SIRT6, a Mammalian Deacylase with Multitasking Abilities.

Mammalian sirtuins have emerged in recent years as critical modulators of multiple biological processes, regulating cellular metabolism, DNA repair, gene expression, and mitochondrial biology. As such, they evolved to play key roles in organismal homeostasis, and defects in these proteins have been linked to a plethora of diseases, including cancer, neurodegeneration, and aging. In this review, we describe the multiple roles of SIRT6, a chromatin deacylase with unique and important functions in maintaining cellular homeostasis. We attempt to provide a framework for such different functions, for the ability of SIRT6 to interconnect chromatin dynamics with metabolism and DNA repair, and the open questions the field will face in the future, particularly in the context of putative therapeutic opportunities.

Racial and Ethnic Disparities for Unmet Needs by Mental Health Condition: 2016 to 2021.

OBJECTIVES: Racial and ethnic minority children receive less care and inferior care in the United States, but less is known about how these disparities vary by mental health conditions. We examined unmet mental health needs by condition types to identify potentially hidden racial and ethnic inequities. METHODS: We used data from the nationally representative National Survey of Children's Health, from 2016 to 2021 (n = 172 107). Logistic regression analyses were applied to mental health conditions in aggregate and individually and adjusted for individual and household characteristics. RESULTS: Relative to non-Hispanic white children with any mental health condition, non-Hispanic Black children had greater odds of unmet needs (adjusted odds ratio [aOR] = 1.56, 95% confidence interval [CI]: 1.18-2.05). Models disaggregated by specific mental health conditions revealed heterogeneous patterns. Specifically, relative to non-Hispanic white children, non-Hispanic Black children displayed elevated odds of unmet needs for behavioral problems (aOR = 1.41, 95% CI: 1.00-2.02), whereas Asian and Hispanic children displayed elevated odds for anxiety (aOR = 2.60, 95% CI: 1.20-4.29 and aOR = 1.41, 95% CI: 1.05-1.90, respectively). CONCLUSIONS: Racial and ethnic minority children are disproportionately affected by unmet treatment needs. These disparities vary by individual mental health conditions and persist after controlling for socioeconomic characteristics. Results reveal clinically underserved racial and ethnic groups across different mental health conditions.

A qualitative analysis of adolescent motherhood within the broader family context in Peru.

Objective: The purpose of this study was to characterize the impact of adolescent pregnancy on families and describe the needs of adolescent mothers and their infants in order to assess the need for intervention and identify potential intervention targets. Background: Adolescent mothers and their offspring face an increased risk of mental health problems. Adolescent mothers and their families also face significant resource constraints; 95% live in low- and middle-income countries (LMICs). Cost-effective interventions are needed to improve outcomes for this vulnerable group. Method: This qualitative study conducted in Lima, Peru, consisted of four clinician focus groups and 18 in-depth interviews with adolescent mothers and their family members. Data were coded thematically, and direct content analysis was employed. Results: The study identified the following issues facing adolescent parents: the transition to parenthood, the need for family support, difficulty accessing support, the difficulty for family members of providing support, and ideas about responsibility and adolescent autonomy. Conclusion: Overall, these findings demonstrate the need for interventions that engage families and address barriers to accessing support, including relationship conflict and differing beliefs about responsibility and autonomy. Implications: Interventions are needed for adolescent mothers in LMICs that mobilize family support. Clinicians who care for these patients need to be aware of the family context and the resources available where they practice.

Racial and ethnic inequities in the quality of paediatric care in the USA: a review of quantitative evidence.

Racial and ethnic inequities in paediatric care have received increased research attention over the past two decades, particularly in the past 5 years, alongside an increased societal focus on racism. In this Series paper, the first in a two-part Series focused on racism and child health in the USA, we summarise evidence on racial and ethnic inequities in the quality of paediatric care. We review studies published between Jan 1, 2017 and July 31, 2022, that are adjusted for or stratified by insurance status to account for group differences in access, and we exclude studies in which differences in access are probably driven by patient preferences or the appropriateness of intervention. Overall, the literature reveals widespread patterns of inequitable treatment across paediatric specialties, including neonatology, primary care, emergency medicine, inpatient and critical care, surgery, developmental disabilities, mental health care, endocrinology, and palliative care. The identified studies indicate that children from minoritised racial and ethnic groups received poorer health-care services relative to non-Hispanic White children, with most studies drawing on data from multiple sites, and accounting for indicators of family socioeconomic position and clinical characteristics (eg, comorbidities or condition severity). The studies discussed a range of potential causes for the observed disparities, including implicit biases and differences in site of care or clinician characteristics. We outline priorities for future research to better understand and address paediatric treatment inequities and implications for practice and policy. Policy changes within and beyond the health-care system, discussed further in the second paper of this Series, are essential to address the root causes of treatment inequities and to promote equitable and excellent health for all children.

Manifestations of Intergenerational Trauma During the Perinatal Period Among Adolescent Mothers in Lima, Peru: A Qualitative Analysis.

Adverse childhood experiences have a lasting impact on health across the life course. The perinatal period offers a unique opportunity to rework problematic dynamics in families experiencing intergenerational trauma. This study explores the family dynamics that are activated during the perinatal period and considers the potential for intervention with adolescent parents and their families in Lima, Peru. This narrative analysis was part of a broader study that included focus groups and in-depth interviews. Of the ten adolescent mothers interviewed, four narratives were selected for presentation in this manuscript. These particular narratives were selected to illustrate the diversity of the experiences among this group and for the exceptional level of detail provided about their life experiences and family relationships. Narrative excerpts were analyzed in the context of the entire interview and the aggregate content of other interviews in order to explore both explicit and implicit meanings. This study identified critical relational shifts among adolescent parents and their families during the perinatal period. In one instance, adolescent parenthood created an opportunity for the family to come together. In the other cases, conflict escalated, relations grew distant, or both. These narrative data demonstrate that intergenerational trauma can interfere with family relationships in the context of adolescent pregnancy and prevent adolescent parents from accessing needed support from their families. Intervention with families could address the impact of trauma and improve communication and collaboration.

Mapping the human T cell repertoire to recurrent driver mutations in MYD88 and EZH2 in lymphoma.

Oncogenic "driver" mutations are theoretically attractive targets for the immunotherapy of lymphoid cancers, yet the proportion that can be recognized by T cells remains poorly defined. To address this issue without any confounding effects of the patient's immune system, we assessed T cells from 19 healthy donors for recognition of three common driver mutations in lymphoma: MYD88L265P, EZH2Y641F , and EZH2Y641N . Donors collectively expressed the 10 most prevalent HLA class I alleles, including HLA-A*02:01. Peripheral blood T cells were primed with peptide-loaded dendritic cells (DC), and reactive T cells were assessed for recognition of naturally processed mutant versus wild type full-length proteins. After screening three driver mutations across 17-26 HLA class I alleles and 3 × 106-3 × 107 T cells per donor, we identified CD4+ T cells against EFISENCGEII from EZH2Y641N (presented by HLA-DRB1*13:02) and CD8+ T cells against RPIPIKYKA from MYD88L265P (presented by HLA-B*07:02). We failed to detect RPIPIKYKA-specific T cells in seven other HLA-B*07:02-positive donors, including two lymphoma patients. Thus, healthy donors harbor T cells specific for common driver mutations in lymphoma. However, such responses appear to be rare due to the combined limitations of antigen processing, HLA restriction, and T cell repertoire size, highlighting the need for highly individualized approaches for selecting targets.