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1.
Neurobiol Dis ; 190: 106363, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37996040

RESUMO

Sporadic Creutzfeldt-Jakob disease (sCJD), the most common human prion disease, is thought to occur when the cellular prion protein (PrPC) spontaneously misfolds and assembles into prion fibrils, culminating in fatal neurodegeneration. In a genome-wide association study of sCJD, we recently identified risk variants in and around the gene STX6, with evidence to suggest a causal increase of STX6 expression in disease-relevant brain regions. STX6 encodes syntaxin-6, a SNARE protein primarily involved in early endosome to trans-Golgi network retrograde transport. Here we developed and characterised a mouse model with genetic depletion of Stx6 and investigated a causal role of Stx6 expression in mouse prion disease through a classical prion transmission study, assessing the impact of homozygous and heterozygous syntaxin-6 knockout on disease incubation periods and prion-related neuropathology. Following inoculation with RML prions, incubation periods in Stx6-/- and Stx6+/- mice differed by 12 days relative to wildtype. Similarly, in Stx6-/- mice, disease incubation periods following inoculation with ME7 prions also differed by 12 days. Histopathological analysis revealed a modest increase in astrogliosis in ME7-inoculated Stx6-/- animals and a variable effect of Stx6 expression on microglia activation, however no differences in neuronal loss, spongiform change or PrP deposition were observed at endpoint. Importantly, Stx6-/- mice are viable and fertile with no gross impairments on a range of neurological, biochemical, histological and skeletal structure tests. Our results provide some support for a pathological role of Stx6 expression in prion disease, which warrants further investigation in the context of prion disease but also other neurodegenerative diseases considering syntaxin-6 appears to have pleiotropic risk effects in progressive supranuclear palsy and Alzheimer's disease.


Assuntos
Síndrome de Creutzfeldt-Jakob , Doenças Priônicas , Príons , Camundongos , Humanos , Animais , Síndrome de Creutzfeldt-Jakob/genética , Síndrome de Creutzfeldt-Jakob/patologia , Príons/genética , Príons/metabolismo , Estudo de Associação Genômica Ampla , Camundongos Transgênicos , Encéfalo/metabolismo , Doenças Priônicas/genética , Doenças Priônicas/patologia , Proteínas Qa-SNARE/genética , Proteínas Qa-SNARE/metabolismo
2.
PLoS Biol ; 18(6): e3000725, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32516343

RESUMO

Inherited prion diseases are caused by autosomal dominant coding mutations in the human prion protein (PrP) gene (PRNP) and account for about 15% of human prion disease cases worldwide. The proposed mechanism is that the mutation predisposes to conformational change in the expressed protein, leading to the generation of disease-related multichain PrP assemblies that propagate by seeded protein misfolding. Despite considerable experimental support for this hypothesis, to-date spontaneous formation of disease-relevant, transmissible PrP assemblies in transgenic models expressing only mutant human PrP has not been demonstrated. Here, we report findings from transgenic mice that express human PrP 117V on a mouse PrP null background (117VV Tg30 mice), which model the PRNP A117V mutation causing inherited prion disease (IPD) including Gerstmann-Sträussler-Scheinker (GSS) disease phenotypes in humans. By studying brain samples from uninoculated groups of mice, we discovered that some mice (≥475 days old) spontaneously generated abnormal PrP assemblies, which after inoculation into further groups of 117VV Tg30 mice, produced a molecular and neuropathological phenotype congruent with that seen after transmission of brain isolates from IPD A117V patients to the same mice. To the best of our knowledge, the 117VV Tg30 mouse line is the first transgenic model expressing only mutant human PrP to show spontaneous generation of transmissible PrP assemblies that directly mirror those generated in an inherited prion disease in humans.


Assuntos
Amiloide/metabolismo , Príons/metabolismo , Adulto , Envelhecimento/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Códon/genética , Heterozigoto , Homozigoto , Humanos , Camundongos Transgênicos , Pessoa de Meia-Idade , Príons/isolamento & purificação
3.
J Pediatr Nurs ; 69: e73-e79, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36635113

RESUMO

BACKGROUND: The experience of living with children with CP is dominated by the voice of the mother while others are rarely reported. Incorporation of the voices of other family members is important for a holistic understanding. METHODS: Drawing on the philosophical perspectives of pragmatism, generic qualitative methodology, and Frank's narratives, this article highlights how restitution was constructed by 30 family members. FINDINGS: They constructed restitution by hoping for a cure through either biomedical and/or alternative models of treatment, followed by intransitive and transcendent restitution. DISCUSSION: This appears to be the first time that restitution has been extended to families living with children with chronic illnesses. APPLICATION TO PRACTICE: This would mean that paediatric nursing professionals and other health professionals dealing with family members living with children with CP could attend to their stories in an open and focused manner to honour and validate their stories as well as their experiences.


Assuntos
Paralisia Cerebral , Humanos , Criança , Paralisia Cerebral/diagnóstico , Paralisia Cerebral/terapia , Família , Doença Crônica , Esperança , Pesquisa Qualitativa
4.
J Infect Dis ; 226(5): 933-937, 2022 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-33502474

RESUMO

Chronic wasting disease (CWD) is the transmissible spongiform encephalopathy or prion disease affecting cervids. In 2016, the first cases of CWD were reported in Europe in Norwegian wild reindeer and moose. The origin and zoonotic potential of these new prion isolates remain unknown. In this study to investigate zoonotic potential we inoculated brain tissue from CWD-infected Norwegian reindeer and moose into transgenic mice overexpressing human prion protein. After prolonged postinoculation survival periods no evidence for prion transmission was seen, suggesting that the zoonotic potential of these isolates is low.


Assuntos
Cervos , Príons , Rena , Doença de Emaciação Crônica , Animais , Cervos/metabolismo , Humanos , Camundongos , Camundongos Transgênicos , Noruega , Príons/genética , Príons/metabolismo , Rena/metabolismo , Doença de Emaciação Crônica/genética
5.
ScientificWorldJournal ; 2022: 9810099, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401058

RESUMO

Excipients are components other than active ingredients that are added to pharmaceutical formulations. Naturally sourced excipients are gradually gaining preeminence over synthetically sourced excipients due to local availability and continuous supply. This study aimed to investigate the binding and disintegrating characteristics of gum extracted from the bark of Melia azedarach tree. The bark of Melia azedarach was harvested from Kwahu Asasraka in Ghana. The gum was extracted with ethanol (96%), and the percentage yield, phytochemical constituents, and flow characteristics were assessed. As a disintegrant, the gum was utilized to formulate granules at varying concentrations of 5% w/w and 10% w/w using starch as the standard. The gum was also utilized to prepare granules at varying concentrations of 10% w/v and 20% w/v as a binder, with tragacanth gum serving as the reference. Eight batches of tablets were produced from the granules. The formulated tablets from each batch were then subjected to quality control testing, which included uniformity of weight, friability, disintegration, hardness, drug content, and dissolution tests, respectively. Tannins, saponins, alkaloids, and glycosides were identified in the Melia azedarach gum. The gum had a percentage yield of 67.75% and also exhibited good flow properties. All tablets passed the uniformity of weight, friability, disintegration, hardness, dissolution, and drug content tests, respectively. According to the findings of the study, Melia azedarach gum can be utilized as an excipient in place of tragacanth and starch as a binder and disintegrant, respectively, in immediate-release tablets.


Assuntos
Melia azedarach , Tragacanto , Química Farmacêutica , Excipientes/química , Solubilidade , Amido , Comprimidos/química
6.
S Afr J Psychiatr ; 28: 1620, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35169506

RESUMO

BACKGROUND: Several reports show that suicide is the second and third leading cause of untimely death in young people below the age of 30. Little, however, is known about the profile and trend of suicide in this country due to lack of systematic studies and a lack of national statistics on suicide. This study seeks to examine the profile and pattern of suicide cases recorded within northern Ghana for the past decade. AIM: This study aimed to report the prevalence of suicide as an independent cause of death; the choice of suicide method and the alleged reasons for suicide within the northern part of Ghana. SETTING: Retrospective review of coroners' reports within the northern part of Ghana. METHOD: In this descriptive study, 309 completed suicides as archived by the office of the coroner were examined. The coroners' reports of 309 individuals, whose deaths received a suicide verdict or an open verdict in which the cause of death was likely to be suicide from 2008 to 2017, were examined. Student's t-test was used to ascertain significant age differences between the genders involved. RESULTS: Amongst the 309 decedents examined, approximately, 61% were male, with ages ranging from 5 to 81 years. Hanging and poisoning were the most commonly used methods to complete suicide accounting for 124 (40.1%) and 102 (33.0%) deaths, respectively. Regarding the reasons for completed suicide, 78 (25.2%) were because of unknown reasons and 66 (21.4%) were because of social stigma. There was a notable decline in the prevalence of suicide from 2014 to 2017 compared with the years from 2010 to 2013. CONCLUSION: Suicide was highest in the 30-39 year age group with hanging and poisoning being the most common method employed. Stigmatisation and psychosocial problems arising from chronic illness and economic hardship were significant triggers of suicide amongst the suicide decedents in the northern part of Ghana.

7.
Nature ; 522(7557): 478-81, 2015 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-26061765

RESUMO

Mammalian prions, transmissible agents causing lethal neurodegenerative diseases, are composed of assemblies of misfolded cellular prion protein (PrP). A novel PrP variant, G127V, was under positive evolutionary selection during the epidemic of kuru--an acquired prion disease epidemic of the Fore population in Papua New Guinea--and appeared to provide strong protection against disease in the heterozygous state. Here we have investigated the protective role of this variant and its interaction with the common, worldwide M129V PrP polymorphism. V127 was seen exclusively on a M129 PRNP allele. We demonstrate that transgenic mice expressing both variant and wild-type human PrP are completely resistant to both kuru and classical Creutzfeldt-Jakob disease (CJD) prions (which are closely similar) but can be infected with variant CJD prions, a human prion strain resulting from exposure to bovine spongiform encephalopathy prions to which the Fore were not exposed. Notably, mice expressing only PrP V127 were completely resistant to all prion strains, demonstrating a different molecular mechanism to M129V, which provides its relative protection against classical CJD and kuru in the heterozygous state. Indeed, this single amino acid substitution (G→V) at a residue invariant in vertebrate evolution is as protective as deletion of the protein. Further study in transgenic mice expressing different ratios of variant and wild-type PrP indicates that not only is PrP V127 completely refractory to prion conversion but acts as a potent dose-dependent inhibitor of wild-type prion propagation.


Assuntos
Polimorfismo Genético/genética , Doenças Priônicas/genética , Doenças Priônicas/prevenção & controle , Príons/genética , Príons/metabolismo , Alelos , Substituição de Aminoácidos/genética , Animais , Bovinos , Síndrome de Creutzfeldt-Jakob/genética , Síndrome de Creutzfeldt-Jakob/prevenção & controle , Encefalopatia Espongiforme Bovina/genética , Feminino , Heterozigoto , Homozigoto , Humanos , Kuru/epidemiologia , Kuru/genética , Kuru/prevenção & controle , Camundongos , Camundongos Transgênicos , Papua Nova Guiné/epidemiologia , Proteínas PrPSc/química , Proteínas PrPSc/genética , Proteínas PrPSc/metabolismo , Doenças Priônicas/epidemiologia , Doenças Priônicas/transmissão , Príons/química , Príons/farmacologia
8.
Int J Mol Sci ; 21(17)2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32899433

RESUMO

Breast cancer is the second leading cause of cancer-related mortality among women globally with obesity being one risk factor. Obese breast cancer patients have at least a 30% increased risk of death from breast cancer compared to non-obese breast cancer patients because they present with larger tumors and generally have increased rates of metastasis. Moreover, obese breast cancer patients respond more poorly to treatment compared to non-obese patients, particularly pre-menopausal women diagnosed with triple negative breast cancer (TNBC). To help understand the molecular mechanisms underlying the increased metastasis associated with obesity, we previously established a three-dimensional culture system that permits the co-culture of adipocytes and TNBC cells in a manner that mimics an in vivo milieu. Using this system, we demonstrate that white adipose tissue from both lean and obese mice can induce a partial mesenchymal-to-epithelial transition (MET). Triple negative breast cancer cells adopt an epithelial morphology and have an increased expression of some epithelial markers, but they maintain the expression of mesenchymal markers, furnishing the breast cancer cells with hybrid properties that are associated with more aggressive tumors. Thus, these data suggest that adipose tissue has the potential to promote secondary tumor formation in lean and obese women. Further work is needed to determine if targeting the partial MET induced by adipose tissue could reduce metastasis.


Assuntos
Tecido Adiposo/fisiopatologia , Transição Epitelial-Mesenquimal , Obesidade/fisiopatologia , Magreza/fisiopatologia , Neoplasias de Mama Triplo Negativas/patologia , Animais , Técnicas de Cultura de Células , Técnicas de Cocultura , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Células Tumorais Cultivadas
9.
Emerg Infect Dis ; 23(9): 1522-1530, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28820136

RESUMO

Bovine spongiform encephalopathy (BSE) is the only known zoonotic prion that causes variant Creutzfeldt-Jakob disease (vCJD) in humans. The major risk determinant for this disease is the polymorphic codon 129 of the human prion protein (Hu-PrP), where either methionine (Met129) or valine (Val129) can be encoded. To date, all clinical and neuropathologically confirmed vCJD cases have been Met129 homozygous, with the exception of 1 recently reported Met/Val heterozygous case. Here, we found that transgenic mice homozygous for Val129 Hu-PrP show severely restricted propagation of the BSE prion strain, but this constraint can be partially overcome by adaptation of the BSE agent to the Met129 Hu-PrP. In addition, the transmission of vCJD to transgenic mice homozygous for Val129 Hu-PrP resulted in a prion with distinct strain features. These observations may indicate increased risk for vCJD secondary transmission in Val129 Hu-PrP-positive humans with the emergence of new strain features.


Assuntos
Síndrome de Creutzfeldt-Jakob/patologia , Resistência à Doença/genética , Encefalopatia Espongiforme Bovina/imunologia , Proteínas Priônicas/imunologia , Valina/imunologia , Substituição de Aminoácidos , Animais , Encéfalo/patologia , Bovinos , Códon , Síndrome de Creutzfeldt-Jakob/transmissão , Encefalopatia Espongiforme Bovina/patologia , Encefalopatia Espongiforme Bovina/transmissão , Expressão Gênica , Humanos , Injeções Intraventriculares , Metionina/genética , Metionina/imunologia , Camundongos , Camundongos Transgênicos , Peptídeo Hidrolases/química , Proteínas Priônicas/química , Proteínas Priônicas/genética , Valina/genética
10.
PLoS Pathog ; 11(7): e1004953, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26135918

RESUMO

Inherited prion disease (IPD) is caused by autosomal-dominant pathogenic mutations in the human prion protein (PrP) gene (PRNP). A proline to leucine substitution at PrP residue 102 (P102L) is classically associated with Gerstmann-Sträussler-Scheinker (GSS) disease but shows marked clinical and neuropathological variability within kindreds that may be caused by variable propagation of distinct prion strains generated from either PrP 102L or wild type PrP. To-date the transmission properties of prions propagated in P102L patients remain ill-defined. Multiple mouse models of GSS have focused on mutating the corresponding residue of murine PrP (P101L), however murine PrP 101L, a novel PrP primary structure, may not have the repertoire of pathogenic prion conformations necessary to accurately model the human disease. Here we describe the transmission properties of prions generated in human PrP 102L expressing transgenic mice that were generated after primary challenge with ex vivo human GSS P102L or classical CJD prions. We show that distinct strains of prions were generated in these mice dependent upon source of the inoculum (either GSS P102L or CJD brain) and have designated these GSS-102L and CJD-102L prions, respectively. GSS-102L prions have transmission properties distinct from all prion strains seen in sporadic and acquired human prion disease. Significantly, GSS-102L prions appear incapable of transmitting disease to conventional mice expressing wild type mouse PrP, which contrasts strikingly with the reported transmission properties of prions generated in GSS P102L-challenged mice expressing mouse PrP 101L. We conclude that future transgenic modeling of IPDs should focus exclusively on expression of mutant human PrP, as other approaches may generate novel experimental prion strains that are unrelated to human disease.


Assuntos
Modelos Animais de Doenças , Doença de Gerstmann-Straussler-Scheinker/transmissão , Príons/química , Príons/genética , Animais , Doença de Gerstmann-Straussler-Scheinker/genética , Humanos , Immunoblotting , Imuno-Histoquímica , Camundongos , Camundongos Transgênicos
11.
PLoS Pathog ; 9(9): e1003643, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24086135

RESUMO

Prions are infectious agents causing fatal neurodegenerative diseases of humans and animals. In humans, these have sporadic, acquired and inherited aetiologies. The inherited prion diseases are caused by one of over 30 coding mutations in the human prion protein (PrP) gene (PRNP) and many of these generate infectious prions as evidenced by their experimental transmissibility by inoculation to laboratory animals. However, some, and in particular an extensively studied type of Gerstmann-Sträussler-Scheinker syndrome (GSS) caused by a PRNP A117V mutation, are thought not to generate infectious prions and instead constitute prion proteinopathies with a quite distinct pathogenetic mechanism. Multiple attempts to transmit A117V GSS have been unsuccessful and typical protease-resistant PrP (PrP(Sc)), pathognomonic of prion disease, is not detected in brain. Pathogenesis is instead attributed to production of an aberrant topological form of PrP, C-terminal transmembrane PrP ((Ctm)PrP). Barriers to transmission of prion strains from one species to another appear to relate to structural compatibility of PrP in host and inoculum and we have therefore produced transgenic mice expressing human 117V PrP. We found that brain tissue from GSS A117V patients did transmit disease to these mice and both the neuropathological features of prion disease and presence of PrP(Sc) was demonstrated in the brains of recipient transgenic mice. This PrP(Sc) rapidly degraded during laboratory analysis, suggesting that the difficulty in its detection in patients with GSS A117V could relate to post-mortem proteolysis. We conclude that GSS A117V is indeed a prion disease although the relative contributions of (Ctm)PrP and prion propagation in neurodegeneration and their pathogenetic interaction remains to be established.


Assuntos
Substituição de Aminoácidos , Encéfalo/metabolismo , Doença de Gerstmann-Straussler-Scheinker/metabolismo , Doença de Gerstmann-Straussler-Scheinker/transmissão , Mutação de Sentido Incorreto , Proteínas PrPSc/metabolismo , Príons/metabolismo , Animais , Encéfalo/patologia , Doença de Gerstmann-Straussler-Scheinker/genética , Doença de Gerstmann-Straussler-Scheinker/patologia , Humanos , Camundongos , Camundongos Transgênicos , Proteínas PrPSc/genética , Proteínas Priônicas , Príons/genética
12.
Acta Neuropathol ; 130(4): 511-23, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26358247

RESUMO

Mutations in the charged multivesicular body protein 2B (CHMP2B) cause frontotemporal dementia (FTD). We report that mice which express FTD-causative mutant CHMP2B at physiological levels develop a novel lysosomal storage pathology characterised by large neuronal autofluorescent aggregates. The aggregates are an early and progressive pathology that occur at 3 months of age and increase in both size and number over time. These autofluorescent aggregates are not observed in mice expressing wild-type CHMP2B, or in non-transgenic controls, indicating that they are a specific pathology caused by mutant CHMP2B. Ultrastructural analysis and immuno- gold labelling confirmed that they are derived from the endolysosomal system. Consistent with these findings, CHMP2B mutation patient brains contain morphologically similar autofluorescent aggregates. These aggregates occur significantly more frequently in human CHMP2B mutation brain than in neurodegenerative disease or age-matched control brains. These data suggest that lysosomal storage pathology is the major neuronal pathology in FTD caused by CHMP2B mutation. Recent evidence suggests that two other genes associated with FTD, GRN and TMEM106B are important for lysosomal function. Our identification of lysosomal storage pathology in FTD caused by CHMP2B mutation now provides evidence that endolysosomal dysfunction is a major degenerative pathway in FTD.


Assuntos
Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Demência Frontotemporal/genética , Demência Frontotemporal/patologia , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Idoso , Idoso de 80 Anos ou mais , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Modelos Animais de Doenças , Progressão da Doença , Feminino , Demência Frontotemporal/metabolismo , Humanos , Lisossomos/metabolismo , Lisossomos/patologia , Masculino , Camundongos Transgênicos , Microglia/metabolismo , Microglia/patologia , Pessoa de Meia-Idade , Mutação , Neurônios/metabolismo , Neurônios/patologia , Multimerização Proteica
13.
Proc Natl Acad Sci U S A ; 109(34): 13722-7, 2012 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-22869728

RESUMO

Prion diseases are fatal neurodegenerative disorders that include bovine spongiform encephalopathy (BSE) and scrapie in animals and Creutzfeldt-Jakob disease (CJD) in humans. They are characterized by long incubation periods, variation in which is determined by many factors including genetic background. In some cases it is possible that incubation time may be directly correlated to the level of gene expression. To test this hypothesis, we combined incubation time data from five different inbred lines of mice with quantitative gene expression profiling in normal brains and identified five genes with expression levels that correlate with incubation time. One of these genes, Hspa13 (Stch), is a member of the Hsp70 family of ATPase heat shock proteins, which have been previously implicated in prion propagation. To test whether Hspa13 plays a causal role in determining the incubation period, we tested two overexpressing mouse models. The Tc1 human chromosome 21 (Hsa21) transchromosomic mouse model of Down syndrome is trisomic for many Hsa21 genes including Hspa13 and following Chandler/Rocky Mountain Laboratory (RML) prion inoculation, shows a 4% reduction in incubation time. Furthermore, a transgenic model with eightfold overexpression of mouse Hspa13 exhibited highly significant reductions in incubation time of 16, 15, and 7% following infection with Chandler/RML, ME7, and MRC2 prion strains, respectively. These data further implicate Hsp70-like molecular chaperones in protein misfolding disorders such as prion disease.


Assuntos
Regulação da Expressão Gênica , Proteínas de Choque Térmico HSP70/biossíntese , Proteínas de Choque Térmico HSP70/fisiologia , Doenças Priônicas/genética , Adenosina Trifosfatases/química , Animais , Proteínas de Choque Térmico HSP70/genética , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Camundongos Transgênicos , Modelos Genéticos , Neurônios/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Fenótipo , Príons/metabolismo , RNA Complementar/metabolismo
14.
Data Brief ; 54: 110261, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38962186

RESUMO

Hyperspectral imaging, combined with deep learning techniques, has been employed to classify maize. However, the implementation of these automated methods often requires substantial processing and computing resources, presenting a significant challenge for deployment on embedded devices due to high GPU power consumption. Access to Ghanaian local maize data for such classification tasks is also extremely difficult in Ghana. To address these challenges, this research aims to create a simple dataset comprising three distinct types of local maize seeds in Ghana. The goal is to facilitate the development of an efficient maize classification tool that minimizes computational costs and reduces human involvement in the process of grading seeds for marketing and production. The dataset is presented in two parts: raw images, consisting of 4,846 images, are categorized into bad and good. Specifically, 2,211 images belong to the bad class, while 2,635 belong to the good class. Augmented images consist of 28,910 images, with 13,250 representing bad data and 15,660 representing good data. All images have been validated by experts from Heritage Seeds Ghana and are freely available for use within the research community.

15.
Cureus ; 16(7): e64029, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38983673

RESUMO

The adoption of minimally invasive treatments for early-stage breast cancer is increasing. Microwave thermal ablation (MWA), a minimally invasive technique, has been studied for treating small breast cancer lesions. However, long-term evidence on its efficacy as a sole treatment is limited, as most studies combine MWA with other therapies and post-treatment surgical excision. This report details the case of an 83-year-old African patient who declined surgery and systemic therapies, opting for MWA using the TATOpro system as the sole treatment for contralateral breast cancer with axillary lymph node metastasis. The report includes a one-year follow-up, assessing disease recurrence with MRI and ultrasound. The findings highlight MWA's potential as an innovative and efficacious breast cancer treatment, emphasizing the need for adaptable strategies in oncology.

16.
F1000Res ; 13: 338, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38910591

RESUMO

Background: Funding committees, comprising members with a range of knowledge, skills, and experience, are considered integral to the decision-making process of funding organisations for recommending or allocating research funding. However, there is limited research investigating the decision-making processes, the role of members and their social interactions during funding committee meetings conducted both virtually and face-to-face. Methods: Using a mixed-methods design and following netnography principles, the study observed nine National Institute for Health and Care Research programmes funding committee meetings conducted virtually during October 2020 to December 2021; complemented by interviews with committee chairs and members (18 interviews) and NIHR staff (12 interviews); an online survey (50 responses); and documentary analysis. Personal reflections through immersive journals also formed part of the analysis. Results: Three main themes were identified from the observations, interviews, and online survey: efficiency of virtual committee meetings (importance of preparation, and the role of formality, process, and structure); understanding the effect of virtual committee meetings on well-being (effects of fatigue and apprehension, and the importance of work life balance); understanding social interactions and engagement (levels of engagement, contribution and inclusivity, awareness of unconscious bias and the value of social networking). Conclusions: Examining the decision-making practices of one funding organisation across several research programmes, across multiple committee meetings over one year has generated new insights around funding committee practices that previous studies have not been able to explore or investigate. Overall, it was observed that fair and transparent funding recommendations and outcomes can be achieved through virtual funding committees. However, whilst virtual funding committees have many benefits and opportunities, such as the potential to increase membership diversity and inclusivity, and be more environmentally sustainable, more evidence is needed to evaluate their effectiveness, with particular focus on issues of fatigue, engagement, and committee cohesion, especially when new committee members join.

17.
J West Afr Coll Surg ; 14(1): 94-101, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38486658

RESUMO

Background: Globally urolithiasis is on the rise and gradually becoming a public health concern due to the associated complications. This study reviewed the demographic characteristics, the chemical composition of stones, treatment modality and duration of hospitalisation of urolithiasis patients at Korle-Bu Teaching Hospital, Accra, Ghana. Materials and Methods: This was a retrospective study conducted between March 2019 and April 2022. Data from consecutive patients treated for urolithiasis were used for this study. Data on demographic characteristics, stones chemical composition, urine factors, urolithiasis treatment modality and duration of hospital stay after therapy were collated and analysed using descriptive and inferential approaches. Results: The age of the patients ranged from 2 to 75 years with a mean of 45 (±13.4). The predominant age group for stone formation was 30-39 years - 52(26.3%). Urolithiasis was common among patients in the formal employment sector: 81(40.9%). All stones had two or more chemical compositions, with the combination of calcium oxalate monohydrate, calcium oxalate dihydrate and uric acid being the predominant stone type: 88(57.5%). Ureteroscopy with semi-rigid and Percutaneous nephrolithotomy were the predominant treatment modalities: 105(53.0%) and 74(37.4%), respectively. Escherichia coli was responsible for most urinary tract infections in urolithiasis patients 8(4.0%) and the least duration of hospital stay after the procedure was associated with the use of semi-rigid ureteroscope as the treatment modality with a median duration of 2 days (1-2 days) with P < 0.0001. Conclusions: Urolithiasis was predominant among professionals in the formal sector. All stones were mixed with Calcium oxalate monohydrate, calcium oxalate dihydrate, and uric acid combination being the majority. Ureteroscopy with semi-rigid and percutaneous nephrolithotomy were the common treatment modality.

18.
Cureus ; 16(6): e62393, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39006703

RESUMO

BACKGROUND: There is significant variability in the pathogenetic characteristics of prostate cancer (PCa) across different anatomical zones. This study aims to understand the metastatic risk associated with these zonal predispositions among African men. METHODS: This hospital-based retrospective observational study included 120 biopsy-confirmed PCa patients examined between 2019 and 2023. Data on cancer history, sociodemographic, and clinical characteristics were collected from medical records. A logistic regression model was used to identify predictors of metastasis. RESULTS: The majority of PCa lesions were found in the left (60.0%) and right peripheral zones (55.8%), followed by the left (42.5%) and right transitional zones (41.7%). Lesions in the anterior fibromuscular stroma (crude odds ratio (cOR): 3.27, 95% confidence interval (CI): 1.13-9.47; p = 0.029), central gland (cOR: 5.38, 95% CI: 1.40-20.60; p = 0.014), and diffuse infiltration involving whole gland (cOR: 6.78, 95% CI: 1.17-30.07; p = 0.032) were associated with significantly increased odds of metastasis. Lesions in the anterior fibromuscular stroma were a marginally independent predictor of metastasis (adjusted odds ratio (aOR): 28.14, 95% CI: 0.96-822.46; p = 0.053). CONCLUSIONS: This study underscores the variability in metastatic risk of PCa lesions across different anatomical zones in African men. Lesions in the anterior fibromuscular stroma, central gland, and diffuse infiltration involving the whole gland have higher odds of metastasis. These findings highlight the need for targeted diagnostic and therapeutic strategies based on lesion localization to improve PCa management in this population.

19.
Cureus ; 16(7): e63759, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39099972

RESUMO

Objective This study explores the correlation between shear wave elastography (SWE) features and histopathological grades and subtypes in breast cancer, aiming to enhance diagnostic accuracy and personalized treatment strategies. Methods The study retrospectively analyzed 59 consecutive women with breast cancer who underwent breast ultrasound with SWE. SWE parameters and histopathologic information, including histological type and grade, were recorded. Qualitative and quantitative SWE findings were analyzed, and B-mode findings were evaluated. Sociodemographic and clinical factors and B-mode findings were assessed as predictors of elastography stiffness using logistic regression analysis. Results Of the 59 participants diagnosed with breast cancer, invasive ductal carcinoma of no special type (IDC-NST) was predominantly found in 50 (84.7%) cases, followed by invasive medullary carcinoma in 5 (8.5%) cases. The majority of participants belonged to the 50-59 age group, comprising 19 (32.2%) patients. Histopathological grading revealed grade II tumors in 27 (45.8%) cases and grade III tumors in 24 (40.7%) cases. Notably, grade III tumors exhibited higher tissue stiffness compared to grade II tumors. Out of 36 stiff lesions, 30 (83.3%%) were IDC-NST while 3 (8.3%) were invasive medullary carcinoma. A significant association was observed between higher histopathological grade (grade III) and increased tissue stiffness (p < 0.05). Furthermore, among participants with stiff lesions, 21 (58.3%) exhibited color defects while 4 (23.5%) cases with soft lesions also displayed color defects Conclusion The correlation between SWE findings and histopathological grades and subtypes underscores the potential of SWE as a valuable tool for predicting tumor aggressiveness and characterizing specific subtypes. SWE enhances diagnostic accuracy and complements traditional imaging modalities, holding promise for personalized treatment strategies.

20.
Cureus ; 16(5): e59470, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38826908

RESUMO

OBJECTIVES:  To document our initial experience using whole-body diffusion-weighted magnetic resonance imaging (WB-DWI/MRI) and bi-parametric magnetic resonance imaging (bpMRI) as a single exam in the staging of biopsy-proven prostate cancers. METHODS: This retrospective study involved 120 African men with biopsy-confirmed prostate cancer (PCa). All the participants had a single exam that included both a bpMRI and a WB-DWI/MRI. The results were analyzed based on the American Urological Association's risk stratification system and evaluated using descriptive statistics. RESULTS: The combined imaging approach confirmed PCa in all cases, identifying pelvic lymph node metastases in 21 (17.5%) patients. Among 72 high-risk patients, bpMRI+WB-DWI/MRI detected pelvic lymph node metastases in 18 (25.0%), bone metastases in 15 (20.8%), retroperitoneal lymph node metastases in six (8.3%), and extraprostatic extension in 18 (25%), with no solid organ metastases observed. CONCLUSION: The combination of WB-DWI/MRI and bpMRI in a single-step approach demonstrates diagnostic potential in primary prostate cancer staging for high-risk groups, with the added advantage of shorter examination times, lower patients' costs, and elimination of the risks of adverse events associated with the use of contrast agents and exposure to radiation.

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