Complications of laparoscopic cholecystectomy : Addington experience.

Master of Medical Sciences in General Surgery. University of KwaZulu-Natal, Medical School 2014.Background Laparoscopic cholecystectomy is a common surgical procedure performed for complicated gallstones. The timing of cholecystectomy is controversial with a trend toward early cholecystectomy in patients with acute cholecystitis. This study examined the presentation, timing of cholecystectomy and outcomes in a resource constrained environment. Methods A retrospective analysis of laparoscopic cholecystectomies performed from January 2010 to June 2011. The mode of presentation, ERCP (endoscopic retrograde cholangiopancreotogram) rate, and timing of cholecystectomy, complications and morbidity were analysed. Results One hundred and sixty seven patients were evaluated. The mean age was 44(17-78) years and 93% were female and 7% male. There were 44%, 24%, 21% and 14% who presented with biliary colic, pancreatitis, acute cholecystitis and jaundice respectively. They had laparoscopic cholecystectomies after a mean 34(4-90) days and 9(5.4%) patients required conversion to an open cholecystectomy. Complications occurred in 16.2% and bile duct injuries and bile leaks in 0.6% and 1.6% respectively. One patient died. Conclusions Most patients had delayed laparoscopic cholecystectomy. There was no difference in outcomes for the different presentations and the complications are similar to other reports in the literature

Exploiting the molecular basis of oesophageal cancer for targeted therapies and biomarkers for drug response : guiding clinical decision-making

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.The South African Medical Research Council (SAMRC), The National Research Foundation (NRF) and Discovery Health.https://www.mdpi.com/journal/biomedicinesam2023Medical OncologySurger

Genetic drivers of head and neck squamous cell carcinoma : aberrant splicing events, mutational burden, hpv infection and future targets

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.The South African Medical Research Councilhttps://www.mdpi.com/journal/genesam2022Community DentistryMaxillo-Facial and Oral SurgerySurger

MicroRNA and alternative mRNA splicing events in cancer drug response/resistance : potent therapeutic targets

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 30UTR 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 30UTR 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.This research was funded by the South African Medical Research Council (SAMRC).The South African Medical Research Council (SAMRC)https://www.mdpi.com/journal/biomedicinesam2022Maxillo-Facial and Oral SurgeryMedical OncologySurger

AI and precision oncology in clinical cancer genomics : from prevention to targeted cancer therapies-an outcomes based patient care

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.The South African Medical Research Council (SAMRC) and the National Research Foundation (NRF).https://www.elsevier.com/locate/imuhj2023Anatomical PathologyMaxillo-Facial and Oral SurgeryMedical OncologyOtorhinolaryngologyRadiologySurgeryUrolog

Determining times of the school day as a function of the governing body : implications for school management

M.Ed.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 researc

Empowering schools’ stakeholders through effective and efficient partnerships, participation and collaboration to avert schooling decadence

D.Ed. (Educational Psychology)Abstract: 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; and investigate the framework of training-modules for stakeholders’ participatory and collaborative partnership There 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 self- managing work teams, schools might substantially exceed the current levels of success. However, empowering them through effective partnership, participation and..

Genetic Drivers of Head and Neck Squamous Cell Carcinoma: Aberrant Splicing Events, Mutational Burden, HPV Infection and Future Targets

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

Prognostic alternative splicing signatures in esophageal carcinoma

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.http://www.dovepress.com/cancer-management-and-research-journalpm2021Surger