A turn-on fluorescence probe for imaging tyrosinase at the wound site in broken tail of zebrafish.

Tyrosinase (TYR) is a copper-containing oxidase that affects the synthesis of melanin in the human body, which is regulate to the pigmentation of the skin. Nevertheless, abnormal expression of TYR can lead to albinism, vitiligo and other skin diseases. Excessive accumulation of TYR is a marker of melanoma cancer and an important factor leading to pigmentation during wound healing, freckles and browning of fruits and vegetables. Efficient tracking of TYR is of significance for studying its pathophysiological mechanism. Herein, we synthesized a benzindole-based fluorescent probe Pro-OH to detect TYR in living cells and zebrafish. The probe displayed a high selectivity and sensitivity in distinguishing TYR from other analytes with the low detection limit of 1.024 U/mL. Importantly, Pro-OH was successfully used to imagine TYR at the wound site of broken tail of zebrafish.

Identification of Complex Pneumonia during the Outbreak of COVID-19: Bacterial Pneumonia Combined with Acute Eosinophilic Pneumonia in Patients with Maintenance Hemodialysis.

It is of crucial importance to diagnose patients in a timely and clear manner during the outbreak of COVID-19. Different causes of pneumonia makes it difficult to differentiate COVID-19 from others. Hemodialysis patients are a special group of people in this outbreak. We present a successfully treated case of a patient with maintenance hemodialysis from acute eosinophilic pneumonia for using meropenem when treating bacterial pneumonia, avoiding possible panic and waste of quarantine materials in dialysis centers.

Intestinal flora alterations in patients with early chronic kidney disease: a case-control study among the Han population in southwestern China.

OBJECTIVE: In this case-control study, we retrospectively analyzed the intestinal flora compositions of patients with early-stage chronic kidney disease (CKD). METHODS: Forty-seven patients with early CKD who were treated at the Traditional Chinese Medicine Hospital between March and October 2018 were enrolled, and 150 healthy volunteers were enrolled in the healthy control group. Fresh stool samples were collected. The V3-V4 region of the bacterial 16S rRNA was amplified via PCR. Biterminal sequencing was performed using the Illumina MiSeq platform. The flora compositions were compared between the two groups. RESULTS: The Chao1 and Shannon indices showed significantly lower intestinal flora diversity and abundances in the CKD group than in the healthy controls. Beta diversity analysis revealed notable differences in the intestinal flora compositions between the groups. At the phylum level, Actinobacteria and Proteobacteria abundances were significantly higher in the CKD group. Thirty-one species differed significantly between both groups, among which, differences in Ruminococcus and Roseburia displayed the highest diagnostic values for distinguishing CKD patients from healthy controls. CONCLUSIONS: Intestinal flora compositions are altered in early-stage CKD patients among the Han population in southwestern China.

A Drug Safety Rating System Based on Postmarketing Costs Associated with Adverse Events and Patient Outcomes.

BACKGROUND: Given the multiple limitations associated with relatively homogeneous preapproval clinical trials, inadequate data disclosures, slow reaction times from regulatory bodies, and deep-rooted bias against disclosing and publishing negative results, there is an acute need for the development of analytics that reflect drug safety in heterogeneous, real-world populations. OBJECTIVE: To develop a drug safety statistic that estimates downstream medical costs associated with serious adverse events (AEs) and unfavorable patient outcomes associated with the use of 706 FDA-approved drugs. METHODS: All primary suspect case reports for each drug were collected from the FDA's Adverse Event Reporting System database (FAERS) from 2010-2014. The Medical Dictionary for Regulatory Activities (MedDRA) was used to code serious AEs and outcomes, which were tallied for each case report. Medical costs associated with AEs and poor patient outcomes were derived from Agency for Healthcare Research and Quality (AHRQ) survey data, and their corresponding ICD-9-CM codes were mapped to MedDRA terms. Nonserious AEs and outcomes were not included. For each case report, either the highest AE cost or, if no eligible AE was listed, the highest outcome cost was used. All costed cases were aggregated for each drug and divided by the number of patients exposed to obtain a downstream estimated direct medical cost burden per exposure. Each drug was assigned a corresponding 1-100 point total. RESULTS: The 706 drugs showed an exponential distribution of downstream costs, and the data were transformed using the natural log to approximate a normal distribution. The minimum score was 8.29, and the maximum score was 99.25, with a mean of 44.32. Drugs with the highest individual scores tended to be kinase inhibitors, thalidomide analogs, and endothelin receptor antagonists. When scores were analyzed across Established Pharmacologic Class (EPC), the kinase inhibitor and endothelin receptor antagonist classes had the highest total. However, other EPCs with median scores of 75 and above included hepatitis C virus NS3/4A protease inhibitor, recombinant human interferon beta, vascular endothelial growth factor-directed antibody, and tumor necrosis factor blocker. When Anatomical Therapeutic Chemical classifications were analyzed, antineoplastic drugs were outliers with approximately 80% of their individual scores 60 and above, while approximately 20%-30% of blood and anti-infective drugs had scores of 60 and above. Within-drug class results served to differentiate similar drugs. For example, 6 serotonin reuptake inhibitors had a score range of 35 to 53. CONCLUSIONS: This scoring system is based on estimated direct medical costs associated with postmarketing AEs and poor patient outcomes and thereby helps fill a large information gap regarding drug safety in real-world patient populations.

CASMIL: a comprehensive software/toolkit for image-guided neurosurgeries.

BACKGROUND: CASMIL aims to develop a cost-effective and efficient approach to monitor and predict deformation during surgery, allowing accurate, and real-time intra-operative information to be provided reliably to the surgeon. METHOD: CASMIL is a comprehensive Image-guided Neurosurgery System with extensive novel features. It is an integration of various modules including rigid and non-rigid body co-registration (image-image, image-atlas, and image-patient), automated 3D segmentation, brain shift predictor, knowledge based query tools, intelligent planning, and augmented reality. One of the vital and unique modules is the Intelligent Planning module, which displays the best surgical corridor on the computer screen based on tumor location, captured surgeon knowledge, and predicted brain shift using patient specific Finite Element Model. Also, it has multi-level parallel computing to provide near real-time interaction with iMRI (Intra-operative MRI). In addition, it has been securely web-enabled and optimized for remote web and PDA access. RESULTS: A version of this system is being used and tested using real patient data and is expected to be in use in the operating room at the Detroit Medical Center in the first half of 2006. CONCLUSION: CASMIL is currently under development and is targeted for minimally invasive surgeries. With minimal changes to the design, it can be easily extended and made available for other surgical procedures.