The oral microbiome in alcohol use disorder: a longitudinal analysis during inpatient treatment.

BACKGROUND: Alcohol use disorder (AUD)-induced disruption of oral microbiota can lead to poor oral health; there have been no studies published examining the longitudinal effects of alcohol use cessation on the oral microbiome. AIM: To investigate the oral microbiome during alcohol cessation during inpatient treatment for AUD. METHODS: Up to 10 oral tongue brushings were collected from 22 AUD patients during inpatient treatment at the National Institutes of Health. Alcohol use history, smoking, and periodontal disease status were measured. Oral microbiome samples were sequenced using 16S rRNA gene sequencing. RESULTS: Alpha diversity decreased linearly during treatment across the entire cohort (P = 0.002). Alcohol preference was associated with changes in both alpha and beta diversity measures. Characteristic tongue dorsum genera from the Human Microbiome Project such as Streptococcus, Prevotella, Veillonella and Haemophilus were highly correlated in AUD. Oral health-associated genera that changed longitudinally during abstinence included Actinomyces, Capnocytophaga, Fusobacterium, Neisseria and Prevotella. CONCLUSION: The oral microbiome in AUD is affected by alcohol preference. Patients with AUD often have poor oral health but abstinence and attention to oral care improve dysbiosis, decreasing microbiome diversity and periodontal disease-associated genera while improving acute oral health.

Avascular tumour growth dynamics and the constraints of protein binding for drug transportation.

The potential for the use of in-silico models of disease in progression monitoring is becoming increasingly recognised, as well as its contribution to the development of complete curative processes. In this paper we report the development of a hybrid cellular automaton model to mimic the growth of avascular tumours, including the infusion of a bioreductive drug to study the effects of protein binding on drug transportation. The growth model is operated within an extracellular tumour microenvironment. An artificial Neural Network based scheme was implemented that modelled the behaviours of each cell (proliferation, quiescence, apoptosis and/or movement) based on the complex heterogeneous microenvironment; consisting of oxygen, glucose, hydrogen ions, inhibitory factors and growth factors. To validate the growth model results, we conducted experiments with multicellular tumour spheroids. These results showed good agreement with the predicted growth dynamics. The outcome of the avascular tumour growth model suggested that tumour microenvironments have a strong impact on cell behaviour. To address the problem of cellular proteins acting as resistive factors preventing efficient drug penetration, a bioreactive drug (tirapazamine) was added to the system. This allowed us to study the drug penetration through multicellular layers of tissue after its binding to cellular proteins. The results of the in vitro model suggested that the proteins reduce the toxicity of the drug, reducing its efficacy for the most severely hypoxic fractions furthest from a functional blood vessel. Finally this research provides a unique comparison of in vitro tumour growth with an intelligent in silico model to measure bioreductive drug availability inside tumour tissue through a set of experiments.

Comparison between two valsalva techniques for improvement of hypopharyngeal nasendoscopy: a preliminary communication.

OBJECTIVE: To compare the nasal valsalva with the trumpet manoeuvre and anterior neck skin traction as aids to nasendoscopic examination of the hypopharynx. DESIGN: Randomised, controlled comparison of examination techniques. SETTING: Single tertiary referral centre. PARTICIPANTS: Twenty-six adult patients requiring hypopharyngeal nasendoscopic examination were recruited. Patients were examined with both techniques in a randomised order that was recorded to video cassette. MAIN OUTCOME MEASURES: Blinded assessment of the percentage visualisation of the pyriform fossae, post-cricoid and upper oesophageal sphincter was carried out by three consultant otolaryngologists independently. RESULTS: Mean percentage scores (and 95% confidence intervals) for nasal valsalva versus trumpet manoeuvre for the three consultants, respectively, were as follows: right pyriform fossa: 77(68, 87) versus 80(71, 91), 61(55, 66) versus 60(54, 66), 46(38, 54) versus 45(37, 54); left pyriform fossa: 76(65, 87) versus 80(69, 91), 59(53, 64) versus 55(49, 61), 42(35, 49) versus 42(35, 50); post-cricoid: 55(44, 67) versus 59(47, 71), 53(46, 60) versus 53(46, 60), 32(25, 39) versus 32(25, 39); upper oesophageal sphincter: 11(1, 21) versus 21(11, 31), 15(9, 21) versus 20(14, 26), 4(0, 8) versus 7(3, 11). No significant difference was found between the two techniques at any subsite. Individual differences were noted in a minority of patients where one or other technique gave a clearly improved view. CONCLUSIONS: The nasal valsalva and the trumpet manoeuvre with anterior neck skin traction are complementary techniques for improving the view of the hypopharynx.

Ascorbate-enhanced chondrogenesis of ATDC5 cells.

The ATDC5 cell line exhibits the multistep chondrogenic differentiation observed during endochondral bone formation. However, it takes up to two months to complete the process of cell expansion, insulin addition to promote differentiation and further changes in culture conditions effectively to induce hypertrophy. We sought to produce consistent chondrogenesis with significant hypertrophic differentiation with simpler conditions in a more practical time period. By adding ascorbate, the prechondrogenic proliferation phase was shortened from 21 to 7 days, with production of cartilaginous nodules during the chondrogenic phase, after insulin addition, that were greater in number and larger in size. Immunohistochemistry indicated much greater matrix elaboration and the mRNA expression of sox9, aggrecan and collagen type II were all significantly increased earlier and to a much higher degree when compared with controls. Moreover, there was a robust induction of hypertrophy: Col10a1, Runx2 and Mmp13 were all induced within 7-10 days. In conclusion, addition of ascorbate to ATDC5 cultures shortened the prechondrogenic proliferation phase, produced earlier chondrogenic differentiation, heightened gene expression and robust hypertrophic differentiation, abrogating the need for extended culture times and the changes in culture conditions. This simple modification considerably enhances the practicality of this cell line for studies of chondrogenesis.

Randomized clinical trial comparing two natural surfactant preparations to treat respiratory distress syndrome.

OBJECTIVES: Natural surfactant preparations have been shown to reduce the severity and mortality of respiratory distress syndrome (RDS) in preterm infants. The objective of this study was to compare the efficacy of two natural surfactants, namely SF-RI 1 (Alveofact) and barectant (Survanta), on the incidence of chronic lung disease (CLD) and other associated complications of RDS in preterm infants. METHODS: Preterm infants with RDS requiring artificial ventilation were randomly selected to receive an initial dose of either Alveofact or Survanta. The two treatment groups were tested for variation in gas exchange, ventilatory settings and neonatal complications such as CLD and mortality. RESULTS: After 5 days the Survanta-treated infants had a lower fraction of inspired oxygen (FiO2) compared with the Alveofact-treated infants. There were no differences in the ventilatory settings. More infants in the Survanta group were extubated at 3 days and fewer required the use of postnatal steroids. Less CLD and duration of oxygenation were experienced by the Survanta-treated group. CONCLUSIONS: Improved oxygenation and reduced ventilatory requirements were greater with Survanta compared to Alveofact, which in turn was associated with a trend towards a lower incidence of serious pulmonary complications.