Carroll, C. | Search bioRxiv

bioRxiv2019

The impact of genistein supplementation on tendon functional properties and gene expression in estrogen deficient rats

PurposeTendinopathy risk increases with menopause. The phytoestrogen genistein prevents collagen loss during estrogen deficiency [ovariectomy (OVX)]. The influence of genistein on tendon function and extracellular matrix (ECM) regulation are not well known. We determined the impact of genistein on tendon function and examined potential mechanisms by which genistein alters tendon ECM.\n\nMaterials and MethodsEight-week-old rats (n=42) were divided into three groups: intact, OVX, or OVX-genistein (6mg/kg/day) for 6-weeks. Tail fascicles were assessed with a Deben tensile stage. Achilles tendon mRNA expression was determined with digital droplet PCR. Tendon-derived fibroblasts were also treated with genistein in the presence of estrogen receptor (ER) antagonists.\n\nResultsCompared to intact, stress tended to be lower in untreated OVX rats (p=0.022). Further, modulus and energy density were greater in genistein-treated rats (p<0.05) compared to intact. Neither OVX nor genistein altered expression of Col1a1, Col3a1, Casp3, Casp8, Mmp1a, Mmp2, or Mmp9 (p>0.05). Compared to intact, Tnmd and Esr1 expression was greater and Pcna and Timp1 expression lower in OVX rats (p<0.05). Genistein treatment returned Tnmd, Pcna, and Timp1 to levels of Intact-Vehicle (p<0.05), but did not alter Scx or Esr1 (p>0.05). Several {beta}-catenin/Wnt signaling related molecules were not altered by OVX or genistein (p>0.05). In vitro, genistein blunted cell proliferation but not via ERs.\n\nConclusionsOur findings demonstrate that genistein improves tendon function. Genistein inhibits cell proliferation in vitro but not via ER. The effect of genistein in vivo was predominately on genes related to cell proliferation rather than collagen remodeling.

physiology↗

bioRxiv2019

Effect of Antimicrobial Stewardship with Rapid MALDI-TOF Identification and Vitek 2 Antimicrobial Susceptibility Testing on Hospitalization Outcome

IntroductionRapid organism identification (ID) and antimicrobial susceptibility testing (AST) along with antibiotic stewardship (ASP) are critical to appropriate treatment. We sought to capture time for bacterial culture and initiation of appropriate therapy for patients, from 2017 (without MALDI-TOF/Vitek 2 and ASP) and 2018 (with MALDI-TOF/Vitek 2 and ASP).\n\nMethodsEligible patients admitted to our hospital with a positive sputum, blood, or urine culture. Sequential patients were retrospectively obtained from March 1 to May 31, 2017. Seventy-seven patients from 2017 were compared to 77 patients from 2018. A time-in-motion study was performed to compare time to identification (ID), AST results, and ASP team intervention for the two periods. Data were entered into SPSS (ver 25) for analysis. Results are reported as mean ({+/-} SD) or percentage.\n\nResultsTime to organism ID was significantly faster in 2018 (2018 24.9 {+/-} 14.4, 2017 33.8 {+/-} 17 h, p=0.001). Time to AST results was also significantly faster for patients in 2018 compared to 2017 (18.2 {+/-} 14 compared to 28.5 {+/-} 14.9 h, p<0.001). ASP team recommended significantly more adjustments to empiric antimicrobial therapy in 2018 (28% of 2018 vs. 2% in 2017, p< 0.001). Length of hospital stay was significantly shorter in 2018 compared to 2017 (2018 10.7 {+/-} 11.1 days and 2017 15.5 {+/-} 18.1 days, p=0.05).\n\nConclusionsUse of MALDI-TOF/Vitek 2 leads to an average 21.5 h faster ID and AST results that can be acted upon by ASP for appropriate antimicrobial recommendations.

microbiology↗