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The mRNA-destabilizing protein tristetraprolin (TTP), encoded by the ZFP36 gene, is known to be able to end inflammatory responses by directly targeting and destabilizing mRNAs encoding pro-inflammatory cytokines. We analyzed its role in psoriasis, a disease characterized by chronic inflammation. We observed that TTP is downregulated in fibroblasts deriving from psoriasis patients compared to those deriving from healthy individuals and that psoriatic fibroblasts exhibit abnormal inflammasome activity compared to their physiological counterpart. This phenomenon depends on TTP downregulation. In fact, following restoration, TTP is capable of directly targeting for degradation NLRP3 mRNA, thereby drastically decreasing inflammasome activation. Moreover, we provide evidence that ZFP36 undergoes methylation in psoriasis, by virtue of the presence of long stretches of CpG dinucleotides both in the promoter and the coding region. Besides confirming that a perturbation of TTP expression might underlie the pathogenesis of psoriasis, we suggest that deregulated inflammasome activity might play a role in the disease alongside deregulated cytokine expression.

LEMUR is a VUV imaging spectrograph with 0.28" resolution. Incident solar radiation is imaged onto the spectrograph slit by a single mirror telescope consisting of a 30-cm steerable f/12 off-axis paraboloid mirror. The spectrograph slit is imaged and dispersed by a highly corrected grating that focuses the solar spectrum over the detectors. The mirror is coated with a suitable multilayer with B4C top-coating providing a reflectance peak around 18.5 nm besides the usual B4C range above 500A. The grating is formed by two halves, one optimized for performances around 185A and the other above 500A. Three intensified CCD cameras will record spectra above 50 nm while a large format CCD array with an aluminum filter will be used around 185A.

In this study we investigated periodontal healing of mandibular second molars following 'orthodontic extraction' of adjacent impacted third molars, under the null hypothesis that there would be no difference in probing pocket depths (PPD) and clinical attachment levels (CAL) at the distal aspect of second molars before and after treatment. A retrospective survey was conducted of 64 patients who consecutively underwent 'orthodontic extraction' of mandibular third molars in close anatomical relationship with the mandibular canal from January 1997 to January 2011. Age, smoking habit, and PPD and CAL at the distal aspect of second molars before and after treatment were recorded. A statistically significant difference was found in PPD and CAL before and after treatment for the overall sample and for the sample classified by age (>25 or ≤25 years), smoking habit (smoker or non-smoker), and type of third molar impaction (horizontal, mesioangular, or vertical). Median PPD and CAL reductions amounted to 6mm and 5mm, respectively. The null hypothesis was rejected and orthodontic extraction proved to be indicated for those impacted mandibular third molars at high risk of a postoperative periodontal defect at the distal aspect of the adjacent second molar.

STUDY OBJECTIVES: To investigate the prevalence of mildly collapsible upper airways (defined by therapeutic continuous positive airway pressure [CPAP] values ≤ 8 cm H(2)O) in moderate to severe obstructive sleep apnea patients treated with CPAP and to determine their clinical, functional, and nocturnal polysomnographic characteristics. METHODS: Eighty-seven patients with moderate to severe obstructive sleep apnea consecutively treated with CPAP were retrospectively investigated. Two nocturnal home sleep portable monitoring studies were performed at baseline and during treatment. Participants were categorized according to therapeutic CPAP values: ≤ 8 cm H(2)O (group 1), 8–12 cm H(2)O (group 2), ≥ 12 cm H(2)O (group 3). Anthropometric, awake respiratory function, symptoms, comorbidities, and nocturnal home sleep portable monitoring studies data were collected. RESULTS: Mild upper airway collapsibility (therapeutic CPAP values ≤ 8 cm H(2)O) was present in 25.3% of patients. They showed more favorable apnea-hypopnea index, oxygen desaturation index, mean nocturnal saturation, sleep time with oxygen saturation < 90%, desaturation nadir, and supine position. Oxygen desaturation index showed a weak association with anatomical collapsibility. Using the receiver operating characteristic curve, the area under the curve for the oxygen desaturation index vs CPAP pressure requirements ≤ 8 cm H(2)O was low and oxygen desaturation index ≤ 40.8/h showed a sensitivity of 63.3% and a specificity of 69.2% to detect patients with mild collapsibility. CONCLUSIONS: A quarter of moderate to severe patients under CPAP therapy had mild collapsibility and were likely to also be good candidates for alternative and better tolerated non-CPAP therapies. Baseline anthropometric, clinical, and respiratory function characteristics did not predict mild upper airway collapsibility determined by CPAP pressure requirements ≤ 8 cm H(2)O. CITATION: Bosi M, Incerti Parenti S, Fiordelli A, Poletti V, Alessandri-Bonetti A. Upper airway collapsibility in patients with OSA treated with continuous positive airway pressure: a retrospective preliminary study. 2020;16(11):1839–1846.

Mandibular advancement devices (MADs) are used to treat patients with obstructive sleep apnoea (OSA). To date, there are no data that identify the most effective MAD design for apnoea-hypopnea index (AHI) reduction. The purpose of this systematic review is to investigate the effectiveness of different MAD designs in AHI reduction and oxygen saturation improvement in OSA patients. An electronic search was performed in MEDLINE, Cochrane Database, Scopus, Web of Knowledge and LILACS. Randomised controlled trials (RCTs) investigating the reduction of AHI on adult patients wearing MAD for OSA were included. The quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) and the risk of bias by the Cochrane Collaboration's tool for assessing risk of bias in randomised controlled trial. The success rate of each study was computed: [(mean baseline AHI−mean AHI after treatment)/mean baseline AHI]. Fifty RCTs were included. The risk of bias resulted with some concerns in most of the studies. The GRADE scores indicated that the quality of evidence was very low. The meta-analysis showed a success rate with mono-bloc and duo-bloc MADs respectively of 0.821 [0.722-0.887] and 0.547 [0.443-0.637]. The mono-bloc compared with duo-bloc better improved the minimum oxygen saturation (10.048 [7.733-12.363] and 3.357 [2.290-4.423], respectively). There is a very low quality body of evidence that mono-bloc MADs are more effective in reducing AHI and improving minimum oxygen saturation compared with duo-bloc MADs. The study protocol was registered on PROSPERO (n. CRD42019118084).

Summary This systematic review and meta-analysis evaluated the diagnostic accuracy of screening questionnaires for pediatric obstructive sleep apnea (OSA). Studies comparing any questionnaire with polysomnography for OSA detection in subjects aged ≤18 y were considered eligible for qualitative analysis. The quality assessment of diagnostic accuracy studies (QUADAS-2) tool was used for bias assessment. Only questionnaires adopted by at least four studies using the currently accepted diagnostic threshold of apnea–hypopnea index (AHI) ≥1 were included for further selective quantitative analyses. A bivariate meta-analysis was performed to calculate sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio; summary receiver operator characteristic curves were constructed. 37 studies (20 questionnaires) were eligible for qualitative analysis; none were considered of low quality. Among these articles, 13 studies and two questionnaires (sleep-related breathing disorder scale of the pediatric sleep questionnaire (SRBD-PSQ) and OSA-18) satisfied the criteria for quantitative synthesis. SRBD-PSQ had higher sensitivity (0.76) than OSA-18 (0.56), while OSA-18 exhibited higher specificity (0.73) than SRBD-PSQ (0.43). SRBD-PSQ performed well and was the most sensitive screening questionnaire using the diagnostic threshold of AHI ≥1 for pediatric OSA. However, further well-designed studies are still required to assess the role of SRBD-PSQ in real-world clinical populations.

Summary The phenotyping of the pathophysiology of obstructive sleep apnoea (OSA) lies at the core of tailored treatments and it is one of the most debated topics in sleep medicine research. Recent sophisticated techniques have broadened the horizon for gaining insight into the variability of the endotypic traits in patients with OSA which account for the heterogeneity in the clinical presentation of the disease and consequently, in the outcome of treatment. However, the implementation of these concepts into clinical practice is still a major challenge for both researchers and clinicians in order to develop tailored therapies targeted to specific endotypic traits that contribute to OSA in each individual patient. This review summarizes available scientific evidence in order to point out the links between endotypic traits (pharyngeal airway collapsibility, upper airway neuromuscular compensation, loop gain and arousal threshold) and the most common non-continuous positive airway pressure (CPAP) treatment options for OSA (mandibular advancement device, upper airway surgery, medication therapy, positional therapy) and to clarify to what extent endotypic traits could help to better predict the success of these therapies. A narrative guide is provided; current design limitations and future avenues of research are discussed, with clinical and research perspectives.

This study summarizes the available evidence from systematic reviews on the in vitro effects of photobiomodulation on the proliferation and differentiation of human bone and stromal cells by appraising their methodological quality. Improvements for future studies are also highlighted, with particular emphasis on in vitro protocols and cell-related characteristics. Six reviews using explicit eligibility criteria and methods selected in order to minimize bias were included. There was no compelling evidence on the cellular mechanisms of action or treatment parameters of photobiomodulation; compliance with quality assessment was poor. A rigorous description of laser parameters (wavelength, power, beam spot size, power density, energy density, repetition rate, pulse duration or duty cycle, exposure duration, frequency of treatments, and total radiant energy), exposure conditions (methods to ensure a uniform irradiation and to avoid cross-irradiation, laser-cell culture surface distance, lid presence during irradiation) and cell-related characteristics (cell type or line, isolation and culture conditions, donor-related factors where applicable, tissue source, cell phenotype, cell density, number of cell passages in culture) should be included among eligibility criteria for study inclusion. These methodological improvements will maximize the contribution of in vitro studies on the effects of photobiomodulation on human bone and stromal cells to evidence-based translational research.

OBJECTIVE: To investigate the effects on plaque index (PI) scores of manual or electric toothbrush with or without repeated oral hygiene instructions (OHI) and motivation on patients wearing fixed orthodontic appliances. MATERIALS AND METHODS: One month after the orthodontic fixed appliance bonding on both arches, 60 patients were randomly assigned to four groups; groups E(1) (n = 15) and E(2) (n = 15) received a powered rotating-oscillating toothbrush, and groups M(1) (n = 15) and M(2) (n = 15) received a manual toothbrush. Groups E(1) and M(1) received OHI and motivation at baseline (T0) and after 4, 8, 12, 16, and 20 weeks (T4, T8, T12, T16, and T20, respectively) by a Registered Dental Hygienist; groups E(2) and M(2) received OHI and motivation only at baseline. At each time point a blinded examiner scored plaque of all teeth using the modified Quigley-Hein PI. RESULTS: In all groups the PI score decreased significantly over time, and there were differences among groups at T8, T12, T16, and T20. At T8, PI scores of group E(1) were lower than those of group E(2), and at T12, T16, and T20, PI scores of groups M(1) and E(1) were lower compared to those of groups M(2) and E(2). A linear mixed model showed that the effect of repeated OHI and motivation during time was statistically significant, independently from the use of manual or electric toothbrush. CONCLUSIONS: The present results showed that repeated OHI and motivation are crucial in reducing PI score in orthodontic patients, independent of the type of toothbrush used.

Magnesium (Mg) is crucial for bone health. Low concentrations of Mg inhibit the activity of osteoblasts while promoting that of osteoclasts, with the final result of inducing osteopenia. Conversely, little is known about the effects of high concentrations of extracellular Mg on osteoclasts and osteoblasts. Since the differentiation and activation of these cells is coordinated by vitamin D3 (VD3), we investigated the effects of high extracellular Mg, as well as its impact on VD3 activity, in these cells. U937 cells were induced to osteoclastic differentiation by VD3 in the presence of supra-physiological concentrations (&gt, 1 mM) of extracellular Mg. The effect of high Mg concentrations was also studied in human bone-marrow-derived mesenchymal stem cells (bMSCs) induced to differentiate into osteoblasts by VD3. We demonstrate that high extra-cellular Mg levels potentiate VD3-induced osteoclastic differentiation, while decreasing osteoblastogenesis. We hypothesize that Mg might reprogram VD3 activity on bone remodeling, causing an unbalanced activation of osteoclasts and osteoblasts.

Acute myeloid leukemia (AML) blasts are immature committed myeloid cells unable to spontaneously undergo terminal maturation, and characterized by heterogeneous sensitivity to natural differentiation inducers. Here, we show a molecular signature predicting the resistance or sensitivity of six myeloid cell lines to differentiation induced in vitro with retinoic acid or vitamin D. The identified signature was further validated by TaqMan assay for the prediction of response to an in vitro differentiation assay performed on 28 freshly isolated AML blast populations. The TaqMan assay successfully predicts the in vitro resistance or responsiveness of AML blasts to differentiation inducers. Furthermore, performing a meta-analysis of publicly available microarray data sets, we also show the accuracy of our prediction on known phenotypes and suggest that our signature could become useful for the identification of patients eligible for new therapeutic strategies.

Because osteoblasts play a key role in bone remodeling and the influence of low-level laser therapy on this process is not clear, Saos-2 human osteoblast-like cells were irradiated by a gallium-aluminum-arsenide diode laser (915 nm) for 10, 48, 96, 193, and 482 s using doses 1, 5, 10, 20, and 50 J/cm2, respectively. A control group was not irradiated. Morphology, viability, and cytotoxicity analyses were carried out after 1 hr, 1 day, and 3 days. Deoxyribose nucleic acid (DNA) content and release of vascular endothelial growth factor (VEGF), receptor activator of nuclear factor kappa B ligand (RANKL), and osteoprotegerin (OPG) were evaluated. Viability was modulated by laser irradiation in a dose-dependent manner, with 10 J/cm2 inducing a biostimulatory response and 20 to 50 J/cm2 determining a bioinhibitory and cytotoxic effect. Accordingly, DNA content was generally increased for the 10 J/cm2 dose and decreased for the 50 J/cm2 dose. A rapid and transitory trend toward increased RANKL/OPG ratio and a tendency toward a delayed increase in VEGF release for doses of 1 to 10 J/cm2 was found. Further investigations using the biostimulatory dose of 10 J/cm2 emerged from this study are needed to establish the ideal treatment regimens in the laboratory as well as in clinical practice.

Single-tooth implantation has become a common treatment solution for replacement of a root-fractured maxillary incisor in adults, but the long-term esthetic results can be unfavorable due to progressive marginal bone loss, resulting in gingival recession. In this case report, a maxillary central incisor with a root fracture in its apical one-third was orthodontically extruded and extracted in a 21-year-old female. Implant surgery was performed after a 3-month healing period, and the final crown was placed about 12 months after extraction. After 12 years, favorable osseous and gingival architectures were visible with adequate bone height and thickness at the buccal cortical plate, and no gingival recession was seen around the implant-supported crown. Although modern dentistry has been shifting toward simplified, clinical procedures and shorter treatment times, both general dentists and orthodontists should be aware of the possible long-term esthetic advantages of orthodontic extrusion of hopelessly fractured teeth for highly esthetically demanding areas and should educate and motivate patients regarding the choice of this treatment solution, if necessary.

Background So far, a few studies have tried to investigate the relationship between the placement of fixed orthodontic appliances and the change of nonmicrobial salivary properties, mostly with conflicting outcomes and short-term assessment (up to 6 months from bracket placement). The purpose of this study was to evaluate the salivary flow rate, pH and buffer capacity prior to the beginning of therapy and after 1 year from bracket placement using a simple and commercially available chairside saliva check kit. Methods The study population consisted of 20 healthy patients (mean age, 16.5 ± 4 years) scheduled for fixed orthodontic treatment. Salivary samples were taken just before bracket bonding (T0; baseline assessment) and after 1 year of treatment (T1; half-treatment assessment) using the GC Saliva-Check Kit (GC Corp., Leuven, Belgium). Results No statistically significant difference was detected between T0 and T1 for the salivary parameters examined in the present study. Conclusions Under the conditions of this study, the placement of fixed orthodontic appliances did not change the salivary pH, buffer capacity and flow rate after 1 year of treatment if compared with the baseline assessment.

This clinical report presents a case treated by a currently available customized orthodontic treatment system. The use of patient-specific brackets, indirect bonding transfer devices, and customized archwires decreases treatment and chairside time, making orthodontic cases more predictable, accurate, and efficient. The need for time-consuming adjustments is greatly reduced, and appliance customization further facilitates the achievement of the final desired occlusion from the first day of treatment.

Introduction Few studies have investigated developmental norms for maxillary permanent canine eruption. In this observational cross-sectional study, we aimed to provide an age-related description of the percentiles relative to canine inclination in a large sample of nonorthodontic patients. Associations between inclination and sector were also analyzed. Methods Canine inclination and sector location were measured on 1020 panoramic radiographs obtained from subjects of white ancestry aged between 8 and 11 years not seeking orthodontic treatment. The total sample comprised 2037 canines. Results Canine inclination increases between 8 and 9 years and decreases between 9 and 11 years. The greatest value for each percentile is at 9 years. A linear model should be hypothesized for differences in canine inclination between 2 successive ages in correspondence to each percentile. The proportion of sector 2 canines decreases and that of sector 1 increases with age. In the same age group, the inclination generally decreases as the sector decreases. Conclusions Percentiles by age show the average canine inclination in a certain population. Further studies are required to verify whether percentiles can be a diagnostic aid for determining normal canine inclination at a given age and for quantifying the risk of canine impaction or adjacent root resorption.

Objective(s): Herpes simplex virus (HSV) infections in immunocompromised individuals may require prolonged antiviral therapy resulting in the emergence of viral strains resistant to the currently employed antiviral drugs. Distamycin A (DA), a basic antibiotic belonging to the lexitropsin DNA minor groove binding drugs, exhibits antiviral properties. In this study we evaluated the in vitro cytotoxicity and antiviral activity of DA against HSV type 1 and HSV type 2 clinical isolates from transplanted patients and compared them with those of acyclovir (ACV) in search of alternative antiviral drugs. Methods: Viral detection and typing was performed by multiplex PCR and immunofluorescence assay; the in vitro cytotoxicity of DA and the antiviral activity of ACV and DA was evaluated respectively by neutral red uptake assay and plaque reduction assay for HSV2 isolates and fluorescence reduction assay for HSV1 isolates. Results: Tissue culture 50% cytotoxic concentration of DA was 58 µM. Tissue culture 50% inhibitory concentration values ranged from 0.16 to 7.4 µM for the ACV-sensitive and from 5.4 to 32 µM for the ACV-resistant viral strains. Conclusions: In spite of the lower activity against ACV-resistant strains, DA may be used as an antiherpetic drug.

Objectives: To determine the prevalence of incidental maxillary sinus findings in a large sample of orthodontic patients by cone-beam computed tomography (CBCT) with a wide field of view and assess the relationships of such abnormalities with age and gender. Methods: Five hundred thirteen CBCT scans obtained for orthodontic diagnosis and treatment planning in a Northern Italian population (N = 513; 292 female and 221 male subjects; 1,026 maxillary sinuses) were studied. The frequencies of pseudocysts and mucosal thickening of the maxillary sinus were recorded. Logistic regression analysis was used to determine the influence of age and gender on these abnormalities. Results: Pseudocysts were detected in 52 patients (10.1%) and 59 sinuses (5.75%). Mucosal thickening was observed in 206 patients (40.1%) and 258 sinuses (25.1%). Gender and age were significantly associated with pseudocysts ( p = 0.027) and mucosal thickening (p < 0.001), respectively. Conclusions: Half of the orthodontic patients had incidental maxillary sinus findings. Men were more likely to show pseudocysts, and older patients (aged 41 - 60 years) were more likely to show mucosal thickening. [Korean J Orthod 2012;42(6):329-334]