The US faces remarkable food and nutrition challenges. A new federal effort to strengthen and coordinate nutrition research could rapidly generate the evidence base needed to address these multiple ...national challenges. However, the relevant characteristics of such an effort have been uncertain.
Our aim was to provide an objective, informative summary of 1) the mounting diet-related health burdens facing our nation and corresponding economic, health equity, national security, and sustainability implications; 2) the current federal nutrition research landscape and existing mechanisms for its coordination; 3) the opportunities for and potential impact of new fundamental, clinical, public health, food and agricultural, and translational scientific discoveries; and 4) the various options for further strengthening and coordinating federal nutrition research, including corresponding advantages, disadvantages, and potential executive and legislative considerations.
We reviewed government and other published documents on federal nutrition research; held various discussions with expert groups, advocacy organizations, and scientific societies; and held in-person or phone meetings with >50 federal staff in executive and legislative roles, as well as with a variety of other stakeholders in academic, industry, and nongovernment organizations.
Stark national nutrition challenges were identified. More Americans are sick than are healthy, largely from rising diet-related illnesses. These conditions create tremendous strains on productivity, health care costs, health disparities, government budgets, US economic competitiveness, and military readiness. The coronavirus disease 2019 (COVID-19) outbreak has further laid bare these strains, including food insecurity, major diet-related comorbidities for poor outcomes from COVID-19 such as diabetes, hypertension, and obesity, and insufficient surveillance on and coordination of our food system. More than 10 federal departments and agencies currently invest in critical nutrition research, yet with relatively flat investments over several decades. Coordination also remains suboptimal, documented by multiple governmental reports over 50 years. Greater harmonization and expansion of federal investment in nutrition science, not a silo-ing or rearrangement of existing investments, has tremendous potential to generate new discoveries to improve and sustain the health of all Americans. Two identified key strategies to achieve this were as follows: 1) a new authority for robust cross-governmental coordination of nutrition research and other nutrition-related policy and 2) strengthened authority, investment, and coordination for nutrition research within the NIH. These strategies were found to be complementary, together catalyzing important new science, partnerships, coordination, and returns on investment. Additional complementary actions to accelerate federal nutrition research were identified at the USDA.
The need and opportunities for strengthened federal nutrition research are clear, with specific identified options to help create the new leadership, strategic planning, coordination, and investment the nation requires to address the multiple nutrition-related challenges and grasp the opportunities before us.
Bioresorbable electronic stimulators are of rapidly growing interest as unusual therapeutic platforms, i.e., bioelectronic medicines, for treating disease states, accelerating wound healing processes ...and eliminating infections. Here, we present advanced materials that support operation in these systems over clinically relevant timeframes, ultimately bioresorbing harmlessly to benign products without residues, to eliminate the need for surgical extraction. Our findings overcome key challenges of bioresorbable electronic devices by realizing lifetimes that match clinical needs. The devices exploit a bioresorbable dynamic covalent polymer that facilitates tight bonding to itself and other surfaces, as a soft, elastic substrate and encapsulation coating for wireless electronic components. We describe the underlying features and chemical design considerations for this polymer, and the biocompatibility of its constituent materials. In devices with optimized, wireless designs, these polymers enable stable, long-lived operation as distal stimulators in a rat model of peripheral nerve injuries, thereby demonstrating the potential of programmable long-term electrical stimulation for maintaining muscle receptivity and enhancing functional recovery.
Temporary cardiac pacemakers used in periods of need during surgical recovery involve percutaneous leads and externalized hardware that carry risks of infection, constrain patient mobility and may ...damage the heart during lead removal. Here we report a leadless, battery-free, fully implantable cardiac pacemaker for postoperative control of cardiac rate and rhythm that undergoes complete dissolution and clearance by natural biological processes after a defined operating timeframe. We show that these devices provide effective pacing of hearts of various sizes in mouse, rat, rabbit, canine and human cardiac models, with tailored geometries and operation timescales, powered by wireless energy transfer. This approach overcomes key disadvantages of traditional temporary pacing devices and may serve as the basis for the next generation of postoperative temporary pacing technology.
It is unknown whether the direct oral anticoagulant edoxaban can reduce leaflet thrombosis and the accompanying cerebral thromboembolic risk after transcatheter aortic valve replacement. In addition, ...the causal relationship of subclinical leaflet thrombosis with cerebral thromboembolism and neurological or neurocognitive dysfunction remains unclear.
We conducted a multicenter, open-label randomized trial comparing edoxaban with dual antiplatelet therapy (aspirin plus clopidogrel) in patients who had undergone successful transcatheter aortic valve replacement and did not have an indication for anticoagulation. The primary end point was an incidence of leaflet thrombosis on 4-dimensional computed tomography at 6 months. Key secondary end points were the number and volume of new cerebral lesions on brain magnetic resonance imaging and the serial changes of neurological and neurocognitive function between 6 months and immediately after transcatheter aortic valve replacement.
A total of 229 patients were included in the final intention-to-treat population. There was a trend toward a lower incidence of leaflet thrombosis in the edoxaban group compared with the dual antiplatelet therapy group (9.8% versus 18.4%; absolute difference, -8.5% 95% CI, -17.8% to 0.8%;
=0.076). The percentage of patients with new cerebral lesions on brain magnetic resonance imaging (edoxaban versus dual antiplatelet therapy, 25.0% versus 20.2%; difference, 4.8%; 95% CI, -6.4% to 16.0%) and median total new lesion number and volume were not different between the 2 groups. In addition, the percentages of patients with worsening of neurological and neurocognitive function were not different between the groups. The incidence of any or major bleeding events was not different between the 2 groups. We found no significant association between the presence or extent of leaflet thrombosis with new cerebral lesions and a change of neurological or neurocognitive function.
In patients without an indication for long-term anticoagulation after successful transcatheter aortic valve replacement, the incidence of leaflet thrombosis was numerically lower with edoxaban than with dual antiplatelet therapy, but this was not statistically significant. The effects on new cerebral thromboembolism and neurological or neurocognitive function were also not different between the 2 groups. Because the study was underpowered, the results should be considered hypothesis generating, highlighting the need for further research.
URL: https://www.
gov. Unique identifier: NCT03284827.
IntroductionOptimal antithrombotic strategy following transcatheter aortic valve replacement (TAVR) is still unknown. We hypothesised that the direct factor Xa inhibitor edoxaban can potentially ...prevent subclinical leaflet thrombosis and cerebral embolisation compared with conventional dual antiplatelet therapy (DAPT) in patients undergoing TAVR.Methods and analysisThe ADAPT-TAVR trial is an international, multicentre, randomised, open-label, superiority trial comparing edoxaban-based strategy and DAPT strategy in patients without an indication for oral anticoagulation who underwent successful TAVR. A total of 220 patients are randomised (1:1 ratio), 1–7 days after successful TAVR, to receive either edoxaban (60 mg daily or 30 mg daily if patients had dose-reduction criteria) or DAPT using aspirin (100 mg daily) plus clopidogrel (75 mg daily) for 6 months. The primary endpoint was an incidence of leaflet thrombosis on four-dimensional, volume-rendered cardiac CT imaging at 6 months post-TAVR. The key secondary endpoints were the number of new lesions and new lesion volume on brain diffusion-weighted MRI and the changes in neurological and neurocognitive function assessment between immediate post-TAVR and 6 months of study drug administration. Detailed clinical information on thromboembolic and bleeding events were also assessed.Ethics and disseminationEthic approval has been obtained from the Ethics Committee/Institutional Review Board of Asan Medical Center (approval number: 2017–1317) and this trial is also approved by National Institute of Food and Drug Safety Evaluation of Republic of Korea (approval number: 31511). Results of this study will be disseminated in scientific publication in reputed journals.Trial registration numberNCT03284827.
Abstract
Background
Polygenic risk scores (PRS) quantify the combined effects of genetic variants to enable the prediction of an individual’s risk of developing the disease. Alzheimer’s disease (AD) ...is a complex disorder in which the relationship among PRS, neuropathological substrates, and related cognitive decline remain especially understudied in Asian populations. We investigated the associations of PRS with AD neuroimaging biomarkers and cognitive phenotypes in a Korean Cohort.
Method
The study included 501 older adults (264 cognitively normal CN, 146 mild cognitive impairment MCI, and 91 AD dementia) from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE). Comprehensive clinical and neuropsychological evaluations, as well as multi‐modal neuroimaging including 3T MRI and
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C‐PiB‐PET were administered. A subset of participants underwent
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F‐AV‐1451 PET (n = 167). Imaging phenotypes including beta‐amyloid (Aβ) positivity, global tau deposition, and adjusted hippocampal volume (HVa) were used for amyloid (A), tau (T), and neurodegeneration (N) biomarkers, respectively., which was imputed using the TOPMed reference panel. PRS was calculated using the summary statistics of a recent large‐scale GWAS study for AD by PRS‐CS. The Apolipoprotein E (APOE) region was excluded in the calculation. The associations between standardized PRS and imaging/cognitive phenotypes were examined using either multiple linear or logistic regression analysis with covariates (age and sex for neuroimaging biomarker phenotypes; age, sex and education for cognitive phenotypes).
Result
PRS was significantly higher in the AD dementia group compared to the CN group. Higher PRS was associated with greater CDR‐sum‐of‐boxes (βSE = 0.2330.083, t = 2.818, p = 0.005) and lower MMSE scores (βSE = ‐0.6480.198, t = ‐3.271, p = 0.001). In terms of AD neuroimaging biomarkers (Figure 1), higher PRS was significantly associated with an increased likelihood of Aβ positivity (OR = 1.233, 95%CI = 1.024‐1.491), and lower HVa (βSE = ‐132.7949.624, t = ‐2.676, p = 0.008), but not with global tau deposition (βSE = 0.0750.048, t = 1.573, p = 0.118).
Conclusion
These findings suggest that higher PRS predicts increased pathological Aβ deposition and accelerated neurodegeneration, as well as greater cognitive decline. Further investigation in larger and multiethnic samples are needed to determine generalizability to other ethnoracial populations.
Omicron has become the globally dominant SARS-CoV-2 variant, creating additional challenges due to its ability to evade neutralization. Here, we report that neutralizing antibodies against Omicron ...variants are undetected following COVID-19 infection with ancestral or past SARS-CoV-2 variant viruses or after two-dose mRNA vaccination. In comparison to two-dose vaccination, a three-dose vaccination course induces broad neutralizing antibody responses with improved durability against different SARS-CoV-2 variants, although neutralizing antibody titers against Omicron remain low. Intriguingly, among individuals with three-dose vaccination, Omicron breakthrough infection substantially augment serum neutralizing activity against a broad spectrum of SARS-CoV-2 variants, including Omicron variants BA.1, BA.2, and BA.5. Additionally, after Omicron breakthrough infection, memory T cells respond to the spike proteins of both ancestral and Omicron SARS-CoV-2 by producing cytokines with polyfunctionality. These results suggest that Omicron breakthrough infection following three-dose mRNA vaccination induces pan-SARS-CoV-2 immunity that may protect against emerging SARS-CoV-2 variants of concern.
Jeong et al. investigate the efficacies of the NAb elicited by SARS-CoV-2 infection or mRNA vaccination. Through the longitudinal analysis, the authors demonstrate that although cross-reactivity of the NAb induced by SARS-CoV-2 infection or two-dose vaccination is variant-specific, Omicron breakthrough infection following booster vaccination can elicit NAb against pan-SARS-CoV-2.
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