31 research outputs found

    Open access guide to audiology and hearing aids for otolaryngologists

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    This is a free textbook and is intended particularly for ENT surgeons practising in the Developing World who are unable to access audiology services or audiology textbooks. The textbook is still in evolution, and chapters will be added as they are completed over the coming months. Clicking on completed chapters (in blue) provides access the PDF documents. There are no copyright restrictions, and colleagues are welcome to use, copy and quote text as they wish

    Open access atlas of otolaryngology, head & neck operative surgery

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    Surgery tools image by docnutpics shared under a CC-BY-NC license.This is a free illustrated operative surgery text, and is intended particularly for those surgeons practising in the Developing World who are unable to afford expensive textbooks. There are no copyright restrictions, and colleagues are welcome to use, copy and quote text as they wish. The textbook is still in evolution, and chapters will be added as they are completed over the coming months. Clicking on completed chapters (in blue)provides access the PDF document

    Professional competence in South Africa

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    Do South African universities provide the required training platforms for otolaryngology specialist training?

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    Background. Concern exists about the quality of specialist training platforms at South African universities and teaching hospitals. Method. We conducted an audit of the quality of training at South African otolaryngology (ENT) training institutions from the perspective of the registrars. Results. Some institutions were deficient in terms of supervision, theatre time, access to teaching aids and research tools, and range of surgery, and do not provide the required training platforms for ENT specialist training. Five out of 8 institutions have produce

    Aminoglycoside-induced hearing loss: South Africans at risk

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    South Africa is currently experiencing a TB epidemic with an estimated incidence of 940/100 000 population/year, and the country has been ranked 4th among the 22 high-burden TB countries worldwide by the World Health Organization (WHO). A potentially devastating threat to TB control is the emergence of multidrug-resistant TB (MDR-TB) and, more recently, extensively drug-resistant TB (XDR-TB), mainly as a result of poor drug adherence by TB patients and incorrect management or treatment regimens by health providers; however, direct transmission of drug-resistant strains also plays an important role. The MDR/XDR-TB strains necessitate prolonged chemotherapy for up to 2 years or more, and the use of more toxic second-line drugs including the aminoglycoside (streptomycin, kanamycin and amikacin) and polypeptide (capreomycin) antibiotics. In South Africa, in accordance with WHO guidelines, streptomycin is used for retreatment of TB while kanamycin, amikacin and capreomycin are used to treat MDR/XDR-TB

    Suprahyoid approach to base-of-tongue squamous cell carcinoma

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    Objective. To evaluate the suprahyoid approach to treatment of squamous cell carcinoma of the base of the tongue at Groote Schuur Hospital between 1999 and 2004. Design and method. Retrospective analysis was done of patients with base-of-tongue squamous cell carcinoma treated using the suprahyoid approach. Results. Seventeen patients underwent treatment for base-of-tongue squamous cell carcinoma utilising the suprahyoid approach. Complete medical records were available for 15 of these patients. The most common presenting symptoms were neck mass (40%) and referred otalgia (33%). Alcohol was a risk factor in more patients (64%) than smoking (47%). Adverse pathological findings were present in less than 50% of patients (involved margins 20%, perineural invasion 40%, vascular invasion 33%). Functional outcome in terms of speech intelligibility was excellent and there were minimal swallowing problems, with most patients using compensatory strategies and dietary modification. There were 2 subsequent deaths (13%) as a result of distant metastasis and a second primary. Conclusion. The suprahyoid approach to treatment of base-of-tongue squamous cell carcinoma provides good exposure, local tumour control and excellent functional outcome

    ENT from afar : opportunities for remote patient assessment, clinical management, teaching and learning

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    Remote communication in ENT has been expanding, spurred by the COVID-19 pandemic. Conferences and teaching have moved online, enabling easier participation and reducing financial and environmental costs. Online multi-disciplinary meetings have recently been instigated in Africa to discuss management of cases in head and neck cancer, or cochlear implantation, expanding access and enhancing patient care. Remote patient consultation has also seen an explosion, but existing literature suggests some caution, particularly because many patients in ENT need an examination to enable definitive diagnosis. Ongoing experience will help us to better understand how remote communication will fit into our future working lives, and also where face-to-face interaction may still be preferable.http://www.wileyonlinelibrary.com/journal/coahj2022Speech-Language Pathology and Audiolog

    Structure–Activity Relationship Studies on Novel Antiviral Agents for Norovirus Infections

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    Human norovirus is the leading cause of acute gastroenteritis worldwide, affecting every year 685 million people. Norovirus outbreaks are associated with very significant economic losses, with an estimated societal cost of 60 billion USD per year. Despite this, no therapeutic options or vaccines are currently available to treat or prevent this infection. An antiviral therapy that can be used as treatment and as a prophylactic measure in the case of outbreaks is urgently needed. We previously described the computer-aided design and synthesis of novel small-molecule agents able to inhibit the replication of human norovirus in cell-based systems. These compounds are non-nucleoside inhibitors of the viral polymerase and are characterized by a terminal para-substituted phenyl group connected to a central phenyl ring by an amide-thioamide linker, and a terminal thiophene ring. Here we describe new modifications of these scaffolds focused on exploring the role of the substituent at the para position of the terminal phenyl ring and on removing the thioamide portion of the amide-thioamide linker, to further explore structure-activity relationships (SARs) and improve antiviral properties. According to three to four-step synthetic routes, we prepared thirty novel compounds, which were then evaluated against the replication of both murine (MNV) and human (HuNoV) norovirus in cells. Derivatives in which the terminal phenyl group has been replaced by an unsubstituted benzoxazole or indole, and the thioamide component of the amide-thioamide linker has been removed, showed promising results in inhibiting HuNoV replication at low micromolar concentrations. Particularly, compound 28 was found to have an EC50 against HuNoV of 0.9 µM. Although the most active novel derivatives were also associated with an increased cytotoxicity in the human cell line, these compounds represent a very promising starting point for the development of new analogues with reduced cytotoxicity and improved selectivity indexes. In addition, the experimental biological data have been used to create an initial 3D quantitative structure-activity relationship model, which could be used to guide the future design of novel potential anti-norovirus agents

    Leveraging large multi-center cohorts of Alzheimer disease endophenotypes to understand the role of Klotho heterozygosity on disease risk

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    Two genetic variants in strong linkage disequilibrium (rs9536314 and rs9527025) in the Klotho (KL) gene, encoding a transmembrane protein, implicated in longevity and associated with brain resilience during normal aging, were recently shown to be associated with Alzheimer disease (AD) risk in cognitively normal participants who are APOE ε4 carriers. Specifically, the participants heterozygous for this variant (KL-SVHET+) showed lower risk of developing AD. Furthermore, a neuroprotective effect of KL-VSHET+ has been suggested against amyloid burden for cognitively normal participants, potentially mediated via the regulation of redox pathways. However, inconsistent associations and a smaller sample size of existing studies pose significant hurdles in drawing definitive conclusions. Here, we performed a well-powered association analysis between KL-VSHET+ and five different AD endophenotypes; brain amyloidosis measured by positron emission tomography (PET) scans (n = 5,541) or cerebrospinal fluid Aβ42 levels (CSF; n = 5,093), as well as biomarkers associated with tau pathology: the CSF Tau (n = 5,127), phosphorylated Tau (pTau181; n = 4,778) and inflammation: CSF soluble triggering receptor expressed on myeloid cells 2 (sTREM2; n = 2,123) levels. Our results found nominally significant associations of KL-VSHET+ status with biomarkers for brain amyloidosis (e.g., CSF Aβ positivity; odds ratio [OR] = 0.67 [95% CI, 0.55–0.78], β = 0.72, p = 0.007) and tau pathology (e.g., biomarker positivity for CSF Tau; OR = 0.39 [95% CI, 0.19–0.77], β = -0.94, p = 0.007, and pTau; OR = 0.50 [95% CI, 0.27–0.96], β = -0.68, p = 0.04) in cognitively normal participants, 60–80 years old, who are APOE e4-carriers. Our work supports previous findings, suggesting that the KL-VSHET+ on an APOE ε4 genotype background may modulate Aβ and tau pathology, thereby lowering the intensity of neurodegeneration and incidence of cognitive decline in older controls susceptible to AD

    A rapid method for detection of five known mutations associated with aminoglycoside-induced deafness

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    <p>Abstract</p> <p>Background</p> <p>South Africa has one of the highest incidences of multidrug-resistant tuberculosis (MDR-TB) in the world. Concomitantly, aminoglycosides are commonly used in this country as a treatment against MDR-TB. To date, at least five mutations are known to confer susceptibility to aminoglycoside-induced hearing loss. The aim of the present study was to develop a rapid screening method to determine whether these mutations are present in the South African population.</p> <p>Methods</p> <p>A multiplex method using the SNaPshot technique was used to screen for five mutations in the <it>MT-RNR1 </it>gene: A1555G, C1494T, T1095C, 961delT+C(n) and A827G. A total of 204 South African control samples, comprising 98 Mixed ancestry and 106 Black individuals were screened for the presence of the five mutations.</p> <p>Results</p> <p>A robust, cost-effective method was developed that detected the presence of all five sequence variants simultaneously. In this pilot study, the A1555G mutation was identified at a frequency of 0.9% in the Black control samples. The 961delT+C(n) variant was present in 6.6% of the Black controls and 2% of the Mixed ancestry controls. The T1095C, C1494T and A827G variants were not identified in any of the study participants.</p> <p>Conclusion</p> <p>The frequency of 0.9% for the A1555G mutation in the Black population in South Africa is of concern given the high incidence of MDR-TB in this particular ethnic group. Future larger studies are warranted to determine the true frequencies of the aminoglycoside deafness mutations in the general South African population. The high frequencies of the 961delT+C(n) variant observed in the controls suggest that this change is a common non-pathogenic polymorphism. This genetic method facilitates the identification of individuals at high risk of developing hearing loss prior to the start of aminoglycoside therapy. This is important in a low-resource country like South Africa where, despite their adverse side-effects, aminoglycosides will continue to be used routinely and are accompanied with very limited or no audiological monitoring.</p
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