The Effectiveness of Manual versus High-Frequency, High-Amplitude Sonic Powered Toothbrushes for Oral Health: A Meta-Analysis.

OBJECTIVES: Evaluate the short-term clinical efficacy of high-frequency, high-amplitude sonic powered toothbrushes compared to manual toothbrushes on plaque removal and gingivitis reduction in everyday use through a meta-analysis of randomized controlled trials. METHODS: Embase, MEDLINE, BIOSIS, Inspec, PQ SciTech, Compendex, SciSearch and IADR abstracts databases were searched. Eligible were clinical trials comparing at least one manual to one sonic powered toothbrush on plaque or gingivitis reduction over four weeks to three months in subjects without disability that could affect tooth brushing. Two authors selected and extracted data from eligible studies. When insufficient information was available, researchers were contacted. Data were pooled using random-effects models to compute standardized mean differences (SMD) and 95% confidence intervals (95% CI) quantifying differences in plaque or gingivitis reduction. Risk for bias and sources of heterogeneity were assessed. RESULTS: The combined results of 18 studies comprising 1,870 subjects showed that sonic powered toothbrushes had statistically significantly greater plaque removal (SMD = -0.89, 95%CI = [-1.27, -0.51]) and gingivitis reduction (-0.67, [-1.01, -0.32]). Heterogeneity was large and bias was not apparent. CONCLUSIONS: High-frequency, high-amplitude sonic powered toothbrushes decreased plaque and gingivitis significantly more effectively than manual toothbrushes in everyday use in studies lasting up to three months.

The blood clotting Factor XIIIa forms unique complexes with amyloid-beta (Aß) and colocalizes with deposited Aß in cerebral amyloid angiopathy.

AIMS: Cerebral amyloid angiopathy (CAA) is a key pathological hallmark of Alzheimer's disease (AD) characterized by accumulation of amyloid-beta (Aß) protein in blood vessel walls. CAA impairs vessel functioning, affects blood brain barrier integrity and accelerates cognitive decline of AD patients. Unfortunately, mechanisms underlying Aß deposition in the vessel wall remain largely unknown. Factor XIIIa (FXIIIa) is a blood-derived transglutaminase crucial in blood coagulation by cross-linking fibrin molecules. Evidence is mounting that blood-derived factors are present in CAA and may play a role in protein deposition in the vessel wall. We therefore investigated whether FXIIIa is present in CAA and if FXIIIa cross-link activity affects Aß aggregation. METHODS: Using immunohistochemistry, we investigated the distribution of FXIIIa, its activator thrombin and in situ FXIIIa activity in CAA in post-mortem AD tissue. We used surface plasmon resonance and Western blot analysis to study binding of FXIIIa to Aß and the formation of FXIIIa-Aß complexes, respectively. In addition, we studied cytotoxicity of FXIIIa-Aß complexes to cerebrovascular cells. RESULTS: FXIIIa, thrombin and in situ FXIIIa activity colocalize with the Aß deposition in CAA. Furthermore, FXIIIa binds to Aß with a higher binding affinity for Aß1-42 compared with Aß1-40 . Moreover, highly stable FXIIIa-Aß complexes are formed independently of FXIIIa cross-linking activity that protected cerebrovascular cells from Aß-induced toxicity in vitro. CONCLUSIONS: Our data showed that FXIIIa colocalizes with Aß in CAA and that FXIIIa forms unique protein complexes with Aß that might play an important role in Aß deposition and persistence in the vessel wall.

Systemic treatments in paediatric psoriasis: a systematic evidence-based update.

In 2008, a systematic review revealed that evidence-based data on efficacy and safety of treatments in paediatric psoriasis are scarce and with low level of evidence. In recent years, publications on this topic have increased exponentially. To present a systematic, evidence-based update on the efficacy and safety of systemic treatments in paediatric psoriasis and to provide treatment recommendations, an update of the previous review was performed. PubMed, EMBASE and the Cochrane Controlled Clinical Trial Register were searched between January 2007 and March 2014 for all available literature on efficacy and safety of all systemic treatments in paediatric psoriasis. The levels of evidence were determined on the Oxford Centre for Evidence-based Medicine Levels of Evidence. The newly retrieved evidence was combined with the evidence available in the former review. Fifty-two studies were included: 36 from the former review, plus 16 new articles. New evidence on induction therapy was mainly available on fumaric acid esters (FAEs), which are shown to be effective in a subgroup of patients. Long-term (96 weeks) safety and efficacy data on etanercept were found. Prospective studies are scarce. Most conclusions are formulated on studies with low level of evidence. Of the conventional systemic treatments, methotrexate still has the most evidence albeit in a low number of patients and with a low level of evidence. FAEs seem to be effective in a subgroup of patients, with gastro-intestinal complaints, flushes and temporary shifts in leucocyte counts and liver enzymes being the main side-effects. Etanercept has still accumulated most evidence of the available systematic treatments, with a large efficacy and reassuring safety profile in a 96-week follow-up.

Renal transplant recipient and deceased-donor risk profiles at Wits Donald Gordon Medical Centre, Johannesburg, South Africa: A 9-year review.

BACKGROUND: Renal transplantation is the gold-standard therapy for end-stage renal disease. Decision-making around the acceptance of deceased-donor organs is complex and time sensitive. Risk scoring systems for both donors and recipients attempt to simplify the allocation of renal grafts to the most appropriate recipient. OBJECTIVES: To investigate the role of these transplant risk scores in the South African (SA) setting. METHODS: A total of 188 adult deceased-donor organ referrals over the 9-year period 1 January 2013 - 31 December 2021 were included. The Kidney Donor Risk Index (KDRI) and the UK KDRI were calculated for each donor. Recipients who were allocated these grafts were characterised, and the Hennepin Transplant Risk Score and the Kidney Transplant Morbidity Index (KTMI) were calculated. RESULTS: The median (interquartile range) KDRI was 1.2 (0.9 - 1.6), confirming that low- to average-risk donors were being utilised. Similarly, the median UK KDRI was 0.9 (0.8 - 1.2). Both these scores performed poorly in predicting graft and patient survival, with a C-statistic of 0.5. Renal recipient risk scores also demonstrated low- to average-risk patients being transplanted, with a median Hennepin score of 2 - 4 points and a KTMI of 2 points. These recipient scores predict increased recipient mortality at high scores, albeit with low sensitivity, and were not significantly associated with graft survival. CONCLUSION: Deceased-donor and renal recipient risk scores commonly used internationally performed poorly in predicting graft survival in our cohort, and should be used with caution in the SA setting. A conservative approach to organ donor referral and utilisation as well as renal transplant recipient listing was noted.

Induction therapy with a combination of DMARDs is better than methotrexate monotherapy: first results of the tREACH trial.

OBJECTIVE: To determine the most effective induction disease-modifying antirheumatic drug (DMARD) strategy in early rheumatoid arthritis (RA), second to compare one single dose of intramuscular glucocorticoids (GCs) with daily oral GCs during the induction phase. METHODS: The 3-month data of a single-blinded clinical trial in patients with recent-onset arthritis (tREACH) were used. Patients were included who had a high probability (>70%) of progressing to persistent arthritis, based on the prediction model of Visser. Patients were randomised into three induction therapy strategies: (A) combination therapy (methotrexate (MTX) + sulfasalazine + hydroxychloroquine) with GCs intramuscularly; (B) combination therapy with an oral GC tapering scheme and (C) MTX with oral GCs similar to B. A total of 281 patients were randomly assigned to strategy (A) (n=91), (B) (n=93) or (C) (n=97). RESULTS: The Disease Activity Score (DAS) after 3 months was lower in patients receiving initial combination therapy than in those receiving MTX monotherapy (0.39 (0.67 to 0.11, 95% CI)). DAS did not differ between the different GC bridging treatments. After 3 months 50% fewer biological agents were prescribed in the combination therapy groups. Although the proportion of patients with medication adjustments differed significantly between the treatment arms, no differences were seen in these adjustments due to adverse events after stratification for drug. CONCLUSION: Triple DMARD induction therapy is better than MTX monotherapy in early RA. Furthermore, no differences were seen in medication adjustments due to adverse events after stratification for drug. Intramuscular and oral GCs are equally effective as bridging treatments and both can be used.

The influence of treatments in daily clinical practice on the Children's Dermatology Life Quality Index in juvenile psoriasis: a longitudinal study from the Child-CAPTURE patient registry.

BACKGROUND: Juvenile psoriasis has a negative effect on the quality of life (QoL). The influence of treatments on QoL of these children has never been investigated before in a prospective observational study. OBJECTIVES: To assess the Children's Dermatology Life Quality Index (CDLQI) in a cohort of patients with juvenile psoriasis and to evaluate the influence of treatments in daily clinical practice on CDLQI. METHODS: We conducted a prospective observational study of children with psoriasis from a registry containing daily clinical practice data. Before and after treatment, QoL was assessed by the CDLQI and disease severity was documented by the Psoriasis Area and Severity Index (PASI). Three clusters of treatments were analysed: topical, dithranol and systemic therapy. RESULTS: In total, 125 patients were enrolled in the registry. Cross-sectionally, a mean ± SD CDLQI score of 7·5 ± 5·0 and a mean ± SD PASI of 7·0 ± 5·8 were recorded. Itching and problems with treatment had the highest impact on the children's QoL. Longitudinally, 85 patients were analysed with a total of 137 treatment episodes. All treatments contributed to a significant decline in total CDLQI score, with the largest decrease seen in dithranol and systemic treatments. A significant correlation was found between ΔCDLQI and ΔPASI for all treatment modalities. The highest positive impact of treatments was found in a decline of itch and sleep disturbance. CONCLUSIONS: In this first prospective observational study on CDLQI in juvenile psoriasis, a positive influence of treatments in daily clinical practice on QoL was demonstrated.

Paediatric-onset psoriasis is associated with ERAP1 and IL23R loci, LCE3C_LCE3B deletion and HLA-C*06.

BACKGROUND: Recent genome-wide association studies have identified several genetic risk factors for psoriasis, but data on their association with age at onset are lacking. OBJECTIVES: To compare the association between known risk alleles and psoriasis in well-defined cohorts with paediatric- and adult-onset psoriasis. METHODS: Based on previous studies we selected seven genes and loci associated with psoriasis. Patients with paediatric-onset (< 18 years) and adult-onset psoriasis (≥ 18 years) and controls were genotyped. Genotype frequencies were compared between controls (n = 450) and all cases (n = 217), and between controls and cases stratified for confirmed age at onset (paediatric onset n = 80, adult onset n = 85). RESULTS: Paediatric-onset psoriasis showed a significant association with single nucleotide polymorphisms in the ERAP1 (P = 0.042) and IL23R loci (P = 0.042), LCE3C_LCE3B-del (P = 0.003) and HLA-C*06 (P = 1.72 × 10(-19)) when compared with the control group. A significant association of these four genes was also demonstrated when all psoriasis cases were compared with controls. In adult-onset psoriasis a significant association was found for HLA-C*06 (P = 5.11 × 10(-6)) and for LCE3C_LCE3B-del (P = 0.042). No associations were found for the IFIH1, IL12B and TRAF3IP2 loci. CONCLUSIONS: Notwithstanding the small cohort sizes, we demonstrated an association with established and recently discovered genetic risk factors in paediatric-onset psoriasis including genes involved in epidermal barrier function and adaptive immunity. Our data suggest that heritable factors may play a more important role in paediatric-onset psoriasis than in adult-onset psoriasis.

Juvenile psoriasis in European and Asian children: similarities and differences.

BACKGROUND: The first manifestations of psoriasis begin in childhood in more than one-third of patients. However, epidemiological data of juvenile psoriasis are lacking. OBJECTIVES: To compare Dutch (NL group) and Singaporean (SG group) children with psoriasis with the aim of studying the characteristics of juvenile psoriasis and to highlight similarities and differences between these different ethnic groups. METHODS: Data were collected from 207 patients younger than 18 years diagnosed with psoriasis from Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands and the National Skin Centre, Singapore. RESULTS: A striking difference in familial distribution was found, with more Dutch children having an affected family member (73·3% vs. 13·6%). Presence of itch and triggering factors were more common among Dutch children (80% vs. 14·2% and 33·3% vs. 7·4%, respectively). However, both groups shared similar triggering factors like stress and infections. Other similarities included mean age at presentation (NL group 11·3 years; SG group 14·1 years) and gender ratio (NL group, M/F 1 : 1·1; SG group, M/F 1 : 1·4). Plaque psoriasis was the most common type in both cohorts while guttate and pustular psoriasis were rare. In both groups, the head, followed by the limbs, was the most common site involved. Similar proportions of children in both countries had nail involvement and psoriatic arthritis was rare. CONCLUSIONS: The disparity in familial distribution may point to genetic differences between the two groups. Further studies to evaluate this difference in familial distribution may contribute to the understanding of the pathogenesis of psoriasis.

An intrapatient comparison of quality of life in psoriasis in childhood and adulthood.

BACKGROUND: Chronic diseases can have a great influence on health-related quality of life. Nevertheless, only little research has been carried out on childhood psoriasis. The perception of quality of life by adults with psoriasis of their childhood psoriasis has never been investigated. OBJECTIVES: The aims of this study were to (i) investigate retrospectively the influence of psoriasis as experienced in childhood as compared with the current quality of life in adulthood; (ii) assess retrospectively the impact of childhood psoriasis on daily life; and (iii) compare the current quality of life in patients with childhood onset psoriasis (COP) and adult onset psoriasis (AOP). METHODS: A survey was performed among all members of the Dutch Psoriasis Society. Validated questionnaires on quality of life, impact on daily life and clinical severity were used. RESULTS: Questionnaires of 1762 patients were suitable for analysis. Adults with an onset of psoriasis before the age of 18 years retrospectively rate their quality of life during childhood much less as compared with their current quality of life (intrapatient comparison). Influence of psoriasis in childhood particularly had a high degree of limitations on recreational and social activities in 15-30% of patients. Quality of life in adulthood is not determined by age of onset of psoriasis. CONCLUSIONS: In childhood, the quality of life is greatly influenced by psoriasis. The social development domain, which is one of the developmental milestones in a child, is particularly impaired. The current quality of life of patients with COP is equal to that of patients with AOP.

Healing journeys: Indigenous Men's reflections on resources and barriers to mental wellness.

Indigenous peoples in Canada and other settler colonial nations experience barriers to healing in the health care system and their communities. Drawing on four sequential sharing circles and indepth interviews with 11 Indigenous men, this article shares the stories of Indigenous men and their healing journeys with the aim of improving culturally safe support in the community. In sharing their stories, these men identified coping with colonialism, as well as trauma and grief, as barriers in their healing journey. They also described finding strength in cultural role models, fathering, as well as ceremony and connecting to the land. We discuss the implications of these findings for service provision and decolonizing community health services.

A cross-sectional study using the Children's Dermatology Life Quality Index (CDLQI) in childhood psoriasis: negative effect on quality of life and moderate correlation of CDLQI with severity scores.

BACKGROUND: Juvenile psoriasis is a chronic and incurable skin disease that affects approximately 0·7% of children. OBJECTIVES: To achieve more insight into the quality of life (QoL) in childhood psoriasis and to investigate whether disease severity scores correlate with QoL scores. METHODS: All consecutive patients with juvenile plaque psoriasis (≤ 18 years old) who visited our outpatient department were included. At baseline, the Children's Dermatology Life Quality Index (CDLQI) questionnaire was completed and disease severity was assessed by the Psoriasis Area and Severity Index (PASI) and the Physician Global Assessment (PGA). RESULTS: Thirty-nine patients were included in the study. A median CDLQI of 6 [interquartile range (IQR) 5­9] was reported. Median PASI was 6·3 (IQR 3·3­8·2) and median PGA was 2 (IQR 1­3). The correlation coefficient between PASI and CDLQI was 0·47 (P = 0·003), whereas the correlation coefficient between PGA and CDLQI was 0·51 (P = 0·001). CONCLUSIONS: The negative effect on QoL in juvenile psoriasis was confirmed in the largest cohort presented up to now. The correlation between disease severity scores and disease-related QoL in children with psoriasis is only moderate. Therefore, both clinical outcome parameters (PASI, PGA) and measures of QoL (CDLQI) should be included in adequate, patient-oriented clinical decision making.

Dithranol therapy in childhood psoriasis: unjustifiably on the verge of falling into oblivion.

BACKGROUND: In childhood psoriasis, physicians aim for an effective and safe treatment such as with dithranol. This study presents the largest study of dithranol-treated patients described in the literature. OBJECTIVE: The aim of the study was to determine the position of dithranol in the treatment strategy for psoriasis. METHODS: All juvenile patients receiving dithranol treatment at our center were evaluated retrospectively. RESULTS: Sixty patients (with 82 treatment episodes in total) were included. The mean age at the start of dithranol treatment was 11.1 years (range: 3.7-17.9 years). The result of the treatment was: excellent (3.7%), good (69.5%), moderate (8.5%), reasonable (13.4%) or disappointing (4.9%). Mild irritation was seen in 39%, and severe irritation in 63% of the patients. CONCLUSIONS: Dithranol can be regarded as an efficacious and safe topical therapy for the treatment of childhood psoriasis. It is a valuable alternative topical treatment which should not be disregarded in the treatment regimen for childhood psoriasis and should be commenced before ultraviolet or systemic treatments are initiated.

Genital psoriasis: a questionnaire-based survey on a concealed skin disease in the Netherlands.

BACKGROUND: Psoriatic lesions may involve nearly all sites of the body. Involvement of the genital skin is frequently classified as part of intertriginous psoriasis without special awareness and treatment for this presentation of the disease. Gaining knowledge about the frequency of the involvement of genital skin in these patients will improve the overall care for patients with psoriasis. OBJECTIVES: We studied the prevalence of genital psoriasis in the Netherlands and epidemiological characteristics of this specific presentation of the disease. Furthermore, we studied the relation between flexural and genital psoriasis. PATIENTS/METHODS: A self-administered questionnaire was sent to all 5300 members of the Dutch Psoriasis Society. Sociodemographic patient characteristics and disease-related data (such as localization of psoriatic lesions, involvement of the genitalia, age at onset of genital psoriasis and severity of genital psoriatic lesions) were collected and analysed. RESULTS: A response rate of 37% was achieved. Almost 46% of the responding patients with psoriasis, that is 16.5% of all potential responders (n = 5300), report genital involvement at some time during the course of their disease. The genitalia can become affected at any age. Many patients with current genital involvement (38%) do not have the flexural skin affected. CONCLUSIONS: A large part of patients with psoriasis suffer from genital psoriasis, which was not associated with flexural involvement in at least one third of them. More attention to the genital region is required in the current standard treatment of both male and female psoriatic patients at any age.

No evidence found that childhood onset of psoriasis influences disease severity, future body mass index or type of treatments used.

BACKGROUND: In more than one-third of the psoriatic population, the first manifestations occur in childhood. Whether the age of onset of psoriasis influences the march of psoriasis is not known. OBJECTIVES: To describe the epidemiology and clinical features as well as prescribed treatments and familial distribution in psoriasis depending on the age of onset of the disease. METHODS: A structured questionnaire was sent to 5300 adult psoriatic patients. Respondents were divided into two groups: patients who experienced an onset of disease before the age of 18 [childhood onset psoriasis (COP)] and patients with an onset of disease from the age of 18 [adult onset psoriasis (AOP)]. RESULTS: Questionnaires of 1926 (36.3%) patients were suitable for analysis. In 37.1% of patients, first signs of the disease occurred before the age of 18. COP occurs predominantly in females, has a longer delay in diagnosis and a higher frequency of familial distribution. The development of guttate and erythrodermic psoriasis in adulthood is more frequently seen in COP. In contrast to common belief, type of psoriasis in COP often remains the same from childhood to adulthood. There was no evidence found that getting psoriasis before the age of 18 years influences development of high body mass index in adulthood, disease severity in later life or type of treatments used. CONCLUSIONS: The age of onset of psoriasis essentially does not influence the subsequent course of the disease in adulthood.

Smoking and drinking habits of women in subsequent pregnancies after specific advice about the dangers of these exposures during pregnancy.

BACKGROUND: Although women are informed about the dangers of drinking and smoking during pregnancy when they book for antenatal care, it is uncertain whether this advice is accepted, or whether attempts are made to apply it in subsequent pregnancies. OBJECTIVES: To assess how pregnant women respond to the advice to refrain from smoking and drinking during pregnancy in subsequent pregnancies. METHODS: Research staff were trained to obtain accurate prospective information on smoking and drinking during pregnancy in a prospective study, using well-standardised methods. Care was taken to inform participants about the dangers of smoking and drinking during pregnancy. They were also given pamphlets on these dangers in their own language and a list of telephone numbers where they could find help to quit should they need it. This information was repeated at subsequent study visits (ranging from 1 to 3, depending on the gestational age at which they enrolled). Gestational age was determined by early ultrasound. Z-scores of birthweight for gestational age were determined according to the INTERGROWTH-21st study. Pregnancy outcomes of women who enrolled twice (n=888) or three times (n=77) in the Safe Passage Study were compared with those of women in the first enrolment (n=889). RESULTS: The proportion of drinkers did not change significantly (p=0.058) from the first to the second and third enrolments (63.8%, 59.0% and 54.6%, respectively). A similar trend was found for smokers (73.3%, 72.2% and 68.4%, respectively). Cannabis use was reported by 15.1%, 9.7% and 12.0% (p<0.005) of women, respectively, and use of methamphetamine by 10.1%, 6.6% and 12.7% (p<0.005). There was an increase in the rate of preterm births from 15.5% to 17.5% and 24.7%, respectively, but the increase was not significant. Although mean birthweight was lower in the third enrolment compared with the second, the difference was not significant. The z-score of birthweight for gestational age was significantly lower in the second enrolment compared with the first. CONCLUSIONS: Detailed information on the adverse effects of smoking and drinking during pregnancy was not effective in the population studied. Other methods to reduce or stop these toxic exposures should therefore be investigated. A short inter-pregnancy interval, as demonstrated by three enrolments in 7.5 years, is associated with preterm labour and fetal growth restriction, and is probably indicative of the role played by confounders such as poor socioeconomic conditions and drug exposure during pregnancy.

Increasing deceased organ donor numbers in Johannesburg, South Africa: 18-month results of the Wits Transplant Procurement Model.

In 2016, deceased-donor organ procurement at Wits Transplant, based at Wits Donald Gordon Medical Centre in Johannesburg, South Africa (SA), was in a state of crisis. As it is the largest-volume solid-organ transplant unit in SA, and as we aspire to provide transplant services of an international standard, the time to address our procurement practice had come. The number of deceased donors consented through our centre was very low, and we needed a radical change to improve our performance. This article describes the Wits Transplant Procurement Model - the result of our work to improve procurement at our centre. The model has two core phases, one to increase referrals and the other to improve our consent rates. Within these phases there are several initiatives. To improve referrals, the threefold approach of procurement management, acknowledgement and resource utilisation was developed. In order to 'convert' referrals into consents, we established the Wits Transplant 'Family Approach to Consent for Transplant Strategy' (FACTS). Since initiation of the Wits Transplant Procurement Model, both our referral numbers from targeted hospitals and our conversion rates have increased. Referrals from targeted hospitals increased by 54% (from 31 to 57). Our consent rate increased from 25% (n=6) to 73% (n=35) after the initiation of Wits Transplant FACTS. We hope that other transplant centres in SA and further afield in the region will find this article helpful, and to this end we have created a handbook on the Wits Transplant Procurement Model that is freely available for download (http://www.dgmc.co.za/docs/Wits-Transplant-Procurement-Handbook.pdf).

Subpiconewton dynamic force spectroscopy using magnetic tweezers.

We introduce a simple method for dynamic force spectroscopy with magnetic tweezers. This method allows application of subpiconewton force and twist control by calibration of the applied force from the height of the magnets. Initial dynamic force spectroscopy experiments on DNA molecules revealed a large hysteresis that is caused by viscous drag on the magnetic bead and will conceal weak interactions. When smaller beads are used, this hysteresis is sufficiently reduced to reveal intramolecular interactions at subpiconewton forces. Compared with typical quasistatic force spectroscopy, a significant reduction of measurement time is achieved, allowing the real-time study of transient structures and reaction intermediates. As a proof of principle, nucleosome-nucleosome interactions on a subsaturated chromatin fiber were analyzed.

Can baseline ultrasound results help to predict failure to achieve DAS28 remission after 1 year of tight control treatment in early RA patients?

BACKGROUND: At present, there are no prognostic parameters unequivocally predicting treatment failure in early rheumatoid arthritis (RA) patients. We investigated whether baseline ultrasonography (US) findings of joints, when added to baseline clinical, laboratory, and radiographical data, could improve prediction of failure to achieve Disease Activity Score assessing 28 joints (DAS28) remission (<2.6) at 1 year in newly diagnosed RA patients. METHODS: A multicentre cohort of newly diagnosed RA patients was followed prospectively for 1 year. US of the hands, wrists, and feet was performed at baseline. Clinical, laboratory, and radiographical parameters were recorded. Primary analysis was the prediction by logistic regression of the absence of DAS28 remission 12 months after diagnosis and start of therapy. RESULTS: Of 194 patients included, 174 were used for the analysis, with complete data available for 159. In a multivariate model with baseline DAS28 (odds ratio (OR) 1.6, 95% confidence interval (CI) 1.2-2.2), the presence of rheumatoid factor (OR 2.3, 95% CI 1.1-5.1), and type of monitoring strategy (OR 0.2, 95% CI 0.05-0.85), the addition of baseline US results for joints (OR 0.96, 95% CI 0.89-1.04) did not significantly improve the prediction of failure to achieve DAS28 remission (likelihood ratio test, 1.04; p = 0.31). CONCLUSION: In an early RA population, adding baseline ultrasonography of the hands, wrists, and feet to commonly available baseline characteristics did not improve prediction of failure to achieve DAS28 remission at 12 months. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01752309 . Registered on 19 December 2012.

DNA-binding and strand-annealing activities of human Mre11: implications for its roles in DNA double-strand break repair pathways.

DNA double-strand breaks (DSBs) in eukaryotic cells can be repaired by non-homologous end-joining or homologous recombination. The complex containing the Mre11, Rad50 and Nbs1 proteins has been implicated in both DSB repair pathways, even though they are mechanistically different. To get a better understanding of the properties of the human Mre11 (hMre11) protein, we investigated some of its biochemical activities. We found that hMre11 binds both double- and single-stranded (ss)DNA, with a preference for ssDNA. hMre11 does not require DNA ends for efficient binding. Interestingly, hMre11 mediates the annealing of complementary ssDNA molecules. In contrast to the annealing activity of the homologous recombination protein hRad52, the activity of hMre11 is abrogated by the ssDNA binding protein hRPA. We discuss the possible implications of the results for the role(s) of hMre11 in both DSB repair pathways.

High-Velocity Microsprays Enhance Antimicrobial Activity in Streptococcus mutans Biofilms.

Streptococcus mutans in dental plaque biofilms play a role in caries development. The biofilm's complex structure enhances the resistance to antimicrobial agents by limiting the transport of active agents inside the biofilm. The authors assessed the ability of high-velocity water microsprays to enhance delivery of antimicrobials into 3-d-old S. mutans biofilms. Biofilms were exposed to a 90° or 30° impact, first using a 1-µm tracer bead solution (109 beads/mL) and, second, a 0.2% chlorhexidine (CHX) or 0.085% cetylpyridinium chloride (CPC) solution. For comparison, a 30-s diffusive transport and simulated mouthwash were also performed. Confocal microscopy was used to determine number and relative bead penetration depth into the biofilm. Assessment of antimicrobial penetration was determined by calculating the killing depth detected by live/dead viability staining. The authors first demonstrated that the microspray was able to deliver significantly more microbeads deeper in the biofilm compared with diffusion and mouthwashing exposures. Next, these experiments revealed that the microspray yielded better antimicrobial penetration evidenced by deeper killing inside the biofilm and a wider killing zone around the zone of clearance than diffusion alone. Interestingly the 30° impact in the distal position delivered approximately 16 times more microbeads and yielded approximately 20% more bacteria killing (for both CHX and CPC) than the 90° impact. These data suggest that high-velocity water microsprays can be used as an effective mechanism to deliver microparticles and antimicrobials inside S. mutans biofilms. High shear stresses generated at the biofilm-burst interface might have enhanced bead and antimicrobial delivery inside the remaining biofilm by combining forced advection into the biofilm matrix and physical restructuring of the biofilm itself. Further, the impact angle has potential to be optimized both for biofilm removal and active agents' delivery inside biofilm in those protected areas where some biofilm might remain.