Feasibility of Dual-Task Gait to Estimate Alzheimer\u27s Related Cognitive Decline in Down Syndrome

Introduction: The striatum and frontal lobes have been shown to have early Alzheimer\u27s disease (AD) neuropathology and are critical for motor and cognitive function. We hypothesized gait would be associated with early-stage dementia in Down syndrome (DS), a cohort at risk for AD. Methods: Twenty-eight participants with DS were enrolled in the study. Participants walked at their self-selected pace and while completing a dual task (counting, obstacle, or counting+obstacle). Results: All participants were able to complete the self-paced condition and 78.57-96.42% completed the dual-task conditions. There was a trend for greater dual-task effects on gait velocity based on dementia diagnosis. Gait velocity had stronger associations with clinical dementia assessments than age or diagnosis. Discussion: A dual-task gait paradigm is feasible to conduct with adults with DS and is associated with age and cognitive impairment. Dual-task gait may serve as an indicator of early stage dementia in DS

A Plasmodium promiscuous T cell epitope delivered within the Ad5 hexon protein enhances the protective efficacy of a protein based malaria vaccine

A malaria vaccine is a public health priority. In order to produce an effective vaccine, a multistage approach targeting both the blood and the liver stage infection is desirable. The vaccine candidates also need to induce balanced immune responses including antibodies, CD4+ and CD8+ T cells. Protein-based subunit vaccines like RTS,S are able to induce strong antibody response but poor cellular reactivity. Adenoviral vectors have been effective inducing protective CD8+ T cell responses in several models including malaria; nonetheless this vaccine platform exhibits a limited induction of humoral immune responses. Two approaches have been used to improve the humoral immunogenicity of recombinant adenovirus vectors, the use of heterologous prime-boost regimens with recombinant proteins or the genetic modification of the hypervariable regions (HVR) of the capsid protein hexon to express B cell epitopes of interest. In this study, we describe the development of capsid modified Ad5 vectors that express a promiscuous Plasmodium yoelii T helper epitope denominated PyT53 within the hexon HVR2 region. Several regimens were tested in mice to determine the relevance of the hexon modification in enhancing protective immune responses induced by the previously described protein-based multi-stage experimental vaccine PyCMP. A heterologous prime-boost immunization regime that combines a hexon modified vector with transgenic expression of PyCMP followed by protein immunizations resulted in the induction of robust antibody and cellular immune responses in comparison to a similar regimen that includes a vector with unmodified hexon. These differences in immunogenicity translated into a better protective efficacy against both the hepatic and red blood cell stages of P. yoelii. To our knowledge, this is the first time that a hexon modification is used to deliver a promiscuous T cell epitope. Our data support the use of such modification to enhance the immunogenicity and protective efficacy of adenoviral based malaria vaccines

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Preparing For Use Of A Computerized Battery To Identify Neurocognitive Impairments Among Children And Adolescents Affected By The Human Immunodeficiency Virus In Botswana

The human immunodeficiency virus (HIV) infection and in utero exposure increase the risk of neurocognitive impairment among pediatric populations. In Sub-Saharan Africa, HIV is prevalent, but standardized cognitive screening does not exist. To facilitate access to neurocognitive screening in this setting, the Penn Computerized Neurocognitive Battery (PennCNB) was culturally adapted and translated for use in Botswana. The PennCNB streamlines the evaluation of neurocognitive functioning by measuring performance accuracy and response speed on major cognitive domains, which offers many advantages for implementation in resource-limited settings (e.g., automated scoring and data interpretation). This body of research prepares for the utilization of the tool in Botswana by examining measures of validity and engaging in pre-implementation inquiry to help address the substantial research-to-practice gap. HIV-affected children and adolescents (HIV-infected and HIV-exposed-uninfected) age 7-17 years were enrolled from a pediatric HIV clinic in Gaborone, Botswana for these studies. Participants completed the PennCNB assessment. Confirmatory and exploratory factor analyses demonstrated strong discriminant and convergent validity of the battery, thus supporting the design of the adapted PennCNB measuring four neurocognitive domains: executive functioning, episodic memory, complex cognition, and sensorimotor/processing speed. When evaluating the classification accuracy of the battery against the best, most feasible local data (e.g., clinical interview, pencil-and-paper psychological assessments, and school reports), the tool exhibited acceptable criterion validity. The children and adolescents rated the PennCNB as highly acceptable, which is promising for the success of implementation. To further understand factors likely to impact the successful integration of the tool into clinical settings, semi-structured interviews were completed with key stakeholders (e.g., mental health clinicians, non-mental health clinicians, and leadership) in the public medical sector. Results underscored the need for cognitive screening, revealed anticipated barriers and facilitators to using the PennCNB, and suggested implementation strategies. Overall, this research provided valuable insight into the psychometric properties of the adapted PennCNB and input to inform specific implementation strategies for Botswana. Future implementation of the tool will facilitate early detection of neurocognitive deficits, which is critical for supporting the functional and educational attainment of HIV-affected children and adolescents in this high-need and other resource-limited settings in the region

Feasibility of dual-task gait to estimate Alzheimer's related cognitive decline in Down syndrome.

IntroductionThe striatum and frontal lobes have been shown to have early Alzheimer's disease (AD) neuropathology and are critical for motor and cognitive function. We hypothesized gait would be associated with early-stage dementia in Down syndrome (DS), a cohort at risk for AD.MethodsTwenty-eight participants with DS were enrolled in the study. Participants walked at their self-selected pace and while completing a dual task (counting, obstacle, or counting+obstacle).ResultsAll participants were able to complete the self-paced condition and 78.57-96.42% completed the dual-task conditions. There was a trend for greater dual-task effects on gait velocity based on dementia diagnosis. Gait velocity had stronger associations with clinical dementia assessments than age or diagnosis.DiscussionA dual-task gait paradigm is feasible to conduct with adults with DS and is associated with age and cognitive impairment. Dual-task gait may serve as an indicator of early stage dementia in DS

Low Prevalence of Human Pathogens on Fresh Produce on Farms and in Packing Facilities: A Systematic Review

Foodborne illness burdens individuals around the world and may be caused by consuming fresh produce contaminated with bacterial, parasite, and viral pathogens. Pathogen contamination on produce may originate at the farm and packing facility. This research aimed to determine the prevalence of human pathogens (bacteria, parasites, and viruses) on fresh produce (fruits, herbs, and vegetables) on farms and in packing facilities worldwide through a systematic review of 38 peer-reviewed articles. The median and range of the prevalence was calculated, and Kruskal–Wallis tests and logistic regression were performed to compare prevalence among pooled samples of produce groups, pathogen types, and sampling locations. Results indicated a low median percentage of fresh produce contaminated with pathogens (0%). Both viruses (p-value = 0.017) and parasites (p-value = 0.033), on fresh produce, exhibited higher prevalence than bacteria. No significant differences between fresh produce types or between farm and packing facility were observed. These results may help to better quantify produce contamination in the production environment and inform strategies to prevent future foodborne illness

Protection induced by the vaccination regimens including Ad5HVR2 modified vectors.

<p>CB6F1/J (n = 10 per group) mice received the regimens described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0154819#pone.0154819.g002" target="_blank">Fig 2</a>. Twenty days after the last immunizations mice were challenged with <i>Plasmodium yoelii</i> sporozoites and the kinetic of parasitemia expressed as an AUC <b>(A)</b> and the pre-patency period <b>(B)</b> were analyzed by Kruskal-Wallis test with Dunns post-test significant statistical differences between the groups are denoted by *(p<0.05) **(p<0.01).</p

Cytokine production in splenocytes induced by the vaccination regimens including Ad5HVR2 modified vectors.

<p>CB6F1/J (n = 5 per group) mice received the regimens described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0154819#pone.0154819.g002" target="_blank">Fig 2</a>. Splenocytes were obtained 5 days after the final immunization and were incubated with the PyT53 epitope present in the vector capsid, the PyCMP protein, or peptide pools (15 amino acids long, overlapping be 10 amino acids) representing the PyCMP sequence. After stimulation, cells were intracellularly stained and acquired by flow cytometry, <b>Top.</b> CD8+ T cells able to produce IL-2 <b>(A)</b> IFN-γ <b>(B)</b> and TNF-α <b>(C)</b> after stimulation. <b>Bottom.</b> CD4+ T cells able to produce IL-2 <b>(D)</b> IFN-γ <b>(E)</b> and TNF-α <b>(F)</b> after stimulation. Results were analyzed after background subtraction. Statistical analysis was performed using the Kruskal–Wallis test with Dunn’s post-test, differences between the vaccination groups and the control group are presented *(p<0.05) **(p<0.01) ***(p<0.001).</p

Protection induced by the vaccination regimens based on the Ad5HVRT53PyCMP vector.

<p>CB6F1/J (n = 10 per group) mice received the immunization regimens described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0154819#pone.0154819.g006" target="_blank">Fig 6</a>. Twenty days after the last immunizations mice were challenged with <i>Plasmodium yoelii</i> sporozoites, the kinetics of parasitemia expressed as an AUC <b>(A)</b> and the pre-patency period <b>(B)</b> were analyzed by Kruskal-Wallis test with Dunns post-test, significant statistical differences between the groups are denoted by *(p<0.05), **(p<0.01).</p