Introduction to Medical Genetics

Medical genetics is the key to modern biochemistry and underlying mechanisms of many diseases

An exploration of the organisational excellence architecture required to support an award-winning business excellence journey : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy at Massey University, Palmerston North, New Zealand

The Business Excellence (BE) approach and its underlying philosophy are now established means of enhancing organisations’ performance. BE is institutionalised through BE models to achieve excellence in strategies; business practices; and, stakeholder-related performance results. In turn, these activities contribute to the organisation becoming best in their respective market. While numerous studies have examined different aspects of BE, there remains a lack of research on the actual BE implementation required to guide researchers, consultants and practitioners. The absence of a unified framework has led to inconsistent practices across organisations, of which some has resulted in results less than expected. To bridge this gap, this research introduces the novel concept of Organisational Excellence Architecture (OEA). OEA refers to the formal support structure, resources, processes and assessment tools used to assist the implementation of BE within an organisation. This research explores the OEA supporting award-winning BE maturity. A sequential mixed methods approach was adopted that resulted in participation from 50 organisations across 17 countries. Contributions were acquired by way of an online survey, followed by optional structured interviews to identify BE their implementation approaches and best practices. The empirical data guided the iterative development of the OEA model established from the literature and the subsequent refinement of the final OEA model. This model is supported with an OEA design toolkit. The toolkit includes OEA design tool guidelines; an OEA design assessment tool; best practices examples; and, four research articles. This study makes a contribution to the BE literature, providing detailed, updated research on BE implementation approaches and best practices. It offers practical insights for BE practitioners and organisations, enhancing the understanding of effective BE implementation strategies. Future research is now invited to validate and refine the OEA model and the OEA design toolkit to improve their applicability and effectiveness across diverse organisational contexts

Informativeness of St14 VNTR Polymorphic Marker in the Carrier Detection of Hemophilia A

Hemophilia A is the most common hereditary severe disorder of blood clotting. In families affected with hemophilia, genetic analysis provides opportunities to prevent recurrence of the disease. This study establishes a diagnostic strategy for carrier-ship determination in Pakistani population using an extragenic polymorphic marker for the first time. The analysis of St14 VNTR (DXS52) was carried out by polymerase chain reaction (PCR), in order to determine its informativeness in terms of heterozygosity in Pakistani population. This may be a milestone for further analysis of other polymorphic markers for carrier detection and prenatal diagnosis of hemophilia. Seventy eight blood samples (Hemophiliac = 23, Normal = 55) from 15 families were analyzed for determining informativeness of St14 VNTR in carrier detection of hemophilia A. A total of nine alleles (2400, 2100, 1750, 1690, 1630, 1570, 1390, 1300, 1220 bp) was detected in the pool of subjects. 19 out of 40 females were found to be carriers with respect to the St14 VNTR polymorphic marker. The marker was informative in 73.33% of families. The expected heterozygosity rate of the St14 VNTR was 0.86 while the observed heterozygosity was 0.7. This shows that St14 VNTR is 70% informative in our population, allowing it to be a useful marker in carrier detection, as informativeness is the direct reflection of heterozygosity of a polymorphic marker

Evaluation of tranexamic acid in reducing blood loss and transfusions in total knee replacement

Background: Total knee replacement (TKR) is associated with substantial blood loss and thus the need for blood transfusions. Risks and costs of allogenic blood transfusions requires strategies to reduce blood loss in surgery. The objective of this study was to assess the efficacy of tranexamic acid treatment in reducing blood loss and blood transfusion requirements during TKR.Methods: A randomized controlled trial was conducted on 60 patients who were operated for unilateral TKR from January 2016 to January 2019 in Shadan Institute of Medical Sciences. 30 patients were in each control and study groups. In study group 12 mg/kg bolus of tranexamic acid was given as a slow IV dose, 40 minutes before deflation of tourniquet followed by 1.2 mg/kg/hr infusion for 12 hours with standard treatment of hospital and compared to the control group. Later blood loss was compared both intra and post operatively. Fall in haemoglobin after surgery was also compared.Results: Total blood loss in tranexamic acid group was 543.3±184.85 ml (control group 685.83±176.74 ml) which is statistically significant (p<0.05). Blood loss was markedly decreased in tranexamic acid group (379.16±174 ml in tranexamic acid vs. 513.33±143.89 ml in control group) statistically significant (p<0.05).Conclusions: Tranexamic acid is an effective strategy to reduce blood loss in patients undergoing total knee replacement and thus minimizing the need for blood transfusions

Molecular analysis of the promoter and the core promoter region Of the smn2 gene in circumscribing the clinical severity of sma

Spinal muscular atrophy (SMA) is a neurodegenerative disorder caused by the absence of the full length SMN protein (FL-SMN) as a result of mutation or deletion of SMN\ gene. The isoform to this gene, SMN2, with mutation in 1 base pair, encodes for 10% of FL-SMN protein and is reported to decrease the severity of the disease when there is an increase gene dosage. There are 3 clinical types of SMA; type I, type II and type III. Type I SMA is the most severe type and only a small amount of FL-SMN protein is present in these individuals. In this study it was hypothesized that the variation in the DNA sequence in the promoter region of the SMN2 gene could be the possible cause of difference in clinical severity of SMA. To verify this hypothesis, a total of ten (10) SMA patients from different clinical types were selected from the retrospective pool data of the SMA patients and their DNA was extracted. The promoter regions of the SACV2 gene in these patients were screened for the presence of any variation, firstly within the proximal promoter region (Pro) which also contains a reported CR.E-II element followed by the screening of the entire promoter region. The screening of the entire promoter was performed in two steps. Firstly, the regions within the promoter with computational cis acting elements were identified (using Cister analysis) and then the DNA sequencing was performed using specific designed primers. Secondly, the regions other than cis acting elements were screened for the presence of any variations. The bioinformatics analysis also revealed the probability for crucial transcriptional factor bindings sites, novel TSS at -557 bp and a TATA box at -411 bp within the 15 ORFs and 24 nested ORFs. The core promoter region of the SMN2 gene needs to be identified to study the diverse functional integrity of this region. For this purpose, the computational promoter prediction and core promoter prediction analysis was performed and the results of this analysis along with the previous reported literature were used to propose a model of the core promoter region of the SMN2 gene. To analyze this model biochemically, the entire Pro region of 720 bp was divided into five regions (Pro 720, Pro 500, Pro 400, Pro 200 and Pro 100). These five regions were PCR amplified and were cloned into pTOPO-2.1 e cloning vector. After confirming the insert and the vector backbone by PCR, restriction analysis and DNA sequencing, the Pro regions were subcloned into pGL4.74 reporter vector by high throughput directional cloning using EcoRI and HindWl restriction sites to be transfected directly into HeLa cell lines. Before the transfection the optimization of the concentration of the test vector pGL4.74 and the control vector pGL4.10 was performed beside the optimum concentration of test to control vectors for the co-transfection. The transfected HeLa cell lines were subjected to lysis followed by the dual luciferase assay. After the normalization of data of the luciferase assay, it was found that the fold change in the mean percent activity of luciferase (from 1.03 to 2.71) between Pro constructs highly suggested the role of newly identified computational TSS (-557 bp) in TATA (-411 bp) specific CREB induced expression of downstream reporter gene through structural and functional role of CRE-II element. Since, there was no variation identified in the promoter region of the SMN2 gene in the SMA patients from different clinical severities, it showed that the promoter region of the SMN2 gene has no role in circumscribing the clinical severity of SMA

Conservative treatment of spinal tuberculosis and its outcome: an observational study

Background: Spinal tuberculosis or Pott’s spine occurs in about 1-2% of patients with tuberculosis and accounts for 40-50% of musculoskeletal tuberculosis.It is caused due to the infection of the bone by Mycobacterium tuberculosis bacteria with the combination of spread through haematogenous route as well as lymphatic drainage.Methods: This observational study was done for a period of 2 years from Jan 2016 to Jan 2018. The total number of study participants was 51. The functional outcome was assessed using modified McCormick’s scale.Results: Majority of study participants were females accounting for 60.7% compared to males (39.21%). The main complaint of study participants was back pain (39.21%) which was followed by fever in 21.5%. Loss of appetite was the most prominent symptom seen in 15.6%. Thoracolumbar vertebrae were the site of involvement in 37.2%.Conclusions: Patients responded well with anti-tubercular treatment in mild and moderate cases of spinal TB, if there was no gross neurological deficit. Thus it is very important to identify the early symptoms of spinal TB so that timely prompt treatment should be initiated

Comparison of histopathologicalfeatures of Vibrio cholerae O1 El Tor andO139 Bengal infections in rabbit intestinal mucosa

Vibrio cholerae is the causative agent of the infectious disease, cholera. The bacteria adhere to the mucosal membrane and release cholera toxin, leading to watery diarrhea. There are >100 serovars of V. cholerae, but the O1 and O139 serovars are the main causative agents of cholera. The present study aimed to compare the severity of intestinal mucosal infection caused by O1 El Tor and O139 V. cholerae in a rabbit ileal loop model.
The results showed that although the fluid accumulation was similar in the loops inoculated with O1 and O139 V. cholerae, the presence of blood was detected only in the loops inoculated with the O139 serovar. Serosal hemorrhage was confirmed by histopathological examination and the loops inoculated with O139 showed massive destruction of villi and loss of intestinal glands.
The submucosa and muscularis mucosa of the ileum showed the presence of edema with congested blood vessels, while severe hemorrhage was seen in the muscularis propria layer. The loops inoculated with O1 El Tor showed only minimal damage, with intact
intestinal villi and glands. Diffuse colonies of the O139 serovar were seen to have infiltrated deep into the submucosal layer of the intestine. Although the infection caused by the O1 serovar was focal and invasive, it was more superficial than that due to O139, and involved only the villi. These observations were confirmed by immunostaining with O1 and O139 V. cholerae-specific monoclonal antibodies. The peroxidase reaction demonstrated involvement of tissues down to the submucosal layer in O139 V. cholerae infection, while in O1 El Tor infection, the reaction was confined mainly to the villi, and was greatly reduced in the submucosal region. This is the first reported study to clearly demonstrate the histopathological differences between infections caused by the O139 Bengal and O1 El Tor pathogenic serovars of V. cholerae (atif et al., 2009)

Recent facts of eating habits and obesity among adolescent; a case of Pakistan

Background: Obesity is an escalating problem that is reaching to pandemic level. Multiple factors may involve in causing obesity such as improper food pattern of physical activities, social and ecological variables, choice of menu and other biological factors. Conducting to a study to evaluate the primary cause. However, a few studies are conducting to see the impact of eating patterns on health and weight. Methods: University students (n=150, ages 18-24 years) 50% males and 50% females were selected for data collection via questionnaire. The outcomes showed that 70 individuals prefer to eat saturated fats that can lead to accumulation of bad cholesterol. 5% females and 5% males prefer using trans-fat that is even worse. On the other hand, 44 respondents prefer to choose low fat food. Results: About 25% individuals are unaware of nutritional on facts of the products but females are more conscious as compared to the men. 55% individuals eat unconsciously while watching television and consume more than the requirement. 94 individuals got attracted by advertisement tactics of food companies and but to eat them. It is also witnessed that males (32%) consume more carbonated drinks than females (13%). 64 students strongly agreed that supplements lead to obesity. In our sample population 10% obese, 14% were overweight and 47% were of normal weight. Conclusion: The major reason of obesity could be that they are eating out more often. It could be due to the fact they are dependent on high calorie food. There is a lack of vegetables and fruits in their diet. On the other hand, fruits, veggies and whole grains are linked to less gain and even weight loss. Making smart food choices can help you stay slim and healthy.

Validation of Vis-Screen Mobile Application for Easy Vision Test by General Public: A pilot study

Visual impairment and blindness is a serious global concern. Poor awareness and late detection are significant factors contributing to the vast number of visually impaired people worldwide. The ubiquitous use of smartphone devices enables the general public to access various services provided easily. Our Vis-Screen mobile application is developed based on the necessity for early detection of any vision problem to avoid further vision loss. Simple built-in algorithm and user-friendly features of this application suits any laypersons to do vision testing among themselves with only minimal training needed, therefore promoting the importance of healthy vision within the community.Keywords: visual acuity; mobile application; vision screening; blindnesseISSN: 2398-4287 © 2019. The Authors. Published for AMER ABRA cE-Bs by e-International Publishing House, Ltd., UK. This is an open-access article under the CC BYNC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Peer–review under responsibility of AMER (Association of Malaysian Environment-Behaviour Researchers), ABRA (Association of Behavioural Researchers on Asians) and cE-Bs (Centre for Environment-Behaviour Studies), Faculty of Architecture, Planning & Surveying, Universiti Teknologi MARA, Malaysia.DOI: https://doi.org/10.21834/e-bpj.v4i12.189