New neurons are added to the adult hippocampus throughout life and contribute to cognitive functions including learning and memory. It remains unclear whether ongoing neurogenesis arises from self-renewing neural stem cells (NSC) or from multipotential progenitor cells that cannot self-renew in the hippocampus. This is largely based on observations that neural precursors derived from the subventricular zone (SVZ) can be passaged long-term whereas hippocampal subgranular zone (SGZ) precursors are rapidly depleted by passaging. We demonstrate here that high levels of BMP signaling occur in hippocampal but not SVZ precursors in vitro, and blocking BMP signaling with Noggin is sufficient to foster hippocampal cell self-renewal, proliferation, and multipotentiality using single cell clonal analysis. Moreover, NSC maintenance requires continual Noggin exposure, which implicates BMPs as crucial requlators of NSC aging. In vivo, Noggin is expressed in the adult dentate gyrus and limits BMP signaling in proliferative cells of the SGZ. Transgenic Noggin overexpression in the SGZ increases multiple precursor cell populations, but proportionally increases the glial fibrillary acidic protein (GFAP)+ cell population at the expense of other precursors, suggesting that Noggin acts on NSCs in vivo. To confirm this, we used a dual thymidine analog paradigm to repeatedly label slowly dividing cells over a long duration. We find that small populations of label-retaining cells exist in the SGZ and that Noggin overexpression increases their numbers. Thus, we propose that the adult hippocampus contains a population of NSCs, which can be expanded both in vitro and in vivo by blocking BMP signaling.
Survivors of preterm birth often present with medical morbidities; however, variation in their long-term educational performance has not been well described.OBJECTIVE To estimate the association between gestational age and 4 outcomes in school-aged children: readiness to enter kindergarten, scores on standardized tests in elementary and middle school, gifted status, and low performance. DESIGN, SETTING, AND PARTICIPANTSIn a retrospective cohort study, children born in Florida between 1992 and 2002 at 23 to 41 weeks' gestation who entered Florida's public schools between 1995 and 2012 were assessed for kindergarten readiness and tested in mathematics and reading in grades 3 through 8. Data analysis was performed from January 12, 2016, to March 1, 2017.EXPOSURES Gestational age at birth. MAIN OUTCOMES AND MEASURES Kindergarten readiness, scores on the FloridaComprehensive Achievement Test (FCAT), classified as gifted, and classified as low performance.RESULTS A total of 1 527 113 singleton infants with gestational ages of 23 to 41 weeks born between 1992 and 2002 were matched to Florida public school records. Of these, 1 301 497 children were included in the analysis; 641 479 (49.3%) were girls. A total of 301 (65.0%) Florida children born at 23 to 24 weeks' gestation were designated as ready to start kindergarten. When the FCAT test scores were adjusted for potentially confounding maternal and infant variables, children born at 23 to 24 weeks' gestation performed 0.66 SD (95% CI, −0.73 to −0.59) lower compared with those born at full term. A total of 123 554 (9.5%) of all Florida-born public school students were considered gifted, including 17 (1.8%) of those born at 23 to 24 weeks' gestation. In comparison, 75 458 (5.8%) of all Florida-born public school students were low performing; 310 (33.5%) of these children had been born at 23 to 24 weeks' gestation. Kindergarten readiness, FCAT scores, and gifted status were positively related to gestational age, whereas low performance was inversely related to gestational age. CONCLUSIONS AND RELEVANCEAlthough gestational age has long been associated with poor educational performance, a sufficient proportion of children born near the limits of viability performed within expected school norms, warranting further investigation into how and why certain children are able to overcome the educational burdens that may follow preterm birth.
Early onset sepsis in the newborn infant continues to be an important clinical problem for neonatologists everywhere in the world. Different routes of transmission, changes in causative agents, and potential antibiotic resistance all influence the choice of antibiotic therapy. Group B Streptococcus and Escherichia coli continue to be the major pathogens dictating antibiotic therapy in the United States. Ampicillin and gentamicin are the antibiotics used by most for empirical therapy; cephalosporins are used in certain clinical situations. In this review, we address the reasons for these choices while highlighting clinically relevant aspects of the antibiotics commonly used in the treatment of early onset sepsis in the newborn.
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