Notes

A single-cell analysis of the Arabidopsis vegetative capture top.
The ATN framework provides an in vivo diagnosis of Alzheimer's disease (AD) using cerebrospinal fluid (CSF) biomarkers of pathologic amyloid plaques (A), tangles (T), and neurodegeneration (N). ATN is rarely evaluated in pathologically confirmed patients and its poor sensitivity to suspected non-Alzheimer's pathophysiologies (SNAP), including frontotemporal lobar degeneration (FTLD), leads to misdiagnoses. We compared accuracy of ATN (ATN
) using CSF total tau (t-tau) to a modified strategy (ATN
) using CSF neurofilament light chain (NfL) in an autopsy cohort.

ATN
and ATN
were trained in an independent sample and validated in autopsy-confirmed AD (n=67) and FTLD (n=27).

ATN
more accurately identified FTLD as SNAP (sensitivity=0.93, specificity=0.94) than ATN
(sensitivity=0.44, specificity=0.97), even in cases with co-occurring AD and FTLD. ATN
misclassified fewer AD and FTLD as "Normal" (2%) than ATN
(14%).

ATN
is a promising diagnostic strategy that may accurately identify both AD and FTLD, even when pathologies co-occur.
ATNNfL is a promising diagnostic strategy that may accurately identify both AD and FTLD, even when pathologies co-occur.
A growing number of dominantly inherited Alzheimer's disease (DIAD) cases have become known in Latin American (LatAm) in recent years. However, questions regarding mutation distribution and frequency by country remain open.

A literature review was completed aimed to provide estimates for DIAD pathogenic variants in the LatAm population. The search strategies were established using a combination of standardized terms for DIAD and LatAm.

Twenty-four DIAD pathogenic variants have been reported in LatAm countries. Our combined dataset included 3583 individuals at risk; countries with highest DIAD frequencies were Colombia (n=1905), Puerto Rico (n=672), and Mexico (n=463), usually attributable to founder effects. We found relatively few reports with extensive documentation on biomarker profiles and disease progression.

Future DIAD studies will be required in LatAm, albeit with a more systematic approach to include fluid biomarker and imaging studies. Regional efforts are under way to extend the DIAD observational studies and clinical trials to Latin America.
Future DIAD studies will be required in LatAm, albeit with a more systematic approach to include fluid biomarker and imaging studies. PB94 Regional efforts are under way to extend the DIAD observational studies and clinical trials to Latin America.Live imaging is critical to determining the dynamics and spatial interactions of cells within the tissue environment. In the lung, this has proven to be difficult due to the motion brought about by ventilation and cardiac contractions. A previous version of this Current Protocols in Cytometry article reported protocols for imaging ex vivo live lung slices and the intact mouse lung. Here, we update those protocols by adding new methodologies, new approaches for quantitative image analysis, and new areas of potential application. © 2020 Wiley Periodicals LLC. Basic Protocol 1 Live imaging of lung slices Support Protocol 1 Staining lung sections with fluorescent antibodies Basic Protocol 2 Live imaging in the mouse lung Support Protocol 2 Intratracheal instillations Support Protocol 3 Intravascular instillations Support Protocol 4 Monitoring vital signs of the mouse during live lung imaging Support Protocol 5 Antibodies Support Protocol 6 Fluorescent reporter mice Basic Protocol 3 Quantification of neutrophil-platelet aggregation in pulmonary vasculature Basic Protocol 4 Quantification of platelet-dependent pulmonary thrombosis Basic Protocol 5 Quantification of pulmonary vascular permeability.There exists a public health imperative to discover and to develop disease-modifying Alzheimer's disease (AD) therapeutics to protect the health of millions of individuals facing AD. Achievement of this goal will be dependent on developing the clinical tools to detect high risk, in the earliest phases of the disease, and at the population level. This article describes the study of retinal biomarkers for the identification of, and tracking of change over time for, individuals in the preclinical stage of AD and substantiates the need for a major cross-disciplinary effort for comparison across labs and clinical sites using diabetes risk monitoring as a perfect analogy. Proposed framework would (1) support AD working groups across disciplines; (2) establish common imaging platforms to develop and test basic standards, and minimum datasets to embrace and test novel innovations as they emerge; and (3) accelerate AD prevention and quality improvement in real-world care.The microbial communities that inhabit the gingival crevice are responsible for the pathological processes that affect the periodontium. The changes in composition and function of subgingival bacteria as disease develops have been extensively studied. Subgingival communities, however, also contain fungi, Archaea, and viruses, which could contribute to the dysbiotic processes associated with periodontal diseases. High-throughput DNA sequencing has facilitated a better understanding of the mycobiome, archaeome, and virome. However, the number of studies available on the nonbacterial components of the subgingival microbiome remains limited in comparison with publications focusing on bacteria. Difficulties in characterizing fungal, archaeal, and viral populations arise from the small portion of the total metagenome mass they occupy and lack of comprehensive reference genome databases. In addition, specialized approaches potentially introducing bias are required to enrich for viral particles, while harsh methods of cell lysis are needed to recover nuclei acids from certain fungi. While the characterization of the subgingival diversity of fungi, Archaea and viruses is incomplete, emerging evidence suggests that they could contribute in different ways to subgingival dysbiosis. Certain fungi, such as Candida albicans are suggested to facilitate colonization of bacterial pathogens. Methanogenic Archaea are associated with periodontitis severity and are thought to partner synergistically with bacterial fermenters, while viruses may affect immune responses or shape microbial communities in ways incompletely understood. This review describes the manner in which omics approaches have improved our understanding of the diversity of fungi, Archaea, and viruses within subgingival communities. Further characterization of these understudied components of the subgingival microbiome is required, together with mechanistic studies to unravel their ecological role and potential contributions to dysbiosis.
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