Search results for: prospective cohort studies

Authors: Paula I. Buonfiglio, Carlos David Bruque, Lucia Salatino, Vanesa Lotersztein, Sebastián Menazzi, Paola Plazas, Ana Belén Elgoyhen, Viviana Dalamón

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Hearing loss (HL) is the most prevalent sensorineural disorder affecting about 10% of the global population, with more than half due to genetic causes. About 1 in 500-1000 newborns present congenital HL. Most of the patients are non-syndromic with an autosomal recessive mode of inheritance. To date, more than 100 genes are related to HL. Therefore, the Whole-exome sequencing (WES) technique has become a cost-effective alternative approach for molecular diagnosis. Nevertheless, new challenges arise from the detection of novel variants, in particular missense changes, which can lead to a spectrum of genotype-to-phenotype correlations, which is not always straightforward. In this work, we aimed to identify the genetic causes of HL in isolated and familial cases by designing a multistep approach to analyze target genes related to hearing impairment. Moreover, we performed in silico and in vivo analyses in order to further study the effect of some of the novel variants identified in the hair cell function using the zebrafish model. A total of 650 patients were studied by Sanger Sequencing and Gap-PCR in GJB2 and GJB6 genes, respectively, diagnosing 15.5% of sporadic cases and 36% of familial ones. Overall, 50 different sequence variants were detected. Fifty of the undiagnosed patients with moderate HL were tested for deletions in STRC gene by Multiplex ligation-dependent probe amplification technique (MLPA), leading to 6% of diagnosis. After this initial screening, 50 families were selected to be analyzed by WES, achieving diagnosis in 44% of them. Half of the identified variants were novel. A missense variant in MYO6 gene detected in a family with postlingual HL was selected to be further analyzed. A protein modeling with AlphaFold2 software was performed, proving its pathogenic effect. In order to functionally validate this novel variant, a knockdown phenotype rescue assay in zebrafish was carried out. Injection of wild-type MYO6 mRNA in embryos rescued the phenotype, whereas using the mutant MYO6 mRNA (carrying c.2782C>A variant) had no effect. These results strongly suggest the deleterious effect of this variant on the mobility of stereocilia in zebrafish neuromasts, and hence on the auditory system. In the present work, we demonstrated that our algorithm is suitable for the sequential multigenic approach to HL in our cohort. These results highlight the importance of a combined strategy in order to identify candidate variants as well as the in silico and in vivo studies to analyze and prove their pathogenicity and accomplish a better understanding of the mechanisms underlying the physiopathology of the hearing impairment.

Keywords: diagnosis, genetics, hearing loss, in silico analysis, in vivo analysis, WES, zebrafish

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Authors: L. Spencer, S. O’ Donohoe

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Much of the research to date on internationalisation relates to large firms with much less known about how small and medium-sized enterprises (SMEs) engage in internationalisation. Given the crucial role of SMEs in contributing to economic growth, there is now an emphasis on the need for SMEs internationalise. Yet little is known about how SMEs undertake and finance such expansion and whether or not internationalisation actually hinders or helps them in securing finance. The purpose of this research is to explore the internationalisation process for SMEs, the sources of funding used in financing this expansion and support received from the state agencies in assisting their overseas expansion. A conceptual framework has been devised which marries the two strands of literature together (internationalisation and financing the firm). The exploratory nature of this research dictates that the most appropriate methodology was to use semi-structured interviews with SME owners; bank representatives and support agencies. In essence, a triangulated approach to the research problem facilitates assessment of the perceptions and experiences from firms, the state and the financial institutions. Our sample is drawn from SMEs operating in Ireland and Scotland, two small but very open economies where SMEs are the dominant form of organisation. The sample includes a range of industry sectors. Key findings to date suggest some SMEs are born global; others are born again global whilst a significant cohort can be classed as traditional internationalisers. Unsurprisingly there is a strong industry effect with firms in the high tech sector more likely to be faster internationalisers in contrast to those in the traditional manufacturing sectors. Owner manager’s own funds are deemed key to financing initial internationalisation lending support for the financial growth life cycle model albeit more important for the faster internationalisers in contrast to the slower cohort who are more likely to deploy external sources especially bank finance. Retained earnings remain the predominant source of on-going financing for internationalising firms but trade credit is often used and invoice discounting is utilised quite frequently. In terms of lending, asset based lending backed by personal guarantees appears paramount for securing bank finance. Whilst the lack of diversified sources of funding for internationalising SMEs was found in both jurisdictions there appears no evidence to suggest that internationalisation impedes firms in securing finance. Finally state supports were cited as important to the internationalisation process, in particular those provided by Enterprise Ireland were deemed very valuable. Considering the paucity of studies to date on SME internationalisation and in particular the funding mechanisms deployed by them; this study seeks to contribute to the body of knowledge in both the international business and finance disciplines.

Keywords: funding, government support, international pathways, modes of entry

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Authors: Dagikhudo Dagiev

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This paper is a thorough contribution to the analysis of Russian, Soviet and post-Soviet scholarship on the study of Ismailism in Central Asia. It focuses on the lengthy development of Russian studies on Ismailism from the Russian colonial domination to the entire period of Soviet rule, down to the collapse of the Soviet Union and the last two decades of post-Soviet history. These studies, conducted along the lines of various disciplines in the span of more than one hundred years, have resulted in a large amount of scholarly contributions. This paper aims at probing the virtues and shortcoming of such scholarship. Particularly, our investigation of the specialised fields in the Russian-Soviet Studies has required laborious researches in Russian and Central Asian libraries, which have enabled us to provide a guide through this literature, assessing its ideological leanings and qualities, institutions and level of scholarship. Despite some shortcomings, due to Marxism and the authoritarian rule of the Communist Party over the socio-religious life of the people and religious communities, Soviet studies have produced many positive insights on Ismailis studies. These captured almost every aspects of the life of the Ismaili community from anthropology to archaeology, ethnography, history, philosophy, ritual practice and, most importantly, collection and preservation of Ismaiili manuscripts, which will be examined and assessed in this study.

Keywords: Central Asian Studies, Ismailism, Russian Studies, Soviet Studies

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Authors: N. E. Gallagher, C. E. Neville, N. Lyner, J. Yarnell, C. C. Patterson, J. E. Gallacher, Y. Ben-Shlomo, A. Fehily, J. V. Woodside

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Hearing loss is highly prevalent in older people and can reduce quality of life substantially. Emerging research suggests that potentially modifiable risk factors, including risk factors previously related to cardiovascular disease risk, may be associated with a decreased or increased incidence of hearing loss. This has prompted investigation into the possibility that certain nutrients, foods or dietary patterns may also be associated with incidence of hearing loss. The aim of this study was to determine any associations between dietary patterns and hearing loss in men enrolled in the Caerphilly study. The Caerphilly prospective cohort study began in 1979-1983 with recruitment of 2512 men aged 45-59 years. Dietary data was collected using a self-administered, semi-quantitative, 56-item food frequency questionnaire (FFQ) at baseline (1979-1983), and 7-day weighed food intake (WI) in a 30% sub-sample, while pure-tone unaided audiometric threshold was assessed at 0.5, 1, 2 and 4 kHz, between 1984 and 1988. Principal components analysis (PCA) was carried out to determine a posteriori dietary patterns and multivariate linear and logistic regression models were used to examine associations with hearing level (pure tone average (PTA) of frequencies 0.5, 1, 2 and 4 kHz in decibels (dB)) for linear regression and with hearing loss (PTA>25dB) for logistic regression. Three dietary patterns were determined using PCA on the FFQ data- Traditional, Healthy, High sugar/Alcohol avoider. After adjustment for potential confounding factors, both linear and logistic regression analyses showed a significant and inverse association between the Healthy pattern and hearing loss (P<0.001) and linear regression analysis showed a significant association between the High sugar/Alcohol avoider pattern and hearing loss (P=0.04). Three similar dietary patterns were determined using PCA on the WI data- Traditional, Healthy, High sugar/Alcohol avoider. After adjustment for potential confounding factors, logistic regression analyses showed a significant and inverse association between the Healthy pattern and hearing loss (P=0.02) and a significant association between the Traditional pattern and hearing loss (P=0.04). A Healthy dietary pattern was found to be significantly inversely associated with hearing loss in middle-aged men in the Caerphilly study. Furthermore, a High sugar/Alcohol avoider pattern (FFQ) and a Traditional pattern (WI) were associated with poorer hearing levels. Consequently, the role of dietary factors in hearing loss remains to be fully established and warrants further investigation.

Keywords: ageing, diet, dietary patterns, hearing loss

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Authors: V. Santamarina Campos, M. de Miguel Molina, B. de Miguel Molina, M. Á. Carabal Montagud

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With this contribution, we want to show a successful example of the application of the Design Thinking methodology, in the European project 'Technology transfer of Remotely Piloted Aircraft Systems (RPAS) for the creative industry'. The use of this methodology has allowed us to design and build a drone, based on the real needs of prospective users. It has demonstrated that this is a powerful tool for generating innovative ideas in the field of robotics, by focusing its effectiveness on understanding and solving real user needs. In this way, with the support of an interdisciplinary team, comprised of creatives, engineers and economists, together with the collaboration of prospective users from three European countries, a non-linear work dynamic has been created. This teamwork has generated a sense of appreciation towards the creative industries, through continuously adaptive, inventive, and playful collaboration and communication, which has facilitated the development of prototypes. These have been designed to enable filming and photography in interior spaces, within 13 sectors of European creative industries: Advertising, Architecture, Fashion, Film, Antiques and Museums, Music, Photography, Televison, Performing Arts, Publishing, Arts and Crafts, Design and Software. Furthermore, it has married the real needs of the creative industries, with what is technologically and commercially viable. As a result, a product of great value has been obtained, which offers new business opportunities for small companies across this sector.

Keywords: design thinking, design for effectiveness, methodology, active toolkit, storyboards, PAR, focus group, innovation, RPAS, indoor drone, aerial film, creative industry, end users, stakeholder

Procedia PDF Downloads 177

Authors: Taik Kim

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Mathematics anxiety has an important consequence for teacher practices that influence students’ attitudes and achievement. Elementary prospective teachers have the highest levels of mathematics anxiety in comparison with other college majors. In his teaching practice, the researcher developed a highly successful teaching model to reduce pre-service teachers’ higher math anxiety and simultaneously to improve their pedagogical math content knowledge. There were eighty one participants from 2015 to 2018 who took the Mathematics for Elementary Teachers I and II. As the analysis data indicated, elementary prospective teachers’ math anxiety was greatly reduced with improving their math pedagogical knowledge. U.S encounters a critical shortage of well qualified educators. To solve the issue, it is essential to engage students in a long-term commitmentto shape better teachers, who will, in turn, produce k-12 school students that are better-prepared for college students. It is imperative that new instructional strategies are implemented to improve student learning and address declining interest, poor preparedness, a lack of diverse representation, and low persistence of students in mathematics. Many four year college students take math courses from the math department in the College of Arts& Science and then take methodology courses from the College of Education. Before taking pedagogy, many students struggle in learning mathematics and lose their confidence. Since the content course focus on college level math, instead of pre service teachers’ teaching area, per se elementary math, they do not have a chance to improve their teaching skills on topics which eventually they teach. The research, a joint appointment of math and math education, has been involved in teaching content and pedagogy. As the result indicated, participants were able to math content at the same time how to teach. In conclusion, the new initiative to use several teaching strategies was able not only to increase elementary prospective teachers’ mathematical skills and knowledge but also to improve their attitude toward mathematics. We need an innovative teaching strategy which implements evidence-based tactics in redesigning a education and math to improve pre service teachers’math skills and which can improve students’ attitude toward math and students’ logical and reasoning skills. Implementation of these best practices in the local school district is particularly important because K-8 teachers are not generally familiar with lab-based instruction. At the same time, local school teachers will learn a new way how to teach math. This study can be a vital teacher education model expanding throughout the State and nationwide. In summary, this study yields invaluable information how to improve teacher education in the elementary level and, eventually, how to enhance K-8 students’ math achievement.

Keywords: quality of education and improvement method, teacher education, innovative teaching and learning methodologies, math education

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Authors: Gracie Tredget, Raymond McGrath, Karen Ang, Julie Williams, Nick Sevdalis, Fiona Gaughran, Jorge Aria de la Torre, Ioannis Bakolis, Andy Healey, Zarnie Khadjesari, Euan Sadler, Natalia Stepan

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Background: Preventable physical health problems have been found to increase morbidity rates amongst adults living with serious mental illness (SMI). Community mental health clinicians have a role in identifying, and preventing physical health problems worsening, and supporting primary care services to administer routine physical health checks for their patients. However, little is known about how mental health staff perceive and approach their role when providing physical healthcare amongst patients with SMI, or the impact these attitudes have on routine practice. Methods: The present study involves a prospective service evaluation specific to Adult Community Mental Health Services at South London and Maudsley NHS Foundation Trust (SLaM). A qualitative methodology will use semi-structured interviews, focus groups and observations to explore attitudes, perceptions and experiences of staff, patients, and carers (n=64) towards physical healthcare, and barriers or facilitators that impact upon it. 1South London and Maudsley NHS Foundation Trust, London, SE5 8AZ, UK 2 Centre for Implementation Science, King’s College London, London, SE5 8AF, UK 3 Psychosis Studies, King's College London, London, SE5 8AF, UK 4 Department of Biostatistics and Health Informatics, King’s College London, London, SE5 8AF, UK 5 Kings Health Economics, King's College London, London, SE5 8AF, UK 6 Behavioural and Implementation Science (BIS) research group, University of East Anglia, Norwich, UK 7 Department of Nursing, Midwifery and Health, University of Southampton, Southampton, UK 8 Mind and Body Programme, King’s Health Partners, Guy’s Hospital, London, SE1 9RT *[email protected] Analysis: Data from across qualitative tasks will be synthesised using Framework Analysis methodologies. Staff, patients, and carers will be invited to participate in co-development of recommendations that can improve routine physical healthcare within Adult Community Mental Health Teams at SLaM. Results: Data collection is underway at present. At the time of the conference, early findings will be available to discuss. Conclusions: An integrated approach to mind and body care is needed to reduce preventable deaths amongst people with SMI. This evaluation will seek to provide a framework that better equips staff to approach physical healthcare within a mental health setting.

Keywords: severe mental illness, physical healthcare, adult community mental health, nursing

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Authors: Mariem Meddeb Sidhom, Souhayel Hedfi, Rjaibia Houda, Mehdi Dridi, Mohamed Ali Yousfi, Sâadia Gargouri

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Considering the important increase in costs of caspofungin treatments and ahead the evolution of its indication, pharmacy department was prompted to realize a review of the adequacy of prescriptions in the medical intensive care units (ICU). A retrospective observational study was conducted in Tunis military hospital concerning ICU prescriptions of caspofungin from 2008 until 2013. A pharmacist had returned to the patient’s medical records to collect data and to the microbiology department for parasitological results. The adequacy of prescriptions was evaluated by a pharmacist and an infectiologist parasitologist, referring to predefined scale of criteria resuming the indications of the marketing authorization (MA) and grade AI-AII of the guidelines of the Infectious Diseases Society of America (IDSA). Sixty two ICU patients have been treated with caspofungin during the period of study; however, 8 files were lost. Thus, 54 patients were included in the study having received 55 prescriptions of caspofungin. Males were a majority with 64.8% of the population. Mean age was 51 years. Caspofungin was indicated in accordance with the IDSA recommendations in 43.6% of the cases. The most case of non respect to the guidelines was the indication of caspofungin as empirical treatment in non neutropenic patients. Caspofungin was utilized as a first line treatment in 9 cases where it was possible to give fluconazole first, as germs were fluconazole- sensitive. Caspofungin was indicated in 2 patients with good renal function and in which nor amphotericin B, liposomal ampho B neither itraconazole had been previously used, as indicates the MA. The posology of caspofungin was respected in all prescriptions with a loading dose of 70 mg in the first day and a maintenance dose of 50 mg daily. Seven patients had received a daily dose of 70 mg, the recommended dose for people weighing more than 80 Kg. Caspofungin prescriptions are far to be adequately done. There is a clear need of optimization in indicating this molecule and that must be done in collaboration between the pharmacy department, the ICUs and parasitology department.

Keywords: caspofungin, prescription, intensive care units, marketing authorization, Tunisian hospital cohort

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Authors: Ghulam Sohail, Christopher Hawkes

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Pakistan has been facing a growing energy crisis for the last decade, and the government is seeking new horizons for increasing oil and gas production to reduce the gap between supply and demand. Recent developments in technologies to produce natural gas from shales at economical rates has unlocked new horizons for hydrocarbon exploration and development throughout the world. Operating companies in the U.S.A. and Canada have been particularly successful at producing shale gas, so comparing against the properties of shale gas reservoirs in these countries is used for an initial assessment of prospective shale gas reservoirs in other parts of the world. In this study, selected source rocks of Pakistan are evaluated for their shale gas potential using analogs selected from various North American shales for which data have been published. Published data for Pakistani shales were compiled, then assessed and supplemented through consultation with industry professionals. Pakistani formations reviewed are the Datta (shaly sandstone), Hangu (sandy shale), Patala (sandy shale), Ranikot (shaly sandstone), Sembar (sandy shale) and Lower Goru (shaly sandstone) formations, all of which are known source rocks in the Indus Basin. For this study, available geological, geochemical, petrophysical and elastic parameters have been investigated and are correlated specifically with the eight most active shale gas plays of the U.S.A., while data for other North American shale gas plays are used for general discussion on prospective Pakistani shales. The results show that the geological and geochemical parameters of all the Pakistani shales reviewed in this work are promising regarding their shale gas. However, more petrophysical and geomechanical data are required before conclusions on economic production from these shales can be made with confidence.

Keywords: Canada shale gas, Indus Basin, Pakistani shales, U.S.A shale gas

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Authors: Soheila Zhaeentan, Anders Von Heijne, Elisabet Hagert, André Stark, Björn Salomonsson

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Recommended treatment for traumatic rotator cuff tear (TRCT) is surgery within a few weeks after injury if the diagnosis is made early, especially if a functional impairment of the shoulder exists. This may lead to the assumption that a poor outcome then can be expected in delayed surgical treatment, when the patient is diagnosed at a later stage. The aim of this study was to investigate if a surgical repair later than three months after injury may result in successful outcomes and patient satisfaction. There is evidence in literature that good results of treatment can be expected up to three months after the injury, but little is known of later treatment with cuff repair. 73 patients (75 shoulders), 58 males/17 females, mean age 59 (range 34-­‐72), who had undergone surgical intervention for TRCT between January 1999 to December 2011 at our clinic, were included in this study. Patients were assessed by MRI investigation, clinical examination, Western Ontario Rotator Cuff index (WORC), Oxford Shoulder Score, Constant-­‐Murley Score, EQ-­‐5D and patient subjective satisfaction at follow-­‐up. The patients treated surgically within three months ( < 12 weeks) after injury (39 cases) were compared with patients treated more than three months ( ≥ 12 weeks) after injury (36 cases). WORC was used as the primary outcome measure and the other variables as secondary. A senior consultant radiologist, blinded to patient category and clinical outcome, evaluated all MRI-­‐images. Rotator cuff integrity, presence of arthritis, fatty degeneration and muscle atrophy was evaluated in all cases. The average follow-­‐up time was 56 months (range 14-­‐149) and the average time from injury to repair was 16 weeks (range 3-­‐104). No statistically significant differences were found for any of the assessed parameters or scores between the two groups. The mean WORC score was 77 (early group, range 25-­‐ 100 and late group, range 27-­‐100) for both groups (p= 0.86), Constant-­‐Murley Score (p= 0.91), Oxford Shoulder Score (p= 0.79), EQ-­‐5D index (p= 0.86). Re-­‐tear frequency was 24% for both groups, and the patients with re-­‐tear reported less satisfaction with outcome. Discussion and conclusion: This study shows that surgical repair of TRCT performed later than three months after injury may result in good functional outcomes and patient satisfaction. However, this does not motivate an intentional delay in surgery when there is an indication for surgical repair as that delay may adversely affect the possibility to perform a repair. Our results show that surgeons may safely consider surgical repair even if a delay in diagnosis has occurred. A retrospective cohort study on 75 shoulders shows good functional result after traumatic rotator cuff tear (TRCT) treated surgically up to one year after the injury.

Keywords: traumatic rotator cuff injury, time to surgery, surgical outcome, retrospective cohort study

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Authors: Anne Heirman, Vincent van der Noort, Rob van Son, Marije Petersen, Lisette van der Molen, Gyorgy Halmos, Richard Dirven, Michiel van den Brekel

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Objective: Voice prosthesis leakage significantly impacts laryngectomies patients' quality of life, causing insecurity and frequent unplanned hospital visits and costs. In this study, the concept of prophylactic voice prosthesis replacement was explored to prevent leakages. Study Design: A retrospective cohort study. Setting: Tertiary hospital. Methods: Device lifetimes and voice prosthesis replacements of a retrospective cohort, including all patients with laryngectomies between 2000 and 2012 in the Netherlands Cancer Institute, were used to calculate the number of needed voice prostheses per patient per year when preventing 70% of the leakages by prophylactic replacement. Various strategies for the timing of prophylactic replacement were considered: Adaptive strategies based on the individual patient’s history of replacement and fixed strategies based on the results of patients with similar voice prosthesis or treatment characteristics. Results: Patients used a median of 3.4 voice prostheses per year (range 0.1-48.1). We found a high inter-and intrapatient variability in device lifetime. When applying prophylactic replacement, this would become a median of 9.4 voice prostheses per year, which means replacement every 38 days, implying more than six additional voice prostheses per patient per year. The individual adaptive model showed that preventing 70% of the leakages was impossible for most patients, and only a median of 25% can be prevented. Monte-Carlo simulations showed that prophylactic replacement is not feasible due to the high Coefficient of Variation (Standard Deviation/Mean) in device lifetime. Conclusion: Based on our simulations, prophylactic replacement of voice prostheses is not feasible due to high inter-and intrapatient variation in device lifetime.

Keywords: voice prosthesis, voice rehabilitation, total laryngectomy, prosthetic leakage, device lifetime

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Authors: Kathrina Aseanne Acapulco-Gomez, Shayne Julieane Morales, Tzar Francis Verame

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Mean platelet volume (MPV) is the most accurate measure of the size of platelets and is routinely measured by most automated hematological analyzers. Several studies have shown associations between MPV and cardiovascular risks and outcomes. Although its measurement may provide useful data, MPV remains to be a diagnostic tool that is yet to be included in routine clinical decision making. The aim of this systematic review and meta-analysis is to determine summary estimates of the diagnostic accuracy of mean platelet volume for the diagnosis of myocardial infarction among adult patients with angina and/or its equivalents in terms of sensitivity, specificity, diagnostic odds ratio, and likelihood ratios, and to determine the difference of the mean MPV values between those with MI and those in the non-MI controls. The primary search was done through search in electronic databases PubMed, Cochrane Review CENTRAL, HERDIN (Health Research and Development Information Network), Google Scholar, Philippine Journal of Pathology, and Philippine College of Physicians Philippine Journal of Internal Medicine. The reference list of original reports was also searched. Cross-sectional, cohort, and case-control articles studying the diagnostic performance of mean platelet volume in the diagnosis of acute myocardial infarction in adult patients were included in the study. Studies were included if: (1) CBC was taken upon presentation to the ER or upon admission (within 24 hours of symptom onset); (2) myocardial infarction was diagnosed with serum markers, ECG, or according to accepted guidelines by the Cardiology societies (American Heart Association (AHA), American College of Cardiology (ACC), European Society of Cardiology (ESC); and, (3) if outcomes were measured as significant difference AND/OR sensitivity and specificity. The authors independently screened for inclusion of all the identified potential studies as a result of the search. Eligible studies were appraised using well-defined criteria. Any disagreement between the reviewers was resolved through discussion and consensus. The overall mean MPV value of those with MI (9.702 fl; 95% CI 9.07 – 10.33) was higher than in those of the non-MI control group (8.85 fl; 95% CI 8.23 – 9.46). Interpretation of the calculated t-value of 2.0827 showed that there was a significant difference in the mean MPV values of those with MI and those of the non-MI controls. The summary sensitivity (Se) and specificity (Sp) for MPV were 0.66 (95% CI; 0.59 - 0.73) and 0.60 (95% CI; 0.43 – 0.75), respectively. The pooled diagnostic odds ratio (DOR) was 2.92 (95% CI; 1.90 – 4.50). The positive likelihood ratio of MPV in the diagnosis of myocardial infarction was 1.65 (95% CI; 1.20 – 22.27), and the negative likelihood ratio was 0.56 (95% CI; 0.50 – 0.64). The intended role for MPV in the diagnostic pathway of myocardial infarction would perhaps be best as a triage tool. With a DOR of 2.92, MPV values can discriminate between those who have MI and those without. For a patient with angina presenting with elevated MPV values, it is 1.65 times more likely that he has MI. Thus, it is implied that the decision to treat a patient with angina or its equivalents as a case of MI could be supported by an elevated MPV value.

Keywords: mean platelet volume, MPV, myocardial infarction, angina, chest pain

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Authors: Robert E. Kenney, Richard B. Aguilar, Efrain Antunez, Gregory Schor-Haskin, Rafael Rey, Catie Falcon, Luis Arce

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This study sought to explore the effect of Sarapin injections on chronic knee pain (CKP). Many adults suffer from CKP which is most often attributed to osteoarthritis. Current treatment regimens for CKP involve the use NSAIDS medications, injections with steroids/analgesic, platelet rich plasma injections, or orthopedic surgical interventions. Sarapin is a commercially available homeopathic aqueous extract from the pitcher plant. Studies on the use of Sarapin as a treatment for cervical, thoracic, and lumbosacral facet joint nerve blocks have been performed with mixed results. There is little available evidence on the use of Sarapin in CKP. This study examines the effect of a series of 3 weekly injections of aqueous Sarapin in 95 elderly patients with CKP in a primary care setting. Cano Health, a primary care group, identified 95 successive patients with CKP from its multimodal physiotherapy program for chronic pain. Patients underwent evaluation by a clinician, underwent diagnostic Xrays of the knees, and the treatment plan with three weekly Sarapin injections was discussed. A pain and functional limitation survey (a modified Lower Extremity Functional Scale (mLEFS)) was administered prior to initiating treatment (Entry Survey (ES)). Each patient received an intraarticular injection of 2 cc of aqueous Sarapin with 1cc 1% lidocaine during weeks 1, 2 and 3. The mLEFS was administered again at week 4, one week after the third Sarapin injection (Exit Survey (ExS)). Demographics: Mean Age 62 +/- 9.8; 73% female; 89% Hispanic/Latino; mean time between ES and ExS was 27.5 +/-8.2 days. Survey: The mLEFS was based on a published Lower Extremity Functional Scale and each patient rated their pain or functional limitation from 0 (no difficulty) to 5 (severe difficulty) for 10 questions. Answers were summed and compared. Maximum score for severe difficulty would be 50 points. Results: Mean pain/functional scores: ES was 30.3 +/-12.1 and ExS was 19.5 +/- 12.5. This represents a relative improvement of 35.7% (P<0.00001). A total of 81% (77/95) of the patients showed improvement in symptoms at week four as assessed by the mLEFS. There were 11 patients who reported an increase in their survey scores while 7 patients reported no change. When evaluating the cohort that reported improvement, the ES was 30.9 +/-11.4 and ExS was 16.3 +/-9.8 yielding a 47.2% relative improvement (P<0.00001). Injections were well tolerated, and no adverse events were reported. Conclusions: In this cohort of 95 elderly patients with CKP, treatment with 3 weekly injections of Sarapin significantly improved pain and function as assessed by a mLEFS survey. The majority (81%) of patients responded positively to therapy, 12% had worsening symptoms and 7% reported no change. The use of intraarticular injections of Sarapin for CKP was shown to be an effective modality of treatment. Sarapin’s low cost, tolerability, and ease of use make it an attractive alternative to NSAIDS, steroids, PRP or surgical intervention for this common debilitating condition.

Keywords: Sarapin, intraarticular, chronic knee pain, osteoarthritis

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Authors: Siddhant Yadav, Rylea Ranum, Hannah Alberts, Abdul Kalaiger, Brent Bauer, Ryan Hurt, Ann Vincent, Loren Toussaint, Sanjeev Nanda

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Background and significance: Fibromyalgia (FM) is a chronic pain disorder also characterized by chronic fatigue, morning stiffness, sleep, and cognitive symptoms, psychological disturbances (anxiety, depression), and is comorbid with multiple medical and psychiatric conditions. It has an incidence of 2-4% in the general population and is reported more commonly in women. Oxidative stress and inflammation are thought to contribute to pain in patients with FM, and the adoption of an antioxidant/anti-inflammatory diet has been suggested as a modality to alleviate symptoms. The aim of this systematic review was to evaluate the efficacy of specialized diets (ketogenic, gluten free, Mediterranean, and low carbohydrate) in improving FM symptoms. Methodology: A comprehensive search of the following databases from inception to July 15th, 2021, was conducted: Ovid MEDLINE and Epub ahead of print, in-process and other non-indexed citations and daily, Ovid Embase, Ovid EBM reviews, Cochrane central register of controlled trials, EBSCO host CINAHL with full text, Elsevier Scopus, website and citation index, web of science emerging sources citation and clinicaltrials.gov. We included randomized controlled trials, non-randomized experimental studies, cross-sectional studies, cohort studies, case series, and case reports in adults with fibromyalgia. The risk of bias was assessed with the Agency for Health Care Research and Quality designed, specific recommended criteria (AHRQ). Results: Thirteen studies were eligible for inclusion. This included a total of 761 participants. Twelve out of the 13 studies reported improvement in widespread body pain, joint stiffness, sleeping pattern, mood, and gastrointestinal symptoms, and one study reported no changes in symptomatology in patients with FM on specialized diets. None of the studies showed the worsening of symptoms associated with a specific diet. Most of the patient population was female, with the mean age at which fibromyalgia was diagnosed being 48.12 years. Improvement in symptoms was reported by the patient's adhering to a gluten-free diet, raw vegan diet, tryptophan- and magnesium-enriched Mediterranean diet, aspartame- and msg- elimination diet, and specifically a Khorasan wheat diet. Risk of bias assessment noted that 6 studies had a low risk of bias (5 clinical trials and 1 case series), four studies had a moderate risk of bias, and 3 had a high risk of bias. In many of the studies, the allocation of treatment (diets) was not adequately concealed, and the researchers did not rule out any potential impact from a concurrent intervention or an unintended exposure that might have biased the results. On the other hand, there was a low risk of attrition bias in all the trials; all were conducted with an intention-to-treat, and the inclusion/exclusion criteria, exposures/interventions, and primary outcomes were valid, reliable, and implemented consistently across all study participants. Concluding statement: Patients with fibromyalgia who followed specialized diets experienced a variable degree of improvement in their widespread body pain. Improvement was also seen in stiffness, fatigue, moods, sleeping patterns, and gastrointestinal symptoms. Additionally, the majority of the patients also reported improvement in overall quality of life.

Keywords: fibromyalgia, specialized diet, vegan, gluten free, Mediterranean, systematic review

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Authors: I. Iroka, L. Mgidlana, J. Willoughby, S. Dhlamini, P. Nxumalo, S. Sefadi, A. Mthembu, E. Gerber, E. Brits

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Introduction: Nephroblastoma is a common paediatric tumor with good survival rates when diagnosed and treated early. Method: This retrospective study aimed to describe the patients with nephroblastoma seen at Universitas Academic Hospital Complex between the years 2000 and 2020. Results: In the study period, there were 207 patients identified. The patient profile had slightly more male than female patients; the median age was under four years of age. The study found a median delay of one month between symptom onset and diagnosis; a common cause was a delay in seeking care. Patients diagnosed and treated more than a month after symptoms started had poorer survival rates. There was a higher rate of Stage IV disease compared to similar studies in South Africa. Good preoperative histology and no relapse had good survival rates.. Patients from Lesotho had longer delays and presented with more severe diseases than the South African cohort. Conclusion: Early identification and treatment lead to better outcomes. Health-seeking behaviour, misdiagnosis, and referral delays might contribute to the long delays. A targeted study for patients from Lesotho is recommended.

Keywords: nephroblastoma, South Africa, Lesotho, developing country

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Authors: Timea Harmath-Tánczos

Abstract:

Drug-resistant epilepsy (DRE) is defined as the persistence of seizures despite at least two syndrome-adapted antiseizure drugs (ASD) used at efficacious daily doses. About a third of patients with epilepsy suffer from drug resistance. Cognitive assessment has a crucial role in the diagnosis and clinical management of epilepsy. Previous studies have addressed the clinical targets and indications for measuring neuropsychological functions; best to our knowledge, no studies have examined it in a Hungarian therapy-resistant population. To fill this gap, we investigated the Hungarian diagnostic protocol between 18 and 65 years of age. This study aimed to describe and analyze neuropsychological functions in patients with drug-resistant epilepsy and identify factors associated with neuropsychology deficits. We perform a prospective case-control study comparing neuropsychological performances in 50 adult patients and 50 healthy individuals between March 2023 and July 2023. Neuropsychological functions were examined in both patients and controls using a full set of specific tests (general performance level, motor functions, attention, executive facts., verbal and visual memory, language, and visual-spatial functions). Potential risk factors for neuropsychological deficit were assessed in the patient group using a multivariate analysis. The two groups did not differ in age, sex, dominant hand and level of education. Compared with the control group, patients with drug-resistant epilepsy showed worse performance on motor functions and visuospatial memory, sustained attention, inhibition and verbal memory. Neuropsychological deficits could therefore be systematically detected in patients with drug-resistant epilepsy in order to provide neuropsychological therapy and improve quality of life. The analysis of the classical and complex indices of the special neuropsychological tasks presented in the presentation can help in the investigation of normal and disrupted memory and executive functions in the DRE.

Keywords: drug-resistant epilepsy, Hungarian diagnostic protocol, memory, executive functions, cognitive neuropsychology

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Authors: Pugazhenthan Thangaraju

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Background: Since the pandemic began, more than millions of people have become infected with COVID-19. Globally, researchers are working for safe and effective treatments for this disease. Remdesivir is a drug that has been approved for the treatment of COVID-19. Many aspects are still being considered that may influence the future use of remdesivir. Aim: To assess the safety and efficacy of Remdesivir in hospitalized adult patients diagnosed with moderate and severe COVID-19. Methods: It was a record-based retrospective cohort study conducted between April 1st, 2020 and June 30th, 2021 at the tertiary care teaching hospital All India Institutes of Medical Sciences (AIIMS), Raipur Results: There were a total of 10,559 medical records of COVID-19 patients of which 1034 records were included in this study. Overall, irrespective of the survival status, there was statistical significant difference observed between the WHO score at the time of admission and discharge. Clinical improvement among the survivors was found to be statistically significant. Conclusion: Remdesivir's potential efficacy against coronaviruses has so far been limited to in vitro studies and animal models. However, information about COVID-19 is rapidly expanding. Several clinical trials for the treatment of COVID-19 with remdesivir are now underway. However, the findings of this study support remdesivir as a promising agent in the fight against SARS-CoV-2.

Keywords: Remdesivir, COVID-19, SARS-CoV-2, antiviral, RNA-dependent RNA polymerase, viral pneumonia

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Authors: Mrudula Kudtarkar, Rajesh Mane

Abstract:

Introduction: Cleft lip repair is one of the common surgeries performed in India and the usual method used for post-operative analgesia is perioperative opioids and NSAIDs. There has been an increase in use of regional techniques and Opioids are the common adjuvants but their efficacy and safety have not been studied extensively in children. Aim: A prospective, randomized, double-blind study was done to compare the efficacy, duration and safety of intraoral infraorbital nerve block on post-operative pain relief using bupivacaine alone or in combination with fentanyl or pethidine in paediatric cleft lip repair. Methodology: 45 children between the age group 5 – 60 months undergoing cleft lip surgery randomly allocated into 3 groups of 15 each received bilateral intraoral infraorbital nerve block with 0.75ml of solution. Group B received 0.25% bupivacaine; group P received 0.25% bupivacaine with 0.25mg/kg pethidine, group F received 0.25% bupivacaine with 0.25microgm/kg fentanyl. Sedation after recovery, post-operative pain intensity and duration of post-operative analgesia were assessed using Modified Hannallah Pain Score. Results: The mean duration of analgesia was 17.8 hrs in Group B, 23.53 hrs in Group F and 35.13 hrs in Group P. There was statistically significant difference between the means of the three groups- ANOVA (p < 0.05). Conclusion: Thus we conclude that addition of fentanyl or pethidine to bupivacaine for Bilateral Intraoral Infraorbital Nerve Block prolong the duration of analgesia with no complications and can be used safely in paediatric patients.

Keywords: cleft lip, infraorbital block, NSAIDS, Opiods

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Authors: A. Drapeaux, S. Aviles, E. Garfoot

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Stem cell injections are a promising alternative treatment for hip osteoarthritis. Current literature has focused on short-term outcomes for both knee and hip osteoarthritis; however, there is a significant gap for longitudinal benefits for hip OA and limited firm conclusions due to small sample sizes. The purpose of this prospective study was to determine longitudinal changes in pain, function, and radiographs following bone marrow concentrate injection (BMAC) into the osteoarthritic hip joint. Methods: A prospective, cross-sectional study was conducted over the course of 12 months at an orthopedic practice. The study recruited 15 osteoarthritic pre-surgical hips with mild to moderate osteoarthritic severity who were scheduled to undergo hip arthroscopy. Data was collected at both pre-operative and post-operative time frames. Data collected included: hip radiographs, i-HOT-33 questionnaire data, BMAC autologous volume, and demographics. Questionnaire data was captured using Qualtrics XM software, and participants were sent an anonymous link at the following time frames: pre-operative, 2 weeks, 6 weeks, 12 weeks, 6 months, 12 months, and 24 months. Radiographic changes and BMAC volume were collected and reviewed by an orthopedic surgeon and sent to the primary investigator. Data was exported and analyzed in IBM-SPSS. Results: A total of 15 hips from 15 participants (mean age: 49, gender: 50% males, 50% females, BMI: 29.7) were used in the final analysis. Summative i-HOT 33 mean scores significantly changed between pre-operative status and 2-6 weeks post-operative status (p <.001) and pre-operative status and 3-6 months post-operative status (p <.001). There were no significant changes between other post-operative phases or between pre-operative status and 12 months post-operative. Significant improvements were found between summative i-HOT 33 mean (p<.001), daily pain (p<.001), daily sitting (p=.02), daily distance walked (p =.003), and daily limp (p=0.03) and post-operative status (2-6 weeks). No significant differences between demographic variables (gender, age, tobacco use, or diabetes) and i-HOT 33 summative mean scores. Discussion/Implications: The purpose of this study was to determine longitudinal changes in pain and function following a hip joint bone marrow concentrate injection. Results indicate that participants experience a significant improvement in pain and function between pre-operative and 2-6 weeks and 3-6 months post-injection. Participants also self-reported a significant change in average daily pain with sitting and walking between pre-operation and 2-6 weeks post-operative. This study includes a larger sample size of hip osteoarthritis cases; however, future research is warranted to include random controlled trials with a larger sample size.

Keywords: adult stem cell, orthopedics, osteoarthritis (hip), patient outcome assessment

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Authors: Ayse Ozge Demir, Nihat Mert

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This study has been carried out in order to determine the polymorphic traits of various biochemical parameters in goat breeds which are native to Turkey. For this purpose, Angora and Hair goats breeds were chosen as live materials. Two different herds for each breed were selected from Ankara and Antalya, respectively. Blood samples were taken from a total of 120 goats aged between 2 and 4 which was made up of 60 Angora goats and 60 Hair goats. All which derived equally from 4 lots of herds. Analyses were performed for the polymorphic determination of the Haemoglobin (Hb), Transferrine (Tf), Ceruloplasmin (Cp) and Glutathione (GSH). Hb types were determined by starch gel electrophoresis and Tf types were detected by SDS-PAGE electrophoresis. Furthermore, Cp and GSH analyses were performed by spectrophotometrically. Following the analysis, Hb types were found as 3 genotypes (AA, AB, BB) controlled by 2 allel genes. Tf types were found as 6 genotypes (AA, AB, AC, BB, BC, CC) controlled by 3 allele genes. Findings for Hb was in line with the Hardy-Weinberg Equilibrium (HWE) in Angora goats while the Hair goat was not found to be in line. Moreover, Tf was found in line with the HWE for 2 separate goat breeds. The levels of Cp and GSH of two breeds were significantly different from other (P<0.0001). The findings are recorded as a source of reference for prospective polymorphism studies.

Keywords: electrophoresis, genetic resources, goats, spectrophotometer

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Authors: Sarah E. Nelson, Casey Weiner, Alexander Sigmon, Jun Hua, Haris I. Sair, Jose I. Suarez, Robert D. Stevens

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Graph-theoretical information from structural connectomes indicated significant connectivity changes and improved acute prognostication in a Random Forest (RF) model in aneurysmal subarachnoid hemorrhage (aSAH), which can lead to significant morbidity and mortality and has traditionally been fraught by poor methods to predict outcome. This study’s hypothesis was that structural connectivity changes occur in canonical brain networks of acute aSAH patients, and that these changes are associated with functional outcome at six months. In a prospective cohort of patients admitted to a single institution for management of acute aSAH, patients underwent diffusion tensor imaging (DTI) as part of a multimodal MRI scan. A weighted undirected structural connectome was created of each patient’s images using Constant Solid Angle (CSA) tractography, with 176 regions of interest (ROIs) defined by the Johns Hopkins Eve atlas. ROIs were sorted into four networks: Default Mode Network, Executive Control Network, Salience Network, and Whole Brain. The resulting nodes and edges were characterized using graph-theoretic features, including Node Strength (NS), Betweenness Centrality (BC), Network Degree (ND), and Connectedness (C). Clinical (including demographics and World Federation of Neurologic Surgeons scale) and graph features were used separately and in combination to train RF and Logistic Regression classifiers to predict two outcomes: dichotomized modified Rankin Score (mRS) at discharge and at six months after discharge (favorable outcome mRS 0-2, unfavorable outcome mRS 3-6). A total of 56 aSAH patients underwent DTI a median (IQR) of 7 (IQR=8.5) days after admission. The best performing model (RF) combining clinical and DTI graph features had a mean Area Under the Receiver Operator Characteristic Curve (AUROC) of 0.88 ± 0.00 and Area Under the Precision Recall Curve (AUPRC) of 0.95 ± 0.00 over 500 trials. The combined model performed better than the clinical model alone (AUROC 0.81 ± 0.01, AUPRC 0.91 ± 0.00). The highest-ranked graph features for prediction were NS, BC, and ND. These results indicate reorganization of the connectome early after aSAH. The performance of clinical prognostic models was increased significantly by the inclusion of DTI-derived graph connectivity metrics. This methodology could significantly improve prognostication of aSAH.

Keywords: connectomics, diffusion tensor imaging, graph theory, machine learning, subarachnoid hemorrhage

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Authors: Weaam Aldeeban, Majd Aljamali, Lama A. Youssef

Abstract:

Background & Objective: Warfarin is considered a problematic drug due to its narrow therapeutic window and wide inter-individual response variations, which are attributed to demographic, environmental, and genetic factors, particularly single nucleotide polymorphism (SNPs) in the genes encoding VKORC1 and CYP2C9 involved in warfarin's mechanism of action and metabolism, respectively. CYP2C9*2rs1799853 and CYP2C9*3rs1057910 alleles are linked to reduced enzyme activity, as carriers of either or both alleles are classified as moderate or slow metabolizers, and therefore exhibit higher sensitivity of warfarin compared with wild type (CYP2C9*1*1). Our study aimed to assess the frequency of *1, *2, and *3 alleles in the CYP2C9 gene in a cohort of Syrian patients receiving a maintenance dose of warfarin for different indications, the impact of genotypes on warfarin dosing, and the frequency of adverse effects (i.e., bleedings). Subjects & Methods: This retrospective cohort study encompassed 94 patients treated with warfarin. Patients’ genotypes were identified by sequencing the polymerase chain reaction (PCR) specific products of the gene encoding CYP2C9, and the effects on warfarin therapeutic outcomes were investigated. Results: Sequencing revealed that 43.6% of the study population has the *2 and/or *3 SNPs. The mean weekly maintenance dose of warfarin was 37.42 ± 15.5 mg for patients with the wild-type allele (CYP2C9*1*1), whereas patients with one or both variants (*2 and/or *3) demanded a significantly lower dose (28.59 ±11.58 mg) of warfarin, (P= 0.015). A higher percentage (40.7%) of patients with allele *2 and/or *3 experienced hemorrhagic accidents compared with only 17.9% of patients with the wild type *1*1, (P = 0.04). Conclusions: Our study proves an association between *2 and *3 genotypes and higher sensitivity to warfarin and a tendency to bleed, which necessitates lowering the dose. These findings emphasize the significance of CYP2C9 genotyping prior to commencing warfarin therapy in order to achieve optimal and faster dose control and to ensure effectiveness and safety.

Keywords: warfarin, CYP2C9, polymorphisms, Syrian, hemorrhage

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Authors: Dalila Lino

Abstract:

Practicum is a central dimension of teacher education programs. Learning how to teach is, in effect, a complex process that integrates periods of observation, experimentation, reflection, planning, and evaluation in a real context of practices, providing opportunities for prospective teachers to understand the various dimensions of education and to implement the knowledge built over the theoretical courses they have taken. At the pre-service training of early childhood teachers, specialized guidance and in particular pedagogical supervision assumes a key role in the professional development of students in training. The main goal of this study is to describe and analyze the supervision process that occurs during the practicum of preschool education master programs in Portugal. The objectives of the study are: (i) to describe the cooperative process of professional development experienced by student teachers during the practicum; (ii) to identify the strengths and weaknesses of supervision process; (iii) to identify the supervision styles used by university supervisors and cooperating teachers. The methodology used is the mix-method research and data was collected through semi-structured interviews and online questionnaires. The participants are newly graduated Portuguese early childhood teachers, university supervisors and cooperating teachers. The results reveal gaps in the specialized training of cooperating teachers and university supervisors, a large number of trainees per supervisor, which makes it difficult to support students, and those interpersonal relationships between university supervisors and students and/or cooperating teachers and students interfere in the development of the supervisory processes. The study highlights the need to invest in the specialized training of university supervisors and cooperating teachers to create better opportunities to support the professional development of prospective teachers.

Keywords: mentoring, pedagogical supervision, practicum, preschool teacher education

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Authors: Beate Englich, Linda Schlittenbauer, Christiane Pfeifer, Isabel Kratochvil, Michael Borte, Gabriele I. Stangl, Martin von Bergen, Thorsten Reemtsma, Irina Lehmann, Kristin M. Junge

Abstract:

The worldwide production of endocrine disrupting compounds (EDC) has risen dramatically over the last decades, as so has the prevalence for obesity. Many EDCs are believed to contribute to this obesity epidemic, by enhancing adipogenesis or disrupting relevant metabolism. This effect is most tremendous in the early prenatal period when priming effects find a highly vulnerable time window. Therefore, we investigate the impact of parabens on childhood overweight development and adipogenesis in general. Parabens are ester of 4-hydroxy-benzoic acid and part of many cosmetic products or food packing. Therefore, ubiquitous exposure can be found in the westernized world, with exposure already starting during the sensitive prenatal period. We assessed maternal cosmetic product consumption, prenatal paraben exposure and infant BMI z-scores in the prospective German LINA cohort. In detail, maternal urinary concentrations (34 weeks of gestation) of methyl paraben (MeP), ethyl paraben (EtP), n-propyl paraben (PrP) and n-butyl paraben (BuP) were quantified using UPLC-MS/MS. Body weight and height of their children was assessed during annual clinical visits. Further, we investigated the direct influence of those parabens on adipogenesis in-vitro using a human mesenchymal stem cell (MSC) differentiation assay to mimic a prenatal exposure scenario. MSC were exposed to 0.1 – 50 µM paraben during the entire differentiation period. Differentiation outcome was monitored by impedance spectrometry, real-time PCR and triglyceride staining. We found that maternal cosmetic product consumption was highly correlated with urinary paraben concentrations at pregnancy. Further, prenatal paraben exposure was linked to higher BMI Z-scores in children. Our in-vitro analysis revealed that especially the long chained paraben BuP stimulates adipogenesis by increasing the expression of adipocyte specific genes (PPARγ, ADIPOQ, LPL, etc.) and triglyceride storage. Moreover, we found that adiponectin secretion is increased whereas leptin secretion is reduced under BuP exposure in-vitro. Further mechanistic analysis for receptor binding and activation of PPARγ and other key players in adipogenesis are currently in process. We conclude that maternal cosmetic product consumption is linked to prenatal paraben exposure of children and contributes to the development of infant overweight development by triggering key pathways of adipogenesis.

Keywords: adipogenesis, endocrine disruptors, paraben, prenatal exposure

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Authors: Simona Capossela, Ramona Schaniel, Singer Franziska, Aquino Fournier Catharine, Daniel Stekhoven, Jivko Stoyanov

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A spinal cord injury (SCI) is a traumatic life event that often results in ageing associated health conditions such as muscle mass decline, adipose tissue increase, decline in immune function, frailty, systemic chronic inflammation, and psychological distress and depression. Psychological, oxidative, and metabolic stressors may facilitate accelerated ageing in the SCI population with reduced life expectancy. Research designs using biomarkers of aging and stress are needed to elucidate the role of psychological distress in accelerated aging. The aim of this project is a feasibility pilot study to observe changes in stress biomarkers and correlate them with aging markers in SCI patients during their first rehabilitation (longitudinal cohort study). Biological samples were collected in the SwiSCI (Swiss Spinal Cord Injury Cohort Study) Biobank in Nottwil at 4 weeks±12 days after the injury (T1) and at the end of the first rehabilitation (discharge, T4). The "distress thermometer" is used as a selfassessment tool for psychological distress. Stress biomarkers, as cortisol and protein carbonyl content (PCC), and markers of cellular aging, such as telomere lengths, will be measured. 2 Preliminary results showed that SCI patients (N= 129) are still generally distressed at end of rehabilitation, however we found a statistically significant (p< 0.001) median decrease in distress from 6 (T1) to 5 (T4) during the rehabilitation. In addition, an explorative transcriptomics will be conducted on N=50 SCI patients to compare groups of persons with SCI who have different trajectories of selfreported distress at the beginning and end of the first rehabilitation after the trauma. We identified 4 groups: very high chronic stress (stress thermometer values above 7 at T1 and T4; n=14); transient stress (high to low; n=14), low stress (values below 5 at T1 and T4; n=14), increasing stress (low to high; n=8). The study will attempt to identify and address issues that may occur in relation to the design and conceptualization of future study on stress and aging in the SCI population.

Keywords: stress, aging, spinal cord injury, biomarkers

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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

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

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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

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Authors: Maria Luz Macasinag

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This study aims to determine and to examine critically successful family-owned higher educational institutions towards identifying the attributes and practices that may likely have led to their success. This research is confined to private, non-sectarian, family-owned higher institutions of learning that have been operating for more than fifty years, had only one founder and had at least two transitions in terms of generation. The criteria for selecting family-owned universities to be part of the cases under investigation include institutions (1) with increasing enrollment over the past five years, with level III accreditation status, (3) with good performance in the Board examinations in most of its programs and (4) with high employability of graduates. The study uses the multiple case study method. A model based on the cross-case analysis of the attributes and practices of all the case studies of successful family- owned higher institutions of learning is the output. The paper provides insights to current and future school owners and administrators in the management of their institutions for competitiveness, sustainability and advancement. This research encourages the evaluation of how the ideas that may lead to the success of schools owned by families in developing a sense of community, a reciprocal relationship among colleagues, the students and other stakeholders will result to the attainment of the vision and mission of the school. The study is beneficial to entrepreneurs and to business students whose know-how may provide insights that would be helpful in guiding prospective school owners. The commission on higher education and the Department of Education stand to benefit from this academic paper for the guidance that they provide to family-owned educational institutions. Banks and other financial institutions may find valuable ideas from this academic paper for the purpose of providing financial assistance to colleges and universities that are family-owned. Researchers in the field of educational management and administration may be able to extract from this study related topics for future research.

Keywords: administration practices, attributes, family-owned schools, success factors

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Authors: Deanne McArthur, Melinda Wall, Claire Hanlon, Dana Agnolin, Krista Davis, Melanie Dennis, Elizabeth Glidden, Anne Marie Smith, Claudette Thomson

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In Canada, as prevalence rates and severity of illness have increased among patients suffering from eating disorders, wait times have grown substantially. Patients in Canada often face wait times in excess of 12 months. It is known that delaying treatment for eating disorders contributes to poor patient outcomes and higher rates of symptom relapse. Improving interim services for adult patients awaiting outpatient treatment is a priority for an outpatient eating disorders clinic in Ontario, Canada. The clinical setting currently provides care for adults diagnosed with anorexia nervosa, bulimia nervosa and binge eating disorder. At present, the only support provided while patients are on the waitlist consists of communication with primary care providers regarding parameters for medical monitoring. The significance of this study will be to test the feasibility, acceptability and efficacy of an intervention to support adult patients awaiting outpatient eating disorder treatment for anorexia nervosa, bulimia nervosa and binge eating disorder. Methods: An intervention including psychoeducation, supportive resources, self-monitoring, and auxiliary referral will be pilot-tested with a group of patients in the summer of 2022 and detailed using a prospective cohort case study research design. The team will host patient focus groups in May 2022 to gather input informing the content of the intervention. The intervention will be pilot tested with newly-referred patients in June and July 2022. Patients who participate in the intervention will be asked to complete a survey evaluating the utility of the intervention and for suggestions, they may have for improvement. Preliminary findings describing the existing literature pertaining to waitlist interventions for patients with eating disorders, data gathered from the focus groups and early pilot testing results will be presented. Data analysis will continue throughout 2022 and early 2023 for follow-up publication and presentation in the summer of 2023. The aim of this study is to contribute to the body of knowledge pertaining to providing interim support to those patients waiting for treatment for eating disorders and, by extension, to improve outcomes for this population.

Keywords: eating disorders, waitlist management, intervention study, pilot test

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Authors: Daria Zabolotnaya, Svetlana Degtyareva, Veronika Kanestri, Danila Konnov

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An adequate choice of the initial antiretroviral treatment determines the treatment efficacy. In the clinical guidelines in Russia non-nucleoside reverse transcriptase inhibitors (NNRTIs) are still considered to be an option for first-line treatment while pretreatment drug resistance (PDR) testing is not routinely performed. We conducted a cohort retrospective study in HIV-positive treatment naïve patients of the H-clinic (Moscow, Russia) who performed PDR testing from July 2017 to November 2021. All the information was obtained from the medical records anonymously. We analyzed the mutations in reverse transcriptase and protease genes. RT-sequences were obtained by AmpliSens HIV-Resist-Seq kit. Drug resistance was defined using the HIVdb Program v. 8.9-1. PDR was estimated using the Stanford algorithm. Descriptive statistics were performed in Excel (Microsoft Office, 2019). A total of 261 HIV-1 infected patients were enrolled in the study including 197 (75.5%) male and 64 (24.5%) female. The mean age was 34.6±8.3 years. The median CD4 count – 521 cells/µl (IQR 367-687 cells/µl). Data on risk factors of HIV-infection were scarce. The total quantity of strains containing mutations in the reverse transcriptase gene was 75 (28.7%). From these 5 (1.9%) mutations were associated with PDR to nucleoside reverse transcriptase inhibitors (NRTIs) and 30 (11.5%) – with PDR to NNRTIs. The number of strains with mutations in protease gene was 43 (16.5%), from these only 3 (1.1%) mutations were associated with resistance to protease inhibitors. For NNRTIs the most prevalent PDR mutations were E138A, V106I. Most of the HIV variants exhibited a single PDR mutation, 2 were found in 3 samples. Most of HIV variants with PDR mutation displayed a single drug class resistance mutation. 2/37 (5.4%) strains had both NRTIs and NNRTIs mutations. There were no strains identified with PDR mutations to all three drug classes. Though earlier data demonstrated a lower level of PDR in HIV treatment naïve population in Russia and our cohort can be not fully representative as it is taken from the private clinic, it reflects the trend of increasing PDR especially to NNRTIs. Therefore, we consider either pretreatment testing or giving the priority to other drugs as first-line treatment necessary.

Keywords: HIV, resistance, mutations, treatment

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