In Situ Classification of Cell Types in Human Kidney Tissue Using 3D Nuclear Staining.

To understand the physiology and pathology of disease, capturing the heterogeneity of cell types within their tissue environment is fundamental. In such an endeavor, the human kidney presents a formidable challenge because its complex organizational structure is tightly linked to key physiological functions. Advances in imaging-based cell classification may be limited by the need to incorporate specific markers that can link classification to function. Multiplex imaging can mitigate these limitations, but requires cumulative incorporation of markers, which may lead to tissue exhaustion. Furthermore, the application of such strategies in large scale 3-dimensional (3D) imaging is challenging. Here, we propose that 3D nuclear signatures from a DNA stain, DAPI, which could be incorporated in most experimental imaging, can be used for classifying cells in intact human kidney tissue. We developed an unsupervised approach that uses 3D tissue cytometry to generate a large training dataset of nuclei images (NephNuc), where each nucleus is associated with a cell type label. We then devised various supervised machine learning approaches for kidney cell classification and demonstrated that a deep learning approach outperforms classical machine learning or shape-based classifiers. Specifically, a custom 3D convolutional neural network (NephNet3D) trained on nuclei image volumes achieved a balanced accuracy of 80.26%. Importantly, integrating NephNet3D classification with tissue cytometry allowed in situ visualization of cell type classifications in kidney tissue. In conclusion, we present a tissue cytometry and deep learning approach for in situ classification of cell types in human kidney tissue using only a DNA stain. This methodology is generalizable to other tissues and has potential advantages on tissue economy and non-exhaustive classification of different cell types.

Substantia nigra depigmentation and exposure to encephalitis lethargica.

OBJECTIVE: Parkinsonism has occasionally been reported as a consequence of infectious diseases. The present study examines the clinical and pathological correlates of parkinsonism across birth cohorts in relation to critical exposure to the encephalitis lethargica epidemic in the early 1900s. METHODS: The study population consisted of 678 participants in the Nun Study, of whom 432 died and came to autopsy. Qualitative indices of substantia nigra (SN) depigmentation were verified in a subset of 40 randomly selected subjects using quantitative stereological techniques. SN depigmentation, detected neuropathologically, was correlated with clinical parameters of Parkinson disease, age, and birth cohort. RESULTS: SN depigmentation was detected in 57 (13.2%) of the cohort. Although qualitative SN depigmentation correlated modestly with age (p = 0.02), it correlated best with birth cohort (p = 0.009) for women born in the years 1895-1899. Quantitative measures of SN depigmentation were increased in this birth cohort compared to age matched subjects from flanking birth cohorts 1890-1894 and 1900-1904 (p < 0.001). SN depigmentation correlated with speed of 6- and 50-foot walk (p < 0.0001), up and go test (p < 0.0001), and hand coordination (p < 0.0001). INTERPRETATION: Subjects in the birth cohort 1895-1899 would have been in their late teens and 20s at the onset and during the peak of the encephalitis lethargica epidemic. These were precisely the age ranges of persons who were most often affected by the illness. These data suggest the possibility that the coexistence of parkinsonism and SN depigmentation in this birth cohort may have resulted from the yet undetermined infectious agent responsible for encephalitis lethargica.

The impact of proactive rounding on rapid response team calls: an observational study.

BACKGROUND: Rapid response teams (RRTs) improve mortality by intervening in the hours preceding arrest. Implementation of these teams varies across institutions. SETTING AND DESIGN: Our health-care system has two different RRT models at two hospitals: Hospital A does not utilize a proactive rounder while Hospital B does. We studied the patterns of RRT calls at each hospital focusing on the differences between night and day and during nursing shift transitions. RESULTS: The presence of proactive surveillance appeared to be associated with an increased total number of RRT calls with more than twice as many calls made at the smaller Hospital B than Hospital A. Hospital B had more calls in the daytime compared to the nighttime. Both hospitals showed a surge in the night-to-day shift transition (7-8am) compared to the preceding nighttime. Hospital A additionally showed a surge in calls during the day-to-night shift transition (7-8pm) compared to the preceding daytime. CONCLUSIONS: Differences in the diurnal patterns of RRT activation exist between hospitals even within the same system. As a continuously learning system, each hospital should consider tracking these patterns to identify their unique vulnerabilities. More calls are noted between 7-8am compared to the overnight hours. This may represent the reestablishment of the 'afferent' arm of the RRT as the hospital returns to daytime staffing and activity. Factors that influence the impact of proactive rounding on RRT performance may deserve further study.

Neurosyphilis.

No portion of the central nervous system is immune to the ravages of syphilis. Infection by Treponema pallidum can affect the meninges, brain, brainstem, spinal cord, nerve roots, and cerebral and spinal blood vessels. As a consequence, the disease may present in diverse and, at times, diagnostically challenging fashions. Neurologic manifestations of syphilis may develop within months of the initial infection or, alternatively, take decades to appear. Although approximately one-third of individuals infected by T. pallidum display cerebrospinal fluid abnormalities suggestive of invasion of the central nervous system by the organism, only a fraction of these develop clinically significant neurologic manifestations. The features of neurosyphilis may be modified by the concomitant presence of immunosuppressive agents or conditions such as HIV/AIDS. The epidemiology of neurosyphilis has largely paralleled that of syphilis in general. A dramatic decline occurred by the early 1950s as a consequence of public health measures and the widespread use of antibiotics. The incidence had increased by the onset of the AIDS pandemic and has since corresponded with the adoption of safe sex practices. The CSF Venereal Disease Research Laboratory (VDRL) test remains the "gold standard" for diagnosis, but is not invariably positive. Penicillin remains the most effective and recommended therapy.