The demographic and epidemiological transitions of the past 200 years are well documented at an aggregate level. Understanding differences in individual and group risks for mortality during these transitions requires linkage between demographic data and detailed individual cause of death information. This paper describes the digitization of almost 185,000 causes of death for Ohio to supplement demographic information in the Longitudinal, Intergenerational Family Electronic Micro-database (LIFE-M). To extract causes of death, our methodology combines handwriting recognition, extensive data cleaning algorithms, and the semi-automated classification of causes of death into International Classification of Diseases (ICD) codes. Our procedures are adaptable to other collections of handwritten data, which require both handwriting recognition and semi-automated coding of the information extracted.

This paper describes the creation of the Longitudinal, Intergenerational Family Electronic Micro-Database (LIFE-M), a new data resource linking vital records and decennial censuses for millions of individuals and families living in the late 19th and 20th centuries in the United States. This combination of records provides a life-course and intergenerational perspective on the evolution of health and economic outcomes. Vital records also enable the linkage of women, because they contain a crosswalk between womens birth (i.e., maiden) and married names. We describe (1) the data sources, coverage, and linking sequence; (2) the process and supervised machine-learning methods to linking records longitudinally and across generations; and (3) the resulting linked samples, including linking rates, representativeness, and weights.

Infectious respiratory diseases such as the current COVID-19 have caused public health crises and interfered with social activity. Given the complexity of these novel infectious diseases, their dynamic nature, along with rapid changes in social and occupational environments, technology, and means of interpersonal interaction, respiratory protective devices (RPDs) play a crucial role in controlling infection, particularly for viruses like SARS-CoV-2 that have a high transmission rate, strong viability, multiple infection routes and mechanisms, and emerging new variants that could reduce the efficacy of existing vaccines. Evidence of asymptomatic and pre-symptomatic transmissions further highlights the importance of a universal adoption of RPDs. RPDs have substantially improved over the past 100 years due to advances in technology, materials, and medical knowledge. However, several issues still need to be addressed such as engineering performance, comfort, testing standards, compliance monitoring, and regulations, especially considering the recent emergence of pathogens with novel transmission characteristics. In this review, we summarize existing knowledge and understanding on respiratory infectious diseases and their protection, discuss the emerging issues that influence the resulting protective and comfort performance of the RPDs, and provide insights in the identified knowledge gaps and future directions with diverse perspectives.

Parkinson's disease (PD) is a movement disorder characterized by neuroinflammation, α-synuclein pathology, and neurodegeneration. Most cases of PD are non-hereditary, suggesting a strong role for environmental factors, and it has been speculated that disease may originate in peripheral tissues such as the gastrointestinal (GI) tract before affecting the brain. The gut microbiome is altered in PD and may impact motor and GI symptoms as indicated by animal studies, although mechanisms of gut-brain interactions remain incompletely defined. Intestinal bacteria ferment dietary fibers into short-chain fatty acids, with fecal levels of these molecules differing between PD and healthy controls and in mouse models. Among other effects, dietary microbial metabolites can modulate activation of microglia, brain-resident immune cells implicated in PD. We therefore investigated whether a fiber-rich diet influences microglial function in α-synuclein overexpressing (ASO) mice, a preclinical model with PD-like symptoms and pathology. Feeding a prebiotic high-fiber diet attenuates motor deficits and reduces α-synuclein aggregation in the substantia nigra of mice. Concomitantly, the gut microbiome of ASO mice adopts a profile correlated with health upon prebiotic treatment, which also reduces microglial activation. Single-cell RNA-seq analysis of microglia from the substantia nigra and striatum uncovers increased pro-inflammatory signaling and reduced homeostatic responses in ASO mice compared to wild-type counterparts on standard diets. However, prebiotic feeding reverses pathogenic microglial states in ASO mice and promotes expansion of protective disease-associated macrophage (DAM) subsets of microglia. Notably, depletion of microglia using a CSF1R inhibitor eliminates the beneficial effects of prebiotics by restoring motor deficits to ASO mice despite feeding a prebiotic diet. These studies uncover a novel microglia-dependent interaction between diet and motor symptoms in mice, findings that may have implications for neuroinflammation and PD.

Delivering genes to and across the brain vasculature efficiently and specifically across species remains a critical challenge for addressing neurological diseases. We have evolved adeno-associated virus (AAV9) capsids into vectors that transduce brain endothelial cells specifically and efficiently following systemic administration in wild-type mice with diverse genetic backgrounds, and in rats. These AAVs also exhibit superior transduction of the CNS across non-human primates (marmosets and rhesus macaques), and in ex vivo human brain slices, although the endothelial tropism is not conserved across species. The capsid modifications translate from AAV9 to other serotypes such as AAV1 and AAV-DJ, enabling serotype switching for sequential AAV administration in mice. We demonstrate that the endothelial-specific mouse capsids can be used to genetically engineer the blood-brain barrier by transforming the mouse brain vasculature into a functional biofactory. We apply this approach to Hevin knockout mice, where AAV-X1-mediated ectopic expression of the synaptogenic protein Sparcl1/Hevin in brain endothelial cells rescued synaptic deficits.