Phosphoethanolamine decoration of Neisseria gonorrhoeae lipid A plays a dual immunostimulatory and protective role during experimental genital tract infection.

The induction of an intense inflammatory response by Neisseria gonorrhoeae and the persistence of this pathogen in the presence of innate effectors is a fascinating aspect of gonorrhea. Phosphoethanolamine (PEA) decoration of lipid A increases gonococcal resistance to complement-mediated bacteriolysis and cationic antimicrobial peptides (CAMPs), and recently we reported that wild-type N. gonorrhoeae strain FA1090 has a survival advantage relative to a PEA transferase A (lptA) mutant in the human urethral-challenge and murine lower genital tract infection models. Here we tested the immunostimulatory role of this lipid A modification. Purified lipooligosaccharide (LOS) containing lipid A devoid of the PEA modification and an lptA mutant of strain FA19 induced significantly lower levels of NF-κB in human embryonic kidney Toll-like receptor 4 (TLR4) cells and murine embryonic fibroblasts than wild-type LOS of the parent strain. Moreover, vaginal proinflammatory cytokines and chemokines were not elevated in female mice infected with the isogenic lptA mutant, in contrast to mice infected with the wild-type and complemented lptA mutant bacteria. We also demonstrated that lptA mutant bacteria were more susceptible to human and murine cathelicidins due to increased binding by these peptides and that the differential induction of NF-κB by wild-type and unmodified lipid A was more pronounced in the presence of CAMPs. This work demonstrates that PEA decoration of lipid A plays both protective and immunostimulatory roles and that host-derived CAMPs may further reduce the capacity of PEA-deficient lipid A to interact with TLR4 during infection.

The impact of a fasting mimicking diet on the metabolic health of a prospective cohort of patients with prostate cancer: a pilot implementation study.

BACKGROUND: This pilot prospective study investigated the effect of a periodic fasting mimicking diet (FMD) on metabolic health factors in patients with Prostate Cancer (PC). There is a well-documented association between PC and metabolic health. Impaired metabolic health is a significant risk factor for the development of PC, and a metabolic syndrome can be induced by hormonal therapies commonly required for its management. (ClinicalTrials.gov Identifier: NCT04292041). METHODS: We introduced a periodic 4-day FMD -low in calories, sugars, and proteins but high in unsaturated fats -to a cohort of PC patients and features of metabolic syndrome. 29/35 patients completed 3-monthly cycles of the 4-consecutive day packaged FMD. We compared the subjects' baseline weight, abdominal circumference (AC), blood pressure (BP) and selected laboratory results to the same measurements 3-months after completing the FMD cycles. RESULTS: Several important metabolic factors showed improvements post-intervention. On average patients' weights dropped by 3.79 kg (95% CI: -5.61, -1.97, p = 0.0002). AC was reduced on average by 4.57 cm, (95% CI: -2.27, -6.87, p = 0.0003). There was also a decrease in systolic and diastolic BP by 9.52 mmHg (95% CI: -16.16, -2.88, p = 0.0066) and 4.48 mmHg (95% CI: -8.85, -0.43, p = 0.0316) respectively. A sub-analysis indicates that FMD had more relevant effects in 'at-risk' patients than those with normal values of risk factors for metabolic syndrome. For example, subjects with baseline levels of systolic BP > 130 mmHg experienced a greater reduction in BP(-16.04 mmHg, p = 0.0001) than those with baseline systolic BP < 130 mmHg (-0.78 mmHg, p = 0.89). CONCLUSIONS: The FMD cycles were safely introduced to this small cohort of PC patients with little or no observed toxicity, and a high overall compliance of 83%. Analysis of the metabolic variables showed an overall decrease in weight, AC, and BP. Larger clinical trials focused on metabolic risk factors, PC quality of life and progression free survival are needed to assess the effect of the FMD on prostate cancer patients.

An artificial intelligence algorithm that identifies middle turbinate pneumatisation (concha bullosa) on sinus computed tomography scans.

OBJECTIVE: Convolutional neural networks are a subclass of deep learning or artificial intelligence that are predominantly used for image analysis and classification. This proof-of-concept study attempts to train a convolutional neural network algorithm that can reliably determine if the middle turbinate is pneumatised (concha bullosa) on coronal sinus computed tomography images. METHOD: Consecutive high-resolution computed tomography scans of the paranasal sinuses were retrospectively collected between January 2016 and December 2018 at a tertiary rhinology hospital in Australia. The classification layer of Inception-V3 was retrained in Python using a transfer learning method to interpret the computed tomography images. Segmentation analysis was also performed in an attempt to increase diagnostic accuracy. RESULTS: The trained convolutional neural network was found to have diagnostic accuracy of 81 per cent (95 per cent confidence interval: 73.0-89.0 per cent) with an area under the curve of 0.93. CONCLUSION: A trained convolutional neural network algorithm appears to successfully identify pneumatisation of the middle turbinate with high accuracy. Further studies can be pursued to test its ability in other clinically important anatomical variants in otolaryngology and rhinology.

Development of a scoring system for predicting difficult intubation using ultrasonography.

BACKGROUND AND AIMS: Ultrasound measurement of anterior neck soft tissue thickness by skin to epiglottis distance (SED) has been shown to predict difficult laryngoscopy. In this study, we developed an airway scoring system incorporating SED into three clinical predictors and assessed whether it would improve accuracy in prediction of difficult intubation. METHODS: Mentohyoid distance, mandibular subluxation, head extension and ultrasound measurement of skin to epiglottis distance were measured a day before surgery in 310 adult patients. During direct laryngoscopy, Cormack-Lehane grading was noted (Grade 1 and 2 = Easy, Grade 3 and 4 = Difficult). We constructed a score named MSH, which included mentohyoid distance, mandibular subluxation and head extension. Then, SED was added to the MSH score to form another new score named USED-MSH. Student's t-test, Mann-Whitney U test and Chi-square test or Fisher exact tests were used. Both scoring systems were compared under the receiver-operating characteristic curve and area under the curve (AUC) were calculated. RESULTS: Difficult intubation was observed in 62/310 patients (20%). The AUC for USED-MSH score was greater than the MSH score (0.93, 95% CI [0.89-0.97] vs 0.76, 95% CI [0.69-0.84], P value <0.001). USED-MSH score had higher sensitivity (93.6% vs 59.7%) and lower specificity (85.9% vs 91.1%) with similar positive predictive value (62.7% vs 62.4%) in comparison with MSH score. CONCLUSION: An airway scoring system using the ultrasound measurements of skin-to-epiglottis distance along with the clinical predictors would be helpful in the prediction of difficult intubation.

Unplanned intubation after surgery: risk factors, prognosis, and medical emergency team effects.

Unplanned intubation after surgery is a marker for severe adverse events. We investigated the incidence, risk factors, and prognosis of unplanned intubation after general and vascular surgery and sought to determine whether the deployment of a hospital-wide medical emergency team (MET) had a preventive effect. We included all patients undergoing general and vascular surgical procedures between April 1, 2006, and June 30, 2008, from our American College of Surgeons National Surgical Quality Improvement Program data. Risk factors and incidence rates of unplanned intubation were compared before (preMET) and after (postMET) June 7, 2007. Chart review identified case details and fatality rates. There were 2426 patients included (1815 preMET, 611 postMET). The overall incidence of unplanned intubation was 2.6 per cent; significant risk factors included chronic obstructive pulmonary disease, dependent functional status, and emergent operation. Most (84%) unplanned intubations occurred in a critical care setting and the most common underlying reason was sepsis (40%). The overall case fatality rate was 43 per cent but varied significantly depending on the underlying reason for unplanned intubation. Incidence rates of unplanned intubation did not change significantly after MET deployment, suggesting that other strategies are needed to prevent this rare but highly morbid and mortal event.

Soft forceps.

OBJECTIVE: The risk of maternal and fetal trauma and, chiefly, the fear of law suits, have contributed to a significant decline in rates of forceps-assisted deliveries and an increase in rates of cesarean sections, especially in the United States. Our experience with gas-sterilized forceps blades covered with a soft rubber coating--the "soft" forceps--is described. METHOD: Ninety-six women who required a forceps-assisted delivery for standard indications were randomly allocated to 2 groups. There were 51 women in the regular forceps group and 45 women in the soft forceps group. Low forceps delivery with a Simpson instrument was used in all cases. The groups were compared for fetal injury. RESULTS: The rates of severe facial abrasion and minimal marking were 4.1% and 61%, respectively, in the regular forceps group and 1.9% and 34% in the soft forceps group. CONCLUSION: The soft forceps may reduce the rates of neonatal facial abrasion and skin bruises. The forceps should be further perfected, as well as vacuum extractors; they should both continue to be part of the obstetrician's armamentarium.

Augmentation of Cationic Antimicrobial Peptide Production with Histone Deacetylase Inhibitors as a Novel Epigenetic Therapy for Bacterial Infections.

The emergence of antibiotic resistance seriously threatens our ability to treat many common and medically important bacterial infections. Novel therapeutics are needed that can be used alone or in conjunction with antibiotics. Cationic antimicrobial peptides (CAMPs) are important effectors of the host innate defense that exhibit broad-spectrum activity against a wide range of microorganisms. CAMPs are carried within phagocytic granules and are constitutively or inducibly expressed by multiple cell types, including epithelial cells. The role of histone modification enzymes, specifically the histone deacetylases (HDAC), in down-regulating the transcription of CAMP-encoding genes is increasingly appreciated as is the capacity of HDAC inhibitors (HDACi) to block the action of HDACs to increase CAMP expression. The use of synthetic and natural HDACi molecules to increase CAMPs on mucosal surfaces, therefore, has potential therapeutic applications. Here, we review host and pathogen regulation of CAMP expression through the induction of HDACs and assess the therapeutic potential of natural and synthetic HDACi based on evidence from tissue culture systems, animal models, and clinical trials.

Changes in dentists' attitudes and practice in paediatric dentistry.

AIM: The purpose of the study was to determine if there had been any changes in the clinical practice and attitudes to the care of children by general dental practitioners over a ten year period from 1986 to 1996, following the introduction of a system of capitation payments in the United Kingdom. METHODS: A questionnaire was mailed to 1,290 general dental practitioners practicing in Yorkshire (UK) in an identical way to a previous survey ten years before. Practitioners were asked questions concerning their practice of dental caries prevention, behaviour management, restoration of primary teeth and pulp therapy. Responses were compared with the results of the 1986 survey. RESULTS: Of the total of 687 replies (53.2% response) 61% practiced, or said they practiced, diet evaluation and gave dietary advice. Oral hygiene instruction was reported by 87% and 57% used fissure sealants. The routine use of amalgam, previously 80%, had declined to 35% in favour of glass ionomer cements (57%). There had been a significant improvement in the use of pulp therapy for primary teeth at 35% compared with previous 3%. The use of rubber dam also increased, but only from 0% before to 9% in the present study. The usage of stainless steel crowns had changed from 2% over ten years to 8% and strip crowns from 1% to 5%. CONCLUSION: The use of paediatric dental techniques by general dental practitioners had generally increased, particularly in preventive measures and pulp treatment. Restorative techniques had marginally changed, but a dramatic shift away from amalgam had occurred. There was still a very low usage of stainless steel crowns and rubber dam was also not used to the extent that it should be.