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"Cyril D"
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Potential Psychiatric Applications of Metabotropic Glutamate Receptor Agonists and Antagonists
Drugs acting at metabotropic glutamate receptors (mGluRs) are among the most promising agents under development for the treatment of psychiatric disorders. The research in this area is at a relatively early stage, as there are no drugs acting at mGluRs that have been approved for the treatment of any psychiatric disorder. However, in the areas of schizophrenia, anxiety disorders and mood disorders, research conducted in animal models appears to translate well into efficacy in human laboratory-based models of psychopathology and in preliminary clinical trials. Further, the genes coding for mGluRs are implicated in the risk for a growing number of psychiatric disorders. This review highlights the best studied mGluR strategies for psychiatry, based on human molecular genetics, studies in animal models and preliminary clinical trials. It describes the potential value of mGluR2 and mGluR5 agonists and positive allosteric modulators for the treatment of schizophrenia. It also reviews evidence that group II mGluR agonists and positive allosteric modulators as well as group I mGluR antagonists might also treat anxiety disorders and some forms of depression, while mGluR2 and group I mGluR antagonists (particularly mGluR5 antagonists) might have antidepressant properties. This review also links growing insights into the role of glutamate in the pathophysiology of these disorders to hypothesized mGluR-related treatment mechanisms.
Journal Article
Automatic lithology identification in meteorite impact craters using machine learning algorithms
Identifying lithologies in meteorite impact craters is an important task to unlock processes that have shaped the evolution of planetary bodies. Traditional methods for lithology identification rely on time-consuming manual analysis, which is costly and limits the efficiency of rapid decision-making. This paper utilizes different machine learning algorithms namely Random Forest, Decision Tree, K Nearest Neighbors, and Logistic Regression with Grid Search to classify rock lithologies using data from the Bosumtwi impact crater in Ghana. A repeated stratified k-fold cross-validation method is applied to Grid Search to select the best combination of hyperparameters. The findings demonstrate that the Random Forest algorithm achieves the most promising results in classifying lithologies in the meteorite impact crater with an accuracy score of 86.89%, a recall score of 84.88%, a precision score of 87.21%, and an F1 score of 85.48%. The findings also suggest that more high-quality data has the potential to further increase the accuracy scores of the machine learning algorithm. In conclusion, this study demonstrates the significant potential of machine learning techniques to revolutionize lithology identification in meteorite impact craters, thus paving the way for their influential role in future space exploration endeavors.
Journal Article
Mesothelioma Tumor Cells Modulate Dendritic Cell Lipid Content, Phenotype and Function
Dendritic cells (DCs) play an important role in the generation of anti-cancer immune responses, however there is evidence that DCs in cancer patients are dysfunctional. Lipid accumulation driven by tumor-derived factors has recently been shown to contribute to DC dysfunction in several human cancers, but has not yet been examined in mesothelioma. This study investigated if mesothelioma tumor cells and/or their secreted factors promote increases in DC lipid content and modulate DC function. Human monocyte-derived DCs (MoDCs) were exposed to human mesothelioma tumor cells and tumor-derived factors in the presence or absence of lipoproteins. The data showed that immature MoDCs exposed to mesothelioma cells or factors contained increased lipid levels relative to control DCs. Lipid accumulation was associated with reduced antigen processing ability (measured using a DQ OVA assay), upregulation of the co-stimulatory molecule, CD86, and production of the tolerogenic cytokine, IL-10. Increases in DC lipid content were further enhanced by co-exposure to mesothelioma-derived factors and triglyceride-rich lipoproteins, but not low-density lipoproteins. In vivo studies using a murine mesothelioma model showed that the lipid content of tumor-infiltrating CD4+ CD8α- DCs, CD4- CD8α- DCs DCs and plasmacytoid DCs increased with tumor progression. Moreover, increasing tumor burden was associated with reduced proliferation of tumor-antigen-specific CD8+ T cells in tumor-draining lymph nodes. This study shows that mesothelioma promotes DC lipid acquisition, which is associated with altered activation status and reduced capacity to process and present antigens, which may impair the ability of DCs to generate effective anti mesothelioma T cell responses.
Journal Article
Microwave-assisted hydrogen peroxide digestion followed by ICP-OES for determination of metals in selected fuel oils
This work describes a greener and cost-effective microwave-assisted hydrogen peroxide digestion (MA-HPD) with the addition of 1 mL of HNO
3
(70% v/v) to enhance extraction of selected metals (Al, Ba, Cd, Co, Cr, Cu, Mg, Na, Ni, Pb, Sb, Ti and V) in crude-oil, diesel, gasoline and kerosene samples prior to inductively coupled plasma-optical emission spectroscopic (ICP-OES) analysis. The most influential parameters of the MA-HPD method were investigated by using multivariate optimization tools (two-level full factorial and central composite designs) and fuel oil certified reference material (NIST1634c). The optimum conditions were observed to be 245 ℃ microwave temperature, 25 min digestion time, 0.1 g sample mass and 5 M H
2
O
2
were the optimum digestion conditions with accepted accuracy (104.8–117.7%) and precision (≤ 4.1%). In overall, the metals that reported high concentrations in the crude oil, diesel, gasoline, and kerosene samples were Na (51.94–58.86 mg/kg) and Mg (36.08–47.4 mg/kg), while Cu was the lowest (0.55–2.89 mg/kg). When comparing the obtained concentration levels with other literature reports, a conclusion can be drawn that South Africa is importing oils of reasonable quality.
Journal Article
Cisplatin-associated ototoxicity: perspectives from a single institution cervical cancer cohort and implications for developing a locally responsive monitoring programme in a public healthcare setting
Background
Ototoxicity monitoring is uncommon in South Africa, despite the increased use of ototoxic medication to manage the burden of disease in the country. The successful implementation of such a protocol requires cognisance of contextual realities and multiple dimensions for consideration from both patients and service providers. As part of an ongoing cohort study on cisplatin-associated ototoxicity and efforts to better inform the implementation of such programmes, the perspectives of cervical cancer patients and healthcare workers towards ototoxicity monitoring were assessed.
Methods
This concurrent-triangulation mixed-methods study was conducted at a tertiary hospital in South Africa. Self-reported questionnaires from patients (
n
= 80) and healthcare personnel comprising clinicians, oncology nurses, pharmacists, and radiotherapists (
n
= 32), results of audiological evaluations, researcher field notes, and estimated patient and service provider costs contributed to data for this study. Data analysis included descriptive statistics, comparison of test characteristics and deductive thematic analysis.
Results
The ototoxicity monitoring programme was positively received by the participants, with 90.6% of healthcare personnel and 89% of patients reporting it to be beneficial. The clinicians (76.6%) were identified as the main providers of information on the effects of chemotherapy medication and made the necessary referrals for audiological evaluation. The approximate cost of setting up such a programme included purchase of equipment (US56 700) and the appointment of an audiologist (US 26 250). The approximate costs to patients included transport costs (US$ 38) and the loss of income for the day (US 60), calculated at the minimum wage per hour, if employed. Creative appointment scheduling, easy facility access and detailed locally comprehensible couselling improved patient compliance to the programme. Whilst the sequential use of American Speech-Language-Hearing Association (ASHA) and National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria aided in an evidence-informed approach to aural rehabilitation, DPOAEs and speech discrimination displayed low sensitivity (range 1.45% – 22.39%) but high specificity (range 77.78% – 100%) when identifying ototoxic change.
Conclusion
This novel study, through a ‘real-world’ experience, has revealed that an ototoxicity monitoring programme is feasible in South Africa, through meaningful engagements with- and considerations from- patients and service providers regarding planning, delineation of responsibilities and cost implications. The findings can potentially serve as a roadmap for other limited resource environments.
Journal Article
Cisplatin-Associated Ototoxicity: A Review for the Health Professional
Cisplatin is an effective drug used in the treatment of many cancers, yet its ototoxic potential places cancer patients, exposed to this drug, at risk of hearing loss, thus negatively impacting further on a patient’s quality of life. It is paramount for health care practitioners managing such patients to be aware of cisplatin’s ototoxic properties and the clinical signs to identify patients at risk of developing hearing loss. English peer-reviewed articles from January 1975 to July 2015 were assessed from PubMed, Science Direct, and Ebscohost. Seventy-nine articles and two books were identified for this review, using MeSH terms and keywords such as “ototoxicity”, “cisplatin”, “hearing loss”, and “ototoxicity monitoring”. This review provides an up-to-date overview of cisplatin-associated ototoxicity, namely, its clinical features, incidence rates, and molecular and cellular mechanisms and risk factors, to health care practitioners managing the patient with cancer, and highlights the need for a team-based approach to complement an audiological monitoring programme to mitigate any further loss in the quality of life of affected patients, as there is currently no otoprotective agent recommended routinely for the prevention of cisplatin-associated ototoxicity. It also sets the platform for effective dialogue towards policy formulation and strengthening of health systems in developing countries.
Journal Article
Shoreline change detection along the eastern coast of Ghana: leveraging GIS and advanced remote sensing techniques
Recent advancements in automated shoreline detection methods have transformed the monitoring of Ghana’s coastline dynamics. This study measures the rates of shoreline change along Ghana’s eastern coastline using the USGS Digital Shoreline Analysis System (DSAS) in conjunction with CoastSat, an automated shoreline extraction tool. This automated approach enhances efficiency, ensures consistency, and improves repeatability compared to manual extraction techniques, allowing for long-term monitoring of coastal dynamics. The study employed three statistical models including the End Point Rate (EPR) and Linear Regression Rate (LRR) to quantify shoreline change with respect to movement captured over the study period. Along with these two models, the Net Shoreline Movement (NSM) was also used to calculate the overall displacement along Ghana’s eastern coastline over a forty (40) year period with a 90% confidence interval. Based on geomorphological traits and current management techniques, the area was divided into three zones (Zone A, Zone B and Zone C), enabling a detailed comparison of the ways in which human activities and natural processes have influenced shoreline change in various coastal environments. Erosion and accretion were observed across Zone A, with the northeastern section showing the highest rates of erosion. The range of EPR values in Zone A was − 10.5 m/year to + 10.8 m/year, whereas the range for LRR was − 10.4 m/year to + 12.0 m/year. With an average distance of 15.2 m, the NSM for Zone A demonstrated a moderate cumulative movement. In Zone B, EPR values varied from − 3.1 m/year to + 4.1 m/year, whereas LRR values ranged from − 1.6 m/year to + 5.0 m/year. During the time frame, Zone B observed a coastline movement of 20.42 m. Zone C exhibited the most significant shoreline dynamics, with LRR values ranging from − 28.7 m/year to + 9.7 m/year and EPR values ranging from − 30.5 m/year to + 8.8 m/year. Significant shifts in the shoreline position during the research period were evidenced by the NSM values for Zone C, which displayed an average cumulative shoreline displacement of 33.5 m. This methodology revealed significant regional diversity in shoreline dynamics, highlighting the importance of automated techniques for precise and repeatable coastal monitoring. These methods can be expanded and used in different areas, allowing coastal managers to create flexible, evidence-based plans for long-term shoreline management.
Journal Article
Feasibility and first results of a prospective cohort study to investigate cisplatin-associated ototoxicity amongst cancer patients in South Africa
Background
Cervical cancer, one of the most common cancers affecting females in South Africa, commonly requires a cisplatin-based-treatment regimen, which has been associated with ototoxic side effects. However, cisplatin-associated ototoxicity is largely under-reported in South Africa, despite its impact of hearing loss having serious overt ramifications on the quality of life of these patients. Hence, a prospective cohort study was undertaken to assess the audiological changes in female cervical cancer patients receiving cisplatin therapy.
Objective
To present details of the feasibility study and initial results on hearing patterns in cervical cancer patients receiving cisplatin chemotherapy. .
Methods
Fifty cervical cancer patients commencing with cisplatin chemotherapy underwent audiological assessments at a hospital in South Africa at various time intervals. Assessments included case history, otoscopic examination, immittance audiometry, pure tone audiometry (including high-frequency audiometry), speech audiometry, and distortion product otoacoustic emission testing. Data analysis involved the use of descriptive statistics and the Cochran-Armitage trend test for a linear trend in proportions.
Results
Fifty participants, aged between 32 and 79 years (Mean: 53 years; SD = 11.00), were recruited. Clinical findings revealed an incidence of 100% ototoxic hearing loss at the one-month post-treatment, i.e., 98% after three cycles of cisplatin and 2% at one-month post-chemotherapy. Sensorineural hearing loss and high-frequency tinnitus were most common. Deterioration in hearing thresholds was more evident in the extended high-frequency range, with the number of “no-responses,” from 11,200 Hz to 20,000 Hz, increasing with each successive audiological evaluation. This study further indicated that recruitment and follow-up of study participants within a limited resource setting are possible. However, cognizance must be given to a multidisciplinary approach and constant engagement with participants through regular contact either telephonically or via a short-message-system.
Conclusion
Exposure to cisplatin treatment contributed to hearing loss in females with cervical cancer, highlighting the need for ototoxicity monitoring during chemotherapy treatments. Furthermore, the results indicate that it is possible to conduct prospective cohort studies, using a multidisciplinary approach in limited-resource environments with appropriate planning and training strategies, as this study was able to achieve its aim successfully.
Journal Article