Search results for: Yu Lung Lau

Authors: Paresh Patel, Priya Patel, Vaidehi Sorathiya, Navin Sheth

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The aim of present work was to fabricate Salmeterol Xinafoate (SX) metered dose inhaler (MDI) for asthma and to evaluate the SX loaded solid lipid nanoparticles (SLNs) for pulmonary delivery. Solid lipid nanoparticles can be used to deliver particles to the lungs via MDI. A modified solvent emulsification diffusion technique was used to prepare Salmeterol Xinafoate loaded solid lipid nanoparticles by using compritol 888 ATO as lipid, tween 80 as surfactant, D-mannitol as cryoprotecting agent and L-leucine was used to improve aerosolization behaviour. Box-Behnken design was applied with 17 runs. 3-D surface response plots and contour plots were drawn and optimized formulation was selected based on minimum particle size and maximum % EE. % yield, in vitro diffusion study, scanning electron microscopy, X-ray diffraction, DSC, FTIR also characterized. Particle size, zeta potential analyzed by Zetatrac particle size analyzer and aerodynamic properties was carried out by cascade impactor. Pre convulsion time was examined for control group, treatment group and compare with marketed group. MDI was evaluated for leakage test, flammability test, spray test and content per puff. By experimental design, particle size and % EE found to be in range between 119-337 nm and 62.04-76.77% by solvent emulsification diffusion technique. Morphologically, particles have spherical shape and uniform distribution. DSC & FTIR study showed that no interaction between drug and excipients. Zeta potential shows good stability of SLNs. % respirable fraction found to be 52.78% indicating reach to the deep part of lung such as alveoli. Animal study showed that fabricated MDI protect the lungs against histamine induced bronchospasm in guinea pigs. MDI showed sphericity of particle in spray pattern, 96.34% content per puff and non-flammable. SLNs prepared by Solvent emulsification diffusion technique provide desirable size for deposition into the alveoli. This delivery platform opens up a wide range of treatment application of pulmonary disease like asthma via solid lipid nanoparticles.

Keywords: salmeterol xinafoate, solid lipid nanoparticles, box-behnken design, solvent emulsification diffusion technique, pulmonary delivery

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Authors: Md. Fazlul Karim, Ashik Sharfaraz, Aysha Ferdoushi

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Background: Computational medicinal chemistry approaches are used for designing and identifying new drug-like molecules, predicting properties and pharmacological activities, and optimizing lead compounds in drug development. SIRT7, a nicotinamide adenine dinucleotide (NAD+)-dependent deacylase which regulates aging, is an emerging target for cancer therapy with mounting evidence that SIRT7 downregulation plays important roles in reversing cancer phenotypes and suppressing tumor growth. Activation or altered expression of SIRT7 is associated with the progression and invasion of various cancers, including liver, breast, gastric, prostate, and non-small cell lung cancer. Objectives: The goal of this work was to identify potent and selective bioactive candidate inhibitors of SIRT7 by in silico screening of small molecule compounds obtained from Nigella sativa (N. sativa). Methods: SIRT7 structure was retrieved from The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), and its active site was identified using CASTp and metaPocket. Molecular docking simulation was performed with PyRx 0.8 virtual screening software. Drug-likeness properties were tested using SwissADME and pkCSM. In silico toxicity was evaluated by Osiris Property Explorer. Bioactivity was predicted by Molinspiration software. Antitumor activity was screened for Prediction of Activity Spectra for Substances (PASS) using Way2Drug web server. Molecular dynamics (MD) simulation was carried out by Desmond v3.6 package. Results: A total of 159 bioactive compounds from the N. Sativa were screened against the SIRT7 enzyme. Five bioactive compounds: chrysin (CID:5281607), pinocembrin (CID:68071), nigellidine (CID:136828302), nigellicine (CID:11402337), and epicatechin (CID:72276) were identified as potent SIRT7 anti-cancer candidates after docking score evaluation and applying Lipinski's Rule of Five. Finally, MD simulation identified Chrysin as the top SIRT7 anti-cancer candidate molecule. Conclusion: Chrysin, which shows a potential inhibitory effect against SIRT7, can act as a possible anti-cancer drug candidate. This inhibitor warrants further evaluation to check its pharmacokinetics and pharmacodynamics properties both in vitro and in vivo.

Keywords: SIRT7, antitumor, molecular docking, molecular dynamics simulation

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Authors: Hani M. Alothaid, Louise Robson, Richmond Muimo

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Cystic fibrosis (CF) is a disease that affects respiratory function and in EU it affects about 1 in 2,500 live births with an average 40-year life expectancy. This disease caused by mutations within the gene encoding the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) chloride channel leading to dysregulation of epithelial fluid transport and chronic lung inflammation, suggesting functional alterations of immune cells. In airways, CFTR been found to form a functional complex with S100A10 and AnxA2 in a cAMP/PKA dependent manner. The multiprotein complex of AnxA2-S100A10 and CFTR is also regulated by calcineurin. The aim of this study was i) to investigate whether chloride ion (Cl−) channels are activated by Pseudomonas aeruginosa lipopolysaccharide (LPS from PA), ii) if this activation is regulated by cAMP/PKA/calcineurin pathway and iii) to investigate the role of LPS-activated Cl− channels in the release of pro-inflammatory cytokines by immune cells. Human peripheral blood monocytes were used in the study. Whole-cell patch records showed that LPS from PA can activate Cl− channels, including CFTR and outwardly-rectifying Cl− channel (ORCC). This activation appears to require an intact PKA/calcineurin signalling pathway. The Gout in the presence of LPS was significantly inhibited by diisothiocyanatostilbene-disulfonic acid (DIDS), an ORCC blocker (p<0.001). The Gout was further suppressed by CFTR(inh)-172, a specific inhibitor for CFTR channels (p<0.001). Monocytes pre-incubated with PKA inhibitor or calcineurin inhibitor before stimulated with LPS from PA that were resulted in DIDS and CFTR(inh)-172 insensitive currents. Activation of both ORCC and CFTR was however, observed in response to monocytes exposure to LPS. Additionally, ELISA showed that the CFTR and ORCC play a role in mediating the release of pro-inflammatory cytokines such as IL-1β upon exposure of monocytes to LPS. However, this secretion was significantly inhibited due to CFTR and ORCC inhibition. However, Cl− may play a role in IL-1β release independent of cAMP/PKA/calcineurin signalling due to the enhancement of IL-1β secretion even when cAMP/PKA/calcineurin pathway was inhibited. In conclusion, our data confirmed that LPS from PA activates Cl− channels in human peripheral blood monocytes. Our data also confirmed that Cl− channels were involved in IL-1β release in monocytes upon exposure to LPS. However, it has been found that PKA and calcineurin does not seem to influence the Cl− dependent cytokine release.

Keywords: cystic fibrosis, CFTR, Annexin A2, S100A10, PP2B, PKA, outwardly-rectifying Cl− channel, Pseudomonas aeruginosa

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Authors: Alexander Heckman, Rohan Goswami, Zachi Attia, Paul Friedman, Peter Noseworthy, Demilade Adedinsewo, Pablo Moreno-Franco, Rickey Carter, Tathagat Narula

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Background: Postoperative atrial fibrillation (POAF) is associated with adverse health consequences, higher costs, and longer hospital stays. Utilizing existing predictive models that rely on clinical variables and circulating biomarkers, multiple societies have published recommendations on the treatment and prevention of POAF. Although reasonably practical, there is room for improvement and automation to help individualize treatment strategies and reduce associated complications. Methods and Results: In this retrospective cohort study of solid organ transplant recipients, we evaluated the diagnostic utility of a previously developed AI-based ECG prediction for silent AF on the development of POAF within 30 days of transplant. A total of 2261 non-cardiac transplant patients without a preexisting diagnosis of AF were found to have a 5.8% (133/2261) incidence of POAF. While there were no apparent sex differences in POAF incidence (5.8% males vs. 6.0% females, p=.80), there were differences by race and ethnicity (p<0.001 and 0.035, respectively). The incidence in white transplanted patients was 7.2% (117/1628), whereas the incidence in black patients was 1.4% (6/430). Lung transplant recipients had the highest incidence of postoperative AF (17.4%, 37/213), followed by liver (5.6%, 56/1002) and kidney (3.6%, 32/895) recipients. The AUROC in the sample was 0.62 (95% CI: 0.58-0.67). The relatively low discrimination may result from undiagnosed AF in the sample. In particular, 1,177 patients had at least 1 AI-ECG screen for AF pre-transplant above .10, a value slightly higher than the published threshold of 0.08. The incidence of POAF in the 1104 patients without an elevated prediction pre-transplant was lower (3.7% vs. 8.0%; p<0.001). While this supported the hypothesis that potentially undiagnosed AF may have contributed to the diagnosis of POAF, the utility of the existing AI-ECG screening algorithm remained modest. When the prediction for POAF was made using the first postoperative ECG in the sample without an elevated screen pre-transplant (n=1084 on account of n=20 missing postoperative ECG), the AUROC was 0.66 (95% CI: 0.57-0.75). While this discrimination is relatively low, at a threshold of 0.08, the AI-ECG algorithm had a 98% (95% CI: 97 – 99%) negative predictive value at a sensitivity of 66% (95% CI: 49-80%). Conclusions: This study's principal finding is that the incidence of POAF is rare, and a considerable fraction of the POAF cases may be latent and undiagnosed. The high negative predictive value of AI-ECG screening suggests utility for prioritizing monitoring and evaluation on transplant patients with a positive AI-ECG screening. Further development and refinement of a post-transplant-specific algorithm may be warranted further to enhance the diagnostic yield of the ECG-based screening.

Keywords: artificial intelligence, atrial fibrillation, cardiology, transplant, medicine, ECG, machine learning

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Authors: Yulistiani Yulistiani, Wenny Nilamsari, Laurin Winarso, Rizkiya Rizkiya, Zamrotul Izzah, Budi Suprapti, Arif Bachtiar

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Approximately, a million new cases of TB have been found out per year, making Indonesia as the second greatest country with TBC after India. Nevertheless, until now, there are still many patients failure to conventional therapy with oral anti tuberculosis. Thus, the discovery of supplement therapy is urgently needed. Many studies showed that probiotic had the positive impact in lung diseases, diarrhea, pneumonia and it was attributed to its capability to balance the level of cytokine pro-inflammatory and anti-inflammatory. It was demonstrated in active disease the production of IFN-γ is strongly depressed and IL-10 level increases. This study aimed to investigate the effect of probiotic (multi strains) and vitamin B complex supplementation on IFN-γ and IL-10 level in patients with TB infection during intensive phase therapy. A randomized controlled trial, open labeled was conducted in TB patients with the following criteria: 1) age 18-55 years old 2) receiving oral antituberculosis during intensive therapy 3) not using probiotic, vitamin B1, B6, B12 2 weeks before enrollment 4) willing to participate in this study and signed an informed consent. While, patients with HIV, pregnant, had the history of diabetes mellitus, using corticosteroid or other immunosuppressants were excluded. IFN-γ and IL-10 levels were drawn before observation and after a month observation. The assay was performed by ELISA. There were seven patients in treated group and five patients in controlled group obtained in this study. Between groups, there was no statistical difference in comorbid, age, and disease duration. The mean level of IFN-γ after a month observation increased in treated group and controlled group, which were 31.47 ± 105.46 pg/ml and 15.09 ± 24.23 pg/ml, respectively (p> 0.005). Although, there were not statistically different, treated group showed a greater increase of IFN-γ level than that of the controlled group. IFN-γ plays an important role in immune response to Mycobacterium Tuberculosis, by activating macrofag, monosit and furthermore killing Mycobacterium Tuberculosis. Thus the level was expected to increase after supplementation with probiotic and Vitamin B complex. While the mean level of IL-10 also increased after one month observation in the treated group and controlled group (4.28 ± 12.29 pg/ml and 5.77± 6.21 pg/ml, respectively) (p>0.005). To be compared, the increased level of IL-10 in the treated group were lower than the controlled group, although it was not statistically different. IL-10 is a cytokine anti-inflammatory, thus, the level after the observation was expected to decrease. In this study, a month therapy of probiotic and vitamin B complex was not able to demonstrate the decrease of the IL-10 level. It is suggested to prolong observation up to 2 months, because, in intensive phase, the level of cytokine anti-inflammatory is very high, so the longer therapy is needed. It is indicated that supplementation therapy with probiotic and vitamin B complex to Oral Anti-Tuberculosis may have a positive effect on increasing IFN-γ level and slowing the progression of IL-10.

Keywords: TB Infection, IFN-γ, IL-10, probiotic, vitamin B complex

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Authors: Kyung Jin Kim, Jiwon Kwak, Jae-Hoon Lee, Soo Suk Lee

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MicroRNAs (miRNA) are a class of endogenous, single-stranded, small, and non-protein coding RNA molecules typically 20-25 nucleotides long. They are thought to regulate the expression of other genes in a broad range by binding to 3’- untranslated regions (3’-UTRs) of specific mRNAs. The detection of miRNAs is very important for understanding of the function of these molecules and in the diagnosis of variety of human diseases. However, detection of miRNAs is very challenging because of their short length and high sequence similarities within miRNA families. So, a simple-to-use, low-cost, and highly sensitive method for the detection of miRNAs is desirable. In this study, we demonstrate a novel bi-directional extension (BDE) assay. In the first step, a specific linear RT primer is hybridized to 6-10 base pairs from the 3’-end of a target miRNA molecule and then reverse transcribed to generate a cDNA strand. After reverse transcription, the cDNA was hybridized to the 3’-end which is BDE sequence; it played role as the PCR template. The PCR template was amplified in an SYBR green-based quantitative real-time PCR. To prove the concept, we used human brain total RNA. It could be detected quantitatively in the range of seven orders of magnitude with excellent linearity and reproducibility. To evaluate the performance of BDE assay, we contrasted sensitivity and specificity of the BDE assay against a commercially available poly (A) tailing method using miRNAs for let-7e extracted from A549 human epithelial lung cancer cells. The BDE assay displayed good performance compared with a poly (A) tailing method in terms of specificity and sensitivity; the CT values differed by 2.5 and the melting curve showed a sharper than poly (A) tailing methods. We have demonstrated an innovative, cost-effective BDE assay that allows improved sensitivity and specificity in detection of miRNAs. Dynamic range of the SYBR green-based RT-qPCR for miR-145 could be represented quantitatively over a range of 7 orders of magnitude from 0.1 pg to 1.0 μg of human brain total RNA. Finally, the BDE assay for detection of miRNA species such as let-7e shows good performance compared with a poly (A) tailing method in terms of specificity and sensitivity. Thus BDE proves a simple, low cost, and highly sensitive assay for various miRNAs and should provide significant contributions in research on miRNA biology and application of disease diagnostics with miRNAs as targets.

Keywords: bi-directional extension (BDE), microRNA (miRNA), poly (A) tailing assay, reverse transcription, RT-qPCR

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Authors: Maierhaba Mijiti

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Objective：The aim is to understand the relationship between the expression level of the long-non-coding RNA LINC AC008063 and the clinicopathological parameters of patients with head and neck squamous cell carcinoma (HNSCC), and to clarify the biological function of LINC AC008063 in HNSCC cells. Moreover, it provides a potential biomarker for the diagnosis, treatment, and prognosis evaluation of HNSCC. Methods: The expression level of LINC AC008063 in the HNSCC was analyzed using transcriptome sequencing data from the TCGA (The cancer genome atlas) database. The expression levels of LINC AC008063 in human embryonic lung diploid cells 2BS, human immortalized keratinocytes HACAT, HNSCC cell lines CAL-27, Detroit562, AMC-HN-8, FD-LSC-1, FaDu and WSU-HN30 were determined by real-time quantitative PCR (qPCR). RNAi (RNA interference) was introduced for LINC AC008063 knockdown in HNSCC cell lines, the localization and abundance analysis of LINC AC008063 was determined by RT-qPCR, and the biological functions were examined by CCK-8, clone formation, flow cytometry, transwell invasion and migration assays, Seahorse assay. Results: LINC AC008063 was upregulated in HNSCC tissue (P<0.001), and verified b CCK-8, clone formation, flow cytometry, transwell invasion and migration assays, Seahorse assayy qPCR in HNSCC cell lines. The survival analysis revealed that the overall survival rate (OS) of patients with high LINC AC008063 expression group was significantly lower than that in the LINC AC008063 expression group, the median survival times for the two groups were 33.10 months and 61.27 months, respectively (P=0.002). The clinical correlation analysis revealed that its expression was positively correlated with the age of patients with HNSCC (P<0.001) and positively correlated with pathological state (T3+T4＞T1+T2, P=0.03). The RT-qPCR results showed that LINC AC008063 was mainly enriched in cytoplasm (P=0.01). Knockdown of LINC AC008063 inhibited proliferation, colony formation, migration and invasion; the glycolytic capacity was significantly decreased in HNSCC cell lines (P＜0.05). Conclusion: High level of LINC AC008063 was associated with the malignant progression of HNSCC as well as promoting the important biological functions of proliferation, colony formation, migration and invasion; in particular, the glycolytic capacity was decreased in HNSCC cells. Therefore, LINC AC008063 may serve as a potential biomarker for HNSCC and a distinct molecular target to inhibit glycolysis.

Keywords: head and neck squamous cell carcinoma, oncogene, long non-coding RNA, LINC AC008063, invasion and metastasis

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Authors: Jayshree P. Zend, Ashatai B. Pawar

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The study was carried out in Parbhani district of Maharashtra state, India with the objectives to study environmental problems faced by flour mill workers, prevalence of work-related health hazards and the physiological cost of workers while performing work in flour mill in traditional method as well as improved method. The use of flour presser, dust controlling bag and noise and dust controlling mask developed by AICRP College of Home Science, VNMKV, Parbhani was considered as an improved method. This investigation consisted survey and experiment which was conducted in the respective locations of flour mills. Healthy, non-smoking 30 flour mill workers ranged between the age group of 20-50 yrs comprising 16 female and 14 male working at flour mill for 4-8 hrs/ day and 6 days/ week and had minimum five years experience of work in flour mill were selected for the study. Pulmonary function test of flour mill workers was carried out by trained technician at Dr. ShankarraoChavan Government Medical College, Nanded by using Electronic Spirometer. The data regarding heart rate (resting, working and recovery), energy expenditure, musculoskeletal problems and occupational health hazards and accidents were recorded by using pretested questionnaire. Scientific equipment used in the experiment were polar sport test heart rate monitor, Hygrometer, Goniometer, Dialed Thermometer, Sound Level Meter, Lux Meter, Ambient Air Sampler and Air Quality Monitor. The collected data were subjected to appropriate statistical analysis such as 't' test and correlation coefficient test. Results indicated that improved method i.e. use of noise and dust controlling mask, flour presser and dust controlling bag were effective in reducing physiological cost of work of flour mill workers. Lung function test of flour mill workers showed decreased values of all parameters, hence the results of present study support paying attention to use of personal protective noise and dust controlling mask by flour mill workers and also to the working conditions in flour mill especially ventilation and illumination level needs to be enhanced in flour mill. The study also emphasizes the need to develop some mechanism for lifting load of grains and unloading in the hopper. It is also suggested that the flour mill workers should use flour presser suitable to their height to avoid frequent bending and should use dust controlling bag to flour outlet of machine to reduce inhalable flour dust level in the flour mill.

Keywords: physiological cost, energy expenditure, musculoskeletal problems

Procedia PDF Downloads 401

Authors: Chrislaura Carmo, Luca Deiana, Mafalda Laranjo, Abilio Sobral, Armando Cordova

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Photodynamic therapy (PDT) is currently used for the treatment of malignancies and premalignant tumors. It is based on the capture of a photosensitizing molecule (PS) which, when excited by light at a certain wavelength, reacts with oxygen and generates oxidizing species (radicals, singlet oxygen, triplet species) in target tissues, leading to cell death. BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indaceno) derivatives are emerging as important candidates for photosensitizer in photodynamic therapy of cancer cells due to their high triplet quantum yield. Today these dyes are relevant molecules in photovoltaic materials and fluorescent sensors. In this study, it will be demonstrated the possibility that BODIPY can be covalently linked to thioglycolic acid through the click reaction. Thiol−ene click chemistry has become a powerful synthesis method in materials science and surface modification. The design of biobased allyl-terminated precursors with high renewable carbon content for the construction of the thiol-ene polymer networks is essential for sustainable development and green chemistry. The work aims to synthesize the BODIPY (10-(4-(allyloxy) phenyl)-2,8-diethyl-5,5-difluoro-1,3,7,9-tetramethyl-5H-dipyrrolo[1,2-c:2',1'-f] [1,3,2] diazaborinin-4-ium-5-uide) and to click reaction with Thioglycolic acid. BODIPY was synthesized by the condensation reaction between aldehyde and pyrrole in dichloromethane, followed by in situ complexation with BF3·OEt2 in the presence of the base. Then it was functionalized with allyl bromide to achieve the double bond and thus be able to carry out the click reaction. The thiol−ene click was performed using DMPA (2,2-Dimethoxy-2-phenylacetophenone) as a photo-initiator in the presence of UV light (320–500 nm) in DMF at room temperature for 24 hours. Compounds were characterized by standard analytical techniques, including UV-Vis Spectroscopy, 1H, 13C, 19F NMR and mass spectroscopy. The results of this study will be important to link BODIPY to polymers through the thiol group offering a diversity of applications and functionalization. This new molecule can be tested as third-generation photosensitizers, in which the dye is targeted by antibodies or nanocarriers by cells, mainly in cancer cells, PDT and Photodynamic Antimicrobial Chemotherapy (PACT). According to our studies, it was possible to visualize a click reaction between allyl BODIPY and thioglycolic acid. Our team will also test the reaction with other thiol groups for comparison. Further, we will do the click reaction of BODIPY with a natural polymer linked with a thiol group. The results of the above compounds will be tested in PDT assays on various lung cancer cell lines.

Keywords: bodipy, click reaction, thioglycolic acid, allyl, thiol-ene click

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Authors: Naima Jannat, Ariful Islam, Sharafat Hossain

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Due to the involvement of the large target volume, Craniospinal Irradiation makes it challenging to achieve a uniform dose, and it requires different isocenters. This isocentric junction needs to shift after every five fractions to overcome the possibility of hot and cold spots. This study aims to evaluate the Planning Target Volume coverage & sparing Organ at Risk between two techniques and shows that the Field Alignment Technique does not need replanning and resetting. Planning method for Craniospinal Irradiation by Eclipse treatment planning system Field Alignment and Extended Source to Surface Distance technique was developed where 36 Gy in 20 Fraction at the rate of 1.8 Gy was prescribed. The patient was immobilized in the prone position. In the Field Alignment technique, the plan consists of half beam blocked parallel opposed cranium and a single posterior cervicospine field was developed by sharing the same isocenter, which obviates divergence matching. Further, a single field was created to treat the remaining lumbosacral spine. Matching between the inferior diverging edge of the cervicospine field and the superior diverging edge of a lumbosacral field, the field alignment option was used, which automatically matches the field edge divergence as per the field alignment rule in Eclipse Treatment Planning System where the couch was set to 2700. In the Extended Source to Surface Distance technique, two parallel opposed fields were created for the cranium, and a single posterior cervicospine field was created where the Source to Surface Distance was from 120-140 cm. Dose Volume Histograms were obtained for each organ contoured and for each technique used. In all, the patient’s maximum dose to Planning Target Volume is higher for the Extended Source to Surface Distance technique to Field Alignment technique. The dose to all surrounding structures was increased with the use of a single Extended Source to Surface Distance when compared to the Field Alignment technique. The average mean dose to Eye, Brain Steam, Kidney, Oesophagus, Heart, Liver, Lung, and Ovaries were respectively (58% & 60 %), (103% & 98%), (13% & 15%), (10% & 63%), (12% & 16%), (33% & 30%), (14% & 18%), (69% & 61%) for Field Alignment and Extended Source to Surface Distance technique. However, the clinical target volume at the spine junction site received a less homogeneous dose with the Field Alignment technique as compared to Extended Source to Surface Distance. We conclude that, although the use of a single field Extended Source to Surface Distance delivered a more homogenous, but its maximum dose is higher than the Field Alignment technique. Also, a huge advantage of the Field Alignment technique for Craniospinal Irradiation is that it doesn’t need replanning and resetting up of patients after every five fractions and 95% prescribed dose was received by more than 95% of the Planning Target Volume in all the plane with the acceptable hot spot.

Keywords: craniospinalirradiation, cranium, cervicospine, immobilize, lumbosacral spine

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Authors: Leonard Tiong, Sonit Singh, Kevin Ho Shon, Sarah Lewis

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Investigation into the use of artificial intelligence in radiology continues to develop at a rapid rate. During the coronavirus pandemic, the combination of an exponential increase in chest x-rays and unpredictable staff shortages resulted in a huge strain on the department's workload. There is a World Health Organisation estimate that two-thirds of the global population does not have access to diagnostic radiology. Therefore, there could be demand for a program that could detect acute changes in imaging compatible with infection to assist with screening. We generated a conventional neural network and tested its efficacy in recognizing changes compatible with coronavirus infection. Following ethics approval, a deidentified set of 77 normal and 77 abnormal chest x-rays in patients with confirmed coronavirus infection were used to generate an algorithm that could train, validate and then test itself. DICOM and PNG image formats were selected due to their lossless file format. The model was trained with 100 images (50 positive, 50 negative), validated against 28 samples (14 positive, 14 negative), and tested against 26 samples (13 positive, 13 negative). The initial training of the model involved training a conventional neural network in what constituted a normal study and changes on the x-rays compatible with coronavirus infection. The weightings were then modified, and the model was executed again. The training samples were in batch sizes of 8 and underwent 25 epochs of training. The results trended towards an 85.71% true positive/true negative detection rate and an area under the curve trending towards 0.95, indicating approximately 95% accuracy in detecting changes on chest X-rays compatible with coronavirus infection. Study limitations include access to only a small dataset and no specificity in the diagnosis. Following a discussion with our programmer, there are areas where modifications in the weighting of the algorithm can be made in order to improve the detection rates. Given the high detection rate of the program, and the potential ease of implementation, this would be effective in assisting staff that is not trained in radiology in detecting otherwise subtle changes that might not be appreciated on imaging. Limitations include the lack of a differential diagnosis and application of the appropriate clinical history, although this may be less of a problem in day-to-day clinical practice. It is nonetheless our belief that implementing this program and widening its scope to detecting multiple pathologies such as lung masses will greatly assist both the radiology department and our colleagues in increasing workflow and detection rate.

Keywords: artificial intelligence, COVID, neural network, machine learning

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Authors: Ying-Chang Yu, Yuan-Lung Lo

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Building envelope design is one of the most popular design fields of architectural profession in nowadays. The main design trend of such system is to highlight the designer's aesthetic intention from the outlook of building project. Due to the trend of current façade design, the building envelope contains more and more layers of components, such as double skin façade, photovoltaic panels, solar control system, or even ornamental components. These exterior components are designed for various functional purposes. Most researchers focus on how these exterior elements should be structurally sound secured. However, not many researchers consider these elements would help to improve the performance of façade system. When the exterior elements are deployed in large scale, it creates an additional layer outside of original façade system and acts like a porous interface which would interfere with the aerodynamic of façade surface in micro-scale. A standard façade performance consists with 'water penetration, air infiltration rate, operation force, and component deflection ratio', and these key performances are majorly driven by the 'Design Wind Load' coded in local regulation. A design wind load is usually determined by the maximum wind pressure which occurs on the surface due to the geometry or location of building in extreme conditions. This research was designed to identify the air damping phenomenon of micro turbulence caused by porous exterior layer leading to surface wind load reduction for improvement of façade system performance. A series of wind tunnel test on dynamic pressure sensor array covered by various scale of porous exterior skin was conducted to verify the effect of wind pressure reduction. The testing specimens were designed to simulate the typical building with two-meter extension offsetting from building surface. Multiple porous exterior skins were prepared to replicate various opening ratio of surface which may cause different level of damping effect. This research adopted 'Pitot static tube', 'Thermal anemometers', and 'Hot film probe' to collect the data of surface dynamic pressure behind porous skin. Turbulence and distributed resistance are the two main factors of aerodynamic which would reduce the actual wind pressure. From initiative observation, the reading of surface wind pressure was effectively reduced behind porous media. In such case, an actual building envelope system may be benefited by porous skin from the reduction of surface wind pressure, which may improve the performance of envelope system consequently.

Keywords: multi-layer facade, porous media, facade performance, turbulence and distributed resistance, wind tunnel test

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Authors: Bistra Kunovska, Kremena Ivanova, Jana Djounova, Desislava Djunakova, Zdenka Stojanovska

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The carcinogenic effects of radon as a radioactive noble gas have been studied and show a strong correlation between radon exposure and lung cancer occurrence, even in the case of low radon levels. The major part of the natural radiation dose in humans is received by inhaling radon and its progenies, which originates from the decay chain of U-238. Indoor radon poses a substantial threat to human health when build-up occurs in confined spaces such as homes, mines and caves and the risk increases with the duration of radon exposure and is proportional to both the radon concentration and the time of exposure. Tourist caves are a case of special environmental conditions that may be affected by high radon concentration. Tourist caves are a recognized danger in terms of radon exposure to cave workers (guides, employees working in shops built above the cave entrances, etc.), but due to the sensitive nature of the cave environment, high concentrations cannot be easily removed. Forced ventilation of the air in the caves is considered unthinkable due to the possible harmful effects on the microclimate, flora and fauna. The risks to human health posed by exposure to elevated radon levels in caves are not well documented. Various studies around the world often detail very high concentrations of radon in caves and exposure of employees but without a follow-up assessment of the overall impact on human health. This study was developed in the implementation of a national project to assess the potential health effects caused by exposure to elevated levels of radon in buildings with public access under the National Science Fund of Bulgaria, in the framework of grant No КП-06-Н23/1/07.12.2018. The purpose of the work is to assess the radon level in Bulgarian caves and the exposure of the visitors and workers. The number of caves (sampling size) was calculated for simple random selection from total available caves 65 (sampling population) are 13 caves with confidence level 95 % and confidence interval (margin of error) approximately 25 %. A measurement of the radon concentration in air at specific locations in caves was done by using CR-39 type nuclear track-etch detectors that were placed by the participants in the research team. Despite the fact that all of the caves were formed in karst rocks, the radon levels were rather different from each other (97–7575 Bq/m3). An assessment of the influence of the orientation of the caves in the earth's surface (horizontal, inclined, vertical) on the radon concentration was performed. Evaluation of health hazards and radon risk exposure causing by inhaling the radon and its daughter products in each surveyed caves was done. Reducing the time spent in the cave has been recommended in order to decrease the exposure of workers.

Keywords: tourist caves, radon concentration, exposure, Bulgaria

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Authors: Sree Sanyal

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Research in ageing often highlights the age-related health dimension more than the psycho-social characteristics of the elderly, which also influences and challenges the health outcomes. Multimorbidity is defined as the person having more than one chronic non-communicable diseases and their prevalence increases with ageing. The study aims to evaluate the influence of social ties on self-reported prevalence of multimorbidity (selected chronic non-communicable diseases) among the selected states of elderly population in India. The data is accessed from Building Knowledge Base on Population Ageing in India (BKPAI), collected in 2011 covering the self-reported chronic non-communicable diseases like arthritis, heart disease, diabetes, lung disease with asthma, hypertension, cataract, depression, dementia, Alzheimer’s disease, and cancer. The data of the above diseases were taken together and categorized as: ‘no disease’, ‘one disease’ and ‘multimorbidity’. The predicted variables were demographic, socio-economic, residential types, and the variable of social ties includes social support, social engagement, perceived support, connectedness, and importance of the elderly. Predicted probability for multiple logistic regression was used to determine the background characteristics of the old in association with chronic morbidities showing multimorbidity. The finding suggests that 24.35% of the elderly are suffering from multimorbidity. Research shows that with reference to ‘no disease’, according to the socio-economic characteristics of the old, the female oldest old (80+) from others in caste and religion, widowed, never had any formal education, ever worked in their life, coming from the second wealth quintile standard, from rural Maharashtra are more prone with ‘one disease’. From the social ties background, the elderly who perceives they are important to the family, after getting older their decision-making status has been changed, prefer to stay with son and spouse only, satisfied with the communication from their children are more likely to have less single morbidity and the results are significant. Again, with respect to ‘no disease’, the female oldest old (80+), who are others in caste, Christian in religion, widowed, having less than 5 years of education completed, ever worked, from highest wealth quintile, residing in urban Kerala are more associated with multimorbidity. The elderly population who are more socially connected through family visits, public gatherings, gets support in decision making, who prefers to spend their later years with son and spouse only but stays alone shows lesser prevalence of multimorbidity. In conclusion, received and perceived social integration and support from associated neighborhood in the older days, knowing about their own needs in life facilitates better health and wellbeing of the elderly population in selected states of India.

Keywords: morbidity, multi-morbidity, prevalence, social ties

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Authors: M. Roberts

Abstract:

We Are Undefeatable - is a mass marketing behaviour change campaign that aims to support the least active people living with long term health conditions to be more active. This is an important issue to address because people with long term conditions are an historically underserved community for the sport and physical activity sector and the least active of those with long term conditions have the most to gain in health and wellbeing benefits. The campaign has generated a significant change in the way physical activity is communicated and people with long term conditions are represented in the media and marketing. The goal is to create a social norm around being active. The campaign is led by a unique partnership of organisations: the Richmond Group of Charities (made up of Age UK, Alzheimer’s Society, Asthma + Lung UK, Breast Cancer Now, British Heart Foundation, British Red Cross, Diabetes UK, Macmillan Cancer Support, Rethink Mental Illness, Royal Voluntary Service, Stroke Association, Versus Arthritis) along with Mind, MS Society, Parkinson’s UK and Sport England, with National Lottery Funding. It is underpinned by the COM-B model of behaviour change. It draws on the lived experience of people with multiple long term conditions to shape the look and feel of the campaign and all the resources available. People with long term conditions are the campaign messengers, central to the ethos of the campaign by telling their individual stories of overcoming barriers to be active with their health conditions. The central messaging is about finding a way to be active that works for the individual. We Are Undefeatable is evaluated through a multi-modal approach, including regular qualitative focus groups and a quantitative evaluation tracker undertaken three times a year. The campaign has highlighted the significant barriers to physical activity for people with long term conditions. This has changed the way our partnership talks about physical activity but has also had an impact on the wider sport and physical activity sector, prompting an increasing departure from traditional messaging and marketing approaches for this audience of people with long term conditions. The campaign has reached millions of people since its launch in 2019, through multiple marketing and partnership channels including primetime TV advertising and promotion through health professionals and in health settings. Its diverse storytellers make it relatable to its target audience and the achievable activities highlighted and inclusive messaging inspire our audience to take action as a result of seeing the campaign. The We Are Undefeatable campaign is a blueprint for physical activity campaigns; it not only addresses individual behaviour change but plays a role in addressing systemic barriers to physical activity by sharing the lived experience insight to shape policy and professional practice.

Keywords: behaviour change, long term conditions, partnership, relatable

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Authors: Shyan-Lung Lin, Cheng-Yi Huang, Tung-Yi Lin

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Physical fitness is the adaptability of the body to physical work and the environment, and is generally known to include cardiopulmonary-fitness, muscular-fitness, body flexibility, and body composition. This paper is aimed to study the ventilatory and cardiovascular activity under various exercise intensities for subjects at distinct ends of cardiopulmonary fitness norm. Three graded upright biking exercises, light, moderate, and vigorous exercise, were designed for subjects at distinct ends of cardiopulmonary fitness norm from their physical education classes. The participants in the experiments were 9, 9, and 11 subjects in the top 20%, middle 20%, and bottom 20%, respectively, among all freshmen of the Feng Chia University in the academic year of 2015. All participants were requested to perform 5 minutes of upright biking exercise to attain 50%, 65%, and 85% of their maximum heart rate (HRmax) during the light, moderate, and vigorous exercise experiment, respectively, and 5 minutes of recovery following each graded exercise. The cardiovascular and ventilatory signals, including breathing frequency (f), tidal volume (VT), heart rate (HR), mean arterial pressure (MAP), and ECG signals were recorded during rest, exercise, and recovery periods. The physiological signals of three groups were analyzed based on their recovery, recovery rate, and percentage variation from rest. Selected time domain parameters, SDNN and RMSSD, were computed and spectral analysis was performed to study the hear rate variability from collected ECG signals. The comparison studies were performed to examine the correlations between physical fitness norm and cardio-pulmonary signals during graded exercises and exercise recovery. No significant difference was found among three groups with VT during all levels of exercise intensity and recovery. The top 20% group was found to have better performance in heart recovery (HRR), frequency recovery rate (fRR) and percentage variation from rest (Δf) during the recovery period of vigorous exercise. The top 20% group was also found to achieve lower mean arterial pressure MAP only at rest but showed no significant difference during graded exercises and recovery periods. In time-domain analysis of HRV, the top 20% group again seemed to have better recovery rate and less variation in terms of SDNN during recovery period of light and vigorous exercises. Most assessed frequency domain parameters changed significantly during the experiment (p<0.05, ANOVA). The analysis showed that the top 20% group, in comparison with middle and bottom 20% groups, appeared to have significantly higher TP, LF, HF, and nHF index, while the bottom 20% group showed higher nLF and LF/HF index during rest, three graded levels of exercises, and their recovery periods.

Keywords: physical fitness, cardio-pulmonary signals, graded exercise, exercise recovery

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Authors: Wei-Chih Huang, Pei-Lung Chung, Ching-Heng Lin, Hsuan-Chia Yang, Der-Ming Liou

Abstract:

Background: In-Hospital Cardiac Arrest (IHCA) threaten life of the inpatients, cause serious effect to patient safety, quality of inpatients care and hospital service. Health providers must identify the signs of IHCA early to avoid the occurrence of IHCA. This study will consider the potential association between early signs of IHCA and the essence of patient care provided by nurses and other professionals before an IHCA occurs. The aim of this study is to identify significant associations between nursing interventions and abnormal early evaluation results of IHCA that can assist health care providers in monitoring inpatients at risk of IHCA to increase opportunities of IHCA early detection and prevention. Materials and Methods: This study used one of the data mining techniques called association rules mining to compute associations between nursing interventions and abnormal early evaluation results of IHCA. The nursing interventions and abnormal early evaluation results of IHCA were considered to be co-occurring if nursing interventions were provided within 24 hours of last being observed in abnormal early evaluation results of IHCA. The rule based methods were utilized 23.6 million electronic medical records (EMR) from a medical center in Taipei, Taiwan. This dataset includes 733 concepts of nursing interventions that coded by clinical care classification (CCC) codes and 13 early evaluation results of IHCA with binary codes. The values of interestingness and lift were computed as Q values to measure the co-occurrence and associations’ strength between all in-hospital patient care measures and abnormal early evaluation results of IHCA. The associations were evaluated by comparing the results of Q values and verified by medical experts. Results and Conclusions: The results show that there are 4195 pairs of associations between nursing interventions and abnormal early evaluation results of IHCA with their Q values. The indication of positive association is 203 pairs with Q values greater than 5. Inpatients with high blood sugar level (hyperglycemia) have positive association with having heart rate lower than 50 beats per minute or higher than 120 beats per minute, Q value is 6.636. Inpatients with temporary pacemaker (TPM) have significant association with high risk of IHCA, Q value is 47.403. There is significant positive correlation between inpatients with hypovolemia and happened abnormal heart rhythms (arrhythmias), Q value is 127.49. The results of this study can help to prevent IHCA from occurring by making health care providers early recognition of inpatients at risk of IHCA, assist with monitoring patients for providing quality of care to patients, improve IHCA surveillance and quality of in-hospital care.

Keywords: in-hospital cardiac arrest, patient safety, nursing intervention, association rule mining

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Authors: Fatemeh Sadeghi, Peyman Sheikhzadeh

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Introduction: Block Sequential Regularized Expectation Maximization (BSREM) reconstruction algorithm was recently developed to suppress excessive noise by applying a relative difference penalty. The aim of this study was to investigate the effect of various strengths of noise penalization factor in the BSREM algorithm under different acquisition duration and lesion sizes in order to determine an optimum penalty factor by considering both quantitative and qualitative image evaluation parameters in clinical uses. Materials and Methods: The NEMA IQ phantom and 15 clinical whole-body patients with prostate cancer were evaluated. Phantom and patients were injected withGallium-68 Prostate-Specific Membrane Antigen(68 Ga-PSMA)and scanned on a non-time-of-flight Discovery IQ Positron Emission Tomography/Computed Tomography(PET/CT) scanner with BGO crystals. The data were reconstructed using BSREM with a β-value of 100-500 at an interval of 100. These reconstructions were compared to OSEM as a widely used reconstruction algorithm. Following the standard NEMA measurement procedure, background variability (BV), recovery coefficient (RC), contrast recovery (CR) and residual lung error (LE) from phantom data and signal-to-noise ratio (SNR), signal-to-background ratio (SBR) and tumor SUV from clinical data were measured. Qualitative features of clinical images visually were ranked by one nuclear medicine expert. Results: The β-value acts as a noise suppression factor, so BSREM showed a decreasing image noise with an increasing β-value. BSREM, with a β-value of 400 at a decreased acquisition duration (2 min/ bp), made an approximately equal noise level with OSEM at an increased acquisition duration (5 min/ bp). For the β-value of 400 at 2 min/bp duration, SNR increased by 43.7%, and LE decreased by 62%, compared with OSEM at a 5 min/bp duration. In both phantom and clinical data, an increase in the β-value is translated into a decrease in SUV. The lowest level of SUV and noise were reached with the highest β-value (β=500), resulting in the highest SNR and lowest SBR due to the greater noise reduction than SUV reduction at the highest β-value. In compression of BSREM with different β-values, the relative difference in the quantitative parameters was generally larger for smaller lesions. As the β-value decreased from 500 to 100, the increase in CR was 160.2% for the smallest sphere (10mm) and 12.6% for the largest sphere (37mm), and the trend was similar for SNR (-58.4% and -20.5%, respectively). BSREM visually was ranked more than OSEM in all Qualitative features. Conclusions: The BSREM algorithm using more iteration numbers leads to more quantitative accuracy without excessive noise, which translates into higher overall image quality and lesion detectability. This improvement can be used to shorter acquisition time.

Keywords: BSREM reconstruction, PET/CT imaging, noise penalization, quantification accuracy

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Authors: E. M. Condori-Peñaloza, S. S. Costa

Abstract:

Eleusine indica L, known as goose-grass, is considered a troublesome weed that can cause important economic losses in the agriculture worldwide. However, this grass is used as a medicinal plant in some regions of Brazil to treat influenza and pneumonia. In Africa and Asia, it is used to treat malaria and as diuretic, anti-helminthic, among other uses. Despite its therapeutic potential, little is known about the chemical composition and bioactive compounds of E. indica. Hitherto, two major flavonoids, schaftoside and vitexin, were isolated from aerial part of the species and showed inhibitory activity on lung neutrophil influxes in mice, suggesting a beneficial effect on airway inflammation. Therefore, the aim of this study was to analyze the chemical profile of aqueous extracts from aerial parts of Eleusine indica specimens using high performance liquid chromatography (HPLC-DAD) and 1H nuclear magnetic resonance spectroscopy (NMR), with emphasis on phenolic compounds. Specimens of E. indica were collected in Minas Gerais state, Brazil. Aerial parts of fresh plants were extracted by decoction (10% p/v). After spontaneous precipitation of the aqueous extract at 10-12°C for 24 hours, the supernatant obtained was frozen and lyophilized. After that, 1 g of the extract was dissolved into 25 mL of water and fractionated on a reverse phase chromatography column (RP-2), eluted with a gradient of H2O/EtOH. Five fractions were obtained. The extract and fractions had their chemical profile analyzed by using HPLC-DAD (C-18 column: 20 μL, 256 -365 nm; gradient water 0.01% phosphoric acid/ acetonitrile. The extract was also analyzed by NMR (1H, 500 MHz, D2O) in order to access its global chemical composition. HPLC-DAD analyses of crude extract allowed the identification of ten phenolic compounds. Fraction 1, eluted with 100% water, was poor in phenolic compounds and no major peak was detected. In fraction 2, eluted with 100% water, it was possible to observe one major peak at retention time (RT) of 23.75 minutes compatible with flavonoid; fraction 3, also eluted with 100% water, showed four peaks at RT= 21.47, 23.52, 24.33 and 25.84 minutes, all of them compatible with flavonoid. In fraction 4, eluted with 50%/ethanol/50% water, it was possible to observe 3 peaks compatible with flavonoids at RT=24.65, 26.81, 27.49 minutes, and one peak (28.83 min) compatible with a phenolic acid derivative. Finally, in fraction 5, eluted with 100% ethanol, no phenolic substance was detected. The UV spectra of all flavonoids detected were compatible with the flavone subclass (λ= 320-345 nm). The 1H NMR spectra of aerial parts extract showed signals in three regions: δ 0.8-3.0 ppm (aliphatic compounds), δ 3.0-5.5 ppm corresponding to carbohydrates (signals most abundant and overlapped), and δ 6.0-8.5 ppm (aromatic compounds). Signals compatible with flavonoids (rings A and B) could also be detected in the crude extract spectra. These results suggest the presence of several flavonoids in E. indica, which reinforces their therapeutic potential. The pharmacological activities of Eleusine indica extracts and fractions will be further evaluated.

Keywords: flavonoids, HPLC, NMR, phenolic compounds

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Authors: Ocsana Opris, Ildiko Lung, Maria L. Soran, Alexandra Ciorita, Lucian Copolovici

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The effects assessment of environmental stress factors on both crop and wild plants of nutritional value are a very important research topic. Continuously worldwide consumption of drugs leads to significant environmental pollution, thus generating environmental stress. Understanding the effects of the important drugs on plant composition and ultrastructural modification is still limited, especially at environmentally relevant concentrations. The aim of the present work was to investigate the influence of three non-steroidal anti-inflammatory drugs (NSAIDs) on chlorophylls content, carotenoids content, total polyphenols content, antioxidant capacity, and ultrastructure of orache (Atriplex patula L.) and spinach (Spinacia oleracea L.). All green leafy vegetables selected for this study were grown in controlled conditions and treated with solutions of different concentrations (0.1‒1 mg L⁻¹) of diclofenac, ibuprofen, and naproxen. After eight weeks of exposure of the plants to NSAIDs, the chlorophylls and carotenoids content were analyzed by high-performance liquid chromatography coupled with photodiode array and mass spectrometer detectors, total polyphenols and antioxidant capacity by ultraviolet-visible spectroscopy. Also, the ultrastructural analyses of the vegetables were performed using transmission electron microscopy in order to assess the influence of the selected NSAIDs on cellular organisms, mainly photosynthetic organisms (chloroplasts), energy supply organisms (mitochondria) and nucleus as a cellular metabolism coordinator. In comparison with the control plants, decreases in the content of chlorophylls were observed in the case of the Atriplex patula L. plants treated with ibuprofen (11-34%) and naproxen (25-52%). Also, the chlorophylls content from Spinacia oleracea L. was affected, the lowest decrease (34%) being obtained in the case of the treatment with naproxen (1 mg L⁻¹). Diclofenac (1 mg L⁻¹) affected the total polyphenols content (a decrease of 45%) of Atriplex patula L. and ibuprofen (1 mg L⁻¹) affected the total polyphenols content (a decrease of 20%) of Spinacia oleracea L. The results obtained also indicate a moderate reduction of carotenoids and antioxidant capacity in the treated plants, in comparison with the controls. The investigations by transmission electron microscopy demonstrated that the green leafy vegetables were affected by the selected NSAIDs. Thus, this research contributes to a better understanding of the adverse effects of these drugs on studied plants. Important to mention is that the dietary intake of these drugs contaminated plants, plants with important nutritional value, may also presume a risk to human health, but currently little is known about the fate of the drugs in plants and their effect on or risk to the ecosystem.

Keywords: abiotic stress, green leafy vegetables, pigments content, ultra structure

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Authors: Spira A., Marabelle A., Kientop D., Moser E., Mumm J.

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Background: Both interleukin-2 (IL-2) and interleukin-10 (IL-10) have been extensively studied for their stimulatory function on T cells and their potential to obtain sustainable tumor control in RCC, melanoma, lung, and pancreatic cancer as monotherapy, as well as combination with PD-1 blockers, radiation, and chemotherapy. While approved, IL-2 retains significant toxicity, preventing its widespread use. The significant efforts undertaken to uncouple IL-2 toxicity from its anti-tumor function have been unsuccessful, and early phase clinical safety observed with PEGylated IL-10 was not met in a blinded Phase 3 trial. Deka Biosciences has engineered a novel molecule coupling wild-type IL-2 to a high affinity variant of Epstein Barr Viral (EBV) IL-10 via a scaffold (scFv) that binds to epidermal growth factor receptors (EGFR). This patented molecule, termed DK210 (EGFR), is retained at high levels within the tumor microenvironment for days after dosing. In addition to overlapping and non-redundant anti-tumor function, IL-10 reduces IL-2 mediated cytokine release syndrome risks and inhibits IL-2 mediated T regulatory cell proliferation. Methods: DK210 (EGFR) is being evaluated in an open-label, dose-escalation (Phase 1) study with 5 (0.025-0.3 mg/kg) monotherapy dose levels and (expansion cohorts) in combination with PD-1 blockers, or radiation or chemotherapy in patients with advanced solid tumors overexpressing EGFR. Key eligibility criteria include 1) confirmed progressive disease on at least one line of systemic treatment, 2) EGFR overexpression or amplification documented in histology reports, 3) at least a 4 week or 5 half-lives window since last treatment, and 4) excluding subjects with long QT syndrome, multiple myeloma, multiple sclerosis, myasthenia gravis or uncontrolled infectious, psychiatric, neurologic, or cancer disease. Plasma and tissue samples will be investigated for pharmacodynamic and predictive biomarkers and genetic signatures associated with IFN-gamma secretion, aiming to select subjects for treatment in Phase 2. Conclusion: Through successful coupling of wild-type IL-2 with a high affinity IL-10 and targeting directly to the tumor microenvironment, DK210 (EGFR) has the potential to harness IL-2 and IL-10’s known anti-cancer promise while reducing immunogenicity and toxicity risks enabling safe concomitant cytokine treatment with other anti-cancer modalities.

Keywords: cytokine, EGFR over expression, interleukine-2, interleukine-10, clinical trial

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Authors: Abdul Aziz, Muhammad Qamar Masood, Saadia Sattar, Saira Fatima, Najmul Islam

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Introduction: The most common endocrine tumor is thyroid cancer. Follicular Thyroid Carcinoma (FTC) accounts for 5%–10% of all thyroid cancers. Patients with FTC frequently present with more advanced stage diseases and a higher occurrence of distant metastases because of the propensity of vascular invasion. FTC is mainly treated with surgery, while radioactive iodine therapy is the main adjuvant therapy as per ATA guidelines. In many developing countries, surgical facilities and radioactive iodine are in short supply; therefore, understanding follicular thyroid cancer trends may help developing countries plan and use resources more effectively. Methodology: It was a retrospective observational study of FTC patients of age 18 years and above conducted at Aga Khan University Hospital, Karachi, from 1st January 2010 to 31st December 2019. Results: There were 404 patients with thyroid carcinoma, out of which forty (10.1%) were FTC. 50% of the patients were in the 41-60 years age group, and the female to male ratio was 1.5: 1. Twenty-four patients (60%) presented with complain of neck swelling followed by metastasis (20%) and compressive symptoms (20%). The most common site of metastasis was bone (87.5%), followed by lung (12.5%). The pre-operative thyroglobulin level was done in six out of eight metastatic patients (75%) in which it was elevated. This emphasizes the importance of checking thyroglobulin level in unusual presentation (bone pain, fractures) of a patient having neck swelling also to help in establishing the primary source of tumor. There was no complete documentation of ultrasound features of the thyroid gland in all the patients, which is an important investigation done in the initial evaluation of thyroid nodule. On FNAC, 50% (20 patients) had Bethesda category III-IV nodules, while 10% ( 4 patients ) had Bethesda category II. In sixteen patients, FNAC was not done as they presented with compressive symptoms or metastasis. Fifty percent had a total thyroidectomy and 50% had subtotal followed by completion thyroidectomy, plus ten patients had lymph node dissection, out of which seven had histopathological lymph node involvement. On histopathology, twenty-three patients (57.5%) had minimally invasive, while seventeen (42.5%) had widely invasive follicular thyroid carcinoma. The capsular invasion was present in thirty-three patients (82.5%); one patient had no capsular invasion, but there was a vascular invasion. Six patients' histopathology had no record of capsular invasion. In contrast, the lymphovascular invasion was present in twenty-six patients (65%). In this study, 65 % of the patients had clinical stage 1 disease, while 25% had stage 2 and 10% had clinical stage 4. Seventeen patients (42.5%) had received RAI 30-100 mCi, while ten patients (25%) received more than 100 mCi. Conclusion: FTC demographic and clinicopathological presentation are the same in Pakistan as compared to other countries. Surgery followed by RAI is the mainstay of treatment. Thus understanding the trend of FTC and proper planning and utilization of the resources will help the developing countries in effectively treating the FTC.

Keywords: thyroid carcinoma, follicular thyroid carcinoma, clinicopathological features, developing countries

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Authors: Shamim Mushtaq, Moazzam Shahid

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Breast cancer (BC) claims the lives of half a million women every year and is the most common cause of death in the developing world. In 2019, it was estimated that BC alone accounts for 15% of all cancer deaths in younger women (aged < 45 years old) with advanced-stage lung metastasis. According to the World Health Organization & International Union against Cancer, in Asia, a high number of cancer-related deaths will be observed in 2020, whereas the burden will be reduced in Western countries due to awareness about the disease, better health facilities and advanced treatments. In the last 15 years, it has been reported that the incidence of BC has increased by 1.1% among Asian compared to the US population from 2003 to 2012. To date, several BC biological subtypes have been reported so far, which are associated with different treatment responses. The heterogeneity and diversity of BC reflected these different subtypes, including Luminal A (23.7% prevalence) and B (38.8% prevalence) that have pathological estrogen receptor (ER+)-positive tumors, the human epidermal growth factor receptor 2 (HER2) (11.2% prevalence) and triple-negative breast cancer (TNBC) (25% prevalence). According to Shaukat Khanum Memorial Cancer Hospital and Research Centre – Pakistan, ten years of data showed that among 636 BC patients, 30.5% had TNBC who were <40 years of age, which is an extremely alarming situation. Therefore, there is a dire need to explore and develop therapeutic targets for the treatment of early TNBC. Since the last decade, unfortunately, there has been little success in understanding the complexity of TNBC and in discovering new biological therapeutic targets. However, conventional chemotherapy is the only choice of treatment for TNBC patients. Many investigators revealed advances in multi-omics (multiple "omes", e.g., genome, proteome, transcriptome, epigenome, and microbiome) which were later identified as actionable targets and increased prevalence in TNBC patients. However, various drugs have been identified so far which are related to a particular diagnostic and prognostic biomarker. For example, Epidermal growth factor receptor ( EGFR or ErbB-1), HER-2/neu (ErbB-2), HER-3 (ErbB-3), and HER-4 (ErbB-4). Protein Transglin-2 (TAGLN 2 ) and Profilins-1 (Pfn-1 ) are the ubiquitously expressed large family of proteins present in all eukaryotes, enabling actin cytoskeletal reorganization. It is known that the oncogenic transformation of cells is accompanied by alteration in the actin cytoskeleton. There are causal connections between altered expression of actin cytoskeletal regulators and cancer progression. Our case-control study identified TAGLN-2 and Pfn-1 proteins in TNBC blood by mass spectrometry. Both TAGLN-2 and Pfn-1 proteins are differentially expressed in early and advanced stages of TNBS patients, which could be potential predictors or therapeutic targets for TNBC.

Keywords: TNBC, blood biomarkers, mass spectrometry, qPCR, ELISA

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Authors: Jaci Mastrandrea

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Background: The National Comprehensive Cancer Network (NCCN) recommends that healthcare institutions have established processes for integrating palliative care (PC) into cancer treatment and that all cancer patients be screened for PC needs upon initial diagnosis as well as throughout the entire continuum of care (National Comprehensive Cancer Network, 2021). Early PC screening is directly correlated with improved patient outcomes. The Sky Lakes Cancer Treatment Center (SLCTC) is an institution that has access to PC services yet does not have protocols in place for identifying patients with palliative needs or a standardized referral process. The aim of this quality improvement project is to improve early access to PC services by establishing a standardized screening and referral process for outpatient oncology patients. Method: The sample population included all adult patients with an oncology diagnosis who presented to the SLCTC for treatment during the project timeline from March 15th, 2022, to April 29th, 2022. The “Palliative and Supportive Needs Assessment'' (PSNA) screening tool was developed from validated and evidence-based PC referral criteria. The tool was initially implemented using paper forms and later was integrated into the Epic-Beacon EHR system. Patients were screened by registered nurses on the SLCTC treatment team. Nurses responsible for screening patients received an educational inservice prior to implementation. Patients with a PSNA score of three or higher were considered to be a positive screen. Scores of five or higher triggered a PC referral order in the patient’s EHR for the oncologist to review and approve. All patients with a positive screen received an educational handout on the topic of PC, and the EHR was flagged for follow-up. Results: Prior to implementation of the PSCNA screening tool, the SLCTC had zero referrals to PC in the past year, excluding referrals to hospice. Data was collected from the first 100 patient screenings completed within the eight-week data collection period. Seventy-three percent of patients met criteria for PC referral with a score greater than or equal to three. Of those patients who met referral criteria, 53.4% (39 patients) were referred for a palliative and supportive care consultation. Patients that were not referred to PC upon meeting the criteria were flagged in the EHR for re-screening within one to three months. Patients with lung cancer, chronic hematologic malignancies, breast cancer, and gastrointestinal malignancy most frequently met criteria for PC referral and scored highest overall on the scale of 0-12. Conclusion: The implementation of a standardized PC screening tool at the SLCTC significantly increased awareness of PC needs among cancer patients in the outpatient setting. Additionally, data derived from this quality improvement project supports the national recommendation for PC to be an integral component of cancer treatment across the entire continuum of care.

Keywords: oncology, palliative care, symptom management, symptom screening, ambulatory oncology, cancer, supportive care

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Authors: Aarthi Mariappan, Janani Selvaraj, P. B. Harathi, M. Prashanthi Devi

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Anthropogenic modification of the urban environment has largely increased in the recent years in order to sustain the growing human population. Intense industrial activity, permanent and high traffic on the roads, a developed subterranean infrastructure network, land use patterns are just some specific characteristics. Every day, the urban environment is polluted by more or less toxic emissions, organic or metals wastes discharged from specific activities such as industrial, commercial, municipal. When these eventually deposit into the soil, the physical and chemical properties of the surrounding soil is changed, transforming it into a human exposure indicator. Metals are non-degradable and occur cumulative in soil due to regular deposits are a result of permanent human activity. Due to this, metals are a contaminant factor for soil when persistent over a long period of time and a possible danger for inhabitant’s health on prolonged exposure. Metals accumulated in contaminated soil may be transferred to humans directly, by inhaling the dust raised from top soil, or by ingesting, or by dermal contact and indirectly, through plants and animals grown on contaminated soil and used for food. Some metals, like Cu, Mn, Zn, are beneficial for human’s health and represent a danger only if their concentration is above permissible levels, but other metals, like Pb, As, Cd, Hg, are toxic even at trace level causing gastrointestinal and lung cancers. In urban areas, metals can be emitted from a wide variety of sources like industrial, residential, commercial activities. Our study interrogates the spatial distribution of heavy metals in soil in relation to their permissible levels and their association with the health risk to the urban population in Coimbatore, India. Coimbatore region is a high cancer risk zone and case records of gastro intestinal and respiratory cancer patients were collected from hospitals and geocoded in ArcGIS10.1. The data of patients pertaining to the urban limits were retained and checked for their diseases history based on their diagnosis and treatment. A disease map of cancer was prepared to show the disease distribution. It has been observed that in our study area Cr, Pb, As, Fe and Mg exceeded their permissible levels in the soil. Using spatial overlay analysis a relationship between environmental exposure to these potentially toxic elements in soil and cancer distribution in Coimbatore district was established to show areas of cancer risk. Through this, our study throws light on the impact of prolonged exposure to soil contamination in soil in the urban zones, thereby exploring the possibility to detect cancer risk zones and to create awareness among the exposed groups on cancer risk.

Keywords: soil contamination, cancer risk, spatial analysis, India

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Authors: E. Omanya, E. Mueni, G. Makau, M. Kariuki

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HIV infection is the strongest risk factor for a person to develop TB. Isoniazid preventive therapy (IPT) for People Living with HIV (PLWHIV) not only reduces the individual patients’ risk of developing active TB but mitigates cross infection. In Kenya, IPT for six months was recommended through the National TB, Leprosy and Lung Disease Program to treat latent TB. In spite of this recommendation by the national government, uptake of IPT among PLHIV remained low in Kenya by the end of 2015. The USAID/Kenya and East Africa Afya Jijini project, which supports 42 TBHIV health facilities in Nairobi County, began addressing low uptake of IPT through Quality Improvement (QI) teams set up at the facility level. Quality is characterized by WHO as one of the four main connectors between health systems building blocks and health systems outputs. Afya Jijini implements the Kenya Quality Model for Health, which involves QI teams being formed at the county, sub-county and facility levels. The teams review facility performance to identify gaps in service delivery and use QI tools to monitor and improve performance. Afya Jijini supported the formation of these teams in 42 facilities and built the teams’ capacity to review data and use QI principles to identify and address performance gaps. When the QI teams began working on improving IPT uptake among PLHIV, uptake was at 31.8%. The teams first conducted a root cause analysis using cause and effect diagrams, which help the teams to brainstorm on and to identify barriers to IPT uptake among PLHIV at the facility level. This is a participatory process where program staff provides technical support to the QI teams in problem identification and problem-solving. The gaps identified were inadequate knowledge and skills on the use of IPT among health care workers, lack of awareness of IPT by patients, inadequate monitoring and evaluation tools, and poor quantification and forecasting of IPT commodities. In response, Afya Jijini trained over 300 health care workers on the administration of IPT, supported patient education, supported quantification and forecasting of IPT commodities, and provided IPT data collection tools to help facilities monitor their performance. The facility QI teams conducted monthly meetings to monitor progress on implementation of IPT and took corrective action when necessary. IPT uptake improved from 31.8% to 61.2% during the second year of the Afya Jijini project and improved to 80.1% during the third year of the project’s support. Use of QI teams and root cause analysis to identify and address service delivery gaps, in addition to targeted program interventions and continual performance reviews, can be successful in increasing TB related service delivery uptake at health facilities.

Keywords: isoniazid, quality, health care workers, people leaving with HIV

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Authors: Despina Giannadaki, Jos Lelieveld, Andrea Pozzer, John Evans

Abstract:

Outdoor air pollution by fine particles ranks among the top ten global health risk factors that can lead to premature mortality. Epidemiological cohort studies, mainly conducted in United States and Europe, have shown that the long-term exposure to PM2.5 (particles with an aerodynamic diameter less than 2.5μm) is associated with increased mortality from cardiovascular, respiratory diseases and lung cancer. Fine particulates can cause health impacts even at very low concentrations. Previously, no concentration level has been defined below which health damage can be fully prevented. The World Health Organization ambient air quality guidelines suggest an annual mean PM2.5 concentration limit of 10μg/m3. Populations in large parts of the world, especially in East and Southeast Asia, and in the Middle East, are exposed to high levels of fine particulate pollution that by far exceeds the World Health Organization guidelines. The aim of this work is to evaluate the implementation of recent air quality standards for PM2.5 in the EU, the US and other countries worldwide and estimate what measures will be needed to substantially reduce premature mortality. We investigated premature mortality attributed to fine particulate matter (PM2.5) under adults ≥ 30yrs and children < 5yrs, applying a high-resolution global atmospheric chemistry model combined with epidemiological concentration-response functions. The latter are based on the methodology of the Global Burden of Disease for 2010, assuming a ‘safe’ annual mean PM2.5 threshold of 7.3μg/m3. We estimate the global premature mortality by PM2.5 at 3.15 million/year in 2010. China is the leading country with about 1.33 million, followed by India with 575 thousand and Pakistan with 105 thousand. For the European Union (EU) we estimate 173 thousand and the United States (US) 52 thousand in 2010. Based on sensitivity calculations we tested the gains from PM2.5 control by applying the air quality guidelines (AQG) and standards of the World Health Organization (WHO), the EU, the US and other countries. To estimate potential reductions in mortality rates we take into consideration the deaths that cannot be avoided after the implementation of PM2.5 upper limits, due to the contribution of natural sources to total PM2.5 and therefore to mortality (mainly airborne desert dust). The annual mean EU limit of 25μg/m3 would reduce global premature mortality by 18%, while within the EU the effect is negligible, indicating that the standard is largely met and that stricter limits are needed. The new US standard of 12μg/m3 would reduce premature mortality by 46% worldwide, 4% in the US and 20% in the EU. Implementing the AQG by the WHO of 10μg/m3 would reduce global premature mortality by 54%, 76% in China and 59% in India. In the EU and US, the mortality would be reduced by 36% and 14%, respectively. Hence, following the WHO guideline will prevent 1.7 million premature deaths per year. Sensitivity calculations indicate that even small changes at the lower PM2.5 standards can have major impacts on global mortality rates.

Keywords: air quality guidelines, outdoor air pollution, particulate matter, premature mortality

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Authors: Eashwar V. Somasundaram, Raoul R. Wadhwa, Jacob G. Scott

Abstract:

The use of radiomics in measuring geometric properties of tumor images such as size, surface area, and volume has been invaluable in assessing cancer diagnosis, treatment, and prognosis. In addition to analyzing geometric properties, radiomics would benefit from measuring topological properties using persistent homology. Intuitively, features uncovered by persistent homology may correlate to tumor structural features. One example is necrotic cavities (corresponding to 2D topological features), which are markers of very aggressive tumors. We develop a data pipeline in R that clusters tumors images based on persistent homology is used to identify meaningful clinical distinctions between tumors and possibly new relationships not captured by established clinical categorizations. A preliminary analysis was performed on 16 Magnetic Resonance Imaging (MRI) breast tissue segments downloaded from the 'Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis' (I-SPY TRIAL or ISPY1) collection in The Cancer Imaging Archive. Each segment represents a patient’s breast tumor prior to treatment. The ISPY1 dataset also provided the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status data. A persistent homology matrix up to 2-dimensional features was calculated for each of the MRI segmentation. Wasserstein distances were then calculated between all pairwise tumor image persistent homology matrices to create a distance matrix for each feature dimension. Since Wasserstein distances were calculated for 0, 1, and 2-dimensional features, three hierarchal clusters were constructed. The adjusted Rand Index was used to see how well the clusters corresponded to the ER/PR/HER2 status of the tumors. Triple-negative cancers (negative status for all three receptors) significantly clustered together in the 2-dimensional features dendrogram (Adjusted Rand Index of .35, p = .031). It is known that having a triple-negative breast tumor is associated with aggressive tumor growth and poor prognosis when compared to non-triple negative breast tumors. The aggressive tumor growth associated with triple-negative tumors may have a unique structure in an MRI segmentation, which persistent homology is able to identify. This preliminary analysis shows promising results in the use of persistent homology on tumor imaging to assess the severity of breast tumors. The next step is to apply this pipeline to other tumor segment images from The Cancer Imaging Archive at different sites such as the lung, kidney, and brain. In addition, whether other clinical parameters, such as overall survival, tumor stage, and tumor genotype data are captured well in persistent homology clusters will be assessed. If analyzing tumor MRI segments using persistent homology consistently identifies clinical relationships, this could enable clinicians to use persistent homology data as a noninvasive way to inform clinical decision making in oncology.

Keywords: cancer biology, oncology, persistent homology, radiomics, topological data analysis, tumor imaging

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Authors: Fayez Hanna, Viet Tran

Abstract:

A 20 years old lady- primigravida 6 weeks pregnant with unremarkable past history, presented to the emergency department at the Royal Hobart Hospital, Tasmania, Australia, with hyperemesis gravidarum associated with, dehydration and complicated with hematemesis and chest pain resistant. Accordingly, we conducted laboratory investigations which revealed: FBC: WBC 23.9, unremarkable U&E, LFT, lipase and her VBG showed a pH 7.4, pCo2 36.7, cK+ 3.2, cNa+ 142. The decision was made to do a chest X-ray (CXR) after explaining the risks/benefit of performing radiographic investigations during pregnancy and considering the patient's plan for the termination of the pregnancy as she was not ready for motherhood for shared decision-making and consent to look for pneumoperitoneum to suggest perforated viscus that might cause the hematemesis. However, the CXR showed pneumomediastinum but no evidence of pneumoperitoneum or pneumothorax. Consequently, a decision was made to proceed with CT oesophagography with imaging pre and post oral contrast administration to identify a potential oesophageal tear since it could not be excluded using a plain film of the CXR. The CT oesophagography could not find a leak for the administered oral contrast and thus, no oesophageal tear could be confirmed but could not exclude the Mallory-Weiss tear (lower oesophageal tear). Further, the CT oesophagography showed an extensive pneumomediastinum that could not be confirmed to be pulmonary in origin noting the presence of bilateral pulmonary interstitial emphysema and pneumothorax in the apex of the right lung that was small. The patient was admitted to the Emergency Department Inpatient Unit for monitoring, supportive therapy, and symptomatic management. Her hyperemesis was well controlled with ondansetron 8mg IV, metoclopramide 10mg IV, doxylamine 25mg PO, pyridoxine 25mg PO, esomeprazole 40mg IV and oxycodone 5mg PO was given for pain control and 2 litter of IV fluid. The patient was stabilized after 24 hours and discharged home on ondansetron 8mg every 8 hours whereas the patient had a plan for medical termination of pregnancy. Three weeks later, the patient represented with nausea and vomiting complicated by a frank hematemesis. Her observation chart showed HR 117- other vital signs were normal. Pathology showed WBC 14.3 with normal U&E and Hb. The patient was managed in the Emergency Department with the same previous regimen and was discharged home on same previous regimes. Five days later, she presented again with nausea, vomiting and hematemesis and was admitted under obstetrics and gynaecology for stabilization then discharged home with a plan for surgical termination of pregnancy after 3-days rather than the previously planned medical termination of pregnancy to avoid extension of potential oesophageal tear. The surgical termination and follow up period were uneventful. The case is considered rare as pneumomediastinum is a very rare complication of hyperemesis gravidarum where vomiting-induced barotrauma leads to a ruptured oesophagus and air leak into the mediastinum. However no rupture oesophagus in our case. Although the combination of pneumothorax and pneumomediastinum without oesophageal tear was reported only 8 times in the literature, but none of them was due to hyperemesis gravidarum.

Keywords: Pneumothorax, pneumomediastinum, hyperemesis gravidarum, pneumopericardium

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Authors: Elisabetta Ceretti, Silvia Bonizzoni, Alberto Bonetti, Milena Villarini, Marco Verani, Maria Antonella De Donno, Sara Bonetta, Umberto Gelatti

Abstract:

Introduction: Air pollution is a global problem. In 2013, the International Agency for Research on Cancer (IARC) classified air pollution and particulate matter as carcinogenic to human. The study of the health effects of air pollution in children is very important because they are a high-risk group in terms of the health effects of air pollution and early exposure during childhood can increase the risk of developing chronic diseases in adulthood. The MAPEC_LIFE (Monitoring Air Pollution Effects on Children for supporting public health policy) is a project founded by EU Life+ Programme which intends to evaluate the associations between air pollution and early biological effects in children and to propose a model for estimating the global risk of early biological effects due to air pollutants and other factors in children. Methods: The study was carried out on 6-8-year-old children living in five Italian towns in two different seasons. Two biomarkers of early biological effects, primary DNA damage detected with the comet assay and frequency of micronuclei, were investigated in buccal cells of children. Details of children diseases, socio-economic status, exposures to other pollutants and life-style were collected using a questionnaire administered to children’s parents. Child exposure to urban air pollution was assessed by analysing PM0.5 samples collected in the school areas for PAHs and nitro-PAHs concentration, lung toxicity and in vitro genotoxicity on bacterial and human cells. Data on the chemical features of the urban air during the study period were obtained from the Regional Agency for Environmental Protection. The project created also the opportunity to approach the issue of air pollution with the children, trying to raise their awareness on air quality, its health effects and some healthy behaviors by means of an educational intervention in the schools. Results: 1315 children were recruited for the study and participate in the first sampling campaign in the five towns. The second campaign, on the same children, is still ongoing. The preliminary results of the tests on buccal mucosa cells of children will be presented during the conference as well as the preliminary data about the chemical composition and the toxicity and genotoxicity features of PM0.5 samples. The educational package was tested on 250 children of the primary school and showed to be very useful, improving children knowledge about air pollution and its effects and stimulating their interest. Conclusions: The associations between levels of air pollutants, air mutagenicity and biomarkers of early effects will be investigated. A tentative model to calculate the global absolute risk of having early biological effects for air pollution and other variables together will be proposed and may be useful to support policy-making and community interventions to protect children from possible health effects of air pollutants.

Keywords: air pollution exposure, biomarkers of early effects, children, public health policy

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