Skin microbiota secretomes modulate cutaneous innate immunity against Borrelia burgdorferi s.s.

In Lyme borreliosis, the skin constitutes a major interface for the host, the bacteria and the tick. Skin immunity is provided by specialized immune cells but also by the resident cells: the keratinocytes and the fibroblasts. Discoveries on the role of the microbiome in the modulation of skin inflammation and immunity have reinforced the potential importance of the skin in vector-borne diseases. In this study, we analyzed in vitro the interaction of human primary keratinocytes and fibroblasts with Borrelia burgdorferi sensu stricto N40 in presence or absence of bacterial commensal supernatants. We aimed to highlight the role of resident skin cells and skin microbiome on the inflammation induced by B. burgdorferi s.s.. The secretomes of Staphylococcus epidermidis, Corynebacterium striatum and Cutibacterium acnes showed an overall increase in the expression of IL-8, CXCL1, MCP-1 and SOD-2 by fibroblasts, and of IL-8, CXCL1, MCP-1 and hBD-2 in the undifferentiated keratinocytes. Commensal bacteria showed a repressive effect on the expression of IL-8, CXCL1 and MCP-1 by differentiated keratinocytes. Besides the inflammatory effect observed in the presence of Borrelia on all cell types, the cutaneous microbiome appears to promote a rapid innate response of resident skin cells during the onset of Borrelia infection.

Delayed eczematous skin reaction as an adverse drug reaction to immunoglobulin infusions: A case series.

BACKGROUND: Pompholyx and eczematous reactions are known adverse reactions to intravenous immunoglobulins (IVIg) infusion, but little is known about their clinical characteristics, associated outcomes and management. OBJECTIVE: To describe IVIg-induced eczematous skin reactions. METHODS: We conducted a retrospective study on cases of delayed skin reactions post-IVIg infusion notified to the French Regional Pharmacovigilance Centre from 1985 to 2020. RESULTS: A total of 27 patients were identified, of whom 85% were male. IVIg infusions were given in a neurological indication in 82% of cases. Eczematous skin reactions occurred in two-thirds of cases after the first infusion, with a median time to onset of 11 days. Palmoplantar pompholyx was the most common presentation, being seen in 63% of patients. Other eruptions were erythemato-squamous or maculopapular. Eight patients were classified as severely affected and developed extensive lesions (>50% BSA). One third of the 27 patients required hospitalization. All of the severe eczematous reactions involved males receiving high doses of IVIg for neurological diseases. Biopsies of severe cases revealed a common non-specific eczematous pattern. Relapses were frequent and more severe than the initial reaction. Reintroduction of the same IVIg product consistently resulted in relapse, whereas switching IVIg type produced relapse in only 53% of patients. CONCLUSION: We present the largest retrospective study of delayed skin reactions after IVIg infusions. This side-effect may be severe and have a polymorphic presentation. Relapse occurs frequently but less consistently after IVIg switch.

Scaling of dynamical decoupling for spin qubits.

We investigate the scaling of coherence time T(2) with the number of π pulses n(π) in a singlet-triplet spin qubit using Carr-Purcell-Meiboom-Gill (CPMG) and concatenated dynamical decoupling (CDD) pulse sequences. For an even numbers of CPMG pulses, we find a power law T(2) is proportional to (n(π))(γ(e)), with γ(e)=0.72±0.01, essentially independent of the envelope function used to extract T(2). From this surprisingly robust value, a power-law model of the noise spectrum of the environment, S(ω)~ω(-ß), yields ß=γ(e)/(1-γ(e))=2.6±0.1. Model values for T(2)(n(π)) using ß=2.6 for CPMG with both even and odd n(π) up to 32 and CDD orders 3 through 6 compare very well with the experiment.

Infliximab as rescue medication for patients with severe ulcerative/indeterminate colitis refractory to tacrolimus.

BACKGROUND: The calcineurin inhibitor tacrolimus and the anti-TNF-antibody infliximab are established options in steroid-refractory ulcerative colitis (UC). AIM: To evaluate the efficacy of infliximab-salvage therapy in patients with refractory UC failing to respond to tacrolimus. METHODS: Twenty-four patients were enrolled in this evaluation. Reasons for tacrolimus therapy were steroid-refractory disease in 19 patients and steroid-dependency in five patients. All patients receiving infliximab had tacrolimus-refractory active disease (Lichtiger score >10) and were treated with 5 mg/kg at weeks 0, 2 and 6 and every 8 weeks thereafter, if tolerated. RESULTS: Six of 24 patients (25%) achieved remission following infliximab infusion and four of 24 (17%) had an initial response only, but underwent proctocolectomy later because of loss of response (3) or development of a delayed hypersensitivity reaction (1). Fourteen patients (58%) completely failed to respond with 10 undergoing colectomy. Eight patients experienced side effects under infliximab, including two infectious complications (herpes zoster and herpes pneumonia). CONCLUSIONS: Infliximab offers a therapeutic option as rescue therapy in about a quarter of patients with active UC after failing to respond to tacrolimus. This benefit has to be weighed against the risks of infectious complications.

Interlaced dynamical decoupling and coherent operation of a singlet-triplet qubit.

We experimentally demonstrate coherence recovery of singlet-triplet superpositions by interlacing qubit rotations between Carr-Purcell (CP) echo sequences. We then compare the performance of Hahn, CP, concatenated dynamical decoupling (CDD), and Uhrig dynamical decoupling for singlet recovery. In the present case, where gate noise and drift combined with spatially varying hyperfine coupling contribute significantly to dephasing, and pulses have limited bandwidth, CP and CDD yield comparable results, with T(2)∼80 µs.

Rapid single-shot measurement of a singlet-triplet qubit.

We report repeated single-shot measurements of the two-electron spin state in a GaAs double quantum dot. The readout allows measurement with a fidelity above 90% with a approximately 7 micros cycle time. Hyperfine-induced precession between singlet and triplet states of the two-electron system are directly observed, as nuclear Overhauser fields are quasistatic on the time scale of the measurement cycle. Repeated measurements on millisecond to second time scales reveal the evolution of the nuclear environment.

Species of Borrelia burgdorferi complex that cause borrelial lymphocytoma in France.

BACKGROUND: Only about 30 cases of borrelial lymphocytoma (BL) with identification of the causative species of Borrelia have been published to date, mainly from Eastern or Central European countries. OBJECTIVES: To identify the species of B. burgdorferi complex responsible for BL in France. METHODS: Nine patients with BL acquired in France and for whom skin samples were sent to the national reference centre laboratory between 1994 and 2007 were included in this retrospective study. Direct detection of Borrelia in skin samples was made by polymerase chain reaction targeting the fla gene. Culture was performed when technically possible, and identification of each species was made by hybridization of a fragment of the fla gene with a panel of species-specific oligonucleotides. RESULTS: Borrelia afzelii was identified in three cases, B. garinii and B. burgdorferi sensu stricto in one case each. Culture was positive in only one case (B. garinii). CONCLUSIONS: Borrelia afzelii seems to be the predominant species of Borrelia responsible for BL in France, as already reported in other European countries.

[Caries risk assessment - are saliva tests as well as microbiological and clinical test procedures worthwhile?]. / Kariesrisikoerkennung - Helfen Speicheltests, mikrobiologische und klinische Testverfahren weiter?

The recent representative survey has proven once more that people in Germany are affected by caries to a very different extent. Since caries can be prevented by risk-adjusted preventive programs, it would be helpful to have a possibility to determine the individual caries risk before cavities occur. Determination of a relative risk, risk screening and risk diagnosis are different levels of caries risk assessment. The present article provides information about which caries risk assessment options are available for different populations. A relative risk can be determined by the detection of Mutants Streptococci in caries-free 2-5-year-old children. With Dentoprog, a valid instrument for caries risk screening is available for 6-12-year-old school children. With respect to all other patients, a quantitative risk diagnosis can be roughly performed using the Cariogram which is based on the assessment of multiple risk parameters. The conclusion is that several options for caries risk assessment for different age groups are available. Nevertheless, there is no solution to how often a patient should appear for prevention in a dental office nor which preventive measures have to be taken to keep him/her healthy. Therefore it seems reasonable to roughly determine the recall frequency on the basis of the respective risk assessment and to adjust this frequency over time after the evaluation of disease progression.

Hyperfine-mediated gate-driven electron spin resonance.

An all-electrical spin resonance effect in a GaAs few-electron double quantum dot is investigated experimentally and theoretically. The magnetic field dependence and absence of associated Rabi oscillations are consistent with a novel hyperfine mechanism. The resonant frequency is sensitive to the instantaneous hyperfine effective field, and the effect can be used to detect and create sizable nuclear polarizations. A device incorporating a micromagnet exhibits a magnetic field difference between dots, allowing electrons in either dot to be addressed selectively.

Detection of Chlamydia trachomatis DNA using MagNA Pure DNA extraction and Cobas Amplicor CT/NG amplification.

The automated MagNA Pure DNA extraction method for Chlamydia trachomatis was compared with the manual Cobas Amplicor protocol using 100 microL of input sample volume from 964 specimens. Agreement between protocols was 96.1%. The automated extraction method had a sensitivity of 99% and a specificity of 100%. Amplification inhibition observed after manual preparation of samples (3.8%) was not apparent following automated extraction. Using 200 microL of sample in the automated extraction process lowered the detection limit without raising the inhibition rate. Furthermore, the automated extraction method halved the hands-on time required for the procedure.

A new approach to define defect extensions of endodontically treated teeth: inter- and intra-examiner reliability.

For endodontically treated teeth, there are no standardized measures available to define the extent of loss in tooth substance prior to final restoration. In this study, defect size was classified and the applicability of the classification was tested related to the inter- and intra-examiner reliability. For classification, three parameters were investigated: (i) remaining tooth substance in the vertical dimension (level A-D, aspect I), (ii) remaining tooth substance as regarded horizontally (mm; bucco-lingual and mesio-distal, aspect II), and (iii) size of the orifice (mm; aspect III). Four non-calibrated or (pre-trained) examiners were asked to gauge and classify 20 casts of clinically broken down teeth. The measurements were repeated twice every alternative week giving three separate readings. Inter-examiner reliability was determined at weeks 1, 3 and 5. The intra-examiner reliability was compared between readings 1 and 2, 1 and 3, and 2 and 3. As statistical tests, intra-class correlation (ICC) and Cohen's kappa (weighted) were used at a significance level of P < 0.05. Inter- and intra-examiner reliability for ordinal data (aspect I) revealed, with one exception, 'moderate' to 'very good' evaluations. Inter- and intra-examiner reliability (ICC) of metric data of aspect II and III was primarily 'excellent'. It may be concluded that the newly developed classification could be applied as an appropriate and reproducible method to define defect extension in endodontically treated teeth.

Evaluation of dentin abrasion during professional tooth cleaning in an in vitro model.

OBJECTIVES: Professional tooth cleaning (PTC) may lead to loss of exposed dentin. The aim of the present study was to determine the absolute loss of dentin during PTC using various product combinations with an in vitro model. MATERIAL AND METHODS: Dentin specimens (72) were randomly assigned to nine groups. In four groups each, prophy brushes and prophy cups were used in combination with four different abrasives (calcium pyrophosphate, pumice, Hawe cleanic, Nupro coarse). In the ninth group, a rubber cup with embedded fluoride and abrasives was used (pasteless prophy cup). The treatment time was 37 s. Surface loss was determined by profilometry. RESULTS: The surface loss in the nine groups was as following: (1) brush/calcium pyrophosphate: 6.18 microm (a); (2) brush/pumice: 5.51 microm; (3) brush/Nupro coarse: 10.10 microm (b); (4) brush/Hawe cleanic: 1.88 (a, b); (5) prophy cup/calcium pyrophosphate 2.07 (c); (6) prophy cup/pumice: 6.07 microm; (7) prophy cup/Nupro coarse: 5.93 microm (c); (8) prophy cup/Hawe cleanic: 4.93 microm (c); (9) pasteless prophy cup: 11.86 microm (c). Groups with the same letter in parentheses are statistically significant different at p<0.05. In a pooled analysis, no statistically significant difference between brushes and prophy cups was found. CONCLUSION: In the present study, the surface loss of about eight PTC procedures was simulated. Hence, the dentin loss ranged between 0.24 and 1.48 microm per PTC. Therefore, PTC does not seem to be a main factor in dentin loss.

Involvement of neurotrophins and their receptors in spondyloarthritis synovitis: relation to inflammation and response to treatment.

OBJECTIVE: To investigate whether expression of the four members of the neurotrophin (NT) family and their four corresponding receptors is related to synovial inflammation in patients with spondyloarthritis (SpA). MATERIAL AND METHODS: Synovial fluid (SF) and serum NTs and their receptors were measured by ELISA. Immunohistochemistry was used for synovial tissue biopsy specimens from patients with SpA, rheumatoid arthritis, and osteoarthritis (OA). In SpA synovium, immunoreactivity of the receptors trkA and NGFRp75 was also assessed before and after 12 weeks of treatment with the monoclonal anti-tumour necrosis factor alpha antibody, infliximab. RESULTS: mRNA transcripts of all NTs and receptors were expressed in the inflamed synovium. At the protein level, brain derived neurotrophic factor and NT-3 were significantly higher in the SF of patients with SpA than in those with OA. In contrast, ELISA of serum samples showed that the highest member in SpA was NT-4. Immunohistochemistry demonstrated that the NT receptors trkA and NGFRp75 were highly expressed in the inflamed synovium of patients with SpA, correlating with vascularity and lymphoid aggregates, respectively. Additionally, immunoreactivity of both receptors was significantly decreased after infliximab treatment. CONCLUSIONS: NTs and their receptors are expressed in inflamed peripheral joints of patients with SpA. Their expression is not constitutive but related to inflammation and they may be involved in the local disease processes.

[Dental group prophylaxis - for children only?]. / Zahnmedizinische Gruppenprophylaxe - nur für Kinder?

In Germany, caries in 12-year olds have declined by 70 % in the last decade. This was the result of a variety of preventive measures such as salt fluoridation, group related prevention in schools and kindergartens, and individualized preventive measures offered in dental offices. On a national scale, salt fluoridation seems to be the measure with the highest efficacy and efficiency. Firstly, it has the potential to reach the entire population, and secondly it is highly cost-effective. The cost-benefit ratio for salt fluoridation ranges from 25 to 80, e. g. for one Euro spent on prevention, 25 to 80 Euro can be saved in therapy. However, salt fluoridation alone cannot stop caries, and it is not at all effective in preventing gingivitis and periodontitis. Therefore, additional measures have to be taken. The cost-benefit ratio for group-related prevention ranges from 2.4 to 19.5 and for individualized prevention from 0.7 to 2.1. Besides the better cost-effectiveness, group-related prevention has the advantage of advanced target group attainment. For example, it is easy to reach children in schools whereas it is difficult to review them in a dental office. Therefore, group related-prevention should have priority. This should not be restricted to children and adolescents, seniors can also be attended in groups. In Germany, about 950,000 people live in old people's homes, and additionally about 570,000 people in nursing homes. This population often suffers from severe oral health problems such as caries, periodontitis, and diseases involving the mucosa. Taking into account that the number of elderly institutionalized people is increasing in Germany, the establishment of group-related prevention for this part of the population seems to be an important goal in health policy.

Kinetic cavity preparation--hit or flop?

The preparation of dental hard tissues is carried out primarily with rotating instruments and is known to have some shortcomings. Kinetic cavity preparation (KCP) seems to be a desirable alternative. Nevertheless, scientific investigations and clinical experiences revealed numerous disadvantages which have led to a clear limitation of its use. For example, KCP can not replace the normal conditioning of enamel by acid etching. The hopes connected with the re-introduction of this technology for conservative dentistry have not been fulfilled.

Can we fulfil even the basics of endodontic therapy?

Micro-organisms and lipopolysaccharides (LPS) are involved in inducing periapical inflammation. Therefore, it is important to eliminate them from the complex root canal system and seal the endodontic space as accurately as possible. This is possible with a combination of the following: instrumentation of the canal, eventually with new, motor driven instruments, abundant rinsing with NaOCl, dressing preferably with Ca(OH)2, sealing the root canal and incorporating the permanent restoration within three months after root canal filling to avoid reinfection.

A new fluoride-releasing rubber cup for professional oral hygiene.

Rubber cups in combination with prophylaxis pastes are commonly used for supragingival professional tooth cleaning. This procedure requires frequent interruption in order to collect fresh paste. Moreover, the paste-saliva slurry blurs the visibility, which implies intermittent rinsing to look for residual discolorations. Hawe Neos Dental (Bioggio, Switzerland) has developed a new prophylaxis cup aimed at cleaning and smoothing the tooth surfaces, while simultaneously fluoridating the enamel without a prophylaxis paste. This new prophylaxis cup was tested with respect to cleaning efficiency, resulting surface roughness, abrasivity, and the promotion of fluoride uptake into enamel. After 15 seconds of use, the new cup showed a cleaning efficiency which was 20 to 30% higher than that of a conventional rubber cup (p < 0.01) used with the prophylaxis pastes Nupro coarse or Hawe cleanic (78% vs. 57 and 49%). The fluoride cup had a smoothing effect on the enamel surface comparable to that effected by the two prophylaxis pastes. The abrasivity on enamel was lowest with the new cup. On dentin, abrasivity was comparable to Nupro coarse, but higher than with Hawe cleanic. The fluoride cup also produced a higher amount of KOH-soluble fluoride on the enamel surface when compared to Hawe cleanic. With respect to the structurally bound fluoride, no difference was found. The newly developed fluoride releasing Hawe Neos cup represents an effective alternative to conventional procedures for supragingival professional tooth cleaning on enamel.

Long-Term bacterial leakage along obturated roots restored with temporary and adhesive fillings.

The aim of this study was to examine whether obturated roots combined with several adhesive and temporary filling materials can be bypassed by bacteria. Standardized cavities were coronally prepared into 130 straight roots mimicking clinical access cavities. After obturation the roots were assigned to six test and three control groups and coronally sealed with either Clearfil, CoreRestore, IRM, Ketac Fil, or a combination of IRM/wax or Ketac Fil/wax. The roots were then fixed between a top and a bottom chamber each. The top chamber contained soy broth with 108 Staphylococcus epidermidis colony-forming units/ml, and the bottom chamber contained sterile soy broth. For 1 yr the mounts were checked on a regular basis for turbidity in their bottom chambers indicating bacterial growth. After 1 yr only three samples from the CoreRestore group and two samples from the Clearfil group resisted leakage. At termination there was no significant difference in number of leaking samples among the groups. At the beginning of the experiment IRM performed worst. Between months 5 and 10 Clearfil showed the least leaking samples; for some months this was statistically significant compared with IRM or Ketac Fil.

[Effective of preventive programs on oral hygiene of adults and school children]. / Einfluss von Prophylaxeprogrammen auf die Mundhygiene von Erwachsenen und Schulkindern.

The improvement of dental hygiene is considered to be one of the most important measures in dental health education. Hence, it was the aim of the present study to investigate the influence of two similar preventive programmes on oral hygiene performed in adults and schoolchildren. In the adult study, the oral hygiene indices PI (Quigley-Hein) and API (Lange) could be significantly improved after six months by an individualized preventive programme performed every three months. Besides repeated instructions and motivations in oral hygiene, the programme included professional toothcleaning. In contrast, nine-year old schoolchildren showed no improvement in the oral hygiene indices PI and PBI (Mühlemann and Son) after applying a similar programme over three years. For the PI, even a deterioration from 1.86 at the beginning of the study to 2.65 at the final examination was seen. Other authors were more successful by applying a programme without professional toothcleaning but with inclusion of the parents. It is therefore concluded that children should be educated to oral self-care by including their parents and by taking their status of psychological development into account.

Bacterial leakage in obturated root canals following the use of different intracanal medicaments.

The aim of this study was to examine whether intracanal medication prior to root canal obturation has an inhibitory effect on corono-apical penetration of bacteria. 93 single rooted teeth were instrumented and sterilized with ethylene oxide. They were assigned to three control groups and four test groups with n = 20 each. For one week, they were dressed with different medicaments: The first group with a 5% chlorhexidine gel, the second with Ledermix, the third with a fresh mix of calcium hydroxide and water and the fourth without any medication. After obturation (lateral condensation, AH26) the roots were fixed between a top and a bottom chamber. The top chamber contained 3 mL trypticase soy broth with 10(8) Staphylococcus epidermidis CFU's/mL, whereas the bottom chamber contained sterile trypticase soy broth. For one year, the mounts were incubated at 37 degrees C. They were checked on a regular basis for turbidity in their bottom chambers indicating bacterial growth. None of the test samples leaked for three months. After one year, the calcium hydroxide group had only 6 leaking samples whereas the chlorhexidine group had 14, the Ledermix group 15, and the unmedicated group had 13 leaking samples. It may be concluded that under the conditions of this study, calcium hydroxide was the medicament of choice to avoid bacterial penetration of the root canal. Ledermix did not perform better than no premedication. Chlorhexidine was superior to Ledermix in the second third of the observation period.