The effect of daily usage of Listerine Cool Mint mouthwash on the oropharyngeal microbiome: a substudy of the PReGo trial.

Introduction. ListerineÒ is a bactericidal mouthwash widely used to prevent oral health problems such as dental plaque and gingivitis. However, whether it promotes or undermines a healthy oral microbiome is unclear.Hypothesis/Gap Statement. We hypothesized that the daily use of Listerine Cool Mint would have a significant impact on the oropharyngeal microbiome.Aim. We aimed to assess if daily usage of Listerine Cool Mint influenced the composition of the pharyngeal microbiome.Methodology. The current microbiome substudy is part of the Preventing Resistance in Gonorrhoea trial. This was a double-blind single-centre, crossover, randomized controlled trial of antibacterial versus placebo mouthwash to reduce the incidence of gonorrhoea/chlamydia/syphilis in men who have sex with men (MSM) taking HIV pre-exposure prophylaxis (PrEP). Fifty-nine MSM taking HIV PrEP were enrolled. In this crossover trial, participants received 3 months of daily Listerine followed by 3 months of placebo mouthwash or vice versa. Oropharyngeal swabs were taken at baseline and after 3 months use of each mouthwash. DNA was extracted for shotgun metagenomic sequencing (Illumina Inc.). Non-host reads were taxonomically classified with MiniKraken and Bracken. The alpha and beta diversity indices were compared between baseline and after each mouthwash use. Differentially abundant bacterial taxa were identified using ANOVA-like differential expression analysis.Results. Streptococcus was the most abundant genus in most samples (n = 103, 61.7 %) with a median relative abundance of 31.5% (IQR 20.6-44.8), followed by Prevotella [13.5% (IQR 4.8-22.6)] and Veillonella [10.0% (IQR 4.0-16.8)]. Compared to baseline, the composition of the oral microbiome at the genus level (beta diversity) was significantly different after 3 months of Listerine (P = 0.006, pseudo-F = 2.29) or placebo (P = 0.003, pseudo-F = 2.49, permutational multivariate analysis of variance) use. Fusobacterium nucleatum and Streptococcus anginosus were significantly more abundant after Listerine use compared to baseline.Conclusion. Listerine use was associated with an increased abundance of common oral opportunistic bacteria previously reported to be enriched in periodontal diseases, oesophageal and colorectal cancer, and systemic diseases. These findings suggest that the regular use of Listerine mouthwash should be carefully considered.

Patient Experience on a Hospital Oncology Service Before and After Implementation of a No-Visitor Policy During COVID-19.

Hospital visitor restriction policies prompted by Coronavirus Disease 2019 (COVID-19) may lead to a less comfortable or informed inpatient experience for oncology patients admitted for non-COVID-19 conditions. We surveyed oncology inpatients before (n = 47) and after (n = 65) implementation of a no-visitor policy using a validated questionnaire to measure patient experience. Results revealed no significant difference in the percentage of patients reporting "no problems" (P < .05) in all questions. Patient experience was not adversely impacted by visitor restrictions enacted in response to COVID-19 on an oncology service, as measured by a questionnaire capturing common concerns among inpatients.

When does obstetric coagulopathy occur and how do I manage it?

Anticipating obstetric coagulopathy is important when obstetric anaesthetists are involved in the clinical management of women with postpartum haemorrhage. Although the incidence of coagulopathy in women with postpartum haemorrhage is low, significant hypofibrinogenaemia is associated with major haemorrhage-related morbidity and thus early identification and treatment is essential to improve outcomes. Point-of-care viscoelastic haemostatic assays, including thromboelastography and rotational thromboelastometry, provide granular information about alterations in clot formation and hypofibrinogenaemia, allow near-patient interpretation of coagulopathy, and can guide goal-directed treatment. If these assays are not available, anaesthetists should closely monitor the maternal coagulation profile with standard laboratory testing during the active phase of postpartum bleeding in order to rule coagulopathy 'in or out', decide if pro-haemostatic therapies are indicated, and assess the response to haemostatic support.

Molecular pathways to high-level azithromycin resistance in Neisseria gonorrhoeae.

BACKGROUND: The prevalence of azithromycin resistance in Neisseria gonorrhoeae is increasing in numerous populations worldwide. OBJECTIVES: To characterize the genetic pathways leading to high-level azithromycin resistance. METHODS: A customized morbidostat was used to subject two N. gonorrhoeae reference strains (WHO-F and WHO-X) to dynamically sustained azithromycin pressure. We tracked stepwise evolution of resistance by whole genome sequencing. RESULTS: Within 26 days, all cultures evolved high-level azithromycin resistance. Typically, the first step towards resistance was found in transitory mutations in genes rplD, rplV and rpmH (encoding the ribosomal proteins L4, L22 and L34 respectively), followed by mutations in the MtrCDE-encoded efflux pump and the 23S rRNA gene. Low- to high-level resistance was associated with mutations in the ribosomal proteins and MtrCDE efflux pump. However, high-level resistance was consistently associated with mutations in the 23S ribosomal RNA, mainly the well-known A2059G and C2611T mutations, but also at position A2058G. CONCLUSIONS: This study enabled us to track previously reported mutations and identify novel mutations in ribosomal proteins (L4, L22 and L34) that may play a role in the genesis of azithromycin resistance in N. gonorrhoeae.

Impacts of climate change on the tourism sector of a Small Island Developing State: A case study for the Bahamas.

This study examines the direct and indirect impacts of climate change to the tourism sector on the islands of New Providence and adjacent Paradise Island in the Bahamas. The assessment was carried out by conducting a geospatial analysis of tourism establishments at risk using Geographic Information Systems (GIS). We combined the geospatial analysis with publicly available databases to assess the integrated climate-related impacts pertaining to a Small Island Developing State (SIDS) economy. Our study estimated that many tourism properties currently lie in a storm surge zone and the extent of properties at risk increases with a future scenario of a 1 m rise in sea level. While sea level rise (SLR) by itself only threatens a small number of properties, when combined with weak (Category 1), moderate (Category 3) and strong (Category 5) storms the resulting coastal flooding impacts 34%, 69%, and 83% of the tourism infrastructure (hotels and resorts), respectively. In addition to flooding, properties are also susceptible to coastal erosion with 28% of the total hotels and resorts on the two islands being situated within 0-50 m and 60% of the tourism infrastructure within 0-100 m of the coastline. Considering the economic importance of the sector, the potential impacts on the tourism infrastructure will cause significant losses in revenue and employment for the two islands. Furthermore, the majority of the tourism on these islands is beach-based and visitor expenditures will decline due to their vulnerability. These losses will have far-reaching social-economic consequences for the Bahamas. Our findings reveal a need for integrated coastal zone management that incorporates tourism management strategies with adaptation measures to deal with climate change.

Novel kinase platform for the validation of the anti-tubercular activities of Pelargonium sidoides (Geraniaceae).

BACKGROUND: Pelargonium sidoides is an important traditional medicine in South Africa with a well-defined history of both traditional and documented use of an aqueous-ethanolic formulation of the roots of P. sidoides (EPs 7630), which is successfully employed for the treatment of respiratory tract infections. There is also historical evidence of use in the treatment of tuberculosis. The aim of this study was to develop a platform of Mycobacterium tuberculosis (Mtb) kinase enzymes that may be used for the identification of therapeutically relevant ethnobotanical extracts that will allow drug target identification, as well as the subsequent isolation of the active compounds. RESULTS: Mtb kinases, Nucleoside diphosphokinase, Homoserine kinase, Acetate kinase, Glycerol kinase, Thiamine monophosphate kinase, Ribokinase, Aspartokinase and Shikimate kinase were cloned, produced in Escherichia coli and characterized. HPLC-based assays were used to determine the enzyme activities and subsequently the inhibitory potentials of varying concentrations of a P. sidoides extract against the produced enzymes. The enzyme activity assays indicated that these enzymes were active at low ATP concentrations. The 50% inhibitory concentration (IC50) of an aqueous root extract of P. sidoides against the kinases indicated SK has an IC50 of 1.2 µg/ml and GK 1.4 µg/ml. These enzyme targets were further assessed for compound identification from the P. sidoides literature. CONCLUSION: This study suggests P. sidoides is potentially a source of anti-tubercular compounds and the Mtb kinase platform has significant potential as a tool for the subsequent screening of P. sidoides extracts and plant extracts in general, for compound identification and elaboration by selected extract target inhibitor profiling.

Creating a community-based comprehensive intervention to improve asthma control in a low-income, low-resourced community.

Introduction: Asthma evidence-based interventions (EBI) are implemented in the home, school, community or primary care setting. Although families are engaged in one setting, they often have to navigate challenges in another setting.Objective: Our objective is to design and implement a comprehensive plan which integrates EBI's and connects the four sectors in underserved communities such as Philadelphia.Methods: September 2015-April 2016 we implemented a three-pronged strategy to understand needs and resources of the community including 1) focus groups and key informant interviews, 2) secondary data analysis and 3) pilot testing for implementation to determine gaps in care, and opportunities to overcome those gaps.Results: Analysis of the focus group and key informant responses showed themes: diagnosis fear, clinician time, home and school asthma trigger exposures, school personnel training and communication gaps across all four sectors. EBI's were evaluated and selected to address identified themes. Pilot testing of a community health worker (CHW) intervention to connect home, primary care and school resulted in an efficient transfer of asthma medications and medication administration forms to the school nurse office for students with uncontrolled asthma addressing a common delay leading to poor asthma management in school.Conclusion: Thus far there has been limited success in reducing asthma disparities for low-income minority children. This study offers hope that strategically positioning CHWs may work synergistically to close gaps in care and result in improved asthma control and reduced asthma disparities.

Containing a measles outbreak in Minnesota, 2017: methods and challenges.

AIMS: We report on a measles outbreak largely occurring in Minnesota's under-vaccinated Somali community in the spring of 2017. The outbreak was already into its third generation when the first two cases were confirmed, and rapid public health actions were needed. The aim of our response was to quickly end transmission and contain the outbreak. METHODS: The state public health department performed laboratory testing on suspect cases and activated an Incident Command staffed by subject matter experts that was operational within 2 h of case confirmation. Epidemiologic interviews identified exposures in settings where risk of transmission was high, that is, healthcare, childcare, and school settings. Vaccination status of exposed persons was assessed, and postexposure prophylaxis (PEP) was offered, if applicable. Exposed persons who did not receive PEP were excluded from childcare centers or schools for 21 days. An accelerated statewide measles, mumps, and rubella (MMR) recommendation was made for Somali Minnesota children and children in affected outbreak counties. Partnerships with the Somali Minnesota community were deepened, building off outreach work done with the community since 2008. RESULTS: Public health identified 75 measles cases from 30 March to 25 August 2017: 43% were female, 81% Somali Minnesotan, 91% unvaccinated, and 28% hospitalized. The median age of cases was 2 years (range: 3 months-57 years). Most transmission (78%) occurred in childcare centers and households. A secondary attack rate of 91% was calculated for unvaccinated household contacts. Over 51,000 doses of MMR were administered during the outbreak above expected baseline. At least 8490 individuals were exposed to measles; 155 individuals received PEP; and over 500 persons were excluded from childcare and school. State and key public health partners spent an estimated $2.3 million on response. CONCLUSION: This outbreak demonstrates the necessity of immediate, targeted disease control actions and strong public health, healthcare, and community partnerships to end a measles outbreak.

Four years' experience of a ROTEM® -guided algorithm for treatment of coagulopathy in obstetric haemorrhage.

We report four years of observational data from a large UK hospital and tertiary referral unit, following the introduction of a rotational thromboelastometry-guided algorithm for treatment of coagulopathy in major obstetric haemorrhage. Fibrinogen concentrate was used to treat acquired hypofibrinogenaemia as defined by a FibTEM A5 value of < 7 mm, or 7-12 mm with ongoing or high risk of haemorrhage. Of 32,647 deliveries over 4 years, 893 (2.7%) women had an estimated blood loss ≥ 1500 ml. Two-hundred and three (23%) of these had a FibTEM A5 ≤ 12 mm and 110 received fibrinogen concentrate. We compared clinical outcomes and blood product use with 52 patients who met the same criteria, over a 12-month pre-intervention period during which shock packs were used. In the algorithm group, there was a significant reduction in the number of units (p < 0.0001) and total volume (p = 0.0007) of blood products transfused, with a reduction in transfusion-associated circulatory overload (p = 0.002). Women with placental abruption exhibited more severe coagulopathy and required higher doses of fibrinogen concentrate than women who bled due to other causes. Analysis of rotational thromboelastometry results demonstrated that coagulopathy is not observed in all women who suffer obstetric haemorrhage and cannot be predicted solely by blood loss. Therefore, formulaic treatment with blood products is not justified. When coagulopathy does occur, it appears to be multifactorial and can be severe. Point-of-care testing allows early identification and individualised treatment of coagulopathy. This is supported by the improved outcomes reported.

The estimated burden of fungal disease in South Africa

Background. With a population of 56.5 million, over 7 million persons living with HIV, one of the world's highest rates of tuberculosis (TB) and a large proportion of the population living in poverty, South Africa (SA)'s fungal disease burden is probably substantial and broad in scope.Objectives. To estimate the burden of fungal disease in SA.Methods. Using total and at-risk populations and national, regional and occasionally global data, we estimated the incidence and prevalence of the majority of fungal diseases in SA.Results. Estimates for the annual incidence of HIV-related life-threatening fungal disease include cryptococcal meningitis (8 357 cases), Pneumocystis pneumonia (4 452 cases) and endemic mycoses (emergomycosis, histoplasmosis and blastomycosis, with 100, 60 and 10 cases per year, respectively). We estimate 3 885 cases of invasive aspergillosis annually. The annual burden of candidaemia and Candida peritonitis is estimated at 5 421 and 1 901 cases, respectively. The epidemic of pulmonary TB has probably driven up the prevalence of chronic pulmonary aspergillosis to 99 351 (175.8/100 000), perhaps the highest in the world. Fungal asthma probably affects >100 000 adults. Mucosal candidiasis is common, with an annual prevalence estimated at 828 666 and 135 289 oral and oesophageal cases, respectively, complicating HIV infection alone (estimates in other conditions not made), and over a million women are estimated to be affected by recurrent vulvovaginal candidiasis each year. Tinea capitis in children is common and conservatively estimated at >1 000 000 cases. The inoculation mycoses sporotrichosis, chromoblastomycosis and eumycetoma occur occasionally (with 40, 40 and 10 cases estimated, respectively). Overall, we estimate that over 3.2 million South Africans are afflicted by a fungal disease each year (7.1% of the population).Conclusions. Significant numbers of South Africans are estimated to be affected each year by fungal infections, driven primarily by the syndemics of HIV, TB and poverty. These estimates emphasise the need for better epidemiological data, and for improving the diagnosis and management of these diseases

The role of sexual networks in studies of how BV and STIs increase the risk of subsequent reinfection.

Prior studies have demonstrated that both bacterial vaginosis (BV) and sexually transmitted infections (STIs) are strong independent risk factors for subsequent STI. In observational studies of this biological enhancement (BE) hypothesis, it is important to adjust for the risk of STI exposure so that the independent effect of BE can be assessed. We sought to model if two markers of local sexual network (partner concurrency and cumulative number of STIs) represented residual confounding in the models of risk for subsequent infection in a study that screened 3620 women for STIs every 3 months for a year. Mixed-effects logistic regression was used to calculate the odds ratios for an incident diagnosis of Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis and BV following a diagnosis of any of these four at the prior visit, controlling for the cumulative number of STIs and partner concurrency variables. We found that partner concurrency and cumulative number of STIs were each associated with incident infection, and in general, controlling for these variables reduced the strength of the association between prior and incident infections. We conclude that the frequently found association between prior and incident STIs is associated with both BE and sexual network structure.

Current levels of gonorrhoea screening in MSM in Belgium may have little effect on prevalence: a modelling study.

There is considerable uncertainty as to the effectiveness of Neisseria gonorrhoeae (NG) screening in men who have sex with men. It is important to ensure that screening has benefits that outweigh the risks of increased antibiotics resistance. We develop a mathematical model to estimate the effectiveness of screening on prevalence. Separable Temporal Exponential family Random Graph Models are used to model the sexual relationships network, both with main and casual partners. Next, the transmission of Gonorrhoea is simulated on this network. The models are implemented using the R package 'statnet', which we adapted among other things to incorporate infection status at the pharynx, urethra and rectum separately and to distinguish between anal sex, oral sex and rimming. The different screening programmes compared are no screening, 3.5% of the population screened, 32% screened and 50% screened. The model simulates day-by-day evolution for 10 years of a population of 10 000. If half of the population would be screened, the prevalence in the pharynx decreases from 11.9% to 10.2%. We conclude that the limited impact of screening on NG prevalence may not outweigh the increased risk of antibiotic resistance.

Differential inhibition of adenylylated and deadenylylated forms of M. tuberculosis glutamine synthetase as a drug discovery platform.

Glutamine synthetase is a ubiquitous central enzyme in nitrogen metabolism that is controlled by up to four regulatory mechanisms, including adenylylation of some or all of the twelve subunits by adenylyl transferase. It is considered a potential therapeutic target for the treatment of tuberculosis, being essential for the growth of Mycobacterium tuberculosis, and is found extracellularly only in the pathogenic Mycobacterium strains. Human glutamine synthetase is not regulated by the adenylylation mechanism, so the adenylylated form of bacterial glutamine synthetase is of particular interest. Previously published reports show that, when M. tuberculosis glutamine synthetase is expressed in Escherichia coli, the E. coli adenylyl transferase does not optimally adenylylate the M. tuberculosis glutamine synthetase. Here, we demonstrate the production of soluble adenylylated M. tuberulosis glutamine synthetase in E. coli by the co-expression of M. tuberculosis glutamine synthetase and M. tuberculosis adenylyl transferase. The differential inhibition of adenylylated M. tuberulosis glutamine synthetase and deadenylylated M. tuberulosis glutamine synthetase by ATP based scaffold inhibitors are reported. Compounds selected on the basis of their enzyme inhibition were also shown to inhibit M. tuberculosis in the BACTEC 460TB™ assay as well as the intracellular inhibition of M. tuberculosis in a mouse bone-marrow derived macrophage assay.

Timing and locations of reef fish spawning off the southeastern United States.

Managed reef fish in the Atlantic Ocean of the southeastern United States (SEUS) support a multi-billion dollar industry. There is a broad interest in locating and protecting spawning fish from harvest, to enhance productivity and reduce the potential for overfishing. We assessed spatiotemporal cues for spawning for six species from four reef fish families, using data on individual spawning condition collected by over three decades of regional fishery-independent reef fish surveys, combined with a series of predictors derived from bathymetric features. We quantified the size of spawning areas used by reef fish across many years and identified several multispecies spawning locations. We quantitatively identified cues for peak spawning and generated predictive maps for Gray Triggerfish (Balistes capriscus), White Grunt (Haemulon plumierii), Red Snapper (Lutjanus campechanus), Vermilion Snapper (Rhomboplites aurorubens), Black Sea Bass (Centropristis striata), and Scamp (Mycteroperca phenax). For example, Red Snapper peak spawning was predicted in 24.7-29.0°C water prior to the new moon at locations with high curvature in the 24-30 m depth range off northeast Florida during June and July. External validation using scientific and fishery-dependent data collections strongly supported the predictive utility of our models. We identified locations where reconfiguration or expansion of existing marine protected areas would protect spawning reef fish. We recommend increased sampling off southern Florida (south of 27° N), during winter months, and in high-relief, high current habitats to improve our understanding of timing and location of reef fish spawning off the southeastern United States.

Early-life glucocorticoids programme behaviour and metabolism in adulthood in zebrafish.

Glucocorticoids (GCs) in utero influence embryonic development with consequent programmed effects on adult physiology and pathophysiology and altered susceptibility to cardiovascular disease. However, in viviparous species, studies of these processes are compromised by secondary maternal influences. The zebrafish, being fertilised externally, avoids this problem and has been used here to investigate the effects of transient alterations in GC activity during early development. Embryonic fish were treated either with dexamethasone (a synthetic GC), an antisense GC receptor (GR) morpholino (GR Mo), or hypoxia for the first 120h post fertilisation (hpf); responses were measured during embryonic treatment or later, post treatment, in adults. All treatments reduced cortisol levels in embryonic fish to similar levels. However, morpholino- and hypoxia-treated embryos showed delayed physical development (slower hatching and straightening of head-trunk angle, shorter body length), less locomotor activity, reduced tactile responses and anxiogenic activity. In contrast, dexamethasone-treated embryos showed advanced development and thigmotaxis but no change in locomotor activity or tactile responses. Gene expression changes were consistent with increased (dexamethasone) and decreased (hypoxia, GR Mo) GC activity. In adults, stressed cortisol values were increased with dexamethasone and decreased by GR Mo and hypoxia pre-treatments. Other responses were similarly differentially affected. In three separate tests of behaviour, dexamethasone-programmed fish appeared 'bolder' than matched controls, whereas Mo and hypoxia pre-treated fish were unaffected or more reserved. Similarly, the dexamethasone group but not the Mo or hypoxia groups were heavier, longer and had a greater girth than controls. Hyperglycaemia and expression of GC responsive gene (pepck) were also increased in the dexamethasone group. We conclude that GC activity controls many aspects of early-life growth and development in the zebrafish and that, like other species, manipulating GC status pharmacologically, physiologically or genetically in early life leads to programmable metabolic and behavioural traits in adulthood.

Did AIDS mortality decrease the number of lifetime sexual partners in Kenya: an ecological analysis?

We assessed if there has been a decline in the median number of reported lifetime sexual partners in Kenya following the AIDS epidemic. The Wilcoxon rank-sum test was used to compare the median and interquartile range (IQR) of the number of lifetime sexual partners for men aged 20-54 years in the 1993 and 2008 Kenyan Demographic Health Surveys. The median number of sexual partners in 1993 increased rapidly to 10 partners reported at age 30 years then plateaued at this level. In 2008, the median number of sexual partners plateaued at around half the value of the 1993 plateau. The median number of lifetime sexual partners for men aged 20-54 years declined from 10 (IQR 4-20) in 1993 to 3 (IQR 2-7) in 2008 (P < 0·001). This decline could be due to a combination of the effects of AIDS mortality and a misreporting bias.