Search results for: premature mortality

Authors: Shi-xia Xu, Zai-wen Zhang, Ru-xue Chen, Shan Zhou, Xiang-feng Tang

Abstract:

Objective: The clinical influence of HLA-DPB1 mismatches on clinical outcome of HSCT is less clear. This is the first meta-analysis to study the HLA-DPB1 matching statues on clinical outcomes after unrelated donor HSCT. Methods: We searched the CIBMTR, Cochrane Central Register of Controlled Trials (CENTRAL) and related databases (1995.01–2017.06) for all relevant articles. Comparative studies were used to investigate the HLA-DPB1 loci mismatches on clinical outcomes after unrelated donor HSCT, such as the disease-free survival (DFS), overall survival, GVHD, relapse, and transplant-related mortality (TRM). We performed meta-analysis using Review Manager 5.2 software and funnel plot to assess the bias. Results: At first, 1246 articles were retrieved, and 18 studies totaling 26368 patients analyzed. Pooled comparisons of studies found that the HLA-DPB1 mismatched group had a lower rate of DFS than the DPB1-matched group, and lower OS in non-T cell depleted transplantation. The DPB1 mismatched group has a higher incidence of aGVHD and more severe ( ≥ III degree) aGvHD, lower rate of relapse and higher TRM. Moreover, compared with 1-antigen mismatch, 2-antigen mismatched led to a higher risk of TRM and lower relapse rate. Conclusions: This meta-analysis indicated HLA-DPB1 has important influence on survival and transplant-related complications during unrelated donor HSCT and HLA-DPB1 donor selection strategies have been proposed based on a personalized algorithm.

Keywords: human leukocyte antigen, DPB1, transplant, meta-analysis, outcome

Procedia PDF Downloads 298

Authors: Hagos Abraham, Solomon Gizaw, Mengistu Urge

Abstract:

A sound breeding objective is the basis for genetic improvement in overall economic merit of farm animals. Begait goat is one of the identified breeds in Ethiopia, which is a multipurpose breed as it serves as source of cash income and source of food (meat and milk). Despite its importance, no formal breeding objectives exist for Begait goat. The objective of the present study was to identify breeding objectives for the breed through two approaches: using own-flock ranking experiment and developing deterministic bio-economic models as a preliminary step towards designing sustainable breeding programs for the breed. In the own-flock ranking experiment, a total of forty five households were visited at their homesteads and were asked to select, with reasons, the first best, second best, third best and the most inferior does from their own flock. Age, previous reproduction and production information of the identified animals were inquired; live body weight and some linear body measurements were taken. The bio-economic model included performance traits (weights, daily weight gain, kidding interval, litter size, milk yield, kid mortality, pregnancy and replacement rates) and economic (revenue and costs) parameters. It was observed that there was close agreement between the farmers’ ranking and bio-economic model results. In general, the results of the present study indicated that Begait goat owners could improve performance of their goats and profitability of their farms by selecting for litter size, six month weight, pre-weaning kid survival rate and milk yield.

Keywords: bio-economic model, economic parameters, own-flock ranking, performance traits

Procedia PDF Downloads 67

Authors: Liudmila Garzanova, Lidia Ananyeva, Olga Koneva, Olga Ovsyannikova, Oxana Desinova, Mayya Starovoytova, Rushana Shayahmetova, Anna Khelkovskaya-Sergeeva

Abstract:

Objectives. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are associated with severe course, increased morbidity and mortality in systemic sclerosis (SSc). The aim of our study was to assess changes in CRP and ESR in SSc patients during long-term RTX therapy. Methods. This study included 113 patients with SSc. Mean age was 48.1±13 years, female-85%. The mean disease duration was 6±5 years. The diffuse cutaneous subset of the disease had 55% of patients. All pts had interstitial lung disease (ILD). All patients received prednisolone at a mean dose of 11.6±4.8 mg/day, and 53 of them - were immunosuppressants at inclusion. Patients received RTX due to the ineffectiveness of previous therapy for ILD. The parameters were evaluated over the periods: at baseline (point 0), 13±2.3 month (point 1, n=113), 42±14 month (point 2, n=80) and 79±6.5 month (point 3, n=25) after initiation of RTX therapy. Cumulative mean dose of RTX at point 1 = 1.7±0.6g, at point 2 = 3±1.5g, and at point 3 = 3.8±2.4g. The results are presented in the form of mean values, delta(Δ)-difference between the baseline parameter and follow-up point. Results. There was an improvement in studied parameters on RTX therapy. There was a significant decrease of ESR, CRP and activity index (EScSG-AI) at all observation points (p=0.001). In point 1: ΔCRP was 6.7 mg/l, ΔESR = 7.4 mm/h, ΔActivity index (EScSG-AI) = 1.7. In point 2: ΔCRP was 8.7 mg/l, ΔESR = 7.5 mm/h, ΔActivity index (EScSG-AI) = 1.9. In point 3: ΔCRP was 16.1 mg/l, ΔESR = 11 mm/h, ΔActivity index (EScSG-AI) = 2.1. Conclusion. There was a significant decrease in CRP and ESR during long-term RTX therapy, which correlated with a decrease in the disease activity index. RTX is an effective treatment option for SSc with an elevation of acute-phase reactants.

Keywords: C-reactive protein, interstitial lung disease, systemic sclerosis, rituximab

Procedia PDF Downloads 26

Authors: Carl J. Caspersen, Kenneth E. Powell, Gregory M. Christenson, Kirupa V. Patel

Abstract:

‘Physical activity’, ‘exercise’, and ‘physical fitness’ are terms that describe different concepts. However, they are often confused with one another, and the terms are sometimes used interchangeably. This paper proposes definitions to distinguish them. Physical activity is defined as any bodily movement produced by skeletal muscles that result in energy expenditure. The energy expenditure can be measured in kilocalories. Physical activity in daily life can be categorized into occupational, sports, Conditioning, household, or other activities. Exercise is a subset of physical activity that is planned, structured, and repetitive and has as a final or an intermediate objective the improvement or maintenance of physical fitness. Physical fitness is a set of attributes that are either health- or skill-related. The degree to which people have these attributes can be measured with specific tests. These definitions are offered as an interpretational framework for comparing studies that relate physical activity, exercise, and physical fitness to health. Physical activity is defined as any bodily movement produced by skeletal muscles that require energy expenditure. Physical inactivity has been identified as the fourth leading risk factor for global mortality causing an estimated 3.2 million deaths globally. Regular moderate intensity physical activity – such as walking, cycling, or participating in sports – has significant benefits for health. For instance, it can reduce the risk of cardiovascular diseases, diabetes, colon and breast cancer, and depression. Moreover, adequate levels of physical activity will decrease the risk of a hip or vertebral fracture and help control weight. Any bodily movement produced by the contraction of skeletal muscle that increases energy expenditure above a basal level. In these guidelines, physical activity generally refers to the subset of physical activity that enhances health.

Keywords: physical activity, exercise, physical fitness, sports

Procedia PDF Downloads 361

Authors: Ahmad Rabby

Abstract:

The demographic trend analyses of Bombay-duck from time series catch data using CMSY and BSM for the first time in Bangladesh. During 2000-2018, CMSY indicates average lowest production in 2000 and highest in 2018. This has been used in the estimation of prior biomass by the default rules. Possible 31030 viable trajectories for 3422 r-k pairs were found by the CMSY analysis and the final estimates for intrinsic rate of population increase (r) was 1.19 year-1 with 95% CL= 0.957-1.48 year-1. The carrying capacity(k) of Bombay-duck was 283×103 tons with 95% CL=173×103 - 464×103 tons and MSY was 84.3×103tons year-1, 95% CL=49.1×103-145×103 tons year-1. Results from Bayesian state-space implementation of the Schaefer production model (BSM) using catch & CPUE data, found catchabilitiy coefficient(q) was 1.63 ×10-6 from lcl=1.27×10-6 to ucl=2.10×10-6 and r= 1.06 year-1 with 95% CL= 0.727 - 1.55 year-1, k was 226×103 tons with 95% CL=170×103-301×103 tons and MSY was 60×103 tons year-1 with 95% CL=49.9 ×103- 72.2 ×103 tons year-1. Results for Bombay-duck fishery management based on BSM assessment from time series catch data illustrated that, Fmsy=0.531 with 95% CL =0.364 - 0.775 (if B > 1/2 Bmsy then Fmsy =0.5r); Fmsy=0.531 with 95% CL =0.364-0.775 (r and Fmsy are linearly reduced if B < 1/2Bmsy). Biomass in 2018 was 110×103 tons with 2.5th to 97.5th percentile=82.3-155×103 tons. Relative biomass (B/Bmsy) in last year was 0.972 from 2.5th percentile to 97.5th percentile=0.728 -1.37. Fishing mortality in last year was 0.738 with 2.5th-97.5th percentile=0.525-1.37. Exploitation F/Fmsy was 1.39, from 2.5th to 97.5th percentile it was 0.988 -1.86. The biological reference points of B/BMSY was smaller than 1.0, while F/FMSY was higher than 1.0 revealed an over-exploitation of the fishery, indicating that more conservative management strategies are required for Bombay-duck fishery.

Keywords: biological reference points, catchability coefficient, carrying capacity, intrinsic rate of population increase

Procedia PDF Downloads 124

Authors: Elena Petersen, Inna Kornienko, Svetlana Guryeva, Sergey Dobdin, Anatoly Skripal, Andrey Usanov, Dmitry Usanov

Abstract:

One of the most important unsolved problems in modern medicine is the increase of chronic diseases that lead to organ dysfunction or even complete loss of function. Current methods of treatment do not result in decreased mortality and disability statistics. Currently, the best treatment for many patients is still transplantation of organs and/or tissues. Therefore, finding a way of correct artificial matrix biofabrication in case of limited number of natural organs for transplantation is a critical task. One important problem that needs to be solved is development of a nondestructive and noninvasive method to analyze dynamic changes of mechanical characteristics of a matrix with minimal side effects on the growing cells. This research was focused on investigating the properties of matrix as a marker of graft condition. In this study, the collagen gel with human primary dermal fibroblasts in suspension (60, 120, 240*103 cells/mL) and collagen gel with cell spheroids were used as model objects. The stiffness and elasticity characteristics were evaluated by a semiconductor laser autodyne. The time and cell concentration dependency of the stiffness and elasticity were investigated. It was shown that these properties changed in a non-linear manner with respect to cell concentration. The maximum matrix stiffness was observed in the collagen gel with the cell concentration of 120*103 cells/mL. This study proved the opportunity to use the mechanical properties of matrix as a marker of graft condition, which can be measured by noninvasive semiconductor laser autodyne technique.

Keywords: graft, matrix, noninvasive method, regenerative medicine, semiconductor laser autodyne

Procedia PDF Downloads 344

Authors: Sayed Ali Garossi, Azar Heidarizadi, Shahla Mohammad Ganji

Abstract:

Context: Colorectal cancer is the second type of cancer-related mortality globally. Expression of cas8 (caspase 8) is closely connected to growth and metastasis of colorectal cancer.Cas8/Rip1 plays a vital role in the apoptosis pathway and resistance to chemotherapy. The aim of the present study is to investigate the pattern of gene expression in colorectal cancer and compare the differences using Real-Time PCR to find a potential biomarker candidate for colorectal cancer. Methodology: This study conducted real-time PCR to evaluate gene expression of Cas8 in colorectal cancer patients. The gene-specific primer sequences exon–exon junction was designed by OLIGO7 software for the expression of the gene under investigation. Forty-six patient samples without any chemotherapy were selected, including tumoral tissue and adjacent normal tissue samples. The age of the patients was 50 and the size of the tumors was 5.5 cm. The categories were before and after age 50. Findings: Here, we found that Caspase 8 was overexpressed in CRC tissues compared to corresponding adjacent colon tissues (Cas8: 5.2 vs. 1 ratio); high expression of Cas8 was associated with poor overall survival and independent risk factors for the prognosis of CRC patients. Conclusion: In conclusion, our study pioneered the reporting of high Casp8 expression as a predictor of poor prognosis and chemical resistance in CRC patients.Cas8 overexpression suppressed Cas 8 / Rip1-dependent apoptosis and activated the proliferation of tumor cells by activating necroptosis. The necroptosis pathway has also emerged as a new approach to anti-tumor in cancer treatment.

Keywords: Cas8, necroptosis, apoptosis, Real-Time PCR

Procedia PDF Downloads 55

Authors: Chih Jou Hsiao, Chung Ming Lo, Li Chun Hsieh

Abstract:

Brain tumor is not the cancer having high incidence rate, but its high mortality rate and poor prognosis still make it as a big concern. On clinical examination, the grading of brain tumors depends on pathological features. However, there are some weak points of histopathological analysis which can cause misgrading. For example, the interpretations can be various without a well-known definition. Furthermore, the heterogeneity of malignant tumors is a challenge to extract meaningful tissues under surgical biopsy. With the development of magnetic resonance imaging (MRI), tumor grading can be accomplished by a noninvasive procedure. To improve the diagnostic accuracy further, this study proposed a computer-aided diagnosis (CAD) system based on MRI features to provide suggestions of tumor grading. Gliomas are the most common type of malignant brain tumors (about 70%). This study collected 34 glioblastomas (GBMs) and 73 lower-grade gliomas (LGGs) from The Cancer Imaging Archive. After defining the region-of-interests in MRI images, multiple quantitative morphological features such as region perimeter, region area, compactness, the mean and standard deviation of the normalized radial length, and moment features were extracted from the tumors for classification. As results, two of five morphological features and three of four image moment features achieved p values of <0.001, and the remaining moment feature had p value <0.05. Performance of the CAD system using the combination of all features achieved the accuracy of 83.18% in classifying the gliomas into LGG and GBM. The sensitivity is 70.59% and the specificity is 89.04%. The proposed system can become a second viewer on clinical examinations for radiologists.

Keywords: brain tumor, computer-aided diagnosis, gliomas, magnetic resonance imaging

Procedia PDF Downloads 260

Authors: Shedy Maharani Nariswari, Prima Agustia Nova, I. Made Kariasa

Abstract:

Background. Heart Failure (HF) is a chronic and progressive condition associated with significant morbidity, mortality, health care expenditures, and a high readmission rate over the years. Self‐care is essential to manage chronic heart failure in the long term, and it is related to better outcomes and can enhance the quality of life. Objective. The aims of this study were to describe the relationship between self-care behavior and quality of life among heart failure patients in East Jakarta, Indonesia. Methods. This study used a correlational-descriptive design with a cross-sectional study, the sampling method used purposive sampling method. Self-care was measured using Self-care Heart Failure Index version 6.2, and quality of life was measured using The Minnesota Living with Heart Failure. Pearson correlation and Spearman-rho correlations are used to analyze the data. Results. We recruited 103 patients with HF in both outpatient and inpatient ward: mean age 59.26 ± 11.643 years, 63.1% male. Patients with higher levels of education were associated with higher self-care maintenance (p= 0.007). The patient's average quality of life is quite high, with a score of 72,07 ± 16,89. There were a significant relationship among self-care maintenance (r=0,305, p=0,001), self-care management (r=0,330, p=0,001), and self-care confidence (r=0,335, p=0,001) towards the quality of life. Most participants have inadequate self-care maintenance, self-care management, and self-care confidence (score < 70), while the score of quality of life is categorized as poor. Conclusion. The self-care behaviors were limited among patients living with HF in Indonesia yet was associated with better quality of life. It is necessary to promote health related to knowledge and adherence to self-care behavior so that it can improve the quality of life of heart failure patients. This study can be used as a reference to promote self-care among patients with heart failure, it can help to enhance their quality of life.

Keywords: heart failure, self-care maintenance, self-care management, self-care confidence, quality of life

Procedia PDF Downloads 106

Authors: Michael Daly

Abstract:

Background/Aims: The interplay of childhood self-control and early life social background in predicting adult health is currently unclear. We drew on rich data from two large nationally representative cohort studies to test whether individual differences in childhood self-control may: (i) buffer the health impact of social disadvantage, (ii) act as a mediating pathway underlying the emergence of health disparities, or (iii) compensate for the health consequences of socioeconomic disadvantage across the lifespan. Methods: We examined data from over 25,000 participants from the British Cohort Study (BCS) and the National Child Development Study (NCDS). Child self-control was teacher-rated at age 10 in the BCS and ages 7/11 in the NCDS. The Early life social disadvantage was indexed using measures of parental education, occupational prestige, and housing characteristics (i.e. housing tenure, home crowding). A range of health outcomes was examined: the presence of chronic conditions, whether illnesses were limiting, physiological dysregulation (gauged by clinical indicators), mortality, and perceptions of pain, psychological distress, and general health. Results: Childhood self-control and social disadvantage predicted each measure of adult health, with similar strength on average. An examination of mediating factors showed that adult smoking, obesity, and socioeconomic status explained the majority of these linkages. There was no systematic evidence that self-control moderated the health consequences of early social disadvantage and limited evidence that self-control acted as a key pathway from disadvantage to later health. Conclusions: Childhood self-control predicts adult health and may compensate for early life social disadvantage by shaping adult health behaviour and social status.

Keywords: personality and health, social disadvantage, health psychology, life-course development

Procedia PDF Downloads 219

Authors: Nicole Banton

Abstract:

The maternal and infant mortality rate of Blacks is three times that of Whites in the US. Research indicates that breastfeeding lowers both. In this paper, the researcher examines how the ideas that Black/African American mothers had about breastfeeding before, during, and after pregnancy (postpartum) affected whether or not they initiated breastfeeding. The researcher used snowball sampling to recruit thirty African-American mothers from the Orlando area. At the time of her interview, each mother had at least one child who was at least three years old. Through in-depth face-to-face interviews, the researcher investigated how mothers’ healthcare providers affected their decision-making about infant feeding, as well as how the type of birth that she had (e.g., preterm, vaginal, c-section, full term) affected her actual versus idealized infant feeding practice. Through our discussions, we explored how pre-pregnancy perceptions, birth and postpartum experiences, social support, and the discourses surrounding motherhood within an African-American context affected the perceptions and experiences that the mothers in the study had with their infant feeding practice(s). Findings suggest that the pregnancy and birth experiences of the mothers in the study influenced whether or not they breastfed exclusively, combined breastfeeding and infant formula use, or used infant formula exclusively. Specifically, the interplay of invocation of agency (the ability to control their bodies before, during, and after birth), birth outcomes, and the interaction that the mothers in this study had with resources, human and material, had the highest impact on the initiation, duration, and attitude toward breastfeeding.

Keywords: African American mothers, maternal health, breastfeeding, birth, midwives, obstetricians, hospital birth, breast pumps, formula use, infant feeding, lactation consultant, postpartum, vaginal birth, c-section, familial support, social support, work, pregnancy

Procedia PDF Downloads 82

Authors: Shittu Bashirat, Shittu Mujeeb, Oluremi Adeolu, Orisadare Olayiwola, Jikeme Osameke, Bello Lateef

Abstract:

Septicemia in neonates refers to generalized bacterial infection documented by positive blood culture in the first 28 days of life and is one of the leading causes of neonatal mortality in sub-Sahara Africa. Thrombocytopenia in newborns is a result of increased platelet consumption; sepsis was found to be the most common risk factor. The objective of the study was to determine if there are organism-specific platelet responses among the 2 groups of bacterial agents: Gram-positive and Gram-negative bacteria, and also to examine the association of platelet count and prothrombin time with neonatal septicemia. 232 blood samples were collected for this study. The blood culture was performed using Bactec 9050, an instrumented blood culture system. The platelet count and prothrombin time were performed using Abacus Junior 5 hematology analyzer and i-STAT 1 analyzer respectively. Of the 231 neonates hospitalized with clinical sepsis, blood culture reports were positive in 51 cases (21.4%). Klebsiella spp. (35.3%) and Staphylococcus aureus (27.5%) were the most common Gram-negative and Gram-positive isolates respectively. Thrombocytopenia was observed in 30 (58.8%) of the neonates with septicemia. Of the 9 (17.6%) patients with severe thrombocytopenia, seven (77.8%) had Klebsiella spp. septicemia. Out of the 21(63.6%) of thrombocytopenia produced by Gram-negative isolate, 17 (80.9) had increased prothrombin time. In conclusion, Gram-negative organisms showed the highest cases of severe thrombocytopenia and prolonged PT. This study has helped to establish a disturbance in hemostatic systems in neonates with septicemia. Further studies, however, may be required to assess other hemostasis parameters in order to understand their interaction with the infectious organisms in neonates.

Keywords: neonates, septicemia, thrombocytopenia, prolonged prothrombin time, platelet count

Procedia PDF Downloads 406

Authors: V. Kuzhandai Velu, R. Ramesh

Abstract:

Background and objectives: Acute myocardial infarction (AMI) is the most common cause of mortality and morbidity. Over the last decade, microRNAs (miRs) have emerged as a potential marker for detecting AMI. The current study evaluates the kinetics and importance of miRs in the differential diagnosis of ST-segment elevated MI (STEMI) and non-STEMI (NSTEMI) and its correlation to conventional biomarkers and to predict the immediate outcome of AMI for arrhythmias and left ventricular (LV) dysfunction. Materials and Method: A total of 100 AMI patients were recruited for the study. Routine cardiac biomarker and miRNA levels were measured during diagnosis and serially at admission, 6, 12, 24, and 72hrs. The baseline biochemical parameters were analyzed. The expression of miRs was compared between STEMI and NSTEMI at different time intervals. Diagnostic utility of miR-1, miR-133, miR-208, and miR-499 levels were analyzed by using RT-PCR and with various diagnostics statistical tools like ROC, odds ratio, and likelihood ratio. Results: The miR-1, miR-133, and miR-499 showed peak concentration at 6 hours, whereas miR-208 showed high significant differences at all time intervals. miR-133 demonstrated the maximum area under the curve at different time intervals in the differential diagnosis of STEMI and NSTEMI which was followed by miR-499 and miR-208. Evaluation of miRs for predicting arrhythmia and LV dysfunction using admission sample demonstrated that miR-1 (OR = 8.64; LR = 1.76) and miR-208 (OR = 26.25; LR = 5.96) showed maximum odds ratio and likelihood respectively. Conclusion: Circulating miRNA showed a highly significant difference between STEMI and NSTEMI in AMI patients. The peak was much earlier than the conventional biomarkers. miR-133, miR-208, and miR-499 can be used in the differential diagnosis of STEMI and NSTEMI, whereas miR-1 and miR-208 could be used in the prediction of arrhythmia and LV dysfunction, respectively.

Keywords: myocardial infarction, cardiac biomarkers, microRNA, arrhythmia, left ventricular dysfunction

Procedia PDF Downloads 128

Authors: M. Khordadmehr, V. R. Ranjbar, R. Norouzi, M. Zeinoddin

Abstract:

Coccidiosis is recognized as a serious parasitic disease problem limiting quail industry recently. But the data on incidence, clinical signs, species of coccidia and pathological changes in Japanese quail are rare, especially in Iran in spite of the significant improvement of commercial quail breeding in this country in recent decades. Therefore, in the present paper was studied natural infection of quail coccidiosis in three commercial rearing farms with 80% morbidity and 3% mortality rate. For this purpose, fecal sample, oocyst examination, and morphological study were performed beside necropsy, histopathology, and PCR to confirm the diagnosis. In the affected birds, clinical signs included brown diarrhea, weakness, and pale face. In the fecal examination, three species of the genus Eimeria were identified including E. uzura, E. bateri, and E. tsunodai. At necropsy, the main gross lesions were edema, congestion and small blood spots in the small intestine. In histopathologic examination, endogenous stages of the parasites associated with hyperplasia of the intestinal glands, mild congestion, infiltration of mononuclear cells, and edema were observed in the intestine. The molecular study using BSEF and BSER specific primers confirmed the presence of the genus Eimeria in the affected birds. Interestingly, phylogenetic analysis showed relatively high bootstrap values in Japanese quail Eimeria with E. acervuline and E. maxima strains in the chicken. The present study is the first phylogenetic findings on Eimeria of quail which could be valuable for further research on Japanese quail coccidiosis.

Keywords: coccidiosis, Japanese Quail, pathomorphology, phylogenetic analysis

Procedia PDF Downloads 244

Authors: M. D. Haneef, R. B. Randall, Z. Peng

Abstract:

Journal bearings used in IC engines are prone to premature failures and are likely to fail earlier than the rated life due to highly impulsive and unstable operating conditions and frequent starts/stops. Vibration signature extraction and wear debris analysis techniques are prevalent in the industry for condition monitoring of rotary machinery. However, both techniques involve a great deal of technical expertise, time and cost. Limited literature is available on the application of these techniques for fault detection in reciprocating machinery, due to the complex nature of impact forces that confounds the extraction of fault signals for vibration based analysis and wear prediction. This work is an extension of a previous study, in which an engine simulation model was developed using a MATLAB/SIMULINK program, whereby the engine parameters used in the simulation were obtained experimentally from a Toyota 3SFE 2.0 litre petrol engines. Simulated hydrodynamic bearing forces were used to estimate vibrations signals and envelope analysis was carried out to analyze the effect of speed, load and clearance on the vibration response. Three different loads 50/80/110 N-m, three different speeds 1500/2000/3000 rpm, and three different clearances, i.e., normal, 2 times and 4 times the normal clearance were simulated to examine the effect of wear on bearing forces. The magnitude of the squared envelope of the generated vibration signals though not affected by load, but was observed to rise significantly with increasing speed and clearance indicating the likelihood of augmented wear. In the present study, the simulation model was extended further to investigate the bearing wear behavior, resulting as a consequence of different operating conditions, to complement the vibration analysis. In the current simulation, the dynamics of the engine was established first, based on which the hydrodynamic journal bearing forces were evaluated by numerical solution of the Reynold’s equation. Also, the essential outputs of interest in this study, critical to determine wear rates are the tangential velocity and oil film thickness between the journal and bearing sleeve, which if not maintained appropriately, have a detrimental effect on the bearing performance. Archard’s wear prediction model was used in the simulation to calculate the wear rate of bearings with specific location information as all determinative parameters were obtained with reference to crank rotation. Oil film thickness obtained from the model was used as a criterion to determine if the lubrication is sufficient to prevent contact between the journal and bearing thus causing accelerated wear. A limiting value of 1 µm was used as the minimum oil film thickness needed to prevent contact. The increased wear rate with growing severity of operating conditions is analogous and comparable to the rise in amplitude of the squared envelope of the referenced vibration signals. Thus on one hand, the developed model demonstrated its capability to explain wear behavior and on the other hand it also helps to establish a correlation between wear based and vibration based analysis. Therefore, the model provides a cost-effective and quick approach to predict the impending wear in IC engine bearings under various operating conditions.

Keywords: condition monitoring, IC engine, journal bearings, vibration analysis, wear prediction

Procedia PDF Downloads 310

Authors: Solomon Assefa Huluka

Abstract:

Wounds account for severe morbidity, socioeconomic distress, and mortality around the globe.For several years, various herbal products are used to expediteand augment the innate wound healing process. In Ethiopian folkloricmedicine, Verbascum sinaiticum L. (V. sinaiticum) is commonlyapplied as a wound-healing agent. The present study investigated the potential wound healing and antioxidant properties of hydroalcoholic leaf extract of V. sinaiticum. The 80% methanol extract, formulated as 5% (w/w) and 10% (w/w) ointments, was evaluated in excision and incision wound models using nitrofurazone and simple ointment as positive and negative controls, respectively. Parameters such as wound contraction, period of epithelialization, and tensile strength were determined. Moreover, its in vitro antioxidant property was evaluated using a DPPH assay. In the excision model, both doses (5% and 10% w/w) of the extract showed a significant (p<0.001) wound healing efficacy compared to the negative control, as evidenced by enhanced wound contraction rate and shorter epithelialization time records. In the incision model, the lower dose (5% w/w) ointment formulation of the extract exhibited the maximum increment in tensile strength (85.6%) that was significant (p<0.001)compared to negative and untreated controls. Animals treated with 5% w/wointment, furthermore, showed a significantly (p < 0.05) higher percentage of tensile strength than nitrofurazone treated ones. Moreover, the hydroalcoholic extract of the plant showed a noticeable free radical scavenging property. The result of the present study upholds the folkloric use of V. sinaiticum in the treatment of wounds.

Keywords: wound healing, antioxidant, excision wound model, incision wound model, verbascum sinaiticum

Procedia PDF Downloads 89

Authors: Sylwia K. Naliwajko, Renata Markiewicz-Zukowska, Justyna Moskwa, Krystyna Gromkowska-Kepka, Konrad Mielcarek, Patryk Nowakowski, Katarzyna Socha, Anna Puscion-Jakubik, Maria H. Borawska

Abstract:

Glioblastoma (grade IV WHO) is a rapidly progressive brain tumor with very high morbidity and mortality. The vast malignant gliomas are not curable despite the therapy (surgical, radiotherapy, chemotherapy) and patients seek alternative or complementary treatments. Patients often use cannabidiol (CBD) oil as an alternative therapy of glioblastoma. CBD is one of the cannabinoids, an active component of Cannabis sativa. THC (Δ9-tetrahydrocannabinol) can be addictive, and in many countries CBD oil without THC ( < 0,2%) is available. Propolis produced by bees from the resin collected from trees has antiglioma properties in vitro and can be used as a supplement in complementary therapy of gliomas. The aim of this study was to examine the influence of extract from CBD oil in combination with propolis extract on two glioblastoma cell lines. The MTT (Thiazolyl Blue Tetrazolium Bromide) test was used to determine the influence of CBD oil extract and polish propolis extract (PPE) on the viability of glioblastoma cell lines – U87MG and LN18. The cells were incubated (24, 48 and 72 h) with CBD oil extract and PPE. CBD extract was used in concentration 1, 1.5 and 3 µM and PPE in 30 µg/mL. The data were presented compared to the control. The statistical analysis was performed using Statistica v. 13.0 software. CBD oil extract in concentrations 1, 1.5 and 3 µM did not inhibit the viability of U87MG and LN18 cells (viability more than 90% cells compared to the control). There was no dose-response viability, and IC50 value was not recognized. PPE in the concentration of 30 µg/mL time-dependently inhibited the viability of U87MG and LN18 cell line (after 48 h the viability as a percent of the control was 59,7±6% and 57,8±7%, respectively). In a combination of CBD with PPE, the viability of the treated cells was similar to PPE used alone (58,2±7% and 56,5±9%, respectively). CBD oil extract did not show anti-glioma activity and in combination with PPE did not change the activity of PPE.

Keywords: anticancer, cannabidiol, cell line, glioblastoma

Procedia PDF Downloads 246

Authors: Olfat Shaker, Miriam Wadie, Reham Ali, Ayman Yosry

Abstract:

Colorectal cancer (CRC) is a major cause of mortality and morbidity and accounts for over 9% of cancer incidence worldwide. Silent information regulator 2 homolog 1 (SIRT1) gene is located in the nucleus and exert its effects via modulation of histone and non-histone targets. They function in the cell via histone deacetylase (HDAC) and/or adenosine diphosphate ribosyl transferase (ADPRT) enzymatic activity. The aim of this work was to study the relationship between SIRT1 polymorphism and its protein level in colorectal cancer patients in comparison to control cases. This study includes 2 groups: thirty healthy subjects (control group) & one hundred CRC patients. All subjects were subjected to: SIRT-1 serum level was measured by ELISA and gene polymorphisms of rs12778366, rs375891 and rs3740051 were detected by real time PCR. For CRC patients clinical data were collected (size, site of tumor as well as its grading, obesity) CRC patients showed high significant increase in the mean level of serum SIRT-1 compared to control group (P<0.001). Mean serum level of SIRT-1 showed high significant increase in patients with tumor size ≥5 compared to the size < 5 cm (P<0.05). In CRC patients, percentage of T allele of rs12778366 was significantly lower than controls, CC genotype and C allele C of rs 375891 were significantly higher than control group. In CRC patients, the CC genotype of rs12778366, was 75% in rectosigmoid and 25% in cecum & ascending colon. According to tumor size, the percentage of CC genotype was 87.5% in tumor size ≥5 cm. Conclusion: serum level of SIRT-1 and T allele, C allele of rs12778366 and rs 375891 respectively can be used as diagnostic markers for CRC patients.

Keywords: CRC, SIRT1, polymorphisms, ELISA

Procedia PDF Downloads 218

Authors: Awais Naeem, Osama Shakeel, Aamir Ali Syed, Shahid Khattak

Abstract:

Introduction: Laparoscopic right hemicolectomy is an advanced cancer surgery in today's era. The aim of this study was to evaluate the surgical and initial oncological outcomes after curative, laparoscopic resection of right sided colonic tumors. Also to compare our results with those of previous randomized trials. Methods And Procedures: We retrospectively analyzed the medical record files of all the patients who presented to our hospital with the diagnosis of right sided colon carcinoma from January 2012 to December 2017 and underwent laparoscopic right hemicolectomy. Demographics, operative findings and histopathological reports were all recorded on a preformed data sheet. All the analysis was performed on SPSS 20. Results: Total of 48 patients were included. There were 37 male and 11 female patients with mean age of 49.7 (range from 25 – 82). Mean hospital stay was 8.25 ± 3.17 days. Blood loss was 80mls and operative mean time was 240 minutes. Eighteen patients had extended right hemicolectomy. Median length of the specimen retrieved was 31cm (range, 14-59cm). Mean size of tumor was 6.44cm + 2.53. Total number of lymph nodes removed was 20.5 + 8.3. All had R0 resection. Post-operatively 2 patients had pelvic collection and there was no 30 day mortality. In 33 patients there was T3 disease, 5 had T2 and 10 had T4 disease. There was distant recurrence in 4 patients with peritoneal metastasis in 3 and liver metastasis in 1 patient. Forty-six patients are still alive and 44 are disease free. The mean follow-up period was 25.31 (12 to 60) months. Conclusion: Our early experience with Laparascopic Right hemicolectomy as a safe and oncologically feasible surgical option. We attained comparable surgical results with curative intent.

Keywords: right hemicolectomy, right sided colonic tumors, laparoscopic, curative intent

Procedia PDF Downloads 128

Authors: Niang Mamadou Sileye

Abstract:

The study turns on the use of the phytase in aquaculture, its zootechnical interests and the possibilities of incorporation in the feed. The goal is to reduce the waste in phosphorus linked to the feeding of fishes, without any loss of zootechnical performances and with a decrease of feed costs. We have studied the literature in order to evaluate the raw materials (total phosphorus, phytate and available phosphorus) used by a company to manufacture feed for rainbow trout; to determine the phosphorus requirements for aquaculture species; to determine the requirements of phosphorus for aquaculture species, to determine the sings of lack of phosphorus for fishes; to study the antagonism between the phosphorus and the calcium and to study also the different forms of waste for the rainbow trout. The results found in the bibliography enable us test several Hypothesis of feed formulation for rainbow trout with different raw materials. This simulation and the calculation for wastes allowed to validate two formulation of feed: a control feed (0.5% of monocalcique phosphate) and a trial feed (supplementation with 0.002% of phytase Ronozyme PL and without inorganic phosphate). The feeds have been produced and sent to a experimental structure (agricultural college of Brehoulou).The result of the formulation give a decrease of the phosphorus waste of 28% for the trial feed compared to the feed. The supplementation enables a gain of 2.3 euro per ton. The partial results of the current test show no significant difference yet for the zootechnical parameters (growth rate, mortality, weight gain and obvious conversion rate) between control feed and the trial one. The waste measures do not show either significant difference between the control feed and the trial one, but however, the average difference would to decrease the wastes of 35.6% thanks to the use of phytase.

Keywords: phosphorus, phytic acid, phytase, need, digestibility, formulation, food, waste, rainbow trout

Procedia PDF Downloads 98

Authors: Nizar Ghali, Bernard Fortin, Guy Lacroix

Abstract:

In Quebec, colonoscopies volumes have continued to rise in recent years in the absence of effective monitoring mechanism for the appropriateness and the quality of these exams. In 2010, November, Quebec Government introduced the colorectal cancer-screening program in the objective to control for volume and cost imperfection. This program is based on clinical standards and was initiated for first group of institutions. One year later, Government adds financial incentives for participants institutions. In this analysis, we want to assess for the causal effect of the two components of this program: clinical pathways and financial incentives. Especially we assess for the reform effect on healthcare quality and population health in the context that medical remuneration is not directly dependent on this additional funding offered by the program. We have data on admissions episodes and deaths for 8 years. We use multistate model analog to difference in difference approach to estimate reform effect on the transition probability between different states for each patient. Our results show that the reform reduced length of stay without deterioration in hospital mortality or readmission rate. In the other hand, the program contributed to decrease the hospitalization rate and a less invasive treatment approach for colorectal surgeries. This is a sign of healthcare quality and population health improvement. We demonstrate in this analysis that physicians’ behavior can be affected by both clinical standards and financial incentives even if offered to facilities.

Keywords: multi-state and multi-episode transition model, healthcare quality, length of stay, transition probability, difference in difference

Procedia PDF Downloads 214

Authors: Pui Hong Chung, Wing Chi Ho, Jun Li, Cyrus Leung, Ek Yeoh

Abstract:

Background: Cigarette smoking is associated with poor tuberculosis (TB) outcomes in terms of progression of active TB, relapse of TB and TB-related mortality, but the association with latent tuberculosis infection (LTBI) is unclear. The systematic review conducted aimed at studying the association between active smoking and LTBI, and likelihood of dose-response relationship. Methods: Two independent reviewers searched three electronic databases comprising PudMed, Medline by EBSCOHOST, ExcerptaMedica Database (EMBASE), from inception up to 31st Dec 2015 for studies reporting data on current smoking and the LTBI with tuberculin skin test (TST) or interferon-γ release assays (IGRAs) results, comparing the odds ratios (ORs) of outcome measure of TST or IGRAs among current smokers with 95% confidence intervals (CI). Results: Seven studies were identified, including six cross-sectional studies and one longitudinal cohort study. The outcome measures from three studies were in TST, three studies in IGRAs and one for both tests. For TST, OR ranging from 1.39 to 3.40 (95% CI) with all studies shown positive association between cigarette smoking and LTBI. For IGRAs, OR ranging from 0.47 to 1.89 (95% CI) with one study shown the negative association that might be related to impaired interferon-gamma production in immunosuppressive persons. One identified study demonstrated positive dose-response relationship in TST result. Conclusions: Cigarette smoking is likely to be a risk factor of LTBI. There is the important implication for TB and tobacco control program to halt TB by empowering public health policy. Further study is also needed to provide more evidence of the dose-response model/relationship.

Keywords: latent tuberculosis infection, systematic review, active smoking, model

Procedia PDF Downloads 256

Authors: Kamel Abd Elaziz Mohamed

Abstract:

Introduction: Drug related problems (DRPs) are of major concern, affecting patients of both sex. They impose considerable economic burden on the society and the health-care systems. Aim of the work: The aim of this work was to identify and categorize drug-related problems in adult intensive care unit. Patients and methods: The study was a prospective, observational study as eighty six patients were included. They were consecutively admitted to ICU through the emergency room or transferred from the general ward due to DRPs. Parameters included in the study as length of stay in ICU, need for cardiovascular support or mechanical ventilation, dialysis, as well as APACHE II score were recorded. Results: Drug related problems represent 3.6% of the total ICU admission. The median (range) of APACHE II score for 86 patients included in the study was 17 (10-23), and length of ICU stay was 2.4 (1.5-4.2) days. In 45 patients (52%), DRP was drug over dose (group 1), while other DRP was present in the other 41 patients (48%, group 11). Patients in group 1 were older (39 years versus 32 years in group 11), with significant impaired renal function. The need of inotropic drugs and mechanical ventilation as well as the length of stay (LOS) in ICU was significantly higher in group 1. There were no significant difference in GCS between both groups, however APACHE II score was significantly higher in group 1. Only four patients (4.6%) were admitted by suicidal attempt as well as three patients (3.4%) due to trauma drug-related admissions, all were in (group 1). Nineteen percent of the patients had drug related problem due to hypoglycaemic medication followed by tranquilizer (15%). Adverse drug effect followed by failure to receive medication were the most causes of drug problem in (group11).The total mortality rate was 4.6%, all of them were eventually non preventable. Conclusion: The critically ill patients admitted due to drug related problems represented a small proportion (3.6%) of admissions to the ICU. Hypoglycaemic medication was one of the most common causes of admission by drug related problems.

Keywords: drug related problems, ICU, cost, safety

Procedia PDF Downloads 333

Authors: Andrea Bertocchi, Alessio Barnaba Di Fonzo, Davide Talarico, Simone Rivaroli, Jeff Konin

Abstract:

The patient is a 89 years old male (180cm/85kg) retired notary former golfer with no past medical history. He describes a progressive ideomotor slowdown for 14 months. The disorder is characterized by short-term memory deficits and, for some months, also by unstable walking with a broad base with skidding and risk of falling at directional changes and urinary urgency. There were also episodes of aggression towards his wife and staff. At the time, the patient takes no prescribed medications. He has difficulty eating, dressing, and some problems with personal hygiene. In the initial visit, the patient was alert, cooperating, and performed simple tasks; however, he has a hearing impairment, slowed spontaneous speech, and amnestic deficit to the short story. Ideomotor apraxia is not present. He scored 20 points in the MMSE. From a motor function, he has deficits using Medical Research Council (MRC) 3-/5 in bilateral lower limbs and requires maximum assistance from sit to stand with existing premature fatigue. He’s unable to walk for about 1 month. Tremors and hypertonia are absent. BERG was unable to be administered, and BARTHEL was obtained 45/100. An Amyloid Angiopathy is suspected and then confirmed at the neurological examination. Therehabilitation objectives were the recovery of mobility and reinforcement of the UE/LE, especially legs, for recovery of standing and walking. The cognitive aspect was also an essential factor for the patient's recovery. The literature doesn’t demonstrate any particular studies regarding motor and cognitive rehabilitation on this pathology. Failing to manage his attention on exercise and tending to be disinterested and falling asleep constantly, we used golf-specific gestures to stimulate his mind to work and get results because the patient has memory recall of golf related movement. We worked for 4 months with a frequency of 3 sessions per week. Every session lasted for 45 minutes. After 4 months of work, the patient walked independently with the use of a stick for about 120 meters without stopping. MRC 4/5 AI bilaterally andpostural steps performed independently with supervision. BERG 36/56. BARTHEL 65/100. 6 Minutes Walking Test (6MWT), at the beginning, it wasn’t measurable, now, he performs 151,5m with Numeric Rating Scale 4 at the beginning and 7 at the end. Cognitively, he no longer has episodes of aggression, although the short-term memory and concentration deficit remains. Amyloid Angiopathy is a mix of motor and cognitive disorder. It is worth the thought that cerebral amyloid angiopathy manifests with functional deficits due to strokes and bleedings and, as such, has an important rehabilitation indication, as classical stroke is not associated with amyloidosis. Exploring the motor patterns learned at a young age and remained in the implicit and explicit memory of the patient allowed us to set up effective work and to obtain significant results in the short-middle term. Surely many studies will still be done regarding this pathology and its rehabilitation, but the importance of the cognitive sphere applied to the motor sphere could represent an important starting point.

Keywords: amyloid angiopathy, cognitive rehabilitation, golf, motor disorder

Procedia PDF Downloads 137

Authors: Brindha Senthil Kumar, Payel Chakraborty, Senthil Kumar Nachimuthu, Arindam Maitra, Prem Nath

Abstract:

Gastric cancer is predominantly caused by demographic and diet factors as compared to other cancer types. The aim of the study is to predict Early Gastric Cancer (ECG) from diet and lifestyle factors using supervised machine learning algorithms. For this study, 160 healthy individual and 80 cases were selected who had been followed for 3 years (2016-2019), at Civil Hospital, Aizawl, Mizoram. A dataset containing 11 features that are core risk factors for the gastric cancer were extracted. Supervised machine algorithms: Logistic Regression, Naive Bayes, Support Vector Machine (SVM), Multilayer perceptron, and Random Forest were used to analyze the dataset using Python Jupyter Notebook Version 3. The obtained classified results had been evaluated using metrics parameters: minimum_false_positives, brier_score, accuracy, precision, recall, F1_score, and Receiver Operating Characteristics (ROC) curve. Data analysis results showed Naive Bayes - 88, 0.11; Random Forest - 83, 0.16; SVM - 77, 0.22; Logistic Regression - 75, 0.25 and Multilayer perceptron - 72, 0.27 with respect to accuracy and brier_score in percent. Naive Bayes algorithm out performs with very low false positive rates as well as brier_score and good accuracy. Naive Bayes algorithm classification results in predicting ECG showed very satisfactory results using only diet cum lifestyle factors which will be very helpful for the physicians to educate the patients and public, thereby mortality of gastric cancer can be reduced/avoided with this knowledge mining work.

Keywords: Early Gastric cancer, Machine Learning, Diet, Lifestyle Characteristics

Procedia PDF Downloads 161

Authors: Bahar Tunctan, Sefika Pinar Kucukkavruk, Meryem Temiz-Resitoglu, Demet Sinem Guden, Ayse Nihal Sari, Seyhan Sahan-Firat, Mahesh P. Paudyal, John R. Falck, Kafait U. Malik

Abstract:

We hypothesized that 20-hydroxyeicosatetraenoic acid (20-HETE) mimetics such as N-(20-hydroxyeicosa-5[Z],14[Z]-dienoyl)glycine (5,14-HEDGE) may be beneficial for preventing mortality due to inflammation induced by lipopolysaccharide (LPS). This study aims to assess the effect of 5,14-HEDGE on the LPS-induced changes in nucleotide binding domain and leucine-rich repeat protein 3 (NLRP3)/apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC)/pro-caspase-1 inflammasome. Rats were injected with saline (4 ml/kg) or LPS (10 mg/kg) at time 0. Blood pressure and heart rate were measured using a tail-cuff device. 5,14-HEDGE (30 mg/kg) was administered to rats 1 h after injection of saline or LPS. The rats were sacrificed 4 h after saline or LPS injection and kidney, heart, thoracic aorta, and superior mesenteric artery were isolated for measurement of caspase-1/11 p20, NLRP3, ASC, and β-actin proteins as well as interleukin-1β (IL-1β) levels. Blood pressure decreased by 33 mmHg and heart rate increased by 63 bpm in the LPS-treated rats. In the LPS-treated rats, tissue protein expression of caspase-1/11 p20, NLRP3, and ASC in addition to IL-1β levels were increased. 5,14-HEDGE prevented the LPS-induced changes. Our findings suggest that inhibition of renal, cardiac, and vascular formation/activity of NLRP3/ASC/pro-caspase-1 inflammasome involved in the protective effect of 5,14-HEDGE on LPS-induced septic shock in rats. This work was financially supported by the Mersin University (2015-AP3-1343) and USPHS NIH (PO1 HL034300).

Keywords: 5, 14-HEDGE, lipopolysaccharide, NLRP3, inflammasome, septic shock

Procedia PDF Downloads 295

Authors: Krishna Gopal Lageju

Abstract:

On 25th April 2015, a 7.6 magnitude earthquake struck Gorkha district of Nepal, which resulted over 8,790 deaths and 22,300 injuries. In addition, almost one-third of the country’s healthcare service has been disrupted. A total of 1,211 health facilities became non-operational, due to 446 completely and other 765 partially damaged. Nearly 84 percent (375 out of 446) of the completely damaged health facilities are in the 14 most affected districts. As a result, the ability of health facilities to respond to health care needs has been harshly affected. In addition, 18 health workers lost their lives and 75 are injured, which added further challenges in the delivery of health services. Thus, to address the immediate health needs in the most devastated areas, Nepal Red Cross Society (NRCS) in coordination with IFRC and Nepal Government, 8 Field hospitals established with surgical capacities, where around 492 international Emergency Response Units (ERUs) Members are mobilized for 3 months period. More than 54,000 patients have been treated in the Red Cross operated field hospitals. Trauma cases accounted 9,180 (17%) of the total patients off which 1,285 (14%) are major surgical cases. Most of the case loads 44,830 (83%) are outpatients and 9,180 patients got inpatients service. Similarly, 112 births have been performed in the field hospitals. Inpatient mortality rate remained 1.5% (21 deaths), many of them are presented with critical injuries or illnesses. No outbreak has been seen during the ERU operation. Deployment of ERUs together with national health workers are very important to address the immediate health needs of the affected communities. This will ease for transition and handover of emergency service and equipments to local provider. Likewise, capacity building of local staff as on the job training on various clinical teachings would be another important issue to look at before phasing out such services.

Keywords: trauma management, critical injuries, earthquake, health

Procedia PDF Downloads 241

Authors: Mei Chen, Yingping Hou, Michelle Hao, Soheil Aghamohammadzadeh, Esteban Terzo, Roger Clark, Vijay Modur

Abstract:

Background: Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a genetic skin condition characterized by skin tearing and unremitting blistering upon minimal trauma. Repeated blistering, fibrosis, and scarring lead to aggressive squamous cell carcinoma later in life. RDEB is caused by mutations in the COL7A1 gene encoding collagen type VII (C7), the major component of anchoring fibrils mediating epidermis-dermis adherence. Nonsense mutations in the COL7A1 gene of a subset of RDEB patients leads to premature termination codons (PTC). Similarly, most Junctional Epidermolysis Bullosa (JEB) cases are caused by nonsense mutations in the LAMB3 gene encoding the β3 subunit of laminin 332. Currently, there is an unmet need for the treatment of RDEB and JEB. Zikani Therapeutics has discovered an array of macrocyclic compounds with ring structures similar to macrolide antibiotics that can facilitate readthrough activity of nonsense mutations in the COL7A1 and LAMB3 genes by acting as Ribosome Modulating Agents (RMAs). The medicinal chemistry synthetic advancements of these macrocyclic compounds have allowed targeting the human ribosome while preserving the structural elements responsible for the safety and pharmacokinetic profile of clinically used macrolide antibiotics. Methods: C7 expression was used as a measure of readthrough activity by immunoblot assays in two primary human fibroblasts from RDEB patients (R578X/R578X and R163X/R1683X-COL7A1). Similarly, immunoblot assays in C325X/c.629-12T > A-LAMB3 keratinocytes were used to measure readthrough activity for JEB. The relative readthrough activity of each compound was measured relative to Gentamicin. An imaging-based fibroblast migration assay was used as an assessment of C7 functionality in RDEB-fibroblasts over 16-20 hrs. The incubation period for the above experiments was 48 hrs for RDEB fibroblasts and 72 hours for JEB keratinocytes. Results: 9 RMAs demonstrated increased protein expression in both patient RDEB fibroblasts. The highest readthrough activity at tested concentrations without cytotoxicities increased protein expression up to 179% of Gentamicin (400 µg/ml), with favored readthrough activity in R163X/R1683X-COL7A1 fibroblasts. Concurrent with protein expression, fibroblast hypermotility phenotype observed in RDEB was rescued by reducing motility by ~35% to WT levels (the same level as 690 µM Gentamicin treated cells). Laminin β3 expression was also shown to be increased by 6 RMAs in keratinocytes to 33-83% of (400 µg/ml) Gentamicin. Conclusions: To date, 9 RMAs have been identified that enhance the expression of functional C7 in a mutation-dependent manner in two different RDEB patient fibroblast backgrounds (R578X/R578X and R163X/R1683X-COL7A1). A further 6 RMAs have been identified that enhance the readthrough of C325X-LAMB3 in JEB patient keratinocytes. Based on the clinical trial conducted by us with topical gentamycin in 2017, Zikani’s RMAs achieve clinically significant levels of read-through for the treatment of recessive dystrophic and Junctional Epidermolysis Bullosa.

Keywords: epidermolysis bullosa, nonsense mutation, readthrough, ribosome modulation

Procedia PDF Downloads 98

Authors: Mamdouh Milad Adly Morkos

Abstract:

Despite having the greatest rates of mortality and morbidity in the world, low- and middle-income (LMIC) nations trail high-income nations in terms of the number of clinical trials, the number of qualified researchers, and the amount of research information specific to their people. Health inequities and the use of precision medicine may be hampered by a lack of local genomic data, clinical pharmacology and pharmacometrics competence, and training opportunities. These issues can be solved by carrying out health care infrastructure development, which includes data gathering and well-designed clinical pharmacology training in LMICs. It will be advantageous if there is international cooperation focused at enhancing education and infrastructure and promoting locally motivated clinical trials and research. This paper outlines various instances where clinical pharmacology knowledge could be put to use, including pharmacogenomic opportunities that could lead to better clinical guideline recommendations. Examples of how clinical pharmacology training can be successfully implemented in LMICs are also provided, including clinical pharmacology and pharmacometrics training programmes in Africa and a Tanzanian researcher's personal experience while on a training sabbatical in the United States. These training initiatives will profit from advocacy for clinical pharmacologists' employment prospects and career development pathways, which are gradually becoming acknowledged and established in LMICs. The advancement of training and research infrastructure to increase clinical pharmacologists' knowledge in LMICs would be extremely beneficial because they have a significant role to play in global health

Keywords: electromagnetic solar system, nano-material, nano pharmacology, pharmacovigilance, quantum theoryclinical simulation, education, pharmacology, simulation, virtual learning low- and middle-income, clinical pharmacology, pharmacometrics, career development pathways

Procedia PDF Downloads 81

Authors: B. Kenny

Abstract:

The complications associated with transfusions are well documented, with the serious hazards of transfusion (SHOT) reporting system continuing to report deaths and serious morbidity due to the transfusion of allogenic blood. Many different sources including the TRICC trial, NHMRC and Cochrane recommending similar transfusion triggers/guidelines. Recent studies found the rate of infection (deep infection, wound infection, chest infection, urinary tract infection, and others) were purely a dose response relationship, increasing the Relative Risk by 3.44. It was also noted that each transfused patient stayed in hospital for one additional day. We hypothesise that providing an approved/standardised, guideline with a graphical summary of decision pathways for anaemic patients will reduce unnecessary transfusions. We retrospectively assessed patients undergoing primary knee or hip arthroplasties over a 4 year period, 1459 patients. Of these, 339 (23.24%) patients received allogenic blood transfusions and 858 units of blood were transfused, 9.14% of patients transfused had haemoglobin levels above 100 g/L, 7.67% of patients were transfused without knowing the haemoglobin level, 24 hours prior to transfusion initiation and 4.5% had possible transfusion reactions. Overall, 17% of allogenic transfusions topatients admitted to the Orthopaedic department within a 4 year period were outside NHMRC and Cochrane guidelines/recommendations. If our transfusion frequency is compared with that of other authors/hospitals, transfusion rates are consistently being high. We subsequently implemented a simple guideline for transfusion initiation. This guideline was then assessed. We found the transfusion rate post transfusion implementation to be significantly lower, without increase in patient morbidity or mortalitiy, p <0.001). Transfusion rates and patient outcome can be optimized by a simple graphical aid for decision making.

Keywords: transfusion, morbidity, mortality, neck of femur, fracture, arthroplasty, rehabilitation

Procedia PDF Downloads 242