Effects on Metabolism in Astrocytes Caused by cGAMP, Which Imitates the Initial Stage of Brain Metastasis.

The second messenger 2'3'-cyclic-GMP-AMP (cGAMP) is thought to be transmitted from brain carcinomas to astrocytes via gap junctions, which functions to promote metastasis in the brain parenchyma. In the current study, we established a method to introduce cGAMP into astrocytes, which simulates the state of astrocytes that have been invaded by cGAMP around tumors. Astrocytes incorporating cGAMP were analyzed by metabolomics, which demonstrated that cGAMP increased glutamate production and astrocyte secretion. The same trend was observed for γ-aminobutyric acid (GABA). Conversely, glutamine production and secretion were decreased by cGAMP treatment. Due to the fundamental role of astrocytes in regulation of the glutamine-glutamate cycle, such metabolic changes may represent a potential mechanism and therapeutic target for alteration of the central nervous system (CNS) environment and the malignant transformation of brain carcinomas.

Metabolome Shift in Both Metastatic Breast Cancer Cells and Astrocytes Which May Contribute to the Tumor Microenvironment.

The role of astrocytes in the periphery of metastatic brain tumors is unclear. Since astrocytes regulate central nervous metabolism, we hypothesized that changes in astrocytes induced by contact with cancer cells would appear in the metabolome of both cells and contribute to malignant transformation. Coculture of astrocytes with breast cancer cell supernatants altered glutamate (Glu)-centered arginine-proline metabolism. Similarly, the metabolome of cancer cells was also altered by astrocyte culture supernatants, and the changes were further amplified in astrocytes exposed to Glu. Inhibition of Glu uptake in astrocytes reduces the variability in cancer cells. Principal component analysis of the cancer cells revealed that all these changes were in the first principal component (PC1) axis, where the responsible metabolites were involved in the metabolism of the arginine-proline, pyrimidine, and pentose phosphate pathways. The contribution of these changes to the tumor microenvironment needs to be further pursued.

Caregiver Burden and Related Factors Among Caregivers of Patients with Myotonic Dystrophy Type 1.

BACKGROUND: Multi-systemic symptoms of varying severity in myotonic dystrophy type 1 (DM1) may pose difficulties in caregiving. However, the factors which affect their care burden are yet to be sufficiently understood. OBJECTIVE: We investigated care burden and its correlates among caregivers of patients with DM1. METHODS: General demographic information was obtained from patients with DM1, as well as Barthel index (ADL), body mass index, and genetic information. Patients completed SF-36v2 (health-related quality of life), CES-D (depressive symptoms), and ESS (daytime sleepiness) questionnaires. Caregivers reported their perception of patient's status through these questionnaires, and completed Zarit Caregiver Burden Interview (ZBI). Correlation analysis of these variables were performed, and regression analysis was utilized to assess the relationship between caregiver burden and other variables. RESULTS: Forty-three patient-caregiver dyads participated. Mean ZBI score was 20.7±17.4, and 32.6% reported a significant care burden. ZBI correlated with caregiver-reported CES-D, but not with patient-reported CES-D. Both patient-reported and caregiver-reported physical QoL of patients correlated with patient ADL. Multiple regression analysis revealed that the combination of caregiver-reported CES-D, caregiver-reported mental QoL, and genetic characteristics predicted caregiver burden. CONCLUSIONS: Caregiver burden was felt although patients were relatively well-functioning. Patients' and caregivers' assessment of patients' physical condition were similar. However, they did not agree on the evaluation of the patients' psychological state. Cognitive characteristic of the patients and the caregivers' perception of the patients' state may have affected the results. Future DM1 care strategies need to work on improvement of patient-caregiver communication and provide support for the caregiver's psychological health.

Health-related quality of life and its correlates in Japanese patients with myotonic dystrophy type 1.

PURPOSE: Myotonic dystrophy type 1 (DM1) is a common form of muscular dystrophy that presents with a variety of symptoms that can affect patients' quality of life (QoL). Despite the importance of clarifying patients' subjective experience in both physical and psychosocial aspects for improved symptom management, there is lack of evidence concerning QoL of patients with DM1 in Japan. PATIENTS AND METHODS: A cross-sectional study was performed with 51 DM1 patients who completed questionnaires that measured health-related QoL (HRQoL), depression, and daytime sleepiness. Activities of daily living, body mass index (BMI), and genetic information were also collected, together with general demographic information. Correlation analyses using these variables were performed. Furthermore, regression analysis was utilized to assess the relationship that HRQoL, depression, and daytime sleepiness scores have with other variables. RESULTS: Physical component summary (PCS) score was affected by the disease more than the mental component summary (MCS) score among study participants. Moderate correlation was observed between PCS and depression, PCS and Barthel index, and depression and daytime sleepiness. Regression analysis revealed that age, sex, cytosine-thymine-guanine repeats, and BMI did not predict the aforementioned dependent variables. CONCLUSION: DM1 symptoms influenced physical component scores more than mental component scores, although the state of physical wellness seemed to affect patients' mood. Explaining the QoL of these patients only using biologic and genetic characteristics was not sufficient. We conclude that social and psychological aspects of these patients' lives and the nature of adjustments made by patients due to DM1 to require further examination in order to improve the standard of care.

Freundlich and dual Langmuir isotherm models for predicting 137Cs binding on Savannah River Site soils.

Distribution of 137Cs and stable cesium between aqueous solution and near-surface soil samples from five locations at the Savannah River Site was measured in order to develop a predictive model for 137Cs uptake by the soils. Sorption of 137Cs in these soils appears to be mostly by hydroxy-interlayered vermiculite. Batch sorption studies with 4 d for equilibration were conducted at three cesium concentrations and at two backing electrolyte (NaNO3) concentrations. The soil-solution mixtures were pH-adjusted to evaluate the effects of pH on cesium sorption. Sorbed cesium was related to the equilibrium aqueous cesium concentrations by a Freundlich isotherm model. Model fits on logarithmic scales have a common slope of 0.60 +/- 0.03 for acidic mixtures and 0.69 +/- 0.04 for neutralized mixtures but have unique intercepts that are influenced by backing electrolyte concentration and pH. An ion-exchange model is proposed that pertains to all five soils and relates the Freundlich isotherms to the cation exchange capacity of soil and the aqueous concentrations of cesium, sodium, and a third ionic species that was hydrogen in the acidic mixtures and potassium in the neutralized mixtures. Model fits are consistent with Kd values in the entire range of 5-2,300 L kg(-1) determined for the five soil types. As an alternate model, dual Langmuir isotherms were fitted to the data. The results suggest cesium sorption by (1) relatively few interlayer-wedge sites, highly selective for cesium, and (2) much more abundant but less selective sites on internal and external planar surfaces.