Differentiation of patient-specific void urine-derived human induced pluripotent stem cells to fibroblasts and skeletal muscle myocytes.

Cell-based therapy is a major focus for treatment of stress urinary incontinence (SUI). However, derivation of primary cells requires tissue biopsies, which often have adverse effects on patients. A recent study used human induced pluripotent stem cells (iPSC)-derived smooth muscle myocytes for urethral sphincter regeneration in rats. Here, we establish a workflow using iPSC-derived fibroblasts and skeletal myocytes for urethral tissue regeneration: (1) Cells from voided urine of women were reprogrammed into iPSC. (2) The iPSC line U1 and hESC line H9 (control) were differentiated into fibroblasts expressing FSP1, TE7, vinculin, vimentin, αSMA, fibronectin and paxillin. (3) Myogenic differentiation of U1 and H9 was induced by small molecule CHIR99021 and confirmed by protein expression of myogenic factors PAX7, MYOD, MYOG, and MF20. Striated muscle cells enriched by FACS expressed NCAM1, TITIN, DESMIN, TNNT3. (4) Human iPSC-derived fibroblasts and myocytes were engrafted into the periurethral region of RNU rats. Injected cells were labelled with ferric nanoparticles and traced by Prussian Blue stain, human-specific nuclear protein KU80, and human anti-mitochondria antibody. This workflow allows the scalable derivation, culture, and in vivo tracing of patient-specific fibroblasts and myocytes, which can be assessed in rat SUI models to regenerate urethral damages and restore continence.

Injury modelling for strategic planning in protecting the national infrastructure from terrorist explosive events.

Terrorist events in the form of explosive devices have occurred and remain a threat currently to the population and the infrastructure of many nations worldwide. Injuries occur from a combination of a blast wave, energised fragments, blunt trauma and burns. The relative preponderance of each injury mechanism is dependent on the type of device, distance to targets, population density and the surrounding environment, such as an enclosed space, to name but a few. One method of primary prevention of such injuries is by modification of the environment in which the explosion occurs, such as modifying population density and the design of enclosed spaces. The Human Injury Predictor (HIP) tool is a computational model which was developed to predict the pattern of injuries following an explosion with the goal to inform national injury prevention strategies from terrorist attacks. HIP currently uses algorithms to predict the effects from primary and secondary blast and allows the geometry of buildings to be incorporated. It has been validated using clinical data from the '7/7' terrorist attacks in London and the 2017 Manchester Arena terrorist event. Although the tool can be used readily, it will benefit from further development to refine injury representation, validate injury scoring and enable the prediction of triage states. The tool can assist both in the design of future buildings and methods of transport, as well as the situation of critical emergency services required in the response following a terrorist explosive event. The aim of this paper is to describe the HIP tool in its current version and provide a roadmap for optimising its utility in the future for the protection of national infrastructure and the population.

Pegylated interferon may be considered in chronic viral hepatitis E resistant to ribavirin in kidney transplant recipients.

BACKGROUND: Hepatitis E virus (HEV) may be resistant to immunosuppression reduction and ribavirin treatment in kidney transplant recipients because of mutant strains and severe side effects of ribavirin which conduct to dose reduction. Sofosbuvir efficacy is controversial. Peg-interferon 2 alpha (PEG-IFN) is currently contraindicated due to a high risk of acute humoral and cellular rejection. The present study assessed, for the first time, the effect of PEG-IFN in a kidney transplant recipient infected with HEV. CASE PRESENTATION: The patient had chronic active HEV that was resistant to immunosuppression reduction and optimal ribavirin treatment. He developed significant liver fibrosis. PEG-IFN was administered for 10 months, and it was well tolerated and did not induce rejection. A sustained virological response was obtained. CONCLUSIONS: We conclude that prolonged treatment with PEG-IFN in kidney transplant recipients infected with HEV could be considered as a salvage option.

Screening of pigmented Bacillus aquimaris SH6 from the intestinal tracts of shrimp to develop a novel feed supplement for shrimp.

AIMS: To develop a novel feed supplement for shrimp using pigmented spore-forming bacterial strains isolated from their gastrointestinal tracts. METHODS AND RESULTS: Eight pigmented Bacillus strains were selected from the isolates based on high production of heat-stable spores, typical UV-Vis spectra of produced carotenoids (400-550 nm), and free radical scavenging activity of their extracts. Of the eight strains, the red-orange pigmented Bacillus aquimaris SH6 was selected because it showed the highest abundance in shrimp guts (70% population). Whiteleg shrimp (n = 30 per group) fed with SH6 spores, at >3 × 106  CFU g-1  pellet for 4 weeks had redder colour (score of 21-23 vs 20-22), 2·7-fold higher astaxanthin level (0·69 vs 0·25 µg g-1 shrimp), 34% higher weight gain (7·18 vs 5·32 g shrimp-1 ), and 85% higher phenoloxidase activity (OD490  = 0·265 vs 0·143) than shrimp in the control group. CONCLUSIONS: The result supports the potential use of B. aquimaris SH6 as a feed supplement for promoting the colourization and weight gain, and for enhancing innate immunity of whiteleg shrimp. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates that carotenoids produced by B. aquimaris SH6 can be successfully absorbed and converted to astaxanthin in whiteleg shrimp.

The long-term survival of plasma cells.

Plasma cells sustain antibody production and hence are an essential part of immune protection. In the mucosa-associated lymphoid tissues plasma cells secrete IgA antibodies which protect the organism from invasion by pathogenic bacteria while in the bone marrow they produce the antibodies which guarantee long-term humoral immune protection. The various lymphoid organs provide specific microenvironments which support plasma cell survival. In particular, in the bone marrow, highly specialized survival niches are established by the underlying stromal reticular cells which permit plasma cells to survive for years. In some situations, however, the antibody may be detrimental to the organism. In those auto immune diseases, where plasma cells play a pathological role by producing the auto antibodies, new strategies are needed to interfere with the lifespan of plasma cells and thus to diminish their numbers. The recent finding that eosinophils are essential for the long-term survival of plasma cells in the bone marrow provides a new therapeutic target to modulate the plasma cell survival niche.