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PURPOSE: Persistent deficits in knee flexor strength following harvest of semitendinosus and gracilis for anterior cruciate ligament reconstruction are inconsistent in the literature. Variation in methodology, including measuring torque at higher knee flexion angles may partially explain these discrepant findings. The objective of this study was to determine whether positioning (seated vs supine), consideration of peak or joint-angle-specific torque or device (Isokinetic Dynamometer vs NordBord Hamstring Dynamometer) impact the magnitude of knee flexor strength differences between limbs. METHODS: Participants (n = 31, 44.2 ± 10.7 years,) who were at 14 ± 4.4 years follow-up for unilateral ACL reconstruction with semitendinosus/gracilis grafts completed the ACL Quality of Life outcome and an assessment including isokinetic concentric knee extensor and flexor strength in seated and supine with peak torque and torque at 60° (T60) and 75° (T75) knee flexion measured, followed by an eccentric Nordic Hamstring Curl. RESULTS: Isokinetic concentric knee flexor torque was reduced in supine relative to seated, on the reconstructed limb against the unaffected, and at higher degrees of knee flexion relative to peak torque (T60 and T75 against peak torque). Limb symmetry varied by methodology (F(6,204) = 8.506, p = 0.001) with reduced symmetry in supine T75 against all measures (71.1 ± 16.5%, p < 0.05), supine T60 against seated peak torque (82.7 ± 14.2%, p < 0.05), and the NordBord was lower than seated peak torque that was not statistically significant (83.9 ± 12.8%, n.s.). Knee extensor peak (r2 = 0.167 (F(1,27) = 5.3, p = 0.03) and Nordic curl eccentric torque (r2 = 0.267, F(2,26) = 4.736, p = 0.02) were predictors of ACL-QoL score, although a combined model did not improve over Nordic torque alone. CONCLUSION: Limb symmetry cannot be assumed in clinical practice across differing assessment methods for knee flexor strength as deficits are greatest in the supine position with torque measured at 75° knee flexion. Isokinetic knee extensor and eccentric knee flexor torque during the Nordic hamstring curl were predictors of ACL-QoL scoring and should be considered alongside patient-reported outcomes for patients following ACL reconstruction with hamstring grafts. LEVEL OF EVIDENCE: Level IV.
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Músculos Isquiosurales , Calidad de Vida , Humanos , Estudios de Seguimiento , Articulación de la Rodilla/cirugía , RodillaRESUMEN
BACKGROUND: Recovery Colleges are a relatively recent initiative within mental health services. The first opened in 2009 in London and since then numbers have grown. They are based on principles of personal recovery in mental health, co-production between people with lived experience of mental health problems and professionals, and adult learning. Student eligibility criteria vary, but all serve people who use mental health services, with empirical evidence of benefit. Previously we developed a Recovery College fidelity measure and a preliminary change model identifying the mechanisms of action and outcomes for this group, which we refer to as service user students. The Recovery Colleges Characterisation and Testing (RECOLLECT) study is a five-year (2020-2025) programme of research in England. The aim of RECOLLECT is to determine Recovery Colleges' effectiveness and cost-effectiveness, and identify organisational influences on fidelity and improvements in mental health outcomes. METHODS: RECOLLECT comprises i) a national survey of Recovery Colleges, ii) a prospective cohort study to establish the relationship between fidelity, mechanisms of action and psychosocial outcomes, iii) a prospective cohort study to investigate effectiveness and cost-effectiveness, iv) a retrospective cohort study to determine the relationship between Recovery College use and outcomes and mental health service use, and v) organisational case studies to establish the contextual and organisational factors influencing fidelity and outcomes. The programme has been developed with input from individuals who have lived experience of mental health problems. A Lived Experience Advisory Panel will provide input into all stages of the research. DISCUSSION: RECOLLECT will provide the first rigorous evidence on the effectiveness and cost effectiveness of Recovery Colleges in England, to inform their prioritising, commissioning, and running. The validated RECOLLECT multilevel change model will confirm the active components of Recovery Colleges. The fidelity measure and evidence about the fidelity-outcome relationship will provide an empirically-based approach to develop Recovery Colleges, to maximise benefits for students. Findings will be disseminated through the study website (researchintorecovery.com/recollect) and via national and international Recovery College networks to maximise impact, and will shape policy on how Recovery Colleges can help those with mental health problems lead empowered, meaningful and fulfilling lives.
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Servicios de Salud Mental , Adulto , Inglaterra , Humanos , Estudios Prospectivos , Estudios Retrospectivos , UniversidadesRESUMEN
The social health of people living with dementia is a more recent addition to the dementia research agenda; to date conceptions of the problem and solutions have relied on underdeveloped theorisations of sociality and social inclusion. In this article, using a material-semiotic approach to care practices and infrastructure, we use an ethnographic case study of one family of a person living with dementia using a day programme and home care supports over a period of 9 months, to examine how infrastructural arrangements provide particular affordances for social relatedness for people living with dementia in the community. The aim of the analysis is to consider how the infrastructural affordances created by the organisation of care may create spatially bounded lives and limit the subject positions available for people living with dementia and their families. It is these narrowed positions of dwelling that we argue may be the necessary starting place for thinking about the social health of people living with dementia and the solutions that might be helpful for them.
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Demencia , Servicios de Atención de Salud a Domicilio , Humanos , Cuidadores , Calidad de VidaRESUMEN
PURPOSE: Contralateral graft harvest in primary ACL reconstruction is relatively uncommon and the long-term comparative of this approach relative to ipsilateral harvest has not been described. The purpose of this study was to evaluate ACL graft and contralateral rupture following ipsilateral or contralateral semitendinosus and gracilis (STG) graft harvest at follow-up of a minimum 10 years post-reconstruction in the treatment of a complete ACL tear. METHODS: Patients from a previous randomized trial were evaluated. The primary outcome measures were ipsilateral and contralateral reinjury as well as the International Knee Documentation Committee (IKDC) knee assessment form, the ACL Quality of Life questionnaire (ACL-QoL) and the Tegner activity scale. Participants completed four different single-leg hop tests and concentric knee flexion and extension strength were assessed on an isokinetic dynamometer. RESULTS: Of the original 100 patients, 50 patients (41.3 ± 9.5 years of age, 31 males, 19 females) reported on re-injury at 12.6 ± 1.4 years post-operative. Thirty-eight patients returned for full assessment and 12 responded by mail or phone survey. There were no differences between groups for graft rupture, contralateral injury, ACL-QoL score, IKDC categorization, or anterior tibial translation, though both groups experienced a reduction in the Tegner Activity Scale from their preinjury scores. There was no difference in knee flexor and extensor isokinetic concentric strength, or single leg hop test performance. Knee flexor strength limb symmetry index was reduced when measured in the supine relative to the seated position in both groups, indicating persistent deficits in knee flexor strength when measured in the supine position. CONCLUSION: Contralateral hamstring harvest does not put patients at an increased risk of a contralateral ACL tear and long-term outcomes of ACL reconstruction do not differ based on the side of graft harvest. Contralateral STG harvest may provide a safe alternative surgical option for select patients. LEVEL OF EVIDENCE: Level II.
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Lesiones del Ligamento Cruzado Anterior , Reconstrucción del Ligamento Cruzado Anterior , Músculos Isquiosurales , Adulto , Ligamento Cruzado Anterior/cirugía , Lesiones del Ligamento Cruzado Anterior/etiología , Lesiones del Ligamento Cruzado Anterior/cirugía , Reconstrucción del Ligamento Cruzado Anterior/efectos adversos , Femenino , Músculos Isquiosurales/cirugía , Humanos , Articulación de la Rodilla/cirugía , Masculino , Calidad de Vida , Rotura/cirugíaRESUMEN
Across most age groups, individuals with intellectual disability (ID) have higher rates of mental health conditions than the general population. Approximately one third of older adults with ID living in the community experience the same mental health conditions as older adults in the general population but have unique needs for assessment and treatment. A health equity framework offers an important social perspective in addressing these needs. Timely recognition and diagnosis of mental health conditions in individuals with ID involves collaboration with family and other supports. Among older adults with ID, polypharmacy is strongly associated with mental health conditions. Older adults with ID are more likely to use the emergency department for treatment of their mental health conditions. The majority of mental health providers are not trained in working with patients with ID. Education, policy changes, and research are needed to improve the mental health care of this population. [Journal of Psychosocial Nursing and Mental Health Services, 60(7), 10-14.].
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Discapacidad Intelectual , Servicios de Salud Mental , Anciano , Humanos , Discapacidad Intelectual/terapia , Salud Mental , PolifarmaciaRESUMEN
PURPOSE: Both intravenous dexamethasone and dexmedetomidine prolong the analgesic duration of interscalene blocks (ISB) after arthroscopic shoulder surgery. This study compared their relative effectiveness and the benefit of their use in combination. METHODS: This single-centre, double-blinded, parallel three-group superiority trial randomized 198 adult patients undergoing ambulatory arthroscopic shoulder surgery. Patients received preoperative ISB with 30 mL 0.5% bupivacaine and 50 µg dexmedetomidine or 4 mg dexamethasone or both of these agents as intravenous adjuncts. The primary outcome was analgesic block duration. Secondary outcomes included the quality of recovery 15 score (range: 0-150) on day 1 and postoperative neurologic symptoms in the surgical arm. RESULTS: Block durations (n = 195) with dexamethasone (median [range], 24.5 [2.0-339.5] hr) and both adjuncts (24.0 [1.5-157.0] hr) were prolonged compared with dexmedetomidine (16.0 [1.5-154.0] hr). When analyzed by linear regression after an unplanned log transformation because of right-skewed data, the corresponding prolongations of block duration were 59% (95% confidence interval [CI], 28 to 97) and 46% (95% CI, 18 to 80), respectively (both P < 0.001). The combined adjuncts were not superior to dexamethasone alone (-8%; 95% CI, -26 to 14; P = 0.42). Median [IQR] quality of recovery 15 scores (n = 197) were significantly different only between dexamethasone (126 [79-149]) and dexmedetomidine (118.5 [41-150], P = 0.004), but by an amount less than the 8-point minimum clinically important difference. CONCLUSION: Dexamethasone is superior to dexmedetomidine as an intravenous adjunct for prolongation of bupivacaine-based ISB analgesic duration. There was no additional benefit to using both adjuncts in combination. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT03270033); registered 1 September 2017.
RéSUMé: OBJECTIF: La dexaméthasone et la dexmédétomidine intraveineuses prolongent toutes deux la durée analgésique des blocs interscaléniques (BIS) après une chirurgie arthroscopique de l'épaule. Cette étude a comparé leur efficacité relative et les avantages d'une utilisation des deux agents en combinaison. MéTHODE: Cette étude de supériorité monocentrique en trois groupes parallèles à double insu a randomisé 198 patients adultes subissant une chirurgie arthroscopique de l'épaule en ambulatoire. Les patients ont reçu un BIS préopératoire composé de 30 mL de bupivacaïne 0,5 % avec 50 µg de dexmédétomidine, 4 mg de dexaméthasone, ou la combinaison de ces deux agents comme adjuvants intraveineux. Le critère d'évaluation principal était la durée analgésique du bloc. Les critères d'évaluation secondaires comprenaient le score de qualité de récupération (QoR) 15 (plage : 0-150) au jour 1 et les symptômes neurologiques postopératoires dans le bras opéré. RéSULTATS: Les durées des blocs (n = 195) avec la dexaméthasone (médiane [plage], 24,5 [2,0-339,5] heures) et la combinaison des deux adjuvants (24,0 [1,5-157,0] heures) ont été prolongées par rapport à la dexmédétomidine (16,0 [1,5-154,0] heures). Lorsqu'elles ont été analysées par régression linéaire après une transformation logarithmique non planifiée en raison de données biaisées vers la droite, les prolongations correspondantes de la durée du bloc étaient de 59 % (intervalle de confiance [IC] 95 %, 28 à 97) et de 46 % (IC 95 %, 18 à 80), respectivement (les deux P < 0,001). La combinaison des adjuvants n'était pas supérieure à la dexaméthasone seule (-8 %; IC 95 %, -26 à 14; P = 0,42). Les scores médians [ÉIQ] de qualité de récupération 15 (n = 197) n'étaient significativement différents qu'entre la dexaméthasone (126 [79-149]) et la dexmédétomidine (118,5 [41-150], P = 0,004), mais la différence observée était inférieure à la différence minimale de 8 points nécessaire pour être considérée cliniquement importante. CONCLUSION: La dexaméthasone est supérieure à la dexmédétomidine en tant qu'adjuvant intraveineux pour prolonger la durée analgésique d'un BIS à base de bupivacaïne. Aucun avantage supplémentaire n'a été observé lors de l'utilisation combinée des deux adjuvants. ENREGISTREMENT DE L'éTUDE: www.clinicaltrials.gov (NCT03270033); enregistrée le 1er septembre 2017.
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Bloqueo del Plexo Braquial , Dexmedetomidina , Adulto , Analgésicos , Anestésicos Locales , Artroscopía , Dexametasona , Método Doble Ciego , Humanos , Pacientes Ambulatorios , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Hombro/cirugíaRESUMEN
Previous research has found that sexual desire ebbs and flows over time within and across relationships, leading to instances of desire discrepancy. The purpose of the present study was to understand factors that may contribute to desire and desire discrepancy and examine differences and similarities across women from diverse sexual identity groups. The present qualitative study involved semi-structured interviews with 31 women (10 bisexual, 8 lesbian, and 13 straight). We identified six main themes (changes across lifespan, hormonal influences, mental and physical health, objective of desire, partner dynamics, external factors) with 21 subthemes. The findings showed more similarities between the women than differences.
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Heterosexualidad/psicología , Homosexualidad Femenina/psicología , Relaciones Interpersonales , Libido , Excitación Sexual , Minorías Sexuales y de Género/psicología , Mujeres/psicología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Investigación CualitativaRESUMEN
Current treatment guidelines for patients with locally advanced head and neck squamous cell carcinoma (HNSCC) recommend multimodal treatment, including chemoradiation therapy (CRT) or surgery followed by radiation, with or without chemotherapy. The immune checkpoint inhibitor pembrolizumab has previously demonstrated antitumor activity in recurrent and/or metastatic HNSCC in large Phase III trials. For patients with locally advanced disease, Phase Ib data on the use of pembrolizumab in combination with chemoradiation have shown the approach to be safe and feasible. We describe here the design and rationale for KEYNOTE-412, a randomized, double-blind, Phase III trial investigating pembrolizumab or placebo administered concurrently with CRT and as maintenance treatment in patients with locally advanced HNSCC. Clinical Trial Registration: NCT03040999 (ClinicalTrials.gov).
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/efectos adversos , Quimioradioterapia , Terapia Combinada/efectos adversos , Terapia Combinada/métodos , Humanos , Quimioterapia de Mantención , Metástasis de la Neoplasia , Estadificación de Neoplasias , Carcinoma de Células Escamosas de Cabeza y Cuello/patologíaRESUMEN
The ability to rationally manipulate the transcriptional states of cells would be of great use in medicine and bioengineering. We have developed an algorithm, NetSurgeon, which uses genome-wide gene-regulatory networks to identify interventions that force a cell toward a desired expression state. We first validated NetSurgeon extensively on existing datasets. Next, we used NetSurgeon to select transcription factor deletions aimed at improving ethanol production in Saccharomyces cerevisiae cultures that are catabolizing xylose. We reasoned that interventions that move the transcriptional state of cells using xylose toward that of cells producing large amounts of ethanol from glucose might improve xylose fermentation. Some of the interventions selected by NetSurgeon successfully promoted a fermentative transcriptional state in the absence of glucose, resulting in strains with a 2.7-fold increase in xylose import rates, a 4-fold improvement in xylose integration into central carbon metabolism, or a 1.3-fold increase in ethanol production rate. We conclude by presenting an integrated model of transcriptional regulation and metabolic flux that will enable future efforts aimed at improving xylose fermentation to prioritize functional regulators of central carbon metabolism.
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Eliminación de Gen , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crecimiento & desarrollo , Factores de Transcripción/genética , Algoritmos , Etanol/metabolismo , Fermentación , Redes Reguladoras de Genes , Glucosa/metabolismo , Ingeniería Metabólica , Modelos Genéticos , Saccharomyces cerevisiae/genética , Transcriptoma , Xilosa/metabolismoRESUMEN
IMPORTANCE: Excessive ocular sun exposure is linked to various eye pathologies. Conjunctival ultraviolet autofluorescence (CUVAF) is a method of detecting sun-related conjunctival damage; however, the custom-built camera system required is not readily available. BACKGROUND: We investigated whether blue laser autofluorescence (BAF) on a commonly used confocal scanning laser ophthalmoscope (cSLO) can be utilized to measure CUVAF area. DESIGN: Cross-sectional evaluation of a diagnostic technology at a medical research institute. PARTICIPANTS: Sixty-four participants recruited from three on-going observational eye studies in Western Australia. METHODS: All participants had four images, two of each eye, captured using the CUVAF camera and BAF on the same day. Participants with pterygium or poor quality images were excluded from the analysis. Two graders measured CUVAF area in each image twice. CUVAF area measured by BAF was then compared to measurements determined with the conventional camera system. MAIN OUTCOME MEASURES: CUVAF area. RESULTS: After exclusions, 50 participants' images were analysed. Intra- and inter-observer repeatability were similar between the two systems. When comparing CUVAF area measured by BAF to the camera measurement, grader 1 had a mean difference of +1.00 mm2 , with 95% limits of agreement -5.75 to 7.77 mm2 . Grader 2 had a mean difference of +0.21mm2 , with 95% limits of agreement -7.22 to 7.64 mm2 . CONCLUSIONS AND RELEVANCE: BAF on a commercially available cSLO is a valid method for measuring CUVAF area. This finding provides broader opportunity for identifying, monitoring and educating patients with sun-exposure-related ocular conditions and for researching the ocular impacts of sun exposure.
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Conjuntiva/efectos de la radiación , Enfermedades de la Conjuntiva/diagnóstico por imagen , Imagen Óptica/métodos , Traumatismos por Radiación/diagnóstico por imagen , Luz Solar/efectos adversos , Adulto , Enfermedades de la Conjuntiva/etiología , Estudios Transversales , Exposición a Riesgos Ambientales , Femenino , Humanos , Masculino , Microscopía Confocal/instrumentación , Variaciones Dependientes del Observador , Traumatismos por Radiación/etiología , Reproducibilidad de los Resultados , Rayos Ultravioleta/efectos adversos , Australia OccidentalAsunto(s)
Equidad en Salud , Discapacidad Intelectual , Niño , Humanos , Discapacidades del Desarrollo , Personal de SaludRESUMEN
A 2-year-old Thoroughbred racehorse had LF lameness that began post high-speed exercise and persisted for two days before the horse once again became sound. Diagnostic analgesia localized the lameness to the LF distal metacarpus, and a standing MRI identified a unicortical condylar fracture. A single 5.5 mm cortical screw was placed in lag fashion. The horse began hand walking at 14 days, racetrack jogging at 30 days, and racing at 5 months after the day of surgery. Placement of a single lag screw ahead of the tip of the crack in unicortical condylar fracture may be useful for reducing the recovery period for horses returning to training and racing.
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BACKGROUND: Smoke-free laws reduce disease prevalence. The impact of municipal smoke-free laws on lung cancer incidence in Kentucky was examined. The authors hypothesized that lung cancer incidence rates would be associated with the strength of smoke-free laws. METHODS: This was a secondary analysis of 83,727 Kentucky residents aged ≥ 50 years who were newly diagnosed with lung cancer from 1995 to 2014. In 2014, 33 municipalities had 1 or more smoke-free laws. County-level characteristics included adult smoking rate, sex, race/ethnicity, income, physician supply, observed radon values, and rurality. RESULTS: Individuals living in communities with comprehensive smoke-free laws were 7.9% less likely than those living in communities without smoke-free protections to be diagnosed with lung cancer. The difference in lung cancer incidence between counties with moderate/weak laws and those without laws was not significant. CONCLUSIONS: Comprehensive smoke-free laws were associated with fewer new cases of lung cancer, whereas weak or moderate smoke-free laws did not confer the same benefit. One hundred percent smoke-free laws, covering all workers and the public with few or no exceptions, may be key in reducing new cases of lung cancer. Cancer 2018;124:374-80. © 2017 American Cancer Society.
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Neoplasias Pulmonares/epidemiología , Política para Fumadores , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Incidencia , Kentucky/epidemiología , Neoplasias Pulmonares/prevención & control , Masculino , Persona de Mediana Edad , Política para Fumadores/legislación & jurisprudenciaRESUMEN
BACKGROUND: The Global Commission for the Certification of the Eradication of Poliomyelitis will declare the world free of wild poliovirus transmission when no wild virus has been found in at least 3 consecutive years, and all laboratories possessing wild poliovirus materials have adopted appropriate measures of containment. Nigeria has made progress towards poliomyelitis eradication with the latest reported WPV type 1 on 21 Aug 2016 after 2 years without any case. This milestone achievement was followed by an inventory of biomedical laboratories completed in November 2015 with the destruction of all identified infectious materials. This paper seeks to describe the poliovirus laboratory containment process in Nigeria on which an effective containment system has been built to minimize the risk of virus re-introduction into the population from the laboratories. METHODS: A national survey of all biomedical facilities, as well as an inventory of laboratories from various sectors, was conducted from June-November 2015. National Task Force (NTF) members and staff working on polio administered an on-site questionnaire in each facility. Laboratory personnel were sensitized with all un-needed materials destroyed by autoclaving and incineration. All stakeholders were also sensitized to continue the destruction of such materials as a requirement for phase one activities. RESULTS: A total of 20,638 biomedical facilities were surveyed with 9575 having laboratories. Thirty laboratories were found to contain poliovirus or potentially infectious materials. The 30 laboratories belonged to the ministries of health, education, defence and private organizations. CONCLUSIONS: This article is amongst the first in Africa that relates poliovirus laboratory containment in the context of the tOPV-bOPV switch in alignment with the Global Action Plan III. All identified infectious materials were destroyed and personnel trained to continue to destroy subsequent materials, a process that needs meticulous monitoring to mitigate the risk of poliovirus re-introduction to the population.
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Contención de Riesgos Biológicos/métodos , Laboratorios , Poliomielitis/prevención & control , Poliovirus , Humanos , NigeriaRESUMEN
A critical step in understanding how a genome functions is determining which transcription factors (TFs) regulate each gene. Accordingly, extensive effort has been devoted to mapping TF networks. In Saccharomyces cerevisiae, protein-DNA interactions have been identified for most TFs by ChIP-chip, and expression profiling has been done on strains deleted for most TFs. These studies revealed that there is little overlap between the genes whose promoters are bound by a TF and those whose expression changes when the TF is deleted, leaving us without a definitive TF network for any eukaryote and without an efficient method for mapping functional TF networks. This paper describes NetProphet, a novel algorithm that improves the efficiency of network mapping from gene expression data. NetProphet exploits a fundamental observation about the nature of TF networks: The response to disrupting or overexpressing a TF is strongest on its direct targets and dissipates rapidly as it propagates through the network. Using S. cerevisiae data, we show that NetProphet can predict thousands of direct, functional regulatory interactions, using only gene expression data. The targets that NetProphet predicts for a TF are at least as likely to have sites matching the TF's binding specificity as the targets implicated by ChIP. Unlike most ChIP targets, the NetProphet targets also show evidence of functional regulation. This suggests a surprising conclusion: The best way to begin mapping direct, functional TF-promoter interactions may not be by measuring binding. We also show that NetProphet yields new insights into the functions of several yeast TFs, including a well-studied TF, Cbf1, and a completely unstudied TF, Eds1.
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Redes Reguladoras de Genes , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Programas Informáticos , Factores de Transcripción/metabolismo , Algoritmos , Sitios de Unión , Inmunoprecipitación de Cromatina , Perfilación de la Expresión Génica , Regulación Fúngica de la Expresión Génica , Genoma Fúngico , Modelos Genéticos , Regiones Promotoras Genéticas , Unión Proteica , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genéticaRESUMEN
PURPOSE: To conduct a longitudinal study on age-related nuclear cataracts using dynamic light scattering (DLS) to determine if cataract progression is associated with loss of the unbound form of the lens molecular chaperone protein, α-crystallin. DESIGN: Natural history and cohort study. PARTICIPANTS: Patients 30 years of age or older of either gender seeking treatment at the Wilmer Eye Institute Cornea-Cataract Department. METHODS: All patients underwent a comprehensive dilated eye examination every 6 months, including slit-lamp grading of their lenses using the Age-Related Eye Disease Study (AREDS) clinical lens grading system and obtaining an estimate of unbound α-crystallin level in the nucleus, the α-crystallin index (ACI), using the National Aeronautics and Space Administration-National Eye Institute DLS device. We used a random effects statistical model to examine the relationship of lens opacity changes over time with ACI changes. MAIN OUTCOME MEASURES: α-Crystallin Index (ACI) and AREDS nuclear cataract grade. RESULTS: Forty-five patients (66 eyes) 34 to 79 years of age with AREDS nuclear lens grades of 0 to 3.0 were followed up every 6 months for a mean of 19 months (range, 6-36 months). We found that lenses with the lowest baseline levels of ACI had the most rapid progression of cataracts, whereas lenses with higher ACI at baseline had no or slower cataract progression. Lenses that lost α-crystallin at the highest rates during the study also had faster progression of nuclear cataracts than lenses with a slower rate of ACI loss. Kaplan-Meier survival curves showed that lenses with the lowest initial ACI had the highest risk of undergoing cataract surgery. CONCLUSIONS: This longitudinal study corroborates our previous cross-sectional study finding that higher levels of unbound α-crystallin as assessed by ACI are associated with lower risk of cataract formation and that loss of ACI over time is associated with cataract formation and progression. This study suggested that assessment of ACI with the DLS device could be used as a surrogate for lens opacity risk in clinical studies, and for assessing nuclear cataract events in studies where cataract development may be a side effect of a drug or device.
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Envejecimiento , Catarata/diagnóstico , Catarata/metabolismo , Dispersión Dinámica de Luz , Núcleo del Cristalino/metabolismo , alfa-Cristalinas/metabolismo , Adulto , Anciano , Catarata/clasificación , Extracción de Catarata , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Núcleo del Cristalino/patología , Luz , Masculino , Persona de Mediana Edad , Proyectos PilotoRESUMEN
PURPOSE: Over the last two decades, magnetic resonance imaging (MRI) has been widely used in neuroscience research to assess both structure and function in the brain in health and disease. With regard to vision research, prior to the advent of MRI, researchers relied on animal physiology and human post-mortem work to assess the impact of eye disease on visual cortex and connecting structures. Using MRI, researchers can non-invasively examine the effects of eye disease on the whole visual pathway, including the lateral geniculate nucleus, striate and extrastriate cortex. This review aims to summarise research using MRI to investigate structural, chemical and functional effects of eye diseases, including: macular degeneration, retinitis pigmentosa, glaucoma, albinism, and amblyopia. RECENT FINDINGS: Structural MRI has demonstrated significant abnormalities within both grey and white matter densities across both visual and non-visual areas. Functional MRI studies have also provided extensive evidence of functional changes throughout the whole of the visual pathway following visual loss, particularly in amblyopia. MR spectroscopy techniques have also revealed several abnormalities in metabolite concentrations in both glaucoma and age-related macular degeneration. GABA-edited MR spectroscopy on the other hand has identified possible evidence of plasticity within visual cortex. SUMMARY: Collectively, using MRI to investigate the effects on the visual pathway following disease and dysfunction has revealed a rich pattern of results allowing for better characterisation of disease. In the future MRI will likely play an important role in assessing the impact of eye disease on the visual pathway and how it progresses over time.
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Imagen por Resonancia Magnética/métodos , Trastornos de la Visión/diagnóstico , Corteza Visual/patología , Animales , Humanos , Vías Visuales/patologíaRESUMEN
The neuronal ceroid lipofuscinoses (NCLs) are hereditary neurodegenerative diseases characterized by seizures and progressive cognitive decline, motor impairment, and vision loss accompanied by accumulation of autofluorescent lysosomal storage bodies in the central nervous system and elsewhere in the body. Mutations in at least 14 genes underlie the various forms of NCL. One of these genes, CLN8, encodes an intrinsic membrane protein of unknown function that appears to be localized primarily to the endoplasmic reticulum. Most CLN8 mutations in people result in a form of NCL with a late infantile onset and relatively rapid progression. A mixed breed dog with Australian Shepherd and Blue Heeler ancestry developed neurological signs characteristic of NCL starting at about 8months of age. The signs became progressively worse and the dog was euthanized at 21months of age due to seizures of increasing frequency and severity. Postmortem examination of the brain and retinas identified massive accumulations of intracellular autofluorescent inclusions characteristic of the NCLs. Whole genome sequencing of DNA from this dog identified a CLN8:c.585G>A transition that predicts a CLN8:p.Trp195* nonsense mutation. This mutation appears to be rare in both ancestral breeds. All of our 133 archived DNA samples from Blue Heelers, and 1481 of our 1488 archived Australian Shepherd DNA samples tested homozygous for the reference CLN8:c.585G allele. Four of the Australian Shepherd samples tested heterozygous and 3 tested homozygous for the mutant CLN8:c.585A allele. All 3 dogs homozygous for the A allele exhibited clinical signs of NCL and in 2 of them NCL was confirmed by postmortem evaluation of brain tissue. The occurrence of confirmed NCL in 3 of 4 CLN8:c.585A homozygous dogs, plus the occurrence of clinical signs consistent with NCL in the fourth homozygote strongly suggests that this rare truncating mutation causes NCL. Identification of this NCL-causing mutation provides the opportunity for identifying dogs that can be used to establish a canine model for the CLN8 disease (also known as late infantile variant or late infantile CLN8 disease).
Asunto(s)
Cruzamiento , Codón sin Sentido/genética , Genoma/genética , Proteínas de la Membrana/genética , Lipofuscinosis Ceroideas Neuronales/veterinaria , Linaje , Animales , Secuencia de Bases , Perros , Resultado Fatal , Femenino , Proteína Ácida Fibrilar de la Glía/metabolismo , Imagen por Resonancia Magnética , Microscopía Fluorescente , Lipofuscinosis Ceroideas Neuronales/genética , Lipofuscinosis Ceroideas Neuronales/patología , Células de Purkinje/patología , Células de Purkinje/ultraestructuraRESUMEN
UNLABELLED: We present a case of a 14-year-old girl who had a severe form of granulomatosis with polyangiitis (GPA) with extensive dermatological involvement, whose initial presentation was nonspecific leading to diagnostic confusion and initial consideration of infectious and other vasculitis causes. The patient presented with fever, congestion, malaise, and sinus pain. She was diagnosed with bacterial sinusitis and treated with antibiotics. Within weeks, she developed abdominal pain, hematuria, migratory arthritis, and palpable purpura and was diagnosed with Henoch-Schonlein purpura. She went on to develop hemoptysis and progression of the rash into erosive bullae. Investigations revealed that she was ANCA positive and had pauci-immune glomerulonephritis. Given her upper airway, pulmonary and renal involvement, and antineutrophil cytoplasmic antibodies positivity, a definitive diagnosis of a severe form of GPA was made. GPA is a chronic relapsing, life threatening vasculitis that predominantly affects small vessels. CONCLUSION: Our case demonstrates that GPA can present initially with nonspecific symptoms, including extensive dermatological involvement, leading to diagnostic confusion, and delays in treatment. In the case of a severe peripheral rash in the juvenile population and/or resistant upper airway symptoms, it is vital to consider a diagnosis of GPA to avoid serious organ or life threatening consequences.
Asunto(s)
Vesícula/etiología , Granulomatosis con Poliangitis/complicaciones , Púrpura/etiología , Piel/patología , Adolescente , Biopsia , Vesícula/diagnóstico , Proteína C-Reactiva/metabolismo , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Granulomatosis con Poliangitis/sangre , Granulomatosis con Poliangitis/diagnóstico , Humanos , Púrpura/diagnósticoRESUMEN
An adult male sun conure (Aratinga solstitialis) was evaluated because of lethargy, ruffled feathers, and decreased appetite. Physical examination revealed hypothermia, dehydration, dyspnea, and crop distention. Results of a complete blood cell count revealed a marked inflammatory leukogram, and cytologic examination of a crop swab sample identified gram-negative bacilli and occasional yeast organisms. Radiographs demonstrated an opaque, ill-defined, soft tissue structure in the caudal coelom just cranial to the renogonadal silhouette, loss of serosal detail, and splenomegaly. Endoscopic examination revealed a pale, granuloma-like structure within the caudal aspect of the left lung, splenomegaly, and an enlarged proventriculus. Intraoperative cytologic examination of a biopsy sample of the lesion demonstrated yeast organisms, and a subsequent culture of the biopsy sample revealed Candida albicans . The bird was treated intraoperatively with intralesional amphotericin B. Postoperative treatment consisted of meloxicam, trimethoprim sulfa, amphotericin B by nebulization, and systemic itraconazole and fluconazole. The bird made a complete recovery, was discontinued from all medications, and has remained asymptomatic for 6 months. Although rare, pulmonary candidiasis should be on the list of differential diagnoses for any respiratory infection in birds. Endoscopic biopsy, cytology, and fungal culture were valuable in making the diagnosis.