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1.
PLoS One ; 17(5): e0265955, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35507583

RESUMO

Damage from infestations of Lymantria dispar L. in oak-dominated stands and southern pine beetle (Dendroctonus frontalis Zimmermann) in pine-dominated stands have far exceeded impacts of other disturbances in forests of the mid-Atlantic Coastal Plain over the last two decades. We used forest census data collected in undisturbed and insect-impacted stands combined with eddy covariance measurements made pre- and post-disturbance in oak-, mixed and pine-dominated stands to quantify how these infestations altered forest composition, structure and carbon dynamics in the Pinelands National Reserve of southern New Jersey. In oak-dominated stands, multi-year defoliation during L. dispar infestations resulted in > 40% mortality of oak trees and the release of pine saplings and understory vegetation, while tree mortality was minimal in mixed and pine-dominated stands. In pine-dominated stands, southern pine beetle infestations resulted in > 85% mortality of pine trees but had minimal effect on oaks in upland stands or other hardwoods in lowland stands, and only rarely infested pines in hardwood-dominated stands. Because insect-driven disturbances are both delaying and accelerating succession in stands dominated by a single genus but having less effect in mixed-composition stands, long-term disturbance dynamics are favoring the formation and persistence of uneven age oak-pine mixedwood stands. Changes in forest composition may have little impact on forest productivity and evapotranspiration; although seasonal patterns differ, with highest daily rates of net ecosystem production (NEP) during the growing season occurring in an oak-dominated stand and lowest in a pine-dominated stand, integrated annual rates of NEP are similar among oak-, mixed and pine-dominated stands. Our research documents the formation of mixedwood stands as a consequence of insect infestations in the mid-Atlantic region and suggests that managing for mixedwood stands could reduce damage to forest products and provide greater continuity in ecosystem functioning.


Assuntos
Besouros , Pinus , Quercus , Animais , Ecossistema , Florestas , Árvores
2.
Ecol Appl ; : e2637, 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35426200

RESUMO

Over the past century, fire suppression has facilitated broad ecological changes in the composition, structure, and function of fire-dependent landscapes throughout the eastern US, which are in decline. These changes have likely contributed mechanistically to the enhancement of habitat conditions that favor pathogen-carrying tick species, key wildlife hosts of ticks, and interactions that have fostered pathogen transmission among them and to humans. While the long-running paradigm for limiting human exposure to tick-borne diseases focuses responsibility on individual prevention, the continued expansion of medically important tick populations, increased incidence of tick-borne disease in humans, and emergence of novel tick-borne diseases highlights the need for additional approaches to stem this public health challenge. Another approach that has the potential to be a cost-effective and widely applied but that remains largely overlooked is the use of prescribed fire to ecologically restore degraded landscapes that favor ticks and pathogen transmission. We examine the ecological role of fire and its effects on ticks within the eastern United States, especially examining the life cycles of forest-dwelling ticks, shifts in regional-scale fire use over the past century, and the concept that frequent fire may have helped moderate tick populations and pathogen transmission prior to the so-called fire-suppression era that has characterized the past century. We explore mechanisms of how fire and ecological restoration can reduce ticks, the potential for incorporating the mechanisms into the broader strategy for managing ticks, and the challenges, limitations, and research needs of prescribed burning for tick reduction.

3.
Eye (Lond) ; 2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-35087213

RESUMO

BACKGROUND/OBJECTIVES: Aim to identify incidence and prevalence of laser-induced retinal injuries in the Northern Ireland paediatric population and to determine negative clinical and OCT indicators in relation to visual acuity. SUBJECTS/METHODS: A retrospective analysis was conducted of retinal injuries secondary to handheld laser pens over a 6-year time period with presenting and final visual acuity (VA), laser source and circumstances of the injury recorded. Fundus photographs and OCT images for each case were also collated. RESULTS: Sixty-five patients (74 eyes) were identified of which 72% were male and mean age was 11.6 years. 40% of patients were symptomatic. Mean presenting VA was 0.16 LogMAR. VA was ≤0.30 LogMAR in 20 eyes (27%) at presentation. Features which impacted VA to a significant level were foveolar location, diffuse morphology, ELM and BM/RPE/IDZ disruption and ORH presence on presenting OCT images. ORHs or ELM disruption resulted in a significant risk ratio of 3.5 (p = 0.002) and 3.4 (p = <0.001) respectively. Mean presenting VA was demonstrated to improve during follow-up from 0.36 to 0.22 LogMAR (n = 20, p = 0.03). When VA was ≤0.30 LogMAR at presentation, mean presenting VA improved from 0.56 to 0.29 LogMAR (p < 0.01) with 58% of eyes improving to a VA of better than 0.30 LogMAR. CONCLUSIONS: The overall visual loss from macular laser injuries was low and we have identified features on retinal imaging that significantly impact presenting VA. When VA is affected following macular laser injury there is evidence of recovery with >50% of those presenting with VA ≤ 0.30 LogMAR improving to better than 0.30 LogMAR.

4.
Viruses ; 13(12)2021 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-34960697

RESUMO

The nonvirulent infectious salmon anaemia virus (ISAV-HPR0) is the putative progenitor for virulent-ISAV, and a potential risk factor for the development of infectious salmon anaemia (ISA). Understanding the transmission dynamics of ISAV-HPR0 is fundamental to proper management and mitigation strategies. Here, we demonstrate that ISAV-HPR0 causes prevalent and transient infections in all three production stages of Atlantic salmon in the Faroe Islands. Phylogenetic analysis of the haemagglutinin-esterase gene from 247 salmon showed a clear geographical structuring into two significantly distinct HPR0-subgroups, which were designated G2 and G4. Whereas G2 and G4 co-circulated in marine farms, Faroese broodfish were predominantly infected by G2, and smolt were predominantly infected by G4. This infection pattern was confirmed by our G2- and G4-specific RT-qPCR assays. Moreover, the HPR0 variants detected in Icelandic and Norwegian broodfish were never detected in the Faroe Islands, despite the extensive import of ova from both countries. Accordingly, the vertical transmission of HPR0 from broodfish to progeny is uncommon. Phylogenetic and statistical analysis suggest that HPR0 persists in the smolt farms as "house-strains", and that new HPR0 variants are occasionally introduced from the marine environment, probably by HPR0-contaminated sea-spray. Thus, high biosecurity-including water and air intake-is required to avoid the introduction of pathogens to the smolt farms.


Assuntos
Doenças dos Peixes/transmissão , Pesqueiros , Transmissão Vertical de Doenças Infecciosas/veterinária , Isavirus/patogenicidade , Infecções por Orthomyxoviridae/veterinária , Salmo salar/virologia , Animais , Dinamarca , Doenças dos Peixes/virologia , Isavirus/classificação , Isavirus/genética , Infecções por Orthomyxoviridae/transmissão , Infecções por Orthomyxoviridae/virologia , Filogenia , Virulência
5.
Viruses ; 13(12)2021 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-34960818

RESUMO

Viral disease poses a major barrier to sustainable aquaculture, with outbreaks causing large economic losses and growing concerns for fish welfare. Genomic epidemiology can support disease control by providing rapid inferences on viral evolution and disease transmission. In this study, genomic epidemiology was used to investigate salmonid alphavirus (SAV), the causative agent of pancreas disease (PD) in Atlantic salmon. Our aim was to reconstruct SAV subtype-2 (SAV2) diversity and transmission dynamics in recent Norwegian aquaculture, including the origin of SAV2 in regions where this subtype is not tolerated under current legislation. Using nanopore sequencing, we captured ~90% of the SAV2 genome for n = 68 field isolates from 10 aquaculture production regions sampled between 2018 and 2020. Using time-calibrated phylogenetics, we infer that, following its introduction to Norway around 2010, SAV2 split into two clades (SAV2a and 2b) around 2013. While co-present at the same sites near the boundary of Møre og Romsdal and Trøndelag, SAV2a and 2b were generally detected in non-overlapping locations at more Southern and Northern latitudes, respectively. We provide evidence for recent SAV2 transmission over large distances, revealing a strong connection between Møre og Romsdal and SAV2 detected in 2019/20 in Rogaland. We also demonstrate separate introductions of SAV2a and 2b outside the SAV2 zone in Sognefjorden (Vestland), connected to samples from Møre og Romsdal and Trøndelag, respectively, and a likely 100 km Northward transmission of SAV2b within Trøndelag. Finally, we recovered genomes of SAV2a and SAV3 co-infecting single fish in Rogaland, involving novel SAV3 lineages that diverged from previously characterized strains >25 years ago. Overall, this study demonstrates useful applications of genomic epidemiology for tracking viral disease spread in aquaculture.


Assuntos
Infecções por Alphavirus/veterinária , Alphavirus/genética , Doenças dos Peixes/transmissão , Salmonidae/virologia , Alphavirus/classificação , Infecções por Alphavirus/transmissão , Animais , Aquicultura , Variação Genética , Genoma Viral , Filogeografia
6.
Aerosp Med Hum Perform ; 92(8): 650-669, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34503618

RESUMO

AbstractINTRODUCTION: For over 50 yr, investigators have studied the physiological adaptations of the human system during short- and long-duration spaceflight exposures. Much of the knowledge gained in developing health countermeasures for astronauts onboard the International Space Station demonstrate terrestrial applications. To date, a systematic process for translating these space applications to terrestrial human health has yet to be defined.METHODS: In the summer of 2017, a team of 38 international scientists launched the Bellagio ll Summit Initiative. The goals of the Summit were: 1) To identify space medicine findings and countermeasures with highest probability for future terrestrial applications; and 2) To develop a roadmap for translation of these countermeasures to future terrestrial application. The team reviewed public domain literature, NASA databases, and evidence books within the framework of the five-stage National Institutes of Health (NIH) translation science model, and the NASA two-stage translation model. Teams then analyzed and discussed interdisciplinary findings to determine the most significant evidence-based countermeasures sufficiently developed for terrestrial application.RESULTS: Teams identified published human spaceflight research and applied translational science models to define mature products for terrestrial clinical practice.CONCLUSIONS: The Bellagio ll Summit identified a snapshot of space medicine research and mature science with the highest probability of translation and developed a Roadmap of terrestrial application from space medicine-derived countermeasures. These evidence-based findings can provide guidance regarding the terrestrial applications of best practices, countermeasures, and clinical protocols currently used in spaceflight.Sides MB, Johnston SL III, Sirek A, Lee PH, Blue RS, Antonsen EL, Basner M, Douglas GL, Epstein A, Flynn-Evans EE, Gallagher MB, Hayes J, Lee SMC, Lockley SW, Monseur B, Nelson NG, Sargsyan A, Smith SM, Stenger MB, Stepanek J, Zwart SR; Bellagio II Team. Bellagio II report: terrestrial applications of space medicine research. Aerosp Med Hum Perform. 2021; 92(8):650669.


Assuntos
Medicina Aeroespacial , Voo Espacial , Astronautas , Humanos , Fatores de Tempo
7.
Transl Oncol ; 14(12): 101229, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34592589

RESUMO

Tumour metastasis accounts for over 90% of cancer related deaths. The platelet is a key blood component, which facilitates efficient metastasis. This study aimed to understand the molecular mechanisms involved in tumour-platelet cell interactions. The interaction between cancer cells and platelets was examined in 15 epithelial cell lines, representing 7 cancer types. Gene expression analysis of EMT-associated and cancer stemness genes was performed by RT-PCR. Whole transcriptome analysis (WTA) was performed using Affymetrix 2.0ST arrays on a platelet co-cultured ovarian model. Platelet adhesion and activation occurred across all tumour types. WTA identified increases in cellular movement, migration, invasion, adhesion, development, differentiation and inflammation genes and decreases in processes associated with cell death and survival following platelet interaction. Increased invasive capacity was also observed in a subset of cell lines. A cross-comparison with a platelet co-cultured mouse model identified 5 common altered genes; PAI-1, PLEK2, CD73, TNC, and SDPR. Platelet cancer cell interactions are a key factor in driving the pro-metastatic phenotype and appear to be mediated by 5 key genes which have established roles in metastasis. Targeting these metastasis mediators could improve cancer patient outcomes.

8.
Proc Natl Acad Sci U S A ; 118(35)2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34452995

RESUMO

The strength of peptide:MHC interactions with the T cell receptor (TCR) is correlated with the time to first cell division, the relative scale of the effector cell response, and the graded expression of activation-associated proteins like IRF4. To regulate T cell activation programming, the TCR and the TCR proximal interleukin-2-inducible T cell kinase (ITK) simultaneously trigger many biochemically separate signaling cascades. T cells lacking ITK exhibit selective impairments in effector T cell responses after activation, but under the strongest signaling conditions, ITK activity is dispensable. To gain insight into whether TCR signal strength and ITK activity tune observed graded gene expression through the unequal activation of distinct signaling pathways, we examined Erk1/2 phosphorylation or nuclear factor of activated T cells (NFAT) and nuclear factor (NF)-κB translocation in naïve OT-I CD8+ cell nuclei. We observed the consistent digital activation of NFAT1 and Erk1/2, but NF-κB displayed dynamic, graded activation in response to variation in TCR signal strength, tunable by treatment with an ITK inhibitor. Inhibitor-treated cells showed the dampened induction of AP-1 factors Fos and Fosb, NF-κB response gene transcripts, and survival factor Il2 transcripts. ATAC sequencing analysis also revealed that genomic regions most sensitive to ITK inhibition were enriched for NF-κB and AP-1 motifs. Specific inhibition of NF-κB during peptide stimulation tuned the expression of early gene products like c-Fos. Together, these data indicate a key role for ITK in orchestrating the optimal activation of separate TCR downstream pathways, specifically aiding NF-κB activation. More broadly, we revealed a mechanism by which variations in TCR signal strength can produce patterns of graded gene expression in activated T cells.


Assuntos
Proteínas Tirosina Quinases/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Transdução de Sinais , Linfócitos T/metabolismo , Animais , Células Cultivadas , DNA/metabolismo , Feminino , Regulação da Expressão Gênica , Ativação Linfocitária , Sistema de Sinalização das MAP Quinases/genética , Masculino , Camundongos , NF-kappa B/metabolismo , Fatores de Transcrição NFATC/metabolismo , Transdução de Sinais/genética , Linfócitos T/enzimologia , Linfócitos T/imunologia
9.
MethodsX ; 8: 101484, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34434882

RESUMO

Traditional forestry, ecology, and fuels monitoring methods can be costly and error-prone, and are often used beyond their original assumptions due to difficulty or unavailability of more appropriate methods. These traditional methods tend to be rigid and may not be useful for detecting new ecological changes or required data at modern levels of precision [1]. The integration of Terrestrial Laser Scanning (TLS) methods into forest monitoring strategies can cost effectively standardize data collection, improve efficiency, and reduce error, with datasets that can easily be analyzed to better inform management decisions. Affordable (sub-$20K) off-the-shelf TLS units-such as the Leica BLK360- have been used commercially in the built environment but have untapped potential in the natural world for monitoring. Here, we provide a methodology that successfully integrates LiDAR scanning with existing monitoring methods. This new method:•Allows for simplified and quick extraction of forestry, fuels and ecological vegetation variables from a single TLS point cloud and quick transect sampling.•Streamlines the data collection process, removes sampling bias, and produces data that can be easily processed to provide inputs for models and decision support frameworks.•Is adaptable to integrate additional or new environmental measurements.

10.
Transl Lung Cancer Res ; 10(4): 1773-1791, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34012792

RESUMO

BACKGROUND: In the absence of targetable mutations or immune checkpoints, cisplatin-doublet chemotherapy remains the standard of care in non-small cell lung cancer (NSCLC). Drug resistance has however become a significant clinical challenge. Exploring a role for small non-coding microRNAs (miRNA) as biomarker candidates in cisplatin resistant (CisR) lung cancer is lacking and warrants further investigation. METHODS: miRNA expression profiling was assessed in a panel of cisplatin sensitive and resistant NSCLC cell lines and validated by qPCR. Modulation of altered miRNAs was studied using antagomiRs and pre-miRs while functional assays were used to assess cisplatin response. The translational relevance of these miRNAs as potential biomarkers was assessed in serum and matched normal and tumour lung tissues from chemo-naïve NSCLC patients, in addition to xenograft formalin-fixed paraffin-embedded (FFPE) tumours derived from cisplatin sensitive and resistant cell lines. RESULTS: Differential expression of a 5-miR signature (miR-30a-3p, miR-30b-5p, miR-30c-5p, miR-34a-5p, miR-4286) demonstrated their ability to distinguish between normal and tumour lung tissue and between NSCLC histologies. In squamous cell carcinoma (SqCC), tissue miRNA expression was associated with poor survival. miR-4286 showed promise as a blood-based diagnostic biomarker that could distinguish between adenocarcinoma and SqCC histologies. In a xenograft model of cisplatin resistance, using 7-9 week old female NOD/SCID mice (NOD.CB17-Prkdcscid/NCrCrl), a 5-miRNA panel showed altered expression between sensitive and resistant tumours. CONCLUSIONS: This study identified a panel of miRNAs which may have diagnostic and prognostic potential as novel biomarkers in lung cancer and furthermore, may have a predictive role in monitoring the emergence of resistance to cisplatin.

12.
BMJ Case Rep ; 14(1)2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431463

RESUMO

Calcifying aponeurotic fibroma (CAF) is a rare benign tumour originating from the aponeuroses of tendons and their bony insertions. A 15-year-old student presented to his general practitioner with a 1-year history of a progressively enlarging painless finger swelling. The lesion was excised by the local paediatric orthopaedic service and recurred over the course of the following 4 months. Histology confirmed a diagnosis of CAF. He was referred to our specialist hand surgery service and the lesion was excised along with the ulnar lateral band and the overlying skin. At 9 months, there was no clinical evidence of recurrence. We are the first group to report the potential benefit of including of the overlying skin in the histological specimen to reduce the residual disease burden. Our case illustrates the technical challenges and considerations of removing a large, recurrent CAF of the hand and highlights the importance of centralised specialist care.


Assuntos
Fibroma Ossificante/cirurgia , Traumatismos dos Dedos/complicações , Recidiva Local de Neoplasia/cirurgia , Procedimentos Ortopédicos , Neoplasias de Tecidos Moles/cirurgia , Adolescente , Diagnóstico Diferencial , Fibroma Ossificante/diagnóstico , Fibroma Ossificante/etiologia , Dedos/diagnóstico por imagem , Dedos/cirurgia , Humanos , Imageamento por Ressonância Magnética , Masculino , Recidiva Local de Neoplasia/diagnóstico , Radiografia , Reoperação , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/etiologia , Resultado do Tratamento
15.
Diagn Interv Radiol ; 27(2): 244-248, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33517258

RESUMO

PURPOSE: We aimed to evaluate the effect on the radiation dose to the patient by reducing the tube current during the placement of the ablation needles (reduced dose group) compared with the patient doses delivered when scanning at the standard fully diagnostic level (full dose group) in computed tomography (CT)-guided percutaneous cryoablation. METHODS: We conducted a retrospective study of 103 patients undergoing cryoablation in a tertiary cancer center. Overall, 62 patients were scanned with standard exposure parameters (full dose group) set on a 64-slice multidetector CT scanner, while 41 patients were scanned on a reduced dose protocol. Dose levels were retrieved from the hospital picture and archiving communication system including the volumetric CT dose index (CTDIvol), total dose length product (DLP), length of cryoablation procedure, number of cryoablation needles and patient size. Wilcoxon Mann-Whitney (rank-sum) tests were used to compare the median DLP, CTDIvol and skin dose between the two groups. RESULTS: Median total DLP for the full dose group was 6025 mGy•cm (1909-13353 mGy•cm) compared with 3391 mGy•cm (1683-6820 mGy•cm) for the reduced dose group. The reduced dose group had a 44% reduction in total DLP and 42% reduction in total CTDIvol (p < 0.001). The estimated skin doses were 384 mGy for the full dose group and 224 mGy for the reduced dose group (42% reduction) (p < 0.001). At 12-month follow-up, the technical success for the full dose (n=62) was 97% with 2 patients requiring a further cryoablation treatment for residual tumor. The technical success for the reduced dose group (n=41) was 100%. CONCLUSION: CT dose reduction technique during image-guided cryoablation treatment of renal tumors can achieve significant radiation dose reduction whilst maintaining sufficient image quality.


Assuntos
Criocirurgia , Neoplasias Renais , Redução da Medicação , Humanos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/cirurgia , Tomografia Computadorizada Multidetectores , Doses de Radiação , Estudos Retrospectivos
17.
J Cardiovasc Comput Tomogr ; 15(2): 114-120, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32943356

RESUMO

BACKGROUND: Values of fractional flow reserve (FFRCT) by coronary computed tomography angiography (CTA) decline from the ostium to the terminal vessel, irrespective of stenosis severity. The purpose of this study is to determine if the site of measurement of FFRCT impacts assessment of ischemia and its diagnostic performance relative to invasive FFR (FFRINV). METHODS: 1484 patients underwent FFRCT; 1910 vessels were stratified by stenosis severity (normal; <25%, 25-50%, 50-70%, and >70% stenosis). The rates of positive FFRCT (≤0.8) were determined by measuring FFRCT from the terminal vessel and from distal-to-the-lesion. Reclassification rates from positive to negative FFRCT were calculated. Diagnostic performance of FFRCT relative to FFRINV was evaluated in 182 vessels using linear regression, Bland Altman analysis, and receiver operating characteristic (ROC) curves. RESULTS: Positive FFRCT was identified in 24.9% of vessels using terminal vessel FFRCT and 10.1% using FFRCT distal-to-the-lesion (p â€‹< â€‹0.001). FFRCT obtained distal-to-the-lesion resulted in reclassification of 59.6% of positive terminal FFRCT to negative FFRCT. Relative to FFRINV, there were improvements in specificity (50% to 86%, p â€‹< â€‹0.001), diagnostic accuracy (65% to 88%, p â€‹< â€‹0.001), positive predictive value (50% to 78%, p â€‹< â€‹0.001), and area-under-the-curve (AUC, 0.83 to 0.91, p â€‹< â€‹0.001) when FFRCT was measured distal-to-the-lesion. CONCLUSION: FFRCT values from the terminal vessel should not be used to assess lesion-specific ischemia due to high rates of false positive results. FFRCT measured distal-to-the-lesion improves the diagnostic performance of FFRCT relative to FFRINV, ensures that FFRCT values are due to lesion-specific ischemia, and could reduce the rate of unnecessary invasive procedures.


Assuntos
Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Estenose Coronária/diagnóstico por imagem , Reserva Fracionada de Fluxo Miocárdico , Idoso , Doença da Artéria Coronariana/fisiopatologia , Estenose Coronária/fisiopatologia , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Interpretação de Imagem Radiográfica Assistida por Computador , Índice de Gravidade de Doença
18.
Eye (Lond) ; 35(3): 811-816, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32424330

RESUMO

BACKGROUND/OBJECTIVES: Paediatric Horner's syndrome (HS) may present atypically with incomplete or intermittent clinical features, yet could represent sinister pathology including neuroblastoma. We aim to report the frequency and features with which atypical HS presents in our population (Northern Ireland) and to propose an investigation algorithm to aid diagnosis in these challenging cases. SUBJECTS/METHODS: Retrospective chart review of all paediatric anisocoria and HS cases presenting to Belfast, Northern Ireland, between 2012 and 2018, identified through searching our paediatric ophthalmology database. RESULTS: Sixty-one eligible cases of anisocoria or HS were analysed. Ten cases of HS were identified, four (40%) of which presented atypically with incomplete or intermittent features. Two of these four atypical cases were secondary to neuroblastoma. Overall incidence of paediatric HS in Northern Ireland during the study period was at least 2.54 per 100,000. CONCLUSIONS: Paediatric HS may present atypically in a significant number of cases. Accordingly, clinicians should consider HS in children with a history of anisocoria or ptosis and have a low threshold for use of pharmacological tests to aid diagnosis.


Assuntos
Blefaroptose , Síndrome de Horner , Anisocoria , Criança , Humanos , Irlanda do Norte , Estudos Retrospectivos
19.
Nat Microbiol ; 6(1): 112-122, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33349681

RESUMO

Coronavirus disease 2019 (COVID-19) was first diagnosed in Scotland on 1 March 2020. During the first month of the outbreak, 2,641 cases of COVID-19 led to 1,832 hospital admissions, 207 intensive care admissions and 126 deaths. We aimed to identify the source and number of introductions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into Scotland using a combined phylogenetic and epidemiological approach. Sequencing of 1,314 SARS-CoV-2 viral genomes from available patient samples enabled us to estimate that SARS-CoV-2 was introduced to Scotland on at least 283 occasions during February and March 2020. Epidemiological analysis confirmed that early introductions of SARS-CoV-2 originated from mainland Europe (the majority from Italy and Spain). We identified subsequent early outbreaks in the community, within healthcare facilities and at an international conference. Community transmission occurred after 2 March, 3 weeks before control measures were introduced. Earlier travel restrictions or quarantine measures, both locally and internationally, would have reduced the number of COVID-19 cases in Scotland. The risk of multiple reintroduction events in future waves of infection remains high in the absence of population immunity.


Assuntos
COVID-19/epidemiologia , COVID-19/virologia , SARS-CoV-2/genética , Adulto , Idoso , Europa (Continente)/epidemiologia , Genoma Viral , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Filogenia , SARS-CoV-2/isolamento & purificação , Espanha/epidemiologia , Viagem/estatística & dados numéricos
20.
PLoS One ; 15(12): e0243715, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33370338

RESUMO

Despite the use of front-line anticancer drugs such as paclitaxel for ovarian cancer treatment, mortality rates have remained almost unchanged for the past three decades and the majority of patients will develop recurrent chemoresistant disease which remains largely untreatable. Overcoming chemoresistance or preventing its onset in the first instance remains one of the major challenges for ovarian cancer research. In this study, we demonstrate a key link between senescence and inflammation and how this complex network involving the biomarkers MAD2, TLR4 and MyD88 drives paclitaxel resistance in ovarian cancer. This was investigated using siRNA knockdown of MAD2, TLR4 and MyD88 in two ovarian cancer cell lines, A2780 and SKOV-3 cells and overexpression of MyD88 in A2780 cells. Interestingly, siRNA knockdown of MAD2 led to a significant increase in TLR4 gene expression, this was coupled with the development of a highly paclitaxel-resistant cell phenotype. Additionally, siRNA knockdown of MAD2 or TLR4 in the serous ovarian cell model OVCAR-3 resulted in a significant increase in TLR4 or MAD2 expression respectively. Microarray analysis of SKOV-3 cells following knockdown of TLR4 or MAD2 highlighted a number of significantly altered biological processes including EMT, complement, coagulation, proliferation and survival, ECM remodelling, olfactory receptor signalling, ErbB signalling, DNA packaging, Insulin-like growth factor signalling, ion transport and alteration of components of the cytoskeleton. Cross comparison of the microarray data sets identified 7 overlapping genes including MMP13, ACTBL2, AMTN, PLXDC2, LYZL1, CCBE1 and CKS2. These results demonstrate an important link between these biomarkers, which to our knowledge has never before been shown in ovarian cancer. In the future, we hope that triaging patients into alterative treatment groups based on the expression of these three biomarkers or therapeutic targeting of the mechanisms they are involved in will lead to improvements in patient outcome and prevent the development of chemoresistance.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Biomarcadores Tumorais/genética , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Linhagem Celular Tumoral , Senescência Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Proteínas Mad2/genética , Fator 88 de Diferenciação Mieloide/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Paclitaxel/uso terapêutico , RNA Interferente Pequeno/metabolismo , Receptor 4 Toll-Like/genética
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