The presence of symptom clusters, regional differences in disease expression and similarities with, for example, Crohn's disease suggest multiple pathological pathways are involved in Behcet syndrome. These features also make formulating disease criteria difficult. Genetic studies have identified HLA-B*51 to be the important genetic risk factor. However, the low prevalence of HLA-B*51 in many patients with bone fide disease, especially in non-endemic regions, suggests other factors must also be operative in Behcet syndrome. This consideration is also true for the newly proposed 'MHC-I-opathy' concept. Despite lacking a clear aetiological mechanism and definition, management of manifestations that include major vascular disease (such as Budd-Chiari syndrome and pulmonary artery involvement), eye disease and central nervous system involvement has improved with the help of new technology. Furthermore, even with our incomplete understanding of disease mechanisms, the prognoses of patients with Behcet syndrome, including those with eye disease, continue to improve.

Behçet syndrome: a contemporary view.

Human oral microbiota and its modulation for oral health.

Flow physics plays a key role in nearly every facet of the COVID-19 pandemic. This includes the generation and aerosolization of virus-laden respiratory droplets from a host, its airborne dispersion and deposition on surfaces, as well as the subsequent inhalation of these bioaerosols by unsuspecting recipients. Fluid dynamics is also key to preventative measures such as the use of face masks, hand-washing, ventilation of indoor environments, and even social distancing. This article summarizes what we know, and more importantly, what we need to learn about the science underlying these issues so that we are better prepared to tackle the next outbreak of COVID-19 or a similar disease.

Flow Physics of COVID-19

Behcet’s disease (BD) is a recalcitrant, multisystemic inflammatory disease that can lead to irreversible blindness. Microbial agents have been considered to contribute to the pathogenesis of this disease, but the underlying mechanisms remain unclear. In this study, we investigated the association of gut microbiome composition with BD as well as its possible roles in the development of this disease. Fecal and saliva samples were collected from 32 active BD patients and 74 healthy controls. DNA extracted from fecal samples was subjected to metagenomic analysis, whereas DNA extracted from saliva samples was subjected to 16S rRNA gene sequencing analysis. The results were used to compare the composition and biological function of the microbiome between patients and healthy controls. Lastly, transplantation of pooled fecal samples from active BD patients into B10RIII mice undergoing experimental autoimmune uveitis (EAU) was performed to determine the causal relationship between the gut microbiome and BD. Fecal samples from active BD patients were shown to be enriched in Bilophila spp., a sulfate-reducing bacteria (SRB) and several opportunistic pathogens (e.g., Parabacteroides spp. and Paraprevotella spp.) along with a lower level of butyrate-producing bacteria (BPB) Clostridium spp. and methanogens (Methanoculleus spp. Methanomethylophilus spp.). Analysis of microbial functions revealed that capsular polysaccharide transport system, oxidation-reduction process, type III, and type IV secretion systems were also increased in active BD patients. Network analysis showed that the BD-enriched SRB and opportunistic pathogens were positively correlated with each other, but they were negatively associated with the BPB and methanogens. Animal experiments revealed that fecal microbiota transplantation with feces from BD patients significantly exacerbated EAU activity and increased the production of inflammatory cytokines including IL-17 and IFN-γ. Our findings revealed that BD is associated with considerable gut microbiome changes, which is corroborated by a mouse study of fecal microbiota transplants. A model explaining the association of the gut microbiome composition with BD pathogenesis is proposed.

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A metagenomic study of the gut microbiome in Behcet's disease.

The emergence of antimicrobial resistance against Mycobacterium tuberculosis, the leading cause of mortality due to a single microbial pathogen worldwide, represents a growing threat to public health and economic growth. The global burden of multidrug-resistant tuberculosis (MDR-TB) has recently increased by an annual rate of more than 20%. According to the World Health Organization approximately only half of all patients treated for MDR-TB achieved a successful outcome. For many years, patients with drug-resistant tuberculosis (TB) have received standardized treatment regimens, thereby accelerating the development of MDR-TB through drug-specific resistance amplification. Comprehensive drug susceptibility testing (phenotypic and/or genotypic) is necessary to inform physicians about the best drugs to treat individual patients with tailor-made treatment regimens. Phenotypic drug resistance can now often, but with variable sensitivity, be predicted by molecular drug susceptibility testing based on whole genome sequencing, which in the future could become an affordable method for the guidance of treatment decisions, especially in high-burden/resource-limited settings. More recently, MDR-TB treatment outcomes have dramatically improved with the use of bedaquiline-based regimens. Ongoing clinical trials with novel and repurposed drugs will potentially further improve cure-rates, and may substantially decrease the duration of MDR-TB treatment necessary to achieve relapse-free cure.

Drug-resistant tuberculosis: An update on disease burden, diagnosis and treatment.

Urgent dental care for patients during the COVID-19 pandemic.

Background : Behcet’s syndrome (BS) is a multisystem immune-related disease of unknown etiology. Recurrent aphthous stomatitis (RAS) is characterized by the presence of idiopathic oral ulceration without extraoral manifestation. The interplay between the oral microbial communities and the immune response could play an important role in the etiology and pathogenesis of both BS and RAS. Objective : To investigate the salivary and oral mucosal microbial communities in BS and RAS. Methods : Purified microbial DNA isolated from saliva samples (54 BS, 25 healthy controls [HC], and 8 RAS) were examined by the human oral microbe identification microarray. Cultivable salivary and oral mucosal microbial communities from ulcer and non-ulcer sites were identified by matrix-assisted laser desorption/ionization time-of-flight analysis. Mycobacterium spp. were detected in saliva and in ulcer and non-ulcer oral mucosal brush biopsies following culture on Lowenstein-Jensen slopes and Mycobacterial Growth Indicator Tubes. Results : There was increased colonization with Rothia denticariosa of the non-ulcer sites of BS and RAS patients ( p <0.05). Ulcer sites in BS were highly colonized with Streptococcus salivarius compared to those of RAS ( p <0.05), and with Streptococcus sanguinis compared to HC ( p <0.0001). Oral mucosa of HC were more highly colonized with Neisseria and Veillonella compared to all studied groups ( p <0.0001). Conclusions : Despite the uncertainty whether the reported differences in the oral mucosal microbial community of BS and RAS are of causative or reactive nature, it is envisaged that restoring the balance of the oral microbial community of the ulcer sites may be used in the future as a new treatment modality for oral ulceration. Keywords : Behcet’s syndrome; recurrent aphthous stomatitis; microbiota; oral mucosa; saliva (Published: 1 June 2015) Citation: Journal of Oral Microbiology 2015, 7: 27150 - http://dx.doi.org/10.3402/jom.v7.27150

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The oral mucosal and salivary microbial community of Behcet’s syndrome and recurrent aphthous stomatitis

Background: The aim of this study was to evaluate and compare oral health-related quality of life (oral QoL) in patients from UK and Turkey with Behcet’s disease (BD).



Methods:  Thirty-one BD patients from UK (F/M: 18/13, mean age: 41.8 ± 11.5 years) and Turkey (F/M: 18/13, mean age: 41.5 ± 10.3) who were matched according to age and gender were included in the study. All patients had active oral ulcers. Oral QoL was assessed by Oral Health Impact Profile-14 (OHIP-14). Oral health was evaluated by dental and periodontal indices.



Results:  No significant difference was found in OHIP-14 scores between patients from UK (22.7 ± 14.4) and Turkey (20.4 ± 14.3) (P = 0.709). The OHIP-14 score correlated with the healing time of oral ulcers in UK (r = 0.4, P = 0.04) and the number of oral ulcers in Turkey (r = 0.4, P = 0.012). The number of oral ulcers per month was significantly higher in UK (3.3 ± 2.8) compared with that in Turkey (1.5 ± 2.5) (P = 0.014). However, the number of filled teeth and frequency of tooth brushing were significantly lower in patients from Turkey compared with those in UK (P = 0.000). Similarly, the duration since the last dental visit (5.1 ± 7.2 months) was significantly lower in UK compared with that in Turkey (28.6 ± 23.7 months) (P = 0.000).



Conclusions:  Oral QoL was similar in patients from UK and Turkey with active oral ulcers. However, the number of oral ulcers was observed to be higher in UK. As expected, a lower utilization rate of dental services might have led to a poorer oral health in patients from Turkey.

Oral health and related quality of life status in patients from UK and Turkey: a comparative study in Behcet's disease.

TLRs are PRRs that play a pivotal role in sensing exogenous pathogens and endogenous danger signals. Their role in the pathogenesis of inflammatory and immune-related diseases is gradually being unravelled. TLR2 and TLR4 are capable of sensing the oral microbial community, which is considered a potential trigger for Behcet's disease (BD). This study aimed to investigate the expression and function of TLR2 and TLR4 in the oral mucosa of BD. A total of 87 patients was included: 55 BD, 24 healthy controls and eight recurrent aphthous stomatitis. Total RNA was purified from non-lesional oral mucosal brush biopsies and analysed for the presence of TLR2 and TLR4 mRNA, along with their splice variants. The response of peripheral blood mononuclear cells to classical TLR2 and TLR4 agonists was also investigated. TLR2b, TLR2d, TLR2e, TLR4.3 and TLR4.4 were significantly elevated in relapsed BD. A significant defect in the response to cognate agonists of TLR1/2 heterodimer and TLR4 was also observed in BD. The expression of unusual splice variants of TLR2 and TLR4 might explain the observed defect in these receptors' function in BD.

https://journals.sagepub.com/doi/pdf/10.1177/1753425913498042

The role of TLR2 and 4 in Behçet's disease pathogenesis.

Introduction This study was conducted in light of the SARS-CoV-2 pandemic, which brought UK dentistry to a standstill. The market has seen a recent influx of unproven extraoral scavengers (EOSs), which claim to reduce the risk of particulate spread.Aims To investigate the efficacy of a commercially available EOS device on contamination reduction during dental aerosol generating procedures (AGPs). The secondary aim was to investigate differences between open and closed dental operatories.Method Dental procedures were simulated on a dental manikin using citric acid (10%) added to the water lines with universal indicating paper (UIP) placed in strategic locations in the operatory, on the clinician and assistant. Chromatic change related to settling of splatter containing citric acid on the UIP was analysed to calculate percentage intensity of splatter contamination.Results EOSs resulted in 20% reduction in frequency and 75% reduction in mean intensity of contamination of operatory sites. There was a 33% and 76% reduction in mean intensity contamination for clinician and assistant, respectively. Use of rubber dam and four-handed dentistry resulted in further reduction.Discussion This exploratory study demonstrates contamination by splatter in a simulated dental setting. The concern in dentistry regarding aerosol requires further quantitative investigation of smaller particles.Conclusions The routine use of four-handed dentistry and rubber dam should continue where possible to maximise risk mitigation during AGPs. However, on the basis of our findings, the use of an EOS device can further mitigate the magnitude and concentration of splatter.

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The efficacy of an extraoral scavenging device on reduction of splatter contamination during dental aerosol generating procedures: an exploratory study.

Noha Seoudi

Papers

Urgent dental care for patients during the COVID-19 pandemic.

The oral mucosal and salivary microbial community of Behcet’s syndrome and recurrent aphthous stomatitis

Oral health and related quality of life status in patients from UK and Turkey: a comparative study in Behcet's disease.

The role of TLR2 and 4 in Behçet's disease pathogenesis.

The efficacy of an extraoral scavenging device on reduction of splatter contamination during dental aerosol generating procedures: an exploratory study.