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1.
JAMA Ophthalmol ; 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38635258

RESUMEN

Importance: Parents may be concerned about the adverse outcomes of occlusion therapy in children treated for unilateral congenital cataract (UCC). Objective: To determine whether occlusion therapy in children treated for UCC with poor visual outcomes is negatively associated with poorer child and/or family functioning. Design, Setting, and Participants: This cohort study was conducted in 2023 using data collected between 2006 and 2016 in the Infant Aphakia Treatment Study (IATS). IATS participants with a visual acuity (VA) of 20/200 or worse were included. Statistical analysis was performed from July 2022 to October 2023. Exposure: Caregivers reported the mean daily minutes of patching during the 12 months prior to the VA assessment at 4.5 years of age. Patching was categorized as minimal (<15 minutes per day), moderate (15 to <120 minutes per day), or extensive (≥120 minutes per day). Main Outcome Measures: At 4.25 and 10.5 years of age, caregivers reported stress associated with the parenting role using the Parenting Stress Index and the Ocular Treatment Index and child behavior problems using the Achenbach Child Behavior Checklist. Motor skills were assessed at age 54 months using the Movement Assessment Battery for Children-Second Edition. Children completed the Harter Self-Perception Profile for Children at age 10.5 years. One-way analysis of variance and χ2 tests were used to compare outcomes by amount of patching. Results: Patching data were available for 47 of 53 children (88.7%) with a VA of 20/200 or worse. Among these 47 children with patching data included in the study, 20 (42.5%) were female, 27 (57.5%) were male, 12 (25.5%) were reported to have been patched fewer than 15 minutes per day, 11 (23.4%) were patched 16 to 119 minutes per day, and 24 (51.1%) were patched at least 120 minutes per day. Parenting stress, child behavior problems, motor functioning, and child self-perception were similar in all groups. For example, after adjusting for gender and insurance status, there was a nonsignificant difference between mean stress scores of 11.0 (95% CI, -4.5 to 26.5) points for parents who reported minimal patching vs parents who reported patching at least 120 minutes per day, and there was no significant difference in children's report of their global self-worth (0.0 [95% CI, -0.4 to 0.3] points). Conclusions and Relevance: Occlusion therapy was not negatively associated with family or child functioning. Although the sample size was limited, these results do not support changes to the current practice guidelines.

2.
Ophthalmology ; 131(5): 611-621, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38086435

RESUMEN

PURPOSE: Vision screening and regular eye care can help detect and treat potentially irreversible vision impairment. This study aims to investigate the associations between sociodemographic and health characteristics and the receipt of eye care among children aged 17 years and younger in the United States. DESIGN: This cross-sectional study used data from the National Survey of Children's Health (NSCH), a nationally representative and population-based survey of randomly sampled households. PARTICIPANTS: Participants were children aged 0 to 17 years, residing in all 50 states and the District of Columbia, whose caregivers or parents answered an address-based survey by mail or online. METHODS: Weighted prevalence calculations were applied to analyze the data, and logistic regression was performed to explore associations between reported eye care and demographic, health, and parent-related variables. MAIN OUTCOME MEASURES: Caregiver-reported vision screenings, referral to an eye doctor after vision screening, eye doctor visits, and prescription of corrective lenses. RESULTS: Caregivers reported that 53.2% of children had a vision screening at least once (if child ≤ 5 years) or within the past 2 years (if child > 5 years). Of those screened, 26.9% were referred to an eye doctor. Overall, 38.6% of all children had a previous eye doctor visit, and among them, 55.4% were prescribed corrective lenses during the visit. Factors associated with decreased odds of vision screening included younger age, lack of health care visits, no insurance coverage, parent education high school or less, and lower household income. Non-White ethnicities, households with a non-English primary language, and lower incomes were more likely to be referred to an eye doctor after vision screening. Lower rates of eye doctor visits were associated with younger age, lack of insurance coverage, and primary household languages other than English. CONCLUSIONS: Children from disadvantaged backgrounds are less likely to receive vision screening and eye care. Targeted strategies are needed to increase vision screening and access to eye care services in these vulnerable groups. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

3.
Br J Dermatol ; 186(3): 553-563, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34726260

RESUMEN

BACKGROUND: Epithelioid haemangioma (EH) arising from the skin is a benign vascular tumour with marked inflammatory cell infiltration, which exhibits a high tendency to persist and frequently recurs after resection. So far, the underlying pathogenesis is largely elusive. OBJECTIVES: To identify genetic alterations by next-generation sequencing and/or droplet digital polymerase chain reaction (ddPCR) in cutaneous EH. METHODS: DNA and RNA from an EH lesion of an index patient were subjected to whole-genome and RNA sequencing. Multiplex PCR-based panel sequencing of genomic DNA isolated from archival formalin-fixed paraffin-embedded tissue of 18 patients with cutaneous EH was performed. ddPCR was used to confirm mutations. RESULTS: We identified somatic mutations in genes of the mitogen-activated protein kinase (MAPK) pathway (MAP2K1 and KRAS) in cutaneous EH biopsies. By ddPCR we could confirm the recurrent presence of activating, low-frequency mutations affecting MAP2K1. In total, nine out of 18 patients analysed showed activating MAPK pathway mutations, which were mutually exclusive. Comparative analysis of tissue areas enriched for lymphatic infiltrate or aberrant endothelial cells, respectively, revealed an association of these mutations with the presence of endothelial cells. CONCLUSIONS: Taken together, our data suggest that EH shows somatic mutations in genes of the MAPK pathway which might contribute to the formation of this benign tumour.


Asunto(s)
Hemangioma , Neoplasias Cutáneas , ADN , Células Endoteliales , Hemangioma/genética , Humanos , Proteínas Quinasas Activadas por Mitógenos/genética , Reacción en Cadena de la Polimerasa Multiplex , Mutación/genética , Recurrencia Local de Neoplasia , Neoplasias Cutáneas/genética
4.
Nat Commun ; 12(1): 5066, 2021 08 20.
Artículo en Inglés | MEDLINE | ID: mdl-34417456

RESUMEN

Prostate cancer (PCa) shows strong dependence on the androgen receptor (AR) pathway. Here, we show that squalene epoxidase (SQLE), an enzyme of the cholesterol biosynthesis pathway, is overexpressed in advanced PCa and its expression correlates with poor survival. SQLE expression is controlled by micro-RNA 205 (miR-205), which is significantly downregulated in advanced PCa. Restoration of miR-205 expression or competitive inhibition of SQLE led to inhibition of de novo cholesterol biosynthesis. Furthermore, SQLE was essential for proliferation of AR-positive PCa cell lines, including abiraterone or enzalutamide resistant derivatives, and blocked transactivation of the AR pathway. Inhibition of SQLE with the FDA approved antifungal drug terbinafine also efficiently blocked orthotopic tumour growth in mice. Finally, terbinafine reduced levels of prostate specific antigen (PSA) in three out of four late-stage PCa patients. These results highlight SQLE as a therapeutic target for the treatment of advanced PCa.


Asunto(s)
Colesterol , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , MicroARNs , Neoplasias de la Próstata , Escualeno-Monooxigenasa , Anciano , Anciano de 80 o más Años , Animales , Humanos , Masculino , Ratones , Persona de Mediana Edad , Secuencia de Bases , Línea Celular Tumoral , Proliferación Celular/genética , Supervivencia Celular , Colesterol/biosíntesis , Estudios de Cohortes , Simulación por Computador , Modelos Animales de Enfermedad , Regulación hacia Abajo/genética , Resistencia a Antineoplásicos/genética , Ratones SCID , MicroARNs/genética , MicroARNs/metabolismo , Invasividad Neoplásica , Metástasis de la Neoplasia , Estadificación de Neoplasias , Antígeno Prostático Específico/metabolismo , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/patología , Receptores Androgénicos/metabolismo , Escualeno-Monooxigenasa/antagonistas & inhibidores , Escualeno-Monooxigenasa/genética , Escualeno-Monooxigenasa/metabolismo , Terbinafina/farmacología , Activación Transcripcional/genética
5.
Science ; 372(6538)2021 04 09.
Artículo en Inglés | MEDLINE | ID: mdl-33833098

RESUMEN

Fatty acid photodecarboxylase (FAP) is a photoenzyme with potential green chemistry applications. By combining static, time-resolved, and cryotrapping spectroscopy and crystallography as well as computation, we characterized Chlorella variabilis FAP reaction intermediates on time scales from subpicoseconds to milliseconds. High-resolution crystal structures from synchrotron and free electron laser x-ray sources highlighted an unusual bent shape of the oxidized flavin chromophore. We demonstrate that decarboxylation occurs directly upon reduction of the excited flavin by the fatty acid substrate. Along with flavin reoxidation by the alkyl radical intermediate, a major fraction of the cleaved carbon dioxide unexpectedly transformed in 100 nanoseconds, most likely into bicarbonate. This reaction is orders of magnitude faster than in solution. Two strictly conserved residues, R451 and C432, are essential for substrate stabilization and functional charge transfer.


Asunto(s)
Carboxiliasas/química , Carboxiliasas/metabolismo , Chlorella/enzimología , Ácidos Grasos/metabolismo , Proteínas Algáceas/química , Proteínas Algáceas/metabolismo , Alcanos/metabolismo , Sustitución de Aminoácidos , Aminoácidos/metabolismo , Bicarbonatos/metabolismo , Biocatálisis , Dióxido de Carbono/metabolismo , Dominio Catalítico , Cristalografía por Rayos X , Descarboxilación , Transporte de Electrón , Flavina-Adenina Dinucleótido/química , Enlace de Hidrógeno , Luz , Modelos Moleculares , Proteínas Mutantes/química , Proteínas Mutantes/metabolismo , Oxidación-Reducción , Fotones , Conformación Proteica , Temperatura
6.
Eur J Nucl Med Mol Imaging ; 48(4): 1178-1187, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33057927

RESUMEN

PURPOSE: In cancer of unknown primary (CUP), positron emission tomography/computed tomography (PET/CT) with the glucose analog [18F]FDG represents the standard imaging approach for localization of the malignant primary. Frequently, however, [18F]FDG PET/CT cannot precisely distinguish between small occult tumors and chronic inflammation, especially in Waldeyer's tonsillar ring. To improve the accuracy for detecting primary tumors in the Waldeyer's tonsillar ring, the novel PET tracer [68Ga]Ga-FAPI-4 for specific imaging of fibroblast activation protein (FAP) expression was used as a more specific target for cancer imaging. METHODS: Eight patients with suspicion of a malignant tumor in Waldeyer's tonsillar ring or a CUP syndrome were examined. PET/CT scans with [18F]-FDG and [68Ga]Ga-FAPI-4 were performed for pre-operative tumor localization. After surgical resection, histopathological and immunohistochemical results were compared to PET/CT findings. RESULTS: Histopathology revealed a palatine or lingual tonsil carcinoma in all patients. In case of lymph node metastases smaller than 7 mm in size, the [18F]FDG PET/CT detection rate of cervical lymph node metastases was higher than that of [68Ga]FAPI PET/CT, while both tracers identified the primary tumors in all eight cases. The size of the primary and the lymph node metastases was directly correlated to the respective FAP expression, as detected by immunohistochemistry. The mean SUVmax for the primary tumors was 21.29 ± 7.97 for 18F-FDG and 16.06 ± 6.29 for 68Ga-FAPI, respectively (p = 0.2). The mean SUVmax for the healthy contralateral tonsils was 8.38 ± 2.45 for [18F]FDG and 3.55 ± 0.47 for [68Ga]FAPI (p < 0.001). The SUVmax ratio of [68Ga]FAPI was significantly different from [18F] FDG (p = 0.03). Mean TBRmax for the [68Ga]Ga-FAPI-4 tracer was markedly higher in comparison to [18F]FDG (10.90 vs. 4.11). CONCLUSION: Non-invasive imaging of FAP expression by [68Ga]FAPI PET/CT resulted in a better visual detection of the malignant primary in CUP, as compared to [18F]FDG imaging. However, the detection rate of lymph node metastases was inferior, presumably due to low FAP expression in small metastases. Nevertheless, by offering a detection method for primary tumors with the potential of lower false positive rates and thus avoiding biopsies, patients with CUP syndrome may benefit from [68Ga]FAPI PET/CT imaging.


Asunto(s)
Neoplasias Primarias Desconocidas , Tomografía Computarizada por Tomografía de Emisión de Positrones , Fluorodesoxiglucosa F18 , Radioisótopos de Galio , Humanos , Ganglios Linfáticos , Neoplasias Primarias Desconocidas/diagnóstico por imagen
7.
J AAPOS ; 24(5): 301-303, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32882364

RESUMEN

To determine whether the fellow eye of children who have undergone unilateral cataract extraction in the first year of life are at increased risk of injury and vision loss, the 10.5-year data on 109 of 114 children enrolled in the Infant Aphakia Treatment Study were examined. Based on this limited data, it was estimated that the fellow eye is at greater risk of injury than the operated eye. Our data do not support the risk being higher in children with the worst vision in the treated eye.


Asunto(s)
Afaquia Poscatarata , Extracción de Catarata , Catarata , Afaquia Poscatarata/etiología , Afaquia Poscatarata/cirugía , Catarata/etiología , Niño , Estudios de Seguimiento , Humanos , Lactante , Implantación de Lentes Intraoculares , Agudeza Visual
8.
JAMA Ophthalmol ; 138(4): 365-372, 2020 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-32077909

RESUMEN

Importance: Although intraocular lenses (IOLs) are often implanted in children, little is known whether primary IOL implantation or aphakia and contact lens correction results in better long-term visual outcomes after unilateral cataract surgery during infancy. Objective: To compare long-term visual outcomes with contact lens vs IOL correction following unilateral cataract surgery during infancy. Design, Setting, and Participants: This multicenter randomized clinical trial enrolled 114 infants with a unilateral congenital cataract who underwent cataract surgery with or without primary IOL implantation between 1 and 6 months of age. Data on long-term visual outcomes were collected when the children were age 10.5 years (July 14, 2015, to July 12, 2019) and analyzed from March 30 through August 6, 2019. Interventions: Intraocular lens implantation at the time of cataract surgery. Main Outcomes and Measures: Best-corrected visual acuity using the electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) testing protocol. Analysis was performed on an intention-to-treat basis. Results: Best-corrected visual acuity was measured at age 10.5 years for 110 of the 114 patients (96%) enrolled as infants. The participants included 58 girls (53%) and 52 boys (47%). Overall, 27 of the children (25%) had good (logMAR 0.30 [Snellen equivalent, 20/40] or better) visual acuity in the treated eye (12 [22%] in the IOL group and 15 [27%] in the aphakia group), but 50 children (44%) had a visual acuity of logMAR 1.00 (Snellen equivalent, 20/200) or worse (25 [44%] in the IOL group and 25 [44%] in the aphakia group). The median logMAR acuity in the treated eye was similar in children randomized to receive an IOL at the time of cataract extraction (0.89; interquartile range [IQR], 0.33-1.43 [Snellen equivalent, 20/159]) and those who remained aphakic (0.86; IQR, 0.30-1.46 [Snellen equivalent, 20/145]) (IQR, 0.30-1.46; P = .82). Although the overall difference in median visual acuity between the 2 groups was small, the estimate was imprecise (99% CI for the difference in medians was -0.54 to 0.47). Conclusions and Relevance: As in previous phases of the study, visual acuity outcomes were highly variable with only 27 children (25%) achieving excellent visual acuity in their treated eye and 50 children (44%) having poor vision in the treated eye. Implanting an IOL at the time of cataract extraction was neither beneficial nor detrimental to the visual outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT00212134.


Asunto(s)
Afaquia Poscatarata/fisiopatología , Extracción de Catarata , Lentes de Contacto Hidrofílicos , Lentes Intraoculares , Seudofaquia/fisiopatología , Agudeza Visual/fisiología , Catarata/congénito , Niño , Femenino , Estudios de Seguimiento , Humanos , Lactante , Implantación de Lentes Intraoculares , Masculino , Visión Binocular/fisiología
9.
Am J Ophthalmol ; 200: 26-33, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30633891

RESUMEN

PURPOSE: To evaluate spectacle adherence with impact-resistant lenses among 4-year-old children after unilateral cataract surgery in the Infant Aphakia Treatment Study. DESIGN: Retrospective cohort analysis of randomized clinical trial data. METHODS: Setting: Multicenter. PATIENTS: One hundred and fourteen children randomized to contact lens correction or intraocular lens implantation following unilateral cataract surgery during infancy. INTERVENTION: One-week diaries completed annually and retrospective telephone interviews conducted every 3 months to age 5 years to assess spectacle adherence with impact-resistant lenses. Visual acuity was assessed by a traveling examiner at age 4.5 years. MAIN OUTCOME MEASURES: Spectacle adherence between ages 4 and 5 years. RESULTS: Children with 20/40 or better vision in their treated eye were more likely to wear spectacles ≥80% of their waking hours than children with vision worse than 20/40 (66% vs 42%, P = .034). Reported adherence to spectacle wear correlated with reported patching (r = 0.30, P = .002). Spectacle adherence did not correlate with sex, type of healthcare insurance, or the refractive error in the treated or fellow eye. Seven patients with reduced vision in their treated eye reported <10% spectacle adherence. CONCLUSIONS: These results confirm that it is possible to achieve high levels of spectacle adherence among 4-year-old children after unilateral cataract surgery during infancy. However, children with vision worse than 20/40 in their worse eye, who needed eye protection the most, had the worst adherence.


Asunto(s)
Afaquia Poscatarata/terapia , Anteojos/estadística & datos numéricos , Cooperación del Paciente/estadística & datos numéricos , Afaquia Poscatarata/fisiopatología , Catarata/congénito , Extracción de Catarata , Preescolar , Lentes de Contacto , Femenino , Humanos , Implantación de Lentes Intraoculares , Masculino , Ajuste de Prótesis , Refracción Ocular/fisiología , Errores de Refracción/terapia , Estudios Retrospectivos , Encuestas y Cuestionarios , Agudeza Visual/fisiología
10.
J AAPOS ; 22(4): 299-303.e2, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-30031874

RESUMEN

PURPOSE: To determine whether grating acuity at age 12 months can be used to predict recognition acuity at age 4.5 years in children treated for unilateral congenital cataract enrolled in the Infant Aphakia Treatment Study (IATS). METHODS: Traveling testers assessed monocular grating acuity at 12 months of age (Teller Acuity Card Test [TACT]) and recognition acuity at 4.5 years of age (Amblyopia Treatment Study Electronic Visual Acuity Testing, HOTV) in children treated for visually significant monocular cataract in the IATS. Spearman rank correlation was used to evaluate the relationship between visual acuities at the two ages in the treated eyes. RESULTS: Visual acuity data at both ages were available for 109 of 114 children (96%). Grating acuity at 12 months of age and recognition acuity at 4.5 years of age were significantly correlated for the treated eyes (rspearman = 0.45; P = 0.001). At age 4.5 years, 67% of the subjects who had grating acuity at 12 months of age within the 95% predictive limits in their treated eye demonstrated recognition acuity better than 20/200. Similarly, at age 4.5 years 67% of the subjects who had grating acuity at age 12 months below the 95% predictive limits in their treated eye demonstrated recognition acuity of 20/200 or worse. CONCLUSIONS: A single grating acuity assessment at age 12 months predicts recognition acuity in a child treated for unilateral congenital cataract in only two-thirds of cases. Clinicians should consider other factors, such as patching compliance and age at surgery, when using an early grating acuity assessment to modify treatment.


Asunto(s)
Afaquia Poscatarata/fisiopatología , Reconocimiento en Psicología/fisiología , Visión Monocular/fisiología , Agudeza Visual/fisiología , Preescolar , Femenino , Humanos , Lactante , Masculino , Valor Predictivo de las Pruebas
11.
Langmuir ; 34(15): 4695-4700, 2018 04 17.
Artículo en Inglés | MEDLINE | ID: mdl-29510056

RESUMEN

It is shown that introducing gravity in the energy minimization of drops on surfaces results in different expressions when minimized with respect to volume or with respect to contact angle. This phenomenon correlates with the probability of drops to bounce on smooth surfaces on which they otherwise form a very small contact angle or wet them completely. Theoretically, none of the two minima is stable: the drop should oscillate from one minimum to the other as long as no other force or friction will dissipate the energy. Experimentally, smooth surfaces indeed show drops that bounce on them. In some cases, they bounce after touching the solid surface, and in some cases they bounce from a nanometric air, or vacuum film. The bouncing energy can be stored in the interfaces: liquid-air, liquid-solid, and solid-air. The lack of a single energy minimum prevents a simple convergence of the drop's shape on the solid surface, and supports its bouncing back to the air. Therefore, the lack of a simple minimum described here supports drop bouncing on hydrophilic surfaces such as that reported by Kolinski et al. Our calculation shows that the smaller the surface tension, the bigger the difference between the contact angles calculated based on the two minima. This agrees with experimental finding where reducing the surface tension, for example, by adding surfactants, increases the probability for bouncing of the drops on smooth surfaces.

12.
J Anim Sci ; 95(3): 1104-1117, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28380504

RESUMEN

Limited information is available on the extent to which blankets are used on horses and the owners' reasoning behind clipping the horse's coat. Research on the effects of those practices on horse welfare is scarce but results indicate that blanketing and clipping may not be necessary from the horse's perspective and can interfere with the horse's thermoregulatory capacities. Therefore, this survey collected robust, quantitative data on the housing routines and management of horses with focus on blanketing and clipping practices as reported by members of the Swedish and Norwegian equestrian community. Horse owners were approached via an online survey, which was distributed to equestrian organizations and social media. Data from 4,122 Swedish and 2,075 Norwegian respondents were collected, of which 91 and 84% of respondents, respectively, reported using blankets on horses during turnout. Almost all respondents owning warmblood riding horses used blankets outdoors (97% in Sweden and 96% in Norway) whereas owners with Icelandic horses and coldblood riding horses used blankets significantly less ( < 0.05). Blankets were mainly used during rainy, cold, or windy weather conditions and in ambient temperatures of 10°C and below. The horse's coat was clipped by 67% of respondents in Sweden and 35% of Norwegian respondents whereby owners with warmblood horses and horses primarily used for dressage and competition reported clipping the coat most frequently. In contrast to scientific results indicating that recovery time after exercise increases with blankets and that clipped horses have a greater heat loss capacity, only around 50% of respondents agreed to these statements. This indicates that evidence-based information on all aspects of blanketing and clipping has not yet been widely distributed in practice. More research is encouraged, specifically looking at the effect of blankets on sweaty horses being turned out after intense physical exercise and the effect of blankets on social interactions such as mutual grooming. Future efforts should be tailored to disseminate knowledge more efficiently, which can ultimately stimulate thoughtful decision-making by horse owners concerning the use of blankets and clipping the horse's coat.


Asunto(s)
Crianza de Animales Domésticos , Regulación de la Temperatura Corporal , Frío , Caballos/fisiología , Animales , Noruega , Propiedad , Conducta Social , Encuestas y Cuestionarios , Suecia , Tiempo (Meteorología) , Viento
13.
Leukemia ; 31(10): 2181-2190, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28119525

RESUMEN

Blinatumomab can induce a complete haematological remission in patients in 46.6% with relapsed/refractory B-precursor acute lymphoblastic leukemia (r/r ALL) resulting in a survival benefit when compared with chemotherapy. Only bone marrow blast counts before therapy have shown a weak prediction of response. Here we investigated the role of regulatory T cells (Tregs), measured by CD4/CD25/FOXP3 expression, in predicting the outcome of immunotherapy with the CD19-directed bispecific T-cell engager construct blinatumomab. Blinatumomab responders (n=22) had an average of 4.82% Tregs (confidence interval (CI): 1.79-8.34%) in the peripheral blood, whereas non-responders (n=20) demonstrated 10.25% Tregs (CI: 3.36-65.9%). All other tested markers showed either no prediction value or an inferior prediction level including blast BM counts and the classical enzyme marker lactate dehydrogenase. With a cutoff of 8.525%, Treg enumeration can identify 100% of all blinatumomab responders and exclude 70% of the non-responders. The effect is facilitated by blinatumomab-activated Tregs, leading to interleukin-10 production, resulting in suppression of T-cell proliferation and reduced CD8-mediated lysis of ALL cells. Proliferation of patients' T cells can be restored by upfront removal of Tregs. Thus, enumeration of Treg identifies r/r ALL patients with a high response rate to blinatumomab. Therapeutic removal of Tregs may convert blinatumomab non-responders to responders.


Asunto(s)
Anticuerpos Biespecíficos/uso terapéutico , Inmunoterapia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Terapia Recuperativa , Linfocitos T Reguladores/inmunología , Adolescente , Adulto , Anciano , Anticuerpos Biespecíficos/inmunología , Antígenos de Diferenciación de Linfocitos T/análisis , Línea Celular Tumoral , Ensayos Clínicos como Asunto , Citotoxicidad Inmunológica , Femenino , Humanos , Inmunofenotipificación , Interleucina-10/biosíntesis , Interleucina-10/genética , Activación de Linfocitos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Pronóstico , Inducción de Remisión , Subgrupos de Linfocitos T/inmunología , Resultado del Tratamiento
14.
Eye (Lond) ; 30(9): 1221-8, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27472216

RESUMEN

PurposeTo identify factors associated with stereopsis in children with good visual acuity after unilateral congenital cataract surgery in the Infant Aphakia Treatment Study.Patients and methodsInfants with a unilateral congenital cataract (n=114) were randomized to IOL implantation or contact lens correction after cataract surgery. At age 4.5 years, a masked examiner assessed HOTV acuity and stereopsis. Adherence to patching was assessed using 48-h recall telephone interviews and 7-day diaries throughout the first 5 years of life. Ocular motility was evaluated at age 5 years. Baseline, postoperative, and adherence findings were compared between patients with 20/40 or better acuity in their treated eyes with or without stereopsis.ResultsThirty (27%) of 112 patients who were evaluated at age 4.5 years had 20/40 or better acuity in their treated eye. Stereopsis was present on one or more tests in 15 of these 30 (50%) children. Baseline characteristics and postoperative findings did not differ between patients with or without stereopsis. Children with stereopsis were more likely to be orthotropic at distance (P=0.003) and were patched for fewer hours per day throughout the first 5 years of life and the difference increased over time (P<0.001). On average children with stereopsis were patched for 3.4 h/day during the first year of life and patching steadily decreased to 1.8 h/day by age 4 years.ConclusionAmong children with good vision following unilateral congenital cataract surgery, orthophoria and fewer hours of patching, particularly during years 2, 3, and 4, are associated with some evidence of stereopsis.


Asunto(s)
Afaquia Poscatarata/fisiopatología , Afaquia Poscatarata/terapia , Lentes de Contacto , Percepción de Profundidad/fisiología , Anteojos , Implantación de Lentes Intraoculares , Agudeza Visual/fisiología , Catarata/congénito , Extracción de Catarata , Femenino , Humanos , Lactante , Masculino , Factores de Riesgo
15.
J AAPOS ; 20(4): 320-5, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-27424046

RESUMEN

PURPOSE: To determine whether behavioral functioning of 4.5-year-olds differs between two treatments for unilateral cataract and whether behavioral functioning is predicted by visual acuity in the treated eye. METHODS: The Infant Aphakia Treatment Study is a multicenter clinical trial in which 114 infants with unilateral congenital cataracts were randomized to undergo cataract extraction with contact lens correction or implantation of an intraocular lens. Patching data were collected during the year preceding a visit at age 4.5 years, when both visual acuity and caregiver-reported behavioral functioning were assessed for 109 participants. Caregiver stress was assessed with the Parenting Stress Index at 4.25 years. RESULTS: There were no treatment group differences in behavioral functioning as measured by the Child Behavior Checklist. Poorer visual acuity was associated with more externalizing behavior problems (attention problems and aggressive behavior) and total behavior problems in regression models that did not include caregiver stress. Both caregiver stress and dichotomized visual acuity significantly predicted externalizing problems. CONCLUSIONS: Treatment assignment did not affect caregiver-reported behavior. Poor visual acuity may confer risk for problems with attention and aggressive behavior in preschoolers treated for unilateral cataract.


Asunto(s)
Afaquia Poscatarata , Extracción de Catarata , Implantación de Lentes Intraoculares , Catarata , Preescolar , Lentes de Contacto , Humanos , Lentes Intraoculares
16.
JAMA Ophthalmol ; 134(8): 863-9, 2016 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-27228110

RESUMEN

IMPORTANCE: Patching has been a mainstay in treating unilateral congenital cataract. However, its efficacy has not been rigorously assessed. OBJECTIVE: To examine the association between patching and visual acuity in a cohort of children treated for unilateral congenital cataract. DESIGN, SETTING, AND PARTICIPANTS: This study was a secondary analysis of a randomized clinical trial (Infant Aphakia Treatment Study) of infants born from August 1, 2004, through December 31, 2008, who were treated with 1 of 2 treatments for unilateral congenital cataract and followed up to 5 years of age. Data analysis was performed from March 1, 2013, to March 1, 2016. INTERVENTIONS: Cataract extraction and randomization to receipt of an intraocular lens vs being left aphakic for the first 5 years of life. MAIN OUTCOMES AND MEASURES: Caregivers reported patching in the previous 48 hours in quarterly semistructured telephone interviews. The mean number of hours of patching per day was calculated from surgery to the first birthday (n = 92) and between 12 and 48 months of age (n = 102). Monocular optotype acuity was assessed at 4½ years of age by a traveling examiner using the Aphakia Treatment Study HOTV protocol. RESULTS: The Infant Aphakia Treatment Study enrolled 114 children; 57 were randomized to each treatment group. At 4½ years of age, optotype visual acuity was assessed in 112 children. The current analyses exclude an additional 3 children (2 who had adverse events that limited visual potential and 1 who had Stickler syndrome), leaving 109 total children analyzed (59 female [54.1%] and 92 white [84.4%]). Caregivers reported patching their children a mean (SD) of 3.73 (1.47) hours per day in the first year of life and 3.43 (2.04) hours per day thereafter. An association between reported patching and treatment was not identified (mean difference in first year, -0.29 hours per day; 95% CI, -0.90 to 0.33 hours per day; mean difference between 12 and 48 months of age, -0.40 hours per day; 95% CI, -1.20 to 0.40 hours per day). Visual acuity was associated with reported hours of patching in the first year of life (r = -0.32; 95% CI, -0.49 to -0.13) and between 12 and 48 months of age (r = -0.36; 95% CI, -0.52 to -0.18). However, patching accounted for less than 15% of the variance in logMAR acuity at 4½ years of age. CONCLUSIONS AND RELEVANCE: These results support the association of occlusion throughout the preschool years with improved visual acuity in infants treated for unilateral congenital cataract. However, similar visual outcomes were achieved with varying amounts of patching. These conclusions should be interpreted in the context of limitations related to generalizability from incomplete data collected in a clinical trial. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00212134.


Asunto(s)
Afaquia Poscatarata/terapia , Extracción de Catarata , Catarata/congénito , Lentes de Contacto , Agudeza Visual/fisiología , Afaquia Poscatarata/diagnóstico , Afaquia Poscatarata/fisiopatología , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Estudios Retrospectivos , Privación Sensorial , Factores de Tiempo
17.
J Dairy Res ; 83(2): 173-9, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-27056664

RESUMEN

Milk with a high concentration of fat and casein is required for cheese production, and these components have a major impact for both quality and yield of the curd. Recent observations have shown that suckling can elevate milk fat concentration in goats and our aim was therefore to check the hypothesis that animal welfare and cheese-processing properties of goat milk could be optimised by appropriate management of suckled/milked goats. Twelve Swedish dairy goats were kept together with one kid each in 4 different mixed management-systems (milking combined with partial suckling) in a cross-over design. Two milk accumulation intervals were tested; Short = dams and kids were together for 16 h (T16) and Long = ; dams and kids were together for 8 h (T8 h). In addition, two milking regimes were used; Suckled Before Milking = S and Milked Before Suckling = M. Milk accumulation interval referred to how long dams and kids were separated. The milk yield available for processing (milk offtake), was weighed and analysed from each milking occasion and the suckled milk yield was estimated by a weigh-suckle-weigh method (WSW) in combination with observing the suckling behaviour during the free suckling periods. Milking managements, such as 'suckling before milking (S)', increased milk fat concentration compared to milking before suckling (M) and 'Short accumulation treatments (T16)' gave higher milk fat, casein concentration and individual curd yield (%) compared to the 'Long accumulation treatment (T8)'. The total individual curd yield (g) was the same despite treatment, but the animal welfare was most likely higher in T16 where dams and kids spent more time together.


Asunto(s)
Industria Lechera/métodos , Cabras , Lactancia , Leche , Animales , Caseínas/análisis , Recuento de Células , Queso , Grasas/análisis , Femenino , Manipulación de Alimentos/métodos , Concentración de Iones de Hidrógeno , Leche/química , Leche/citología , Conducta en la Lactancia , Suecia
18.
Dev Med Child Neurol ; 58(2): 154-9, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26084944

RESUMEN

AIM: To assess motor functioning in children aged 4 years 6 months enrolled in the Infant Aphakia Treatment Study, and to determine contributions of visual acuity and stereopsis to measured motor skills. METHOD: One hundred and four children (53% female) with unilateral aphakia randomized to intraocular lens or contact lens treatment were evaluated at 4 years 6 months (age range 4y 6mo-4y 11mo) for monocular recognition visual acuity, motor skills, and stereopsis by a traveling examiner masked to treatment condition. Motor skills were assessed with the Movement Assessment Battery for Children--Second Edition (MABC-2). Visual acuity was operationalized as log10 of the minimum angle of resolution (logMAR) value for treated eye, best logMAR value for either eye, and intraocular logMAR difference. RESULTS: Student's t-tests showed no significant differences in MABC-2 scores between the intraocular lens and contact lens groups. The mean total score was low (6.43; 18th centile) compared with the normative reference group. Motor functioning was not related to visual acuity in the treated eye or to intraocular logMAR difference, but was predicted in a regression model by the better visual acuity of either eye (usually the fellow eye), even after accounting for the influence of age at surgery, examiner, orthotropic ocular alignment, and stereopsis. INTERPRETATION: Children with unilateral congenital cataract may have delayed motor functioning at 4 years 6 months, which may adversely affect their social and academic functioning.


Asunto(s)
Afaquia/fisiopatología , Desarrollo Infantil/fisiología , Destreza Motora/fisiología , Trastornos de la Visión/fisiopatología , Agudeza Visual/fisiología , Afaquia/complicaciones , Afaquia/congénito , Preescolar , Percepción de Profundidad/fisiología , Femenino , Humanos , Masculino , Trastornos de la Visión/etiología , Visión Monocular/fisiología
19.
J Anim Sci ; 93(9): 4564-74, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26440355

RESUMEN

Keeping horses in groups is widely recommended but limited information is available about how this is implemented in practice. The aim of this survey was to describe how horses are kept in the Nordic countries in relation to sex, age, breed, and equestrian discipline and to assess owners' attitudes toward keeping horses in groups. Horse owners in Denmark, Finland, Norway, and Sweden were approached using a web-based questionnaire, which was translated into 4 languages and distributed online via equestrian forums, organizations, and social media. The number of respondents was 3,229, taking care of 17,248 horses. Only 8% of horses were never kept in groups, 47% were permanently grouped for 24 h/d, and 45% were stabled singly but grouped during turnout. Yearlings were most often permanently kept in groups (75%), mares and geldings more commonly during parts of the day (50 and 51%, respectively), and stallions were often kept alone (38%). Icelandic horses were more likely to be permanently kept in groups (36%) than warmbloods (16%) and ponies (15%). Twice as many competition horses (51%) were never grouped compared with horses used for breeding (20%) or leisure purposes (15%). The majority of respondents (86%) strongly agreed that group housing benefits horse welfare and that it is important for horses to have the company of conspecifics (92%). Nevertheless, not all horses were kept in groups, showing that attitudes toward group housing may not necessarily reflect current management. The risk of injury was a concern of many respondents (45%), as was introducing unfamiliar horses into already established groups (40%) and challenges in relation to feeding in groups (44%). Safety of people (23%) and difficulties handling group-kept horses (19%) were regarded as less problematic. Results suggest that the majority of horses have the possibility to freely interact with other horses, either as fulltime members of a group during 24 h/d or during turnout. Future research should address the extent to which being a part-time member of a group affects horse welfare. For permanent group housing to become more widespread, such as it is the case for most farm animals, future research could focus on solving some of the reoccurring problems perceived with keeping horses in groups. The dissemination of evidence-based information on all aspects around keeping horses in groups can ultimately stimulate further positive changes in the management of group-kept horses.


Asunto(s)
Crianza de Animales Domésticos/métodos , Caballos/fisiología , Vivienda para Animales , Animales , Actitud , Femenino , Masculino , Países Escandinavos y Nórdicos , Conducta Social , Encuestas y Cuestionarios
20.
Anaesthesia ; 70(10): 1171-9, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26179167

RESUMEN

Novel devices for small-lumen ventilation may enable effective inspiration and expiratory ventilation assistance despite airway obstruction. In this study, we investigated a porcine model of complete upper airway obstruction. After ethical approval, we randomly assigned 13 anaesthetised pigs either to small-lumen ventilation following airway obstruction (n = 8) for 30 min, or to volume-controlled ventilation (sham setting, n = 5). Small-lumen ventilation enabled adequate gas exchange over 30 min. One animal died as a result of a tension pneumothorax in this setting. Redistribution of ventilation from dorsal to central compartments and significant impairment of the distribution of ventilation/perfusion occurred. Histopathology demonstrated considerable lung injury, predominantly through differences in the dorsal dependent lung regions. Small-lumen ventilation maintained adequate gas exchange in a porcine airway obstruction model. The use of this technique for 30 min by inexperienced clinicians was associated with considerable end-expiratory collapse leading to lung injury, and may also carry the risk of severe injury.


Asunto(s)
Obstrucción de las Vías Aéreas/terapia , Respiración Artificial/métodos , Lesión Pulmonar Aguda/etiología , Obstrucción de las Vías Aéreas/sangre , Obstrucción de las Vías Aéreas/fisiopatología , Animales , Modelos Animales de Enfermedad , Hemodinámica/fisiología , Masculino , Oxígeno/sangre , Presión Parcial , Intercambio Gaseoso Pulmonar/fisiología , Respiración Artificial/efectos adversos , Sus scrofa , Volumen de Ventilación Pulmonar/fisiología , Traqueotomía/métodos
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