Central nervous system manifestations of LRBA deficiency: case report of two siblings and literature review.

BACKGROUND: LPS-responsive beige-like anchor protein (LRBA) deficiency is a primary immunodeficiency disease (PID) characterized by a regulatory T cell defect resulting in immune dysregulation and autoimmunity. We present two siblings born to consanguineous parents of North African descent with LRBA deficiency and central nervous system (CNS) manifestations. As no concise overview of these manifestations is available in literature, we compared our patient's presentation with a reviewed synthesis of the available literature. CASE PRESENTATIONS: The younger brother presented with enteropathy at age 1.5 years, and subsequently developed Evans syndrome and diabetes mellitus. These autoimmune manifestations led to the genetic diagnosis of LRBA deficiency through whole exome sequencing with PID gene panel. At 11 years old, he had two tonic-clonic seizures. Brain MRI showed multiple FLAIR-hyperintense lesions and a T2-hyperintense lesion of the cervical medulla.  His sister presented with immune cytopenia at age 9 years, and developed diffuse lymphadenopathy and interstitial lung disease. Genetic testing confirmed the same mutation as her brother. At age 13 years, a brain MRI showed multiple T2-FLAIR-hyperintense lesions. She received an allogeneic hematopoietic stem cell transplantation (allo-HSCT) 3 months later. Follow-up MRI showed regression of these lesions. CONCLUSIONS: Neurological disease is documented in up to 25% of patients with LRBA deficiency. Manifestations range from cerebral granulomas to acute disseminating encephalomyelitis, but detailed descriptions of neurological and imaging phenotypes are lacking. LRBA deficiency amongst other PIDs should be part of the differential diagnosis in patients with inflammatory brain lesions. We strongly advocate for a more detailed description of CNS manifestations in patients with LRBA deficiency, when possible with MR imaging. This will aid clinical decision concerning both anti-infectious and anti-inflammatory therapy and in considering the indication for allo-HSCT.

Postoperative pain after ultrasonically and laser-activated irrigation during root canal treatment: a randomized clinical trial.

AIM: To compare the intensity of postoperative pain after primary root canal treatment of asymptomatic teeth when using ultrasonically (UAI) or laser-activated irrigation (LAI). METHODOLOGY: In this superiority randomized clinical trial (ClinicalTrials.gov ID: NCT03981237) with parallel design, fifty-six patients with an asymptomatic tooth in need of primary root canal treatment were enrolled. After chemo-mechanical canal preparation using rotary instruments and NaOCl irrigation, teeth were randomly assigned to two groups and patients were blinded to the final irrigation protocol. In the UAI group (n = 28), 60s activation with an Irrisafe tip was done per canal. In the LAI group (n = 28), NaOCl was activated with a pulsed Er:YAG (2940 nm) laser, equipped with a conical tip, with settings of 50 µs, 20 mJ at 15 Hz for 60 s. Patients recorded their pain intensity 6, 24, 48 and 72 h after treatment on a 100 mm visual analogue scale (VAS), as well as their analgesic consumption. Pain levels and incidence were compared across groups using the Mann-Whitney U-test and chi-square test. RESULTS: Overall, mean postoperative pain intensity was low, with the majority of patients having no or minimal pain 24 h postoperatively. At 6 h postoperatively, pain intensity and incidence were significantly higher in the UAI group compared to the LAI group (P < 0.05). For the other time intervals, no significant differences in postoperative pain incidence or intensity were found. The frequency of analgesic intake did not differ significantly between the two groups. Neither of the activation methods resulted in any adverse effects. CONCLUSIONS: Ultrasonically and laser-activated irrigation resulted in low and comparable levels of postoperative pain in asymptomatic patients receiving primary root canal treatment.

Author Correction: A human immune dysregulation syndrome characterized by severe hyperinflammation with a homozygous nonsense Roquin-1 mutation.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A human immune dysregulation syndrome characterized by severe hyperinflammation with a homozygous nonsense Roquin-1 mutation.

Hyperinflammatory syndromes are life-threatening disorders caused by overzealous immune cell activation and cytokine release, often resulting from defects in negative feedback mechanisms. In the quintessential hyperinflammatory syndrome familial hemophagocytic lymphohistiocytosis (HLH), inborn errors of cytotoxicity result in effector cell accumulation, immune dysregulation and, if untreated, tissue damage and death. Here, we describe a human case with a homozygous nonsense R688* RC3H1 mutation suffering from hyperinflammation, presenting as relapsing HLH. RC3H1 encodes Roquin-1, a posttranscriptional repressor of immune-regulatory proteins such as ICOS, OX40 and TNF. Comparing the R688* variant with the murine M199R variant reveals a phenotypic resemblance, both in immune cell activation, hypercytokinemia and disease development. Mechanistically, R688* Roquin-1 fails to localize to P-bodies and interact with the CCR4-NOT deadenylation complex, impeding mRNA decay and dysregulating cytokine production. The results from this unique case suggest that impaired Roquin-1 function provokes hyperinflammation by a failure to quench immune activation.

Endodontic performance by Flemish dentists: have they evolved?

AIM: To gather information on aspects of endodontic practice and referral behaviour by Flemish (Dutch-speaking Belgian) dentists and to compare the results with an earlier investigation. METHODOLOGY: A postal questionnaire was distributed to 4468 active Flemish dentists. It consisted of multiple-choice questions on endodontic practice and endodontic referral need. Basic information on age, gender, year of qualification and clinical specialty was also obtained. The questionnaire was free of charge to return. Data were imported in a database, subjected to descriptive and analytical statistics and compared to those of an earlier, comparable survey. RESULTS: The response rate was 18.5%. Of all respondents, 95% were general practitioners. More than half (56%) of the respondents never or seldom used rubber dam during endodontic treatment. The use of sodium hypochlorite as an irrigant was well established (80% of respondents using it), whereas the use of EDTA was limited. Female respondents were more likely to refer to an endodontist than male (70 versus 49%). Referrals for treatment of root canal obstruction (48%), perforations and root resorption (42%) and retreatment (39%) were rated 'very important'. Younger respondents more frequently made use of magnification, rotary instruments and rubber dam. Activation of irrigants was incorporated by a small number of respondents (50% never, 12.6% seldom). Cold lateral condensation was used by most GDPs (35.3% always, 19.5% frequently). CONCLUSIONS: Endodontic practice of general dentists in Flanders did not always comply with quality guidelines. However, when comparing the present data with those of a previous study, an obvious trend towards a more present-day treatment protocol is noticeable, as well as an increased appeal for endodontic referral.

Disruption of olfactory receptor neuron patterning in Scutoid mutant Drosophila.

Olfactory neurons show an extreme diversity of cell types with each cell usually expressing one member from a large family of 60 Odorant receptor (Or) genes in Drosophila. Little is known about the developmental processes and transcription factors that generate this stereotyped pattern of cellular diversity. Here we investigate the molecular and cellular basis of defects in olfactory system function in an unusual dominant mutant, Scutoid. We show that the defects map to olfactory neurons innervating a specific morphological class of sensilla on the antenna, large basiconics. Molecular analysis indicates defects in neurons expressing specific classes of receptor genes that map to large basiconic sensilla. Previous studies have shown that in Scutoid mutants the coding region of the transcriptional repressor snail is translocated near the no-ocelli promoter, leading to misexpression of snail in the developing eye-antenna disc. We show that ectopic expression of snail in developing olfactory neurons leads to severe defects in neurons of the antennal large basiconics, supporting the model that the dominant olfactory phenotype in Scutoid is caused by misexpression of snail.

Long-term sealing ability of Resilon apical root-end fillings.

AIM: To evaluate ex vivo the long-term sealing ability of the SE Resilon Epiphany system as an apical root-end filling material. METHODOLOGY: A total of 60 standardized horizontal bovine root sections were divided into three groups filled with either gutta-percha with AH 26, tooth-coloured mineral trioxide aggregate (MTA) or Resilon pellets with Epiphany SE, and submitted to capillary flow porometry at 48 h, 1 and 6 months to assess the minimum, mean flow and maximum pore diameters. Results of the different materials and results by material and time were analysed statistically using nonparametric tests; the level of significance was set at 0.05. RESULTS: Resilon had smaller pore diameters than gutta-percha and MTA at 48 h and smaller mean flow and maximum pore diameters than gutta-percha and MTA at 1 month. At 6 months Resilon had larger minimum pore diameters than gutta-percha. Although not always statistically significant, the minimum, mean flow and maximum pore diameters of gutta-percha and MTA diminished with time. This was not the case for Resilon, where the same parameters increased. CONCLUSIONS: All materials leaked at all times. Resilon performed better than gutta-percha and MTA in the short-term, but the seal of MTA and gutta-percha improved over time whereas the seal of Resilon deteriorated. It is critical to evaluate the performance of materials in the long-term contrary to most studies which are short-term.

[Cavity preparation using an Er:YAG laser in the adult dentition]. / La préparation de cavités à l'aide du laser Er:YAG dans la denture adulte.

Many lasers (i.e., different wavelengths) are available today for clinical applications. Not all lasers are to be used for cavity preparation and removal of carious tissues. Erbiumlasers (Er:YAG and Er,Cr:YSGG) are suitable for these purposes (the wavelengths coincide with the highest absorption peaks of water and hydroxyapatite). The advantages during cavity preparation and caries removal are smear layer free cavity walls, selective and localised removal of tooth substance, a restricted need or the absence of anaesthesia, and cavity walls with a higher acid resistance resulting in a better protection against secondary decay. Possible side effects of erbium lasers with water cooling and used with respect for correct power setting are minimal and can be compared with those of rotary instruments. Erbium laser tooth preparation is now one of the options in the minimal invasive approach. The needs for acid etching has been debated for long. At present it has become clear that acid etching is mandatory to obtain a good adhesion and retention with resin composites.

Odor detection in insects: volatile codes.

Insect olfactory systems present models to study interactions between animal genomes and the environment. They have evolved for fast processing of specific odorant blends and for general chemical monitoring. Here, we review molecular and physiological mechanisms in the context of the ecology of chemical signals. Different classes of olfactory receptor neurons (ORNs) detect volatile chemicals with various degrees of specialization. Their sensitivities are determined by an insect-specific family of receptor genes along with other accessory proteins. Whereas moth pheromones are detected by highly specialized neurons, many insects share sensitivities to chemical signals from microbial processes and plant secondary metabolism. We promote a more integrated research approach that links molecular physiology of receptor neurons to the ecology of odorants.

Long-term assessment of the seal provided by root-end filling materials in large cavities through capillary flow porometry.

AIM: To evaluate the long-term sealing ability of a variety of materials when used as root-end fillings. METHODOLOGY: A total of 140 standardized horizontal bovine root sections (external diameter: 7 mm, height: 3 mm; internal diameter: 2.5 mm) were divided into seven groups, filled with either gutta-percha with AH26, Ketac Fil, Fuji IX, Tooth-Colored MTA, IRM, Ketac Fil with conditioner or Fuji IX with conditioner and submitted to capillary flow porometry at 1 and 6 months to assess minimum, mean flow and maximum pore diameters. Results of the different materials and results by material were analysed statistically using non-parametric tests; the level of significance was set at 0.05. RESULTS: There were no significant differences between the minimum pore diameters associated with the materials at each time. At 1 month the mean flow pore diameters of Ketac Fil were significantly larger than those of gutta-percha, Ketac Fil with conditioner, Fuji IX with conditioner and IRM. There were significant differences between the maximum pore diameters at 1 month (all>IRM; Fuji IX>gutta-percha, Ketac Fil with conditioner, Fuji IX with conditioner) and 6 months (Fuji IX>gutta-percha, IRM; Ketac Fil>gutta-percha, IRM). There were significant differences in the minimum pore diameters between the different points in time for each material except IRM, in the mean flow pore diameters for each material and in the maximum pore diameters for each material except MTA. CONCLUSIONS: All materials were associated with capillary flow. IRM root-end fillings had through pores that were smaller than those associated with other materials. Conventionally setting glass-ionomer cements had the largest pores, although dentine conditioning improved their performance. The seal of all materials improved after 6 months.

Dental and oral complications of lip and tongue piercings.

Piercing of the tongue and perioral regions is an increasingly popular expression of body art, with more patients coming in for a routine check-up with tongue and/or lip piercings. Several complications of oral piercing have been reported, some of which are life-threatening. In the present clinical survey the prevalence of both tongue and lip piercing complications in oral health was assessed in a group of 50 patients. The most common dental problem registered was chipping of the teeth, especially in association with tongue piercing. Gingival recession was seen as a result of lip piercing with studs. Post-procedural complications included oedema, haemorrhage and infection. Therefore, dentists and oral and maxillofacial surgeons should be given more authority to advise patients with oral and facial piercings or those who plan to acquire this type of body art.

The sealing ability of an epoxy resin root canal sealer after Nd:YAG laser irradiation of the root canal.

AIM: To evaluate ex vivo the effect of Nd:YAG laser irradiation with and without black ink on instrumented root canal walls, and the degree of both coronal and apical microleakage of filled root canals. METHODOLOGY: Seventy-two single-rooted teeth were instrumented up to a size 40 K-file, and then divided into six groups of 10 teeth: groups 1 and 4 remained unlased and acted as control groups, groups 2 and 5 were treated with a Nd:YAG laser (Fidelis Plus, Herzele, Belgium), groups 3 and 6 were treated with a laser and black ink; the remaining 12 teeth served as positive and negative controls. The laser was operated at 1.5 W, 15 Hz, four times for 5 s with a 20-s interval. Groups 4-6 were filled using cold lateral condensation of gutta-percha and AH26. After storage in water for 48 h at 37 degrees C, through-and-through leakage (L in microL day-1) was measured for 48 h under a pressure of 1.2 atm using a fluid transport model and recorded as L=0 (L1), 010 (L3). After the assessment of leakage with the fluid transport model, the teeth were immersed in rhodamine B solution for 48 h at 37 degrees C. Apical and coronal dye leakage was scored after longitudinal splitting of these teeth. All teeth of groups 1-3 were split longitudinally and observed under SEM for evaluation of remaining smear layer. RESULTS: Through-and-through leakage was only observed in the group lased with black ink (two samples-L2). Apical and coronal dye leakage was observed in all groups; there were no statistically significant differences amongst the three experimental groups. The through-and-through leakage, measured with the fluid transport model in two teeth of group 6, was confirmed in the dye leakage test (rhodamine B dye was observed along the total length of the root filling). There was evidence of melted and ablated root canal dentine in the laser-treated groups. These findings were more obvious in root canals lased in association with black ink. All apical foramina in the lased group remained patent. CONCLUSIONS: Nd:YAG laser irradiation with black ink increased the amount of melted and ablated dentine areas compared with that without black ink. Nd:YAG lasing in association with black ink did not result in a reduction of either coronal or apical microleakage in root filled teeth.

SEM analysis of the integrity of resected root apices of cadaver and extracted teeth after ultrasonic root-end preparation at different intensities.

AIM: To compare the integrity of root apices of cadaver and extracted teeth after resection, ultrasonic root-end cavity preparation at medium and low ultrasonic power settings and retrieval. METHODOLOGY: Root canal treatment, perpendicular root-end resection and root-end preparation were performed on single-rooted anterior and premolar teeth (49 teeth in situ in maxillary and mandibular jaws from cadavers and 45 extracted teeth). Apical root-end cavities were prepared with the S12/90 degrees D tip and the Suni-Max ultrasonic unit (Satelec, Merignac, France) at the intensity prescribed by the manufacturer (power 7 at power mode S) (34 cadaver teeth, 30 extracted teeth) and at a lower intensity (power 4 at power mode S) (15 cadaver teeth, 15 extracted teeth). After ultrasonic preparation the cadaver teeth were retrieved from the jaws. Exaflex impressions (GC Corporation, Tokyo, Japan) were made of the root apices after resection, root-end preparation and retrieval. These impressions were processed for SEM analysis, and the recordings evaluated for cracks and marginal chipping. RESULTS: In general, extracted teeth showed significantly more cracks and chipping than cadaver teeth. Lowering the ultrasonic power from medium to low intensity resulted in equal scores for cracks on extracted teeth and for chipping on cadaver teeth, in higher scores for cracks on cadavers and in lower scores for chipping on extracted teeth. Complete cracks and cracks originating from the root surface occurred only in extracted teeth. CONCLUSIONS: The number of cracks and degree of chipping caused by ultrasonic root-end preparation was higher on extracted teeth than on cadaver teeth. Lowering the ultrasonic power from medium to low intensity cannot be recommended as it resulted in more cracks and equal chipping on cadaver teeth. Investigation of techniques and materials should be conducted in situ and not on extracted teeth.

Longitudinal study on microleakage of three root-end filling materials by the fluid transport method and by capillary flow porometry.

AIM: (i) To compare the root-end sealing ability of IRM Caps (IRM), Fuji IX Capsules (Fuji IX) and Pro Root MTA Tooth-Coloured Formula (MTA) in teeth obtained from cadavers. (ii) Further research on leakage study methodology by means of comparison of the fluid transport method (FTM) and capillary flow porometry (CFP). METHODOLOGY: Root canal treatment was performed on 33 cadaver teeth in situ 2 weeks prior to root resection and ultrasonic retropreparation (S12/90 degrees D-tip on Suni-Max), after which the teeth were retrieved from the cadavers. Two teeth were kept as positive and negative controls. The other teeth were divided in three different groups at random, with each group receiving one of the retrofill materials. Retrofills were exposed to water 5 min after placement. The teeth were stored at 37 degrees C for 12 h after which the root filling was removed. Microleakage (L in microL day(-1)) was measured for 24 h under a pressure of 1.2 atm using FTM and recorded as L = 0, 0 < L < or = 10, L > 10. The measurements were repeated after 1 and 6 months. After 6 months, leakage was also assessed by CFP in order to measure through pores and their diameters. Results were analysed statistically using nonparametric Kruskal-Wallis and Mann-Whitney U-tests, and Spearman correlation coefficients between the results of both methods were calculated. The level of significance was set at 0.05. RESULTS: (i) A statistically significant difference could be demonstrated between Fuji IX and IRM at 1 month with FTM. FTM revealed a significant difference between Fuji IX and the other materials at 6 months, whereas CFP did not. However, using both methods, Fuji IX showed the best result. (ii) When comparing both techniques, CFP demonstrated through pores in all teeth, whereas with FTM in only 14 of the 31 teeth could through pores be demonstrated. A positive correlation between both methods was demonstrated. CONCLUSIONS: Under the conditions of this study (i) the conventionally setting glass-ionomer cement Fuji IX showed the best results when used as a root-end material and (ii) CFP appeared to be a useful method for leakage evaluation of through pores in endodontics.

The use of glass ionomer cements in both conventional and surgical endodontics.

The capacity to bond to dental tissues, especially to dentine, their long-term fluoride release and their biocompatibility make glass ionomer cements (GICs) advantageous for use in endodontics, as well as in restorative dentistry. This review provides information on the basic properties of GICs, such as adhesion, antimicrobial effects and biocompatibility, particularly as they relate to use in endodontics. Indications for the use of GICs in endodontics are orthograde root canal sealing, root-end filling, repair of perforations and root resorption defects, treatment of vertical fractures and maintenance of the coronal seal. The paper includes a review on each of these indications. It is concluded that in spite of the critical handling characteristics and the inconclusive findings regarding sealing ability and antimicrobial activity, there is substantial evidence to confirm their satisfactory clinical performance. Both soft tissue and bone compatibility make them suitable for use during endodontic surgery.

Factors associated with switching from oral hypoglycaemic agents to insulin therapy.

BACKGROUND: The aim of our study was to determine which factors are associated with switching from oral hypoglycaemic agents to insulin therapy in patients with type 2 diabetes mellitus in general practice. METHODS: Longitudinal, observational study in a Dutch general healthcare centre. All pharmacologically treated patients with type 2 diabetes mellitus were included (n = 152). Comorbidity, laboratory results and medication use were obtained from the general practitioners' files. RESULTS: A total of 31 (20.4%) patients switched from oral hypoglycaemic agents to insulin therapy; they were significantly younger at the onset of diabetes, 50.5 versus 57.7 years. Fasting blood glucose levels and HbA(1c) values were significantly higher after the switch compared with patients on oral treatment, 10.0 mmol/l versus 8.4 mmol/l and 8.8% versus 7.9%, respectively. Concerning comorbidity, they suffered more frequently from acute myocardial infarction, lipid disorders, depression, retinopathy and atrial fibrillation. Cardiovascular disease in general was more often present in patients who switched over to insulin, 77.4% versus 52.9% (OR 3.1; CI 1.2-7.6). CONCLUSIONS: Patients who switch over to insulin therapy are younger at diagnosis, suffer from more health problems besides diabetes, especially cardiovascular disease, and have worse metabolic control, compared with users of oral hypoglycaemic agents.

[Cardiovascular risk factors. II. Signs of vascular damage: practical implications]. / Cardiovasculaire risicofactoren. II. Tekenen van vaatschade: praktische implicaties.

In recent years, an increasing amount of information has become available on new indicators of cardiovascular damage, their determinants and the value of these indicators in the prediction of the development of cardiovascular disease. These indicators include carotid intima-media thickness, ECG characteristics, endothelial function and the measurement of coronary calcium. These indicators are currently used predominantly in cardiovascular disease research. At present, only limited information is available as to whether these indicators are useful in clinical practice for estimating the absolute risk of cardiovascular disease in an individual. The relative value of these newer indicators compared to the routinely collected risk factor information such as medical history, lifestyle, anthropometric variables, blood pressure and lipids is also not yet well established. The recent Dutch guidelines for the initiation of treatment with blood pressure lowering and lipid lowering drugs as a function of the absolute risk of cardiovascular disease within 10 years for the individual patient point toward the urgent necessity for research in the area of new risk indicators of vascular damage.

Inactivation of olfactory sensilla of a single morphological type differentially affects the response of Drosophila to odors.

The olfactory organs on the head of Drosophila, antennae and maxillary palps, contain several hundred olfactory hairs, each with one or more olfactory receptor neurons. Olfactory hairs belong to one of three main morphological types, trichoid, basiconic, and coeloconic sensilla, and show characteristic spatial distribution patterns on the surface of the antenna and maxillary palps. Here we show that targeting expression of the cell-death gene reaper to basiconic sensilla (BS) causes the specific inactivation of most olfactory sensilla of this type with no detectable effect on other types of olfactory sensilla or the structure of the antennal lobe. Our data suggest that BS are required for a normal sensitivity to many odorants with a variety of chemical structures, through a wide range of concentrations. Interestingly, however, in contrast to other odorants tested, the behavioral response of ablated flies to intermediate concentrations of propionic and butyric acids is normal, suggesting the involvement of sensilla unaffected by ectopic reaper expression, probably coeloconic sensilla that respond strongly to these two organic acids. As inactivation of BS causes an underestimation of the concentration of both acids detectable at both the highest and lowest odorants concentrations, our results suggest that concentration coding for these two odorants relies on the integration of signals from different subsets of sensilla, most likely of different morphological types.

Odor coding in the Drosophila antenna.

Odor coding in the Drosophila antenna is examined by a functional analysis of individual olfactory receptor neurons (ORNs) in vivo. Sixteen distinct classes of ORNs, each with a unique response spectrum to a panel of 47 diverse odors, are identified by extracellular recordings. ORNs exhibit multiple modes of response dynamics: an individual neuron can show either excitatory or inhibitory responses, and can exhibit different modes of termination kinetics, when stimulated with different odors. The 16 ORN classes are combined in stereotyped configurations within seven functional types of basiconic sensilla. One sensillum type contains four ORNs and the others contain two neurons, combined according to a strict pairing rule. We provide a functional map of ORNs, showing that each ORN class is restricted to a particular spatial domain on the antennal surface.