From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways

The human body hosts an enormous abundance and diversity of microbes, which perform a range of essential and beneficial functions. Our appreciation of the importance of these microbial communities to many aspects of human physiology has grown dramatically in recent years. We know, for example, that animals raised in a germ-free environment exhibit substantially altered immune and metabolic function, while the disruption of commensal microbiota in humans is associated with the development of a growing number of diseases. Evidence is now emerging that, through interactions with the gut-brain axis, the bidirectional communication system between the central nervous system and the gastrointestinal tract, the gut microbiome can also influence neural development, cognition and behaviour, with recent evidence that changes in behaviour alter gut microbiota composition, while modifications of the microbiome can induce depressive-like behaviours. Although an association between enteropathy and certain psychiatric conditions has long been recognized, it now appears that gut microbes represent direct mediators of psychopathology. Here, we examine roles of gut microbiome in shaping brain development and neurological function, and the mechanisms by which it can contribute to mental illness. Further, we discuss how the insight provided by this new and exciting field of research can inform care and provide a basis for the design of novel, microbiota-targeted, therapies.GB Rogers, DJ Keating, RL Young, M-L Wong, J Licinio, and S Wesseling

Geriatric Oncology: Past, Present, Future

Efforts to integrate geriatric oncology principles in the training of all medical oncologists are underway

Screening Mammography for Frail Older Women: What are the Burdens?(*)

OBJECTIVE: The potential benefits and harms of screening mammography in frail older women are unknown. Therefore, we studied the outcomes of a screening mammography policy that was instituted in a population of community-living nursing home–eligible women as a result of requirements of state auditors. We focused on the potential burdens that may be experienced. METHODS: Between January 1995 and December 1997, we identified 216 consecutive women who underwent screening mammography after enrolling in a program designed to provide comprehensive care to nursing home–eligible patients who wished to stay at home. Mammograms were performed at 4 radiology centers. From computerized medical records, we tracked each woman through September 1999 for performance and results of mammography, additional breast imaging and biopsies, documentation of psychological reactions to screening, as well as vital status. Mean follow-up was 2.6 years. RESULTS: The mean age of the 216 women was 81 years. Sixty-three percent were Asian, 91% were dependent in at least 1 activity of daily living, 49% had cognitive impairment, and 11% died within 2 years. Thirty-eight women (18%) had abnormal mammograms requiring further work-up. Of these women, 6 refused work-up, 28 were found to have false-positive mammograms after further evaluation, 1 was diagnosed with ductal carcinoma in situ (DCIS), and 3 were diagnosed with local breast cancer. The woman diagnosed with DCIS and 1 woman diagnosed with breast cancer were classified as not having benefited, because screening identified clinically insignificant disease that would not have caused symptoms in the women's lifetimes, since these women died of unrelated causes within 2 years of diagnosis. Therefore, 36 women (17%; 95% confidence interval [CI], 12 to 22) experienced burden from screening mammography (28 underwent work-up for false-positive mammograms, 6 refused further work-up of an abnormal mammogram, and 2 had clinically insignificant cancers identified and treated). Forty-two percent of these women had chart-documented pain or psychological distress as a result of screening. Two women (0.9%; 95% CI, 0 to 2) may have received benefit from screening mammography. CONCLUSION: We conclude that screening mammography in frail older women frequently necessitates work-up that does not result in benefit, raising questions about policies that use the rate of screening mammograms as an indicator of the quality of care in this population. Encouraging individualized decisions may be more appropriate and may allow screening to be targeted to older women for whom the potential benefit outweighs the potential burdens