Genetic evolution of breast cancers III: Age-dependent variations in the correlations between biological indicators of prognosis

The influence of age on the occurrence of phenotypic features of prognostic significance was studied in relation to the DNA index values, measured on DNA histograms from a series of 1019 breast cancer patients. Globally, the distributions of all parameters showed variations with age, the most prominent being the decreases in the percentage of estrogen receptor-negative and high proliferative activity cases with increasing age. When analyzed according to the DNA index classes, all parameters were found to some extent linked with the stage of genetic evolution. However, the associations varied with age, defining two extreme groups. The younger patients (less than 40 years) presented a more complete acquisition of the aggressive phenotype and near-triploid tumors from this group were very frequently steroid hormone receptor-negative, high proliferation, and grade III. By contrast, near-triploid tumors in patients above 65 presented relatively frequently as receptor-positive, low proliferative activity, and even grade I. The correlation of the proliferative status with steroid hormone receptor content led to similar conclusions, high proliferation being more strongly correlated with the absence of estrogen and progesterone receptors in younger patients. Interestingly, the association between high proliferation and negative progesterone receptors was much weaker in patients above 55. Our results suggest that the currently established biological prognostic factors, including DNA profile, steroid hormone receptors, and histopathological grade, show patterns of association which vary with age. Of these, only progesterone receptor could be influenced by menopausal status. These findings have to be taken into consideration for future prognostic factor-related treatment decisions, but also for future methodological improvements of multivariate survival analyses.     

Promoting Father Involvement for Child and Family Health

Paternal involvement in children's lives is associated with a variety of child outcomes, including improved cognition, improved mental health, reduced obesity rates, and asthma exacerbation. Given this evidence, the American Academy of Pediatrics has promoted actions by pediatricians to engage fathers in pediatric care. Despite these recommendations, the mother–child dyad, rather than the mother–father–child triad, remains a frequent focus of care. Furthermore, pediatric care is often leveraged to improve maternal health, such as screening for maternal depression, but paternal health is infrequently addressed even as men tend to exhibit riskier behaviors, poorer primary care utilization, and lower life expectancy. Therefore, increasing efforts by pediatric clinicians to engage fathers may affect the health of both father and child. These efforts to engage fathers are informed by currently used definitions and measures of father involvement, which are discussed here. Factors described in the literature that affect father involvement are also summarized, including culture and context; interpersonal factors; logistics; knowledge and self-efficacy; and attitudes, beliefs, and incentives. Innovative ways to reach fathers both in the clinic and in other settings are currently under investigation, including use of behavior change models, motivational interviewing, mobile technologies, peer support groups, and policy advocacy efforts. These modalities show promise in effectively engaging fathers and improving family health.     

Social,Occupational, and Spatial Exposures and Mental Health Disparities of Working-Class Latinas in the US

Grounded in ecosocial theory, this paper discusses the mental health disparities of working-class Latinas from multiple perspectives. An overview of working-class Latinas’ prevalent mental health disorders, barriers to care and suggestions for interventions and future studies are provided.     

Clinical Research Risk Assessment Among Individuals With Mild Cognitive Impairment

OBJECTIVE:: To determine whether individuals with mild cognitive impairment (MCI) differ from cognitively normal (NC) elders on a risk assessment task and whether participants and their study partners evaluate risk and benefit similarly. DESIGN:: Cross-sectional. SETTING:: University medical setting. PARTICIPANTS:: Seventy-nine participants (NC, n = 40; MCI, n = 39), age 60-90 years (73 ± 7 years; 53% women), and 64 study partners (NC, n = 36; MCI, n = 28), age 38-84 years (68 ± 10 years; 67% women). MEASUREMENTS:: Participants and study partners completed a risk assessment task that involved ranking from least to most risk four hypothetical vignettes for memory loss research (brain autopsy, blood draw, oral medication, neurosurgery). Participants also completed decisional capacity for research and neuropsychological protocols. RESULTS:: MCI participants' risk rankings differed from NC risk rankings (p <0.001) with MCI participants ranking brain autopsy higher and an oral medication trial lower. Demographic, decisional capacity, and neuropsychological variables could not explain MCI participant performances. Participants and their study partners had comparable risk assessment performance (p = 1.0). MCI study partners performed similar to their MCI participant counterparts but were different from NC study partners (p = 0.002; i.e., ranking autopsy higher and oral medication lower). CONCLUSION:: Findings suggest that individuals with MCI assess risk differently than NC peers by overestimating the risk (or underestimating the benefit) of brain autopsy and underestimating the risk (or overestimating the benefit) of oral medication. Study partners display a similar pattern. These observations may be secondary to MCI participants' (and their study partners') personal connection to the potential benefits of an experimental medication for memory loss.     

REPIMPACT - a prospective longitudinal multisite study on the effects of repetitive head impacts in youth soccer

Brain Imaging and Behavior - Repetitive head impacts (RHI) are common in youth athletes participating in contact sports. RHI differ from concussions; they are considered hits to the head that...     

Evolution of neuronal and glial tau isoforms in chronic traumatic encephalopathy

Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy characterized by accumulation of hyperphosphorylated tau (p‐tau) in perivascular aggregates in neurons and glia at the depths of neocortical sulci and progresses to diffuse neocortical, allocortical and brainstem structures. The strongest risk factor is exposure to repetitive head impacts acquired most commonly through contact sports and military service. Given that CTE can only be definitively diagnosed after death, a better understanding of the cellular and molecular changes in CTE brains may lead to identification of mechanisms that could be used for novel biomarkers, monitoring progression or therapeutic development. Disruption of alternative pre‐mRNA splicing of tau mRNA plays a pathogenic role in tauopathy, with multiple characteristic patterns of isoform accumulation varying among tauopathies. Limited data are available on CTE, particularly at early stages. Using biochemical and histological approaches, we performed a detailed characterization of tau isoform signatures in post‐mortem human brain tissue from individuals with a range of CTE stages (n = 99). In immunoblot analyses, severity was associated with decreased total monomeric tau and increased total oligomeric tau. Immunoblot with isoform‐specific antisera revealed that oligomeric tau with three and four microtubule binding domain repeats (3R and 4R) also increased with CTE severity. Similarly, immunohistochemical studies revealed p‐tau accumulation consisting of both 3R and 4R in perivascular lesions. When the ratio of 4R:3R was analyzed, there was mixed expression throughout CTE stages, although 4R predominated in early CTE stages (I‐II), a 3R shift was observed in later stages (III‐IV). While neurons were found to contain both 3R and 4R, astrocytes only contained 4R. These 4R‐positive cells were exclusively neuronal at early stages. Overall, these findings demonstrate that CTE is a mixed 4R/3R tauopathy. Furthermore, histologic analysis reveals a progressive shift in tau isoforms that correlates with CTE stage and extent of neuronal pathology.     

STI/HIV Risks for Mexican Migrant Laborers: Exploratory Ethnographies

The influx of Latino laborers into the U.S. and the confluence of migration-driven factors in an environment ripe for risk-taking have the potential to exacerbate already rising STI/HIV rates among migrants and their social networks at both the home and receiving regions. This paper focuses on Mexican migrant laborers who are among the most marginalized and exploited Latinos in the U.S. This study used ethnographic methods to delineate the sociocultural and spatial contexts and social organization of migrant farmwork, and examined how intertwined individual and environmental factors render migrant farmworkers vulnerable to STI/HIV risks. Findings indicate the presence of a number of factors in the study population of Mexican migrant workers (N = 23)—such as poverty, limited education, physical/social/cultural isolation, long work hours, constant mobility, hazardous work conditions, limited access to health care, low rates of condom use, multipartnering, and use of sexworkers—which increase their risks for STI/HIV transmission. To be successful, prevention efforts need to focus not only on condom education and HIV awareness and testing, but also on reducing migrants’ social isolation and understanding their social networks.