Circulating levels of dickkopf-1, osteoprotegerin and sclerostin are higher in old compared with young men and women and positively associated with whole-body bone mineral density in older adults

Summary: Bone mineral density declines with increasing older age. We examined the levels of circulating factors known to regulate bone metabolism in healthy young and older adults. The circulating levels of dickkopf-1, osteocalcin, osteoprotegerin and sclerostin were positively associated with WBMD in older adults, despite the average WBMD being lower and circulating dickkopf-1, osteoprotegerin and sclerostin being higher in old than young. Purpose: To investigate the relationship between whole-body bone mineral density (WBMD) and levels of circulating factors with known roles in bone remodelling during 'healthy' ageing. Methods: WBMD and fasting plasma concentrations of dickkopf-1, fibroblast growth factor-23, osteocalcin, osteoprotegerin, osteopontin and sclerostin were measured in 272 older subjects (69 to 81 years; 52% female) and 171 younger subjects (18-30 years; 53% female). Results: WBMD was lower in old than young. Circulating osteocalcin was lower in old compared with young, while dickkopf-1, osteoprotegerin and sclerostin were higher in old compared with young. These circulating factors were each positively associated with WBMD in the older adults and the relationships remained after adjustment for covariates (r-values ranging from 0.174 to 0.254, all p<0.01). In multivariate regression, the body mass index, circulating sclerostin and whole-body lean mass together accounted for 13.8% of the variation with WBMD in the older adults. In young adults, dickkopf-1 and body mass index together accounted for 7.7% of variation in WBMD. Conclusion: Circulating levels of dickkopf-1, osteocalcin, osteoprotegerin and sclerostin are positively associated with WBMD in community-dwelling older adults, despite the average WBMD being lower and circulating dickkopf-1, osteoprotegerin and sclerostin being higher in old than young

The Human Phenotype Ontology in 2024: phenotypes around the world

\ua9 The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research. The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs

Genome-wide analysis identifies 12 loci influencing human reproductive behavior.

The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits

A methodology for the disaggregate, multidimensional measurement of residential neighbourhood type

Binary designation of a residential neighbourhood as either traditional or suburban is a distortion of reality, since a location may have some characteristics of both types and since residents in different parts of the neighbonrhood may perceive its character differently. This paper presents and applies a methodology for assessing neighbourhood type that results in a measure that is continuous rather than binary, disaggregate rather than aggregate, and potentially multidimensional. Specifically, 18 variables identified by the literature as distinguishing traditional and suburban locations are measured for 852 residents of 5 San Francisco area neighbourhoods. These data are factor-analysed to develop scales on which each individual has a person-specific score. Although we expected a single ’tradifionainess’ dimension to result, instead we found two factors: traditional and suburban. Study neighbourhoods could and did score highly on both dimensions, and considerable individual variation within neighbourhood was observed. By more accurate|y capturing the complexity in classifying a neighbourhood and the heterogeneity of individual perception within a neighbourhood, use of this methodology to measure neighbourhood type is expected to improve models involving residential location as an endogenous or exogenous variable

Nanoparticles and microfluidic devices in cancer research

Cancer is considered the disease of the century, which can be easily understood considering its increasing incidence worldwide. Over the last years, nanotechnology has been presenting promising theranostic approaches to tackle cancer, as the development of nanoparticle-based therapies. But, regardless of the promising outcomes within in vitro settings, its translation into the clinics has been delayed. One of the main reasons is the lack of an appropriate in vitro model, capable to mimic the true environment of the human body, to test the designed nanoparticles. In fact, most of in vitro models used for the validation of nanoparticle-based therapies do not address adequately the complex barriers that naturally occur in a tumor scenario, as such as blood vessels, the interstitial fluid pressure or the interactions with surrounding cells that can hamper the proper delivery of the nanoparticles into the desired site. In this reasoning, to get a step closer to the in vivo reality, it has been proposed of the use of microfluidic devices. In fact, microfluidic devices can be designed on-demand to exhibit complex structures that mimic tissue/organ-level physiological architectures. Even so, despite microfluidic-based in vitro models do not compare with the reality and complexity of the human body, the most complex systems created up to now have been showing similar results to in vivo animal models. Microfluidic devices have been proven to be a valuable tool to accomplish more realistic tumourâ s environment. The recent advances in this field, and in particular, the ones enabling the rapid test of new therapies, and show great promise to be translated to the clinics will be overviewed herein.The authors thank the funds obtained through the FROnTHERA (NORTE-01-0145- FEDER-0000232) project supported by Norte Portugal Regional Operational Program (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). FRM acknowledges Portuguese Foundation for Science and Technology (FCT) for her contract under the Transitional Rule DL 57/2016 (CTTI-57/18-I3BS(5)), JMO thanks FCT for the distinction attributed under the Investigator FCT program (IF/01285/2015)