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1.
Opt Express ; 32(4): 5729-5736, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38439291

RESUMO

Monolayers containing subnanometer striations of silica and hafnia to form composite materials at varying ratios are explored as a method to develop high-index dielectric layers with increased laser-induced-damage thresholds (LIDTs). These layers can then be used in multilayer dielectric coatings for short-pulse, high-peak-power laser applications, particularly in regions of the highest electric-field intensity. Fabrication is achieved by means of exposure to two different evaporant vapor plumes, where local exposure to each plume is controlled via shielding to prevent simultaneous exposure. The LIDT of the resulting layers has been evaluated at 1053 nm with 600-fs pulses. The results indicate that such hafnia/silica layers exhibit LIDTs similar to silica for a refractive index of ≤1.65. These results suggest that the use of these layers in locations subjected to high electric-field intensity within multilayer dielectric coatings may significantly improve the LIDT, with this deposition process providing particular benefit for scaling to large-aperture, high-fluence components.

2.
J Hum Evol ; 190: 103498, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38581918

RESUMO

The Homa Peninsula, in southwestern Kenya, continues to yield insights into Oldowan hominin landscape behaviors. The Late Pliocene locality of Nyayanga (∼3-2.6 Ma) preserves some of the oldest Oldowan tools. At the Early Pleistocene locality of Kanjera South (∼2 Ma) toolmakers procured a diversity of raw materials from over 10 km away and strategically reduced them in a grassland-dominated ecosystem. Here, we report findings from Sare-Abururu, a younger (∼1.7 Ma) Oldowan locality approximately 12 km southeast of Kanjera South and 18 km east of Nyayanga. Sare-Abururu has yielded 1754 artifacts in relatively undisturbed low-energy silts and sands. Stable isotopic analysis of pedogenic carbonates suggests that hominin activities were carried out in a grassland-dominated setting with similar vegetation structure as documented at Kanjera South. The composition of a nearby paleo-conglomerate indicates that high-quality stone raw materials were locally abundant. Toolmakers at Sare-Abururu produced angular fragments from quartz pebbles, representing a considerable contrast to the strategies used to reduce high quality raw materials at Kanjera South. Although lithic reduction at Sare-Abururu was technologically simple, toolmakers proficiently produced cutting edges, made few mistakes and exhibited a mastery of platform management, demonstrating that expedient technical strategies do not necessarily indicate a lack of skill or suitable raw materials. Lithic procurement and reduction patterns on the Homa Peninsula appear to reflect variation in local resource contexts rather than large-scale evolutionary changes in mobility, energy budget, or toolmaker cognition.


Assuntos
Hominidae , Animais , Quênia , Ecossistema , Evolução Biológica , Carbonatos , Arqueologia , Fósseis
3.
MAGMA ; 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38904745

RESUMO

RATIONALE AND OBJECTIVES: Defacing research MRI brain scans is often a mandatory step. With current defacing software, there are issues with Windows compatibility and researcher doubt regarding the adequacy of preservation of brain voxels in non-T1w scans. To address this, we developed PyFaceWipe, a multiplatform software for multiple MRI contrasts, which was evaluated based on its anonymisation ability and effect on downstream processing. MATERIALS AND METHODS: Multiple MRI brain scan contrasts from the OASIS-3 dataset were defaced with PyFaceWipe and PyDeface and manually assessed for brain voxel preservation, remnant facial features and effect on automated face detection. Original and PyFaceWipe-defaced data from locally acquired T1w structural scans underwent volumetry with FastSurfer and brain atlas generation with ANTS. RESULTS: 214 MRI scans of several contrasts from OASIS-3 were successfully processed with both PyFaceWipe and PyDeface. PyFaceWipe maintained complete brain voxel preservation in all tested contrasts except ASL (45%) and DWI (90%), and PyDeface in all tested contrasts except ASL (95%), BOLD (25%), DWI (40%) and T2* (25%). Manual review of PyFaceWipe showed no failures of facial feature removal. Pinna removal was less successful (6% of T1 scans showed residual complete pinna). PyDeface achieved 5.1% failure rate. Automated detection found no faces in PyFaceWipe-defaced scans, 19 faces in PyDeface scans compared with 78 from the 224 original scans. Brain atlas generation showed no significant difference between atlases created from original and defaced data in both young adulthood and late elderly cohorts. Structural volumetry dice scores were ≥ 0.98 for all structures except for grey matter which had 0.93. PyFaceWipe output was identical across the tested operating systems. CONCLUSION: PyFaceWipe is a promising multiplatform defacing tool, demonstrating excellent brain voxel preservation and competitive defacing in multiple MRI contrasts, performing favourably against PyDeface. ASL, BOLD, DWI and T2* scans did not produce recognisable 3D renders and hence should not require defacing. Structural volumetry dice scores (≥ 0.98) were higher than previously published FreeSurfer results, except for grey matter which were comparable. The effect is measurable and care should be exercised during studies. ANTS atlas creation showed no significant effect from PyFaceWipe defacing.

4.
Vet Ophthalmol ; 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39161042

RESUMO

OBJECTIVE: To compare characteristics and treatment outcomes of spontaneous chronic corneal epithelial defects (SCCEDs) in brachycephalic non-Boxers and Boxers. We hypothesized that brachycephalic non-Boxers develop SCCEDs at a younger age and develop complications more frequently than Boxers. ANIMALS STUDIED: Retrospective review of medical records of brachycephalic dogs treated for SCCEDs between January 2018 and December 2022 in multiple ophthalmology referral centers in the UK. PROCEDURE: Data recorded included breed, age, time of onset, treatment prior to referral, treatment at referral, time to heal, need for further procedures, and complications. RESULTS: A total of 464 SCCEDs in 420 dogs were included composed of 173 Boxers with 200 SCCEDs and 247 brachycephalic non-Boxer dogs with 264 SCCEDs. Boxers were significantly older (median 8.2, range 4.5-12.7 years) than brachycephalic non-Boxers (median 7.2, range 1.6-15.9 years) (p < .001). The first treatment (cotton-tipped applicator [CTA] debridement, diamond burr debridement, superficial keratectomy, grid keratotomy, punctate keratotomy, or combinations of these) selected was significantly different between groups (p < .001). Healing, excluding cases addressed by CTA debridement, following the first procedure was significantly more successful in Boxers (p = .049). Excluding cases addressed by CTA debridement, 9.6% of SCCEDs in Boxers (20/200) and 13.4% (32/239) of non-Boxers required more than one procedure. In the non-Boxer group, 9.5% (25/264) developed complications, contrasting with 4% (8/200) in the Boxer group. Non-Boxers were more likely to develop complications after the first treatment (p = .006). CONCLUSION: Non-Boxer brachycephalic dogs develop SCCEDs younger than Boxers. This study suggests SCCEDs in brachycephalic non-Boxers may be less likely to heal following one mechanical treatment and are more likely to develop complications.

5.
Opt Express ; 31(1): 714-726, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36607004

RESUMO

Contamination of pulse compression gratings during the manufacturing process is known to give rise to reduced laser damage performance and represents an issue that has not yet been adequately resolved. The present work demonstrates that the currently used etching methods introduce carbon contamination inside the etched region extending to a 50- to 80-nm layer below the surface. This study was executed using custom samples prepared in both, a laboratory setting and by established commercial vendors, showing results that are very similar. The laser-induced-damage performance of the etched and unetched regions in the grating-like samples suggest that contaminants introduced by etching process are contributing to the reduction of the laser-induced damage threshold.

6.
Vet Ophthalmol ; 26 Suppl 1: 134-142, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35713165

RESUMO

OBJECTIVE: To assess in vitro antibacterial efficacy of three cross-linking (XL) protocols on bacteria associated with canine ulcerative keratitis. METHODS: Three XL protocols: UVA 3 mW/cm2 for 60 min, UVA 3 mW/cm2 for 30 min, and UVA 30 mW/cm2 for 3 min with and without application of riboflavin and a riboflavin-only protocol were performed in vitro on the four most common bacterial genera isolated from cases of canine ulcerative keratitis treated at Dick White Referrals, UK. Zones of bacterial growth inhibition (GIZ) associated with treatment were measured and compared. RESULTS: The four most common isolates were Pseudomonas aeruginosa (PA) (48/140, 34.3%), Streptococcus spp. (32/140, 22.9%), Staphylococcus spp. (24/140, 17.1%) and Escherichia coli (EC) (11/140, 7.9%). PA, EC, Streptococcus canis (SC), and Staphylococcus pseudintermedius (SP), isolated from canine corneas, were selected for testing. EC and SC demonstrated growth inhibition following all UVA/riboflavin protocols. PA and SP only displayed growth inhibition following the 60 min UVA/riboflavin protocol. GIZ areas for 60 min UVA/riboflavin protocols were significantly greater than 30 and 3 min UVA/riboflavin protocols (p < .01) and there was no significant difference between 30 and 3 min UVA/riboflavin protocols. In respect to GIZ areas, EC was significantly more susceptible to XL than SP (p = <.01). CONCLUSIONS: All UVA/riboflavin XL protocols caused growth inhibition of EC and SC in vitro. PA and SP did not show clear growth inhibition in vitro following exposure to XL protocol settings of UVA 3 mW/cm2 for 30 min and UVA 30 mW/cm2 for 3 min.


Assuntos
Úlcera da Córnea , Doenças do Cão , Animais , Cães , Fármacos Fotossensibilizantes/farmacologia , Úlcera da Córnea/tratamento farmacológico , Úlcera da Córnea/veterinária , Raios Ultravioleta , Reagentes de Ligações Cruzadas , Córnea , Riboflavina/farmacologia , Bactérias , Substância Própria , Doenças do Cão/tratamento farmacológico
7.
Vet Ophthalmol ; 26(3): 262-267, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36999558

RESUMO

OBJECTIVE: We hypothesized that keratouveitis still occurs despite current widespread use of Canine adenovirus (CAV)-2 vaccinations and assessed the utility of CAV-1 and CAV-2 titers in elucidation of its etiopathogenesis. ANIMALS STUDIED: Nine dogs with unexplained keratouveitis (14 eyes) and nine control dogs. PROCEDURES: The Animal Health Trust clinical database was searched between 2008 and 2018 to identify cases of keratouveitis. Inclusion criteria included known vaccination status, interval from vaccination to development of clinical signs and availability of CAV titers. Cases were excluded if they were older than 1 year of age, or other causative ocular pathology for corneal edema was identified. Nine age-matched dogs without corneal edema but with CAV titers were included as controls. RESULTS: Mean CAV-1 and CAV-2 titers were not statistically different between dogs with keratouveitis and controls (p = .16 and p = .76, respectively). Three cases had CAV-1 titers >5000 and two of these cases had rising convalescence titers (greater than an 11-fold increase) suggesting infection with wild-type CAV-1. The six other cases did not appear to be associated with CAV infection or vaccination. CONCLUSION: Keratouveitis continues to occur despite the advent of CAV-2 vaccinations. While this study found no evidence to indicate CAV-2 vaccination causes keratouveitis, the data indicates that in a proportion of cases, contemporaneous wild-type CAV-1 infection is a possible cause.


Assuntos
Infecções por Adenoviridae , Adenovirus Caninos , Edema da Córnea , Doenças do Cão , Ceratite , Cães , Animais , Doenças do Cão/diagnóstico , Edema da Córnea/veterinária , Vacinação/veterinária , Ceratite/veterinária , Infecções por Adenoviridae/complicações , Infecções por Adenoviridae/diagnóstico , Infecções por Adenoviridae/veterinária
8.
Rheumatology (Oxford) ; 61(12): 4935-4944, 2022 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-35377444

RESUMO

BACKGROUND: No reliable biomarkers to predict response to TNF inhibitors (TNFi) in RA patients currently exist. The aims of this study were to replicate changes in gene co-expression modules that were previously reported in response to TNFi therapy in RA; to test if changes in module expression are specific to TNFi therapy; and to determine whether module expression transitions towards a disease-free state in responding patients. METHOD: Published transcriptomic data from the whole blood of disease-free controls (n = 10) and RA patients, treated with the TNFi adalimumab (n = 70) or methotrexate (n = 85), were studied. Treatment response was assessed using the EULAR response criteria following 3 or 6 months of treatment. Change in transcript expression between pre- and post-treatment was recorded for previously defined modules. Linear mixed models tested whether modular expression after treatment transitioned towards a disease-free state. RESULTS: For 25 of the 27 modules, change in expression between pre- and post-treatment in the adalimumab cohort replicated published findings. Of these 25 modules, six transitioned towards a disease-free state by 3 months (P < 0.05), irrespective of clinical response. One module (M3.2), related to inflammation and TNF biology, significantly correlated with response to adalimumab. Similar patterns of modular expression, with reduced magnitude, were observed in the methotrexate cohort. CONCLUSION: This study provides independent validation of changes in module expression in response to therapy in RA. However, these effects are not specific to TNFi. Further studies are required to determine whether specific modules could assist molecular classification of therapeutic response.


Assuntos
Antirreumáticos , Artrite Reumatoide , Humanos , Adalimumab/uso terapêutico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Antirreumáticos/efeitos adversos , Metotrexato/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismo , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Resultado do Tratamento
9.
Vet Ophthalmol ; 25(5): 398-405, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35670323

RESUMO

OBJECTIVE: The objective of the study was to compare corneal culture results using the ESwab™ and Amies charcoal swab. ANIMALS STUDIED: One hundred fourteen canine and fifteen feline eyes. PROCEDURES: Retrospective analysis of Dick White Referrals bacterial and fungal corneal culture data was conducted. Results were included from canine and feline patients, which presented with suspected infectious keratitis that had samples taken using an Amies charcoal swab followed by an ESwab™ in the same eye. In respect to positive and negative cultures, a McNemar test was conducted comparing instances of disagreement between swab types, and the Kappa coefficient (κ) was calculated to assess the level of agreement between swab types. RESULTS: The ESwab™ produced more positive corneal cultures (71/129 [55.0%]) than the Amies charcoal swab (41/129 [31.8%]). 2/129 eyes produced positive fungal cultures. Considering 37/129 eyes in which both swab types detected a positive corneal culture, the same bacterial species were cultured from each swab type in 34/37 (91.9%) eyes, and an additional bacterial species was cultured by the ESwab™ in 3/37 (8.1%) eyes. In 34/38 (89.5%), instances of disagreement between swab types, the ESwab™ showed a positive culture, and the Amies charcoal swab showed a negative culture from the same eye, and this difference was significant (p < 0.0001). There was a moderate level of agreement between results from both swab types (κ = 0.432). CONCLUSIONS: ESwab™ sampling alone may be superior to Amies charcoal swabs for detecting presence of bacteria in suspected infectious keratitis in cats and dogs.


Assuntos
Doenças do Gato , Doenças do Cão , Ceratite , Animais , Bactérias , Doenças do Gato/diagnóstico , Gatos , Carvão Vegetal , Doenças do Cão/diagnóstico , Doenças do Cão/microbiologia , Cães , Ceratite/microbiologia , Ceratite/veterinária , Estudos Retrospectivos
10.
Vet Ophthalmol ; 25(6): 454-467, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35695836

RESUMO

PURPOSE: In humans, idiopathic orbital inflammation (IOI) is a diagnosis attributed to benign, inflammatory orbital conditions without identifiable local or systemic cause. We describe the clinical signs, imaging and histopathological findings, management and outcome of four dogs diagnosed with IOI. METHODS: Multicentric retrospective study. RESULTS: A total of four dogs (five orbits) of three different breeds (three cases were English Springer Spaniels [ESS] or ESS-cross) and ages ranging from 3 to 12 years were included. Initial presenting signs were unilateral and included exophthalmos, enophthalmos, globe deviation, thickening and protrusion of the third eyelid and conjunctival hyperemia. Computed tomography and magnetic resonance imaging identified heterogeneous space-occupying, contrast-enhancing orbital lesions in all cases. Sparing of the retrobulbar space was detected in four of five orbits. Histopathology revealed mixed inflammatory infiltrates of lymphocytes, plasma cells, and histiocytes. Immunohistochemistry was performed in two cases highlighting the presence of histiocytes and lymphocytes, predominantly T cells. Resolution of clinical signs was achieved in two cases managed with oral immunosuppressant medication (corticosteroids alone or combined with cyclosporine or azathioprine), one went into spontaneous remission, one resolved with topical corticosteroids, and one underwent exenteration. Recurrence occurred in two cases within 15 months of initial diagnosis and required further immunosuppressant medication. One case developed signs in the contralateral orbit within 8 months of presentation. CONCLUSIONS: IOI is an uncommon condition in dogs. Its diagnosis relies on the combination of advanced imaging and histology. As in humans, it appears that spontaneous remission and recurrence may occur requiring long-term immunosuppressant medication.


Assuntos
Doenças do Cão , Pseudotumor Orbitário , Animais , Cães , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/tratamento farmacológico , Imunossupressores/uso terapêutico , Inflamação/veterinária , Órbita , Pseudotumor Orbitário/diagnóstico , Pseudotumor Orbitário/tratamento farmacológico , Pseudotumor Orbitário/patologia , Pseudotumor Orbitário/veterinária , Remissão Espontânea , Estudos Retrospectivos
11.
Oncologist ; 25(5): e777-e781, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31771991

RESUMO

INTRODUCTION: The National Lung Screening Trial (NLST) demonstrated that screening high-risk patients with low-dose computed tomography (CT) of the chest reduces lung cancer mortality compared with screening with chest x-ray. Uninsured and Medicaid patients usually lack access to this hospital-based screening test because of geographic and socioeconomic factors. We hypothesized that a mobile screening unit would improve access and confer the benefits demonstrated by the NLST to this underserved group, which is most at risk of lung cancer deaths. PATIENTS AND METHODS: We created a mobile unit by building a Samsung BodyTom portable 32-slice low-dose CT scanner into a 35-foot coach; it delivers high-quality images for both soft tissue and bone and includes a waiting area and high-speed wireless internet connection for fast image transfer. The unit was extensively tested to show robustness and stability of mobile equipment. This project was designed to screen uninsured and underinsured patients, otherwise with eligibility criteria identical to that of the National Lung Screening Trial, with the only difference being exclusion of patients eligible for Medicare (which provides financial coverage for CT-based lung cancer screening). RESULTS: We screened 550 patients (20% black, 3% Hispanic, 70% rural) with a male-to-female ratio of 1.1:1, median age 61 years (range, 55-64), and found 12 lung cancers at initial screen (2.2%), including 6 at stage I-II (58% of total lung cancers early stage) and 38 Lung-RADS 4 (highly suspicious) lesions that are being followed closely. Incidental findings included nonlung cancers and coronary artery disease. DISCUSSION: In this initial pilot study, using the first mobile low-dose whole body CT screening unit in the U.S., the initial cancer detection rate is comparable to that reported in the NLST, despite excluding patients over the age of 64 years who have Medicare coverage, but with marked improvement of screening rates specifically in underserved sociodemographic, racial, and ethnic groups and with better outcomes than conventionally found in the underserved and at lower cost per case. IMPLICATIONS FOR PRACTICE: This study shows clearly that a mobile low-dose CT scanning unit allows effective lung cancer screening for underserved populations, such as impoverished African Americans, Hispanics, Native Americans, or isolated rural groups, and has a pick-up rate of 1% for early stage disease. If confirmed in a planned randomized trial, this will be policy changing, as these groups usually present with advanced disease; this approach will produce better survival data at lower cost per case.


Assuntos
Detecção Precoce de Câncer , Neoplasias Pulmonares , Idoso , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Programas de Rastreamento , Medicare , Pessoa de Meia-Idade , Projetos Piloto , Tomografia Computadorizada por Raios X , Estados Unidos , Populações Vulneráveis
12.
J Cardiovasc Electrophysiol ; 31(8): 2086-2092, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32583559

RESUMO

INTRODUCTION: The adult congenital heart disease (ACHD) population is rapidly expanding. However, a significant proportion of these patients suffer sudden cardiac death. Recommending implantable cardioverter-defibrillator (ICD) insertion requires balancing the need for appropriate therapy in malignant arrhythmia against the consequences of inappropriate therapy and procedural complications. Here we present long-term follow-up data for ICD insertion in patients with ACHD from a large Level 1 congenital cardiac center. METHODS AND RESULTS: All patients with ACHD undergoing ICD insertion over an 18-year period were identified. Data were extracted for baseline characteristics including demographics, initial diagnosis, ventricular function, relevant medication, and indication for ICD insertion. Details regarding device insertion were gathered along with follow-up data including appropriate and inappropriate therapy and complications. A total of 136 ICDs were implanted during this period: 79 for primary and 57 for secondary prevention. The most common congenital cardiac conditions in both groups were tetralogy of Fallot and transposition of the great arteries. Twenty-two individuals in the primary prevention group received appropriate antitachycardia pacing (ATP), 14 underwent appropriate cardioversion, 17 received inappropriate ATP, and 15 received inappropriate cardioversion. In the secondary prevention group, 18 individuals received appropriate ATP, 8 underwent appropriate cardioversion, 8 received inappropriate ATP, and 7 were inappropriately cardioverted. Our data demonstrate low complication rates, particularly with leads without advisories. CONCLUSION: ICD insertion in the ACHD population involves a careful balance of the risks and benefits. Our data show a significant proportion of patients receiving appropriate therapy indicating that ICDs were inserted appropriately.


Assuntos
Desfibriladores Implantáveis , Cardiopatias Congênitas , Transposição dos Grandes Vasos , Adulto , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/prevenção & controle , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/terapia , Humanos , Sistema de Registros
13.
Respirology ; 25(10): 1066-1072, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32249494

RESUMO

BACKGROUND AND OBJECTIVE: There are limited data regarding patients with PAPVD with suspected and diagnosed PH. METHODS: Patients with PAPVD presenting to a large PH referral centre during 2007-2017 were identified from the ASPIRE registry. RESULTS: Ninety patients with PAPVD were identified; this was newly diagnosed at our unit in 71 patients (78%), despite 69% of these having previously undergone CT. Sixty-seven percent had a single right superior and 23% a single left superior anomalous vein. Patients with an SV-ASD had a significantly larger RV area, pulmonary artery and L-R shunt and a higher % predicted DLCO (all P < 0.05). Sixty-five patients were diagnosed with PH (defined as mPAP ≥ 25 mm Hg), which was post-capillary in 24 (37%). No additional causes of PH were identified in 28 patients; 17 of these (26% of those patients with PH) had a PVR > 3 WU. Seven of these patients had isolated PAPVD, five of whom (8% of those patients with PH) had anomalous drainage of a single pulmonary vein. CONCLUSION: Undiagnosed PAPVD with or without ASD may be present in patients with suspected PH; cross-sectional imaging should therefore be specifically assessed whenever this diagnosis is considered. Radiological and physiological markers of L-R shunt are higher in patients with an associated SV-ASD. Although many patients with PAPVD and PH may have other potential causes of PH, a proportion of patients diagnosed with PAH have isolated PAPVD in the absence of other causative conditions.


Assuntos
Hipertensão Pulmonar/complicações , Veias Pulmonares/anormalidades , Sistema de Registros , Comorbidade , Feminino , Seguimentos , Hemodinâmica , Humanos , Hipertensão Pulmonar/fisiopatologia , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Veias Pulmonares/fisiopatologia , Resultado do Tratamento
14.
Vet Ophthalmol ; 23(1): 25-36, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31141290

RESUMO

PURPOSE: Canine primary closed-angle glaucoma (PCAG) is a complex disease caused by multiple genetic factors. A c.590G>A variant in OLFML3 was recently reported to be a candidate for pectinate ligament abnormality (PLA) and PCAG in the Border Collie. We investigated the association of this variant with PLA and PCAG in Border Collies from the United Kingdom. METHODS: The OLFML3 variant was genotyped in 106 Border Collies comprising 90 with normal eyes (controls) and 16 with PLA (n = 11) and/or PCAG (n = 5) (cases). Genotyping was performed in an additional 103 Border Collies to estimate variant frequency within the population. To investigate the association of the variant with disease in other breeds, genotyping was performed in 337 non-Border Collies with PLA and/or PCAG. RESULTS: Of the 90 controls, 71 were homozygous for the wild-type allele, two were homozygous for the variant, and 17 were heterozygous. Of the 16 cases, three were homozygous for the wild-type allele, 11 were homozygous for the variant, and two were heterozygous. The association of the variant allele with disease was significant (P = 1.1 x 10-9 ). We estimated the frequency of this variant to be 4.4% within the United Kingdom Border Collie population, and it was not identified in clinically affected dogs of any other breed. CONCLUSIONS: This study confirms the association of the OLFML3 variant with PLA and PCAG in Border Collies from the United Kingdom. DNA testing for the variant and selective breeding can reasonably be expected to result in a reduction of PLA and PCAG prevalence in the breed.


Assuntos
Doenças do Cão/genética , Predisposição Genética para Doença , Glaucoma de Ângulo Fechado/veterinária , Glicoproteínas/metabolismo , Ligamentos/anormalidades , Animais , DNA/genética , Doenças do Cão/epidemiologia , Cães , Feminino , Variação Genética , Genótipo , Glaucoma de Ângulo Fechado/epidemiologia , Glaucoma de Ângulo Fechado/genética , Glicoproteínas/genética , Masculino , Reino Unido/epidemiologia
15.
Int J Mol Sci ; 22(1)2020 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-33396557

RESUMO

An enigmatic localized pneumonia escalated into a worldwide COVID-19 pandemic from Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This review aims to consolidate the extensive biological minutiae of SARS-CoV-2 which requires decipherment. Having one of the largest RNA viral genomes, the single strand contains the genes ORF1ab, S, E, M, N and ten open reading frames. Highlighting unique features such as stem-loop formation, slippery frameshifting sequences and ribosomal mimicry, SARS-CoV-2 represents a formidable cellular invader. Hijacking the hosts translational engine, it produces two polyprotein repositories (pp1a and pp1ab), armed with self-cleavage capacity for production of sixteen non-structural proteins. Novel glycosylation sites on the spike trimer reveal unique SARS-CoV-2 features for shielding and cellular internalization. Affording complexity for superior fitness and camouflage, SARS-CoV-2 challenges diagnosis and vaccine vigilance. This review serves the scientific community seeking in-depth molecular details when designing drugs to curb transmission of this biological armament.


Assuntos
COVID-19/virologia , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Proteínas Virais/metabolismo , COVID-19/genética , COVID-19/metabolismo , Humanos , Fases de Leitura Aberta , Pandemias , Filogenia , RNA Viral/genética
16.
Mol Vis ; 25: 93-105, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30820145

RESUMO

Purpose: To investigate the genetic basis of primary closed angle glaucoma (PCAG) in European Basset Hounds using genome-wide association and RNA sequencing strategies. Methods: DNA samples from 119 European Basset Hounds were genotyped on the 170 K SNP CanineHD BeadChip array (Illumina) comprising 37 with normal iridocorneal angles (controls), 57 with pectinate ligament abnormality (PLA cases), and 25 with PCAG (PCAG cases). Genome-wide association studies (GWASs) of the PLA and PCAG cases were conducted. Whole transcriptome sequences of iridocorneal angle tissues from five Basset Hounds with PCAG were compared with those from four dogs with normal eyes to investigate differences in gene expression between the affected and unaffected eyes in GWAS-associated loci. A variant in NEB, previously reported to be associated with PCAG in American Basset Hounds, was genotyped in cohorts of European Basset Hounds and non-Basset Hounds. Results: The GWASs revealed 1.4 and 0.2 Mb regions, on chromosomes 24 and 37, respectively, that are statistically associated with PCAG. The former locus has previously been associated with glaucoma in humans. Whole transcriptome analysis revealed differential gene expression of eight genes within these two loci. The NEB variant was not associated with PLA or PCAG in this set of European Basset Hounds. Conclusions: We identified two novel loci for canine PCAG. Further investigation is required to elucidate candidate variants that underlie canine PCAG.


Assuntos
Doenças do Cão/genética , Proteínas do Olho/genética , Predisposição Genética para Doença , Genoma , Glaucoma de Ângulo Fechado/veterinária , Transcriptoma , Animais , Estudos de Casos e Controles , Doenças do Cão/patologia , Cães , Europa (Continente) , Proteínas do Olho/metabolismo , Feminino , Ontologia Genética , Loci Gênicos , Estudo de Associação Genômica Ampla , Glaucoma de Ângulo Fechado/genética , Glaucoma de Ângulo Fechado/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Masculino , Anotação de Sequência Molecular , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Polimorfismo de Nucleotídeo Único , Análise de Sequência de RNA , Estados Unidos
17.
J Hum Evol ; 131: 61-75, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31182207

RESUMO

The archaeological record has documented Oldowan hominin occupation of habitats ranging from open grasslands to riparian forest by 2.0 Ma. Despite this we have a poor understanding of whether hominin foraging behavior varied in different environmental settings. We compared bovid mortality profiles from the two largest Oldowan zooarchaeological samples, one from a grassland (Excavation 1, Kanjera South, Kenya) and another from a woodland (FLK Zinj, Olduvai Gorge, Tanzania) with bovid mortality samples created by African carnivores in different habitats. Kanjera hominins frequently had early access, likely through hunting, to small (size 1 ≤ 23 kg and size 2 = 24-112 kg) juvenile bovids, creating a mortality pattern similar to that created by grassland dwelling carnivores. Kanjera hominins had more mixed access to large (size 3 = 113-340 kg), often juvenile, bovids and frequently scavenged heads. In contrast, previous work has shown that the few small bovids at FLK-Zinj were predominantly older individuals. Prime adults dominated the FLK-Zinj large bovid sample, leading to a mortality pattern similar to that created by carnivores occupying more closed habitats. Variation in bovid body size and mortality profiles between these archaeological assemblages may reflect the challenges of acquiring fauna in open versus closed habitats with a simple hunting toolkit. The heterogeneous woodland habitat of FLK-Zinj would have provided more opportunities to ambush prey, whereas on grasslands with more limited concealment opportunities Kanjera hominins focused their efforts on vulnerable juvenile prey, some likely acquired after short chases.


Assuntos
Dieta , Cadeia Alimentar , Fósseis , Ruminantes , Animais , Arqueologia , Meio Ambiente , Humanos , Quênia , Paleontologia , Tanzânia
18.
Eur J Clin Microbiol Infect Dis ; 38(4): 711-717, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30771121

RESUMO

Students should graduate from medical school feeling prepared to prescribe antibiotics responsibly. We assessed self-reported preparedness among students at medical schools in Europe, and we focus here on the results from students in Sweden and France, countries with wide differences in the intensity of antibiotic consumption and burden of antibiotic resistance. We conducted a cross-sectional web-based survey in 2015, based on a comprehensive set of topics related to prudent antibiotic use. All final year students at a medical school in France or Sweden were eligible to participate. Preparedness scores were calculated for each student, and mean scores were compared at medical school and country levels. Comparisons were also made on availability of teaching methods. We received responses from 2085/7653 (response rate 27.2%) students from 31/34 eligible medical schools in France and 302/1124 (26.9%) students from 7/7 schools in Sweden. The relative ranking order of curriculum topics by preparedness level was consistent between countries, but students in Sweden had higher self-reported levels of preparedness in 21/27 topics. There was higher availability for eight of nine teaching methods at Swedish medical schools. Students in France were more likely to report a need for further education on antibiotic use (63.5% vs. 20.3%, p < 0.001). Final year students in France report lower levels of preparedness, less availability of teaching methods and higher needs for more education on antibiotic use. Furthermore, we have identified specific areas for improvement in education on prudent antibiotic use in both Sweden and France.


Assuntos
Antibacterianos/uso terapêutico , Gestão de Antimicrobianos , Prescrições de Medicamentos/estatística & dados numéricos , Educação de Graduação em Medicina , Conhecimentos, Atitudes e Prática em Saúde , Estudantes de Medicina/estatística & dados numéricos , Adulto , Estudos Transversais , Resistência Microbiana a Medicamentos , Feminino , França , Humanos , Masculino , Faculdades de Medicina , Inquéritos e Questionários , Suécia
19.
Vet Pathol ; 56(5): 749-760, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31132943

RESUMO

This study describes clinical and histopathological features, treatment, and outcome of cats diagnosed with ocular mycobacteriosis. Cases diagnosed from 2012 to 2017 were reviewed for (a) histopathological evidence of ocular (pyo)granulomatous inflammation containing acid-fast bacilli with mycobacterial morphology, (b) positive mycobacterial culture and/or mycobacterial DNA identified by polymerase chain reaction of ocular tissue, or (c) presumed mycobacteriosis based on ophthalmic examination and positive interferon-gamma release assay. Twenty-five cats (31 eyes) were included; 14 cats (17/31 eyes, 55%) were blind at presentation (unilateral: n = 12 cats; bilateral: n = 2 cats); one unilaterally affected cat later became bilaterally blind. Another 5 cats (7/31 eyes, 23%) became blind after initially being bilaterally visual (unilateral: n = 3 cats; bilateral: n = 2 cats). The commonest ocular finding was uveitis (87%). The main histopathological features were granulomatous to pyogranulomatous chorioretinitis with retinal detachment, anterior uveitis, optic neuritis, episcleritis, scleritis, and/or retrobulbar cellulitis. Nineteen cats (76%) had systemic signs, with disseminated disease being diagnosed in 9, defined by interstitial pulmonary disease, generalized lymphadenopathy, and/or nonocular infection. Nine cats were diagnosed with Mycobacterium bovis, 2 with Mycobacterium microti, 1 with Mycobacterium tuberculosis complex, and 1 with Mycobacterium avium-intracellulare complex. The infecting species was unknown in the remaining cats. Combined surgery (enucleation: n = 5 cats; biopsy: n = 3 cats) and systemic treatment with 2 or 3 appropriate antibiotics for 2 to 7 months resulted in remission in 8 of the 10 cats treated; however, the cat treated with dual therapy relapsed after 8 months. A total of 16 cats (64%) were euthanized; 2 were lost to follow-up.


Assuntos
Doenças do Gato/microbiologia , Oftalmopatias/veterinária , Infecções por Mycobacterium/veterinária , Mycobacterium/isolamento & purificação , Animais , Antibacterianos/uso terapêutico , Doenças do Gato/patologia , Doenças do Gato/terapia , Gatos , Oftalmopatias/microbiologia , Mycobacterium/classificação , Infecções por Mycobacterium/microbiologia , Infecções por Mycobacterium/terapia , Estudos Retrospectivos , Resultado do Tratamento
20.
Vet Ophthalmol ; 22(5): 591-599, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30706615

RESUMO

OBJECTIVE: To describe the visual outcome following phacoemulsification in English Cocker Spaniels (ECS) affected by cataracts and suspected progressive retinal atrophy (PRA). ANIMALS STUDIED: Fifty-four client-owned dogs. PROCEDURES: A multicenter, retrospective study was performed including ECS with suspected PRA which underwent phacoemulsification. PRA was suspected on ophthalmic examination before and after surgery, and/or after electroretinography (ERG) was performed. Visual outcome was assessed by menace response per eye at seven time periods post-surgery (P1= 25-90 days, P2 = 91-180 days, P3 = 181-364 days, P4 = 365-549 days, P5 = 550-729 days, P6 = 730-1094 days, and P7 ≥ 1095 days). Descriptive statistics were performed. Generalized estimating equations were used to identify predictors associated with vision after surgery. Odds ratio and confidence intervals were reported. Significance was set at P < 0.05. Owners were invited to participate in a questionnaire. RESULTS: Phacoemulsification was performed in 85 eyes. Median age at surgery was 9.09 years (min. 2.17 years, max. 13.49 years). At all re-examinations, up to and including P5, significantly more eyes were visual than before surgery (P ≤ 0.003). Odds for vision were significantly increased for eyes that underwent surgery. Electroretinograms were performed in 75/85 eyes that underwent surgery, demonstrating low b-wave amplitudes. There was no significant effect of the age, gender, vision before surgery, presence of dazzle reflex, cataract stage or abnormality on gonioscopy on visual outcome. The questionnaire response rate was 48.2%. Most participants (92.5%) felt that cataract surgery led to improvement of the dog's quality of life. CONCLUSIONS: English Cocker Spaniels with suspected PRA may benefit from phacoemulsification with vision up to 2 years following surgery.


Assuntos
Doenças do Cão/cirurgia , Facoemulsificação/veterinária , Degeneração Retiniana/veterinária , Animais , Catarata/veterinária , Extração de Catarata/veterinária , Cães , Feminino , Masculino , Degeneração Retiniana/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Visão Ocular
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