Health-related quality of life in hereditary transthyretin amyloidosis polyneuropathy: a prospective, observational study

Background Hereditary Transthyretin Amyloidosis Polyneuropathy is a rare life-threatening neurologic disease that imposes considerable mortality and it is associated with progressive related disabilities. In this study, we aimed to assess the effect of the disease across health-related quality of life dimensions, in both carriers of the mutation and patients, to compare health-related quality of life with general population, as well as to explore health-related quality of life prognostic factors among patients, including disease progression and treatment. Methods This study was a multi-institutional, longitudinal, prospective, observational study of hereditary Transthyretin Amyloidosis Polyneuropathy Portuguese adult subjects (621 asymptomatic carriers and 733 symptomatic patients) enrolled in the Transthyretin Amyloidosis Outcomes Survey. Health-related quality of life was captured with the preference-based instrument EQ-5D-3 L. For general population the dataset included all subjects enrolled in a representative national study (n = 1500). Different econometric models were specified; multivariate probit, generalized linear model and generalized estimating equations model; including demographic and clinical covariates. Results Hereditary Transthyretin Amyloidosis Polyneuropathy patients have their health status severely impaired in all quality of life dimensions and more anxiety/depression problems were found among asymptomatic carriers. No differences on utility were found between carriers and general population (p = 0.209). Among patients, the utility value is estimated to be 0.51 (0.021), a decrement of 0.27 as compared with general population utility. Higher disease duration, advanced disease stage and not receiving treatment are associated with impaired health-related quality of life. No differences were found between genders (p = 0.910) or between late (≥50 years) and early-onset patients (p = 0.254). The utility estimate ranged from 0.63 (0.009) in stage I to 0.01 (0.005) in stage IV. Conclusions Hereditary Transthyretin Amyloidosis Polyneuropathy symptoms and progressive associated disabilities substantially decrease patient’s health-related quality of life. Clinical strategies focused on health-related quality of life preservation such as close follow-up of asymptomatic carriers, prompt diagnosis and adequate, early treatment would benefit patient’s long-term outcomes, slowing the progressive decline in health-related quality of life.info:eu-repo/semantics/publishedVersio

An integrated 4249 marker FISH/RH map of the canine genome

BACKGROUND: The 156 breeds of dog recognized by the American Kennel Club offer a unique opportunity to map genes important in genetic variation. Each breed features a defining constellation of morphological and behavioral traits, often generated by deliberate crossing of closely related individuals, leading to a high rate of genetic disease in many breeds. Understanding the genetic basis of both phenotypic variation and disease susceptibility in the dog provides new ways in which to dissect the genetics of human health and biology. RESULTS: To facilitate both genetic mapping and cloning efforts, we have constructed an integrated canine genome map that is both dense and accurate. The resulting resource encompasses 4249 markers, and was constructed using the RHDF5000-2 whole genome radiation hybrid panel. The radiation hybrid (RH) map features a density of one marker every 900 Kb and contains 1760 bacterial artificial chromosome clones (BACs) localized to 1423 unique positions, 851 of which have also been mapped by fluorescence in situ hybridization (FISH). The two data sets show excellent concordance. Excluding the Y chromosome, the map features an RH/FISH mapped BAC every 3.5 Mb and an RH mapped BAC-end, on average, every 2 Mb. For 2233 markers, the orthologous human genes have been established, allowing the identification of 79 conserved segments (CS) between the dog and human genomes, dramatically extending the length of most previously described CS. CONCLUSIONS: These results provide a necessary resource for the canine genome mapping community to undertake positional cloning experiments and provide new insights into the comparative canine-human genome maps

Coincidence between transcriptome analyses on different microarray platforms using a parametric framework

A parametric framework for the analysis of transcriptome data is demonstrated to yield coincident results when applied to data acquired using two different microarray platforms. Discrepancies among transcriptome studies are frequently reported, casting doubt on the reliability of collected data. The inconsistency among observations can be largely attributed to differences among the analytical frameworks employed for data analysis. The existing frameworks normalizes data against a standard determined from the data to be analyzed. In the present study, a parametric framework based on a strict model for normalization is applied to data acquired using an in-house printed chip and GeneChip. The framework is based on a common statistical characteristic of microarray data, and each data is normalized on the basis of a linear relationship with this model. In the proposed framework, the expressional changes observed and genes selected are coincident between platforms, achieving superior universality of data compared to other methods

Retinoblastoma: Identifying the Diagnostic Signs for Early Treatment

Retinoblastoma is a rare but significant cause of childhood eye cancer world-wide. The prognosis depends upon early diagnosis and treatment but also upon accurate classification of the tumours. Unilateral incidence is normally non-hereditary compared with bilateral incidence where secondary tumours are more common. Survivorship is much better for unilateral compared with bilateral and trilateral retinoblastoma. Early signs are important to detect and photography can assist in identifying no return of “red-eye” during flash photography and yellow appearance of the tumour. Treatment options are discussed together with new psycho-oncology approaches that address potential trauma in the survivor as well as in the family of the survivor

Chronic rhinosinusitis with nasal polyps in older adults : clinical presentation, pathophysiology, and comorbidity

Purpose of Review Chronic rhinosinusitis and nasal polyps (CRSwNP) is a common condition that significantly affects patients' life. This work aims to provide an up-to-date overview of CRSwNP in older adults, focusing on its aging-related clinical presentations, pathophysiology, and comorbidity associations including asthma. Recent Findings Recent large population-based studies using nasal endoscopy have shown that CRSwNP is a mostly late-onset disease. Age-related changes in physiologic functions, including nasal epithelial barrier dysfunction, may underlie the incidence and different clinical presentations of CRSwNP in older adults. However, there is still a paucity of evidence on the effect of aging on phenotypes and endotypes of CRSwNP. Meanwhile, late-onset asthma is a major comorbid condition in patients with CRSwNP; they frequently present with type 2 inflammatory signatures that are refractory to conventional treatments when they are comorbid. However, as they are more commonly non-atopic, causative factors other than classical atopic sensitization, such as Staphylococcus aureus specific IgE sensitization, are suggested to drive the type 2 inflammation. There are additional comorbidity associations in older patients with CRSwNP, including those with chronic otitis media and head and neck malignancy. Age is a major determinant for the incidence and clinical presentations of CRSwNP. Given the heterogeneity in phenotypes and endotypes, longitudinal investigations are warranted to elucidate the effects of aging on CRSwNP