Search results for: patients needs

Authors: Sarocha Vivatvakin, Thanaporn Ratchataswan, Thiratest Leesutipornchai, Komkrit Ruangritchankul, Somboon Keelawat, Virachai Kerekhanjanarong, Patnarin Mahattanasakul, Saknan Bongsebandhu-Phubhakdi

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In this globalization era, much attention has been drawn to various molecular biomarkers, which may have the potential to predict the progression of cancer. Epidermal growth factor receptor (EGFR) is the classic member of the ErbB family of membrane-associated intrinsic tyrosine kinase receptors. EGFR expression was found in several organs throughout the body as its roles involve in the regulation of cell proliferation, survival, and differentiation in normal physiologic conditions. However, anomalous expression, whether over- or under-expression is believed to be the underlying mechanism of pathologic conditions, including carcinogenesis. Even though numerous discussions regarding the EGFR as a prognostic tool in head and neck cancer have been established, the consensus has not yet been met. The aims of the present study are to assess the correlation between the level of EGFR expression and demographic data as well as clinicopathological features and to evaluate the ability of EGFR as a reliable prognostic marker. Furthermore, another aim of this study is to investigate the probable pathophysiology that explains the finding results. This retrospective study included 30 squamous cell laryngeal carcinoma patients treated at King Chulalongkorn Memorial Hospital from January 1, 2000, to December 31, 2004. EGFR expression level was observed to be significantly downregulated with the progression of the laryngeal cancer stage. (one way ANOVA, p = 0.001) A statistically significant lower EGFR expression in the late stage of the disease compared to the early stage was recorded. (unpaired t-test, p = 0.041) EGFR overexpression also showed the tendency to increase recurrence of cancer (unpaired t-test, p = 0.128). A significant downregulation of EGFR expression was documented in advanced stage laryngeal cancer. The results indicated that EGFR level correlates to prognosis in term of stage progression. Thus, EGFR expression might be used as a prevailing biomarker for laryngeal squamous cell carcinoma prognostic prediction.

Keywords: downregulation, epidermal growth factor receptor, immunohistochemistry, laryngeal squamous cell carcinoma

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Authors: Rohan Bhasin

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Agrammatism in non-fluent Aphasia Cases can be defined as a language disorder wherein a patient can only use content words ( nouns, verbs and adjectives ) for communication and their speech is devoid of functional word types like conjunctions and articles, generating speech of with extremely rudimentary grammar . Past approaches involve Speech Therapy of some order with conversation analysis used to analyse pre-therapy speech patterns and qualitative changes in conversational behaviour after therapy. We describe this approach as a novel method to generate functional words (prepositions, articles, ) around content words ( nouns, verbs and adjectives ) using a combination of Natural Language Processing and Deep Learning algorithms. The applications of this approach can be used to assist communication. The approach the paper investigates is : LSTMs or Seq2Seq: A sequence2sequence approach (seq2seq) or LSTM would take in a sequence of inputs and output sequence. This approach needs a significant amount of training data, with each training data containing pairs such as (content words, complete sentence). We generate such data by starting with complete sentences from a text source, removing functional words to get just the content words. However, this approach would require a lot of training data to get a coherent input. The assumptions of this approach is that the content words received in the inputs of both text models are to be preserved, i.e, won't alter after the functional grammar is slotted in. This is a potential limit to cases of severe Agrammatism where such order might not be inherently correct. The applications of this approach can be used to assist communication mild Agrammatism in non-fluent Aphasia Cases. Thus by generating these function words around the content words, we can provide meaningful sentence options to the patient for articulate conversations. Thus our project translates the use case of generating sentences from content-specific words into an assistive technology for non-Fluent Aphasia Patients.

Keywords: aphasia, expressive aphasia, assistive algorithms, neurology, machine learning, natural language processing, language disorder, behaviour disorder, sequence to sequence, LSTM

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Authors: Pintusorn Hansakul, Ruchilak Rattarom, Arunporn Itharat

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Background: Benjakul, a Thai traditional herbal formulation, comprises of five plants: Piper chaba, Piper sarmentosum, Piper interruptum, Plumbago indica, and Zingiber officinale. It has been widely used to treat cancer patients in the context of folk medicine in Thailand. This study aimed to investigate the cytotoxic effect of the ethanol extract of Benjakul against three non-small cell lung cancer (NSCLC) cell lines (NCI-H226, A549, COR-L23), small cell lung cancer (SCLC) cell line NCI-H1688 and normal lung fibroblast cell line MRC-5. The study further examined the molecular mechanisms underlying its cytotoxicity via induction of apoptosis in NCI-H226 cells. Methods: The cytotoxic effect of Benjakul was determined by SRB assay. The effect of Benjakul on cell cycle distribution was assessed by flow cytometric analysis. The apoptotic effects of Benjakul were determined by sub-G1 quantitation and Annexin V-FITC/PI flow cytometric analyses as well as by changes in caspase-3 activity. Results: Benjakul exerted potent cytotoxicity on NCI-H226 and A549 cells but lower cytotoxicity on COR-L23 and NCI-H1688 cells without any cytotoxic effect on normal cells. Molecular studies showed that Benjakul extract induced G2/M phase arrest in human NCI-H226 cells in a dose-dependent manner. The highest concentration of Benjakul (150 μg/ml) led to the highest increase in the G2/M population at 12 h, followed by the highest increase in the sub-G1 population (apoptotic cells) at 60 h. Benjakul extract also induced early apoptosis (AnnexinV +/PI−) in NCI-H226 cells in a dose- and time- dependent manner. Moreover, treatment with 150 μg/ml Benjakul extract for 36 h markedly increased caspase-3 activity by 3.5-fold, and pretreatment with the general caspase inhibitor z-VAD-fmk completely abolished such activity. Conclusions: This study reveals for the first time the regulation of apoptosis in human lung cancer NCI-H226 cells through caspase-dependent mechanism by Benjakul extract.

Keywords: apoptosis, Benjakul, caspase activation, cytotoxicity

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Authors: Diana Peninger

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Over 10% of couples in the U.S. have infertility problems, with roughly 40% traceable to the male partner. Yet, little attention has been given to improving men’s contribution to the conception process. One solution that is showing promise in increasing conception rates for IVF and other assisted reproductive technology treatments is a first-of-its-kind semen collection that has been engineered to mitigate sperm damage caused by traditional collection methods. Patients are able to collect semen at home and deliver to clinics within 48 hours for use in fertility analysis and treatment, with less stress and improved specimen viability. This abstract will share these findings along with expert insight and tips to help attendees understand the key role sperm collection plays in addressing and treating reproductive issues, while helping to improve patient outcomes and success. Our research was to determine if male reproductive outcomes can be increased by improving sperm specimen health with a focus on technology. We utilized a redesigned semen collection cup (patented as the Device for Improved Semen Collection/DISC—U.S. Patent 6864046 – known commercially as a ProteX) that met a series of physiological parameters. Previous research demonstrated significant improvement in semen perimeters (motility forward, progression, viability, and longevity) and overall sperm biochemistry when the DISC is used for collection. Animal studies have also shown dramatic increases in pregnancy rates. Our current study compares samples collected in the DISC, next-generation DISC (DISCng), and a standard specimen cup (SSC), dry, with the 1 mL measured amount of media and media in excess ( 5mL). Both human and animal testing will be included. With sperm counts declining at alarming rates due to environmental, lifestyle, and other health factors, accurate evaluations of sperm health are critical to understanding reproductive health, origins, and treatments of infertility. An increase in the health of the sperm as measured by extensive semen parameter analysis and improved semen parameters stable for 48 hours, expanding the processing time from 1 hour to 48 hours were also demonstrated.

Keywords: reprodutive, sperm, male, infertility

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Authors: Dativa Maria Aliddeki, Fred Monje, Godfrey Nsereko, Benon Kwesiga, Daniel Kadobera, Alex Riolexus Ario

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Background: Cholera is a severe gastrointestinal disease caused by Vibrio cholera. It has caused several pandemics. On 26 February 2018, a suspected cholera outbreak, with one death, occurred in School X in Hoima Municipality, western Uganda. We investigated to identify the scope and mode of transmission of the outbreak, and recommend evidence-based control measures. Methods: We defined a suspected case as onset of diarrhea, vomiting, or abdominal pain in a student or staff of School X or their family members during 14 February–10 March. A confirmed case was a suspected case with V. cholerae cultured from stool. We reviewed medical records at Hoima Hospital and searched for cases at School X. We conducted descriptive epidemiologic analysis and hypothesis-generating interviews of 15 case-patients. In a retrospective cohort study, we compared attack rates between exposed and unexposed persons. Results: We identified 15 cases among 75 students and staff of School X and their family members (attack rate=20%), with onset from 25-28 February. One patient died (case-fatality rate=6.6%). The epidemic curve indicated a point-source exposure. On 24 February, a student brought fried fish from her home in a fishing village, where a cholera outbreak was ongoing. Of the 21 persons who ate the fish, 57% developed cholera, compared with 5.6% of 54 persons who did not eat (RR=10; 95% CI=3.2-33). None of 4 persons who recooked the fish before eating, compared with 71% of 17 who did not recook it, developed cholera (RR=0.0, 95%CIFisher exact=0.0-0.95). Of 12 stool specimens cultured, 6 yielded V. cholerae. Conclusion: This cholera outbreak was caused by eating fried fish, which might have been contaminated with V. cholerae in a village with an ongoing outbreak. Lack of thorough cooking of the fish might have facilitated the outbreak. We recommended thoroughly cooking fish before consumption.

Keywords: cholera, disease outbreak, foodborne, global health security, Uganda

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Authors: Amina Unis, Samah S. El Basateeny, Noha A. H. Nassef

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Introduction: Acute Renal Failure (ARF) is one of the most common problems encountered in hospitalized critically ill patients. In recent years great effort has been focused on the introduction of herbal medicine as a novel therapeutic agent for prevention of ARF. Hence, the current study was designed to investigate the effect of Green Coffee Bean Extract (GCBE) on gentamicin induced ARF in rats. Methods: The study was conducted on 60 male rats divided into six equal groups. Group 1 served as normal control group and GCBE was administered for 7 days at a dose of 20 mg/kg/day in group 2 and 40 mg/kg/day in group 3 to test the effect of GCBE on normal kidneys. ARF was induced by a daily intraperitoneal injection of gentamicin (80 mg/kg) for 7 days in group 4 (model group), group 5 (GCBE 20 mg/kg/day) and group 6 (GCBE 20 mg/kg/day). All rats were sacrificed after 7 days and blood was withdrawn for kidney function tests. Kidneys were removed for determination of renal oxidative stress markers and histopathological examination. Results: The present study showed that rats that received oral GCBE for 7 days without induction of ARF showed no significant change in all the assessed parameters in comparison to the normal control group, while rats in the groups that received oral GCBE for 7 days with induction of ARF showed a significant improvement in kidney functions tests (decrease in serum urea, serum creatinine, and blood urea nitrogen) when compared to the ARF model group. Moreover, there was significant amelioration in renal oxidative stress markers (renal malondialdehyde, renal superoxide dismutase) and renal histopathological changes in the GCBE treated groups along induction of ARF when compared to ARF model group. The most significant improvement was reported in the group where GCBE was administered for 7 days in a dose 40 mg/kg/day, along with induction of ARF. Conclusion: GCBE has a potential role in ameliorating renal damage involved in ARF mostly through its antioxidant effect.

Keywords: green coffee bean extract, gentamicin, acute renal failure, pharmacology

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Authors: Michael Ward, Eliana Kalakouti, Andrew Alabi

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Aim: The handover process is recognized as a vulnerable step in the patient care pathway where errors are likely to occur. As such, it is a major preventable cause of patient harm due to human factors of poor communication and systematic error. The aim of this study was to audit the general surgery department’s weekend handover process compared to the recommended criteria for safe handover as set out by the Royal College of Surgeons (RCS). Method: A retrospective audit of the General Surgery department’s Friday patient lists and patient medical notes used for weekend handover in a London-based District General Hospital (DGH). Medical notes were analyzed against RCS's suggested criteria for handover. A standardized paper weekend handover proforma was then developed in accordance with guidelines and circulated in the department. A post-intervention audit was then conducted using the same methods for cycle 1. For cycle 2, we introduced an electronic weekend handover tool along with Electronic Patient Records (EPR). After a one-month period, a second post-intervention audit was conducted. Results: Following cycle 1, the paper weekend handover proforma was only used in 23% of patient notes. However, when it was used, 100% of them had a plan for the weekend, diagnosis and location but only 40% documented potential discharge status and 40% ceiling of care status. Qualitative feedback was that it was time-consuming to fill out. Better results were achieved following cycle 2, with 100% of patient notes having the electronic proforma. Results improved with every patient having documented ceiling of care, discharge status and location. Only 55% of patients had a past surgical history; however, this was still an increase when compared to paper proforma (45%). When comparing electronic versus paper proforma, there was an increase in documentation in every domain of the handover outlined by RCS with an average relative increase of 1.72 times (p<0.05). Qualitative feedback was that the autofill function made it easy to use and simple to view. Conclusion: These results demonstrate that the implementation of an electronic autofill handover proforma significantly improved handover compliance with RCS guidelines, thereby improving the transmission of information from week-day to weekend teams.

Keywords: surgery, handover, proforma, electronic handover, weekend, general surgery

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Authors: Katarzyna Palus, Jarosław Całka

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Gastrointestinal disorders, especially acid-related diseases, including peptic and duodenal ulcers, gastroesophageal reflux disease, upper GI bleeding or stress-related mucosal disease, are currently serious health issues encountered very frequently in patients worldwide. However, to date, the response of sympathetic neurons to gastric mucosal injury and local inflammation following hyperacidity is unknown. Thus, the present study was designed to determine possible changes in expression of galanin (GAL) in the CSMG neurons supplying the prepyloric area of the porcine stomach in a physiological state and following experimentally-induced hyperacidity by using combined retrograde tracing and double-labelling immunohistochemistry. The choice of the domestic pig as an experimental model in the present study is not accidental and is justified by the high degree of physiological and anatomical similarity to human digestive system functions. In this experiment ten juvenile female pigs of the Large White Polish breed were used. The animals were divided into two groups: control and animals with hydrochloric acid infusion (HCl). The neuronal retrograde marker Fast Blue (FB) was injected into the anterior prepyloric wall of the stomach of all animals. After 23 days, animals of the HCl-group were reintroduced into a state of general anesthesia and intragastrically given 5 ml/kg of body weight of 0.25 M aqueous solution of hydrochloric acid. On the 28th day, all animals were euthanized. The CSMG complexes were then collected and the CSMG cryostat sections were stained immunocytochemically for GAL and TH (tyrosine hydroxylase). Immunohistochemistry revealed that in the control group 8.40 ± 0.53 % out of 200 FB-positive CSMG neurons contained GAL. In HCl group upregulation of the GAL-IR neurons to 22.52 ± 1.18 % were observed. All GAL-IR neurons in both groups showed the simultaneously TH immunoreactivity. Increase in the expression of GAL in FB-positive neurons of the HCL group may suggest its participation in the protective mechanisms of neurons in different pathological processes, such as gastric hyperacidity.

Keywords: coeliac-superior mesenteric ganglion complex, gastric innervation, hyperacidity, immunohistochemistry

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Authors: Telma Fontao de Castro, Kylee Miller, Maria Xavier Araújo, Isabel Brandao, Sandra Torres

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Objective: There is a dearth of research investigating the long-term emotional functioning of individuals recovered from anorexia nervosa (AN). This 15-year longitudinal study aimed to examine whether difficulties in cognitive processing of emotions persisted after long-term AN recovery and its link to anxiety and depression. Method: Twenty-four females, who were tested longitudinally during their acute and recovered AN phases, and 24 healthy control (HC) women, were screened for anxiety, depression, alexithymia, and emotion regulation difficulties (ER; only assessed in recovery phase). Results: Anxiety, depression, and alexithymia levels decreased significantly with AN recovery. However, scores on anxiety and difficulty in identifying feelings (alexithymia factor) remained high when compared to the HC group. Scores on emotion regulation difficulties were also lower in HC group. The abovementioned differences between AN recovered group and HC group in difficulties in identifying and accepting feelings and lack of emotional clarity were no longer present when the effect of anxiety and depression was controlled. Conclusions: Findings suggest that emotional dysfunction tends to decrease in AN recovered phase. However, using an HC group as a reference, we conclude that several emotional difficulties are still increased after long-term AN recovery, in particular, limited access to emotion regulation strategies, and difficulty controlling impulses and engaging in goal-directed behavior, thus suggesting to be a trait vulnerability. In turn, competencies related to emotional clarity and acceptance of emotional responses seem to be state-dependent phenomena linked to anxiety and depression. In sum, managing emotions remains a challenge for individuals recovered from AN. Under this circumstance, maladaptive eating behavior can serve as an affect regulatory function, increasing the risk of relapse. Emotional education and stabilization of depressive and anxious symptomatology after recovery emerge as an important avenue to protect from long-term AN relapse.

Keywords: alexithymia, anorexia nervosa, emotion recognition, emotion regulation

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Authors: Uraib Sharaha, Guy Beck, Joseph Kapelushnik, Adam H. Agbaria, Itshak Lapidot, Shaul Mordechai, Ahmad Salman, Mahmoud Huleihel

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Infectious diseases cause a significant burden on the public health and the economic stability of societies all over the world for several centuries. A reliable detection of the causative agent of infection is not possible based on clinical features, since some of these infections have similar symptoms, including fever, sneezing, inflammation, vomiting, diarrhea, and fatigue. Moreover, physicians usually encounter difficulties in distinguishing between viral and bacterial infections based on symptoms. Therefore, there is an ongoing need for sensitive, specific, and rapid methods for identification of the etiology of the infection. This intricate issue perplex doctors and researchers since it has serious repercussions. In this study, we evaluated the potential of the mid-infrared spectroscopic method for rapid and reliable identification of bacterial and viral infections based on simple peripheral blood samples. Fourier transform infrared (FTIR) spectroscopy is considered a successful diagnostic method in the biological and medical fields. Many studies confirmed the great potential of the combination of FTIR spectroscopy and machine learning as a powerful diagnostic tool in medicine since it is a very sensitive method, which can detect and monitor the molecular and biochemical changes in biological samples. We believed that this method would play a major role in improving the health situation, raising the level of health in the community, and reducing the economic burdens in the health sector resulting from the indiscriminate use of antibiotics. We collected peripheral blood samples from young 364 patients, of which 93 were controls, 126 had bacterial infections, and 145 had viral infections, with ages lower than18 years old, limited to those who were diagnosed with fever-producing illness. Our preliminary results showed that it is possible to determine the infectious agent with high success rates of 82% for sensitivity and 80% for specificity, based on the WBC data.

Keywords: infectious diseases, (FTIR) spectroscopy, viral infections, bacterial infections.

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Authors: Saimir Heta, Kers Kapaj, Rialda Xhizdari, Ilma Robo

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Despite the existence of different dental specialties, the dentist-patient relationship is unique, in the very fact that the treatment is performed by one doctor and the patient identifies the malpractice presented as part of that doctor's practice; this is in complete contrast to cases of medical treatments where the patient can be presented to a team of doctors, to treat a specific pathology. The rules of dental ethics are almost the same as the rules of medical ethics. The appearance of dental malpractice affects exactly this two-party relationship, created on the basis of professionalism, without deviations in this direction, between the dentist and the patient, but with very narrow individual boundaries, compared to cases of medical malpractice. Main text: Malpractice can have different reasons for its appearance, starting from professional negligence, but also from the lack of professional knowledge of the dentist who undertakes the dental treatment. It should always be seen in perspective that we are not talking about the individual - the dentist who goes to work with the intention of harming their patients. Malpractice can also be a consequence of the impossibility, for anatomical or physiological reasons of the tooth under dental treatment, to realize the predetermined dental treatment plan. On the other hand, the dentist himself is an individual who can be affected by health conditions, or have vices that affect the systemic health of the dentist as an individual, which in these conditions can cause malpractice. So, depending on the reason that led to the appearance of malpractice, the method of treatment from a legal point of view also varies, for the dentist who committed the malpractice, evaluating the latter if the malpractice came under the conditions of applying the rules of dental ethics. Conclusions: The deviation from the predetermined dental plan is the minimum sign of malpractice and the latter should not be definitively related only to cases of difficult dental treatments. The identification of the reason for the appearance of malpractice is the initial element, which makes the difference in the way of its treatment, from a legal point of view, and the involvement of the dentist in the assessment of the malpractice committed, must be based on the legislation in force, which must be said to have their specific changes in different states. Malpractice should be referred to, or included in the lectures or in the continuing education of professionals, because it serves as a method of obtaining professional experience in order not to repeat the same thing several times, by different professionals.

Keywords: dental ethics, malpractice, negligence, legal basis, continuing education, dental treatments

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Authors: Kai Pai Huang

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Background: There are several types of plasma cell neoplasms including multiple myeloma, plasmacytoma, lymphoplasmacytic lymphoma, and monoclonal gammopathy of undetermined significance (MGUS) are found in our lab. Today, we want to compare with two cases using the method of capillary electrophoresis. Method: Serum is prepared and electrophoresis is performed at alkaline PH in a capillary using the Sebia® Capillary 2. Albumin and globulins are detected by the detector which is located in the cathode of the capillary and the signals are transformed to peaks. Serum was treated with beta-mercaptoethanol which reducing the polymerized immunoglobulin to monomer immunoglobulin to clarify two M-protein are secreted from the same plasma cell clone in bone marrow. Result: Case 1: A 78-year-old female presenting dysuria, oliguria and leg edema for several months. Laboratory data showed proteinuria, leukocytosis, results of high serum IgA and lambda light chain. A renal biopsy found amyloid fibrils in the glomerular mesangial area. Serum protein electrophoresis shows a major monoclonal peak in the β region and minor small peak in gamma region, and the immunotyping studies for serum showed two IgA/λ type. Case 2: A 55-year-old male presenting abdominal distension and low back pain for more than one month. Laboratory data showed T12 T8 compression fracture, results of high serum IgM and kappa light chain. Bone marrow aspiration showed the cells from the bone marrow are B cells with monotypic kappa chain expression. Bone marrow biopsy found this is lymphoplasmacytic lymphoma (Waldenstrom macroglobulin). Serum protein electrophoresis shows a monoclonal peak in the β region and the immunotyping studies for serum showed IgM/κ type. Conclusion: Plasma cell neoplasm can be diagnosed by many examinations. Among them, using capillary electrophoresis by a lab can separate several types of gammopathy and the quantification of a monoclonal peak can be used to evaluate the patients’ prognosis or treatment.

Keywords: plasma cell neoplasm, capillary electrophoresis, serum protein electrophoresis, immunotyping

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Authors: Anupam Chanda

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Presently Packaging plays a significant role for drug discoveries. The process of selecting materials and the type of packaging also offers an opportunity for the Packaging scientist to look for biological delivery choices. Most injectable protein products were supplied in some sort of glass vial, prefilled syringe, cartridge. Those product having high Ph content there is a chance of “delamination “from inner surface of glass vial. With protein-based drugs, the biggest issue is the effect of packaging derivatives on the protein’s threedimensional and surface structure. These are any effects that relate to denaturation or aggregation of the protein due to oxidation or interactions from contaminants or impurities in the preparation. The potential for these effects needs to be carefully considered in choosing the container and the container closure system to avoid putting patients in jeopardy. Cause of Delamination : -Formulations with a high pH include phosphate and citrate buffers increase the risk of glass delamination. -High alkali content in glass could accelerate erosion. -High temperature during the vial-forming process increase the risk of glass delamination. -Terminal sterilization (irradiated at 20-40 kGy for 150 min) also is a risk factor for specific products(veterinary parenteral administration),could cause delamination. -High product-storage temperatures and long exposure times can increase the rate and severity of glass delamination. How to prevent Delamination -Treating the surface of the glass vials with materials, such as ammonium sulfate or siliconization can reduce the rate of glass erosion. -Consider alternative sterilization methods only in rare cases. -The correct specification for the glass to ensure its suitability for the pH of the product. -Use Cyclic olefin copolymer(COC)/Cyclic olefin Polymer(COP) Adsorption of protein and Solutions: Option#1 Coat with linear methoxylated polyglycerol and hyperbranchedmethoxylated polyglycerol. Option#2 Thehyperbranched non-methoxylated coating performed best. Option#3 Coat with hyperbranched polyglycerol Option#4 Right selection of Sterilization of glass vial/syringe.

Keywords: delamination of glass, ptrotien adoptions inside the glass surface, extractable & leachable solutions, injectable designs for new drugs

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Authors: Suharni Mohamad Suharni Mohamad, Nurul Izzati Hamzan Nurul Izzati Hamzan, Norhayu Abdul Rahman Norhayu Abdul Rahman, Siti Suraiya Md Noor Siti Suraiya Md Noor

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Human papillomavirus (HPV) is an important risk factor for development of oral cancer. HPV16 is the most common type found in HPV-positive squamous cell carcinoma. In the present study, we established a real-time loop-mediated isothermal amplification (real-time LAMP) for detection of HPV16. A set of six primers was specially designed to recognize eight distinct sequences of HPV16-E6. Detection and quantification was achieved by real-time monitoring using a real-time turbidimeter based on threshold time required for turbidity in the LAMP reaction. LAMP reagents (MgSO4, dNTPs, Bst polymerase concentrations) and various incubation times and temperatures were optimized. The sensitivity was determined using 10-fold serial dilutions of HPV16 standard strain. The specificity of was evaluated using other HPV genotypes. The optimized method was established with specifically designed primers by real-time detection in approximately 30 min at 65°C. The limit of detection of HPV16 using the LAMP assay was 10 pg/ml that could be detected in 30 min. The LAMP assay was 10 times more sensitive than the conventional PCR in detecting HPV16. No cross-reactivity with other HPV genotypes was observed. This quantitative real-time LAMP assay may improve diagnostic potential for the detection and quantification of HPV16 in clinical samples and epidemiological studies due to its rapidity, simplicity, high sensitivity and specificity. This assay will be further evaluated with HPV DNAs of saliva from patients with oral squamous cell carcinoma. Acknowledgement: This study was financially supported by the ScienceFund Grant, Ministry of Science, Technology and Innovation (305/PPSG/6113219).

Keywords: Oral Squamous Cell Carcinoma (OSCC), Human Papillomavirus 16 (HPV16), Loop-Mediated Isothermal Amplification (LAMP), rapid detection

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Authors: Hend Albassam, Nouf Alrumaih

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Nowadays we are in the age of technologies and communication and there is no doubt that technologies such as the Internet can offer many advantages for many business fields, and the health field is no execution. In fact, using the Internet provide us with a new path to improve the quality of health care throughout the world. The e-healthcare offers many advantages such as: efficiency by reducing the cost and avoiding duplicate diagnostics, empowerment of patients by enabling them to access their medical records, enhancing the quality of healthcare and enabling information exchange and communication between healthcare organizations. There are many problems that result from using papers as a way of communication, for example, paper-based prescriptions. Usually, the doctor writes a prescription and gives it to the patient who in turn carries it to the pharmacy. After that, the pharmacist takes the prescription to fill it and give it to the patient. Sometimes the pharmacist might find difficulty in reading the doctor’s handwriting; the patient could change and counterfeit the prescription. These existing problems and many others heighten the need to improve the quality of the healthcare. This project is set out to develop a distributed e-healthcare system that offers some features of e-health and addresses some of the above-mentioned problems. The developed system provides an electronic health record (EHR) and enables communication between separate health care organizations such as the clinic, pharmacy and laboratory. To develop this system, the Service Oriented Architecture (SOA) is adopted as a design approach, which helps to design several independent modules that communicate by using web services. The layering design pattern is used in designing each module as it provides reusability that allows the business logic layer to be reused by different higher layers such as the web service or the website in our system. The experimental analysis has shown that the project has successfully achieved its aims toward solving the problems related to the paper-based healthcare systems and it enables different health organization to communicate effectively. It implements four independent modules including healthcare provider, pharmacy, laboratory and medication information provider. Each module provides different functionalities and is used by a different type of user. These modules interoperate with each other using a set of web services.

Keywords: e-health, services oriented architecture (SOA), web services, interoperability

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Authors: Hossein Rassi, Marjan Moradi Fard, Masoud Houshmand

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Background: Cervical cancer is multistep disease that is thought to result from an interaction between genetic background and environmental factors. Human papillomavirus (HPV) infection is the leading risk factor for cervical intraepithelial neoplasia(CIN)and cervical cancer. In other hand, some of p53 and miRNA polymorphism may plays an important role in carcinogenesis. This study attempts to clarify the relation of p53 genotypes and miR-146a rs2910164 polymorphism in cervical lesions. Method: Forty two archival samples with cervical lesion retired from Khatam hospital and 40 sample from healthy persons used as control group. A simple and rapid method was used to detect the simultaneous amplification of the HPV consensus L1 region and HPV-16,-18, -11, -31, 33 and -35 along with the b-globin gene as an internal control. We use Multiplex PCR for detection of P53 and miR-146a rs2910164 genotypes in our lab. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Results: Cervix lesions were collected from 42 patients with Squamous metaplasia, cervical intraepithelial neoplasia, and cervical carcinoma. Successful DNA extraction was assessed by PCR amplification of b-actin gene (99bp). According to the results, p53 GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of cervical lesions in the study population. In this study, we detected 13 HPV 18 from 42 cervical cancer. Conclusion: The connection between several SNP polymorphism and human virus papilloma in rare researches were seen. The reason of these differences in researches' findings can result in different kinds of races and geographic situations and also differences in life grooves in every region. The present study provided preliminary evidence that a p53 GG genotype and miR-146a rs2910164 CC genotype may effect cervical cancer risk in the study population, interacting synergistically with HPV 18 genotype. Our results demonstrate that the testing of p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes in combination with HPV18 can serve as major risk factors in the early identification of cervical cancers. Furthermore, the results indicate the possibility of primary prevention of cervical cancer by vaccination against HPV18 in Iran.

Keywords: cervical cancer, p53, miR-146a, rs2910164, polymorphism

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Authors: Hossein Rassi, Marjan Moradi fard, Masoud Houshmand

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Background: Cervical cancer is multistep disease that is thought to result from an interaction between genetic background and environmental factors. Human Papillomavirus (HPV) infection is the leading risk factor for Cervical Intraepithelial Neoplasia (CIN) and cervical cancer. In other hand, some of p53 and miRNA polymorphism may plays an important role in carcinogenesis. This study attempts to clarify the relation of p53 genotypes and miR-146a rs2910164 polymorphism in cervical lesions. Method: Forty two archival samples with cervical lesion retired from Khatam hospital and 40 sample from healthy persons used as control group. A simple and rapid method was used to detect the simultaneous amplification of the HPV consensus L1 region and HPV-16,-18, -11, -31, 33, and -35 along with the b-globin gene as an internal control. We use Multiplex PCR for detection of P53 and miR-146a rs2910164 genotypes in our lab. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Results: Cervix lesions were collected from 42 patients with Squamous metaplasia, cervical intraepithelial neoplasia, and cervical carcinoma. Successful DNA extraction was assessed by PCR amplification of b-actin gene (99 bp). According to the results, p53 GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of cervical lesions in the study population. In this study, we detected 13 HPV 18 from 42 cervical cancer. Conclusion: The connection between several SNP polymorphism and human virus papilloma in rare researches were seen. The reason of these differences in researches' findings can result in different kinds of races and geographic situations and also differences in life grooves in every region. The present study provided preliminary evidence that a p53 GG genotype and miR-146a rs2910164 CC genotype may effect cervical cancer risk in the study population, interacting synergistically with HPV 18 genotype. Our results demonstrate that the testing of p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes in combination with HPV18 can serve as major risk factors in the early identification of cervical cancers. Furthermore, the results indicate the possibility of primary prevention of cervical cancer by vaccination against HPV18 in Iran.

Keywords: cervical cancer, miR-146a rs2910164 polymorphism, p53 polymorphism, intraepithelial, neoplasia, HPV

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Authors: Ahmed Sami Hammami, Mohamed Jellazi

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Background: The aim of the study is to evaluate the magnitude of different psychological outcomes among Tunisian health care professionals (HCP) during the COVID-19 pandemic and to identify the associated factors. Methods: HCP completed a cross-sectional questionnaire from April 4th to April, 28th 2020. The survey collected demographic information, factors that may interfere with the psychological outcomes, behavior changes and mental health measurements. The latter was assessed through 3 scales; the 7-item questions Insomnia Severity Index, the 2-item Patient Health Questionnaire and the 2-item Generalized Anxiety Disorder. Multivariable logistic regression was conducted to identify factors associated with psychological outcomes. Results: A total of 503 HCP successfully completed the survey; among those, n=493 consented to enroll in the study, 411 [83.4%] were physicians, 323 [64.2%] were women and 271 [55%] had a second-line working position. A significant proportion of HCP had anxiety 35.7%, depression 35.1% and insomnia 23.7%. Females, those with psychiatric history and those using public transport exhibited the highest proportions for overall symptoms compared to other groups e.g., depression among females vs. males: 44,9% vs. 18,2%, P=0.00. Those with a previous medical history and nurses, had more anxiety and insomnia compared to other groups e.g. anxiety among nurses vs. interns/residents vs. attending 45,1% vs 36,1% vs 27,5%; p=0.04. Multivariable logistic regression showed that female gender was a risk factor for all psychological outcomes e.g. female sex increased the odds of anxiety by 2.86; 95% confidence interval [CI], 1, 78-4, 60; P=0.00, whereas having a psychiatric history was a risk factor for both anxiety and insomnia. (e.g. for insomnia OR=2,86; 95% [CI], 1,78-4,60; P=0.00), Having protective equipment was associated with lower risk for depression (OR=0,41; 95% CI, 0,27-0,62; P=0.00) and anxiety. Physical activity was also protective against depression and anxiety (OR=0,41, 95% CI, 0,25-0,67, P=0.00). Conclusion: Psychological symptoms are usually undervalued among HCP, though the COVID-19 pandemic played a major role in exacerbating this burden. Prompt psychological support should be endorsed and simple measures such as physical activity and ensuring the necessary protection are paramount to improve mental health outcomes and the quality of care provided to patients.

Keywords: COVID-19 pandemic, health care professionals, mental health, protective factors, psychological symptoms, risk factors

Procedia PDF Downloads 196

Authors: Swarkar Sharma, Ekta Rai, Ankit Mahajan, Parvinder Kumar, Manoj K Dhar, Sushil Razdan, Kumarasamy Thangaraj, Carol Wise, Shiro Ikegawa M.D., K.K. Pandita M.D.

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Rare disorders are poorly understood hence, remain uncharacterized or patients are misdiagnosed and get poor medical attention. A rare mysterious skeletal disorder that remained unidentified for decades and rendered many people physically challenged and disabled for life has been reported in an isolated remote village ‘Arai’ of Poonch district of Jammu and Kashmir. This village is located deep in mountains and the population residing in the region is highly consanguineous. In our survey of the region, 70 affected people were reported, showing similar phenotype, in the village with a population of approximately 5000 individuals. We were able to collect samples from two multi generational extended families from the village. Through Whole Exome sequencing (WES), we identified a rare variation NM_003880.3:c.156C>A NP_003871.1:p.Cys52Ter, which results in introduction of premature stop codon in WISP3 gene. We found this variation perfectly segregating with the disease in one of the family. However, this variation was absent in other family. Interestingly, a novel splice site mutation at position c.643+1G>A of WISP3 gene, perfectly segregating with the disease was observed in the second family. Thus, exploiting WES and putting different evidences together (familial histories and genetic data, clinical features, radiological and biochemical tests and findings), the disease has finally been diagnosed as a very rare recessive hereditary skeletal disease “Progressive Pseudorheumatoid Arthropathy of Childhood” (PPAC) also known as “Spondyloepiphyseal Dysplasia Tarda with Progressive Arthropathy” (SEDT-PA). This genetic characterization and identification of the disease causing mutations will aid in genetic counseling, critically required to curb this rare disorder and to prevent its appearance in future generations in the population. Further, understanding of the role of WISP3 gene the biological pathways should help in developing treatment for the disorder.

Keywords: whole exome sequencing, Next Generation Sequencing, rare disorders

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Authors: David Mafullul, Jiang Lei, Edward Goacher, Jibin Francis

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PURPOSE: Timely decompressive surgery for cauda equina syndrome (CES) is dependent on efficient referral pathways for patients presenting at local primary or secondary centres to tertiary spinal centres in the United Kingdom (UK). Identifying modifiable points of delay within this process is important as minimising time between presentation and surgery may improve patient outcomes. This study aims to analyse whether adequacy of referral impacts on time to surgery in CES. MATERIALS AND METHODS: Data from all cases of confirmed CES referred to a single tertiary UK hospital between August 2017 to December 2019, via a suspected CES e-referral pathway, were obtained retrospectively. Referral adequacy was defined by the inclusion of sufficient information to determine the presence or absence of several NICE ‘red flags’. Correlation between referral adequacy and delay from referral-to-surgery was then analysed. RESULTS: In total, 118 confirmed CES cases were included. Adequate documentation for saddle anaesthesia was associated with reduced delays of more than 48 hours from referral-to-surgery [X2(1, N=116)=7.12, p=.024], an effect partly attributable to these referrals being accepted sooner [U=16.5; n1=27, n2=4, p=.029, r=.39]. Other red flags had poor association with delay. Referral adequacy was better for somatic red flags [bilateral sciatica (97.5%); severe or progressive bilateral neurological deficit of the legs (95.8%); saddle anaesthesia (91.5%)] compared to autonomic red flags [loss of anal tone (80.5%); urinary retention (79.7%); faecal incontinence or lost sensation of rectal fullness (57.6%)]. Although referral adequacy for urinary retention was 79.7%, only 47.5% of referrals documented a post-void residual numerical value. CONCLUSIONS: Adequate documentation of saddle anaesthesia in e-referrals is associated with reduced delay-to-surgery for confirmed CES, partly attributable to these referrals being accepted sooner. Other red flags had poor association with delay to surgery. Referral adequacy for autonomic red flags, including documentation for post-void residuals, has significant room for improvement.

Keywords: cauda equina, cauda equina syndrome, neurosurgery, spinal surgery, decompression, delay, referral, referral adequacy

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Authors: Wisam Ismail, Sarah Hosgood, Michael Nicholson

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The research hypothesis is that early post-transplant allograft fibrosis will be linked to donor factors and that acute rejection and/or delayed graft function in the recipient will be independent risk factors for the development of fibrosis. This research hypothesis is to explore whether acute rejection/delay graft function has an effect on the renal transplant fibrosis within the first year post live donor kidney transplant between 1998 and 2009. Methods: The study has been designed to identify five time points of the renal transplant biopsies [0 (pre-transplant), 1 month, 3 months, 6 months and 12 months] for 300 live donor renal transplant patients over 12 years period between March 1997 – August 2009. Paraffin fixed slides were collected from Leicester General Hospital and Leicester Royal Infirmary. These were routinely sectioned at a thickness of 4 Micro millimetres for standardization. Conclusions: Fibrosis at 1 month after the transplant was found significantly associated with baseline fibrosis (p<0.001) and HTN in the transplant recipient (p<0.001). Dialysis after the transplant showed a weak association with fibrosis at 1 month (p=0.07). The negative coefficient for HTN (-0.05) suggests a reduction in fibrosis in the absence of HTN. Fibrosis at 1 month was significantly associated with fibrosis at baseline (p 0.01 and 95%CI 0.11 to 0.67). Fibrosis at 3, 6 or 12 months was not found to be associated with fibrosis at baseline (p=0.70. 0.65 and 0.50 respectively). The amount of fibrosis at 1 month is significantly associated with graft survival (p=0.01 and 95%CI 0.02 to 0.14). Rejection and severity of rejection were not found to be associated with fibrosis at 1 month. The amount of fibrosis at 1 month was significantly associated with graft survival (p=0.02) after adjusting for baseline fibrosis (p=0.01). Both baseline fibrosis and graft survival were significant predictive factors. The amount of fibrosis at 1 month was not found to be significantly associated with rejection (p=0.64) after adjusting for baseline fibrosis (p=0.01). The amount of fibrosis at 1 month was not found to be significantly associated with rejection severity (p=0.29) after adjusting for baseline fibrosis (p=0.04). Fibrosis at baseline and HTN in the recipient were found to be predictive factors of fibrosis at 1 month. (p 0.02, p <0.001 respectively). Age of the donor, their relation to the patient, the pre-op Creatinine, artery, kidney weight and warm time were not found to be significantly associated with fibrosis at 1 month. In this complex model baseline fibrosis, HTN in the recipient and cold time were found to be predictive factors of fibrosis at 1 month (p=0.01,<0.001 and 0.03 respectively). Donor age was found to be a predictive factor of fibrosis at 6 months. The above analysis was repeated for 3, 6 and 12 months. No associations were detected between fibrosis and any of the explanatory variables with the exception of the donor age which was found to be a predictive factor of fibrosis at 6 months.

Keywords: fibrosis, transplant, renal, rejection

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Authors: Monica Gonzalez Machorro

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Dementia is hard to diagnose because of the lack of early physical symptoms. Early dementia recognition is key to improving the living condition of patients. Speech technology is considered a valuable biomarker for this challenge. Recent works have utilized conventional acoustic features and machine learning methods to detect dementia in speech. BERT-like classifiers have reported the most promising performance. One constraint, nonetheless, is that these studies are either based on human transcripts or on transcripts produced by automatic speech recognition (ASR) systems. This research contribution is to explore a method that does not require transcriptions to detect early Alzheimer’s disease (AD) and mild cognitive impairment (MCI). This is achieved by fine-tuning a pre-trained ASR model for the downstream early AD and MCI tasks. To do so, a subset of the thoroughly studied Pitt Corpus is customized. The subset is balanced for class, age, and gender. Data processing also involves cropping the samples into 10-second segments. For comparison purposes, a baseline model is defined by training and testing a Random Forest with 20 extracted acoustic features using the librosa library implemented in Python. These are: zero-crossing rate, MFCCs, spectral bandwidth, spectral centroid, root mean square, and short-time Fourier transform. The baseline model achieved a 58% accuracy. To fine-tune HuBERT as a classifier, an average pooling strategy is employed to merge the 3D representations from audio into 2D representations, and a linear layer is added. The pre-trained model used is ‘hubert-large-ls960-ft’. Empirically, the number of epochs selected is 5, and the batch size defined is 1. Experiments show that our proposed method reaches a 69% balanced accuracy. This suggests that the linguistic and speech information encoded in the self-supervised ASR-based model is able to learn acoustic cues of AD and MCI.

Keywords: automatic speech recognition, early Alzheimer’s recognition, mild cognitive impairment, speech impairment

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Authors: Sheraz Gul

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The requirements for progressing a compound to clinical trials is well established and relies on the results from in-vitro and in-vivo animal tests to indicate that it is likely to be safe and efficacious when testing in humans. The typical data package required will include demonstrating compound safety, toxicity, bioavailability, pharmacodynamics (potential effects of the compound on body systems) and pharmacokinetics (how the compound is potentially absorbed, distributed, metabolised and eliminated after dosing in humans). If the desired criteria are met and the compound meets the clinical Candidate criteria and is deemed worthy of further development, a submission to regulatory bodies such as the US Food & Drug Administration for an exploratory Investigational New Drug Study can be made. The purpose of this study is to collect data to establish that the compound will not expose humans to unreasonable risks when used in limited, early-stage clinical studies in patients or normal volunteer subjects (Phase I). These studies are also designed to determine the metabolism and pharmacologic actions of the drug in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on their effectiveness. In order to reach the above goals, we have developed a pre-clinical high throughput Absorption, Distribution, Metabolism and Excretion–Toxicity (ADME–Toxicity) panel of assays to identify compounds that are likely to meet the Lead and Candidate compound acceptance criteria. This panel includes solubility studies in a range of biological fluids, cell viability studies in cancer and primary cell-lines, mitochondrial toxicity, off-target effects (across the kinase, protease, histone deacetylase, phosphodiesterase and GPCR protein families), CYP450 inhibition (5 different CYP450 enzymes), CYP450 induction, cardio-toxicity (hERG) and gene-toxicity. This panel of assays has been applied to multiple compound series developed in a number of projects delivering Lead and clinical Candidates and examples from these will be presented.

Keywords: absorption, distribution, metabolism and excretion–toxicity , drug discovery, food and drug administration , pharmacodynamics

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Authors: Swathi Ganesan, Nalinda Somasiri, Rebecca Jeyavadhanam, Gayathri Karthick

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The COVID-19 crisis presents a substantial and critical hazard to worldwide health. Since the occurrence of the disease in late January 2020 in the UK, the number of infected people confirmed to acquire the illness has increased tremendously across the country, and the number of individuals affected is undoubtedly considerably high. The purpose of this research is to figure out a predictive machine learning archetypal that could forecast COVID-19 cases within the UK. This study concentrates on the statistical data collected from 31st January 2020 to 31st March 2021 in the United Kingdom. Information on total COVID cases registered, new cases encountered on a daily basis, total death registered, and patients’ death per day due to Coronavirus is collected from World Health Organisation (WHO). Data preprocessing is carried out to identify any missing values, outliers, or anomalies in the dataset. The data is split into 8:2 ratio for training and testing purposes to forecast future new COVID cases. Support Vector Machines (SVM), Random Forests, and linear regression algorithms are chosen to study the model performance in the prediction of new COVID-19 cases. From the evaluation metrics such as r-squared value and mean squared error, the statistical performance of the model in predicting the new COVID cases is evaluated. Random Forest outperformed the other two Machine Learning algorithms with a training accuracy of 99.47% and testing accuracy of 98.26% when n=30. The mean square error obtained for Random Forest is 4.05e11, which is lesser compared to the other predictive models used for this study. From the experimental analysis Random Forest algorithm can perform more effectively and efficiently in predicting the new COVID cases, which could help the health sector to take relevant control measures for the spread of the virus.

Keywords: COVID-19, machine learning, supervised learning, unsupervised learning, linear regression, support vector machine, random forest

Procedia PDF Downloads 121

Authors: M. A. Riurean, S. Heijnen, C. A. Knott, J. Makinde, D. Gotti, J. VD. Kamp

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Objectives: The current study is done in preparation for a randomized controlled study investigating the effects of an implicit motor learning protocol implemented using an extension-supporting glove. It will explore different protocols to find out which is preferred when studying motor learn-ing in the chronic stroke population that struggles with hand spasticity. Design: This exploratory study will follow 24 individuals who have a chronic stroke (> 6 months) during their usual care journey. We will record the results of two 9-Hole Peg Tests (9HPT) done during their therapy ses-sions with a physiotherapist or in their home before and after 4 weeks of them wearing an exten-sion-supporting glove used to employ the to-be-studied protocols. The participants will wear the glove 3 times/week for one hour while performing their activities of daily living and record the times they wore it in a diary. Their experience will be monitored through telecommunication once every week. Subjects: Individuals that have had a stroke at least 6 months prior to participation, hand spasticity measured on the modified Ashworth Scale of maximum 3, and finger flexion motor control measured on the Motricity Index of at least 19/33. Exclusion criteria: extreme hemi-neglect. Methods: The participants will be randomly divided into 3 groups: one group using the glove in a pre-set way of decreasing support (implicit motor learning), one group using the glove in a self-controlled way of decreasing support (autonomous motor learning), and the third using the glove with constant support (as control). Before and after the 4-week period, there will be an intake session and a post-assessment session. Analysis: We will compare the results of the two 9HPTs to check whether the protocols were effective. Furthermore, we will compare the results between the three groups to find the preferred one. A qualitative analysis will be run of the experience of participants throughout the 4-week period. Expected results: We expect that the group using the implicit learning protocol will show superior results.

Keywords: implicit learning, hand spasticity, stroke, error minimization, motor task

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Authors: Beth Taylor, Kojima Mituaki, Atsushi Senda, Koji Morishita, Yasuhiro Otomo

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Intestinal ischaemia-reperfusion injury drives systemic inflammation and organ failure following trauma/haemorrhagic shock (T/HS), through the release of pro-inflammatory mediators into the mesenteric lymph (ML). However, changes in the biological function of ML are not fully understood, and therefore, a specific model of intestinal ischaemia-reperfusion injury is required to obtain ML for the study of its biological function upon inflammatory cells. ML obtained from a model of intestinal ischaemia-reperfusion injury was used to assess biological function upon inflammatory cells and investigate changes in the biological function of individual ML components. An additional model was used to determine the effect of vagal nerve stimulation (VNS) upon biological function. Rat ML was obtained by mesenteric lymphatic duct cannulation before and after occlusion of the superior mesenteric artery (SMAO). ML was incubated with human polymorphonuclear neutrophils (PMNs), monocytes and lymphocytes, and the biological function of these cells was assessed. ML was then separated into supernatant, exosome and micro-vesicle components, and biological activity was compared in monocytes. A model with an additional VNS phase was developed, in which the right cervical vagal nerve was exposed and stimulated, and ML collected for comparison of biological function with the conventional model. The biological function of ML was altered by intestinal ischaemia-reperfusion injury, increasing PMN activation, monocyte activation, and lymphocyte apoptosis. Increased monocyte activation was only induced by the exosome component of ML, with no significant changes induced by the supernatant or micro-vesicle components. VNS partially attenuated monocyte activation, but no attenuation of PMN activation was observed. Intestinal ischaemia-reperfusion injury induces changes in the biological function of ML upon both innate and adaptive inflammatory cells, supporting the role of intestinal ischaemia-reperfusion injury in driving systemic inflammation following T/HS. The exosome component of ML appears to be critical to the transport of pro-inflammatory mediators in ML. VNS partially attenuates changes in innate inflammatory cell biological activity observed, presenting possibilities for future novel treatment development in multiple organ failure patients.

Keywords: exosomes, inflammation, intestinal ischaemia, mesenteric lymph, vagal stimulation

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Authors: Vitor Rafael Regiani, Carlos Henrique Viesi Do Nascimento Filho, Patricia Matos Biselli-Chicote, Claudia Aparecida Rainho, Luiz Sergio Raposo, José Victor Maniglia, Eny Maria Goloni-Bertollo, Erika Cristina Pavarino

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Promoter hypermethylation of tumor-related genes has been associated with prognosis in early-stage head-and-neck cancers, providing strong evidence that these hypermethylated genes are valuable biomarkers for prognostic evaluation. Hence, we selected the MGMT and RASSF1A genes to examine the methylation status in head and neck squamous cell carcinomas (HNSCC) samples matched with non-tumor tissues (tumor-surrounding tissues or peripheral blood samples). DNA methylation analysis was based on Methylation-Sensitive High Resolution Melting, and the methylation status was correlated with clinic-pathological characteristics of the patients. RASSF1A and MGMT promoter methylation was detected in 43.24% (16/37) and in 44.44% (16/36) of the tumors, respectively. RASSF1A and MGMT methylation was significantly more frequent in tumor tissue than non-tumor tissues, as well as, simultaneous methylation of RASSF1A and MGMT also was higher in tumor tissue than non-tumor tissues. In relation to anatomic site, larynx cancer presented significant methylation of MGMT gene compared to tumor-surrounding tissue. The frequency of RASSF1A and MGMT promoter methylated was higher in tumor tissues in relation to peripheral blood from the same patient. No association was found between methylation and the variables analyzed, including gender, age, smoking or alcohol drinking habits. Clinic-pathological characteristics also showed no association in the presence of methylation. The Kaplan–Meier's method showed no association of methylation and both disease-free and overall survival. In conclusion, the presence of epigenetic abnormalities in normal-appearing tissue corroborates the hypothesis of the ‘field cancerization', or it can reflect preneoplastic and/or preinvasive. Moreover, MGMT methylation may serve as an important laryngeal cancer biomarker because it showed significant difference between laryngeal cancer and surrounding tumor tissues.

Keywords: head and neck cancer, DNA methylation, MGMT promoter methylation, RASSF1A promoter methylation

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Authors: Islam Nowisser, Noha Farag, Mohamed El Azizi

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Helicobacter pylori is a highly important human pathogen which inhabits about 50% of the population worldwide. Infection with this bacteria is very hard to treat, with high probability of recurrence. H. pylori causes severe gastric diseases, including peptic ulcer, gastritis, and gastric cancer, which has been linked to chronic inflammation. The infection has been reported to be associated with high levels of pro-inflammatory cytokines, especially IL-1β and TNF-α. The aim of the current study is to investigate the molecular mechanisms by which H. pylori activates NLRP3 inflammasome and its contribution to Il-1 β production in an innate cellular model. H. pylori PMSS1 and G27 standard strains, as well as the PMSS1 isogenic mutant strain PMSS1ΔVacA and G27ΔVacA, G27ΔCagA in addition to clinical isolates obtained from biopsy samples from the antrum and corpus mucosa of chronic gastritis patients, were used to establish infection in RAW-264.7 macrophages. The production levels of TNF-α and IL-1β was assessed using ELISA. Since expression of these cytokines is often regulated by the transcription factor complex, nuclear factor-kB (NF-kB), the activation of NF-κB in H. pylori infected cells was also evaluated by luciferase assay. Genomic DNA was extracted from bacterial cultures of H. pylori clinical isolates as well as the standard strains and their corresponding mutants, where they were evaluated for the cagA pathogenicity island and vacA expression. The correlation between these findings and expression of the cagA Pathogenicity Island and vacA in the bacteria was also investigated. The results showed IL-1β, and TNF-α production significantly increased in raw macrophages following H. pylori infection. The cagA+ and vacA+ H. pylori strains induced significant production of IL-1β compared to cagA- and vacA- strains. The activation pattern of NF-κB was correlated in the isolates to their cagA and vacA expression profiles. A similar finding could not be confirmed for TNF-α production. Our study shows the ability of H. pylori to activate NF-kB and induce significant IL-1β production as a possible mechanism for the augmented inflammatory response seen in subjects infected with cagA+ and vacA+ H. pylori strains that would lead to the progression to more severe form of the disease.

Keywords: Helicobacter pylori, IL-1β, inflammatory cytokines, nuclear factor KB, TNF-α

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Authors: Antonio Lopez-Villegas, Rafael Bautista-Mesa, Emilio Robles-Musso, Daniel Catalan-Matamoros, Cesar Leal-Costa

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Objectives: The purpose of this trial was to evaluate the burden borne by and the costs to informal caregivers of users with telemonitoring of pacemakers. Methods: This is a controlled, non-randomised clinical trial, with data collected from informal caregivers, five years after implantation of pacemakers. The Spanish version of the Survey on Disabilities, Personal Autonomy, and Dependency Situations was used to get information on clinical and social characteristics, levels of professionalism, duration and types of care, difficulties in providing care, health status, economic and job aspects, impact on the family or leisure due to informal caregiving for patients with pacemakers. Results: After five years of follow-up, 55 users with pacemakers finished the study. Of which, 50 were helped by a caregiver, 18 were included in the telemonitoring group (TM) and 32 in the conventional follow-up group (HM). Overall, females represented 96.0% of the informal caregivers (88.89% in TM and 100.0% in HM group). The mean ages were 63.17 ± 15.92 and 63.13 ± 14.56 years, respectively (p = 0.83) in the groups. The majority (88.0%) of the caregivers declared that they had to provide their services between 6 and 7 days per week (83.33% in TM group versus 90.63% in HM group), without significant differences between both groups. The costs related to care provided by the informal caregivers were 47.04% higher in the conventional follow-up group than in the TM group. Conclusions: The results of this trial confirm that there were no significant differences between the informal caregivers regarding to baseline characteristics, workload and time worked in both groups of follow-up. The costs incurred by the informal caregivers providing care for users with pacemakers included in telemonitoring group are significantly lower than those in the conventional follow-up group. Trial registration: ClinicalTrials.gov NCT02234245. Funding: The PONIENTE study, has been funded by the General Secretariat for Research, Development and Innovation, Regional Government of Andalusia (Spain), project reference number PI/0256/2017, under the research call 'Development and Innovation Projects in the Field of Biomedicine and Health Sciences', 2017.

Keywords: costs, disease burden, informal caregiving, pacemaker follow-up, remote monitoring, telemedicine

Procedia PDF Downloads 142

Authors: Yassir Adam Shuaib, Stefan Niemann, Eltahir Awad Khalil, Ulrich Schaible, Lothar Heinz Wieler, Mohammed Ahmed Bakhiet, Abbashar Osman Mohammed, Mohamed Abdelsalam Abdalla, Elvira Richter

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Tuberculosis (TB) is a chronic bacterial disease of humans and animals and it is characterized by the progressive development of specific granulomatous tubercle lesions in affected tissues. In a six-month study, from June to November 2014, a total of 2,304 carcasses of cattle, camel, sheep, and goats slaughtered at East and West Gaash slaughterhouses, Kassala, were investigated during postmortem, in parallel, 101 sputum samples from TB suspected patients at Kassala and El-Gadarif Teaching Hospitals were collected in order to investigate tuberculosis in animals and humans. Only 0.1% carcasses were found with suspected TB lesions in the liver and lung and peritoneal cavity of two sheep and no tuberculous lesions were found in the carcasses of cattle, goats or camels. All samples, tissue lesions and sputum, were decontaminated by the NALC-NaOH method and cultured for mycobacterial growth at the NRZ for Mycobacteria, Research Center Borstel, Germany. Genotyping and molecular characterization of the grown strains were done by line probe assay (GenoType CM and MTBC) and 16S rDNA, rpoB gene, and ITS sequencing, spoligotyping, MIRU-VNTR typing and next generation sequencing (NGS). Culture of the specimens revealed growth of organisms from 81.6% of all samples. Mycobacterium tuberculosis (76.2%), M. intracellulare (14.2%), mixed infection with M. tuberculosis and M. intracellulare (6.0%) and mixed infection with M. tuberculosis and M. fortuitum and with M. intracellulare and unknown species (1.2%) were detected in the sputum samples and unknown species (1.2%) were detected in the samples of one of the animals tissues. From the 69 M. tuberculosis strains, 25 (36.2%) were showing either mono-drug-resistant or multi-drug-resistant or poly-drug-resistant but none was extensively drug-resistant. In conclusion, the prevalence of TB in animals was very low while in humans M. tuberculosis-Delhi/CAS lineage was responsible for most cases and there was an evidence of MDR transmission and acquisition.

Keywords: animal, human, slaughterhouse, Sudan, tuberculosis

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