Concordance of the hormone receptors and correlation of HER-2/neu overexpression of the metachronous cancers of contralateral breasts

The primary objective of this study was to evaluate the relative prevalence of estrogen receptor-negative contralateral breast cancer to the first primary cancer and to assess the correlation between the relative overexpression of HER-2/neu in the first primary cancer and contralateral breast cancer. A total of 144 women diagnosed with cancers in contralateral breasts were identified from the Henry Ford Health System tumor registry. Data were retrieved from electronic databases and medical records. Women were dichotomized into users and nonusers of tamoxifen. Hormone receptors were scored as positive or negative. HER-2/neu overexpression, assessed by immunohistochemistry, was scored as 0, 1(+), 2(+), or 3(+). Concordance between hormone receptors of the two cancers was low (kappa = 0.27, p = 0.06). Stratification of women by tamoxifen therapy yielded an almost fivefold increase in the proportion of estrogen receptor-negative cancers among the users, while the proportion of cancers expressing no estrogen receptor remained the same among the nonusers (39.6% versus 40.6%). Matched, archived, paraffin-embedded specimens of the first and contralateral breast cancers were available for 57 women. The correlation between the relative overexpression of HER-2/neu between the first primary and the contralateral breast cancer was 0.4 (p = 0.002). The higher prevalence of estrogen receptor-negative contralateral breast cancer among tamoxifen users concurs with previous reports. The biological mechanism for this observation is not understood; however, it has been proposed that tamoxifen inhibits the proliferation of estrogen receptor-positive breast cancer cells, while estrogen receptor-negative cells may continue to grow because of selective pressure. The correlation between HER-2/neu overexpression in the matched first primary and contralateral breast cancers was statistically significant, suggesting that the diagnosis of HER-2/neu overexpression in contralateral breast cancer is associated with HER-2/neu overexpression in the first primary cancer.     

Annexin 1-dependent actions of glucocorticoids in the anterior pituitary gland: roles of the N-terminal domain and protein kinase C

Annexin 1 (ANXA1) is an important mediator of glucocorticoid action in the neuroendocrine system. As the activity of this protein in other systems is modulated by phosphorylation of its N-terminal domain, we have explored the significance of this domain and its phosphorylation status to ANXA1 actions within the pituitary gland, using an established in vitro preparation. Two N-terminal peptides, ANXA1(Ac2-26) and ANXA1(Ac1-50), inhibited forskolin-evoked ACTH and prolactin release; however, they lacked the potency and full efficacy of the parent molecule (ANXA1(1-346)), whereas other shorter N-terminal sequences were without effect. A chimeric protein comprising ANXA1(1-44) and the C-terminal core of ANXA5 (ANXA5(20-320)) also produced a partial inhibition of peptide release. Protein kinase C (PKC) blockade (PKC(19-36)) abolished the inhibitory effects of dexamethasone on forskolin-evoked peptide release and attenuated the antisecretory actions of ANXA1(Ac2-26.) ANXA5, which sequesters PKC in other systems, produced similar effects. PKC(19-36) also blocked the dexamethasone- induced translocation of a serine phosphorylated species of ANXA1 from the cytoplasm to the outer cell surface. These results suggest that 1) the N-terminal domain plays a fundamental role in effecting the inhibitory actions of ANXA1 on pituitary peptide release; 2) PKC-dependent mechanisms are essential for both the cellular exportation and the biological activity of ANXA1; and 3) ANXA1 exported from the cells is serine phosphorylated.     

Violence,mental health,and physical symptoms in an academic internal medicine practice

OBJECTIVE: To assess how physical and/or sexual intimate partner violence (IPV), child abuse, and community violence relate to long-term mental and physical problems; to examine the overlap between different forms of violence and the impact of experiencing multiple forms of violence. DESIGN: Cross-sectional survey. SETTING: Three general internal medicine practices affiliated with an academic medical center. PARTICIPANTS: English-speaking women aged 25 to 60. MEASUREMENTS: Telephone or in-person interview and chart review. RESULTS: One hundred seventy-four women completed interviews. A majority of participants experienced more than one form of violence. In separate multivariate analyses, each form of violence was associated with depressive symptoms or with at least 6 chronic physical symptoms, after adjustment for demographic factors and substance abuse. The degree of association with health outcomes was similar for each form of violence (odds ratio [OR], 2.4 to 3.9; P < .003). The association with chronic physical symptoms remained significant for IPV (OR, 3.3; P < .002) and community violence (OR, 3.4; P < .003), even after adjustment for depression and posttraumatic stress disorder. There were dose-response relationships between the number of forms of violence experienced and the odds of depressive symptoms and the odds of multiple chronic physical symptoms. CONCLUSIONS: Multiple types of victimizations may contribute to patients' current mental health and physical problems. Research or clinical protocols that only focus on one form of violence may underestimate the complexity of women's experiences and needs.     

Lipase-catalyzed acylation of levoglucosan in continuous flow: antibacterial and biosurfactant studies

Studies involving the transformation of lignocellulosic biomass into high value-added chemical products have been intensively conducted in recent years. Its matrix is mainly composed of cellulose, hemicellulose and lignin, being, therefore, an abundant and renewable source for obtaining several platform molecules, with levoglucosan (LG) standing out. This anhydrous carbohydrate can be acylated to obtain carbohydrate fatty acid esters (CFAEs). Here, these compounds were obtained via enzymatic acylation of LG, commercially obtained (Start BioScience®), with different acyl donors in continuous flow. Through the experimental design using a model reaction, it was possible to optimize the reaction conditions, temperature and residence time, obtaining a maximum conversion at 61 °C and 77 min. In addition, there was a productivity gain of up to 100 times in all comparisons made with the batch system. Finally, CFAEs were applied in tests of interfacial tension and biological activity. For a mixture of 4- and 2-O-lauryl-1,6-anhydroglucopyranose (MONLAU), the minimum interfacial tension (IFT^min) obtained was 96 mN m⁻¹ and the critical micelle concentration (CMC) was 50 mM. Similar values were obtained for a mixture of 4- and 2-O-palmitoyl-1,6-anhydroglucopyranose (MONPAL), not yet reported in the literature, of 88 mN m⁻¹ in 50 mM. For a mixture of 4- and 2-O-estearyl-1,6-anhydroglucopyranose (MONEST) and 4- and 2-O-oleoyl-1,6-anhydroglucopyranose (MONOLE), CMC was higher than 60 mM and IFT^min of 141 mN m⁻¹ and 102 mN m⁻¹, respectively. Promising data were obtained for minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of MONLAU against Staphylococcus aureus strains at 0.25 mM.

Ipase-catalyzed transesterification of LG under continuous flow conditions.     

A study of moral development and personality relationships in adolescents and young adult catholic students

Explored the relationship between personality and moral development. Using Kohlberg's stages of moral development, it was conceived as possible that some of the characteristics measured by the California Psychological Inventory would be related significantly to preference for principled levels of moral judgment (stages 5 and 6 of Kohlberg's schema) for three groups of Catholic students (N = 549) in attendance at Catholic high schools and universities. The results indicated that those who preferred principled levaels of moral reasoning were seen as being dependable, rational, creative, intelligent, and accepting of rules and constraints of society, but at the same time, able to think independently and aware of the need for change.     

Disseminated Histoplasmosis in Persons with HIV/AIDS,Southern Brazil, 2010–2019

We evaluated disseminated histoplasmosis (DH) in HIV patients over 10 years in southern Brazil. The incidence was 12 cases/1,000 hospitalizations (2010–2019); the mortality rate was 35%. Tuberculosis frequently obscured the diagnosis of DH. We emphasize the need in our region to suspect and investigate DH using more sensitive methods.