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Objective: To determine sex differences in the neurochemical concentrations measured by in vivo proton magnetic resonance spectroscopy (1H MRS) of healthy mice on a genetic background commonly used for neurodegenerative disease models. Methods: 1H MRS data collected from wild type mice with C57BL/6 or related genetic backgrounds in seven prior studies were used in this retrospective analysis. To be included, data had to be collected at 9.4 tesla magnetic field using advanced 1H MRS protocols, with isoflurane anesthesia and similar animal handling protocols, and a similar number of datasets from male and female mice had to be available for the brain regions analyzed. Overall, 155 spectra from female mice and 166 spectra from male mice (321 in total), collected from six brain regions (brainstem, cerebellum, cortex, hippocampus, hypothalamus, and striatum) at various ages were included. Results: Concentrations of taurine, total creatine (creatine + phosphocreatine), ascorbate, glucose and glutamate were consistently higher in male vs. female mice in most brain regions. Striatum was an exception with similar total creatine in male and female mice. The sex difference pattern in the hypothalamus was notably different from other regions. Interaction between sex and age was significant for total creatine and taurine in the cerebellum and hippocampus. Conclusion: Sex differences in regional neurochemical levels are small but significant and age-dependent, with consistent male-female differences across most brain regions. The neuroendocrine region hypothalamus displays a different pattern of sex differences in neurochemical levels. Differences in energy metabolism and cellular density may underlie the differences, with higher metabolic rates in females and higher osmoregulatory and antioxidant capacity in males.
RESUMEN
OBJECTIVE: Active treatment for periviable infants may be influenced by neonatal and obstetric provider perceptions of prognosis. The two aims of this study are to (1) quantify prognostic discordance between provider and data-driven survival estimates and (2) evaluate if prognostic discordance is associated with the threshold probability of survival at which neonatal providers recommend active treatment or obstetric providers recommend antenatal corticosteroids. STUDY DESIGN: Provider survival estimates and threshold probabilities of survival for active treatment and antenatal steroid use were obtained from a case-based survey for an infant or pregnancy at 22 weeks' gestation that was administered at two Atlanta hospitals. Data-driven survival estimates, including ranges, were acquired through the National Institute of Child Health and Human Development Extremely Preterm Birth Outcomes Tool. Prognostic discordance was calculated as the difference between a provider and data-driven estimates and classified as pessimistic (provider estimate below data-driven estimate range), accurate (within range), or optimistic (above range). The association between prognostic discordance and the threshold probability of survival was evaluated using nonparametric tests. RESULTS: We had 137 neonatal respondents (51% response rate) and 57 obstetric responses (23% response rate). The overall median prognostic discordance was 1.5% (interquartile range: 17, 13) and 52 (27%) of all respondents were pessimistic, 100 (52%) were accurate, and 42 (22%) were optimistic. The survival threshold above which neonatal and obstetric providers recommended active treatment or antenatal corticosteroids was 30% (20-45%) and 10% (0-20%), respectively. Thresholds did not significantly differ among the three prognostic discordance groups (p = 0.45 for neonatal and p = 0.53 for obstetric providers). There was also no significant correlation between the magnitude of prognostic discordance and thresholds. CONCLUSION: Prognostic discordance exists among both neonatal and obstetric providers. However, this discordance is not associated with the threshold probability of survival at which providers recommend active treatment or antenatal corticosteroids at 22 weeks' gestation. KEY POINTS: · Prognostic discordance at 22 weeks' gestation exists for neonatal and obstetric providers.. · Prognostic discordance is not associated with survival thresholds for neonatal active treatment.. · Prognostic discordance is not associated with survival thresholds for the use of antenatal corticosteroids..
