British Gynaecological Cancer Society recommendations and guidance on patient-initiated follow-up (PIFU)

The National Cancer Survivorship Initiative through the National Health Service (NHS) improvement in the UK started the implementation of stratified pathways of patient-initiated follow-up (PIFU) across various tumor types. Now the initiative is continued through the Living With and Beyond Cancer program by NHS England. Evidence from non-randomized studies and systematic reviews does not demonstrate a survival advantage to the long-established practice of hospital-based follow-up regimens, traditionally over 5 years. Evidence shows that patient needs are inadequately met under the traditional follow-up programs and there is therefore an urgent need to adapt pathways to the needs of patients. The assumption that hospital-based follow-up is able to detect cancer recurrences early and hence improve patient prognosis has not been validated. A recent survey demonstrates that follow-up practice across the UK varies widely, with telephone follow-up clinics, nurse-led clinics and PIFU becoming increasingly common. There are currently no completed randomized controlled trials in PIFU in gynecological malignancies, although there is a drive towards implementing PIFU. PIFU aims to individualize patient care, based on risk of recurrence and holistic needs, and optimizing resources. The British Gynaecological Cancer Society wishes to provide the gynecological oncology community with guidance and a recommendations statement regarding the value, indications, and limitations of PIFU in endometrial, cervical, ovarian, and vulvar cancers in an effort to standardize practice and improve patient care. [Abstract copyright: © IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Investigation of G72 (DAOA) expression in the human brain

<p>Abstract</p> <p>Background</p> <p>Polymorphisms at the G72/G30 locus on chromosome 13q have been associated with schizophrenia or bipolar disorder in more than ten independent studies. Even though the genetic findings are very robust, the physiological role of the predicted G72 protein has thus far not been resolved. Initial reports suggested G72 as an activator of D-amino acid oxidase (DAO), supporting the glutamate dysfunction hypothesis of schizophrenia. However, these findings have subsequently not been reproduced and reports of endogenous human G72 mRNA and protein expression are extremely limited. In order to better understand the function of this putative schizophrenia susceptibility gene, we attempted to demonstrate G72 mRNA and protein expression in relevant human brain regions.</p> <p>Methods</p> <p>The expression of G72 mRNA was studied by northern blotting and semi-quantitative SYBR-Green and Taqman RT-PCR. Protein expression in human tissue lysates was investigated by western blotting using two custom-made specific anti-G72 peptide antibodies. An in-depth <it>in silico </it>analysis of the G72/G30 locus was performed in order to try and identify motifs or regulatory elements that provide insight to G72 mRNA expression and transcript stability.</p> <p>Results</p> <p>Despite using highly sensitive techniques, we failed to identify significant levels of G72 mRNA in a variety of human tissues (e.g. adult brain, amygdala, caudate nucleus, fetal brain, spinal cord and testis) human cell lines or schizophrenia/control post mortem BA10 samples. Furthermore, using western blotting in combination with sensitive detection methods, we were also unable to detect G72 protein in a number of human brain regions (including cerebellum and amygdala), spinal cord or testis. A detailed <it>in silico </it>analysis provides several lines of evidence that support the apparent low or absent expression of G72.</p> <p>Conclusion</p> <p>Our results suggest that native G72 protein is not normally present in the tissues that we analysed in this study. We also conclude that the lack of demonstrable G72 expression in relevant brain regions does not support a role for G72 in modulation of DAO activity and the pathology of schizophrenia via a DAO-mediated mechanism. <it>In silico </it>analysis suggests that G72 is not robustly expressed and that the transcript is potentially labile. Further studies are required to understand the significance of the G72/30 locus to schizophrenia.</p

Dietary glutamine enhances cytokine production by murine macrophages

To examine the effects of dietary glutamine on cytokine production by macrophages, mice were fed for 2 wk on a control diet that included 200.0 g casein/kg providing 19.6 g glutamine/kg or a glutamine-enriched diet that provided 54.8 g glutamine/kg partly at the expense of casein. There were no differences in weight gain between animals fed the two diets. The plasma concentrations of a number of amino acids differed according to the diet fed; this variation largely reflected the variation in the levels of the different amino acids in the diets. Plasma glutamine concentration was not significantly affected by dietary glutamine level. The production of three cytokines, tumor necrosis factor-α, interleukin-1β, and interleukin-6, was greater for lipopolysaccharide-stimulated macrophages from mice fed the glutamine-enriched diet. Thus, increasing the amount of glutamine in the murine diet enhances the ability of macrophages to respond to stimulation, at least in terms of cytokine production. These observations suggest that increasing the availability of glutamine orally could promote immune responses involving macrophage-derived cytokines