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Enhancement of endogenous midbrain neurogenesis by microneurotrophin BNN-20 after neural progenitor grafting in a mouse model of nigral degeneration

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Neural Regeneration Research 2024年第6期19卷 1318-1324页

作者： Theodora Mourtzi nasia antoniou Christina Dimitriou Panagiotis Gkaravelas Georgia Athanasopoulou Panagiota Nti Kostantzo Olga Stathi Efthymia Theodorou Maria Anesti Rebecca Matsas Fevronia Angelatou Georgia Kouroupi Ilias Kazanis Laboratory of Developmental Biology Department of Biology University of Patras Laboratory of Cellular and Molecular Neurobiology-Stem Cells Hellenic Pasteur Institute 3. Department of Physiology School of Medicine University of Patras

We have previously shown the neuroprotective and pro-neurogenic activity of microneurotrophin BNN-20 in the substantia nigra of the “weaver” mouse, a model of progressive nigrostriatal degeneration. Here, we extended our investigation in two clinically-relevant ways. First, we assessed the effects of BNN-20 on human induced pluripotent stem cell-derived neural progenitor cells and neurons derived from healthy and parkinsonian donors. Second, we assessed if BNN-20 can boost the outcome of mouse neural progenitor cell intranigral transplantations in weaver mice, at late stages of degeneration. We found that BNN-20 has limited direct effects on cultured human induced pluripotent stem cell-derived neural progenitor cells, marginally enhancing their differentiation towards neurons and partially reversing the pathological phenotype of dopaminergic neurons generated from parkinsonian donors. In agreement, we found no effects of BNN-20 on the mouse neural progenitor cells grafted in the substantia nigra of weaver mice. However, the graft strongly induced an endogenous neurogenic response throughout the midbrain, which was significantly enhanced by the administration of microneurotrophin BNN-20. Our results provide straightforward evidence of the existence of an endogenous midbrain neurogenic system that can be specifically strengthened by BNN-20. Interestingly, the lack of major similar activity on cultured human induced pluripotent stem cell-derived neural progenitors and their progeny reveals the in vivo specificity of the aforementioned pro-neurogenic effect.

关键词： adult neurogenesis BNN-20 brain-derived neurotrophic factor cell replacement induced pluripotent stem cells (iPSCs) neurotrophic factors Parkinson’s disease substantia

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Factors Affecting Antibiotic Prescribing for Acute Respiratory Infection by Emergency Physicians

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Health 2014年第8期6卷 774-780页

作者： nasia Safdar Thomas G. Tape Barry C. Fox James E. Svenson Robert S. Wigton College of Medicine University of Nebraska Medical Center Omaha USA Division of Infectious Diseases Department of Medicine University of Wisconsin-Madison Madison USA Section of Emergency Medicine Department of Medicine University of Wisconsin-Madison Madison USA William S. Middleton Memorial Veterans Hospital Madison USA

Background: Antibiotics are frequently prescribed for upper acute respiratory tract infections (ARI) in the emergency department. To reduce inappropriate overprescribing, it is necessary to understand factors influencing physicians’ decisions to prescribe antibiotics. Objective: Analyze the judgment policies of emergency physicians to determine factors predicting antibiotic use. Design: Paper case vignette study. Participants: 104 emergency physicians from Wisconsin. Measurements: We used judgment analysis to derive the policies of 104 emergency physicians from their responses to 20 case vignettes. We designed the cases such that each physician’s use of clinical findings and patient factors could be inferred from the decisions they made about each case. Findings were compared to primary care practitioners (PCPs) in Colorado responding to the same paper cases to examine differences in factors influencing prescribing among the two groups. Results: The emergency physicians said they would prescribe an antibiotic (yes/no) in 51.4% of cases compared with 44.5% in the Colorado study. The majority of emergency physicians gave the greatest weight to duration of illness (51%), followed by temperature (20%) and cough (12%). Conclusions: These emergency physicians prescribed antibiotics more frequently than the Colorado PCPs. There was little difference in how clinical findings were weighted, suggesting this was not the source of the higher prescription rate among the emergency physicians. The considerable emphasis on duration of illness suggests that this would be a productive area for educational efforts to reduce antibiotic prescribing for ARI in the emergency department.

关键词： Antibiotic Infection Prescribing

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