Spheno-orbital mesenchymal chondrosarcoma. A case report

Mesenchymal chondrosarcoma is a highly malignant and extremely rare tumor of the orbit: only 18 cases have been reported to date. We report a case of spheno-orbital mesenchymal chondrosarcoma in a 36-year-old woman presented with a 4-month history of progressive left exophthalmia and temporal mass. A CT-scan of the orbit and MRI showed a spheno-orbital mass, with temporal fossa extension, fed by the internal maxillary artery visible on cerebral angiography. Surgery via a transcranial, left frontotemporozygomatic approach after selective embolization enabled subtotal removal. Definitive histologic examination revealed mesenchymal chondrosarcoma. Postoperatively, exophthalmia spectacularly regressed. We report our clinical findings and present a review of the literature.     

Reverse Engineering of the Spindle Assembly Checkpoint

The Spindle Assembly Checkpoint (SAC) is an intracellular mechanism that ensures proper chromosome segregation. By inhibiting Cdc20, a co-factor of the Anaphase Promoting Complex (APC), the checkpoint arrests the cell cycle until all chromosomes are properly attached to the mitotic spindle. Inhibition of Cdc20 is mediated by a conserved network of interacting proteins. The individual functions of these proteins are well characterized, but understanding of their integrated function is still rudimentary. We here describe our attempts to reverse-engineer the SAC network based on gene deletion phenotypes. We begun by formulating a general model of the SAC which enables us to predict the rate of chromosomal missegregation for any putative set of interactions between the SAC proteins. Next the missegregation rates of seven yeast strains are measured in response to the deletion of one or two checkpoint proteins. Finally, we searched for the set of interactions that correctly predicted the observed missegregation rates of all deletion mutants. Remarkably, although based on only seven phenotypes, the consistent network we obtained successfully reproduces many of the known properties of the SAC. Further insights provided by our analysis are discussed.     

Oncotype Dx recurrence score among BRCA1/2 germline mutation carriers with hormone receptors positive breast cancer

Gene expression assays are widely used to predict risk of recurrence in early breast cancer (BC). We report the 21‐gene expression assay (Oncotype Dx) recurrence score (RS) distribution of 27 BRCA carriers with estrogen receptor (ER) positive BCs, identified at Hadassah Medical Center, combined with 2 previous studies. Treatment decision and outcomes of the 27 BRCA carriers were compared with an Israeli cohort of 1594 patients published recently. We found Oncotype Dx RS low (<18), intermediate (18–30) and high (>30) among 12 (21.4%), 23 (41.1%) and 21 (37.5%) of 56 BRCA1 carriers compared with 15 (17.2%), 49 (56.3%) and 23 (26.4%) of 87 BRCA2 carriers (p = 0.2). The corresponding distribution in a population of 82,434 women published by Genomic Health was 53.4%, 36.3% and 10.3% for low, intermediate and high RS (p < 0.001 for BRCA1 and BRCA2). Treatment decision regarding chemotherapy according to RS was similar in BRCA1, BRCA2 and the control group. Two of 27 carriers had distant recurrence: a BRCA1 carrier with RS of 18 and a BRCA2 carrier with RS of 22; both have an excellent response to chemotherapy. We found an approximately ～3 fold increased rate of high RS among BRCA1 and 2 carriers with ER positive BC compared with the general BC population. These data might indicate that hormone positive BC in BRCA carriers are molecularly unique. The surprisingly good response to chemotherapy in the metastatic setting in 2 patients may suggest that the predictive value of low‐intermediate RS in carriers merits further studies.     

The hygiene hypothesis,the COVID pandemic,and consequences for the human microbiome

The COVID-19 pandemic has the potential to affect the human microbiome in infected and uninfected individuals, having a substantial impact on human health over the long term. This pandemic intersects with a decades-long decline in microbial diversity and ancestral microbes due to hygiene, antibiotics, and urban living (the hygiene hypothesis). High-risk groups succumbing to COVID-19 include those with preexisting conditions, such as diabetes and obesity, which are also associated with microbiome abnormalities. Current pandemic control measures and practices will have broad, uneven, and potentially long-term effects for the human microbiome across the planet, given the implementation of physical separation, extensive hygiene, travel barriers, and other measures that influence overall microbial loss and inability for reinoculation. Although much remains uncertain or unknown about the virus and its consequences, implementing pandemic control practices could significantly affect the microbiome. In this Perspective, we explore many facets of COVID-19−induced societal changes and their possible effects on the microbiome, and discuss current and future challenges regarding the interplay between this pandemic and the microbiome. Recent recognition of the microbiome’s influence on human health makes it critical to consider both how the microbiome, shaped by biosocial processes, affects susceptibility to the coronavirus and, conversely, how COVID-19 disease and prevention measures may affect the microbiome. This knowledge may prove key in prevention and treatment, and long-term biological and social outcomes of this pandemic.     

Cortical magnetic resonance imaging findings in familial pediatric bipolar disorder.

BACKGROUND: Morphometric magnetic resonance imaging (MRI) studies of pediatric bipolar disorder (BD) have not reported on gray matter volumes but have reported increased lateral ventricular size and presence of white matter hyperintensities (WMH). We studied gray matter volume, ventricular-to-brain ratios (VBR), and number of WMH in patients with familial, pediatric BD compared with control subjects. METHODS: Twenty subjects with BD (aged 14.6 +/- 2.8 years; 4 female) according to the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia, each with a parent with BD, and 20 age-, gender-, and intelligence quotient-matched healthy control subjects (aged 14.1 +/- 2.8 years; 4 female) were scanned at 3 T. Most subjects were taking psychotropic medications. A high-resolution T1-weighted spoiled gradient echo three-dimensional MRI sequence was analyzed by BrainImage for volumetric measurements, and T2-weighted images were read by a neuroradiologist to determine presence of WMH. RESULTS: After covarying for age and total brain volume, there were no significant differences between subjects with BD and control subjects in volume of cerebral (p = .09) or prefrontal gray matter (p = .34). Subjects with BD did not have elevated numbers of WMH or greater VBR when compared with control subjects. CONCLUSIONS: Children and adolescents with familial BD do not seem to have decreased cerebral grey matter or increased numbers of WMH, dissimilar to findings in adults with BD. Gray matter decreases and development of WMH might be later sequelae of BD or unique to adult-onset BD.     

Postpartum Depression,Complications During Pregnancy,and Offspring Behavior Problems in Early Childhood

Child & Youth Care Forum - Complications during pregnancy, postpartum and current maternal depression are risk factors that may affect child behavior in early and middle childhood. This...