Search results for: clinical skills
585 Monitoring Key Biomarkers Related to the Risk of Low Breastmilk Production in Women, Leading to a Positive Impact in Infant’s Health
Authors: R. Sanchez-Salcedo, N. H. Voelcker
Abstract:
Currently, low breast milk production in women is one of the leading health complications in infants. Recently, It has been demonstrated that exclusive breastfeeding, especially up to a minimum of 6 months, significantly reduces respiratory and gastrointestinal infections, which are the main causes of death in infants. However, the current data shows that a high percentage of women stop breastfeeding their children because they perceive an inadequate supply of milk, and only 45% of children are breastfeeding under 6 months. It is, therefore, clear the necessity to design and develop a biosensor that is sensitive and selective enough to identify and validate a panel of milk biomarkers that allow the early diagnosis of this condition. In this context, electrochemical biosensors could be a powerful tool for assessing all the requirements in terms of reliability, selectivity, sensitivity, cost efficiency and potential for multiplex detection. Moreover, they are suitable for the development of POC devices and wearable sensors. In this work, we report the development of two types of sensing platforms towards several biomarkers, including miRNAs and hormones present in breast milk and dysregulated in this pathological condition. The first type of sensing platform consists of an enzymatic sensor for the detection of lactose, one of the main components in milk. In this design, we used gold surface as an electrochemical transducer due to the several advantages, such as the variety of strategies available for its rapid and efficient functionalization with bioreceptors or capture molecules. For the second type of sensing platform, nanoporous silicon film (pSi) was chosen as the electrode material for the design of DNA sensors and aptasensors targeting miRNAs and hormones, respectively. pSi matrix offers a large superficial area with an abundance of active sites for the immobilization of bioreceptors and tunable characteristics, which increase the selectivity and specificity, making it an ideal alternative material. The analytical performance of the designed biosensors was not only characterized in buffer but also validated in minimally treated breastmilk samples. We have demonstrated the potential of an electrochemical transducer on pSi and gold surface for monitoring clinically relevant biomarkers associated with the heightened risk of low milk production in women. This approach, in which the nanofabrication techniques and the functionalization methods were optimized to increase the efficacy of the biosensor highly provided a foundation for further research and development of targeted diagnosis strategies.Keywords: biosensors, electrochemistry, early diagnosis, clinical markers, miRNAs
Procedia PDF Downloads 18584 Photovoice-Through Photographs to Feelings: Investigation of Experience Reporting in a Randomized Controlled Study
Authors: Selina Studer, Maria Kleinstäuber, Cornelia Weise
Abstract:
Background: Finding words to report what you have been through may be challenging, especially when dealing with stressful or highly emotional experiences. Photovoice (PV) represents a possible way of facilitating experience reporting. In this approach, people take photos about a particular topic (in our study: worries about the future) and talk about the topic based on the photos. So far, the benefits of Photovoice have been quantitatively insufficiently tested. There is a lack of randomized controlled trials investigating PV in comparison to other methods. This study aimed to fill this research gap. Methods: 65 participants took part in the study and were randomly assigned to the PV group, the writing group (WG), or the control group (CG). The PV group received the task to take photos of worries regarding the future for one week and send max. 5 of them to the interviewer before the interview. The WG had to write down the worries about the future and send max. 5 of them to the interviewer before the interview. The control group did not receive a specific assignment. The semi-structured interview consisted of six open-ended questions and was applied to all future worries. The questions included the content of the future worries, the meaning, and how the worry expressed itself emotionally and physically. The interview was recorded and later transcribed. After the interview, online questionnaires were filled out. They covered a range of variables such as access to emotional content, ability to describe feelings, the extent of self-disclosure, and relationship quality. Results: Contrary to our hypotheses, one-way ANOVA revealed no differences between the three conditions concerning all variables (access to emotional content, ability to describe feelings, the extent of self-disclosure, and so on), all p's > 0.14, BF₀₁ = 1.78-7.66. In a subsequent step, the words in the transcribed interviews were analyzed. The LIWC program counted how many emotional words occurred in the text and assigned them to predefined categories. Planned contrasts revealed that the PV reported more negative emotional words compared to the two groups t(62) = 2.62, p = .011, and also compared to the WG only, t(62) = 2.36, p = .022, BF₀₁ = 0.62. Conclusions and implications: The applied self-report instruments did not reveal any differences between the groups. However, the PV group used more negative emotional words than the other two groups. The discrepancy between self-report and observation variables regarding emotionality is noticeable. It is suggested that the highly educated and above-average female sample may not have needed PV to access emotional content. It is possible that the approach would yield clearer results in a clinical sample. This and other approaches are currently being investigated in a follow-up study.Keywords: photovoice, controlled randomized study, online intervention, emotional awareness, self-disclosure, data triangulation, interviews
Procedia PDF Downloads 72583 Elderly in Sub Saharan Africa
Authors: Obinna Benedict Duru
Abstract:
This study focuses on the elderly and the challenges that confront them. The elderly are that particular segment of our population who by virtue of the aging process have attained the stage in most cases where they are confronted with the challenges of economic dependency and social marginality. These challenges are as a result of the physical and biological decline occasioned by social myths and realities which portray the elderly as a dependent population whose members could not and should not work and who need social assistance that the younger population is obliged to provide. From the moment of birth to the moment of death, our bodies are constantly changing. We are all enmeshed in the process of growing old, a transition from youthfulness to elderliness. In youth-oriented modern societies like ours, we tend to attach positive importance and significance to the biological changes that occur early in life and define later physical changes in negative terms. Children growing up and young adults receive more attention, greater responsibilities and more legal rights to reward them on their way. But few people are congratulated on getting old. We commiserate with people who are getting old and make jokes about their supposedly physical, mental and biological decline. Wrinkles, loss of weight and vitality are all parts of the aging process. In almost all parts of the world, earlier researches have shown that about fifty percent of the elderly who suffer from stroke, arthritis, senility and other age related diseases are the disengaged and neglected elderly. Rapid technological changes render the knowledge and skills of the elderly obsolete; education is geared toward the young and the generational competition for jobs leads to pressures on the elderly to retire. Control of initial resources are shifted to the middle-aged and older workers are pushed into positions of economic dependency. This study therefore, among other things tend to discover how some government policies have affected the elderly particularly in Africa. To discover the prospects and possibilities of the elderly for a better living. To make a comparison of the advances in healthcare giving made in the advanced western societies to the practice in Sub Saharan Africa etc. The hypotheses of this study include: that the elderly in Sub Saharan Africa are more vulnerable than their counterparts in Europe and America. The elderly are more prone to social isolation, and that the elderly are mostly affected by age-related sickness etc. With a survey method as the research design, and sample size of about 500 respondents,probability sampling technique was used. Data which were analyzed using chi-square and tables were collected through primary and secondary sources. The findings made include: that the elderly suffer pains of old age especially when disengaged from work or social activity. That loss of income condemn the elderly to a life of vegetable existence, and that those who do not have other means of re-integration usually see old age with regret and despair. It is therefore, recommended among other things that social welfare scheme and the process of re-integration at old age be introduced for the non pensionable elderly in Africa.Keywords: elderly, social isolation, dependency, re-integration
Procedia PDF Downloads 334582 Teaching English as a Foreign Language: Insights from the Philippine Context
Authors: Arlene Villarama, Micol Grace Guanzon, Zenaida Ramos
Abstract:
This paper provides insights into teaching English as a Foreign Language in the Philippines. The authors reviewed relevant theories and literature, and provide an analysis of the issues in teaching English in the Philippine setting in the light of these theories. The authors made an investigation in Bagong Barrio National High School (BBNHS) - a public school in Caloocan City. The institution has a population of nearly 3,000 students. The performances of randomly chosen 365 respondents were scrutinised. The study regarding the success of teaching English as a foreign language to Filipino children were highlighted. This includes the respondents’ family background, surroundings, way of living, and their behavior and understanding regarding education. The results show that there is a significant relationship between demonstrative, communal, and logical areas that touch the efficacy of introducing English as a foreign Dialectal. Filipino children, by nature, are adventurous and naturally joyful even for little things. They are born with natural skills and capabilities to discover new things. They highly consider activities and work that ignite their curiosity. They love to be recognised and are inspired the most when given the assurance of acceptance and belongingness. Fun is the appealing influence to ignite and motivate learning. The magic word is excitement. The study reveals the many facets of the accumulation and transmission of erudition, in introduction and administration of English as a foreign phonological; it runs and passes through different channels of diffusion. Along the way, there are particles that act as obstructions in protocols where knowledge are to be gathered. Data gained from the respondents conceals a reality that is beyond one’s imagination. One significant factor that touches the inefficacy of understanding and using English as a foreign language is an erroneous outset gained from an old belief handed down from generation to generation. This accepted perception about the power and influence of the use of language, gives the novices either a negative or a positive notion. The investigation shows that a higher number of dislikes in the use of English can be tracked down from the belief of the story on how the English language came into existence. The belief that only the great and the influential have the right to use English as a means of communication kills the joy of acceptance. A significant notation has to be examined so as to provide a solution or if not eradicate the misconceptions that lie behind the substance of the matter. The result of the authors’ research depicts a substantial correlation between the emotional (demonstrative), social (communal), and intellectual (logical). The focus of this paper is to bring out the right notation and disclose the misconceptions with regards to teaching English as a foreign language. This will concentrate on the emotional, social, and intellectual areas of the Filipino learners and how these areas affect the transmittance and accumulation of learning. The authors’ aim is to formulate logical ways and techniques that would open up new beginnings in understanding and acceptance of the subject matter.Keywords: accumulation, behaviour, facets, misconceptions, transmittance
Procedia PDF Downloads 204581 Structural and Biochemical Characterization of Red and Green Emitting Luciferase Enzymes
Authors: Wael M. Rabeh, Cesar Carrasco-Lopez, Juliana C. Ferreira, Pance Naumov
Abstract:
Bioluminescence, the emission of light from a biological process, is found in various living organisms including bacteria, fireflies, beetles, fungus and different marine organisms. Luciferase is an enzyme that catalyzes a two steps oxidation of luciferin in the presence of Mg2+ and ATP to produce oxyluciferin and releases energy in the form of light. The luciferase assay is used in biological research and clinical applications for in vivo imaging, cell proliferation, and protein folding and secretion analysis. The luciferase enzyme consists of two domains, a large N-terminal domain (1-436 residues) that is connected to a small C-terminal domain (440-544) by a flexible loop that functions as a hinge for opening and closing the active site. The two domains are separated by a large cleft housing the active site that closes after binding the substrates, luciferin and ATP. Even though all insect luciferases catalyze the same chemical reaction and share 50% to 90% sequence homology and high structural similarity, they emit light of different colors from green at 560nm to red at 640 nm. Currently, the majority of the structural and biochemical studies have been conducted on green-emitting firefly luciferases. To address the color emission mechanism, we expressed and purified two luciferase enzymes with blue-shifted green and red emission from indigenous Brazilian species Amydetes fanestratus and Phrixothrix, respectively. The two enzymes naturally emit light of different colors and they are an excellent system to study the color-emission mechanism of luciferases, as the current proposed mechanisms are based on mutagenesis studies. Using a vapor-diffusion method and a high-throughput approach, we crystallized and solved the crystal structure of both enzymes, at 1.7 Å and 3.1 Å resolution respectively, using X-ray crystallography. The free enzyme adopted two open conformations in the crystallographic unit cell that are different from the previously characterized firefly luciferase. The blue-shifted green luciferase crystalized as a monomer similar to other luciferases reported in literature, while the red luciferases crystalized as an octamer and was also purified as an octomer in solution. The octomer conformation is the first of its kind for any insect’s luciferase, which might be relate to the red color emission. Structurally designed mutations confirmed the importance of the transition between the open and close conformations in the fine-tuning of the color and the characterization of other interesting mutants is underway.Keywords: bioluminescence, enzymology, structural biology, x-ray crystallography
Procedia PDF Downloads 326580 Indigenous Firms Out-leverage other New Zealand firms through Cultural Practices: A Mixed Methods Study
Authors: Jarrod Haar, David Brougham, Azka Ghafoor
Abstract:
Māori are the indigenous people of Aotearoa (New Zealand) and have a unique perspective called Te Ao Māori (the Māori worldview) and important cultural values around utu (reciprocation), collectivism, long-term orientation, and whanaungatanga (networking, relationships). The present research conducts two studies to better understand how Māori businesses might have similarities and differences to New Zealand businesses. In study 1, we conducted 50 interviews with 25 Māori business owners and 25 New Zealand (non-Māori) owners. For the indigenous population, we used a kaupapa Māori research approach using Māori protocols. This ensured the research is culturally safe. Interviews were conducted around semi-structured questions tapping into the existing business challenges, the role of innovation, and business values and approaches. Transcripts were analyzed using interpretative phenomenological analytic techniques. We identified several themes shared across all business owners: (1) the critical challenge around staff attraction and retention; (2) cost pressures including inflation; (3) and a focus on human resource (HR) practices to address issues including retention. Amongst the Māori businesses, the analysis also identified (4) a unique cultural approach to business relationships. Specifically, amongst the indigenous businesses we find a strong Te Ao Māori perspective amongst Māori business towards innovation. Analysis within this group only identified, within the following sub-themes: (a) whanaungatanga, around the development of strong relationships as a way to aid recruitment and retention, and business fluctuations; (b) mātauranga (knowledge) whereby Māori businesses seek to access advanced knowledge via universities; (c) taking a long-term orientation to business relationships – including with universities. The findings suggest people practices might be a way that firms address workforce retention issues, and we also acknowledge that Māori businesses might also leverage cultural practices to achieve better gains. Thus, in study 2, we survey 606 New Zealand private sector firms including 85 who self-identify as Māori Firms. We test the benefits of high-performance work-systems (HPWS), which represent bundle of human-resource practices designed to bolster workforce productivity through enhancing knowledge, skills, abilities, and commitment of the workforce. We test these on workforce retention and include Māori firm status and cultural capital (reflecting workforce knowledge around Māori cultural values) as moderators. Overall, we find all firms achieve superior workforce retention when they have high levels of HPWS, but Māori firms with high cultural capital are better able to leverage these HR practices to achieve superior workforce retention. In summary, the present study highlights how indigenous businesses in New Zealand might achieve superior performance by leveraging their unique cultural values. The study provides unique insights into established literatures around retention and HR practices and highlights the lessons around indigenous cultural values that appear to aid businesses.Keywords: Māori business, cultural values, employee retention, human resource practices
Procedia PDF Downloads 67579 In Vitro Evaluation of a Chitosan-Based Adhesive to Treat Bone Fractures
Authors: Francisco J. Cedano, Laura M. Pinzón, Camila I. Castro, Felipe Salcedo, Juan P. Casas, Juan C. Briceño
Abstract:
Complex fractures located in articular surfaces are challenging to treat and their reduction with conventional treatments could compromise the functionality of the affected limb. An adhesive material to treat those fractures is desirable for orthopedic surgeons. This adhesive must be biocompatible and have a high adhesion to bone surface in an aqueous environment. The proposed adhesive is based on chitosan, given its adhesive and biocompatibility properties. Chitosan is mixed with calcium carbonate and hydroxyapatite, which contribute to structural support and a gel like behavior, and glutaraldehyde is used as a cross-linking agent to keep the adhesive mechanical performance in aqueous environment. This work aims to evaluate the rheological, adhesion strength and biocompatibility properties of the proposed adhesive using in vitro tests. The gelification process of the adhesive was monitored by oscillatory rheometry in an ARG-2 TA Instruments rheometer, using a parallel plate geometry of 22 mm and a gap of 1 mm. Time sweep experiments were conducted at 1 Hz frequency, 1% strain and 37°C from 0 to 2400 s. Adhesion strength is measured using a butt joint test with bovine cancellous bone fragments as substrates. The test is conducted at 5 min, 20min and 24 hours after curing the adhesive under water at 37°C. Biocompatibility is evaluated by a cytotoxicity test in a fibroblast cell culture using MTT assay and SEM. Rheological results concluded that the average gelification time of the adhesive is 820±107 s, also it reaches storage modulus magnitudes up to 106 Pa; The adhesive show solid-like behavior. Butt joint test showed 28.6 ± 9.2 kPa of tensile bond strength for the adhesive cured for 24 hours. Also there was no significant difference in adhesion strength between 20 minutes and 24 hours. MTT showed 70 ± 23 % of active cells at sixth day of culture, this percentage is estimated respect to a positive control (only cells with culture medium and bovine serum). High vacuum SEM observation permitted to localize and study the morphology of fibroblasts presented in the adhesive. All captured fibroblasts presented in SEM typical flatted structure with filopodia growth attached to adhesive surface. This project reports an adhesive based on chitosan that is biocompatible due to high active cells presented in MTT test and these results were correlated using SEM. Also, it has adhesion properties in conditions that model the clinical application, and the adhesion strength do not decrease between 5 minutes and 24 hours.Keywords: bioadhesive, bone adhesive, calcium carbonate, chitosan, hydroxyapatite, glutaraldehyde
Procedia PDF Downloads 321578 Theorizing Optimal Use of Numbers and Anecdotes: The Science of Storytelling in Newsrooms
Authors: Hai L. Tran
Abstract:
When covering events and issues, the news media often employ both personal accounts as well as facts and figures. However, the process of using numbers and narratives in the newsroom is mostly operated through trial and error. There is a demonstrated need for the news industry to better understand the specific effects of storytelling and data-driven reporting on the audience as well as explanatory factors driving such effects. In the academic world, anecdotal evidence and statistical evidence have been studied in a mutually exclusive manner. Existing research tends to treat pertinent effects as though the use of one form precludes the other and as if a tradeoff is required. Meanwhile, narratives and statistical facts are often combined in various communication contexts, especially in news presentations. There is value in reconceptualizing and theorizing about both relative and collective impacts of numbers and narratives as well as the mechanism underlying such effects. The current undertaking seeks to link theory to practice by providing a complete picture of how and why people are influenced by information conveyed through quantitative and qualitative accounts. Specifically, the cognitive-experiential theory is invoked to argue that humans employ two distinct systems to process information. The rational system requires the processing of logical evidence effortful analytical cognitions, which are affect-free. Meanwhile, the experiential system is intuitive, rapid, automatic, and holistic, thereby demanding minimum cognitive resources and relating to the experience of affect. In certain situations, one system might dominate the other, but rational and experiential modes of processing operations in parallel and at the same time. As such, anecdotes and quantified facts impact audience response differently and a combination of data and narratives is more effective than either form of evidence. In addition, the present study identifies several media variables and human factors driving the effects of statistics and anecdotes. An integrative model is proposed to explain how message characteristics (modality, vividness, salience, congruency, position) and individual differences (involvement, numeracy skills, cognitive resources, cultural orientation) impact selective exposure, which in turn activates pertinent modes of processing, and thereby induces corresponding responses. The present study represents a step toward bridging theoretical frameworks from various disciplines to better understand the specific effects and the conditions under which the use of anecdotal evidence and/or statistical evidence enhances or undermines information processing. In addition to theoretical contributions, this research helps inform news professionals about the benefits and pitfalls of incorporating quantitative and qualitative accounts in reporting. It proposes a typology of possible scenarios and appropriate strategies for journalists to use when presenting news with anecdotes and numbers.Keywords: data, narrative, number, anecdote, storytelling, news
Procedia PDF Downloads 79577 Development and Validation of a Green Analytical Method for the Analysis of Daptomycin Injectable by Fourier-Transform Infrared Spectroscopy (FTIR)
Authors: Eliane G. Tótoli, Hérida Regina N. Salgado
Abstract:
Daptomycin is an important antimicrobial agent used in clinical practice nowadays, since it is very active against some Gram-positive bacteria that are particularly challenges for the medicine, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE). The importance of environmental preservation has receiving special attention since last years. Considering the evident need to protect the natural environment and the introduction of strict quality requirements regarding analytical procedures used in pharmaceutical analysis, the industries must seek environmentally friendly alternatives in relation to the analytical methods and other processes that they follow in their routine. In view of these factors, green analytical chemistry is prevalent and encouraged nowadays. In this context, infrared spectroscopy stands out. This is a method that does not use organic solvents and, although it is formally accepted for the identification of individual compounds, also allows the quantitation of substances. Considering that there are few green analytical methods described in literature for the analysis of daptomycin, the aim of this work was the development and validation of a green analytical method for the quantification of this drug in lyophilized powder for injectable solution, by Fourier-transform infrared spectroscopy (FT-IR). Method: Translucent potassium bromide pellets containing predetermined amounts of the drug were prepared and subjected to spectrophotometric analysis in the mid-infrared region. After obtaining the infrared spectrum and with the assistance of the IR Solution software, quantitative analysis was carried out in the spectral region between 1575 and 1700 cm-1, related to a carbonyl band of the daptomycin molecule, and this band had its height analyzed in terms of absorbance. The method was validated according to ICH guidelines regarding linearity, precision (repeatability and intermediate precision), accuracy and robustness. Results and discussion: The method showed to be linear (r = 0.9999), precise (RSD% < 2.0), accurate and robust, over a concentration range from 0.2 to 0.6 mg/pellet. In addition, this technique does not use organic solvents, which is one great advantage over the most common analytical methods. This fact contributes to minimize the generation of organic solvent waste by the industry and thereby reduces the impact of its activities on the environment. Conclusion: The validated method proved to be adequate to quantify daptomycin in lyophilized powder for injectable solution and can be used for its routine analysis in quality control. In addition, the proposed method is environmentally friendly, which is in line with the global trend.Keywords: daptomycin, Fourier-transform infrared spectroscopy, green analytical chemistry, quality control, spectrometry in IR region
Procedia PDF Downloads 381576 Deep Learning for Image Correction in Sparse-View Computed Tomography
Authors: Shubham Gogri, Lucia Florescu
Abstract:
Medical diagnosis and radiotherapy treatment planning using Computed Tomography (CT) rely on the quantitative accuracy and quality of the CT images. At the same time, requirements for CT imaging include reducing the radiation dose exposure to patients and minimizing scanning time. A solution to this is the sparse-view CT technique, based on a reduced number of projection views. This, however, introduces a new problem— the incomplete projection data results in lower quality of the reconstructed images. To tackle this issue, deep learning methods have been applied to enhance the quality of the sparse-view CT images. A first approach involved employing Mir-Net, a dedicated deep neural network designed for image enhancement. This showed promise, utilizing an intricate architecture comprising encoder and decoder networks, along with the incorporation of the Charbonnier Loss. However, this approach was computationally demanding. Subsequently, a specialized Generative Adversarial Network (GAN) architecture, rooted in the Pix2Pix framework, was implemented. This GAN framework involves a U-Net-based Generator and a Discriminator based on Convolutional Neural Networks. To bolster the GAN's performance, both Charbonnier and Wasserstein loss functions were introduced, collectively focusing on capturing minute details while ensuring training stability. The integration of the perceptual loss, calculated based on feature vectors extracted from the VGG16 network pretrained on the ImageNet dataset, further enhanced the network's ability to synthesize relevant images. A series of comprehensive experiments with clinical CT data were conducted, exploring various GAN loss functions, including Wasserstein, Charbonnier, and perceptual loss. The outcomes demonstrated significant image quality improvements, confirmed through pertinent metrics such as Peak Signal-to-Noise Ratio (PSNR) and Structural Similarity Index (SSIM) between the corrected images and the ground truth. Furthermore, learning curves and qualitative comparisons added evidence of the enhanced image quality and the network's increased stability, while preserving pixel value intensity. The experiments underscored the potential of deep learning frameworks in enhancing the visual interpretation of CT scans, achieving outcomes with SSIM values close to one and PSNR values reaching up to 76.Keywords: generative adversarial networks, sparse view computed tomography, CT image correction, Mir-Net
Procedia PDF Downloads 162575 Vitamin D Levels of Patients with Rheumatoid Arthritis in Kosova
Authors: Mjellma Rexhepi, Blerta Rexhepi Kelmendi, Blana Krasniqi, Shaip Krasniqi
Abstract:
Rheumatoid arthritis is a chronic disease that causes inflammation of the joints which can be so severe that can cause not only deformities but also impairment of function that limits movement. This also contributes to the pain that accompanies this disease. This remains a problematic and challenging disease of modern medicine because treatment is still symptomatic. The main purpose of drug treatment is to reduce the activity of the disease, achieve remission, avoid disability and death. The etiology of the disease is idiopathic, but can also be linked to genetic, nongenetic factors such as hormonal, environmental or infectious. Current scientific evidence shows that vitamin D plays an important role in immune regulation mechanisms. Lack of this vitamin has been linked to loss of immune tolerance and the appearance of autoimmune processes, including rheumatoid arthritis. The purpose of the work was to define Vitamin D in patients hospitalized with rheumatoid arthritis in University Clinical Center of Kosova, as a basis of their connection with lifestyle and physical inactivity. The sample for the work was selected from patients with criteria met for rheumatoid arthritis who were hospitalized at the tertiary level of health care in Kosova. During the work have been investigated 100 consecutive patients fulfilling diagnostic criteria for rheumatoid arthritis, whereas in addition to the general characteristics are also determined the values of vitamin D at the beginning of hospitalization. The average age of the sample analyzed was 50.9±5.7 years old, with an average duration of rheumatoid arthritis disease 7.8±3.4 years. At the beginning of hospitalization, before treatment was initiated, the average value of vitamin D was 15.86±3.43, which according to current reference values is classified into the category of insufficient values. Correlating the duration of the disease, from the time of diagnosis to the day of hospitalization, on one side and the level of vitamin D on the other side, the negative correlation of a lower degree derived (r =-0.1). Physical activity affects the concentration of vitamin D in the blood through increased metabolism of fat and the release of vitamin D and its metabolites from adipose tissue. To now it is evident that physical activity is also accompanied by higher levels of vitamin D. In patients with rheumatoid arthritis, vitamin D levels were low compared to normal. Future works should be oriented toward investigating in detail the bone structure, quality of life and pain in patients with rheumatoid arthritis. More detailed scientific projects, with larger numbers of participants, should be designed for the future to clarify more possible mechanisms as factors related to this phenomenon such as inactivity, lifestyle and the duration of the disease, as well as the importance of keeping vitamin D values at normal limits.Keywords: hospitalization, lifestyle, rheumatoid arthritis, vitamin D
Procedia PDF Downloads 15574 Theta-Phase Gamma-Amplitude Coupling as a Neurophysiological Marker in Neuroleptic-Naive Schizophrenia
Authors: Jun Won Kim
Abstract:
Objective: Theta-phase gamma-amplitude coupling (TGC) was used as a novel evidence-based tool to reflect the dysfunctional cortico-thalamic interaction in patients with schizophrenia. However, to our best knowledge, no studies have reported the diagnostic utility of the TGC in the resting-state electroencephalographic (EEG) of neuroleptic-naive patients with schizophrenia compared to healthy controls. Thus, the purpose of this EEG study was to understand the underlying mechanisms in patients with schizophrenia by comparing the TGC at rest between two groups and to evaluate the diagnostic utility of TGC. Method: The subjects included 90 patients with schizophrenia and 90 healthy controls. All patients were diagnosed with schizophrenia according to the criteria of Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) by two independent psychiatrists using semi-structured clinical interviews. Because patients were either drug-naïve (first episode) or had not been taking psychoactive drugs for one month before the study, we could exclude the influence of medications. Five frequency bands were defined for spectral analyses: delta (1–4 Hz), theta (4–8 Hz), slow alpha (8–10 Hz), fast alpha (10–13.5 Hz), beta (13.5–30 Hz), and gamma (30-80 Hz). The spectral power of the EEG data was calculated with fast Fourier Transformation using the 'spectrogram.m' function of the signal processing toolbox in Matlab. An analysis of covariance (ANCOVA) was performed to compare the TGC results between the groups, which were adjusted using a Bonferroni correction (P < 0.05/19 = 0.0026). Receiver operator characteristic (ROC) analysis was conducted to examine the discriminating ability of the TGC data for schizophrenia diagnosis. Results: The patients with schizophrenia showed a significant increase in the resting-state TGC at all electrodes. The delta, theta, slow alpha, fast alpha, and beta powers showed low accuracies of 62.2%, 58.4%, 56.9%, 60.9%, and 59.0%, respectively, in discriminating the patients with schizophrenia from the healthy controls. The ROC analysis performed on the TGC data generated the most accurate result among the EEG measures, displaying an overall classification accuracy of 92.5%. Conclusion: As TGC includes phase, which contains information about neuronal interactions from the EEG recording, TGC is expected to be useful for understanding the mechanisms the dysfunctional cortico-thalamic interaction in patients with schizophrenia. The resting-state TGC value was increased in the patients with schizophrenia compared to that in the healthy controls and had a higher discriminating ability than the other parameters. These findings may be related to the compensatory hyper-arousal patterns of the dysfunctional default-mode network (DMN) in schizophrenia. Further research exploring the association between TGC and medical or psychiatric conditions that may confound EEG signals will help clarify the potential utility of TGC.Keywords: quantitative electroencephalography (QEEG), theta-phase gamma-amplitude coupling (TGC), schizophrenia, diagnostic utility
Procedia PDF Downloads 143573 The Effect of Teachers' Personal Values on the Perceptions of the Effective Principal and Student in School
Authors: Alexander Zibenberg, Rima’a Da’As
Abstract:
According to the author’s knowledge, individuals are naturally inclined to classify people as leaders and followers. Individuals utilize cognitive structures or prototypes specifying the traits and abilities that characterize the effective leader (implicit leadership theories) and effective follower in an organization (implicit followership theories). Thus, the present study offers insights into understanding how teachers' personal values (self-enhancement and self-transcendence) explain the preference for styles of effective leader (i.e., principal) and assumptions about the traits and behaviors that characterize effective followers (i.e., student). Beyond the direct effect on perceptions of effective types of leader and follower, the present study argues that values may also interact with organizational and personal contexts in influencing perceptions. Thus authors suggest that teachers' managerial position may moderate the relationships between personal values and perception of the effective leader and follower. Specifically, two key questions are addressed in the present research: (1) Is there a relationship between personal values and perceptions of the effective leader and effective follower? and (2) Are these relationships stable or could they change across different contexts? Two hundred fifty-five Israeli teachers participated in this study, completing questionnaires – about the effective student and effective principal. Results of structural equations modeling (SEM) with maximum likelihood estimation showed: first: the model fit the data well. Second: researchers found a positive relationship between self-enhancement and anti-prototype of the effective principal and anti-prototype of the effective student. The relationship between self-transcendence value and both perceptions were found significant as well. Self-transcendence positively related to the way the teacher perceives the prototype of the effective principal and effective student. Besides, authors found that teachers' managerial position moderates these relationships. The article contributes to the literature both on perceptions and on personal values. Although several earlier studies explored issues of implicit leadership theories and implicit followership theories, personality characteristics (values) have garnered less attention in this matter. This study shows that personal values which are deeply rooted, abstract motivations that guide justify or explain attitudes, norms, opinions and actions explain differences in perception of the effective leader and follower. The results advance the theoretical understanding of the relationship between personal values and individuals’ perceptions in organizations. An additional contribution of this study is the application of the teacher's managerial position to explain a potential boundary condition of the translation of personal values into outcomes. The findings suggest that through the management process in the organization, teachers acquire knowledge and skills which augment their ability (beyond their personal values) to predict perceptions of ideal types of principal and student. The study elucidates the unique role of personal values in understanding an organizational thinking in organization. It seems that personal values might explain the differences in individual preferences of the organizational paradigm (mechanistic vs organic).Keywords: implicit leadership theories, implicit followership theories, organizational paradigms, personal values
Procedia PDF Downloads 157572 Effects of Cranberry Juice Enriched with n-3 PUFA Consumption in Adjunct with Non-Surgical Periodontal Therapy on Glycemic Control, Antioxidant Status and Periodontal indices in Type 2 Diabetes Patients with Periodontitis
Authors: A. Zare Javid, H. Babaee, E. Ashrafzadeh, H. Yousefimanesh, M. Zakerkish, K. Ahmadi Angali, M. Ravanbakhsh
Abstract:
Introduction: Type 2 diabetes mellitus and periodontal disease hold a physiologically relationship. Periodontal disease, a common widespread chronic disease, is considered as an important complication in diabetes mellitus. The prevalence and severity of periodontal disease are increased among diabetic patients. A balanced nutrition may improve either diabetes or periodontal disease by controlling one of them. The aim of this study was to evaluate the effects of cranberry juice enriched with n-3 PUFA and their individual consumption on glycemic control and antioxidant status in diabetic patients with periodontal disease. Methods: In this randomized clinical trial 41 diabetic patients (35 – 65 y) with chronic adult periodontal disease were recruited from Endocrinology Clinic of Golestan Hospital in Ahvaz city, Iran. Subjects were randomly assigned to four groups as follow: one control group (n=12) and three intervention groups as receiving 1 g n-3 PUFA capsule (n=10), 400 ml cranberry juice (n=9), 400 ml cranberry juice enriched with 1g n-3 PUFA (n=10) for 8 weeks. Non-surgical periodontal therapy was provided for all patients during study. Fasting blood glucose, glycated hemoglobin, plasma and saliva TAOC and MDA, pocket depth and bleeding on probing were measured at baseline and post intervention. Results: There was a significant reduction in glycated hemoglobin observed in intervention groups of receiving n-3 PUFA and cranberry enriched with n-3 PUFA (11 %, P = 0.01 and 7 %, P = 0.01, respectively). The intervention group receiving n-3 PUFA had significantly lower glycated hemoglobin compared with control group. There was no significant difference found in FBS between and within groups. Furthermore, there was a significant increase in plasma TAOC only in cranberry enriched with n-3 PUFA group. Moreover, plasma MDA significantly decreased in intervention groups of receiving cranberry and cranberry enriched with n-3 PUFA. A significant increase was observed in TAOC of salvia in cranberry enriched with n-3 PUFA group compared to control group .The intervention group receiving cranberry enriched with n-3 PUFA had significantly lower MDA of salvia compared with control group. Pocket depth were significantly decreased in all groups, however, bleeding on probing didn’t significantly changed in patients post intervention. Conclusion: It is suggested that consumption of cranberry juice enriched with n-3 PUFA as a nutritional approach in adjunct with non-surgical periodontal therapy may help to improve glycosylated hemogolobin and TAOC in salvia and plasma in diabetic patients with periodontal disease.Keywords: antioxidant, cranberry, oxidant status, periodontal disease, type 2 diabetes mellitus
Procedia PDF Downloads 424571 Change of Education Business in the Age of 5G
Authors: Heikki Ruohomaa, Vesa Salminen
Abstract:
Regions are facing huge competition to attract companies, businesses, inhabitants, students, etc. This way to improve living and business environment, which is rapidly changing due to digitalization. On the other hand, from the industry's point of view, the availability of a skilled labor force and an innovative environment are crucial factors. In this context, qualified staff has been seen to utilize the opportunities of digitalization and respond to the needs of future skills. World Manufacturing Forum has stated in the year 2019- report that in next five years, 40% of workers have to change their core competencies. Through digital transformation, new technologies like cloud, mobile, big data, 5G- infrastructure, platform- technology, data- analysis, and social networks with increasing intelligence and automation, enterprises can capitalize on new opportunities and optimize existing operations to achieve significant business improvement. Digitalization will be an important part of the everyday life of citizens and present in the working day of the average citizen and employee in the future. For that reason, the education system and education programs on all levels of education from diaper age to doctorate have been directed to fulfill this ecosystem strategy. Goal: The Fourth Industrial Revolution will bring unprecedented change to societies, education organizations and business environments. This article aims to identify how education, education content, the way education has proceeded, and overall whole the education business is changing. Most important is how we should respond to this inevitable co- evolution. Methodology: The study aims to verify how the learning process is boosted by new digital content, new learning software and tools, and customer-oriented learning environments. The change of education programs and individual education modules can be supported by applied research projects. You can use them in making proof- of- the concept of new technology, new ways to teach and train, and through the experiences gathered change education content, way to educate and finally education business as a whole. Major findings: Applied research projects can prove the concept- phases on real environment field labs to test technology opportunities and new tools for training purposes. Customer-oriented applied research projects are also excellent for students to make assignments and use new knowledge and content and teachers to test new tools and create new ways to educate. New content and problem-based learning are used in future education modules. This article introduces some case study experiences on customer-oriented digital transformation projects and how gathered knowledge on new digital content and a new way to educate has influenced education. The case study is related to experiences of research projects, customer-oriented field labs/learning environments and education programs of Häme University of Applied Sciences.Keywords: education process, digitalization content, digital tools for education, learning environments, transdisciplinary co-operation
Procedia PDF Downloads 176570 Additional Pathological Findings Using MRI on Patients with First Time Traumatic Lateral Patella Dislocation: A Study of 150 Patients
Authors: Ophir Segal, Daniel Weltsch, Shay Tenenbaum, Ran Thein
Abstract:
Purpose: Patients with lateral patellar dislocation (LPD) are not always referred to perform an MRI. This might be the case in first time LPD patients without surgical indications or in patients with recurrent LPD who had MRI in previous episodes. Unfortunately, in some cases, there are additional knee pathological findings, which include tearing of the collateral or cruciate ligaments and injury to the tendons or menisci. These findings might be overlooked during the physical examination or masked by nonspecific clinical findings like knee pain, effusion, or hemarthrosis. The prevalence of these findings, which can be revealed by MRI, is misreported in literature and is considered rare. In our practice, all patients with LPD are sent for MRI after LPD. Therefore, we have designed a retrospective comparative study to evaluate the prevalence of additional pathological findings in patients with acute traumatic LPD that had performed MRI, comparing different groups of patients according to age, sex, and Tibial Tuberosity-Trochlear Groove(TT-TG) distance. Methods: MRI of the knee in patients after traumatic LPD were evaluated for the presence of additional pathological findings such as injuries to ligaments: Anterior/Posterior cruciate ligament(ACL, PCL), Medial/Lateral collateral ligament(MCL, LCL), injuries to tendons(QUADICEPS, PATELLAR), menisci(Medial/Lateral meniscus(MM, LM)) and tibial plateau, by a fellowship-trained, senior musculoskeletal radiologist. A comparison between different groups of patients was performed according to age (age group < 25 years, age group > 25 years), sex (Male/Female group), and TT-TG distance (TT-TG<15 groups, TT-TG>15 groups). A descriptive and comparative statistical analysis was performed. Results: 150 patients were included in this study. All suffered from LPD between the years 2012-2017 (mean age 21.3( ± SD 8.9), 86 males). ACL, PCL, MCL, and LCL complete or partial tears were found in 17(11.3%), 3(2%), 22(14.6%), and 4(2.7%) of the patients, respectively. MM and LM tears were found in 10(6.7%) and 3(2%) of the patients, respectively. A higher prevalence of PCL injury, MM tear, and LM tear were found in the older age group compared to the younger group of patients (10.5% vs. 1.8%, 18.4% vs. 2.7%, and 7.9% vs. 0%, respectively, p<0.05). A higher prevalence of non-displaced MM tear and LCL injury was found in the male group compared to the female group (8.1% vs. 0% and 8.1% vs. 0% respectively, p<0.05). A higher prevalence of ACL injury was found in the normal TT-TG group compared to the pathologic TT-TG group (17.5% vs. 2.3%, p= 0.0184). Conclusions: Overall, 43 out of 150 (28.7%) of the patient's MRI’s were positive for additional pathological radiological findings. Interestingly, a higher prevalence of additional pathologies was found in the groups of patients with a lower risk for recurrent LPD, including males, patients older than 25, and patients with TT-TG lower than 15mm, and therefore might not be referred for an MRI scan. Thus, we recommend a strict physical examination, awareness to the high prevalence of additional pathological findings, and to consider performing an MRI in all patients after LPD.Keywords: additional findings, lateral patellar dislocation (LPD), MRI scan, traumatic patellar dislocation, cruciate ligaments injuries, menisci injuries, collateral ligaments injuries
Procedia PDF Downloads 146569 Fibrin Glue Reinforcement of Choledochotomy Closure Suture Line for Prevention of Bile Leak in Patients Undergoing Laparoscopic Common Bile Duct Exploration with Primary Closure: A Pilot Study
Authors: Rahul Jain, Jagdish Chander, Anish Gupta
Abstract:
Introduction: Laparoscopic common bile duct exploration (LCBDE) allows cholecystectomy and the removal of common bile duct (CBD) stones to be performed during the same sitting, thereby decreasing hospital stay. CBD exploration through choledochotomy can be closed primarily with an absorbable suture material, but can lead to biliary leakage postoperatively. In this study we tried to find a solution to further lower the incidence of bile leakage by using fibrin glue to reinforce the sutures put on choledochotomy suture line. It has haemostatic and sealing action, through strengthening the last step of the physiological coagulation and biostimulation, which favours the formation of new tissue matrix. Methodology: This study was conducted at a tertiary care teaching hospital in New Delhi, India, from 2011 to 2013. 20 patients with CBD stones documented on MRCP with CBD diameter of 9 mm or more were included in this study. Patients were randomized into two groups namely Group A in which choledochotomy was closed with polyglactin 4-0 suture and suture line reinforced with fibrin glue, and Group ‘B’ in which choledochotomy was closed with polyglactin 4-0 suture alone. Both the groups were evaluated and compared on clinical parameters such as operative time, drain content, drain output, no. of days drain was required, blood loss & transfusion requirements, length of postoperative hospital stay and conversion to open surgery. Results: The operative time for Group A ranged from 60 to 210 min (mean 131.50 min) and Group B 65 to 300 min (mean 140 minutes). The blood loss in group A ranged from 10 to 120 ml (mean 51.50 ml), in group B it ranged from 10 to 200 ml (mean 53.50 ml). In Group A, there was no case of bile leak but there was bile leak in 2 cases in Group B, minimum 0 and maximum 900 ml with a mean of 97 ml and p value of 0.147 with no statistically significant difference in bile leak in test and control groups. The minimum and maximum serous drainage in Group A was nil & 80 ml (mean 11 ml) and in Group B was nil & 270 ml (mean 72.50 ml). The p value came as 0.028 which is statistically significant. Thus serous leakage in Group A was significantly less than in Group B. The drains in Group A were removed from 2 to 4 days (mean: 3 days) while in Group B from 2 to 9 days (mean: 3.9 days). The patients in Group A stayed in hospital post operatively from 3 to 8 days (mean: 5.30) while in Group B it ranged from 3 to 10 days with a mean of 5 days. Conclusion: Fibrin glue application on CBD decreases bile leakage but in statistically insignificant manner. Fibrin glue application on CBD can significantly decrease post operative serous drainage after LCBDE. Fibrin glue application on CBD is safe and easy technique without any significant adverse effects and can help less experienced surgeons performing LCBDE.Keywords: bile leak, fibrin glue, LCBDE, serous leak
Procedia PDF Downloads 215568 Clinical Efficacy and Tolerability of Dropsordry™ in Spanish Perimenopausal Women with Urgency Urinary Incontinence (UUI)
Authors: J. A. Marañón, L. Lozano C. De Los Santos, L. Martínez-Campesino, E. Caballero-Garrido, F. Galán-Estella
Abstract:
Urinary incontinence (UI) is a significant health problem with considerable social and economic impact. An estimated 30% of women aged 30 to 60 years old have urinary incontinence (UI), while more than 50% of community-dwelling older women have the condition. Stress urinary incontinence and overactive bladder are the common types of incontinence The prevalence of stress and mixed (stress and urge) incontinence is higher than urge incontinence, but the latter is more likely to require treatment. In women, moderate and severe have a prevalence ranging from about 12% to 17% The objectives of this study was to examine the effect of the supplementation of tablets containing Dropsordry in women with urge urinary incontinence (UUI). Dropsordry is a novel active containing phytoestrogens from SOLGEN, the high genistin soy bean extract and pyrogallol plus polyphenols from standarized pumpkin seed extract,. The study was a single-center, not randomiized open prospective, study. 28 women with urinary incontinence ≥45 years were enrolled in this study (45-62 y. old age . Mean 52 y old). Items related to UI symptoms, were previously collected (T0) and these ítems were reviewed at the final of the study – 8 weeks. (T2). The presence of UI was previously diagnosed using the International Continence Society standards (ICS). Relationships between presence of UI and potential related factors as diabetes were also explored. Daily urinary test control was performed during the 8 weeks of treatment. Daily dosage was 1 g/ day (500 mg twice per day) from 0 to 4 week (T1), following a 500 mg/day daily intake from 4 to 8 week (T2). After eight weeks of treatment, the urgency grade score was reduced a 24,7%. The total urge episodes was reduced a 46%. Surprisingly there was no a significant change in daytime urinations (< 5%), however nocturia was reduced a 69,35%. Strenght Urinary Incontinence (SUI) was also tested showing a remarkably 52,17% reduction. Moreover the use of daily pantyliners was reduced a 66,25%. In addition, it was performed a panel test survey with quests when subjects of the study were enrolled (T0) and the same quests was performed after 8 weeks of supplementation (T2). 100% of the enrolled women fullfilled the ICIQ-SF quest (Spanish versión) and they were also questioned about the effects they noticed in response to taking the supplement and the change in quality of life. Interestingly no side effects were reported. There was a 96,2% of subjective satisfaction and a 85,8% objective score in the improvement of quality of life. CONCLUSION: the combination of High genistin isoflavones and pumpkin seed pyrogallol in Dropsordry tablets seems to be a safe and highly effective supplementation for the relieve of the urinary incontinence symptoms and a better quality of life in perimenopause women .Keywords: isoflavones, pumpkin, menopause, incontinence, genistin
Procedia PDF Downloads 405567 Production of Recombinant Human Serum Albumin in Escherichia coli: A Crucial Biomolecule for Biotechnological and Healthcare Applications
Authors: Ashima Sharma, Tapan K. Chaudhuri
Abstract:
Human Serum Albumin (HSA) is one of the most demanded therapeutic protein with immense biotechnological applications. The current source of HSA is human blood plasma. Blood is a limited and an unsafe source as it possesses the risk of contamination by various blood derived pathogens. This issue led to exploitation of various hosts with the aim to obtain an alternative source for the production of the rHSA. But, till now no host has been proven to be effective commercially for rHSA production because of their respective limitations. Thus, there exists an indispensable need to promote non-animal derived rHSA production. Of all the host systems, Escherichia coli is one of the most convenient hosts which has contributed in the production of more than 30% of the FDA approved recombinant pharmaceuticals. E. coli grows rapidly and its culture reaches high cell density using inexpensive and simple substrates. The fermentation batch turnaround number for E. coli culture is 300 per year, which is far greater than any of the host systems available. Therefore, E. coli derived recombinant products have more economical potential as fermentation processes are cheaper compared to the other expression hosts available. Despite of all the mentioned advantages, E. coli had not been successfully adopted as a host for rHSA production. The major bottleneck in exploiting E. coli as a host for rHSA production was aggregation i.e. majority of the expressed recombinant protein was forming inclusion bodies (more than 90% of the total expressed rHSA) in the E. coli cytosol. Recovery of functional rHSA form inclusion body is not preferred because it is tedious, time consuming, laborious and expensive. Because of this limitation, E. coli host system was neglected for rHSA production for last few decades. Considering the advantages of E. coli as a host, the present work has targeted E. coli as an alternate host for rHSA production through resolving the major issue of inclusion body formation associated with it. In the present study, we have developed a novel and innovative method for enhanced soluble and functional production of rHSA in E.coli (~60% of the total expressed rHSA in the soluble fraction) through modulation of the cellular growth, folding and environmental parameters, thereby leading to significantly improved and enhanced -expression levels as well as the functional and soluble proportion of the total expressed rHSA in the cytosolic fraction of the host. Therefore, in the present case we have filled in the gap in the literature, by exploiting the most well studied host system Escherichia coli which is of low cost, fast growing, scalable and ‘yet neglected’, for the enhancement of functional production of HSA- one of the most crucial biomolecule for clinical and biotechnological applications.Keywords: enhanced functional production of rHSA in E. coli, recombinant human serum albumin, recombinant protein expression, recombinant protein processing
Procedia PDF Downloads 347566 The Lived Experiences and Coping Strategies of Women with Attention Deficit and Hyperactivity Disorder (ADHD)
Authors: Oli Sophie Meredith, Jacquelyn Osborne, Sarah Verdon, Jane Frawley
Abstract:
PROJECT OVERVIEW AND BACKGROUND: Over one million Australians are affected by ADHD at an economic and social cost of over $20 billion per annum. Despite health outcomes being significantly worse compared with men, women have historically been overlooked in ADHD diagnosis and treatment. While research suggests physical activity and other non-prescription options can help with ADHD symptoms, the frontline response to ADHD remains expensive stimulant medications that can have adverse side effects. By interviewing women with ADHD, this research will examine women’s self-directed approaches to managing symptoms, including alternatives to prescription medications. It will investigate barriers and affordances to potentially helpful approaches and identify any concerning strategies pursued in lieu of diagnosis. SIGNIFICANCE AND INNOVATION: Despite the economic and societal impact of ADHD on women, research investigating how women manage their symptoms is scant. This project is significant because although women’s ADHD symptoms are markedly different to those of men, mainstream treatment has been based on the experiences of men. Further, it is thought that in developing nuanced coping strategies, women may have masked their symptoms. Thus, this project will highlight strategies which women deem effective in ‘thriving’ rather than just ‘hiding’. By investigating the health service use, self-care and physical activity of women with ADHD, this research aligns with a priority research areas as identified by the November 2023 senate ADHD inquiry report. APPROACH AND METHODS: Semi-structured interviews will be conducted with up to 20 women with ADHD. Interviews will be conducted in person and online to capture experience across rural and metropolitan Australia. Participants will be recruited in partnership with the peak representative body, ADHD Australia. The research will use an intersectional framework, and data will be analysed thematically. This project is led by an interdisciplinary and cross-institutional team of women with ADHD. Reflexive interviewing skills will be employed to help interviewees feel more comfortable disclosing their experiences, especially where they share common ground ENGAGEMENT, IMPACT AND BENEFIT: This research will benefit women with ADHD by increasing knowledge of strategies and alternative treatments to prescription medications, reducing the social and economic burden of ADHD on Australia and on individuals. It will also benefit women by identifying risks involved with some self-directed approaches in lieu of medical advice. The project has an accessible impact plan to directly benefit end-users, which includes the development of a podcast and a PDF resource translating findings. The resources will reach a wide audience through ADHD Australia’s extensive national networks. We will collaborate with Charles Sturt’s Accessibility and Inclusion Division of Safety, Security and Well-being to create a targeted resource for students with ADHD.Keywords: ADHD, women's health, self-directed strategies, health service use, physical activity, public health
Procedia PDF Downloads 72565 Multi-Dimensional (Quantatative and Qualatative) Longitudinal Research Methods for Biomedical Research of Post-COVID-19 (“Long Covid”) Symptoms
Authors: Steven G. Sclan
Abstract:
Background: Since December 2019, the world has been afflicted by the spread of the Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2), which is responsible for the condition referred to as Covid-19. The illness has had a cataclysmic impact on the political, social, economic, and overall well-being of the population of the entire globe. While Covid-19 has had a substantial universal fatality impact, it may have an even greater effect on the socioeconomic, medical well-being, and healthcare planning for remaining societies. Significance: As these numbers illustrate, many more persons survive the infection than die from it, and many of those patients have noted ongoing, persistent symptoms after successfully enduring the acute phase of the illness. Recognition and understanding of these symptoms are crucial for developing and arranging efficacious models of care for all patients (whether or not having been hospitalized) surviving acute covid illness and plagued by post-acute symptoms. Furthermore, regarding Covid infection in children (< 18 y/o), although it may be that Covid “+” children are not major vectors of infective transmission, it now appears that many more children than initially thought are carrying the virus without accompanying obvious symptomatic expression. It seems reasonable to wonder whether viral effects occur in children – those children who are Covid “+” and now asymptomatic – and if, over time, they might also experience similar symptoms. An even more significant question is whether Covid “+” asymptomatic children might manifest increased multiple health problems as they grow – i.e., developmental complications (e.g., physical/medical, metabolic, neurobehavioral, etc.) – in comparison to children who had been consistently Covid “ - ” during the pandemic. Topics Addressed and Theoretical Importance: This review is important because of the description of both quantitative and qualitative methods for clinical and biomedical research. Topics reviewed will consider the importance of well-designed, comprehensive (i.e., quantitative and qualitative methods) longitudinal studies of Post Covid-19 symptoms in both adults and children. Also reviewed will be general characteristics of longitudinal studies and a presentation of a model for a proposed study. Also discussed will be the benefit of longitudinal studies for the development of efficacious interventions and for the establishment of cogent, practical, and efficacious community healthcare service planning for post-acute covid patients. Conclusion: Results of multi-dimensional, longitudinal studies will have important theoretical implications. These studies will help to improve our understanding of the pathophysiology of long COVID and will aid in the identification of potential targets for treatment. Such studies can also provide valuable insights into the long-term impact of COVID-19 on public health and socioeconomics.Keywords: COVID-19, post-COVID-19, long COVID, longitudinal research, quantitative research, qualitative research
Procedia PDF Downloads 59564 Prenatal Genetic Screening and Counselling Competency Challenges of Nurse-Midwife
Authors: Girija Madhavanprabhakaran, Frincy Franacis, Sheeba Elizabeth John
Abstract:
Introduction: A wide range of prenatal genetic screening is introduced with increasing incidences of congenital anomalies even in low-risk pregnancies and is an emerging standard of care. Being frontline caretakers, the role and responsibilities of nurses and midwives are critical as they are working along with couples to provide evidence-based supportive educative care. The increasing genetic disorders and advances in prenatal genetic screening with limited genetic counselling facilities urge nurses and midwifery nurses with essential competencies to help couples to take informed decision. Objective: This integrative literature review aimed to explore nurse midwives’ knowledge and role in prenatal screening and genetic counselling competency and the challenges faced by them to cater to all pregnant women to empower their autonomy in decision making and ensuring psychological comfort. Method: An electronic search using keywords prenatal screening, genetic counselling, prenatal counselling, nurse midwife, nursing education, genetics, and genomics were done in the PUBMED, SCOPUS and Medline, Google Scholar. Finally, based on inclusion criteria, 8 relevant articles were included. Results: The main review results suggest that nurses and midwives lack essential support, knowledge, or confidence to be able to provide genetic counselling and help the couples ethically to ensure client autonomy and decision making. The majority of nurses and midwives reported inadequate levels of knowledge on genetic screening and their roles in obtaining family history, pedigrees, and providing genetic information for an affected client or high-risk families. The deficiency of well-recognized and influential clinical academic midwives in midwifery practice is also reported. Evidence recommended to update and provide sound educational training to improve nurse-midwife competence and confidence. Conclusion: Overcoming the challenges to achieving informed choices about fetal anomaly screening globally is a major concern. Lack of adequate knowledge and counselling competency, communication insufficiency, need for education and policy are major areas to address. Prenatal nurses' and midwives’ knowledge on prenatal genetic screening and essential counselling competencies can ensure services to the majority of pregnant women around the globe to be better-informed decision-makers and enhances their autonomy, and reduces ethical dilemmas.Keywords: challenges, genetic counselling, prenatal screening, prenatal counselling
Procedia PDF Downloads 200563 The Diagnostic Utility and Sensitivity of the Xpert® MTB/RIF Assay in Diagnosing Mycobacterium tuberculosis in Bone Marrow Aspirate Specimens
Authors: Nadhiya N. Subramony, Jenifer Vaughan, Lesley E. Scott
Abstract:
In South Africa, the World Health Organisation estimated 454000 new cases of Mycobacterium tuberculosis (M.tb) infection (MTB) in 2015. Disseminated tuberculosis arises from the haematogenous spread and seeding of the bacilli in extrapulmonary sites. The gold standard for the detection of MTB in bone marrow is TB culture which has an average turnaround time of 6 weeks. Histological examinations of trephine biopsies to diagnose MTB also have a time delay owing mainly to the 5-7 day processing period prior to microscopic examination. Adding to the diagnostic delay is the non-specific nature of granulomatous inflammation which is the hallmark of MTB involvement of the bone marrow. A Ziehl-Neelson stain (which highlights acid-fast bacilli) is therefore mandatory to confirm the diagnosis but can take up to 3 days for processing and evaluation. Owing to this delay in diagnosis, many patients are lost to follow up or remain untreated whilst results are awaited, thus encouraging the spread of undiagnosed TB. The Xpert® MTB/RIF (Cepheid, Sunnyvale, CA) is the molecular test used in the South African national TB program as the initial diagnostic test for pulmonary TB. This study investigates the optimisation and performance of the Xpert® MTB/RIF on bone marrow aspirate specimens (BMA), a first since the introduction of the assay in the diagnosis of extrapulmonary TB. BMA received for immunophenotypic analysis as part of the investigation into disseminated MTB or in the evaluation of cytopenias in immunocompromised patients were used. Processing BMA on the Xpert® MTB/RIF was optimised to ensure bone marrow in EDTA and heparin did not inhibit the PCR reaction. Inactivated M.tb was spiked into the clinical bone marrow specimen and distilled water (as a control). A volume of 500mcl and an incubation time of 15 minutes with sample reagent were investigated as the processing protocol. A total of 135 BMA specimens had sufficient residual volume for Xpert® MTB/RIF testing however 22 specimens (16.3%) were not included in the final statistical analysis as an adequate trephine biopsy and/or TB culture was not available. Xpert® MTB/RIF testing was not affected by BMA material in the presence of heparin or EDTA, but the overall detection of MTB in BMA was low compared to histology and culture. Sensitivity of the Xpert® MTB/RIF compared to both histology and culture was 8.7% (95% confidence interval (CI): 1.07-28.04%) and sensitivity compared to histology only was 11.1% (95% CI: 1.38-34.7%). Specificity of the Xpert® MTB/RIF was 98.9% (95% CI: 93.9-99.7%). Although the Xpert® MTB/RIF generates a faster result than histology and TB culture and is less expensive than culture and drug susceptibility testing, the low sensitivity of the Xpert® MTB/RIF precludes its use for the diagnosis of MTB in bone marrow aspirate specimens and warrants alternative/additional testing to optimise the assay.Keywords: bone marrow aspirate , extrapulmonary TB, low sensitivity, Xpert® MTB/RIF
Procedia PDF Downloads 172562 Prediction of Live Birth in a Matched Cohort of Elective Single Embryo Transfers
Authors: Mohsen Bahrami, Banafsheh Nikmehr, Yueqiang Song, Anuradha Koduru, Ayse K. Vuruskan, Hongkun Lu, Tamer M. Yalcinkaya
Abstract:
In recent years, we have witnessed an explosion of studies aimed at using a combination of artificial intelligence (AI) and time-lapse imaging data on embryos to improve IVF outcomes. However, despite promising results, no study has used a matched cohort of transferred embryos which only differ in pregnancy outcome, i.e., embryos from a single clinic which are similar in parameters, such as: morphokinetic condition, patient age, and overall clinic and lab performance. Here, we used time-lapse data on embryos with known pregnancy outcomes to see if the rich spatiotemporal information embedded in this data would allow the prediction of the pregnancy outcome regardless of such critical parameters. Methodology—We did a retrospective analysis of time-lapse data from our IVF clinic utilizing Embryoscope 100% of the time for embryo culture to blastocyst stage with known clinical outcomes, including live birth vs nonpregnant (embryos with spontaneous abortion outcomes were excluded). We used time-lapse data from 200 elective single transfer embryos randomly selected from January 2019 to June 2021. Our sample included 100 embryos in each group with no significant difference in patient age (P=0.9550) and morphokinetic scores (P=0.4032). Data from all patients were combined to make a 4th order tensor, and feature extraction were subsequently carried out by a tensor decomposition methodology. The features were then used in a machine learning classifier to classify the two groups. Major Findings—The performance of the model was evaluated using 100 random subsampling cross validation (train (80%) - test (20%)). The prediction accuracy, averaged across 100 permutations, exceeded 80%. We also did a random grouping analysis, in which labels (live birth, nonpregnant) were randomly assigned to embryos, which yielded 50% accuracy. Conclusion—The high accuracy in the main analysis and the low accuracy in random grouping analysis suggest a consistent spatiotemporal pattern which is associated with pregnancy outcomes, regardless of patient age and embryo morphokinetic condition, and beyond already known parameters, such as: early cleavage or early blastulation. Despite small samples size, this ongoing analysis is the first to show the potential of AI methods in capturing the complex morphokinetic changes embedded in embryo time-lapse data, which contribute to successful pregnancy outcomes, regardless of already known parameters. The results on a larger sample size with complementary analysis on prediction of other key outcomes, such as: euploidy and aneuploidy of embryos will be presented at the meeting.Keywords: IVF, embryo, machine learning, time-lapse imaging data
Procedia PDF Downloads 92561 Dangerous Words: A Moral Economy of HIV/AIDS in Swaziland
Authors: Robin Root
Abstract:
A fundamental premise of medical anthropology is that clinical phenomena are simultaneously cultural, political, and economic: none more so than the linked acronyms HIV/AIDS. For the medical researcher, HIV/AIDS signals an epidemiological pandemic and a pathophysiology. For persons diagnosed with an HIV-related condition, the acronym often conjures dread, too often marking and marginalizing the afflicted irretrievably. Critical medical anthropology is uniquely equipped to theorize the linkages that bind individual and social wellbeing to global structural and culture-specific phenomena. This paper reports findings from an anthropological study of HIV/AIDS in Swaziland, site of the highest HIV prevalence in the world. The project, initiated in 2005, has documented experiences of HIV/AIDS, religiosity, and treatment and care as well as drought and famine. Drawing on interviews with Swazi religious and traditional leaders about their experiences of leadership amidst worsening economic conditions, environmental degradation, and an ongoing global health crisis, the paper provides uncommon insights for global health practitioners whose singular paradigm for designing and delivering interventions is biomedically-based. In contrast, this paper details the role of local leaders in mediating extreme social suffering and resilience in ways that medical science cannot model but which radically impact how sickness is experienced and health services are delivered and accessed. Two concepts help to organize the paper’s argument. First, a ‘moral economy of language’ is central to showing up the implicit ‘technologies of knowledge’ that inhere in scientific and religious discourses of HIV/AIDS; people draw upon these discourses strategically to navigate highly vulnerable conditions. Second, Paulo Freire’s ethnographic focus on a culture’s 'dangerous words' opens up for examination how ‘sex’ is dangerous for religion and ‘god’ is dangerous for science. The paper interrogates hegemonic and ‘lived’ discourses, both biomedical and religious, and contributes to an important literature on the moral economies of health, a framework of explication and, importantly, action appropriate to a wide-range of contemporary global health phenomena. The paper concludes by asserting that it is imperative that global health planners reflect upon and ‘check’ their hegemonic policy platforms by, one, collaborating with local authoritative agents of ‘what sickness means and how it is best treated,’ and, two, taking account of the structural barriers to achieving good health.Keywords: Africa, biomedicine, HIV/AIDS, qualitative research , religion
Procedia PDF Downloads 103560 Association between G2677T/A MDR1 Polymorphism with the Clinical Response to Disease Modifying Anti-Rheumatic Drugs in Rheumatoid Arthritis
Authors: Alan Ruiz-Padilla, Brando Villalobos-Villalobos, Yeniley Ruiz-Noa, Claudia Mendoza-Macías, Claudia Palafox-Sánchez, Miguel Marín-Rosales, Álvaro Cruz, Rubén Rangel-Salazar
Abstract:
Introduction: In patients with rheumatoid arthritis, resistance or poor response to disease modifying antirheumatic drugs (DMARD) may be a reflection of the increase in g-P. The expression of g-P may be important in mediating the effluence of DMARD from the cell. In addition, P-glycoprotein is involved in the transport of cytokines, IL-1, IL-2 and IL-4, from normal lymphocytes activated to the surrounding extracellular matrix, thus influencing the activity of RA. The involvement of P-glycoprotein in the transmembrane transport of cytokines can serve as a modulator of the efficacy of DMARD. It was shown that a number of lymphocytes with glycoprotein P activity is increased in patients with RA; therefore, P-glycoprotein expression could be related to the activity of RA and could be a predictor of poor response to therapy. Objective: To evaluate in RA patients, if the G2677T/A MDR1 polymorphisms is associated with differences in the rate of therapeutic response to disease-modifying antirheumatic agents in patients with rheumatoid arthritis. Material and Methods: A prospective cohort study was conducted. Fifty seven patients with RA were included. They had an active disease according to DAS-28 (score >3.2). We excluded patients receiving biological agents. All the patients were followed during 6 months in order to identify the rate of therapeutic response according to the American College of Rheumatology (ACR) criteria. At the baseline peripheral blood samples were taken in order to identify the G2677T/A MDR1 polymorphisms using PCR- Specific allele. The fragment was identified by electrophoresis in polyacrylamide gels stained with ethidium bromide. For statistical analysis, the genotypic and allelic frequencies of MDR1 gene polymorphism between responders and non-responders were determined. Chi-square tests as well as, relative risks with 95% confidence intervals (95%CI) were computed to identify differences in the risk for achieving therapeutic response. Results: RA patients had a mean age of 47.33 ± 12.52 years, 87.7% were women with a mean for DAS-28 score of 6.45 ± 1.12. At the 6 months, the rate of therapeutic response was 68.7 %. The observed genotype frequencies were: for G/G 40%, T/T 32%, A/A 19%, G/T 7% and for A/A genotype 2%. Patients with G allele developed at 6 months of treatment, higher rate for therapeutic response assessed by ACR20 compared to patients with others alleles (p=0.039). Conclusions: Patients with G allele of the - G2677T/A MDR1 polymorphisms had a higher rate of therapeutic response at 6 months with DMARD. These preliminary data support the requirement for a deep evaluation of these and other genotypes as factors that may influence the therapeutic response in RA.Keywords: pharmacogenetics, MDR1, P-glycoprotein, therapeutic response, rheumatoid arthritis
Procedia PDF Downloads 208559 Investigating the Neural Heterogeneity of Developmental Dyscalculia
Authors: Fengjuan Wang, Azilawati Jamaludin
Abstract:
Developmental Dyscalculia (DD) is defined as a particular learning difficulty with continuous challenges in learning requisite math skills that cannot be explained by intellectual disability or educational deprivation. Recent studies have increasingly recognized that DD is a heterogeneous, instead of monolithic, learning disorder with not only cognitive and behavioral deficits but so too neural dysfunction. In recent years, neuroimaging studies employed group comparison to explore the neural underpinnings of DD, which contradicted the heterogenous nature of DD and may obfuscate critical individual differences. This research aimed to investigate the neural heterogeneity of DD using case studies with functional near-infrared spectroscopy (fNIRS). A total of 54 aged 6-7 years old of children participated in this study, comprising two comprehensive cognitive assessments, an 8-minute resting state, and an 8-minute one-digit addition task. Nine children met the criteria of DD and scored at or below 85 (i.e., the 16th percentile) on the Mathematics or Math Fluency subtest of the Wechsler Individual Achievement Test, Third Edition (WIAT-III) (both subtest scores were 90 and below). The remaining 45 children formed the typically developing (TD) group. Resting-state data and brain activation in the inferior frontal gyrus (IFG), superior frontal gyrus (SFG), and intraparietal sulcus (IPS) were collected for comparison between each case and the TD group. Graph theory was used to analyze the brain network under the resting state. This theory represents the brain network as a set of nodes--brain regions—and edges—pairwise interactions across areas to reveal the architectural organizations of the nervous network. Next, a single-case methodology developed by Crawford et al. in 2010 was used to compare each case’s brain network indicators and brain activation against 45 TD children’s average data. Results showed that three out of the nine DD children displayed significant deviation from TD children’s brain indicators. Case 1 had inefficient nodal network properties. Case 2 showed inefficient brain network properties and weaker activation in the IFG and IPS areas. Case 3 displayed inefficient brain network properties with no differences in activation patterns. As a rise above, the present study was able to distill differences in architectural organizations and brain activation of DD vis-à-vis TD children using fNIRS and single-case methodology. Although DD is regarded as a heterogeneous learning difficulty, it is noted that all three cases showed lower nodal efficiency in the brain network, which may be one of the neural sources of DD. Importantly, although the current “brain norm” established for the 45 children is tentative, the results from this study provide insights not only for future work in “developmental brain norm” with reliable brain indicators but so too the viability of single-case methodology, which could be used to detect differential brain indicators of DD children for early detection and interventions.Keywords: brain activation, brain network, case study, developmental dyscalculia, functional near-infrared spectroscopy, graph theory, neural heterogeneity
Procedia PDF Downloads 53558 Conservative and Surgical Treatment of Antiresorptive Drug-Related Osteonecrosis of the Jaw with Ultrasonic Piezoelectric Bone Surgery under Polyvinylpyrrolidone Iodine Irrigation: A Case Series of 13 Treated Sites
Authors: Esra Yuce, Isil D. S. Yamaner, Murude Yazan
Abstract:
Aims and objective: Antiresorptive agents including bisphosphonates and denosumab as strong suppressors of osteoclasts are the most commonly used antiresorptive medications for the treatment of osteoporosis which counteract the negative quantitative alteration of trabecular and cortical bone by inhibition of bone turnover. Oral bisphosphonate therapy for the treatment of osteopenia, osteoporosis or Paget's disease is associated with the low-grade risk of osteonecrosis of the jaw, while higher-grade risk is associated with receiving intravenous bisphosphonates therapy in the treatment of multiple myeloma and bone metastases. On the other hand, there has been a remarkable increase in incidences of antiresorptive related osteonecrosis of the jaw (ARONJ) in oral bisphosphonate users. This clinical presentation will evaluate the healing outcomes via piezoelectric bone surgery under the irrigation of PVP-I solution irrigation in patients received bisphosphonate therapy. Material-Method: The study involved 8 female and 5 male patients that have been treated for ARONJ. Among 13 necrotic sites, 9 were in the mandible and 4 were in the maxilla. All of these 13 patients treated with surgical debridement via piezoelectric bone surgery under irrigation by solution with 3% PVP-I concentration in combination with long-term antibiotic therapy and 5 also underwent removal of mobile segments of bony sequestrum. All removable prosthesis in 8 patients were relined with soft liners during the healing periods in order to eliminate chronic minor traumas. Results: All patients were on oral bisphosphonate therapy for at least 2 years and 5 of which had received intravenous bisphosphonates up to 1 year before therapy with oral bisphosphonates was started. According to the AAOMS staging system, four cases were stage II, eight cases were stage I, and one case was stage III. The majority of lesions were identified at sites of dental prostheses (38%) and dental extractions (62%). All patients diagnosed with ARONJ stage I had used unadjusted removable prostheses. No recurrence of the symptoms was observed during the present follow-up (9–37 months). Conclusion: Despite their confirmed effectiveness, the prevention and treatment of osteonecrosis of the jaw secondary to oral bisphosphonate therapy remain major medical challenges. Treatment with piezoelectric bone surgery with irrigation of povidone-iodine solution was effective for management of bisphosphonate-related osteonecrosis of the jaw. Taking precautions for patients treated with oral bisphosphonates, especially also denture users, may allow for a reduction in the rate of developing osteonecrosis of the maxillofacial region.Keywords: antiresorptive drug related osteonecrosis, bisphosphonate therapy, piezoelectric bone surgery, povidone iodine
Procedia PDF Downloads 267557 Compression-Extrusion Test to Assess Texture of Thickened Liquids for Dysphagia
Authors: Jesus Salmeron, Carmen De Vega, Maria Soledad Vicente, Mireia Olabarria, Olaia Martinez
Abstract:
Dysphagia or difficulty in swallowing affects mostly elder people: 56-78% of the institutionalized and 44% of the hospitalized. Liquid food thickening is a necessary measure in this situation because it reduces the risk of penetration-aspiration. Until now, and as proposed by the American Dietetic Association in 2002, possible consistencies have been categorized in three groups attending to their viscosity: nectar (50-350 mPa•s), honey (350-1750 mPa•s) and pudding (>1750 mPa•s). The adequate viscosity level should be identified for every patient, according to her/his impairment. Nevertheless, a systematic review on dysphagia diet performed recently indicated that there is no evidence to suggest that there is any transition of clinical relevance between the three levels proposed. It was also stated that other physical properties of the bolus (slipperiness, density or cohesiveness, among others) could influence swallowing in affected patients and could contribute to the amount of remaining residue. Texture parameters need to be evaluated as possible alternative to viscosity. The aim of this study was to evaluate the instrumental extrusion-compression test as a possible tool to characterize changes along time in water thickened with various products and in the three theoretical consistencies. Six commercial thickeners were used: NM® (NM), Multi-thick® (M), Nutilis Powder® (Nut), Resource® (R), Thick&Easy® (TE) and Vegenat® (V). All of them with a modified starch base. Only one of them, Nut, also had a 6,4% of gum (guar, tara and xanthan). They were prepared as indicated in the instructions of each product and dispensing the correspondent amount for nectar, honey and pudding consistencies in 300 mL of tap water at 18ºC-20ºC. The mixture was stirred for about 30 s. Once it was homogeneously spread, it was dispensed in 30 mL plastic glasses; always to the same height. Each of these glasses was used as a measuring point. Viscosity was measured using a rotational viscometer (ST-2001, Selecta, Barcelona). Extrusion-compression test was performed using a TA.XT2i texture analyzer (Stable Micro Systems, UK) with a 25 mm diameter cylindrical probe (SMSP/25). Penetration distance was set at 10 mm and a speed of 3 mm/s. Measurements were made at 1, 5, 10, 20, 30, 40, 50 and 60 minutes from the moment samples were mixed. From the force (g)–time (s) curves obtained in the instrumental assays, maximum force peak (F) was chosen a reference parameter. Viscosity (mPa•s) and F (g) showed to be highly correlated and had similar development along time, following time-dependent quadratic models. It was possible to predict viscosity using F as an independent variable, as they were linearly correlated. In conclusion, compression-extrusion test could be an alternative and a useful tool to assess physical characteristics of thickened liquids.Keywords: compression-extrusion test, dysphagia, texture analyzer, thickener
Procedia PDF Downloads 368556 MCD-017: Potential Candidate from the Class of Nitroimidazoles to Treat Tuberculosis
Authors: Gurleen Kour, Mowkshi Khullar, B. K. Chandan, Parvinder Pal Singh, Kushalava Reddy Yumpalla, Gurunadham Munagala, Ram A. Vishwakarma, Zabeer Ahmed
Abstract:
New chemotherapeutic compounds against multidrug-resistant Mycobacterium tuberculosis (Mtb) are urgently needed to combat drug resistance in tuberculosis (TB). Apart from in-vitro potency against the target, physiochemical properties and pharmacokinetic properties play an imperative role in the process of drug discovery. We have identified novel nitroimidazole derivatives with potential activity against mycobacterium tuberculosis. One lead candidates, MCD-017, which showed potent activity against H37Rv strain (MIC=0.5µg/ml) and was further evaluated in the process of drug development. Methods: Basic physicochemical parameters like solubility and lipophilicity (LogP) were evaluated. Thermodynamic solubility was determined in PBS buffer (pH 7.4) using LC/MS-MS. The partition coefficient (Log P) of the compound was determined between octanol and phosphate buffered saline (PBS at pH 7.4) at 25°C by the microscale shake flask method. The compound followed Lipinski’s rule of five, which is predictive of good oral bioavailability and was further evaluated for metabolic stability. In-vitro metabolic stability was determined in rat liver microsomes. The hepatotoxicity of the compound was also determined in HepG2 cell line. In vivo pharmacokinetic profile of the compound after oral dosing was also obtained using balb/c mice. Results: The compound exhibited favorable solubility and lipophilicity. The physical and chemical properties of the compound were made use of as the first determination of drug-like properties. The compound obeyed Lipinski’s rule of five, with molecular weight < 500, number of hydrogen bond donors (HBD) < 5 and number of hydrogen bond acceptors(HBA) not more then 10. The log P of the compound was less than 5 and therefore the compound is predictive of exhibiting good absorption and permeation. Pooled rat liver microsomes were prepared from rat liver homogenate for measuring the metabolic stability. 99% of the compound was not metabolized and remained intact. The compound did not exhibit cytoxicity in hepG2 cells upto 40 µg/ml. The compound revealed good pharmacokinetic profile at a dose of 5mg/kg administered orally with a half life (t1/2) of 1.15 hours, Cmax of 642ng/ml, clearance of 4.84 ml/min/kg and a volume of distribution of 8.05 l/kg. Conclusion : The emergence of multi drug resistance (MDR) and extensively drug resistant (XDR) Tuberculosis emphasize the requirement of novel drugs active against tuberculosis. Thus, the need to evaluate physicochemical and pharmacokinetic properties in the early stages of drug discovery is required to reduce the attrition associated with poor drug exposure. In summary, it can be concluded that MCD-017 may be considered a good candidate for further preclinical and clinical evaluations.Keywords: mycobacterium tuberculosis, pharmacokinetics, physicochemical properties, hepatotoxicity
Procedia PDF Downloads 457