Search results for: adult with intellectual disability
Commenced in January 2007
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Edition: International
Paper Count: 2477

Search results for: adult with intellectual disability

17 A Study on the Relation among Primary Care Professionals Serving Disadvantaged Community, Socioeconomic Status, and Adverse Health Outcome

Authors: Chau-Kuang Chen, Juanita Buford, Colette Davis, Raisha Allen, John Hughes, James Tyus, Dexter Samuels

Abstract:

During the post-Civil War era, the city of Nashville, Tennessee, had the highest mortality rate in the country. The elevated death and disease among ex-slaves were attributable to the unavailability of healthcare. To address the paucity of healthcare services, the College, an institution with the mission of educating minority professionals and serving the under served population, was established in 1876. This study was designed to assess if the College has accomplished its mission of serving under served communities and contributed to the elimination of health disparities in the United States. The study objective was to quantify the impact of socioeconomic status and adverse health outcomes on primary care professionals serving disadvantaged communities, which, in turn, was significantly associated with a health professional shortage score partly designated by the U.S. Department of Health and Human Services. Various statistical methods were used to analyze the alumni data in years 1975 – 2013. K-means cluster analysis was utilized to identify individual medical and dental graduates into the cluster groups of the practice communities (Disadvantaged or Non-disadvantaged Communities). Discriminant analysis was implemented to verify the classification accuracy of cluster analysis. The independent t test was performed to detect the significant mean differences for clustering and criterion variables between Disadvantaged and Non-disadvantaged Communities, which confirms the “content” validity of cluster analysis model. Chi-square test was used to assess if the proportion of cluster groups (Disadvantaged vs Non-disadvantaged Communities) were consistent with that of practicing specialties (primary care vs. non-primary care). Finally, the partial least squares (PLS) path model was constructed to explore the “construct” validity of analytics model by providing the magnitude effects of socioeconomic status and adverse health outcome on primary care professionals serving disadvantaged community. The social ecological theory along with statistical models mentioned was used to establish the relationship between medical and dental graduates (primary care professionals serving disadvantaged communities) and their social environments (socioeconomic status, adverse health outcome, health professional shortage score). Based on social ecological framework, it was hypothesized that the impact of socioeconomic status and adverse health outcomes on primary care professionals serving disadvantaged communities could be quantified. Also, primary care professionals serving disadvantaged communities related to a health professional shortage score can be measured. Adverse health outcome (adult obesity rate, age-adjusted premature mortality rate, and percent of people diagnosed with diabetes) could be affected by the latent variable, namely socioeconomic status (unemployment rate, poverty rate, percent of children who were in free lunch programs, and percent of uninsured adults). The study results indicated that approximately 83% (3,192/3,864) of the College’s medical and dental graduates from 1975 to 2013 were practicing in disadvantaged communities. In addition, the PLS path modeling demonstrated that primary care professionals serving disadvantaged community was significantly associated with socioeconomic status and adverse health outcome (p < .001). In summary, the majority of medical and dental graduates from the College provide primary care services to disadvantaged communities with low socioeconomic status and high adverse health outcomes, which demonstrate that the College has fulfilled its mission.

Keywords: disadvantaged community, K-means cluster analysis, PLS path modeling, primary care

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16 Housing Recovery in Heavily Damaged Communities in New Jersey after Hurricane Sandy

Authors: Chenyi Ma

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Background: The second costliest hurricane in U.S. history, Sandy landed in southern New Jersey on October 29, 2012, and struck the entire state with high winds and torrential rains. The disaster killed more than 100 people, left more than 8.5 million households without power, and damaged or destroyed more than 200,000 homes across the state. Immediately after the disaster, public policy support was provided in nine coastal counties that constituted 98% of the major and severely damaged housing units in NJ overall. The programs include Individuals and Households Assistance Program, Small Business Loan Program, National Flood Insurance Program, and the Federal Emergency Management Administration (FEMA) Public Assistance Grant Program. In the most severely affected counties, additional funding was provided through Community Development Block Grant: Reconstruction, Rehabilitation, Elevation, and Mitigation Program, and Homeowner Resettlement Program. How these policies individually and as a whole impacted housing recovery across communities with different socioeconomic and demographic profiles has not yet been studied, particularly in relation to damage levels. The concept of community social vulnerability has been widely used to explain many aspects of natural disasters. Nevertheless, how communities are vulnerable has been less fully examined. Community resilience has been conceptualized as a protective factor against negative impacts from disasters, however, how community resilience buffers the effects of vulnerability is not yet known. Because housing recovery is a dynamic social and economic process that varies according to context, this study examined the path from community vulnerability and resilience to housing recovery looking at both community characteristics and policy interventions. Sample/Methods: This retrospective longitudinal case study compared a literature-identified set of pre-disaster community characteristics, the effects of multiple public policy programs, and a set of time-variant community resilience indicators to changes in housing stock (operationally defined by percent of building permits to total occupied housing units/households) between 2010 and 2014, two years before and after Hurricane Sandy. The sample consisted of 51 municipalities in the nine counties in which between 4% and 58% of housing units suffered either major or severe damage. Structural equation modeling (SEM) was used to determine the path from vulnerability to the housing recovery, via multiple public programs, separately and as a whole, and via the community resilience indicators. The spatial analytical tool ArcGIS 10.2 was used to show the spatial relations between housing recovery patterns and community vulnerability and resilience. Findings: Holding damage levels constant, communities with higher proportions of Hispanic households had significantly lower levels of housing recovery while communities with households with an adult >age 65 had significantly higher levels of the housing recovery. The contrast was partly due to the different levels of total public support the two types of the community received. Further, while the public policy programs individually mediated the negative associations between African American and female-headed households and housing recovery, communities with larger proportions of African American, female-headed and Hispanic households were “vulnerable” to lower levels of housing recovery because they lacked sufficient public program support. Even so, higher employment rates and incomes buffered vulnerability to lower housing recovery. Because housing is the "wobbly pillar" of the welfare state, the housing needs of these particular groups should be more fully addressed by disaster policy.

Keywords: community social vulnerability, community resilience, hurricane, public policy

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15 Risk Factors Associated to Low Back Pain among Active Adults: Cross-Sectional Study among Workers in Tunisian Public Hospital

Authors: Lamia Bouzgarrou, Irtyah Merchaoui, Amira Omrane, Salma Kammoun, Amine Daafa, Neila Chaari

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Backgrounds: Currently, low back pain (LBP) is one of the most prevalent public health problems, which caused severe morbidity among a large portion of the adult population. It is also associated with heavy direct and indirect costs, in particular, related to absenteeism and early retirement. Health care workers are one of most occupational groups concerned by LBP, especially because of biomechanical and psycho-organizational risk factors. Our current study aims to investigate risk factors associated with chronic low back pain among Tunisian caregivers in university-hospitals. Methods: Cross-sectional study conducted over a period of 14 months, with a representative sample of caregivers, matched according to age, sex and work department, in two university-hospitals in Tunisia. Data collection included items related to socio-professional characteristics, the evaluation of the working capacity index (WAI), the occupational stress (Karazek job strain questionnaire); the quality of life (SF12), the musculoskeletal disorders Nordic questionnaire, and the examination of the spine flexibility (distance finger-ground, sit-stand maneuver and equilibrium test). Results: Totally, 293 caregivers were included with a mean age equal to 42.64 ± 11.65 years. A body mass index (BMI) exceeding 30, was noted in 20.82% of cases. Moreover, no regular physical activity was practiced in 51.9% of cases. In contrast, domestic activity equal or exceeding 20 hours per week, was reported by 38.22%. Job strain was noted in 19.79 % of cases and the work capacity was 'low' to 'average' among 27.64% of subjects. During the 12 months previous to the investigation, 65% of caregivers complained of LBP, with pain rated as 'severe' or 'extremely severe' in 54.4% of cases and with a frequency of discomfort exceeding one episode per week in 58.52% of cases. During physical examination, the mean distance finger-ground was 7.10 ± 7.5cm. Caregivers assigned to 'high workload' services had the highest prevalence of LBP (77.4%) compared to other categories of hospital services, with no statistically significant relationship (P = 0.125). LBP prevalence was statistically correlated with female gender (p = 0.01) and impaired work capacity (p < 10⁻³). Moreover, the increase of the distance finger-ground was statistically associated with LBP (p = 0.05), advanced age (p < 10⁻³), professional seniority (p < 10⁻³) and the BMI ≥ 25 (p = 0.001). Furthermore, others physical tests of spine flexibility were underperformed among LBP suffering workers with a statistically significant difference (sit-stand maneuver (p = 0.03); equilibrium test (p = 0.01)). According to the multivariate analysis, only the domestic activity exceeding 20H/week, the degraded quality of physical life, and the presence of neck pain were significantly corelated to LBP. The final model explains 36.7% of the variability of this complaint. Conclusion: Our results highlighted the elevate prevalence of LBP among caregivers in Tunisian public hospital and identified both professional and individual predisposing factors. The preliminary analysis supports the necessity of a multidimensional approach to prevent this critical occupational and public health problem. The preventive strategy should be based both on the improvement of working conditions, and also on lifestyle modifications, and reinforcement of healthy behaviors in these active populations.

Keywords: health care workers, low back pain, prevention, risk factor

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14 A Computational Investigation of Potential Drugs for Cholesterol Regulation to Treat Alzheimer’s Disease

Authors: Marina Passero, Tianhua Zhai, Zuyi (Jacky) Huang

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Alzheimer’s disease has become a major public health issue, as indicated by the increasing populations of Americans living with Alzheimer’s disease. After decades of extensive research in Alzheimer’s disease, only seven drugs have been approved by Food and Drug Administration (FDA) to treat Alzheimer’s disease. Five of these drugs were designed to treat the dementia symptoms, and only two drugs (i.e., Aducanumab and Lecanemab) target the progression of Alzheimer’s disease, especially the accumulation of amyloid-b plaques. However, controversial comments were raised for the accelerated approvals of either Aducanumab or Lecanemab, especially with concerns on safety and side effects of these two drugs. There is still an urgent need for further drug discovery to target the biological processes involved in the progression of Alzheimer’s disease. Excessive cholesterol has been found to accumulate in the brain of those with Alzheimer’s disease. Cholesterol can be synthesized in both the blood and the brain, but the majority of biosynthesis in the adult brain takes place in astrocytes and is then transported to the neurons via ApoE. The blood brain barrier separates cholesterol metabolism in the brain from the rest of the body. Various proteins contribute to the metabolism of cholesterol in the brain, which offer potential targets for Alzheimer’s treatment. In the astrocytes, SREBP cleavage-activating protein (SCAP) binds to Sterol Regulatory Element-binding Protein 2 (SREBP2) in order to transport the complex from the endoplasmic reticulum to the Golgi apparatus. Cholesterol is secreted out of the astrocytes by ATP-Binding Cassette A1 (ABCA1) transporter. Lipoprotein receptors such as triggering receptor expressed on myeloid cells 2 (TREM2) internalize cholesterol into the microglia, while lipoprotein receptors such as Low-density lipoprotein receptor-related protein 1 (LRP1) internalize cholesterol into the neuron. Cytochrome P450 Family 46 Subfamily A Member 1 (CYP46A1) converts excess cholesterol to 24S-hydroxycholesterol (24S-OHC). Cholesterol has been approved for its direct effect on the production of amyloid-beta and tau proteins. The addition of cholesterol to the brain promotes the activity of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), secretase, and amyloid precursor protein (APP), which all aid in amyloid-beta production. The reduction of cholesterol esters in the brain have been found to reduce phosphorylated tau levels in mice. In this work, a computational pipeline was developed to identify the protein targets involved in cholesterol regulation in brain and further to identify chemical compounds as the inhibitors of a selected protein target. Since extensive evidence shows the strong correlation between brain cholesterol regulation and Alzheimer’s disease, a detailed literature review on genes or pathways related to the brain cholesterol synthesis and regulation was first conducted in this work. An interaction network was then built for those genes so that the top gene targets were identified. The involvement of these genes in Alzheimer’s disease progression was discussed, which was followed by the investigation of existing clinical trials for those targets. A ligand-protein docking program was finally developed to screen 1.5 million chemical compounds for the selected protein target. A machine learning program was developed to evaluate and predict the binding interaction between chemical compounds and the protein target. The results from this work pave the way for further drug discovery to regulate brain cholesterol to combat Alzheimer’s disease.

Keywords: Alzheimer’s disease, drug discovery, ligand-protein docking, gene-network analysis, cholesterol regulation

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13 Feasibility and Acceptability of an Emergency Department Digital Pain Self-Management Intervention: An Randomized Controlled Trial Pilot Study

Authors: Alexandria Carey, Angela Starkweather, Ann Horgas, Hwayoung Cho, Jason Beneciuk

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Background/Significance: Over 3.4 million acute axial low back pain (aLBP) cases are treated annually in the United States (US) emergency departments (ED). ED patients with aLBP receive varying verbal and written discharge routine care (RC), leading to ineffective patient self-management. Ineffective self-management increase chronic low back pain (cLPB) transition risks, a chief cause of worldwide disability, with associated costs >$60 million annually. This research addresses this significant problem by evaluating an ED digital pain self-management intervention (EDPSI) focused on improving self-management through improved knowledge retainment, skills, and self-efficacy (confidence) (KSC) thus reducing aLBP to cLBP transition in ED patients discharged with aLBP. The research has significant potential to increase self-efficacy, one of the most potent mechanisms of behavior change and improve health outcomes. Focusing on accessibility and usability, the intervention may reduce discharge disparities in aLBP self-management, especially with low health literacy. Study Questions: This research will answer the following questions: 1) Will an EDPSI focused on improving KSC progress patient self-management behaviors and health status?; 2) Is the EDPSI sustainable to improve pain severity, interference, and pain recurrence?; 3) Will an EDPSI reduce aLBP to cLBP transition in patients discharged with aLBP? Aims: The pilot randomized-controlled trial (RCT) study’s objectives assess the effects of a 12-week digital self-management discharge tool in patients with aLBP. We aim to 1) Primarily assess the feasibility [recruitment, enrollment, and retention], and [intervention] acceptability, and sustainability of EDPSI on participant’s pain self-management; 2) Determine the effectiveness and sustainability of EDPSI on pain severity/interference among participants. 3) Explore patient preferences, health literacy, and changes among participants experiencing the transition to cLBP. We anticipate that EDPSI intervention will increase likelihood of achieving self-management milestones and significantly improve pain-related symptoms in aLBP. Methods: The study uses a two-group pilot RCT to enroll 30 individuals who have been seen in the ED with aLBP. Participants are randomized into RC (n=15) or RC + EDPSI (n=15) and receive follow-up surveys for 12-weeks post-intervention. EDPSI innovative content focuses on 1) highlighting discharge education; 2) provides self-management treatment options; 3) actor demonstration of ergonomics, range of motion movements, safety, and sleep; 4) complementary alternative medicine (CAM) options including acupuncture, yoga, and Pilates; 5) combination therapies including thermal application, spinal manipulation, and PT treatments. The intervention group receives Booster sessions via Zoom to assess and reinforce their knowledge retention of techniques and provide return demonstration reinforcing ergonomics, in weeks two and eight. Outcome Measures: All participants are followed for 12-weeks, assessing pain severity/ interference using the Brief Pain Inventory short-form (BPI-sf) survey, self-management (measuring KSC) using the short 13-item Patient Activation Measure (PAM), and self-efficacy using the Pain Self-Efficacy Questionnaire (PSEQ) weeks 1, 6, and 12. Feasibility is measured by recruitment, enrollment, and retention percentages. Acceptability and education satisfaction are measured using the Education-Preference and Satisfaction Questionnaire (EPSQ) post-intervention. Self-management sustainment is measured including PSEQ, PAM, and patient satisfaction and healthcare utilization (PSHU) requesting patient overall satisfaction, additional healthcare utilization, and pain management related to continued back pain or complications post-injury.

Keywords: digital, pain self-management, education, tool

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12 Using Health Literacy and Medico-Legal Guidance to Improve Restorative Dentistry Patient Information Leaflets

Authors: Hasneet K. Kalsi, Julie K. Kilgariff

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Introduction: Within dentistry, the process for gaining informed consent has become more complex. To consent for treatment, patients must understand all reasonable treatment options and associated risks and benefits. Consenting is therefore deeply embedded in health literacy. Patients attending for dental consultation are often presented with an array of information and choices, yet studies show patients recall less than half of the information provided immediately after. Appropriate and comprehensible patient information leaflets (PILs) may be useful aid memories. In 2016 the World Health Organisation set improving health literacy as a global priority. Soon after, Scotland’s 2017-2025 Making it Easier: A Health Literacy Action Plan followed. This project involved the review of Restorative PILs used within Dundee Dental Hospital to assess the Content and Readability. Method: The current PIL on Root Canal Treatment (RCT) was created in 2011. This predates the Montgomery vs. NHS Lanarkshire case, a ruling which significantly impacted dental consenting processes, as well as General Dental Council’s (GDC’s) Standards for the Dental Team and Faculty of General Dental Practice’s Good Practice Guidance on Clinical Examination and Record-Keeping. Current evidence-based guidance, including that stipulated by the GDC, was reviewed. A 20-point Essential Content Checklist was designed to conform to best practice guidance for valid consenting processes. The RCT leaflet was scored against this to ascertain if the content was satisfactory. Having ensured the content satisfied medicolegal requirements, health literacy considerations were reviewed regarding readability. This was assessed using McLaughlin’s Simple Measure of Gobbledygook (SMOG) formula, which identifies school stages that would have to be achieved to comprehend the PIL. The sensitivity of the results to alternative readability methods were assessed. Results: The PIL was not sufficient for modern consenting processes and reflected a suboptimal level of health literacy. Evaluation of the leaflet revealed key content was missing, including information pertaining to risks and benefits. Only five points out of the 20-point checklist were present. The readability score was 16, equivalent to a level 2 in National Adult Literacy Standards/Scottish Credit and Qualification Framework Level 5; 62% of Scottish adults are able to read to this standard. Discussion: Assessment of the leaflet showed it was no longer fit for purpose. Reasons include a lack of pertinent information, a text-heavy leaflet lacking flow, and content errors. The SMOG score indicates a high level of comprehension is required to understand this PIL, which many patients may not possess. A new PIL, compliant with medicolegal and health literacy guidance, was designed with patient-driven checklists, notes spaces for annotations/ questions and areas for clinicians to highlight important case-specific information. It has been tested using the SMOG formula. Conclusion: PILs can be extremely useful. Studies show that interactive use can enhance their effectiveness. PILs should reflect best practice guidance and be understood by patients. The 2020 leaflet designed and implemented aims to fulfill the needs of a modern healthcare system and its service users. It embraces and embeds Scotland’s Health Literacy Action Plan within the consenting process. A review of further leaflets using this model is ongoing.

Keywords: consent, health literacy, patient information leaflet, restorative dentistry

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11 The Usefulness of Medical Scribes in the Emengecy Department

Authors: Victor Kang, Sirene Bellahnid, Amy Al-Simaani

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Efficient documentation and completion of clerical tasks are pillars of efficient patient-centered care in acute settings such as the emergency department (ED). Medical scribes aid physicians with documentation, navigation of electronic health records, results gathering, and communication coordination with other healthcare teams. However, the use of medical scribes is not widespread, with some hospitals even continuing to discontinue their programs. One reason for this could be the lack of studies that have outlined concrete improvements in efficiency and patient and provider satisfaction in emergency departments before and after incorporating scribes. Methods: We conducted a review of the literature concerning the implementation of a medical scribe program and emergency department performance. For this review, a narrative synthesis accompanied by textual commentaries was chosen to present the selected papers. PubMed was searched exclusively. Initially, no date limits were set, but seeing as the electronic medical record was officially implemented in Canada in 2013, studies published after this date were preferred as they provided insight into the interplay between its implementation and scribes on quality improvement. Results: Throughput, efficiency, and cost-effectiveness were the most commonly used parameters in evaluating scribes in the Emergency Department. Important throughput metrics, specifically door-to-doctor and disposition time, were significantly decreased in emergency departments that utilized scribes. Of note, this was shown to be the case in community hospitals, where the burden of documentation and clerical tasks would fall directly upon the attending physician. Academic centers differ in that they rely heavily on residents and students; so the implementation of scribes has been shown to have limited effect on these metrics. However, unique to academic centers was the provider’s perception of incrased time for teaching was unique to academic centers. Consequently, providers express increased work satisfaction in relation to time spent with patients and in teaching. Patients, on the other hand, did not demonstrate a decrease in satisfaction in regards to the care that was provided, but there was no significant increase observed either. Of the studies we reviewed, one of the biggest limitations was the lack of significance in the data. While many individual studies reported that medical scribes in emergency rooms improved relative value units, patient satisfaction, provider satisfaction, and increased number of patients seen, there was no statistically significant improvement in the above criteria when compiled in a systematic review. There is also a clear publication bias; very few studies with negative results were published. To prove significance, data from more emergency rooms with scribe programs would need to be compiled which also includes emergency rooms who did not report noticeable benefits. Furthermore, most data sets focused only on scribes in academic centers. Conclusion: Ultimately, the literature suggests that while emergency room physicians who have access to medical scribes report higher satisfaction due to lower clerical burdens and can see more patients per shift, there is still variability in terms of patient and provider satisfaction. Whether or not this variability exists due to differences in training (in-house trainees versus contractors), population profile (adult versus pediatric), setting (academic versus community), or which shifts scribe work cannot be determined based on the studies that exist. Ultimately, more scribe programs need to be evaluated to determine whether these variables affect outcomes and prove whether scribes significantly improve emergency room efficiency.

Keywords: emergency medicine, medical scribe, scribe, documentation

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10 Molecular Signaling Involved in the 'Benzo(a)Pyrene' Induced Germ Cell DNA Damage and Apoptosis: Possible Protection by Natural Aryl Hydrocarbon Receptor Antagonist and Anti-Tumor Agent

Authors: Kuladip Jana

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Benzo(a)pyrene [B(a)P] is an environmental toxicant present mostly in cigarette smoke and car exhaust, is an aryl hydrocarbon receptor (AhR) ligand that exerts its toxic effects on both male and female reproductive systems. In this study, the effect of B(a)P at different doses (0.1, 0.25, 0.5, 1 and 5 mg /kg body weight) was studied on male reproductive system of rat. A significant decrease in cauda epididymal sperm count and motility along with the presence of sperm head abnormalities and altered epididymal and testicular histology were documented following B(a)P treatment. B(a)P treatment resulted apoptotic sperm cells as observed by TUNEL and Annexin V-PI assay with increased ROS, altered sperm mitochondrial membrane potential (ΔΨm) with a simultaneous decrease in the activity of antioxidant enzymes and GSH status. TUNEL positive apoptotic cells also observed in testis as well as isolated germ and Leydig cells following B(a)P exposure. Western Blot analysis revealed the activation of p38MAPK, cytosolic translocation of cytochrome-c, up-regulation of Bax and inducible nitric oxide synthase (iNOS) with cleavage of PARP and down-regulation of BCl2 in testis upon B(a)P treatment. The protein and mRNA levels of testicular key steroidogenesis regulatory proteins like StAR, cytochrome P450 IIA1 (CYPIIA1), 3β HSD, 17β HSD showed a significant decrease in a dose dependent manner while an increase in the expression of cytochrome P450 1A1 (CYP1A1), Aryl hydrocarbon Receptor (AhR), active caspase- 9 and caspase- 3 following B(a)P exposure. We conclude that exposure of benzo(a)pyrene caused testicular gamatogenic and steroidogenic disorders by induction of oxidative stress, inhibition of StAR and other steroidogenic enzymes along with activation of p38MAPK and initiated caspase-3 mediated germ and Leydig cell apoptosis.The possible protective role of naturally occurring phytochemicals against B(a)P induced testicular toxicity needs immediate consideration. Curcumin and resveratrol separately were found to protect against B(a)P induced germ cell apoptosis, and their combinatorial effect was more significant. Our present study in isolated testicular germ cell population from adult male Wistar rats, highlighted their synergistic protective effect against B(a)P induced germ cell apoptosis. Curcumin-resveratrol co-treatment decreased the expression of pro-apoptotic proteins like cleaved caspase 3,8,9, cleaved PARP, Apaf1, FasL, tBid. Curcumin-resveratrol co-treatment decreased Bax/Bcl2 ratio, mitochondria to cytosolic translocation of cytochrome c and activated the survival protein Akt. Curcumin-resveratrol decreased the expression of p53 dependent apoptotic genes like Fas, FasL, Bax, Bcl2, Apaf1.Curcumin-resveratrol co-treatment thus prevented B(a)P induced germ cell apoptosis. B(a)P induced testicular ROS generation and oxidative stress were significantly ameliorated with curcumin and resveratrol. Curcumin-resveratrol co-treatment prevented B(a)P induced nuclear translocation of AhR and CYP1A1 production. The combinatorial treatment significantly inhibited B(a)P induced ERK 1/2, p38 MAPK and JNK 1/2 activation. B(a)P treatment increased the expression of p53 and its phosphorylation (p53 ser 15). Curcumin-resveratrol co-treatment significantly decreased p53 level and its phosphorylation (p53 ser 15). The study concludes that curcumin-resveratrol synergistically modulated MAPKs and p53, prevented oxidative stress, regulated the expression of pro and anti-apoptotic proteins as well as the proteins involved in B(a)P metabolism thus protected germ cells from B(a)P induced apoptosis.

Keywords: benzo(a)pyrene, germ cell, apoptosis, oxidative stress, resveratrol, curcumin

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9 Modern Cardiac Surgical Outcomes in Nonagenarians: A Multicentre Retrospective Observational Study

Authors: Laurence Weinberg, Dominic Walpole, Dong-Kyu Lee, Michael D’Silva, Jian W. Chan, Lachlan F. Miles, Bradley Carp, Adam Wells, Tuck S. Ngun, Siven Seevanayagam, George Matalanis, Ziauddin Ansari, Rinaldo Bellomo, Michael Yii

Abstract:

Background: There have been multiple recent advancements in the selection, optimization and management of cardiac surgical patients. However, there is limited data regarding the outcomes of nonagenarians undergoing cardiac surgery, despite this vulnerable cohort increasingly receiving these interventions. This study describes the patient characteristics, management and outcomes of a group of nonagenarians undergoing cardiac surgery in the context of contemporary peri-operative care. Methods: A retrospective observational study was conducted of patients 90 to 99 years of age (i.e., nonagenarians) who had undergone cardiac surgery requiring a classic median sternotomy (i.e., open-heart surgery). All operative indications were included. Patients who underwent minimally invasive surgery, transcatheter aortic valve implantation and thoracic aorta surgery were excluded. Data were collected from four hospitals in Victoria, Australia, over an 8-year period (January 2012 – December 2019). The primary objective was to assess six-month mortality in nonagenarians undergoing open-heart surgery and to evaluate the incidence and severity of postoperative complications using the Clavien-Dindo classification system. The secondary objective was to provide a detailed description of the characteristics and peri-operative management of this group. Results: A total of 12,358 adult patients underwent cardiac surgery at the study centers during the observation period, of whom 18 nonagenarians (0.15%) fulfilled the inclusion criteria. The median (IQR) [min-max] age was 91 years (90.0:91.8) [90-94] and 14 patients (78%) were men. Cardiovascular comorbidities, polypharmacy and frailty, were common. The median (IQR) predicted in-hospital mortality by EuroSCORE II was 6.1% (4.1-14.5). All patients were optimized preoperatively by a multidisciplinary team of surgeons, cardiologists, geriatricians and anesthetists. All index surgeries were performed on cardiopulmonary bypass. Isolated coronary artery bypass grafting (CABG) and CABG with aortic valve replacement were the most common surgeries being performed in four and five patients, respectively. Half the study group underwent surgery involving two or more major procedures (e.g. CABG and valve replacement). Surgery was undertaken emergently in 44% of patients. All patients except one experienced at least one postoperative complication. The most common complications were acute kidney injury (72%), new atrial fibrillation (44%) and delirium (39%). The highest Clavien-Dindo complication grade was IIIb occurring once each in three patients. Clavien-Dindo grade IIIa complications occurred in only one patient. The median (IQR) postoperative length of stay was 11.6 days (9.8:17.6). One patient was discharged home and all others to an inpatient rehabilitation facility. Three patients had an unplanned readmission within 30 days of discharge. All patients had follow-up to at least six months after surgery and mortality over this period was zero. The median (IQR) duration of follow-up was 11.3 months (6.0:26.4) and there were no cases of mortality observed within the available follow-up records. Conclusion: In this group of nonagenarians undergoing cardiac surgery, postoperative six-month mortality was zero. Complications were common but generally of low severity. These findings support carefully selected nonagenarian patients being offered cardiac surgery in the context of contemporary, multidisciplinary perioperative care. Further, studies are needed to assess longer-term mortality and functional and quality of life outcomes in this vulnerable surgical cohort.

Keywords: cardiac surgery, mortality, nonagenarians, postoperative complications

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8 Beyond Bindis, Bhajis, Bangles, and Bhangra: Exploring Multiculturalism in Southwest England Primary Schools, Early Research Findings

Authors: Suparna Bagchi

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Education as a discipline will probably be shaped by the importance it places on a conceptual, curricular, and pedagogical need to shift the emphasis toward transformative classrooms working for positive change through cultural diversity. Awareness of cultural diversity and race equality has heightened following George Floyd’s killing in the USA in 2020. This increasing awareness is particularly relevant in areas of historically low ethnic diversity which have lately experienced a rise in ethnic minority populations and where inclusive growth is a challenge. This research study aims to explore the perspectives of practitioners, students, and parents towards multiculturalism in four South West England primary schools. A qualitative case study methodology has been adopted framed by sociocultural theory. Data were collected through virtually conducted semi-structured interviews with school practitioners and parents, observation of students’ classroom activities, and documentary analysis of classroom displays. Although one-third of the school population includes ethnically diverse children, BAME (Black, Asian, and Minority Ethnic) characters featured in children's books published in Britain in 2019 were almost invisible, let alone a BAME main character. The Office for Standards in Education, Children's Services and Skills (Ofsted) are vocal about extending the Curriculum beyond the academic and technical arenas for pupils’ broader development and creation of an understanding and appreciation of cultural diversity. However, race equality and community cohesion which could help in the students’ broader development are not Ofsted’s school inspection criteria. The absence of culturally diverse content in the school curriculum highlighted by the 1985 Swann Report and 2007 Ajegbo Report makes England’s National Curriculum look like a Brexit policy three decades before Brexit. A revised National Curriculum may be the starting point with the teachers as curriculum framers playing a significant part. The task design is crucial where teachers can place equal importance on the interwoven elements of “how”, “what” and “why” the task is taught. Teachers need to build confidence in encouraging difficult conversations around racism, fear, indifference, and ignorance breaking the stereotypical barriers, thus helping to create students’ conception of a multicultural Britain. Research showed that trainee teachers in predominantly White areas often exhibit confined perspectives while educating children. Irrespective of the geographical location, school teachers can be equipped with culturally responsive initial and continuous professional development necessary to impart multicultural education. This may aid in the reduction of employees’ unconscious bias. This becomes distinctly pertinent to avoid horrific cases in the future like the recent one in Hackney where a Black teenager was strip-searched during period wrongly suspected of cannabis possession. Early research findings show participants’ eagerness for more ethnic diversity content incorporated in teaching and learning. However, schools are considerably dependent on the knowledge-focused Primary National Curriculum in England. Moreover, they handle issues around the intersectionality of disability, poverty, and gender. Teachers were trained in times when foregrounding ethnicity matters was not happening. Therefore, preoccupied with Curriculum requirements, intersectionality issues, and teacher preparations, schools exhibit an incapacity due to which keeping momentum on ethnic diversity is somewhat endangered.

Keywords: case study, curriculum decolonisation, inclusive education, multiculturalism, qualitative research in Covid19 times

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7 Design, Implementation and Evaluation of Health and Social Justice Trainings in Nigeria

Authors: Juliet Sorensen, Anna Maitland

Abstract:

Introduction: Characterized by lack of water and sanitation, food insecurity, and low access to hospitals and clinics, informal urban settlements in Lagos, Nigeria have very poor health outcomes. With little education and a general inability to demand basic rights, these communities are often disempowered and isolated from understanding, claiming, or owning their health needs. Utilizing community-based participatory research characterized by interdisciplinary, cross-cultural partnerships, evidence-based assessments, and both primary and secondary source research, a holistic health education and advocacy program was developed in Lagos to address health barriers for targeted communities. This includes a first of its kind guide formulated to teach community-based health educators how to transmit health information to low-literacy Nigerian audiences while supporting behavior change models and social support mechanisms. This paper discusses the interdisciplinary contributions to developing a health education program while also looking at the need for greater beneficiary ownership and implementation of health justice and access. Methods: In March 2016, an interdisciplinary group of medical, legal, and business graduate students and faculty from Northwestern University conduced a Health Needs Assessment (HNA) in Lagos with a partner and a local non-governmental organization. The HNA revealed that members of informal urban communities in Lagos were lacking basic health literacy, but desired to remedy this lacuna. Further, the HNA revealed that even where the government mandates specific services, many vulnerable populations are unable to access these services. The HNA concluded that a program focused on education, advocacy, and organizing around anatomy, maternal and sexual health, infectious disease and malaria, HIV/AIDS, emergency care, and water and sanitation would respond to stated needs while also building capacity in communities to address health barriers. Results: Based on the HNA, including both primary and secondary source research on integrated health education approaches and behavior change models and responsive, adaptive material development, a holistic program was developed for the Lagos partners and first implemented in November 2016. This program trained community-nominated health educators in adult, low-literacy, knowledge exchange approaches, utilizing information identified by communities as a priority. After a second training in March 2017, these educators will teach community-based groups and will support and facilitate behavior change models and peer-support methods around basic issues like hand washing and disease transmission. They will be supported by community paralegals who will help ensure that newly trained community groups can act on education around access, such as receiving free vaccinations, maternal health care, and HIV/AIDS medicines. Materials will continue to be updated as needs and issues arise, with a focus on identifying best practices around health improvements that can be shared across these partner communities. Conclusion: These materials are the first of their kind, and address a void of health information and understanding pervasive in informal-urban Lagos communities. Initial feedback indicates high levels of commitment and interest, as well as investment by communities in these materials, largely because they are responsive, targeted, and build community capacity. This methodology is an important step in dignity-based health justice solutions, albeit in the process of refinement.

Keywords: community health educators, interdisciplinary and cross cultural partnerships, health justice and access, Nigeria

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6 A Case Report on the Course and Outcome of a Patient Diagnosed with Trichotillomania and Major Depressive Disorder

Authors: Ziara Carmelli G. Tan, Irene Carmelle S. Tan

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Background: Trichotillomania (TTM) and Major Depressive Disorder (MDD) are two psychiatric conditions that frequently co-occur, presenting a significant challenge for treatment due to their complex interplay. TTM involves repetitive hair-pulling, leading to noticeable hair loss and distress, while MDD is characterized by persistent low mood and loss of interest or pleasure, leading to dysfunctionality. This case report examines the intricate relationship between TTM and MDD in a young adult female, emphasizing the need for a comprehensive, multifaceted therapeutic approach to address both disorders effectively. Case Presentation: The patient is a 21-year-old female college student and youth church leader who presented with chronic hair-pulling and depressive symptoms. Her premorbid personality was marked by low self-esteem and a strong need for external validation. Despite her academic and social responsibilities and achievements, she struggled with managing her emotional distress, which was exacerbated by her family dynamics and her role within her church community. Her hair-pulling and mood symptoms were particularly triggered by self-esteem threats and feelings of inadequacy. She was diagnosed with Trichotillomania, Scalp and Major Depressive Disorder. Intervention/Management: The patient’s treatment plan was comprehensive, incorporating both pharmacological and non-pharmacological interventions. Initial pharmacologic management was Fluoxetine 20mg/day up, titrated to 40mg/day with no improvement; hence, shifted to Escitalopram 20mg/day and started with N-acetylcysteine 600mg/day with noted significant improvement in symptoms. Psychotherapeutic strategies played a crucial role in her treatment. These included supportive-expressive psychodynamic psychotherapy, which helped her explore and understand underlying emotional conflicts. Cognitive-behavioral techniques were employed to modify her maladaptive thoughts and behaviors. Grief processing was integrated to help her cope with significant losses. Family therapy was done to address conflicts and collaborate with the treatment process. Psychoeducation was provided to enhance her understanding of her condition and to empower her in her treatment journey. A suicide safety plan was developed to ensure her safety during critical periods. An interprofessional approach, which involved coordination with the Dermatology service for co-management, was also a key component of her treatment. Outcome: Over the course of 15 therapy sessions, the patient demonstrated significant improvement in both her depressive symptoms and hair-pulling behavior. Her active engagement in therapy, combined with pharmacological support, facilitated better emotional regulation and a more cohesive sense of self. Her adherence to the treatment plan, along with the collaborative efforts of the interprofessional team, contributed to her positive outcomes. Discussion: This case underscores the significance of addressing both TTM and its comorbid conditions to achieve effective treatment outcomes. The intricate interplay between TTM and MDD in the patient’s case highlights the importance of a comprehensive treatment plan that includes both pharmacological and psychotherapeutic approaches. Supportive-expressive psychodynamic psychotherapy, Cognitive-behavioral techniques, and Family therapy were particularly beneficial in addressing the complex emotional and behavioral aspects of her condition. The involvement of an interprofessional team, including dermatology co-management, was crucial in providing holistic care. Future practice should consider the benefits of such a multidisciplinary approach to managing complex cases like this, ensuring that both the psychological and physiological aspects of the disorders are adequately addressed.

Keywords: cognitive-behavioral therapy, interprofessional approach, major depressive disorder, psychodynamic psychotherapy, trichotillomania

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5 Establishment of a Classifier Model for Early Prediction of Acute Delirium in Adult Intensive Care Unit Using Machine Learning

Authors: Pei Yi Lin

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Objective: The objective of this study is to use machine learning methods to build an early prediction classifier model for acute delirium to improve the quality of medical care for intensive care patients. Background: Delirium is a common acute and sudden disturbance of consciousness in critically ill patients. After the occurrence, it is easy to prolong the length of hospital stay and increase medical costs and mortality. In 2021, the incidence of delirium in the intensive care unit of internal medicine was as high as 59.78%, which indirectly prolonged the average length of hospital stay by 8.28 days, and the mortality rate is about 2.22% in the past three years. Therefore, it is expected to build a delirium prediction classifier through big data analysis and machine learning methods to detect delirium early. Method: This study is a retrospective study, using the artificial intelligence big data database to extract the characteristic factors related to delirium in intensive care unit patients and let the machine learn. The study included patients aged over 20 years old who were admitted to the intensive care unit between May 1, 2022, and December 31, 2022, excluding GCS assessment <4 points, admission to ICU for less than 24 hours, and CAM-ICU evaluation. The CAMICU delirium assessment results every 8 hours within 30 days of hospitalization are regarded as an event, and the cumulative data from ICU admission to the prediction time point are extracted to predict the possibility of delirium occurring in the next 8 hours, and collect a total of 63,754 research case data, extract 12 feature selections to train the model, including age, sex, average ICU stay hours, visual and auditory abnormalities, RASS assessment score, APACHE-II Score score, number of invasive catheters indwelling, restraint and sedative and hypnotic drugs. Through feature data cleaning, processing and KNN interpolation method supplementation, a total of 54595 research case events were extracted to provide machine learning model analysis, using the research events from May 01 to November 30, 2022, as the model training data, 80% of which is the training set for model training, and 20% for the internal verification of the verification set, and then from December 01 to December 2022 The CU research event on the 31st is an external verification set data, and finally the model inference and performance evaluation are performed, and then the model has trained again by adjusting the model parameters. Results: In this study, XG Boost, Random Forest, Logistic Regression, and Decision Tree were used to analyze and compare four machine learning models. The average accuracy rate of internal verification was highest in Random Forest (AUC=0.86), and the average accuracy rate of external verification was in Random Forest and XG Boost was the highest, AUC was 0.86, and the average accuracy of cross-validation was the highest in Random Forest (ACC=0.77). Conclusion: Clinically, medical staff usually conduct CAM-ICU assessments at the bedside of critically ill patients in clinical practice, but there is a lack of machine learning classification methods to assist ICU patients in real-time assessment, resulting in the inability to provide more objective and continuous monitoring data to assist Clinical staff can more accurately identify and predict the occurrence of delirium in patients. It is hoped that the development and construction of predictive models through machine learning can predict delirium early and immediately, make clinical decisions at the best time, and cooperate with PADIS delirium care measures to provide individualized non-drug interventional care measures to maintain patient safety, and then Improve the quality of care.

Keywords: critically ill patients, machine learning methods, delirium prediction, classifier model

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4 Unidentified Remains with Extensive Bone Disease without a Clear Diagnosis

Authors: Patricia Shirley Almeida Prado, Selma Paixão Argollo, Maria De Fátima Teixeira Guimarães, Leticia Matos Sobrinho

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Skeletal differential diagnosis is essential in forensic anthropology in order to differentiate skeletal trauma from normal osseous variation and pathological processes. Thus, part of forensic anthropological field is differentiate skeletal criminal injuries from the normal skeletal variation (bone fusion or nonunion, transitional vertebrae and other non-metric traits), non-traumatic skeletal pathology (myositis ossificans, arthritis, bone metastasis, osteomyelitis) from traumatic skeletal pathology (myositis ossificans traumatic) avoiding misdiagnosis. This case shows the importance of effective pathological diagnosis in order to accelerate the identification process of skeletonized human remains. THE CASE: An unidentified skeletal remains at the medico legal institute Nina Rodrigues-Salvador, of a male young adult (29 to 40 years estimated) showing a massive heterotopic ossification on its right tibia at upper epiphysis and adjacent articular femur surface; an extensive ossification on the right clavicle (at the sternal extremity) also presenting an heterotopic ossification at right scapulae (upper third of scapulae lateral margin and infraglenoid tubercule) and at the head of right humerus at the shoulder joint area. Curiously, this case also shows an unusual porosity in certain vertebrae´s body and in some tarsal and carpal bones. Likewise, his left fifth metacarpal bones (right and left) showed a healed fracture which led both bones distorted. Based on identification, of pathological conditions in human skeletal remains literature and protocols these alterations can be misdiagnosed and this skeleton may present more than one pathological process. The anthropological forensic lab at Medico-legal Institute Nina Rodrigues in Salvador (Brazil) adopts international protocols to ancestry, sex, age and stature estimations, also implemented well-established conventions to identify pathological disease and skeletal alterations. The most compatible diagnosis for this case is hematogenous osteomyelitis due to following findings: 1: the healed fracture pattern at the clavicle showing a cloaca which is a pathognomonic for osteomyelitis; 2: the metacarpals healed fracture does not present cloaca although they developed a periosteal formation. 3: the superior articular surface of the right tibia shows an extensive inflammatory healing process that extends to adjacent femur articular surface showing some cloaca at tibia bone disease. 4: the uncommon porosities may result from hematogenous infectious process. The fractures probably have occurred in a different moments based on the healing process; the tibia injury is more extensive and has not been reorganized, while metacarpals and clavicle fracture is properly healed. We suggest that the clavicle and tibia´s fractures were infected by an existing infectious disease (syphilis, tuberculosis, brucellosis) or an existing syndrome (Gorham’s disease), which led to the development of osteomyelitis. This hypothesis is supported by the fact that different bones are affected in diverse levels. Like the metacarpals that do not show the cloaca, but then a periosteal new bone formation; then the unusual porosities do not show a classical osteoarthritic processes findings as the marginal osteophyte, pitting and new bone formation, they just show an erosive process without bone formation or osteophyte. To confirm and prove our hypothesis we are working on different clinical approaches like DNA, histopathology and other image exams to find the correct diagnostic.

Keywords: bone disease, forensic anthropology, hematogenous osteomyelitis, human identification, human remains

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3 Optimizing AI Voice for Adolescent Health Education: Preferences and Trustworthiness Across Teens and Parent

Authors: Yu-Lin Chen, Kimberly Koester, Marissa Raymond-Flesh, Anika Thapar, Jay Thapar

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Purpose: Effectively communicating adolescent health topics to teens and their parents is crucial. This study emphasizes critically evaluating the optimal use of artificial intelligence tools (AI), which are increasingly prevalent in disseminating health information. By fostering a deeper understanding of AI voice preference in the context of health, the research aspires to have a ripple effect, enhancing the collective health literacy and decision-making capabilities of both teenagers and their parents. This study explores AI voices' potential within health learning modules for annual well-child visits. We aim to identify preferred voice characteristics and understand factors influencing perceived trustworthiness, ultimately aiming to improve health literacy and decision-making in both demographics. Methods: A cross-sectional study assessed preferences and trust perceptions of AI voices in learning modules among teens (11-18) and their parents/guardians in Northern California. The study involved the development of four distinct learning modules covering various adolescent health-related topics, including general communication, sexual and reproductive health communication, parental monitoring, and well-child check-ups. Participants were asked to evaluate eight AI voices across the modules, considering a set of six factors such as intelligibility, naturalness, prosody, social impression, trustworthiness, and overall appeal, using Likert scales ranging from 1 to 10 (the higher, the better). They were also asked to select their preferred choice of voice for each module. Descriptive statistics summarized participant demographics. Chi-square/t-tests explored differences in voice preferences between groups. Regression models identified factors impacting the perceived trustworthiness of the top-selected voice per module. Results: Data from 104 participants (teen=63; adult guardian = 41) were included in the analysis. The mean age is 14.9 for teens (54% male) and 41.9 for the parent/guardian (12% male). At the same time, similar voice quality ratings were observed across groups, and preferences varied by topic. For instance, in general communication, teens leaned towards young female voices, while parents preferred mature female tones. Interestingly, this trend reversed for parental monitoring, with teens favoring mature male voices and parents opting for mature female ones. Both groups, however, converged on mature female voices for sexual and reproductive health topics. Beyond preferences, the study delved into factors influencing perceived trustworthiness. Interestingly, social impression and sound appeal emerged as the most significant contributors across all modules, jointly explaining 71-75% of the variance in trustworthiness ratings. Conclusion: The study emphasizes the importance of catering AI voices to specific audiences and topics. Social impression and sound appeal emerged as critical factors influencing perceived trustworthiness across all modules. These findings highlight the need to tailor AI voices by age and the specific health information being delivered. Ensuring AI voices resonate with both teens and their parents can foster their engagement and trust, ultimately leading to improved health literacy and decision-making for both groups. Limitations and future research: This study lays the groundwork for understanding AI voice preferences for teenagers and their parents in healthcare settings. However, limitations exist. The sample represents a specific geographic location, and cultural variations might influence preferences. Additionally, the modules focused on topics related to well-child visits, and preferences might differ for more sensitive health topics. Future research should explore these limitations and investigate the long-term impact of AI voice on user engagement, health outcomes, and health behaviors.

Keywords: artificial intelligence, trustworthiness, voice, adolescent

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2 Glycyrrhizic Acid Inhibits Lipopolysaccharide-Stimulated Bovine Fibroblast-Like Synoviocyte, Invasion through Suppression of TLR4/NF-κB-Mediated Matrix Metalloproteinase-9 Expression

Authors: Hosein Maghsoudi

Abstract:

Rheumatois arthritis (RA) is progressive inflammatory autoimmune diseases that primarily affect the joints, characterized by synovial hyperplasia and inflammatory cell infiltration, deformed and painful joints, which can lead tissue destruction, functional disability systemic complications, and early dead and socioeconomic costs. The cause of rheumatoid arthritis is unknown, but genetic and environmental factors are contributory and the prognosis is guarded. However, advances in understanding the pathogenesis of the disease have fostered the development of new therapeutics, with improved outcomes. The current treatment strategy, which reflects this progress, is to initiate aggressive therapy soon after diagnosis and to escalate the therapy, guided by an assessment of disease activity, in pursuit of clinical remission. The pathobiology of RA is multifaceted and involves T cells, B cells, fibroblast-like synoviocyte (FLSc) and the complex interaction of many pro-inflammatory cytokine. Novel biologic agents that target tumor necrosis or interlukin (IL)-1 and Il-6, in addition T- and B-cells inhibitors, have resulted in favorable clinical outcomes in patients with RA. Despite this, at least 30% of RA patients are résistance to available therapies, suggesting novel mediators should be identified that can target other disease-specific pathway or cell lineage. Among the inflammatory cell population that might participated in RA pathogenesis, FLSc are crucial in initiaing and driving RA in concert of cartilage and bone by secreting metalloproteinase (MMPs) into the synovial fluid and by direct invasion into extracellular matrix (ECM), further exacerbating joint damage. Invasion of fibroblast-like synoviocytes (FLSc) is critical in the pathogenesis of rheumatoid-arthritis. The metalloproteinase (MMPs) and activator of Toll-like receptor 4 (TLR4)/nuclear factor- κB pthway play a critical role in RA-FLS invasion induced by lipopolysaccharide (LPS). The present study aimed to explore the anti-invasion activity of Glycyrrhizic Acid as a pharmacologically safe phytochemical agent with potent anti-inflammatory properties on IL-1beta and TNF-alpha signalling pathways in Bovine fibroblast-like synoviocyte ex- vitro, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Results showed that Glycyrrhizic Acid suppressed LPS-stimulated bovine FLS migration and invasion by inhibition MMP-9 expression and activity. In addition our results revealed that Glycyrrhizic Acid inhibited the transcriptional activity of MMP-9 by suppression the nbinding activity of NF- κB in the MMP-9 promoter pathway. The extract of licorice (Glycyrrhiza glabra L.) has been widely used for many centuries in the traditional Chinese medicine as native anti-allergic agent. Glycyrrhizin (GL), a triterpenoidsaponin, extracted from the roots of licorice is the most effective compound for inflammation and allergic diseases in human body. The biological and pharmacological studies revealed that GL possesses many pharmacological effects, such as anti-inflammatory, anti-viral and liver protective effects, and the biological effects, such as induction of cytokines (interferon-γ and IL-12), chemokines as well as extrathymic T and anti-type 2 T cells. GL is known in the traditional Chinese medicine for its anti-inflammatory effect, which is originally described by Finney in 1959. The mechanism of the GL-induced anti-inflammatory effect is based on different pathways of the GL-induced selective inhibition of the prostaglandin E2 production, the CK-II- mediated activation of both GL-binding lipoxygenas (gbLOX; 17) and PLA2, an anti-thrombin action of GL and production of the reactive oxygen species (ROS; GL exerts liver protection properties by inhibiting PLA2 or by the hydroxyl radical trapping action, leading to the lowering of serum alanine and aspartate transaminase levels. The present study was undertaken to examine the possible mechanism of anti-inflammatory properties GL on IL-1beta and TNF-alpha signalling pathways in bovine fibroblast-like synoviocyte ex-vivo, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Our results clearly showed that treatment of bovine fibroblast-like synoviocyte with GL suppressed LPS-induced cell migration and invasion. Furthermore, it revealed that GL inhibited the transcription activity of MMP-9 by suppressing the binding activity of NF-κB in the MM-9 promoter. MMP-9 is an important ECM-degrading enzyme and overexpression of MMPs in important of RA-FLSs. LPS can stimulate bovine FLS to secret MMPs, and this induction is regulated at the transcription and translational levels. In this study, LPS treatment of bovine FLS caused an increase in MMP-2 and MMP-9 levels. The increase in MMP-9 expression and secretion was inhibited by ex- vitro. Furthermore, these effects were mimicked by MMP-9 siRNA. These result therefore indicate the the inhibition of LPS-induced bovine FLS invasion by GL occurs primarily by inhibiting MMP-9 expression and activity. Next we analyzed the functional significance of NF-κB transcription of MMP-9 activation in Bovine FLSs. Results from EMSA showed that GL suppressed LPS-induced NF-κB binding to the MMP-9 promotor, as NF-κB regulates transcriptional activation of multiple inflammatory cytokines, we predicted that GL might target NF-κB to suppress MMP-9 transcription by LPS. Myeloid differentiation-factor 88 (MyD88) and TIR-domain containing adaptor protein (TIRAP) are critical proteins in the LPS-induced NF-κB and apoptotic signaling pathways, GL inhibited the expression of TLR4 and MYD88. These results demonstrated that GL suppress LPS-induced MMP-9 expression through the inhibition of the induced TLR4/NFκB signaling pathway. Taken together, our results provide evidence that GL exerts anti-inflammatory effects by inhibition LPS-induced bovine FLSs migration and invasion, and the mechanisms may involve the suppression of TLR4/NFκB –mediated MMP-9 expression. Although further work is needed to clarify the complicated mechanism of GL-induced anti-invasion of bovine FLSs, GL might be used as a further anti-invasion drug with therapeutic efficacy in the treatment of immune-mediated inflammatory disease such as RA.

Keywords: glycyrrhizic acid, bovine fibroblast-like synoviocyte, tlr4/nf-κb, metalloproteinase-9

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1 Developing VR-Based Neurorehabilitation Support Tools: A Step-by-Step Approach for Cognitive Rehabilitation and Pain Distraction during Invasive Techniques in Hospital Settings

Authors: Alba Prats-Bisbe, Jaume López-Carballo, David Leno-Colorado, Alberto García Molina, Alicia Romero Marquez, Elena Hernández Pena, Eloy Opisso Salleras, Raimon Jané Campos

Abstract:

Neurological disorders are a leading cause of disability and premature mortality worldwide. Neurorehabilitation (NRHB) is a clinical process aimed at reducing functional impairment, promoting societal participation, and improving the quality of life for affected individuals. Virtual reality (VR) technology is emerging as a promising NRHB support tool. Its immersive nature fosters a strong sense of agency and embodiment, motivating patients to engage in meaningful tasks and increasing adherence to therapy. However, the clinical benefits of VR interventions are challenging to determine due to the high heterogeneity among health applications. This study explores a stepwise development approach for creating VR-based tools to assist individuals with neurological disorders in medical practice, aiming to enhance reproducibility, facilitate comparison, and promote the generalization of findings. Building on previous research, the step-by-step methodology encompasses: Needs Identification– conducting cross-disciplinary meetings to brainstorm problems, solutions, and address barriers. Intervention Definition– target population, set goals, and conceptualize the VR system (equipment and environments). Material Selection and Placement– choose appropriate hardware and software, place the device within the hospital setting, and test equipment. Co-design– collaboratively create VR environments, user interfaces, and data management strategies. Prototyping– develop VR prototypes, conduct user testing, and make iterative redesigns. Usability and Feasibility Assessment– design protocols and conduct trials with stakeholders in the hospital setting. Efficacy Assessment– conduct clinical trials to evaluate outcomes and long-term effects. Cost-Effectiveness Validation– assess reproducibility, sustainability, and balance between costs and benefits. NRHB is complex due to the multifaceted needs of patients and the interdisciplinary healthcare architecture. VR has the potential to support various applications, such as motor skill training, cognitive tasks, pain management, unilateral spatial neglect (diagnosis and treatment), mirror therapy, and ecologically valid activities of daily living. Following this methodology was crucial for launching a VR-based system in a real hospital environment. Collaboration with neuropsychologists lead to develop A) a VR-based tool for cognitive rehabilitation in patients with acquired brain injury (ABI). The system comprises a head-mounted display (HTC Vive Pro Eye) and 7 tasks targeting attention, memory, and executive functions. A desktop application facilitates session configuration, while database records in-game variables. The VR tool's usability and feasibility were demonstrated in proof-of-concept trials with 20 patients, and effectiveness is being tested through a clinical protocol with 12 patients completing 24-session treatment. Another case involved collaboration with nurses and paediatric physiatrists to create B) a VR-based distraction tool during invasive techniques. The goal is to alleviate pain and anxiety associated with botulinum toxin (BTX) injections, blood tests, or intravenous placements. An all-in-one headset (HTC Vive Focus 3) deploys 360º videos to improve the experience for paediatric patients and their families. This study presents a framework for developing clinically relevant and technologically feasible VR-based support tools for hospital settings. Despite differences in patient type, intervention purpose, and VR system, the methodology demonstrates usability, viability, reproducibility and preliminary clinical benefits. It highlights the importance approach centred on clinician and patient needs for any aspect of NRHB within a real hospital setting.

Keywords: neurological disorders, neurorehabilitation, stepwise development approach, virtual reality

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