IgY antibodies against cytolysin reduce ethanol-induced liver disease in mice.

BACKGROUND AND AIMS: Patients with severe alcohol-associated hepatitis have high morbidity and mortality. Novel therapeutic approaches are urgently needed. The aims of our study were to confirm the predictive value of cytolysin-positive Enterococcus faecalis ( E. faecalis ) for mortality in patients with alcohol-associated hepatitis and to assess the protective effect of specific chicken immunoglobulin Y (IgY) antibodies against cytolysin in vitro and in a microbiota-humanized mouse model of ethanol-induced liver disease. APPROACH AND RESULTS: We investigated a multicenter cohort of 26 subjects with alcohol-associated hepatitis and confirmed our previous findings that the presence of fecal cytolysin-positive E. faecalis predicted 180-day mortality in those patients. After combining this smaller cohort with our previously published multicenter cohort, the presence of fecal cytolysin has a better diagnostic area under the curve, better other accuracy measures, and a higher odds ratio to predict death in patients with alcohol-associated hepatitis than other commonly used liver disease models. In a precision medicine approach, we generated IgY antibodies against cytolysin from hyperimmunized chickens. Neutralizing IgY antibodies against cytolysin reduced cytolysin-induced cell death in primary mouse hepatocytes. The oral administration of IgY antibodies against cytolysin decreased ethanol-induced liver disease in gnotobiotic mice colonized with stool from cytolysin-positive patients with alcohol-associated hepatitis. CONCLUSIONS: E. faecalis cytolysin is an important mortality predictor in alcohol-associated hepatitis patients, and its targeted neutralization through specific antibodies improves ethanol-induced liver disease in microbiota-humanized mice.

COVID-19 and the Economy: Summary of research and future directions.

This article presents a literature review of the 81 articles accepted in the Finance Research Letters Special Issue titled "COVID-19 and the Economy". The articles are classified into five broad areas (investments and asset pricing, the macroeconomy and banking, commodities, corporate finance, and other topics). We summarize the key findings of the articles by area and highlight the influence of the articles as measured by Google Scholar citations. We conclude by presenting directions for future research.

AI computing reaches for the edge.

A chip design integrates computation and memory to efficiently process data at low energy cost.

Management of complex and redo cases of pelvic fracture urethral injuries.

OBJECTIVES: Pelvic fracture urethral injuries (PFUI) result from traumatic disruption of the urethra. A significant proportion of cases are complex rendering their management challenging. We described management strategies for eight different complex PFUI scenarios. METHODS: Our centre is a tertiary referral centre for complex PFUI cases. We maintain a prospective database (1995-2016), which we retrospectively analysed. All patients with PFUI managed at our institute were included. RESULTS: Over two decades 1062 cases of PFUI were managed at our institute (521 primary and 541 redo cases). Most redo cases were referred to us from other centres. Redo cases had up to five prior attempts at urethroplasty. We managed complex cases, which included bulbar ischemia, young boys and girls with PFUI, PFUI with double block, concomitant PFUI and iatrogenic anterior urethral strictures. Bulbar ischemia merits substitution urethroplasty, most commonly, using pedicled preputial tube. PFUI in young girls is usually associated with urethrovaginal fistula. Young boys with PFUI commonly have a long gap necessitating trans-abdominal approach. Our success rate with individualised management is 85.60% in primary cases, 79.13% in redo cases and 82.40% in cases of bulbar ischemia. CONCLUSION: The definition of complex PFUI is ever expanding. The best chance of success is at the first attempt. Anastomotic urethroplasty for PFUI should be performed in experienced hands at high volume centres.

A novel method in decision making for the diagnosis of anterior urethral stricture: using methylene blue dye.

OBJECTIVE: The use of methylene blue dye (MB) to highlight anatomical structures in urology has been well-established. Urethral stricture may extend about a centimeter beyond the abnormal area seen on urethrogram. Although the current literature suggests a tension-free and end- to- end anastomosis after excision of the strictured urethral segment with spongiofibrosis and surrounding corpus spongiosum in short bulbar strictures, some centers dealing with urethroplasty prefer anastomosis for short bulbar strictures while others prefer augmentation. With this study, use of MB for delineating stricture line and assessing spongiofibrosis in the diagnosis of urethral stricture was evaluated. MATERIAL AND METHODS: Five cc MB including 10 mg/mL is diluted with 10 cc saline. In the first scenario, MB is gently injected into urethra via the meatus before the urethroplasty procedure. Meanwhile, the extent of urethral segment stained by MB is noted. In the second scenario (MB spongiosography) in short bulbar stricture, insulin needles are inserted in spongiosa of the stricture site distally and proximally. MB is gently injected with distal needle. The two remaining needles are then observed. Presence of MB efflux in proximal needle implies deficiency of significant spongiofibrosis, so buccal augmentation is performed. Absence of efflux of MB implies significant spongiofibrosis and anastomotik site excised. RESULTS: Four hundred and ninety-two consecutive cases prospectively evaluated between 2010 and 2014. Precise staining of stricture was successfully observed in 464 (94%) patients. Grossly normal appearing urothelium remained pink. Histopathology confirmed that the stained urethra had a stricture. Of the 22 short bulbar idiopathic strictures, in 18 (82%) MB was seen across the stricture and urethral transection was avoided. Anastomosis was performed in 4 (18%) cases where no MB went across the primary excision. There were no known allergic complications. CONCLUSION: MB aids in delineating the urethral lumen and exact site of stricture that needs augmentation. MB Spongiography in short bulbar strictures could be used as a beneficial guide in relation to the type of urethral repair to be performed in terms of augmentation versus excision and anastomosis.

Resistance/response molecular signature for oral tongue squamous cell carcinoma.

Worldwide, the incidence of oral tongue cancer is on the rise, adding to the existing burden due to prevailing low survival and high recurrence rates. This study uses high-throughput expression profiling to identify candidate markers of resistance/response in patients with oral tongue cancer. Analysis of primary and post-treatment samples (12 tumor and 8 normal) by the Affymetrix platform (HG U133 plus 2) identified 119 genes as differentially regulated in recurrent tumors. The study groups had distinct profiles, with induction of immune response and apoptotic pathways in the non-recurrent and metastatic/invasiveness pathways in the recurrent group. Validation was carried out in tissues by Quantitative Real-Time PCR (QPCR) (n=30) and immunohistochemistry (IHC) (n=35) and in saliva by QPCR (n=37). The markers, COL5A1, HBB, IGLA and TSC individually and COL5A1 and HBB in combination had the best predictive power for treatment response in the patients. A subset of markers identified (COL5A1, ABCG1, MMP1, IL8, FN1) could be detected in the saliva of patients with oral cancers with their combined sensitivity and specificity being 0.65 and 0.87 respectively. The study thus emphasizes the extreme prognostic value of exploring markers of treatment resistance that are expressed in both tissue and saliva.