Search results for: congenital heart disease

Authors: Abdulaziz Alakeel, Roaa Alamri, Abdulrahman Alomair, Mohammed Fouda

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Introduction: Ibrutinib is a selective, potent, and irreversible small-molecule inhibitor of Bruton's tyrosine kinase (BTK). It forms a covalent bond with a cysteine residue (CYS-481) at the active site of Btk, leading to inhibition of Btk enzymatic activity. The drug is indicated to treat certain type of cancers such as mantle cell lymphoma (MCL), chronic lymphocytic leukaemia and Waldenström's macroglobulinaemia (WM). Cardiac failure is a condition referred to inability of heart muscle to pump adequate blood to human body organs. There are multiple types of cardiac failure including left and right-sided heart failure, systolic and diastolic heart failures. The aim of this review is to evaluate the risk of cardiac failure associated with the use of ibrutinib and to suggest regulatory recommendations if required. Methodology: Signal Detection team at the National Pharmacovigilance Center (NPC) of Saudi Food and Drug Authority (SFDA) performed a comprehensive signal review using its national database as well as the World Health Organization (WHO) database (VigiBase), to retrieve related information for assessing the causality between cardiac failure and ibrutinib. We used the WHO- Uppsala Monitoring Centre (UMC) criteria as standard for assessing the causality of the reported cases. Results: Case Review: The number of resulted cases for the combined drug/adverse drug reaction are 212 global ICSRs as of July 2020. The reviewers have selected and assessed the causality for the well-documented ICSRs with completeness scores of 0.9 and above (35 ICSRs); the value 1.0 presents the highest score for best-written ICSRs. Among the reviewed cases, more than half of them provides supportive association (four probable and 15 possible cases). Data Mining: The disproportionality of the observed and the expected reporting rate for drug/adverse drug reaction pair is estimated using information component (IC), a tool developed by WHO-UMC to measure the reporting ratio. Positive IC reflects higher statistical association while negative values indicates less statistical association, considering the null value equal to zero. The results of (IC=1.5) revealed a positive statistical association for the drug/ADR combination, which means “Ibrutinib” with “Cardiac Failure” have been observed more than expected when compared to other medications available in WHO database. Conclusion: Health regulators and health care professionals must be aware for the potential risk of cardiac failure associated with ibrutinib and the monitoring of any signs or symptoms in treated patients is essential. The weighted cumulative evidences identified from causality assessment of the reported cases and data mining are sufficient to support a causal association between ibrutinib and cardiac failure.

Keywords: cardiac failure, drug safety, ibrutinib, pharmacovigilance, signal detection

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Authors: Mahdi Farajzadeh Ajirlou

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The detailed serious adverse effects raised the stresses around the safety of individuals who have gotten COVID-19 vaccines. Numerous verification referrers that disease with COV-19 causes neurological dysfunction in a significant proportion of influenced patients, where these side effects show up seriously amid the disease, and still less is known approximately the potential long-term results for the brain, where the loss of olfaction could be a neurological sign and simple indications of COVID-19. Since publishing effective clinical trial results of mRNA coronavirus disease 2019 (COVID-19) and injecting it to the volunteers in 2020, numerous reports have emerged approximately about cardiovascular complications followed by the mRNA vaccination. Vaccination-associated adenopathy could be a constant imaging finding after the organization of COVID-19 antibodies that will lead to a symptomatic problem in patients with shown or suspected cancer, in whom it may be vague from dangerous nodal inclusion. In spite of all the benefits and viability of the coronavirus infection 2019 (COVID-19) antibodies specified in later clinical trials, a few other post-vaccination side impacts, such as lymphadenopathy (LAP), were observed. Also, numerous variables, including financial conditions, have played a critical part in expanding the number of people with COVID-19 infection and also much more side effects in that country. Amid the Coronavirus widespread, Iran has been experiencing extreme sanctions, which has faced this nation with an extreme financial crisis. Additionally, with COVID-19 widespread, there was a developing concern around the abuse of imaging exams extraordinarily within the pediatric populace, which highlights the issues pointed out by this review.

Keywords: radiology, vaccines, COVID-19, side effect

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Authors: Cinthya Olivares Garita

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Untangling language processing in second language development has been either a taken-for-granted and overlooked task for some English language teaching (ELT) instructors or a considerable feat for others. From the most traditional language instruction to the most communicative methodologies, how to assist L2 learners in processing language in the classroom has become a challenging matter in second language teaching. Amidst an ample array of methods, strategies, and techniques to teach a target language, finding a suitable model to lead learners to process, interpret, and negotiate meaning to communicate in a second language has imposed a great responsibility on language teachers; committed teachers are those who are aware of their role in equipping learners with the appropriate tools to communicate in the target language in a 21stcentury society. Unfortunately, one might find some English language teachers convinced that their job is only to lecture students; others are advocates of textbook-based instruction that might hinder second language processing, and just a few might courageously struggle to facilitate second language learning effectively. Grounded on the most representative empirical studies on comprehensible input, processing instruction, and focus on form, this analysis aims to facilitate the understanding of how second language learners process and automatize input and propose a pedagogical framework for the successful development of a second language. In light of this, this paper is structured to tackle noticing and attention and structured input as the heart of processing instruction, comprehensible input as the missing link in second language learning, and form-meaning connections as opposed to traditional grammar approaches to language teaching. The author finishes by suggesting a pedagogical framework involving noticing-attention-comprehensible-input-form (NACIF based on their acronym) to support ELT instructors, teachers, and scholars on the challenging task of facilitating the understanding of effective second language development.

Keywords: second language development, pedagogical framework, noticing, attention, comprehensible input, form

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Authors: A. F. Agboola, B. R. O. Omidiwura, A. Oyeyemi, E. A. Iyayi, A. S. Adelani

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Dietary cholesterol has elicited the most public interest as it relates with coronary heart disease. Thus, humans have been paying more attention to health, thereby reducing consumption of cholesterol enriched food. Egg is considered as one of the major sources of human dietary cholesterol. However, an alternative way to reduce the potential cholesterolemic effect of eggs is to modify the fatty acid composition of the yolk. The effect of palm oil (PO), soybean oil (SO), sesame seed oil (SSO) and fish oil (FO) supplementation in the diets of layers on egg yolk fatty acid, cholesterol, egg production and egg quality parameters were evaluated in a 42-day feeding trial. One hundred and five Isa Brown laying hens of 34 weeks of age were randomly distributed into seven groups of five replicates and three birds per replicate in a completely randomized design. Seven corn-soybean basal diets (BD) were formulated: BD+No oil (T1), BD+1.5% PO (T2), BD+1.5% SO (T3), BD+1.5% SSO (T4), BD+1.5% FO (T5), BD+0.75% SO+0.75% FO (T6) and BD+0.75% SSO+0.75% FO (T7). Five eggs were randomly sampled at day 42 from each replicate to assay for the cholesterol, fatty acid profile of egg yolk and egg quality assessment. Results showed that there were no significant (P>0.05) differences observed in production performance, egg cholesterol and egg quality parameters except for yolk height, albumen height, yolk index, egg shape index, haugh unit, and yolk colour. There were no significant differences (P>0.05) observed in total cholesterol, high density lipoprotein and low density lipoprotein levels of egg yolk across the treatments. However, diets had effect (P<0.05) on TAG (triacylglycerol) and VLDL (very low density lipoprotein) of the egg yolk. The highest TAG (603.78 mg/dl) and VLDL values (120.76 mg/dl) were recorded in eggs of hens on T4 (1.5% sesame seed oil) and was similar to those on T3 (1.5% soybean oil), T5 (1.5% fish oil) and T6 (0.75% soybean oil + 0.75% fish oil). However, results revealed a significant (P<0.05) variations on eggs’ summation of polyunsaturated fatty acid (PUFA). In conclusion, it is suggested that dietary oils could be included in layers’ diets to produce designer eggs low in cholesterol and high in PUFA especially omega-3 fatty acids.

Keywords: dietary oils, egg cholesterol, egg fatty acid profile, egg quality parameters

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Authors: Tahir Majeed, Michael Handschuh, René Meier

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Rheumatoid arthritis patients have swelling and pain at the joints of the hand. The regions where the patient feels pain also show increased body temperature. Thermal cameras can be used to detect the rise in temperature of the affected regions. To monitor the disease progression of rheumatoid arthritis patients, they must visit the clinic regularly for scanning and examination. After scanning and evaluation, the dosage of the medicine is regulated accordingly. To monitor the disease progression over time, the correlation between the images between different visits must be established. It has been observed that by using low-cost thermal cameras, the thermal measurements do not remain the same over time, even within a single scanning. In some situations, temperatures can vary as much as 2°C within the same scanning sequence. In this paper, it has been shown that although the absolute temperature varies over time, the relative difference between the different regions remains similar. Results have been computed over four scanning sequences and are presented.

Keywords: relative thermal difference, rheumatoid arthritis, thermal imaging, thermal sensors

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Authors: Oleg Sapelnikov, Ruslan Latypov, Darina Ardus, Samvel Aivazian, Andrey Shiryaev, Renat Akchurin

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OBJECTIVE: MAZE procedure is one of the most effective surgical methods in atrial fibrillation (AF) treatment. Nowadays we are all aware of its modifications. In our study we conducted clinical analysis of “Box lesion+” approach during MAZE procedure in two-year follow-up. METHODS: We studied the results of the open-heart on-pump procedures performed in our hospital from 2017 to 2018 years. Thirty-two (32) patients with atrial fibrillation (AF) were included in this study. Fifteen (15) patients had concomitant coronary bypass grafting and seventeen (17) patients had mitral valve repair. Mean age was 62.3±8.7 years; prevalence of men was admitted (56.1%). Mean duration of AF was 4.75±5.44 and 7.07±8.14 years. In all cases, we performed endocardial Cryo-MAZE procedure with one-time myocardium revascularization or mitral-valve surgery. All patients of this study underwent pulmonary vein (PV) isolation and ablation of mitral isthmus with additional isolation of LA posterior wall (Box-lesion+ procedure). Mean follow-up was 2 years. RESULTS: All cases were performed without any complications. Additional isolation of posterior wall did not prolong the operative time and artificial circulation significantly. Cryo-MAZE procedure directly lasted 20±2.1 min, the whole operation time was 192±24 min and artificial circulation time was 103±12 min. According to design of the study, we performed clinical investigation of the patients in 12 months and in 2 years from the initial procedure. In 12 months, the number of AF free patients 81.8% and 75.8% in two years of follow-up. CONCLUSIONS: Isolation of the left atrial posterior wall and perimitral area may considerably improve the efficacy of surgical treatment, which was demonstrated in significant decrease of AF recurrences during the whole period of follow-up.

Keywords: atrial fibrillation, cryoablation, left atrium isolation, open heart procedure

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Authors: Salam N. Abdo, Orien L. Tulp, George P. Einstein

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The purpose of this exploratory study was to gather the insights into psoriasis etiology, treatment, and patient experience, for developing psoriasis and psoriatic arthritis diagnostic test. Data collection methods consisted of a comprehensive meta-analysis of relevant studies and psoriasis patient survey. Established meta-analysis guidelines were used for the selection and qualitative comparative analysis of psoriasis and psoriatic arthritis research studies. Only studies that clearly discussed psoriasis etiology, treatment, and patient experience were reviewed and analyzed, to establish a qualitative data base for the study. Using the insights gained from meta-analysis, an existing psoriasis patient survey was modified and administered to collect additional data as well as triangulate the results. The hypothesis is that specific types of psoriatic disease have specific etiology and pathophysiologic pattern. The following etiology categories were identified: bacterial, environmental/microbial, genetic, immune, infectious, trauma/stress, and viral. Additional results, obtained from meta-analysis and confirmed by patient survey, were the common age of onset (early to mid-20s) and type of psoriasis (plaque; mild; symmetrical; scalp, chest, and extremities, specifically elbows and knees). Almost 70% of patients reported no prescription drug use due to severe side effects and prohibitive cost. These results will guide the development of psoriasis and psoriatic arthritis diagnostic test. The significant number of medical publications classified psoriatic arthritis disease as inflammatory of an unknown etiology. Thus numerous meta-analyses struggle to report any meaningful conclusions since no definitive results have been reported to date. Therefore, return to the basics is an essential step to any future meaningful results. To date, medical literature supports the fact that psoriatic disease in its current classification could be misidentifying subcategories, which in turn hinders the success of studies conducted to date. Moreover, there has been an enormous commercial support to pursue various immune-modulation therapies, thus following a narrow hypothesis/mechanism of action that is yet to yield resolution of disease state. Recurrence and complications may be considered unacceptable in a significant number of these studies. The aim of the ongoing study is to focus on a narrow subgroup of patient population, as identified by this exploratory study via meta-analysis and patient survey, and conduct an exhaustive work up, aiming at mechanism of action and causality before proposing a cure or therapeutic modality. Remission in psoriasis has been achieved and documented in medical literature, such as immune-modulation, phototherapy, various over-the-counter agents, including salts and tar. However, there is no psoriasis and psoriatic arthritis diagnostic test to date, to guide the diagnosis and treatment of this debilitating and, thus far, incurable disease. Because psoriasis affects approximately 2% of population, the results of this study may affect the treatment and improve the quality of life of a significant number of psoriasis patients, potentially millions of patients in the United States alone and many more millions worldwide.

Keywords: biologics, early diagnosis, etiology, immune disease, immune modulation therapy, inflammation skin disorder, phototherapy, plaque psoriasis, psoriasis, psoriasis classification, psoriasis disease marker, psoriasis diagnostic test, psoriasis marker, psoriasis mechanism of action, psoriasis treatment, psoriatic arthritis, psoriatic disease, psoriatic disease marker, psoriatic patient experience, psoriatic patient quality of life, remission, salt therapy, targeted immune therapy

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Authors: Manik Sharma

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Understanding the anatomy and normal anatomical variations of the lower limb arterial system is undeniably important not only to understand the pathology involving the vessels of the lower limb but also as a part of endovascular intervention and surgical planning in cases that demand them as a part of treatment. There have been very few cases of duplication of SFA cited in the literature, close to six worldwide and this being the seventh case in the world and first to be reported in the Indian population. We incidentally came across this normal variant during US lower limb (US-LL) duplex scan in a patient with claudicating pain in bilateral lower limbs hence suspected of having peripheral vascular disease. It was confirmed on CT-Peripheral Angiography (CT-PA), which was done successively.

Keywords: peripheral vascular disease, claudicating pain, normal anatomical variants, endovascular intervention, duplication, CT-peripheral angiography, duplex scan, Iohexol

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Authors: Fatema-Tuz-Zohra Khanam, Ali Al-Naji, Asanka G. Perera, Kim Gibson, Javaan Chahl

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Conventional contact-based vital signs monitoring sensors such as pulse oximeters or electrocardiogram (ECG) may cause discomfort, skin damage, and infections, particularly in neonates with fragile, sensitive skin. Therefore, remote monitoring of the vital sign is desired in both clinical and non-clinical settings to overcome these issues. Camera-based vital signs monitoring is a recent technology for these applications with many positive attributes. However, there are still limited camera-based studies on neonates in a clinical setting. In this study, the heart rate (HR) and respiratory rate (RR) of eight infants at the Neonatal Intensive Care Unit (NICU) in Flinders Medical Centre were remotely monitored using a digital camera applying color and motion-based computational methods. The region-of-interest (ROI) was efficiently selected by incorporating an image decomposition method. Furthermore, spatial averaging, spectral analysis, band-pass filtering, and peak detection were also used to extract both HR and RR. The experimental results were validated with the ground truth data obtained from an ECG monitor and showed a strong correlation using the Pearson correlation coefficient (PCC) 0.9794 and 0.9412 for HR and RR, respectively. The RMSE between camera-based data and ECG data for HR and RR were 2.84 beats/min and 2.91 breaths/min, respectively. A Bland Altman analysis of the data also showed a close correlation between both data sets with a mean bias of 0.60 beats/min and 1 breath/min, and the lower and upper limit of agreement -4.9 to + 6.1 beats/min and -4.4 to +6.4 breaths/min for both HR and RR, respectively. Therefore, video camera imaging may replace conventional contact-based monitoring in NICU and has potential applications in other contexts such as home health monitoring.

Keywords: neonates, NICU, digital camera, heart rate, respiratory rate, image decomposition

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Authors: Gianni Izzo

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The relation of Islam to its legal precepts, reflected in the various jurisprudential 'schools of thought' (madhahib), is one expressed in a version of 'positivism' (fiqh) providing the primary theory for deducing Qurʾan rulings and those from the narrations (hadith) of the Prophet Muhammad. Scholars of Islam, including Patricia Crone (2004) and others chronicled by Anver Emon (2005), deny the influence of natural law theories as extra-scriptural indices of revelation’s content. This paper seeks to dispute these claims by reference to historical and canonical examples within Shiʿa legal thought that emphasize the salient roles of ‘aql (reason), fitrah (primordial human nature), and lutf (divine grace). These three holistic features, congenital to every human, and theophanically reflected in nature make up a mode of moral intelligibility antecedent to prophetic revelation. The debate between the 'traditionalist' Akhbaris and 'rationalist' Usulis over the nature of deriving legal edicts in Islam is well-covered academic ground. Instead, an attempt is made to define and detail the built-in assumptions of natural law revealed in the jurisprudential summa of Imami Shiʿism, whether of either dominant school, that undergird its legal prescriptions and methods of deduction.

Keywords: Islam, fiqh, natural law, legal positivism, aql

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Authors: Simon B. N. Thompson

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Retinoblastoma is a rare type of childhood genetic cancer that affects children worldwide. The diagnosis is often missed due to lack of education and difficulty in presentation of the tumor. Frequently, the tumor on the retina is noticed by photography when the red-eye flash, commonly seen in normal eyes, is not produced. Instead, a yellow or white colored patch is seen or the child has a noticeable strabismus. Early detection can be life-saving though often results in removal of the affected eye. Remaining functioning in the healthy eye when the child is young has resulted in super-vision and high or above-average intelligence. Technological advancement of cameras has helped in early detection. Brain imaging has also made possible early detection of neurological diseases and, together with the monitoring of cortisol levels and yawning frequency, promises to be the next new early diagnostic tool for the detection of neurological diseases where cortisol insufficiency is particularly salient, such as multiple sclerosis and Cushing’s disease.

Keywords: cortisol, neurological disease, retinoblastoma, Thompson cortisol hypothesis, yawning

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Authors: James Boag

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The needs of people with a diagnosis of dementia and their carers and families are physical, psychosocial, and psychological and begin at the time of diagnosis. There is frequently a lack of emotional support and counselling. Care- giving support is required from the presentation of the first symptoms of dementia until death. Alzheimer's disease begins decades before the clinical symptoms begin to appear, and in many cases, it remains undiagnosed, or diagnosed too late for any possible interventions to have any effect. However, if an incorrect diagnosis is given, it may result in a person being treated, without effect, for a type of dementia they do not have and delaying the interventions they should have received. Being diagnosed with dementia can cause emotional distress to the person, and physical and emotional support is needed, which will become more important as the disease progresses. The severity of the patient's dementia and their symptoms has a bearing of the impact on the carer and the support needed. A lack of insight and /or a denial of the diagnosis, grief, reacting to anticipated future losses, and coping methods to maximise the disease outcome, are things that should be addressed. Because of the stigma, it is important for carers not to lose contact with family and others because social isolation leads to depression and burnout. The impact on a carer's well- being and quality of life can be influenced by the severity of the illness, its type of dementia, its symptoms, healthcare support, financial and social status, career, age, health, residential setting, and relationship to the patient. Carer burnout due to lack of support leads to people diagnosed with dementia being put into residential care prematurely. Often dementia is not recognised as a terminal illness, limiting the ability of the person diagnosed with dementia and their carers to work on advance care planning and getting access to palliative and other support. Many carers have been satisfied with the physical support they were given in their everyday life, however, it was agreed that there was an immense unmet need for psychosocial support, especially after diagnosis and approaching end of life. Providing continuity and coordination of care is important. Training is necessary for providers to understand that every case is different, and they should understand the complexities. Grief, the emotional response to loss, is suffered during the progression of the disease and long afterwards, and carers should continue to be supported after the death of the person they were caring for.

Keywords: dementia, caring, challenges, needs

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Authors: Y. I. Tretyakova, S. G. Shulkina, T. Y. Kravtsova, A. A. Antipova, N. Y. Kolomeets

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The research aimed to assess the functional significance of tumor necrosis factor-alpha (TNF-α) gene polymorphism at the -308G/A (rs1800629) region and vascular endothelial growth factor A (VEGFA) gene polymorphism at the -634G/C (rs 2010963) region in the development of ulcerative colitis (UC), focusing on patients from the Perm region, Russia. We examined 70 UC patients and 50 healthy donors during the active phase of the disease. Our focus was on TNF-α and VEGF concentration in the blood serum, as well as TNF-α and VEGFA gene polymorphisms at the -308G/А and -634G/C regions, respectively. We found that TNF-α and VEGF levels were significantly higher in patients with severe UC and high endoscopic activity compared to those with milder forms of the disease and low endoscopic activity. These tests could serve as additional non-invasive markers for assessing mucosal damage in the large intestine of UC patients. The frequency of allele variations in the TNF-α gene -308G/A (rs1800629) revealed a significantly higher occurrence of the unfavorable homozygote AA in UC patients compared to donors. Additionally, the major allele G and the allele pair GG were more frequent in patients with mild to moderate disease and 1-2 degree of endoscopic activity than in those with severe UC and 3-4 degree of endoscopic activity (χ2=14.19; p=0.000). We also observed a mutant allele A and the unfavorable homozygote AA associated with severe progressive UC. The occurrence of the mutant allele increased the risk of severe UC by 5 times (OR 5.03; CI 12.07-12.21). We did not find any significant differences in the frequency of the CC homozygote (χ2=1.02; p=0.6; OR=1.32) and the mutant allele C of the VEGFA gene -634G/C (rs 2010963) (χ2=0.01; p=0.913; OR=0.97) between groups of UC patients and healthy individuals. However, we detected that the mutant allele C and the unfavorable homozygote CC of the VEGFA gene were associated with more severe endoscopic changes in the colonic mucosa of UC patients (χ2=25,76; р=0,000; OR=0,15). The presence of the mutant allele increased the risk of severe UC by 6 times (OR 6,78; CI 3,13–14,7). We found a direct correlation between TNF-α and VEGFA gene polymorphisms, increased production of the same factors, disease severity, and endoscopic activity (р=0.000). Therefore, the presence of the mutant allele A and homozygote AA of the TNF-α gene at the -308G/A region and the mutant allele C and homozygote CC of the VEGFA gene at the -634G/C region are associated with risks related to an unfavorable clinical course of UC, frequent recurrences, and rapid progression. These findings should be considered when making prognoses regarding the clinical course of the disease and selecting treatment strategies. The presence of the homozygote AA in the TNF-α gene (rs1800629) is considered a sign of genetic predisposition to UC.

Keywords: gene polymorphism, TNF-α, ulcerative colitis, VEGF

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Authors: Moushira Zaki, Wafaa Ezzat, Yasser Elhosary, Omnia Saleh

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Nonalcoholic fatty liver disease (NAFLD) has increased in conjunction with obesity. The accuracy of risk factors for detecting NAFLD in obese adolescents has not undergone a formal evaluation. The aim of this study was to evaluate predictors of NAFLD among Egyptian female obese adolescents. The study included 162 obese female adolescents. All were subjected to anthropometry, biochemical analysis and abdominal ultrasongraphic assessment. Metabolic syndrome (MS) was diagnosed according to the IDF criteria. Significant association between presence of MS and NAFLD was observed. Obese adolescents with NAFLD had significantly higher levels of ALT, triglycerides, fasting glucose, insulin, blood pressure and HOMA-IR, whereas decreased HDL-C levels as compared with obese cases without NAFLD. Receiver–operating characteristic (ROC) curve analysis shows that ALT is a sensitive predictor for NAFLD, confirming that ALT can be used as a marker of NAFLD.

Keywords: obesity, NAFLD, predictors, adolescents, Egyptians, risk factors, prevalence

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Authors: Hitoshi Minakuchi, Izumi Takei, Shu Wakino, Koichi Hayashi, Hiroshi Itoh

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Objectives: Among type 2 diabetics, patients with CKD(chronic kidney disease), insulin resistance, impaired glyconeogenesis in kidney and reduced degradation of insulin are recognized, and we observed different fluctuational patterns of blood sugar between CKD patients and non-CKD patients. On the other hand, non-dipper type blood pressure change is the risk of organ damage and mortality. We performed cross-sectional study to elucidate the characteristic of the fluctuation of blood glucose and blood pressure at insulin-treated diabetic patients with chronic kidney disease. Methods: From March 2011 to April 2013, at the Ichikawa General Hospital of Tokyo Dental College, we recruited 20 outpatients. All participants are insulin-treated type 2 diabetes with CKD. We collected serum samples, urine samples for several hormone measurements, and performed CGMS(Continuous glucose measurement system), ABPM (ambulatory blood pressure monitoring), brain computed tomography, carotid artery thickness, ankle brachial index, PWV, CVR-R, and analyzed these data statistically. Results: Among all 20 participants, hypoglycemia was decided blood glucose 70mg/dl by CGMS of 9 participants (45.0%). The event of hypoglycemia was recognized lower eGFR (29.8±6.2ml/min：41.3±8.5ml/min, P<0.05), lower HbA1c (6.44±0.57%：7.53±0.49%), higher PWV (1858±97.3cm/s：1665±109.2cm/s), higher serum glucagon (194.2±34.8pg/ml：117.0±37.1pg/ml), higher free cortisol of urine (53.8±12.8μg/day：34.8±7.1μg/day), and higher metanephrin of urine (0.162±0.031mg/day：0.076±0.029mg/day). Non-dipper type blood pressure change in ABPM was detected 8 among 9 participants with hypoglycemia (88.9%), 4 among 11 participants (36.4%) without hypoglycemia. Multiplex logistic-regression analysis revealed that the event of hypoglycemia is the independent factor of non-dipper type blood pressure change. Conclusions: Among insulin-treated type 2 diabetic patients with CKD, the events of hypoglycemia were frequently detected, and can associate with the organ derangements through the medium of non-dipper type blood pressure change.

Keywords: chronic kidney disease, hypoglycemia, non-dipper type blood pressure change, diabetic patients

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Authors: Anna Amato

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Every child needs communication. If spoken language is not or not fully available due to congenital or acquired limitations, those affected need appropriate ways. These can be found in many possibilities of Augmentative and Alternative Communications (AAC). In the communication promotion of severely impaired children, who can use their own body communication forms only to a limited extent for the differentiated understanding, computers with eye control play an essential role. It takes some time to understand the individual forms of communication of the child. Children who depend on the AAC need competent support to learn to communicate in a motivated way in their everyday life. The aim of the present parents' survey (n = 4), which was evaluated descriptively, is to demonstrate the development of communicative abilities as well as the motivation to use complex communication aids with eye control by patients with atypical Rett Syndrome. An increase in communication skills, well-being, self-reliance, and self-esteem, an improvement in social participation, as well as a reduction in anger and screaming events, were noted. The complex visual communication tools were available daily for 3 out of 4 patients with atypical Rett Syndrome. It raises research questions regarding speech understanding and the ability to drive eye control technology in a larger group of atypical Rett Syndrome patients.

Keywords: augmentative and alternative communications, AAC, atypical Rett-syndrome, children, development

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Authors: Atsuko Okazaki, Jurg Ott

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Some genetic diseases (‘digenic traits’) are due to the interaction between two DNA variants. For example, certain forms of Retinitis Pigmentosa (a genetic form of blindness) occur in the presence of two mutant variants, one in the ROM1 gene and one in the RDS gene, while the occurrence of only one of these mutant variants leads to a completely normal phenotype. Detecting such digenic traits by genetic methods is difficult. A common approach to finding disease-causing variants is to compare 100,000s of variants between individuals with a trait (cases) and those without the trait (controls). Such genome-wide association studies (GWASs) have been very successful but hinge on genetic effects of single variants, that is, there should be a difference in allele or genotype frequencies between cases and controls at a disease-causing variant. Frequent pattern mining (FPM) methods offer an avenue at detecting digenic traits even in the absence of single-variant effects. The idea is to enumerate pairs of genotypes (genotype patterns) with each of the two genotypes originating from different variants that may be located at very different genomic positions. What is needed is for genotype patterns to be significantly more common in cases than in controls. Let Y = 2 refer to cases and Y = 1 to controls, with X denoting a specific genotype pattern. We are seeking association rules, ‘X → Y’, with high confidence, P(Y = 2|X), significantly higher than the proportion of cases, P(Y = 2) in the study. Clearly, generally available FPM methods are very suitable for detecting disease-associated genotype patterns. We use fpgrowth as the basic FPM algorithm and built a framework around it to enumerate high-frequency digenic genotype patterns and to evaluate their statistical significance by permutation analysis. Application to a published dataset on opioid dependence furnished results that could not be found with classical GWAS methodology. There were 143 cases and 153 healthy controls, each genotyped for 82 variants in eight genes of the opioid system. The aim was to find out whether any of these variants were disease-associated. The single-variant analysis did not lead to significant results. Application of our FPM implementation resulted in one significant (p < 0.01) genotype pattern with both genotypes in the pattern being heterozygous and originating from two variants on different chromosomes. This pattern occurred in 14 cases and none of the controls. Thus, the pattern seems quite specific to this form of substance abuse and is also rather predictive of disease. An algorithm called Multifactor Dimension Reduction (MDR) was developed some 20 years ago and has been in use in human genetics ever since. This and our algorithms share some similar properties, but they are also very different in other respects. The main difference seems to be that our algorithm focuses on patterns of genotypes while the main object of inference in MDR is the 3 × 3 table of genotypes at two variants.

Keywords: digenic traits, DNA variants, epistasis, statistical genetics

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Authors: Chawarat Rotejanaprasert, Andrew Lawson

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Early detection of unusual health events depends on the ability to detect rapidly any substantial changes in disease, thus facilitating timely public health interventions. To assist public health practitioners to make decisions, statistical methods are adopted to assess unusual events in real time. We introduce a surveillance Kullback-Leibler (SKL) measure for timely detection of disease outbreaks for small area health data. The detection methods are compared with the surveillance conditional predictive ordinate (SCPO) within the framework of Bayesian hierarchical Poisson modeling and applied to a case study of a group of respiratory system diseases observed weekly in South Carolina counties. Properties of the proposed surveillance techniques including timeliness and detection precision are investigated using a simulation study.

Keywords: Bayesian, spatial, temporal, surveillance, prospective

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Authors: Seyhan Sahan-Firat, Meryem Temiz-Resitoglu, Demet Sinem Guden, Sefika Pinar Kucukkavruk, Bahar Tunctan, Ayse Nihal Sari, Zumrut Kocak

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We hypothesized that mTOR inhibition may prevent the multiple organ failures following severe multiple tissue injury associated with increased NADPH oxidase system activity occur in zymosan-induced systemic inflammation. Therefore, we investigated the role of mTOR in oxidative/nitrosative stress associated with increase in NADPH oxidase activity in zymosan-induced systemic inflammation model in rats. Male Wistar rats received saline (4 ml/kg, i.p.) and zymosan (500 mg/kg, i.p.) at time 0. Saline, or zymosan-treated rats were given rapamycin (1 mg/kg, i.p.) 1 h after saline or zymosan injections. Rats were sacrified 4 h after zymosan challenge and kidney, heart, thoracic aorta, and superior mesenteric artery were collected. NADPH oxidase activity, p22phox, gp91phox, and p47phox protein expression and nitrotyrosine levels were measured in tissue samples. Zymosan administration caused an increase in NADPH oxidase activity, p22phox, gp91phox, and p47phox protein expression and nitrotyrosine levels in kidney, heart, thoracic aorta, and superior mesenteric artery. These changes caused by zymosan reversed by rapamycin, a selective mTOR inhibitor. Rapamycin alone had no effect on the parameters measured. Our results demonstrated that zymosan-induced oxidative/nitrosative stress presumably due to enhanced activity of NADPH oxidase, expression of p22phox, gp91phox, and p47phox and production of peroxynitrite were mediated by mTOR. [This work was financially supported by Research Foundation of Mersin University (2016-2-AP3-1900)].

Keywords: oxidative stress, mTOR, nitrosative stress, zymosan

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Authors: Rajesh Kumar Suman, Ipseeta Ray Mohanty, Manjusha K. Borde, Ujjawala maheswari, Y. A. Deshmukh

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Background: Metabolic syndrome encompasses cluster of risk factors for cardiovascular disease which includes abdominal obesity, dyslipidemia, hypertension, and hyperglycemia. The incidence of metabolic syndrome is on the rise globally. Objective: The present study was designed to develop a unique animal model that will mimic the pathological features seen in a large pool of individuals with diabetes and metabolic syndrome; suitable for pharmacological screening of drugs beneficial in this condition. Material and Methods: A combination of high fat diet (HFD) and low dose of streptozotocin (STZ) at 30, 35 and 40 mg/kg was used to induce metabolic syndrome co-existing with diabetes mellitus in Wistar rats. Results: The 40 mg/kg STZ produced sustained hyperglycemia and the dose was thus selected for our study to induce diabetes mellitus. Rat fed HFD (HF-DC) group showed significant (p < 0.001) increase in body weight on 4th and 7th week as compared with NC (Normal Control) group rats. However, the increase in body weight of HF-DC group rats was not sustained at the end of 10th weeks. Various components of metabolic syndrome such as dyslipidemia {(Increased Triglyceride, total Cholesterol, LDL Cholesterol and decreased HDL Cholesterol)}, diabetes mellitus (Blood Glucose, HbA1c, Serum Insulin, C-peptide), hypertension {Systolic Blood pressure (p < 0.001)} were mimicked in the developed model of metabolic syndrome co existing with diabetes mellitus. In addition significant cardiac injury as indicated by CPK-MB levels, artherogenic index, hs-CRP. The decline in hepatic function {(p < 0.01) increase in the level of SGPT (U/L)} and renal function {(increase in creatinine levels (p < 0.01)} when compared to NC group rats. The histopathological assessment confirmed presence of edema, necrosis and inflammation in Heart, Pancreas, Liver and Kidney of HFD-DC group as compared to NC. Conclusion: The present study has developed a unique rodent model of metabolic syndrome; with diabetes as an essential component.

Keywords: diabetes, metabolic syndrome, high fat diet, streptozotocin, rats

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Authors: Olofintoye Lawrence Kayode, Olorunniyi Omojola Felix

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Schistosomiasis is a vector-borne water-based disease transmitted by Bulinus globosus, causing haematuria in the urine of man, while fascioliasis is a trematode zoonosis infectious transmitted by Lymnaea natalensis causing liver disease in man and animals. Adult Bulinus globosus and Lymnaea natalensis were used for the experiment. Aqueous leaf extract of Ageratum conyzoides and Datura stramonium were prepared into 25, 50, 75, 100, 200 and 400 ppm concentrations. Ten snails of each species were exposed to different concentrations in triplicates, and dechlorinated water was used as control at 24h, 48h, and 72h exposure. The results revealed that 100 ppm of both plants leaves extracts indicated mortality rates between 76.7% and 100% at 24h, 48h, and 72h for both snail species. (P<0.05). In conclusion, the extract exercised molluscicidal activity to control the snail vector at lethal doses LC₅₀ (66.611- 72.021 ppm), CI = 63.083-77.90ppm and LC₉₀ (92.623-102.350), CI = 87.715 -110.12 ppm.

Keywords: snail, plant leaf, aqueous extract, mortality

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Authors: Tsu-Yun Chiu, Tsung-Hsueh Lu, Tain-Junn Cheng

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Background: Traditional chronic disease management did not pay attention to effects of geographic factors on the compliance of treatment regime, which resulted in geographic inequality in outcomes of chronic disease management. This study aims to examine the geographic distribution and clustering of quality indicators of diabetes care. Method: We first extracted address, demographic information and quality of care indicators (number of visits, complications, prescription and laboratory records) of patients with diabetes for 2014 from medical information system in a medical center in Tainan City, Taiwan, and the patients’ addresses were transformed into district- and village-level data. We then compared the differences of geographic distribution and clustering of quality of care indicators between districts and villages. Despite the descriptive results, rate ratios and 95% confidence intervals (CI) were estimated for indices of care in order to compare the quality of diabetes care among different areas. Results: A total of 23,588 patients with diabetes were extracted from the hospital data system; whereas 12,716 patients’ information and medical records were included to the following analysis. More than half of the subjects in this study were male and between 60-79 years old. Furthermore, the quality of diabetes care did indeed vary by geographical levels. Thru the smaller level, we could point out clustered areas more specifically. Fuguo Village (of Yongkang District) and Zhiyi Village (of Sinhua District) were found to be “hotspots” for nephropathy and cerebrovascular disease; while Wangliau Village and Erwang Village (of Yongkang District) would be “coldspots” for lowest proportion of ≥80% compliance to blood lipids examination. On the other hand, Yuping Village (in Anping District) was the area with the lowest proportion of ≥80% compliance to all laboratory examination. Conclusion: In spite of examining the geographic distribution, calculating rate ratios and their 95% CI could also be a useful and consistent method to test the association. This information is useful for health planners, diabetes case managers and other affiliate practitioners to organize care resources to the areas most needed.

Keywords: catchment area of healthcare, chronic disease management, Geographic information system, quality of diabetes care

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Authors: Frida Carrillo Morales, Maria Maricela Carrasco Yépez, Saúl Rojas Hernández

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Naegleria fowleri is the causative agent of primary amebic meningoencephalitis, this disease is acute and fulminant that affects humans. It has been reported that despite the existence of therapeutic options against this disease, its mortality rate is 97%. Therefore, the need arises to have vaccines that confer protection against this disease and, in addition to developing adjuvants to enhance the immune response. In this regard, in our work group, we obtained a peptide designed from the membrane protein MP2CL5 of Naegleria fowleri called Smp145 that was shown to be immunogenic; however, it would be of great importance to enhance its immunological response, being able to co-administer it with a non-toxic adjuvant. Therefore, the objective of this work was to carry out the bioinformatic design of a peptide of the Naegleria fowleri membrane protein MP2CL5 conjugated with a non-toxic modified adjuvant from the native A1 structure of Cholera Toxin. For which different bioinformatics tools were used to obtain a model with a modification in amino acid 61 of the A1 subunit of the CT (CTA1), to which the Smp145 peptide was added and both molecules were joined with a 13-glycine linker. As for the results obtained, the modification in CTA1 bound to the peptide produces a reduction in the toxicity of the molecule in in silico experiments, likewise, the prediction in the binding of Smp145 to the receptor of B cells suggests that the molecule is directed in specifically to the BCR receptor, decreasing its native enzymatic activity. The stereochemical evaluation showed that the generated model has a high number of adequately predicted residues. In the ERRAT test, the confidence with which it is possible to reject regions that exceed the error values was evaluated, in the generated model, a high score was obtained, which determines that the model has a good structural resolution. Therefore, the design of the conjugated peptide in this work will allow us to proceed with its chemical synthesis and subsequently be able to use it in the mouse meningitis protection model caused by N. fowleri.

Keywords: immunology, vaccines, pathogens, infectious disease

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Authors: Federico Herrera, Valle Gomez García de Soria, Itxaso Portero Sainz, Carlos Fernández Arandojo, Mercedes Royg, Ana Marcos Jimenez, Anna Kreutzman, Cecilia MuñozCalleja

Abstract:

Introduction: Graft-versus-host disease (GVHD) still remains the major complication associated with allogeneic stem cell transplantation (SCT). The pathogenesis involves migration of donor naïve T-cells into recipient secondary lymphoid organs. Two molecules are important in this process: CD62L and CCR7, which are characteristically expressed in naïve/central memory T-cells. With this background, we aimed to study the influence of CCR7 and CD62L on donor lymphocytes in the development and severity of GVHD. Material and methods: This single center study included 98 donor-recipient pairs. Samples were collected prospectively from the apheresis product and phenotyped by flow cytometry. CCR7 and CD62L expression in CD4+ and CD8+ T-cells were compared between patients who developed acute (n=40) or chronic GVHD (n=33) and those who did not (n=38). Results: The patients who developed acute GVHD were transplanted with a higher percentage of CCR7+CD4+ T-cells (p = 0.05) compared to the no GVHD group. These results were confirmed when these patients were divided in degrees according to the severity of the disease; the more severe disease, the higher percentage of CCR7+CD4+ T-cells. Conversely, chronic GVHD patients received a higher percentage of CCR7+CD8+ T-cells (p=0.02) in comparison to those who did not develop the complication. These data were also confirmed when patients were subdivided in degrees of the disease severity. A multivariable analysis confirmed that percentage of CCR7+CD4+ T-cells is a predictive factor of acute GVHD whereas the percentage of CCR7+CD8+ T-cells is a predictive factor of chronic GVHD. In vitro functional assays (migration and activation assays) supported the idea of CCR7+ T-cells were involved in the development of GVHD. As low levels of CD62L expression were detected in all apheresis products, we tested the hypothesis that CD62L was shed during apheresis procedure. Comparing CD62L surface levels in T-cells from the same donor immediately before collecting the apheresis product, and the final apheresis product we found that this process down-regulated CD62L in both CD4+ and CD8+ T cells (p=0.008). Interestingly, when CD62L levels were analysed in days 30 or 60 after engraftment, they recovered to baseline (p=0.008). However, to investigate the relation between CD62L expression and the development of GVHD in the recipient samples after the engraftment, no differences were observed comparing patients with GVHD to those who did not develop the disease. Discussion: Our prospective study indicates that the CCR7+ T-cells from the donor, which include naïve and central memory T-cells, contain the alloreactive cells with a high ability to mediate GVHD (in the case of both migration and activation). Therefore we suggest that the proportion and functional properties of CCR7+CD4+ and CCR7+CD8+ T-cells in the apheresis could act as a predictive biomarker to both acute and chronic GVHD respectively. Importantly, our study precludes that CD62L is lost in the apheresis and therefore it is not a reliable biomarker for the development of GVHD.

Keywords: CCR7, CD62L, GVHD, SCT

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Authors: Yasir Karabacak

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Objective: The aim of periodontal therapy is to control and eliminate inflammation in order halt disease progression. The initial periodontal therapy (IPT) including scaling and root planing (SRP) can control periodontal disease in most cases of periodontitis; also maintaining good oral hygiene by the patient is fundamental. The aim of this case report is to present IPT and to present 3-month follow-up results in a patient with periodontitis. Materials and Methods IPT of a 63-year-old non-smoker male with generalized periodontitis is presented. The patient had no history of systemic disease. The intraoral examination reveals marked gingival inflammation as well as plaque accumulation and significant calculus deposits. On radiographic examination, severe bone loss was evident. The patient was diagnosed with generalized advanced periodontitis. Initial periodontal therapy including oral hygiene instructions and quadrant-based SRP under local anesthesia was performed using hand and ultrasonic instruments. No antibiotics were prescribed. The patient was recalled 4 weeks after IPT. Results Favorable clinical improvement was obtained. Gingival inflammation was resolved significantly. A reduction of the mean probing depth from 2.4 mm at baseline to 1.9 mm was observed. The patient presented with a good standard of oral hygiene. The plaque scores decreased from 54.0% at baseline to 17.0%. In addition, the percentage of sites with bleeding on probing decreased from 80.0% at baseline to 44.0%. The patient was scheduled for maintenance therapy every three months. Conclusion: The level of oral hygiene has a great impact on periodontal treatment outcome and supports periodontal therapy properly.

Keywords: initial periodontal, therapy and follow-up in a periodontitis, patient, a case report

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Authors: Daly M. J, Condron C, Mulhall C, Eppich W, O'Neill J.

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Introduction: In contemporary clinical cardiology, comprehensive and holistic bedside evaluation including accurate cardiac auscultation is in decline despite having positive effects on patients and their outcomes. Methods: Scripted histories and scoring checklists for three clinical scenarios in cardiology were co-created and refined through iterative consensus by a panel of clinical experts; these were then paired with recordings of auscultatory findings from three actual patients with known valvular heart disease. A wearable vest with embedded pressure-sensitive panel speakers was developed to transmit these recordings when examined at the standard auscultation points. RCSI medical students volunteered for a series of three formative long case examinations in cardiology (LC1 – LC3) using this hybrid simulation. Participants were randomised into two groups: Group 1 received individual teaching from an expert trainer between LC1 and LC2; Group 2 received the same intervention between LC2 and LC3. Each participant’s long case examination performance was recorded and blindly scored by two peer participants and two RCSI examiners. Results: Sixty-eight participants were included in the study (age 27.6 ± 0.1 years; 74% female) and randomised into two groups; there were no significant differences in baseline characteristics between groups. Overall, the median total faculty examiner score was 39.8% (35.8 – 44.6%) in LC1 and increased to 63.3% (56.9 – 66.4%) in LC3, with those in Group 1 showing a greater improvement in LC2 total score than that observed in Group 2 (p < .001). Using the novel checklist, intraclass correlation coefficients (ICC) were excellent between examiners in all cases: ICC .994 – .997 (p < .001); correlation between peers and examiners improved in LC2 following peer grading of LC1 performances: ICC .857 – .867 (p < .001). Conclusion: Hybrid simulation and quantitative grading improve learning, standardisation of assessment, and direct comparisons of both performance and acumen in clinical cardiology.

Keywords: cardiology, clinical skills, long case examination, hybrid simulation, checklist

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Authors: Mehdi Razeghi

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Background: The purpose of this case series was to quantify gait to study muscular dystrophy disease. In this research, the quantitative differences between normal and waddling gaits were assessed by force plate analysis. Methods: Nineteen myopathy patients and twenty normal subjects serving as the control group participated in this research. In this study, quantitative analyses of gait have been used to investigate the differences between the mobility of normal subjects and myopathy patients. This study was carried out at the Iranian Muscular Dystrophy Association in Boali Hospital, Tehran, Iran, from October 2015 to July 2020. Patient data were collected from Iranian Muscular Dystrophy Association members. individuals signed an informed consent form approved by the ethics committee of the Azad University. All of the gait tests were performed using a Kistler force platform. Participants walked at a self-selected speed, barefoot, independently, and without assistive devices. Results: Our findings indicate that there were no significant differences between the patients and the control group in the anterior-posterior components of the ground reaction forces; however, there were considerable differences in the force components between the groups in the medial-lateral and vertical directions of the ground reaction force. In addition, there were significant differences in the time parameters between the groups in the vertical and medial-lateral directions.

Keywords: biomechanics, force plate analysis, gait disorder, ground reaction force, kinetic analysis, myopathy disease, rehabilitation engineering

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Authors: Gilbert Makanda

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The problem of the teaching of mathematics is studied using differential equations. A mathematical model for knowledge acquisition in mathematics is developed. In this study we adopt the mathematical model that is normally used for disease modelling in the teaching of mathematics. It is assumed that teaching is 'infecting' students with knowledge thereby spreading this knowledge to the students. It is also assumed that students who gain this knowledge spread it to other students making disease model appropriate to adopt for this problem. The results of this study show that increasing recruitment rates, learning contact with teachers and learning materials improves the number of knowledgeable students. High dropout rates and forgetting taught concepts also negatively affect the number of knowledgeable students. The developed model is then solved using Matlab ODE45 and \verb"lsqnonlin" to estimate parameters for the actual data.

Keywords: differential equations, knowledge acquisition, least squares, dynamical systems

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Authors: Varsha Chorsiya, Pooja Aneja, Dhananjay Kaushik, Abhinav Yadav

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Intoduction: Women’s Health Initiatives (WHI) focuses on defining the risks and benefits of strategies that could potentially reduce the incidence of obesity, heart disease, breast cancer and colorectal cancer, and fractures in menopause women. The utility of the present research work determines to find the role of Hormone Replacement Therapy (HRT) in changing the different component of body composition during perimenopause period. Methods: A comparative cross-sectional study included 30 subjects, aged between 40 and 50 years which were assigned into 2 groups i.e. 15 subjects in HRT (Group A) and 15 subjects in non-HRT (Group B). The subjects were taken from the hospitals and clinics of Faridabad undergoing HRT in supervision of the consultant gynecologist. The informed consents were signed before including the participants in the study. The body composition and lipid profile were evaluated for all the subjects. Result and Discussion: The BMI, body density, percent body fats and fat mass in both groups showed statistically significant differences i.e. p < 0.05. Our study did not reveal any statistically significant difference between non-HRT and HRT for lipid profile composition of HDL, LDL, VLDL, ratio, triglycerides and total cholesterol although these indicators (LDL, VLDL, ratio, triglycerides and total cholesterol) showed difference clinically with a higher mean values for non-HRT as compared to HRT group. The mean value for HDL was higher for HRT group in contrast to non-HRT group. The result clearly showed that HRT group has a good lipid profile composition. Conclusion: In conclusion, our data show that HRT has statistically significant role in determining BMI, fat percent mass and fat mass. The lipid profile including LDL, HDL, VLDL, ratio, triglycerides and total cholesterol found to be clinically better in HRT group as compared to the non-HRT group. The rationale for non-significant lipid profile probably lie in the fact that hormonal changes need a particular time period and might become significant in post-menopausal period.

Keywords: body composition, hormone replacement therapy, perimenopause, women health

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Authors: Ognen Kostovski, Svetozar Antovic, Rubens Jovanovic, Irena Kostovska, Nikola Jankulovski

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Introduction:Colorectal carcinoma (CRC) is one of the most common malignancies in the world. The cancer stem cell (CSC) markers are associated with aggressive cancer types and poor prognosis. The aim of study was to determine whether the expression of colorectal cancer stem cell markers CD133 and CD44 could be significant in prediction of clinically aggressive form of CRC. Materials and methods: Our study included ninety patients (n=90) with CRC. Patients were divided into two subgroups: with metatstatic CRC and non-metastatic CRC. Tumor samples were analyzed with standard histopathological methods, than was performed immunohistochemical analysis with monoclonal antibodies against CD133 and CD44 stem cell markers. Results: High coexpression of CD133 and CD44 was observed in 71.4% of patients with metastatic disease, compared to 37.9% in patients without metastases. Discordant expression of both markers was found in 8% of the subgroup with metastatic CRC, and in 13.4% of the subgroup without metastatic CRC. Statistical analyses showed a significant association of increased expression of CD133 and CD44 with the disease stage, T - category and N - nodal status. With multiple regression analysis the stage of disease was designate as a factor with the greatest statistically significant influence on expression of CD133 (p <0.0001) and CD44 (p <0.0001). Conclusion: Our results suggest that the coexpression of CD133 and CD44 have an important role in prediction of clinically aggressive form of CRC. Both stem cell markers can be routinely implemented in standard pathohistological diagnostics and can be useful markers for pre-therapeutic oncology screening.

Keywords: colorectal carcinoma, stem cells, CD133+, CD44+

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