Yale Journal of Biology and Medicine最新文献

Maternal prenatal exposure to household air pollution (HAP) is a critical public health concern with potential long-term implications for child respiratory health. The objective of this study is to assess the level of association between prenatal household air pollution and child respiratory health, and to identify which HAP pollutants are associated with specific respiratory illnesses or symptoms and to what degree. Relevant studies were retrieved from PubMed databases up to April 27, 2010, and their reference lists were reviewed. Random effects models were applied to estimate summarized relative risks (RRs) and 95% confidence intervals (CIs). The analysis involved 11 studies comprising 387 767 mother-child pairs in total, assessing various respiratory health outcomes in children exposed to maternal prenatal HAP. Children with prenatal exposure to HAP pollutants exhibited a summary RR of 1.26 (95% CI=1.08-1.33) with moderate between-study heterogeneity (I²=49.22%) for developing respiratory illnesses. Specific associations were found between prenatal exposure to carbon monoxide (CO) (RR=1.11, 95% CI: 1.09-1.13), Nitrogen Oxides (NO_x) (RR=1.46, 95% CI: 1.09-1.60), and particulate matter (PM) (RR=1.26, 95% CI: 1.2186-1.3152) and child respiratory illnesses (all had I² close to 0%, indicating no heterogeneity). Positive associations with child respiratory illnesses were also found with ultrafine particles (UFP), polycyclic aromatic hydrocarbons (PAH), and ozone (O₃). However, no significant association was observed for prenatal exposure to sulfur dioxide (SO₂). In summary, maternal prenatal exposure to HAP may contribute to a higher risk of child respiratory health issues, emphasizing the need for interventions to reduce this exposure during pregnancy. Targeted public health strategies such as improved ventilation, cleaner cooking technologies, and awareness campaigns should be implemented to minimize adverse respiratory effects on children.

Pregnant individuals and infants in the US are experiencing rising morbidity and mortality rates. Breastfeeding is a cost-effective intervention associated with a lower risk of health conditions driving dyadic morbidity and mortality, including cardiometabolic disease and sudden infant death. Pregnant individuals and infants from racial/ethnic subgroups facing the highest risk of mortality also have the lowest breastfeeding rates, likely reflective of generational socioeconomic marginalization and its impact on health outcomes. Promoting breastfeeding among groups with the lowest rates could improve the health of dyads with the greatest health risk and facilitate more equitable, person-centered lactation outcomes. Multiple barriers to lactation initiation and duration exist for families who have been socioeconomically marginalized by health and public systems. These include the lack of paid parental leave, increased access to subsidized human milk substitutes, and reduced access to professional and lay breastfeeding expertise. Breast pumps have the potential to mitigate these barriers, making breastfeeding more accessible to all interested dyads. In 2012, The Patient Protection and Affordable Care Act (ACA) greatly expanded access to pumps through the preventative services mandate, with a single pump now available to most US families. Despite their near ubiquitous use among lactating individuals, little research has been conducted on how and when to use pumps appropriately to optimize breastfeeding outcomes. There is a timely and critical need for policy, scholarship, and education around pump use given their widespread provision and potential to promote equity for those families facing the greatest barriers to achieving their personal breastfeeding goals.

Background: Becoming a parent has been highlighted as a period associated with increased risks for loneliness, with around one-third of parents reporting feeling lonely often or always. However, as most understanding of loneliness is based on elderly or student cohorts, further insights into the costs of parental loneliness is needed. Method: We conducted a literature review of impacts of loneliness in pregnancy and parenthood and present a synthesis of the health, social, societal, and economic costs. We draw on evidence about impacts and costs of loneliness in other cohorts to help provide a wider context to understand the impacts and costs and how parental loneliness differs from other populations. Results: Similar to literature with elderly cohorts, parental loneliness has impacts on health and wellbeing, such as depression in new parents and increased general practitioner (GP) visits in pregnancy. But also has intergenerational impacts via its association with poor mental health and social competence and increased respiratory tract infections in the child. Physical health impacts widely associated with loneliness in other cohorts have yet to be examined in parents. Loneliness in parents is likely to result in social withdrawal further isolating parents and wider societal and economic costs relating to absence from employment and informal caring roles. Conclusion: Parental loneliness has the potential for negative and pervasive impacts. As parental loneliness has wide ranging and intergenerational impacts it is important that a multi-sectoral perspective is used when examining its costs.

Theoretical frameworks concerning cell fate typically center on proximate causes to explain how cells know what type they are meant to become. While major advances in cell fate theory have been achieved by these mechanism-focused frameworks, there are some aspects of cell decision-making that require an evolutionary interpretation. While mechanistic biologists sometimes turn to evolutionary theory to gain insights about cell fate (cancer is a good example), it is not entirely clear in cell fate theory what insights evolutionary theory can add, and why in some cases it is required for understanding cell fate. In this perspective we draw on our work on cellular mortality to illustrate how evolutionary theory provides an explanation for death being selected as one of the potential cell fates. Using our hypothesis for why some microbes in a community choose death as their fate, we suggest that some insights in cell fate theory are inaccessible to a theoretical framework that focuses solely on proximate causes.

Although rare, breast metastases can mimic primary tumors, both clinically, radiologically, and histopathologically. Melanoma is a highly metastasizing tumor, and it is known as a great mimicker of tumors. Metastatic melanoma in the breast can mimic primary breast cancer and pose a diagnostic challenge. In most cases, it is associated with disseminated disease and a poor prognosis, therefore, histologic, immunohistochemical and clinical correlation is crucial in diagnosing these cases. In this case report, we discuss a 63-year-old female who presented with clinical features of probable breast cancer, describe immunohistochemistry workup, and discuss pitfalls in interpretation.

Scar formation is a normal response to skin injuries. During the scar-remodeling phase, scar tissue is usually replaced with normal, functional tissue. However, after deep burn injuries, the scar tissue may persist and lead to contractures around joints, a condition known as hypertrophic scar tissue. Unfortunately, current treatment options for hypertrophic scars, such as surgery and pressure garments, often fail to prevent their reappearance. One of the primary challenges in treating hypertrophic scars is a lack of knowledge about the molecular mechanisms underlying their formation. In this review, we critically analyze studies that have attempted to uncover the molecular mechanisms behind hypertrophic scar formation after severe burn injuries, as well as clinical trials conducted to treat post-burn hypertrophic scars. We found that most clinical trials used pressure garments, laser treatments, steroids, and proliferative inhibitors for hypertrophic scars, with outcomes measured using subjective scar scales. However, fundamental research using human burn injury biopsies has shown that pathways such as Transforming Growth factor β (TGFβ), Phosphatase and tensin homolog (PTEN), and Toll-like receptors (TLRs) could be potentially regulated to reduce scarring. Therefore, we conclude that more testing is necessary to determine the efficacy of these molecular targets in reducing hypertrophic scarring. Specifically, double-blinded clinical trials are needed, where the outcomes can be measured with more robust quantitative molecular parameters.

Micropatterns, characterized as distinct physical microstructures or chemical adhesion matrices on substance surfaces, have emerged as a powerful tool for manipulating cellular activity. By creating specific extracellular matrix microenvironments, micropatterns can influence various cell behaviors, including orientation, proliferation, migration, and differentiation. This review provides a comprehensive overview of the latest advancements in the use of micropatterns for cell behavior regulation. It discusses the influence of micropattern morphology and coating on cell behavior and the underlying mechanisms. It also highlights future research directions in this field, aiming to inspire new investigations in materials medicine, regenerative medicine, and tissue engineering. The review underscores the potential of micropatterns as a novel approach for controlling cell behavior, which could pave the way for breakthroughs in various biomedical applications.

T cells undergo extensive chromatin remodeling over several days following stimulation through the T cell receptor. However, the kinetics and gene loci targeted by early remodeling events within the first 24 hours of T cell priming to orchestrate effector differentiation have not been well described. We identified that chromatin accessibility is rapidly and extensively remodeled within 1 hour of stimulation of naïve CD8⁺ T cells, leading to increased global chromatin accessibility at many effector T cell-associated genes that are enriched for AP-1, early growth response (EGR), and nuclear factor of activated T cells (NFAT) binding sites, but this short duration of stimulation is insufficient for commitment to clonal expansion in vivo. Sustained 24-hour stimulation led to further chromatin remodeling and was sufficient to enable clonal expansion. These data suggest that the duration of antigen receptor signaling is intimately coupled to chromatin remodeling and activation of genes involved in effector cell differentiation and highlight a potential mechanism that helps CD8⁺ T cells discriminate between foreign- and self-antigens.

Proper formation of the blastocyst, including the specification of the first embryonic cellular lineages, is required to ensure healthy embryo development and can significantly impact the success of assisted reproductive technologies (ARTs). However, the regulatory role of microRNAs in early development, particularly in the context of preimplantation lineage specification, remains largely unknown. Taking a cross-species approach, this review aims to summarize the expression dynamics and functional significance of microRNAs in the differentiation and maintenance of lineage identity in both the mouse and the human. Findings are consolidated from studies conducted using in vitro embryonic stem cell models representing the epiblast, trophectoderm, and primitive endoderm lineages (modeled by naïve embryonic stem cells, trophoblast stem cells, and extraembryonic endoderm stem cells, respectively) to provide insight on what may be occurring in the embryo. Additionally, studies directly conducted in both mouse and human embryos are discussed, emphasizing similarities to the stem cell models and the gaps in our understanding, which will hopefully lead to further investigation of these areas. By unraveling the intricate mechanisms by which microRNAs regulate the specification and maintenance of cellular lineages in the blastocyst, we can leverage this knowledge to further optimize stem cell-based models such as the blastoids, enhance embryo competence, and develop methods of non-invasive embryo selection, which can potentially increase the success rates of assisted reproductive technologies and improve the experiences of those receiving fertility treatments.