Use of a case-mix approach to study the trends in the incidence of second primary cancers

Purpose

To analyze trends in second primary cancer (SPC) incidence by using a case-mix approach to standardize on first cancer site distribution.

Phenotype of mice with inducible ablation of GluA1 AMPA receptors during late adolescence: Relevance for mental disorders

Adolescence is characterized by important molecular and anatomical changes with relevance for the maturation of brain circuitry and cognitive function. This time period is of critical importance in the emergence of several neuropsychiatric disorders accompanied by cognitive impairment, such as affective disorders and schizophrenia. The molecular mechanisms underlying these changes at neuronal level during this specific developmental stage remains however poorly understood. GluA1‐containing AMPA receptors, which are located predominantly on hippocampal neurons, are the primary molecular determinants of synaptic plasticity. We investigated here the consequences of the inducible deletion of GluA1 AMPA receptors in glutamatergic neurons during late adolescence. We generated mutant mice with a tamoxifen‐inducible deletion of GluA1 under the control of the CamKII promoter for temporally and spatially restricted gene manipulation. GluA1 ablation during late adolescence induced cognitive impairments, but also marked hyperlocomotion and sensorimotor gating deficits. Unlike the global genetic deletion of GluA1, inducible GluA1 ablation during late adolescence resulted in normal sociability. Deletion of GluA1 induced redistribution of GluA2 subunits, suggesting AMPA receptor trafficking deficits. Mutant animals showed increased hippocampal NMDA receptor expression and no change in striatal dopamine concentration. Our data provide new insight into the role of deficient AMPA receptors specifically during late adolescence in inducing several cognitive and behavioral alterations with possible relevance for neuropsychiatric disorders. © 2013 Wiley Periodicals, Inc.     

MORC1 exhibits cross-species differential methylation in association with early life stress as well as genome-wide association with MDD

Early life stress (ELS) is associated with increased vulnerability for diseases in later life, including psychiatric disorders. Animal models and human studies suggest that this effect is mediated by epigenetic mechanisms. In humans, epigenetic studies to investigate the influence of ELS on psychiatric phenotypes are limited by the inaccessibility of living brain tissue. Due to the tissue-specific nature of epigenetic signatures, it is impossible to determine whether ELS induced epigenetic changes in accessible peripheral cells, for example, blood lymphocytes, reflect epigenetic changes in the brain. To overcome these limitations, we applied a cross-species approach involving: (i) the analysis of CD34+ cells from human cord blood; (ii) the examination of blood-derived CD3+ T cells of newborn and adolescent nonhuman primates (Macaca mulatta); and (iii) the investigation of the prefrontal cortex of adult rats. Several regions in MORC1 (MORC family CW-type zinc finger 1; previously known as: microrchidia (mouse) homolog) were differentially methylated in response to ELS in CD34+ cells and CD3+ T cells derived from the blood of human and monkey neonates, as well as in CD3+ T cells derived from the blood of adolescent monkeys and in the prefrontal cortex of adult rats. MORC1 is thus the first identified epigenetic marker of ELS to be present in blood cell progenitors at birth and in the brain in adulthood. Interestingly, a gene-set-based analysis of data from a genome-wide association study of major depressive disorder (MDD) revealed an association of MORC1 with MDD.     

Results from the American Society of Breast Surgeons Oncoplastic Surgery Committee 2017 Survey: Current Practice and Future Directions

Introduction

Oncoplastic surgery is emerging as a validated, safe, patient-centric approach to breast cancer surgery in the United States. The American Society of Breast Surgeons Oncoplastic Surgery Committee (ASBrS-OSC) conducted a survey to assess the scope of practice and level of interest in oncoplastic surgery among its members. Furthermore, the group sought to identify barriers to incorporating oncoplastic skills in a surgeon’s practice.

Methods

A 10-question survey was administered in March 2017 to the entire ASBrS membership using an online format. Three solicitations were sent. Unique identifiers allowed a single response.

Results

Of the 2655 surveys sent out, 708 members responded. Nearly all (99%) respondents had at least some interest in oncoplastic surgery. The current rates of performing nipple-sparing mastectomy, adjacent tissue transfer, and breast reduction with lumpectomy were 80, 60, and 51%, respectively. A minority of respondents reported independently performing breast reductions/mammaplasties (19%) or contralateral symmetrization (10%). Barriers to learning oncoplastic surgery included surgeon’s time and access to oncoplastic educational material/courses. Most respondents felt that training courses and videos may allow them to better incorporate oncoplastic techniques in their practices.

Conclusions

The interest in oncoplastic surgery among U.S. surgeons is significant, yet there are barriers to incorporate these surgical techniques into a breast surgeon’s practice. As professional organizations provide access to effective training and enduring educational resources, breast surgeons will be enabled to develop their oncoplastic skill set and safely offer these techniques to their patients.

     

Surgical repair of candida mycotic pseudoaneurysm with extensive vegetations of the ascending aorta and pulmonary artery after heart and kidney transplant

We report a case of invasive candidiasis causing a mycotic pseudoaneurysm involving the ascending aorta and pulmonary artery. The patient presented two years after heart-kidney transplant with acute limb ischemia resulting from embolization of fungal vegetations. Operative findings included a pseudoaneurysm resulting from near-complete dehiscence of the aortic suture line, and large vegetations within the ascending aorta extended to the aortic arch and pulmonary artery, with localized dehiscence of the pulmonic suture line. The ascending aorta was replaced, and the pulmonary artery was repaired with bovine pericardium. The patient did well, and blood cultures were negative at 6 months follow-up.     

ASO Author Reflections: Breast-Specific Sensuality in the Sexually Inactive Breast Cancer Survivor

Annals of Surgical Oncology -     

Induction of Apoptosis in HT-29 Cells by Extracts from Isothiocyanates-rich Varieties of Brassica Oleracea

Among the vegetables with anti-carcinogenic properties, members of the genus Brassica are the most effective at reducing the risk of cancer. This property may be explained by their principle bioactive compounds, isothiocyanates (ITCs). The aim of this study was to measure the amounts of ITCs in extracts from vegetables of the Brasssica genus and assay them for potency of induction of apoptosis in a colorectal cancer cell line (HT-29). ITCs were determined by the cyclocondensation assay with 1,2-benzenedithiol and induction of apoptosis by assessment of cell viability, caspase-3 activity and DNA fragmentation. Purple cabbage extract showed the highest ITC concentration per gram, fresh weight, followed by black cabbage and Romanesco cauliflower. At ITC concentrations of 7.08 μ g/mL these extracts decreased cell viability and induced caspase-3 and DNA fragmentation at 48h. Brussels sprouts showed the strongest effects on cell viability and caspase-3 activity. Varieties of Brassica Oleracea are rich sources of ITCs that potently inhibit the growth of colon cancer cells by inducting apoptosis. All the extracts showed anticancer activity at ITC concentrations of between 3.54 to 7.08 μ g/mL, which are achievable in vivo. Our results showed that ITC concentration and the chemopreventive responses of plant extracts vary among the varieties of Brassica Oleracea studied and among their cultivars.