Aberrations of large‐scale brain networks are found in the majority of neurodegenerative disorders. The brain connectivity alterations underlying dementia with Lewy bodies (DLB) remain, however, still elusive, with contrasting results possibly due to the pathological and clinical heterogeneity characterizing this disorder. Here, we provide a molecular assessment of brain network alterations, based on cerebral metabolic measurements as proxies of synaptic activity and density, in a large cohort of DLB patients (N = 72). We applied a seed‐based interregional correlation analysis approach (p < .01, false discovery rate corrected) to evaluate large‐scale resting‐state networks' integrity and their interactions. We found both local and long‐distance metabolic connectivity alterations, affecting the posterior cortical networks, that is, primary visual and the posterior default mode network, as well as the limbic and attention networks, suggesting a widespread derangement of the brain connectome. Notably, patients with the lowest visual and attention cognitive scores showed the most severe connectivity derangement in regions of the primary visual network. In addition, network‐level alterations were differentially associated with the core clinical manifestations, namely, hallucinations with more severe metabolic dysfunction of the attention and visual networks, and rapid eye movement sleep behavior disorder with alterations of connectivity of attention and subcortical networks. These multiple network‐level vulnerabilities may modulate the core clinical and cognitive features of DLB and suggest that DLB should be considered as a complex multinetwork disorder. 相似文献
Chitosan oligosaccharide (C) was functionalized with l-arginine (A) and short hydrocarbon chains (C8) to design an amphiphilic copolymer, henceforth CAC8, leading to microparticles (MPs) consisting of an arginine-decorated hydrophilic shell and inner hydrophobic domains allowing the encapsulation of high amount hydrophobic drugs such as sorafenib tosylate (>10% w/w). l-arginine side chains were selected in order to impart the final MPs enhanced transcorneal penetration properties, thus overcoming the typical biological barriers which hamper the absorption of drugs upon topical ocular administration. The mucoadhesive properties and drug release profile of the CAC8 MPs (CAC8-MPs) were studied, showing that CAC8-MPs can strongly interact with mucin, and thus gradually release their payload in situ to potentially improve the bioavailability of the drug after topical administration. In vitro transcorneal studies also showed that CAC8-MPs are endowed with effective permeation enhancer ability combined with negligible toxicity. 相似文献
Little is known about dementia incidence in diverse populations of oldest-old, the age group with highest dementia incidence.
Methods
Incident dementia diagnoses from 1/1/2010 to 9/30/2015 were abstracted from medical records for 2350 members of an integrated health care system in California (n = 1702 whites, n = 375 blacks, n = 105 Latinos, n = 168 Asians) aged ≥90 in 2010. We estimated race/ethnicity-specific age-adjusted dementia incidence rates and implemented Cox proportional hazards models and Fine and Gray competing risk of death models adjusted for demographics and comorbidities in midlife and late-life.
Results
Dementia incidence rates (n = 771 cases) were lowest among Asians (89.9/1000 person-years), followed by whites (96.9/1000 person-years), Latinos (105.8/1000 person-years), and blacks (121.5/1000 person-years). Cox regression and competing risk models estimated 28% and 36% higher dementia risk for blacks versus whites adjusting for demographics and comorbidities.
Discussion
Patterns of racial/ethnic disparities in dementia seen in younger older adults continue after the age of 90 years, though smaller in magnitude. 相似文献
Introduction: Allergic rhinitis (AR) is the most common allergic disease, and it has a relevant impact on the quality of life of the patient. Treatment of AR includes a combination of strategies of proven efficacy and effectiveness; however, a relevant proportion of patients remain uncontrolled.
Areas covered: This review article summarizes emerging therapeutic approaches to AR; these approaches include nasal sprays, oral drugs, alternative allergen immunotherapy administration routes, and biologic agents.
Expert opinion: The agents discussed require further clinical trials to prove their efficacy in the treatment of AR. Some of these agents, in particular, allergen immunotherapies and biologics, have the potential to form crucial precision medicine approaches to AR. Those that prove their efficacy in clinical trials must also be evaluated from a pharmacoeconomic perspective, possibly in real-life studies; this will define which therapeutic strategies achieve the most convenient and cost-effective ratio, thus yielding a novel opportunity for the most severe and previously treatment-resistant allergic patients. 相似文献
«Effectiveness of the measures aimed at containing Sars-cov-2 virus spreading in work settings: a survey in companies based in the Veneto region of Italy».Introduction:During the Sars-Cov-2 pandemic, occupational health physicians worked to respond to different needs of workers, employers, and health authorities. In collaboration with the Prevention Department of the Veneto region of Italy, a survey was promoted in nine manufacturing companies in the province of Padua, to investigate the prevalence of asymptomatic SarsCov-2 virus and the immunological status of 1,267 workers.Scope:The study was aimed at verifying the effectiveness of measures to contain the virus spread among workers in the workplace as required by the agreement between the social partners signed on March 14, 2020.Methods:The survey was carried out at workplaces by trained health physicians and almost all company workers enrolled on a voluntary basis. Each worker was tested for viral RNA using nasopharyngeal swab and for IgM and IgG antibodies by drawing venous or capillary blood, according to the availability of tests at that difficult period.Results:Swab-positive workers were 0.3%, and subjects with positive serological tests were 1.6% of the total workers examined.Discussion:The diagnostic test is based on the search for viral RNA through nasopharyngeal swab. To evaluate the immunological status of workers the CLIA or Elisa quantitative serological test should be preferred. Measures to contain the virus spreading at the workplace seem to be effective, as working settings do not entail any additional risk of SarsCov-2 infection.Key words: COVID-19, epidemiology, prevention at workplace相似文献