Search results for: extremely drug- resistant

Authors: Elena Chernyak

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The status of Russian women has changed dramatically over the course of Russian history and under different leadership and economic, political, and social conditions. The perception of women, their submissive roles, and low social status cause gender conflict that affects society: demographical issues, increased numbers of divorces, alcoholism, drug abuse, and crime. Despite the fact that around the world women are becoming more independent, protected by law, and play more important roles in society, Russian women are still dependent on men financially, socially, and psychologically. This paper critically explores the experience of Russian women over the course of over a thousand year of Russian history and how the position and image of women changed in Russian Empire, Soviet and post-Soviet Russia and what role women play in contemporary Russia. This paper is a result of deep examination of historical and religious literature, mass media, internet sources, and documents. This analysis shows that throughout history, the role and image of women in society have repeatedly varied depending on ideological and social conditions. In particular, the history of Russian women may be divided into five main periods. The first was the period of paganism, when almost all areas of life were open for women and when women were almost equal in social roles with men. During the second period, starting with the beginning of the Mongol invasion in the 13th century, the position of women was diminishing due to social transformation to the patriarchal society in which women started playing subordinate role in family and society. The third period – the period from the fourteenth through the sixteenth centuries - is a period of the total seclusion of Russian women from each part of social life. The fourth, Soviet period started after the Revolution of 1917. During that time, the position of women was drastically changed due to the transformation of traditional gender roles under the Bolshevik government. Woman's role was seen as worker-mothers who had a double duty: a worker and a mother. The final period began after the collapse of the Soviet Union. The restructuring (Perestroika) and post-Restructuring periods have had contradictory consequences and tremendous impact on Russian society. The image of women as partners and equal to men, which was promoted during the Soviet regime, has been replaced with the traditional functionalist views on family and the role of women, in which men and women have different but supposedly complementary roles. Modern Russia, despite publicly stating its commitment to equal rights, during last two decades has been reverting to an older social model with its emphasis on traditional gender roles, patriarchal ideas of dominant masculinity, and adverse attitudes to women, which are further supported and reinforced by the reviving Russian Orthodox Church. As demonstrated in this review, Russian women have never possessed the same rights as men and have always been subordinate to men. During all period of Russian history, patriarchal ideology maintained and reinforced in Russian society has always subjected women to manipulation, oppression, and victimization and portrayed women as not a ‘full human being’.

Keywords: women, Russia, patriarchy, religion, Russian Orthodox Church

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Authors: Daniel Sava, Dragos Gudovan, Iulia Alexandra Gudovan, Ioana Ardelean, Maria Sonmez, Denisa Ficai, Laurentia Alexandrescu, Ecaterina Andronescu

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Graphene and graphene oxide have been intensively studied due to the very good properties, which are intrinsic to the material or come from the easy doping of those with other functional groups. Graphene and graphene oxide have known a broad band of useful applications, in electronic devices, drug delivery systems, medical devices, sensors and opto-electronics, coating materials, sorbents of different agents for environmental applications, etc. The board range of applications does not come only from the use of graphene or graphene oxide alone, or by its prior functionalization with different moieties, but also it is a building block and an important component in many composite devices, its addition coming with new functionalities on the final composite or strengthening the ones that are already existent on the parent product. An attempt to improve the mechanical properties of polyamide elastomers by compounding with graphene oxide in the parent polymer composition was attempted. The addition of the graphene oxide contributes to the properties of the final product, improving the hardness and aging resistance. Graphene oxide has a lower hardness and textile strength, and if the amount of graphene oxide in the final product is not correctly estimated, it can lead to mechanical properties which are comparable to the starting material or even worse, the graphene oxide agglomerates becoming a tearing point in the final material if the amount added is too high (in a value greater than 3% towards the parent material measured in mass percentages). Two different types of tests were done on the obtained materials, the hardness standard test and the tensile strength standard test, and they were made on the obtained materials before and after the aging process. For the aging process, an accelerated aging was used in order to simulate the effect of natural aging over a long period of time. The accelerated aging was made in extreme heat. For all materials, FT-IR spectra were recorded using FT-IR spectroscopy. From the FT-IR spectra only the bands corresponding to the polyamide were intense, while the characteristic bands for graphene oxide were very small in comparison due to the very small amounts introduced in the final composite along with the low absorptivity of the graphene backbone and limited number of functional groups. In conclusion, some compositions showed very promising results, both in tensile strength test and in hardness tests. The best ratio of graphene to elastomer was between 0.6 and 0.8%, this addition extending the life of the product. Acknowledgements: The present work was possible due to the EU-funding grant POSCCE-A2O2.2.1-2013-1, Project No. 638/12.03.2014, code SMIS-CSNR 48652. The financial contribution received from the national project ‘New nanostructured polymeric composites for centre pivot liners, centre plate and other components for the railway industry (RONERANANOSTRUCT)’, No: 18 PTE (PN-III-P2-2.1-PTE-2016-0146) is also acknowledged.

Keywords: graphene, graphene oxide, mechanical properties, dopping effect

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Authors: Magdy I. A. Alshourbagi

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Background: The National Institute for Deafness and Communication Disorders defines idiopathic sudden sensorineural hearing loss as the idiopathic loss of hearing of at least 30 dB across 3 contiguous frequencies occurring within 3 days.The most common clinical presentation involves an individual experiencing a sudden unilateral hearing loss, tinnitus, a sensation of aural fullness and vertigo. The etiologies and pathologies of ISSNHL remain unclear. Several pathophysiological mechanisms have been described including: vascular occlusion, viral infections, labyrinthine membrane breaks, immune associated disease, abnormal cochlear stress response, trauma, abnormal tissue growth, toxins, ototoxic drugs and cochlear membrane damage. The rationale for the use of hyperbaric oxygen to treat ISSHL is supported by an understanding of the high metabolism and paucity of vascularity to the cochlea. The cochlea and the structures within it require a high oxygen supply. The direct vascular supply, particularly to the organ of Corti, is minimal. Tissue oxygenation to the structures within the cochlea occurs via oxygen diffusion from cochlear capillary networks into the perilymph and the cortilymph. . The perilymph is the primary oxygen source for these intracochlear structures. Unfortunately, perilymph oxygen tension is decreased significantly in patients with ISSHL. To achieve a consistent rise of perilymph oxygen content, the arterial-perilymphatic oxygen concentration difference must be extremely high. This can be restored with hyperbaric oxygen therapy. Subject and Methods: A 37 year old man was presented at the clinic with a five days history of muffled hearing and tinnitus of the right ear. Symptoms were sudden onset, with no associated pain, dizziness or otorrhea and no past history of hearing problems or medical illness. Family history was negative. Physical examination was normal. Otologic examination revealed normal tympanic membranes bilaterally, with no evidence of cerumen or middle ear effusion. Tuning fork examination showed positive Rinne test bilaterally but with lateralization of Weber test to the left side, indicating right ear sensorineural hearing loss. Audiometric analysis confirmed sensorineural hearing loss across all frequencies of about 70- dB in the right ear. Routine lab work were all within normal limits. Clinical diagnosis of idiopathic sudden sensorineural hearing loss of the right ear was made and the patient began a medical treatment (corticosteroid, vasodilator and HBO therapy). The recommended treatment profile consists of 100% O2 at 2.5 atmospheres absolute for 60 minutes daily (six days per week) for 40 treatments .The optimal number of HBOT treatments will vary, depending on the severity and duration of symptomatology and the response to treatment. Results: As HBOT is not yet a standard for idiopathic sudden sensorineural hearing loss, it was introduced to this patient as an adjuvant therapy. The HBOT program was scheduled for 40 sessions, we used a 12-seat multi place chamber for the HBOT, which was started at day seven after the hearing loss onset. After the tenth session of HBOT, improvement of both hearing (by audiogram) and tinnitus was obtained in the affected ear (right). Conclusions: In conclusion, HBOT may be used for idiopathic sudden sensorineural hearing loss as an adjuvant therapy. It may promote oxygenation to the inner ear apparatus and revive hearing ability. Patients who fail to respond to oral and intratympanic steroids may benefit from this treatment. Further investigation is warranted, including animal studies to understand the molecular and histopathological aspects of HBOT and randomized control clinical studies.

Keywords: idiopathic sudden sensorineural hearing loss (issnhl), hyperbaric oxygen therapy (hbot), the decibel (db), oxygen (o2)

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Authors: Eduardo Lanzagorta Garcia, Chaitra Venkatesh, Romina Pezzoli, Laura Gabriela Rodriguez Barroso, Declan Devine, Margaret E. Brennan Fournet

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New antimicrobial interventions are urgently required to combat rising global health and medical infection challenges. Here, an innovative antimicrobial technology, providing price competitive alternatives to antibiotics and readily integratable with currently technological systems is presented. Two cutting edge antimicrobial materials, antimicrobial peptides (AMPs) and uncompromised sustained Ag+ action from triangular silver nanoplates (TSNPs) reservoirs, are merged for versatile effective antimicrobial action where current approaches fail. Antimicrobial peptides (AMPs) exist widely in nature and have recently been demonstrated for broad spectrum of activity against bacteria, viruses, and fungi. TSNP’s are highly discrete, homogenous and readily functionisable Ag+ nanoreseviors that have a proven amenability for operation within in a wide range of bio-based settings. In a design for advanced antimicrobial sustainable plastics, antimicrobial TSNPs are formulated for processing within biodegradable biopolymers. Histone H5 AMP was selected for its reported strong antimicrobial action and functionalized with the TSNP (AMP-TSNP) in a similar fashion to previously reported TSNP biofunctionalisation methods. A synergy between the propensity of biopolymers for degradation and Ag+ release combined with AMP activity provides a novel mechanism for the sustained antimicrobial action of biopolymeric thin films. Nanoplates are transferred from aqueous phase to an organic solvent in order to facilitate integration within hydrophobic polymers. Extrusion is used in combination with calendering rolls to create thin polymerc film where the nanoplates are embedded onto the surface. The resultant antibacterial functional films are suitable to be adapted for food packing and biomedical applications. TSNP synthesis were synthesized by adapting a previously reported seed mediated approach. TSNP synthesis was scaled up for litre scale batch production and subsequently concentrated to 43 ppm using thermally controlled H2O removal. Nanoplates were transferred from aqueous phase to an organic solvent in order to facilitate integration within hydrophobic polymers. This was acomplised by functionalizing the TSNP with thiol terminated polyethylene glycol and using centrifugal force to transfer them to chloroform. Polycaprolactone (PCL) and Polylactic acid (PLA) were individually processed through extrusion, TSNP and AMP-TSNP solutions were sprayed onto the polymer immediately after exiting the dye. Calendering rolls were used to disperse and incorporate TSNP and TSNP-AMP onto the surface of the extruded films. Observation of the characteristic blue colour confirms the integrity of the TSNP within the films. Antimicrobial tests were performed by incubating Gram + and Gram – strains with treated and non-treated films, to evaluate if bacterial growth was reduced due to the presence of the TSNP. The resulting films successfully incorporated TSNP and AMP-TSNP. Reduced bacterial growth was observed for both Gram + and Gram – strains for both TSNP and AMP-TSNP compared with untreated films indicating antimicrobial action. The largest growth reduction was observed for AMP-TSNP treated films demonstrating the additional antimicrobial activity due to the presence of the AMPs. The potential of this technology to impede bacterial activity in food industry and medical surfaces will forge new confidence in the battle against antibiotic resistant bacteria, serving to greatly inhibit infections and facilitate patient recovery.

Keywords: antimicrobial, biodegradable, peptide, polymer, nanoparticle

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Authors: Kaushiki Sanyal, Rajesh Chakrabarti

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In India, on average, about 60 Bills are passed every year in both Houses of Parliament – Lok Sabha and Rajya Sabha (calculated from information on websites of both Houses). These are debated in both Lok Sabha (House of Commons) and Rajya Sabha (Council of States) before they are passed. However, lawmakers rarely use empirical evidence to make a case for a law. Most of the time, they support a law on the basis of anecdote, intuition, and common sense. While these do play a role in law-making, without the necessary empirical evidence, laws often fail to achieve their desired results. The quality of legislative debates is an indicator of the efficacy of the legislative process through which a Bill is enacted. However, the study of legislative debates has not received much attention either in India or worldwide due to the difficulty of objectively measuring the quality of a debate. Broadly, three approaches have emerged in the study of legislative debates. The rational-choice or formal approach shows that speeches vary based on different institutional arrangements, intra-party politics, and the political culture of a country. The discourse approach focuses on the underlying rules and conventions and how they impact the content of the debates. The deliberative approach posits that legislative speech can be reasoned, respectful, and informed. This paper aims to (a) develop a framework to judge the quality of debates by using the deliberative approach; (b) examine the legislative debates of three Bills passed in different periods as a demonstration of the framework, and (c) examine the broader structural issues that disincentive MPs from scrutinizing Bills. The framework would include qualitative and quantitative indicators to judge a debate. The idea is that the framework would provide useful insights into the legislators’ knowledge of the subject, the depth of their scrutiny of Bills, and their inclination toward evidence-based research. The three Bills that the paper plans to examine are as follows: 1. The Narcotics Drugs and Psychotropic Substances Act, 1985: This act was passed to curb drug trafficking and abuse. However, it mostly failed to fulfill its purpose. Consequently, it was amended thrice but without much impact on the ground. 2. The Criminal Laws (Amendment) Act, 2013: This act amended the Indian Penal Code to add a section on human trafficking. The purpose was to curb trafficking and penalise traffickers, pimps, and middlemen. However, the crime rate remains high while the conviction rate is low. 3. The Surrogacy (Regulation) Act, 2021: This act bans commercial surrogacy allowing only relatives to act as surrogates as long as there is no monetary payment. Experts fear that instead of preventing commercial surrogacy, it would drive the activity underground. The consequences would be borne by the surrogate, who would not be protected by law. The purpose of the paper is to objectively analyse the quality of parliamentary debates, get insights into how MPs understand the evidence and deliberate on steps to incentivise them to use empirical evidence.

Keywords: legislature, debates, empirical, India

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Authors: Christine F. Boos, Fernando M. Azevedo

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Electroencephalogram (EEG) is a record of the electrical activity of the brain that has many applications, such as monitoring alertness, coma and brain death; locating damaged areas of the brain after head injury, stroke and tumor; monitoring anesthesia depth; researching physiology and sleep disorders; researching epilepsy and localizing the seizure focus. Epilepsy is a chronic condition, or a group of diseases of high prevalence, still poorly explained by science and whose diagnosis is still predominantly clinical. The EEG recording is considered an important test for epilepsy investigation and its visual analysis is very often applied for clinical confirmation of epilepsy diagnosis. Moreover, this EEG analysis can also be used to help define the types of epileptic syndrome, determine epileptiform zone, assist in the planning of drug treatment and provide additional information about the feasibility of surgical intervention. In the context of diagnosis confirmation the analysis is made using long term EEG recordings with at least 24 hours long and acquired by a minimum of 24 electrodes in which the neurophysiologists perform a thorough visual evaluation of EEG screens in search of specific electrographic patterns called epileptiform discharges. Considering that the EEG screens usually display 10 seconds of the recording, the neurophysiologist has to evaluate 360 screens per hour of EEG or a minimum of 8,640 screens per long term EEG recording. Analyzing thousands of EEG screens in search patterns that have a maximum duration of 200 ms is a very time consuming, complex and exhaustive task. Because of this, over the years several studies have proposed automated methodologies that could facilitate the neurophysiologists’ task of identifying epileptiform discharges and a large number of methodologies used neural networks for the pattern classification. One of the differences between all of these methodologies is the type of input stimuli presented to the networks, i.e., how the EEG signal is introduced in the network. Five types of input stimuli have been commonly found in literature: raw EEG signal, morphological descriptors (i.e. parameters related to the signal’s morphology), Fast Fourier Transform (FFT) spectrum, Short-Time Fourier Transform (STFT) spectrograms and Wavelet Transform features. This study evaluates the application of these five types of input stimuli and compares the classification results of neural networks that were implemented using each of these inputs. The performance of using raw signal varied between 43 and 84% efficiency. The results of FFT spectrum and STFT spectrograms were quite similar with average efficiency being 73 and 77%, respectively. The efficiency of Wavelet Transform features varied between 57 and 81% while the descriptors presented efficiency values between 62 and 93%. After simulations we could observe that the best results were achieved when either morphological descriptors or Wavelet features were used as input stimuli.

Keywords: Artificial neural network, electroencephalogram signal, pattern recognition, signal processing

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Authors: Norma Kok, Diemo Masuko, Thandokazi Dlongwana, Komala Pillay

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CONTEXT: While many school principals have been outstanding teachers and have inherent leadership potential, many have not had access to the quality of leadership development or support that empowers them to produce high-quality education outcomes in extremely challenging circumstances. Further, school leaders in under-served communities face formidable challenges arising from insufficient infrastructure, overcrowded classrooms, socio-economic challenges within the community, and insufficient parental involvement, all of which put a strain on principals’ ability to lead their schools effectively. In addition few school leaders have access to other supportive networks, and many do not know how to build and leverage social capital to create opportunities for their schools and learners. Moreover, we know that fostering parental involvement in their children’s learning improves a child’s morale, attitude, and academic achievement across all subject areas, and promotes better behaviour and social adjustment. Citizen Leader Lab facilitates the Partners for Possibility (PfP) programme to provide leadership development and support to school leaders serving under-resourced communities in South Africa to create effective environments of learning. This is done by creating partnerships between school leaders and private-sector business leaders over a 12-month period. (185) OBJECTIVES: To explore school leaders’ perceptions of their leadership capacities and changes at their schools after being exposed to a year-long leadership development training programme. METHODS: School leaders gained new leadership capacities e.g. resilience, improved confidence, communication and conflict resolution skills - catalysing into improved cultures of collaborative decision-making and environments for enhanced teaching and learningprogramme based on the 70:20:10 model whereby: 10% of learning comes from workshops, 20% of learning takes place through peer learning and 70% of learning occurs through experiential learning as partnerships work together to identify and tackle challenges in targeted schools. Participants completed a post-programme questionnaire consisting of structured and unstructured questions and semi-structured interviews were conducted with them and their business leader. The interviews were audio-recorded, transcribed and thematic content analysis was undertaken. The analysis was inductive and emerging themes were identified. A code list was generated after coding was undertaken using computer software (Dedoose). Quantitative data gathered from surveys was aggregated and analysed. RESULTS: School leadership found the programme interesting and rewarding. They gained new leadership capacities such as resilience, improved confidence, communication and conflict resolution skills - catalyzing into improved cultures of collaborative decision-making and environments for enhanced teaching and learning. New networks resulted in tangible outcomes such as upgrades to school infrastructure, water and sanitation, vegetable gardens at schools resulting in nutrition for learners and/or intangible outcomes such as skills for members of school management teams (SMTs). Collaborative leadership led to SMTs being more aligned, efficient, and cohesive; and teachers being more engaged and motivated. Notable positive changes at the school inspired parents and community members to become more actively involved in the school and in their children’s education. CONCLUSION: The PfP programme leads to improved leadership capacities and improved school culture which leads to improved teaching and learning and new resources for schools.

Keywords: collaborative decision-making, collaborative leadership, community involvement, confidence

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Authors: Ofelia Loani Elvir Lazo, Roya Yumul, Sevan Komshian, Ruby Wang, Jun Tang

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Background: Monitoring the anti-nociceptive drug effect is useful because a sudden and strong nociceptive stimulus may result in untoward autonomic responses and muscular reflex movements. Monitoring the anti-nociceptive effects of perioperative medications has long been desiredas a way to provide anesthesiologists information regarding a patient’s level of antinociception and preclude any untoward autonomic responses and reflexive muscular movements from painful stimuli intraoperatively.To this end, electroencephalogram (EEG) based tools includingBIS and qCON were designed to provide information about the depth of sedation whileqNOXwas produced to informon the degree of antinociception.The goal of this study was to compare the reliability of qCON/qNOX to BIS asspecific indicators of response to nociceptive stimulation. Methods: Sixty-two patients undergoing general anesthesia with LMA were included in this study. Institutional Review Board(IRB) approval was obtained, and informed consent was acquired prior to patient enrollment. Inclusion criteria included American Society of Anesthesiologists (ASA) class I-III, 18 to 80 years of age, and either gender. Exclusion criteria included the inability to consent. Withdrawal criteria included conversion to endotracheal tube and EEG malfunction. BIS and qCON/qNOX electrodes were simultaneously placed o62n all patientsprior to induction of anesthesia and were monitored throughout the case, along with other perioperative data, including patient response to noxious stimuli. All intraoperative decisions were made by the primary anesthesiologist without influence from qCON/qNOX. Student’s t-distribution, prediction probability (PK), and ANOVA were used to statistically compare the relative ability to detect nociceptive stimuli for each index. Twenty patients were included for the preliminary analysis. Results: A comparison of overall intraoperative BIS, qCON and qNOX indices demonstrated no significant difference between the three measures (N=62, p> 0.05). Meanwhile, index values for qNOX (62±18) were significantly higher than those for BIS (46±14) and qCON (54±19) immediately preceding patient responses to nociceptive stimulation in a preliminary analysis (N=20, * p= 0.0408). Notably, certain hemodynamic measurements demonstrated a significant increase in response to painful stimuli (MAP increased from74±13 mm Hg at baseline to 84± 18 mm Hg during noxious stimuli [p= 0.032] and HR from 76±12 BPM at baseline to 80±13BPM during noxious stimuli[p=0.078] respectively). Conclusion: In this observational study, BIS and qCON/qNOX provided comparable information on patients’ level of sedation throughout the course of an anesthetic. Meanwhile, increases in qNOX values demonstrated a superior correlation to an imminent response to stimulation relative to all other indices.

Keywords: antinociception, bispectral index (BIS), general anesthesia, laryngeal mask airway, qCON/qNOX

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Authors: Lydia Tan, Philippe Lemey, Lieselot Houspie, Marco Viveen, Darren Martin, Frank Coenjaerts

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Introduction: Human respiratory syncytial virus (hRSV) is the leading cause of severe respiratory tract infections in infants under the age of two. Genomic substitutions and related evolutionary dynamics of hRSV are of great influence on virus transmission behavior. The evolutionary patterns formed are due to a precarious interplay between the host immune response and RSV, thereby selecting the most viable and less immunogenic strains. Studying genomic profiles can teach us which genes and consequent proteins play an important role in RSV survival and transmission dynamics. Study design: In this study, genetic diversity and evolutionary rate analysis were conducted on 36 RSV subgroup B whole genome sequences and 37 subgroup A genome sequences. Clinical RSV isolates were obtained from nasopharyngeal aspirates and swabs of children between 2 weeks and 5 years old of age. These strains, collected during epidemic seasons from 2001 to 2011 in the Netherlands and Belgium by either conventional or 454-sequencing. Sequences were analyzed for genetic diversity, recombination events, synonymous/non-synonymous substitution ratios, epistasis, and translational consequences of mutations were mapped to known 3D protein structures. We used Bayesian statistical inference to estimate the rate of RSV genome evolution and the rate of variability across the genome. Results: The A and B profiles were described in detail and compared to each other. Overall, the majority of the whole RSV genome is highly conserved among all strains. The attachment protein G was the most variable protein and its gene had, similar to the non-coding regions in RSV, more elevated (two-fold) substitution rates than other genes. In addition, the G gene has been identified as the major target for diversifying selection. Overall, less gene and protein variability was found within RSV-B compared to RSV-A and most protein variation between the subgroups was found in the F, G, SH and M2-2 proteins. For the F protein mutations and correlated amino acid changes are largely located in the F2 ligand-binding domain. The small hydrophobic phosphoprotein and nucleoprotein are the most conserved proteins. The evolutionary rates were similar in both subgroups (A: 6.47E-04, B: 7.76E-04 substitution/site/yr), but estimates of the time to the most recent common ancestor were much lower for RSV-B (B: 19, A: 46.8 yrs), indicating that there is more turnover in this subgroup. Conclusion: This study provides a detailed description of whole RSV genome mutations, the effect on translation products and the first estimate of the RSV genome evolution tempo. The immunogenic G protein seems to require high substitution rates in order to select less immunogenic strains and other conserved proteins are most likely essential to preserve RSV viability. The resulting G gene variability makes its protein a less interesting target for RSV intervention methods. The more conserved RSV F protein with less antigenic epitope shedding is, therefore, more suitable for developing therapeutic strategies or vaccines.

Keywords: drug target selection, epidemiology, respiratory syncytial virus, RSV

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Authors: Jeet Chakraborty, Sanjay Dutta

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Antibiotic resistance by bacteria has proved to be a severe threat to mankind in recent times, and this fortifies an urgency to design and develop potent antibacterial small molecules/compounds with nonconventional mechanisms than the conventional ones. DNA carries the genetic signature of any organism, and bacteria maintain their genomic DNA inside the cell in a well-regulated compact form with the help of various nucleoid associated proteins like HU, HNS, etc. These proteins control various fundamental processes like gene expression, replication, etc., inside the cell. Alteration of the native DNA structure of bacteria can lead to severe consequences in cellular processes inside the bacterial cell that ultimately result in the death of the organism. The change in the global DNA structure by small molecules initiates a plethora of cellular responses that have not been very well investigated. Echinomycin and Triostin-A are biologically active Quinoxaline small molecules that typically consist of a quinoxaline chromophore attached with an octadepsipeptide ring. They bind to double-stranded DNA in a sequence-specific way and have high activity against a wide variety of bacteria, mainly against Gram-positive ones. To date, few synthetic quinoxaline scaffolds were synthesized, displaying antibacterial potential against a broad scale of pathogenic bacteria. QNOs (Quinoxaline N-oxides) are known to target DNA and instigate reactive oxygen species (ROS) production in bacteria, thereby exhibiting antibacterial properties. The divergent role of Quinoxaline small molecules in medicinal research qualifies them for the evaluation of their antimicrobial properties as a potential candidate. The previous study from our lab has given new insights on a 6-nitroquinoxaline derivative 1d as an intercalator of DNA, which induces conformational changes in DNA upon binding.7 The binding event observed was dependent on the presence of a crucial benzyl substituent on the quinoxaline moiety. This was associated with a large induced CD (ICD) appearing in a sigmoidal pattern upon the interaction of 1d with dsDNA. The induction of DNA superstructures by 1d at high Drug:DNA ratios was observed that ultimately led to DNA condensation. Eviction of invitro-assembled nucleosome upon treatment with a high dose of 1d was also observed. In this work, monoquinoxaline derivatives of 1d were synthesized by various modifications of the 1d scaffold. The set of synthesized 6-nitroquinoxaline derivatives along with 1d were all subjected to antibacterial evaluation across five different bacteria species. Among the compound set, 3a displayed potent antibacterial activity against Staphylococcus aureus bacteria. 3a was further subjected to various biophysical studies to check whether the DNA structural alteration potential was still intact. The biological response of S. aureus cells upon treatment with 3a was studied using various cell biology processes, which led to the conclusion that 3d can initiate DNA damage in the S. aureus cells. Finally, the potential of 3a in disrupting preformed S.aureus and S.epidermidis biofilms was also studied.

Keywords: DNA structural change, antibacterial, intercalator, DNA superstructures, biofilms

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Authors: Fawzyah Albaldi

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Urinary tract infections (UTIs) are the most prevalent of infectious diseases and > 80% are caused by uropathogenic E. coli (UPEC). Infection occurs following adhesion to urothelial plaques on bladder epithelial cells, whose major protein constituent are the uroplakins (UPs). Two of the four uroplakins (UPIa and UPIb) are members of the tetraspanin superfamily. The UPEC adhesin FimH is known to interact directly with UPIa. Tetraspanins are a diverse family of transmembrane proteins that generally act as “molecular organizers” by binding different proteins and lipids to form tetraspanin enriched microdomains (TEMs). Previous work by our group has shown that TEMs are involved in the adhesion of many pathogenic bacteria to human cells. Adhesion can be blocked by tetraspanin-derived synthetic peptides, suggesting that tetraspanins may be valuable drug targets. In this study, we investigate the role of tetraspanins in UPEC adherence to bladder epithelial cells. Human bladder cancer cell lines (T24, 5637, RT4), commonly used as in-vitro models to investigate UPEC infection, along with primary human bladder cells, were used in this project. The aim was to establish a model for UPEC adhesion/infection with the objective of evaluating the impact of tetraspanin-derived reagents on this process. Such reagents could reduce the progression of UTI, particularly in patients with indwelling catheters. Tetraspanin expression on the bladder cells was investigated by q-PCR and flow cytometry, with CD9 and CD81 generally highly expressed. Interestingly, despite these cell lines being used by other groups to investigate FimH antagonists, uroplakin proteins (UPIa, UPIb and UPIII) were poorly expressed at the cell surface, although some were present intracellularly. Attempts were made to differentiate the cell lines, to induce cell surface expression of these UPs, but these were largely unsuccessful. Pre-treatment of bladder epithelial cells with anti-CD9 monoclonal antibody significantly decreased UPEC infection, whilst anti-CD81 had no effects. A short (15aa) synthetic peptide corresponding to the large extracellular region (EC2) of CD9 also significantly reduced UPEC adherence. Furthermore, we demonstrated specific binding of that fluorescently tagged peptide to the cells. CD9 is known to associate with a number of heparan sulphate proteoglycans (HSPGs) that have also been implicated in bacterial adhesion. Here, we demonstrated that unfractionated heparin (UFH)and heparin analogs significantly inhibited UPEC adhesion to RT4 cells, as did pre-treatment of the cells with heparinases. Pre-treatment with chondroitin sulphate (CS) and chondroitinase also significantly decreased UPEC adherence to RT4 cells. This study may shed light on a common pathogenicity mechanism involving the organisation of HSPGs by tetraspanins. In summary, although we determined that the bladder cell lines were not suitable to investigate the role of uroplakins in UPEC adhesion, we demonstrated roles for CD9 and cell surface proteoglycans in this interaction. Agents that target these may be useful in treating/preventing UTIs.

Keywords: UTIs, tspan, uroplakins, CD9

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Authors: S. K. M. Basha

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Nallamalas one of the centres of Plant Diversity (CPD) (WWF&IUCN,1995) is located in the central eastern Ghats between latitudes 15.20’-16.30’N and Longitude 78.30-80.10E in Andhra Pradesh, extended to an area of 7640 Sq.Km. No Comprehensive work available for RET Plants in the study area, therefore the objective of the present paper is to document the RET Medicinal Plants of Nallamalias and their uses by the local people of the area. In India, one of the major resources to know about the number of plant species and their medicinal values is the groups who are habituated in near and deep forests. The most common groups in south Indian forests are Yanadis and Yerukulas. These two groups of people are residing in the forest, which is located very far from the modern society, towns and cities. They are following traditional methods obtained from their forefathers in all respects, including medication. They are the only source to know many medicinal plants in the areas where they reside and are also important to record the medicinal properties of various plant species which are not reported. The new reports may help in drug industry in order to develop pharmaceutical herbal medicine for human health. In the present study, nearly 150 rare species have been found to be used for various ailments. Out of these 23 species are critically endangered, over 25 are vulnerable and around 22 comes under the category of near threatened. Some important species like Christella dentate, Careya arborea are used for curing cough and cold. Piper attnuatum, piper nigrum are used for curing skin disease. Ipomoea mauritiana is used against male impotency.Glycosmis cochinensis, Entada perseatha are used as contraceptives. The roots of Andrographis nallamalayana and Acrocephalus indicus are used for leucorrhoea. While the stem barks of Gyrocarpus americanus is given orally for spider bite. Piper hymenophyllum leaves mixed with turmeric and gingerly oil is used externally for mouth ulcers in cattle. Piper nigrum fruits are used for skin diseases. Vernonia anthelmentica seeds are used for indigestion. It was widely distributed in this hills. Due to over exploitation this species was in declined condition. Sterculia urens which is a sorce of gum for tribal, due to over exploitation this species declaimed in these hills. Hence, there is an urgent need to conserve the medicinal plants and prevent their exploitation and extinction with the help of tribals. There is a need to adopt sustainable utilization, cultivation and micro propagation techniques. Medicinal plants are as potent and effective today as they were thousands of years ago. They are natures wonderful gift to mankind and are involved in India as a very rich ancient heritage of traditional systems medicine i.e., ayurveda, siddha and unani. Unfortunately, these traditions have been largely eroded because of lack of support and recognition as well as rapid destruction of natural habitats which has led to shrinkage of medicinal plants therefore the conservation of medicinal plants and the revitalization of local health traditions has been taken up on priority basis.

Keywords: RET plants CPD, IUCN, nallamalas, yanadis, yerukulas

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Authors: Kylie Mueller, Nijole Bernaitis, Shailendra Anoopkumar-Dukie

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Background: Vitamin K antagonists particularly warfarin is the most frequently used oral medication for deep vein thrombosis (DVT) treatment and prophylaxis. Time in therapeutic range (TITR) of the international normalised ratio (INR) is widely accepted as a measure to assess the quality of warfarin therapy. Multiple factors can affect warfarin control and the subsequent adverse outcomes including thromboembolic and bleeding events. Predictor models have been developed to assess potential contributing factors and measure the individual risk of these adverse events. These predictive models have been validated in atrial fibrillation (AF) patients, however, there is a lack of literature on whether these can be successfully applied to other warfarin users including DVT patients. Therefore, the aim of the study was to assess the ability of these risk models (HAS BLED and CHADS2) to predict haemorrhagic and ischaemic incidences in DVT patients treated with warfarin. Methods: A retrospective analysis of DVT patients receiving warfarin management by a private pathology clinic was conducted. Data was collected from November 2007 to September 2014 and included demographics, medical and drug history, INR targets and test results. Patients receiving continuous warfarin therapy with an INR reference range between 2.0 and 3.0 were included in the study with mean TITR calculated using the Rosendaal method. Bleeding and thromboembolic events were recorded and reported as incidences per patient. The haemorrhagic risk model HAS BLED and ischaemic risk model CHADS2 were applied to the data. Patients were then stratified into either the low, moderate, or high-risk categories. The analysis was conducted to determine if a correlation existed between risk assessment tool and patient outcomes. Data was analysed using GraphPad Instat Version 3 with a p value of <0.05 considered to be statistically significant. Patient characteristics were reported as mean and standard deviation for continuous data and categorical data reported as number and percentage. Results: Of the 533 patients included in the study, there were 268 (50.2%) female and 265 (49.8%) male patients with a mean age of 62.5 years (±16.4). The overall mean TITR was 78.3% (±12.7) with an overall haemorrhagic incidence of 0.41 events per patient. For the HAS BLED model, there was a haemorrhagic incidence of 0.08, 0.53, and 0.54 per patient in the low, moderate and high-risk categories respectively showing a statistically significant increase in incidence with increasing risk category. The CHADS2 model showed an increase in ischaemic events according to risk category with no ischaemic events in the low category, and an ischaemic incidence of 0.03 in the moderate category and 0.47 high-risk categories. Conclusion: An increasing haemorrhagic incidence correlated to an increase in the HAS BLED risk score in DVT patients treated with warfarin. Furthermore, a greater incidence of ischaemic events occurred in patients with an increase in CHADS2 category. In an Australian population of DVT patients, the HAS BLED and CHADS2 accurately predicts incidences of haemorrhage and ischaemic events respectively.

Keywords: anticoagulant agent, deep vein thrombosis, risk assessment, warfarin

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Authors: Hisham Arab Alkabeya, A. M. Hughes, J. Adams

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Background: People with Rheumatoid Arthritis (RA) continue to experience problems with hand function despite new drug advances and targeted medical treatment. Consequently, it is important to identify the factors that influence the impact of RA disease on hand function. This systematic review identified observational studies that reported factors that influenced the impact of RA on hand function. Methods: MEDLINE, EMBASE, CINAL, AMED, PsychINFO, and Web of Science database were searched from January 1990 up to March 2017. Full-text articles published in English that described factors related to hand functional disability in people with RA were selected following predetermined inclusion and exclusion criteria. Pertinent data were thoroughly extracted and documented using a pre-designed data extraction form by the lead author, and cross-checked by the review team for completion and accuracy. Factors related to hand function were classified under the domains of the International Classification of Functioning, Disability, and Health (ICF) framework and health-related factors. Three reviewers independently assessed the methodological quality of the included articles using the quality of cross-sectional studies (AXIS) tool. Factors related to hand function that was investigated in two or more studies were explored using a best-evidence synthesis. Results: Twenty articles form 19 studies met the inclusion criteria from 1,271 citations; all presented cross-sectional data (five high quality and 15 low quality studies), resulting in at best limited evidence in the best-evidence synthesis. For the factors classified under the ICF domains, the best-evidence synthesis indicates that there was a range of body structure and function factors that were related with hand functional disability. However, key factors were hand strength, disease activity, and pain intensity. Low functional status (physical, emotional and social) level was found to be related with limited hand function. For personal factors, there is limited evidence that gender is not related with hand function; whereas, conflicting evidence was found regarding the relationship between age and hand function. In the domain of environmental factors, there was limited evidence that work activity was not related with hand function. Regarding health-related factors, there was limited evidence that the level of the rheumatoid factor (RF) was not related to hand function. Finally, conflicting evidence was found regarding the relationship between hand function and disease duration and general health status. Conclusion: Studies focused on body structure and function factors, highlighting a lack of investigation into personal and environmental factors when considering the impact of RA on hand function. The level of evidence which exists was limited, but identified that modifiable factors such as grip or pinch strength, disease activity and pain are the most influential factors on hand function in people with RA. The review findings suggest that important personal and environmental factors that impact on hand function in people with RA are not yet considered or reported in clinical research. Well-designed longitudinal, preferably cohort, studies are now needed to better understand the causality between personal and environmental factors and hand functional disability in people with RA.

Keywords: factors, hand function, rheumatoid arthritis, systematic review

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Authors: Pakize Ozlem Kurt Polat

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GMO (genetically modified organism) is the result of a laboratory process where genes from the DNA of one species are extracted and artificially forced into the genes of an unrelated plant or animal. This technology includes; nucleic acid hybridization, recombinant DNA, RNA, PCR, cell culture and gene cloning techniques. The studies are divided into three groups of properties transferred to the transgenic plant. Up to 59% herbicide resistance characteristic of the transfer, 28% resistance to insects and the virus seems to be related to quality characteristics of 13%. Transgenic crops are not included in the commercial production of each product; mostly commercial plant is soybean, maize, canola, and cotton. Day by day increasing GMO interest can be listed as follows; Use in the health area (Organ transplantation, gene therapy, vaccines and drug), Use in the industrial area (vitamins, monoclonal antibodies, vaccines, anti-cancer compounds, anti -oxidants, plastics, fibers, polyethers, human blood proteins, and are used to produce carotenoids, emulsifiers, sweeteners, enzymes , food preservatives structure is used as a flavor enhancer or color changer),Use in agriculture (Herbicide resistance, Resistance to insects, Viruses, bacteria, fungi resistance to disease, Extend shelf life, Improving quality, Drought , salinity, resistance to extreme conditions such as frost, Improve the nutritional value and quality), we explain all this methods step by step in this research. GMO has advantages and disadvantages, which we explain all of them clearly in full text, because of this topic, worldwide researchers have divided into two. Some researchers thought that the GMO has lots of disadvantages and not to be in use, some of the researchers has opposite thought. If we look the countries law about GMO, we should know Biosafety law for each country and union. For this Biosecurity reasons, the problems caused by the transgenic plants, including Turkey, to minimize 130 countries on 24 May 2000, ‘the United Nations Biosafety Protocol’ signed nudes. This protocol has been prepared in addition to Cartagena Biosafety Protocol entered into force on September 11, 2003. This protocol GMOs in general use by addressing the risks to human health, biodiversity and sustainable transboundary movement of all GMOs that may affect the prevention, transit covers were dealt and used. Under this protocol we have to know the, ‘US Regulations GMO’, ‘European Union Regulations GMO’, ‘Turkey Regulations GMO’. These three different protocols have different applications and rules. World population increasing day by day and agricultural fields getting smaller for this reason feeding human and animal we should improve agricultural product yield and quality. Scientists trying to solve this problem and one solution way is molecular biotechnology which is including the methods of GMO too. Before decide to support or against the GMO, should know the GMO protocols and it effects.

Keywords: biotechnology, GMO (genetically modified organism), molecular marker

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Authors: Md. Kabir Azaharul Islam

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Background: The purpose of this interventions was to describe the source and extent to increase health seeking rights and uptake of quality integrated maternal health, family planning and HIV information, clinical-non clinical services, and commodities amongst young people age 10-24 among brothel based Female Sex Worker’s in Bangladesh. Such Knowledge will equip with information to develop more appropriate and effective interventions that address the problem of HIV/AIDS and SRHR within the brothel based female sex worker’s community. Methods: Before start the intervention we observed situation in brothel and identify lack of knowledge about health issues, modern health facility, sexual harassment and violence & health rights. To enable access to the intervention obtained permission from a series of stakeholders within the brothel system. This intervention to the most vulnerable young key people during January 2014 to December, 2015, it designed an intervention that focuses on using peer education and sensitization meeting with self help group leader’s, pimbs, swardarni, house owner, local leaders, law enforcement agencies and target young key people (YKPs) through peer educator’s distributed BCC materials and conducted one to one and group session issues of HIV/AIDS, life skill education, maternal health, sexual reproductive health & rights, gender based violence, STD/STI and drug users in the community. Set up community based satellite clinic to provided clinical-non clinical services and commodities for SRH, FP and HIV including general health among brothel based FSWs. Peer educator frequently move and informed target beneficiaries’ age 10-24 YKPs about satellite clinic as well as time & date in the community. Results: This intervention highly promotes of brothel based FSW utilization of local facility based health providers private and public health facilities.2400 FSWs age 10-24 received information on SRHR, FP and HIV as well as existing health facilities, most of FSWs to received service from traditional healer before intervention. More than 1080 FSWs received clinical-non clinical services and commodities from satellite clinic including 12 ANC, 12 PNC and 25 MR. Most of young FSW age 10-24 are treated bonded girls under swardarni, house owner and pimbs, they have no rights to free movement as per need. As a result, they have no rights for free movement. However the brothel self help group (SHG) has become sensitized flowing this intervention. Conclusions: The majority of female sex workers well being regarding information on SRHR, FP and HIV as well as local health facilities now they feel free to go outside facilities for better health service. not only increased FSWs’ vulnerability to HIV infection and sexual reproductive health rights but also had huge implications for their human rights. This means that even when some clients impinged FSW’s rights (for example avoiding payment for services under the pretext of dissatisfaction), they might not be able to seek redress for fear of being ejected from the brothel. They raise voice national & local level different forum.

Keywords: ANC, HIV, PNC, SRHR

Procedia PDF Downloads 317

Authors: Michael Josef Schwerer

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Background: The identification of unknown victims from mass disasters, violent crimes, or terrorist attacks is frequently facilitated through information from missing persons lists, portrait photos, old or recent pictures showing unique characteristics of a person such as scars or tattoos, or simply reference samples from blood relatives for DNA analysis. In contrast, the identification or at least the characterization of an unknown perpetrator from criminal or terrorist actions remains challenging, particularly in the absence of material or data for comparison, such as fingerprints, which had been previously stored in criminal records. In scenarios that result in high levels of destruction of the perpetrator’s corpse, for instance, blast or fire events, the chance for a positive identification using standard techniques is further impaired. Objectives: This study shows the forensic genetic procedures in the Legal Medicine Service of the German Air Force for the identification of unknown individuals, including such cases in which reference samples are not available. Scenarios requiring such efforts predominantly involve aircraft crash investigations, which are routinely carried out by the German Air Force Centre of Aerospace Medicine as one of the Institution’s essential missions. Further, casework by military police or military intelligence is supported based on administrative cooperation. In the talk, data from study projects, as well as examples from real casework, will be demonstrated and discussed with the audience. Methods: Forensic genetic identification in our laboratories involves the analysis of Short Tandem Repeats and Single Nucleotide Polymorphisms in nuclear DNA along with mitochondrial DNA haplotyping. Extended DNA analysis involves phenotypic markers for skin, hair, and eye color together with the investigation of a person’s biogeographic ancestry. Assessment of the biological age of an individual employs CpG-island methylation analysis using bisulfite-converted DNA. Forensic Investigative Genealogy assessment allows the detection of an unknown person’s blood relatives in reference databases. Technically, end-point-PCR, real-time PCR, capillary electrophoresis, pyrosequencing as well as next generation sequencing using flow-cell-based and chip-based systems are used. Results and Discussion: Optimization of DNA extraction from various sources, including difficult matrixes like formalin-fixed, paraffin-embedded tissues, degraded specimens from decomposed bodies or from decedents exposed to blast or fire events, provides soil for successful PCR amplification and subsequent genetic profiling. For cases with extremely low yields of extracted DNA, whole genome preamplification protocols are successfully used, particularly regarding genetic phenotyping. Improved primer design for CpG-methylation analysis, together with validated sampling strategies for the analyzed substrates from, e.g., lymphocyte-rich organs, allows successful biological age estimation even in bodies with highly degraded tissue material. Conclusions: Successful identification of unknown individuals or at least their phenotypic characterization using pigmentation markers together with age-informative methylation profiles, possibly supplemented by family tree search employing Forensic Investigative Genealogy, can be provided in specialized laboratories. However, standard laboratory procedures must be adapted to work with difficult and highly degraded sample materials.

Keywords: identification, forensic genetics, phenotypic markers, CPG methylation, biological age estimation, forensic investigative genealogy

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Authors: Digdem M. Siyez, Bariscan Ozturk, Erol Esen, Ender Siyez, Yelda Kagnici, Bahar Baran

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Infertility is a reproductive disease identified with the absence of pregnancy after regular unprotected sexual intercourse that has been lasting for 12 months or more. Some of the factors that cause infertility, which has been considered as a social and societal issue since the first days of the humankind, are preventable. These are veneral diseases, age, the frequency of the intercourse and its timing, drug use, bodyweight, environmental and professional conditions. Having actual information about the reproductive health is essential to take protective and preventive measures, and it is accepted as the most effective way to reduce the rate of infertility. However, during the literature review, it has been observed that there are so few studies that focus on the prevention of the infertility. The aim of this study is to develop a psycho-education program to reduce infertility among university students and also to evaluate the program’s effectiveness. It is believed that this program will increase the information level about infertility among the university students, help them to adopt healthy attitudes, develop life skills, create awareness about the risk factors and also contribute to the literature. Throughout the study, first, the contents of sexual/reproductive health programs developed for university students were examined by the researches. Besides, “Views about Reproductive Health Psycho-education Program Survey” was developed and applied to 10221 university students from 21 universities. In accordance with the literature and the university students’ views about reproductive health psycho-education program consisting of 9 sessions each of which lasts for 90 minutes was developed. The pilot program was carried out with 16 volunteer undergraduate students attending to a state university. During the evaluation of the pilot study, at the end of each session “Session Evaluation Form” and at the end of the entire program “Program Evaluation Form” were administered to the participants. Besides, one week after the end of the program, a focus group with half of the group, and individual interviews with the rest were conducted. Based on the evaluations, it was determined that the session duration is enough, the teaching methods meet the expectation, the techniques applied are appropriate and clear, and the materials are adequate. Also, an extra session was added to psycho-education program based on the feedbacks of the participants. In order to evaluate program’s effectiveness, Solomon control group design will be used. According to this design, the research has 2 experiment groups and 2 control groups. The participants who voluntarily participated in the research after the announcement of the psycho-education program were divided into experiment and control groups. In the experiment 1 and control 1 groups, “Personal Information Test”, “Infertility Information Test” and “Infertility Attitude Scale”, “Self Identification Inventory” and “Melbourne Decision Scale” were administered as a preliminary test. Currently, at the present stage, psycho-education still continues. After this 10-week program, the same tests will be administered again as the post-tests. The decision upon which statistical method will be applied in the analysis will be made afterwards according to whether the data meets the presuppositions or not.

Keywords: infertility, prevention, psycho-education, reproductive health

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Authors: Leo Nnamdi Ozurumba-Dwight

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Single-cell genomic analytical systems have proved to be a platform to isolate bulk cells into selected single cells for genomic, proteomic, and related metabolomic studies. This is enabling systematic investigations of the level of heterogeneity in a diverse and wide pool of cell populations. Single cell technologies, embracing techniques such as high parameter flow cytometry, single-cell sequencing, and high-resolution images are playing vital roles in these investigations on messenger ribonucleic acid (mRNA) molecules and related gene expressions in tracking the nature and course of disease conditions. This entails targeted molecular investigations on unit cells that help us understand cell behavoiur and expressions, which can be examined for their health implications on the health state of patients. One of the vital good sides of single-cell RNA sequencing (scRNA seq) is its probing capacity to detect deranged or abnormal cell populations present within homogenously perceived pooled cells, which would have evaded cursory screening on the pooled cell populations of biological samples obtained as part of diagnostic procedures. Despite conduction of just single-cell transcriptome analysis, scRNAseq now permits comparison of the transcriptome of the individual cells, which can be evaluated for gene expressional patterns that depict areas of heterogeneity with pharmaceutical drug discovery and clinical treatment applications. It is vital to strictly work through the tools of investigations from wet lab to bioinformatics and computational tooled analyses. In the precise steps for scRNAseq, it is critical to do thorough and effective isolation of viable single cells from the tissues of interest using dependable techniques (such as FACS) before proceeding to lysis, as this enhances the appropriate picking of quality mRNA molecules for subsequent sequencing (such as by the use of Polymerase Chain Reaction machine). Interestingly, scRNAseq can be deployed to analyze various types of biological samples such as embryos, nervous systems, tumour cells, stem cells, lymphocytes, and haematopoietic cells. In haematopoietic cells, it can be used to stratify acute myeloid leukemia patterns in patients, sorting them out into cohorts that enable re-modeling of treatment regimens based on stratified presentations. In immunotherapy, it can furnish specialist clinician-immunologist with tools to re-model treatment for each patient, an attribute of precision medicine. Finally, the good predictive attribute of scRNAseq can help reduce the cost of treatment for patients, thus attracting more patients who would have otherwise been discouraged from seeking quality clinical consultation help due to perceived high cost. This is a positive paradigm shift for patients’ attitudes primed towards seeking treatment.

Keywords: immunotherapy, transcriptome, re-modeling, mRNA, scRNA-seq

Procedia PDF Downloads 166

Authors: Safak Akdemir

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The main purpose of this research is to evaluate the relationships between childhood traumas and dissociative experiences, self-perceptions and early maladaptive schemas in male convicts convicted of sexual assault crimes in prison. In our study, male convicts in prison for the crime of sexual assault constitute the experimental group, and the participants matched with this experimental group in terms of education, age and gender constitute the control group. The experimental group of the research consists of 189 male individuals who are convicted in the Ministry of Justice, General Directorate of Prisons, Istanbul/Maltepe L Type Closed Prison. The control group of this study consists of 147 adult males matched with the experimental group in terms of age, gender and education parameters. A total of 336 adult male individuals are included in the sample of this study. 46% of the experimental group were convicted of only sexual assault, 54% of them were convicted of both sexual assault and murder, injury and drug crimes. Total of five data collection tools, namely the Personal Information Form created by S. A. & E. O., Childhood Trauma Questionnaire (CTQ), the Dissociative Experiences Scale (DES), the Rosenberg Self-Esteem Scale (RSES), and the Young Schema Questionnaire-Short Form (YSQ-SF3), were completed. DES cut-off score of 99 (52.39%) of 189 convicts in the experimental group and 12 (8.17%) of 147 people in the control group was found to be 30 and above, and this result indicates the presence of pathological dissociative experiences. 180 (95.23%) of the sexual assault convicts in the experimental group had at least one childhood trauma, 154 (81.48%) were emotional neglect, 140 (74.07%) were emotional abuse, 121 (64.02%) were physical neglect, 91 (4814%) physical abuse and 70 (37.03%) sexual abuse. 168 (88.88%) of the experimental group reported multiple type of trauma and 12 (6.34%) reported single type of trauma. While the childhood traumas, isolation, abandonment and emotional deprivation schema levels of the convicts with a DES cut-off score of 30 and above are higher than the convicts with a DES cut-off score of 30 and above, their self-esteem is lower than this group. Experimental group while childhood traumas, dissociative experiences and early maladaptive schemas are higher than the control group, their self-esteem levels are lower. Dissociative experiences, abandonment and emotional deprivation early maladaptive schemas are more common in convicts aged between 18-30 years compared to convicts aged 31 and over. In addition, dissociative experiences and early maladaptive schemas of male convicts who reported physical and sexual abuse were higher than those who did not report physical and sexual abuse, while their self-esteem was at a lower level. As a result, in terms of psychotraumatology and clinical forensic psychology, dissociative disorders developed under the influence of chronic childhood traumas, with clinical interviews and psychometric measurements to be made in terms of forensic psychiatry; it is of fundamental importance to evaluate it in terms of neurosis-psychosis distinction, disability retirement, custody, malpractice, criminal and legal capacity criteria.

Keywords: crime, sexual assault, criminology, rape crimes, dissocitative disorders, maladative schemas

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Authors: Cory B. Portner, Julie A. Grauert, Lisa M. Stromme, Shelby D. Anderson, Franji H. Mayes

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Introduction: WASHINGTON state in the Pacific Northwest of the United States is internationally known for its technology industry, fisheries, agriculture, and vistas. On January 21, 2020, Washington state also became known as the first state with a confirmed COVID-19 case in the United States, thrusting the state into the international spotlight as the world came to grips with the global threat of this disease presented. Tourism is Washington state’s fourth-largest industry. Tourism to the state generates over 1.8 billion dollars (USD) in local and state tax revenue and employs over 180,000 people. Communicating with residents, stakeholders, and visitors on the status of disease activity, prevention measures, and response updates was vital to stopping the pandemic and increasing compliance and awareness. Significance: In order to communicate vital public health updates, guidance implementation, and safety measures to the public, the Washington State Department of Health established routine live virtual media briefings to reach audiences via social media, internet television, and broadcast television. Through close partnership with regional broadcast news stations and the state public affairs news network, the Washington State Department of Health hosted 95 media briefings from January 2020 through September 2022 and continues to regularly host live virtual media briefings to accommodate the needs of the public and media. Methods: Our methods quickly evolved from hosting briefings in the cement closet of a military base to being able to produce and stream the briefings live from any home-office location. The content was tailored to the hot topic of the day and to the reporter's questions and needs. Virtual media briefings hosted through inexpensive or free platforms online are extremely cost-effective: the only mandatory components are WiFi, a laptop, and a monitor. There is no longer a need for a fancy studio or expensive production software to achieve the goal of communicating credible, reliable information promptly. With minimal investment and a small learning curve, facilitators and panelists are able to host highly produced and engaging media availabilities from their living rooms. Results: The briefings quickly developed a reputation as the best source for local and national journalists to get the latest and most factually accurate information about the pandemic. In the height of the COVID-19 response, 135 unique media outlets logged on to participate in the briefing. The briefings typically featured 4-5 panelists, with as many as 9 experts in attendance to provide information and respond to media questions. Preparation was always a priority: Public Affairs staff for the Washington State Department of Health produced over 170 presenter remarks, including guidance on talking points for 63 expert guest panelists. Implication For Practice: Information is today’s most valuable currency. The ability to disseminate correct information urgently and on a wide scale is the most effective tool in crisis communication. Due to our role as the first state with a confirmed COVID-19 case, we were forced to develop the most accurate and effective way to get life-saving information to the public. The cost-effective, web-based methods we developed can be applied in any crisis to educate and protect communities under threat, ultimately saving lives from a laptop.

Keywords: crisis communications, public relations, media management, news media

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Authors: Mehmet Salih Bayraktutan

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Geomechanical properties of Rock Salt Deposits in Tuzluca Salt Mine Area (Eastern Turkey) are studied for modeling the operation- excavation strategy. The purpose of this research focused on calculating the critical value of span height- which will meet the safety requirements. The Mine Site Tuzluca Hills consist of alternating parallel bedding of Salt ( NaCl ) and Gypsum ( CaS04 + 2 H20) rocks. Rock Salt beds are more resistant than narrow Gypsum interlayers. Rock Salt beds formed almost 97 percent of the total height of the Hill. Therefore, the geotechnical safety of Galleries depends on the mechanical criteria of Rock Salt Cores. General deposition of Tuzluca Basin was finally completed by Tuzluca Evaporites, as for the uppermost stratigraphic unit. They are currently running mining operations performed by classic mechanical excavation, room and pillar method. Rooms and Pillars are currently experiencing an initial stage of fracturing in places. Geotechnical safety of the whole mining area evaluated by Rock Mass Rating (RMR), Rock Quality Designation (RQD) spacing of joints, and the interaction of groundwater and fracture system. In general, bedded rock salt Show large lateral deformation capacity (while deformation modulus stays in relative small values, here E= 9.86 GPa). In such litho-stratigraphic environments, creep is a critical mechanism in failure. Rock Salt creep rate in steady-state is greater than interbedding layers. Under long-lasted compressive stresses, creep may cause shear displacements, partly using bedding planes. Eventually, steady-state creep in time returns to accelerated stages. Uniaxial compression creep tests on specimens were performed to have an idea of rock salt strength. To give an idea, on Rock Salt cores, average axial strength and strain are found as 18 - 24 MPa and 0.43-0.45 %, respectively. Uniaxial Compressive strength of 26- 32 MPa, from bedded rock salt cores. Elastic modulus is comparatively low, but lateral deformation of the rock salt is high under the uniaxial compression stress state. Poisson ratio = 0.44, break load = 156 kN, cohesion c= 12.8 kg/cm2, specific gravity SG=2.17 gr/cm3. Fracture System; spacing of fractures, joints, faults, offsets are evaluated under acting geodynamic mechanism. Two sand beds, each 4-6 m thick, exist near to upper level and at the top of the evaporating sequence. They act as aquifers and keep infiltrated water on top for a long duration, which may result in the failure of roofs or pillars. Two major active seismic ( N30W and N70E ) striking Fault Planes and parallel fracture strands have seismically triggered moderate risk of structural deformation of rock salt bedding sequence. Earthquakes and Floods are two prevailing sources of geohazards in this region—the seismotectonic activity of the Mine Site based on the crossing framework of Kagizman Faults and Igdir Faults. Dominant Hazard Risk sources include; a) Weak mechanical properties of rock salt, gypsum, anhydrite beds-creep. b) Physical discontinuities cutting across the thick parallel layers of Evaporite Mass, c) Intercalated beds of weak cemented or loose sand, clayey sandy sediments. On the other hand, absorbing the effects of salt-gyps parallel bedded deposits on seismic wave amplitudes has a reducing effect on the Rock Mass.

Keywords: bedded rock salt, creep, failure mechanism, geotechnical safety

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Authors: Jennifer Wheeldon, Nick de Viggiani, Nikki Cotterill

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Background: Urinary and fecal incontinence affect a significant proportion of older adults aged 65 and over who permanently reside in residential and nursing home facilities. Incontinence symptoms have been linked to comorbidities, an increased risk of infection and reduced quality of life and mental wellbeing of residents. However, continence care provision can often be poor, further compromising the health and wellbeing of this vulnerable population. Objectives: To identify experiences and perceptions of continence care provision in older adult residential care settings and to identify factors that help or hinder good continence care provision. Settings included both residential care homes and nursing homes for older adults. Methods: A qualitative evidence synthesis using systematic review methodology established the current evidence-base. Data from 20 qualitative and mixed-method studies was appraised and synthesized. Following the review process, 10* qualitative interviews with staff working in older adult residential care settings were conducted across six* sites, which included registered managers, registered nurses and nursing/care assistants/aides. Purposive sampling recruited individuals from across England. Both evidence synthesis and interview data was analyzed thematically, both manually and with NVivo software. Results: The evidence synthesis revealed complex barriers and facilitators for continence care provision at three influencing levels: macro (structural and societal external influences), meso (organizational and institutional influences) and micro (day-to-day actions of individuals impacting service delivery). Macro-level barriers included negative stigmas relating to incontinence, aging and working in the older adult social care sector, restriction of continence care resources such as containment products (i.e. pads), short staffing in care facilities, shortfalls in the professional education and training of care home staff and the complex health and social care needs of older adult residents. Meso-level barriers included task-centered organizational cultures, ageist institutional perspectives regarding old age and incontinence symptoms, inadequate care home management and poor communication and teamwork among care staff. Micro-level barriers included poor knowledge and negative attitudes of care home staff and residents regarding incontinence symptoms and symptom management and treatment. Facilitators at the micro-level included proactive and inclusive leadership skills of individuals in management roles. Conclusions: The findings of the evidence synthesis study help to outline the complexities of continence care provision in older adult care homes facilities. Macro, meso and micro level influences demonstrate problematic and interrelated barriers across international contexts, indicating that improving continence care in this setting is extremely challenging due to the multiple levels at which care provision and services are impacted. Both international and national older adult social care policy-makers, researchers and service providers must recognize this complexity, and any intervention seeking to improve continence care in older adult care home settings must be planned accordingly and appreciatively of the complex and interrelated influences. It is anticipated that the findings of the qualitative interviews will shed further light on the national context of continence care provision specific to England; data collection is ongoing*. * Sample size is envisaged to be between 20-30 participants from multiple sites by Spring 2023.

Keywords: continence care, residential and nursing homes, evidence synthesis, qualitative

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Authors: Poojan Gharat, Haridas Pal, Sharmistha Dutta Choudhury

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Tuning photophysical properties of guest dyes through host-guest interactions involving macrocyclic hosts are the attractive research areas since past few decades, as these changes can directly be implemented in chemical sensing, molecular recognition, fluorescence imaging and dye laser applications. Excited state intramolecular proton transfer (ESIPT) is an intramolecular prototautomerization process display by some specific dyes. The process is quite amenable to tunability by the presence of different macrocyclic hosts. The present study explores the interesting effect of p-sulfonatocalix[n]arene (SCXn) and cyclodextrin (CD) hosts on the excited-state prototautomeric equilibrium of Chrysazine (CZ), a model antitumour drug. CZ exists exclusively in its normal form (N) in the ground state. However, in the excited state, the excited N* form undergoes ESIPT along with its pre-existing intramolecular hydrogen bonds, giving the excited state prototautomer (T*). Accordingly, CZ shows a single absorption band due to N form, but two emission bands due to N* and T* forms. Facile prototautomerization of CZ is considerably inhibited when the dye gets bound to SCXn hosts. However, in spite of lower binding affinity, the inhibition is more profound with SCX6 host as compared to SCX4 host. For CD-CZ system, while prototautomerization process is hindered by the presence of β-CD, it remains unaffected in the presence of γCD. Reduction in the prototautomerization process of CZ by SCXn and βCD hosts is unusual, because T* form is less dipolar in nature than the N*, hence binding of CZ within relatively hydrophobic hosts cavities should have enhanced the prototautomerization process. At the same time, considering the similar chemical nature of two CD hosts, their effect on prototautomerization process of CZ would have also been similar. The atypical effects on the prototautomerization process of CZ by the studied hosts are suggested to arise due to the partial inclusion or external binding of CZ with the hosts. As a result, there is a strong possibility of intermolecular H-bonding interaction between CZ dye and the functional groups present at the portals of SCXn and βCD hosts. Formation of these intermolecular H-bonds effectively causes the pre-existing intramolecular H-bonding network within CZ molecule to become weak, and this consequently reduces the prototautomerization process for the dye. Our results suggest that rather than the binding affinity between the dye and host, it is the orientation of CZ in the case of SCXn-CZ complexes and the binding stoichiometry in the case of CD-CZ complexes that play the predominant role in influencing the prototautomeric equilibrium of the dye CZ. In the case of SCXn-CZ complexes, the results obtained through experimental findings are well supported by quantum chemical calculations. Similarly for CD-CZ systems, binding stoichiometries obtained through geometry optimization studies on the complexes between CZ and CD hosts correlate nicely with the experimental results. Formation of βCD-CZ complexes with 1:1 stoichiometry while formation of γCD-CZ complexes with 1:1, 1:2 and 2:2 stoichiometries are revealed from geometry optimization studies and these results are in good accordance with the observed effects by the βCD and γCD hosts on the ESIPT process of CZ dye.

Keywords: intermolecular proton transfer, macrocyclic hosts, quantum chemical studies, photophysical studies

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Authors: Celine Shi Ying Lee, Jong Jian Lee

Abstract:

Background: Infectious keratitis is one of the leading causes of blindness worldwide. Prompt treatment with effective medication will control the infection early, preventing corneal scarring and visual loss. fluoroquinolones ophthalmic medication is used because of its broad-spectrum properties, potency, good intraocular penetration, and low toxicity. The study aims to evaluate the treatment outcome of corneal ulcers using Levofloxacin 1.5% ophthalmic solution (LVFX) with adjuvant oral ciprofloxacin when indicated and apply this treatment strategy in primary health care as first-line treatment. Methods: Patients with infective corneal ulcer treated in an eye center were recruited. Inclusion criteria includes Corneal infection consistent with bacterial keratitis, single or multiple small corneal ulcers. Treatment regime: LVFX hourly for the first 2 days, 2 hourly from the 3rd day, and 3 hourly on the 5th day of review. Adjuvant oral ciprofloxacin 500mg BD was administered for 5 days if there were multiple corneal ulcers or when the location of the cornea ulcer was central or paracentral. Results: 47 subjects were recruited. There were 16 (34%) males and 31 (66%) females. 40 subjects (85%) were contact lens (CL) related to corneal ulcer, and 7 subjects (15%) were non-contact lens related. 42 subjects (89%) presented with one ulcer, of which 20 of them (48%) needed adjuvant therapy. 5 subjects presented with 2 or 3 ulcers, of which 3 needed adjuvant therapy. A total of 23 subjects (49%) was given adjuvant therapy (oral ciprofloxacin 500mg BD for 5 days).21 of them (91%) were CL related. All subjects recovered fully, and the average duration of treatment was 3.7 days, with 49% of the subjects resolved on the 3rd day, 38% on the 5thday of and 13% on the 7thday. All subjects showed symptoms of relief of pain, light-sensitivity, and redness on the 3rd day with full visual recovery post-treatment. No adverse drug reactions were recorded. Conclusion: Our treatment regime demonstrated good clinical outcome as first-line treatment for corneal ulcers. A corneal ulcer is a common eye condition in Singapore, mainly due to CL wear. Pseudomonas aeruginosa is the most frequent and potentially sight-threatening pathogen involved in CL related corneal ulcer. Coagulase-negative Staphylococci, Staphylococcus aureus, and Streptococcus Pneumoniae were seen in non-CL users. All these bacteria exhibit good sensitivity rates to ciprofloxacin and levofloxacin. It is therefore logical in our study to use LVFX Eyedrops and adjuvant ciprofloxacin oral antibiotics when indicated as first line treatment for most corneal ulcers. Our study of patients, both CL related and non-CL related, have shown good clinical response and full recovery using the above treatment strategy. There was also a full restoration of visual acuity in all the patients. Eye-trained primary Healthcare practitioners can consider adopting this treatment strategy as first line treatment in patients with corneal ulcers. This is relevant during the COVID pandemic, where hospitals are overwhelmed with patients and in regions with limited access to specialist eye care. This strategy would enable early treatment with better clinical outcome.

Keywords: corneal ulcer, levofloxacin hydrate, treatment strategy, ciprofloxacin

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Authors: Akanksha Bhatnagar, Sandhya Kortegare, Felice Elefant

Abstract:

Context: Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by progressive cognitive decline and memory loss. The cause of AD is not fully understood, but it is thought to be caused by a combination of genetic, environmental, and lifestyle factors. One of the hallmarks of AD is the loss of neurons in the hippocampus, a brain region that is important for memory and learning. This loss of neurons is thought to be caused by a decrease in histone acetylation, which is a process that regulates gene expression. Research Aim: The research aim of the study was to develop mall molecule compounds that can enhance the activity of Tip60, a histone acetyltransferase that is important for memory and learning. Methodology/Analysis: The researchers used in silico structural modeling and a pharmacophore-based virtual screening approach to design and synthesize small molecule compounds strongly predicted to target and enhance Tip60’s HAT activity. The compounds were then tested in vitro and in vivo to assess their ability to enhance Tip60 activity and rescue cognitive deficits in AD models. Findings: The researchers found that several of the compounds were able to enhance Tip60 activity and rescue cognitive deficits in AD models. The compounds were also developed to cross the blood-brain barrier, which is an important factor for the development of potential AD therapeutics. Theoretical Importance: The findings of this study suggest that Tip60 HAT activators have the potential to be developed as therapeutic agents for AD. The compounds are specific to Tip60, which suggests that they may have fewer side effects than other HDAC inhibitors. Additionally, the compounds are able to cross the blood-brain barrier, which is a major hurdle for the development of AD therapeutics. Data Collection: The study collected data from a variety of sources, including in vitro assays and animal models. The in vitro assays assessed the ability of compounds to enhance Tip60 activity using histone acetyltransferase (HAT) enzyme assays and chromatin immunoprecipitation assays. Animal models were used to assess the ability of the compounds to rescue cognitive deficits in AD models using a variety of behavioral tests, including locomotor ability, sensory learning, and recognition tasks. The human clinical trials will be used to assess the safety and efficacy of the compounds in humans. Questions: The question addressed by this study was whether Tip60 HAT activators could be developed as therapeutic agents for AD. Conclusions: The findings of this study suggest that Tip60 HAT activators have the potential to be developed as therapeutic agents for AD. The compounds are specific to Tip60, which suggests that they may have fewer side effects than other HDAC inhibitors. Additionally, the compounds are able to cross the blood-brain barrier, which is a major hurdle for the development of AD therapeutics. Further research is needed to confirm the safety and efficacy of these compounds in humans.

Keywords: Alzheimer's disease, cognition, neuroepigenetics, drug discovery

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Authors: Ayse Gul Bilen

Abstract:

Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed antidepressants that are used clinically for the treatment of anxiety disorders, obsessive-compulsive disorder (OCD), panic disorders and eating disorders. The first SSRI, fluoxetine (sold under the brand names Prozac and Sarafem among others), had an adverse effect profile better than any other available antidepressant when it was introduced because of its selectivity for serotonin receptors. They have been considered almost free of side effects and have become widely prescribed, however questions about the safety and tolerability of SSRIs have emerged with their continued use. Most SSRI side effects are dose-related and can be attributed to serotonergic effects such as nausea. Continuous use might trigger adverse effects such as hyponatremia, tremor, nausea, weight gain, sleep disturbance and sexual dysfunction. Moderate toxicity can be safely observed in the hospital for 24 hours, and mild cases can be safely discharged (if asymptomatic) from the emergency department once cleared by Psychiatry in cases of intentional overdose and after 6 to 8 hours of observation. Although fluoxetine is relatively safe in terms of overdose, it might still be cardiotoxic and inhibit platelet secretion, aggregation, and plug formation. There have been reported clinical cases of seizures, cardiac conduction abnormalities, and even fatalities associated with fluoxetine ingestions. While the medical literature strongly suggests that most fluoxetine overdoses are benign, emergency physicians need to remain cognizant that intentional, high-dose fluoxetine ingestions may induce seizures and can even be fatal due to cardiac arrhythmia. Our case is a 35-year old female patient who was sent to ER with symptoms of confusion, amnesia and loss of orientation for time and location after being found wandering in the streets unconsciously by police forces that informed 112. Upon laboratory examination, no pathological symptom was found except sinus tachycardia in the EKG and high levels of aspartate transaminase (AST) and alanine transaminase (ALT). Diffusion MRI and computed tomography (CT) of the brain all looked normal. Upon physical and sexual examination, no signs of abuse or trauma were found. Test results for narcotics, stimulants and alcohol were negative as well. There was a presence of dysrhythmia which required admission to the intensive care unit (ICU). The patient gained back her conscience after 24 hours. It was discovered from her story afterward that she had been using fluoxetine due to post-traumatic stress disorder (PTSD) for 6 months and that she had attempted suicide after taking 3 boxes of fluoxetine due to the loss of a parent. She was then transferred to the psychiatric clinic. Our study aims to highlight the need to consider toxicologic drug use, in particular, the abuse of selective serotonin reuptake inhibitors (SSRIs), which have been widely prescribed due to presumed safety and tolerability, for diagnosis of patients applying to the emergency room (ER).

Keywords: abuse, amnesia, fluoxetine, intoxication, SSRI

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Authors: Jong H. Kim, Kathleen L. Chan, Luisa W. Cheng

Abstract:

Control of fungal pathogens, such as foodborne mycotoxin producers, is problematic as effective antimycotic agents are often very limited. Mycotoxin contamination significantly interferes with the safe production of foods or crops worldwide. Moreover, expansion of fungal resistance to commercial drugs or fungicides is a global human health concern. Therefore, there is a persistent need to enhance the efficacy of commercial antimycotic agents or to develop new intervention strategies. Disruption of the cellular antioxidant system should be an effective method for pathogen control. Such disruption can be achieved with safe, redox-active compounds. Natural phenolic derivatives are potent redox cyclers that inhibit fungal growth through destabilization of the cellular antioxidant system. The goal of this study is to identify novel, redox-active compounds that disrupt the fungal antioxidant system. The identified compounds could also function as sensitizing agents to conventional antimycotics (i.e., chemosensitization) to improve antifungal efficacy. Various benzo derivatives were tested against fungal pathogens. Gene deletion mutants of the yeast Saccharomyces cerevisiae were used as model systems for identifying molecular targets of benzo analogs. The efficacy of identified compounds as potent antifungal agents or as chemosensitizing agents to commercial drugs or fungicides was examined with methods outlined by the Clinical Laboratory Standards Institute or the European Committee on Antimicrobial Susceptibility Testing. Selected benzo derivatives possessed potent antifungal or antimycotoxigenic activity. Molecular analyses by using S. cerevisiae mutants indicated antifungal activity of benzo derivatives was through disruption of cellular antioxidant or cell wall integrity system. Certain benzo analogs screened overcame tolerance of Aspergillus signaling mutants, namely mitogen-activated protein kinase mutants, to fludioxonil fungicide. Synergistic antifungal chemosensitization greatly lowered minimum inhibitory or fungicidal concentrations of test compounds, including inhibitors of mitochondrial respiration. Of note, salicylaldehyde is a potent antimycotic volatile that has some practical application as a fumigant. Altogether, benzo derivatives targeting cellular antioxidant system of fungi (along with cell wall integrity system) effectively suppress fungal growth. Candidate compounds possess the antifungal, antimycotoxigenic or chemosensitizing capacity to augment the efficacy of commercial antifungals. Therefore, chemogenetic approaches can lead to the development of novel antifungal intervention strategies, which enhance the efficacy of established microbe intervention practices and overcome drug/fungicide resistance. Chemosensitization further reduces costs and alleviates negative side effects associated with current antifungal treatments.

Keywords: antifungals, antioxidant system, benzo derivatives, chemosensitization

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Authors: Amirah Azzeri, Fatiha H. Shabaruddin, Scott A. McDonald, Rosmawati Mohamed, Maznah Dahlui

Abstract:

Objective: A scaled-up treatment cascade with direct-acting antiviral (DAA) therapy is necessary to achieve global WHO targets for hepatitis C virus (HCV) elimination in Malaysia. Recently, limited access to Sofosbuvir/Daclatasvir (SOF/DAC) is available through compulsory licensing, with future access to Sofosbuvir/Velpatasvir (SOF/VEL) expected through voluntary licensing due to recent agreements. SOF/VEL has superior clinical outcomes, particularly for cirrhotic stages, but has higher drug acquisition costs compared to SOF/DAC. It has been proposed that a stratified treatment cascade might be the most cost-efficient approach for Malaysia whereby all HCV patients are treated with SOF/DAC except for patients with cirrhosis who are treated with SOF/VEL. This study aimed to conduct a five-year budget impact analysis from the provider perspective of the proposed stratified treatment cascade for HCV treatment in Malaysia. Method: A disease progression model that was developed based on model-predicted HCV epidemiology data in Malaysia was used for the analysis, where all HCV patients in scenario A were treated with SOF/DAC for all disease stages while in scenario B, SOF/DAC was used only for non-cirrhotic patients and SOF/VEL was used for the cirrhotic patients. The model projections estimated the annual numbers of patients in care and the numbers of patients to be initiated on DAA treatment nationally. Healthcare costs associated with DAA therapy and disease stage monitoring was included to estimate the downstream cost implications. For scenario B, the estimated treatment uptake of SOF/VEL for cirrhotic patients were 25%, 50%, 75%, 100% and 100% for 2018, 2019, 2020, 2021 and 2022 respectively. Healthcare costs were estimated based on standard clinical pathways for DAA treatment described in recent guidelines. All costs were reported in US dollars (conversion rate US$1=RM4.09, the price year 2018). Scenario analysis was conducted for 5% and 10% reduction of SOF/VEL acquisition cost anticipated from the competitive market pricing of generic DAA in Malaysia. Results: The stratified treatment cascade with SOF/VEL in Scenario B was found to be cost-saving compared to Scenario A. A substantial portion of the cost reduction was due to the costs associated with DAA therapy which resulted in USD 40 thousand (year 1) to USD 443 thousand (year 5) savings annually, with cumulative savings of USD 1.1 million after 5 years. Cost reductions for disease stage monitoring were seen in year three onwards which resulted in cumulative savings of USD 1.1 thousand. Scenario analysis estimated cumulative savings of USD 1.24 to USD 1.35 million when the acquisition cost of SOF/VEL was reduced. Conclusion: A stratified treatment cascade with SOF/VEL was expected to be cost-saving and can results in a budget impact reduction in overall healthcare expenditure in Malaysia compared to treatment with SOF/DAC. The better clinical efficacy with SOF/VEL is expected to halt patients’ HCV disease progression and may reduce downstream costs of treating advanced disease stages. The findings of this analysis may be useful to inform healthcare policies for HCV treatment in Malaysia.

Keywords: Malaysia, direct acting antiviral, compulsory licensing, voluntary licensing

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Authors: Anupalli Roja Rani, Pavithra Dasari

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Background: Among several, breast cancer has emerged as the most common female cancer in developing countries. It is the most common cause of cancer-related deaths worldwide among women. It is a molecularly and clinically heterogeneous disease. Moreover, it is a hormone–dependent tumor in which estrogens can regulate the growth of breast cells by binding with estrogen receptors (ERs). Moreover, the use of natural products in cancer therapeutics is due to their properties of biocompatibility and less toxicity. Plants are the vast reservoirs for various bioactive compounds. Coleus barbatus (Lamiaceae) contains anticancer properties against several cancer cell lines. Method: In the present study, an attempt is being made to enrich the knowledge of the anticancer activity of pure compounds extracted from Coleus barbatus (Andrew). On human breast cancer cell lines MCF-7. Here in, we are assessing the antiproliferative activity of Coleus barbatus (Andrew) plant extracts against MCF 7 and also evaluating their toxicity in normal human mammary cell lines such as Human Mammary Epithelial Cells (HMEC). The active fraction of plant extract was further purified with the help of Flash chromatography, Medium Pressure Liquid Chromatography (MPLC) and preparative High-Performance Liquid Chromatography (HPLC). The structure of pure compounds will be elucidated by using modern spectroscopic methods like Nuclear magnetic resonance (NMR), Electrospray Ionisation Mass Spectrometry (ESI-MS) methods. Later, the growth inhibition morphological assessment of cancer cells and cell cycle analysis of purified compounds were assessed using FACS. The growth and progression of signaling molecules HER2, GRP78 was studied by secretion assay using ELISA and expression analysis by flow cytometry. Result: Cytotoxic effect against MCF-7 with IC50 values were derived from dose response curves, using six concentrations of twofold serially diluted samples, by SOFTMax Pro software (Molecular device) and respectively Ellipticine and 0.5% DMSO were used as a positive and negative control. Conclusion: The present study shows the significance of various bioactive compounds extracted from Coleus barbatus (Andrew) root material. It acts as an anti-proliferative and shows cytotoxic effects on human breast cancer cell lines MCF7. The plant extracts play an important role pharmacologically. The whole plant has been used in traditional medicine for decades and the studies done have authenticated the practice. Earlier, as described, the plant has been used in the ayurveda and homeopathy medicine. However, more clinical and pathological studies must be conducted to investigate the unexploited potential of the plant. These studies will be very useful for drug designing in the future.

Keywords: coleus barbatus, HPLC, MPLC, NMR, MCF7, flash chromatograph, ESI-MS, FACS, ELISA.

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