Worldwide, oesophageal cancer is the sixth leading cause of deaths related to cancer and represents a major health concern. Sub-Saharan Africa is one of the regions of the world with the highest ...incidence and mortality rates for oesophageal cancer and most of the cases of oesophageal cancer in this region are oesophageal squamous cell carcinoma (OSCC). The development and progression of OSCC is characterized by genomic changes which can be utilized as diagnostic or prognostic markers. These include changes in the expression of various genes involved in signaling pathways that regulate pathways that regulate processes that are related to the hallmarks of cancer, changes in the tumor mutational burden, changes in alternate splicing and changes in the expression of non-coding RNAs such as miRNA. These genomic changes give rise to characteristic profiles of altered proteins, transcriptomes, spliceosomes and genomes which can be used in clinical applications to monitor specific disease related parameters. Some of these profiles are characteristic of more aggressive forms of cancer or are indicative of treatment resistance or tumors that will be difficult to treat or require more specialized specific treatments. In Sub-Saharan region of Africa there is a high incidence of viral infections such as HPV and HIV, which are both risk factors for OSCC. The genomic changes that occur due to these infections can serve as diagnostic markers for OSCC related to viral infection. Clinically this is an important distinction as it influences treatment as well as disease progression and treatment monitoring practices. This underlines the importance of the characterization of the molecular landscape of OSCC in order to provide the best treatment, care, diagnosis and screening options for the management of OSCC.
Head and neck cancers include cancers that originate from a variety of locations. These include the mouth, nasal cavity, throat, sinuses, and salivary glands. These cancers are the sixth most ...diagnosed cancers worldwide. Due to the tissues they arise from, they are collectively named head and neck squamous cell carcinomas (HNSCC). The most important risk factors for head and neck cancers are infection with human papillomavirus (HPV), tobacco use and alcohol consumption. The genetic basis behind the development and progression of HNSCC includes aberrant non-coding RNA levels. However, one of the most important differences between healthy tissue and HNSCC tissue is changes in the alternative splicing of genes that play a vital role in processes that can be described as the hallmarks of cancer. These changes in the expression profile of alternately spliced mRNA give rise to various protein isoforms. These protein isoforms, alternate methylation of proteins, and changes in the transcription of non-coding RNAs (ncRNA) can be used as diagnostic or prognostic markers and as targets for the development of new therapeutic agents. This review aims to describe changes in alternative splicing and ncRNA patterns that contribute to the development and progression of HNSCC. It will also review the use of the changes in gene expression as biomarkers or as the basis for the development of new therapies.
Alternative splicing (AS) is a method of increasing the number of proteins that the genome is capable of coding for, by altering the pre-mRNA during its maturation. This process provides the ability ...of a broad range of proteins to arise from a single gene. AS events are known to occur in up to 94% of human genes. Cumulative data have shown that aberrant AS functionality is a major factor in human diseases. This review focuses on the contribution made by aberrant AS functionality in the development and progression of esophageal cancer. The changes in the pattern of expression of alternately spliced isoforms in esophageal cancer can be used as diagnostic or prognostic biomarkers. Additionally, these can be used as targets for the development of new treatments for esophageal cancer.
Cancer is a multifaceted disease that involves several molecular mechanisms including changes in gene expression. Two important processes altered in cancer that lead to changes in gene expression ...include altered microRNA (miRNA) expression and aberrant splicing events. MiRNAs are short non-coding RNAs that play a central role in regulating RNA silencing and gene expression. Alternative splicing increases the diversity of the proteome by producing several different spliced mRNAs from a single gene for translation. MiRNA expression and alternative splicing events are rigorously regulated processes. Dysregulation of miRNA and splicing events promote carcinogenesis and drug resistance in cancers including breast, cervical, prostate, colorectal, ovarian and leukemia. Alternative splicing may change the target mRNA 3'UTR binding site. This alteration can affect the produced protein and may ultimately affect the drug affinity of target proteins, eventually leading to drug resistance. Drug resistance can be caused by intrinsic and extrinsic factors. The interplay between miRNA and alternative splicing is largely due to splicing resulting in altered 3'UTR targeted binding of miRNAs. This can result in the altered targeting of these isoforms and altered drug targets and drug resistance. Furthermore, the increasing prevalence of cancer drug resistance poses a substantial challenge in the management of the disease. Henceforth, molecular alterations have become highly attractive drug targets to reverse the aberrant effects of miRNAs and splicing events that promote malignancy and drug resistance. While the miRNA-mRNA splicing interplay in cancer drug resistance remains largely to be elucidated, this review focuses on miRNA and alternative mRNA splicing (AS) events in breast, cervical, prostate, colorectal and ovarian cancer, as well as leukemia, and the role these events play in drug resistance. MiRNA induced cancer drug resistance; alternative mRNA splicing (AS) in cancer drug resistance; the interplay between AS and miRNA in chemoresistance will be discussed. Despite this great potential, the interplay between aberrant splicing events and miRNA is understudied but holds great potential in deciphering miRNA-mediated drug resistance.
Precision medicine is the personalization of medicine to suit a specific group of people or even an individual patient, based on genetic or molecular profiling. This can be done using genomic, ...transcriptomic, epigenomic or proteomic information. Personalized medicine holds great promise, especially in cancer therapy and control, where precision oncology would allow medical practitioners to use this information to optimize the treatment of a patient. Personalized oncology for groups of individuals would also allow for the use of population group specific diagnostic or prognostic biomarkers. Additionally, this information can be used to track the progress of the disease or monitor the response of the patient to treatment. This can be used to establish the molecular basis for drug resistance and allow the targeting of the genes or pathways responsible for drug resistance. Personalized medicine requires the use of large data sets, which must be processed and analysed in order to identify the particular molecular patterns that can inform the decisions required for personalized care. However, the analysis of these large data sets is difficult and time consuming. This is further compounded by the increasing size of these datasets due to technologies such as next generation sequencing (NGS). These difficulties can be met through the use of artificial intelligence (AI) and machine learning (ML). These computational tools use specific neural networks, learning methods, decision making tools and algorithms to construct and improve on models for the analysis of different types of large data sets. These tools can also be used to answer specific questions. Artificial intelligence can also be used to predict the effects of genetic changes on protein structure and therefore function. This review will discuss the current state of the application of AI to omics data, specifically genomic data, and how this is applied to the development of personalized or precision medicine on the treatment of cancer.
Laparoscopic cholecystectomy (LC) is a common surgical procedure performed for symptomatic gallstones. There is a trend towards early cholecystectomy for patients with acute cholecystitis who present ...timeously. Local inflammation has been identified as a risk factor for bile duct injuries. This study sought to assess the outcomes of LC in patients managed within a resource constrained environment where late presentation is common.
We performed a retrospective analysis of laparoscopic cholecystectomy performed from January 2010 to June 2011. The mode of presentation, co-morbidities, timing of cholecystectomy and complications were analysed.
One hundred and sixty seven patients were evaluated. The median age was 43 years with range (17-78) years and 93% were female and 7% male. There were 44%, 23%, 20% and 13% who presented with biliary colic, acute pancreatitis, acute cholecystitis and obstructive jaundice respectively. Nine (5.4%) patients required conversion to an open cholecystectomy. Complications occurred in 16.2% and bile duct injuries and bile leaks in 1.2% and 1.8% respectively. One patient died.
Most patients had a delayed laparoscopic cholecystectomy. There was no difference in outcomes for the different presentations and the complications are similar to other reports.
The primary aim of this research was to investigate the empowerment of school stakeholders through effective and efficient partnerships, participation and collaboration to avert schooling ...decadence.In order to achieve the general aim of the research project, the following specific aims were investigated, namely to: define and analyse stakeholder-partnerships in the school-context;describe the recourse and resources that stakeholders have to forge towards hallmark-schooling;investigate partnerships, participatory and collaborative efforts that beget the credo for competent and efficient schooling; andinvestigate the framework of training-modules for stakeholders’ participatory and collaborative partnershipThere is no denying that great strides have been made in our education system - there is one curriculum for all children and at least 98% of children between the ages of seven and 15 attend school. However, the achievements of learners are still powerfully (and sadly) linked to the circumstances of their birth. Every assessment as well as learner outcomes carried out over the past two decades has shown this to be the case.Over the past 24 years in our democracy we have come to realise that education is not only about numbers or financial resources. The millennium goal, i.e. ‘education for all’, involves much more, including but not limited to, policy intent, planning, implementation and monitoring. The point of departure is for stakeholders to be able to detect the signs of decadence early enough to be able to address them.In this research an attempt has been made to investigate empowering schools’ stakeholders through effective and efficient partnerships, participation and collaboration and the implication thereof on the root-cause of schooling decadence. By empowering schools’ stakeholders to create success through their own selfmanaging work teams, schools might substantially exceed the current levels of success.However, empowering them through effective partnership, participation and collaboration in averting the perceived schooling decadence, does not promise the impossible. We need to see our role as vital partners in terms of building the new society. Stakeholders should have the temerity to try and transform education.Education empowers individuals and communities, and getting education right will have a dramatic impact on households, cities, provinces, and a country as a whole. Partners need to be re-oriented, re-capacitated and re-educated. They need to be shown what make this country great and how to access opportunities. This, however, requires resolve, leadership and commitment.Integrity, a crucial currency in leadership, has to exist from its firmament. Management capacity is also vital. The purpose of schools and schooling ought to be about preparation for life - preparation to cope and engage with life and contribute towards a quality of life which all fellow citizens can enjoy. So we need to develop a new vision, a new imagination about schools and school life.We need to let go of old ways and habits, and make changes which honour human dignity. We need to have a picture of the kind of society we would like to live in. We need to have imagination and be idealistic. The new challenges of altering complex social systems such as schools require new mind-sets and innovative initiatives from all those involved in the education of the young.Schools cannot solve these problems alone, but they need to see themselves as part of the solution. The answers to the challenging questions for education rest not in the ministers and their advisors’ faculties but with school stakeholders. It is not only the key officials and the department who need to be committed to a new plan. A much wider set of social groupings is needed to support both the departmental apparatchiks and political leaders.There are interests’ groups outside of government - especially parents and others in civil society – who have an interest in schooling reform and who can be mobilised in support of good school leadership, good teaching, and improved learner performance. Competence ought to be made a respectable word once again.The school has the unique societal relationship with its own terrain, competence, v nature and task. The latter is determined by the ontic law applicable to it. The school, therefore, has its own unique structure. The task of the school is to see to it that teaching and learning takes place.We need, at the very least, to benchmark our curricula, to ensure that there is effective leadership and management of schools, to attract and keep quality committed educators, to hold principals and teachers accountable, to establish a culture of respect and discipline, and to adequately resource schools. We cannot afford to be bogged down and limited by the horrors of the past.It is time to finally eradicate the legacy of Bantu Education. To do so requires a sober analysis of the economy’s structural unemployment problem as being a hostage to the vicious circle of incompetence, in which under-resourced, largely under-qualified educators work in schools that have deplorable teaching infrastructure and produce poorly equipped learners.The aforesaid (learners) arrive in HEIs poorly prepared and intellectually intimidated and bankrupt only to predictably under-perform and emerge as unemployable members of the workforce. South Africa cannot afford to continue to pat itself on the back about how low its public debt is while its children needlessly fall further behind. It is time to use the national balance sheet wisely by investing in the very best quality asset, i.e. South Africa’s children.It has become a truism to say how important education is for the future of our country. It is no exaggeration to say that the future of our children and of our country depends on education. For many learners in South Africa, education is a lifeline. It is a key to their future. The schools ought to work to unlock that door for them. A good education opens many doors and is the surest path out of poverty.It equips citizens to shape a successful society. We can only hope that those in the corridors of power will prioritize service delivery to the poor over patronage to the elite; accountability over cadre and acolytes’ leniency and, perhaps most importantly, new and innovative ways of raising the quality of the teaching force.As research has shown time and again - no education system can exceed the quality vi of its teachers. Futurists have a tantalising way of describing the future as though being there has little to do with getting there. The future simply arrives full-blown. But it is the succession of days and years between now and then that will determine what life will be like.Improving the quality of South African schooling is vital for the poor as well as the previously disadvantaged majority. Decisions not/made will shape the schools of tomorrow. The latter ought to be the cornerstones of our freedom/s; the guarantees of our future; the cause of our prosperity and power; the bastion of our security; our clarion call; the bright and shining beacons…and the source of our enlightenment!The great country, the great society, the great community is, first of all, the welleducated country, the learned society, and the paragon-community. This nation knows it, proclaims it and even rhapsodize it.
The central theme throughout this research has been to investigate how governing bodies perceive the function(s) bestowed on them by the Schools Act.The introductory chapter entailed the research ...problem, aims and questions guiding the study, its significance and methodology. The intention is to assist SGB's to be pro-active enough in executing the function of determining times of the school day, as the Act prescribes.In chapter two, an in-depth literature survey was undertaken. This literature assisted in providing background as to how the SGB's (school boards / management councils) in other countries (England, Japan and Kenya) are involved in the management of their schools. The situation in South African schools was also compared and contrasted at face value to the situations in these countries.Lastly, this literature also helped in analyzing the research data and an effort was made to expose ways in which time is not effectively used and possible strategies of using time competently were explored.Chapter three of this research highlighted the research method and techniques used to collect data for this research. The research instrument was described regarding the design of the questionnaire and a discussion of time management in schools was also stated, based on the questions that were given to the respondents.In chapter four an analysis and interpretation of the empirical data were discussed. Issues of reliability and validity of data were discussed and hypotheses were also given.Chapter five interprets and analyses the research findings. The responses of participants are analysed for their implications on determining times of the school day. Lastly, this chapter provides the summary, recommendations and concluding remarks of this research
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