algorithm to assist pharmacovigilance physicians in identifying high-risk hepatotoxicity cases associated with DILI from the sponsor’s safety database (Argus). Methods: Multifactorial selection criteria were established using Structured Query Language (SQL) and the TIBCO Spotfire® visualization tool, via a combination of word fragments, wildcard strings, and mathematical constructs, based on Hy’s law criteria and pattern of injury (R-value). These criteria excluded non-eligible cases from monthly line listings mined from the Argus safety database. The capabilities and limitations of these criteria were verified by comparing a manual review of all monthly cases with system-generated monthly listings over six months. Results: On an average, over a period of six months, the algorithm accurately identified 92% of DILI cases meeting established criteria. The automated process easily compared liver enzyme elevations with baseline values, reducing the screening time to under 15 minutes as opposed to multiple hours exhausted using a cognitively laborious, manual process. Limitations of the algorithm include its inability to identify cases associated with non-standard laboratory tests, naming conventions, and/or incomplete/incorrectly entered laboratory values. Conclusions: The newly developed multifactorial algorithm proved to be extremely useful in detecting potential DILI cases, while heightening the vigilance of the drug safety department. Additionally, the application of this algorithm may be useful in identifying a potential signal for DILI in drugs not yet known to cause liver injury (e.g., drugs in the initial phases of development). This algorithm also carries the potential for universal application, due to its product-agnostic data and keyword mining features. Plans for the tool include improving it into a fully automated application, thereby completely eliminating a manual screening process.

Keywords: automation, drug-induced liver injury, pharmacovigilance, post-marketing

Procedia PDF Downloads 127

Authors: Hajir Abdllha, Alaa Mohamed, Khansa Almoniem, Naga Adam, Wdeea Alhaadi, Ahmed Elshikh, Ahmed Ali, Ismail Makuar, Anas Elnazeer, Nagat Elrofaei, Samir Abdoelftah, Monier Hemidan

Abstract:

The present study was designed to investigate antimicrobial, and antioxidant activities of five species from Acacia (Acacia albidia, Acacia mellifera, Acacia nubica, Acacia seyal var. seyal and Acacia tortilis). Phytochemical study was piloted to detect the bioactive compounds, which have been responsible from the biological activities. The ethanol, chloroform and acetone plant extracts were seasoned against standard bacteria strains of gram +ve bacteria Staphylococcus aureus (ATCC 25923), Gram -ve bacteria Pseudomonas aeruginosa (ATCC 27853) and standard fungi Candida albicans (ATCC 90028), using cup-plate method. The antioxidant activities were conducted via DPPH radical scavenging and metal chelating assays. Prospective activity against the five species was observed in acetone extract. Ethanol extract showed highest activities against Staphylococcus aureus, and Candida albicans. Potential antioxidant activity was presented by ethanol. Cholorophorm and acetone extracts via DPPH, the radical scavenging activities were found to be 91±0.03, 88±0.01 and 85±0.04 respectively. The results of phytochemical screening showed that all extracts of studied plant contain flavonoids, saponins, terpenoids, steroids, alkaloids, phenols and tannins. This study gives rise to antioxidant, antimicrobial properties of studied plant, and showed interesting correlation with the phytochemical constituents and biological activities.

Keywords: antimicrobial, antioxidant, Acacia albidia, Acacia mellifera, Acacia nubica, Acacia seyal var. seyal, Acacia tortilis

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Authors: Aussara Panya, Nunghathai Sawasdee, Mutita Junking, Chatchawan Srisawat, Kiattawee Choowongkomon, Pa-Thai Yenchitsomanus

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Dengue virus (DENV) infection is a global public health problem with approximately 100 million infected cases a year. Presently, there is no approved vaccine or effective drug available; therefore, the development of anti-DENV drug is urgently needed. The clinical reports revealing the positive association between the disease severity and viral titer has been reported previously suggesting that the anti-DENV drug therapy can possibly ameliorate the disease severity. Although several anti-DENV agents showed inhibitory activities against DENV infection, to date none of them accomplishes clinical use in the patients. The surface envelope (E) protein of DENV is critical for the viral entry step, which includes attachment and membrane fusion; thus, the blocking of envelope protein is an attractive strategy for anti-DENV drug development. To search the safe anti-DENV agent, this study aimed to search for novel peptide inhibitors to counter DENV infection through the targeting of E protein using a structure-based in silico design. Two selected strategies has been used including to identify the peptide inhibitor which interfere the membrane fusion process whereby the hydrophobic pocket on the E protein was the target, the destabilization of virion structure organization through the disruption of the interaction between the envelope and membrane proteins, respectively. The molecular docking technique has been used in the first strategy to search for the peptide inhibitors that specifically bind to the hydrophobic pocket. The second strategy, the peptide inhibitor has been designed to mimic the ectodomain portion of membrane protein to disrupt the protein-protein interaction. The designed peptides were tested for the effects on cell viability to measure the toxic to peptide to the cells and their inhibitory assay to inhibit the DENV infection in Vero cells. Furthermore, their antiviral effects on viral replication, intracellular protein level and viral production have been observed by using the qPCR, cell-based flavivirus immunodetection and immunofluorescence assay. None of tested peptides showed the significant effect on cell viability. The small peptide inhibitors achieved from molecular docking, Glu-Phe (EF), effectively inhibited DENV infection in cell culture system. Its most potential effect was observed for DENV2 with a half maximal inhibition concentration (IC50) of 96 μM, but it partially inhibited other serotypes. Treatment of EF at 200 µM on infected cells also significantly reduced the viral genome and protein to 83.47% and 84.15%, respectively, corresponding to the reduction of infected cell numbers. An additional approach was carried out by using peptide mimicking membrane (M) protein, namely MLH40. Treatment of MLH40 caused the reduction of foci formation in four individual DENV serotype (DENV1-4) with IC50 of 24-31 μM. Further characterization suggested that the MLH40 specifically blocked viral attachment to host membrane, and treatment with 100 μM could diminish 80% of viral attachment. In summary, targeting the hydrophobic pocket and M-binding site on the E protein by using the peptide inhibitors could inhibit DENV infection. The results provide proof of-concept for the development of antiviral therapeutic peptide inhibitors to counter DENV infection through the use of a structure-based design targeting conserved viral protein.

Keywords: dengue virus, dengue virus infection, drug design, peptide inhibitor

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Authors: Parimalakrishnan Sundararjan, Madheswaran Murugan, Dhanya Dharman, Yatindra Kumar, Sudhir Singh Gangwar, Guru Prasad Mohanta

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Antibiotic resistance AR is a global issue, India started to redress the issues of antibiotic resistance late and it plans to have: active surveillance of microbial resistance and promote appropriate use of antibiotics. The present study attempted to achieve appropriate use of antibiotics through pharmacists’ intervention at practice point. In a quasi-experimental prospective cohort study, the cases with bacteremia from four hospitals were identified during 2015 and 2016 for intervention. The pharmacists centered intervention: active screening of each prescription and comparing with the selection of antibiotics with susceptibility of the bacteria. Wherever irrationality noticed, it was brought to the notice of the treating physician for making changes. There were two groups: intervention group and control group without intervention. The active screening and intervention in 915 patients has reduced therapeutic regimen time in patients with bacteremia. The intervention group showed the decreased duration of hospital stay 3.4 days from 5.1 days. Further, multivariate modeling of patients who were in control group showed that patients in the intervention group had a significant decrease in both duration of hospital stay and infection-related mortality. Unlike developed countries, pharmacists are not active partners in patient care in India. This unique attempt of pharmacist’ invention was planned in consultation with hospital authorities which proved beneficial in terms of reducing the duration of treatment, hospital stay, and infection-related mortality. This establishes the need for a collaborative decision making among the health workforce in patient care at least for promoting rational use of antibiotics, an attempt to combat resistance.

Keywords: antibiotics resistance, intervention, bacteremia, multivariate modeling

Procedia PDF Downloads 164

Authors: Iram Batool, Aamer Saeed, Irfan Zia Qureshi, Ayesha Razzaq, Saima Kalsoom

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Heterocyclic compounds analogues and their derivatives have attracted strong interest in medicinal chemistry due to their biological and pharmacological properties. A series of new thiazolopyrimidine carboxylates were conveniently synthesized by one-pot three-component reaction of ethyl acetoacetate, 2-aminothiazole and benzaldehyde substituted with electron-donating and electron-withdrawing groups in order to find some more potent antidiabetic and antibacterial drugs. The structures of synthesized compounds were characterized by elemental analysis, IR, 1H NMR, 13C NMR spectroscopy. An in vitro antidiabetic effect was evaluated in adult male BALB/c mice and antibacterial activities were tested against Micrococcus luteus, Salmonella typhimurium, Bacillus subtilis, Bordetella bronchiseptica and Escherichia coli. Some of the tested compounds proved to possess good to excellent activities more than the reference drugs. An in silico molecular docking was also performed on synthesized compounds. The current study is expected to provide useful insights into the design of antidiabetic and antibacterial drugs and understanding the mechanism by which such drugs interact with RNA and diabetes target and exert their biochemical action.

Keywords: antidiabetic, antibacterial, MOE docking, thiazolopyrimidine

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Authors: Hajir, B. Abdllha, , Alaa, I. Mohamed, Khansa, A. Almoniem, Naga, I. Adam, Wdeea, Alhaadi, Ahmed, A. Elshikh, Ahmed, J. Ali, Ismail, G. Makuar, Anas, M. Elnazeer, Nagat, A. Elrofaei, Samir, F. Abdoelftah, Monier, N. Hemidan

Abstract:

The present study was designed to investigate antimicrobial, and antioxidant activities of five species from Acacia (Acacia albidia, Acacia mellifera, Acacia nubica, Acacia seyal var.seyal and Acacia tortilis). Phytochemical study was piloted to detect the bioactive compounds, which have been responsible from the biological activities. The ethanol, chloroform and acetone plant extracts were seasoned against standard bacteria strains of gram +ve bacteria Staphylococcus aureus (ATCC 25923) ,Gram -ve bacteria Pseudomonas aeruginosa (ATCC 27853) and standard fungi Candida albicans (ATCC 90028), using cup-plate method. The antioxidant activities were conducted via DPPH radical scavenging and metal chelating assays. Prospective activity against the five species was observed in acetone extract. Ethanol extract showed highest activities against Staphylococcus aureus, and Candida albicans. Potential antioxidant activity was presented by ethanol. Cholorophorm and acetone extracts via DPPH, the radical scavenging activities were found to be 91±0.03, 88±0.01 and 85±0.04 respectively. The results of phytochemical screening showed that all extracts of studied plant contain flavonoids, saponins, terpenoids, steroids, alkaloids, phenols and tannins. This study give rise to antioxidant, antimicrobial properties of studied plant, and showed interesting correlation with the phytochemical constituents and biological activities.

Keywords: antimicrobial, Antioxidant, Acacia albidia, Acacia mellifera, acacia nubica, acacia seyal var.seyal, Acacia tortilis

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Authors: Attapon Kamlangdee, Brock Kingstad-Bakke, Tavis K. Anderson, Tony L. Goldberg, Jorge E. Osorio

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A critical failure in our preparedness for an influenza pandemic is the lack of a universal vaccine. Influenza virus strains diverge by 1 to 2% per year, and commercially available vaccines often do not elicit protection from one year to the next, necessitating frequent formulation changes. This represents a major challenge to the development of a cross-protective vaccine that can protect against circulating viral antigenic diversity. We have constructed a recombinant modified vaccinia virus Ankara (MVA) that expresses an H5N1 mosaic hemagglutinin (H5M) (MVA-H5M). This mosaic was generated in silico using 2,145 field-sourced H5N1 isolates. A single dose of MVA-H5M provided 100% protection in mice against clade 0, 1, and 2 avian influenza viruses and also protected against seasonal H1N1 virus (A/Puerto Rico/8/34). It also provided short-term (10 days) and long-term (6 months) protection post vaccination. Both neutralizing antibodies and antigen-specific CD4+and CD8+ T cells were still detected at 5 months post vaccination, suggesting that MVA-H5M provides long-lasting immunity.

Keywords: modified vaccinia Ankara, MVA, H5N1, hemagglutinin, influenza vaccine

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Authors: Aakriti Chetan Shah, Elle Sein

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Background/purpose: Group B Streptococcus(GBS) is the leading cause of severe early onset infection in newborns, with the incidence of Early Onset Group B Streptococcus (EOGBS) in the UK and Ireland rising from 0.48 to 0.57 per 1000 births from 2000 to 2015. A WHO study conducted in 2017, has shown that 38.5% of cases can result in stillbirth and infant deaths. This is an important problem to consider as 20% of women worldwide have GBS colonisation and can suffer from these detrimental effects. Current Royal College of Obstetricians and Midwives (RCOG) guidelines do not recommend bacteriological screening for pregnant women due to its low sensitivity in antenatal screening correlating with the neonate having GBS but advise a patient information leaflet be given to pregnant women. However, a Healthcare Safety Investigation Branch (HSIB) 2019 learning report found that only 50% of trusts and health boards reported giving GBS information leaflets to all pregnant mothers. Therefore, this audit aimed to assess current practices of information dissemination about GBS at Chelsea & Westminster (C&W) Hospital. Methodology: A quantitative cross-sectional study was carried out using a questionnaire based on the RCOG GBS guidelines and the HSIB Learning report. The study was conducted in antenatal clinics at Chelsea & Westminster Hospital, from 29th January 2021 to 14th February 2021, with twenty-two practicing obstetricians and midwives participating in the survey. The main outcome measure was the proportion of obstetricians and midwives who disseminate information about GBS to pregnant women, and the reasons behind why they do or do not. Results: 22 obstetricians and midwives responded with 18 complete responses. Of which 12 were obstetricians and 6 were midwives. Only 17% of clinical staff routinely inform all pregnant women about GBS, and do so at varying timeframes of the pregnancy, with an equal split in the first, second and third trimester. The primary reason for not informing women about GBS was influenced by three key factors: Deemed relevant only for patients at high risk of GBS, lack of time in clinic appointments and no routine NHS screening available. Interestingly 58% of staff in the antenatal clinic believe it is necessary to inform all women about GBS and its importance. Conclusion: It is vital for obstetricians and midwives to inform all pregnant women about GBS due to the high prevalence of incidental carriers in the population, and the harmful effects it can cause for neonates. Even though most clinicians believe it is important to inform all pregnant women about GBS, most do not. To ensure that RCOG and HSIB recommendations are followed, we recommend that women should be given this information at 28 weeks gestation in the antenatal clinic. Proposed implementations include an information leaflet to be incorporated into the Mum and Baby app, an informative video and end-to-end digital clinic documentation to include this information sharing prompt.

Keywords: group B Streptococcus, early onset sepsis, Antenatal care, Neonatal morbidity, GBS

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Authors: Ngabilas Salama

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Background: Indonesia has the 2nd highest number of incidents of tuberculosis (TB). It accounts for 1.020.000 new cases per year, only 30% of which has been reported. To find the lost 70%, a massive active case discovery was conducted through two programs: Ketuk Pintu Layani Dengan Hati (KPLDH) and Kader Juru Pemantau Batuk (Jumantuk cadres), who also plays a role in child TB screening. Methods: Data was collected and analyzed through Tuberculosis Integrated Online System from 2014 to 2017 involving 129 DOTS facility with 86 primary health centers in East Jakarta. Results: East Jakarta consists of 2.900.722 people. KPLDH program started in February 2016 consisting of 84 teams (310 people). Jumantuk cadres was formed 4 months later (218 orang). The number of new TB cases in East Jakarta (primary health center) from 2014 to June 2017 respectively is as follows: 6.499 (2.637), 7.438 (2.651), 8.948 (3.211), 5.701 (1.830). Meanwhile, the percentage of child TB case discovery in primary health center was 8,5%, 9,8%, 12,1% from 2014 to 2016 respectively. In 2017, child TB case discovery was 13,1% for the first 3 months and 16,5% for the next 3 months. Discussion: Increased TB incidence rate from 2014 to 2017 was 14,4%, 20,3%, and 27,4% respectively in East Jakarta, and 0,5%, 21,1%, and 14% in primary health center. This reveals the positive role of KPLDH and Jumantuk in TB detection and reporting. Likewise, these programs were responsible for the increase in child TB case discovery, especially in the first 3 months of 2017 (Ketuk Pintu TB Day program) and the next 3 months (active TB screening). Conclusion: KPLDH dan Jumantuk are actively involved in increasing TB case discovery in both adults and children.

Keywords: tuberculosis, case discovery program, primary health center, cadre

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Authors: A. Kistaubayeva, I. Savitskaya, D. Ibrayeva, M. Abdulzhanova, N. Voronova

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36 strains of sulfur-oxidizing bacteria were isolated in Southern Kazakhstan soda-saline soils and identified. Screening of strains according bio-oxidation (destruction thiosulfate to sulfate) and enzymatic (Thiosulfate dehydrogenises and thiosulfate reductase) activity was conducted. There were selected modes of aeration and culture conditions (pH, temperature), which provide optimum harvest cells. These strains can be used in bio-melioration technology.

Keywords: elemental sulfur, oxidation activity, Тhiobacilli, fertilizers, heterotrophic S-oxidizers

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

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Background: DCIS accounts for 20% of malignancies diagnosed by the breast screening programme and is primarily managed by surgical excision. There is variable guidance on defining excision margins, and adjuvant treatments vary widely. This study aimed to investigate the clinical outcomes for patients following surgical excision of small volume DCIS. Methods: This single-centreretrospective cohort study of 101 consecutive breast screened patients diagnosed with DCIS who underwent surgical excision. All patients diagnosed with DCIS had radiological abnormalities <15mm. Clinical, radiological, and histological data were collected from patients who had been diagnosed within a 5 year period, and ASCO guidelines for margin involvement of <2mm was used to guide the need for re-excision. Outcomes included re-excision rates, radiotherapy usage, and the presence of invasive cancer. Results: Breast conservation surgery was performed in 94.1% (n=95). Following surgical excision, 74(73.27%)patients had complete DCIS excision (>2mm margin), 4(4.0%) had margins 1-2mm, and 17(16.84%)had margins <1mm. The median size of DCIS in the specimen sample was 4mm. In 86% of patients with involved margins (n=18), the mammogram underestimated the DCIS size by a median of 12.5mm (range: 1-42mm). Of the patients with involved margins, 11(10.9%)had a re-excision, and 6 of these (50%) required two re-excisions to completely excise the DCIS. Post-operative radiotherapy was provided to 53(52.48%)patients. Four (3.97%) patients were found to have invasive ductal carcinoma on surgical excision, which was not present on core biopsy – all had high-grade DCIS. Recurrence of DCIS was seen in the same site during follow-up in 1 patient (1%), 1 year after their first DCIS diagnosis. Conclusion: Breast conservation surgery is safe in patients with DCIS, with low rates of re-excision, recurrence, and upstaging to invasive cancer. Furthermore, the median size of DCIS found in the specimens of patients who had DCIS fully removed in surgery was low, suggesting it may be possible that total removal through VAE was possible for these patients.

Keywords: surgical excision, breast conservation surgery, DCIS, Re-excision, radiotherapy, invasive cancer

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Authors: Muhammad Asif Rasheed

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Newcastle disease virus (NDV), an avian orthoavulavirus, is a causative agent of Newcastle disease named (NDV) and can cause even the epidemics when the disease is not treated. Previously several vaccines based on attenuated and inactivated viruses have been reported, which are rendered useless with the passage of time due to versatile changes in viral genome. Therefore, we aimed to develop an effective multi-epitope vaccine against the haemagglutinin neuraminidase (HN) protein of 26 NDV strains from Pakistan through a modern immunoinformatic approaches. As a result, a vaccine chimaera was constructed by combining T-cell and B-cell epitopes with the appropriate linkers and adjuvant. The designed vaccine was highly immunogenic, non-allergen, and antigenic; therefore, the potential 3D-structureof multi epitope vaccine was constructed, refined, and validated. A molecular docking study of a multiepitope vaccine candidate with the chicken Toll-like receptor-4 indicated successful binding. An In silico immunological simulation was used to evaluate the candidate vaccine's ability to elicit an effective immune response. According to the computational studies, the proposed multiepitope vaccine is physically stable and may induce immune responses, whichsuggested it a strong candidate against 26 Newcastle disease virus strains from Pakistan. A wet lab study is under process to confirm the results.

Keywords: epitopes, newcastle disease virus, paramyxovirus virus, vaccine

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Authors: Leigh G. Hayden, Susan E. Shepley, Cristina Passarelli, William Tingo

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Introduction: Sensory interventions are popular therapeutic and recreational approaches for people living with all stages of dementia. However, it is unknown which sensory interventions are used to achieve which outcomes across all subtypes of dementia. Methods: To address this gap, we conducted a scoping review of sensory interventions for people living with dementia. We conducted a search of the literature for any article published in English from 1 January 1990 to 1 June 2019, on any sensory or multisensory intervention targeted to people living with any kind of dementia, which reported on patient health outcomes. We did not include complex interventions where only a small aspect was related to sensory stimulation. We searched the databases Medline, CINHAL, and Psych Articles using our institutional discovery layer. We conducted all screening in duplicate to reduce Type 1 and Type 2 errors. The data from all included papers were extracted by one team member, and audited by another, to ensure consistency of extraction and completeness of data. Results: Our initial search captured 7654 articles, and the removal of duplicates (n=5329), those that didn’t pass title and abstract screening (n=1840) and those that didn’t pass full-text screening (n=281) resulted in 174 articles included. The countries with the highest publication in this area were the United States (n=59), the United Kingdom (n=26) and Australia (n=15). The most common type of interventions were music therapy (n=36), multisensory rooms (n=27) and multisensory therapies (n=25). Seven articles were published in the 1990’s, 55 in the 2000’s, and the remainder since 2010 (n=112). Discussion: Multisensory rooms have been present in the literature since the early 1990’s. However, more recently, nature/garden therapy, art therapy, and light therapy have emerged since 2008 in the literature, an indication of the increasingly diverse scholarship in the area. The least popular type of intervention is a traditional food intervention. Taste as a sensory intervention is generally avoided for safety reasons, however it shows potential for increasing quality of life. Agitation, behavior, and mood are common outcomes for all sensory interventions. However, light therapy commonly targets sleep. The majority (n=110) of studies have very small sample sizes (n=20 or less), an indicator of the lack of robust data in the field. Additional small-scale studies of the known sensory interventions will likely do little to advance the field. However, there is a need for multi-armed studies which directly compare sensory interventions, and more studies which investigate the use of layering sensory interventions (for example, adding an aromatherapy component to a lighting intervention). In addition, large scale studies which enroll people at early stages of dementia will help us better understand the potential of sensory and multisensory interventions to slow the progression of the disease.

Keywords: sensory interventions, dementia, scoping review

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Authors: Md. Z. Alam, Amal A. Elgharbawy, Muhammad Moniruzzaman, Nassereldeen A. Kabbashi, Parveen Jamal

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The enzymatic hydrolysis of lignocellulosic biomass is one of the obstacles in the process of sugar production, due to the presence of lignin that protects the cellulose molecules against cellulases. Although the pretreatment of lignocellulose in ionic liquid (IL) system has been receiving a lot of interest; however, it requires IL removal with an anti-solvent in order to proceed with the enzymatic hydrolysis. At this point, introducing a compatible cellulase enzyme seems more efficient in this process. A cellulase enzyme that was produced by Trichoderma reesei on palm kernel cake (PKC) exhibited a promising stability in several ILs. The enzyme called PKC-Cel was tested for its optimum pH and temperature as well as its molecular weight. One among evaluated ILs, 1,3-diethylimidazolium dimethyl phosphate [DEMIM] DMP was applied in this study. Evaluation of six factors was executed in Stat-Ease Design Expert V.9, definitive screening design, which are IL/ buffer ratio, temperature, hydrolysis retention time, biomass loading, cellulase loading and empty fruit bunches (EFB) particle size. According to the obtained data, IL-enzyme system shows the highest sugar concentration at 70 °C, 27 hours, 10% IL-buffer, 35% biomass loading, 60 Units/g cellulase and 200 μm particle size. As concluded from the obtained data, not only the PKC-Cel was stable in the presence of the IL, also it was actually stable at a higher temperature than its optimum one. The reducing sugar obtained was 53.468±4.58 g/L which was equivalent to 0.3055 g reducing sugar/g EFB. This approach opens an insight for more studies in order to understand the actual effect of ILs on cellulases and their interactions in the aqueous system. It could also benefit in an efficient production of bioethanol from lignocellulosic biomass.

Keywords: cellulase, hydrolysis, lignocellulose, pretreatment

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Authors: Aarti M. Shetty, Estela Davoodi, Subrata Gangooly, Anita Rao-Coppisetty

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Background: Testing Patency of Fallopian Tubes is among one of the several protocols for investigating Subfertile Couples. Both, Hysterosalpingogram (HSG) and Laparoscopy and dye test have been used as Tubal patency test for several years, with well-known limitation. Hysterosalpingo Contrast Sonography (HyCoSy) can be used as an alternative tool to HSG, to screen patency of Fallopian tubes, with an advantage of being non-ionising, and also, use of transvaginal scan to diagnose pelvic pathology. Aim: To determine the indication and analyse the performance of transvaginal scan and HyCoSy in Broomfield Hospital. Methods: We retrospectively analysed fertility workup of 282 women, who attended HyCoSy clinic at our institution from January 2015 to June 2016. An Audit proforma was designed, to aid data collection. Data was collected from patient notes and electronic records, which included patient demographics; age, parity, type of subfertility (primary or secondary), duration of subfertility, past medical history and base line investigation (hormone profile and semen analysis). Findings of the transvaginal scan, HyCoSy and Laparoscopy were also noted. Results: The most common indication for referral were as a part of primary fertility workup on couples who had failure to conceive despite intercourse for a year, other indication for referral were recurrent miscarriage, history of ectopic pregnancy, post reversal of sterilization(vasectomy and tuboplasty), Post Gynaecology surgery(Loop excision, cone biopsy) and amenorrhea. Basic Fertility workup showed 34% men had abnormal semen analysis. HyCoSy was successfully completed in 270 (95%) women using ExEm foam and Transvaginal Scan. Of the 270 patients, 535 tubes were examined in total. 495/535 (93%) tubes were reported as patent, 40/535 (7.5%) tubes were reported as blocked. A total of 17 (6.3%) patients required laparoscopy and dye test after HyCoSy. In these 17 patients, 32 tubes were examined under laparoscopy, and 21 tubes had findings similar to HyCoSy, with a concordance rate of 65%. In addition to this, 41 patients had some form of pelvic pathology (endometrial polyp, fibroid, cervical polyp, fibroid, bicornuate uterus) detected during transvaginal scan, who referred to corrective surgeries after attending HyCoSy Clinic. Conclusion: Our audit shows that HyCoSy and Transvaginal scan can be a reliable screening test for low risk women. Furthermore, it has competitive diagnostic accuracy to HSG in identifying tubal patency, with an additional advantage of screening for pelvic pathology. With addition of 3D Scan, pulse Doppler and other non-invasive imaging modality, HyCoSy may potentially replace Laparoscopy and chromopertubation in near future.

Keywords: hysterosalpingo contrast sonography (HyCoSy), transvaginal scan, tubal infertility, tubal patency test

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Authors: Svetlana Zhikrivetskaya, Nataliya Shirokova, Roman Bikanov, Elizaveta Musatova, Yana Kovaleva, Nataliya Vetrova, Ekaterina Pomerantseva

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Nowadays there is a growing number of couples with conceiving problems due to male or female infertility. Genetic abnormalities are responsible for about 31% of all cases of male infertility. These abnormalities include both chromosomal aberrations or aneuploidies and mutations in certain genes. Chromosomal abnormalities can be easily identified, thus the development of screening panels able to reveal genetic reasons of male infertility on gene level is of current interest. There are approximately 2,000 genes involved in male fertility that is the reason why it is very important to determine the most clinically relevant in certain population and ethnic conditions. An infertility screening panel containing 48 mutations in genes AMHR2, CFTR, DNAI1, HFE, KAL1, TSSK2 and AZF locus which are the most clinically relevant for the European population according to databases NCBI and ClinVar was designed. The aim of this research was to confirm clinic relevance of these mutations in the Russian population. Genotyping was performed in 220 patients with different types of male infertility and in 57 healthy males with normozoospermia. Mutations were identified by end-point PCR with TaqMan probes in microfluidic plates. The frequency of 5 mutations in healthy males and 13 mutations in patients with infertility was revealed and estimated. The frequency of mutation c.187C>G in HFE gene was significantly lower for healthy males (8.8%) compared with patients (17.7%) and the values for the European population according to ExAc database (13.7%) and dbSNP (17.2%). Analysis of c.3454G>C, and c.1545_1546delTA mutations in the CFTR gene revealed increased frequency (0.9 and 0.2%, respectively) in patients with infertility compared with data for the European population (0.04%, respectively (ExAc, European (Non-Finnish) and for the Aggregated Populations (0.002% (ExAc), because there is no data for European population for c.1545_1546delTA mutation. The frequency of del508 mutation (CFTR) in patients (1.59%) were lower comparing with male infertility Europeans (3.34-6.25% depending on nationality) and at the same level with healthy Europeans (1.06%, ExAc, European (Non-Finnish). Analysis of c.845G>A (HFE) mutation resulted in decreased frequency in patients (1.8%) in contrast with the European population data (5.1%, respectively, ExAc, European (Non-Finnish). Moreover, obtained data revealed no statistically significant frequency difference for c.845G>A mutation (HFE) between healthy males in the Russian and the European populations. Allele frequencies of mutations c.350G>A (CFTR), c.193A>T (HFE), c.774C>T, and c.80A>G (gene TSSK2) showed no significantly difference among patients with infertility, healthy males and Europeans. Analysis of AZF locus revealed increased frequency for AZFc microdeletion in patients with male infertility. Thereby, the new data of the allele frequencies in infertility patients in the Russian population was obtained. As well as the frequency differences of mutations associated with male infertility among patients, healthy males in the Russian population and the European one were estimated. The revealed differences showed that for high effectiveness of screening panel detecting genetically caused male infertility it is very important to consider ethnic and population characteristics of patients which will be screened.

Keywords: allele frequency, azoospermia, male infertility, mutation, population

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Authors: Riaz A. Agha, Alexander J. Fowler, Seon-Young Lee, Buket Gundogan, Katharine Whitehurst, Harkiran K. Sagoo, Kyung Jin Lee Jeong, Douglas G. Altman, Dennis P. Orgill

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Introduction: Case Series are an important and common study type. Currently, no guideline exists for reporting case series and there is evidence of key data being missed from such reports. We propose to develop a reporting guideline for case series using a methodologically robust technique. The first step in this process is a systematic review of literature relevant to the reporting deficiencies of case series. Methods: A systematic review of methodological and reporting quality in surgical case series was performed. The electronic search strategy was developed by an information specialist and included MEDLINE, EMBASE, Cochrane Methods Register, Science Citation index and Conference Proceedings Citation index, from the start of indexing until 5th November 2014. Independent screening, eligibility assessments and data extraction was performed. Included articles were analyzed for five areas of deficiency: failure to use standardized definitions missing or selective data transparency or incomplete reporting whether alternate study designs were considered. Results: The database searching identified 2,205 records. Through the process of screening and eligibility assessments, 92 articles met inclusion criteria. Frequency of methodological and reporting issues identified was a failure to use standardized definitions (57%), missing or selective data (66%), transparency, or incomplete reporting (70%), whether alternate study designs were considered (11%) and other issues (52%). Conclusion: The methodological and reporting quality of surgical case series needs improvement. Our data shows that clear evidence-based guidelines for the conduct and reporting of a case series may be useful to those planning or conducting them.

Keywords: case series, reporting quality, surgery, systematic review

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Authors: Abir Dey, Shams Noman

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Introduction: Offshore Island is the remote and isolated area from the terrestrial mainland. They are deprived of their needs. The children from an offshore island are usually underserved in the case of health care because it is a remote area where the health care systems are quite poor compared to mainland. So, the proper information is required for appropriate planning to reduce underlying causes behind visual deprivation among the surviving children of the Offshore Island. Purpose: The purpose of this study was to determine ocular morbidities, knowledge, and barriers of eye care services among children in an Offshore Island. Methods: The study team visited, and all data were collected from different rural communities at Sandwip Upazila, Chittagong district for screening the children aged 5-16 years old by doing spot examination. The whole study was conducted in both qualitative and quantitative methods. To determine ocular status of children, examinations were done under skilled Ophthalmologists and Optometrists. A focus group discussion was held. The sample size was 490. It was a community based descriptive study and the sampling method was purposive sampling. Results: In total 490 children, about 56.90% were female and 43.10% were male. Among them 456 were school-going children (93.1%) and 34 were non-school going children (6.9%). In this study the most common ocular morbidity was Allergic Conjunctivitis (35.2%). Other mentionable ocular morbidities were Refractive error (27.7%), Blepharitis (13.8%), Meibomian Gland Dysfunction (7.5%), Strabismus (6.3%) and Amblyopia (6.3%). Most of the non-school going children were involved in different types of domestic work like farming, fishing, etc. About 90.04% children who had different ocular abnormalities could not attend to the doctor due to various reasons. Conclusions: The ocular morbidity was high in rate on the offshore island. Eye health care facility was also not well established there. Awareness should be raised about necessity of maintaining hygiene and eye healthcare among the island people. Timely intervention through available eye care facilities and management can reduce the ocular morbidity rate in that area.

Keywords: morbidities, screening, barriers, offshore island, knowledge

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