Hemispheric bases for emotion and memory

The goal of this Research Topic was to bring together diverse scientific perspectives on lateralized brain mechanisms underlying emotion, motivation, and memory. The Topic resulted in eight articles, three of which report original research and five of which review and synthesize past research with the aim of developing new hypotheses and theory. A range of international experts with diverse backgrounds, theoretical perspectives, and experimental methods contributed to the Topic. Contributions strongly reflect this diversity, ranging from examining pupil dilation in response to viewing Rembrandt portraits to understanding how caffeine supplementation influences levels of spatial processing. In all cases, the authors developed strong, empirically guided insights into the lateralized brain mechanisms underlying behavioral effects. Two primary themes emerge to guide and constrain continuing research

Hemispheric bases for emotion and memory

The goal of this Research Topic was to bring together diverse scientific perspectives on lateralized brain mechanisms underlying emotion, motivation, and memory. The Topic resulted in eight articles, three of which report original research and five of which review and synthesize past research with the aim of developing new hypotheses and theory. A range of international experts with diverse backgrounds, theoretical perspectives, and experimental methods contributed to the Topic. Contributions strongly reflect this diversity, ranging from examining pupil dilation in response to viewing Rembrandt portraits to understanding how caffeine supplementation influences levels of spatial processing. In all cases, the authors developed strong, empirically guided insights into the lateralized brain mechanisms underlying behavioral effects. Two primary themes emerge to guide and constrain continuing research

Chemical Toxicants in Water: A \u3ci\u3eGeoHealth\u3c/i\u3e Perspective in the Context of Climate Change

The editorial focuses on four major themes contextualized in a virtual GeoHealth workshop that occurred from June 14 to 16, 2021. Topics in that workshop included drinking water and chronic chemical exposure, environmental injustice, public health and drinking water policy, and the fate, transport, and human impact of aqueous contaminants in the context of climate change. The intent of the workshop was to further define the field of GeoHealth. This workshop emphasized on chemical toxicants that drive human health. The major calls for action emerged from the workshop include enhancing community engagement, advocating for equity and justice, and training the next generation

PANTHER: AZD8931, inhibitor of EGFR, ERBB2 and ERBB3 signalling, combined with FOLFIRI: a Phase I/II study to determine the importance of schedule and activity in colorectal cancer

BACKGROUND: Epidermal growth factor receptor (EGFR) is a therapeutic target to which HER2/HER3 activation may contribute resistance. This Phase I/II study examined the toxicity and efficacy of high-dose pulsed AZD8931, an EGFR/HER2/HER3 inhibitor, combined with chemotherapy, in metastatic colorectal cancer (CRC). METHODS: Treatment-naive patients received 4-day pulses of AZD8931 with irinotecan/5-FU (FOLFIRI) in a Phase I/II single-arm trial. Primary endpoint for Phase I was dose limiting toxicity (DLT); for Phase II best overall response. Samples were analysed for pharmacokinetics, EGFR dimers in circulating exosomes and Comet assay quantitating DNA damage. RESULTS: Eighteen patients received FOLFIRI and AZD8931. At 160 mg bd, 1 patient experienced G3 DLT; 160 mg bd was used for cohort expansion. No grade 5 adverse events (AE) reported. Seven (39%) and 1 (6%) patients experienced grade 3 and grade 4 AEs, respectively. Of 12 patients receiving 160 mg bd, best overall response rate was 25%, median PFS and OS were 8.7 and 21.2 months, respectively. A reduction in circulating HER2/3 dimer in the two responding patients after 12 weeks treatment was observed. CONCLUSIONS: The combination of pulsed high-dose AZD8931 with FOLFIRI has acceptable toxicity. Further studies of TKI sequencing may establish a role for pulsed use of such agents rather than continuous exposure. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number: NCT01862003

Behavioral and Psychophysiological Responsiveness During Child Feeding in Mothers with Histories of Eating Disorders: A Pilot Study

The aim of this pilot project was to describe maternal responsiveness during child feeding in mothers with eating disorder histories through the combined use of observational, self-report, and physiologic methods. For this non-randomized cohort pilot study, 25 mothers with histories of eating disorders and 25 mothers with no history of an eating disorder with children ages 6–36 months were selected such that the groups were similar based on child age group (within 6 months) and child sex. Maternal behavioral responsiveness to child cues was assessed by video-recording and behavioral coding of both a free-play and feeding episode. Physiologic engagement was assessed through measurement of respiratory sinus arrhythmia (RSA) reactivity during free-play and feeding episodes. No differences were detected in observed behavioral responsiveness during feeding or free-play in mothers with eating disorder histories compared with controls. Mothers with eating disorder histories did report more parenting stress, increased anxiety, and exhibited a blunted physiologic stress response (less RSA reactivity) during both feeding and free-play interactions with their children. These results support future larger-scale investigations of RSA reactivity in mothers with eating disorders

The multikinase inhibitor midostaurin (PKC412A) lacks activity in metastatic melanoma: a phase IIA clinical and biologic study

Midostaurin (PKC412A), N-benzoyl-staurosporine, potently inhibits protein kinase C alpha (PKCα), VEGFR2, KIT, PDGFR and FLT3 tyrosine kinases. In mice, midostaurin slows growth and delays lung metastasis of melanoma cell lines. We aimed to test midostaurin's safety, efficacy and biologic activity in a Phase IIA clinical trial in patients with metastatic melanoma. Seventeen patients with advanced metastatic melanoma received midostaurin 75 mg p.o. t.i.d., unless toxicity or disease progression supervened. Patient safety was assessed weekly, and tumour response was assessed clinically or by CT. Tumour biopsies and plasma samples obtained at entry and after 4 weeks were analysed for midostaurin concentration, PKC activity and multidrug resistance. No tumour responses were seen. Two (12%) patients had stable disease for 50 and 85 days, with minor response in one. The median overall survival was 43 days. Seven (41%) discontinued treatment with potential toxicity, including nausea, vomiting, diarrhoea and/or fatigue. One patient had >50% reduction in PKC activity. Tumour biopsies showed two PKC isoforms relatively insensitive to midostaurin, out of three patients tested. No modulation of multidrug resistance was demonstrated. At this dose schedule, midostaurin did not show clinical or biologic activity against metastatic melanoma. This negative trial reinforces the importance of correlating biologic and clinical responses in early clinical trials of targeted therapies