Lactobacillus sp. Facilitate the Repair of DNA Damage Caused by Bile-Induced Reactive Oxygen Species in Experimental Models of Gastroesophageal Reflux Disease.

Gastroesophageal reflux disease (GERD) leads to the accumulation of bile-induced reactive oxygen species and oxidative stress in esophageal tissues, causing inflammation and DNA damage. The progression sequence from healthy esophagus to GERD and eventually cancer is associated with a microbiome shift. Lactobacillus species are commensal organisms known for their probiotic and antioxidant characteristics in the healthy esophagus. This prompted us to investigate how Lactobacilli survive in a bile-rich environment during GERD, and to identify their interaction with the bile-injured esophageal cells. To model human reflux conditions, we exposed three Lactobacillus species (L. acidophilus, L. plantarum, and L. fermentum) to bile. All species were tolerant to bile possibly enabling them to colonize the esophageal epithelium under GERD conditions. Next, we assessed the antioxidant potential of Lactobacilli and role in bile injury repair: we measured bile-induced DNA damage using the ROS marker 8-oxo guanine and COMET assay. Lactobacillus addition after bile injury accelerated repair of bile-induced DNA damage through recruitment of pH2AX/RAD51 and reduced NFκB-associated inflammation in esophageal cells. This study demonstrated anti-genotoxic and anti-inflammatory effects of Lactobacilli, making them of significant interest in the prevention of Barrett's esophagus and esophageal adenocarcinoma in patients with GERD.

Augmented CPT1A Expression Is Associated with Proliferation and Colony Formation during Barrett's Tumorigenesis.

Obesity is a known risk factor for the development of gastroesophageal reflux disease (GERD), Barrett's Esophagus (BE) and the progression to esophageal adenocarcinoma. The mechanisms by which obesity contributes to GERD, BE and its progression are currently not well understood. Recently, changes in lipid metabolism especially in the context of a high fat diet have been linked to GERD and BE leading us to explore whether fatty acid oxidation plays a role in the disease progression from GERD to esophageal adenocarcinoma. To that end, we analyzed the expression of the rate-limiting enzyme, carnitine palmytoyltransferase 1A (CPT1A), in human tissues and cell lines representing different stages in the sequence from normal squamous esophagus to cancer. We determined uptake of palmitic acid, the most abundant fatty acid in human serum, with fluorescent dye-labeled lipids as well as functional consequences of stimulation with palmitic acid relevant to Barrett's tumorigenesis, e.g., proliferation, characteristics of stemness and IL8 mediated inflammatory signaling. We further employed different mouse models including a genetic model of Barrett's esophagus based on IL1ß overexpression in the presence and absence of a high fat diet and deoxycholic acid to physiologically mimic gastrointestinal reflux in the mice. Together, our data demonstrate that CPT1A is upregulated in Barrett's tumorigenesis and that experimental palmitic acid is delivered to mitochondria and associated with increased cell proliferation and stem cell marker expression.

E-Cigarette Aerosol Exposure Favors the Growth and Colonization of Oral Streptococcus mutans Compared to Commensal Streptococci.

E-cigarettes (e-cigs) have drastically increased in popularity during the last decade, especially among teenagers. While recent studies have started to explore the effect of e-cigs in the oral cavity, little is known about their effects on the oral microbiota and how they could affect oral health and potentially lead to disease, including periodontitis and head and neck cancers. To explore the impact of e-cigs on oral bacteria, we selected members of the genus Streptococcus, which are abundant in the oral cavity. We exposed the commensals Streptococcus sanguinis and Streptococcus gordonii and the opportunistic pathogen Streptococcus mutans, best known for causing dental caries, to e-liquids and e-cig aerosols with and without nicotine and with and without menthol flavoring and measured changes in growth patterns and biofilm formation. Our results demonstrate that e-cig aerosols hindered the growth of S. sanguinis and S. gordonii, while they did not affect the growth of S. mutans. We also show that e-cig aerosols significantly increased biofilm formation by S. mutans but did not affect the biofilm formation of the two commensals. We found that S. mutans exhibits higher hydrophobicity and coaggregation abilities along with higher attachment to OKF6 cells than S. sanguinis and S. gordonii. Therefore, our data suggest that e-cig aerosols have the potential to dysregulate oral bacterial homeostasis by suppressing the growth of commensals while enhancing the biofilm formation of the opportunistic pathogen S. mutans. This study highlights the importance of understanding the consequences of e-cig aerosol exposure on selected commensals and pathogenic species. Future studies modeling more complex communities will provide more insight into how e-cig aerosols and vaping affect the oral microbiota. IMPORTANCE Our study shows that e-cigarette aerosol exposure of selected bacteria known to be residents of the oral cavity hinders the growth of two streptococcal commensals while enhancing biofilm formation, hydrophobicity, and attachment for the pathogen S. mutans. These results indicate that e-cigarette vaping could open a niche for opportunistic bacteria such as S. mutans to colonize the oral cavity and affect oral health.

E-Cigarette Aerosols Promote Oral S. aureus Colonization by Delaying an Immune Response and Bacterial Clearing.

E-cigarette (e-cig) vapor has been shown to play a pathological role in oral health and alter the oral microbiota, providing growth advantages for opportunistic pathogens. Enrichment of Staphylococcus aureus, a commensal resident in the oral cavity, correlates with the progression of periodontal disease, suggesting a role as an opportunistic pathogen. Environmental conditions, such as cigarette smoke, are known to increase S. aureus virulence, yet the role of S. aureus in periodontitis and oral preneoplasia is unknown. We exposed oral epithelial cells to e-cig aerosols and showed a dose-dependent cell viability reduction, regardless of nicotine content, in a possible attempt to repair DNA damage, as measured by pH2AX. S. aureus attachment to oral epithelial cells and bacterial biofilm formation were enhanced upon e-cig exposure, indicating an increased capacity for oral colonization. Mechanistically, e-cig aerosol exposure resulted in an immunosuppression, as determined by a reduction in IL8, IL6, and IL1ß secretion by oral epithelial cells during co-culture with S. aureus. Consistent with this, e-cig vape reduced the oral epithelial cell clearance of S. aureus. Furthermore, we observed an increased expression of the inflammatory regulator COX2. This work suggests that e-cigs promote S. aureus colonization and modulate the oral inflammatory response, possibly promoting oral periodontitis and preneoplasia.

Financial incentives and wearable activity monitors to increase ambulation after cystectomy: A randomized controlled trial.

OBJECTIVES: Financial incentive programs are effective in increasing physical activity for overweight, ambulatory adults. We sought to determine the potential effect size and direction of financial incentives on ambulation after radical cystectomy. MATERIALS AND METHODS: We performed a pilot randomized controlled trial of daily financial incentives to meet postoperative step goals among adults with Eastern Cooperative Oncology Group performance status ≤2 who underwent radical cystectomy for bladder cancer at a single center. Step counts were measured over a 3- to 14-day preoperative period and 30-day postoperative period using a wearable activity monitor. Postoperative daily step goals of 10%, 25%, 40%, and 55% of mean preoperative daily step counts were set for postoperative weeks 1 through 4, respectively. The primary outcome was the number of postoperative days on which the step goals were met. Secondary outcomes included the number of daily postoperative steps taken and the length of stay. Participants randomized to the intervention arm received $1.50 for every day the goal was met with a 20% chance of a $100 reward if the step goal was met on >75% of the first 30 postoperative days. Questionnaires assessing self-reported physical activity, disability, and social support were administered preoperatively at 30 days postoperatively. RESULTS: Thirty-three patients were analyzed, 11 in the control and 22 in the intervention arms. There were no statistically significant differences between incentive and control arms for the primary outcome (4.5/30 days vs. 9/30 days, P = 0.53). Results after adjusting for differences in baseline characteristics were similar (RR 1.00, 95% CI 0.24-4.19, P = 1.00). There were also no differences in average daily postoperative steps (median 979 vs. 1191, 95% CI -810 to 1,400, P = 0.59), length of stay (7.5 vs. 7, 95% CI -2.7 to 5.1, P = 0.56), or self-reported measures of disability, activity, and social support. CONCLUSIONS: While this trial was a pilot study and not powered to detect a difference between groups, there was no suggestion of any clinically important impact of this financial incentive on postoperative ambulation. While a fully-powered trial is feasible, given the small range of plausible benefit, such a trial would be unlikely to influence clinical practice.

Association Between Daily Water Intake and 24-hour Urine Volume Among Adolescents With Kidney Stones.

OBJECTIVE: To determine the association between daily water intake and 24-hour urine volume among adolescents with nephrolithiasis in order to estimate a "fluid prescription," the additional water intake needed to increase urine volume to a target goal. METHODS: We conducted a secondary analysis of an ecological momentary assessment study that prospectively measured daily water intake of 25 adolescents with nephrolithiasis over 7 days. We identified 24-hour urine volumes obtained for clinical care within 12 months of water intake assessment. A linear regression model was fit to estimate the magnitude of the association between daily water intake and 24-hour urine volume, adjusting for age, sex, race, and daily temperature. RESULTS: Twenty-two participants completed fifty-seven 24-hour urine collections within 12 months of the study period. Median daily water intake was 1.4 L (IQR 0.67-1.94). Median 24-hour urine volume was 2.01 L (IQR 1.20-2.73). A 1 L increase in daily water intake was associated with a 710 mL increase in 24-hour urine output (95%CI 0.55-0.87). Using the model output, the equation was generated to estimate the additional fluid intake needed fluid prescription (FP) to produce the desired increase in urine output (dUOP): FP = dUOP/0.71. CONCLUSION: The FP equation (FP = dUOP)/0.71), which reflects the relationship between water intake and urine volume, could be used to help adolescents with nephrolithiasis achieve urine output goals to decrease stone recurrence.

Underlying synovial sarcoma in a patient with a history of complex regional pain syndrome: a case report.

Synovial sarcoma, although commonly found in the lower extremities, is considered a rare neoplasm. One of the distinguishing features of a synovial sarcoma is its initial benign features that can later turn into a more aggressive lesion. Because of the subtle early features, synovial sarcoma can be mistaken for other pathologic entities that present with clinical signs of erythema, warmth, edema, and pain. We present a patient who was originally diagnosed with complex regional pain syndrome. That diagnosis and subsequent treatment of complex regional pain syndrome likely delayed the appropriate evaluation, which led to a 9-month lag in the proper diagnosis. After magnetic resonance imaging and biopsy were performed, synovial sarcoma was diagnosed. The patient was referred to an orthopedic oncologist, who performed a transtibial amputation and chemotherapy. Although rare, neoplasm should always be considered in the differential diagnosis of a clinical presentation of a painful erythematous and edematous mass.