Hydronephrosis with an undetermined pathology is a common condition detected in imaging studies. In urological clinical practice, it is a persistent dilemma to predict whether this condition will progress to result in the deterioration of renal function. Perfusion pressure flow study of the upper urinary tract, known as the Whitaker test, provides an alternative diagnostic tool for solving this condition. Perfusion pressure flow study has been criticized for its invasiveness, nonphysiological approach, and inconsistency in predicting outcomes. However, it continues to be used to evaluate difficult or equivocal cases and to provide an objective assessment of the upper urinary tract. 相似文献
The accumulation of abnormal prion protein (PrPSc) produced by the structure conversion of PrP (PrPC) in the brain induces prion disease. Although the conversion process of the protein is still not fully elucidated, it has been known that the intramolecular chemical bridging in the most fragile pocket of PrP, known as the “hot spot,” stabilizes the structure of PrPC and inhibits the conversion process. Using our original structure-based drug discovery algorithm, we identified the low molecular weight compounds that predicted binding to the hot spot. NPR-130 and NPR-162 strongly bound to recombinant PrP in vitro, and fragment molecular orbital (FMO) analysis indicated that the high affinity of those candidates to the PrP is largely dependent on nonpolar interactions, such as van der Waals interactions. Those NPRs showed not only significant reduction of the PrPSc levels but also remarkable decrease of the number of aggresomes in persistently prion-infected cells. Intriguingly, treatment with those candidate compounds significantly prolonged the survival period of prion-infected mice and suppressed prion disease-specific pathological damage, such as vacuole degeneration, PrPSc accumulation, microgliosis, and astrogliosis in the brain, suggesting their possible clinical use. Our results indicate that in silico drug discovery using NUDE/DEGIMA may be widely useful to identify candidate compounds that effectively stabilize the protein.Electronic supplementary materialThe online version of this article (10.1007/s13311-020-00903-9) contains supplementary material, which is available to authorized users. 相似文献
ObjectiveWe aimed to establish an objective neurophysiological test protocol that can be used to assess the somatosensory nervous system.MethodsIn order to assess most fiber subtypes of the somatosensory nervous system, repetitive stimuli of seven different modalities (touch, vibration, pinprick, cold, contact heat, laser, and warmth) were synchronized with the electroencephalogram (EEG) and applied on the cheek and dorsum of the hand and dorsum of the foot in 21 healthy subjects and three polyneuropathy (PNP) patients. Latencies and amplitudes of the modalities were assessed and compared. Patients received quantitative sensory testing (QST) as reference.ResultsWe found reproducible evoked potentials recordings for touch, vibration, pinprick, contact-heat, and laser stimuli. The recording of warm-evoked potentials was challenging in young healthy subjects and not applicable in patients. Latencies were shortest within Aβ-fiber-mediated signals and longest within C-fibers. The test protocol detected function loss within the Aβ-fiber and Aδ-fiber-range in PNP patients. This function loss corresponded with QST findings.ConclusionIn this pilot study, we developed a neurophysiological test protocol that can specifically assess most of the somatosensory modalities. Despite technical challenges, initial patient data appear promising regarding a possible future clinical application.SignificanceEstablished and custom-made stimulators were combined to assess different fiber subtypes of the somatosensory nervous system using modality-specific evoked potentials. 相似文献
Objective: Keyes’ two continua model is a useful concept in which mental health and mental illness exist on two separate axes. Based on this model, this study examined the prevalence and correlates of three mental health categories among older adults in China.
Methods: Cross-sectional data were derived from Wave 1 of the Study on Global AGEing and Adult Health. Participants were categorized into complete mental health (CMH), complete mental illness (CMI), and moderate mental health (MMH) groups. Multinomial logistic regressions were used.
Results: The prevalence of CMH, CMI, and MMH in China was 18%, 16%, and 66%, respectively. Being female, unmarried, younger, and feeling unhealthy were more likely to result in placement in the CMI category. Employment, education, and cognitive function were identified as important protective factors of CMH. Age, income, urban or rural residence, and physical function difficulty were associated with all three categories.
Discussion: We demonstrated the utility of the two continua model in identifying mental health needs in Chinese contexts. The findings suggest that future policy reforms and clinical interventions should establish a more comprehensive mental health category as a screening tool nationwide. The promotion of social engagement could play an important role in treating mental illness and improving positive mental health. 相似文献