Intestinal epithelial responses to Salmonella enterica serovar Enteritidis: Effects on intestinal permeability and ion transport

Salmonella infection of chickens that leads to potential human foodborne salmonellosis continues to be a major concern. Chickens serve as carriers but, in contrast to humans, rarely show any clinical signs including diarrhea. The present investigations aimed to elucidate whether the absence of diarrhea during acute Salmonella enterica serovar Enteritidis (Salmonella Enteritidis) infection may be linked to specific changes in the electrophysiological properties of the chicken gut. Immediately after slaughter, intestinal pieces of the mid-jejunum and cecum of either commercial broiler or specific pathogen-free (SPF) chickens were mounted in Ussing chambers in 2 separate experimental series. Living Salmonella Enteritidis (3 × 109) or Salmonella Enteritidis endotoxin (20 mg/L), or both, were added to the mucosal side for 1 h. In both experimental series, the Salmonella infection decreased the trans-epithelial ion conductance Gt (P < 0.05). In the jejunum of SPF chickens, there was also a marked decrease in net charge transfer across the epithelium, evidenced by decreased short-circuit current (Isc, P < 0.05). Interestingly, the mucosal application of Salmonella endotoxin to the epithelial preparations from jejunum and cecum of SPF chicken had an effect similar to living bacteria. However, the endotoxin had no additional effect on the intestinal function in the presence of bacteria. The decreasing effect of Salmonella and or its endotoxin on Gt could be partly reversed by serosal addition of histamine. To our knowledge, this is the first study to address the functional response of native intestinal epithelium of chicken to an in vitro Salmonella infection. For the first time, it can be reported that intestinal ion permeability of chicken decreases acutely by the presence of Salmonella. This type of response could counteract ion and fluid secretion and may thus, at least in part, explain why chickens do not develop overt diarrhea after Salmonella infection

Campylobacter jejuni colonization promotes the translocation of Escherichia coli to extra-intestinal organs and disturbs the short-chain fatty acids profiles in the chicken gut

For a long time Campylobacter was only considered as a commensal microorganism in avian hosts restricted to the ceca, without any pathogenic features. The precise reasons for the symptomless chicken carriers are still unknown, but investigations of the gastrointestinal ecology of broiler chickens may improve our understanding of the microbial interactions with the host. Therefore, the current studies were conducted to investigate the effects of Campylobacter jejuni colonization on Escherichia coli translocation and on the metabolic end products (short-chain fatty acids, SCFAs). Following oral infection of 14 day old broiler chickens with 1 × 108 CFU of Campylobacter jejuni NCTC 12744 in two independent animal trials, it was found that C. jejuni heavily colonized the intestine and disseminate to extra-intestinal organs. Moreover, in both animal trials, the findings revealed that C. jejuni promoted the translocation of E. coli with a higher number encountered in the spleen and liver at 14 days post infection (dpi). In addition, Campylobacter affected the microbial fermentation in the gastrointestinal tract of broilers by reducing the amount of propionate, isovalerate, and isobutyrate in the cecal digesta of the infected birds at 2 dpi and, at 7 and 14 dpi, butyrate, isobutyrate, and isovalerate were also decreased. However, in the jejunum, the C. jejuni infection lowered only butyrate concentrations at 14 dpi. These data indicated that C. jejuni may utilize SCFAs as carbon sources to promote its colonization in the chicken gut, suggesting that Campylobacter cannot only alter gut colonization dynamics but might also influence physiological processes due to altered microbial metabolite profiles. Finally, the results demonstrated that C. jejuni can cross the intestinal epithelial barrier and facilitates the translocation of Campylobacter itself as well as of other enteric microorganisms such as E. coli to extra-intestinal organs of infected birds. Altogether, our findings suggest that the Campylobacter carrier state in chicken is characterised by multiple changes in the intestinal barrier function, which supports multiplication and survival within the host

Monitoring and evaluation of irrigation and drainage facilities for pilot distributaries in Sindh Province, Pakistan. Volume 4 - Heran Distributary, Sanghar District

Irrigation management / Monitoring / Evaluation / Irrigation canals / Distributary canals / Drainage / Irrigation practices / Water delivery / Watercourses / Maintenance / Water table / Groundwater / Water quality / Pakistan / Sindh Province / Sanghar District / Heran Distributary

Change in BMI Accurately Predicted by Social Exposure to Acquaintances

Research has mostly focused on obesity and not on processes of BMI change more generally, although these may be key factors that lead to obesity. Studies have suggested that obesity is affected by social ties. However these studies used survey based data collection techniques that may be biased toward select only close friends and relatives. In this study, mobile phone sensing techniques were used to routinely capture social interaction data in an undergraduate dorm. By automating the capture of social interaction data, the limitations of self-reported social exposure data are avoided. This study attempts to understand and develop a model that best describes the change in BMI using social interaction data. We evaluated a cohort of 42 college students in a co-located university dorm, automatically captured via mobile phones and survey based health-related information. We determined the most predictive variables for change in BMI using the least absolute shrinkage and selection operator (LASSO) method. The selected variables, with gender, healthy diet category, and ability to manage stress, were used to build multiple linear regression models that estimate the effect of exposure and individual factors on change in BMI. We identified the best model using Akaike Information Criterion (AIC) and R[superscript 2]. This study found a model that explains 68% (p<0.0001) of the variation in change in BMI. The model combined social interaction data, especially from acquaintances, and personal health-related information to explain change in BMI. This is the first study taking into account both interactions with different levels of social interaction and personal health-related information. Social interactions with acquaintances accounted for more than half the variation in change in BMI. This suggests the importance of not only individual health information but also the significance of social interactions with people we are exposed to, even people we may not consider as close friends.MIT Masdar ProgramMIT Media Lab Consortiu

Maintenance plans for irrigation facilities of pilot distributaries in Sindh, Pakistan: Volume two - Heran Distributary, Sanghar District

Irrigation management / Maintenance / Planning / Irrigation canals / Distributary canals / Flow control / Measurement / Watercourses / Rehabilitation / Pakistan / Sindh / Sanghar District / Heran Distributary

Novel derivative of aminobenzenesulfonamide (3c) induces apoptosis in colorectal cancer cells through ROS generation and inhibits cell migration

Background: Colorectal cancer (CRC) is the 3rd most common type of cancer worldwide. New anti-cancer agents are needed for treating late stage colorectal cancer as most of the deaths occur due to cancer metastasis. A recently developed compound, 3c has shown to have potent antitumor effect; however the mechanism underlying the antitumor effect remains unknown. Methods: 3c-induced inhibition of proliferation was measured in the absence and presence NAC using MTT in HT-29 and SW620 cells and xCELLigence RTCA DP instrument. 3c-induced apoptotic studies were performed using flow cytometry. 3c-induced redox alterations were measured by ROS production using fluorescence plate reader and flow cytometry and mitochondrial membrane potential by flow cytometry; NADPH and GSH levels were determined by colorimetric assays. Bcl2 family protein expression and cytochrome c release and PARP activation was done by western blotting. Caspase activation was measured by ELISA. Cell migration assay was done using the real time xCELLigence RTCA DP system in SW620 cells and wound healing assay in HT-29. Results: Many anticancer therapeutics exert their effects by inducing reactive oxygen species (ROS). In this study, we demonstrate that 3c-induced inhibition of cell proliferation is reversed by the antioxidant, N-acetylcysteine, suggesting that 3c acts via increased production of ROS in HT-29 cells. This was confirmed by the direct measurement of ROS in 3c-treated colorectal cancer cells. Additionally, treatment with 3c resulted in decreased NADPH and glutathione levels in HT-29 cells. Further, investigation of the apoptotic pathway showed increased release of cytochrome c resulting in the activation of caspase-9, which in turn activated caspase-3 and −6. 3c also (i) increased p53 and Bax expression, (ii) decreased Bcl2 and BclxL expression and (iii) induced PARP cleavage in human colorectal cancer cells. Confirming our observations, NAC significantly inhibited induction of apoptosis, ROS production, cytochrome c release and PARP cleavage. The results further demonstrate that 3c inhibits cell migration by modulating EMT markers and inhibiting TGFβ-induced phosphorylation of Smad2 and Samd3. Conclusions: Our findings thus demonstrate that 3c disrupts redox balance in colorectal cancer cells and support the notion that this agent may be effective for the treatment of colorectal cancer

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic