epDevAtlas: Mapping GABAergic cells and microglia in postnatal mouse brains.

During development, brain regions follow encoded growth trajectories. Compared to classical brain growth charts, high-definition growth charts could quantify regional volumetric growth and constituent cell types, improving our understanding of typical and pathological brain development. Here, we create high-resolution 3D atlases of the early postnatal mouse brain, using Allen CCFv3 anatomical labels, at postnatal days (P) 4, 6, 8, 10, 12, and 14, and determine the volumetric growth of different brain regions. We utilize 11 different cell type-specific transgenic animals to validate and refine anatomical labels. Moreover, we reveal region-specific density changes in γ-aminobutyric acid-producing (GABAergic), cortical layer-specific cell types, and microglia as key players in shaping early postnatal brain development. We find contrasting changes in GABAergic neuronal densities between cortical and striatal areas, stabilizing at P12. Moreover, somatostatin-expressing cortical interneurons undergo regionally distinct density reductions, while vasoactive intestinal peptide-expressing interneurons show no significant changes. Remarkably, microglia transition from high density in white matter tracks to gray matter at P10, and show selective density increases in sensory processing areas that correlate with the emergence of individual sensory modalities. Lastly, we create an open-access web-visualization (https://kimlab.io/brain-map/epDevAtlas) for cell-type growth charts and developmental atlases for all postnatal time points.

Developmental Mouse Brain Common Coordinate Framework.

3D standard reference brains serve as key resources to understand the spatial organization of the brain and promote interoperability across different studies. However, unlike the adult mouse brain, the lack of standard 3D reference atlases for developing mouse brains has hindered advancement of our understanding of brain development. Here, we present a multimodal 3D developmental common coordinate framework (DevCCF) spanning mouse embryonic day (E) 11.5, E13.5, E15.5, E18.5, and postnatal day (P) 4, P14, and P56 with anatomical segmentations defined by a developmental ontology. At each age, the DevCCF features undistorted morphologically averaged atlas templates created from Magnetic Resonance Imaging and co-registered high-resolution templates from light sheet fluorescence microscopy. Expert-curated 3D anatomical segmentations at each age adhere to an updated prosomeric model and can be explored via an interactive 3D web-visualizer. As a use case, we employed the DevCCF to unveil the emergence of GABAergic neurons in embryonic brains. Moreover, we integrated the Allen CCFv3 into the P56 template with stereotaxic coordinates and mapped spatial transcriptome cell-type data with the developmental ontology. In summary, the DevCCF is an openly accessible resource that can be used for large-scale data integration to gain a comprehensive understanding of brain development.

Seeing the Forest and Its Trees Together: Implementing 3D Light Microscopy Pipelines for Cell Type Mapping in the Mouse Brain.

The brain is composed of diverse neuronal and non-neuronal cell types with complex regional connectivity patterns that create the anatomical infrastructure underlying cognition. Remarkable advances in neuroscience techniques enable labeling and imaging of these individual cell types and their interactions throughout intact mammalian brains at a cellular resolution allowing neuroscientists to examine microscopic details in macroscopic brain circuits. Nevertheless, implementing these tools is fraught with many technical and analytical challenges with a need for high-level data analysis. Here we review key technical considerations for implementing a brain mapping pipeline using the mouse brain as a primary model system. Specifically, we provide practical details for choosing methods including cell type specific labeling, sample preparation (e.g., tissue clearing), microscopy modalities, image processing, and data analysis (e.g., image registration to standard atlases). We also highlight the need to develop better 3D atlases with standardized anatomical labels and nomenclature across species and developmental time points to extend the mapping to other species including humans and to facilitate data sharing, confederation, and integrative analysis. In summary, this review provides key elements and currently available resources to consider while developing and implementing high-resolution mapping methods.

Diagnosis and management of external iliac endofibrosis: A case report.

External iliac artery endofibrosis is an uncommon, nonatherosclerotic disease seen in endurance cyclists. It is poorly identified by providers. These otherwise healthy patients usually present with symptoms of arterial insufficiency, such as thigh or buttock pain, loss of power, or weakness occurring during strenuous exercises. These symptoms subside rapidly with rest. As these patients lack traditional risk factors of peripheral artery disease, their symptoms are often overlooked or are attributed to other etiologies, resulting in mismanagement and delayed treatment. In this case study, we report our experience with the successful management of a 48-year-old male who is a longstanding, avid cyclist. He self-referred to our institution after extensive research of providers familiar with his problem and at the recommendation of other cyclists with similar experiences. The patient underwent a successful left external iliac to common femoral artery endarterectomy and patch angioplasty. Three months after operation, he returned to cycling and, for the most part, has remained without symptoms.

Exercise therapy for claudication: Should home-based exercise therapy be prescribed in clinical practice?

Peripheral artery disease is a cause of morbidity and mortality in the United States. The literature suggests evidence that an exercise program can be beneficial in the treatment of patients with claudication. Supervised exercise therapy is well documented in the literature, and national guidelines recommend it as an initial conservative management. When a supervised exercise program is unavailable or not covered by insurance, an alternative to supervised exercise is vital. The purpose of this review is to examine the evidence regarding the efficacy of a home-based exercise program. Four studies were included in this review, and although the evidence supporting a home-based exercise program is limited in the literature, the findings indicate that a home-based exercise program increases claudication onset time, resulting in greater mobility and improvement in the patient's quality of life.

In vitro determination of active bile acid absorption in small biopsy specimens obtained endoscopically or surgically from the human intestine.

BACKGROUND: In the construction of a Kock reservoir for continent urinary diversion, 70 cm of the distal ileum are used. Impaired absorption of bile acids in these patients might cause diarrhoea. Data on the absorption of bile acids in different parts of the human intestine are limited. METHODS: Biopsies were taken during endoscopy from the duodenum, the terminal ileum or the right colon, and during surgery 10, 50, 100 and 150 cm proximally to the ileo-caecal valve using standard endoscopy biopsy forceps. The biopsy specimens were incubated in vitro with radio-labelled taurocholic acid at 37 degrees C for 22 or 45 min The radioactivity was determined using the liquid scintillation technique. RESULTS: A linear increase in the uptake was observed, with increased concentrations of taurocholic acid between 100 and 500 microm in all specimens tested, that represented passive uptake or unspecific binding. The active uptake could be calculated from the intercept of the line representing passive uptake with the ordinate. The active uptake in the terminal ileum was 3-4 times greater than 100 cm proximal to the valve. CONCLUSIONS: The active absorption of bile acids in humans can be determined in small biopsy specimens taken using standard biopsy forceps during endoscopy or surgery. This method is suitable for clinical studies of bile acid absorption. Active uptake of bile acids not only takes place in the very distal part of the ileum but also to a considerable degree 100 cm proximally to the ileo-colonic valve. This should be taken into account when selecting the ileal segment for continent urinary diversion.

Smoking behavior in nine year old children: a replication and extension study.

This study replicates and extends the results of our earlier findings which showed that 35% of children at age 9 had experimented with cigarettes for various reasons. Seven hundred eighty-seven children from the earlier sample and 361 children from the current sample participated in this study. Forty-one percent of the current sample had puffed a cigarette, 18% had tried it in the last year, 6% in the last 4 weeks and 3.5% in the last week. The study also showed that children who had puffed a cigarette had a significantly positive attitude towards smoking when compared with children who had not experimented with cigarettes. The puffers believed smoking is good, wise and fun.