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Authors: Murat Emre, Zeynep Tufekcioglu

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Objective: We describe a patient with late onset phenylketonuria which presented with rapidly progressive dementia and parkinsonism that were reversible after management. Background: Phenylketonuria is an autosomal recessive disorder due to mutations in the phenylalanine hydroxlase gene. It normally presents in childhood, in rare cases, however, it may have its onset in adulthood and may mimic other neurological disorders. Case description: A previously normal functioning, 59 year old man was admitted for blurred vision, cognitive impairment and gait difficulty which emerged over the past eight months. In neurological examination he had brisk reflexes, slow gait and left-dominant parkinsonism. Mini-mental state examination score was 25/30, neuropsychological testing revealed a dysexecutive syndrome with constructional apraxia and simultanagnosia. In cranial MRI there were bilateral diffuse hyper-intense lesions in parietal and occipital white matter with no significant atrophy. Electroencephalography showed diffuse slowing with predominance of teta waves. In cerebrospinal fluid examination protein level was slightly elevated (61mg/dL), oligoclonal bands were negative. Electromyography was normal. Routine laboratory examinations for rapidly progressive dementia and parkinsonism were also normal. Serum amino acid levels were determined to explore metabolic leukodystrophies and phenylalanine level was found to be highly elevated (1075 µmol/L) with normal tyrosine (61,20 µmol/L). His cognitive impairment and parkinsonian symptoms improved following three months of phenylalanine restricted diet. Conclusions: Late onset phenylketonuria is a rare, potentially reversible cause of rapidly progressive parkinsonism with dementia. It should be considered in the differential diagnosis of patients with suspicious features.

Keywords: dementia, neurology, Phenylketonuria, rapidly progressive parkinsonism

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Authors: I. Dangeard, S. Meineri, M. Dupré

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large body of research on energy consumption reveals that regular information on energy consumption produces a positive effect on behavior. The present research aims to test this feedback paradigm on waste management. A small-scale experiment on residual household waste was performed in a large french urban area, in partnership with local authorities, as part of the development of larger-scale project. A two-step door-to-door recruitment scheme led to 85 households answering a questionnaire. Among them, 54 accepted to participate in a study on waste (second step). Participants were then randomly assigned to one of the 3 experimental conditions : self-reported feedback on curbside waste, external feedback on waste weight based on information technologies, and no feedback for the control group. An additional control group was added, including households who were not requested to answer the questionnaire. Household residual waste was collected every week, and tags on curbside bins fed a database with waste weight of households. The feedback period lasted 14 weeks (february-may 2014). Quantitative data on waste weight were analysed, including these 14 weeks and the 7 previous weeks. Households were then contacted by phone in order to confirm the quantitative results. Regarding the recruitment questionnaire, results revealed high pro-environmental attitude on the NEP scale, high recycling behavior level and moderate level of source reduction behavior on the adapted 3R scale, but no statistical difference between the 3 experimental groups. Regarding the feedback manipulation paradigm, waste weight reveals important differences between households, but doesn't prove any statistical difference between the experimental conditions. Qualitative phone interviews confirm that recycling is a current practice among participants, whereas source reduction of waste is not, and mainly appears as a producer problem of packaging limitation. We conclude that triggering waste prevention behaviors among recycling households involves long-term feedback and should promote benchmarking, in order to clearly set waste reduction as an objective to be managed through feedback figures.

Keywords: eco-feedback, household waste, waste reduction, experimental research

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Authors: Farhood Rismanchian, Seong Hyeon Park, Young Hoon Lee

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This paper proposes a method to optimize the layout of an emergency department (ED) based on real executions of care processes by considering several planning objectives simultaneously. Recently, demand for healthcare services has been dramatically increased. As the demand for healthcare services increases, so do the need for new healthcare buildings as well as the need for redesign and renovating existing ones. The importance of implementation of a standard set of engineering facilities planning and design techniques has been already proved in both manufacturing and service industry with many significant functional efficiencies. However, high complexity of care processes remains a major challenge to apply these methods in healthcare environments. Process mining techniques applied in this study to tackle the problem of complexity and to enhance care process analysis. Process related information such as clinical pathways extracted from the information system of an ED. A 0-1 goal programming approach is then proposed to find a single layout that simultaneously satisfies several goals. The proposed model solved by optimization software CPLEX 12. The solution reached using the proposed method has 42.2% improvement in terms of walking distance of normal patients and 47.6% improvement in walking distance of critical patients at minimum cost of relocation. It has been observed that lots of patients must unnecessarily walk long distances during their visit to the emergency department because of an inefficient design. A carefully designed layout can significantly decrease patient walking distance and related complications.

Keywords: healthcare operation management, goal programming, facility layout problem, process mining, clinical processes

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Authors: Atitallah Sofien, Bouyahia Olfa, Krifi Farah, Missaoui Nada, Ben Rabeh Rania, Yahyaoui Salem, Mazigh Sonia, Boukthir Samir

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Introduction: Cutis marmorata telangiectatica congenita (CMTC) is a rare cutaneous vascular malformation. It most often appears at birth or during the first days of life. Its origin is still unknown. It associates a livedo with telangiectasias of diffuse or segmental topography. In rare cases, it can be associated with neurological disorders such as macrocephaly and, less frequently, with epilepsy. Methodology: We report a case of an infant with Macrocephaly- Cutis marmorata telangiectatica congenita syndrome associated with epilepsy. Results: This is the case of a one month and 15 days old female infant from a non-consanguineous marriage, admitted for a status epilepticus in the context of apyrexia. Infectious and metabolic causes had been eliminated. Physical examination had shown non-infiltrated and reticular livedoid erythematous patches affecting the left upper limb and atrophic on the back of the left hand. Cerebral magnetic resonance imaging (MRI) showed thin layers of bifrontal, temporal, and left parietal hygromas associated with the widening of the bifrontal subarachnoid spaces. The electroencephalogram showed a well-organized sleep tracing with a single right occipital paroxysmal abnormality. Antiepileptic treatment has been administered with good clinical evolution and regression of the skin lesion and a control electroencephalogram without abnormality. Conclusion: This observation illustrates an association of CMTC with both macrocephaly and epilepsy. This pathology, which is relatively benign and has a good prognosis, generally does not require treatment. However, a detailed examination must be carried out, and a follow-up plan must be put in place for each patient presenting with CMTC, given the risk of association with other abnormalities, which can be potentially serious.

Keywords: cutis marmorata telangiectatica congenita, macrocephaly, epilepsy, children

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Authors: Ramuel Spirituel Mattathiah A. San Juan, Neil Ambasing

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Background: Reversal of vision metamorphopsia is a transient form of metamorphopsia described as an upside-down alteration of the visual field in the coronal plane. Patients would describe objects, such as cups, upside down, but the tea would not spill, and people would walk on their heads. It is extremely rare as a stable finding, lasting days or weeks. We report a case wherein this type of metamorphopsia occurred only in written words and lasted for six months. Objective: To the best of our knowledge, we report the first rare occurrence of reversal of vision metamorphopsia described as inverted words as the sole initial presentation of an underlying stroke. Case Presentation: We report a 59-year-old male with poorly controlled hypertension and diabetes mellitus who presented with a 3-day history of difficulty reading, described as the words were turned upside down as if the words were inverted horizontally then with the progression of deficits such as right homonymous hemianopia and achromatopsia, prosopagnosia. Cranial magnetic resonance imaging (MRI) revealed an acute infarct on the left posterior cerebral artery territory. Follow-up after six months revealed improvement of the visual field cut but with the persistence of the higher cortical function deficits. Conclusion: We report the first rare occurrence of metamorphopsia described as purely inverted words as the sole initial presentation of an underlying stroke. The differential diagnoses of a patient presenting with text reversal metamorphopsia should include stroke in the occipitotemporal areas. It further expands the landscape of metamorphopsias due to its exclusivity to written words and prolonged duration. Knowing these clinical features will help identify the lesion locus and improve subsequent stroke care, especially in time-bound management like intravenous thrombolysis.

Keywords: rare presentation, text reversal metamorphopsia, ischemic stroke, stroke

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Authors: Ena Arora, Rong Fan, Aleksandr Fuks, Kolawole Felix Akinnawonu

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Introduction: Leiomyomas are benign tumors that are derived from the overgrowth of uterine smooth muscle cells. Women with symptomatic leiomyomas who desire future fertility, myomectomy should be the standard surgical treatment. Perioperative hemorrhage is a common complication in myomectomy. We performed the study to investigate blood transfusion rate in abdominal myomectomies, risk factors influencing blood loss and modalities to improve perioperative blood loss. Methods: Retrospective chart review was done for patients who underwent myomectomy from 2016 to 2022 at Queens hospital center, New York. We looked at preoperative patient demographics, clinical characteristics, intraoperative variables, and postoperative outcomes. Mann-Whitney U test were used for parametric and non-parametric continuous variable comparisons, respectively. Results: A total of 159 myomectomies were performed between 2016 and 2022, including 1 laparoscopic, 65 vaginal and 93 abdominal. 44 patients received blood transfusion during or within 72 hours of abdominal myomectomy. The blood transfusion rate was 47.3%. Blood transfusion rate was found to be twice higher than the average documented rate in literature which is 20%. Risk factors identified were black race, preoperative hematocrit<30%, preoperative blood transfusion within 72 hours, large fibroid burden, prolonged surgical time, and abdominal approach. Conclusion: Preoperative optimization with iron supplements or GnRH agonists is important for patients undergoing myomectomy. Interventions to decrease intra operative blood loss should include cell saver, tourniquet, vasopressin, misoprostol, tranexamic acid and gelatin-thrombin matrix hemostatic sealant.

Keywords: myomectomy, perioperative blood loss, cell saver, tranexamic acid

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Authors: E. A. Alaswad, H. M. Choudhry, F. Z. Filimban

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Sickle Cell Anemia (SCA) is one type of blood diseases related to autosomal disorder. The sickle shaped red blood cells are the main cause of many problems in the blood vessels and capillaries. Aerva Javanica (J) and Ficus Palmata (P) are medicinal plants that have many popular uses and have been proved their efficacy. The aim of this study was to assess the antioxidants activity and the antisickling effect of J and P extractions. The period of this study, air-dried leaves of J, and P plants were ground and the active components were extracted by maceration in water (W) and methanol (M) as solvents. The antioxidants activity of JW, PW, JM, and PM were assessed by way of the radical scavenging method using 2,2-diphenyl-1-picrylhydrazyl (DPPH). To determine the antisickling effect of J and P extracts. 20 samples were collected from sickle cell anemia patients. Different concentrations of J and P extracts (200 and 110 μg/mL) were added on the sample and incubated. A drop of each sample was examined with light microscope. Normal and sickled RBCs were calculated and expressed as the percent of sickling. The stabilization effect of the extracts was measured by the osmotic fragility test for erythrocytes. The finding suggests as estimated by DPPH method, all the extracts showed an antioxidant activity with a significant inhibition of the DPPH radicals. PM has the least IC50% with 71.49 μg/ml while JM was the most with 408.49 μg/ml. Sickle cells treated with extracts at different concentrations significantly reduced the percentage of sickling compering to control samples. However, JM 200 μg/mL give the highest anti-sickling affect with 17.4% of sickling compared to control 67.5 of sickling while PM at 200 μg/mL showed the highest membrane cell stability. In a conclusion, the results showed that J and P extracts have antisickling effects. Therefore, the Aerva javanica and Ficus palmata may have a role in SCA management and a good impact on the patient's lives.

Keywords: Aerva javanica, antioxidant, antisickling, Ficus palmata, sickle cell anemia

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Authors: Naser Shagerdi Esmaeli, Mohsen Hamidpour, Parisa Hasankhani Tehrani

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Background And Objective: Haematopoietic stem cell transplant is a potentially curative treatment option in various benign and malignant haematological diseases. Patients undergoing stem cell transplant procedure require blood transfusion on a daily basis. Currently, there is paucity of data from developing countries on transfusion practices. This audit was undertaken to determine the consumption of packed red blood cells (PRBCs) transfusion in the bone marrow transplant unit of the Shahid Ghazi Tabatabaei Hospital, Tabriz, Iran. Subjects And Methods: A retrospective audit was conducted for packed red cell transfusion ordering practice over a period from March 2017 to march 2018. All consecutive patients admitted for stem cell transplant procedure for various underlying diseases were included. Outcome measures used in this study were (i) cross match to transfusion (C: T) ratio and (ii) transfusion trigger. Results: During the study period, n=13 patients underwent a haematopoietic stem cell transplant. There were n=10 males and n=3 females. One patient was less than 15 years of age, while rests were adults. Median age±SD was 26.5±14.5 years (12∼54 years). The underlying diagnosis included Aplastic anemia (n=4), Thalassemia major (n=1), Multiple Myeloma (n=3), Acute leukemia (n=3), Hodgkin's lymphoma (n=1), PRCA (n=1). Grand total consumption of PRBCs during the study period was 204, while 258 products were crossmatch. The C:T ratio was 1.26. The transfusion trigger was Hb level of less than 8 gr/dl. Conclusion: The results of our BMT unit indicate that the C:T ratio and transfusion trigger is comparable to the international criteria and pioneer country in BMT transplantation. Also, we hope that our blood consumption become less than it is now.

Keywords: blood consumption, C: T ratio, PRBCs, stem cell transplant, tabriz, Iran

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Authors: Matteo Nicoli, Gianvito Colucci, Valeria Di Cosmo, Daniele Lerede, Laura Savoldi

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The transport sector is currently responsible for approximately 1/3 of greenhouse gas emissions in Europe. In the wider context of achieving carbon neutrality of the global energy system, different alternatives are available to decarbonizethe transport sector. In particular, while electricity is already the most consumed energy commodity in rail transport, battery electric vehicles are one of the zero-emissions options on the market for road transportation. On the other hand, hydrogen-based fuel cell vehicles are available for road and non-road vehicles. The European Commission is strongly pushing toward the integration of hydrogen in the energy systems of European countries and its widespread adoption as an energy vector to achieve the Green Deal targets. Furthermore, the Italian government is defining hydrogen-related objectives with the publication of a dedicated Hydrogen Strategy. The adoption of energy system optimization models to study the possible penetration of alternative zero-emitting transport technologies gives the opportunity to perform an overall analysis of the effects that the development of innovative technologies has on the entire energy system and on the supply-side, devoted to the production of energy carriers such as hydrogen and electricity. Using an open-source modeling framework such as TEMOA, this work aims to compare the role of hydrogen and electric vehicles in the decarbonization of the transport sector. The analysis investigates the advantages and disadvantages of adopting the two options, from the economic point of view (costs associated with the two options) and the environmental one (looking at the emissions reduction perspectives). Moreover, an analysis on the profitability of the investments in hydrogen and electric vehicles will be performed. The study investigates the evolution of energy consumption and greenhouse gas emissions in different transportation modes (road, rail, navigation, and aviation) by detailed analysis of the full range of vehicles included in the techno-economic database used in the TEMOA model instance adopted for this work. The transparency of the analysis is guaranteed by the accessibility of the TEMOA models, based on an open-access source code and databases.

Keywords: battery electric vehicles, decarbonization, energy system optimization models, fuel cell vehicles, hydrogen, open-source modeling, TEMOA, transport

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Authors: Usama Bin Zubair, Syed Azhar Ali

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Introduction: Depression is emerging as a major public health problem in all parts of the world. Developing countries have a unique socioeconomic structure that affects the lives of its inhabitants in several ways. Going abroad for employment is one of the common social problems which have been faced by young males in developing countries. This included both highly qualified individuals as well as the labor class. Objective: To determine the difference in the presence of depressive symptoms among pregnant women with husbands living abroad and those with husbands living with them in Azad Jammu and Kashmir. Methods: The sample population comprised of pregnant women reporting for an antenatal checkup at Amna hospital Rawalakot. Cases constituted the pregnant women with husbands living abroad while controls were the pregnant women with husbands living with them. Patient health questionnaire-9 (PHQ-9) was used to record the presence and severity of depressive symptoms. Age, gestation, parity, rural or urban origin, education, level of family income, daily contact hours on the telephone or what’s app, previous pregnancy loss or complications, number of years abroad and visits to home per year were associated with the presence of depressive symptoms. Findings: The mean age of the study participants was 29.73 ±5.395 years. Sixty-six had significant depression in the case group, while 14 had in the control group (p-value<0.001). Education and rural background had a significant difference between the case and the control group. Less number of visits per year of the husband was strongly linked with the presence of depressive symptoms among the cases. Conclusion: Pregnant women with husbands abroad were found more prone to develop depressive symptoms as compared to those with husbands living with them. Special attention should be paid to the women whose husband had a lesser number of visits to the country.

Keywords: depression, pregnancy, lack of support, war zone

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Authors: Shaista Meghani, Rozina Karmaliani, Khairulnissa Ajani, Shireen Shahzad, Nadeem Ullah Khan

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Background: The concept of Family Presence During Resuscitation (FPDR) is gradually gaining recognition in western countries, however, it is rarely considered in South Asian countries including Pakistan. Over time, patients’ and families’ rights have gained recognition and healthcare has progressed to become more patient-family centered. Objectives: The objective of this study was to evaluate the impact of an educational program on the Knowledge, Attitude, and Practices (KAP) of healthcare professionals (HCPs) towards FPDR in Emergency Department (ED), at a tertiary care setting, in Karachi, Pakistan. Methods: This was a Pre-test and Post-test study design. A convenient universal sampling was done, and all ED nurses and physicians with more than one year of experience were eligible. The intervention included one-hour training sessions for physicians (three sessions) and nurses (eight sessions), The KAP of nurses and physicians were assessed immediately after (post-test I), and two weeks(post-test II) after the intervention using a pretested questionnaire. Results: The findings of the study revealed that the mean scores of knowledge and attitude of HCPs at both time points were statistically significant (p-value=<0.001), however, an insignificant difference was found on practice of FPDR (p-value=>0.05). Conclusion: The study findings recommend that the educational program on FPDR for HCPs needs to be offered on an ongoing basis. Moreover, training modules need to be developed for the staff, and formal guidelines need to be proposed for FPDR, through a multidisciplinary team approach.

Keywords: family presence, cardiopulmonary resuscitation, attitude, education, practices, health care professionals

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Authors: M. Abuqebitah, H. Tanyildizi, N. Yeyin, I. Cavdar, M. Demir, L. Kabasakal

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Aim: Targeted radionuclide therapy (TRT) is an increasingly used treatment modality for wide range of cancers. Presently dosimetry is highly required either to plan treatment or to ascertain the absorbed dose delivered to critical organs during treatment. Methods and Materials: The study comprised 7 patients suffered from prostate cancer with progressive disease and candidate to undergo Lu-177-DOTA-617 therapy following to PSMA- PET/CT imaging for all patients. (5.2±0.3 mCi) was intravenously injected. To evaluate bone marrow absorbed dose 2 cc blood samples were withdrawn in short variable times (3, 15, 30, 60, 180 minutes) after injection. Furthermore, whole body scans were performed using scintillation gama camera in 4, 24, 48, and 120 hours after injection and in order to quantify the activity taken up in the body, kidneys , liver, right parotid, and left parotid the geometric mean of anterior and posterior counts were determined through ROI analysis, after that background subtraction and attenuation correction were applied using patients PSMA- PET/CT images taking in a consideration: organ thickness, body thickness, and Hounsfield unites from CT scan. OLINDA/EXM dosimetry program was used for curve fitting, residence time calculation, and absorbed dose calculations. Findings: Absorbed doses of bone marrow, left kidney, right kidney, liver, left parotid, right parotid, total body were 1.28±0.52, 32.36±16.36, 32.7±13.68, 10.35±3.45, 38.67±21.29, 37.55±19.77, 2.25±0.95 (mGy/mCi), respectively. Conclusion: Our first results clarify that Lu-177-DOTA-617 is safe and reliable therapy as there were no complications seen. In the other hand, the observable variation in the absorbed dose of the critical organs among the patients necessitate patient-specific dosimetry approach to save body organs and particularly highly exposed kidneys and parotid gland.

Keywords: Lu-177-PSMA, prostate cancer, radionuclide therapy

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Authors: Titinan Pothong, Prasit Wangpakapattanawong, Stephen Elliott

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Shifting cultivation is an indigenous agricultural practice among upland people and has long been one of the major land-use systems in Southeast Asia. As a result, fallows and secondary forests have come to cover a large part of the region. However, they are increasingly being replaced by monocultures, such as corn cultivation. This is believed to be a main driver of deforestation and forest degradation, and one of the reasons behind the recurring winter smog crisis in Thailand and around Southeast Asia. Accurate biomass estimation of trees is important to quantify valuable carbon stocks and changes to these stocks in case of land use change. However, presently, Thailand lacks proper tools and optimal equations to quantify its carbon stocks, especially for secondary evergreen forests, including fallow areas after shifting cultivation and smaller trees with a diameter at breast height (DBH) of less than 5 cm. Developing new allometric equations to estimate biomass is urgently needed to accurately estimate and manage carbon storage in tropical secondary forests. This study established new equations using a destructive method at three study sites: approximately 50-year-old secondary forest, 4-year-old fallow, and 7-year-old fallow. Tree biomass was collected by harvesting 136 individual trees (including coppiced trees) from 23 species, with a DBH ranging from 1 to 31 cm. Oven-dried samples were sent for carbon analysis. Wood density was calculated from disk samples and samples collected with an increment borer from 79 species, including 35 species currently missing from the Global Wood Densities database. Several models were developed, showing that aboveground biomass (AGB) was strongly related to DBH, height (H), and wood density (WD). Including WD in the model was found to improve the accuracy of the AGB estimation. This study provides insights for reforestation management, and can be used to prepare baseline data for Thailand’s carbon stocks for the REDD+ and other carbon trading schemes. These may provide monetary incentives to stop illegal logging and deforestation for monoculture.

Keywords: aboveground biomass, allometric equation, carbon stock, secondary forest

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Authors: Ganetsou Evanthia, Koutsikos Emmanouil, Austin Anna Maria

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Information technology has long served the needs of individuals for learning and entertainment, but much less for children in sickness. The aim of the proposed online video game is to provide immersive learning opportunities as well as essential social and emotional scenarios for hospital-bound children with long-term illness. Online self-paced courses on chosen school subjects, including specialised software and multisensory assessments, aim at enhancing children’s academic achievement and sense of inclusion, while doctor minigames familiarise and educate young patients on their medical conditions. Online ethical dilemmas will offer children opportunities to contemplate on the importance of medical procedures and following assigned medication, often challenging for young patients; they will therefore reflect on their condition, reevaluate their perceptions about hospitalisation, and assume greater personal responsibility for their progress. Children’s emotional and psychosocial needs are addressed by engaging in social conventions, such as interactive, daily, collaborative mini games with other hospitalised peers, like virtual competitive sports games, weekly group psychodrama sessions, and online birthday parties or sleepovers. Social bonding is also fostered by having a virtual pet to interact with and take care of, as well as a virtual nurse to discuss and reflect on the mood of the day, engage in constructive dialogue and perspective taking, and offer reminders. Access to the platform will be available throughout the day depending on the patient’s health status. The program is designed to minimise escapism and feelings of exclusion, and can flexibly be adapted to offer post-treatment and a support online system at home.

Keywords: long-term illness, children, hospital, interactive games, cognitive, socioemotional development

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Authors: Daniele Zullino, Gabriel Thorens, Léonice Furtado, Federico Seragnoli, Radu Iuga, Louise Penzenstadler

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Context: Since the start of the 21st century, there has been a resurgence of interest in psychedelics, marked by a renewed focus on scientific investigations into their therapeutic potential. While psychedelic therapy has gained recognition for effectively treating depression and anxiety disorders, notable progress has been made in the clinical development of substances like psilocybin. Moreover, mounting evidence suggests promising applications of Lysergic acid diethylamide (LSD) and psilocybin in the field of addiction medicine. In Switzerland, compassionate treatment with LSD and psilocybin has been permitted since 2014 through exceptional licenses granted by the Federal Office of Public Health. This treatment approach is also available within the Geneva treatment program, extending its accessibility to patients undergoing opioid-assisted treatment involving substances like morphine and diacetylmorphine. The aim of this study is to assess the feasibility of psychedelic-assisted therapy in patients with opioid use disorder who are undergoing opioid-assisted treatment. This study addresses the question of whether psychedelic-assisted therapy can be successfully implemented in patients with opioid use disorder. It also explores the effects of psychedelic therapy on the patient's experiences and outcomes. Methodology: This is an open case series on six patients who have undergone at least one session with either LSD (100-200 micrograms) or psilocybin (20-40 mg). The patients were assessed using the Five Dimensional Altered States of Consciousness (5D-ASC)-Scale. The data were analyzed descriptively to identify patterns and trends in the patients' experiences. Results: The patients experienced substantial positive psychedelic effects during the psychedelic sessions without significant adverse effects. The patients reported positive experiences and improvements in their condition. Conclusion: The findings of this study support the feasibility and potential efficacy of psychedelic-assisted therapy in patients undergoing opioid-assisted treatment.

Keywords: psychedelics, psychedelic-assisted treatment, opioid use disorder, addiction, LSD, psilocybin

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Authors: Parul Goel, Jyeshtharaj B. Joshi, Arun K. Nayak

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Nucleate boiling is characterized by the nucleation, growth and departure of the tiny individual vapor bubbles that originate in the cavities or imperfections present in the heating surface. It finds a wide range of applications, e.g. in heat exchangers or steam generators, core cooling in power reactors or rockets, cooling of electronic circuits, owing to its highly efficient transfer of large amount of heat flux over small temperature differences. Hence, it is important to be able to predict the rate of heat transfer and the safety limit heat flux (critical heat flux, heat flux higher than this can lead to damage of the heating surface) applicable for any given system. A large number of experimental and analytical works exist in the literature, and are based on the idea that the knowledge of the bubble dynamics on the microscopic scale can lead to the understanding of the full picture of the boiling heat transfer. However, the existing data in the literature are scattered over various sets of conditions and often in disagreement with each other. The correlations obtained from such data are also limited to the range of conditions they were established for and no single correlation is applicable over a wide range of parameters. More recently, a number of researchers have been trying to remove empiricism in the heat transfer models to arrive at more phenomenological models using extensive numerical simulations; these models require state-of-the-art experimental data for a wide range of conditions, first for input and later, for their validation. With this idea in mind, experiments with sub-cooled and saturated demineralized water have been carried out under atmospheric pressure to study the bubble dynamics- growth rate, departure size and frequencies for nucleate pool boiling. A number of heating elements have been used to study the dependence of vapor bubble dynamics on the heater surface finish and heater geometry along with the experimental conditions like the degree of sub-cooling, super heat and the heat flux. An attempt has been made to compare the data obtained with the existing data and the correlations in the literature to generate an exhaustive database for the pool boiling conditions.

Keywords: experiment, boiling, bubbles, bubble dynamics, pool boiling

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Authors: Po-Ching Chou, Wen-Chen Liang, I. Chen Chen, Jong-Hau Hsu, Yuh-Jyh Jong

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Background：Cardiopulmonary complications seem to cause high morbidity and mortality in patients with neuromuscular diseases (NMD) but so far there is no domestic data reported in Taiwan. We, therefore attempted to analyze the factors to cause the death in NMD patients from our cohort. Methods：From 1998 to 2013, we retrospectively collected the information of the NMD patients treated and followed up in Kaohsiung Medical University Hospital. Forty-two patients with NMD who expired during these fifteen years were enrolled. The medical records of these patients were reviewed and the causes of death and the associated affecting factors were analyzed. Results：Eighteen patients with NMD (mean age=13.3, SD=12.4) with complete medical record and detailed information were finally included in this study, including spinal muscular atrophy (SMA) (n=9, 7/9: type 1), Duchenne muscular dystrophy (n=6), congenital muscular dystrophy (n=1), carnitine acyl-carnitine translocase (CACT) deficiency (n=1) and spinal muscular atrophy with respiratory distress (SMARD)(n=1). The place of death was in ICU (n=11, 61%), emergency room (n=3, 16.6%) or home (n=4, 22.2%). For SMA type 1 patients, most of them (71.4%, 5/7) died in emergency room or home and the other two expired during an ICU admission. The causes of death included acute respiratory failure due to pneumonia (n=13, 72.2 %), ventilator failure or dislocation (n=2, 11.1%), suffocation/choking (n=2, 11.1%), and heart failure with hypertrophic cardiomyopathy (n=1, 5.55%). Among the 15 patients died of respiratory failure or choking, 73.3% of the patients (n=11) received no ventilator care at home. 80% of the patients (n=12) received no cough assist at home. The patient died of cardiomyopathy received no medications for heart failure until the last admission. Conclusion: Respiratory failure and choking are the leading causes of death in NMD patients. Appropriate respiratory support and airway clearance play the critical role to reduce the mortality.

Keywords: neuromuscular disease, cause of death, tertiary care hospital, medical sciences

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Authors: A. D. Zikiryahodjaev, L. V. Bolotina, A. S. Sukhotko

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Purpose. To evaluate the expediency and timeliness of performance of surgical treatment as a component of multi-therapy treatment of patients with stage IV breast cancers. Materials and Methods. This investigation comparatively analyzed the results of complex treatment with or without surgery in patients with metastatic breast cancer. We analyzed retrospectively treatment experience of 196 patients with generalized breast cancer in the department of oncology and breast reconstructive surgery of P.A. Herzen Moscow Cancer Research Institute from 2000 to 2012. The average age was (58±1,1) years. Invasive ductul carcinoma was verified in128 patients (65,3%), invasive lobular carcinoma-33 (16,8%), complex form - 19 (9,7%). Complex palliative care involving drug and radiation therapies was performed in two patient groups. The first group includes 124 patients who underwent surgical intervention as complex treatment, the second group includes 72 patients with only medical therapy. Standard systemic therapy was given to all patients. Results. Overall, 3-and 5-year survival in fist group was 43,8 and 21%, in second - 15,1 and 9,3% respectively [p=0,00002 log-rank]. Median survival in patients with surgical treatment composed 32 months, in patients with only systemic therapy-21. The factors having influencing an influence on the prognosis and the quality of life outcomes for of patients with generalized breast cancer were are also studied: hormone-dependent tumor, Her2/neu hyper-expression, reproductive function status (age, menopause existence). Conclusion.Removing primary breast tumor in patients with generalized breast cancer improve long-term outcomes. Three- and five-year survival increased by 28,7 and 16,3% respectively, and median survival–for 11 months. These patients may benefit from resection of the breast tumor. One explanation for the effect of this resection is that reducing the tumor load influences metastatic growth.

Keywords: breast cancer, combination therapy, factors of prognosis, primary tumor

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Authors: Wayde Veldman, Ozlem T. Bishop, Igor Polikarpov

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In bacteria, mono and disaccharides are phosphorylated during uptake into the cell via the widely used phosphoenolpyruvate (PEP)-dependent phosphotransferase transport system. As an initial step in the phosphorylated disaccharide metabolism pathway, certain glycoside hydrolase family 1 (GH1) enzymes play a crucial role in releasing phosphorylated and non-phosphorylated monosaccharides. However, structural determinants for the specificity of these enzymes still need to be clarified. GH1 enzymes are known to have a wide array of functions. According to the CAZy database, there are twenty-one different enzymatic activities in the GH1 family. Here, the structure and substrate specificity of a GH1 enzyme from Bacillus licheniformis, hereafter known as BlBglH, was investigated. The sequence of the enzyme BlBglH was compared to the sequences of other characterized GH1 enzymes using sequence alignment, sequence identity calculations, phylogenetic analysis, and motif discovery. Through these various analyses, BlBglH was found to have sequence features characteristic of the 6-phospho-β-glucosidase activity enzymes. Additionally, motif and structure comparisons of the three most commonly studied GH1 enzyme-activities revealed a shared loop amongst the different structures that consist of different sequence motifs – this loop is thought to guide specific substrates (depending on activity) towards the active-site. To further affirm BlBglH enzyme activity, molecular docking and molecular dynamics simulations were performed. Docking was carried out using 6-phospho-β-glucosidase enzyme-activity positive (p-Nitrophenyl-beta-D-glucoside-6-phosphate) and negative (p-Nitrophenyl-beta-D-galactoside-6-phosphate) control ligands, followed by 400 ns molecular dynamics simulations. The positive-control ligand maintained favourable interactions within the active site until the end of the simulation. The negative-control ligand was observed exiting the enzyme at 287 ns. Binding free energy calculations showed that the positive-control complex had a substantially more favourable binding energy compared to the negative-control complex. Jointly, the findings of this study suggest that the BlBglH enzyme possesses 6-phospho-β-glucosidase enzymatic activity.

Keywords: 6-P-β-glucosidase, glycoside hydrolase 1, molecular dynamics, sequence analysis, substrate specificity

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Authors: Amit Syal, Madeline Grade, Alister Martin

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Background: Cross-sectional and longitudinal studies demonstrate an association between health and voting. Furthermore, voting enables populations to support policies that impact their health via social determinants like income, education, housing, and healthcare access. Unfortunately, many barriers exist which disproportionately affect the civic participation of certain minority groups. Health professionals have an important role to play in addressing the civic health of all patients and empowering underrepresented communities. Description: Vot-ER is a non-partisan, nonprofit organization that aims to reduce barriers to civic participation by helping patients register to vote while in healthcare settings. The initial approach involved iPad-based kiosks in the emergency department waiting rooms, allowing patients to register themselves while waiting. After the COVID-19 pandemic began, Vot-ER expanded its touchless digital approaches. Vot-ER provides healthcare workers across the country with “Healthy Democracy Kits” consisting of badge backers, posters, discharge paperwork, and other resources. These contain QR and text codes that direct users to an online platform for registering to vote or requesting a mail-in ballot, available in English or Spanish. Outcomes: From May to November 2020, Vot-ER helped prepare 46,320 people to vote. 13,192 individual healthcare providers across all 50 states signed up for and received Healthy Democracy Kits. 80 medical schools participated in the Healthy Democracy Campaign competition. Over 500 institutions ordered site-based materials. Conclusions: A healthy democracy is one in which all individuals in a community have equal and fair opportunities for their voices to be heard. Healthcare settings, such as hospitals, are appropriate and effective venues for increasing both voter registration and education.

Keywords: civic health, enfranchisement, physician, voting

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Authors: Eunkyo Kang, Jihye Lee, Jiyeon Choo

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Background: Pediatric palliative care has been increasing, and the number of studies has focused on the age at which pediatric patient can be notified their terminal illness, pediatric advanced care planning (ACP) and palliative care. However, there is a lack of research on health professionals’ perception. Aim: We aimed to investigate the perceptions of healthcare professionals about appropriate age disclosing terminal illness, awareness of ACP, and the relationship between ACP knowledge and the preference for palliative care for children. Methods: We administered nationwide questionnaires to 928 physicians from the 12 hospitals and the Korean Medical Association and 1,241 individuals of the general Korean population. We asked about the age at which the pediatric patients could be notified of their terminal illness, by 4 groups; 4 years old or older, 12 years old or older, 15 years old or older, or not. In addition, we surveyed the questionnaires about the knowledge of ACP of the medical staff, the preference of the pediatric hospice palliative care, aggressive treatment, and life-sustaining treatment preference. Results: In the appropriate age disclosing terminal illness, there were more respondents in the physicians than in the general population who thought that it was possible even at a younger age. Palliative care preference in pediatric patients who were expected to expire within months was higher when health care professionals had knowledge of ACPs compared to those without knowledge. The same results were obtained when deaths were expected within weeks or days. The age of the terminal status notification, the health care professionals who thought to be available at a lower age have a higher preference for palliative care and has less preference for aggressive treatment and life-sustaining treatment. Conclusion: Despite the importance of pediatric palliative care, our study confirmed that there is a difference in the preference of the health care professionals for pediatric palliative care according to the ACP knowledge of the medical staff or the appropriate age disclosing terminal illness. Future research should focus on strategies for inducing changes in perceptions of health care professionals and identifying other obstacles for the pediatric palliative care.

Keywords: pediatric palliative care, disclosing terminal illness, palliative care, advanced care planning

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Authors: P. Moskal, T. Bednarski, P. Bialas, E. Czerwinski, A. Gajos, A. Gruntowski, D. Kaminska, L. Kaplon, G. Korcyl, P. Kowalski, T. Kozik, W. Krzemien, E. Kubicz, Sz. Niedzwiecki, M. Palka, L. Raczynski, Z. Rudy, P. Salabura, N. G. Sharma, M. Silarski, A. Slomski, J. Smyrski, A. Strzelecki, A. Wieczorek, W. Wislicki, M. Zielinski, N. Zon

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A new concept and results of the performance tests of the TOF-PET detection system developed at the Jagiellonian University will be presented. The novelty of the concept lies in employing long strips of polymer scintillators instead of crystals as detectors of annihilation quanta, and in using predominantly the timing of signals instead of their amplitudes for the reconstruction of Lines-of-Response. The diagnostic chamber consists of plastic scintillator strips readout by pairs of photo multipliers arranged axially around a cylindrical surface. To take advantage of the superior timing properties of plastic scintillators the signals are probed in the voltage domain with the accuracy of 20 ps by a newly developed electronics, and the data are collected by the novel trigger-less and reconfigurable data acquisition system. The hit-position and hit-time are reconstructed by the dedicated reconstruction methods based on the compressing sensing theory and the library of synchronized model signals. The solutions are subject to twelve patent applications. So far a time-of-flight resolution of ~120 ps (sigma) was achieved for a double-strip prototype with 30 cm field-of-view (FOV). It is by more than a factor of two better than TOF resolution achievable in current TOF-PET modalities and at the same time the FOV of 30 cm long prototype is significantly larger with respect to typical commercial PET devices. The Jagiellonian PET (J-PET) detector with plastic scintillators arranged axially possesses also another advantage. Its diagnostic chamber is free of any electronic devices and magnetic materials thus giving unique possibilities of combining J-PET with CT and J-PET with MRI for scanning the same part of a patient at the same time with both methods.

Keywords: PET-CT, PET-MRI, TOF-PET, scintillator

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Authors: V. Veeraprathap, G. S. Harish, G. Narendra Kumar

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Uncontrolled growth of abnormal cells in the lung in the form of tumor can be either benign (non-cancerous) or malignant (cancerous). Patients with Lung Cancer (LC) have an average of five years life span expectancy provided diagnosis, detection and prediction, which reduces many treatment options to risk of invasive surgery increasing survival rate. Computed Tomography (CT), Positron Emission Tomography (PET), and Magnetic Resonance Imaging (MRI) for earlier detection of cancer are common. Gaussian filter along with median filter used for smoothing and noise removal, Histogram Equalization (HE) for image enhancement gives the best results without inviting further opinions. Lung cavities are extracted and the background portion other than two lung cavities is completely removed with right and left lungs segmented separately. Region properties measurements area, perimeter, diameter, centroid and eccentricity measured for the tumor segmented image, while texture is characterized by Gray-Level Co-occurrence Matrix (GLCM) functions, feature extraction provides Region of Interest (ROI) given as input to classifier. Two levels of classifications, K-Nearest Neighbor (KNN) is used for determining patient condition as normal or abnormal, while Artificial Neural Networks (ANN) is used for identifying the cancer stage is employed. Discrete Wavelet Transform (DWT) algorithm is used for the main feature extraction leading to best efficiency. The developed technology finds encouraging results for real time information and on line detection for future research.

Keywords: artificial neural networks, ANN, discrete wavelet transform, DWT, gray-level co-occurrence matrix, GLCM, k-nearest neighbor, KNN, region of interest, ROI

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Authors: Mohamed El Kory Yacoub, Ahmed Bezeid El Mamy Beyatt, Djibril Barry, Yanogo Pauline, Nicolas Meda

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Introduction: Rift Valley Fever is a zoonotic arbovirosis that severely affects ruminants, as well as humans. It causes abortions in pregnant females and deaths in young animals. The disease occurs during heavy rains followed by large numbers of mosquito vectors. The objective of this work is to evaluate the surveillance system for Rift Valley Fever. Methods: We conducted an evaluation of the Rift Valley Fiver surveillance system. Data were collected from the analysis of the national database of the Mauritanian Network of Animal Disease Epidemiological Surveillance at the Ministry of Rural Development, of RVF cases notified from the whole national territory, of questionnaires and interviews with all persons involved in RVF surveillance at the central level. The quality of the system was assessed by analyzing the quantitative attributes defined by the Centers for Disease Control and Prevention. Results: In 2019, 443 cases of RVF were notified by the surveillance system, of which 36 were positive. Among the notified cases of Rift Valley Fever, the 0- to the 3-year-old age group of small ruminants was the most represented with 49.21% of cases, followed by 33.33%, which was recorded in large ruminants in the 0 to 7-year-old age group, 11.11% of cases were older than seven years. The completeness of the data varied between 14.2% (age) and 100% (species). Most positive cases were recorded between October and November 2019 in seven different regions. Attribute analysis showed that 87% of the respondents were able to use the case definition well, and 78.8% said they were familiar with the reporting and feedback loop of the Rift Valley Fever data. 90.3% of the respondents found it easy, while 95% of them responded that it was easy for them to transmit their data to the next level. Conclusions: The epidemiological surveillance system for Rift Valley Fever in Mauritania is simple and representative. However, data quality, stability, and responsiveness are average, as the diagnosis of the disease requires laboratory confirmation and the average delay for this confirmation is long (13 days). Consequently, the lack of completeness of the recorded data and of description of cases in terms of time-place-animal, associated with the delay between the stages of the surveillance system can make prevention, early detection of epidemics, and the initiation of measures for an adequate response difficult.

Keywords: evaluation, epidemiological surveillance system, rift valley fever, mauritania, ruminants

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Authors: Ying Liang, Na Li

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Lipo-alkaloid is a kind of C19-norditerpenoid alkaloids existed in Aconitum species, which usually contains an aconitane skeleton and one or two fatty acid residues. The structures are very similar to that of diester-type alkaloids, which are considered as the main bioactive components in Aconitum carmichaelii. They have anti-inflammatory, anti-nociceptive, and anti-proliferative activities. So far, more than 200 lipo-alkaloids were reported from plants, semisynthesis, and biotransformations. In our research, by the combination of ultra-high performance liquid chromatography-quadruple-time of flight mass spectrometry (UHPLC-Q-TOF-MS) and an in-house database, 148 lipo-alkaloids were identified from A. carmichaelii, including 93 potential new compounds and 38 compounds with oxygenated fatty acid moieties. To our knowledge, this is the first time of the reporting of the oxygenated fatty acids as the side chains in naturally-occurring lipo-alkaloids. Considering the fatty acid residues in lipo-alkaloids should come from the free acids in the plant, the fatty acids and their relationship with lipo-alkaloids were further investigated by GC-MS and LC-MS. Among 17 fatty acids identified by GC-MS, 12 were detected as the side chains of lipo-alkaloids, which accounted for about 1/3 of total lipo-alkaloids, while these fatty acid residues were less than 1/4 of total fatty acid residues. And, total of 37 fatty acids were determined by UHPCL-Q-TOF-MS, including 18 oxidized fatty acids firstly identified from A. carmichaelii. These fatty acids were observed as the side chains of lipo-alkaloids. In addition, although over 140 lipo-alkaloids were identified, six lipo-alkaloids, 8-O-linoleoyl-14-benzoylmesaconine (1), 8-O-linoleoyl-14-benzoylaconine (2), 8-O-palmitoyl-14-benzoylmesaconine (3), 8-O-oleoyl-14-benzoylmesaconine (4), 8-O-pal-benzoylaconine (5), and 8-O-ole-Benzoylaconine (6), were found to be the main components, which accounted for over 90% content of total lipo-alkaloids. Therefore, using these six components as standards, a UHPLC-Triple Quadrupole-MS (UHPLC-QQQ-MS) approach was established to investigate the influence of processing on the contents of lipo-alkaloids. Although it was commonly supposed that the contents of lipo-alkaloids increased after processing, our research showed that no significant change was observed before and after processing. Using the same methods, the lipo-alkaloids in the lateral roots of A. carmichaelii and the roots of A. kusnezoffii were determined and quantified. The contents of lipo-alkaloids in A. kusnezoffii were close to that of the parent roots of A. carmichaelii, while the lateral roots had less lipo-alkaloids than the parent roots. This work was supported by Macao Science and Technology Development Fund (086/2013/A3 and 003/2016/A1).

Keywords: Aconitum carmichaelii, fatty acids, GC-MS, LC-MS, lipo-alkaloids

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Authors: Ya-Ching Fu, An-Kuo Chou, Boon-Fatt Tan, Chi-Nien Chen, Wen-Chien Yang, Pou-Leng Cheong

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Blind oro-/naso-pharyngeal suction and feeding tube placement are very common practices in neonatal intensive care unit. Though esophageal perforation is a rare complication of these instrumentations, its prevalence is highest in extremely premature neonates. Due to its association with significant morbidity (including respiratory deterioration, pneumothorax, and sepsis) and even mortality, it is an important issue to prevent this iatrogenic complication in the field of premature care. We demonstrate an esophageal perforation in an extreme-low-birth-weight neonate after oro-gastric tube placement. This female baby weighing 680 grams was delivered by caesarean section at 25 weeks of gestational age. She initially received oro-tracheal intubation with mechanical ventilation which was smoothly weaned to non-invasive positive-pressure ventilation at 7-day-old. However, after insertion of a 5-French oro-gastric tube, the baby’s condition suddenly worsened with apnea requiring mechanical ventilation. Her chest radiogram showed the oro-gastric tube in right pleural space, and thus another oro-gastric tube was replaced, and its position was radiographically confirmed. The malpositioned tube was then removed. The baby received 2-week course of intravenous antibiotics for her esophageal perforation. Feeding was then reintroduced and increased to full feeds in a smooth course. She was discharged at 107-day-old. Esophageal perforation in newborn is very rare. Sudden respiratory deterioration in a neonate after naso-/oro-gastric tube placement should alarm us to consider esophageal perforation, and further radiological investigation is required for the diagnosis. Tube materials, patient condition, and age are major risk factors of esophageal perforation. The use of softer tube material, such as silicone, in extreme premature baby might prevent this fetal complication.

Keywords: esophageal perforation, preterm, newborn, feeding tube

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Authors: Swati Kapoor, Rajeev Upreti, Monica Mahajan, Abhaya Indrayan, Dinesh Srivastava

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Enteric Fever is caused by gram negative bacilli Salmonella typhi and paratyphi. It is associated with high morbidity and mortality worldwide. Timely initiation of treatment is a crucial step for prevention of any complications. Cultures of body fluids are diagnostic, but not always conclusive or practically feasible in most centers. Moreover, the results of cultures delay the treatment initiation. Serological tests lack diagnostic value. The blood counts can offer a promising option in diagnosis. A retrospective study to find out the relevance of leucopenia and eosinopenia was conducted on 203 culture proven enteric fever patients and 159 culture proven non-enteric fever patients in a tertiary care hospital in New Delhi. The patient details were retrieved from the electronic medical records section of the hospital. Absolute eosinopenia was considered as absolute eosinophil count (AEC) of less than 40/mm³ (normal level: 40-400/mm³) using LH-750 Beckman Coulter Automated machine. Leucopoenia was defined as total leucocyte count (TLC) of less than 4 X 10⁹/l. Blood cultures were done using BacT/ALERT FA plus automated blood culture system before first antibiotic dose was given. Case and control groups were compared using Pearson Chi square test. It was observed that absolute eosinophil count (AEC) of 0-19/mm³ was a significant finding (p < 0.001) in enteric fever patients, whereas leucopenia was not a significant finding (p=0.096). Using Receiving Operating Characteristic (ROC) curves, it was observed that patients with both AEC < 14/mm³ and TCL < 8 x 10⁹/l had 95.6% chance of being diagnosed as enteric fever and only 4.4% chance of being diagnosed as non-enteric fever. This result was highly significant with p < 0.001. This is a very useful association of AEC and TLC found in enteric fever patients of this study which can be used for the early initiation of treatment in clinically suspected enteric fever patients.

Keywords: absolute eosinopenia, absolute eosinophil count, enteric fever, leucopenia, total leucocyte count

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Authors: Julio Silva, Lia Hasenclever, Gilson G. Silva Jr.

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The aim of this paper is to check possible convergence in health measures (aged-standard rate of morbidity and mortality) for communicable diseases between developed and developing countries, conditional to productive structures features. Understanding the interrelations between health patterns and economic development is particularly important in the context of low- and middle-income countries, where economic development comes along with deep social inequality. Developing countries with less diversified productive structures (measured through complexity index) but high heterogeneous inter-sectorial labor productivity (using as a proxy inter-sectorial coefficient of variation of labor productivity) has on average low health levels in communicable diseases compared to developed countries with high diversified productive structures and low labor market heterogeneity. Structural heterogeneity and productive diversification may have influence on health levels even considering per capita income. We set up a panel data for 139 countries from 1995 to 2015, joining several data about the countries, as economic development, health, and health system coverage, environmental and socioeconomic aspects. This information was obtained from World Bank, International Labour Organization, Atlas of Economic Complexity, United Nation (Development Report) and Institute for Health Metrics and Evaluation Database. Econometric panel models evidence shows that the level of communicable diseases has a positive relationship with structural heterogeneity, even considering other factors as per capita income. On the other hand, the recent process of convergence in terms of communicable diseases have been motivated for other reasons not directly related to productive structure, as health system coverage and environmental aspects. These evidences suggest a joint dynamics between the unequal distribution of communicable diseases and countries' productive structure aspects. These set of evidence are quite important to public policy as meet the health aims in Millennium Development Goals. It also highlights the importance of the process of structural change as fundamental to shift the levels of health in terms of communicable diseases and can contribute to the debate between the relation of economic development and health patterns changes.

Keywords: economic development, inequality, population health, structural change

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Authors: En-Tzu Wang, Ting-Ann Wang, Yi-Hui Shen, Yu-Min Chou, Chi-Tai Fang, Chin-Hui Yang

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Background and purpose: A mass varicella immunization program was established to provide free 1-dose vaccination for all 1-year-old children throughout Taiwan since 2004. The epidemiological characteristics and disease burden of varicella from 2000 to 2012 was investigated and the results will be essential to refine the national immunization policy. Method: We included patients (n = 17,838–164,245) with ICD-9-CM codes 052 (chickenpox) from the 2000 to 2012 National Health Insurance Database. The age, period, and cohort-specific incidence of varicella were calculated. The hospital admission rate, medical costs and indirect costs from the societal perspective of varicella including travel costs to the medical facility, registration fee, productivity losses of the patients and caregivers were also estimated. Result: There were 979,252 patients for medical treatment due to varicella from 2000 to 2012 in Taiwan. The implementation of a routine childhood varicella vaccination program has resulted in 87% decline in morbidity (881.49 to 115.17 per 100,000). The average age of patients increased from 7.9 years to 16.3 years. The overall varicella-related hospital admission rate was 15.5 per 1000 patients, and peaked in the groups of infants younger than 1 year, adults aged from 20 to 39 years and elders over 70 years. Among patients admitted to hospital, 33.5% of them had one or more complications. Patients with underlying diseases had higher admission rate (241.6 per 1,000) and longer duration of hospital stay (6.61 days vs. 4.76 days). The annual varicella-related medical expense declined after 2002 and the proportion of medical costs for admission has increased to 42%. The annual indirect costs from the societal perspective of varicella were 5.29 to 9.63 times higher than varicella-related medical costs. Every one dollar invested in the varicella immunization program, 2.97 dollars of medical and social costs were saved on average. Conclusion: The dramatic decline in morbidity, hospitalization, medical and social costs of varicella can be directly attributed to the implementation of the mass immunization program. Two-dose vaccination is recommended for both children with underlying diseases and susceptible adults to prevent serious complications and hospitalizations.

Keywords: disease burden, epidemiology, medical and social costs, varicella, varicella vaccine

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Authors: Kristina Jansen, Maximilian Lennartz, Patrick Lebok, Guido Sauter, Ronald Simon, David Dum, Stefan Steurer

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DOG1 (Discovered on GIST1) is a voltage-gated calcium-activated chloride and bicarbonate channel that is highly expressed in interstitial cells of Cajal and in gastrointestinal stromal tumors (GIST) derived from Cajal cells. To systematically determine in what tumor entities and normal tissue types DOG1 may be further expressed, a tissue microarray (TMA) containing 15,965 samples from 121 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry. DOG1 immunostaining was found in 67 tumor types, including GIST (95.7%), esophageal squamous cell carcinoma (31.9%), pancreatic ductal adenocarcinoma (33.6%), adenocarcinoma of the Papilla Vateri (20%), squamous cell carcinoma of the vulva (15.8%) and the oral cavity (15.3%), mucinous ovarian cancer (15.3%), esophageal adenocarcinoma (12.5%), endometrioid endometrial cancer (12.1%), neuroendocrine carcinoma of the colon (11.1%) and diffuse gastric adenocarcinoma (11%). Low level-DOG1 immunostaining was seen in 17 additional tumor entities. DOG1 expression was unrelated to histopathological parameters of tumor aggressiveness and/or patient prognosis in cancers of the breast (n=1,002), urinary bladder (975), ovary (469), endometrium (173), stomach (233), and thyroid gland (512). High DOG1 expression was linked to estrogen receptor expression in breast cancer (p<0.0001) and the absence of HPV infection in squamous cell carcinomas (p=0.0008). In conclusion, our data identify several tumor entities that can show DOG1 expression levels at similar levels as in GIST. Although DOG1 is tightly linked to a diagnosis of GIST in spindle cell tumors, the differential diagnosis is much broader in DOG1 positive epithelioid neoplasms.

Keywords: biomarker, DOG1, immunohistochemistry, tissue microarray

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