Asking About Childhood Adversity in the Prenatal Care Setting: Cross-Sectional Associations with Maternal Health and Mental Health Outcomes

Maternal and Child Health Journal - Adverse childhood experiences (ACEs) are associated with poor physical and mental health outcomes in pregnancy, prompting many care agencies to ask about ACEs as...     

Bleomycin and brain tumors

A logical inference from the recent reports indicating that malignant brain tumors are composed of a heterogeneous cell population is that combination chemotherapy will be required for effective brain tumor control. For several years we have been investigating the use of Bleomycin as an agent to be used in conjunction with radiation therapy and a nitrosourea compound. Since systemically administered Bleomycin does not cross the blood-brain-barrier and has significant toxicity when used parenterally in high doses, we have studied the use of smaller doses of Bleomycin injected directly into the brain tumor cavity. Such an intracerebral dose was more effective in prolonging survival of rats burdened with experimental 9L gliosarcomas than an intravenous dose that is 25 times as great. The combination of intracerebrally administered Bleomycin and radiation therapy was more effective than either modality alone. Furthermore, the combination of Bleomycin delivered intracerebrally and BCNU given systemically was more effective than eitheragent used alone. Finally, in a Phase I clinical trial of Bleomycin given via an Ommaya reservoir to eight patients with recurrent malignant brain tumors, we have demonstrated that individual doses of up to 7.5 units and cumulative doses of up to 255 units can be administered without significant toxicity.     

Inhibition of Neu-Induced Mammary Carcinogenesis in Transgenic Mice Expressing ERΔ3, a Dominant Negative Estrogen Receptor α Variant

The estrogen receptor ?? (ER??) splicing variant with an in-frame deletion of exon 3 (ER??3) is frequently expressed in the normal breast, but its influence on tumorigenesis has not been explored. In vitro, ER??3 has dominant negative activity, suggesting it may suppress estrogen stimulation in the breast. ER??3 may inhibit classical signaling on estrogen response element (ERE)-regulated genes as well as activate non-classical pathways at Sp1 and AP-1 sites. Transgenic mice were developed that express mouse ER??3 in all tissues examined, including the mammary gland. To investigate if ER??3 expression affects tumorigenesis, ER??3 mice were crossbred with MMTV-Neu mice. Mammary tumor onset was significantly delayed in ER??3/Neu versus MMTV-Neu females and metastatic incidence and burden was significantly reduced. Consequently, ER??3 expression suppressed tumor development and metastasis in this aggressive model of HER2/Neu-positive breast cancer. To determine if ER ligands with anticancer activity may augment ER??3 protection, the bitransgenic mice were treated with tamoxifen and soy isoflavones starting at age 2?months. Soy protein with isoflavones (181?mg/1,800?kcal) did not affect tumor development in MMTV-Neu or ER??3/Neu mice; however, metastatic progression was not inhibited in soy-treated ER??3/Neu mice, as it was in untreated ER??3/Neu mice. In contrast, tamoxifen (20?mg/1,800?kcal) significantly enhanced tumor prevention in ER??3/Neu versus MMTV-Neu mice (98?% vs. 81?% tumor free). The results in ER??3/Neu mice demonstrate that ER??3 influences estrogen-dependent mammary carcinogenesis and, thus, may be protective in women expressing ER??3 in the breast. However, exposure to different estrogens may augment or block its beneficial effects.     

SPERM CRYOPRESERVATION PRACTICES AMONG ADOLESCENT CANCER PATIENTS AT RISK FOR INFERTILITY

To assess sperm cryopreservation among males newly diagnosed with cancer aged 13 years and older, attending oncologists assigned infertility risk (yes/no) to patients and reported whether their patients engaged in sperm cryopreservation. Only 28.1% of informed at-risk patients banked sperm. Utilization of sperm banking was significantly associated with a diagnosis of central nervous system (CNS) malignancy or non-CNS solid tumor diagnosis, higher socioeconomic status, and not being a member of an Evangelical religious group. These results suggest that sperm banking is underutilized among adolescent males newly diagnosed with cancer, and that strategies to increase the engagement in this fertility preservation method are needed.     

Performance of a Rapid Self-Test for Detection of Trichomonas vaginalis in South Africa and Brazil

Women participating in studies in Brazil (n = 695) and South Africa (n = 230) performed rapid point-of-care tests for Trichomonas vaginalis on self-collected vaginal swabs. Using PCR as the gold standard, rapid self-testing achieved high specificity (99.1%; 95% confidence interval [CI], 98.2 to 99.6%) and moderate sensitivity (76.7%; 95% CI, 61.4 to 88.2%). These tests may be considered an alternative to syndromic management in resource-poor settings.     

Schizophrenia and bipolar disorder are associated with opposite brain reward anticipation-associated response

Blunted and exaggerated neuronal response to rewards are hypothesized to be core features of schizophrenia spectrum disorders (SZ) and bipolar disorder (BD), respectively. Nonetheless, direct tests of this hypothesis, in which response between SZ and BD is compared in the same study, are lacking. Here we examined the functional correlates of reward processing during the Incentivized Control Engagement Task (ICE-T) using 3T fMRI. Reward-associated activation was examined in 49 healthy controls (HCs), 52 recent-onset individuals with SZ, and 22 recent-onset individuals with Type I BD using anterior cingulate (ACC), anterior insula, and ventral striatal regions of interest. Significant group X reward condition (neutral vs. reward) interactions were observed during reward anticipation in the dorsal ACC (F(2,120) = 4.21, P = 0.017) and right insula (F(2,120) = 4.77, P = 0.010). The ACC interaction was driven by relatively higher activation in the BD group vs. HCs (P = 0.007) and vs. individuals with SZ (P = 0.010). The insula interaction was driven by reduced activation in the SZ group relative to HCs (P = 0.018) and vs. people with BD (P = 0.008). A composite of reward anticipation-associated response across all associated ROIs also differed significantly by diagnosis (F(1,120) = 5.59, P = 0.02), BD > HC > SZ. No effects of group or group X reward interactions were observed during reward feedback. These results suggest that people with SZ and BD have opposite patterns of activation associated with reward anticipation but not reward receipt. Implications of these findings in regard to Research Domain Criteria-based classification of illness and the neurobiology of reward in psychosis are discussed.Subject terms: Schizophrenia, Bipolar disorder     

Incomplete response to endoscopic sphincterotomy in patients with sphincter of Oddi dysfunction: evidence for a chronic pain disorder

OBJECTIVES: The efficacy of endoscopic treatment of sphincter of Oddi dysfunction (SOD) with endoscopic sphincterotomy (ES) remains controversial. Although some studies have shown a positive impact on patient symptoms after treatment, these reports have been largely qualitative and evaluated on short-term response. The aim of our study was to quantitatively measure the long-term outcomes of endoscopic therapy in patients with SOD. METHODS: Thirty-three patients with suspected SOD underwent selective sphincter of Oddi manometry (SOM) of the biliary and/or pancreatic sphincter. Each patient completed a telephone-based survey measuring symptomatic pain before and after SOM +/- ES. The questioner was blinded to the results of SOM. The patients with normal SOM or SOD but who did not undergo ES served as controls. RESULTS: Of these 33 patients (27 women, mean age 48.7 yr, range 13-74), 19 (57.5%) were found to have SOD (12 biliary, six pancreatic, one both). The average follow-up was 18.1 months (range 7-34). Of the patients with SOD, 17 (89%) underwent ES. At follow-up of the 19 patients undergoing ES, five were taking narcotics for persistent pain, two were taking antidepressants, and 15 identified the endoscopic therapy as the reason for their relief. Of the 14 controls, seven were taking narcotics, seven were taking antidepressants, and two identified the endoscopy as the reason for their relief; some patients were taking both antidepressants and narcotics. CONCLUSIONS: Patients found to have SOD who undergo ES are more likely to be improved on long-term follow-up when compared with patients with suspected SOD but normal manometry without ES. However, almost uniformly, despite ES, patients continue to have pain, which is consistent with most chronic pain disorders and which suggests a multifactorial cause for the pain.