SalmoNet, an integrated network of ten Salmonella enterica strains reveals common and distinct pathways to host adaptation

Salmonella enterica is a prominent bacterial pathogen with implications on human and animal health. Salmonella serovars could be classified as gastro-intestinal or extra-intestinal. Genome-wide comparisons revealed that extra-intestinal strains are closer relatives of gastro-intestinal strains than to each other indicating a parallel evolution of this trait. Given the complexity of the differences, a systems-level comparison could reveal key mechanisms enabling extra-intestinal serovars to cause systemic infections. Accordingly, in this work, we introduce a unique resource, SalmoNet, which combines manual curation, high-throughput data and computational predictions to provide an integrated network for Salmonella at the metabolic, transcriptional regulatory and protein-protein interaction levels. SalmoNet provides the networks separately for five gastro-intestinal and five extra-intestinal strains. As a multi-layered, multi-strain database containing experimental data, SalmoNet is the first dedicated network resource for Salmonella. It comprehensively contains interactions between proteins encoded in Salmonella pathogenicity islands, as well as regulatory mechanisms of metabolic processes with the option to zoom-in and analyze the interactions at specific loci in more detail. Application of SalmoNet is not limited to strain comparisons as it also provides a Salmonella resource for biochemical network modeling, host-pathogen interaction studies, drug discovery, experimental validation of novel interactions, uncovering new pathological mechanisms from emergent properties and epidemiological studies. SalmoNet is available at http://salmonet.org

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

An intensive swallowing exercise protocol for improving swallowing physiology in older adults with radiographically confirmed dysphagia

Matina Balou,1 Erica G Herzberg,2 David Kamelhar,3 Sonja M Molfenter4 1Department of Otolaryngology, New York University School of Medicine, Head &amp; Neck Surgery, New York, NY, USA; 2Department of Speech-Language Pathology, New York University Langone Health, Rusk Rehabilitation, New York, NY, USA; 3New York University School of Medicine, Department of Pulmonary Medicine, New York, NY, USA; 4Department of Communicative Sciences and Disorder, Communicative Sciences and Disorders, New York University Steinhardt, New York, NY, USA Purpose: The aim of this study was to investigate improvements in swallowing function and physiology in a series of healthy older adults with radiographically confirmed dysphagia, following completion of an exercise-based swallowing intervention.Patients and methods: Nine otherwise healthy older adults (six females, mean age =75.3, SD =5.3) had confirmed impairments in swallowing safety and/or efficiency on a modified barium swallow study. Each participant completed an 8-week swallowing treatment protocol including effortful swallows, Mendelsohn maneuvers, tongue-hold swallows, supraglottic swallows, Shaker exercises and effortful pitch glides. Treatment sessions were conducted once per week with additional daily home practice. Penetration&ndash;Aspiration Scale and the Modified Barium Swallowing Impairment Profile (MBSImP) were scored in a blind and randomized fashion to examine changes to swallowing function and physiology from baseline to post-treatment.Results: There were significant improvements in swallowing physiology as represented by improved oral and pharyngeal composite scores of the MBSImP. Specific components to demonstrate statistical improvement included initiation of the pharyngeal swallow, laryngeal elevation and pharyngeal residue. There was a nonsignificant reduction in median PAS scores.Conclusion: Swallowing physiology can be improved using this standardized high-intensity exercise protocol in healthy adults with evidence of dysphagia. Future research is needed to examine the individual potential of each exercise in isolation and to determine ideal dose and frequency. Studies on various etiological groups are warranted. Keywords: dysphagia, modified barium swallow, rehabilitation, deglutition, exercise, presbyphagi

Komatiites reveal a hydrous Archaean deep-mantle reservoir

Archaean komatiites (ultramafic lavas) result from melting under extreme conditions of the Earth’s mantle. Their chemical compositions evoke very high eruption temperatures, up to 1,600 degrees Celsius, which suggests even higher temperatures in their mantle source1, 2. This message is clouded, however, by uncertainty about the water content in komatiite magmas. One school of thought holds that komatiites were essentially dry and originated in mantle plumes3, 4, 5, 6 while another argues that these magmas contained several per cent water, which drastically reduced their eruption temperature and links them to subduction processes7, 8, 9. Here we report measurements of the content of water and other volatile components, and of major and trace elements in melt inclusions in exceptionally magnesian olivine (up to 94.5 mole per cent forsterite). This information provides direct estimates of the composition and crystallization temperature of the parental melts of Archaean komatiites. We show that the parental melt for 2.7-billion-year-old komatiites from the Abitibi greenstone belt in Canada contained 30 per cent magnesium oxide and 0.6 per cent water by weight, and was depleted in highly incompatible elements. This melt began to crystallize at around 1,530 degrees Celsius at shallow depth and under reducing conditions, and it evolved via fractional crystallization of olivine, accompanied by minor crustal assimilation. As its major- and trace-element composition and low oxygen fugacities are inconsistent with a subduction setting, we propose that its high H2O/Ce ratio (over 6,000) resulted from entrainment into the komatiite source of hydrous material from the mantle transition zone10. These results confirm a plume origin for komatiites and high Archaean mantle temperatures, and evoke a hydrous reservoir in the deep mantle early in Earth’s history