Relationship between interleukin 1 (IL-1) genetic polymorphism and periimplantitis: systematic literature review and meta-analysis.

OBJECTIVE: Periimplantitis (PI) is a complex multifactorial chronic disease caused by interactions between bacteria, host immune-inflammatory responses, and genetic or environmental factors that modify buccal eutrophism. In daily clinical practice, an increase in the prevalence of PI (8%) determined the need to establish the PI causes and set optimal therapeutic strategies. The interleukin family (IL-1), a group of cytokines, triggers and perpetuates peri-implantitis. Therefore, they could be used as biomarkers for diagnosis and treatment. This systematic review aimed to analyze the correlation between IL-1 allelic polymorphism (IL-1A -889, IL-1ß -511, IL-1ß +3954) and the PI disease. MATERIALS AND METHODS: Selected databases were PubMed, Scopus, and Cochrane Library. The search strategy included the following terms: "dental implants"; "periimplantitis"; "interleukin-IL-1"; "polymorphism"; "perimplant bone loss". Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. A meta-analysis was conducted on five of 40 review articles. p-values, confidence intervals (CI), and Odds ratios (OR) were assessed. In 4 articles, the p-value was lower than 0.05, confirming the statistical significance of the result. RESULTS: The prevalence of the selected studies reported the existence of a causal association between polymorphisms of IL-1 and the onset of peri-implantitis, especially for IL-1 allelic variants associated with further polymorphic genes encoding for IL-6, tumor necrosis factor-alpha (TNF-α), matrix metalloproteinases (MMP)-8, IL-1Na, IL-8, IL-18, osteopontin (OPN). In addition, the presence of the IL-1 polymorphism and PI is particularly higher in smokers, diabetes, and autoimmune disease patients. CONCLUSIONS: The detection of salivary biomarkers is, therefore, a diagnostic tool with a high potential to intercept the PI early and act with appropriate and non-invasive treatment. Due to the continued technological innovation in biomarkers and diagnostic sciences, further studies are needed to investigate the role of these biochemical mediators. The results of studies and the recent technological innovation in biomarkers and diagnostic sciences will allow further research to investigate the role of these biochemical mediators.

Induction of FoxP3 Pre-mRNA Alternative Splicing to Enhance the Suppressive Activity of Regulatory T Cells from Amyotrophic Lateral Sclerosis Patients.

Forkhead box protein 3 (FoxP3) is a key transcription factor responsible for the development, maturation, and function of regulatory T cells (Tregs). The FoxP3 pre-mRNA is subject to alternative splicing, resulting in the translation of multiple splice variants. We have shown that Tregs from patients with amyotrophic lateral sclerosis (ALS) have reduced expression of full-length (FL) FoxP3, while other truncated splice variants are expressed predominantly. A correlation was observed between the reduced number of Tregs in the peripheral blood of ALS patients, reduced total FoxP3 mRNA, and reduced mRNA of its FL splice variant. Induction of FL FoxP3 was achieved using splice-switching oligonucleotides capable of base pairing with FoxP3 pre-mRNA and selectively modulating the inclusion of exons 2 and 7 in the mature mRNA. Selective expression of FL FoxP3 resulted in the induction of CD127low, CD152, and Helios-positive cells, while the cell markers CD4 and CD25 were not altered. Such Tregs had an increased proliferative activity and a higher frequency of cell divisions per day. The increased suppressive activity of Tregs with the induced FL FoxP3 splice variant was associated with the increased synthesis of the pro-apoptotic granzymes A and B, and perforin, IL-10, and IL-35, which are responsible for contact-independent suppression, and with the increased ability to suppress telomerase in target cells. The upregulation of Treg suppressive and proliferative activity using splice-switching oligonucleotides to induce the predominant expression of the FoxP3 FL variant is a promising approach for regenerative cell therapy in Treg-associated diseases.

The Role of Regulatory T Cells in the Onset and Progression of Primary Sjögren's Syndrome.

Regulatory T cells (Tregs) play a key role in maintaining immune balance and regulating the loss of self-tolerance mechanisms in various autoimmune diseases, including primary Sjögren's syndrome (pSS). With the development of pSS primarily in the exocrine glands, lymphocytic infiltration occurs in the early stages, mainly due to activated CD4+ T cells. Subsequently, in the absence of rational therapy, patients develop ectopic lymphoid structures and lymphomas. While the suppression of autoactivated CD4+ T cells is involved in the pathological process, the main role belongs to Tregs, making them a target for research and possible regenerative therapy. However, the available information about their role in the onset and progression of this disease seems unsystematized and, in certain aspects, controversial. In our review, we aimed to organize the data on the role of Tregs in the pathogenesis of pSS, as well as to discuss possible strategies of cell therapy for this disease. This review provides information on the differentiation, activation, and suppressive functions of Tregs and the role of the FoxP3 protein in these processes. It also highlights data on various subpopulations of Tregs in pSS, their proportion in the peripheral blood and minor salivary glands of patients as well as their role in the development of ectopic lymphoid structures. Our data emphasize the need for further research on Tregs and highlight their potential use as a cell-based therapy.

Advantages and Potential Benefits of Using Organoids in Nanotoxicology.

Organoids are microtissues that recapitulate the complex structural organization and functions of tissues and organs. Nanoparticles have several specific properties that must be considered when replacing animal models with in vitro studies, such as the formation of a protein corona, accumulation, ability to overcome tissue barriers, and different severities of toxic effects in different cell types. An increase in the number of articles on toxicology research using organoid models is related to an increase in publications on organoids in general but is not related to toxicology-based publications. We demonstrate how the quantitative assessment of toxic changes in the structure of organoids and the state of their cell collections provide more valuable results for toxicological research and provide examples of research methods. The impact of the tested materials on organoids and their differences are also discussed. In conclusion, we highlight the main challenges, the solution of which will allow researchers to approach the replacement of in vivo research with in vitro research: biobanking and standardization of the structural characterization of organoids, and the development of effective screening imaging techniques for 3D organoid cell organization.

Modulation of Suppressive Activity and Proliferation of Human Regulatory T Cells by Splice-Switching Oligonucleotides Targeting FoxP3 Pre-mRNA.

The maturation, development, and function of regulatory T cells (Tregs) are under the control of the crucial transcription factor Forkhead Box Protein 3 (FoxP3). Through alternative splicing, the human FoxP3 gene produces four different splice variants: a full-length variant (FL) and truncated variants with deletions of each of exons 2 (∆2 variant) or 7 (∆7 variant) or a deletion of both exons (∆2∆7 variant). Their involvement in the biology of Tregs as well as their association with autoimmune diseases remains to be clarified. The aim of this work was to induce a single FoxP3 splice variant in human Tregs by splice switching oligonucleotides and to monitor their phenotype and proliferative and suppressive activity. We demonstrated that Tregs from peripheral blood from patients with multiple sclerosis preferentially expressed truncated splice variants, while the FL variant was the major variant in healthy donors. Tregs with induced expression of truncated FoxP3 splice variants demonstrated lower suppressive activity than those expressing FL variants. Reduced suppression was associated with the decreased expression of Treg-associated suppressive surface molecules and the production of cytokines. The deletion of exons 2 and/or 7 also reduced the cell proliferation rate. The results of this study show an association between FoxP3 splice variants and Treg function and proliferation. The modulation of Treg suppressive activity by the induction of the FoxP3 FL variant can become a promising strategy for regenerative immunotherapy.

Maxillary sinusitis caused by retained dental impression material: An unusual case report and literature review.

Surgical procedures in posterior area of maxillary might cause an oroantral communication and iatrogenic sinusitis. An undetected oroantral communication can cause the penetration of foreign bodies, such as dental impression materials, in the maxillary sinus, thereby contributing to persistent sinusitis. Given the occurrence of a very rare clinical and medicolegal case of persistent and drug-resistant sinusitis due to radiologically undetected fragments of silicone paste for dental impression in the maxillary antrum, a literature review was pursued through sensitive keywords in relevant databases for health sciences. All retrieved articles were considered and data about the kind of impression materials thrusted into the maxillary sinus, the diagnostic issues, the reported range of symptoms, and the occurrence of medicolegal issues were analyzed. The diagnosis resulted to be quite challenging and belatedly especially in case of healed oroantral communication and when the material retained in the maxillary sinus has similar radiodensity compared to the surrounding normal or inflammatory tissues. The case was then discussed in comparison with the reviewed literature for both clinical and medicolegal issues. Hints were provided to professionals to face the challenging diagnosis in similar rare cases and to avoid the possible related litigation.

Cytoprotective Activity of Polyamines Is Associated with the Alternative Splicing of RAD51A Pre-mRNA in Normal Human CD4+ T Lymphocytes.

Physiological polyamines are ubiquitous polycations with pleiotropic biochemical activities, including regulation of gene expression and cell proliferation as well as modulation of cell signaling. They can also decrease DNA damage and promote cell survival. In the present study, we demonstrated that polyamines have cytoprotective effects on normal human CD4+ T lymphocytes but not on cancer Jurkat or K562 cells. Pretreatment of lymphocytes with polyamines resulted in a significant reduction in cells with DNA damage induced by doxorubicin, cisplatin, or irinotecan, leading to an increase in cell survival and viability. The induction of RAD51A expression was in response to DNA damage in both cancer and normal cells. However, in normal cells, putrescin pretreatment resulted in alternative splicing of RAD51A and the switch of the predominant expression from the splice variant with the deletion of exon 4 to the full-length variant. Induction of RAD51A alternative splicing by splice-switching oligonucleotides resulted in a decrease in DNA damage and cell protection against cisplatin-induced apoptosis. The results of this study suggest that the cytoprotective activity of polyamines is associated with the alternative splicing of RAD51A pre-mRNA in normal human CD4+ T lymphocytes. The difference in the sensitivity of normal and cancer cells to polyamines may become the basis for the use of these compounds to protect normal lymphocytes during lymphoblastic chemotherapy.

Nanosafety vs. nanotoxicology: adequate animal models for testing in vivo toxicity of nanoparticles.

Nanotoxicological studies using existing models of normal cells and animals often encounter a paradox: retention of nanoparticles in intracellular compartments for a long time is not accompanied by any significant toxicological effects. Can we expect that the revealed changes will be not harmful after translation to practice, outside of a sterile laboratory and ideally healthy organisms? Age-associated and pathological processes can affect target organs, metabolism, and detoxification in the mononuclear phagocyte system organs and change biodistribution routes, thus making the use of nanomaterial not safe. The potential solution to this issue can be testing the toxic properties of nanoparticles in animal models with chronic diseases. However, current studies of nanotoxicity in animal models with a brain, cardiovascular system, liver, digestive tract, reproductive system, and skin diseases are unsystematic. Even though these studies demonstrate the emergence of new toxic effects that are not present in healthy animals. In this regard, we set the goal of this review as the formulation of the requirements for an animal model capable of assessing the potential toxicity of nanoparticles based on the nanosafety approach.

Comparative surface detail reproduction for elastomeric impression materials: Study on reproducibility performance.

For dental impression of a prepared tooth, the goal is a void-free negative representation from which an accurate cast of a tooth and its surrounding tissue can be reproduced. This in-vitro study assessed and compared the reproduction accuracies of surface detail obtained with three different dental elastomeric impression materials: vinyl polysiloxane (VPS), vinyl polyether silicone (VPES), and polyether (PE). A stainless-steel model with two abutments was used, with impressions taken 10 times for each material, for 20 abutment impressions per group, using a two-phase, one-step technique (heavy body/light body). The impressions were removed and assessed for numbers of enclosed voids and open voids visible on the surface. The defect frequency was 95% for impressions with the VPS and VPES materials, and 30% for the PE material. No significant differences were seen for number of impressions with defects for VPS versus VPES. Significant differences were seen for VPS and VPES versus the PE material (P <.05). No significant differences were seen for the defect type distributions across these three impression materials. The PE impression material showed better accuracy for reproduction of surface detail of these dental impressions compared to the VPS and VPES impression materials.

Organ-specific toxicity of magnetic iron oxide-based nanoparticles.

The unique properties of magnetic iron oxide nanoparticles determined their widespread use in medical applications, the food industry, textile industry, which in turn led to environmental pollution. These factors determine the long-term nature of the effect of iron oxide nanoparticles on the body. However, studies in the field of chronic nanotoxicology of magnetic iron particles are insufficient and scattered. Studies show that toxicity may be increased depending on oral and inhalation routes of administration rather than injection. The sensory nerve pathway can produce a number of specific effects not seen with other routes of administration. Organ systems showing potential toxic effects when injected with iron oxide nanoparticles include the nervous system, heart and lungs, the thyroid gland, and organs of the mononuclear phagocytic system (MPS). A special place is occupied by the reproductive system and the effect of nanoparticles on the health of the first and second generations of individuals exposed to the toxic effects of iron oxide nanoparticles. This knowledge should be taken into account for subsequent studies of the toxicity of iron oxide nanoparticles. Particular attention should be paid to tests conducted on animals with pathologies representing human chronic socially significant diseases. This part of preclinical studies is almost in its infancy but of great importance for further medical translation on nanomaterials to practice.

Experimental proof of emergent subharmonic attenuation zones in a nonlinear locally resonant metamaterial.

High-performance locally resonant metamaterials represent the next frontier in materials technology due to their extraordinary properties obtained through materials design, enabling a variety of potential applications. The most exceptional feature of locally resonant metamaterials is the subwavelength size of their unit cells, which allows to overcome the limits in wave focusing, imaging and sound/vibration isolation. To respond to the fast evolution of these artificial materials and the increasing need for advanced and exceptional properties, the emergence of a new mechanism for wave mitigation and control consisting in a nonlinear interaction between propagating and evanescent waves has recently been theoretically demonstrated. Here, we present the experimental proof of this phenomenon: the appearance of a subharmonic transmission attenuation zone due to energy exchange induced by autoparametric resonance. These results pave the path to a new generation of nonlinear locally resonant metamaterials.

Perceptive and subjective evaluation of speech disorders in Parkinson's disease.

Parkinson's disease (PD), which is not only a motor disease, is one of the most frequent neurodegenerative diseases and affects 1.5-2% of people worldwide. The role of its non motor-symptoms is of first importance on quality of life. Speech impairment is considered a part of motor impairment and is widespread in PD where most frequent speech impairment is Hypokinetic dysarthria, a disorder characterized by reduced articulation movements and phonetic monotony. Many PD patients show difficulty in accessing the lexicon related to cognitive impairment. Clinical evaluation of speech disorders in PD includes the clinical history, verbal and non-verbal assessment of the voice, evaluation of the calibre of the language. It is also important to self-assess speech disturbances because PD patients often do not realize their own deficits. Self-assessment tests comprise subjective assessment of communicative disorder in different social situations, description of adopted strategies, perception of the reactions of interlocutors. The comparison between perceptive and subjective examination of speech disorders in PD patients are described in order to evaluate the presence of these deficits and their impact on quality of life in order to initiate early treatment with specific speech therapy.

A 10-year retrospective comparative human study on screw-retained versus cemented dental implant abutments.

The aim of this 10-year retrospective study was to evaluate the long-term reliability, survival rate and mechanical and biological complications of single-crown implant rehabilitations with two different types of fixture-abutment connections: screw-retained abutments (SRAs) with internal hexagonal connection, and cemented retained abutments (CRAs). A total of 300 single implant-supported crowns were analysed, which had been inserted between 2004 and 2007. Patients were classified according to two groups: the SRA group (n = 150) and the CRA group (n = 150). The primary outcome was marginal bone loss (MBL) on peri-apical radiographs. Bleeding on probing (BOP) and probing depth (PD) were also evaluated. Moreover, prosthetic complications were recorded. Analysis of variance (ANOVA) was used to evaluate the differences between the groups. The overall implant failure rate was 4.2%. The overall positive BOP index was 81.9% of the sites under investigation, as 83.4% for SRA and 80.4% for CRA. Moreover, >5 mm PD demonstrated a rate of 21.0% for CRA, and 13.8% for SRA. The primary outcome of mean MBL was 2.09±1.07 mm for SRA and 1.54±1.20 mm for CRA. Analysis of variance of MBL showed statistical significance for the difference between these two groups (P less than 0.001). For the mechanical aspects, an overall 12.5% of complications occurred. No implant or abutment fractures were recorded. Although complications occurred, the results from this 10-year retrospective study show that these two methods have positive long-term follow-up. With MBL significantly greater for the SRA group than the CRA group, the clinical use of CRA is encouraged in terms of the lower bone resorption rate.

Rare and life-threatening complication after an attempted lower third molar extraction: Lemierre syndrome.

Lemierre's syndrome is also known as the forgotten disease, and is a rare but life-threatening complication that can arise after surgical extractions of infected mandibular third molars. Owing to its rarity, oral and maxillofacial surgeons might not immediately recognise or can underestimate the pathological signs, and consequently do not apply the appropriate therapy to treat the syndrome. Here, we report on the occurrence and management of a case of Lemierre's syndrome, where the complications affected the right sigmoid sinus. Since the condition appear to be underreported and not properly highlighted, eventual systematic review and meta-analysis of the occurrence of the Lemierre's syndrome are highly recommended.

Stimulated mast cells release inflammatory cytokines: potential suppression and therapeutical aspects.

Mast cells (MCs) are derived from bone marrow precursors and are immune cells involved in acute and chronic inflammation. MCs are ubiquitous and play a crucial role in innate and acquired immunity. They are activated through cross-linking of their surface high affinity receptors (FcεRI), leading to immediate secretion of stored inflammatory mediators, and late production and release of pro-inflammatory cytokines/chemokines without degranulation. Therefore, MCs are important in inflammatory responses. Members of the interleukin (IL)-1 cytokine family, such as IL-1 and IL-33, and various antigens markedly increase IL-1 and tumor necrosis factor (TNF) expression and secretion from MCs. One of the latest cytokines is IL-33, an IL-1 family member acting via its ST2/IL-1R4, which has been shown to regulate MCs. IL-1 and IL-33 are cytokines found to be implicated in many inflammatory disorders including rheumatoid arthritis, atherosclerosis and psoriasis. In general, IL-1 family member cytokines play a pro-inflammatory role and increase the pathological state. IL-37 is a member of the IL-1 family with anti-inflammatory activity through inhibition of pro-inflammatory cytokines. IL-37 particularly suppresses IL-1-mediated innate inflammatory response, but also acts on the acquired immune response. IL-37 is activated by pro-inflammatory agents and cytokines, playing a protective role against inflammation. This cytokine is a natural regulator of immunity and is a therapeutic promise against inflammatory diseases. Since IL-1 is produced by and activates MCs to release IL-33 and TNF, here we hypothesize that MCs can be inhibited by IL-37 and therefore reduce their pro-inflammatory activity. However, the maturation, transport and secretion of IL-37 remain to be clarified.

Anti-inflammatory steroid use in impacted third molar surgery: a systematic review.

Oral surgery procedures involve traumatization of mucosal and bony tissues, and lengthy interventions can lead to inflammatory post-operative sequelae. In the bony tissues in particular, the inflammatory processes can affect healing. Modern drug therapies provide valid support for lowering the risk of occurrence of post-operative inflammatory signs. The two main types of agents used are nonsteroidal anti-inflammatory drugs and/or corticosteroids, which act on two different molecular pathways in the inflammatiory process. The aim of this systematic review is to examine the different corticosteroids used in oral surgery procedures, their indications for use, and their route of administration, to provide the clinician with a useful scheme for correct pharmacological management of post-operative inflammation. To identify studies eligible for inclusion in this systematic review, we performed a literature search up to April 2017 of the electronic databases, considering published papers from 2007 to 2017. The search terms included steroids, third molar, oral surgery, RCT [randomized controlled trial], human, and clinical trial. Only articles in English language were considered.

Newborn screening of inherited metabolic disorders: the Italian situation.

Starting from an international overview of the current status of screening programs, the present paper focuses on the legal situation in Italy and the great differences among Italian regions. Since the introduction of tandem mass spectrometry (MS/MS) in the ‘90s the paradigm “one spot-one disease” changed. Only recently, some regions issued legislative acts to promote expanded newborn screening with MS/MS. This approach raises medico-legal and ethical issues because a fast neonatal diagnosis of an inborn error of metabolism (IEM) could increase chances of an early treatment and reduce disabilities, therefore citizens ought to have the same access to care countrywide. Enacting a mandatory standard for a disease screening panel using MS/MS and a few centers specialized in diagnosis, treatment and follow-up of patients affected by IEM (inborn errors of metabolism) can reduce legal and ethical issues.

Mandibular third molar displaced in the sublingual space: clinical management and medicolegal considerations.

This paper describes the management of a failed mandibular third molar extraction, resulting in tooth displacement in the sublingual space, the discussion of the diagnosis, surgery and medico-legal considerations. A 28-year-old male patient underwent an unsuccessful attempt of the 4.8 tooth extraction. The clinician lost visual contact after luxation and the patient was not recalled for post-operative follow-up. After 24 hours, a severe trismus started. Ortopantomography and cone beam computer tomography revealed the displacement in the sublingual space. The tooth was removed under general anaesthesia with intraoral approach. The follow-up was uneventful and the paraesthetic area on the tongue did not enlarge after the retrieval. The displaced mandibular third molar is a rare but potentially serious complication of extraction. This event should be avoided with correct diagnosis and surgical technique. Cone beam computed tomography was useful to determine the three-dimensional position of the displaced tooth.

Is vitamin E an anti-allergic compound?

Vitamin E is found in eight forms in nature which include four tocopherols (alpha, beta, gamma and delta) and four tocotrianols (alpha, beta, gamma and delta). The classic effect of vitamin E is to reduce and prevent oxygen damage to the tissue and is useful for the treatment of pain, inflammation and allergic reactions. In addition to antioxidant activity, vitamin E also has a number of different and related functions. It protects against cancer, improves immune response, lowers the incidence of infectious diseases, cardiovascular diseases and is protective in allergy and asthma risk, and other disorders. Vitamin E increases n-6 polyunsaturated fatty acid (PUFA) and decreases n-3 PUFA, an effect that diminishes asthma and allergic diseases. Moreover, vitamin E regulates vascular cell adhesion molecule-1 (VCAM-1)-dependent leukocyte migration through its oxidant and non-antioxidant effect. Furthermore, vitamin E modulates the endothelial function by altering VCAM-1-induced oxidative activation of endothelial cell PKCα. However, vitamin E is not consistently associated with asthma and/or allergy, and in some cases there are conflicting results on allergy and inflammatory diseases. The association of vitamin E and allergy appears to be very complex, and further study needs to clarify this dilemma.