Severe paraneoplastic hypoglycemia in a patient with a gastrointestinal stromal tumor with an exon 9 mutation: a case report

BACKGROUND: Non-islet cell tumor induced hypoglycemia (NICTH) is a very rare phenomenon, but even more so in gastrointestinal stromal tumors. It tends to present in large or metastatic tumors, and can appear at any time in the progression of the disease. We present herein a case of NICTH in a GIST tumor and report an exon 9 mutation associated to it. CASE PRESENTATION: A thirty nine year-old man with a recurrent, metastatic gastrointestinal stromal tumor presented to the hospital with nausea, dizziness, loss of consciousness, and profound hypoglycemia (20 mg/dL). There was no evidence of factitious hypoglycemia. He was stabilized with a continuous glucose infusion and following selective vascular embolization, the patient underwent debulking of a multicentric 40 cm × 25 cm × 10 cm gastrointestinal stromal tumor. After resection, the patient became euglycemic and returned to his normal activities. Tumor analysis confirmed excessive production of insulin-like growth factor II m-RNA and the precursor protein, "big" insulin-like growth factor II. Mutational analysis also identified a rare, 6 bp tandem repeat insert (gcctat) at position 1530 in exon 9 of KIT. CONCLUSION: Optimal management of gastrointestinal stromal tumor-induced hypoglycemia requires a multidisciplinary approach, and surgical debulking is the treatment of choice to obtain immediate symptom relief. Imatinib or combinations of glucocorticoids and growth hormone are alternative palliative strategies for symptomatic hypoglycemia. In addition, mutations in exon 9 of the tyrosine kinase receptor KIT occur in 11–20% of GIST and are often associated with poor patient outcomes. The association of this KIT mutation with non-islet cell tumor induced hypoglycemia has yet to be established

PI3Kγ is a molecular switch that controls immune suppression

Macrophages play critical, but opposite, roles in acute and chronic inflammation and cancer1,2,3,4,5. In response to pathogens or injury, inflammatory macrophages express cytokines that stimulate cytotoxic T cells, whereas macrophages in neoplastic and parasitic diseases express anti-inflammatory cytokines that induce immune suppression and may promote resistance to T cell checkpoint inhibitors1,2,3,4,5,6,7. Here we show that macrophage PI 3-kinase γ controls a critical switch between immune stimulation and suppression during inflammation and cancer. PI3Kγ signalling through Akt and mTor inhibits NFκB activation while stimulating C/EBPβ activation, thereby inducing a transcriptional program that promotes immune suppression during inflammation and tumour growth. By contrast, selective inactivation of macrophage PI3Kγ stimulates and prolongs NFκB activation and inhibits C/EBPβ activation, thus promoting an immunostimulatory transcriptional program that restores CD8+ T cell activation and cytotoxicity. PI3Kγ synergizes with checkpoint inhibitor therapy to promote tumour regression and increased survival in mouse models of cancer. In addition, PI3Kγ-directed, anti-inflammatory gene expression can predict survival probability in cancer patients. Our work thus demonstrates that therapeutic targeting of intracellular signalling pathways that regulate the switch between macrophage polarization states can control immune suppression in cancer and other disorders

Understanding adaptation to first episode psychosis through the creation of images

This article aims to understand and explore the meaning of adaptation to First Episode Psychosis (FEP). An innovative method of data collection was used with ten participants who experienced FEP which integrated drawings of their lived experience within semi-structured interviews. The data were analysed through Interpretative Phenomenological Analysis and hermeneutic-phenomenological image analysis. Participants’ experience was captured in four superordinate themes which identified that adaptation to FEP entailed: ‘Finding out how psychosis fits into my story’, ‘Breaking free from psychosis’, ‘Fighting my way through psychosis’, and ‘Finding a new way of being ‘me’’. The participants’ path of adaptation to FEP was an interplay of pains, challenges, and gains, and there was resonance with posttraumatic growth in their accounts. This article illustrates that creating images may offer a powerful way of conveying the multifaceted aspects of adaptation to FEP and could help individuals in communicating and processing their experience

Like Mother(-in-Law) Like Daughter? Influence of the Older Generation’s Fertility Behaviours on Women’s Desired Family Size in Bihar, India

This paper investigates the associations between preferred family size of women in rural Bihar, India and the fertility behaviours of their mother and mother-in-law. Scheduled interviews of 440 pairs of married women aged 16–34 years and their mothers-in-law were conducted in 2011. Preferred family size is first measured by Coombs scale, allowing us to capture latent desired number of children and then categorized into three categories (low, medium and high). Women’s preferred family size is estimated using ordered logistic regression. We find that the family size preferences are not associated with mother’s fertility but with mother’s education. Mother-in-law’s desired number of grandchildren is positively associated with women’s preferred family size. However, when the woman has higher education than her mother-in-law, her preferred family size gets smaller, suggesting that education provides women with greater autonomy in their decision-making on childbearing

Effect of hosts on competition among clones and evidence of differential selection between pathogenic and saprophytic phases in experimental populations of the wheat pathogen Phaeosphaeria nodorum

<p>Abstract</p> <p>Background</p> <p>Monoculture, multi-cropping and wider use of highly resistant cultivars have been proposed as mechanisms to explain the elevated rate of evolution of plant pathogens in agricultural ecosystems. We used a mark-release-recapture experiment with the wheat pathogen <it>Phaeosphaeria nodorum </it>to evaluate the impact of two of these mechanisms on the evolution of a pathogen population. Nine <it>P. nodorum </it>isolates marked with ten microsatellite markers and one minisatellite were released onto five replicated host populations to initiate epidemics of Stagonospora nodorum leaf blotch. The experiment was carried out over two consecutive host growing seasons and two pathogen collections were made during each season.</p> <p>Results</p> <p>A total of 637 pathogen isolates matching the marked inoculants were recovered from inoculated plots over two years. Genetic diversity in the host populations affected the evolution of the corresponding <it>P. nodorum </it>populations. In the cultivar mixture the relative frequencies of inoculants did not change over the course of the experiment and the pathogen exhibited a low variation in selection coefficients.</p> <p>Conclusions</p> <p>Our results support the hypothesis that increasing genetic heterogeneity in host populations may retard the rate of evolution in associated pathogen populations. Our experiment also provides indirect evidence of fitness costs associated with host specialization in <it>P. nodorum </it>as indicated by differential selection during the pathogenic and saprophytic phases.</p

Change & Maintaining Change in School Cafeterias: Economic and Behavioral-Economic Approaches to Increasing Fruit and Vegetable Consumption

Developing a daily habit of consuming fruits and vegetables (FV) in children is an important public-health goal. Eating habits acquired in childhood are predictive of adolescent and adult dietary patterns. Thus, healthy eating patterns developed early in life can protect the individual against a number of costly health deficits and may reduce the prevalence of obesity. At present, children in the United States (US) under-consume FV despite having access to them through the National School Lunch Program. Because access is an obstacle to developing healthy eating habits, particularly in low-income households, targeting children’s FV consumption in schools has the advantage of near-universal FV availability among more than 30 million US children. This chapter reviews economic and behavioral-economic approaches to increasing FV consumption in schools. Inclusion criteria include objective measurement of FV consumption (e.g., plate waste measures) and minimal demand characteristics. Simple but effective interventions include (a) increasing the variety of vegetables served, (b) serving sliced instead of whole fruits, (c) scheduling lunch after recess, and (d) giving children at least 25 minutes to eat. Improving the taste of FV and short-term incentivizing consumption of gradually increasing amounts can produce large increases in consumption of these foods. Low-cost game-based incentive program may increase the practicality of the latter strategy