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2.
Nucleic Acids Res ; 52(D1): D1438-D1449, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37897341

RESUMO

The IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb; https://www.guidetopharmacology.org) is an open-access, expert-curated, online database that provides succinct overviews and key references for pharmacological targets and their recommended experimental ligands. It includes over 3039 protein targets and 12 163 ligand molecules, including approved drugs, small molecules, peptides and antibodies. Here, we report recent developments to the resource and describe expansion in content over the six database releases made during the last two years. The database update section of this paper focuses on two areas relating to important global health challenges. The first, SARS-CoV-2 COVID-19, remains a major concern and we describe our efforts to expand the database to include a new family of coronavirus proteins. The second area is antimicrobial resistance, for which we have extended our coverage of antibacterials in partnership with AntibioticDB, a collaboration that has continued through support from GARDP. We discuss other areas of curation and also focus on our external links to resources such as PubChem that bring important synergies to the resources.


Assuntos
Bases de Dados de Produtos Farmacêuticos , Descoberta de Drogas , Proteínas , Ligantes
3.
Br J Pharmacol ; 180 Suppl 2: S145-S222, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-38123150

RESUMO

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and over 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16178. Ion channels are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.


Assuntos
Bases de Dados de Produtos Farmacêuticos , Farmacologia , Humanos , Canais Iônicos/química , Ligantes , Receptores Acoplados a Proteínas G , Bases de Dados Factuais
4.
Br J Pharmacol ; 180 Suppl 2: S223-S240, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-38123152

RESUMO

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and nearly 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16179. Nuclear hormone receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.


Assuntos
Bases de Dados de Produtos Farmacêuticos , Farmacologia , Humanos , Ligantes , Proteínas de Membrana Transportadoras , Receptores Acoplados a Proteínas G , Receptores Citoplasmáticos e Nucleares
5.
Br J Pharmacol ; 180 Suppl 2: S289-S373, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-38123154

RESUMO

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16176. In addition to this overview, in which are identified 'Other protein targets' which fall outside of the subsequent categorisation, there are six areas of focus: G protein-coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.


Assuntos
Bases de Dados de Produtos Farmacêuticos , Canais Iônicos , Humanos , Ligantes , Receptores Citoplasmáticos e Nucleares , Receptores Acoplados a Proteínas G
6.
Br J Pharmacol ; 180 Suppl 2: S1-S22, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-38123153

RESUMO

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16176. In addition to this overview, in which are identified 'Other protein targets' which fall outside of the subsequent categorisation, there are six areas of focus: G protein-coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.


Assuntos
Bases de Dados de Produtos Farmacêuticos , Farmacologia , Humanos , Bases de Dados Factuais , Canais Iônicos , Ligantes , Receptores Citoplasmáticos e Nucleares
7.
Br J Pharmacol ; 180 Suppl 2: S23-S144, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-38123151

RESUMO

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.16177. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.


Assuntos
Bases de Dados de Produtos Farmacêuticos , Receptores Acoplados a Proteínas G , Humanos , Ligantes , Canais Iônicos/química , Receptores Citoplasmáticos e Nucleares
8.
Br J Pharmacol ; 180 Suppl 2: S374-S469, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-38123156

RESUMO

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and over 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16182. Transporters are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors and enzymes. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.


Assuntos
Bases de Dados de Produtos Farmacêuticos , Farmacologia , Humanos , Ligantes , Canais Iônicos/química , Receptores Acoplados a Proteínas G , Receptores Citoplasmáticos e Nucleares
9.
Br J Pharmacol ; 180 Suppl 2: S241-S288, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-38123155

RESUMO

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and nearly 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16180. Catalytic receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ion channels, nuclear hormone receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.


Assuntos
Bases de Dados de Produtos Farmacêuticos , Farmacologia , Humanos , Ligantes , Receptores Acoplados a Proteínas G , Canais Iônicos/química , Receptores Citoplasmáticos e Nucleares
10.
Wellcome Open Res ; 8: 172, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37663790

RESUMO

Cerebral malaria (CM) remains a significant global health challenge with high morbidity and mortality. Malarial retinopathy has been shown to be diagnostically and prognostically significant in the assessment of CM. The major mechanism of death in paediatric CM is brain swelling. Long term morbidity is typically characterised by neurological and neurodevelopmental sequelae. Optical coherence tomography can be used to quantify papilloedema and macular ischaemia, identified as hyperreflectivity. Here we describe a protocol to test the hypotheses that quantification of optic nerve head swelling using optical coherence tomography can identify severe brain swelling in CM, and that quantification of hyperreflectivity in the macula predicts neurodevelopmental outcomes post-recovery. Additionally, our protocol includes the development of a novel, low-cost, handheld optical coherence tomography machine and artificial intelligence tools to assist in image analysis.

11.
Br J Pharmacol ; 180(15): 1899-1929, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37197802

RESUMO

Antimalarial drug discovery has until recently been driven by high-throughput phenotypic cellular screening, allowing millions of compounds to be assayed and delivering clinical drug candidates. In this review, we will focus on target-based approaches, describing recent advances in our understanding of druggable targets in the malaria parasite. Targeting multiple stages of the Plasmodium lifecycle, rather than just the clinically symptomatic asexual blood stage, has become a requirement for new antimalarial medicines, and we link pharmacological data clearly to the parasite stages to which it applies. Finally, we highlight the IUPHAR/MMV Guide to MALARIA PHARMACOLOGY, a web resource developed for the malaria research community that provides open and optimized access to published data on malaria pharmacology.


Assuntos
Antimaláricos , Malária , Humanos , Malária/tratamento farmacológico , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Descoberta de Drogas , Ensaios de Triagem em Larga Escala
12.
Acta Diabetol ; 60(6): 837-844, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36959506

RESUMO

AIMS: Neurodegeneration and glial activation are primary events in the pathogenesis of diabetic retinopathy. Serum glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are biomarkers of underlying neuroinflammatory and neurodegenerative disease processes. The aim of the present study was to assess the usefulness of these serum biomarkers for the identification and monitoring of retinal neurodysfunction in subjects with type 2 diabetes. METHODS: A case-control study was designed including 38 patients from the placebo arm of the EUROCONDOR clinical trial: 19 with and 19 without retinal neurodysfunction assessed by multifocal electroretinography. GFAP and NfL were measured by Simoa. RESULTS: Serum levels of GFAP and NfL directly correlated with age (r = 0.37, p = 0.023 and r = 0.54, p < 0.001, respectively). In addition, a direct correlation between GFAP and NfL was observed (r = 0.495, p = 0.002). Serum levels of GFAP were significantly higher at baseline in those subjects in whom neurodysfunction progressed after the 2 years of follow-up (139.1 ± 52.5 pg/mL vs. 100.2 ± 54.6 pg/mL; p = 0.04). CONCLUSIONS: GFAP could be a useful serum biomarker for retinal neurodysfunction. Monitoring retinal neurodysfunction using blood samples would be of benefit in clinical decision-making. However, further research is needed to validate this result as well as to establish the best cutoff values.


Assuntos
Biomarcadores , Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Proteína Glial Fibrilar Ácida , Humanos , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/etiologia , Filamentos Intermediários , Doenças Neurodegenerativas
13.
Ambio ; 51(12): 2414-2430, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36181658

RESUMO

Recognition of the multiple types of value of marine resources is crucial to help design locally meaningful and sustainable management approaches for marine and coastal habitats. There is a lack of information on the amount of living marine resources harvested by coastal communities in many Pacific Island Countries and Territories (PICTs), as well as on their economic and non-economic value. This paper explores the monetary, subsistence, and sociocultural value of selected marine resources (finfish and invertebrates) in Kadavu province, Fiji, based on a household survey and semi-structured interviews conducted in 2019 within one specific district. The paper provides estimates of the annual catch and monetary value of marine resources harvested by local communities at both the district and provincial levels, derived from catch and effort information collected from fishers and gleaners in situ. It also highlights the importance of integrating the sociocultural significance of marine resources into future value assessments.


Assuntos
Ecossistema , Pesqueiros , Animais , Fiji , Peixes , Conservação dos Recursos Naturais
14.
Methods Mol Biol ; 2470: 731-748, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35881386

RESUMO

Retinal examination and imaging are relatively simple methods for studying the dynamic impact of cerebral malaria on the microcirculation of the central nervous system. Retina and brain are affected similarly by Plasmodium falciparum. Unlike the brain, the human retina can be directly observed using commercially available clinical instruments in the setting of a critical care unit, and this can be done repeatedly and non-invasively. Additional information about blood-tissue barriers can be gained from fluorescein angiography. Non-ophthalmologist clinician scientists are usually unfamiliar with ophthalmoscopy and retinal imaging, and some readers may feel that these techniques are beyond them. This chapter aims to quell these fears by providing a step-by-step description of how to examine and photograph the human retina in children with cerebral malaria.


Assuntos
Malária Cerebral , Doenças Retinianas , Criança , Humanos , Malária Cerebral/diagnóstico , Oftalmoscopia , Plasmodium falciparum , Retina , Doenças Retinianas/diagnóstico
15.
Ophthalmol Retina ; 6(8): 664-675, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35314388

RESUMO

PURPOSE: To describe the frequency of long-term morphologic features and their relationships with visual function in participants who exited the Inhibition of VEGF in Age-Related Choroidal Neovascularisation (IVAN; ISRCTN92166560) trial. DESIGN: Multicenter cohort study up to 7 years after enrollment. PARTICIPANTS: Patients enrolled in the IVAN trial, excluding participants who died or withdrew during the trial. METHODS: Multimodal fundus images, best-corrected visual acuity (BCVA), and low-luminance visual acuity (LLVA) were obtained for a subset of 199 participants who attended a research visit. Clinical sites (n = 20) also provided all visual acuity and clinical information from usual care records for 532 participants and submitted the most recent color, OCT, and other fundus images for 468 participants to a reading center. MAIN OUTCOME MEASURES: Assessed the following from the most recent images: intralesional macular atrophy (ILMA) within the footprint of the neovascular lesion; hyperreflective material (HRM); intraretinal fluid (IRF); subretinal fluid (SRF); pigment epithelial detachment (PED); and disorganized retinal outer layers (DROLs). Cross-sectional relationships between morphologic features and BCVA/LLVA were estimated. RESULTS: Intralesional macular atrophy was present in 31.8% of the study eyes at IVAN exit (mean follow-up, 1.96 years) and 89.5% at the most recent imaging visit (mean follow-up, 6.18 years). Hyperreflective material, IRF, SRF, PED, and DROLs were present in 78.8%, 47.7%, 7.6%, 94.5%, and 55% of the study eyes, respectively. In the subset with complete imaging data, in eyes without DROL, the BCVA was worst in the thinnest outer fovea tertile (thinnest minus middle and thickest tertiles, -19.7 and -19.5 letters, respectively), whereas in eyes with DROL, the BCVA was worst in the thickest (thinnest and middle tertiles minus thickest, 12.5 and 12.2, respectively). Regression models showed that the presence of ILMA and HRM was independently associated with BCVA (22 letters worse [95% confidence interval {CI}, -11.2 to -32.8; P < 0.001] and 9.8 letters worse [95% CI, -0.1 to -19.4; P = 0.047], respectively). Subretinal fluid and foveal PED were associated with better BCVA (5.9 letters [95% CI, -7.9 to 19.7; P = 0.399] and 6.4 letters [95% CI, -1.1 to 14.0; P = 0.094], respectively). The model with LLVA was similar. A sensitivity analysis involving the entire eligible cohort yielded similar estimates. CONCLUSIONS: Macular atrophy and HRM were common after 7 years of follow-up and strongly associated with visual outcomes.


Assuntos
Neovascularização de Coroide , Degeneração Macular , Descolamento Retiniano , Inibidores da Angiogênese/uso terapêutico , Atrofia/tratamento farmacológico , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/tratamento farmacológico , Estudos de Coortes , Humanos , Degeneração Macular/tratamento farmacológico , Ranibizumab/uso terapêutico , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular
16.
BMC Geriatr ; 22(1): 134, 2022 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-35177024

RESUMO

BACKGROUND: Falls are the second leading cause of accidental deaths worldwide mainly in older people. Older people have poor vision and published evidence suggests that it is a risk factor for falls. Less than half of falls clinics assess vision as part of the multi-factorial assessment of older adults at risk of falls despite vision being an essential input for postural stability. The aim of our study was to investigate the relationship between all clinically assessed visual functions and falls amongst older adults in a prospective observational individually age-matched case control study. METHODS: Visual acuity (VA), contrast sensitivity (CS), depth perception, binocular vision and binocular visual field were measured using routinely used clinical methods in falls participants (N = 83) and non-falls participants (N = 83). Data were also collected on socio-demographic factors, general health, number of medications, health quality, fear of falling and physical activity. Logistic regression analysis was carried out to determine key visual and non-visual risk factors for falls whilst adjusting for confounding covariates. RESULTS: Older adults have an increased risk of experiencing a fall if they have reduced visual function (odds ratio (OR): 3.49, 1.64-7.45, p = 0.001), specifically impaired stereoacuity worse than 85" of arc (OR: 3.4, 1.20-9.69, p = 0.02) and reduced (by 0.15 log unit) high spatial frequency CS (18 cpd) (OR:1.40, 1.12-1.80, p = 0.003). Older adults with a hearing impairment are also at higher risk of falls (OR: 3.18, 95% CI: 1.36-7.40, p = 0.007). The risk decreases with living in a less deprived area (OR: 0.74, 0.64-0.86, <0.001), or socialising more out of the home (OR: 0.75, 0.60-0.93, p = 0.01). CONCLUSIONS: The combination of social, behavioural and biological determinants are significant predictors of a fall. The non-visual risk factors include older adults, living in deprived neighbourhoods, socialising less outside of the home and those who have a hearing impairment. Impaired functional visual measures; depth perception and contrast are significant visual risk factors for falls above visual acuity.


Assuntos
Sensibilidades de Contraste , Medo , Idoso , Estudos de Casos e Controles , Humanos , Fatores de Risco
17.
J Infect Dis ; 225(6): 1070-1080, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-32845969

RESUMO

BACKGROUND: In cerebral malaria, the retina can be used to understand disease pathogenesis. The mechanisms linking sequestration, brain swelling, and death remain poorly understood. We hypothesized that retinal vascular leakage would be associated with brain swelling. METHODS: We used retinal angiography to study blood-retinal barrier integrity. We analyzed retinal leakage, histopathology, brain magnatic resonance imaging (MRI), and associations with death and neurological disability in prospective cohorts of Malawian children with cerebral malaria. RESULTS: Three types of retinal leakage were seen: large focal leak (LFL), punctate leak (PL), and vessel leak. The LFL and PL were associated with death (odds ratio [OR] = 13.20, 95% confidence interval [CI] = 5.21-33.78 and OR = 8.58, 95% CI = 2.56-29.08, respectively) and brain swelling (P < .05). Vessel leak and macular nonperfusion were associated with neurological disability (OR = 3.71, 95% CI = 1.26-11.02 and OR = 9.06, 95% CI = 1.79-45.90). Large focal leak was observed as an evolving retinal hemorrhage. A core of fibrinogen and monocytes was found in 39 (93%) white-centered hemorrhages. CONCLUSIONS: Blood-retina barrier breakdown occurs in 3 patterns in cerebral malaria. Associations between LFL, brain swelling, and death suggest that the rapid accumulation of cerebral hemorrhages, with accompanying fluid egress, may cause fatal brain swelling. Vessel leak, from barrier dysfunction, and nonperfusion were not associated with severe brain swelling but with neurological deficits, suggesting hypoxic injury in survivors.


Assuntos
Edema Encefálico , Malária Cerebral , Barreira Hematorretiniana/patologia , Edema Encefálico/complicações , Edema Encefálico/patologia , Criança , Humanos , Malária Cerebral/complicações , Estudos Prospectivos , Retina/patologia
18.
Diabetes Ther ; 13(1): 1-23, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34928488

RESUMO

To systematically review the epidemiology of early worsening of diabetic retinopathy (EWDR) after substantial improvements in glycaemic control and evaluate characteristics including risk factors. This systematic review was registered with PROSPERO (CRD42020158252). An electronic literature search was performed according to PRISMA guidelines using MEDLINE, EMBASE, PubMed, Web of Science, Scopus and Cochrane databases and manual reference for the articles published until 2020. Published full-text English language articles that report data on diabetic retinopathy in people with diabetes experiencing a rapid, substantial decrease in HbA1c after going through intensive therapy were included. All articles were screened, data were extracted and methodological quality was evaluated by two independent reviewers using a priori criteria. A total of 346 articles were identified after the removal of duplicates. Data were extracted from 19 full-text articles with a total of 15,588 participants. Included studies varied considerably in terms of patient selection, timing and method of assessing the eye and retinopathy classification. EWDR was reported to occur in a wide range of prevalences; 3.3-47% of participants within 3-84 months after intensification of glycaemic control. Risk factors for EWDR included long duration of diabetes, long-term uncontrolled hyperglycemia, amplitude of and baseline retinopathy severity in both type 1 and type 2 diabetes. The occurrence of EWDR and progression of retinopathy were found to have an association with the amplitude of HbA1c reduction. EWDR has been described in a proportion of people with intensification of glycaemic control. However, the prevalence remains unclear because of methodological differences in the identified studies. Future interventional studies should report retinopathy and visual outcomes using standardized protocols.

19.
Nucleic Acids Res ; 50(D1): D1282-D1294, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34718737

RESUMO

The IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb; www.guidetopharmacology.org) is an open-access, expert-curated database of molecular interactions between ligands and their targets. We describe expansion in content over nine database releases made during the last two years, which has focussed on three main areas of infection. The COVID-19 pandemic continues to have a major impact on health worldwide. GtoPdb has sought to support the wider research community to understand the pharmacology of emerging drug targets for SARS-CoV-2 as well as potential targets in the host to block viral entry and reduce the adverse effects of infection in patients with COVID-19. We describe how the database rapidly evolved to include a new family of Coronavirus proteins. Malaria remains a global threat to half the population of the world. Our database content continues to be enhanced through our collaboration with Medicines for Malaria Venture (MMV) on the IUPHAR/MMV Guide to MALARIA PHARMACOLOGY (www.guidetomalariapharmacology.org). Antibiotic resistance is also a growing threat to global health. In response, we have extended our coverage of antibacterials in partnership with AntibioticDB.


Assuntos
Antibacterianos/farmacologia , Antimaláricos/farmacologia , Antivirais/farmacologia , Tratamento Farmacológico da COVID-19 , Antibacterianos/química , COVID-19/etiologia , Curadoria de Dados , Bases de Dados de Produtos Farmacêuticos , Humanos , Ligantes , Malária/tratamento farmacológico , Malária/metabolismo , Interface Usuário-Computador , Proteínas Virais/química , Proteínas Virais/metabolismo
20.
Br J Pharmacol ; 178 Suppl 1: S246-S263, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34529827

RESUMO

The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15540. Nuclear hormone receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.


Assuntos
Bases de Dados de Produtos Farmacêuticos , Farmacologia , Humanos , Ligantes , Proteínas de Membrana Transportadoras , Receptores Citoplasmáticos e Nucleares , Receptores Acoplados a Proteínas G
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