Changes in Gut Bacterial Translation Occur before Symptom Onset and Dysbiosis in Dextran Sodium Sulfate-Induced Murine Colitis.

Longitudinal studies on the gut microbiome that follow the effect of a perturbation are critical in understanding the microbiome's response and succession to disease. Here, we use a dextran sodium sulfate (DSS) mouse model of colitis as a tractable perturbation to study how gut bacteria change their physiology over the course of a perturbation. Using single-cell methods such as flow cytometry, bioorthogonal noncanonical amino acid tagging (BONCAT), and population-based cell sorting combined with 16S rRNA sequencing, we determine the diversity of physiologically distinct fractions of the gut microbiota and how they respond to a controlled perturbation. The physiological markers of bacterial activity studied here include relative nucleic acid content, membrane damage, and protein production. There is a distinct and reproducible succession in bacterial physiology, with an increase in bacteria with membrane damage and diversity changes in the translationally active fraction, both, critically, occurring before symptom onset. Large increases in the relative abundance of Akkermansia were seen in all physiological fractions, most notably in the translationally active bacteria. Performing these analyses within a detailed, longitudinal framework determines which bacteria change their physiology early on, focusing therapeutic efforts in the future to predict or even mitigate relapse in diseases like inflammatory bowel diseases. IMPORTANCE Most studies on the gut microbiome focus on the composition of this community and how it changes in disease. However, how the community transitions from a healthy state to one associated with disease is currently unknown. Additionally, common diversity metrics do not provide functional information on bacterial activity. We begin to address these two unknowns by following bacterial activity over the course of disease progression, using a tractable mouse model of colitis. We find reproducible changes in gut bacterial physiology that occur before symptom onset, with increases in the proportion of bacteria with membrane damage, and changes in community composition of the translationally active bacteria. Our data provide a framework to identify possible windows of intervention and which bacteria to target in microbiome-based therapeutics.

The interaction between clothing and air weapon pellets.

Comparatively few studies have been carried out on air weapon injuries yet there are significant number of injuries and fatalities caused by these low power weapons because of their availability and the public perception that because they need no licence they are assumed to be safe. In this study ballistic gel was tested by Bloom and rupture tests to check on consistency of production. Two series of tests were carried out firing into unclothed gel blocks and blocks loosely covered by different items of clothing to simulate attire (tee shirt, jeans, fleece, and jacket). The damage to the clothing caused by different shaped pellets when fired at different ranges was examined. The apparent hole size was affected by the shape of pellet (round, pointed, flat and hollow point) and whether damage was predominantly caused by pushing yarn to one side or by laceration of the yarn through cutting or tearing. The study also compared penetration into clothed gel and unclothed gel under identical conditions, and loose clothing greatly reduced penetration. With loose clothing at 9.1 m range clothing reduced penetration to 50-70% of the penetration of unclothed gel but at 18.3m range only 7 out of 36 shots penetrated the gel. This cannot be accounted for by the energy loss at the longer range (3-7% reduction from 9.1 m to 18.3 m range in unclothed gels) and it is suggested that impulse may have a role to play. Shots that did not penetrate the gel were used to estimate the possible stopping time for the pellet (around 75 µs) and force (1700 N) or stress (100 MPa) required to bring the pellet to a halt. Even with these low energy projectiles, cloth fibres were entrained in the gel showing the potential for penetration of the body and subsequent infection.

Recombinant Semliki Forest virus vector exhibits potential for avian virus vaccine development.

The Semliki Forest virus (SFV) expression system was evaluated as a basis for avian vaccine development. Initial studies indicated that 1-day-old specific pathogen-free (SPF) chicks were susceptible to infection with an infectious strain of SFV, producing SFV-specific antibodies but no clinical disease. One-day-old SPF chicks immunised intramuscularly with recombinant replication-defective SFV (rSFV) particles expressing the Escherichia coli (E. coli) lacZ reporter gene developed high titres of beta-gal- specific antibodies at 4 weeks p.i. after two inoculations. In contrast, significantly lower antibody levels were elicited in chicks immunised with a recombinant SFV-based DNA construct or a conventional CMV promoter-based DNA plasmid. rSFV particles encoding the protective VP2 protein or the VP2/VP4/VP3 polyprotein of infectious bursal disease virus (IBDV) were produced and the expressed antigens were characterised in cell culture. Proteins of the correct size were generated and found to react against a range of IBDV-specific monoclonal antibodies. Immunisation of 1-day-old SPF chicks with rSFV particles encoding the IBDV proteins resulted in specific antibodies being elicited in all birds, neutralising antibodies being induced in some but not all birds.

Attitudes of part-time community internal medicine faculty about their teaching.

The authors sent a six-item questionnaire regarding attitudes about teaching to 130 part-time community internal medicine faculty at the University of Illinois College of Medicine at Rockford in August 1991; of the 90 (69%) who responded, 53 were salaried and 37 nonsalaried. Substantial numbers of the salaried faculty responded (1) that teaching is important for their career development (25, 48%), compared with nine (22%) of the nonsalaried faculty, and (2) that they expected to increase their commitments to the medical school (50, 75%), compared with 24 (65%) of the nonsalaried faculty. Of all the faculty, fewer than the authors expected--22 (24%)--felt that their teaching interfered with their clinical practices. As expected, most (76, 84%) responded that salary was necessary. The authors suggest that their results may be helpful to other medical schools, because with the setting of medical education changing from the hospital to the community, the importance of part-time faculty is increasing.

Unexpected difficult intubation. Asymptomatic epiglottic cysts as a cause of upper airway obstruction during anaesthesia.

Two cases of asymptomatic epiglottic cysts which presented as partial upper airway obstruction following induction of anaesthesia are described. The incidence, pathology and anaesthetic management are discussed.

Hemodynamic effects of atracurium, vecuronium and pancuronium during sufentanil anesthesia for coronary artery bypass.

A study was undertaken to evaluate the cardiovascular effects of sufentanil, in combination with three different muscle relaxants, used as sole anesthetic with 100% O2 in 30 patients undergoing elective coronary artery vein graft surgery. Patients were randomly allocated to receive pancuronium (P), vecuronium (V) or atracurium (A) for muscle relaxation. All patients received 15 micrograms/kg sufentanil at induction followed by 5-10 micrograms/kg sufentanil prior to sternotomy. At the 95% level of significance no statistical difference was found for any of the measured and derived cardiovascular parameters between groups P, V and A, except for a decreased systolic blood pressure in the atracurium group after induction. Sufentanil in combination with pancuronium or vecuronium provided stable hemodynamic conditions throughout anesthesia. Atracurium was less satisfactory. We conclude that there is no advantage to be gained, in the presence of beta blockade, from the use of the new generation muscle relaxants as compared to pancuronium during high-dose sufentanil anesthesia for coronary artery vein grafting.

The effect of halothane on cerebral electrical activity. An assessment using the cerebral function analysing monitoring (CFAM).

Recordings of cerebral electrical activity were obtained using the cerebral function analysing monitor from eight unpremedicated patients anaesthetised with increasing concentrations of halothane in oxygen. The amplitude of the processed EEG increased at one and decreased at two minimal alveolar concentrations. The frequency distribution of the weighted EEG signal showed a linear increase of delta activity with a corresponding decrease in beta activity with increasing concentrations of halothane.

The haemodynamic effects of bronchoscopy. Effect of pretreatment with fentanyl and alfentanil.

The cardiovascular responses to bronchoscopy under general anaesthesia were investigated in 36 premedicated patients. Twelve patients acting as controls received a standard intravenous anaesthetic of intermittent thiopentone and suxamethonium. A further 24 patients were given either fentanyl 6 micrograms/kg or alfentanil 18 micrograms/kg intravenously, one minute prior to induction. There were significant rises in systolic arterial blood pressure (p less than 0.05) and in rate pressure product (p less than 0.05) in the patients in the control group, but these changes were not seen in those patients receiving either fentanyl or alfentanil. However, dysrhythmias and ST segment changes indicative of myocardial ischaemia were present in some patients in all three groups.