Search results for: pediatric deformity
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 349

Search results for: pediatric deformity

19 Working Memory and Audio-Motor Synchronization in Children with Different Degrees of Central Nervous System's Lesions

Authors: Anastasia V. Kovaleva, Alena A. Ryabova, Vladimir N. Kasatkin

Abstract:

Background: The most simple form of entrainment to a sensory (typically auditory) rhythmic stimulus involves perceiving and synchronizing movements with an isochronous beat with one level of periodicity, such as that produced by a metronome. Children with pediatric cancer usually treated with chemo- and radiotherapy. Because of such treatment, psychologists and health professionals declare cognitive and motor abilities decline in cancer patients. The purpose of our study was to measure working memory characteristics with association with audio-motor synchronization tasks, also involved some memory resources, in children with different degrees of central nervous system lesions: posterior fossa tumors, acute lymphoblastic leukemia, and healthy controls. Methods: Our sample consisted of three groups of children: children treated for posterior fossa tumors (PFT-group, n=42, mean age 12.23), children treated for acute lymphoblastic leukemia (ALL-group, n=11, mean age 11.57) and neurologically healthy children (control group, n=36, mean age 11.67). Participants were tested for working memory characteristics with Cambridge Neuropsychological Test Automated Battery (CANTAB). Pattern recognition memory (PRM) and spatial working memory (SWM) tests were applied. Outcome measures of PRM test include the number and percentage of correct trials and latency (speed of participant’s response), and measures of SWM include errors, strategy, and latency. In the synchronization tests, the instruction was to tap out a regular beat (40, 60, 90 and 120 beats per minute) in synchrony with the rhythmic sequences that were played. This meant that for the sequences with an isochronous beat, participants were required to tap into every auditory event. Variations of inter-tap-intervals and deviations of children’s taps from the metronome were assessed. Results: Analysis of variance revealed the significant effect of group (ALL, PFT and control) on such parameters as short-term PRM, SWM strategy and errors. Healthy controls demonstrated more correctly retained elements, better working memory strategy, compared to cancer patients. Interestingly that ALL patients chose the bad strategy, but committed significantly less errors in SWM test then PFT and controls did. As to rhythmic ability, significant associations of working memory were found out only with 40 bpm rhythm: the less variable were inter-tap-intervals of the child, the more elements in memory he/she could retain. The ability to audio-motor synchronization may be related to working memory processes mediated by the prefrontal cortex whereby each sensory event is actively retrieved and monitored during rhythmic sequencing. Conclusion: Our results suggest that working memory, tested with appropriate cognitive methods, is associated with the ability to synchronize movements with rhythmic sounds, especially in sub-second intervals (40 per minute).

Keywords: acute lymphoblastic leukemia (ALL), audio-motor synchronization, posterior fossa tumor, working memory

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18 The Relationship between Body Fat Percent and Metabolic Syndrome Indices in Childhood Morbid Obesity

Authors: Mustafa Metin Donma

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Metabolic syndrome (MetS) is characterized by a series of biochemical, physiological and anthropometric indicators and is a life-threatening health problem due to its close association with chronic diseases such as diabetes mellitus, hypertension, cancer and cardiovascular diseases. The syndrome deserves great interest both in adults and children. Central obesity is the indispensable component of MetS. Particularly, children, who are morbidly obese have a great tendency to develop the disease, because they are under the threat in their future lives. Preventive measures at this stage should be considered. For this, investigators seek for an informative scale or an index for the purpose. So far, several, but not many suggestions come into the stage. However, the diagnostic decision is not so easy and may not be complete particularly in the pediatric population. The aim of the study was to develop a MetS index capable of predicting MetS, while children are at the morbid obesity stage. This study was performed on morbid obese (MO) children, which were divided into two groups. Morbid obese children, who do not possess MetS criteria comprised the first group (n=44). The second group was composed of children (n=42) with MetS diagnosis. Parents were informed about the signed consent forms, which are required for the participation of their children in the study. The approval of the study protocol was taken from the institutional ethics committee of Tekirdag Namik Kemal University. Helsinki Declaration was accepted prior to and during the study. Anthropometric measurements including weight, height, waist circumference (WC), hip C, head C, neck C, biochemical tests including fasting blood glucose (FBG), insulin (INS), triglycerides (TRG), high density lipoprotein cholesterol (HDL-C) and blood pressure measurements (systolic (SBP) and diastolic (DBP)) were performed. Body fat percentage (BFP) values were determined by TANITA’s Bioelectrical Impedance Analysis technology. Body mass index and MetS indices were calculated. The equations for MetS index (MetSI) and advanced Donma MetS index (ADMI) were [(INS/FBG)/(HDL-C/TRG)]*100 and MetSI*[(SBP+DBP/Height)], respectively. Descriptive statistics including median values, compare means tests, correlation-regression analysis were performed within the scope of data evaluation using the statistical package program, SPSS. Statistically significant mean differences were determined by a p value smaller than 0.05. Median values for MetSI and ADMI in MO (MetS-) and MO (MetS+) groups were calculated as (25.9 and 36.5) and (74.0 and 106.1), respectively. Corresponding mean±SD values for BFPs were 35.9±7.1 and 38.2±7.7 in groups. Correlation analysis of these two indices with corresponding general BFP values exhibited significant association with ADMI, close to significance with MetSI in MO group. Any significant correlation was found with neither of the indices in MetS group. In conclusion, important associations observed with MetS indices in MO group were quite meaningful. The presence of these associations in MO group was important for showing the tendency towards the development of MetS in MO (MetS-) participants. The other index, ADMI, was more helpful for predictive purpose.

Keywords: body fat percentage, child, index, metabolic syndrome, obesity

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17 Strengthening Facility-Based Systems to Improve Access to In-Patient Care for Sick Newborns in Brong Ahafo Region, Ghana

Authors: Paulina Clara Appiah, Kofi Issah, Timothy Letsa, Kennedy Nartey, Amanua Chinbuah, Adoma Dwomo-Fokuo, Jacqeline G. Asibey

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Background: The Every Newborn Action Plan provides evidence–based interventions to end preventable deaths in high burden countries. Brong Ahafo Region is one of ten regions in Ghana with less than half of its district hospitals having sick newborn units. Facility-based neonatal care is not prioritized and under-funded, and there is also inadequate knowledge and competence to manage the sick. The aim of this intervention was to make available in–patient care for sick newborns in all 19 district hospitals through the strengthening of facility-based systems. Methods: With the development and dissemination of the National Newborn Strategy and Action Plan 2014-2018, the country was able to attract PATH which provided the region with basic resuscitation equipment, supported hospital providers’ capacity building in Helping Babies Breathe, Essential Care of Every Baby, Infection Prevention and Management and held a symposia on managing the sick newborn. Newborn advocacy was promoted through newborn champions at the facility and community levels. Hospital management was then able to mobilize resources from communities, corporate organizations and from internally generated funds; created or expanded sick newborn care units and provided essential medicines and equipment. Kangaroo Mother Care was initiated in 6 hospitals. Pediatric specialist outreach services initiated comprised telephone consultations, teaching ward rounds and participating in perinatal death audits meetings. Newborn data capture and management was improved through the provision and training on the use of standard registers provided from the national level. Results: From February 2015 to November 2017, hospitals with sick newborn units increased from 7 to 19 (37%-100%). 180 pieces each of newborn ventilation bags and masks size 0, 1 and penguin suction bulbs were distributed to the hospitals, in addition to 20 newborn mannequin sets and 90 small clinical reminder posters. 802 providers (96.9%) were trained in resuscitation, of which 96% were successfully followed up in 6 weeks, 91% in 6 months and 80% in 12 months post-training. 53 clinicians (65%) were trained and mentored to manage sick newborns. 56 specialist teaching ward rounds were conducted. Data completeness improved from 92.6% - 99.9%. Availability of essential medicines improved from 11% to 100%. Number of hospital cots increased from 116 to 248 (214%). Cot occupancy rate increased from 57.4% to 92.5%. Hospitals with phototherapy equipment increased from 0 to 12 (63%). Hospitals with incubators increased from 1 to 12 (5%-63%). Newborn deaths among admissions reduced from 6.3% to 5.4%. Conclusion: Access to in-patient care increased significantly. Newborn advocacy successfully mobilized resources required for strengthening facility –based systems.

Keywords: facility-based systems, Ghana, in-patient care, newborn advocacy

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16 Creating Moments and Memories: An Evaluation of the Starlight 'Moments' Program for Palliative Children, Adolescents and Their Families

Authors: C. Treadgold, S. Sivaraman

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The Starlight Children's Foundation (Starlight) is an Australian non-profit organisation that delivers programs, in partnership with health professionals, to support children, adolescents, and their families who are living with a serious illness. While supporting children and adolescents with life-limiting conditions has always been a feature of Starlight's work, providing a dedicated program, specifically targeting and meeting the needs of the paediatric palliative population, is a recent area of focus. Recognising the challenges in providing children’s palliative services, Starlight initiated a research and development project to better understand and meet the needs of this group. The aim was to create a program which enhances the wellbeing of children, adolescents, and their families receiving paediatric palliative care in their community through the provision of on-going, tailored, positive experiences or 'moments'. This paper will present the results of the formative evaluation of this unique program, highlighting the development processes and outcomes of the pilot. The pilot was designed using an innovation methodology, which included a number of research components. There was a strong belief that it needed to be delivered in partnership with a dedicated palliative care team, helping to ensure the best interests of the family were always represented. This resulted in Starlight collaborating with both the Victorian Paediatric Palliative Care Program (VPPCP) at the Royal Children's Hospital, Melbourne, and the Sydney Children's Hospital Network (SCHN) to pilot the 'Moments' program. As experts in 'positive disruption', with a long history of collaborating with health professionals, Starlight was well placed to deliver a program which helps children, adolescents, and their families to experience moments of joy, connection and achieve their own sense of accomplishment. Building on Starlight’s evidence-based approach and experience in creative service delivery, the program aims to use the power of 'positive disruption' to brighten the lives of this group and create important memories. The clinical and Starlight team members collaborate to ensure that the child and family are at the centre of the program. The design of each experience is specific to their needs and ensures the creation of positive memories and family connection. It aims for each moment to enhance quality of life. The partnership with the VPPCP and SCHN has allowed the program to reach families across metropolitan and regional locations. In late 2019 a formative evaluation of the pilot was conducted utilising both quantitative and qualitative methodologies to document both the delivery and outcomes of the program. Central to the evaluation was the interviews conducted with both clinical teams and families in order to gain a comprehensive understanding of the impact of and satisfaction with the program. The findings, which will be shared in this presentation, provide practical insight into the delivery of the program, the key elements for its success with families, and areas which could benefit from additional research and focus. It will use stories and case studies from the pilot to highlight the impact of the program and discuss what opportunities, challenges, and learnings emerged.

Keywords: children, families, memory making, pediatric palliative care, support

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15 Modern Technology-Based Methods in Neurorehabilitation for Social Competence Deficit in Children with Acquired Brain Injury

Authors: M. Saard, A. Kolk, K. Sepp, L. Pertens, L. Reinart, C. Kööp

Abstract:

Introduction: Social competence is often impaired in children with acquired brain injury (ABI), but evidence-based rehabilitation for social skills has remained undeveloped. Modern technology-based methods create effective and safe learning environments for pediatric social skills remediation. The aim of the study was to implement our structured model of neuro rehab for socio-cognitive deficit using multitouch-multiuser tabletop (MMT) computer-based platforms and virtual reality (VR) technology. Methods: 40 children aged 8-13 years (yrs) have participated in the pilot study: 30 with ABI -epilepsy, traumatic brain injury and/or tic disorder- and 10 healthy age-matched controls. From the patients, 12 have completed the training (M = 11.10 yrs, SD = 1.543) and 20 are still in training or in the waiting-list group (M = 10.69 yrs, SD = 1.704). All children performed the first individual and paired assessments. For patients, second evaluations were performed after the intervention period. Two interactive applications were implemented into rehabilitation design: Snowflake software on MMT tabletop and NoProblem on DiamondTouch Table (DTT), which allowed paired training (2 children at once). Also, in individual training sessions, HTC Vive VR device was used with VR metaphors of difficult social situations to treat social anxiety and train social skills. Results: At baseline (B) evaluations, patients had higher deficits in executive functions on the BRIEF parents’ questionnaire (M = 117, SD = 23.594) compared to healthy controls (M = 22, SD = 18.385). The most impaired components of social competence were emotion recognition, Theory of Mind skills (ToM), cooperation, verbal/non-verbal communication, and pragmatics (Friendship Observation Scale scores only 25-50% out of 100% for patients). In Sentence Completion Task and Spence Anxiety Scale, the patients reported a lack of friends, behavioral problems, bullying in school, and social anxiety. Outcome evaluations: Snowflake on MMT improved executive and cooperation skills and DTT developed communication skills, metacognitive skills, and coping. VR, video modelling and role-plays improved social attention, emotional attitude, gestural behaviors, and decreased social anxiety. NEPSY-II showed improvement in Affect Recognition [B = 7, SD = 5.01 vs outcome (O) = 10, SD = 5.85], Verbal ToM (B = 8, SD = 3.06 vs O = 10, SD = 4.08), Contextual ToM (B = 8, SD = 3.15 vs O = 11, SD = 2.87). ToM Stories test showed an improved understanding of Intentional Lying (B = 7, SD = 2.20 vs O = 10, SD = 0.50), and Sarcasm (B=6, SD = 2.20 vs O = 7, SD = 2.50). Conclusion: Neurorehabilitation based on the Structured Model of Neurorehab for Socio-Cognitive Deficit in children with ABI were effective in social skills remediation. The model helps to understand theoretical connections between components of social competence and modern interactive computerized platforms. We encourage therapists to implement these next-generation devices into the rehabilitation process as MMT and VR interfaces are motivating for children, thus ensuring good compliance. Improving children’s social skills is important for their and their families’ quality of life and social capital.

Keywords: acquired brain injury, children, social skills deficit, technology-based neurorehabilitation

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14 Relationship between Hepatokines and Insulin Resistance in Childhood Obesity

Authors: Mustafa Metin Donma, Orkide Donma

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Childhood obesity is an important clinical problem because it may lead to chronic diseases during the adulthood period of the individual. Obesity is a metabolic disease associated with low-grade inflammation. The liver occurs at the center of metabolic pathways. Adropin, fibroblast growth factor-21 (FGF-21), and fetuin-A are hepatokines. Due to the immense participation of the liver in glucose metabolism, these liver-derived factors may be associated with insulin resistance (IR), which is a phenomenon discussed within the scope of obesity problems. The aim of this study is to determine the concentrations of adropin, FGF-21, and fetuin-A in childhood obesity, to point out possible differences between the obesity groups, and to investigate possible associations among these three hepatokines in obese and morbidly obese children. A total of one hundred and thirty-two children were included in the study. Two obese groups were constituted. The groups were matched in terms of mean ± SD values of ages. Body mass index values of obese and morbidly obese groups were 25.0 ± 3.5 kg/m² and 29.8 ± 5.7 kg/m², respectively. Anthropometric measurements including waist circumference, hip circumference, head circumference, and neck circumference were recorded. Informed consent forms were taken from the parents of the participants. The ethics committee of the institution approved the study protocol. Blood samples were obtained after overnight fasting. Routine biochemical tests, including glucose- and lipid-related parameters, were performed. Concentrations of the hepatokines (adropin, FGF-21, fetuin A) were determined by enzyme-linked immunosorbent assay. Insulin resistance indices such as homeostasis model assessment for IR (HOMA-IR), alanine transaminase-to aspartate transaminase ratio (ALT/AST), diagnostic obesity notation model assessment laboratory index, diagnostic obesity notation model assessment metabolic syndrome index as well as obesity indices such as diagnostic obesity notation model assessment-II index, and fat mass index were calculated using the previously derived formulas. Statistical evaluation of the study data as well as findings of the study was performed by SPSS for Windows. Statistical difference was accepted significant when p is smaller than 0.05. Statistically significant differences were found for insulin, triglyceride, high-density lipoprotein cholesterol levels of the groups. A significant increase was observed for FGF-21 concentrations in the morbidly obese group. Higher adropin and fetuin-A concentrations were observed in the same group in comparison with the values detected in the obese group (p > 0.05). There was no statistically significant difference between the ALT/AST values of the groups. In all of the remaining IR and obesity indices, significantly increased values were calculated for morbidly obese children. Significant correlations were detected between HOMA-IR and each of the hepatokines. The highest one was the association with fetuin-A (r=0.373, p=0.001). In conclusion, increased levels observed in adropin, FGF-21, and fetuin-A have shown that these hepatokines possess increasing potential going from obese to morbid obese state. Out of the correlations found with the IR index, the most affected hepatokine was fetuin-A, the parameter possibly used as the indicator of the advanced obesity stage.

Keywords: adropin, fetuin A, fibroblast growth factor-21, insulin resistance, pediatric obesity

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13 Developing Effective Strategies to Reduce Hiv, Aids and Sexually Transmitted Infections, Nakuru, Kenya

Authors: Brian Bacia, Esther Githaiga, Teresia Kabucho, Paul Moses Ndegwa, Lucy Gichohi

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Purpose: The aim of the study is to ensure an appropriate mix of evidence-based prevention strategies geared towards the reduction of new HIV infections and the incidence of Sexually transmitted Illnesses Background: In Nakuru County, more than 90% of all HIV-infected patients are adults and on a single-dose medication-one pill that contains a combination of several different HIV drugs. Nakuru town has been identified as the hardest hit by HIV/Aids in the County according to the latest statistics from the County Aids and STI group, with a prevalence rate of 5.7 percent attributed to the high population and an active urban center. Method: 2 key studies were carried out to provide evidence for the effectiveness of antiretroviral therapy (ART) when used optimally on preventing sexual transmission of HIV. Discussions based on an examination, assessments of successes in planning, program implementation, and ultimate impact of prevention and treatment were undertaken involving health managers, health workers, community health workers, and people living with HIV/AIDS between February -August 2021. Questionnaires were carried out by a trained duo on ethical procedures at 15 HIV treatment clinics targeting patients on ARVs and caregivers on ARV prevention and treatment of pediatric HIV infection. Findings: Levels of AIDS awareness are extremely high. Advances in HIV treatment have led to an enhanced understanding of the virus, improved care of patients, and control of the spread of drug-resistant HIV. There has been a tremendous increase in the number of people living with HIV having access to life-long antiretroviral drugs (ARV), mostly on generic medicines. Healthcare facilities providing treatment are stressed challenging the administration of the drugs, which require a clinical setting. Women find it difficult to take a daily pill which reduces the effectiveness of the medicine. ART adherence can be strengthened largely through the use of innovative digital technology. The case management approach is useful in resource-limited settings. The county has made tremendous progress in mother-to-child transmission reduction through enhanced early antenatal care (ANC) attendance and mapping of pregnant women Recommendations: Treatment reduces the risk of transmission to the child during pregnancy, labor, and delivery. Promote research of medicines through patients and community engagement. Reduce the risk of transmission through breastfeeding. Enhance testing strategies and strengthen health systems for sustainable HIV service delivery. Need exists for improved antenatal care and delivery by skilled birth attendants. Develop a comprehensive maternal reproductive health policy covering equitability, efficient and effective delivery of services. Put in place referral systems.

Keywords: evidence-based prevention strategies, service delivery, human management, integrated approach

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12 The Monitor for Neutron Dose in Hadrontherapy Project: Secondary Neutron Measurement in Particle Therapy

Authors: V. Giacometti, R. Mirabelli, V. Patera, D. Pinci, A. Sarti, A. Sciubba, G. Traini, M. Marafini

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The particle therapy (PT) is a very modern technique of non invasive radiotherapy mainly devoted to the treatment of tumours untreatable with surgery or conventional radiotherapy, because localised closely to organ at risk (OaR). Nowadays, PT is available in about 55 centres in the word and only the 20\% of them are able to treat with carbon ion beam. However, the efficiency of the ion-beam treatments is so impressive that many new centres are in construction. The interest in this powerful technology lies to the main characteristic of PT: the high irradiation precision and conformity of the dose released to the tumour with the simultaneous preservation of the adjacent healthy tissue. However, the beam interactions with the patient produce a large component of secondary particles whose additional dose has to be taken into account during the definition of the treatment planning. Despite, the largest fraction of the dose is released to the tumour volume, a non-negligible amount is deposed in other body regions, mainly due to the scattering and nuclear interactions of the neutrons within the patient body. One of the main concerns in PT treatments is the possible occurrence of secondary malignant neoplasm (SMN). While SMNs can be developed up to decades after the treatments, their incidence impacts directly life quality of the cancer survivors, in particular in pediatric patients. Dedicated Treatment Planning Systems (TPS) are used to predict the normal tissue toxicity including the risk of late complications induced by the additional dose released by secondary neutrons. However, no precise measurement of secondary neutrons flux is available, as well as their energy and angular distributions: an accurate characterization is needed in order to improve TPS and reduce safety margins. The project MONDO (MOnitor for Neutron Dose in hadrOntherapy) is devoted to the construction of a secondary neutron tracker tailored to the characterization of that secondary neutron component. The detector, based on the tracking of the recoil protons produced in double-elastic scattering interactions, is a matrix of thin scintillating fibres, arranged in layer x-y oriented. The final size of the object is 10 x 10 x 20 cm3 (squared 250µm scint. fibres, double cladding). The readout of the fibres is carried out with a dedicated SPAD Array Sensor (SBAM) realised in CMOS technology by FBK (Fondazione Bruno Kessler). The detector is under development as well as the SBAM sensor and it is expected to be fully constructed for the end of the year. MONDO will make data tacking campaigns at the TIFPA Proton Therapy Center of Trento, at the CNAO (Pavia) and at HIT (Heidelberg) with carbon ion in order to characterize the neutron component and predict the additional dose delivered on the patients with much more precision and to drastically reduce the actual safety margins. Preliminary measurements with charged particles beams and MonteCarlo FLUKA simulation will be presented.

Keywords: secondary neutrons, particle therapy, tracking detector, elastic scattering

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11 A Nutrient Formulation Affects Brain Myelination in Infants: An Investigative Randomized Controlled Trial

Authors: N. Schneider, M. Bruchhage, M. Hartweg, G. Mutungi, J. O Regan, S. Deoni

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Observational neuroimaging studies suggest differences between breast-fed and formula-fed infants in developmental myelination, a key brain process for learning and cognitive development. However, the possible effects of a nutrient formulation on myelin development in healthy term infants in an intervention study have not been investigated. Objective was, therefore, to investigate the efficacy of a nutrient formulation with higher levels of myelin-relevant nutrients as compared to a control formulation with lower levels of the same nutrients on brain myelination and cognitive development in the first 6 months of life. The study is an ongoing randomized, controlled, double-blind, two-center, parallel-group clinical trial with a nonrandomized, non-blinded arm of exclusively breastfed infants. The current findings result from a staged statistical analysis at 6 months; the recruitment and intervention period has been completed for all participants. Follow-up visits at 12, 18 and 24 months are still ongoing. N= 81 enrolled full term, neurotypical infants of both sexes were randomized into either the investigational (N= 42) or the control group (N= 39), and N= 108 children in the breast-fed arm served as a natural reference group. The effect of a blend of docosahexaenoic acid, arachidonic acid, iron, vitamin B12, folic acid as well as sphingomyelin from a uniquely proceed whey protein concentrate enriched in alpha-lactalbumin and phospholipids in an infant nutrition product matrix was investigated. The main outcomes for the staged statistical analyses at 6 months included brain myelination measures derived from MRI. Additional outcomes were brain volume, cognitive development and safety. The full analyses set at 6 months comprised N= 66 infants. Higher levels of myelin-relevant nutrients compared to lower levels resulted in significant differences in myelin structure, volume, and rate of myelination as early as 3 and 6 months of life. The cross-sectional change of means between groups for whole-brain myelin volume was 8.4% for investigational versus control formulation (3.5% versus the breastfeeding reference) group at 3 months and increased to 36.4% for investigational versus control formulation (14.1% versus breastfeeding reference) at 6 months. No statistically significant differences were detected for early cognition scores. Safety findings were largely similar across groups. This is the first pediatric nutritional neuroimaging study demonstrating the efficacy of a myelin nutrient blend on developmental myelination in well-nourished term infants. Myelination is a critical process in learning and development. The effects were demonstrated across the brain, particularly in temporal and parietal regions, known to be functionally involved in sensory, motor and language skills. These first results add to the field of nutritional neuroscience by demonstrating early life nutrition benefits for brain architecture which may be foundational for later cognitive and behavioral outcomes. ClinicalTrials.gov Identifier: NCT03111927 (Infant Nutrition and Brain Development - Full-Text View - ClinicalTrials.gov).

Keywords: brain development, infant nutrition, MRI, myelination

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10 Study of the Association between Salivary Microbiological Data, Oral Health Indicators, Behavioral Factors, and Social Determinants among Post-COVID Patients Aged 7 to 12 Years in Tbilisi City

Authors: Lia Mania, Ketevan Nanobashvili

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Background: The coronavirus disease COVID-19 has become the cause of a global health crisis during the current pandemic. This study aims to fill the paucity of epidemiological studies on the impact of COVID-19 on the oral health of pediatric populations. Methods: It was conducted an observational, cross-sectional study in Georgia, in Tbilisi (capital of Georgia), among 7 to 12-year-old PCR or rapid test-confirmed post-Covid populations in all districts of Tbilisi (10 districts in total). 332 beneficiaries who were infected with Covid within one year were included in the study. The population was selected in schools of Tbilisi according to the principle of cluster selection. A simple random selection took place in the selected clusters. According to this principle, an equal number of beneficiaries were selected in all districts of Tbilisi. By July 1, 2022, according to National Center for Disease Control and Public Health data (NCDC.Ge), the number of test-confirmed cases in the population aged 0-18 in Tbilisi was 115137 children (17.7% of all confirmed cases). The number of patients to be examined was determined by the sample size. Oral screening, microbiological examination of saliva, and administration of oral health questionnaires to guardians were performed. Statistical processing of data was done with SPSS-23. Risk factors were estimated by odds ratio and logistic regression with 95% confidence interval. Results: Statistically reliable differences between the averages of oral health indicators in asymptomatic and symptomatic covid-infected groups are: for caries intensity (DMF+def) t=4.468 and p=0.000, for modified gingival index (MGI) t=3.048, p=0.002, for simplified oral hygiene index (S-OHI) t=4.853; p=0.000. Symptomatic covid-infection has a reliable effect on the oral microbiome (Staphylococcus aureus, Candida albicans, Pseudomonas aeruginosa, Streptococcus pneumoniae, Staphylococcus epidermalis); (n=332; 77.3% vs n=332; 58.0%; OR=2.46, 95%CI: 1.318-4.617). According to the logistic regression, it was found that the severity of the covid infection has a significant effect on the frequency of pathogenic and conditionally pathogenic bacteria in the oral cavity B=0.903 AOR=2.467 (CL 1.318-4.617). Symptomatic covid-infection affects oral health indicators, regardless of the presence of other risk factors, such as parental employment status, tooth brushing behaviors, carbohydrate meal, fruit consumption. (p<0.05). Conclusion: Risk factors (parental employment status, tooth brushing behaviors, carbohydrate consumption) were associated with poorer oral health status in a post-Covid population of 7- to 12-year-old children. However, such a risk factor as symptomatic ongoing covid-infection affected the oral microbiome in terms of the abundant growth of pathogenic and conditionally pathogenic bacteria (Staphylococcus aureus, Candida albicans, Pseudomonas aeruginosa, Streptococcus pneumoniae, Staphylococcus epidermalis) and further worsened oral health indicators. Thus, a close association was established between symptomatic covid-infection and microbiome changes in the post-covid period; also - between the variables of oral health indicators and the symptomatic course of covid-infection.

Keywords: oral microbiome, COVID-19, population based research, oral health indicators

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9 A Case Report: The Role of Gut Directed Hypnotherapy in Resolution of Irritable Bowel Syndrome in a Medication Refractory Pediatric Male Patient

Authors: Alok Bapatla, Pamela Lutting, Mariastella Serrano

Abstract:

Background: Irritable Bowel Syndrome (IBS) is a functional gastrointestinal disorder characterized by abdominal pain associated with altered bowel habits in the absence of an underlying organic cause. Although the exact etiology of IBS is not fully understood, one of the leading theories postulates a pathology within the Brain-Gut Axis that leads to an overall increase in gastrointestinal sensitivity and pejorative changes in gastrointestinal motility. Research and clinical practice have shown that Gut Directed Hypnotherapy (GDH) has a beneficial clinical role in improving Mind-Gut control and thereby comorbid conditions such as anxiety, abdominal pain, constipation, and diarrhea. Aims: This study presents a 17-year old male with underlying anxiety and a one-year history of IBS-Constipation Predominant Subtype (IBS-C), who has demonstrated impressive improvement of symptoms following GDH treatment following refractory trials with medications including bisacodyl, senna, docusate, magnesium citrate, lubiprostone, linaclotide. Method: The patient was referred to a licensed clinical psychologist specializing in clinical hypnosis and cognitive-behavioral therapy (CBT), who implemented “The Standardized Hypnosis Protocol for IBS” developed by Dr. Olafur S. Palsson, Psy.D at the University of North Carolina at Chapel Hill. The hypnotherapy protocol consisted of a total of seven weekly 45-minute sessions supplemented with a 20-minute audio recording to be listened to once daily. Outcome variables included the GAD-7, PHQ-9 and DCI-2, as well as self-ratings (ranging 0-10) for pain (intensity and frequency), emotional distress about IBS symptoms, and overall emotional distress. All variables were measured at intake prior to administration of the hypnosis protocol and at the conclusion of the hypnosis treatment. A retrospective IBS Questionnaire (IBS Severity Scoring System) was also completed at the conclusion of the GDH treatment for pre-and post-test ratings of clinical symptoms. Results: The patient showed improvement in all outcome variables and self-ratings, including abdominal pain intensity, frequency of abdominal pain episodes, emotional distress relating to gut issues, depression, and anxiety. The IBS Questionnaire showed a significant improvement from a severity score of 400 (defined as severe) prior to GDH intervention compared to 55 (defined as complete resolution) at four months after the last session. IBS Questionnaire subset questions that showed a significant score improvement included abdominal pain intensity, days of pain experienced per 10 days, satisfaction with bowel habits, and overall interference of life affected by IBS symptoms. Conclusion: This case supports the existing research literature that GDH has a significantly beneficial role in improving symptoms in patients with IBS. Emphasis is placed on the numerical results of the IBS Questionnaire scoring, which reflects a patient who initially suffered from severe IBS with failed response to multiple medications, who subsequently showed full and sustained resolution

Keywords: pediatrics, constipation, irritable bowel syndrome, hypnotherapy, gut-directed hypnosis

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8 Developing Primary Care Datasets for a National Asthma Audit

Authors: Rachael Andrews, Viktoria McMillan, Shuaib Nasser, Christopher M. Roberts

Abstract:

Background and objective: The National Review of Asthma Deaths (NRAD) found that asthma management and care was inadequate in 26% of cases reviewed. Major shortfalls identified were adherence to national guidelines and standards and, particularly, the organisation of care, including supervision and monitoring in primary care, with 70% of cases reviewed having at least one avoidable factor in this area. 5.4 million people in the UK are diagnosed with and actively treated for asthma, and approximately 60,000 are admitted to hospital with acute exacerbations each year. The majority of people with asthma receive management and treatment solely in primary care. This has therefore created concern that many people within the UK are receiving sub-optimal asthma care resulting in unnecessary morbidity and risk of adverse outcome. NRAD concluded that a national asthma audit programme should be established to measure and improve processes, organisation, and outcomes of asthma care. Objective: To develop a primary care dataset enabling extraction of information from GP practices in Wales and providing robust data by which results and lessons could be drawn and drive service development and improvement. Methods: A multidisciplinary group of experts, including general practitioners, primary care organisation representatives, and asthma patients was formed and used as a source of governance and guidance. A review of asthma literature, guidance, and standards took place and was used to identify areas of asthma care which, if improved, would lead to better patient outcomes. Modified Delphi methodology was used to gain consensus from the expert group on which of the areas identified were to be prioritised, and an asthma patient and carer focus group held to seek views and feedback on areas of asthma care that were important to them. Areas of asthma care identified by both groups were mapped to asthma guidelines and standards to inform and develop primary and secondary care datasets covering both adult and pediatric care. Dataset development consisted of expert review and a targeted consultation process in order to seek broad stakeholder views and feedback. Results: Areas of asthma care identified as requiring prioritisation by the National Asthma Audit were: (i) Prescribing, (ii) Asthma diagnosis (iii) Asthma Reviews (iv) Personalised Asthma Action Plans (PAAPs) (v) Primary care follow-up after discharge from hospital (vi) Methodologies and primary care queries were developed to cover each of the areas of poor and variable asthma care identified and the queries designed to extract information directly from electronic patients’ records. Conclusion: This paper describes the methodological approach followed to develop primary care datasets for a National Asthma Audit. It sets out the principles behind the establishment of a National Asthma Audit programme in response to a national asthma mortality review and describes the development activities undertaken. Key process elements included: (i) mapping identified areas of poor and variable asthma care to national guidelines and standards, (ii) early engagement of experts, including clinicians and patients in the process, and (iii) targeted consultation of the queries to provide further insight into measures that were collectable, reproducible and relevant.

Keywords: asthma, primary care, general practice, dataset development

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7 Early Predictive Signs for Kasai Procedure Success

Authors: Medan Isaeva, Anna Degtyareva

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Context: Biliary atresia is a common reason for liver transplants in children, and the Kasai procedure can potentially be successful in avoiding the need for transplantation. However, it is important to identify factors that influence surgical outcomes in order to optimize treatment and improve patient outcomes. Research aim: The aim of this study was to develop prognostic models to assess the outcomes of the Kasai procedure in children with biliary atresia. Methodology: This retrospective study analyzed data from 166 children with biliary atresia who underwent the Kasai procedure between 2002 and 2021. The effectiveness of the operation was assessed based on specific criteria, including post-operative stool color, jaundice reduction, and bilirubin levels. The study involved a comparative analysis of various parameters, such as gestational age, birth weight, age at operation, physical development, liver and spleen sizes, and laboratory values including bilirubin, ALT, AST, and others, measured pre- and post-operation. Ultrasonographic evaluations were also conducted pre-operation, assessing the hepatobiliary system and related quantitative parameters. The study was carried out by two experienced specialists in pediatric hepatology. Comparative analysis and multifactorial logistic regression were used as the primary statistical methods. Findings: The study identified several statistically significant predictors of a successful Kasai procedure, including the presence of the gallbladder and levels of cholesterol and direct bilirubin post-operation. A detectable gallbladder was associated with a higher probability of surgical success, while elevated post-operative cholesterol and direct bilirubin levels were indicative of a reduced chance of positive outcomes. Theoretical importance: The findings of this study contribute to the optimization of treatment strategies for children with biliary atresia undergoing the Kasai procedure. By identifying early predictive signs of success, clinicians can modify treatment plans and manage patient care more effectively and proactively. Data collection and analysis procedures: Data for this analysis were obtained from the health records of patients who received the Kasai procedure. Comparative analysis and multifactorial logistic regression were employed to analyze the data and identify significant predictors. Question addressed: The study addressed the question of identifying predictive factors for the success of the Kasai procedure in children with biliary atresia. Conclusion: The developed prognostic models serve as valuable tools for early detection of patients who are less likely to benefit from the Kasai procedure. This enables clinicians to modify treatment plans and manage patient care more effectively and proactively. Potential limitations of the study: The study has several limitations. Its retrospective nature may introduce biases and inconsistencies in data collection. Being single centered, the results might not be generalizable to wider populations due to variations in surgical and postoperative practices. Also, other potential influencing factors beyond the clinical, laboratory, and ultrasonographic parameters considered in this study were not explored, which could affect the outcomes of the Kasai operation. Future studies could benefit from including a broader range of factors.

Keywords: biliary atresia, kasai operation, prognostic model, native liver survival

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6 Clinico-pathological Study of Xeroderma Pigmentosa: A Case Series of Eight Cases

Authors: Kakali Roy, Sahana P. Raju, Subhra Dhar, Sandipan Dhar

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Introduction: Xeroderma pigmentosa (XP) is a rare inherited (autosomal recessive) disease resulting from impairment in DNA repair that involves recognition and repair of ultraviolet radiation (UVR) induced DNA damage in the nucleotide excision repair pathway. Which results in increased photosensitivity, UVR induced damage to skin and eye, increased susceptibility of skin and ocular cancer, and progressive neurodegeneration in some patients. XP is present worldwide, with higher incidence in areas having frequent consanguinity. Being extremely rare, there is limited literature on XP and associated complications. Here, the clinico-pathological experience (spectrum of clinical presentation, histopathological findings of malignant skin lesions, and progression) of managing 8 cases of XP is presented. Methodology: A retrospective study was conducted in a pediatric tertiary care hospital in eastern India during a ten-year period from 2013 to 2022. A clinical diagnosis was made based on severe sun burn or premature photo-aging and/or onset of cutaneous malignancies at early age (1st decade) in background of consanguinity and autosomal recessive inheritance pattern in family. Results: The mean age of presentation was 1.2 years (range of 7month-3years), while three children presented during their infancy. Male to female ratio was 5:3, and all were born of consanguineous marriage. They presented with dermatological manifestations (100%) followed by ophthalmic (75%) and/or neurological symptoms (25%). Patients had normal skin at birth but soon developed extreme sensitivity to UVR in the form of exaggerated sun tanning, burning, and blistering on minimal sun exposure, followed by abnormal skin pigmentation like freckles and lentiginosis. Subsequently, over time there was progressive xerosis, atrophy, wrinkling, and poikiloderma. Six patients had varied degree of ocular involvement, while three of them had severe manifestation, including madarosis, tylosis, ectropion, Lagopthalmos, Pthysis bulbi, clouding and scarring of the cornea with complete or partial loss of vision, and ophthalmic malignancies. 50% (n=4) cases had skin and ocular pre-malignant (actinic keratosis) and malignant lesions, including melanoma and non melanoma skin cancer (NMSC) like squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) in their early childhood. One patient had simultaneous occurrence of multiple malignancies together (SCC, BCC, and melanoma). Subnormal intelligence was noticed as neurological feature, and none had sensory neural hearing loss, microcephaly, neuroregression, or neurdeficit. All the patients had been being managed by a multidisciplinary team of pediatricians, dermatologists, ophthalmologists, neurologists and psychiatrists. Conclusion: Although till date there is no complete cure for XP and the disease is ultimately fatal. But increased awareness, early diagnosis followed by persistent vigorous protection from UVR, and regular screening for early detection of malignancies along with psychological support can drastically improve patients’ quality of life and life expectancy. Further research is required on formulating optimal management of XP, specifically the role and possibilities of gene therapy in XP.

Keywords: childhood malignancies, dermato-pathological findings, eastern India, Xeroderma pigmentosa

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5 A Fresh Approach to Learn Evidence-Based Practice, a Prospective Interventional Study

Authors: Ebtehal Qulisy, Geoffrey Dougherty, Kholoud Hothan, Mylene Dandavino

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Background: For more than 200 years, journal clubs (JCs) have been used to teach the fundamentals of critical appraisal and evidence-based practice (EBP). However, JCs curricula face important challenges, including poor sustainability, insufficient time to prepare for and conduct the activities, and lack of trainee skills and self-efficacy with critical appraisal. Andragogy principles and modern technology could help EBP be taught in more relevant, modern, and interactive ways. Method: We propose a fresh educational activity to teach EBP. Educational sessions are designed to encourage collaborative and experiential learning and do not require advanced preparation by the participants. Each session lasts 60 minutes and is adaptable to in-person, virtual, or hybrid contexts. Sessions are structured around a worksheet and include three educational objectives: “1. Identify a Clinical Conundrum”, “2. Compare and Contrast Current Guidelines”, and “3. Choose a Recent Journal Article”. Sessions begin with a short presentation by a facilitator of a clinical scenario highlighting a “grey-zone” in pediatrics. Trainees are placed in groups of two to four (based on the participants’ number) of varied training levels. The first task requires the identification of a clinical conundrum (a situation where there is no clear answer but only a reasonable solution) related to the scenario. For the second task, trainees must identify two or three clinical guidelines. The last task requires trainees to find a journal article published in the last year that reports an update regarding the scenario’s topic. Participants are allowed to use their electronic devices throughout the session. Our university provides full-text access to major journals, which facilitated this exercise. Results: Participants were a convenience sample of trainees in the inpatient services at the Montréal Children’s Hospital, McGill University. Sessions were conducted as a part of an existing weekly academic activity and facilitated by pediatricians with experience in critical appraisal. There were 28 participants in 4 sessions held during Spring 2022. Time was allocated at the end of each session to collect participants’ feedback via a self-administered online survey. There were 22 responses, were 41%(n=9) pediatric residents, 22.7%(n=5) family medicine residents, 31.8%(n=7) medical students, and 4.5%(n=1) nurse practitioner. Four respondents participated in more than one session. The “Satisfied” rates were 94.7% for session format, 100% for topic selection, 89.5% for time allocation, and 84.3% for worksheet structure. 60% of participants felt that including the sessions during the clinical ward rotation was “Feasible.” As per self-efficacy, participants reported being “Confident” for the tasks as follows: 89.5% for the ability to identify a relevant conundrum, 94.8% for the compare and contrast task, and 84.2% for the identification of a published update. The perceived effectiveness to learn EBP was reported as “Agreed” by all participants. All participants would recommend this session for further teaching. Conclusion: We developed a modern approach to teach EBP, enjoyed by all levels of participants, who also felt it was a useful learning experience. Our approach addresses known JCs challenges by being relevant to clinical care, fostering active engagement but not requiring any preparation, using available technology, and being adaptable to hybrid contexts.

Keywords: medical education, journal clubs, post-graduate teaching, andragogy, experiential learning, evidence-based practice

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4 Chronic Fatigue Syndrome/Myalgic Encephalomyelitis in Younger Children: A Qualitative Analysis of Families’ Experiences of the Condition and Perspective on Treatment

Authors: Amberly Brigden, Ali Heawood, Emma C. Anderson, Richard Morris, Esther Crawley

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Background: Paediatric chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) is characterised by persistent, disabling fatigue. Health services see patients below the age of 12. This age group experience high levels of disability, with low levels of school attendance, high levels of fatigue, anxiety, functional disability and pain. CFS/ME interventions have been developed for adolescents, but the developmental needs of younger children suggest treatment should be tailored to this age group. Little is known about how intervention should be delivered to this age group, and further work is needed to explore this. Qualitative research aids patient-centered design of health intervention. Methods: Five to 11-year-olds and their parents were recruited from a specialist CFS/ME service. Semi-structured interviews explored the families’ experience of the condition and perspectives on treatment. Interactive and arts-based methods were used. Interviews were audio-recorded, transcribed and analysed thematically. Qualitative Results: 14 parents and 7 children were interviewed. Early analysis of the interviews revealed the importance of the social-ecological setting of the child, which led to themes being developed in the context of Systems Theory. Theme one relates to the level of the child, theme two the family system, theme three the organisational and societal systems, and theme four cuts-across all levels. Theme1: The child’s capacity to describe, understand and manage their condition. Younger children struggled to describe their internal experiences, such as physical symptoms. Parents felt younger children did not understand some concepts of CFS/ME and did not have the capabilities to monitor and self-regulate their behaviour, as required by treatment. A spectrum of abilities was described; older children (10-11-year-olds) were more involved in clinical sessions and had more responsibility for self-management. Theme2: Parents’ responsibility for managing their child’s condition. Parents took responsibility for regulating their child’s behaviour in accordance with the treatment programme. They structured their child’s environment, gave direct instructions to their child, and communicated the needs of their child to others involved in care. Parents wanted their child to experience a 'normal' childhood and took steps to shield their child from medicalization, including diagnostic labels and clinical discussions. Theme3: Parental isolation and the role of organisational and societal systems. Parents felt unsupported in their role of managing the condition and felt negative responses from primary care health services and schools were underpinned by a lack of awareness and knowledge about CFS/ME in younger children. This sometimes led to a protracted time to diagnosis. Parents felt that schools have the potential important role in managing the child’s condition. Theme4: Complexity and uncertainty. Many parents valued specialist treatment (which included activity management, physiotherapy, sleep management, dietary advice, medical management and psychological support), but felt it needed to account for the complexity of the condition in younger children. Some parents expressed uncertainty about the diagnosis and the treatment programme. Conclusions: Interventions for younger children need to consider the 'systems' (family, organisational and societal) involved in the child’s care. Future research will include interviews with clinicians and schools supporting younger children with CFS/ME.

Keywords: chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME), pediatric, qualitative, treatment

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3 Targeting Matrix Metalloprotease-9 to Reduce Coronary Artery Manifestations of Kawasaki’s Disease

Authors: Mohammadjavad Sotoudeheian, Navid Farahmandian

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Kawasaki disease (KD) is the primary cause of acquired pediatric heart disease as an acute vasculitis. In children with prolonged fever, rash, and inflammation of the mucosa KD must be considered as a clinical diagnosis. There is a persuasive suggestion of immune-mediated damage as the pathophysiologic cascade of KD. For example, the invasion of cytotoxic T-cells supports a viral etiology and the inflammasome of the innate immune system is a critical component in the vasculitis formation in KD. Animal models of KD propose the cytokine profiles, such as increased IL-1 and GM-CSF, which cause vascular damage. CRP and IFN-γ elevated expression and the upregulation of IL-6, and IL-10 production are also described in previous studies. Untreated KD is a critical risk factor for coronary artery diseases and myocardial infarction. Vascular damage may encompass amplified T-cell activity. SMAD3 is an essential molecule in down-regulating T-cells and increasing expression of FoxP3. It has a critical effect in the differentiation of regulatory T-cells. The discrepancy of regulatory T-cells and pro-inflammatory Th17 has been studied in acute coronary syndrome during KD. However in the coronary artery damaged lymphocytes and IgA plasma cells are seen at the lesion locations, the major immune cells in the coronary lesions are monocytes/macrophages and neutrophils. These cells secrete TNF-α, and activates matrix metalloprotease (MMP)-9, reducing the integrity of vessels and prompting patients to arise aneurysm. MMPs can break down the components of the extracellular matrix and assist immune cell movement. IVIG as an effective form of treatment clarified the role of the immune system, which may target pathogenic antigens and regulate cytokine production. Several reports have revealed that in the coronary arteries, high expression of MMP-9 in monocyte/macrophage results in pathologic cascades. Curcumin is a potent antioxidant and anti-inflammatory molecule. Curcumin decreases the production of reactive oxygen and nitrogen species and inhibits transcription factors like AP-1 and NF-κB. Curcumin also contains the characteristics of inhibitory effects on MMPs, especially MMP-9. The upregulation of MMP-9 is an important cellular response. Curcumin treatment caused a reverse effect and down-regulates MMP-9 gene expression which may fund the anti-inflammatory effect. Curcumin inhibits MMP-9 expression via PKC and AMPK-dependent pathways in Human monocytes cells. Elevated expression and activity of MMP-9 are correlated with advanced vascular lesions. AMPK controls lipid metabolism and oxidation, and protein synthesis. AMPK is also necessary for the MMP-9 activity and THP-1 cell adhesion to endothelial cells. Curcumin was shown to inhibit the activation of AMPKα. Compound C (AMPK inhibitor) inhibits MMP-9 expression level. Therefore, through inactivating AMPKs and PKC, curcumin decreases the MMP-9 level, which results in inhibiting monocyte/macrophage differentiation. Compound C also suppress the phosphorylation of three major classes of MAP kinase signaling, suggesting that curcumin may suppress MMP-9 level by inactivation of MAPK pathways. MAPK cascades are activated to induce the expression of MMP-9. Curcumin inhibits MAPKs phosphorylation, which contributes to the down-regulation of MMP-9. This study demonstrated that the potential inhibitory properties of curcumin over MMP-9 lead to a therapeutic strategy to reduce the risk of coronary artery involvement during KD.

Keywords: MMP-9, coronary artery aneurysm, Kawasaki’s disease, curcumin, AMPK, immune system, NF-κB, MAPK

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2 Deciphering Tumor Stroma Interactions in Retinoblastoma

Authors: Rajeswari Raguraman, Sowmya Parameswaran, Krishnakumar Subramanian, Jagat Kanwar, Rupinder Kanwar

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Background: Tumor microenvironment has been implicated in several cancers to regulate cell growth, invasion and metastasis culminating in outcome of therapy. Tumor stroma consists of multiple cell types that are in constant cross-talk with the tumor cells to favour a pro-tumorigenic environment. Not much is known about the existence of tumor microenvironment in the pediatric intraocular malignancy, Retinoblastoma (RB). In the present study, we aim to understand the multiple stromal cellular subtypes and tumor stromal interactions expressed in RB tumors. Materials and Methods: Immunohistochemistry for stromal cell markers CD31, CD68, alpha-smooth muscle (α-SMA), vimentin and glial fibrillary acidic protein (GFAP) was performed on formalin fixed paraffin embedded tissues sections of RB (n=12). The differential expression of stromal target molecules; fibroblast activation protein (FAP), tenascin-C (TNC), osteopontin (SPP1), bone marrow stromal antigen 2 (BST2), stromal derived factor 2 and 4 (SDF2 and SDF4) in primary RB tumors (n=20) and normal retina (n=5) was studied by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blotting. The differential expression was correlated with the histopathological features of RB. The interaction between RB cell lines (Weri-Rb-1, NCC-RbC-51) and Bone marrow stromal cells (BMSC) was also studied using direct co-culture and indirect co-culture methods. The functional effect of the co-culture methods on the RB cells was evaluated by invasion and proliferation assays. Global gene expression was studied by using Affymetrix 3’ IVT microarray. Pathway prediction was performed using KEGG and the key molecules were validated using qRT-PCR. Results: The immunohistochemistry revealed the presence of several stromal cell types such as endothelial cells (CD31+;Vim+/-); macrophages (CD68+;Vim+/-); Fibroblasts (Vim+; CD31-;CD68- );myofibroblasts (α-SMA+/ Vim+) and invading retinal astrocytes/ differentiated retinal glia (GFAP+; Vim+). A characteristic distribution of these stromal cell types was observed in the tumor microenvironment, with endothelial cells predominantly seen in blood vessels and macrophages near actively proliferating tumor or necrotic areas. Retinal astrocytes and glia were predominant near the optic nerve regions in invasive tumors with sparse distribution in tumor foci. Fibroblasts were widely distributed with rare evidence of myofibroblasts in the tumor. Both gene and protein expression revealed statistically significant (P<0.05) up-regulation of FAP, TNC and BST2 in primary RB tumors compared to the normal retina. Co-culture of BMSC with RB cells promoted invasion and proliferation of RB cells in direct and indirect contact methods respectively. Direct co-culture of RB cell lines with BMSC resulted in gene expression changes in ECM-receptor interaction, focal adhesion, IL-8 and TGF-β signaling pathways associated with cancer. In contrast, various metabolic pathways such a glucose, fructose and amino acid metabolism were significantly altered under the indirect co-culture condition. Conclusion: The study suggests that the close interaction between RB cells and the stroma might be involved in RB tumor invasion and progression which is likely to be mediated by ECM-receptor interactions and secretory factors. Targeting the tumor stroma would be an attractive option for redesigning treatment strategies for RB.

Keywords: gene expression profiles, retinoblastoma, stromal cells, tumor microenvironment

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1 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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