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Silicosis due to artificial stone (AS) has emerged over the last decade as an increasing global issue. We report the first eight UK cases. All were men; median age was 34 years (range 27-56) and median stone dust exposure was 12.5 years (range 4-40) but in 4 cases was 4-8 years. One is deceased; two were referred for lung transplant assessment. All cases were dry cutting and polishing AS worktops with inadequate safety measures. Clinical features of silicosis can closely mimic sarcoidosis. UK cases are likely to increase, with urgent action needed to identify cases and enforce regulations.
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Silicosis , Humanos , Silicosis/diagnóstico , Masculino , Persona de Mediana Edad , Adulto , Reino Unido , Polvo , Exposición Profesional/efectos adversos , Diagnóstico Diferencial , Tomografía Computarizada por Rayos XRESUMEN
Spectrally-resolved single-molecule localization microscopy (srSMLM) has emerged as a powerful tool for exploring the spectral properties of single emitters in localization microscopy. By simultaneously capturing the spatial positions and spectroscopic signatures of individual fluorescent molecules, srSMLM opens up the possibility of investigating an additional dimension in super-resolution imaging. However, appropriate and dedicated tools are required to fully capitalize on the spectral dimension. Here, we propose the application of the spectral phasor analysis as an effective method for summarizing and analyzing the spectral information obtained from srSMLM experiments. The spectral phasor condenses the complete spectrum of a single emitter into a two-dimensional space, preserving key spectral characteristics for single-molecule spectral exploration. We demonstrate the effectiveness of spectral phasor in efficiently classifying single Nile Red fluorescence emissions from largely overlapping cyanine fluorescence signals in dual-color PAINT experiments. Additionally, we employed spectral phasor with srSMLM to reveal subtle alterations occurring in the membrane of Gram-positive Enterococcus hirae in response to gramicidin exposure, a membrane-perturbing antibiotic treatment. Spectral phasor provides a robust, model-free analytic tool for the detailed analysis of the spectral component of srSMLM, enhancing the capabilities of multi-color spectrally-resolved single-molecule imaging.
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Microscopía Fluorescente , Imagen Individual de Molécula , Imagen Individual de Molécula/métodos , Microscopía Fluorescente/métodos , Colorantes Fluorescentes/química , Gramicidina/química , Oxazinas/químicaRESUMEN
BACKGROUND: Over 80% of blindness in Kenya is due to curable or preventable causes and 7.5 m Kenyans currently need eye services. Embedding sociodemographic data collection into screening programmes could help identify the groups facing systematic barriers to care. We aimed to determine the sociodemographic characteristics that were associated with access among patients diagnosed with an eye problem and referred for treatment in the Vision Impact Programme, currently operating in Meru County. METHOD: We used an embedded, pragmatic, cross-sectional design. A list of sociodemographic questions was developed with input from key stakeholders. The final question set included the following domains: age, gender, religion, marital status, disability, education, occupation, income, housing, assets, and health insurance. These were integrated into an app that is used to screen, refer, and check-in (register) participants within a major eye screening programme. We gathered data from 4,240 people who screened positive and were referred to their local outreach treatment clinic. We used logistic regression to identify which groups were facing the greatest barriers to accessing care. RESULTS: A quarter of those screened between April - July 2023 were found to have an eye problem and were referred, however only 46% of these people were able to access care. In our fully adjusted model, at the 0.05 level there were no statistically significant differences in the odds of attendance within the domains of disability, health insurance, housing, income, or religion. Strong evidence (p < 0.001) was found of an association between access and age, gender, and occupation; with males, younger adults, and those working in sales, services and manual jobs the least likely to receive care. CONCLUSIONS: Access to essential eye services is low and unequal in Meru, with less than a third of those aged 18-44 receiving the care they need. Future work should explore the specific barriers faced by this group.
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Accesibilidad a los Servicios de Salud , Humanos , Estudios Transversales , Kenia , Masculino , Femenino , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Adulto , Persona de Mediana Edad , Adolescente , Adulto Joven , Anciano , Servicios de Salud Comunitaria , Modelos Logísticos , NiñoRESUMEN
PURPOSE: Uncorrected refractive error is the leading cause of vision impairment globally; however, little attention has been given to equity and access to services. This study aimed to identify and prioritise: (1) strategies to address inequity of access to refractive error services and (2) population groups to target with these strategies in five sub-regions within the Western Pacific. METHODS: We invited eye care professionals to complete a two-round online prioritisation process. In round 1, panellists nominated population groups least able to access refractive error services, and strategies to improve access. Responses were summarised and presented in round 2, where panellists ranked the groups (by extent of difficulty and size) and strategies (in terms of reach, acceptability, sustainability, feasibility and equity). Groups and strategies were scored according to their rank within each sub-region. RESULTS: Seventy five people from 17 countries completed both rounds (55% women). Regional differences were evident. Indigenous peoples were a priority group for improving access in Australasia and Southeast Asia, while East Asia identified refugees and Oceania identified rural/remote people. Across the five sub-regions, reducing out-of-pocket costs was a commonly prioritised strategy for refraction and spectacles. Australasia prioritised improving cultural safety, East Asia prioritised strengthening school eye health programmes and Oceania and Southeast Asia prioritised outreach to rural areas. CONCLUSION: These results provide policy-makers, researchers and funders with a starting point for context-specific actions to improve access to refractive error services, particularly among underserved population groups who may be left behind in existing private sector-dominated models of care.
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Técnica Delphi , Errores de Refracción , Humanos , Errores de Refracción/terapia , Masculino , Femenino , Adulto , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Persona de Mediana Edad , Disparidades en Atención de Salud/estadística & datos numéricosRESUMEN
BACKGROUND: Health inequalities are ubiquitous, and as countries seek to expand service coverage, they are at risk of exacerbating existing inequalities unless they adopt equity-focused approaches to service delivery. MAIN TEXT: Our team has developed an equity-focused continuous improvement model that reconciles prioritisation of disadvantaged groups with the expansion of service coverage. Our new approach is based on the foundations of routinely collecting sociodemographic data; identifying left-behind groups; engaging with these service users to elicit barriers and potential solutions; and then rigorously testing these solutions with pragmatic, embedded trials. This paper presents the rationale for the model, a holistic overview of how the different elements fit together, and potential applications. Future work will present findings as the model is operationalised in eye-health programmes in Botswana, India, Kenya, and Nepal. CONCLUSION: There is a real paucity of approaches for operationalising equity. By bringing a series of steps together that force programme managers to focus on groups that are being left behind, we present a model that can be used in any service delivery setting to build equity into routine practice.
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Atención a la Salud , Disparidades en Atención de Salud , Humanos , Botswana , India , Kenia , Nepal , Poblaciones VulnerablesRESUMEN
PURPOSE: To investigate if topical chlorhexidine 0.2%, which is low cost and easy to formulate, is noninferior to topical natamycin 5% for the treatment of filamentous fungal keratitis. DESIGN: Randomized controlled, single-masked, noninferiority clinical trial. PARTICIPANTS: Adults attending a tertiary-level ophthalmic hospital in Nepal with filamentous fungal infection confirmed on smear or confocal microscopy. METHODS: Participants were randomly allocated to receive topical chlorhexidine 0.2% or topical natamycin 5%. Primary analysis (intention-to-treat) was by linear regression, using baseline logarithm of the minimum angle of resolution (logMAR) best spectacle-corrected visual acuity (BSCVA) and treatment arm as prespecified covariates. Mixed fungal-bacterial infections were excluded from the primary analysis but included in secondary analyses and secondary safety-related outcomes. The noninferiority margin was 0.15 logMAR. This trial was registered with ISRCTN, number ISRCTN14332621. MAIN OUTCOME MEASURES: The primary outcome measure was BSCVA at 3 months. Secondary outcome measures included perforation or therapeutic penetrating keratoplasty by 90 days. RESULTS: Between June 3, 2019, and November 9, 2020, 354 eligible participants were enrolled and randomly assigned: 178 to chlorhexidine and 176 to natamycin. Primary outcome data were available for 153 and 151 of the chlorhexidine and natamycin groups, respectively. Of these, mixed bacterial-fungal infections were found in 20 cases (12/153 chlorhexidine, 8/151 natamycin) and excluded from the primary analysis. Therefore, 284 patients were assessed for the primary outcome (141 chlorhexidine, 143 natamycin). We did not find evidence to suggest chlorhexidine was noninferior to natamycin and in fact found strong evidence to suggest that natamycin-treated participants had significantly better 3-month BSCVA than chlorhexidine-treated participants, after adjusting for baseline BSCVA (regression coefficient, -0.30; 95% confidence interval [CI], -0.42 to -0.18; P < 0.001). There were more perforations and emergency corneal grafts in the chlorhexidine arm (24/175, 13.7%) than in the natamycin arm (10/173, 5.8%; P = 0.018, mixed infections included), whereas natamycin-treated cases were less likely to perforate or require an emergency corneal graft, after adjusting for baseline ulcer depth (odds ratio, 0.34; 95% CI, 0.15-0.79; P = 0.013). CONCLUSIONS: Treatment with natamycin is associated with significantly better visual acuity, with fewer adverse events, compared with treatment with chlorhexidine. Natamycin remains the preferred first-line monotherapy treatment for filamentous fungal keratitis.
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Úlcera de la Córnea , Infecciones Fúngicas del Ojo , Queratitis , Micosis , Adulto , Antifúngicos/uso terapéutico , Clorhexidina/uso terapéutico , Úlcera de la Córnea/tratamiento farmacológico , Úlcera de la Córnea/microbiología , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Infecciones Fúngicas del Ojo/microbiología , Hongos , Humanos , Queratitis/tratamiento farmacológico , Queratitis/microbiología , Micosis/microbiología , Natamicina , Nepal , Resultado del Tratamiento , VoriconazolRESUMEN
PURPOSE: To assess the diversity of leadership bodies of member organisations of the International Council of Ophthalmology (ICO) and the World Council of Optometry (WCO) in terms of: (1) the proportion who are women in all world regions, and (2) the proportion who are ethnic minority women and men in Eurocentric high-income regions. METHODS: We undertook a cross-sectional study of board members and chairs of ICO and WCO member organisations using a desk-based assessment of member organisation websites during February and March 2020. Gender and ethnicity of board members and chairs were collected using a combination of validated algorithmic software and manual assessment, based on names and photographs where available. Gender proportions were calculated across Global Burden of Disease super-regions, and gender and ethnicity proportions in the high-income regions of Australasia, North America and Western Europe. RESULTS: Globally, approximately one in three board members were women for both ICO (34%) and WCO (35%) members, and one in three ICO (32%) and one in five WCO (22%) chairpersons were women. Women held at least 50% of posts in only three of the 26 (12%) leadership structures assessed; these were based in Latin America and the Caribbean (59% of WCO board positions held by women, and 56% of WCO chairs), and Southeast Asia, East Asia and Oceania (55% of ICO chairs). In the Eurocentric high-income regions, white men held more than half of all board (56%) and chair (58%) positions and white women held a further quarter of positions (26% of board and 27% of chair positions). Ethnic minority women held the fewest number of board (6%) and chair (7%) positions. CONCLUSIONS: Improvements in gender parity are needed in member organisations of the WCO and ICO across all world regions. In high-income regions, efforts to address inequity at the intersection of gender and ethnicity are also needed. Potential strategies to enable inclusive leadership must be centred on structurally enabled diversity and inclusion goals to support the professional progression of women, and people from ethnic minorities in global optometry and ophthalmology.
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Algoritmos , Etnicidad , Liderazgo , Oftalmología/ética , Optometría/ética , Sociedades Médicas/ética , Estudios Transversales , Femenino , Salud Global , Humanos , Masculino , Estudios RetrospectivosRESUMEN
BACKGROUND: Cataract is a leading cause of blindness and vision impairment globally. Cataract surgery is one of the most frequently performed operations worldwide, but good quality services are not universally available. This scoping review aims to summarise the nature and extent of published literature on interventions to improve the quality of services for age-related cataract globally. METHODS: We used the dimensions of quality adopted by WHO-effectiveness, safety, people-centredness, timeliness, equity, integration and efficiency-to which we added planetary health. On 17 November 2019, we searched MEDLINE, Embase and Global Health for manuscripts published since 1990, without language or geographic restrictions. We included studies that reported quality-relevant interventions and excluded studies focused on technical aspects of surgery or that only involved children (younger than 18 years). Screening of titles/abstracts, full-text review and data extraction were performed by two reviewers independently. Studies were grouped thematically and results synthesised narratively. RESULTS: Most of the 143 included studies were undertaken in high-income countries (n = 93, 65%); 29 intervention groups were identified, most commonly preoperative education (n = 17, 12%) and pain/anxiety management (n = 16, 11%). Efficiency was the quality element most often assessed (n = 58, 41%) followed by people-centredness (n = 40, 28%), while integration (n = 4) and timeliness (n = 3) were infrequently reported, and no study reported outcomes related to planetary health. CONCLUSION: Evidence on interventions to improve quality of cataract services shows unequal regional distribution. There is an urgent need for more evidence relevant to low- and middle-income countries as well as across all quality elements, including planetary health.
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Extracción de Catarata , Catarata , Catarata/epidemiología , Catarata/terapia , Niño , Salud Global , HumanosRESUMEN
As progress to eliminate trachoma is made, addressing hard-to-reach communities becomes of greater significance. Areas in Tanzania, inhabited by the Maasai, remain endemic for trachoma. This study assessed the effectiveness of Mass Drug Administration (MDA) through an ethnographic study of trachoma amongst a Maasai community. The MDA experience in the context of the livelihoods of the Maasai in a changing political economy was explored using participant observation and household interviews. Factors influencing MDA effectiveness within five domains were analysed. 1) Terrain of intervention: Human movement hindered MDA, including seasonal migration, domestic chores, grazing and school. Encounters with wildlife were significant. 2) Socio-cultural factors and community agency: Norms around pregnancy led women to accept the drug but hide refusal to swallow the drug. Timing of Community Drug Distributor (CDD) visits conflicted with livestock grazing. Refusals occurred among the ilmurrani age group and older women. Mistrust significantly hindered uptake of drugs. 3) Strategies and motivation of drug distributors: Maa-speaking CDDs were critical to effective drug delivery. Maasai CDDs, whilst motivated, faced challenges of distances, encounters with wildlife and compensation. 4) Socio-materiality of technology: Decreases in side-effects over years have improved trust in the drug. Restrictions to swallowing drugs and/or water were relevant to post-partum women and the ilmurrani. 5) History and health governance: Whilst perceptions of the programme were positive, communities questioned government priorities for resources for hospitals, medicines, clean water and roads. They complained of a lack of information and involvement of community members in health care services. With elimination in sight, hard-to-reach communities are paramount as these are probably the last foci of infection. Effective delivery of MDA programmes in such communities requires a critical understanding of community experiences and responses that can inform tailored approaches to trachoma control. Application of a critical social science perspective should be embedded in planning and evaluation of all NTD programmes.
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Tracoma , Anciano , Composición Familiar , Femenino , Humanos , Administración Masiva de Medicamentos , Grupos de Población , Tanzanía/epidemiología , Tracoma/tratamiento farmacológico , Tracoma/epidemiología , Tracoma/prevención & controlRESUMEN
Defects in the motor domain of kinesin family member 1A (KIF1A), a neuron-specific ATP-dependent anterograde axonal transporter of synaptic cargo, are well-recognized to cause a spectrum of neurological conditions, commonly known as KIF1A-associated neurological disorders (KAND). Here, we report one mutation-negative female with classic Rett syndrome (RTT) harboring a de novo heterozygous novel variant [NP_001230937.1:p.(Asp248Glu)] in the highly conserved motor domain of KIF1A. In addition, three individuals with severe neurodevelopmental disorder along with clinical features overlapping with KAND are also reported carrying de novo heterozygous novel [NP_001230937.1:p.(Cys92Arg) and p.(Pro305Leu)] or previously reported [NP_001230937.1:p.(Thr99Met)] variants in KIF1A. In silico tools predicted these variants to be likely pathogenic, and 3D molecular modeling predicted defective ATP hydrolysis and/or microtubule binding. Using the neurite tip accumulation assay, we demonstrated that all novel KIF1A variants significantly reduced the ability of the motor domain of KIF1A to accumulate along the neurite lengths of differentiated SH-SY5Y cells. In vitro microtubule gliding assays showed significantly reduced velocities for the variant p.(Asp248Glu) and reduced microtubule binding for the p.(Cys92Arg) and p.(Pro305Leu) variants, suggesting a decreased ability of KIF1A to move along microtubules. Thus, this study further expanded the phenotypic characteristics of KAND individuals with pathogenic variants in the KIF1A motor domain to include clinical features commonly seen in RTT individuals.
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Cinesinas , Mutación Missense , Familia , Femenino , Heterocigoto , Humanos , Cinesinas/genética , Mutación , Trastornos del Neurodesarrollo/genética , Síndrome de Rett/genéticaRESUMEN
Childhood pulmonary diseases not only cause childhood morbidity and mortality but also can cause long-term pulmonary impairment. The clinical management of many childhood pulmonary diseases is hampered by a limited understanding of the underlying pathophysiological mechanisms. Flow cytometry, which can be used to phenotype individual cell populations or isolate cells for downstream analysis, represents a crucial technology that can help to elucidate the pathophysiology of these conditions. Here, we describe a flow cytometry-based method for purification and characterization of cell populations in BAL from children. This includes assessment of the effect of cryopreservation on cell phenotype and frequency, a knowledge gap recently identified by an American Thoracic Society report on flow cytometry in lung samples. To our knowledge, this is the first study to simultaneously quantify alveolar macrophages, T cells (CD4 and CD8), B cells, natural killer cells, dendritic cells, granulocytes, and monocytes (CD16+/CD16-) in the BAL of children. The protocols described can be used to advance investigation of the pathophysiology of childhood pulmonary diseases.
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Líquido del Lavado Bronquioalveolar/inmunología , Lavado Broncoalveolar/métodos , Preescolar , Femenino , Citometría de Flujo/métodos , Granulocitos/inmunología , Humanos , Lactante , Recuento de Leucocitos/métodos , Pulmón/inmunología , Enfermedades Pulmonares/inmunología , Macrófagos Alveolares/inmunología , Masculino , Monocitos/inmunología , Análisis de la Célula Individual/métodos , Linfocitos T/inmunologíaRESUMEN
Trachoma is initiated during childhood following repeated conjunctival infection with Chlamydia trachomatis, which causes a chronic inflammatory response in some individuals that leads to scarring and in-turning of the eyelids in later life. There is currently no treatment to halt the progression of scarring trachoma due to an incomplete understanding of disease pathogenesis. A cohort study was performed in northern Tanzania in 616 children aged 6 to 10 years at enrollment. Every 3 months for 4 years, children were examined for clinical signs of trachoma, and conjunctival swabs were collected for C. trachomatis detection and to analyze the expression of 46 immunofibrogenic genes. Data were analyzed in relation to progressive scarring status between baseline and the final time point. Genes that were significantly associated with scarring progression included those encoding proinflammatory chemokines (CXCL5, CCL20, CXCL13, and CCL18), cytokines (IL23A, IL19, and IL1B), matrix modifiers (MMP12 and SPARCL1), immune regulators (IDO1, SOCS3, and IL10), and a proinflammatory antimicrobial peptide (S100A7). In response to C. trachomatis infection, IL23A and PDGF were significantly upregulated in scarring progressors relative to in nonprogressors. Our findings highlight the importance of innate proinflammatory signals from the epithelium and implicate interleukin 23A (IL-23A)-responsive cells in driving trachomatous scarring, with potential key mechanistic roles for PDGFB, MMP12, and SPARCL1 in orchestrating fibrosis.
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Cicatriz/patología , Cicatriz/fisiopatología , Conjuntiva/patología , Inmunidad Innata , Factores Inmunológicos/biosíntesis , Tracoma/patología , Tracoma/fisiopatología , Niño , Chlamydia trachomatis/crecimiento & desarrollo , Femenino , Perfilación de la Expresión Génica , Humanos , Factores Inmunológicos/genética , Estudios Longitudinales , Masculino , TanzaníaRESUMEN
Chlamydia trachomatis is the world's most prevalent bacterial sexually transmitted infection and leading infectious cause of blindness, yet it is one of the least understood human pathogens, in part due to the difficulties of in vitro culturing and the lack of available tools for genetic manipulation. Genome sequencing has reinvigorated this field, shedding light on the contemporary history of this pathogen. Here, we analyze 563 full genomes, 455 of which are novel, to show that the history of the species comprises two phases, and conclude that the currently circulating lineages are the result of evolution in different genomic ecotypes. Temporal analysis indicates these lineages have recently expanded in the space of thousands of years, rather than the millions of years as previously thought, a finding that dramatically changes our understanding of this pathogen's history. Finally, at a time when almost every pathogen is becoming increasingly resistant to antimicrobials, we show that there is no evidence of circulating genomic resistance in C. trachomatis.
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Chlamydia trachomatis/genética , Farmacorresistencia Bacteriana/genética , Ecotipo , Evolución Molecular , Genoma Bacteriano , Chlamydia trachomatis/aislamiento & purificación , Femenino , Humanos , MasculinoRESUMEN
Microbial keratitis is a severe, sight-threatening condition caused by various pathogens. Eyedrops are the standard delivery modality for treating these disorders; however, blinking reflex, elevated tear production, and nasolacrimal drainage eliminate much of the instilled dose within a few seconds. Therefore, eyedrops must be applied repeatedly for prolonged periods. The present study aimed to probe more effective ocular delivery of chlorhexidine based upon drug-loaded hydrogel contact lenses and ß-cyclodextrin (ß-CD), while also determining the effect of constant irrigation with simulated tear fluid (STF) in in vitro experiments. Chlorhexidine digluconate (as 0.2 and 2% solutions, ß-CD inclusion complexes, and loaded hydrogel contact lenses) were applied to enucleated porcine eyes as single or multiple 10 µL doses, or as drug-loaded contact lenses, with and without ß-CD. The corneas were then excised and drug-extracted quantified by high-performance liquid chromatography (HPLC). The effect of constant irrigation by STF was evaluated to test the effect of increased tear production on corneal delivery. Potential antimicrobial activity of the delivered drug was also assessed. Results showed that drug-loaded contact lenses delivered the greatest amount of chlorhexidine into the cornea over a 24 h period, while the eyedrop solution comparator delivered the least. The ß-CD significantly enhanced chlorhexidine delivery to the cornea from eyedrop solution, although contact lenses loaded with chlorhexidine-ß-CD failed to enhance delivery. ß-CD within the hydrogel matrix impeded drug release. Constant irrigation with STF significantly reduced the amount of drug delivered to the cornea in all cases. Chlorhexidine retained antimicrobial activity in all delivery methods. Hydrogel contact lenses loaded with chlorhexidine delivered significantly higher levels to the cornea compared to eyedrops, either multiple hourly doses or a single dose. They also offer reduced application, in particular, to a nonulcerated corneal infection. Finally, the importance of fully accounting for tear production in in vitro ocular delivery experiments was highlighted.
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Clorhexidina/administración & dosificación , Córnea/efectos de los fármacos , Lágrimas/efectos de los fármacos , beta-Ciclodextrinas/administración & dosificación , Animales , Antiinfecciosos/administración & dosificación , Lentes de Contacto , Sistemas de Liberación de Medicamentos/métodos , Hidrogeles/administración & dosificación , Soluciones Oftálmicas/administración & dosificación , PorcinosRESUMEN
IMPORTANCE: In vivo confocal microscopy (IVCM) provides high-resolution images of the ocular surface and has been validated in trachomatous conjunctival scarring. BACKGROUND: This study used IVCM to identify parameters associated with clinical scarring progression. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 800 participants in Northern Tanzania with trachomatous scarring. METHODS: Participants underwent clinical examination, photography and IVCM at baseline and 24-months. Clinical progression of scarring was defined by comparing baseline and 24-month photographs. Masked grading of IVCM images was used to identify scarring at both time points. Multivariable logistic regression was used to assess factors associated with clinical progression. MAIN OUTCOME MEASURES: Risk factors associated with clinical scarring progression. RESULTS: Clinical and IVCM assessment of 800 participants were performed at baseline, with 617 (77.1%) seen at 24-months. Of these, 438 of 617 (71.0%) had gradable IVCM images at both time points and 342 of 438 (78.1%) of these could be graded as showing definite clinical progression or no progression on image comparison. Clinical progression was found to occur in 79 of 342 (23.1%). After adjusting for age and sex, clinical scarring progression was strongly associated with a high IVCM connective tissue organization score at both baseline (odds ratio [OR] = 1.84 for each increase in scarring category; P = .002) and 24-months (OR = 1.60; P = .02). Dendritiform cells present at 24-months were strongly associated with clinical scarring progression after adjustment (OR = 2.62; P = .03). CONCLUSIONS AND RELEVANCE: Quantitative IVCM parameters, including connective tissue organization score and the presence of dendritiform cells, are associated with disease progression and may be useful markers in trachoma and other conjunctival fibrotic diseases.
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Gonorrea , Tracoma , Cicatriz/diagnóstico , Humanos , Microscopía Confocal , Estudios Prospectivos , Tracoma/diagnóstico , Tracoma/epidemiologíaRESUMEN
Fungal keratitis is a common but severe eye infection in tropical and subtropical areas of the world. In regions with a temperate climate, the frequency of infection is rising in patients with contact lenses and following trauma. Early and adequate therapy is important to prevent disease progression and loss of vision. The management of Fusarium keratitis is complex, and the optimal treatment is not well defined. We investigated the in vitro activity of chlorhexidine and seven antifungal agents against a well-characterized collection of Fusarium isolates recovered from patients with Fusarium keratitis. The fungus culture collection of the Center of Expertise in Mycology Radboudumc/CWZ was searched for Fusarium isolates that were cultured from cornea scrapings, ocular biopsy specimens, eye swabs, and contact lens fluid containers from patients with suspected keratitis. The Fusarium isolates that were cultured from patients with confirmed keratitis were all identified using conventional and molecular techniques. Antifungal susceptibility testing was performed according to the EUCAST broth microdilution reference method. The antifungal agents tested included amphotericin B, voriconazole, posaconazole, miconazole, natamycin, 5-fluorocytosine, and caspofungin. In addition, the activity of chlorhexidine was determined. The fungal culture collection contained 98 Fusarium isolates of confirmed fungal keratitis cases from 83 Dutch patients and 15 Tanzanian patients. The isolates were collected between 2007 and 2017. Fusarium oxysporum (n = 24, 24.5%) was the most frequently isolated species followed by Fusarium solanisensu stricto (n = 18, 18.4%) and Fusarium petroliphilum (n = 11, 11.2%). Amphotericin B showed the most favorable in vitro inhibition of Fusarium species followed by natamycin, voriconazole, and chlorhexidine, while 5-fluorocytosine, posaconazole, miconazole, and caspofungin showed no relevant inhibiting effect. However, chlorhexidine showed fungicidal activity against 90% of F. oxysporum strains and 100% of the F. solani strains. Our study supports the clinical efficacy of chlorhexidine and therefore warrants its further clinical evaluation for primary therapy of fungal keratitis, particularly in low and middle income countries where fungal keratitis is much more frequent and, currently, antifungal eye drops are often unavailable.
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Antifúngicos/farmacología , Clorhexidina/farmacología , Fusarium/efectos de los fármacos , Fusarium/patogenicidad , Queratitis/microbiología , Anfotericina B/farmacología , Caspofungina/farmacología , Flucitosina/farmacología , Fusariosis/microbiología , Humanos , Miconazol/farmacología , Pruebas de Sensibilidad Microbiana , Natamicina/farmacología , Triazoles/farmacología , Voriconazol/farmacologíaRESUMEN
BACKGROUND: In 2013 five polar explorers attempted to complete the first Trans-Antarctic Winter Traverse (TAWT). This study presents the ophthalmological findings for this group, who overwintered in Antarctica as part of the White Mars Human Science Protocol. Antarctic crews are exposed to extreme cold, chronic hypoxia and altered day-night cycles. Previous studies of Antarctic explorers have focused on the prolonged effect of ultraviolet radiation including the development of ultraviolet keratitis and accelerated cataract formation. This is the first study of its kind to investigate the effect of overwintering in Antarctica on the human eye. METHODS: Pre and post-expedition clinical observations were made including visual acuity, contrast sensitivity, colour vision, auto-refraction, subjective refraction, retinal examination, retinal autofluoresence and retinal thickness, which were graded for comparison. During the expedition additional observations were made on a monthly basis including LogMAR visual acuity, autorefraction and intraocular pressure. RESULTS: No significant differences between pre and post-expedition observations were found, including visual acuity, contrast sensitivity, colour vision, refraction, visual fields, intraocular pressure and retinal examination. There was a small but statistically significant decrease in retinal thickness across all regions of the retina, except for the macular and fovea, in all explorers. Intra-expedition observations remained within normal limits. CONCLUSION: Reassuringly, the human eye remains largely unchanged by exposure to the extreme conditions encountered during the Antarctic winter, however, further research is needed to investigate changes in retinal thickness. This may have implications for scientists who spend prolonged periods of time in the polar regions, as well as those who have prolonged exposure to the extreme cold or chronic hypoxia in other settings.
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Sensibilidad de Contraste/efectos de la radiación , Exposición a Riesgos Ambientales/efectos adversos , Oftalmopatías/etiología , Presión Intraocular/efectos de la radiación , Rayos Ultravioleta/efectos adversos , Agudeza Visual/efectos de la radiación , Campos Visuales/efectos de la radiación , Adulto , Regiones Antárticas , Oftalmopatías/diagnóstico , Oftalmopatías/epidemiología , Femenino , Estudios de Seguimiento , Fóvea Central/patología , Fóvea Central/efectos de la radiación , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estaciones del Año , Tomografía de Coherencia Óptica , Reino Unido/epidemiologíaRESUMEN
PURPOSE: Unfavorable outcomes after trachomatous trichiasis (TT) surgery are undermining the global trachoma elimination effort. This analysis investigates predictors of postoperative TT (PTT), eyelid contour abnormalities (ECAs), and granuloma in the 2 most common TT surgery procedures: posterior lamellar tarsal rotation (PLTR) and bilamellar tarsal rotation (BLTR). DESIGN: Secondary data analysis from a randomized, controlled, single-masked clinical trial. PARTICIPANTS: A total of 1000 patients with TT, with lashes touching the eye or evidence of epilation, in association with tarsal conjunctival scarring. METHODS: Participants were randomly allocated and received BLTR (n = 501) or PLTR (n = 499) surgery. Disease severity at baseline, surgical incisions, sutures, and corrections were graded during and immediately after surgery. Participants were examined at 6 and 12 months by assessors masked to allocation. MAIN OUTCOME MEASURES: Predictors of PTT, ECA, and granuloma. RESULTS: Data were available for 992 (99.2%) trial participants (496 in each arm). There was strong evidence that performing more peripheral dissection with scissors in PLTR (odd ratio [OR], 0.70; 95% confidence interval [CI], 0.54-0.91; P = 0.008) and BLTR (OR, 0.83; 95% CI, 0.72-0.96; P = 0.01) independently protected against PTT. Baseline major trichiasis and mixed location lashes and immediate postoperative central undercorrection independently predicted PTT in both surgical procedures. Peripheral lashes in PLTR (OR, 5.91; 95% CI, 1.48-23.5; P = 0.01) and external central incision height ≥4 mm in BLTR (OR, 2.89; 95% CI, 1.55-5.41; P = 0.001) were independently associated with PTT. Suture interval asymmetry of >2 mm (OR, 3.18; 95% CI, 1.31-7.70; P = 0.01) in PLTR and baseline conjunctival scarring in BLTR (OR, 1.72; 95% CI, 1.06-2.81; P = 0.03) were independently associated with ECA. Older age was independently associated with ECA in both PLTR (P value for trend < 0.0001) and BLTR (P value for trend = 0.03). There was substantial intersurgeon variability in ECA rates for both PLTR (range, 19.0%-36.2%) and BLTR (range, 6.1%-28.7%) procedures. In PLTR surgery, irregular posterior lamellar incision at the center of the eyelid (OR, 6.72; 95% CI, 1.55-29.04; P = 0.01) and ECA (OR, 3.08; 95% CI, 1.37-6.94; P = 0.007) resulted in granuloma formation. CONCLUSIONS: Poor postoperative outcomes in TT surgery were associated with inadequate peripheral dissection, irregular incision, asymmetric suture position and tension, inadequate correction, and lash location. Addressing these will improve TT surgical outcomes.
Asunto(s)
Párpados/cirugía , Procedimientos Quirúrgicos Oftalmológicos , Tracoma/cirugía , Triquiasis/cirugía , Adolescente , Adulto , Anciano , Femenino , Granuloma/etiología , Humanos , Complicaciones Intraoperatorias , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Factores de Riesgo , Método Simple Ciego , Tracoma/etiología , Tracoma/fisiopatología , Resultado del Tratamiento , Triquiasis/etiología , Triquiasis/fisiopatología , Adulto JovenRESUMEN
A series of lanthanide complexes bearing organic radical ligands, [Ln(CpR)2(bipy·-)] [Ln = La, CpR = Cptt (1); Ln = Ce, CpR = Cptt (2); Ln = Ce, CpR = Cpâ³ (3); Ln = Ce, CpR = Cpâ´ (4)] [Cptt = {C5H3tBu2-1,3}-; Cpâ³ = {C5H3(SiMe3)2-1,3}-; Cpâ´ = {C5H2(SiMe3)3-1,2,4}-; bipy = 2,2'-bipyridyl], were prepared by reduction of [Ln(CpR)2(µ-I)]2 or [Ce(Cpâ´)2(I) (THF)] with KC8 in the presence of bipy (THF = tetrahydrofuran). Complexes 1-4 were thoroughly characterized by structural, spectroscopic, and computational methods, together with magnetism and cyclic voltammetry, to define an unambiguous Ln(III)/bipy·- radical formulation. These complexes can act as selective reducing agents; for example, the reaction of 3 with benzophenone gives [{Ce(Cp")2(bipy)}2{κ2-O,O'-OPhC(C6H5)CPh2O}] (7), a rare example of a "head-to-tail" coupling product. We estimate the intramolecular exchange coupling for 2-4 using multiconfigurational and spin Hamiltonian methods and find that the commonly used Lines-type isotropic exchange is not appropriate, even for single 4f e-/organic radical pairs.
RESUMEN
BACKGROUND: The epidemic rise of diabetes carries major negative public health and economic consequences particularly for low and middle-income countries. The highest predicted percentage growth in diabetes is in the sub-Saharan Africa (SSA) region where to date there has been no data on the incidence of diabetic retinopathy from population-based cohort studies and minimal data on incident diabetes. The primary aims of this study were to estimate the cumulative six-year incidence of Diabetes Mellitus (DM) and DR (Diabetic Retinopathy), respectively, among people aged ≥50 years in Kenya. METHODS: Random cluster sampling with probability proportionate to size were used to select a representative cross-sectional sample of adults aged ≥50 years in 2007-8 in Nakuru District, Kenya. A six-year follow-up was undertaken in 2013-14. On both occasions a comprehensive ophthalmic examination was performed including LogMAR visual acuity, digital retinal photography and independent grading of images. Data were collected on general health and risk factors. The primary outcomes were the incidence of diabetes mellitus and the incidence of diabetic retinopathy, which were calculated by dividing the number of events identified at 6-year follow-up by the number of people at risk at the beginning of follow-up. Age-adjusted risk ratios of the outcomes (DM and DR respectively) were estimated for each covariate using a Poisson regression model with robust error variance to allow for the clustered design and including inverse-probability weighting. RESULTS: At baseline, 4414 participants aged ≥50 years underwent complete examination. Of the 4104 non-diabetic participants, 2059 were followed-up at six-years (50 · 2%). The cumulative incidence of DM was estimated at 61 · 0 per 1000 (95% CI: 50 · 3-73 · 7) in people aged ≥50 years. The cumulative incidence of DR in the sample population was estimated at 15 · 8 per 1000 (95% CI: 9 · 5-26 · 3) among those without DM at baseline, and 224 · 7 per 1000 (116.9-388.2) among participants with known DM at baseline. A multivariable risk factor analysis demonstrated increasing age and higher body mass index to be associated with incident DM. DR incidence was strongly associated with increasing age, and with higher BMI, urban dwelling and higher socioeconomic status. CONCLUSIONS: Diabetes Mellitus is a growing public health concern with a major complication of diabetic retinopathy. In a population of 1 · 6 million, of whom 150,000 are ≥50 years, we estimated that 1650 people aged ≥50 develop DM per year, and 450 develop DR. Strengthening of health systems is necessary to reduce incident diabetes and its complications in this and similar settings.