Adjuvant treatment recommendations in older women with breast cancer: a survey of oncologists

OBJECTIVE: Previous studies demonstrate differing treatment patterns between older and younger patients with breast cancer. To explore the reasons for these disparities we conducted a survey of 28 oncologists specializing in breast cancer. DESIGN AND METHODS: Twenty-eight medical oncologists from Memorial Sloan-Kettering Cancer Center and the University of California Los Angeles who specialize in the treatment of breast cancer were asked to provide adjuvant treatment recommendations in hypothetical scenarios featuring older patients with high-risk breast cancer. For each of these hypothetical patients, the patient's age was varied over four possible values (70, 75, 80, or 85 years of age) and health and functional status varied across three possible states (perfect health, average health, or major health problems). Survey data were compiled and analyzed to determine the impact of theoretical patient age, baseline health, and functional status on their treatment recommendations. RESULTS: The proportion of oncologists who recommended adjuvant chemotherapy decreased as the patient's age increased or as the patient's functional status and health status decreased. For 96% of physicians (95% CI, 82-100%), patient age influenced chemotherapy recommendations, controlling for health/functional status; the same proportion of respondents were influenced by health/functional status, controlling for patient age. There was increased variability in treatment recommendations as the patient's age increased or functional status and health status decreased. CONCLUSION: Among these medical oncologists who primarily treat breast cancer adjuvant treatment recommendations vary based on patient age, health, and functional status. Future studies are needed to correlate age, health, and functional status with the risks and benefits of adjuvant therapy so that consensus guidelines can be formed. A more comprehensive baseline assessment of the older patient, such as can be derived from a comprehensive geriatric assessment may be useful in this regard.     

Imaging honey bee brain anatomy with micro-X-ray-computed tomography

Technologies for imaging in three dimensions are greatly desired by researchers in many biological disciplines. However, when imaging small animals such as invertebrates, the achievement of satisfactory spatial resolution and adequate contrast between tissues often requires the use of expensive and time-consuming procedures. Micro-X-ray-computed tomography (μCT) is a convenient technique which is finding greater use alongside conventional microscopies. Staining with heavy metal salts, such as osmium tetroxide improves imaging in μCT, and allows visualization of the 3D structure of the honey bee brain undistorted within the intact head capsule. We obtained detailed information about the morphology of the different brain compartments and were able to show their orientations, relative to each other, within the head capsule. This technique offers a significant improvement in resolution, time, and expense for the quantitative, three-dimensional analysis of developing bee brain centers. In this article, we introduce a rapid, high-resolution, and inexpensive technique for the three-dimensional visualization of different compartments of the honey bee brain. A detailed discussion of the honey bee brain anatomy is provided, demonstrating that μCT, with osmium staining, can indeed visualise these structures. Hence, our results show that μCT is ideally suited for researchers who are interested in the 3D visualization of small invertebrate brains.     

Upregulation of calpastatin in regenerating and developing rat liver: role in resistance against hepatotoxicity

Acute liver failure induced by hepatotoxic drugs results from rapid progression of injury. Substantial research has shown that timely liver regeneration can prevent progression of injury leading to a favorable prognosis. However, the mechanism by which compensatory regeneration prevents progression of injury is not known. We have recently reported that calpain released from necrotic hepatocytes mediates progression of liver injury even after the hepatotoxic drug is cleared from the body. By examining expression of calpastatin (CAST), an endogenous inhibitor of calpain in three liver cell division models known to be resistant to hepatotoxicity, we tested the hypothesis that increased CAST in the dividing hepatocytes affords resistance against progression of injury. Liver regeneration that follows CCl(4)-induced liver injury, 70% partial hepatectomy, and postnatal liver development were used. In all three models, CAST was upregulated in the dividing/newly divided hepatocytes and declined to normal levels with the cessation of cell proliferation. To test whether CAST overexpression confers resistance against hepatotoxicity, CAST was overexpressed in the livers of normal SW mice using adenovirus before challenging them with acetaminophen (APAP) overdose. These mice exhibited markedly attenuated progression of liver injury and 57% survival. Whereas APAP-bioactivating enzymes and covalent binding of the APAP-derived reactive metabolites remained unaffected, degradation of calpain specific target substrates such as fodrin was significantly reduced in these mice. In conclusion, CAST overexpression could be used as a therapeutic strategy to prevent progression of liver injury where liver regeneration is severely hampered.     

Understanding evolution of SARS-CoV-2: A perspective from analysis of genetic diversity of RdRp gene

Coronavirus disease 2019 emerged as the first example of “Disease X”, a hypothetical disease of humans caused by an unknown infectious agent that was named as novel coronavirus and subsequently designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The origin of the outbreak at the animal market in Wuhan, China implies it as a case of zoonotic spillover. The study was designed to understand evolution of Betacoronaviruses and in particular diversification of SARS-CoV-2 using RNA dependent RNA polymerase (RdRp) gene, a stable genetic marker. Phylogenetic and population stratification analyses were carried out using maximum likelihood and Bayesian methods, respectively. Molecular phylogeny using RdRp showed that SARS-CoV-2 isolates cluster together. Bat-CoV isolate RaTG13 and Pangolin-CoVs are observed to branch off prior to SARS-CoV-2 cluster. While SARS-CoV form a single cluster, Bat-CoVs form multiple clusters. Population-based analyses revealed that both SARS-CoV-2 and SARS-CoV form separate clusters with no admixture. Bat-CoVs were found to have single and mixed ancestry and clustered as four sub-populations. Population-based analyses of Betacoronaviruses using RdRp revealed that SARS-CoV-2 is a homogeneous population. SARS-CoV-2 appears to have evolved from Bat-CoV isolate RaTG13, which diversified from a common ancestor from which Pangolin-CoVs have also evolved. The admixed Bat-CoV sub-populations indicate that bats serve as reservoirs harboring virus ensembles that are responsible for zoonotic spillovers such as SARS-CoV and SARS-CoV-2. The extent of admixed isolates of Bat-CoVs observed in population diversification studies underline the need for periodic surveillance of bats and other animal reservoirs for potential spillovers as a measure towards preparedness for emergence of zoonosis.