Search results for: apnea patient

Authors: Nervana Elbakary, Sami Ouanes, Sadaf Riaz, Oraib Abdallah, Islam Mahran, Noriya Al-Khuzaei, Yassin Eltorki

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Major Depressive Disorder (MDD) requires therapeutic interventions during the initial month after being diagnosed for better disease outcomes. International guidelines recommend a duration of 4–12 weeks for an initial antidepressant (IAD) trial at an optimized dose to get a response. If depressive symptoms persist after this duration, guidelines recommend switching, augmenting, or combining strategies as the next step. Most patients with MDD in the mental health setting have been labeled incorrectly as treatment-resistant where in fact they have not been subjected to an adequate trial of guideline-recommended therapy. Premature discontinuation of IAD due to ineffectiveness can cause unfavorable consequences. Avoiding irrational practices such as subtherapeutic doses of IAD, premature switching between the ADs, and refraining from unjustified polypharmacy can help the disease to go into a remission phase We aimed to determine the prevalence and the patterns of strategies applied after an IAD was changed because of a suboptimal response as a primary outcome. Secondary outcomes included the median survival time on IAD before any change; and the predictors that were associated with IAD change. This was a retrospective cross- sectional study conducted in Mental Health Services in Qatar. A dataset between January 1, 2018, and December 31, 2019, was extracted from the electronic health records. Inclusion and exclusion criteria were defined and applied. The sample size was calculated to be at least 379 patients. Descriptive statistics were reported as frequencies and percentages, in addition, to mean and standard deviation. The median time of IAD to any change strategy was calculated using survival analysis. Associated predictors were examined using two unadjusted and adjusted cox regression models. A total of 487 patients met the inclusion criteria of the study. The average age for participants was 39.1 ± 12.3 years. Patients with first experience MDD episode 255 (52%) constituted a major part of our sample comparing to the relapse group 206(42%). About 431 (88%) of the patients had an occurrence of IAD change to any strategy before end of the study. Almost half of the sample (212 (49%); 95% CI [44–53%]) had their IAD changed less than or equal to 30 days. Switching was consistently more common than combination or augmentation at any timepoint. The median time to IAD change was 43 days with 95% CI [33.2–52.7]. Five independent variables (age, bothersome side effects, un-optimization of the dose before any change, comorbid anxiety, first onset episode) were significantly associated with the likelihood of IAD change in the unadjusted analysis. The factors statistically associated with higher hazard of IAD change in the adjusted analysis were: younger age, un-optimization of the IAD dose before any change, and comorbid anxiety. Because almost half of the patients in this study changed their IAD as early as within the first month, efforts to avoid treatment failure are needed to ensure patient-treatment targets are met. The findings of this study can have direct clinical guidance for health care professionals since an optimized, evidence-based use of AD medication can improve the clinical outcomes of patients with MDD; and also, to identify high-risk factors that could worsen the survival time on IAD such as young age and comorbid anxiety

Keywords: initial antidepressant, dose optimization, major depressive disorder, comorbid anxiety, combination, augmentation, switching, premature discontinuation

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Authors: Wen-Chung Chiang, Lun-Jou Lo, Hsiu-Hsia Lin

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This study aimed to improve the evaluation of facial symmetry, which is crucial for planning and assessing outcomes in orthognathic surgery (OGS). Facial symmetry plays a key role in both aesthetic and functional aspects of OGS, making its accurate evaluation essential for optimal surgical results. To address the limitations of traditional methods, a different approach was developed, combining three-dimensional (3D) facial contour mapping with hyperdimensional (HD) computing to enhance precision and efficiency in symmetry assessments. The study was conducted at Chang Gung Memorial Hospital, where data were collected from 2018 to 2023 using 3D cone beam computed tomography (CBCT), a highly detailed imaging technique. A large and comprehensive dataset was compiled, consisting of 150 normal individuals and 2,800 patients, totaling 5,750 preoperative and postoperative facial images. These data were critical for training a machine learning model designed to analyze and quantify facial symmetry. The machine learning model was trained to process 3D contour data from the CBCT images, with HD computing employed to power the facial symmetry quantification system. This combination of technologies allowed for an objective and detailed analysis of facial features, surpassing the accuracy and reliability of traditional symmetry assessments, which often rely on subjective visual evaluations by clinicians. In addition to developing the system, the researchers conducted a retrospective review of 3D CBCT data from 300 patients who had undergone OGS. The patients’ facial images were analyzed both before and after surgery to assess the clinical utility of the proposed system. The results showed that the facial symmetry algorithm achieved an overall accuracy of 82.5%, indicating its robustness in real-world clinical applications. Postoperative analysis revealed a significant improvement in facial symmetry, with an average score increase of 51%. The mean symmetry score rose from 2.53 preoperatively to 3.89 postoperatively, demonstrating the system's effectiveness in quantifying improvements after OGS. These results underscore the system's potential for providing valuable feedback to surgeons and aiding in the refinement of surgical techniques. The study also led to the development of a web-based system that automates facial symmetry assessment. This system integrates HD computing and 3D contour mapping into a user-friendly platform that allows for rapid and accurate evaluations. Clinicians can easily access this system to perform detailed symmetry assessments, making it a practical tool for clinical settings. Additionally, the system facilitates better communication between clinicians and patients by providing objective, easy-to-understand symmetry scores, which can help patients visualize the expected outcomes of their surgery. In conclusion, this study introduced a valuable and highly effective approach to facial symmetry evaluation in OGS, combining 3D contour mapping, HD computing, and machine learning. The resulting system achieved high accuracy and offers a streamlined, automated solution for clinical use. The development of the web-based platform further enhances its practicality, making it a valuable tool for improving surgical outcomes and patient satisfaction in orthognathic surgery.

Keywords: facial symmetry, orthognathic surgery, facial contour mapping, hyperdimensional computing

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Authors: Kiran Datta, Daniella Holland-Hart, Anthony Byrne

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Introduction: Oesophago-gastric (OG) cancers are the fifth commonest in the UK, accounting for over 12,000 deaths each year. Most patients will present at later stages of the disease, with only 21% of patients with stage 4 disease surviving longer than a year. As a result, many patients are unsuitable for curative surgery and instead receive palliative treatment to improve prognosis and symptom burden. However, palliative chemotherapy can result in significant toxicity: almost half of the patients are unable to complete their chemotherapy regimen, with this proportion rising significantly in older and frailer patients. In addition, clinical trials often exclude older and frailer patients due to strict inclusion criteria, meaning there is limited evidence to guide which patients are most likely to benefit from palliative chemotherapy. Inappropriate chemotherapy administration is at odds with the goals of palliative treatment and care, which are to improve quality of life, and this also represents a significant resource expenditure. This literature review aimed to examine and appraise evidence regarding treatment resilience in order to guide clinicians in identifying the most suitable candidates for palliative chemotherapy. Factors influencing treatment resilience were assessed, as measured by completion rates, dose reductions, and toxicities. Methods: This literature review was conducted using rapid review methodology, utilising modified systematic methods. A literature search was performed across the MEDLINE, EMBASE, and Cochrane Library databases, with results limited to papers within the last 15 years and available in English. Key inclusion criteria included: 1) participants with either oesophageal, gastro-oesophageal junction, or gastric cancers; 2) patients treated with palliative chemotherapy; 3) available data evaluating the association between baseline participant characteristics and treatment resilience. Results: Of the 2326 papers returned, 11 reports of 10 studies were included in this review after excluding duplicates and irrelevant papers. Treatment resilience factors that were assessed included: age, performance status, frailty, inflammatory markers, and sarcopenia. Age was generally a poor predictor for how well patients would tolerate chemotherapy, while poor performance status was a better indicator of the need for dose reduction and treatment non-completion. Frailty was assessed across one cohort using multiple screening tools and was an effective marker of the risk of toxicity and the requirement for dose reduction. Inflammatory markers included lymphopenia and the Glasgow Prognostic Score, which assessed inflammation and hypoalbuminaemia. Although quick to obtain and interpret, these findings appeared less reliable due to the inclusion of patients treated with palliative radiotherapy. Sarcopenia and body composition were often associated with chemotherapy toxicity but not the rate of regimen completion. Conclusion: This review demonstrates that there are numerous measures that can estimate the ability of patients with oesophago-gastric cancer to tolerate palliative chemotherapy, and these should be incorporated into clinical assessments to promote personalised decision-making around treatment. Age should not be a barrier to receiving chemotherapy and older and frailer patients should be included in future clinical trials to better represent typical patients with oesophago-gastric cancers. Decisions regarding palliative treatment should be guided by these factors identified as well as patient preference.

Keywords: frailty, oesophago-gastric cancer, palliative chemotherapy, treatment resilience

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Authors: Jan C. Droste, Justine Burns, Nithin Narayan

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Introduction: Life-threatening detrimental effects of inappropriate adrenaline (epinephrine) administration, e.g., by giving the wrong dose, in the context of anaphylaxis management is well documented in the medical literature. Half of the fatal anaphylactic reactions in the UK are iatrogenic, and the median time to a cardio-respiratory arrest can be as short as 5 minutes. It is therefore imperative that hospital doctors of all grades have active and accurate knowledge of the correct route, site, and dosage of administration of adrenaline. Given this time constraint and the potential fatal outcome with inappropriate management of anaphylaxis, it is alarming that surveys over the last 15 years have repeatedly shown only a minority of doctors to have accurate knowledge of adrenaline administration as recommended by the UK Resuscitation Council guidelines (2008 updated 2012). This comparison of survey results of the medical workforce over several years in a small NHS District General Hospital was conducted in order to establish the effect of the employment of multiple educational methods regarding adrenaline administration in anaphylaxis in adults. Methods: Between 2010 and 2017, several education methods and tools were used to repeatedly inform the medical workforce (doctors and advanced clinical practitioners) in a single district general hospital regarding the treatment of anaphylaxis in adults. Whilst the senior staff remained largely the same cohort, junior staff had changed fully in every survey. Examples included: (i) Formal teaching -in Grand Rounds; during the junior doctors’ induction process; advanced life support courses (ii) In-situ simulation training performed by the clinical skills simulation team –several ad hoc sessions and one 3-day event in 2017 visiting 16 separate clinical areas performing an acute anaphylaxis scenario using actors- around 100 individuals from multi-disciplinary teams were involved (iii) Hospital-wide distribution of the simulation event via the Trust’s Simulation Newsletter (iv) Laminated algorithms were attached to the 'crash trolleys' (v) A short email 'alert' was sent to all medical staff 3 weeks prior to the survey detailing the emergency treatment of anaphylaxis (vi) In addition, the performance of the surveys themselves represented a teaching opportunity when gaps in knowledge could be addressed. Face to face surveys were carried out in 2010 ('pre-intervention), 2015, and 2017, in the latter two occasions including advanced clinical practitioners (ACP). All surveys consisted of convenience samples. If verbal consent to conduct the survey was obtained, the medical practitioners' answers were recorded immediately on a data collection sheet. Results: There was a sustained improvement in the knowledge of the medical workforce from 2010 to 2017: Answers improved regarding correct drug by 11% (84%, 95%, and 95%); the correct route by 20% (76%, 90%, and 96%); correct site by 40% (43%, 83%, and 83%) and the correct dose by 45% (27%, 54%, and 72%). Overall, knowledge of all components -correct drug, route, site, and dose-improved from 13% in 2010 to 62% in 2017. Conclusion: This survey comparison shows knowledge of the medical workforce regarding adrenaline administration for treatment of anaphylaxis in adults can be considerably improved by employing a variety of educational methods.

Keywords: adrenaline, anaphylaxis, epinephrine, medical education, patient safety

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Authors: Paul Licina, Emma M. Johnston, David Lisle, Mark Young, Chris Brady

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Background: Lumbar pars pathology is a common cause of pain in the growing spine. It can be seen in young athletes participating in at-risk sports and can affect sporting performance and long-term health due to its resistance to traditional management. There is a current lack of consensus of classification and treatment for pars injuries. Previous systems used CT to stage pars defects but could not assess early stress reactions. A modified classification is proposed that considers findings on MRI, significantly improving early treatment guidance. The treatment protocol is designed for patients aged 5 to 19 years. Method: Clinical screening identifies patients with a low, medium, or high index of suspicion for lumbar pars injury using patient age, sport participation and pain characteristics. MRI of the at-risk cohort enables augmentation of existing CT-based classification while avoiding ionising radiation. Patients are classified into five categories based on MRI findings. A type 0 lesion (stress reaction) is present when CT is normal and MRI shows high signal change (HSC) in the pars/pedicle on T2 images. A type 1 lesion represents the ‘early defect’ CT classification. The group previously referred to as a 'progressive stage' defect on CT can be split into 2A and 2B categories. 2As have HSC on MRI, whereas 2Bs do not. This distinction is important with regard to healing potential. Type 3 lesions are terminal stage defects on CT, characterised by pseudarthrosis. MRI shows no HSC. Results: Stress reactions (type 0) and acute fractures (1 and 2a) can heal and are treated in a custom-made hard brace for 12 weeks. It is initially worn 23 hours per day. At three weeks, patients commence basic core rehabilitation. At six weeks, in the absence of pain, the brace is removed for sleeping. Exercises are progressed to positions of daily living. Patients with continued pain remain braced 23 hours per day without exercise progression until becoming symptom-free. At nine weeks, patients commence supervised exercises out of the brace for 30 minutes each day. This allows them to re-learn muscular control without rigid support of the brace. At 12 weeks, bracing ceases and MRI is repeated. For patients with near or complete resolution of bony oedema and healing of any cortical defect, rehabilitation is focused on strength and conditioning and sport-specific exercise for the full return to activity. The length of this final stage is approximately nine weeks but depends on factors such as development and level of sports participation. If significant HSC remains on MRI, CT scan is considered to definitively assess cortical defect healing. For these patients, return to high-risk sports is delayed for up to three months. Chronic defects (2b and 3) cannot heal and are not braced, and rehabilitation follows traditional protocols. Conclusion: Appropriate clinical screening and imaging with MRI can identify pars pathology early. In those with potential for healing, we propose hard bracing and appropriate rehabilitation as part of a multidisciplinary management protocol. The validity of this protocol will be tested in future studies.

Keywords: adolescents, MRI classification, pars interticularis, treatment protocol

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Authors: I. Stathopoulos, V. Syrgiamiotis, E. Karavasilis, A. Ploussi, I. Nikas, C. Hatzigiorgi, K. Platoni, E. P. Efstathopoulos

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Introduction: Brain and central nervous system (CNS) tumors form the second most common group of cancer in children, accounting for 30% of all childhood cancers. MRI is the key imaging technique used for the visualization and management of pediatric brain tumors. Initial characterization of tumors from MRI scans is usually performed via a radiologist’s visual assessment. However, different brain tumor types do not always demonstrate clear differences in visual appearance. Using only conventional MRI to provide a definite diagnosis could potentially lead to inaccurate results, and so histopathological examination of biopsy samples is currently considered to be the gold standard for obtaining definite diagnoses. Machine learning is defined as the study of computational algorithms that can use, complex or not, mathematical relationships and patterns from empirical and scientific data to make reliable decisions. Concerning the above, machine learning techniques could provide effective and accurate ways to automate and speed up the analysis and diagnosis for medical images. Machine learning applications in radiology are or could potentially be useful in practice for medical image segmentation and registration, computer-aided detection and diagnosis systems for CT, MR or radiography images and functional MR (fMRI) images for brain activity analysis and neurological disease diagnosis. Purpose: The objective of this study is to provide an automated tool, which may assist in the imaging evaluation and classification of brain neoplasms in pediatric patients by determining the glioma type, grade and differentiating between different brain tissue types. Moreover, a future purpose is to present an alternative way of quick and accurate diagnosis in order to save time and resources in the daily medical workflow. Materials and Methods: A cohort, of 80 pediatric patients with a diagnosis of posterior fossa tumor, was used: 20 ependymomas, 20 astrocytomas, 20 medulloblastomas and 20 healthy children. The MR sequences used, for every single patient, were the following: axial T1-weighted (T1), axial T2-weighted (T2), FluidAttenuated Inversion Recovery (FLAIR), axial diffusion weighted images (DWI), axial contrast-enhanced T1-weighted (T1ce). From every sequence only a principal slice was used that manually traced by two expert radiologists. Image acquisition was carried out on a GE HDxt 1.5-T scanner. The images were preprocessed following a number of steps including noise reduction, bias-field correction, thresholding, coregistration of all sequences (T1, T2, T1ce, FLAIR, DWI), skull stripping, and histogram matching. A large number of features for investigation were chosen, which included age, tumor shape characteristics, image intensity characteristics and texture features. After selecting the features for achieving the highest accuracy using the least number of variables, four machine learning classification algorithms were used: k-Nearest Neighbour, Support-Vector Machines, C4.5 Decision Tree and Convolutional Neural Network. The machine learning schemes and the image analysis are implemented in the WEKA platform and MatLab platform respectively. Results-Conclusions: The results and the accuracy of images classification for each type of glioma by the four different algorithms are still on process.

Keywords: image classification, machine learning algorithms, pediatric MRI, pediatric oncology

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Authors: Jenee Gooden, Kevin Vasquez-monterroso, Lady Paula Dejesus, Sandra Wainwright, Daniel Kim, Mackenzie Walker

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Introduction: Pyoderma gangrenosum (PG) is a rare, rapidly progressive, neutrophilic ulcerative colitis condition with an incidence of 3 to 10 cases per year ¹ ². Due to the similar appearance, PG is often misdiagnosed as a diabetic ulcer in diabetic patients. Though they may clinically appear similar in appearance, the treatment protocol and diagnostic criteria differ. Also, end-stage renal disease (ESRD) is often a condition seen in diabetic patients, which can have a significant impact on wound healing due to the wide range of uremic toxins³. This case study demonstrates a multidisciplinary team and multimodal treatment approach by podiatric surgery, general surgery, rheumatology, infectious disease, interventional cardiology, wound care and hyperbaric medicine for an uncontrolled diabetic with pyoderma gangrenosum of a significant circumferential wound, covering almost the entire right lower extremity. Methods:56 y.o male presents with multiple PG ulcerations, including the chest, right posterior lower extremity and sacrum. All ulcerations were previously managed by the same wound care specialist. His chief complaint was worsening PG ulcerations accompanied by a fever of 103 °F . This case study focuses on the wound to his RLE. Past medical history significant for diabetes mellitus type 2 with hemoglobin A1c of 10% and end stage renal disease (ESRD) on hemodialysis. A multidisciplinary team approach by podiatric surgery, general surgery, rheumatology, infectious disease, interventional cardiology, wound care and hyperbaric medicine was successfully used to perform right lower extremity limb salvage. The patient was managed by rheumatology for the continuation of prior medication, as well as the mutual agreement with wound care for the addition of dapsone. A coronary CT angiogram was performed by interventional cardiology, but no significant disease was noted, and no further vascular workup was necessary. Multiple surgical sharp wide excisional debridements with application of allografts and split thickness skin grafts for the circumferential ulceration that encompassed almost the entire right lower extremity were performed by both podiatric surgery and general surgery. Wound cultures and soft tissue biopsies were performed, and infectious disease managed antibiotic therapy. Hyperbaric oxygen therapy and wound vac therapy by wound care were also completed as adjunct management. Results: Prevention of leg amputation by limb salvage of the RLE was accomplished by a multidisciplinary team approach, with the wound size decreasing over a total of 29 weeks from 600 cm² to 12.0 x 3.5 x 0.2 cm. Our multidisciplinary team included podiatric surgery, general surgery, rheumatology, infectious disease, interventional cardiology, wound care and hyperbaric medicine. Discussion: Wound healing, in general, can have its challenges, and those challenges are only magnified when accompanied by multiple systemic illnesses. Though the negative impact of diabetes on wound healing is well known, the compound impact of being a diabetic with ESRD and having pyoderma gangrenosum is not. This case demonstrates the necessity for a multidisciplinary team approach with a wide array of treatment modalities to optimize wound healing and perform limb salvage with prevention of lower extremity amputation.

Keywords: diabetes, podiatry, pyoderma gangrenosum, end stage renal disease

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Authors: Bidisha Chatterjee, Sonal Grover, Rekha Gurung

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Postpartum dissection of the internal carotid artery is a relatively rare condition and is considered as an underlying aetiology in 5% to 25% of strokes under the age of 30 to 45 years. However, 86% of these cases recover completely and 14% have mild focal neurological symptoms. Prognosis is generally good with early intervention. The risk quoted for a repeat carotid artery dissection in subsequent pregnancies is less than 2%. 36-year Caucasian primipara presented on postnatal day one of forceps delivery with tachycardia. In the intrapartum period she had a history of prolonged rupture of membranes and developed intrapartum sepsis and was treated with antibiotics. Postpartum ECG showed septal inferior T wave inversion and a troponin level of 19. Subsequently Echocardiogram ruled out post-partum cardiomyopathy. Repeat ECG showed improvement of the previous changes and in the absence of symptoms no intervention was warranted. On day 4 post-delivery, she had developed symptoms of droopy right eyelid, pain around the right eye and itching in the right ear. On examination, she had developed right sided ptosis, unequal pupils (Rt miotic pupil). Cranial nerve examination, reflexes, sensory examination and muscle power was normal. Apart from migraine, there was no medical or family history of note. In view of Horner’s on the right, she had a CT Angiogram and subsequently MR/MRA and was diagnosed with dissection of the cervical portion of the right internal carotid artery. She was discharged on a course of Aspirin 75mg. By 6 week post-natal follow up patient had recovered significantly with occasional episodes of unequal pupils and tingling of right toes which resolved spontaneously. Cervical artery dissection, including VAD and carotid artery dissection, are rare complications of pregnancy with an estimated annual incidence of 2.6–3 per 100,000 pregnancy hospitalizations. Aetiology remains unclear though trauma during straining at labour, underlying arterial disease and preeclampsia have been implicated. Hypercoagulable state during pregnancy and puerperium could also be an important factor. 60-90% cases present with severe headache and neck pain and generally precede neurological symptoms like ipsilateral Horner’s syndrome, retroorbital pain, tinnitus and cranial nerve palsy. Although rare, the consequences of delayed diagnosis and management can lead to severe and permanent neurological deficits. Patients with a strong index of suspicion should undergo an MRI or MRA of head and neck. Antithrombotic and antiplatelet therapy forms the mainstay of therapy with selected cases needing endovascular stenting. Long term prognosis is favourable with either complete resolution or minimal deficit if treatment is prompt. Patients should be counselled about the recurrence risk and possibility of stroke in future pregnancy. Coronary artery dissection is rare and treatable but needs early diagnosis and treatment. Post-partum headache and neck pain with neurological symptoms should prompt urgent imaging followed by antithrombotic and /or antiplatelet therapy. Most cases resolve completely or with minimal sequelae.

Keywords: postpartum, dissection of internal carotid artery, magnetic resonance angiogram, magnetic resonance imaging, antiplatelet, antithrombotic

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Authors: Neelofar, Khursheed Alam, Jamal Ahmad

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Protein modification in diabetes mellitus may lead to early glycation products (EGPs) or amadori product as well as advanced glycation end products (AGEs). Early glycation involves the reaction of glucose with N-terminal and lysyl side chain amino groups to form Schiff’s base which undergoes rearrangements to form more stable early glycation product known as Amadori product. After Amadori, the reactions become more complicated leading to the formation of advanced glycation end products (AGEs) that interact with various AGE receptors, thereby playing an important role in the long-term complications of diabetes. Millard reaction or nonenzymatic glycation reaction accelerate in diabetes due to hyperglycation and alter serum protein’s structure, their normal functions that lead micro and macro vascular complications in diabetic patients. In this study, Human Serum Albumin (HSA) with a constant concentration was incubated with different concentrations of glucose at 370C for a week. At 4th day, Amadori product was formed that was confirmed by colorimetric method NBT assay and TBA assay which both are authenticate early glycation product. Conformational changes in native as well as all samples of Amadori albumin with different concentrations of glucose were investigated by various biophysical and biochemical techniques. Main biophysical techniques hyperchromacity, quenching of fluorescence intensity, FTIR, CD and SDS-PAGE were used. Further conformational changes were observed by biochemical assays mainly HMF formation, fructoseamine, reduction of fructoseamine with NaBH4, carbonyl content estimation, lysine and arginine residues estimation, ANS binding property and thiol group estimation. This study find structural and biochemical changes in Amadori modified HSA with normal to hyperchronic range of glucose with respect to native HSA. When glucose concentration was increased from normal to chronic range biochemical and structural changes also increased. Highest alteration in secondary and tertiary structure and conformation in glycated HSA was observed at the hyperchronic concentration (75mM) of glucose. Although it has been found that Amadori modified proteins is also involved in secondary complications of diabetes as AGEs but very few studies have been done to analyze the conformational changes in Amadori modified proteins due to early glycation. Most of the studies were found on the structural changes in Amadori protein at a particular glucose concentration but no study was found to compare the biophysical and biochemical changes in HSA due to early glycation with a range of glucose concentration at a constant incubation time. So this study provide the information about the biochemical and biophysical changes occur in Amadori modified albumin at a range of glucose normal to chronic in diabetes. Although many implicates currently in use i.e. glycaemic control, insulin treatment and other chemical therapies that can control many aspects of diabetes. However, even with intensive use of current antidiabetic agents more than 50 % of diabetic patient’s type 2 suffers poor glycaemic control and 18 % develop serious complications within six years of diagnosis. Experimental evidence related to diabetes suggests that preventing the nonenzymatic glycation of relevant proteins or blocking their biological effects might beneficially influence the evolution of vascular complications in diabetic patients or quantization of amadori adduct of HSA by authentic antibodies against HSA-EGPs can be used as marker for early detection of the initiation/progression of secondary complications of diabetes. So this research work may be helpful for the same.

Keywords: diabetes mellitus, glycation, albumin, amadori, biophysical and biochemical techniques

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Authors: Wiseman Emmanuel Nkhomah, Chiyembekezo Kachimanga, Julia Huggins, Fabien Munyaneza

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Background: Partners In Health – Malawi introduced one of Operational Researches called Primary Health Care (PHC) Surveys in 2020, which seeks to assess progress of delivery of care in the district. The study consists of 5 long surveys, namely; Facility assessment, General Patient, Provider, Sick Child, Antenatal Care (ANC), primarily conducted in 4 health facilities in Neno district. These facilities include Neno district hospital, Dambe health centre, Chifunga and Matope. Usually, these annual surveys are conducted from January, and the target is to present final report by June. Once data is collected and analyzed, there are a series of reviews that take place before reaching final report. In the first place, the manual process took over 9 months to present final report. Initial findings reported about 76.9% of the data that added up when cross-checked with paper-based sources. Purpose: The aim of this approach is to run away from manually pulling the data, do fresh analysis, and reporting often associated not only with delays in reporting inconsistencies but also with poor quality of data if not done carefully. This automation approach was meant to utilize features of new technologies to create visualizations, reports, and dashboards in Power BI that are directly fished from the data source – CommCare hence only require a single click of a ‘refresh’ button to have the updated information populated in visualizations, reports, and dashboards at once. Methodology: We transformed paper-based questionnaires into electronic using CommCare mobile application. We further connected CommCare Mobile App directly to Power BI using Application Program Interface (API) connection as data pipeline. This provided chance to create visualizations, reports, and dashboards in Power BI. Contrary to the process of manually collecting data in paper-based questionnaires, entering them in ordinary spreadsheets, and conducting analysis every time when preparing for reporting, the team utilized CommCare and Microsoft Power BI technologies. We utilized validations and logics in CommCare to capture data with less errors. We utilized Power BI features to host the reports online by publishing them as cloud-computing process. We switched from sharing ordinary report files to sharing the link to potential recipients hence giving them freedom to dig deep into extra findings within Power BI dashboards and also freedom to export to any formats of their choice. Results: This data automation approach reduced research timelines from the initial 9 months’ duration to 5. It also improved the quality of the data findings from the original 76.9% to 98.9%. This brought confidence to draw conclusions from the findings that help in decision-making and gave opportunities for further researches. Conclusion: These results suggest that automating the research data process has the potential of reducing overall amount of time spent and improving the quality of the data. On this basis, the concept of data automation should be taken into serious consideration when conducting operational research for efficiency and decision-making.

Keywords: reporting, decision-making, power BI, commcare, data automation, visualizations, dashboards

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Authors: Maria Karnachoriti, Ellas Spyratou, Dimitrios Lykidis, Maria Lambropoulou, Yiannis S. Raptis, Ioannis Seimenis, Efstathios P. Efstathopoulos, Athanassios G. Kontos

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Colorectal cancer is the third most common cancer diagnosed in Europe, according to the latest incidence data provided by the World Health Organization (WHO), and early diagnosis has proved to be the key in reducing cancer-related mortality. In cases where surgical interventions are required for cancer treatment, the accurate discrimination between healthy and cancerous tissues is critical for the postoperative care of the patient. The current study focuses on the ex vivo handling of surgically excised colorectal specimens and the acquisition of their spectral fingerprints using Raman spectroscopy. Acquired data were analyzed in an effort to discriminate, in microscopic scale, between healthy and malignant margins. Raman spectroscopy is a spectroscopic technique with high detection sensitivity and spatial resolution of few micrometers. The spectral fingerprint which is produced during laser-tissue interaction is unique and characterizes the biostructure and its inflammatory or cancer state. Numerous published studies have demonstrated the potential of the technique as a tool for the discrimination between healthy and malignant tissues/cells either ex vivo or in vivo. However, the handling of the excised human specimens and the Raman measurement conditions remain challenging, unavoidably affecting measurement reliability and repeatability, as well as the technique’s overall accuracy and sensitivity. Therefore, tissue handling has to be optimized and standardized to ensure preservation of cell integrity and hydration level. Various strategies have been implemented in the past, including the use of balanced salt solutions, small humidifiers or pump-reservoir-pipette systems. In the current study, human colorectal specimens of 10X5 mm were collected from 5 patients up to now who underwent open surgery for colorectal cancer. A novel, non-toxic zinc-based fixative (Z7) was used for tissue preservation. Z7 demonstrates excellent protein preservation and protection against tissue autolysis. Micro-Raman spectra were recorded with a Renishaw Invia spectrometer from successive random 2 micrometers spots upon excitation at 785 nm to decrease fluorescent background and secure avoidance of tissue photodegradation. A temperature-controlled approach was adopted to stabilize the tissue at 2 °C, thus minimizing dehydration effects and consequent focus drift during measurement. A broad spectral range, 500-3200 cm-1,was covered with five consecutive full scans that lasted for 20 minutes in total. The average spectra were used for least square fitting analysis of the Raman modes.Subtle Raman differences were observed between normal and cancerous colorectal tissues mainly in the intensities of the 1556 cm-1 and 1628 cm-1 Raman modes which correspond to v(C=C) vibrations in porphyrins, as well as in the range of 2800-3000 cm-1 due to CH2 stretching of lipids and CH3 stretching of proteins. Raman spectra evaluation was supported by histological findings from twin specimens. This study demonstrates that Raman spectroscopy may constitute a promising tool for real-time verification of clear margins in colorectal cancer open surgery.

Keywords: colorectal cancer, Raman spectroscopy, malignant margins, spectral fingerprints

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Authors: V. Saccà, A. Sarica, F. Novellino, S. Barone, T. Tallarico, E. Filippelli, A. Granata, P. Valentino, A. Quattrone

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The work aim was to evaluate how well Random Forest (RF) and Support Vector Machine (SVM) algorithms could support the early diagnosis of Multiple Sclerosis (MS) from resting-state functional connectivity data. In particular, we wanted to explore the ability in distinguishing between controls and patients of mean signals extracted from ICA components corresponding to 15 well-known networks. Eighteen patients with early-MS (mean-age 37.42±8.11, 9 females) were recruited according to McDonald and Polman, and matched for demographic variables with 19 healthy controls (mean-age 37.55±14.76, 10 females). MRI was acquired by a 3T scanner with 8-channel head coil: (a)whole-brain T1-weighted; (b)conventional T2-weighted; (c)resting-state functional MRI (rsFMRI), 200 volumes. Estimated total lesion load (ml) and number of lesions were calculated using LST-toolbox from the corrected T1 and FLAIR. All rsFMRIs were pre-processed using tools from the FMRIB's Software Library as follows: (1) discarding of the first 5 volumes to remove T1 equilibrium effects, (2) skull-stripping of images, (3) motion and slice-time correction, (4) denoising with high-pass temporal filter (128s), (5) spatial smoothing with a Gaussian kernel of FWHM 8mm. No statistical significant differences (t-test, p < 0.05) were found between the two groups in the mean Euclidian distance and the mean Euler angle. WM and CSF signal together with 6 motion parameters were regressed out from the time series. We applied an independent component analysis (ICA) with the GIFT-toolbox using the Infomax approach with number of components=21. Fifteen mean components were visually identified by two experts. The resulting z-score maps were thresholded and binarized to extract the mean signal of the 15 networks for each subject. Statistical and machine learning analysis were then conducted on this dataset composed of 37 rows (subjects) and 15 features (mean signal in the network) with R language. The dataset was randomly splitted into training (75%) and test sets and two different classifiers were trained: RF and RBF-SVM. We used the intrinsic feature selection of RF, based on the Gini index, and recursive feature elimination (rfe) for the SVM, to obtain a rank of the most predictive variables. Thus, we built two new classifiers only on the most important features and we evaluated the accuracies (with and without feature selection) on test-set. The classifiers, trained on all the features, showed very poor accuracies on training (RF:58.62%, SVM:65.52%) and test sets (RF:62.5%, SVM:50%). Interestingly, when feature selection by RF and rfe-SVM were performed, the most important variable was the sensori-motor network I in both cases. Indeed, with only this network, RF and SVM classifiers reached an accuracy of 87.5% on test-set. More interestingly, the only misclassified patient resulted to have the lowest value of lesion volume. We showed that, with two different classification algorithms and feature selection approaches, the best discriminant network between controls and early MS, was the sensori-motor I. Similar importance values were obtained for the sensori-motor II, cerebellum and working memory networks. These findings, in according to the early manifestation of motor/sensorial deficits in MS, could represent an encouraging step toward the translation to the clinical diagnosis and prognosis.

Keywords: feature selection, machine learning, multiple sclerosis, random forest, support vector machine

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Authors: Karlee J. Hall, Mark Laylor, Jessy Varghese, Paula Polastri, Karen Van Ooteghem, William McIlroy

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Balance training is a common part of physiotherapy treatment and often involves a set of proprioceptive exercises which the patient carries out in the clinic and as part of their exercise program. Understanding all contributing factors to altered balance is of utmost importance to the clinical success of treatment of balance dysfunctions. A critical role for the autonomic nervous system (ANS) in the control of balance reactions has been proposed previously, with evidence for potential involvement being inferred from the observation of phasic galvanic skin responses (GSR) evoked by external balance perturbations. The current study explored whether the coupling between ANS reactivity and balance reactions would be observed during spontaneously occurring instability while standing, including standard positions typical of physiotherapy balance assessments. It was hypothesized that time-varying changes in GSR (ANS reactivity) would be associated with time-varying changes in the mediolateral center of pressure (ML-COP) (somatomotor reactivity). Nine individuals (5 females, 4 males, aged 19-37 years) were recruited. To induce varying balance demands during standing, the study compared ML-COP and GSR data across different task conditions varying the availability of vision and width of the base of support. Subjects completed 3, 30-second trials for each of the following stance conditions: standard, narrow, and tandem eyes closed, tandem eyes open, tandem eyes open with dome to shield visual input, and restricted peripheral visual field. ANS activity was evaluated by measures of GSR recorded from Ag-AgCl electrodes on the middle phalanges of digits 2 and 4 on the left hand; balance measures include ML-COP excursion frequency and amplitude recorded from two force plates embedded in the floor underneath each foot. Subjects were instructed to stand as still as possible with arms crossed in front of their chest. When comparing mean task differences across subjects, there was an expected increase in postural sway from tasks with a wide stance and no sensory restrictions (least challenging) to those with a narrow stance and no vision (most challenging). The correlation analysis revealed a significant positive relationship between ML-COP variability and GSR variability when comparing across tasks (r=0.94, df=5, p < 0.05). In addition, correlations coincided within each subject and revealed a significant positive correlation in 7 participants (r= 0.47, 0.57, 0.62, 0.62, 0.81, 0.64, 0.69 respectively, df=19, p < 0.05) and no significant relationship in 2 participants (r=0.36, 0.29 respectively, df=19, p > 0.05). The current study revealed a significant relationship between ML-COP and GSR during balance tasks, revealing the ANS reactivity associated with naturally occurring instability when standing still, which is proportional to the degree of instability. Understanding the link between ANS activity and control of COP is an important step forward in the enhancement of assessment of contributing factors to poor balance and treatment of balance dysfunctions. The next steps will explore the temporal association between the time-varying changes in COP and GSR to establish if the ANS reactivity phase leads or lags the evoked motor reactions, as well as exploration of potential biomarkers for use in screening of ANS activity as a contributing factor to altered balance control clinically.

Keywords: autonomic nervous system, balance control, center of pressure, somatic nervous system

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Authors: Charalabos Antonatos, Mariza Panoutsopoulou, Georgios K. Georgakilas, Evangelos Evangelou, Yiannis Vasilopoulos

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The extended tissue damage and severe clinical outcomes of autoimmune diseases, accompanied by the high annual costs to the overall health care system, highlight the need for an efficient therapy. Increasing knowledge over the pathophysiology of specific chronic inflammatory diseases, namely Psoriasis (PsO), Inflammatory Bowel Diseases (IBD) consisting of Crohn’s disease (CD) and Ulcerative colitis (UC), and Rheumatoid Arthritis (RA), has provided insights into the underlying mechanisms that lead to the maintenance of the inflammation, such as Tumor Necrosis Factor alpha (TNF-α). Hence, the anti-TNFα biological agents pose as an ideal therapeutic approach. Despite the efficacy of anti-TNFα agents, several clinical trials have shown that 20-40% of patients do not respond to treatment. Nowadays, high-throughput technologies have been recruited in order to elucidate the complex interactions in multifactorial phenotypes, with the most ubiquitous ones referring to transcriptome quantification analyses. In this context, a random effects meta-analysis of available gene expression cDNA microarray datasets was performed between responders and non-responders to anti-TNFα therapy in patients with IBD, PsO, and RA. Publicly available datasets were systematically searched from inception to 10th of November 2020 and selected for further analysis if they assessed the response to anti-TNFα therapy with clinical score indexes from inflamed biopsies. Specifically, 4 IBD (79 responders/72 non-responders), 3 PsO (40 responders/11 non-responders) and 2 RA (16 responders/6 non-responders) datasetswere selected. After the separate pre-processing of each dataset, 4 separate meta-analyses were conducted; three disease-specific and a single combined meta-analysis on the disease-specific results. The MetaVolcano R package (v.1.8.0) was utilized for a random-effects meta-analysis through theRestricted Maximum Likelihood (RELM) method. The top 1% of the most consistently perturbed genes in the included datasets was highlighted through the TopConfects approach while maintaining a 5% False Discovery Rate (FDR). Genes were considered as Differentialy Expressed (DEGs) as those with P ≤ 0.05, |log2(FC)| ≥ log2(1.25) and perturbed in at least 75% of the included datasets. Over-representation analysis was performed using Gene Ontology and Reactome Pathways for both up- and down-regulated genes in all 4 performed meta-analyses. Protein-Protein interaction networks were also incorporated in the subsequentanalyses with STRING v11.5 and Cytoscape v3.9. Disease-specific meta-analyses detected multiple distinct pro-inflammatory and immune-related down-regulated genes for each disease, such asNFKBIA, IL36, and IRAK1, respectively. Pathway analyses revealed unique and shared pathways between each disease, such as Neutrophil Degranulation and Signaling by Interleukins. The combined meta-analysis unveiled 436 DEGs, 86 out of which were up- and 350 down-regulated, confirming the aforementioned shared pathways and genes, as well as uncovering genes that participate in anti-inflammatory pathways, namely IL-10 signaling. The identification of key biological pathways and regulatory elements is imperative for the accurate prediction of the patient’s response to biological drugs. Meta-analysis of such gene expression data could aid the challenging approach to unravel the complex interactions implicated in the response to anti-TNFα therapy in patients with PsO, IBD, and RA, as well as distinguish gene clusters and pathways that are altered through this heterogeneous phenotype.

Keywords: anti-TNFα, autoimmune, meta-analysis, microarrays

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Authors: Michele L. Tilstra, Tiffany J. Peets

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Interprofessional collaboration in behavioral healthcare education is increasingly recognized for its value in training students to address diverse client needs. While interprofessional education (IPE) is well-documented in occupational therapy education to address physical health, limited research exists on collaboration with counselors to address mental health concerns and the psychosocial needs of individuals receiving care. Counseling education literature primarily examines the collaboration of counseling students with psychiatrists, psychologists, social workers, and marriage and family therapists. This pretest/posttest survey research study explored changes in attitudes toward interprofessional teams among 56 Master of Occupational Therapy (MOT) (n = 42) and Counseling and Human Development (CHD) (n = 14) students participating in the Counselors and Occupational Therapists Professionally Engaged in the Community (COPE) program. The COPE program was designed to strengthen the behavioral health workforce in high-need and high-demand areas. Students accepted into the COPE program were divided into small MOT/CHD groups to complete multiple interprofessional multicultural learning modules using videos, case studies, and online discussion board posts. The online modules encouraged reflection on various behavioral healthcare roles, benefits of team-based care, cultural humility, current mental health challenges, personal biases, power imbalances, and advocacy for underserved populations. Using the Student Perceptions of Interprofessional Clinical Education- Revision 2 (SPICE-R2) scale, students completed pretest and posttest surveys using a 5-point Likert scale (Strongly Agree = 5 to Strongly Disagree = 1) to evaluate their attitudes toward interprofessional teamwork and collaboration. The SPICE-R2 measured three different factors: interprofessional teamwork and team-based practice (Team), roles/responsibilities for collaborative practice (Roles), and patient outcomes from collaborative practice (Outcomes). The mean total scores for all students improved from 4.25 (pretest) to 4.43 (posttest), Team from 4.66 to 4.58, Roles from 3.88 to 4.30, and Outcomes from 4.08 to 4.36. A paired t-test analysis for the total mean scores resulted in a t-statistic of 2.54, which exceeded both one-tail and two-tail critical values, indicating statistical significance (p = .001). When the factors of the SPICE-R2 were analyzed separately, only the Roles (t Stat=4.08, p =.0001) and Outcomes (t Stat=3.13, p = .002) were statistically significant. The item ‘I understand the roles of other health professionals’ showed the most improvement from a mean score for all students of 3.76 (pretest) to 4.46 (posttest). The significant improvement in students' attitudes toward interprofessional teams suggests that the unique integration of OT and CHD students in the COPE program effectively develops a better understanding of the collaborative roles necessary for holistic client care. These results support the importance of IPE through structured, engaging interprofessional experiences. These experiences are essential for enhancing students' readiness for collaborative practice and align with accreditation standards requiring interprofessional education in OT and CHD programs to prepare practitioners for team-based care. The findings contribute to the growing body of evidence supporting the integration of IPE in behavioral healthcare curricula to improve holistic client care and encourage students to engage in collaborative practice across healthcare settings.

Keywords: behavioral healthcare, counseling education, interprofessional education, mental health education, occupational therapy education

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Authors: Judy M. Obliosca, Olivia Vest, Sandra Poulos, Kelsi Smith, Tammy Ferguson, Abigail Powers Lott, Alicia K. Smith, Yang Xu, Christopher K. Tison

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Post-Traumatic Stress Disorder (PTSD) is a mental health problem that people may develop after experiencing traumatic events such as combat, natural disasters, and major emotional challenges. Tragically, the number of military personnel with PTSD correlates directly with the number of veterans who attempt suicide, with the highest rate in the Army. Research has shown epigenetic risks in those who are prone to several psychiatric dysfunctions, particularly PTSD. Once initiated in response to trauma, epigenetic alterations in particular, the DNA methylation in the form of 5-methylcytosine (5mC) alters chromatin structure and represses gene expression. Current methods to detect DNA methylation, such as bisulfite-based genomic sequencing techniques, are laborious and have massive analysis workflow while still having high error rates. A faster and simpler detection method of high sensitivity and precision would be useful in a clinical setting to confirm potential PTSD etiologies, prevent other psychiatric disorders, and improve military health. A nano-enhanced Surface Plasmon Resonance imaging (SPRi)-based assay that simultaneously detects site-specific 5mC base (termed as PTSD base) in methylated genes related to PTSD is being developed. The arrays on a sensing chip were first constructed for parallel detection of PTSD bases using synthetic and genomic DNA (gDNA) samples. For the gDNA sample extracted from the whole blood of a PTSD patient, the sample was first digested using specific restriction enzymes, and fragments were denatured to obtain single-stranded methylated target genes (ssDNA). The resulting mixture of ssDNA was then injected into the assay platform, where targets were captured by specific DNA aptamer probes previously immobilized on the surface of a sensing chip. The PTSD bases in targets were detected by anti-5-methylcytosine antibody (anti-5mC), and the resulting signals were then enhanced by the universal nanoenhancer. Preliminary results showed successful detection of a PTSD base in a gDNA sample. Brighter spot images and higher delta values (control-subtracted reflectivity signal) relative to those of the control were observed. We also implemented the in-house surface activation system for detection and developed SPRi disposable chips. Multiplexed PTSD base detection of target methylated genes in blood DNA from PTSD patients of severity conditions (asymptomatic and severe) was conducted. This diagnostic capability being developed is a platform technology, and upon successful implementation for PTSD, it could be reconfigured for the study of a wide variety of neurological disorders such as traumatic brain injury, Alzheimer’s disease, schizophrenia, and Huntington's disease and can be extended to the analyses of other sample matrices such as urine and saliva.

Keywords: epigenetic assay, DNA methylation, PTSD, whole blood, multiplexing

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Authors: Nitika Sharma, Yogesh Jain

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Introduction: An efficient Information System helps in improving the service delivery as well provides the foundation for policy and regulation of other building blocks of Health System. Health care organizations require an integrated working of its various sub-systems. An efficient EMR software boosts the teamwork amongst the various sub-systems thereby resulting in improved service delivery. Although there has been a huge impetus to EMR under the Digital India initiative, it has still not been mandated in India. It is generally implemented in huge funded public or private healthcare organizations only. Objective: The study was conducted to understand the factors that lead to the successful adoption of an affordable EMR in the low level healthcare organization. It intended to understand the design of the EMR and address the solutions to the challenges faced in adoption of the EMR. Methodology: The study was conducted in a non-profit registered Healthcare organization that has been providing healthcare facilities to more than 2500 villages including certain areas that are difficult to access. The data was collected with help of field notes, in-depth interviews and participant observation. A total of 16 participants using the EMR from different departments were enrolled via purposive sampling technique. The participants included in the study were working in the organization before the implementation of the EMR system. The study was conducted in one month period from 25 June-20 July 2018. The Ethical approval was taken from the institute along with prior approval of the participants. Data analysis: A word document of more than 4000 words was obtained after transcribing and translating the answers of respondents. It was further analyzed by focused coding, a line by line review of the transcripts, underlining words, phrases or sentences that might suggest themes to do thematic narrative analysis. Results: Based on the answers the results were thematically grouped under four headings: 1. governance of organization, 2. architecture and design of the software, 3. features of the software, 4. challenges faced in adoption and the solutions to address them. It was inferred that the successful implementation was attributed to the easy and comprehensive design of the system which has facilitated not only easy data storage and retrieval but contributes in constructing a decision support system for the staff. Portability has lead to increased acceptance by physicians. The proper division of labor, increased efficiency of staff, incorporation of auto-correction features and facilitation of task shifting has lead to increased acceptance amongst the users of various departments. Geographical inhibitions, low computer literacy and high patient load were the major challenges faced during its implementation. Despite of dual efforts made both by the architects and administrators to combat these challenges, there are still certain ongoing challenges faced by organization. Conclusion: Whenever any new technology is adopted there are certain innovators, early adopters, late adopters and laggards. The same pattern was followed in adoption of this software. He challenges were overcome with joint efforts of organization administrators and users as well. Thereby this case study provides a framework of implementing similar systems in public sector of countries that are struggling for digitizing the healthcare in presence of crunch of human and financial resources.

Keywords: EMR, healthcare technology, e-health, EHR

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Authors: Elena Bellini, Daniele Mugnaini, Michele Boschetto

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People with an Autistic Spectrum Disorder and an Intellectual Disability who need to attend a Hospital Emergency Waiting Room frequently present high levels of discomfort and challenging behaviors due to stress-related hyperarousal, sensory sensitivity, novelty-anxiety, communication and self-regulation difficulties. Increased agitation and acting out also disturb the diagnostic and therapeutic processes, and the emergency room climate. Architectural design disciplines aimed at reducing distress in hospitals or creating autism-friendly environments are called for to find effective answers to this particular need. A growing number of researchers are considering the physical environment as an important point of intervention for people with autism. It has been shown that providing the right setting can help enhance confidence and self-esteem and can have a profound impact on their health and wellbeing. Environmental psychology has evaluated the perceived quality of care, looking at the design of hospital rooms, paths and circulation, waiting rooms, services and devices. Furthermore, many studies have investigated the influence of the hospital environment on patients, in terms of stress-reduction and therapeutic intervention’ speed, but also on health professionals and their work. Several services around the world are organizing autism-friendly hospital environments which involve the architecture and the specific staff training. In Italy, the association Spes contra spem has promoted and published, in 2013, the ‘Chart of disabled people in the hospital’. It stipulates that disabled people should have equal rights to accessible and high-quality care. There are a few Italian examples of therapeutic programmes for autistic people as the Dama project in Milan and the recent experience of Children and Autism Foundation in Pordenone. Careggi’s Emergency Waiting Room in Florence has been built to satisfy this challenge. This project of research comes from a collaboration between the technical staff of Careggi Hospital, the Center for autism PAMAPI and some architects expert in the sensory environment. The methodology of focus group involved architects, psychologists and professionals through a transdisciplinary research, centered on the links between the spatial characteristics and clinical state of people with ASD. The relationship between architectural space and quality of life is studied to pay maximum attention to users’ needs and to support the medical staff in their work by a specific program of training. The result of this research is a sum of criteria used to design the emergency waiting room, that will be illustrated. A protected room, with a clear space design, maximizes comprehension and predictability. The multisensory environment is thought to help sensory integration and relaxation. Visual communication through Ipad allows an anticipated understanding of medical procedures, and a specific technological system supports requests, choices and self-determination in order to fit sensory stimulation to personal preferences, especially for hypo and hypersensitive people. All these characteristics should ensure a better regulation of the arousal, less behavior problems, improving treatment accessibility, safety, and effectiveness. First results about patient-satisfaction levels will be presented.

Keywords: accessibility of care, autism-friendly architecture, personalized therapeutic process, sensory environment

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Authors: Caroline Smith, Professor Debi Bhattacharya, Sion Scott

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Introduction: Oropharyngeal Dysphagia (OD) effects around 15% of older people, however it is often unrecognised and under diagnosed until they are hospitalised. There is a need for primary care healthcare practitioners (HCPs) to assume a proactive role in identifying and managing OD to prevent adverse outcomes such as aspiration pneumonia. Understanding the determinants of primary care HCPs undertaking this new behaviour provides the intervention targets for addressing. This realist review, underpinned by the Theoretical Domains Framework (TDF), aims to synthesise relevant literature and develop programme theories to understand what interventions work, how they work and under what circumstances to facilitate HCPs to prevent harm from OD. Combining realist methodology with behavioural science will permit conceptualisation of intervention components as theoretical behavioural constructs, thus informing the design of a future behaviour change intervention. Furthermore, through the TDF’s linkage to a taxonomy of behaviour change techniques, we will identify corresponding behaviour change techniques to include in this intervention. Methods & analysis: We are following the five steps for undertaking a realist review: 1) clarify the scope 2) Literature search 3) appraise and extract data 4) evidence synthesis 5) evaluation. We have searched Medline, Google scholar, PubMed, EMBASE, CINAHL, AMED, Scopus and PsycINFO databases. We are obtaining additional evidence through grey literature, snowball sampling, lateral searching and consulting the stakeholder group. Literature is being screened, evaluated and synthesised in Excel and Nvivo. We will appraise evidence in relation to its relevance and rigour. Data will be extracted and synthesised according to its relation to Initial programme theories (IPTs). IPTs were constructed after the preliminary literature search, informed by the TDF and with input from a stakeholder group of patient and public involvement advisors, general practitioners, speech and language therapists, geriatricians and pharmacists. We will follow the Realist and Meta-narrative Evidence Syntheses: Evolving Standards (RAMESES) quality and publication standards to report study results. Results: In this ongoing review our search has identified 1417 manuscripts with approximately 20% progressing to full text screening. We inductively generated 10 IPTs that hypothesise practitioners require: the knowledge to spot the signs and symptoms of OD; the skills to provide initial advice and support; and access to resources in their working environment to support them conducting these new behaviours. We mapped the 10 IPTs to 8 TDF domains and then generated a further 12 IPTs deductively using domain definitions to fulfil the remaining 6 TDF domains. Deductively generated IPTs broadened our thinking to consider domains such as ‘Emotion,’ ‘Optimism’ and ‘Social Influence’, e.g. If practitioners perceive that patients, carers and relatives expect initial advice and support, then they will be more likely to provide this, because they will feel obligated to do so. After prioritisation with stakeholders using a modified nominal group technique approach, a maximum of 10 IPTs will progress to test against the literature.

Keywords: behaviour change, deglutition disorders, primary healthcare, realist review

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Authors: Narottam Puri, Gurvinder Kaur

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Background: The National Accreditation Board for Hospitals & Healthcare Providers (NABH) is India’s apex standard setting accrediting body in health care which evaluates and accredits healthcare organizations. NABH requires accredited organizations to become reaccredited every three years. It is often though that once the initial accreditation is complete, the foundation is set and reaccreditation is a much simpler process. Fortis Hospital, Shalimar Bagh, a part of the Fortis Healthcare group is a 262 bed, multi-specialty tertiary care hospital. The hospital was successfully accredited in the year 2012. On completion of its first cycle, the hospital underwent a reaccreditation assessment in the year 2015. This paper aims to gain a better understanding of the challenges that accredited hospitals face when preparing for a renewal of their accreditations. Methods: The study was conducted using a cross-sectional mixed methods approach; semi-structured interviews were conducted with senior leadership team and staff members including doctors and nurses. Documents collated by the QA team while preparing for the re-assessment like the data on quality indicators: the method of collection, analysis, trending, continual incremental improvements made over time, minutes of the meetings, amendments made to the existing policies and new policies drafted was reviewed to understand the challenges. Results: The senior leadership had a concern about the cost of accreditation and its impact on the quality of health care services considering the staff effort and time consumed it. The management was however in favor of continuing with the accreditation since it offered competitive advantage, strengthened community confidence besides better pay rates from the payors. The clinicians regarded it as an increased non-clinical workload. Doctors felt accountable within a professional framework, to themselves, the patient and family, their peers and to their profession; but not to accreditation bodies and raised concerns on how the quality indicators were measured. The departmental leaders had a positive perception of accreditation. They agreed that it ensured high standards of care and improved management of their functional areas. However, they were reluctant in sparing people for the QA activities due to staffing issues. With staff turnover, a lot of work was lost as sticky knowledge and had to be redone. Listing the continual quality improvement initiatives over the last 3 years was a challenge in itself. Conclusion: The success of any quality assurance reaccreditation program depends almost entirely on the commitment and interest of the administrators, nurses, paramedical staff, and clinicians. The leader of the Quality Movement is critical in propelling and building momentum. Leaders need to recognize skepticism and resistance and consider ways in which staff can become positively engaged. Involvement of all the functional owners is the start point towards building ownership and accountability for standards compliance. Creativity plays a very valuable role. Communication by Mail Series, WhatsApp groups, Quizzes, Events, and any and every form helps. Leaders must be able to generate interest and commitment without burdening clinical and administrative staff with an activity they neither understand nor believe in.

Keywords: NABH, reaccreditation, quality assurance, quality indicators

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Authors: Ugo Galvanetto, Pirto G. Pavan, Mirco Zaccariotto

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The discipline of Computer-integrated surgery (CIS) will provide equipment able to improve the efficiency of healthcare systems and, which is more important, clinical results. Surgeons and machines will cooperate in new ways that will extend surgeons’ ability to train, plan and carry out surgery. Patient specific CIS of the brain requires several steps: 1 - Fast generation of brain models. Based on image recognition of MR images and equipped with artificial intelligence, image recognition techniques should differentiate among all brain tissues and segment them. After that, automatic mesh generation should create the mathematical model of the brain in which the various tissues (white matter, grey matter, cerebrospinal fluid …) are clearly located in the correct positions. 2 – Reliable and fast simulation of the surgical process. Computational mechanics will be the crucial aspect of the entire procedure. New algorithms will be used to simulate the mechanical behaviour of cutting through cerebral tissues. 3 – Real time provision of visual and haptic feedback A sophisticated human-machine interface based on ergonomics and psychology will provide the feedback to the surgeon. The present work will address in particular point 2. Modelling the cutting of soft tissue in a structure as complex as the human brain is an extremely challenging problem in computational mechanics. The finite element method (FEM), that accurately represents complex geometries and accounts for material and geometrical nonlinearities, is the most used computational tool to simulate the mechanical response of soft tissues. However, the main drawback of FEM lies in the mechanics theory on which it is based, classical continuum Mechanics, which assumes matter is a continuum with no discontinuity. FEM must resort to complex tools such as pre-defined cohesive zones, external phase-field variables, and demanding remeshing techniques to include discontinuities. However, all approaches to equip FEM computational methods with the capability to describe material separation, such as interface elements with cohesive zone models, X-FEM, element erosion, phase-field, have some drawbacks that make them unsuitable for surgery simulation. Interface elements require a-priori knowledge of crack paths. The use of XFEM in 3D is cumbersome. Element erosion does not conserve mass. The Phase Field approach adopts a diffusive crack model instead of describing true tissue separation typical of surgical procedures. Modelling discontinuities, so difficult when using computational approaches based on classical continuum Mechanics, is instead easy for novel computational methods based on Peridynamics (PD). PD is a non-local theory of mechanics formulated with no use of spatial derivatives. Its governing equations are valid at points or surfaces of discontinuity, and it is, therefore especially suited to describe crack propagation and fragmentation problems. Moreover, PD does not require any criterium to decide the direction of crack propagation or the conditions for crack branching or coalescence; in the PD-based computational methods, cracks develop spontaneously in the way which is the most convenient from an energy point of view. Therefore, in PD computational methods, crack propagation in 3D is as easy as it is in 2D, with a remarkable advantage with respect to all other computational techniques.

Keywords: computational mechanics, peridynamics, finite element, biomechanics

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Authors: Anushka Naidoo, Veron Ramsuran, Maxwell Chirehwa, Paolo Denti, Kogieleum Naidoo, Helen McIlleron, Nonhlanhla Yende-Zuma, Ravesh Singh, Sinaye Ngcapu, Nesri Padayatachi

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Background: Despite efforts to introduce new drugs and shorter drug regimens for drug-susceptible tuberculosis (TB), the standard first-line treatment has not changed in over 50 years. Rifampicin, isoniazid, and pyrazinamide are critical components of the current standard treatment regimens. Some studies suggest that microbiologic failure and acquired drug resistance are primarily driven by low drug concentrations that result from pharmacokinetic (PK) variability independent of adherence to treatment. Wide between-patient pharmacokinetic variability for rifampin, isoniazid, and pyrazinamide has been reported in prior studies. There may be several reasons for this variability. However, genetic variability in genes coding for drug metabolizing and transporter enzymes have been shown to be a contributing factor for variable tuberculosis drug exposures. Objective: We describe the pharmacokinetics of first-line TB drugs rifampicin, isoniazid, and pyrazinamide and assess the effect of genetic variability in relevant selected drug metabolizing and transporter enzymes on pharmacokinetic parameters of isoniazid and rifampicin. Methods: We conducted the randomized-controlled Improving retreatment success TB trial in Durban, South Africa. The drug regimen included rifampicin, isoniazid, and pyrazinamide. Drug concentrations were measured in plasma, and concentration-time data were analysed using nonlinear-mixed-effects models to quantify the effects of relevant covariates and single nucleotide polymorphisms (SNP’s) of drug metabolizing and transporter genes on rifampicin, isoniazid and pyrazinamide exposure. A total of 25 SNP’s: four NAT2 (used to determine acetylator status), four SLCO1B1, three Pregnane X receptor (NR1), six ABCB1 and eight UGT1A, were selected for analysis in this study. Genotypes were determined for each of the SNP’s using a TaqMan® Genotyping OpenArray™. Results: Among fifty-eight patients studied; 41 (70.7%) were male, 97% black African, 42 (72.4%) HIV co-infected and 40 (95%) on efavirenz-based ART. Median weight, fat-free mass (FFM), and age at baseline were 56.9 kg (interquartile range, IQR: 51.1-65.2), 46.8 kg (IQR: 42.5-50.3) and 37 years (IQR: 31-42), respectively. The pharmacokinetics of rifampicin and pyrazinamide was best described using one-compartment models with first-order absorption and elimination, while for isoniazid two-compartment disposition was used. The median (interquartile range: IQR) AUC (h·mg/L) and Cmax (mg/L) for rifampicin, isoniazid, and pyrazinamide were; 25.62 (23.01-28.53) and 4.85 (4.36-5.40), 10.62 (9.20-12.25) and 2.79 (2.61-2.97), 345.74 (312.03-383.10) and 28.06 (25.01-31.52), respectively. Eighteen percent of patients were classified as rapid acetylators, and 34% and 43% as slow and intermediate acetylators, respectively. Rapid and intermediate acetylator status based on NAT 2 genotype resulted in 2.3 and 1.6 times higher isoniazid clearance than slow acetylators. We found no effects of the SLCO1B1 genotypes on rifampicin pharmacokinetics. Conclusion: Plasma concentrations of rifampicin, isoniazid, and pyrazinamide were low overall in our patients. Isoniazid clearance was high overall and as expected higher in rapid and intermediate acetylators resulting in lower drug exposures. In contrast to reports from previous South African or Ugandan studies, we did not find any effects of the SLCO1B1 or other genotypes tested on rifampicin PK. However, our findings are in keeping with more recent studies from Malawi and India emphasizing the need for geographically diverse and adequately powered studies. The clinical relevance of the low tuberculosis drug concentrations warrants further investigation.

Keywords: rifampicin, isoniazid pharmacokinetics, genetics, NAT2, SLCO1B1, tuberculosis

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Authors: Lewis Mehl-Madrona, Barbara Mainguy, Patrick McFarlane

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Introduction: There are many risk factors for attempting suicide, including young age, “minority stress,” which would include Transgender and Gender Diverse orientations (TGD). The rate of TGD youths for suicide attempts is 3 times higher than heterosexual cis-gender youth. Half of TGD youth have seriously contemplated taking their own lives; of those, about half attempted suicide; and 18% of the TGD teenagers reported suicidal thoughts linked to their gender identity. Native American TGD have a six times higher suicide attempt rate. Conventional mental health has not generally helped these individuals. Stigma and discrimination contribute to healthcare disparities. Storytelling plays a crucial role in the development of human culture and individual identities. Sharing narrative artwork, creative writing, and personal stories allow people to build trust and to share their vulnerabilities. This helps people become aware of themselves in relation to others and gain a sense of comfort that their stories are similar; they may also be transformed in the process. Art provides a means to reach people who are otherwise difficult to engage in services. Methods: TGD individuals are recruited through a snowballing procedure. Following a life story interview, participants complete a scale of gender dysphoria, identification with conventional masculinity, patient-reported anxiety, and depression measure, and a quality-of-life scale. The interview completes the Columbia Suicide Scale. Following this, an artist and a therapist works with the participant to create a story related to their gender identity using the six-part story method. This story is then rendered to an artists’ book, which combines narrative with art (drawings, collage, computer images, etc.) and can take the form of a graphic novella, a zine, or a comic book. The pages can range from plain to ornate, as can the covers. Participants describe their process of making the books as the work unfolds and then participate in an exit interview at the completion of their book, remarking on what has changed for them and how the process affected them. Results: Preliminary results show high levels of suicidal thoughts among this population, as expected. Participants participate enthusiastically in the life story interview process and in the construction of a story related to gender identity. They enthusiastically participate in the studio process of putting their story into the form of a graphic novel, zine, or comic book. Participants reported feeling more comfortable with their TGD identity after the process and more able to resist negative judgments of family members and society. Suicidal thoughts diminish, and participants reported improved emotional wellbeing. Quantitative analysis of questionnaire data is underway Conclusions: A process in which narrative therapy is combined with art therapy shows promise for attracting and helping TGD individuals to reduce their risk for suicide without the stigma of going for mental health treatment. This process can be done outside of conventional mental health settings, on college and University campuses. This can provide an exciting alternative pathway for minority stressed and stigmatized individuals to engage in reflective, psychotherapeutic work without the trappings of psychotherapy or mental health treatment.

Keywords: minority stress, narrative process, artists' books, life story interview

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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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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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Authors: Parag Katira, Frederika Rentzeperis, Zuzanna Nowicka, Giada Fiandaca, Thomas Veith, Jack Farinhas, Noemi Andor

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Resource limitations shape the outcome of competitions between genetically heterogeneous pre-malignant cells. One example of such heterogeneity is in the ploidy (DNA content) of pre-malignant cells. A whole-genome duplication (WGD) transforms a diploid cell into a tetraploid one and has been detected in 28-56% of human cancers. If a tetraploid subclone expands, it consistently does so early in tumor evolution, when cell density is still low, and competition for nutrients is comparatively weak – an observation confirmed for several tumor types. WGD+ cells need more resources to synthesize increasing amounts of DNA, RNA, and proteins. To quantify resource limitations and how they relate to ploidy, we performed a PAN cancer analysis of WGD, PET/CT, and MRI scans. Segmentation of >20 different organs from >900 PET/CT scans were performed with MOOSE. We observed a strong correlation between organ-wide population-average estimates of Oxygen and the average ploidy of cancers growing in the respective organ (Pearson R = 0.66; P= 0.001). In-vitro experiments using near-diploid and near-tetraploid lineages derived from a breast cancer cell line supported the hypothesis that DNA content influences Glucose- and Oxygen-dependent proliferation-, death- and migration rates. To model how subpopulations with variable DNA content compete in the resource-limited environment of the human brain, we developed a stochastic state-space model of the brain (S3MB). The model discretizes the brain into voxels, whereby the state of each voxel is defined by 8+ variables that are updated over time: stiffness, Oxygen, phosphate, glucose, vasculature, dead cells, migrating cells and proliferating cells of various DNA content, and treat conditions such as radiotherapy and chemotherapy. Well-established Fokker-Planck partial differential equations govern the distribution of resources and cells across voxels. We applied S3MB on sequencing and imaging data obtained from a primary GBM patient. We performed whole genome sequencing (WGS) of four surgical specimens collected during the 1ˢᵗ and 2ⁿᵈ surgeries of the GBM and used HATCHET to quantify its clonal composition and how it changes between the two surgeries. HATCHET identified two aneuploid subpopulations of ploidy 1.98 and 2.29, respectively. The low-ploidy clone was dominant at the time of the first surgery and became even more dominant upon recurrence. MRI images were available before and after each surgery and registered to MNI space. The S3MB domain was initiated from 4mm³ voxels of the MNI space. T1 post and T2 flair scan acquired after the 1ˢᵗ surgery informed tumor cell densities per voxel. Magnetic Resonance Elastography scans and PET/CT scans informed stiffness and Glucose access per voxel. We performed a parameter search to recapitulate the GBM’s tumor cell density and ploidy composition before the 2ⁿᵈ surgery. Results suggest that the high-ploidy subpopulation had a higher Glucose-dependent proliferation rate (0.70 vs. 0.49), but a lower Glucose-dependent death rate (0.47 vs. 1.42). These differences resulted in spatial differences in the distribution of the two subpopulations. Our results contribute to a better understanding of how genomics and microenvironments interact to shape cell fate decisions and could help pave the way to therapeutic strategies that mimic prognostically favorable environments.

Keywords: tumor evolution, intra-tumor heterogeneity, whole-genome doubling, mathematical modeling

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Authors: Humaira Saeed Malik, Salma Saad

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Introduction: Fowler's syndrome, first described by Clare Fowler in 1985, is a rare urological condition characterized by difficulty in urination due to the abnormal function of the urethral sphincter. It predominantly affects young women and leads to chronic urinary retention. The main concern in managing this condition is ensuring regular bladder emptying. Clam cystoplasty is a bladder augmentation surgery in which the bladder is clam-shelled open, and a segment of the intestine is used to increase the bladder's capacity and reduce bladder pressure. The Mitrofanoff procedure, a surgical creation of a continent urinary diversion, is often performed in patients with Fowler's syndrome who require long-term catheterization. This procedure involves creating a conduit (from the appendix or a segment of the small intestine) between the bladder and the skin, allowing for intermittent self-catheterization to manage urinary retention. Study: This case study examines a 39-year-old gravida 3, para 0+2 woman with a BMI of 40, Fowler's syndrome, type I diabetes, and post-traumatic stress disorder (PTSD), presenting at Dumfries and Galloway Royal Infirmary at 8 weeks of gestation. Diagnosed with Fowler's syndrome at 23, . A sacral nerve stimulator (SNS) device was initially placed but was subsequently removed after one year due to malfunction caused by trauma, subsequently she had undergone clam cystoplasty and the Mitrofanoff procedure for bladder management. Her pregnancy was complicated by vaginal bleeding at 10 weeks, treated with progesterone pessaries, and a urinary tract infection at 14 weeks, managed with antibiotics. Despite these challenges, she continued self-catheterization through the Mitrofanoff stoma and was placed on prophylactic antibiotics. Her diabetes was well-controlled on insulin, and a 20-week fetal anomaly scan was normal. The multidisciplinary team, including an obstetrician and a urologist, planned for serial growth scans and the initiation of low molecular weight heparin (LMWH) from 28 weeks due to the intermediate risk of venous thromboembolism (VTE) and to continue six weeks after delivery. A planned cesarean delivery at 37 weeks was arranged, with an MRI scan scheduled later in the pregnancy to assist in surgical planning, ensuring the preservation of the Mitrofanoff stoma's function. The surgery will occur in an elective setting and include a consultant urologist. Conclusion: Pregnancy in women with Fowler's syndrome who have undergone Clam cystoplasty and the Mitrofanoff procedure is rare, and management requires careful planning and a multidisciplinary approach. This case highlights the importance of individualized care plans and close monitoring of both mother and fetus. The patient's risk of recurrent UTIs, coupled with her diabetes and high BMI, necessitated coordinated care across specialties to ensure the best possible outcomes. The Mitrofanoff procedure proved effective in managing her urinary retention, allowing her to maintain self-catheterization during pregnancy. The multidisciplinary team approach was crucial in addressing her complex medical needs, involving obstetrics, urology, and endocrinology. This case adds valuable information to the limited literature on pregnancy management in patients with Fowler's syndrome who have undergone the Mitrofanoff procedure, highlighting the need for comprehensive, individualized care and the involvement of a multidisciplinary team to achieve the best results.

Keywords: fowler's syndrome, clam cystoplasty, mitrofanoff procedure, pregnancy

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Authors: Kashima Arora, Monika Tomar, Vinay Gupta

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Biosensors have found potential applications ranging from environmental testing and biowarfare agent detection to clinical testing, health care, and cell analysis. This is driven in part by the desire to decrease the cost of health care and to obtain precise information more quickly about the health status of patient by the development of various biosensors, which has become increasingly prevalent in clinical testing and point of care testing for a wide range of biological elements. Uric acid is an important byproduct in human body and a number of pathological disorders are related to its high concentration in human body. In past few years, rapid growth in the development of new materials and improvements in sensing techniques have led to the evolution of advanced biosensors. In this context, metal oxide thin film based matrices due to their bio compatible nature, strong adsorption ability, high isoelectric point (IEP) and abundance in nature have become the materials of choice for recent technological advances in biotechnology. In the past few years, wide band-gap metal oxide semiconductors including ZnO, SnO₂ and CeO₂ have gained much attention as a matrix for immobilization of various biomolecules. Tin oxide (SnO₂), wide band gap semiconductor (Eg =3.87 eV), despite having multifunctional properties for broad range of applications including transparent electronics, gas sensors, acoustic devices, UV photodetectors, etc., it has not been explored much for biosensing purpose. To realize a high performance miniaturized biomolecular electronic device, rf sputtering technique is considered to be the most promising for the reproducible growth of good quality thin films, controlled surface morphology and desired film crystallization with improved electron transfer property. Recently, iron oxide and its composites have been widely used as matrix for biosensing application which exploits the electron communication feature of Fe, for the detection of various analytes using urea, hemoglobin, glucose, phenol, L-lactate, H₂O₂, etc. However, to the authors’ knowledge, no work is being reported on modifying the electronic properties of SnO₂ by implanting with suitable metal (Fe) to induce the redox couple in it and utilizing it for reagentless detection of uric acid. In present study, Fe implanted SnO₂ based matrix has been utilized for reagentless uric acid biosensor. Implantation of Fe into SnO₂ matrix is confirmed by energy-dispersive X-Ray spectroscopy (EDX) analysis. Electrochemical techniques have been used to study the response characteristics of Fe modified SnO₂ matrix before and after uricase immobilization. The developed uric acid biosensor exhibits a high sensitivity to about 0.21 mA/mM and a linear variation in current response over concentration range from 0.05 to 1.0 mM of uric acid besides high shelf life (~20 weeks). The Michaelis-Menten kinetic parameter (Km) is found to be relatively very low (0.23 mM), which indicates high affinity of the fabricated bioelectrode towards uric acid (analyte). Also, the presence of other interferents present in human serum has negligible effect on the performance of biosensor. Hence, obtained results highlight the importance of implanted Fe:SnO₂ thin film as an attractive matrix for realization of reagentless biosensors towards uric acid.

Keywords: Fe implanted tin oxide, reagentless uric acid biosensor, rf sputtering, thin film

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Authors: Charles Shang, Salina Ramirez, Stephen Shang, Maria Estrada, Timothy R. Williams

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Purpose: Over the past decade, proton therapy utilizing pencil beam scanning has emerged as a preferred treatment modality in radiation oncology, particularly for prostate cancer. This retrospective study aims to assess the clinical and radiobiological efficacy of proton scanning beam therapy in the treatment of localized salvage prostate cancer, following initial radiation therapy with a different modality. Despite the previously delivered high radiation doses, this investigation explores the potential of proton reirradiation in controlling recurrent prostate cancer and detrimental quality of life side effects. Methods and Materials: A retrospective analysis was conducted on 45 cases of locally recurrent prostate cancer that underwent salvage proton reirradiation. Patients were followed for 24.6 ± 13.1 months post-treatment. These patients had experienced an average remission of 8.5 ± 7.9 years after definitive radiotherapy for localized prostate cancer (n=41) or post-prostatectomy (n=4), followed by rising PSA levels. Recurrent disease was confirmed by FDG-PET (n=31), PSMA-PET (n=10), or positive local biopsy (n=4). Gross tumor volume (GTV) was delineated based on PET and MR imaging, with the planning target volume (PTV) expanding to an average of 10.9 cm³. Patients received proton reirradiation using two oblique coplanar beams, delivering total doses ranging from 30.06 to 60.00 GyE in 17–30 fractions. All treatments were administered using the ProBeam Compact system with CT image guidance. The International Prostate Symptom Scores (IPSS) and prostate-specific antigen (PSA) levels were evaluated to assess treatment-related toxicity and tumor control. Results and Discussions: In this cohort (mean age: 76.7 ± 7.3 years), 60% (27/45) of patients showed sustained reductions in PSA levels post-treatment, while 36% (16/45) experienced a PSA decline of more than 0.8 ng/mL. Additionally, 73% (33/45) of patients exhibited an initial PSA reduction, though some showed later PSA increases, indicating the potential presence of undetected metastatic lesions. The median post-retreatment IPSS score was 4, significantly lower than scores reported in other treatment studies. Overall, 69% of patients reported mild urinary symptoms, with 96% (43/45) experiencing mild to moderate symptoms. Three patients experienced grade I or II proctitis, while one patient reported grade III proctitis. These findings suggest that regional organs, including the urethra, bladder, and rectum, demonstrate significant radiobiological recovery from prior radiation exposure, enabling tolerance to additional proton scanning beam therapy. Conclusions: This retrospective analysis of 45 patients with recurrent localized prostate cancer treated with salvage proton reirradiation demonstrates favorable outcomes, with a median follow-up of two years. The post-retreatment IPSS scores were comparable to those reported in follow-up studies of initial radiation therapy treatments, indicating stable or improved urinary symptoms compared to the end of initial treatment. These results highlight the efficacy of proton scanning beam therapy in providing effective salvage treatment while minimizing adverse effects on critical organs. The findings also enhance the understanding of radiobiological responses to reirradiation and support proton therapy as a viable option for patients with recurrent localized prostate cancer following previous definitive radiation therapy.

Keywords: prostate salvage radiotherapy, proton therapy, biological radiation tolerance, radiobiology of organs

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Authors: William Michael Short

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Semantic Web’ technologies such as the Unified Medical Language System Metathesaurus, SNOMED-CT, and MeSH have been touted as transformational for the way users access online medical and health information, enabling both the automated analysis of natural-language data and the integration of heterogeneous healthrelated resources distributed across the Internet through the use of standardized terminologies that capture concepts and relationships between concepts that are expressed differently across datasets. However, the approaches that have so far characterized ‘semantic bioinformatics’ have not yet fulfilled the promise of the Semantic Web for medical and health information retrieval applications. This paper argues within the perspective of cognitive linguistics and cognitive anthropology that four features of human meaning-making must be taken into account before the potential of semantic technologies can be realized for this domain. First, many semantic technologies operate exclusively at the level of the word. However, texts convey meanings in ways beyond lexical semantics. For example, transitivity patterns (distributions of active or passive voice) and modality patterns (configurations of modal constituents like may, might, could, would, should) convey experiential and epistemic meanings that are not captured by single words. Language users also naturally associate stretches of text with discrete meanings, so that whole sentences can be ascribed senses similar to the senses of words (so-called ‘discourse topics’). Second, natural language processing systems tend to operate according to the principle of ‘one token, one tag’. For instance, occurrences of the word sound must be disambiguated for part of speech: in context, is sound a noun or a verb or an adjective? In syntactic analysis, deterministic annotation methods may be acceptable. But because natural language utterances are typically characterized by polyvalency and ambiguities of all kinds (including intentional ambiguities), such methods leave the meanings of texts highly impoverished. Third, ontologies tend to be disconnected from everyday language use and so struggle in cases where single concepts are captured through complex lexicalizations that involve profile shifts or other embodied representations. More problematically, concept graphs tend to capture ‘expert’ technical models rather than ‘folk’ models of knowledge and so may not match users’ common-sense intuitions about the organization of concepts in prototypical structures rather than Aristotelian categories. Fourth, and finally, most ontologies do not recognize the pervasively figurative character of human language. However, since the time of Galen the widespread use of metaphor in the linguistic usage of both medical professionals and lay persons has been recognized. In particular, metaphor is a well-documented linguistic tool for communicating experiences of pain. Because semantic medical knowledge-bases are designed to help capture variations within technical vocabularies – rather than the kinds of conventionalized figurative semantics that practitioners as well as patients actually utilize in clinical description and diagnosis – they fail to capture this dimension of linguistic usage. The failure of semantic technologies in these respects degrades the efficiency and efficacy not only of medical research, where information retrieval inefficiencies can lead to direct financial costs to organizations, but also of care provision, especially in contexts of patients’ self-management of complex medical conditions.

Keywords: ambiguity, bioinformatics, language, meaning, metaphor, ontology, semantic web, semantics

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