Characterising sources of PM2·5 exposure for school children with asthma: a personal exposure study across six cities in sub-Saharan Africa.

BACKGROUND: Air pollution is the second largest risk to health in Africa, and children with asthma are particularly susceptible to its effects. Yet, there is a scarcity of air pollution exposure data from cities in sub-Saharan Africa. We aimed to identify potential exposure reduction strategies for school children with asthma living in urban areas in sub-Saharan Africa. METHODS: This personal exposure study was part of the Achieving Control of Asthma in Children in Africa (ACACIA) project. Personal exposure to particulate matter (PM) was monitored in school children in six cities in sub-Saharan Africa (Blantyre, Malawi; Durban, South Africa; Harare, Zimbabwe; Kumasi, Ghana; Lagos, Nigeria; and Moshi, Tanzania). Participants were selected if they were aged 12-16 years and had symptoms of asthma. Monitoring was conducted between June 21, and Nov 26, 2021, from Monday morning (approximately 1000 h) to Friday morning (approximately 1000 h), by use of a bespoke backpack with a small air pollution monitoring unit with an inbuilt Global Positioning System (GPS) data logger. Children filled in a questionnaire detailing potential sources of air pollution during monitoring and exposures were tagged into three different microenvironments (school, commute, and home) with GPS coordinates. Mixed-effects models were used to identify the most important determinants of children's PM2·5 (PM <2·5 µm in diameter) exposure. FINDINGS: 330 children were recruited across 43 schools; of these, 297 had valid monitoring data, and 1109 days of valid data were analysed. Only 227 (20%) of 1109 days monitored were lower than the current WHO 24 h PM2·5 exposure health guideline of 15 µg/m3. Children in Blantyre had the highest PM2·5 exposure (median 41·8 µg/m3), whereas children in Durban (16·0 µg/m3) and Kumasi (17·9 µg/m3) recorded the lowest exposures. Children had significantly higher PM2·5 exposures at school than at home in Kumasi (median 19·6 µg/m3vs 14·2 µg/m3), Lagos (32·0 µg/m3vs 18·0 µg/m3), and Moshi (33·1 µg/m3vs 23·6 µg/m3), while children in the other three cities monitored had significantly higher PM2·5 exposures at home and while commuting than at school (median 48·0 µg/m3 and 43·2 µg/m3vs 32·3 µg/m3 in Blantyre, 20·9 µg/m3 and 16·3 µg/m3vs 11·9 µg/m3 in Durban, and 22·7 µg/m3 and 25·4 µg/m3vs 16·4 µg/m3 in Harare). The mixed-effects model highlighted the following determinants for higher PM2·5 exposure: presence of smokers at home (23·0% higher exposure, 95% CI 10·8-36·4), use of coal or wood for cooking (27·1%, 3·9-56·3), and kerosene lamps for lighting (30·2%, 9·1-55·2). By contrast, 37·2% (95% CI 22·9-48·2) lower PM2·5 exposures were found for children who went to schools with paved grounds compared with those whose school grounds were covered with loose dirt. INTERPRETATION: Our study suggests that the most effective changes to reduce PM2·5 exposures in these cities would be to provide paving in school grounds, increase the use of clean fuel for cooking and light in homes, and discourage smoking within homes. The most efficient way to improve air quality in these cities would require tailored interventions to prioritise different exposure-reduction policies in different cities. FUNDING: UK National Institute for Health and Care Research.

Does decision tree analysis predict oral ulcer activity-related factors in patients with Behçet's syndrome?

OBJECTIVES: The study aimed to identify the interactions among treatment protocols and oral ulcer activity related factors in patients with Behçet's syndrome (BS) using the Classification and Regression Tree (CART) algorithm. METHODS: In this cross-sectional study, 979 patients with BS were included from16 centres in Turkey, Jordan, Brazil and the United Kingdom. In the CART algorithm, activities of oral ulcer (active vs. inactive), genital ulcer (active vs. inactive), cutaneous involvement (active vs. inactive), musculoskeletal involvement (active vs. inactive), gender (male vs. female), disease severity (mucocutaneous and musculoskeletal involvement vs. major organ involvement), smoking habits (current smoker vs. non-smoker), tooth brushing habits (irregular vs. regular), were input variables. The treatment protocols regarding immunosuppressive (IS) or non-IS medications were the target variable used to split from parent nodes to purer child nodes in the study. RESULTS: In mucocutaneous and musculoskeletal involvement (n=538), the ratio of IS use was higher in patients with irregular toothbrushing (ITB) habits (27.1%) than in patients with regular toothbrushing (RTB) habits (14.2%) in oral ulcer activity. In major organ involvement (n=441), male patients with ITB habits were more likely treated with IS medications compared to those with RTB habits (91.6% vs. 77.6%, respectively). CONCLUSIONS: Male BS patients on IS who have major organ involvement and oral ulcer activity with mucocutaneous and musculoskeletal involvement have irregular toothbrushing habits. Improved oral hygiene practices should be considered to be an integral part for implementing patient empowerment strategies for BS.

Gastrointestinal dysmotility complicating Behçet's syndrome: description of a newly recognised clinical phenotype.

OBJECTIVES: Gastrointestinal dysmotility may arise in a variety of auto-immune and auto-inflammatory diseases and hitherto has not been described in Behçet's syndrome (BS). METHODS: We present data on a cohort of seven patients under our care who presented with symptoms of and investigations compatible with an immune associated disorder of gastrointestinal motility, or enteric neuropathy. RESULTS: We describe the clinical features and investigation results. We undertook a trial of a novel treatment in the disease, apheresis, and noted a response not only to the enteric neuropathy but also to the systemic features of the disease, despite previous maximal immunosuppressive therapy in most cases. CONCLUSIONS: Gastrointestinal dysmotility may arise in BS and is effectively treated by apheresis. The mechanism by which this response is made immunologically requires to be elucidated in future studies.

Behçet's patients' response to COVID-19 vaccination.

Immune hyperstimulation by SARS-CoV2 results in multi-system involvement with consequent organ damage not dissimilar to Behçet's Disease (BD). Management of BD includes immunosuppressive medication, which led to concerns that; firstly, SARS-CoV-2 would stimulate BD activity, thrombin, clotting times, TPO antibodies, and the effectiveness and duration of the COVID-19 vaccines' response in this potentially vulnerable group. The main objectives of this study were: to assess BD patients' immune response to the COVID-19 vaccines based on age, gender, disease activity, BD phenotype, and immunomodulatory medication compared to healthy control participants by measuring anti-spike IgG levels. Further to evaluate the effect of the COVID-19 vaccines on T and B cells, immunoglobulins, thrombophilia, thyroid function and COVID-19 antibody production. Patients on immunosuppressive medication had a reduced immune response to COVID-19 vaccines. -Also, patients over 40 years and with the neurologic BD phenotype had lower responses. mRNA COVID-19 vaccines were more effective and had fewer side effects compared to conventional COVID-19 vaccines.

Profiling the microbiome of oral and genital mucosal surfaces in Behçet's disease.

Almost 90% of Behçet's patients present with oral and/or genital ulcers which influence the disease outcome. We hypothesised that the dysregulation of the oral and genital microbiome, coupled with dysregulation of the immune response, contributes to the aetiopathogenesis of Behçet's Disease (BD) and drives disease activation. METHOD: 152 BD patient samples; 70 matched oral and genital samples plus 12 unmatched samples (Female: Male, 58:12; mean age, 42 ± 13.9: 39.3 ± 10.3) to profile microbial community high-throughput sequencing of the microbiome using 16 s rRNA sequencing targeting the V1/V2 and V3/V4 hyper variable regions were used and results reviewed in relation to disease severity, Work and Social Adjustment Scale (WSAS) outcomes and medication. RESULTS: Alpha and beta diversity were significantly decreased in genital compared to oral samples; p value<0.05. However, grouping the samples as to whether ulceration was present was not significant. Escherichia-Shigella was the only Amplicon Sequence Variants (ASVs) in the V1/V2 region that was shared between the oral mucosa with ulcer (O_U) and genital mucosa with ulcer (G_U) groups. This was in contrast to the V3/V4 region which indicated that Lachnospiraceae, Saccharimonadales, and Coriobacteriales were shared between the O_U and G_U groups. In addition, gender had no impact on the bacterial abundance in V1/V2 analysis of the oral and genital samples. V3/V4 analysis of genital samples demonstrated that Lactobacilli and Gardnerella were significantly increased in females (20 times) compared to the males in samples; p-adj <0.05. Interestingly in BD patients, Rothia which is commonly found in the mouth was present in both oral and genital samples. Streptococci were significantly increased while Veillonella significantly decreased in the presence of oral ulceration in the BD cohort. The clinical phenotype had no effect on V1/V2 and V3/V4 on the bacterial abundance of oral samples. However, medication e.g. colchicine had a significant effect on the oral microbial abundance (V1/V2; P = 0.020, V3/V4; P = 0.003). There was no relationship between colchicine and the presence/absence of genital ulcers. BD patients with active disease had higher WSAS scores, and their bacterial abundance differed significantly from the non-active BD patients (ADONIS, R2 = 0.05, p value =0.029). CONCLUSION: The presence of the microbes Streptococcus, Veillonella, Gardnerella, Lactobacillus, Atopobium, Peptoniphilus, Corynebacterium and Staphylococcus may provide early evidence of BD patients are with active disease.

A cross-sectional study on activity impairment in primary Sjogren's syndrome.

OBJECTIVE: The aim of this cross-sectional study was to show relations between activity impairment and salivary gland involvement for patient empowerment in primary Sjogren's syndrome (pSS). METHODS: In the study, 86 patients with pSS were included. The data were collected through clinical examinations and a questionnaire regarding Work Productivity and Activity Impairment (WPAI), EULAR Sjogren's syndrome patient-reported index (ESSPRI) and Oral Health Impact Profile-14 (OHIP-14). Relations were analysed by using mediation and moderation analyses. In simple mediation analysis, an independent variable (X) influences outcome variable (Y) through a mediator variable (M) whereas a moderator variable (W) affects the direction of the relationship between the dependent (Y) and independent variables (X). RESULTS: Increases in ESSPRI-Dryness score (X) (p = 0.0189) and OHIP-14 score (M) (p = 0.0004) were associated with the poor WPAI activity impairment score (Y) in the first mediation analysis. The WPAI activity impairment score was mediated by the elevated ESSPRI-Fatigue score (X) (p = 0.03641) and low U-SFR (M) (p = 0.0000) in the second mediation analysis. In addition, ESSPRI-Pain score (W) was the significant moderator for WPAI activity impairment (Y) in patients without hyposalivation in the moderation analysis (p = 0.0010). CONCLUSION: WPAI activity impairment was affected by both ESSPRI-Dryness with OHRQoL and ESSPRI-Fatigue with SFR in glandular involvement.

The impact of the COVID-19 pandemic on patients with Behçet's syndrome within the framework of Maslow's hierarchy of needs: implications for patient empowerment in national or global emergencies.

OBJECTIVES: The aim of this online survey was to assess the impact of the COVID-19 pandemic on patients with Behçet's syndrome (BS) using Maslow's hierarchy of needs. METHODS: Sixty-eight BS patients from the UK completed an online questionnaire that covered three components of Maslow's hierarchy of needs regarding Physiological needs (sleep, food, mobility), Safety needs (employment, health), Social needs (relationships), personal precautions and main concerns regarding COVID-19. RESULTS: The patients received a letter from the NHS (66.2%) advising shielding. Health concerns were addressed using Tele-medicine by telephone consultations and e-mails to access BS specialists during lockdown (44.1%; 27.9%). In addition, patients also obtained information through official government and Behçet corporate health web pages related to Behçet's disease for self-empowerment. During lockdown, their weekly working hours were reduced (26.65±13.86 vs. 20.79±17.94) (p=0.017) and the employment rate was decreased (32.6% vs. 26.7%) in comparison to pre-lockdown. Moreover, the reduction in frequency of exercise per week (4.39±1.94 vs. 3.71±2.26) and healthy food consumption (73.5 % vs. 47.1%) per week were also reported (p=0.007; p=0.001, respectively). Furthermore, patients experienced sleeping less (54.4%) and feeling lonely (66.1%). CONCLUSIONS: Using Maslow's hierarchy of needs provided a framework for reviewing the quality of basic needs in patients' life during lockdown. These needs are required for healthy social lives and the deprivation should be considered while considering healthcare planning. Since lockdown appeared to have a negative influence on patients' lives and disease management in the framework of patient-centred, the empowerment of patients gained importance at this point.

The impact of multifactorial factors on the Quality of Life of Behçet's patients over 10 years.

Objective: This study analyses the 2020 survey and reviews the 2009, 2014 surveys to ascertain which Behçet's symptoms, personal and family status, patients' lifestyle, and work-related outcomes impacted on Health-Related Quality of Life (HRQoL). Methods: Four hundred and fifty-nine Behçet's patients submitted an online survey/questionnaire. Patients provided information on socio-demographic characteristics, disease duration, historical and current symptoms, systemic and topical medication, health related lifestyle, work-related outcomes regarding employment status and claiming benefits and Quality of Life (QoL) measured by EQ-5D index. Results: Four hundred and nineteen patients met the inclusion criteria, and 371 who had full data (Males: Females: Others = 84:285:2, mean-age = 41.1 ± 23.3:38 ± 13.2:40 ± 5). The main symptoms associated with patients seeking medical care were mouth ulcers 30% and genital ulcers 23%, joint 14%, and eye problems 9%. The EQ-5D index for 2009, 2014, 2020 was (mean ± SD); 0.47 ± 0.38, 0.42 ± 0.37, 0.34 ± 0.40, respectively, p < 0.05. 2020 patients had the worst values of the five domains compared to 2014 and 2009. Interestingly, mobility value was the same over the 10 years of monitoring patients. Behçet's syndrome (BS) symptoms that had significant negative impact on QoL were; 2009 (arthropathy, neurological problems, pathergy reaction, and stomach/bowel symptoms), 2014 (arthropathy, headache, neurological problems, pathergy reaction, and skin lesions), 2020 (arthropathy, neurological problems, and stomach/bowel symptoms). The 2014 and 2020 surveys reported the QoL is significantly better in patients on immunosuppressant, who did sport, continued in employment and not receiving benefits. Conclusion: Joints and neurological symptoms are the main symptoms which had negative impact on BS patients over the 10 years, sociodemographic (gender, age, marital, and education status), lifestyle (medication, cannabis, drinking wine, and regular exercise), employment status (employee and no career change), and accessing benefits (never claim benefit) had significant influence on patients' HRQoL.

The assessment of presenteeism and activity impairment in Behçet's syndrome and recurrent aphthous stomatitis: a multicentre study.

OBJECTIVE: To evaluate key factors for presenteeism and activity impairment in multinational patients with Behçet's syndrome (BS) and recurrent aphthous stomatitis (RAS). METHODS: In this cross-sectional study, 364 BS patients from Jordan, Brazil, the United Kingdom and Turkey and 143 RAS patients from the United Kingdom and Turkey were included. The Work Productivity Activity Impairment (WPAI) scale was used for presenteeism and activity impairment. Mediation analyses were performed to evaluate both direct and indirect causal effects. RESULTS: Presenteeism score was higher in active patients with genital ulcers and eye involvement as well as patients with comorbidities and current smokers than the others in BS (P < 0.05). In RAS, presenteeism score was elevated by oral ulcer activity in the direct path (P = 0.0073) and long disease duration as a mediator in the indirect path (P = 0.0191). Patients with active joint involvement had poor scores in absenteeism, presenteeism, overall impairment and activity impairment compared with those of inactive patients (P < 0.05). Using mediation analysis, the activity impairment score was directly mediated by joint activity (P = 0.0001) and indirectly mediated through oral ulcer-related pain in BS (P = 0.0309). CONCLUSION: In BS, presenteeism was associated with disease activity, presence of comorbidities and being a current smoker, whereas in RAS, presenteeism was associated with oral ulcer activity and increased length of the disease. Moreover, activity impairment was adversely affected by joint activity and oral ulcer related pain in BS. Patients need to be empowered by using appropriate treatment strategies in their working environment and daily life.

Oral Health and Its Aetiological Role in Behçet's Disease.

Behçet's disease (BD) is a chronic multi-systemic inflammatory disorder characterised by oro-genital ulcers, cutaneous manifestations, ocular, vascular, neurologic and gastrointestinal involvement. Complex interactions operating on the genetic background e.g.(HLA51), of infectious and other environmental agents, together with immune dysregulation impacts on the pathogenesis of BD. This suggests that the environmental factors triggering immune responses may activate clinical manifestations in genetically susceptible individuals. Since oral health forms the basis of all general health both dental and systemic, it is an important component of both Dentistry and Medicine. Oral ulcers are the most common clinical manifestation of oral mucosal health. Changes in the oral environment consequently acts as an infective and immune trigger. In this review, complex interactions between the oral ulcers, the oral microbiome and immune responses together with the course of oral and systemic disease manifestations in BD are discussed in the context of the aetiologic role of oral health.

Oxidative Stress-Mediated YAP Dysregulation Contributes to the Pathogenesis of Pemphigus Vulgaris.

Pemphigus Vulgaris (PV) is a life-threatening autoimmune disease manifested with blisters in the skin and mucosa and caused by autoantibodies against adhesion protein desmoglein-3 (Dsg3) expressed in epithelial membrane linings of these tissues. Despite many studies, the pathogenesis of PV remains incompletely understood. Recently we have shown Dsg3 plays a role in regulating the yes-associated protein (YAP), a co-transcription factor and mechanical sensor, and constraining reactive oxygen species (ROS). This study investigated the effect of PV sera as well as the anti-Dsg3 antibody AK23 on these molecules. We detected elevated YAP steady-state protein levels in PV cells surrounding blisters and perilesional regions and in keratinocytes treated with PV sera and AK23 with concomitant transient ROS overproduction. Cells treated with hydrogen peroxide also exhibited augmented nuclear YAP accompanied by reduction of Dsg3 and α-catenin, a negative regulator of YAP. As expected, transfection of α-catenin-GFP plasmid rendered YAP export from the nucleus evoked by hydrogen peroxide. In addition, suppression of total YAP was observed in hydrogen peroxide treated cells exposed to antioxidants with enhanced cell-cell adhesion being confirmed by decreased fragmentation in the dispase assay compared to hydrogen peroxide treatment alone. On the other hand, the expression of exogenous YAP disrupted intercellular junction assembly. In contrast, YAP depletion resulted in an inverse effect with augmented expression of junction assembly proteins, including Dsg3 and α-catenin capable of abolishing the effect of AK23 on Dsg3 expression. Finally, inhibition of other kinase pathways, including p38MAPK, also demonstrated suppression of YAP induced by hydrogen peroxide. Furthermore, antioxidant treatment of keratinocytes suppressed PV sera-induced total YAP accumulation. In conclusion, this study suggests that oxidative stress coupled with YAP dysregulation attributes to PV blistering, implying antioxidants may be beneficial in the treatment of PV.

Behçet's syndrome in children and young people in the United Kingdom and the Republic of Ireland: a prospective epidemiological study.

OBJECTIVES: To define the incidence and prevalence of Behçet's syndrome (BS) in children and young people (CYP) up to the age of 16 years in the United Kingdom (UK) and Republic of Ireland (ROI). METHODS: A prospective epidemiological study was undertaken with the support of the British Paediatric Surveillance Unit (BPSU) and the British Society of Paediatric Dermatologists (BSPD). Consultants reported anonymised cases of BS seen. A follow-up study at one year examined progression of disease and treatment. RESULTS: Over a two-year period, 56 cases met the International Criteria for Behçet's Disease. For children under 16 years of age, the two-year period prevalence estimate was 4.2 per million (95% CI: 3.2, 5.4) and the incidence was 0.96 per million person years (95% CI: 0.66, 1.41). Mucocutaneous disease was the most common phenotype (56/100%), with ocular (10/56; 17.9%), neurological (2/56; 3.6%) and vascular involvement (3/56; 5.4%) being less common. Median age at onset was 6.34 years and at diagnosis was 11.72 years. There were slightly more female than male children reported (32/56; 55.6%). The majority of cases (85.7%) were white Caucasian. Apart from genital ulcers, which were more common in females, there were no significant differences in frequency of manifestations between male or females, nor between ethnicities. Over 83% of cases had three or more non-primary care healthcare professionals involved in their care. CONCLUSION: BS is extremely rare in CYP in the UK and ROI and most have mucocutaneous disease. Healthcare needs are complex, and coordinated care is key.

Saliva and Serum Cytokine Profiles During Oral Ulceration in Behçet's Disease.

Behçet's disease (BD) is a chronic, multi-systemic disorder of unknown aetiology typified by recurrent oral and genital mucocutaneous lesions, uveitis and vasculitis. Innate and adaptive immune system dysregulation has been implicated in pathogenesis with alterations in serum cytokine profiles. Few studies have investigated salivary cytokines in BD, despite more than 90% of BD patients first presenting with oral ulceration. The aim of this pilot study was twofold; firstly to investigate whether cytokine levels in matched serum and saliva samples show a differential profile in BD (with and without oral ulcers), recurrent aphthous stomatitis (RAS) and healthy controls (HCs), and secondly, to explore if any differential profiles in serum and/or saliva could provide a panel of cytokines with diagnostic and therapeutic potential for BD. Concentrations of 12 cytokines (IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IFN-γ, TNF-α, TNF-ß) were measured using the Human Th1/Th2 11-Plex FlowCytomix™ kit with IL-17A, in BD (N=20), RAS (N=6) and HCs (N=10). A differential range of cytokines was detected in serum and saliva with the majority of cytokine levels higher in saliva. The most prevalent salivary cytokines were IL-1ß, IL-2, IL-8, IL-10 and TNF-α present in all samples in contrast to serum where the most prevalent cytokine detected was IL-8 (91.9%). The least abundant cytokine was IFN-γ in both saliva (43.2%) and serum (2.7%). After normalizing saliva for protein content, BD patients with oral ulcers (BD-MA) had significantly higher levels of salivary IL-1ß (p=0.01), IL-8 (p=0.02), TNF-α (p=0.004) and IL-6 (p=0.01) than HCs. Notably, BD patients without oral ulcers (BD-MQ) also had significantly higher salivary IL-1ß, IL-8 and TNF-α (p ≤ 0.05) than HCs. During relapsed (BD-RE) and quiet (BD-Q) systemic episodes, salivary IL-ß and TNF-α were also significantly increased with IL-8 significantly higher only in BD-Q (p=0.02). BD oral ulcers signify a potential reactivation of systemic inflammation. Identifying cytokines released during asymptomatic episodes and oral ulceration might lead to targeted drug therapy to prevent recurrent oral ulcers and possible disease relapse. This is the first study to report salivary cytokine levels in BD. The detectable levels suggests cytokine profiling of BD saliva may provide an alternative, less invasive, sensitive procedure for frequent monitoring of disease activity and progression.

New mouthwash: an efficacious intervention for oral ulceration associated with Behçet's disease.

Topical interventions to treat oral ulcers in Behçet's disease (BD) are crucial to control disease activity and improve patients' quality of life. Our aim was to evaluate the effectiveness of a new BD mouthwash (BD MW) for oral ulceration. A retrospective cross-sectional study was carried out on 261 BD patients (141 women, mean (SD) age 39.9 (11.8) years, and 120 men, mean (SD) age 41.141(3.7) years). All were assessed using the oral ulcer severity score (OUSS), oral health quality of life (OHQoL), and the Behçet's disease current activity form (BDCAF). Patients were divided into three groups: one group used the BD MW, one group used a betamethasone mouthwash, and the other used no therapeutic mouthwash. Patients were assessed at three and six months. The OUSS in those using the BD MW was nine times lower than it was in those using betamethasone mouthwash (p=0.001), and 12 times lower than it was in the no mouthwash group (p=0.001). Compared with the baseline data, use of the BD MW during the first three months significantly reduced the OUSS, the BDCAF score, and intraoral scarring, and also improved OHQoL (p=0.001, 0.019, 0.012, and 0.001, respectively). Ongoing use of the BD MW after six months significantly improved the OUSS, OHQoL, and intraoral scars, and kept oral and systemic disease activity under control. A total of 20/31 patients reported high levels of satisfaction with its use, and a patients' satisfaction score showed a preference for it. This study confirms the efficacy of the BD MW in patients with recurrent oral ulceration (ROU). It is more efficacious than betamethasone mouthwash used alone.

The dental team as part of the medical workforce during national and global crises.

In a national or global crisis, a healthcare system and its workforce should have the flexibility and resilience to deliver the required level of care for all its constituents. The current COVID-19 pandemic necessitated rapid decisions and early redeployment of staff to deliver essential healthcare. Having the dental team as part of this strategy would increase availability of healthcare workers. They have the potential to make a significant contribution as part of the medical workforce during national and global crises. The desirability of redeploying dentists at short notice is supported by several factors: they are accustomed to working in stressful situations, are effective communicators, are familiar with infection control procedures and work wearing PPE, are immunised and Disclosure and Barring Service (DBS)-checked, and undergo regular training in the management of medical emergencies. Dentists are also experienced in administrative tasks and have knowledge of legislation. They have additional resilience from working in different settings. They have the potential to make a significant contribution as part of the medical workforce during national and global crises.

Induction of p53 in keratinocyte cultures treated with Behçet's patient sera.

BACKGROUND: Behçet's disease (BD) is a rare, multisystem vasculitis disease characterized by recurrent orogenital ulcerations with its etiology remained unclear. The transcription factor p53 has been reported to be upregulated in some autoimmune diseases, such as lupus erythematosus, dermatomyositis, and psoriasis. However, little is known about its alteration in BD. METHODS: Keratinocyte cultures of both skin and oral origins were treated sera of 18 Behcet patients for 24 hours and analyzed by indirect immunofluorescence for p53 expression. The specificity of p53 expression was confirmed by siRNA-mediated p53 knockdown and the serum IgG removal studies. The expression of p53 levels was quantitatively analyzed with ImageJ. RESULTS: It was shown that the expression of p53 is increased in skin and oral keratinocyte cell lines, in both the nucleus and cytoplasm of cells treated with patient sera compared to controls. Either p53 knockdown or IgG removal results in a reduction of p53 levels relative to cells treated with patient sera without p53 knockdown or IgG depletion. CONCLUSIONS: This in vitro study provides the first evidence that BD sera can induce the p53 expression in keratinocytes that may have implications in Behcet pathogenesis.

KIR3DL1/S1 Allotypes Contribute Differentially to the Development of Behçet Disease.

Behçet disease is a chronic, relapsing-remitting autoinflammatory syndrome with a strong HLA-B*51 association. In this paper, we describe a human cohort of 267 individuals with Behçet disease and 445 matched controls from a tertiary referral center in the U.K. HLA-B*51 was confirmed as a genetic risk factor in this group (p = 0.0006, Bonferroni-Dunn correction for multiple testing [Pc] = 0.0192, odds ratio [OR] 1.92, 95% confidence interval [CI] 1.33-2.76). KIR3DL1/S1 allele-level analysis indicated that low-expressing KIR3DL1/S1 alleles in combination with KIR3DS1 increased the risk of developing Behçet disease (KIR3DL1LOW/KIR3DS1: p = 0.0004, Pc = 0.0040, OR 2.47, 95% CI 1.43-4.25), whereas high-expressing KIR3DL1/S1 alleles in combination with a null-expressing KIR3DL1 reduced the risk of disease (KIR3DL1HIGH/KIR3DL1NULL: p = 0.0035, Pc = 0.0350, OR 0.53, 95% CI 0.33-0.87). Behçet disease can manifest as a purely mucocutaneous disease or can involve other organ systems such as the eyes. In the U.K. cohort studied in this study, KIR3DL1LOW/KIR3DS1 increased the risk of ophthalmic disease (p = 1.2 × 10-5, OR 3.92, 95% CI 2.06-7.47), whereas KIR3DL1HIGH/KIR3DL1NULL reduced the risk of having purely mucocutaneous disease (p = 0.0048, OR 0.45, 95% CI 0.25-0.81). To our knowledge, this is the first analysis of KIR3DL1/S1 allelic variation in Behçet disease and may provide insight into the pathogenic role of HLA-B*51 and its interaction with KIR3DL1/S1.

Management of skin, mucosa and joint involvement of Behçet's syndrome: A systematic review for update of the EULAR recommendations for the management of Behçet's syndrome.

OBJECTIVES: The aim of this systematic review was to inform the update of European League Against Rheumatism (EULAR) Recommendations for the management of Behçet's syndrome (BS), on the evidence for the treatment of skin, mucosa and joint involvement of BS. METHODS: A systematic literature search, data extraction, statistical analyses and assessment of the quality of evidence were performed according to a pre-specified protocol using the PRISMA guidelines. Studies that assessed the efficacy of an intervention in comparison to an active comparator or placebo for oral ulcers, genital ulcers, papulopustular lesions, nodular lesions or arthritis were included. Where possible, risk ratios were calculated for binary outcomes and mean difference for continuous outcomes. RESULTS: Among the 3927 references that were screened, 37 were included in the analyses. Twenty-seven of these assessed mucocutaneous and 17 assessed joint involvement. Twenty-one of these studies were randomised controlled trials (RCTs). RCTs with colchicine, azathioprine, interferon-alpha, thalidomide, etanercept and apremilast showed beneficial results with some differences according to lesion type and gender. These agents were generally well tolerated with few adverse events causing withdrawal from the study. CONCLUSIONS: RCTs comprised more than a half (21/37, 57%) of the sources included in the evidence synthesis related to skin, mucosa and joint involvement applicable for the EULAR Recommendations for the management of BS. Differences in the outcome measures that were used across the included studies often made it difficult to combine and compare the results.

Why are Behçet's disease patients always exhausted?

OBJECTIVES: Patients with Behçet's disease (BD) constantly complain of fatigue and many have problems with poor sleep. This ultimately has a major impact on all aspects of normal living. To attempt to understand this, Artificial Intelligence (AI) was used to identify potential biomarkers. These were alpha-melanocyte stimulating hormone (α-MSH), vasoactive intestinal peptide (VIP) and some inflammatory cytokines. We assessed the association of fatigue, quality of sleep and disease activity with circulating concentration of α-MSH, VIP and inflammatory cytokines. METHODS: There were 127 participants, 97 BD patients, and 30 healthy controls (HC). All completed the Multi-Dimensional Assessment of Fatigue questionnaire (MAF) and the Pittsburgh Sleep Quality Index (PSQI) on the day of their clinical assessment. Enzyme-linked immunosorbent assays (ELISA) were used to evaluate the serum concentrations of α-MSH, VIP and cytokines (IL-1ß, IL-6, IL-10, and TNF-α). RESULTS: 64% of BD patients experienced high fatigue scores, and 63% had poor quality of sleep. When BD and HC were compared the MAF and PSQI scores as well as the serum concentrations of α-MSH, VIP, and IL-6 were significantly higher in BD (p values were: 0.001, 0.001, 0.001, 0.004 and 0.036, respectively). Both α-MSH and IL-6 had significant impact on MAF and PSQI. Interestingly, VIP had a significant influence on PSQI and disease activity, but not on MAF. CONCLUSIONS: A better understanding of these complex clinical and biochemical interactions between α-MSH, VIP and IL-6 might lead to the development of novel approaches to manage fatigue and sleep disorders as well as disease activity in BD patients.

The influence of oral health and psycho-social well-being on clinical outcomes in Behçet's disease.

This study was designed to investigate the association of oral ulceration and oral health factors, together with psycho-social well-being in Behçet's disease (BD), and to clarify the importance of psycho-social support of patients in the overall management of BD. The study comprised of a cohort of 146 BD patients (mean age ± SD = 39.65 ± 13.20) and 20 recurrent aphthous stomatitis (RAS) patients (mean age ± SD = 42.32 ± 11.32). Oral ulcer severity score (OUSS), Behçet's disease current activities form (BDCAF), hospital anxiety and depression scale (HADS), and the work and social adjustment scale (WSAS) were investigated. Oral health risk factors were also included. The analysis of variance, regression, and factor analysis were used to scrutinise the data. Almost 73% of patients were at high caries risk in BD and RAS groups. Thirty-nine percent of BD and forty percent of RAS had a score of BPE3 (probing depth 3.5-5.5 mm). Regression analysis revealed that OUSS and WSAS had a positive impact to increase the BDCAF score in BD patients (ß = 0.395, P = 0.001; ß = 0.240, P = 0.019), respectively. Dental health, periodontal health, anxiety, depression, and WSAS variables had strong loadings by factor analysis based on gender and at the time of present and absent of oral ulceration. The main oral ulcer characteristics that had significant influences on the total of oral health quality of life by 68.6% were: size, duration, ulcer-free period, and pain. The results highlighted the significant influence of oral ulceration, patients' oral health, diet, and psycho-social well-being as multi-factorial causes on increasing disease activity in BD patients.