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1.
Ophthalmic Genet ; : 1-5, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38853699

RESUMEN

INTRODUCTION: In addition to sensorineural hearing loss, Waardenburg Syndrome (WS) may present with variable pigmentation of skin and choroid, which may simulate other life-threating conditions (e.g. melanoma). CASE REPORT: Two siblings ostensibly presented with unilateral choroidal pigmentary abnormalities concerning for choroidal tumour. Serial ophthalmic examination documented no lesion growth (base or height) whilst the apparent syndromic features (i.e. iris hypochromia, profound sensorineural hearing loss, SNHL), family history (autosomal dominant inheritance) and positive genetic testing (pathogenic MITF variant) led to a revised diagnosis of Waardenburg Syndrome type 2A. CONCLUSION: Sectoral preservation of choroidal pigmentation in WS is rarely associated with choroidal malignancy. Awareness of syndromic features (e.g. SNHL) and access to genetic testing may facilitate early accurate diagnosis (i.e. allay concern for malignancy), enable treatment of modifiable features (e.g. SNHL) and identify other affected relatives.

2.
J Otolaryngol Head Neck Surg ; 53: 19160216241258431, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38888945

RESUMEN

IMPORTANCE: Mesenchymal stem cells (MSCs) have the capability of providing ongoing paracrine support to degenerating tissues. Since MSCs can be extracted from a broad range of tissues, their specific surface marker profiles and growth factor secretions can be different. We hypothesized that MSCs derived from different sources might also have different neuroprotective potential. OBJECTIVE: In this study, we extracted MSCs from rodent olfactory mucosa and compared their neuroprotective effects on auditory hair cell survival with MSCs extracted from rodent adipose tissue. METHODS: Organ of Corti explants were dissected from 41 cochlea and incubated with olfactory mesenchymal stem cells (OMSCs) and adipose mesenchymal stem cells (AMSCs). After 72 hours, Corti explants were fixed, stained, and hair cells counted. Growth factor concentrations were determined in the supernatant and cell lysate using Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS: Co-culturing of organ of Corti explants with OMSCs resulted in a significant increase in inner and outer hair cell stereocilia survival, compared to control. Comparisons between both stem cell lines, showed that co-culturing with OMSCs resulted in superior inner and outer hair cell stereocilia survival rates over co-culturing with AMSCs. Assessment of growth factor secretions revealed that the OMSCs secrete significant amounts of insulin-like growth factor 1 (IGF-1). Co-culturing OMSCs with organ of Corti explants resulted in a 10-fold increase in IGF-1 level compared to control, and their secretion was 2 to 3 times higher compared to the AMSCs. CONCLUSIONS: This study has shown that OMSCs may mitigate auditory hair cell stereocilia degeneration. Their neuroprotective effects may, at least partially, be ascribed to their enhanced IGF-1 secretory abilities compared to AMSCs.


Asunto(s)
Células Ciliadas Auditivas , Factor I del Crecimiento Similar a la Insulina , Células Madre Mesenquimatosas , Animales , Factor I del Crecimiento Similar a la Insulina/metabolismo , Células Madre Mesenquimatosas/metabolismo , Ratas , Células Ciliadas Auditivas/metabolismo , Mucosa Olfatoria/citología , Ensayo de Inmunoadsorción Enzimática , Técnicas de Cocultivo , Supervivencia Celular , Células Cultivadas , Tejido Adiposo/citología , Trasplante de Células Madre Mesenquimatosas/métodos
3.
J Diagn Med Sonogr ; 39(6): 549-559, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38074490

RESUMEN

Objective: This study examined the implementation of a Doppler sonography imaging protocol to assess intraneural blood flow, within the median nerve, in healthy individuals. Materials and Methods: A total of 176 participants were examined, and this involved 717 retrospective observations of the images collected. The implemented imaging protocol was assessed, and the data that were collected were cleaned and checked for fidelity and validity. Results: A large percentage of missing evidence (11%-35%) across proximal, mid, and distal carpal tunnel locations. Only a quarter of cases with evidence of intraneural blood flow had the strongest evidence of a power Doppler video clip, of which only three-quarters were valid. The study identified potential areas for improving the imaging protocol to reduce missing data and improve data quality. Conclusion: This study demonstrates the significance of a standardized imaging protocol to guide the sonographic acquisition of Doppler images and provides important insights into potential issues with data quality. The recommendations have the potential to help future studies assess intraneural blood flow in healthy populations in a more rigorous and reliable way. Incorporating the study's recommendations into a standardized protocol, there is potential to enhance the diagnostic accuracy of carpal tunnel syndrome and improve diagnosis and treatment.

4.
Can J Ophthalmol ; 2023 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-37678418

RESUMEN

OBJECTIVE: To evaluate the success of diagnostic genetic testing in inherited retinal dystrophy (IRD) patients in the clinical setting. DESIGN: Retrospective cohort analysis. PARTICIPANTS: A total of 446 consecutive participants from diverse ethnic backgrounds living in western Canada. METHODS: Clinical information was collected from participants, including family history, and they underwent a full ophthalmic examination with chart review. Those with a suspected IRD were offered panel-based genetic testing of 351 genes between March 1, 2019, and February 28, 2022. The main outcome measure was effect of the genetic testing results on clinical diagnosis. RESULTS: Genetic testing established a conclusive molecular diagnosis in 249 of 446 cases (55.8%), a clearly negative result in 90 of 446 cases (20.1%), and an inconclusive diagnosis in 108 of 446 cases (24.2%). Conclusive disease-causing variants were identified in 69 genes, and the most commonly affected genes were ABCA4 (31 variants), USH2A (25 variants), and RPGR (19 variants). The inconclusive group included likely novel autosomal dominant variants or a pathogenic variant with a variant of uncertain significance in the same gene for a recessive phenotype. Notably, an inconclusive molecular genetic diagnosis was seen in as many as 47.3% of East Asian participants with an outer retinal dystrophy. CONCLUSIONS: This study represents the largest review of molecular genetic testing in IRDs in Canada. That negative or inconclusive results obtained in approximately 45% of cases demonstrates that there is an important need for new research into molecular genetic causes of IRDs. This is particularly true in addressing the problem of interpreting a variant of uncertain significance in ethnic minorities.

5.
Mol Vis ; 29: 329-337, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38264610

RESUMEN

Purpose: Autosomal recessive cone and cone-rod dystrophies (CD/CRD) are inherited forms of vison loss. Here, we report on and correlate the clinical phenotypes with the underlying genetic mutations. Methods: Clinical information was collected from subjects, including a family history with a chart review. They underwent a full ophthalmic examination, including best-corrected visual acuity, direct and indirect ophthalmoscopy, color vision testing, color fundus photography, contrast sensitivity, autofluorescence, and spectral domain-optical coherence tomography (SD-OCT), and full-field electroretinography. Next-generation panel-based genetic testing was used to identify DNA variants in subject buccal swab samples. Results: Genetic testing in two patients revealed three novel variants in the TTLL5 gene associated with CD/CRD: two missense variants (c.1433G>A;p.(Arg478Gln), c.241C>G;p.(Leu81Val), and one loss-of-function variant (c.2384_2387del;p.(Ala795Valfs*9). Based on in-silico analysis, structural modeling, and comparison to previously reported mutations, these novel variants are very likely to be disease-causing mutations. Combining retinal imaging with SD-OCT analysis, we observed an unusual sheen in the CD/CRD phenotypes. Conclusion: Based on the protein domain location of novel TTLL5 variants and the localization of TTLL5 to the connecting cilium, we conclude that the CD/CRD disease phenotype is characterized as a ciliopathy caused by protein tracking dysfunction. This initially affects cone photoreceptors, where photoreceptor cilia express a high level of TTLL5, but extends to rod photoreceptors over time. Fundus photography correlated with SD-OCT imaging suggests that the macular sheen characteristically seen with TTLL5 mutations derives from the photoreceptor's outer segments at the posterior pole.


Asunto(s)
Distrofia del Cono , Distrofias de Conos y Bastones , Distrofias Retinianas , Humanos , Células Fotorreceptoras Retinianas Conos , Tomografía de Coherencia Óptica , Tubulina (Proteína) , Fenotipo , Tirosina , Proteínas Portadoras
6.
Radiol Technol ; 93(5): 454-461, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35508410

RESUMEN

PURPOSE: To improve cardiovascular disease (CVD) risk prediction by combining screening techniques and to determine whether the combination of sonographic aortic calcification quantification, measurement of aortic intimal thickness, and monocyte laboratory values provides improved diagnostic detection compared with computed tomography (CT) calcium scoring. METHODS: A pre-experimental design was used to collect imaging, demographic, and biometric data. Data were collected from a convenience sample of 11 volunteers aged 40 to 60 years, including 6 men and 5 women. Collected data included anthropometric measures, laboratory values, flow cytometry, coronary artery calcium scores, atherosclerotic cardiovascular disease (ASCVD) 10-year risk scores, and aortic intimal-medial thickness (IMT). RESULTS: Aortic IMT in the distal portion of the aorta or region 1 was related significantly to mass (r = 0.725, P = .012), body mass index (r = 0.668, P = .025), and ASCVD 10-year risk score (r = 0.747, P = .033). The aortic IMT in mid portion of the aorta or region 2 was related significantly to mass (r = 0.651, P = .030), antihypertensive medications (r = 0.682, P = .021), ASCVD 10-year risk score (r = 0.753, P = .031), and total coronary artery calcification (CAC) (r = 0.626, P = .039). In addition, the proportions of circulating CD14+CD16- (traditional) and CD14+CD16+ (inflammatory) monocytes, and the monocyte surface expression of the adhesion molecules CD11a and CD11c, were correlated with the number of calcifications in regions 1 and 2. DISCUSSION: The use of a modified grading system for sonography provided a nonionizing, noninvasive option to easily assess patients' risks of CVD in an office environment. Although CAC has been used widely as a screening mechanism for CVD, ionizing radiation use might not be justified for those who are asymptomatic. The combination of sonography with flow cytometry demonstrated a promising alternative for assessing CVD risk. CONCLUSION: tBetter quantification of inflammatory markers and atherosclerotic plaques is needed. The combination of noninvasive imaging and advanced laboratory analysis holds promise for assessing and managing CVD risk. This study provides further evidence of the need for continued research with larger sample sizes and diversified populations to improve the quality of CVD risk assessment.


Asunto(s)
Aterosclerosis , Calcinosis , Enfermedades Cardiovasculares , Enfermedad de la Arteria Coronaria , Aorta/diagnóstico por imagen , Calcinosis/diagnóstico por imagen , Calcio , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Femenino , Citometría de Flujo , Humanos , Masculino , Proyectos Piloto , Medición de Riesgo , Factores de Riesgo , Tomografía Computarizada por Rayos X
7.
Radiol Technol ; 93(2): 161-176, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34728578

RESUMEN

PURPOSE: To explore self-reported musculoskeletal symptoms in radiographers registered by the American Registry of Radiologic Technologists (ARRT) in the United States. There is a gap in the literature focusing on the unique set of risk factors for radiographers. METHODS: A subset of ARRT radiographers received an email invitation to complete an online survey that included questions about their experience with musculoskeletal symptoms and their exposure to potential risk factors for those symptoms. RESULTS: Out of the 635 ARRT credentialed, nonretired radiographers who completed the survey, 81% reported experiencing pain or discomfort while performing patient cases. Through logistic regression statistical modeling, a set of 4 personal factors (including poorer perceptions of health and sleep quality), 1 work demographic factor (working in fluoroscopy), and 3 psychosocial work factors (including perceptions of higher physically demanding workload and work pressure and stress) were identified in differentiating radiographers who experience pain or discomfort when performing patient cases from those who do not. DISCUSSION: Consistent with prior research, these results indicate multiple work-related factors, including physical and psychosocial work factors, appear to be associated with the prevalence of musculoskeletal symptoms in radiographers. Ideas for addressing these risk factors are discussed, as well as opportunities for radiography managers and academics to collaborate in evaluating the effectiveness of intervention ideas when deployed in practice. CONCLUSION: Although this study is cross-sectional, these results can be used to inform intervention efforts, such as limiting or rotating work duties in fluoroscopy, reducing other physically demanding aspects of work, addressing understaffing, which increases work pressure in many ways, and promoting employee self-care practices.


Asunto(s)
Enfermedades Musculoesqueléticas , Enfermedades Profesionales , Técnicos Medios en Salud , Estudios Transversales , Humanos , Enfermedades Musculoesqueléticas/epidemiología , Enfermedades Profesionales/epidemiología , Factores de Riesgo , Autoinforme , Encuestas y Cuestionarios
8.
Handb Clin Neurol ; 178: 1-11, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33832671

RESUMEN

Diseases of the retina are common and numerous, with causes ranging over inherited, inflammatory, vascular, infectious, neoplastic, traumatic, toxic, and idiopathic etiologies. A key issue in the diagnosis of retinal disease is the duration of symptoms, which can be acute, chronic, or acute presentations of chronic disease. Clinical examination with direct ophthalmoscopy or, even better, biomicroscopy with a slit lamp and condensing lens, is a key component of diagnosis, which can be enhanced through investigational methods such as fluorescein angiography, optical coherence tomography, or electroretinography. Consideration of the history, visual acuity and visual field, and fundoscopic findings is usually sufficient to determine whether patients need referral on an emergency, urgent, or routine basis. Emphasis is given to vascular disease, age-related macular degeneration, diabetic retinopathy, genetic eye disease, and retinal detachment.


Asunto(s)
Retinopatía Diabética , Edema Macular , Angiografía con Fluoresceína , Humanos , Neurólogos , Retina/diagnóstico por imagen
9.
J Tissue Eng Regen Med ; 15(6): 556-566, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33779072

RESUMEN

Cell replacement therapy is emerging as an important approach in novel treatments for neurodegenerative diseases. Many problems remain, in particular improvements are needed in the survival of transplanted cells and increasing functional integration into host tissue. These problems arise because of immune rejection, suboptimal precursor cell type, trauma during cell transplantation, and toxic compounds released by dying tissues and nutritional deficiencies. We recently developed an ex vivo system to facilitate identification of factors contributing to the death of transplanted neuronal (photoreceptor) and showed 2.8-fold improvement in transplant cell survival after pretreatment with a novel glycopeptide (PKX-001). In this study, we extended these studies to look at cell survival, maturation, and functional integration in an in vivo rat model of rhodopsin-mutant retinitis pigmentosa causing blindness. We found that only when human photoreceptor precursor cells were preincubated with PKX-001 prior to transplantation, did the cells integrate and mature into cone photoreceptors expressing S-opsin or L/M opsin. In addition, ribbon synapses were observed in the transplanted cells suggesting they were making synaptic connections with the host tissue. Furthermore, optokinetic tracking and electroretinography responses in vivo were significantly improved compared to cell transplants without PKX-001 pre-treatment. These data demonstrate that PKX-001 promotes significant long-term stem cell survival in vivo, providing a platform for further investigation towards the clinical application to repair damaged or diseased retina.


Asunto(s)
Glicopéptidos/farmacología , Células Fotorreceptoras de Vertebrados/citología , Animales , Supervivencia Celular/efectos de los fármacos , Electrorretinografía , Femenino , Humanos , Masculino , Células Fotorreceptoras de Vertebrados/trasplante , Ratas
10.
Appl Ergon ; 85: 103069, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32174357

RESUMEN

The prevalence of musculoskeletal (MSK) symptoms in radiographers is high, similar to other healthcare occupations that involve high levels of physical exertion (e.g. patient handling; grasping and moving equipment). Reports of interventions to reduce MSK discomfort in radiographers are limited. A participatory approach was used to investigate daily challenges, needs, and opportunities for developing interventions to address exposures to many of the risk factors that contribute to MSK symptoms in radiographers. In this paper, we present the expressed needs of experienced radiographers (including assistance with patient handling, security, supportive design of equipment and work spaces), along with their evaluations of several intervention concepts intended to address some of those needs. We also report results from tests of three prototype interventions stemming from this participatory process that demonstrate the potential for new engineering control concepts to reduce the physical effort associated with some of the most common tasks radiographers perform.


Asunto(s)
Ergonomía/métodos , Movimiento y Levantamiento de Pacientes/efectos adversos , Enfermedades Musculoesqueléticas/etiología , Enfermedades Profesionales/etiología , Radiografía , Adulto , Técnicos Medios en Salud/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esfuerzo Físico , Factores de Riesgo , Trabajo/fisiología , Adulto Joven
11.
Precis Clin Med ; 3(2): 113-126, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35692607

RESUMEN

Leber congenital amaurosis (LCA) is a severe, genetically heterogeneous recessive eye disease in which ~ 35% of gene mutations are in-frame nonsense mutations coding for loss-of-function premature termination codons (PTCs) in mRNA. Nonsense suppression therapy allows read-through of PTCs leading to production of full-length protein. A limitation of nonsense suppression is that nonsense-mediated decay (NMD) degrades PTC-containing RNA transcripts. The purpose of this study was to determine whether inhibition of NMD could improve nonsense suppression efficacy in vivo. Using a high-throughput approach in the recessive cep290 zebrafish model of LCA (cep290;Q1223X), we first tested the NMD inhibitor Amlexanox in combination with the nonsense suppression drug Ataluren. We observed reduced retinal cell death and improved visual function. With these positive data, we next investigated whether this strategy was also applicable across species in two mammalian models: Rd12 (rpe65;R44X) and Rd3 (rd3;R107X) mouse models of LCA. In the Rd12 model, cell death was reduced, RPE65 protein was produced, and in vivo visual function testing was improved. We establish for the first time that the mechanism of action of Amlexanox in Rd12 retina was through reduced UPF1 phosphorylation. In the Rd3 model, however, no beneficial effect was observed with Ataluren alone or in combination with Amlexanox. This variation in response establishes that some forms of nonsense mutation LCA can be targeted by RNA therapies, but that this needs to be verified for each genotype. The implementation of precision medicine by identifying better responders to specific drugs is essential for development of validated retinal therapies.

12.
Front Digit Health ; 2: 12, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-34713025

RESUMEN

We identify useful functions and usability characteristics of a historical cognitive artifact used by nurses working in a hospital unit, the Kardex. By identifying aspects of a widely used artifact, we uncover opportunities to improve the usefulness of current systems for hospital nurses. We conducted semi-structured interviews with registered nurses about their prior experience with the Kardex. Questions included what elements of the Kardex are missing from their current electronic support. Memos were generated iteratively from interview transcript data and grouped into themes. Eighteen nurses from multiple clinical areas participated and had a median of 25-29 years of nursing experience. The themes were: (1) a status at a glance summary for each patient, (2) a prospective memory aid, (3) efficiency and ease of use, (4) updating information required to maintain value, (5) activity management, (6) verbal handover during shift-to-shift report, (7) narrative charting and personalized care, and (8) non-clinical care communication. Implications for digital support are to provide immediate, portable access to a standardized patient summary, support for nurses to manage their planned activities during a series of shifts, provide unstructured text fields for narrative charting, and to support adding informal notes for personalized care.

13.
HERD ; 13(1): 145-178, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31195834

RESUMEN

OBJECTIVES: This research investigated medical/surgical (Med/Surg) patient room design to accommodate the needs of hospital staff, while at the same time accommodating the needs of patients and their visitors. BACKGROUND: Designing hospital patient rooms that provide a comfortable healing experience for patients, while at the same time meeting the needs of the hospital staff, is a challenging process. Prior research has shown that many hospital patient room designs adversely affect the ability of hospital staff to perform their tasks effectively, efficiently, and safely. METHOD: Twenty-seven design sessions were conducted in which 104 participants, representing 24 different occupations, worked in small mixed occupational groups to design an ideal single patient Med/Surg patient room to fit their collective needs using a full-scale mock-up. During analysis, the investigators reduced the resulting 27 room designs to 5 hybrid designs that were sequentially reviewed by patients and visitors and by staff to address design conflicts. RESULTS: This design process identified 51 desirable room design features that were incorporated into 66 evidence-based design guidelines for the different areas within the Med/Surg patient room including the entry way (16 guidelines), the patient clinical area (22 guidelines), the bathroom (17 guidelines), the family area (8 guidelines), and storage areas for patients and their visitors (3 guidelines). CONCLUSIONS: The guidelines developed through this study identified many opportunities for improving the design of hospital Med/Surg rooms to allow staff to be more effective, efficient, and safer, while at the same time addressing the design needs of patients and their visitors.


Asunto(s)
Diseño de Instalaciones Basado en Evidencias , Diseño Interior y Mobiliario , Habitaciones de Pacientes/normas , Ergonomía , Humanos , Seguridad del Paciente , Satisfacción del Paciente , Personal de Hospital/psicología , Cuartos de Baño/normas , Visitas a Pacientes/psicología
14.
Am J Sports Med ; 47(11): 2608-2616, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31373856

RESUMEN

BACKGROUND: While between-limb landing asymmetries after anterior cruciate ligament reconstruction (ACLR) are linked with poor function and risk of additional injury, it is not currently understood how landing symmetry changes over time after ACLR. PURPOSE/HYPOTHESIS: The purpose was to investigate how double-legged drop vertical jump (DVJ) landing and single-legged drop-landing symmetry changed from the time of return-to-sport (RTS) clearance to 2 years later in a prospective cohort of young athletes after ACLR. It was hypothesized that double-legged DVJ landing and single-legged drop-landing symmetry would improve from the time of RTS to 2 years later. STUDY DESIGN: Descriptive laboratory study. METHODS: The authors followed 64 young athletes with primary, unilateral ACLR for 2 years after RTS clearance. At the time of RTS and 2 years later, between-limb symmetry values for biomechanical variables of interest (VOIs) were calculated with 3-dimensional motion analysis during double-legged DVJ and single-legged drop-landing tasks. VOIs included knee flexion excursion, peak internal knee extension moment, peak vertical ground-reaction force, and peak trunk flexion (for single-legged task only). Symmetry values and proportions of participants meeting 90% symmetry cutoffs were compared between time points. RESULTS: For double-legged DVJ landing, symmetry values for all VOIs and the proportions meeting 90% cutoffs for peak internal knee extension moment and peak vertical ground-reaction force were higher at 2 years after RTS as compared with RTS. For single-legged drop-landing, symmetry values were higher for knee flexion excursion and lower for peak trunk flexion at 2 years after RTS as compared with RTS, but the proportions meeting 90% cutoffs for all VOIs did not differ between time points. CONCLUSION: Double-legged DVJ landing symmetry improved across VOIs over the 2 years after RTS following ACLR, while single-legged drop-landing did not improve as consistently. The implications of longitudinal landing asymmetry after ACLR should be further studied.


Asunto(s)
Lesiones del Ligamento Cruzado Anterior/cirugía , Reconstrucción del Ligamento Cruzado Anterior , Atletas , Volver al Deporte , Adolescente , Fenómenos Biomecánicos , Estudios de Cohortes , Femenino , Humanos , Masculino , Estudios Prospectivos , Rango del Movimiento Articular , Adulto Joven
15.
Hum Genet ; 138(8-9): 865-880, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31073883

RESUMEN

Ocular coloboma is an uncommon, but often severe, sight-threatening condition that can be identified from birth. This congenital anomaly is thought to be caused by maldevelopment of optic fissure closure during early eye morphogenesis. It has been causally linked to both inherited (genetic) and environmental influences. In particular, as a consequence of work to identify genetic causes of coloboma, new molecular pathways that control optic fissure closure have now been identified. Many more regulatory mechanisms still await better understanding to inform on the development of potential therapies for patients with this malformation. This review provides an update of known coloboma genes, the pathways they influence and how best to manage the condition. In the age of precision medicine, determining the underlying genetic cause in any given patient is of high importance.


Asunto(s)
Coloboma/genética , Ojo/fisiopatología , Animales , Genética , Humanos , Morfogénesis/genética
16.
Knee ; 26(2): 355-363, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30772182

RESUMEN

PURPOSE: The purpose of this study was to investigate how patient-reported knee function changed over a two-year period in young athletes after anterior cruciate ligament reconstruction (ACLR) and return-to-sport (RTS), and to determine the impact of clinical measures, after controlling for demographic and surgical covariates. METHODS: At the time of RTS after primary, unilateral ACLR, the following data were collected in 67 young athletes: Quadriceps (QF), hamstring (HS), and hip abduction (HA) strength; knee range-of-motion, effusion, and anterior laxity; and patient-reported function using the Knee injury and Osteoarthritis Outcome Score (KOOS). At two years post-RTS, patient-reported function was reevaluated using the KOOS. Absolute KOOS scores and proportions of participants meeting functional recovery cutoffs were compared between time-points. Multivariable linear regression was used to determine clinical measures at RTS associated with two-year post-RTS KOOS scores. RESULTS: KOOS scores for all subscales were higher at two years post-RTS (all p < 0.003), and the proportions of participants demonstrating functional recovery were higher at two years post-RTS for the KOOS-Symptoms, KOOS-Sport, KOOS-QOL, and all KOOS subscales combined (all p < 0.03). After controlling for graft type, clinical measures at RTS associated with higher two-year post-RTS KOOS scores were: KOOS-Pain (lower HA peak torque); KOOS-Symptoms (higher QF strength symmetry and higher QF peak torque); and KOOS-ADL (lower HA peak torque). CONCLUSIONS: In this cohort, after controlling for graft type, higher QF strength symmetry, higher involved-limb QF peak torque, and lower involved-limb HA peak torque from the time of RTS were associated with higher function at two years post-RTS.


Asunto(s)
Lesiones del Ligamento Cruzado Anterior/fisiopatología , Reconstrucción del Ligamento Cruzado Anterior/métodos , Atletas , Articulación de la Rodilla/fisiopatología , Músculo Cuádriceps/fisiopatología , Rango del Movimiento Articular/fisiología , Recuperación de la Función , Adolescente , Lesiones del Ligamento Cruzado Anterior/diagnóstico , Lesiones del Ligamento Cruzado Anterior/cirugía , Femenino , Estudios de Seguimiento , Músculos Isquiosurales/fisiopatología , Humanos , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/cirugía , Masculino , Fuerza Muscular/fisiología , Dinamómetro de Fuerza Muscular , Volver al Deporte/fisiología , Factores de Tiempo , Adulto Joven
17.
Hum Genet ; 138(8-9): 1019-1026, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30603775

RESUMEN

Over the last three decades, genetic studies have made great strides toward the identification of genes and genetic mechanisms underlying congenital disorders of the eye. However, despite the vast knowledge available this has not translated into treatments to prevent or repair the damage in the clinical setting. Recently, new research in technologies, such as tissue regeneration, next generation designer drugs, and genome editing, have become available for some genetic disorders that might be applicable to congenital ocular diseases in the near future. Here, we provide an overview of the emerging therapeutic modalities and the future prospects they hold for debilitating ocular defects.


Asunto(s)
Oftalmopatías/genética , Ojo/fisiopatología , Enfermedades Genéticas Congénitas/genética , Animales , Edición Génica/métodos , Humanos , Regeneración/genética
18.
Mol Neurobiol ; 56(3): 1637-1652, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29911255

RESUMEN

Retinitis pigmentosa (RP) is a group of inherited neurological disorders characterized by rod photoreceptor cell death, followed by secondary cone cell death leading to progressive blindness. Currently, there are no viable treatment options for RP. Due to incomplete knowledge of the molecular signaling pathways associated with RP pathogenesis, designing therapeutic strategies remains a challenge. In particular, preventing secondary cone photoreceptor cell loss is a key goal in designing potential therapies. In this study, we identified the main drivers of rod cell death and secondary cone loss in the transgenic S334ter rhodopsin rat model, tested the efficacy of specific cell death inhibitors on retinal function, and compared the effect of combining drugs to target multiple pathways in the S334ter and P23H rhodopsin rat models. The primary driver of early rod cell death in the S334ter model was a caspase-dependent process, whereas cone cell death occurred though RIP3-dependent necroptosis. In comparison, rod cell death in the P23H model was via necroptotic signaling, whereas cone cell loss occurred through inflammasome activation. Combination therapy of four drugs worked better than the individual drugs in the P23H model but not in the S334ter model. These differences imply that treatment modalities need to be tailored for each genotype. Taken together, our data demonstrate that rationally designed genotype-specific drug combinations will be an important requisite to effectively target primary rod cell loss and more importantly secondary cone survival.


Asunto(s)
Células Fotorreceptoras Retinianas Conos/metabolismo , Degeneración Retiniana/metabolismo , Células Fotorreceptoras Retinianas Bastones/metabolismo , Retinitis Pigmentosa/metabolismo , Rodopsina/metabolismo , Animales , Muerte Celular , Modelos Animales de Enfermedad , Genotipo , Ratas , Ratas Transgénicas , Células Fotorreceptoras Retinianas Conos/patología , Degeneración Retiniana/genética , Degeneración Retiniana/patología , Células Fotorreceptoras Retinianas Bastones/patología , Retinitis Pigmentosa/genética , Retinitis Pigmentosa/patología , Rodopsina/genética
19.
J Cogn Eng Decis Mak ; 13(2): 67-80, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33024425

RESUMEN

We identify the value and usage of a cognitive artifact used by hospital nurses. By analyzing the value and usage of workaround artifacts, unmet needs using intended systems can be uncovered. A descriptive study employed direct observations of registered nurses at two hospitals using a paper workaround ("brains") and the Electronic Health Record. Field notes and photographs were taken; the format, size, layout, permanence, and content of the artifact were analyzed. Thirty-nine observations, spanning 156 hr, were conducted with 20 nurses across four clinical units. A total of 322 photographs of paper-based artifacts for 161 patients were collected. All participants used and updated "brains" during report, and throughout the shift, most were self-generated. These artifacts contained patient identifiers in a header with room number, last name, age, code status, and physician; clinical data were recorded in the body with historical chronic issues, detailed assessment information, and planned activities for the shift. Updates continuously made during the shift highlighted important information, updated values, and tracked the completion of activities. The primary functional uses of "brains" are to support nurses' needs for clinical immediacy through personally generated snapshot overviews for clinical summaries and updates to the status of planned activities.

20.
HERD ; 12(1): 124-144, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30103657

RESUMEN

OBJECTIVE:: To identify family members' and visitors' needs with relation to the design of a hospital room. BACKGROUND:: There is a trend toward incorporating family zones in hospital patient rooms in order to improve patient satisfaction and encourage family caregivers to stay longer and overnight. METHOD:: A mixed-method study was employed. Interviews of patients and family caregivers were conducted to understand opportunities to improve hospital room designs based on recent experiences. Features intended to support short-term and overnight visitors were embedded in five full-scale simulated room design concepts. Small groups of family caregivers and patients toured two room design concepts and reacted real time to room features. A grounded theory approach was employed to identify emerging themes. RESULTS:: A theoretical design framework is developed for the needs of family members and visitors for a range of time periods. This framework is founded upon desires to help make the patient feel more comfortable. There are various levels of helping the patient feel more comfortable, including visiting, keeping company, providing support, providing assistance, and being a caregiver. Beyond this core need, family members and visitors must take care of their own needs in order to feel comfortable in the hospital room. Activities associated with these needs include sitting, relaxing, eating, working, tending to daily needs, and resting overnight. CONCLUSIONS:: Potential implications for architects, healthcare planners, and interior space designers are described. Design and renovation guidance for the hospital room environment in order to support the needs and expectations of families and visitors is provided.


Asunto(s)
Familia/psicología , Arquitectura y Construcción de Hospitales/normas , Habitaciones de Pacientes/normas , Adulto , Femenino , Grupos Focales , Humanos , Diseño Interior y Mobiliario/normas , Masculino , Persona de Mediana Edad , Visitas a Pacientes/psicología
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