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Pending the long-term solution of the problem of coronary atherosclerosis, and considering the unlikelihood of a universally effective, nontoxic, anti-arrhythmic regimen, it seems likely that ambulatory real-time monitoring is a promising avenue of approach for attacking the largest share of IHD mortality, namely the 2/3 who currently die before any medical attention.
OBJECTIVE: To compare the following five major national health insurance proposals and their implications for children and pregnant women: the MAtsui "play or pay" bill (HR 3393); the Russo Canadian-type bill (HR 1300); the Rockefeller "play or pay" bill (S 1177); the Stark Medicare-type bill (HR 650); and the president's market reform proposal. RESEARCH DESIGN: Using an analytic framework developed by the Association of Maternal and Child Health Programs, we examine the differences among the five proposals in basic approach, eligibility and enrollment, benefits, cost-sharing requirements, provider reimbursement, and cost-control measures. RESULTS: All of the plans, except for President Bush's, would provide coverage for virtually all children and pregnant women, using a combination of private and public approaches. President Bush's market approach provides financial incentives to purchase health insurance benefit plans that states can design within actuarial limits. The remaining four plans strive for uniformity in benefits, covering physician and hospital services in a manner similar to most plans today. Preventive care benefits extend beyond what has been offered in the past. The four plans differ sharply in their coverage of extended care services, with the Matsui and Russo bills covering the most generous package of benefits. The Rockefeller and Stark plans, on the other hand, require less cost-sharing for their basically preventive and primary care plans. CONCLUSIONS: Most of the health insurance proposals are aimed at extending preventive and primary care health insurance plans to more uninsured Americans. Only the Matsui bill devotes significant attention to developing a comprehensive benefit plan for children and pregnant women. Additional attention should be directed at extended care services for those with special health care needs, the future role of Medicaid, and the public health system infrastructure.
BACKGROUND: Historic and ongoing problematic practices regarding the collection, storage, and use of Indigenous health data have led to the need to ensure principles of Indigenous Data Sovereignty (IDS) are followed in research practices and technology development. OBJECTIVE: This project, a partnership between UC San Diego and the Native BioData Consortium (NativeBio), sought to explore the practical application of blockchain technology and its potential to facilitate Indigenous-led research collaboration. METHODS: This project first undertook purposeful relationship building with NativeBio to form a Community Advisory Board (CAB) for identifying community and technology needs for a blockchain research collaboration platform with an initial focus on genomic data. Over a 2-year project period, a series of public meetings and presentations at Indigenous-led conferences introduced the concept of exploring compatibility between blockchain and IDS principles, followed by iterative prototyping and co-design of a blockchain platform with NativeBio, using Ethereum as the underlying protocol. RESULTS: Direct engagement with NativeBio and the CAB informed the initial design and development of a "b-IDS" proof-of-concept (POC) blockchain platform. The POC consists of three main components: (1) the web front-end layer, (2) the Ethereum network that executes the smart contract and blockchain storage aspects of the framework, and (3) the back-end database that stores off-chain interactions and data for future use with external genomic data repositories. After refinement of the POC, a community-based participatory research (CBPR) use case aligned with IDS principles was identified as a practical workflow and incorporated into the design of the POC for implementation. CONCLUSIONS: The findings from this project demonstrated the potential use of operationalizing IDS through blockchain technology with proactive and sustained engagement with Indigenous partners. Blockchain technology may have certain advantages over other data governance approaches and systems, facilitating timely oversight, shared decision-making and consent structures, and direct involvement of Indigenous communities in technology design, respecting the core principles of IDS and CBPR. Future development of the blockchain-IDS POC will need to incorporate other research practices and ethics frameworks to expand its use to other public health and biomedical research use cases.
Although many facets of sleep, including subjective, behavioral, and neurophysiological features, are closely linked with psychiatric disorders, the natures of these relationships are generally unclear. A given alteration in sleep could reflect a cause (that may mediate genetic risk), consequence, symptom, trigger, epiphenomenon due to shared determinants, or some combination of these. In principle, genetic approaches can be informative: 1) by identifying specific genetic influences on disease mediated by or shared with sleep, which could help the search for biological mechanisms and therapeutic targets, and 2) by providing evidence for causality, which could suggest interventions for modifiable sleep traits. Here, we summarize recent human quantitative and molecular genetic studies on sleep and psychiatric disease, including twin and genome-wide association studies. Despite evidence for shared heritability across many domains, notably depression and insomnia, the field is in its early stages and faces significant challenges including the following: 1) putative causal effects are small, phenotypically nonspecific, not resolved to specific gene pathways, and often bidirectional; 2) most current discovery cohorts are demographically biased and do not capture profound age-related changes in sleep and its genetic architecture; 3) group-level analyses ignore patient-to-patient heterogeneity, including the presence or absence of specific sleep alterations; and 4) a paucity of objective, brain-based data in genetically informative samples hampers making connections with sleep neurophysiology. Nonetheless, as ever-growing genetic tools and resources still hold great potential for translational bridges between basic model systems, human epidemiology, and personalized clinical care, genetic approaches will still likely be needed to reveal sleep's roles in maintaining mental health.
The thirteen year history of assessing evolution by amino acid sequence analysis has made apparent the limitations imposed upon this system by the finite nature of the characters. This finiteness exists on several levels and ultimately expresses itself as parallelism, back mutation and the retention of primitive characters in the sequences of proteins from present day species and the putative ancestral protein chains. Sequence analysis shares these problems with other molecular approaches, but because it is concerned both with the nucleotide substitutions in the genome and with the functional roles of proteins, it has unique advantages. For example, the large fluctuation in the rate of fixation of mutations in a protein's evolution can be detected and used to point out the unreliability of any molecular clock for estimating divergence dates. Moreover, when consideration is given to studies which assign functional significance to specific amino acid sites in a protein, changes in function during the descent of a protein can be appreciated and their significance correlated with organismal evolution.
Human cDNA clones encoding two novel proteins with a region strongly homologous to the tyrosine kinase domain of growth factor receptors, in particular of the Trk family, were obtained by a polymerase chain reaction-based approach. These proteins, Ror1 and Ror2, share 58% overall amino acid identity and a structure indicative of cell surface molecules. A secretion signal sequence and a transmembrane domain delimit the extracellular portion, which contains immunoglobulin-like, cysteine-rich, and kringle domains. The cytoplasmic portion contains the tyrosine kinase-like domain which (in Ror2) appears to be associated with protein kinase activity in vitro, followed by serine/threonine- and proline-rich motifs. Partial nucleotide sequences of the rat genes reveal striking evolutionary conservation of the proteins between human and rat. The level of expression of the rat genes is high in the head and body of early embryo and decreases dramatically after embryonic day 16. Based on these data, Ror1 and Ror2 appear to define a new developmentally regulated family of cell surface receptors for unidentified ligands.
BACKGROUND: Rehabilomics, or the integration of rehabilitation with genomics, proteomics, metabolomics, and other "-omics" fields, aims to promote personalized approaches to rehabilitation care. Cloud-based rehabilitation offers streamlined patient data management and sharing and could potentially play a significant role in advancing rehabilomics research. This study explored the current status and potential benefits of implementing rehabilomics strategies through cloud-based rehabilitation. OBJECTIVE: This scoping review aimed to investigate the implementation of rehabilomics strategies through cloud-based rehabilitation and summarize the current state of knowledge within the research domain. This analysis aims to understand the impact of cloud platforms on the field of rehabilomics and provide insights into future research directions. METHODS: In this scoping review, we systematically searched major academic databases, including CINAHL, Embase, Google Scholar, PubMed, MEDLINE, ScienceDirect, Scopus, and Web of Science to identify relevant studies and apply predefined inclusion criteria to select appropriate studies. Subsequently, we analyzed 28 selected papers to identify trends and insights regarding cloud-based rehabilitation and rehabilomics within this study's landscape. RESULTS: This study reports the various applications and outcomes of implementing rehabilomics strategies through cloud-based rehabilitation. In particular, a comprehensive analysis was conducted on 28 studies, including 16 (57%) focused on personalized rehabilitation and 12 (43%) on data security and privacy. The distribution of articles among the 28 studies based on specific keywords included 3 (11%) on the cloud, 4 (14%) on platforms, 4 (14%) on hospitals and rehabilitation centers, 5 (18%) on telehealth, 5 (18%) on home and community, and 7 (25%) on disease and disability. Cloud platforms offer new possibilities for data sharing and collaboration in rehabilomics research, underpinning a patient-centered approach and enhancing the development of personalized therapeutic strategies. CONCLUSIONS: This scoping review highlights the potential significance of cloud-based rehabilomics strategies in the field of rehabilitation. The use of cloud platforms is expected to strengthen patient-centered data management and collaboration, contributing to the advancement of innovative strategies and therapeutic developments in rehabilomics.
The sharing of genomic data across international borders presents significant privacy law challenges.Secured computed environments on smartphones allow the storing and processing of sensitive data without the underlying data being shared with processors.A novel technology, described here, to process genomic data within a secured computing environment seems to comport with EU and US privacy laws, despite their differing aims and rules.This technology suggests there may be technological solutions to privacy law fragmentation across jurisdictions, so long as data subjects socially trust the technology and have control over their data.
BACKGROUND: Psoriasis (PS) and metabolic syndrome (MetS) frequently co-occur. Characterizing their shared genetic architecture and spatially enriched cellular populations may clarify the context of their co-occurrence and generate hypotheses for functional validation. METHODS: We integrated genome-wide association study (GWAS) summary statistics for PS, MetS, and five related components with spatially resolved single-cell transcriptomic data. Global and local genetic correlations were assessed using linkage disequilibrium score regression, genetic covariance analysis, high-definition likelihood, and local analysis of variant association. A bivariate causal mixture model quantified polygenic overlap. Conditional/conjunctional false discovery rate and composite-null pleiotropy analyses identified shared susceptibility loci. Finally, gsMap evaluated trait-associated enrichment across annotated embryonic tissues at single-cell resolution. RESULTS: Genetic approaches identified significant genome-wide correlations and polygenic sharing between PS, MetS, and its components. Local and cross-trait analyses identified region-specific signals and cross-validated shared loci. gsMap revealed trait-specific tissue enrichment. PS showed the strongest enrichment in the epidermis (pCauchy = 1.0573 × 10  - ⁴), adipose tissue (pCauchy = 1.5366 × 10 - ⁴), and liver (pCauchy = 1.0167 × 10 - ³). Across MetS, FBG, HDL-C, hypertension, and TG, enriched regions mainly involved the liver, adipose tissue, and epidermis. WC enrichment was predominantly observed in adipose tissue (pCauchy = 1.7823 × 10 - ⁴), with no significant liver or epidermal enrichment. CONCLUSION: Integrating GWAS with single-cell transcriptomic and spatial information characterized shared genetic architecture between PS and MetS-related phenotypes and their spatial enrichment patterns. These findings provide a framework for generating testable hypotheses about comorbidity biology and guiding future functional and clinical validation.
Two meanings of the term comprehensive care are delineated. The first refers to a wide scope of health services, the second to a humanistic approach to the patient. Findings from a sample of patients from one pediatric practice suggest that the two meanings constitute two independent variables with respect to patient expeciations. Patient responses to questions regarding their expectations of the pediatrician revealed a tendency to hold a traditional disease orientation. Comprehensive care as a broad scope of health services that include mother guidance in child rearing is not a common goal for mothers utilizing the pediatric practice under study. On the other hand, a comprehensive approach by the pediatrician is a standard shared by most respondents in the sample: high priority is accorded the pattern of the personal physician with whom a patient forms a continuous doctor-patient relationship which instills in the patient trust that the physician's recommendations are based on thorough knowledge of the patient as an individual.
A graphics-tablet treatment planning system is described. The cost effectiveness of this approach is especially attractive where time-sharing use of a central computer facility is available.
Sex differentially shapes aging, neurodevelopment and neurodegenerative diseases such as Alzheimer's disease (AD). However, most biological aging clocks (artificial intelligence-predicted age minus chronological age) were trained on sex-pooled samples and implicitly assume sex invariance.Here we developed 38 sex-specific biological aging clocks across 15 organ systems. We first demonstrate the importance of sex-stratified training for constructing sex-specific healthy normative references and then reveal marked divergence between female and male clocks. Key genetic parameters and Mendelian randomization results indicate that organ-specific aging liability and its relationships to cardiometabolic, endocrine and mental traits are configured differently in females and males. Proteomic analyses identify distinct, organ-resolved synaptic, immune, vascular and metabolic networks that differentially track female and male biological aging. In longitudinal survival analyses, sex-specific clocks predict whole-body systemic diseases and all-cause mortality in a sex-dependent and organ-dependent manner. Further analyses reveal sex-dependent associations between the brain aging clock and cognitive decline trajectory during a preclinical AD clinical trial. Sex-stratified clocks may offer distinct value by defining biological age against sex-appropriate normative references and revealing sex-dependent genetic, molecular and clinical signatures that pooled models may obscure. Meanwhile, sex-pooled and sex-interaction approaches remain valuable, as human aging and disease also share fundamental biological similarities between females and males. Together, these findings reveal sex-specific biological aging signatures in aging, AD and systemic health, highlighting the need for explicitly sex-stratified modeling approaches.
Sex difference (SD) is ubiquitous in humans despite shared genetic architecture (SGA) between the sexes. A univariate approach, i.e., studying SD in single traits by estimating genetic correlation, does not provide a complete biological overview, because traits are not independent and are genetically correlated. The multivariate genetic architecture between the sexes can be summarized by estimating the additive genetic (co)variance across shared traits, which, apart from the cross-trait and cross-sex covariances, also includes the cross-sex-cross-trait covariances, e.g., between height in males and weight in females. Using such a multivariate approach, we investigated SD in the genetic architecture of 12 anthropometric, fat depositional, and sex-hormonal phenotypes. We uncovered sexual antagonism (SA) in the cross-sex-cross-trait covariances in humans, most prominently between testosterone and the anthropometric traits - a trend similar to phenotypic correlations. 27% of such cross-sex-cross-trait covariances were of opposite sign, contributing to asymmetry in the SGA. Intriguingly, using multivariate evolutionary simulations, we observed that the SGA acts as a genetic constraint to the evolution of SD in humans only when selection is sexually antagonistic and not concordant. Remarkably, we found that the lifetime reproductive success in both the sexes shows a positive genetic correlation with anthropometric traits, but not with testosterone. Moreover, we demonstrated that genetic variance is depleted along multivariate trait combinations in both the sexes but in different directions, suggesting absolute genetic constraint to evolution. Our results indicate that testosterone drives SA in contemporary humans and emphasize the necessity and significance of using a multivariate framework in studying SD.
A prototype for the implementation of a comprehensive health maintenance program is described in which the expertise of veterinary medicine is brought to bear on preventive medicine and on special generic environmental disease factors as they impact on human health. For the sake of organization and the ease of presentation, certain specific activities have been divided into two overlapping categories: environmental health and health education. The implementation of a comprehensive health care delivery system will become a reality only when the full array of health resources is matched with health needs. It cannot be overemphasized that the delivery of health care services is not exclusively within the purview of any one profession; rather, interdependence and sharing of responsibilities and activities in a team approach are characteristics of the human health system.
Parasitic mites Varroa destructor and Tropilaelaps mercedesae represent major threats to global honey bee (Apis mellifera) health and productivity, yet comparative molecular insights into host responses remain limited. To address this, we systematically compiled published studies (2015-2025) reporting genes associated with honey bee interactions with V. destructor (11 studies, 87 genes), T. mercedesae (4 studies, 35 genes), and hygienic behavior (6 studies, 44 genes). Gene identifiers were harmonized to the Amel_HAv3.1 genome assembly, yielding three non-redundant sets: 64 Varroa-associated, 34 Tropilaelaps-associated, and 44 hygienic behavior-associated genes. Venn analysis identified 10 overlapping genes (including A0A088A8D5, A0A088ADL8, ABAE_APIME, Def1, Def2, Gapdh, HYTA_APIME, Imd, LOC726783, and Vg), suggesting conserved defense mechanisms, while 41 and 24 genes were uniquely associated with Varroa and Tropilaelaps, respectively. Enrichment analyses revealed Varroa-responsive genes were enriched in immune processes, chitin catabolism, and signaling pathways (Toll/Imd, MAPK, Wnt). Tropilaelaps-associated genes were enriched for antibacterial defense and stress response, with Toll/Imd signaling as the sole significantly enriched pathway. Overlapping genes reinforced core innate immunity activation. Protein-protein interaction network centrality analysis identified key hub genes: Def1, HYTA_APIME, ABAE_APIME, PPO, Imd, PGRP-LC, Vg for Varroa; and ACPH1_APIME, MRJP1, Vg, LOC726783 for Tropilaelaps. Results demonstrate that, despite differences in mite biology, honey bees show a conserved immune response against both parasites, centered on antibacterial defense, humoral immunity, and activation of the Toll/Imd pathway. Although limited by the in-silico nature and research asymmetries reflecting Tropilaelaps' emergence, this curated resource establishes a comprehensive framework for elucidating shared and distinct molecular defense mechanisms. Ultimately, this approach prioritizes diagnostic markers and candidate genes for functional validation and breeding strategies to enhance colony resilience against mite‑driven disease globally.
Traditionally, health education for practicing health professionals, as well as members of the public, focuses on the individual and relies on changing personal behavior. However, health care for persons with acquired immunodeficiency syndrome (AIDS), and members of their families, mainly is delivered within health and human services organizations. Providing AIDS education for health care professionals in an organizational or systems context shifts the focus from the individual to the group and from changing a person's behavior to offering health care professionals opportunities for interaction. In an organizational or systems approach, they can address patient care issues collectively, share interdisciplinary knowledge, identify problems of common concern, plan coordinated and integrated responses, and provide mutual support. A strategy for planning AIDS education is proposed for key administrators, supervisors, and care providers, who are the gatekeepers, opinion makers, and role models of organizations. Addressing organizational, community, and health care delivery system issues as part of an education program provides a forum for defining problems and a basis for uniting professionals and developing solutions.
Just within thid decade, a variety of multihospital arrangements have been developed that make clinical engineering services available to hospitals on a shared basis. This article summarizes available data to describe the diverse approaches and organizational structures into which these programs are evolving.
PURPOSE: This descriptive qualitative study explored knowledge users' perspectives on precision rehabilitation concepts, barriers, facilitators, and future directions as part of a convergent mixed methods scoping review. MATERIALS AND METHODS: Sixteen clinicians, administrators, and researchers from three North American tertiary care rehabilitation centers were recruited using convenience and snowball sampling to participate in individual semi-structured interviews. Conventional qualitative content analysis followed a deductive thematic approach based on predetermined categories. RESULTS: Analyses revealed three main themes: (1) Although precision rehabilitation shares foundational concepts with precision medicine, there are certain elements, such as personalization, that are uniquely expressed; (2) Rehabilitation-specific facilitators to precision approaches include the use of unobtrusive technology to collect large amounts of data in real-world contexts, while barriers include rehabilitation's typically small, heterogeneous sample sizes; and (3) The future of precision rehabilitation will require collaborative data-sharing to focus on determining care trajectories that enhance functional outcomes. CONCLUSION: Findings provide the first qualitative synthesis of knowledge users perspectives to complement quantitative evidence and inform the emerging field of precision rehabilitation.