Search results for: young patients

Authors: Hamda Ajmal, Karen Young, Ruth Melia, John Bogue, Mary O'Sullivan, Jim Duggan, Hannah Wood

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The Covid-19 pandemic led to a range of public health mitigation strategies in order to suppress the SARS-CoV-2 virus. The drastic changes in everyday life due to lockdowns had the potential for a significant negative impact on public mental health, and a key public health goal is to now assess the evidence from available Irish datasets to provide useful insights on this issue. Text-50808 is an online text-based mental health support service, established in Ireland in 2020, and can provide a measure of revealed distress and mental health concerns across the population. The aim of this study is to explore statistical associations between public mental health in Ireland and the Covid-19 pandemic. Uniquely, this study combines two measures of emotional wellbeing in Ireland: (1) weekly text volume at Text-50808, and (2) emotional wellbeing indicators reported by respondents of the Amárach public opinion survey, carried out on behalf of the Department of Health, Ireland. For this analysis, a multivariate graphical exploratory data analysis (EDA) was performed on the Text-50808 dataset dated from 15th June 2020 to 30th June 2021. This was followed by time-series analysis of key mental health indicators including: (1) the percentage of daily/weekly texts at Text-50808 that mention Covid-19 related issues; (2) the weekly percentage of people experiencing anxiety, boredom, enjoyment, happiness, worry, fear and stress in Amárach survey; and Covid-19 related factors: (3) daily new Covid-19 case numbers; (4) daily stringency index capturing the effect of government non-pharmaceutical interventions (NPIs) in Ireland. The cross-correlation function was applied to measure the relationship between the different time series. EDA of the Text-50808 dataset reveals significant peaks in the volume of texts on days prior to level 3 lockdown and level 5 lockdown in October 2020, and full level 5 lockdown in December 2020. A significantly high positive correlation was observed between the percentage of texts at Text-50808 that reported Covid-19 related issues and the percentage of respondents experiencing anxiety, worry and boredom (at a lag of 1 week) in Amárach survey data. There is a significant negative correlation between percentage of texts with Covid-19 related issues and percentage of respondents experiencing happiness in Amárach survey. Daily percentage of texts at Text-50808 that reported Covid-19 related issues to have a weak positive correlation with daily new Covid-19 cases in Ireland at a lag of 10 days and with daily stringency index of NPIs in Ireland at a lag of 2 days. The sudden peaks in text volume at Text-50808 immediately prior to new restrictions in Ireland indicate an association between a rise in mental health concerns following the announcement of new restrictions. There is also a high correlation between emotional wellbeing variables in the Amárach dataset and the number of weekly texts at Text-50808, and this confirms that Text-50808 reflects overall public sentiment. This analysis confirms the benefits of the texting service as a community surveillance tool for mental health in the population. This initial EDA will be extended to use multivariate modeling to predict the effect of additional Covid-19 related factors on public mental health in Ireland.

Keywords: COVID-19 pandemic, data analysis, digital health, mental health, public health, digital health

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Authors: Miguel Limbert Ramos, Joseph Amado Galvez

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Background: The nasal septal cartilage is an autologous graft that is widely used in different otolaryngologic procedures of the different subspecialties, such as in septorhinoplasty and ear rehabilitation procedures. The cartilage can be easily accessed and harvested to be utilized for such procedures. However, the dimension of the nasal septal cartilage differs, corresponding to race, gender, and age. Measurements can be done via direct measurement of harvested septal cartilage in cadavers or utilizing radiographic imaging studies giving baseline measurement of the nasal septal cartilage distinct to every race. A preliminary baseline measurement of the dimensions of Filipino nasal septal cartilage was previously established by measuring harvested nasal septal cartilage in Filipino Malay cadavers. This study intends to reinforce this baseline measurement by utilizing computed tomography (CT) scans of adult Filipinos in a tertiary government hospital in the City of Manila, Philippines, which will cover a larger sampling population. Methods: The unit of observation and analysis will be the computed tomography (CT) scans of patients ≥ 18years old who underwent cranial, facial, orbital, paranasal sinus, and temporal bone studies for the year 2019. The measurements will be done in a generated best midsagittal image (155 subjects) which is a view through the midline of the cerebrum that is simultaneously viewed with its coronal and axial views for proper orientation. The view should reveal important structures that will be used to plot the anatomic boundaries, which will be measured by a DICOM image viewing software (RadiAnt). The measured area of nasal septal cartilage will be compared by gender and age. Results: The total area of the nasal septal cartilage is larger in males compared to females, with a mean value of 6.52 cm² and 5.71 cm², respectively. The harvestable nasal septal cartilage area is also larger in males with a mean value of 3.57 cm² compared to females with only a measured mean value of 3.13 cm². The total and harvestable area of the nasal septal cartilage is largest in the 18-30 year-old age group with a mean value of 6.47 cm² and 3.60 cm² respectively and tends to decrease with the advancement of age, which can be attributed to continuous ossification changes. Conclusion: The best time to perform septorhinoplasty and other otolaryngologic procedures which utilize the nasal septal cartilage as graft material is during post-pubertal age, hence surgeries should be avoided or delayed to allow growth and maturation of the cartilage. A computed tomography scan is a cost-effective and non-invasive tool that can provide information on septal cartilage areas prior to these procedures.

Keywords: autologous graft, computed tomography, nasal septal cartilage, septorhinoplasty

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Authors: Karen Boaz, C. R. Charan

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Background: The infiltration of tumour stroma by eosinophils, Tumor-Associated Tissue Eosinophilia (TATE), is known to modulate the progression of Oral Squamous Cell Carcinoma (OSCC). Eosinophils have direct tumoricidal activity by release of cytotoxic proteins and indirectly they enhance permeability into tumor cells enabling penetration of tumoricidal cytokines. Also, eosinophils may promote tumor angiogenesis by production of several angiogenic factors. Identification of eosinophils in the inflammatory stroma has been proven to be an important prognosticator in cancers of mouth, oesophagus, larynx, pharynx, breast, lung, and intestine. Therefore, the study aimed to correlate TATE with clinical and histopathological variables, and blood eosinophil count to assess the role of TATE as a prognosticator in Oral Squamous Cell Carcinoma (OSCC). Methods: Seventy two biopsy-proven cases of OSCC formed the study cohort. Blood eosinophil counts and TNM stage were obtained from the medical records. Tissue sections (5µm thick) were stained with Haematoxylin and Eosin. The eosinophils were quantified at invasive tumour front (ITF) in 10HPF (40x magnification) with an ocular grid. Bryne’s grading of ITF was also performed. A subset of thirty cases was also assessed for association of TATE with recurrence, involvement of lymph nodes and surgical margins. Results: 1) No statistically significant correlation was found between TATE and TNM stage, blood eosinophil counts and most parameters of Bryne’s grading system. 2) Statistically significant relation of intense degree of TATE was associated with the absence of distant metastasis, increased lympho-plasmacytic response and increased survival (diseasefree and overall) of OSCC patients. 3) In the subset of 30 cases, tissue eosinophil counts were higher in cases with lymph node involvement, decreased survival, without margin involvement and in cases that did not recur. Conclusion: While the role of eosinophils in mediating immune responses seems ambiguous as eosinophils support cell-mediated tumour immunity in early stages while inhibiting the same in advanced stages, TATE may be used as a surrogate marker for determination of prognosis in oral squamous cell carcinoma.

Keywords: tumour-associated tissue eosinophilia, oral squamous cell carcinoma, prognosticator, tumoral immunity

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Authors: Navid P Roodaki, Rochelle Abila, Daisy Evangeline Garcia

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Background and Objective: Respiratory Distress Syndrome (RDS) among premature infants is a major causes of neonatal death. The use of Continuous Positive Airway Pressure (CPAP) has become a standard of care for preterm newborns with RDS hence cost-effective innovations are needed. This study compared a novel low-cost Bubble CPAP (bCPAP) device to ventilator driven CPAP in the treatment of RDS. Methods: This is a single-blind, randomized controlled trial done on May 2022 to October 2022 in a Level III Neonatal Intensive Care Unit in the Philippines. Preterm newborns (<36 weeks) with RDS were randomized to receive Vayu bCPAP device or Ventilator-derived CPAP. Arterial Blood Gases, Oxygen Saturation, administration of surfactant, and CPAP failure rates were measured. Results: Seventy preterm newborns were included. No differences were observed between the Ventilator driven CPAP and Vayu bCPAP on the PaO2 (97.51mmHg vs 97.37mmHg), So2 (97.08% vs 95.60%) levels, amount of surfactant administered between groups. There were no observed differences in CPAP failure rates between Vayu bPCAP (x̄ 3.23 days) and ventilator-driven CPAP (x̄ 2.98 days). However, a significant difference was noted on the CO2 level (40.32mmHg vs 50.70mmHg), which was higher among those hooked to Ventilator-driven CPAP (p 0.004). Conclusion: This study has shown that the novel low-cost bubble CPAP (Vayu bCPAP) can be used as an efficacious alternate non invasive oxygen therapy among preterm neonates with RDS, although the CO2 levels were higher among those hooked to ventilator driven CPAP, other outcome parameters measured showed that both devices are comparable. Recommendation: A multi-center or national study to account for geographic region, which may alter the outcomes of patients connected to different ventilatory support. Cost comparison between devices is also suggested. A mixed-method research assessing the experiences of health care professionals in assembling and utilizing the gadget is a second consideration.

Keywords: bubble CPAP, ventilator-derived CPAP; infant, premature, respiratory distress syndrome

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Authors: Waraporn Boonchieng, Ekkarat Boonchieng, Wilawan Senaratana, Jaras Singkaew

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Geographical information system (GIS) is a designated system widely used for collecting and analyzing geographical data. Since the introduction of ultra-mobile, 'smart' devices, investigators, clinicians, and even the general public have had powerful new tools for collecting, uploading and accessing information in the field. Epidemiology paired with GIS will increase the efficacy of preventive health care services. The objective of this study is to apply GPS location services that are available on the common mobile device with district health systems, storing data on our private cloud system. The mobile application has been developed for use on iOS, Android, and web-based platforms. The system consists of two parts of district health information, including recorded resident data forms and individual health recorded data forms, which were developed and approved by opinion sharing and public hearing. The application's graphical user interface was developed using HTML5 and PHP with MySQL as a database management system (DBMS). The reporting module of the developed software displays data in a variety of views, from traditional tables to various types of high-resolution, layered graphics, incorporating map location information with street views from Google Maps. Multi-extension exporting is also supported, utilizing standard platforms such as PDF, PNG, JPG, and XLS. The data were collected in the database beginning in March 2013, by district health volunteers and district youth volunteers who had completed the application training program. District health information consisted of patients’ household coordinates, individual health data, social and economic information. This was combined with Google Street View data, collected in March 2014. Studied groups consisted of 16,085 (67.87%) and 47,811 (59.87%) of the total 23,701 households and 79,855 people were collected by the system respectively, in Saraphi district, Chiang Mai Province. The report generated from the system has had a major benefit directly to the Saraphi District Hospital. Healthcare providers are able to use the basic health data to provide a specific home health care service and also to create health promotion activities according to medical needs of the people in the community.

Keywords: health, public health, GIS, geographic information system

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Authors: Nick Woodier, Paul Sampson, Iain Moppett

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Background: For years, healthcare across the world has recognised that patients are coming to harm from the very processes meant to help them. In response, healthcare tells itself that it needs to ‘be more like aviation.’ Aviation safety is highly regarded by those in healthcare and is seen as an exemplar. Specifically, healthcare is keen to learn from how aviation uses near misses to make their industry safer. Healthcare is rife with near misses; however, there has been little progress addressing them, with most research having focused on reporting. Addressing the factors that contribute to near misses will potentially help reduce the number of significant, harm patientsafety incidents. While the healthcare literature states the need to learn from aviation’s use of near misses, there is nothing that describes how best to do this. The authors, as part of a larger study of near-miss management in healthcare, sought to learn from aviation to develop principles for how healthcare can identify, report, and learn from near misses to improve patient safety. Methods: A Grounded Theory (GT) methodology, augmented by a scoping review, was used. Data collection included interviews, field notes, and the literature. The review protocol is accessible online. The GT aimed to develop theories about how aviation, amongst other safety-critical industries, manages near misses. Results: Twelve aviation interviews contributed to the GT across passenger airlines, air traffic control, and bodies involved in policy, regulation, and investigation. The scoping review identified 83 articles across a range of safety-critical industries, but only seven focused on aviation. The GT identified that aviation interprets the term ‘near miss’ in different ways, commonly using it to specifically refer to near-miss air collisions, also known as Airproxes. Other types of near misses exist, such as health and safety, but the reporting of these and the safety climate associated with them is not as mature. Safety culture in aviation was regularly discussed, with evidence that culture varies depending on which part of the industry is being considered (e.g., civil vs. business aviation). Near misses are seen as just one part of an extensive safety management system, but processes to support their reporting and their analysis are not consistent. Their value alone is also questionable, with the challenge to long-held beliefs originating from the ‘common cause hypothesis.’ Conclusions: There is learning that healthcare can take from how parts of aviation manage and learn from near misses. For example, healthcare would benefit from a formal safety management system that currently does not exist. However, it may not be as simple as ‘healthcare should learn from aviation’ due to variation in safety maturity across the industry. Healthcare needs to clarify how to incorporate near misses into learning and whether allocating resources to them is of value; it was heard that catastrophes have led to greater improvements in safety in aviation.

Keywords: aviation safety, patient safety, near miss, safety management systems

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Authors: Junie B. Billones, Maria Constancia O. Carrillo, Voltaire G. Organo, Stephani Joy Y. Macalino, Inno A. Emnacen, Jamie Bernadette A. Sy

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The drug discovery and development process is generally known to be a very lengthy and labor-intensive process. Therefore, in order to be able to deliver prompt and effective responses to cure certain diseases, there is an urgent need to reduce the time and resources needed to design, develop, and optimize potential drugs. Computer-aided drug design (CADD) is able to alleviate this issue by applying computational power in order to streamline the whole drug discovery process, starting from target identification to lead optimization. This drug design approach can be predominantly applied to diseases that cause major public health concerns, such as tuberculosis. Hitherto, there has been no concrete cure for this disease, especially with the continuing emergence of drug resistant strains. In this study, CADD is employed for tuberculosis by first identifying a key enzyme in the mycobacterium’s metabolic pathway that would make a good drug target. One such potential target is the lipoate protein ligase B enzyme (LipB), which is a key enzyme in the M. tuberculosis metabolic pathway involved in the biosynthesis of the lipoic acid cofactor. Its expression is considerably up-regulated in patients with multi-drug resistant tuberculosis (MDR-TB) and it has no known back-up mechanism that can take over its function when inhibited, making it an extremely attractive target. Using cutting-edge computational methods, compounds from AnalytiCon Discovery Natural Derivatives database were screened and docked against the LipB enzyme in order to rank them based on their binding affinities. Compounds which have better binding affinities than LipB’s known inhibitor, decanoic acid, were subjected to in silico toxicity evaluation using the ADMET and TOPKAT protocols. Out of the 31,692 compounds in the database, 112 of these showed better binding energies than decanoic acid. Furthermore, 12 out of the 112 compounds showed highly promising ADMET and TOPKAT properties. Future studies involving in vitro or in vivo bioassays may be done to further confirm the therapeutic efficacy of these 12 compounds, which eventually may then lead to a novel class of anti-tuberculosis drugs.

Keywords: pharmacophore, molecular docking, lipoate protein ligase B (LipB), ADMET, TOPKAT

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Authors: Jia-Ling Ho, Xiu-Ru Zhang, Zwe-Ling Kong

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Diabetes mellitus (DM) is a major health problem that affects patients’ life quality throughout the world due to its many complications. It characterized by chronic hyperglycemia with oxidative stress, which impaired male reproductive function. Fibroblast growth factor 21 (FGF21) is a metabolic regulator that is required for normal spermatogenesis and protects against diabetes-induced germ cell apoptosis. Echinacea purpurea ethanol extract (EE), which contain phenolic acid and isobutylamide, had been proven to have antidiabetic property. Silica-chitosan nanoparticles (Nano-CS) has drug delivery and controlled release properties. This study aims to investigate whether silica-chitosan nanoparticles encapsulated EE (Nano-EE) had more ameliorating male infertility by analyzing the effect of testicular FGF21. The Nano-EE was characterized before used to treatment the diabetic rat model. Male Sprague-Dawley (SD) rats were obtained and divided into seven groups. A group was no induced Streptozotocin (STZ), marked as normal group. Diabetic rats were induced into diabetes by STZ (33 mg/kg). A diabetic group was no treatment with sample (diabetic control group), and other groups were treatment by Nano-CS (465 mg/kg), Nano-EE (93, 279, 465 mg/kg), and metformin (Met) (200 mg/kg) used as reference drug for 7 weeks. Our results indicated that the average nanoparticle size and zeta potential of Nano-EE were 2630 nm and -21.3 mV, respectively. The encapsulation ratio of Nano-EE was about 70%. It also confirmed the antioxidative activity was unchanged by comparing the DPPH and ABTS scavenging of Nano-EE and EE. In vivo test, Nano-EE can improve the STZ induced hyperglycemia, insulin resistance, and plasma FGF21 levels. Nano-EE has increased sperm motility, mitochondria membrane potential (MMP), plasma testosterone level, and reduction of abnormal sperm, nitric oxide (NO), superoxide production as well as reactive oxygen species (ROS). In addition, in plasma antioxidant enzymes glutathione peroxidase (GPx) and superoxide dismutase (SOD) was increased whereas pro-inflammatory cytokines TNF-α, and IL-1β were decreased. Further, in testis, protein content of FGF21, PGC-1α, and SIRT1 were improved. Nano-EE might improve diabetes-induced down-regulation of testicular FGF21 and SIRT1/PGC-1α signaling hence maintain spermatogenesis.

Keywords: diabetes mellitus, Echinacea purpurea, reproductive dysfunction, silica-chitosan nanoparticles

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Authors: Yen-Mei Lee

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The concept of a knowledge-behavior gap has been discussed for several years. It is addressed that an individual’s knowledge does not sufficiently transfer to his or her actual actions. This concept is mostly focused on fields related to medicine or applied to health care issues to explain how people or patients connect their personal knowledge to actual health care behaviors. To our knowledge, seldomly has this research been applied to discuss people’s online information seeking behavior. In the current study, the main purpose is to investigate the relationship between web users’ personal values and their actual performances when seeking information on the Internet. The total number of twenty-eight participants, divided into one experienced group (n=14) and one novice group (n=14), were recruited and asked to complete a self-report questionnaire of fifty items related to information seeking actions and behaviors. During the execution, participants needed to rate the importance level (how important each item is) and the performance level (how often they actually do each item) from 1 to 10 points on each item. In this paper, the mean scores of the importance and the performance level are analyzed and discussed. The results show that there is a gap between web user’s knowledge and their actual online seeking behaviors. Both experienced group and novice group have higher average scores of the importance level (experienced group = 7.57, novice group = 6.01) than the actual performance level (experienced group = 6.89, novice group = 5.00) in terms of the fifty online information seeking actions. On the other hand, the experienced group perceives more importance of the fifty online seeking actions and performs actual behaviors better than the novice group. Moreover, experienced participants express a consistent result between their concept knowledge and actual behaviors. For instance, they feel extending a seeking strategy is important and frequently perform this action when seeking online. However, novice participants do not have a consistency between their knowledge and behaviors. For example, though they perceive browsing and judging information are less important than they get lost in the online information seeking process. However, in the actual behavior rating, the scores show that novices do browsing and judge information more often than they get lost when seeking information online. These results, therefore, help scholars and educators have a better understanding of the difference between experienced and novice web users regarding their concept knowledge and actual behaviors. In future study, figuring out how to narrow down the knowledge-behavior gap and create practical guidance for novice users to increase their online seeking efficiency is crucial. Not only could it help experienced users be aware of their actual information seeking behaviors, but also help the novice become mastery to concisely obtain information on the Internet.

Keywords: experienced web user, information seeking behavior, knowledge-behavior gap, novice, online seeking efficiency

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Authors: Md. Abdul Karim, Syed Imran Ahmed, Pandora T. Hardtman

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Informed consent is one of the basic human and ethical rights for childbearing women. It plays a central role in promoting informed decision making between patients and service providers during the labor process. It gives mothers rights to accept or reject any examination and/or procedure, increases the respect and dignity of the mother during pregnancy, delivery and postpartum care. To assess the practices of this right during normal vaginal delivery and immediate postpartum care in tertiary level hospital setting in Bangladesh, a quantitative study with cross-sectional design was conducted in Dhaka Medical College & Hospital (DMCH) and Sir Salimullah Medical College & Mitford Hospital (SSMCH) in Dhaka in November 2015. A prevalence-based sample size of 190 was calculated where prevalence, confidence interval and level of significance were at 9.7%, 98% and 5% respectively. The respondents were the mothers who gave normal vaginal childbirth within past 24 hours and received postpartum care there. They were selected through systematic random sampling technique and their face-to-face interview of 190 mothers was done using a structured questionnaire. Data were entered into the spreadsheet (MS Excel 2013 version) and descriptive analysis of findings was done. The result shows the complete absence of informed consent practices and mostly absence of consented care such as right to information, respect for choices of preferences for examination and/or procedure of childbearing women. Although 95% of the mothers were informed that they were being proceeded with normal vaginal delivery, their choice of preference was absent during the process. Only consent (not informed consent) was taken from 50%-72% mothers for examination (except breast examination ‘0%’) and 8%-83% for any procedures during postpartum care. Only one-ninth (11%) of the mothers could ask service providers regarding the services they received. No consent was taken from 3% of the mothers- neither in the labor process nor in postpartum care. This current practice doesn’t comply with the Respectful Maternity Care (RMC) Charter 2011. The issue is not even clarified in the current Standard Clinical Management Protocols of the country. So, improvement of the existing protocol and increased awareness are essential to address this right of child-bearing women and to practice it during normal vaginal delivery and postpartum care.

Keywords: informed consent, normal vaginal delivery, respectful maternity care, tertiary level hospital

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Authors: Areti Okalidou, Paul D. Hatzigiannakoglou, Aikaterini Vatou, George Kyriafinis

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Young children are nowadays adept at using technology. Hence, computer-based auditory training programs (CBATPs) have become increasingly popular in aural rehabilitation for children with hearing loss and/or with cochlear implants (CI). Yet, their clinical utility for prognostic, diagnostic, and monitoring purposes has not been explored. The purposes of the study were: a) to develop an updated version of the auditory rehabilitation tool for Greek-speaking children with cochlear implants, b) to develop a database for behavioral responses, and c) to compare accuracy rates and reaction times in children differing in hearing status and other medical and demographic characteristics, in order to assess the tool’s clinical utility in prognosis, diagnosis, and progress monitoring. The updated version of the auditory rehabilitation tool was developed on a tablet, retaining the User-Centered Design approach and the elements of the Virtual Reality (VR) serious game. The visual stimuli were farm animals acting in simple game scenarios designed to trigger children’s responses to animal sounds, names, and relevant sentences. Based on an extended version of Erber’s auditory development model, the VR game consisted of six stages, i.e., sound detection, sound discrimination, word discrimination, identification, comprehension of words in a carrier phrase, and comprehension of sentences. A familiarization stage (learning) was set prior to the game. Children’s tactile responses were recorded as correct, false, or impulsive, following a child-dependent set up of a valid delay time after stimulus offset for valid responses. Reaction times were also recorded, and the database was in Εxcel format. The tablet version of the auditory rehabilitation tool was piloted in 22 preschool children with Νormal Ηearing (ΝΗ), which led to improvements. The study took place in clinical settings or at children’s homes. Fifteen children with CI, aged 5;7-12;3 years with post-implantation 0;11-5;1 years used the auditory rehabilitation tool. Eight children with CI were monolingual, two were bilingual and five had additional disabilities. The control groups consisted of 13 children with ΝΗ, aged 2;6-9;11 years. A comparison of both accuracy rates, as percent correct, and reaction times (in sec) was made at each stage, across hearing status, age, and also, within the CI group, based on presence of additional disability and bilingualism. Both monolingual Greek-speaking children with CI with no additional disabilities and hearing peers showed high accuracy rates at all stages, with performances falling above the 3rd quartile. However, children with normal hearing scored higher than the children with CI, especially in the detection and word discrimination tasks. The reaction time differences between the two groups decreased in language-based tasks. Results for children with CI with additional disability or bilingualism varied. Finally, older children scored higher than younger ones in both groups (CI, NH), but larger differences occurred in children with CI. The interactions between familiarization of the software, age, hearing status and demographic characteristics are discussed. Overall, the VR game is a promising tool for tracking the development of auditory skills, as it provides multi-level longitudinal empirical data. Acknowledgment: This work is part of a project that has received funding from the Research Committee of the University of Macedonia under the Basic Research 2020-21 funding programme.

Keywords: VR serious games, auditory rehabilitation, auditory training, children with cochlear implants

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Authors: Hamsa T. Tayeb, Mohammad A. Arafah, Dana M. Bakheet, Duaa M. Khalaf, Agnieszka Tarnoska, Nduna Dzimiri

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Background: CYP2D6 is a member of the cytochrome P450 mixed-function oxidase system. The enzyme is responsible for the metabolism and elimination of approximately 25% of clinically used drugs, especially in breast cancer and psychiatric therapy. Different phenotypes have been described displaying alleles that lead to a complete loss of enzyme activity, reduced function (poor metabolizers – PM), hyperfunctionality (ultrarapid metabolizers–UM) and therefore drug intoxication or loss of drug effect. The prevalence of these variants may vary among different ethnic groups. Furthermore, the xTAG system has been developed to categorized all patients into different groups based on their CYP2D6 substrate metabolization. Aim of the study: To determine the prevalence of the different CYP2D6 variants in our population, and to evaluate their clinical relevance in personalized medicine. Methodology: We used the Luminex xMAP genotyping system to sequence 305 Saudi individuals visiting the Blood Bank of our Institution and determine which polymorphisms of CYP2D6 gene are prevalent in our region. Results: xTAG genotyping showed that 36.72% (112 out of 305 individuals) carried the CYP2D6_*2. Out of the 112 individuals with the *2 SNP, 6.23% had multiple copies of *2 SNP (19 individuals out of 305 individuals), resulting in an UM phenotype. About 33.44% carried the CYP2D6_*41, which leads to decreased activity of the CYP2D6 enzyme. 19.67% had the wild-type alleles and thus had normal enzyme function. Furthermore, 15.74% carried the CYP2D6_*4, which is the most common nonfunctional form of the CYP2D6 enzyme worldwide. 6.56% carried the CYP2D6_*17, resulting in decreased enzyme activity. Approximately 5.73% carried the CYP2D6_*10, consequently decreasing the enzyme activity, resulting in a PM phenotype. 2.30% carried the CYP2D6_*29, leading to decreased metabolic activity of the enzyme, and 2.30% carried the CYP2D6_*35, resulting in an UM phenotype, 1.64% had a whole-gene deletion CYP2D6_*5, thus resulting in the loss of CYP2D6 enzyme production, 0.66% carried the CYP2D6_*6 variant. One individual carried the CYP2D6_*3(B), producing an inactive form of the enzyme, which leads to decrease of enzyme activity, resulting in a PM phenotype. Finally, one individual carried the CYP2D6_*9, which decreases the enzyme activity. Conclusions: Our study demonstrates that different CYP2D6 variants are highly prevalent in ethnic Saudi Arabs. This finding sets a basis for informed genotyping for these variants in personalized medicine. The study also suggests that xTAG is an appropriate procedure for genotyping the CYP2D6 variants in personalized medicine.

Keywords: CYP2D6, hormonal breast cancer, pharmacogenetics, polymorphism, psychiatric treatment, Saudi population

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Authors: Iva Blazkova, Amitava Moulick, Vedran Milosavljevic, Pavel Kopel, Marketa Vaculovicova, Vojtech Adam, Rene Kizek

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Doxorubicin is one of the most commonly used and the most effective chemotherapeutic drugs. This antracycline drug isolated from the bacteria Streptomyces peuceticus var. caesius is sold under the trade name Adriamycin (hydroxydaunomycin, hydroxydaunorubicin). Doxorubicin is used in single therapy to treat hematological malignancies (blood cancers, leukaemia, lymphoma), many types of carcinoma (solid tumors) and soft tissue sarcomas. It has many serious side effects like nausea and vomiting, hair lost, myelosupression, oral mucositis, skin reactions and redness, but the most serious one is the cardiotoxicity. Because of the risk of heart attack and congestive heart failure, the total dose administered to patients has to be accurately monitored. With the aim to lower the side effects and to targeted delivery of doxorubicin into the tumor tissue, the different nanoparticles are studied. The drug can be bound on a surface of nanoparticle, encapsulated in the inner cavity, or incorporated into the structure of nanoparticle. Among others, carbon nanoparticles (graphene, carbon nanotubes, fullerenes) are highly studied. Besides the number of inorganic nanoparticles, a great potential exhibit also organic ones mainly lipid-based and polymeric nanoparticle. The aim of this work was to perform a toxicity study of free doxorubicin compared to doxorubicin conjugated with various nanotransporters. The effect of liposomes, fullerenes, graphene, and carbon nanotubes on the toxicity was analyzed. As a first step, the binding efficacy of between doxorubicin and the nanotransporter was determined. The highest efficacy was detected in case of liposomes (85% of applied drug was encapsulated) followed by graphene, carbon nanotubes and fullerenes. For the toxicological studies, the chicken embryos incubated under controlled conditions (37.5 °C, 45% rH, rotation every 2 hours) were used. In 7th developmental day of chicken embryos doxorubicin or doxorubicin-nanotransporter complex was applied on the chorioallantoic membrane of the eggs and the viability was analyzed every day till the 17th developmental day. Then the embryos were extracted from the shell and the distribution of doxorubicin in the body was analyzed by measurement of organs extracts using laser induce fluorescence detection. The chicken embryo mortality caused by free doxorubicin (30%) was significantly lowered by using the conjugation with nanomaterials. The highest accumulation of doxorubicin and doxorubicin nanotransporter complexes was observed in the liver tissue

Keywords: doxorubicin, chicken embryos, nanotransporters, toxicity

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Authors: M. M. Essa, S. Subash, M. Akbar, S. Al-Adawi, A. Al-Asmi, G. J. Guillemein

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Objective: Transgenic (tg) mice which contain an amyloid precursor protein (APP) gene mutation, develop extracellular amyloid beta (Aβ) deposition in the brain, and severe memory and behavioural deficits with age. These mice serve as an important animal model for testing the efficacy of novel drug candidates for the treatment and management of symptoms of Alzheimer's disease (AD). Several reports have suggested that oxidative stress is the underlying cause of Aβ neurotoxicity in AD. Pomegranates contain very high levels of antioxidants and several medicinal properties that may be useful for improving the quality of life in AD patients. In this study, we investigated the effect of dietary supplementation of Omani pomegranate extract on the memory, anxiety and learning skills along with inflammation in an AD mouse model containing the double Swedish APP mutation (APPsw/Tg2576). Methods: The experimental groups of APP-transgenic mice from the age of 4 months were fed custom-mix diets (pellets) containing 4% pomegranate. We assessed spatial memory and learning ability, psychomotor coordination, and anxiety-related behavior in Tg and wild-type mice at the age of 4-5 months and 18-19 months using the Morris water maze test, rota rod test, elevated plus maze test, and open field test. Further, inflammatory parameters also analysed. Results: APPsw/Tg2576 mice that were fed a standard chow diet without pomegranates showed significant memory deficits, increased anxiety-related behavior, and severe impairment in spatial learning ability, position discrimination learning ability and motor coordination along with increased inflammation compared to the wild type mice on the same diet, at the age of 18-19 months In contrast, APPsw/Tg2576 mice that were fed a diet containing 4% pomegranates showed a significant improvements in memory, learning, locomotor function, and anxiety with reduced inflammatory markers compared to APPsw/Tg2576 mice fed the standard chow diet. Conclusion: Our results suggest that dietary supplementation with pomegranates may slow the progression of cognitive and behavioural impairments in AD. The exact mechanism is still unclear and further extensive research needed.

Keywords: Alzheimer's disease, pomegranates, oman, cognitive decline, memory loss, anxiety, inflammation

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Authors: Hugo Reis, Isabel Rabiais

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The main purpose of the present study is to understand the nurse’s responsibility in preventing the septic shock in an oncological patient with febrile neutropenia submitted to chemotherapy. In order to do it, an integrative review of literature has been conducted. In the research done in many databases, it was concluded that only 7 out of 5202 articles compiled the entire inclusion standard present in the strict protocol of research, being this made up by all different methodologies. On the research done in the 7 articles it has resulted 8 text macro-units associated to different nursing interventions: ‘Health Education’; ‘Prophylactic Therapy Administration’; ‘Scales Utilization’; ‘Patient Evaluation’; ‘Environment Control’; ‘Performance of Diagnostic Auxiliary Exams’; ‘Protocol Enforcement/Procedure Guidelines’; ‘Antibiotic Therapy Administration’. Concerning the prevalence/result’s division there can be identified many conclusions: the macro-units ‘Patient Evaluation’, ‘Performance of Diagnostic Auxiliary Exams’, and ‘Antibiotic Therapy Administration’ present themselves to be the most prevalent in the research – 6 in 7 occurrences (approximately 85.7%). Next, the macro-unit ‘Protocol Enforcement/Procedure Guidelines’ presents itself as an important expression unit – being part of 5 out of the 7 analyzed studies (approximately 71.4%). The macro-unit ‘Health Education’, seems to be in the same way, an important expression unit – 4 out of the 7 (or approximately 57%). The macro-unit ‘Scales Utilization’, represents a minor part in the research done – it’s in only 2 out of the 7 cases (approximately 28.6%). On the other hand, the macro-units ‘Prophylactic Therapy Administration’ and ‘Environment Control’ are the two categories with fewer results in the research - 1 out of the 7 cases, the same as approximately 14.3% of the research results. Every research done to the macro-unit ‘Antibiotic Therapy Administration’ agreed to refer that the intervention should be strictly done, in a period of time less than one hour after diagnosing the fever, with the purpose of controlling the quick spread of infection – minimizing its seriousness. Identifying these interventions contributes, concluding that, to adopt strategies in order to prevent the phenomenon that represents a daily scenario responsible for the cost´s increase in health institutions, being at the same time responsible for the high morbidity rates and mortality increase associated with this specific group of patients.

Keywords: febrile neutropenia, oncology nursing, patient, septic shock

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Authors: Antoine Villa, Moustapha Mohamedou, Florence Pilliere, Catherine Verdun-Esquer, Mathieu Molimard, Mohamed Sidatt Cheikh El Moustaph, Mireille Canal-Raffin

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Context: In Mauritania, the activity of the National Center of Oncology (NCO) has steadily risen leading to an increase in the handling of antineoplastic drugs (AD) by healthcare professionals. In this context, the AD contamination of those professionals is a major concern for occupational physicians. It has been evaluated using biological monitoring of occupational exposure (BMOE). Methods: The intervention took place in 2015, in 2 care units, and evaluated nurses preparing and/or infusing AD and agents in charge of hygiene. Participants provided a single urine sample, at the end of the week, at the end of their shift. Five molecules were sought using specific high sensitivity methods (UHPLC-MS/MS) with very low limits of quantification (LOQ) (cyclophosphamide (CP), Ifosfamide (IF), methotrexate (MTX): 2.5ng/L; doxorubicin (Doxo): 10ng/L; α-fluoro-β-alanine (FBAL, 5-FU metabolite): 20ng/L). A healthcare worker was considered as 'contaminated' when an AD was detected at a urine concentration equal to or greater than the LOQ of the analytical method or at trace concentration. Results: Twelve persons participated (6 nurses, 6 agents in charge of hygiene). Twelve urine samples were collected and analyzed. The percentage of contamination was 66.6% for all participants (n=8/12), 100% for nurses (6/6) and 33% for agents in charge of hygiene (2/6). In 62.5% (n=5/8) of the contaminated workers, two to four of the AD were detected in the urine. CP was found in the urine of all contaminated workers. FBAL was found in four, MTX in three and Doxo in one. Only IF was not detected. Urinary concentrations (all drugs combined) ranged from 3 to 844 ng/L for nurses and from 3 to 44 ng/L for agents in charge of hygiene. The median urinary concentrations were 87 ng/L, 15.1 ng/L and 4.4 ng/L for FBAL, CP and MTX, respectively. The Doxo urinary concentration was found 218ng/L. Discussion: There is no current biological exposure index for the interpretation of AD contamination. The contamination of these healthcare professionals is therefore established by the detection of one or more AD in urine. These urinary contaminations are higher than the LOQ of the analytical methods, which must be as low as possible. Given the danger of AD, the implementation of corrective measures is essential for the staff. Biological monitoring of occupational exposure is the most reliable process to identify groups at risk, tracing insufficiently controlled exposures and as an alarm signal. These results show the necessity to educate professionals about the risks of handling AD and/or to care for treated patients.

Keywords: antineoplastic drugs, Mauritania, biological monitoring of occupational exposure, contamination

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Authors: Elzbieta Sikorska-Simmons

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Dementia is a progressive terminal disease. Despite this recognition, research shows that most family caregivers do not know it, and it is unclear how this knowledge affects the quality of patient care. The aim of this qualitative study of 20 family caregivers for patients with advanced dementia is to examine how the caregiver's knowledge about dementia affects the quality of patient care in the context of healthcare decision-making, advanced care planning, and access to adequate support systems. Knowledge about dementia implies family caregivers' understanding of dementia trajectories, common symptoms/complications, and alternative treatment options (e.g., comfort feeding versus tube feeding). Data were collected in semi-structured interviews with 20 family caregivers. The interviews were conducted in person by the author and designed to elicit rich descriptions of family caregivers' experiences with healthcare decision-making and the management of common symptoms/complications of end-stage dementia as patient healthcare proxies. The study findings suggest that caregivers who recognize that dementia is a terminal disease are less likely to opt for life-extending treatments during the advanced stages. They are also more likely to seek palliative/hospice care, and consequently, they are better able to avoid unnecessary hospitalizations or medical procedures. For example, those who know that dementia is a terminal disease tend to opt for "comfort feeding" rather than "tube feeding" in managing the swallowing difficulties that accompany advanced dementia. In the context of advance care planning, family caregivers who know that dementia is a terminal disease tend to have more meaningful advance directives (e.g., Power of Attorney and Do Not Resuscitate orders). They are better prepared to anticipate common problems and pursue treatments that foster the best quality of patient life and care. Greater knowledge about advanced dementia helps them make more informed decisions that focus on enhancing the quality of patient life rather than just survival. In addition, those who know that dementia is a terminal disease are more likely to establish adequate support systems to help them cope with the complex demands of caregiving. For example, they are more likely to seek dementia-oriented primary care programs that offer house visits or respite services. Based on the study findings, knowledge about dementia as a terminal disease is critical in the optimal management of patient care needs and the establishment of adequate support systems. More research is needed to better understand what caregivers need to know to better prepare them for the complex demands of dementia caregiving.

Keywords: dementia education, family caregiver, management of dementia, quality of care

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Authors: Qi En Han, Si En Wai, Eugene Quek

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As one of the two Academic Medical Centres (AMCs) in Singapore, SingHealth Duke-NUS AMC strives to improve patients’ lives through excellent clinical care, research and education. These efforts are enhanced with the establishment of Academic Clinical Programmes (ACPs). Each ACP brings together specialists in a particular discipline from different institutions to maximize the power of shared knowledge and resources. Initiated by Surgery ACP, the student research mentorship programme is a programme designed to facilitate engagement between medical students and the surgical faculty. The programme offers mentors not only the opportunity to supervise research but also to nurture future clinician scientists. In turn, medical students acquire valuable research experience which may be useful in their future careers. The programme typically lasts one year, depending on the students’ commitment. Surgery ACP matches students’ research interests with the mentor's area of expertise whenever possible. Surgery ACP organizes informal tea sessions to bring students and prospective mentors together. Once a match is made, the pair is required to submit a project proposal which includes the title, proposed start and end dates, ethical and biosafety considerations and project details. The mentees either think of their own research question with guidance from the mentors or join an existing project. The mentees may participate in data collection, data analysis, manuscript writing and conference presentation. The progress of each research project is monitored through half-yearly progress report. The mentees report problems encountered or changes made to existing proposal on top of the progress made. A total of 18 mentors were successfully paired with 36 mentees since 2013. Currently, there are 23 on-going and 13 completed projects. The mentees are encouraged to present their projects at conferences and to publish in peer-reviewed journals. Six mentees have presented their completed projects at local or international conferences and one mentee has her work published. To further support student research, Surgery ACP organized a Research Day in 2015 to recognize their research efforts and to showcase their wide-range of research. Surgery ACP recognizes that early exposure of medical students to research is important in developing them into clinician scientists. As interest in research take time to develop and are usually realized during various research attachments, it is crucial that programmes such as the student research mentorship programme exist. Surgery ACP will continue to build on this programme.

Keywords: academic clinical programme, clinician scientist, medical student, mentoring

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Authors: Marin Kanarev, Delyan Stoyanov, Ivanna Popova, Nadezhda Petrova

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Thanks to increased survival rates in patients bearing oncological malignancies due to recent developments in anti-cancer therapies and diagnostic techniques, observation of clinical cases of metachronous cancers is more common and can provide more in-depth knowledge of their development and, as a result, help clinicians apply suitable therapy. This unusual case of three metachronous tumors presented the opportunity to follow their occurrence, progression, and treatment thoroughly. A 77-year-old male presented with carcinoma ventriculi of the pylorus region, which was surgically removed via upper subtotal stomach resection, a lateral antecolical gastro-enteroanastomosis, and a subsequent Braun anastomosis. An EOX chemotherapy regimen followed. A CT scan four months later showed no indication of recurrence or dissemination. The same scan, performed as a part of the follow-up plan two years later, showed an indication of neoplastic growth in the urinary bladder. After the patient had been directed to a urologist, the suspicion was confirmed, and the growth was histologically diagnosed as a carcinoma of the urinary bladder. An immunohistochemistry test showed an expression of PDL1 of less than 5%, which resulted in treatment with GemCis chemotherapy regimen that led to full remission. Two years and seven months after the first surgery, a CT scan showed again that the two carcinomas were gone. However, four months later, elevated tumor markers prompted a PET/CT scan, which showed data indicative of recurring neoplastic growth in the region of the stomach cardia. It was diagnosed as an adenocarcinoma infiltrating the esophagus. Preoperative chemotherapy with the ECF regimen was completed in four courses, and a CT scan showed no progression of the disease. In less than a month after therapy, the patient underwent laparotomy, debridement, gastrectomy, and a subsequent mechanical terminal-lateral esophago-jejunoanasthomosis. It was verified that the tumor originated from metastasis from the carcinoma ventriculi, which was located in the pylorus. In conclusion, this case report highlights the importance of patient follow-up and studying recurring neoplastic growth. Despite the absence of symptoms, clinicians should maintain a high level of suspicion when evaluating the patient data and choosing the most suitable therapy.

Keywords: carcinoma, follow-up, metachronous, neoplastic growth, recurrence

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Authors: Men An Pan, Ho Hsiung Huang, Jui Chuan Lin, Tsui Hsun Wu, Hsing Yuan Yen

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Pingtung County, located in the southernmost region of Taiwan, has the largest number of pig farms in the country. In the past, livestock operators in Dongpian Village discharged their wastewater into the nearby water bodies, causing water pollution in the local rivers and polluting the air with the stench of the pig excrement. These resulted in many complaints from the local residents. In response to a long time fighting back of the community against the livestock farms due to the confrict, the County Government's Environmental Protection Bureau (PTEPB) examined potential wayouts in addition to heavy fines to the perpetrators. Through helping the livestock farms to upgrade their pollution prevention equipment, promoting the reuse of biogas residue and slurry from the pig excrement, and environmental education, the confrict was successfully resolved. The properly treated wastewater from the livestock farms has been freely provided to the neighboring farmlands via pipelines and tankers. Thus, extensive cultivation of bananas, papaya, red dragon fruit, Inca nut, and cocoa has resulted in 34% resource utilization of biogas residue as a fertilizer. This has encouraged farmers to reduce chemical fertilizers and use microbial materials like photosynthetic bacteria after banning herbicides while lowering the cost of wastewater treatment in livestock farms and alleviating environmental pollution simultaneously. That is, the livestock farms fully demonstrate the determination to fulfill their corporate social responsibility (CSR). Due to the success, Eight farms jointly established a social enterprise - "Dongpian Gemstone Village Co., Ltd." to promote organic farming through a "shared farm." The company appropriates 5% of its total revenue back to the community through caregiving services for the elderly and a fund for young local farmers. The community adopted the Satoyama Initiative in accordance with the Conference of the CBD COP10. Through the positive impact of environmental education, the community seeks to realize the coexistence between society and nature while maintaining and developing socio-economic activities (including agriculture) with respect for nature and building a harmonic relationship between humans and nature. By way of sustainable management of resources and ensuring biodiversity, the community is transforming into a socio-ecological production landscape. Apart from nature conservation and watercourse ecology, preserving local culture is also a key focus of the environmental education. To mitigate the impact of global warming and climate change, the community and the government have worked together to develop a disaster prevention and relief system, strive to establish a low-carbon emitting homeland, and become a model for resilient communities. By the power of environmental education, this community has turned its residents’ hearts and minds into concrete action, fulfilled social responsibility, and moved towards realizing the UN SDGs. Even though it is not the only community to integrate government agencies, research institutions, and NGOs for environmental education, it is a prime example of a low-carbon sustainable community that achieves more than 9 SDGs, including responsible consumption and production, climate change action, and diverse partnerships. The community is also leveraging environmental education to become a net-zero carbon community targeted by COP26.

Keywords: environmental education, biogas residue, biogas slurry, CSR, SDGs, climate change, net-zero carbon emissions

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Authors: Deepak Jugran, Rajesh Gill

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Purpose: To study the demographic, sociological, gender and clinical profile of the children presented for childhood cataract at a public sector tertiary eye care centre in India. Methodology: The design of the study is retrospective, and hospital-based data is available with the Central Registration Department of the PGIMER, Chandigarh. The majority of the childhood cataract cases are being reported in this hospital, yet not each and every case of childhood cataract approaches PGI, Chandigarh. Nevertheless, this study is going to be pioneering research in India, covering five-year data of the childhood cataract patients who visited the Advanced Eye Centre, PGIMER, Chandigarh, from 1.1.2015 to 31.12.2019. The SPSS version 23 was used for all statistical calculations. Results: A Total of 354 children were presented for childhood cataract from 1.1.2015 to 31.12.2019. Out of 354 children, 248 (70%) were male, and 106 (30%) were female. In-spite of 2 flagship programmes, namely the National Programme for Control of Blindness (NPCB) and Aayushman Bharat (PM JAY) for eradication of cataract, no children received any financial assistance from these two programmes. A whopping 99% of these children belong to the poor families. In most of these families, the mothers were house-wives and did not employ anywhere. These interim results will soon be conveyed to the Govt. of India so that a suitable mechanism can be evolved to address this pertinent issue. Further, the disproportionate ratio of male and female children in this study is an area of concern as we don’t know whether the prevalence of childhood cataract is lower in female children or they are not being presented on time in the hospital by the families. Conclusion: The World Health Organization (WHO) has categorized Childhood blindness resulting from cataract as a priority area and urged all member countries to develop institutionalized mechanisms for its early detection, diagnosis and management. The childhood cataract is an emerging and major cause of preventable and avoidable childhood blindness, especially in low and middle-income countries. In the formative years, the children require a sound physical, mental and emotional state, and in the absence of either one of them, it can severely dent their future growth. The recent estimate suggests that India could suffer an economic loss of US$12 billion (Rs. 88,000 Crores) due to blindness, and almost 35% of cases of blindness are preventable and avoidable if detected at an early age. Besides reporting these results to the policy makers, synchronized efforts are needed for early detection and management of avoidable causes of childhood blindness such as childhood cataract.

Keywords: childhood blindness, cataract, Who, Npcb

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Authors: T. Heikkinen, J. Oksman, T. Bragge, A. Nurmi, O. Kontkanen, T. Ahtoniemi

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Motor impairment is an inherent phenotypic feature of several chronic neurodegenerative diseases, and pharmacological therapies aimed to counterbalance the motor disability have a great market potential. Animal models of chronic neurodegenerative diseases display a number deteriorating motor phenotype during the disease progression. There is a wide array of behavioral tools to evaluate motor functions in rodents. However, currently existing methods to study motor functions in rodents are often limited to evaluate gross motor functions only at advanced stages of the disease phenotype. The most commonly applied traditional motor assays used in CNS rodent models, lack the sensitivity to capture fine motor impairments or improvements. Fine motor skill characterization in rodents provides a more sensitive tool to capture more subtle motor dysfunctions and therapeutic effects. Importantly, similar approach, kinematic movement analysis, is also used in clinic, and applied both in diagnosis and determination of therapeutic response to pharmacological interventions. The aim of this study was to apply kinematic gait analysis, a novel and automated high precision movement analysis system, to characterize phenotypic deficits in three different chronic neurodegenerative animal models, a transgenic mouse model (SOD1 G93A) for amyotrophic lateral sclerosis (ALS), and R6/2 and Q175KI mouse models for Huntington’s disease (HD). The readouts from walking behavior included gait properties with kinematic data, and body movement trajectories including analysis of various points of interest such as movement and position of landmarks in the torso, tail and joints. Mice (transgenic and wild-type) from each model were analyzed for the fine motor kinematic properties at young ages, prior to the age when gross motor deficits are clearly pronounced. Fine motor kinematic Evaluation was continued in the same animals until clear motor dysfunction with conventional motor assays was evident. Time course analysis revealed clear fine motor skill impairments in each transgenic model earlier than what is seen with conventional gross motor tests. Motor changes were quantitatively analyzed for up to ~80 parameters, and the largest data sets of HD models were further processed with principal component analysis (PCA) to transform the pool of individual parameters into a smaller and focused set of mutually uncorrelated gait parameters showing strong genotype difference. Kinematic fine motor analysis of transgenic animal models described in this presentation show that this method isa sensitive, objective and fully automated tool that allows earlier and more sensitive detection of progressive neuromuscular and CNS disease phenotypes. As a result of the analysis a comprehensive set of fine motor parameters for each model is created, and these parameters provide better understanding of the disease progression and enhanced sensitivity of this assay for therapeutic testing compared to classical motor behavior tests. In SOD1 G93A, R6/2, and Q175KI mice, the alterations in gait were evident already several weeks earlier than with traditional gross motor assays. Kinematic testing can be applied to a wider set of motor readouts beyond gait in order to study whole body movement patterns such as with relation to joints and various body parts longitudinally, providing a sophisticated and translatable method for disseminating motor components in rodent disease models and evaluating therapeutic interventions.

Keywords: Gait analysis, kinematic, motor impairment, inherent feature

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Authors: K. Rawojć, J. Miszczyk, A. Możdżeń, A. Panek, J. Swakoń, M. Rydygier

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Due to the mitotic delay, poor mitotic index and disappearance of lymphocytes from peripheral blood circulation, assessing the DNA damage after high dose exposure is less effective. Conventional chromosome aberration analysis or cytokinesis-blocked micronucleus assay do not provide an accurate dose estimation or radiosensitivity prediction in doses higher than 6.0 Gy. For this reason, there is a need to establish reliable methods allowing analysis of biological effects after exposure in high dose range i.e., during particle radiotherapy. Lately, Premature Chromosome Condensation (PCC) has become an important method in high dose biodosimetry and a promising treatment modality to cancer patients. The aim of the study was to evaluate the usefulness of drug-induced PCC scoring procedure in an experimental mode, where 100 G2/M cells were analyzed in different dose ranges. To test the consistency of obtained results, scoring was performed by 3 independent persons in the same mode and following identical scoring criteria. Whole-body exposure was simulated in an in vitro experiment by irradiating whole blood collected from healthy donors with 60 MeV protons and 250 keV X-rays, in the range of 4.0 – 20.0 Gy. Drug-induced PCC assay was performed on human peripheral blood lymphocytes (HPBL) isolated after in vitro exposure. Cells were cultured for 48 hours with PHA. Then to achieve premature condensation, calyculin A was added. After Giemsa staining, chromosome spreads were photographed and manually analyzed by scorers. The dose-effect curves were derived by counting the excess chromosome fragments. The results indicated adequate dose estimates for the whole-body exposure scenario in the high dose range for both studied types of radiation. Moreover, compared results revealed no significant differences between scores, which has an important meaning in reducing the analysis time. These investigations were conducted as a part of an extended examination of 60 MeV protons from AIC-144 isochronous cyclotron, at the Institute of Nuclear Physics in Kraków, Poland (IFJ PAN) by cytogenetic and molecular methods and were partially supported by grant DEC-2013/09/D/NZ7/00324 from the National Science Centre, Poland.

Keywords: cell response to radiation exposure, drug induced premature chromosome condensation, premature chromosome condensation procedure, proton therapy

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Authors: Mario Hanna Louis Hanna

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The use of CAD (pc Aided layout) generation is ubiquitous inside the structure, engineering and construction (AEC) industry. This has led to its inclusion in the curriculum of structure faculties in Nigeria as an important part of the training module. This newsletter examines the moral troubles involved in implementing CAD (pc Aided layout) content into the architectural training curriculum. Using current literature, this study begins with the advantages of integrating CAD into architectural education and the responsibilities of various stakeholders in the implementation process. It also examines issues related to the terrible use of records generation and the perceived bad effect of CAD use on design creativity. The use of a survey technique, information from the architecture department of Chukwuemeka Odumegwu Ojukwu Uli college changed into accumulated to serve as a case observe on how the problems raised have been being addressed. The object draws conclusions on what guarantees a hit moral implementation. Tens of millions of human beings around the sector suffer from hepatitis C, one of the international's deadliest sicknesses. Interferon (IFN) is a remedy alternative for patients with hepatitis C, but these treatments have their aspect outcomes. Our research targeted growing an oral small molecule drug that goals hepatitis C virus (HCV) proteins and has fewer facet effects. Our contemporary study targets to broaden a drug primarily based on a small molecule antiviral drug precise for the hepatitis C virus (HCV). Drug improvement and the use of laboratory experiments isn't always best high-priced, however also time-eating to behavior those experiments. instead, on this in silicon have a look at, we used computational strategies to recommend a particular antiviral drug for the protein domain names of discovered in the hepatitis C virus. This examines used homology modeling and abs initio modeling to generate the 3-D shape of the proteins, then figuring out pockets within the proteins. Proper lagans for pocket pills were advanced the usage of the de novo drug design method. Pocket geometry is taken into consideration while designing ligands. A few of the various lagans generated, a different for each of the HCV protein domains has been proposed.

Keywords: drug design, anti-viral drug, in-silicon drug design, Hepatitis C virus (HCV) CAD (Computer Aided Design), CAD education, education improvement, small-size contractor automatic pharmacy, PLC, control system, management system, communication.

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Authors: Suat Erel, Gozde Gur

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Background: Recently a supramalleolar type of dynamic ankle foot orthosis (DAFO) has been increasingly used to support all of the dynamic arches of the foot and redistribute the pressure under the plantar surface of the foot to reduce the muscle tone. DAFO helps to maintain balance and postural control by providing stability and proprioceptive feedback in children with disease like Cerebral Palsy, Muscular Dystrophies, Down syndrome, and congenital hypotonia. Aim: The aim of this study was to investigate the role of Dynamic ankle foot orthosis (DAFO) on temporo-spatial parameters of gait and balance in three children with hereditary spastic paraparesis (HSP). Material Method: 13, 14, and 8 years old three children with HSP were included in the study. To provide correction on weight bearing and to improve gait, DAFO was made. Lower extremity spasticity (including gastocnemius, hamstrings and hip adductor muscles) using modified Ashworth Scale (MAS) (0-5), The temporo-spatial gait parameters (walking speed, cadence, base of support, step length) and Timed Up & Go test (TUG) were evaluated. All of the assessments about gait were compared with (with DAFO and shoes) and without DAFO (with shoes only) situations. Also after six months follow up period, assessments were repeated by the same physical therapist. Results: MAS scores for lower extremity were between “2-3” for the first child, “0-2” for the second child and “1-2” for the third child. TUG scores (sec) decreased from 20.2 to 18 for case one, from 9.4 to 9 for case two and from 12,4 to 12 for case three in the condition with shoes only and also from 15,2 to 14 for case one, from 7,2 to 7,1 for case two and from 10 to 7,3 for case three in the condition with DAFO and shoes. Gait speed (m/sec) while wearing shoes only was similar but while wearing DAFO and shoes increased from 0,4 to 0,5 for case one, from 1,5 to 1,6 for case two and from 1,0 to 1,2 for case three. Base of support scores (cm) wearing shoes only decreased from 18,5 to 14 for case one, from 13 to 12 for case three and were similar as 11 for case two. While wearing DAFO and shoes, base of support decreased from 10 to 9 for case one, from 11,5 to 10 for case three and was similar as 8 for case two. Conclusion: The use of a DAFO in a patient with HSP normalized the temporo-spatial gait parameters and improved balance. Walking speed is a gold standard for evaluating gait quality. With the use of DAFO, walking speed increased in this three children with HSP. With DAFO, better TUG scores shows that functional ambulation improved. Reduction in base of support and more symmetrical step lengths with DAFO indicated better balance. These encouraging results warrant further study on wider series.

Keywords: dynamic ankle foot orthosis, gait, hereditary spastic paraparesis, balance in patient

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Authors: Samane Eftekhari Ranjbar

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Diabetes mellitus, a metabolic disorder characterized by elevated blood glucose levels, ranks among the leading causes of adult mortality. This study investigates the impact of an eight-week high-intensity interval training (HIIT) program combined with sodium nitrite supplementation on TNF- α, MURF1, and PI3K in a type 2 diabetes rodent model. Elevated TNF-α levels have been associated with insulin resistance, while MURF1 and PI3K play roles in muscle atrophy and insulin signaling pathways, respectively. In this experimental study, 15 eight-week-old rats from the Sara Laboratory Center in Tabriz were assigned to one of five groups: healthy control, diabetic control, diabetic with sodium nitrite supplementation, diabetic with eight weeks of intermittent exercise, and diabetic with eight weeks of interval training plus sodium nitrite supplementation. The HIIT protocol was designed to span eight weeks, with five weekly sessions at specified intensities and durations. Sodium nitrite, known for its vasodilatory and cytoprotective properties, was administered via injection. The findings revealed that the HIIT program and sodium nitrite supplementation influenced the examined biomarkers. ANOVA test outcomes indicated statistically significant differences in TNF- α (P=0.001), MURF1 (P=0.001), and PI3K (P=0.001) concentrations among the various groups. The healthy control group exhibited substantially decreased TNF- α, and MURF1 levels, as well as elevated PI3K levels compared to the diabetic control group. The exercise group, in conjunction with sodium nitrite supplementation, demonstrated a significant rise in PI3K levels (P=0.001) and a decline in TNF- α levels (P=0.018) relative to the diabetic control group. These results suggest that the combined intervention may help improve insulin sensitivity and reduce inflammation. However, MURF1 levels, which are related to muscle atrophy, showed no significant difference (P=0.24). In conclusion, in type 2 diabetic rats, an eight-week high-intensity interval training program with sodium nitrite supplementation does not affect MURF1 levels but does influence PI3K and TNF- α levels. This combination may hold potential for improving insulin sensitivity and reducing inflammation in type 2 diabetes patients, warranting further investigation and potential translation to human clinical trials.

Keywords: high-intensity interval training, sodium nitrate supplementation, type 2 diabetes, tumor necrosis factor-alpha, phosphatidylinositol-3-kinase, muscle RING-finger protein-1

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Authors: Sebastian Wójtowicz, Anna Mosiołek, Anna Słupik, Zbigniew Wroński, Dariusz Białoszewski

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Introduction: In whole-body vibration (WBV) high-frequency mechanical stimuli is generated by a vibration plate and is transferred through bone, muscle and connective tissues to the whole body. The research has shown that the implementation of a vibration plate training over a long period of time leads to improvement of neuromuscular facilitation, especially in afferent neural pathways, which are responsible for the conduction of vibration and proprioceptive stimuli, muscle function, balance, and proprioception. The vibration stimulus is suggested to briefly inhibit the conduction of afferent signals from proprioceptors and may hinder the maintenance of body balance. The purpose of this study was to evaluate the result of a single set of exercises connected with whole-body vibration on the proprioception. Material and Methods: The study enrolled 60 people aged 19-24 years. These individuals were divided into a test group (group A) and a control group (group B). Both groups consisted of 30 persons and performed the same set of exercises on a vibration plate. The following vibration parameters: frequency of 20Hz and amplitude of 3mm, were used in the group A. The vibration plate was turned off while the control group did their exercises. All participants performed six dynamic 30-seconds-long exercises with a 60-second resting period between them. Large muscle groups of the trunk, pelvis, and lower limbs were involved while taking the exercises. The results were measured before and immediately after the exercises. The proprioception of lower limbs was measured in a closed kinematic chain using a Humac 360®. Participants were instructed to perform three squats with biofeedback in a defined range of motion. Then they did three squats without biofeedback which were measured. The final result was the average of three measurements. Statistical analysis was performed using Statistica 10.0 PL software. Results: There were no significant differences between the groups, both before and after the exercise (p > 0.05). The proprioception did not change in both the group A and the group B. Conclusions: 1. Deterioration in proprioception was not observed immediately after the vibration stimulus. This suggests that vibration-induced blockage of proprioceptive stimuli conduction can only have a short-lasting effect occurring only in the presence of the vibration stimulus. 2. Short-term use of vibration seems to be safe for patients with proprioceptive impairment due to the fact that the treatment does not decrease proprioception. 3. There is a need for supplementing the results with evaluation of proprioception while vibration stimuli are being applied. Moreover, the effects of vibration parameters used in the exercises should be evaluated.

Keywords: joint position sense, proprioception, squat, whole body vibration

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Authors: Madeleine Cox

Abstract:

Objective: Discussion of diagnosis and management options for myometrial ectopic pregnancy Case: A 30 yo G1P0 presented to the emergency department with vaginal bleeding for the last 4 days. She had a positive home urine pregnancy test, confirmed with a serum HCG. When she presented for an ultrasound, there was no intrauterine pregnancy, no evidence of adnexal pregnancy, however, the anterior myometrium of the uterus was noted to be markedly abnormal. When she presented to the emergency department of a busy tertiary hospital in Queensland, she had a small amount of vaginal bleeding, was anxious but well, observations normal. Repeat blood testes demonstrated a serum HCG of 9246 IU/L, haemoglobin of 143g/L. The patient had an interesting history of a right oophorectomy and open myomectomy in another country. A repeat ultrasound again showed an abnormality within the myometrium of the uterus, which was initially reported as concerning for an AVM, or potentially invasive gestational trophoblastic disease. An MRI was organised 2 days later, which demonstrated a intramural/subserosal irregularity in the right lateral body measuring 35x38x42mm with peripheral enhancement and central cystic components, favouring a myometrial ectopic most likely at the site of previous myomectomy. Alternative diagnosis of AVM, GTD were considered less likely. After discussion with the patient, IV methotrexate was administered as an in patient 4 days after her initial presentation to emergency. After this, her HCG fell to 1236 IU/L on day 6 post treatment. Weekly reviews showed stable ultrasound appearances with a steadily dropping HCG level. A repeat MRI was performed 3 weeks after methotrexate administration which confirmed involution of the myometrial ectopic, however, showed ongoing progression of vascularity surrounding the site. Despite resolution of HCG, the patient persisted to have ongoing bleeding associated with this and went to have uterine artery embolisation. Follow up ultrasound showed resolution of abnormal vascularity and negative HCG levels. Conclusion: Myometrial ectopic pregnancies are a rare occurrence and require a multidisciplinary approach to achieve timely management for these patients. This patient was in a very well resourced setting with excellent access to Interventional Radiology and specialist Radiologists who could work together with the Obstetrics, Gynaecology, and Maternal Fetal Medicine team to provide multiple options of management which preserved her fertility. This case has a very good outcome, with the patient being referred back to our service 12 months later with an early intrauterine pregnancy.

Keywords: ectopic, pregnancy, miscarriage, gynaecology

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Authors: Mengestie Mulugeta Belay, Serebe Abay Gebrie, Biruk Lambbiso Wamisho, Amare Worku

Abstract:

Background: Low back pain (LBP) related to nursing profession, is a very common public health problem throughout the world. Various risk factors have been implicated in the etiology and LBP is assumed to be of multi-factorial origin as individual, work-related and psychosocial factors can contribute to its development. Objectives: To determine the prevalence and to identify risk factors of LBP among nurses working in Addis Ababa City Public Hospitals, Ethiopia, in the year 2015. Settings: Addis Ababa University, Black-Lion (‘Tikur Anbessa’) Hospital-BLH, is the country’s highest tertiary level referral and teaching Hospital. The three departments in connection with this study: Radiology, Pathology and Orthopedics, run undergraduate and residency programs and receive referred patients from all over the country. Methods: A cross-sectional study with internal comparison was conducted throughout the period October-December, 2015. Sample was chosen by simple random sampling technique by taken the lists of nurses from human resource departments as a sampling frame. A well-structured, pre-tested and self-administered questionnaire was used to collect quantifiable information. The questionnaire included socio-demographic, back pain features, consequences of back pain, work-related and psychosocial factors. The collected data was entered into EpiInfo version 3.5.4 and was analyzed by SPSS. A probability level of 0.05 or less and 95% confidence level was used to indicate statistical significance. Ethical clearance was obtained from all respected administrative bodies, Hospitals and study participants. Results: The study included 395 nurses and gave a response rate of 91.9%. The mean age was 30.6 (±8.4) years. Majority of the respondents were female (285, 72.2%). Nearly half of the participants (n=181, 45.8% (95% CI (40.8%- 50.6%))) were complained low back pain. There was statistical significant association between low back pain and working shift, physical activities at work; sleep disturbance and felt little pleasure by doing things. Conclusion: A high prevalence of low back pain was found among nurses working in Addis Ababa Public Hospitals. Recognition and preventive measures like providing resting periods should be taken to reduce the risk of low back pain in nurses working in Public hospitals.

Keywords: low back pain, risk factors, nurses, public hospitals

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Authors: Mike Wei, Nebu Koshy, Koen van Besien, Giorgio Inghirami, Steven M. Horwitz

Abstract:

T-cell prolymphocytic leukemia (T-PLL) is a rare hematologic disease characterized by a T-cell phenotype, rapid progression, and poor prognosis with median survival of less than a year. Alemtuzumab-based chemotherapy has increased the rate of complete remissions but these are often short-lived, and allogeneic transplant is considered the only curative therapy. In recent studies, JAK3 activating mutations have been identified in T-cell cancers, with T-PLL having the highest rate of JAK3 mutations (30 – 42%). As such, T-PLL is a model disease for evaluating the utility of JAK3 inhibitors. We present a case of a 64-year-old man with relapsed-refractory T-PLL. He was initially treated with alemtuzumab and obtained complete response and was consolidated with matched unrelated donor stem cell transplant. His disease stayed in remission for approximately 1.5 years before relapse, which was then treated with a clinical trial of romidepsin-lenalidomide (partial responses then progression at 6 months) and later alemtuzumab. Due to complications of myelosuppression and CMV reactivation, his treatment was interrupted leading to disease progression. The doubling time of lymphocyte count was approximately 20 days and over a span of 60 days the lymphocyte count rose from 8 x 109/L to 68 x 109/L. Exon sequencing showed a JAK3 mutation. The patient consented to and was treated with FDA-approved tofacitinib (initially 5 mg BID, increased to 10 mg BID after 15 days of treatment). An initial decrease in lymphocyte count was followed by progression. In vitro treatment of the patient’s cells showed modest effects of tofacitinib and ruxolitinib as single agents, in the range of doxorubicin, but synergy between the agents. After 40 days of treatment with tofacitinib and with a lymphocyte count of 150 x 109/L, ruxolitinib (5mg BID) was added. Over the 60 days since dual inhibition was started, the lymphocyte count has stabilized. The patient has remained completely asymptomatic during treatment with tofacitinib and ruxolitinib. Neutrophil count has remained normal. Platelet count and hemoglobin have however declined from ~50 x109/L to ~30 x109/L and from 11 g/dL to 8.1 g/dL respectively, since the introduction of ruxolitinib. The stabilization in lymphocyte count confirms the clinical activity of JAK inhibitors in T-PLL as suggested by the presence of JAK3 mutations and by in-vitro assays. It also suggests clinical synergy between ruxolitinib and tofacitinib in this setting. Prospective studies of JAK inhibitors in PLL patients with formal dose-finding studies are needed.

Keywords: tofacitinib, ruxolitinib, T-cell prolymphocytic leukemia, JAK3

Procedia PDF Downloads 310