Search results for: bowel obstruction
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 215

Search results for: bowel obstruction

35 Spontaneous Rupture of Splenic Artery Pseudoaneurysm; A Rare Presentation of Acute Abdominal Pain in the Emergency Department: Case Report

Authors: Zainab Elazab, Azhar Aziz

Abstract:

Background: Spontaneous Splenic artery pseudoaneurysm rupture is a rare condition which is potentially life threatening, if not detected and managed early. We report a case of abdominal pain with intraperitoneal free fluid, which turned out to be spontaneous rupture of a splenic artery pseudoaneurysm, and was treated with arterial embolization. Case presentation: A 28-year old, previously healthy male presented to the ED with a history of sudden onset upper abdominal pain and fainting attack. The patient denied any history of trauma or prior similar attacks. On examination, the patient had tachycardia and a low-normal BP (HR 110, BP 106/66) but his other vital signs were normal (Temp. 37.2, RR 18 and SpO2 100%). His abdomen was initially soft with mild tenderness in the upper region. Blood tests showed leukocytosis of 12.3 X109/L, Hb of 12.6 g/dl and lactic acid of 5.9 mmol/L. Ultrasound showed trace of free fluid in the perihepatic and perisplenic areas, and a splenic hypoechoic lesion. The patient remained stable; however, his abdomen became increasingly tender with guarding. We made a provisional diagnosis of a perforated viscus and the patient was started on IV fluids and IV antibiotics. An erect abdominal x-ray did not show any free air under the diaphragm so a CT abdomen was requested. Meanwhile, bedside ultrasound was repeated which showed increased amount of free fluid, suggesting intra-abdominal bleeding as the most probable etiology for the condition. His CT abdomen revealed a splenic injury with multiple lacerations, a focal intrasplenic enhancing area on venous phase scan (suggesting a pseudoaneurysm with associated splenic intraparenchymal, sub capsular and perisplenic hematomas). Free fluid in the subhepatic and intraperitoneal regions along the small bowel was also detected. Angiogram was done which confirmed a diagnosis of pseudoaneurysm of intrasplenic arterial branch, and angio-embolization was done to control the bleeding. The patient was later discharged in good condition with a surgery follow-up. Conclusion: Splenic artery pseudoaneurysm rupture is a rare cause of abdominal pain which should be considered in any case of abdominal pain with intraperitoneal bleeding. Early management is crucial as it carries a high mortality. Bedside ultrasound is a useful tool to help for early diagnosis of such cases.

Keywords: abdominal pain, pseudo aneurysm, rupture, splenic artery

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34 Prevailing Clinical Evidence on Medicinal Hemp (Cannabis Sativa L.)

Authors: Siti Hajar Muhamad Rosli, Xin Yi Lim, Terence Yew Chin Tan, Muhammad nor Farhan Sa’At, Syazwani Sirdar Ali, Ami Fazlin Syed Mohamed

Abstract:

A growing interest on therapeutic benefits of hemp (Cannabis sativa subsp. sativa) is evident in the pharmaceutical market, attributed to its lower levels of psychoactive constituent delta-9-tetrahydronannabidiol (THC). Deemed as a legal and safer alternative to its counterpart marijuana, the use of medicinal hemp is highly debatable as current scientific evidence on the efficacy for clinical use is yet to be established This study was aimed to provide an overview of the current landscape of hemp research, through recent clinical findings specific to the pharmacological properties of the hemp plant and its derived compounds. A systematic search was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis-ScR (PRISMA) checklist on electronic databases (MEDLINE, OVID, Cochrane Library Central, and Clinicaltrials.gov) for articles published from 2009 to 2019. With predetermined inclusion criteria, all human trials with hemp intervention were included. A total of 18 human trials were identified, investigating therapeutic effects on the neuronal, gastrointestinal, musculoskeletal and immune system, with sample sizes ranging from one to 194 subjects. Three randomised controlled trials showed hempseed pills (in Traditional Chinese Medicine formulation MaZiRenWan) consumption significantly improved spontaneous bowel movement in functional constipation. The use of commercial cannabidiol (CBD) sourced from hemp suggested benefits in cannabis dependence, epilepsy, and anxiety disorders. However, there was insufficient evidence to suggest analgesic or anxiolytics effects of hemp being equivalent to marijuana. All clinical trials reviewed varied in terms of test item formulation and standardisation, which made it challenging to confirm overall efficacy for a specific disease or condition. Published efficacy data on hemp are still at a preliminary level, with limited high quality clinical evidence for any specific therapeutic indication. With multiple variants of this plant having different phytochemical and bioactive compounds, future empirical research should focus on uniformity in experimental designs to further strengthen the notion of using medicinal hemp.

Keywords: cannabis, complementary medicine, hemp, herbal medicine.

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33 Characterization of Polymorphic Forms of Rifaximin

Authors: Ana Carolina Kogawa, Selma Gutierrez Antonio, Hérida Regina Nunes Salgado

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Rifaximin is an oral antimicrobial, gut - selective and not systemic with adverse effects compared to placebo. It is used for the treatment of hepatic encephalopathy, travelers diarrhea, irritable bowel syndrome, Clostridium difficile, ulcerative colitis and acute diarrhea. The crystalline form present in the rifaximin with minimal systemic absorption is α, being the amorphous form significantly different. Regulators are increasingly attention to polymorphisms. Polymorphs can change the form by altering the drug characteristics compromising the effectiveness and safety of the finished product. International Conference on Harmonization issued the ICH Guidance Q6A, which aim to improve the control of polymorphism in new and existing pharmaceuticals. The objective of this study was to obtain polymorphic forms of rifaximin employing recrystallization processes and characterize them by thermal analysis (thermogravimetry - TG and differential scanning calorimetry - DSC), X-ray diffraction, scanning electron microscopy and solubility test. Six polymorphic forms of rifaximin, designated I to VI were obtained by the crystallization process by evaporation of the solvent. The profiles of the TG curves obtained from polymorphic forms of rifaximin are similar to rifaximin and each other, however, the DTG are different, indicating different thermal behaviors. Melting temperature values of all the polymorphic forms were greater to that shown by the rifaximin, indicating the higher thermal stability of the obtained forms. The comparison of the diffractograms of the polymorphic forms of rifaximin with rifaximin α, β and γ constant in patent indicate that forms III, V and VI are formed by mixing polymorph β and α and form III is formed by polymorph β. The polymorphic form I is formed by polymorph β, but with a significant amount of amorphous material. Already, the polymorphic form II consists of polymorph γ, amorphous. In scanning electron microscope is possible to observe the heterogeneity of morphological characteristics of crystals of polymorphic forms among themselves and with rifaximin. The solubility of forms I and II was greater than the solubility of rifaximin, already, forms III, IV and V presented lower solubility than of rifaximin. Similarly, the bioavailability of the amorphous form of rifaximin is considered significantly higher than the form α, the polymorphic forms obtained in this work can not guarantee the excellent tolerability of the reference medicine. Therefore, studies like these are extremely important and they point to the need for greater requirements by the regulatory agencies competent about polymorphs analysis of the raw materials used in the manufacture of medicines marketed globally. These analyzes are not required in the majority of official compendia. Partnerships between industries, research centers and universities would be a viable way to consolidate researches in this area and contribute to improving the quality of solid drugs.

Keywords: electronic microscopy, polymorphism, rifaximin, solubility, X-ray diffraction

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32 Role of Zinc Adminstration in Improvement of Faltering Growth in Egyption Children at Risk of Environmental Enteric Dysfunction

Authors: Ghada Mahmoud El Kassas, Maged Atta El Wakeel

Abstract:

Background: Environmental enteric dysfunction (EED) is impending trouble that flared up in the last decades to be pervasive in infants and children. EED is asymptomatic villous atrophy of the small bowel that is prevalent in the developing world and is associated with altered intestinal function and integrity. Evidence has suggested that supplementary zinc might ameliorate this damage by reducing gastrointestinal inflammation and may also benefit cognitive development. Objective: We tested whether zinc supplementation improves intestinal integrity, growth, and cognitive function in stunted children predicted to have EED. Methodology: This case–control prospective interventional study was conducted on 120 Egyptian Stunted children aged 1-10 years who recruited from the Nutrition clinic, the National research center, and 100 age and gender-matched healthy children as controls. At the primary phase of the study, Full history taking, clinical examination, and anthropometric measurements were done. Standard deviation score (SDS) for all measurements were calculated. Serum markers as Zonulin, Endotoxin core antibody (EndoCab), highly sensitive C-reactive protein (hsCRP), alpha1-acid glycoprotein (AGP), Tumor necrosis factor (TNF), and fecal markers such as myeloperoxidase (MPO), neopterin (NEO), and alpha-1-anti-trypsin (AAT) (as predictors of EED) were measured. Cognitive development was assessed (Bayley or Wechsler scores). Oral zinc at a dosage of 20 mg/d was supplemented to all cases and followed up for 6 months, after which the 2ry phase of the study included the previous clinical, laboratory, and cognitive assessment. Results: Serum and fecal inflammatory markers were significantly higher in cases compared to controls. Zonulin (P < 0.01), (EndoCab) (P < 0.001) and (AGP) (P < 0.03) markedly decreased in cases at the end of 2ry phase. Also (MPO), (NEO), and (AAT) showed a significant decline in cases at the end of the study (P < 0.001 for all). A significant increase in mid-upper arm circumference (MUAC) (P < 0.01), weight for age z-score, and skinfold thicknesses (P< 0.05 for both) was detected at end of the study, while height was not significantly affected. Cases also showed significant improvement of cognitive function at phase 2 of the study. Conclusion: Intestinal inflammatory state related to EED showed marked recovery after zinc supplementation. As a result, anthropometric and cognitive parameters showed obvious improvement with zinc supplementation.

Keywords: stunting, cognitive function, environmental enteric dysfunction, zinc

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31 Neuromyelitis Optica area Postrema Syndrome(NMOSD-APS) in a Fifteen-year-old Girl: A Case Report

Authors: Merilin Ivanova Ivanova, Kalin Dimitrov Atanasov, Stefan Petrov Enchev

Abstract:

Backgroud: Neuromyelitis optica spectrum disorder, also known as Devic’s disease, is a relapsing demyelinating autoimmune inflammatory disorder of the central nervous system associated with anti-aquaporin 4 (AQP4) antibodies that can manifest with devastating secondary neurological deficits. Most commonly affected are the optic nerves and the spinal cord-clinically this is often presented with optic neuritis (loss of vision), transverse myelitis(weakness or paralysis of extremities),lack of bladder and bowel control, numbness. APS is a core clinical entity of NMOSD and adds to the clinical representation the following symptoms: intractable nausea, vomiting and hiccup, it usually occurs isolated at onset, and can lead to a significant delay in the diagnosis. The condition may have features similar to multiple sclerosis (MS) but the episodes are worse in NMO and it is treated differently. It could be relapsing or monophasic. Possible complications are visual field defects and motor impairment, with potential blindness and irreversible motor deficits. In severe cases, myogenic respiratory failure ensues. The incidence of reported cases is approximately 0.3–4.4 per 100,000. Paediatric cases of NMOSD are rare but have been reported occasionally, comprising less than 5% of the reported cases. Objective: The case serves to show the difficulty when it comes to the diagnostic processes regarding a rare autoimmune disease with non- specific symptoms, taking large interval of rimes to reveal as complete clinical manifestation of the aforementioned syndrome, as well as the necessity of multidisciplinary approach in the setting of а general paediatric department in аn emergency hospital. Methods: itpatient's history, clinical presentation, and information from the used diagnostic tools(MRI with contrast of the central nervous system) lead us to the conclusion .This was later on confirmed by the positive results from the anti-aquaporin 4 (AQP4) antibody serology test. Conclusion: APS is a common symptom of NMOSD and is considered a challenge in a differential-diagnostic plan. Gaining an increased awareness of this disease/syndrome, obtaining a detailed patient history, and performing thorough physical examinations are essential if we are to reduce and avoid misdiagnosis.

Keywords: neuromyelitis, devic's disease, hiccup, autoimmune, MRI

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30 Bibliometric Analysis of Risk Assessment of Inland Maritime Accidents in Bangladesh

Authors: Armana Huq, Wahidur Rahman, Sanwar Kader

Abstract:

Inland waterways in Bangladesh play an important role in providing comfortable and low-cost transportation. However, a maritime accident takes away many lives and creates unwanted hazards every year. This article deals with a comprehensive review of inland waterway accidents in Bangladesh. Additionally, it includes a comparative study between international and local inland research studies based on maritime accidents. Articles from inland waterway areas are analyzed in-depth to make a comprehensive overview of the nature of the academic work, accident and risk management process and different statistical analyses. It is found that empirical analysis based on the available statistical data dominates the research domain. For this study, major maritime accident-related works in the last four decades in Bangladesh (1981-2020) are being analyzed for preparing a bibliometric analysis. A study of maritime accidents of passenger's vessels during (1995-2005) indicates that the predominant causes of accidents in the inland waterways of Bangladesh are collision and adverse weather (77%), out of which collision due to human error alone stands (56%) of all accidents. Another study refers that the major causes of waterway accidents are the collision (60.3%) during 2005-2015. About 92% of this collision occurs due to direct contact with another vessel during this period. Rest 8% of the collision occurs by contact with permanent obstruction on waterway roots. The overall analysis of another study from the last 25 years (1995-2019) shows that one of the main types of accidents is collisions, with about 50.3% of accidents being caused by collisions. The other accident types are cyclone or storm (17%), overload (11.3%), physical failure (10.3%), excessive waves (5.1%), and others (6%). Very few notable works are available in testing or comparing the methods, proposing new methods for risk management, modeling, uncertainty treatment. The purpose of this paper is to provide an overview of the evolution of marine accident-related research domain regarding inland waterway of Bangladesh and attempts to introduce new ideas and methods to abridge the gap between international and national inland maritime-related work domain which can be a catalyst for a safer and sustainable water transportation system in Bangladesh. Another fundamental objective of this paper is to navigate various national maritime authorities and international organizations to implement risk management processes for shipping accident prevention in waterway areas.

Keywords: inland waterways, safety, bibliometric analysis, risk management, accidents

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29 Anti-Inflammatory Studies on Chungpye-Tang in Asthmatic Human Lung Tissue

Authors: J. H. Bang, H. J. Baek, K. I. Kim, B. J. Lee, H. J. Jung, H. J. Jang, S. K. Jung

Abstract:

Asthma is a chronic inflammatory lung disease characterized by airway hyper responsiveness (AHR), airway obstruction and airway wall remodeling responsible for significant morbidity and mortality worldwide. Genetic and environment factors may result in asthma, but there are no the exact causes of asthma. Chungpye-tang (CPT) has been prescribed as a representative aerosol agent for patients with dyspnea, cough and phlegm in the respiratory clinic at Kyung Hee Korean Medicine Hospital. This Korean herbal medicines have the effect of dispelling external pathogen and dampness pattern. CPT is composed of 4 species of herbal medicines. The 4 species of herbal medicines are Ephedrae herba, Pogostemonis(Agatachis) herba, Caryophylli flos and Zingiberis rhizoma crudus. CPT suppresses neutrophil infiltration and the production of pro-inflammatory cytokines in lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. Moreover, the anti-inflammatory effects of CPT on a mouse model of Chronic Obstructive Pulmonary Disease (COPD) was proved. Activation of the NF-κB has been proven that it plays an important role in inflammation via inducing transcription of pro-inflammatory genes. Over-expression of NF-κB has been believed be related to many inflammatory diseases such as arthritis, gastritis, asthma and COPD. So we firstly hypothesize whether CPT has an anti-inflammatory effect on asthmatic human airway epithelial tissue via inhibiting NF-κB pathway. In this study, CPT was extracted with distilled water for 3 hours at 100°C. After process of filtration and evaporation, it was freeze dried. And asthmatic human lung tissues were provided by MatTek Corp. We investigated the precise mechanism of the anti-inflammatory effect of CPT by western blotting analysis. We observed whether the decoction extracts could reduce NF-κB activation, COX-2 protein expression and NF-κB-mediated pro-inflammatory cytokines such as TNF-α, eotaxin, IL-4, IL-9 and IL-13 in asthmatic human lung tissue. As results of this study, there was a trend toward decreased NF-κB expression in asthmatic human airway epithelial tissue. We found that the inhibition effects of CPT on COX-2 expression was not determined. IL-9 and IL-13 secretion was significantly reduced in the asthmatic human lung tissue treated with CPT. Overall, our results indicate that CPT has an anti-inflammatory effect through blocking the signaling pathway of NF-κB, thereby CPT may be a potential remedial agent for allergic asthma.

Keywords: Chungpye-tang, allergic asthma, asthmatic human airway epithelial tissue, nuclear factor kappa B (NF-κB) pathway, COX-2

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28 Frequency of Surgical Complications in Diabetic Patients after Kidney Transplantation

Authors: Hakan Duger, Alparslan Ersoy, Canan Ersoy

Abstract:

The improvement of surgical techniques in recent years has reduced the frequency of postoperative complications in kidney transplant recipients. Novel immunosuppressive agents have reduced rates of graft loss due to acute rejection to less than 1%. However, surgical complications may still lead graft loss and morbidity in recipients. Because of potent immunosuppression, impaired wound healing and complications are frequent after transplantation. We compared the frequency of post-operative surgical complications in diabetic and non-diabetic patients after kidney transplantation. Materials and Methods: This retrospective study conducted in consecutive patients (213 females, 285 males, median age 39 years) who underwent kidney transplant surgery at our center between December 2005 and October 2015. The patients were divided into two groups: diabetics (46 ± 10 year, 26 males, 16 females) and non-diabetics (39 ± 12 year, 259 males, 197 females). Characteristics of both groups were obtained from medical records. Results: We performed 225 living and 273 deceased donor transplantations. Renal replacement type was hemodialysis in 60.8%, peritoneal dialysis in 17.3% and preemptive in 12%. The mean body mass indexes of the recipients were 24 ± 4.6 kg/m², donor age was 48.6 ± 14.3 years, cold ischemic time was 11.3 ± 6.1 hours, surgery time was 4.9 ± 1.2 hours, and recovery time was 54±31 min. The mean hospitalization duration was 19.1 ± 13.5 days. The frequency of postoperative surgical complications was 43.8%. There was no significant difference between the ratios of post-operative surgical complications in non-diabetic (43.5%) and diabetic (47.4%) groups (p=0.648). Post-operative surgical complications were lymphocele (24.6% vs. 23.7%), delayed wound healing (13.2% vs. 7.6%), hematoma (7.8% vs.15.8 %), urinary leak (4.6% vs. 5.3%), hemorrhage (5.1% vs. 0%), hydronephrosis (2.2% vs. 0%), renal artery thrombosis (1.5% vs. 0%), renal vein thrombosis (1% vs. 2.6%), urinoma (0.7% vs. 0%), urinary obstruction (0.5% vs. 0%), ureteral stenosis (0.5% vs. 0%) and ureteral reflux (0.2% vs. 0%) in non-diabetic and diabetic groups, respectively (p > 0.05). Mean serum creatinine levels in non-diabetics and diabetics were 1.43 ± 0.81 and 1.61 ± 0.96 mg/dL at 1st month (p=0.198). At the 6th month, the mean graft and patient survival times in patients with post-operative surgical complications were significantly lower than in those who did not (162.9 ± 3.4 vs. 175.6 ± 1.5 days, p=0.008, and 171 ± 2.9 vs. 176.1 ± 1.6 days, p=0.047, respectively). However, patient survival durations of non-diabetic (173 ± 27) and diabetic (177 ± 13 day) groups were comparable (p=0.396). Conclusion: As a result, we concluded that surgical complications such as lymphocele and delayed wound healing were common and that frequency of these complications in diabetic recipients did not differ from non-diabetic one. All persons involved in the postoperative care of kidney transplant recipients be aware of the potential surgical complications for rapid diagnosis and treatment.

Keywords: kidney transplantation, diabetes mellitus, surgery, complication

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27 Gluten Intolerance, Celiac Disease, and Neuropsychiatric Disorders: A Translational Perspective

Authors: Jessica A. Hellings, Piyushkumar Jani

Abstract:

Background: Systemic autoimmune disorders are increasingly implicated in neuropsychiatric illness, especially in the setting of treatment resistance in individuals of all ages. Gluten allergy in fullest extent results in celiac disease, affecting multiple organs including central nervous system (CNS). Clinicians often lack awareness of the association between neuropsychiatric illness and gluten allergy, partly since many such research studies are published in immunology and gastroenterology journals. Methods: Following a Pubmed literature search and online searches on celiac disease websites, 40 articles are critically reviewed in detail. This work reviews celiac disease, gluten intolerance and current evidence of their relationship to neuropsychiatric and systemic illnesses. The review also covers current work-up and diagnosis, as well as dietary interventions, gluten restriction outcomes, and future research directions. Results: Gluten allergy in susceptible individuals damages the small intestine, producing a leaky gut and malabsorption state, as well as allowing antibodies into the bloodstream, which attack major organs. Lack of amino acid precursors for neurotransmitter synthesis together with antibody-associated brain changes and hypoperfusion may result in neuropsychiatric illness. This is well documented; however, studies in neuropsychiatry are often small. In the large CATIE trial, subjects with schizophrenia had significantly increased antibodies to tissue transglutaminase (TTG), and antigliadin antibodies, both significantly greater gluten antibodies than in control subjects. On later follow up, TTG-6 antibodies were identified in these subjects’ brains but not in their intestines. Significant evidence mostly from small studies also exists for gluten allergy and celiac-related depression, anxiety disorders, attention-deficit/hyperactivity disorder, autism spectrum disorders, ataxia, and epilepsy. Dietary restriction of gluten resulted in remission in several published cases, including for treatment-resistant schizophrenia. Conclusions: Ongoing and larger studies are needed of the diagnosis and treatment efficacy of the gluten-free diet in neuropsychiatric illness. Clinicians should ask about the patient history of anemia, hypothyroidism, irritable bowel syndrome and family history of benefit from the gluten-free diet, not limited to but especially in cases of treatment resistance. Obtaining gluten antibodies by a simple blood test, and referral for gastrointestinal work-up in positive cases should be considered.

Keywords: celiac, gluten, neuropsychiatric, translational

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26 Outcome of Dacryocystorhinostomy with Peroperative Local Use of Mitomycin-C

Authors: Chandra Shekhar Majumder, Orin Sultana Jamie

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Background: Dacryocystorhinostomy (DCR) has been a widely accepted surgical intervention for nasolacrimal duct obstructions. Some previous studies demonstrated the potential benefits of the peroperative application of agents like Mitomycin-C (MMC) with DCR to improve surgical outcomes. Relevant studies are rare in Bangladesh, and there are controversies about the dose, duration of MMC, and outcome. Therefore, the present study aimed to investigate the comparative efficacy of DCR with and without MMC in a tertiary hospital in Bangladesh. Objective: The study aims to determine the outcome of a dacryocystorhinostomy with preoperative local use of mitomycin–C. Methods: An analytical study was conducted in the Department of Ophthalmology, Sir Salimullah Medical College & Mitford Hospital, Dhaka, from January 2023 to September 2023. Seventy patients who were admitted for DCR operation were included according to the inclusion and exclusion criteria. Patients were divided into two groups: those who underwent DCR with peroperative administration of 0.2 mg/ml Mitomycin-C for 5 minutes (Group I) and those who underwent DCR alone (Group II). All patients were subjected to detailed history taking, clinical examination, and relevant investigations. All patients underwent DCR according to standard guidelines and ensured the highest peroperative and postoperative care. Then, patients were followed up at 7th POD, 1-month POD, 3 months POD, and 6 months POD to observe the success rate between the two groups by assessing tearing condition, irrigation, height of tear meniscus, and FDDT- test. Data was recorded using a pre-structured questionnaire, and collected data were analyzed using SPSS 23. Results: The mean age of the study patients was 42.17±6.7 (SD) years and 42.29±7.1 (SD) years in Groups I and II, respectively, with no significant difference (p=0.945). At the 6th month’s follow-up, group I patients were observed with 94.3% frequency of symptom-free, 85.6% patency of lacrimal drainage system, 68.6% had tear meniscus <0.1mm and 88.6% had positive Fluorescence Dye Disappearance Test (FDDT test). In group II, 91.4% were symptom-free, 68.6% showed patency, 57.1% had a height of tear meniscus < 0.1 mm, and 85.6% had FDDT test positive. But no statistically significant difference was observed (p<.05). Conclusion: The use of Mitomycin-C preoperatively during DCR offers better postoperative outcomes, particularly in maintaining patency and achieving symptom resolution with more FDDT test positive and improvement of tear meniscus in the MMC group than the control group. However, this study didn’t demonstrate a statistically significant difference between the two groups. Further research with larger sample sizes and longer follow-up periods would be beneficial to corroborate these findings.

Keywords: dacryocystorhinostomy, mitomycin-c, dacryocystitis, nasolacrimal duct obstruction

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25 Impact of the Dog-Technic for D1-D4 and Longitudinal Stroke Technique for Diaphragm on Peak Expiratory Flow (PEF) in Asthmatic Patients

Authors: Victoria Eugenia Garnacho-Garnacho, Elena Sonsoles Rodriguez-Lopez, Raquel Delgado-Delgado, Alvaro Otero-Campos, Jesus Guodemar-Perez, Angelo Michelle Vagali, Juan Pablo Hervas-Perez

Abstract:

Asthma is a heterogeneous disease which has always had a drug treatment. Osteopathic treatment that we propose is aimed, seen through a dorsal manipulation (Dog Technic D1-D4) and a technique for diaphragm (Longitudinal Stroke) forced expiratory flow in spirometry changes there are in particular that there is an increase in the volumes of the Peak Flow and Post intervention and effort and that the application of these two techniques together is more powerful if we applied only a Longitudinal (Stroke). Also rating if this type of treatment will have repercussions on breathlessness, a very common symptom in asthma. And finally to investigate if provided vertebra pain decreased after a manipulation. Methods—Participants were recruited between students and professors of the University, aged 18-65, patients (n = 18) were assigned randomly to one of the two groups, group 1 (longitudinal Stroke and manipulation dorsal Dog Technic) and group 2 (diaphragmatic technique, Longitudinal Stroke). The statistical analysis is characterized by the comparison of the main indicator of obstruction of via area PEF (peak expiratory flow) in various situations through the peak flow meter Datospir Peak-10. The measurements were carried out in four phases: at rest, after the stress test, after the treatment, after treatment and the stress test. After each stress test was evaluated, through the Borg scale, the level of Dyspnea on each patient, regardless of the group. In Group 1 in addition to these parameters was calculated using an algometer spinous pain before and after the manipulation. All data were taken at the minute. Results—12 Group 1 (Dog Technic and Longitudinal Stroke) patients responded positively to treatment, there was an increase of 5.1% and 6.1% of the post-treatment PEF and post-treatment, and effort. The results of the scale of Borg by which we measure the level of Dyspnea were positive, a 54.95%, patients noted an improvement in breathing. In addition was confirmed through the means of both groups group 1 in which two techniques were applied was 34.05% more effective than group 2 in which applied only a. After handling pain fell by 38% of the cases. Conclusions—The impact of the technique of Dog-Technic for D1-D4 and the Longitudinal Stroke technique for diaphragm in the volumes of peak expiratory flow (PEF) in asthmatic patients were positive, there was a change of the PEF Post intervention and post-treatment, and effort and showed the most effective group in which only a technique was applied. Furthermore this type of treatment decreased facilitated vertebrae pain and was efficient in the improvement of Dyspnea and the general well-being of the patient.

Keywords: ANS, asthma, manipulation, manual therapy, osteopathic

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24 Growth and Bone Health in Children following Liver Transplantation

Authors: Faris Alkhalil, Rana Bitar, Amer Azaz, Hisham Natour, Noora Almeraikhi, Mohamad Miqdady

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Background: Children with liver transplantation are achieving very good survival and so there is now a need to concentrate on achieving good health in these patients and preventing disease. Immunosuppressive medications have side effects that need to be monitored and if possible avoided. Glucocorticoids and calcineurin inhibitors are detrimental to bone and mineral homeostasis in addition steroids can also affect linear growth. Steroid sparing regimes in renal transplant children has shown to improve children’s height. Aim: We aim to review the growth and bone health of children post liver transplant by measuring bone mineral density (BMD) using dual energy X-ray absorptiometry (DEXA) scan and assessing if there is a clear link between poor growth and impaired bone health and use of long term steroids. Subjects and Methods: This is a single centre retrospective Cohort study, we reviewed the medical notes of children (0-16 years) who underwent a liver transplantation between November 2000 to November 2016 and currently being followed at our centre. Results: 39 patients were identified (25 males and 14 females), the median transplant age was 2 years (range 9 months - 16 years), and the median follow up was 6 years. Four patients received a combined transplant, 2 kidney and liver transplant and 2 received a liver and small bowel transplant. The indications for transplant included, Biliary Atresia (31%), Acute Liver failure (18%), Progressive Familial Intrahepatic Cholestasis (15%), transplantable metabolic disease (10%), TPN related liver disease (8%), Primary Hyperoxaluria (5%), Hepatocellular carcinoma (3%) and other causes (10%). 36 patients (95%) were on a calcineurin inhibitor (34 patients were on Tacrolimus and 2 on Cyclosporin). The other three patients were on Sirolimus. Low dose long-term steroids was used in 21% of the patients. A considerable proportion of the patients had poor growth. 15% were below the 3rd centile for weight for age and 21% were below the 3rd centile for height for age. Most of our patients with poor growth were not on long term steroids. 49% of patients had a DEXA scan post transplantation. 21% of these children had low bone mineral density, one patient had met osteoporosis criteria with a vertebral fracture. Most of our patients with impaired bone health were not on long term steroids. 20% of the patients who did not undergo a DEXA scan developed long bone fractures and 50% of them were on long term steroid use which may suggest impaired bone health in these patients. Summary and Conclusion: The incidence of impaired bone health, although studied in limited number of patients; was high. Early recognition and treatment should be instituted to avoid fractures and improve bone health. Many of the patients were below the 3rd centile for weight and height however there was no clear relationship between steroid use and impaired bone health, reduced weight and reduced linear height.

Keywords: bone, growth, pediatric, liver, transplantation

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23 Uterine Torsion: A Rare Differential Diagnosis for Acute Abdominal Pain in Pregnancy

Authors: Tin Yee Ling, Kavita Maravar, Ruzica Ardalic

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Background: Uterine torsion (UT) in pregnancy of more than 45-degree along the longitudinal axis is a rare occurrence, and the aetiology remains unclear. Case: A 34-year-old G2P1 woman with a history of one previous caesarean section presented at 36+2 weeks with sudden onset lower abdominal pain, syncopal episode, and tender abdomen on examination. She was otherwise haemodynamically stable. Cardiotocography showed a pathological trace with initial prolonged bradycardia followed by a subsequent tachycardia with reduced variability. An initial diagnosis of uterine dehiscence was made, given the history and clinical presentation. She underwent an emergency caesarean section which revealed a 180-degree UT along the longitudinal axis, with oedematous left round ligament lying transverse anterior to the uterus and a segment of large bowel inferior to the round ligament. Detorsion of uterus was performed prior to delivery of the foetus, and anterior uterine wall was intact with no signs of rupture. There were no anatomical uterine abnormalities found other than stretched left ovarian and round ligaments, which were repaired. Delivery was otherwise uneventful, and she was discharged on day 2 postpartum. Discussion: UT is rare as the number of reported cases is within the few hundreds worldwide. Generally, the uterus is supported in place by uterine ligaments, which limit the mobility of the structure. The causes of UT are unknown, but risk factors such as uterine abnormalities, increased uterine ligaments’ flexibility in pregnancy, and foetal malposition has been identified. UT causes occlusion of uterine vessels, which can lead to ischaemic injury of the placenta causing premature separation of the placenta, preterm labour, and foetal morbidity and mortality if delivery is delayed. Diagnosing UT clinically is difficult as most women present with symptoms similar to placenta abruption or uterine rupture (abdominal pain, vaginal bleeding, shock), and one-third are asymptomatic. The management of UT involves surgical detorsion of the uterus and delivery of foetus via caesarean section. Extra vigilance should be taken to identify the anatomy of the uterus experiencing torsion prior to hysterotomy. There have been a few cases reported with hysterotomy on posterior uterine wall for delivery of foetus as it may be difficult to identify and reverse a gravid UT when foetal well-being is at stake. Conclusion: UT should be considered a differential diagnosis of acute abdominal pain in pregnancy. It is crucial that the torsion is addressed immediately as it is associated with maternal and foetal morbidity and mortality.

Keywords: uterine torsion, pregnancy complication, abdominal pain, torted uterus

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22 Assessment of Physical Activity Patterns in Patients with Cardiopulmonary Diseases

Authors: Ledi Neçaj

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Objectives: The target of this paper is (1) to explain objectively physical activity model throughout three chronic cardiopulmonary conditions, and (2) to study the connection among physical activity dimensions with disease severity, self-reported physical and emotional functioning, and exercise performance. Material and Methods: This is a cross-sectional study of patients in their domestic environment. Patients with cardiopulmonary diseases were: chronic obstructive pulmonary disease (COPD), (n-63), coronary heart failure (n=60), and patients with implantable cardioverter defibrillator (n=60). Main results measures: Seven ambulatory physical activity dimensions (total steps, percentage time active, percentage time ambulating at low, medium, and hard intensity, maximum cadence for 30 non-stop minutes, and peak performance) have been measured with an accelerometer. Results: Subjects with COPD had the lowest amount of ambulatory physical activity compared with topics with coronary heart failure and cardiac dysrhythmias (all 7 interest dimensions, P<.05); total step counts have been: 5319 as opposed to 7464 as opposed to 9570, respectively. Six-minute walk distance becomes correlated (r=.44-.65, P<.01) with all physical activity dimensions inside the COPD pattern, the most powerful correlations being with total steps and peak performance. In topics with cardiac impairment, maximal oxygen intake had the most effective small to slight correlations with five of the physical activity dimensions (r=.22-.40, P<.05). In contrast, correlations among 6-minute walk test distance and physical activity have been higher (r=.48-.61, P<.01) albeit in a smaller pattern of most effective patients with coronary heart failure. For all three samples, self-reported physical and mental health functioning, age, frame mass index, airflow obstruction, and ejection fraction had both exceptionally small and no significant correlations with physical activity. Conclusions: Findings from this study present a profitable benchmark of physical activity patterns in individuals with cardiopulmonary diseases for comparison with future studies. All seven dimensions of ambulatory physical activity have disfavor between subjects with COPD, heart failure, and cardiac dysrhythmias. Depending on the research or clinical goal, the use of one dimension, such as total steps, may be sufficient. Although physical activity had high correlations with performance on a six-minute walk test relative to other variables, accelerometers-based physical activity monitoring provides unique, important information about real-world behavior in patients with cardiopulmonary not already captured with existing measures.

Keywords: ambulatory physical activity, walking, monitoring, COPD, heart failure, implantable defibrillator, exercise performance

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21 Signal Transduction in a Myenteric Ganglion

Authors: I. M. Salama, R. N. Miftahof

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A functional element of the myenteric nervous plexus is a morphologically distinct ganglion. Composed of sensory, inter- and motor neurons and arranged via synapses in neuronal circuits, their task is to decipher and integrate spike coded information within the plexus into regulatory output signals. The stability of signal processing in response to a wide range of internal/external perturbations depends on the plasticity of individual neurons. Any aberrations in this inherent property may lead to instability with the development of a dynamics chaos and can be manifested as pathological conditions, such as intestinal dysrhythmia, irritable bowel syndrome. The aim of this study is to investigate patterns of signal transduction within a two-neuronal chain - a ganglion - under normal physiological and structurally altered states. The ganglion contains the primary sensory (AH-type) and motor (S-type) neurons linked through a cholinergic dendro somatic synapse. The neurons have distinguished electrophysiological characteristics including levels of the resting and threshold membrane potentials and spiking activity. These are results of ionic channel dynamics namely: Na+, K+, Ca++- activated K+, Ca++ and Cl-. Mechanical stretches of various intensities and frequencies are applied at the receptive field of the AH-neuron generate a cascade of electrochemical events along the chain. At low frequencies, ν < 0.3 Hz, neurons demonstrate strong connectivity and coherent firing. The AH-neuron shows phasic bursting with spike frequency adaptation while the S-neuron responds with tonic bursts. At high frequency, ν > 0.5 Hz, the pattern of electrical activity changes to rebound and mixed mode bursting, respectively, indicating ganglionic loss of plasticity and adaptability. A simultaneous increase in neuronal conductivity for Na+, K+ and Ca++ ions results in tonic mixed spiking of the sensory neuron and class 2 excitability of the motor neuron. Although the signal transduction along the chain remains stable the synchrony in firing pattern is not maintained and the number of discharges of the S-type neuron is significantly reduced. A concomitant increase in Ca++- activated K+ and a decrease in K+ in conductivities re-establishes weak connectivity between the two neurons and converts their firing pattern to a bistable mode. It is thus demonstrated that neuronal plasticity and adaptability have a stabilizing effect on the dynamics of signal processing in the ganglion. Functional modulations of neuronal ion channel permeability, achieved in vivo and in vitro pharmacologically, can improve connectivity between neurons. These findings are consistent with experimental electrophysiological recordings from myenteric ganglia in intestinal dysrhythmia and suggest possible pathophysiological mechanisms.

Keywords: neuronal chain, signal transduction, plasticity, stability

Procedia PDF Downloads 392
20 Advantages of Computer Navigation in Knee Arthroplasty

Authors: Mohammad Ali Al Qatawneh, Bespalchuk Pavel Ivanovich

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Computer navigation has been introduced in total knee arthroplasty to improve the accuracy of the procedure. Computer navigation improves the accuracy of bone resection in the coronal and sagittal planes. It was also noted that it normalizes the rotational alignment of the femoral component and fully assesses and balances the deformation of soft tissues in the coronal plane. The work is devoted to the advantages of using computer navigation technology in total knee arthroplasty in 62 patients (11 men and 51 women) suffering from gonarthrosis, aged 51 to 83 years, operated using a computer navigation system, followed up to 3 years from the moment of surgery. During the examination, the deformity variant was determined, and radiometric parameters of the knee joints were measured using the Knee Society Score (KSS), Functional Knee Society Score (FKSS), and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) scales. Also, functional stress tests were performed to assess the stability of the knee joint in the frontal plane and functional indicators of the range of motion. After surgery, improvement was observed in all scales; firstly, the WOMAC values decreased by 5.90 times, and the median value to 11 points (p < 0.001), secondly KSS increased by 3.91 times and reached 86 points (p < 0.001), and the third one is that FKSS data increased by 2.08 times and reached 94 points (p < 0.001). After TKA, the axis deviation of the lower limbs of more than 3 degrees was observed in 4 patients at 6.5% and frontal instability of the knee joint just in 2 cases at 3.2%., The lower incidence of sagittal instability of the knee joint after the operation was 9.6%. The range of motion increased by 1.25 times; the volume of movement averaged 125 degrees (p < 0.001). Computer navigation increases the accuracy of the spatial orientation of the endoprosthesis components in all planes, reduces the variability of the axis of the lower limbs within ± 3 °, allows you to achieve the best results of surgical interventions, and can be used to solve most basic tasks, allowing you to achieve excellent and good outcomes of operations in 100% of cases according to the WOMAC scale. With diaphyseal deformities of the femur and/or tibia, as well as with obstruction of their medullary canal, the use of computer navigation is the method of choice. The use of computer navigation prevents the occurrence of flexion contracture and hyperextension of the knee joint during the distal sawing of the femur. Using the navigation system achieves high-precision implantation for the endoprosthesis; in addition, it achieves an adequate balance of the ligaments, which contributes to the stability of the joint, reduces pain, and allows for the achievement of a good functional result of the treatment.

Keywords: knee joint, arthroplasty, computer navigation, advantages

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19 Measures of Reliability and Transportation Quality on an Urban Rail Transit Network in Case of Links’ Capacities Loss

Authors: Jie Liu, Jinqu Cheng, Qiyuan Peng, Yong Yin

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Urban rail transit (URT) plays a significant role in dealing with traffic congestion and environmental problems in cities. However, equipment failure and obstruction of links often lead to URT links’ capacities loss in daily operation. It affects the reliability and transport service quality of URT network seriously. In order to measure the influence of links’ capacities loss on reliability and transport service quality of URT network, passengers are divided into three categories in case of links’ capacities loss. Passengers in category 1 are less affected by the loss of links’ capacities. Their travel is reliable since their travel quality is not significantly reduced. Passengers in category 2 are affected by the loss of links’ capacities heavily. Their travel is not reliable since their travel quality is reduced seriously. However, passengers in category 2 still can travel on URT. Passengers in category 3 can not travel on URT because their travel paths’ passenger flow exceeds capacities. Their travel is not reliable. Thus, the proportion of passengers in category 1 whose travel is reliable is defined as reliability indicator of URT network. The transport service quality of URT network is related to passengers’ travel time, passengers’ transfer times and whether seats are available to passengers. The generalized travel cost is a comprehensive reflection of travel time, transfer times and travel comfort. Therefore, passengers’ average generalized travel cost is used as transport service quality indicator of URT network. The impact of links’ capacities loss on transport service quality of URT network is measured with passengers’ relative average generalized travel cost with and without links’ capacities loss. The proportion of the passengers affected by links and betweenness of links are used to determine the important links in URT network. The stochastic user equilibrium distribution model based on the improved logit model is used to determine passengers’ categories and calculate passengers’ generalized travel cost in case of links’ capacities loss, which is solved with method of successive weighted averages algorithm. The reliability and transport service quality indicators of URT network are calculated with the solution result. Taking Wuhan Metro as a case, the reliability and transport service quality of Wuhan metro network is measured with indicators and method proposed in this paper. The result shows that using the proportion of the passengers affected by links can identify important links effectively which have great influence on reliability and transport service quality of URT network; The important links are mostly connected to transfer stations and the passenger flow of important links is high; With the increase of number of failure links and the proportion of capacity loss, the reliability of the network keeps decreasing, the proportion of passengers in category 3 keeps increasing and the proportion of passengers in category 2 increases at first and then decreases; When the number of failure links and the proportion of capacity loss increased to a certain level, the decline of transport service quality is weakened.

Keywords: urban rail transit network, reliability, transport service quality, links’ capacities loss, important links

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18 Reagentless Detection of Urea Based on ZnO-CuO Composite Thin Film

Authors: Neha Batra Bali, Monika Tomar, Vinay Gupta

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A reagentless biosensor for detection of urea based on ZnO-CuO composite thin film is presented in following work. Biosensors have immense potential for varied applications ranging from environmental to clinical testing, health care, and cell analysis. Immense growth in the field of biosensors is due to the huge requirement in today’s world to develop techniques which are both cost effective and accurate for prevention of disease manifestation. The human body comprises of numerous biomolecules which in their optimum levels are essential for functioning. However mismanaged levels of these biomolecules result in major health issues. Urea is one of the key biomolecules of interest. Its estimation is of paramount significance not only for healthcare sector but also from environmental perspectives. If level of urea in human blood/serum is abnormal, i.e., above or below physiological range (15-40mg/dl)), it may lead to diseases like renal failure, hepatic failure, nephritic syndrome, cachexia, urinary tract obstruction, dehydration, shock, burns and gastrointestinal, etc. Various metal nanoparticles, conducting polymer, metal oxide thin films, etc. have been exploited to act as matrix to immobilize urease to fabricate urea biosensor. Amongst them, Zinc Oxide (ZnO), a semiconductor metal oxide with a wide band gap is of immense interest as an efficient matrix in biosensors by virtue of its natural abundance, biocompatibility, good electron communication feature and high isoelectric point (9.5). In spite of being such an attractive candidate, ZnO does not possess a redox couple of its own which necessitates the use of electroactive mediators for electron transfer between the enzyme and the electrode, thereby causing hindrance in realization of integrated and implantable biosensor. In the present work, an effort has been made to fabricate a matrix based on ZnO-CuO composite prepared by pulsed laser deposition (PLD) technique in order to incorporate redox properties in ZnO matrix and to utilize the same for reagentless biosensing applications. The prepared bioelectrode Urs/(ZnO-CuO)/ITO/glass exhibits high sensitivity (70µAmM⁻¹cm⁻²) for detection of urea (5-200 mg/dl) with high stability (shelf life ˃ 10 weeks) and good selectivity (interference ˂ 4%). The enhanced sensing response obtained for composite matrix is attributed to the efficient electron exchange between ZnO-CuO matrix and immobilized enzymes, and subsequently fast transfer of generated electrons to the electrode via matrix. The response is encouraging for fabricating reagentless urea biosensor based on ZnO-CuO matrix.

Keywords: biosensor, reagentless, urea, ZnO-CuO composite

Procedia PDF Downloads 290
17 Recognising and Managing Haematoma Following Thyroid Surgery: Simulation Teaching is Effective

Authors: Emily Moore, Dora Amos, Tracy Ellimah, Natasha Parrott

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Postoperative haematoma is a well-recognised complication of thyroid surgery with an incidence of 1-5%. Haematoma formation causes progressive airway obstruction, necessitating emergency bedside haematoma evacuation in up to ¼ of patients. ENT UK, BAETS and DAS have developed consensus guidelines to improve perioperative care, recommending that all healthcare staff interacting with patients undergoing thyroid surgery should be trained in managing post-thyroidectomy haematoma. The aim was to assess the effectiveness of a hybrid simulation model in improving clinician’s confidence in dealing with this surgical emergency. A hybrid simulation was designed, consisting of a standardised patient wearing a part-task trainer to mimic a post-thyroidectomy haematoma in a real patient. The part-task trainer was an adapted C-spine collar with layers of silicone representing the skin and strap muscles and thickened jelly representing the haematoma. Both the skin and strap muscle layers had to be opened in order to evacuate the haematoma. Boxes have been implemented into the appropriate post operative areas (recovery and surgical wards), which contain a printed algorithm designed to assist in remembering a sequence of steps for haematoma evacuation using the ‘SCOOP’ method (skin exposure, cut sutures, open skin, open muscles, pack wound) along with all the necessary equipment to open the front of the neck. Small-group teaching sessions were delivered by ENT and anaesthetic trainees to members of the multidisciplinary team normally involved in perioperative patient care, which included ENT surgeons, anaesthetists, recovery nurses, HCAs and ODPs. The DESATS acronym of signs and symptoms to recognise (difficulty swallowing, EWS score, swelling, anxiety, tachycardia, stridor) was highlighted. Then participants took part in the hybrid simulation in order to practice this ‘SCOOP’ method of haematoma evacuation. Participants were surveyed using a Likert scale to assess their level of confidence pre- and post teaching session. 30 clinicians took part. Confidence (agreed/strongly agreed) in recognition of post thyroidectomy haematoma improved from 58.6% to 96.5%. Confidence in management improved from 27.5% to 89.7%. All participants successfully decompressed the haematoma. All participants agreed/strongly agreed, that the sessions were useful for their learning. Multidisciplinary team simulation teaching is effective at significantly improving confidence in both the recognition and management of postoperative haematoma. Hybrid simulation sessions are useful and should be incorporated into training for clinicians.

Keywords: thyroid surgery, haematoma, teaching, hybrid simulation

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16 Choking among Babies, Toddlers and Children with Special Needs: A Review of Mechanisms, Implications, Incidence, and Recommendations of Professional Prevention Guidelines

Authors: Ella Abaev, Shany Segal, Miri Gabay

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Background: Choking is a blockage of airways that prevents efficient breathing and air flow to the lungs. Choking may be partial or full and is an emergency situation. Complete or prolonged choking leads to apnea, lack of oxygen in the tissues of the body and brain, and can cause death. There are three mechanisms of choking: obstruction of internal respiratory tracts by food or object aspiration, any material that blocks or covers external air passages, external pressure on the neck or trapping between objects. Children's airways are narrower than that of adults and therefore the risk of choking is greater, due to the aspiration of food and other foreign bodies into the lungs. In the Child Development Center at Safra Children’s Hospital, Tel Hashomer in Israel are treated infants, toddlers, and children aged 0-18 years with various developmental disabilities. Due to the increase in reports of ‘almost an event’ of choking in the past year and the serious consequences of choking event, it was decided to give an emphasis to the issue. Incidence and methods: The number of reports of ‘almost an event’ or a choking event was examined at the center during the years 2013-2018 and a thorough research work was conducted on the subject in order to build a prevention program. Findings: Between 2013 and 2018 the center reported about ten cases of ‘almost choking events’. In the middle of 2018 alone three cases of ‘almost an event’ were reported. Objective: Providing knowledge leads to awareness raise, change of perception, change in behavior and prevention. The center employs more than 130 staff members from various sectors so that it is the work of multi-professional teams to promote the quality and safety of the treatment. The familiarity of the staff with risk factors, prevention guidelines, identification of choking signs, and treatment are most important and significant in determining the outcome of a choking event. Conclusions and recommendations: After in-depth research work was carried out in cooperation with the Risk Management Unit on the subject of choking, which include a description of the definitions, mechanisms, risk factors, treatment methods and extensive recommendations for prevention (e.g. using treatment and stimulation accessories with standards association stamps and adjustment of the type of food and the way it is served to match to the child's age and the ability to swallow). The expected stages of development and emphasis on the population of children with special needs were taken into account. The research findings will be published by the staff and parents of the patients, professional publications, and lectures and there is an expectation to decrease the number of choking events in the next years.

Keywords: children with special needs, choking, educational system, prevention guidelines

Procedia PDF Downloads 179
15 Fucoidan: A Potent Seaweed-Derived Polysaccharide with Immunomodulatory and Anti-inflammatory Properties

Authors: Tauseef Ahmad, Muhammad Ishaq, Mathew Eapen, Ahyoung Park, Sam Karpiniec, Vanni Caruso, Rajaraman Eri

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Fucoidans are complex, fucose-rich sulfated polymers discovered in brown seaweeds. Fucoidans are popular around the world, particularly in the nutraceutical and pharmaceutical industries, due to their promising medicinal properties. Fucoidans have been shown to have a variety of biological activities, including anti-inflammatory effects. They are known to inhibit inflammatory processes through a variety of mechanisms, including enzyme inhibition and selectin blockade. Inflammation is a part of the complicated biological response of living systems to damaging stimuli, and it plays a role in the pathogenesis of a variety of disorders, including arthritis, inflammatory bowel disease, cancer, and allergies. In the current investigation, various fucoidan extracts from Undaria pinnatifida, Fucus vesiculosus, Macrocystis pyrifera, Ascophyllum nodosum, and Laminaria japonica were assessed for inhibition of pro-inflammatory cytokine production (TNF-α, IL-1β, and IL-6) in LPS induced human macrophage cell line (THP-1) and human peripheral blood mononuclear cells (PBMCs). Furthermore, we also sought to catalogue these extracts based on their anti-inflammatory effects in the current in-vitro cell model. Materials and Methods: To assess the cytotoxicity of fucoidan extracts, MTT (3-[4,5-dimethylthiazol-2-yl]-2,5, -diphenyltetrazolium bromide) cell viability assay was performed. Furthermore, a dose-response for fucoidan extracts was performed in LPS induced THP-1 cells and PBMCs after pre-treatment for 24 hours, and levels of TNF-α, IL-1β, and IL-6 cytokines were measured using Enzyme-Linked Immunosorbent Assay (ELISA). Results: The MTT cell viability assay demonstrated that fucoidan extracts exhibited no evidence of cytotoxicity in THP-1 cells or PBMCs after 48 hours of incubation. The results of the sandwich ELISA revealed that all fucoidan extracts suppressed cytokine production in LPS-stimulated PBMCs and human THP-1 cells in a dose-dependent manner. Notably, at lower concentrations, the lower molecular fucoidan (5-30 kDa) extract from Macrocystis pyrifera was a highly efficient inhibitor of pro-inflammatory cytokines. Fucoidan extracts from all species including Undaria pinnatifida, Fucus vesiculosus, Macrocystis pyrifera, Ascophyllum nodosum, and Laminaria japonica exhibited significant anti-inflammatory effects. These findings on several fucoidan extracts provide insight into strategies for improving their efficacy against inflammation-related diseases. Conclusion: In the current research, we have successfully catalogued several fucoidan extracts based on their efficiency in LPS-induced macrophages and PBMCs in downregulating the key pro-inflammatory cytokines (TNF-, IL-1 and IL-6), which are prospective targets in human inflammatory illnesses. Further research would provide more information on the mechanism of action, allowing it to be tested for therapeutic purposes as an anti-inflammatory medication.

Keywords: fucoidan, PBMCs, THP-1, TNF-α, IL-1β, IL-6, inflammation

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14 Data Calibration of the Actual versus the Theoretical Micro Electro Mechanical Systems (MEMS) Based Accelerometer Reading through Remote Monitoring of Padre Jacinto Zamora Flyover

Authors: John Mark Payawal, Francis Aldrine Uy, John Paul Carreon

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This paper shows the application of Structural Health Monitoring, SHM into bridges. Bridges are structures built to provide passage over a physical obstruction such as rivers, chasms or roads. The Philippines has a total of 8,166 national bridges as published on the 2015 atlas of the Department of Public Works and Highways (DPWH) and only 2,924 or 35.81% of these bridges are in good condition. As a result, PHP 30.464 billion of the 2016 budget of DPWH is allocated on roads and/or bridges maintenance alone. Intensive spending is owed to the present practice of outdated manual inspection and assessment, and poor structural health monitoring of Philippine infrastructures. As the School of Civil, Environmental, & Geological Engineering of Mapua Institute of Technology (MIT) continuous its well driven passion in research based projects, a partnership with the Department of Science and Technology (DOST) and the DPWH launched the application of Structural Health Monitoring, (SHM) in Padre Jacinto Zamora Flyover. The flyover is located along Nagtahan Boulevard in Sta. Mesa, Manila that connects Brgy. 411 and Brgy. 635. It gives service to vehicles going from Lacson Avenue to Mabini Bridge passing over Legarda Flyover. The flyover is chosen among the many located bridges in Metro Manila as the focus of the pilot testing due to its site accessibility, and complete structural built plans and specifications necessary for SHM as provided by the Bureau of Design, BOD department of DPWH. This paper focuses on providing a method to calibrate theoretical readings from STAAD Vi8 Pro and sync the data to actual MEMS accelerometer readings. It is observed that while the design standards used in constructing the flyover was reflected on the model, actual readings of MEMS accelerometer display a large difference compared to the theoretical data ran and taken from STAAD Vi8 Pro. In achieving a true seismic response of the modeled bridge or hence syncing the theoretical data to the actual sensor reading also called as the independent variable of this paper, analysis using single degree of freedom (SDOF) of the flyover under free vibration without damping using STAAD Vi8 Pro is done. The earthquake excitation and bridge responses are subjected to earthquake ground motion in the form of ground acceleration or Peak Ground Acceleration, PGA. Translational acceleration load is used to simulate the ground motion of the time history analysis acceleration record in STAAD Vi8 Pro.

Keywords: accelerometer, analysis using single degree of freedom, micro electro mechanical system, peak ground acceleration, structural health monitoring

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13 Use of Proton Pump Inhibitors Medications during the First Years of Life and Late Complications

Authors: Kamelia Hamza

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Background: Proton pump inhibitors (PPIs) are the most prescribed drug classes for pediatric gastroesophageal reflux disease (GERD).Many patients are treated with these drugs for atypical manifestations attributed to gastroesophageal reflux (GER), even in the absence of proved causal relationship. There is an impression of increase use of PPI's treatment for reflux in "clalit health services," the largest health organization in Israel. In the recent years, the medicine is given without restriction, it's not limited to pediatric gastroenterologists only, but pediatricians and family doctors. The objective of this study is to evaluate the hypothesis that exposure to PPIs during the first year of life is associated with an increased risk of developing late adverse diseases: pneumonia, asthma, AGE, IBD, celiac disease, allergic disorders, obesity, attention deficit hyperactivity disorders (ADHD), autism spectrum disorders (ASD). Methods: The study is a retrospective case-control cohort study based on a computerized database of Clalit Health Services (CHS). It includes 9844 children born between 2002-2018 and reported to complain of at least one of the symptoms (reflux/ spitting up, irritability, feeding difficulties, colics). The study population included the study group (n=4922) of children exposed to PPIs at any time prior to the first year of life and a control group (n=4922) child not exposed to PPIs who were matched to each case of the study group on age, race, socioeconomic status, and year of birth. The prevalence of late complications/diseases in the study group was compared with the prevalence of late complications/diseases diagnosis between 2002-2020 in the control group. Odds ratios and 95% confidence intervals were calculated by using logistic regression models. Results: We found that compared to the control group, children exposed to PPIs in the first year of life had an increased risk of developing several late complications/ disorders: pneumonia, asthma, various allergies (urticaria, allergic rhinitis, or allergic conjunctivitis) OR, inhalant allergies, and food allergies. In addition, they showed an increased risk of being diagnosed with ADHD or ASD, but children exposed to PPIs in the first year of life had decrease the risk of obesity by 17% (OR 0.825, 95%CI 0.697-0.976). Conclusions: We found significant associations between the use of PPIs during the first year of life and subsequent development of late complications/diseases such as respiratory diseases, allergy diseases, ADHD, and ASD. More studies are needed to prove causality and determine the mechanism behind the effect of PPIs and the development of late complications.

Keywords: acid suppressing medications, proton pump inhibitors, histamine 2 blocker, late complications, gastroesophageal reflux, gastroesophageal reflux disease, acute gastroenteritis, community acquired pneumonia, asthma, allergic diseases, obesity, inflammatory bowel diseases, ulcerative colitis, crohn disease, attention deficit hyperactivity disorders, autism spectrum disorders

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12 Head and Neck Extranodal Rosai-Dorfman Disease- Utility of immunohistochemistry

Authors: Beverly Wang

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Background: Rosai-Dorfman disease (RDD), aka sinus histiocytosis with massive lymphadenopathy, is a rare, idiopathic histiocytic proliferative disorder. Although RDD can be seen involving the head and neck lymph nodes, rarely it can affect other extranodal sites. It present 3 unique cases of RDD affecting the nasal cavity, paranasal sinuses, and ear canal. The initial clinical presentation on two cases mimicked a malignant neoplasm. The 3rd case of RDD co-existed with a cholesteatoma of the ear canal. The clinical presentation, histology and immunohistochemical stains, and radiographic findings are discussed. Design: An overview of 3 cases of RDD affected sinonasal cavity and ear canal from UCI Medical Center was conducted. Case 1: A 61 year old male complaining of breathing difficulty presented with bilateral polypoid sinonasal masses and severe nasal obstruction. The masses elevated the nasal floor, and involved the anterior nasal septum to lateral wall. It was endoscopically excised. At intraoperative consultation, frozen section reported a pleomorphic spindle cell neoplasm with scattered large atypical spindle cells, resembling a high grade sarcoma. Case 2: A 46 year old male presented with recurrent bilateral maxillary chronic sinusitis with mass formation, clinically suspicious for malignant lymphoma. Excisional tissue sample showed large irregular spindled histiocytes with abundant granular and vacuolated cytoplasm. Case 3: A 36 year old female with a history of asthma initially presented with left-sided chronic otalgia, occasional nausea, vertigo, and fluctuating pain exacerbated by head movement and temperature changes. CT scan revealed an external auditory canal mass extending to the middle ear, coexisting with a small cholesteatoma. Results: The morphology of all cases revealed large atypical spindled histiocytes resembling fibrohistiocytic or myofibroblastic proliferative neoplasms. Scattered emperipolesis was seen. All 3 cases were confirmed as extranodal sinus RDD, confirmed by immunohistochemistry. The large atypical cells were positive for S100, CD68, and CD163. No evidence for malignancy was identified. Case 3 showed concurrent RDD co-existing with a cholesteatoma. Conclusion: Due to its rarity and variable clinical presentations, the diagnosis of RDD is seldom clinically considered. Extranodal sinus RDD morphologically can be pitfall as mimicker of spindly neoplasm, especially at intraoperative consultation. It can create diagnostic and therapeutic challenges. Correlation of radiological findings with histologic features will help to reach the diagnosis.

Keywords: head and neck, extranodal, rosai-dorfman disease, mimicker, immunohistochemistry

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11 Indoor Air Pollution and Reduced Lung Function in Biomass Exposed Women: A Cross Sectional Study in Pune District, India

Authors: Rasmila Kawan, Sanjay Juvekar, Sandeep Salvi, Gufran Beig, Rainer Sauerborn

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Background: Indoor air pollution especially from the use of biomass fuels, remains a potentially large global health threat. The inefficient use of such fuels in poorly ventilated conditions results in high levels of indoor air pollution, most seriously affecting women and young children. Objectives: The main aim of this study was to measure and compare the lung function of the women exposed in the biomass fuels and LPG fuels and relate it to the indoor emission measured using a structured questionnaire, spirometer and filter based low volume samplers respectively. Methodology: This cross-sectional comparative study was conducted among the women (aged > 18 years) living in rural villages of Pune district who were not diagnosed of chronic pulmonary diseases or any other respiratory diseases and using biomass fuels or LPG for cooking for a minimum period of 5 years or more. Data collection was done from April to June 2017 in dry season. Spirometer was performed using the portable, battery-operated ultrasound Easy One spirometer (Spiro bank II, NDD Medical Technologies, Zurich, Switzerland) to determine the lung function over Forced expiratory volume. The primary outcome variable was forced expiratory volume in 1 second (FEV1). Secondary outcome was chronic obstruction pulmonary disease (post bronchodilator FEV1/ Forced Vital Capacity (FVC) < 70%) as defined by the Global Initiative for Obstructive Lung Disease. Potential confounders such as age, height, weight, smoking history, occupation, educational status were considered. Results: Preliminary results showed that the lung function of the women using Biomass fuels (FEV1/FVC = 85% ± 5.13) had comparatively reduced lung function than the LPG users (FEV1/FVC = 86.40% ± 5.32). The mean PM 2.5 mass concentration in the biomass user’s kitchen was 274.34 ± 314.90 and 85.04 ± 97.82 in the LPG user’s kitchen. Black carbon amount was found higher in the biomass users (black carbon = 46.71 ± 46.59 µg/m³) than LPG users (black carbon=11.08 ± 22.97 µg/m³). Most of the houses used separate kitchen. Almost all the houses that used the clean fuel like LPG had minimum amount of the particulate matter 2.5 which might be due to the background pollution and cross ventilation from the houses using biomass fuels. Conclusions: Therefore, there is an urgent need to adopt various strategies to improve indoor air quality. There is a lacking of current state of climate active pollutants emission from different stove designs and identify major deficiencies that need to be tackled. Moreover, the advancement in research tools, measuring technique in particular, is critical for researchers in developing countries to improve their capability to study the emissions for addressing the growing climate change and public health concerns.

Keywords: black carbon, biomass fuels, indoor air pollution, lung function, particulate matter

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10 Mechanical Transmission of Parasites by Cockroaches’ Collected from Urban Environment of Lahore, Pakistan

Authors: Hafsa Memona, Farkhanda Manzoor

Abstract:

Cockroaches are termed as medically important pests because of their wide distribution in human habitation including houses, hospitals, food industries and kitchens. They may harbor multiple drug resistant pathogenic bacteria and protozoan parasites on their external surfaces, disseminate on human food and cause serious diseases and allergies to human. Hence, they are regarded as mechanical vector in human habitation due to their nocturnal activity and nutritional behavior. Viable eggs and dormant cysts of parasites can hitch a ride on cockroaches. Ova and cysts of parasitic organism may settle into the crevices and cracks between thorax and head. There are so many fissures and clefts and crannies on a cockroach which provide site for these organisms. This study aimed with identifying role of cockroaches in mechanically transmitting and disseminating gastrointestinal parasites in two environmental settings; hospitals and houses in urban area of Lahore. Totally, 250 adult cockroaches were collected from houses and hospitals by sticky traps and food baited traps and screened for parasitic load. All cockroaches were captured during their feeding time in natural habitat. Direct wet smear, 1% lugols iodine and modified acid-fast bacilli staining were used to identify the parasites from the body surfaces of cockroaches. Among human habitation two common species of cockroaches were collected i.e. P. americana and B. germanica. The results showed that 112 (46.8%) cockroaches harbored at least one human intestinal parasite on their body surfaces. The cockroaches from hospital environment harboured more parasites than houses. 47 (33.57%) cockroaches from houses and 65 (59.09%) from hospitals were infected with parasitic organisms. Of these, 76 (67.85%) were parasitic protozoans and 36(32.15%) were pathogenic and non-pathogenic intestinal parasites. P. americana harboured more parasites as compared to B. germanica in both environment. Most common human intestinal parasites found on cockroaches include ova of Ascaris lumbricoides (giant roundworm), Trichuris trichura (whipworm), Anchylostoma deodunalae (hookworm), Enterobius vermicularis (pinworm), Taenia spp. and Strongyloides stercoralis (threadworm). The cysts of protozoans’ parasites including Balantidium coli, Entomoeba hystolitica, C. parvum, Isospora belli, Giardia duodenalis and C. cayetenensis were isolated and identified from cockroaches. Both experimental sites were significantly different in carriage of parasitic load on cockroaches. Difference in the hygienic condition of the environments, including human excrement disposal, variable habitat interacted, indoor and outdoor species, may account for the observed variation in the parasitic carriage rate of cockroaches among different experimental site. Thus a finding of this study is that Cockroaches are uniformly distributed in human habitation and act as a mechanical vector of pathogenic parasites that cause common illness such as diarrhea and bowel disorders. This fact contributes to epidemiological chain therefore control of cockroaches will significantly lessen the prevalence of illness in human. Effective control strategies will reduce the public health burden of the gastro-intestinal parasites in the developing countries.

Keywords: cockroaches, health risks, hospitals, houses, parasites, protozoans, transmission

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9 High Speed Motion Tracking with Magnetometer in Nonuniform Magnetic Field

Authors: Jeronimo Cox, Tomonari Furukawa

Abstract:

Magnetometers have become more popular in inertial measurement units (IMU) for their ability to correct estimations using the earth's magnetic field. Accelerometer and gyroscope-based packages fail with dead-reckoning errors accumulated over time. Localization in robotic applications with magnetometer-inclusive IMUs has become popular as a way to track the odometry of slower-speed robots. With high-speed motions, the accumulated error increases over smaller periods of time, making them difficult to track with IMU. Tracking a high-speed motion is especially difficult with limited observability. Visual obstruction of motion leaves motion-tracking cameras unusable. When motions are too dynamic for estimation techniques reliant on the observability of the gravity vector, the use of magnetometers is further justified. As available magnetometer calibration methods are limited with the assumption that background magnetic fields are uniform, estimation in nonuniform magnetic fields is problematic. Hard iron distortion is a distortion of the magnetic field by other objects that produce magnetic fields. This kind of distortion is often observed as the offset from the origin of the center of data points when a magnetometer is rotated. The magnitude of hard iron distortion is dependent on proximity to distortion sources. Soft iron distortion is more related to the scaling of the axes of magnetometer sensors. Hard iron distortion is more of a contributor to the error of attitude estimation with magnetometers. Indoor environments or spaces inside ferrite-based structures, such as building reinforcements or a vehicle, often cause distortions with proximity. As positions correlate to areas of distortion, methods of magnetometer localization include the production of spatial mapping of magnetic field and collection of distortion signatures to better aid location tracking. The goal of this paper is to compare magnetometer methods that don't need pre-productions of magnetic field maps. Mapping the magnetic field in some spaces can be costly and inefficient. Dynamic measurement fusion is used to track the motion of a multi-link system with us. Conventional calibration by data collection of rotation at a static point, real-time estimation of calibration parameters each time step, and using two magnetometers for determining local hard iron distortion are compared to confirm the robustness and accuracy of each technique. With opposite-facing magnetometers, hard iron distortion can be accounted for regardless of position, Rather than assuming that hard iron distortion is constant regardless of positional change. The motion measured is a repeatable planar motion of a two-link system connected by revolute joints. The links are translated on a moving base to impulse rotation of the links. Equipping the joints with absolute encoders and recording the motion with cameras to enable ground truth comparison to each of the magnetometer methods. While the two-magnetometer method accounts for local hard iron distortion, the method fails where the magnetic field direction in space is inconsistent.

Keywords: motion tracking, sensor fusion, magnetometer, state estimation

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8 Pharmacokinetic Assessment of Antimicrobial Treatment of Acute Exacerbations of Chronic Obstructive Pulmonary Disease in Hospitalized Patients Colonized with Pseudomonas aeruginosa

Authors: Juliette Begin, Juliano Colapelle, Andrea Taratanu, Daniel Thirion, Amelie Marsot, Bryan A. Ross

Abstract:

Chronic obstructive pulmonary disease (COPD), a leading cause of death globally, is characterized by chronic airflow obstruction and acute exacerbations (AECOPDs) that are often triggered by respiratory infections. Pseudomonas aeruginosa (P. aeruginosa), a potentially serious bacterial cause of AECOPDs, is treated with targeted anti-pseudomonal antibiotics. These select few antimicrobials are often used as first-line therapy in patients who are clinically unwell and/or in those suspected of P. aeruginosa-related infection prior to confirmation, potentially contributing to antimicrobial resistance. The present study evaluates prescribing practices in patients with a confirmed sputum history of P. aeruginosa admitted for AECOPD at the McGill University Health Centre (MUHC) and treated with anti-pseudomonal antibiotics. Serum antibiotic concentrations were measured from the same-day peak, trough, and mid-dose blood sampling intervals after reaching steady-state (on or after day 3) and were quantified using ultra-high-performance liquid chromatography (UHPLC). Demographic, clinical, and treatment outcomes were extracted from patient medical charts. Treatment failure was defined by respiratory-related death or mechanical ventilation after ≥3 days of antibiotics; antibiotic therapy extended beyond 2 weeks or a new antibiotic regimen started; or urgent care readmission within 30 days for AECOPD. To date, 9 of 30 planned participants have completed testing: seven received ciprofloxacin, one received meropenem, and one received piperacillin-tazobactam. Due to serum sample batching requirements, the serum ciprofloxacin concentration results for the first 2/8 participants are presented at the time of writing. The first participant had serum levels of 5.45mg/L (T₀), 4.74mg/L (T₅₀), and 4.49mg/L (T₁₀₀), while the second had serum levels of 5mg/L (T₀), 2.6mg/L (T₅₀), and 2.51mg/L (T₁₀₀). Pharmacokinetic parameters Cmax (5.18±0.43mg/L), T₁/₂ (23.56±18.94hours), and AUC (181.9±155.95mg*h/l) were higher than reported monograph values and met target AUC-to-MIC ratio of >125. The patients treated with meropenem and with piperacillin-tazobactam experienced treatment failure. Preliminary results suggest that standard ciprofloxacin dosing in patients experiencing an AECOPD and colonized with P. aeruginosa appears to achieve effective serum concentrations. Final cohort results will inform the pharmacokinetic appropriateness and clinical sufficiency of current AECOPD antimicrobial strategies in P. aeruginosa-colonized patients. This study will guide clinicians in determining the appropriate dosing for AECOPD treatment to achieve therapeutic levels, optimizing outcomes, and minimizing adverse effects. It could also highlight the value of routine antibiotic level monitoring in patients with treatment failure to ensure optimal serum concentrations.

Keywords: acute exacerbation, antimicrobial resistance, chronic obstructive pulmonary disease, pharmacokinetics/pharmacodynamics, Pseudomonas aeruginosa

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7 In vivo Evaluation of LAB Probiotic Potential with the Zebrafish Animal Model

Authors: Iñaki Iturria, Pasquale Russo, Montserrat Nacher-Vázquez, Giuseppe Spano, Paloma López, Miguel Angel Pardo

Abstract:

Introduction: It is known that some Lactic Acid Bacteria (LAB) present an interesting probiotic effect. Probiotic bacteria stimulate host resistance to microbial pathogens and thereby aid in immune response, and modulate the host's immune responses to antigens with a potential to down-regulate hypersensitivity reactions. Therefore, probiotic therapy is valuable against intestinal infections and may be beneficial in the treatment of Inflammatory Bowel Disease (IBD). Several in vitro tests are available to evaluate the probiotic potential of a LAB strain. However, an in vivo model is required to understand the interaction between the host immune system and the bacteria. During the last few years, zebrafish (Danio rerio) has gained interest as a promising vertebrate model in this field. This organism has been extensively used to study the interaction between the host and the microbiota, as well as the host immune response under several microbial infections. In this work, we report on the use of the zebrafish model to investigate in vivo the colonizing ability and the immunomodulatory effect of probiotic LAB. Methods: Lactobacillus strains belonging to different LAB species were fluorescently tagged and used to colonize germ-free zebrafish larvae gastrointestinal tract (GIT). Some of the strains had a well-documented probiotic effect (L. acidophilus LA5); while others presented an exopolysaccharide (EPS) producing phenotype, thus allowing evaluating the influence of EPS in the colonization and immunomodulatory effect. Bacteria colonization was monitored for 72 h by direct observation in real time using fluorescent microscopy. CFU count per larva was also evaluated at different times. The immunomodulatory effect was assessed analysing the differential expression of several innate immune system genes (MyD88, NF-κB, Tlr4, Il1β and Il10) by qRT- PCR. The anti-inflammatory effect was evaluated using a chemical enterocolitis zebrafish model. The protective effect against a pathogen was also studied. To that end, a challenge test was developed using a fluorescently tagged pathogen (Vibrio anguillarum-GFP+). The progression of the infection was monitored up to 3 days using a fluorescent stereomicroscope. Mortality rates and CFU counts were also registered. Results and conclusions: Larvae exposed to EPS-producing bacteria showed a higher fluorescence and CFU count than those colonized with no-EPS phenotype LAB. In the same way, qRT-PCR results revealed an immunomodulatory effect on the host after the administration of the strains with probiotic activity. A downregulation of proinflammatory cytoquines as well as other cellular mediators of inflammation was observed. The anti-inflammatory effect was found to be particularly marked following exposure to LA% strain, as well as EPS producing strains. Furthermore, the challenge test revealed a protective effect of probiotic administration. As a matter of fact, larvae fed with probiotics showed a decrease in the mortality rate ranging from 20 to 35%. Discussion: In this work, we developed a promising model, based on the use of gnotobiotic zebrafish coupled with a bacterial fluorescent tagging in order to evaluate the probiotic potential of different LAB strains. We have successfully used this system to monitor in real time the colonization and persistence of exogenous LAB within the gut of zebrafish larvae, to evaluate their immunomodulatory effect and for in vivo competition assays. This approach could bring further insights into the complex microbial-host interactions at intestinal level.

Keywords: gnotobiotic, immune system, lactic acid bacteria, probiotics, zebrafish

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6 Gene Expression Meta-Analysis of Potential Shared and Unique Pathways Between Autoimmune Diseases Under anti-TNFα Therapy

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

Abstract:

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

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

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