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Lori F. Maxfield Peter Abbink Kathryn E. Stephenson Erica N. Borducchi David Ng'ang'a Marinela M. Kirilova Noelix Paulino Michael Boyd Paul Shabram Qian Ruan Mayank Patel Dan H. Barouch 《Clinical and Vaccine Immunology : CVI》2015,22(11):1166-1175
Replication-competent adenovirus (rcAd)-based vaccine vectors may theoretically provide immunological advantages over replication-incompetent Ad vectors, but they also raise additional potential clinical and regulatory issues. We produced replication-competent Ad serotype 26 (rcAd26) vectors by adding the E1 region back into a replication-incompetent Ad26 vector backbone with the E3 or E3/E4 regions deleted. We assessed the effect of vectorization on the replicative capacity of the rcAd26 vaccines. Attenuation occurred in a stepwise fashion, with E3 deletion, E4 deletion, and human immunodeficiency virus type 1 (HIV-1) envelope (Env) gene insertion all contributing to reduced replicative capacity compared to that with the wild-type Ad26 vector. The rcAd26 vector with E3 and E4 deleted and containing the Env transgene exhibited 2.7- to 4.4-log-lower replicative capacity than that of the wild-type Ad26 in vitro. This rcAd26 vector is currently being evaluated in a phase 1 clinical trial. Attenuation as a result of vectorization and transgene insertion has implications for the clinical development of replication-competent vaccine vectors. 相似文献
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The International Network for Food and Obesity/NCDs Research, Monitoring and Action Support aims to benchmark national food environments. This study proposes a blueprint country profile to measure progress on creating healthy food environments, based on the results of the first, comprehensive survey in New Zealand (NZ). We assessed the implementation of national food environment policies and food industry commitments to improve population nutrition and the strength and comprehensiveness of public sector settings' nutrition policies. The healthiness of the packaged food supply, including health‐related labelling, was evaluated. Food environments were measured in 833 schools, 204 supermarkets, 1500 takeaway outlets, 28 hospitals, 70 sport centres, and around all NZ schools. Food swamps, defined as areas with high relative density of unhealthy food outlets, were identified, and food marketing to children on television, websites, social media and packages, in magazines, and in and around schools was measured. The cost differential between healthy and current household diets was calculated for different population groups. NZ's food environment profile is largely unhealthy, and there are inequalities in access to healthy food environments. It is anticipated that the proposed country profile can help other countries tackle unhealthy food environments through increasing accountability of governments and the industry. 相似文献
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Angela M. Auriat Jennifer K. Ferris Sue Peters Joel Ramirez Sandra E. Black Claudia Jacova Lara A. Boyd 《Journal of stroke and cerebrovascular diseases》2019,28(2):381-388
Background and Aims
In addition to overt stroke lesions, co-occurring covert lesions, including white matter hyperintensities (WMH) and covert lacunar infarcts (CLI), contribute to poststroke outcome. The purpose of this study was to examine the relationship between covert lesions, and motor and cognitive outcomes in individuals with chronic stroke.Methods
Volumetric quantification of clinically overt strokes, covert lesions (periventricular and deep: pWMH, dWMH, pCLI, dCLI), ventricular and sulcal CSF (vCSF, sCSF), and normal appearing white (NAWM) and gray matter (NAGM) was performed using structural magnetic resonance imaging. We assessed motor impairment and function, and global cognition, memory, and other cognitive domains. When correlation analysis identified more than one MR parameter relating to stroke outcomes, we used regression modeling to identify which factor had the strongest impact.Results
Neuropsychological and brain imaging data were collected from 30 participants at least 6 months following a clinically diagnosed stroke. Memory performance related to vCSF (r = ?0.52, P = .004). The strongest predictor of nonmemory domains was pCLI (r2 = 0.28, P = .004). Motor impairment and function were most strongly predicted by the volume of stroke and NAWM (r2 = 0.36; P = .001), and dWMH (r2 = 0.39; P = .001) respectively.Conclusions
Covert lesion type and location have important consequences for post-stroke cognitive and motor outcome. Limiting the progression of covert lesions in aging populations may enhance the degree of recovery post-stroke. 相似文献6.
Danielle E Whittier Elizabeth J Samelson Marian T Hannan Lauren A Burt David A Hanley Emmanuel Biver Pawel Szulc Elisabeth Sornay-Rendu Blandine Merle Roland Chapurlat Eric Lespessailles Andy Kin On Wong David Goltzman Sundeep Khosla Serge Ferrari Mary L Bouxsein Douglas P Kiel Steven K Boyd 《Journal of bone and mineral research》2022,37(3):428-439
Prevalence of osteoporosis is more than 50% in older adults, yet current clinical methods for diagnosis that rely on areal bone mineral density (aBMD) fail to detect most individuals who have a fragility fracture. Bone fragility can manifest in different forms, and a “one-size-fits-all” approach to diagnosis and management of osteoporosis may not be suitable. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides additive information by capturing information about volumetric density and microarchitecture, but interpretation is challenging because of the complex interactions between the numerous properties measured. In this study, we propose that there are common combinations of bone properties, referred to as phenotypes, that are predisposed to different levels of fracture risk. Using HR-pQCT data from a multinational cohort (n = 5873, 71% female) between 40 and 96 years of age, we employed fuzzy c-means clustering, an unsupervised machine-learning method, to identify phenotypes of bone microarchitecture. Three clusters were identified, and using partial correlation analysis of HR-pQCT parameters, we characterized the clusters as low density, low volume, and healthy bone phenotypes. Most males were associated with the healthy bone phenotype, whereas females were more often associated with the low volume or low density bone phenotypes. Each phenotype had a significantly different cumulative hazard of major osteoporotic fracture (MOF) and of any incident osteoporotic fracture (p < 0.05). After adjustment for covariates (cohort, sex, and age), the low density followed by the low volume phenotype had the highest association with MOF (hazard ratio = 2.96 and 2.35, respectively), and significant associations were maintained when additionally adjusted for femoral neck aBMD (hazard ratio = 1.69 and 1.90, respectively). Further, within each phenotype, different imaging biomarkers of fracture were identified. These findings suggest that osteoporotic fracture risk is associated with bone phenotypes that capture key features of bone deterioration that are not distinguishable by aBMD. © 2021 American Society for Bone and Mineral Research (ASBMR). 相似文献
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Carlo De-Carolis Geraldine-A. Boyd Luca Mancinelli Stefano Pagano Stefano Eramo 《Medicina oral, patología oral y cirugía bucal》2015,20(2):e205-e210
With easy chemical synthesis from its precursor, methamphetamine (MA) is now widespread in many countries. The abuse of methamphetamine is associated with several negative effects on health, because MA is a neurotoxin and a dangerous central nervous system stimulant. It changes levels of neurotransmitters in the brain, releasing dopamine and inhibiting nor epinephrine uptake which increases sympathetic nervous system activity and can lead to cardiac arrhythmia, hypertension and tachypnea. The consequences of MA abuse are clearly manifested in oral diseases (like “meth mouth”) which is characterised by extensive caries, teeth grinding with ensuing dental wear and trismus. The present review was designed to fill the gap in knowledge about methamphetamine abuse in the European Union (EU) and to illustrate the main clinical effects of prolonged use. After describing the pharmacology and systemic effects of methamphetamine and concentrating on its effects on the mouth, the present review compares the epidemiology and incidence of abuse in the world, particularly the USA and the EU.
Key words:Methamphetamine, “Meth mouth”, drug abuse, oral health. 相似文献
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ObjectiveTo provide an overview of the healthcare and societal consequences and costs of untreated obstructive sleep apnea syndrome.Data sourcesPubMed database for English-language studies with no start date restrictions and with an end date of September 2014.MethodsA comprehensive literature review was performed to identify all studies that discussed the physiologic, clinical and societal consequences of obstructive sleep apnea syndrome as well as the costs associated with these consequences. There were 106 studies that formed the basis of this analysis.ConclusionsUndiagnosed and untreated obstructive sleep apnea syndrome can lead to abnormal physiology that can have serious implications including increased cardiovascular disease, stroke, metabolic disease, excessive daytime sleepiness, work-place errors, traffic accidents and death. These consequences result in significant economic burden. Both, the health and societal consequences and their costs can be decreased with identification and treatment of sleep apnea.Implications for practiceTreatment of obstructive sleep apnea syndrome, despite its consequences, is limited by lack of diagnosis, poor patient acceptance, lack of access to effective therapies, and lack of a variety of effective therapies. Newer modes of therapy that are effective, cost efficient and more accepted by patients need to be developed. 相似文献