Impact of TNF and IL-33 Cytokines on Mast Cells in Neuroinflammation.

Mast cells (MCs) are derived from hematopoietic progenitors, mature in vascularized tissues, and participate in innate and acquired immunity. Neuroinflammation is a highly debated topic in the biomedical literature; however, the impact of tumor necrosis factor (TNF) and IL-33 on MCs in the brain has not been widely addressed. MCs can be activated by IgE binding to FcεRI, as well as by different antigens. After activation, MCs mediate various immunological and inflammatory responses through TNF and IL-33. TNF has two receptors: TNFR1, a p55 molecule, and TNFR2, a p75 molecule. This cytokine is the only one of its kind to be stored in the granules of MCs and can also be generated by de novo synthesis via mRNA. In the central nervous system (CNS), TNF is produced almost exclusively by microglial cells, neurons, astrocytes, and, minimally, by endothelial cells. After its release into brain tissue, TNF rapidly induces the adhesion molecules endothelial leukocyte adhesion molecule 1 (ELAM-1), intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) in endothelial cells. TNF causes the chemoattraction of neutrophils by inducing several molecules, including CXC chemokines (IL-8). Both MCs and microglial cells act as a primary barrier against foreign molecules in the CNS, producing pro-inflammatory cytokines such as IL-33. IL-33 belongs to the IL-1 family, is activated through the ST2L/IL1-RAcP receptor complex, and mediates both the innate and adaptive immune response. IL-33 is a nuclear transcription factor expressed in the brain, where it induces pro-inflammatory cytokines (TNF and IL-1) and chemokines (CCL2, CCL3, CCL5, and CXCL10). Therefore, MCs and microglia in the CNS are a source of pro-inflammatory cytokines, including TNF and IL-33, that mediate many brain diseases. The inhibition of TNF and IL-33 may represent a new therapeutic approach that could complement existing neuroinflammatory therapies.

Activation of Mast Cells by Neuropeptides: The Role of Pro-Inflammatory and Anti-Inflammatory Cytokines.

Mast cells (MCs) are tissue cells that are derived from bone marrow stem cells that contribute to allergic reactions, inflammatory diseases, innate and adaptive immunity, autoimmunity, and mental disorders. MCs located near the meninges communicate with microglia through the production of mediators such as histamine and tryptase, but also through the secretion of IL-1, IL-6 and TNF, which can create pathological effects in the brain. Preformed chemical mediators of inflammation and tumor necrosis factor (TNF) are rapidly released from the granules of MCs, the only immune cells capable of storing the cytokine TNF, although it can also be produced later through mRNA. The role of MCs in nervous system diseases has been extensively studied and reported in the scientific literature; it is of great clinical interest. However, many of the published articles concern studies on animals (mainly rats or mice) and not on humans. MCs are known to interact with neuropeptides that mediate endothelial cell activation, resulting in central nervous system (CNS) inflammatory disorders. In the brain, MCs interact with neurons causing neuronal excitation with the production of neuropeptides and the release of inflammatory mediators such as cytokines and chemokines. This article explores the current understanding of MC activation by neuropeptide substance P (SP), corticotropin-releasing hormone (CRH), and neurotensin, and the role of pro-inflammatory cytokines, suggesting a therapeutic effect of the anti-inflammatory cytokines IL-37 and IL-38.

Short-term variation in the subgingival microbiota in two groups of patients treated with clear aligners and vestibular fixed appliances: A longitudinal study.

OBJECTIVE: To evaluate the subgingival microbiological changes during the first six months of therapy with clear aligners (CAs) and fixed appliances (FAs). The null hypothesis was that there would be no microbiological differences between the two. SETTING/SAMPLE: Two groups of patients to be treated, respectively, with CAs (14 patients; 9 females and 5 males; mean age 21 years ± 0.25) and FAs (13 patients; 8 females and 5 males; mean 14 years ± 0.75) were consecutively recruited. MATERIALS AND METHODS: Subgingival microbiological samples were obtained at the right upper central incisor and right first molar at four different time points: before appliance fitting (T0), and at 1 month (T1), 3 months (T3) and 6 months (T6) thereafter. Total bacterial load (TBL) and counts of the bacteria Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Fusobacterium nucleatum, Campylobacter rectus, Treponema denticola and Tannerella forsythia were determined using real-time PCR. RESULTS: Total bacterial load did not vary in the CA group, while a significant increase was detected after 3 and 6 months of treatment in the FA group. Unlike red complex species, C rectus and F nucleatum were often detected: levels remained stable in the CA group but increased progressively in the FA group. CONCLUSION: The type of orthodontic appliance influences the subgingival microbiota. TBL increased in the FA group but not in the CA group, although the levels of the individual periodontal pathogenic bacteria species did not significantly increase during the observation period.

Mast Cells Mediate Rheumatoid Arthritis-Inhibitory Role of IL-37.

Rheumatoid arthritis (RA) is an autoimmune, chronic inflammatory, disabling arthropathy that severely affects the quality of life. This disease involves several proinflammatory cytokines, including interleukin (IL)-1ß and tumor necrosis factor (TNF). IL-1 induces TNF and vice versa, causing joint damage and cartilage degradation. Current antirheumatic drugs may be effective, but they possess many unwanted side effects. In recent years, inhibitors of proinflammatory cytokines have increasingly entered mainstream clinical practice. Recent evidence indicates that IL-37, which has anti-inflammatory properties, is increased in the serum and is released from white blood cells in patients with RA. Mast cells (MCs), stimulated by the neuropeptide substance P (SP) and IL-33, release IL-1ß and TNF. Recent evidence indicates that large amounts of IL-1ß and TNF can be released from human MCs, which also secrete CXCL8, which promotes migration of immune cells, causing erosion of the bone and cartilage. Treatment with IL-37 can block the MC stimulation and release of inflammatory compounds, attenuating the severity of the disease and/or altering its progression.

ROCK1 is associated with non-syndromic cleft palate.

BACKGROUND: Craniofacial morphogenesis is the result of an intricate multistep network of tightly controlled spatial and temporal signalling that involves several molecules and transcription factors organized into highly coordinated pathways. Any alteration in even one step of this delicate process can lead to congenital malformations such as cleft palate. One of the first steps in embryonal orofacial development is the migration of cells from the neural crests to the branchial arches. Next, the cells have to proliferate, differentiate, move and connect to each other in order to correctly form the palate. Cell contraction, promoted by the interaction of non-muscle myosin II and actin A, is a crucial step in morphogenesis and is regulated by ROCK1 protein. METHODS: A family-based association study was carried out in order to verify whether or not genetic variants of ROCK1 were associated with non-syndromic cleft palate (nsCP). Two cohorts from Italy and Iran, a total of 189 nsCP cases and their parents were enrolled. RESULTS: The rs35996865-G allele was under-transmitted in cases of nsCP [P = .006, odds ratio (OR) = 0.63 (95% CI 0.45-0.88)]. CONCLUSION: This investigation reveals for the first time data supporting a role for ROCK1 in nsCP aetiology.

Short-term comparison of two non-surgical treatment modalities of peri-implantitis: Clinical and microbiological outcomes in a two-factorial randomized controlled trial.

AIM: To compare the efficacy of two different therapies (amino acid glycine abrasive powder and a desiccant material) and their combination in the non-surgical treatment of peri-implantitis. MATERIALS AND METHODS: This was an examiner-blind randomized clinical trial, with 2-factorial design with a follow-up of 6 months. The combination of the two factors resulted in four interventions: (a) non-surgical debridement alone (C); (b) non-surgical debridement and a desiccant material (H); (c) non-surgical debridement and glycine powder (G); and (d) non-surgical debridement, desiccant material and glycine powder (HG). RESULTS: Sixty-four patients with peri-implantitis were randomized, 16 for each intervention. After six months, two implants failed in the G intervention. Mean pocket depth reduction was higher in patients treated with the desiccant material (estimated difference: 0.5 mm; 95% CI from 0.1 to 0.9 mm, p = .0229) while there was no difference in the patients treated with glycine powder (estimated difference: 0.1 mm; 95% CI from -0.3 to 0.5 mm, p = .7333). VAS for pain during intervention and VAS for pain after one week were higher for patients treated with glycine powder (p = .0056 and p = .0339, respectively). The success criteria and other variables did not reveal differences between interventions. CONCLUSIONS: In this 6-month follow-up study, pocket reduction was more pronounced in patients using the desiccant material. Pain was higher in patients using glycine. All the interventions resulted in low success rate.

Eradication of Benign Skin Lesions of the Face by Voltaic Arc Dermabrasion (Atmospheric Plasma): Postoperative Pain Assessment by Thermal Infrared Imaging.

OBJECTIVES: The face aging processes are associated with physiologic and biochemical alteration that produces wrinkles, skin pigmentation and benign growths. The aim of this study was to evaluate the clinical efficacy of voltaic arc dermabrasion with plasma to remove benign facial skin lesions. STUDY DESIGN: Voltaic arc dermabrasion plasma technique was used to remove the facial benign skin lesions. The study involved 45 patients (26 females;19 males) treated for benign facial skin lesions with voltaic arc dermabrasion also called plasma exeresis technique. The subjects age ranged between 43 and 65 years. The clinical observations and comparison of pretreatment and post-treatment photographs of the treated regions were performed by a joint examiner at each follow-up visit. RESULTS: During plasma irradiation, the average temperature of the skin was 290.3 ± 21.7 °C, while immediately after it was 90.6 ± 21.8 °C. Overall clinical improvement was 100% in six lesions with complete resolution of all lesions. Three patients observed a transient post-inflammatory pigmentation with a peak at 1 month after VAD treatment, gradually fading spontaneously over 2 to 3 months. CONCLUSIONS: The voltaic arc dermabrasion technique (atmospheric plasma) should be considered for lesions, especially relatively superficial ones, and small lesions that are located on the face. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Role of Cyclosporine in Gingival Hyperplasia: An In Vitro Study on Gingival Fibroblasts.

BACKGROUND: Gingival hyperplasia could occur after the administration of cyclosporine A. Up to 90% of the patients submitted to immunosuppressant drugs have been reported to suffer from this side effect. The role of fibroblasts in gingival hyperplasia has been widely discussed by literature, showing contrasting results. In order to demonstrate the effect of cyclosporine A on the extracellular matrix component of fibroblasts, we investigated the gene expression profile of human fibroblasts after cyclosporine A administration. MATERIALS AND METHODS: Primary gingival fibroblasts were stimulated with 1000 ng/mL cyclosporine A solution for 16 h. Gene expression levels of 57 genes belonging to the "Extracellular Matrix and Adhesion Molecules" pathway were analyzed using real-time PCR in treated cells, compared to untreated cells used as control. RESULTS: Expression levels of different genes were significantly de-regulated. The gene CDH1, which codes for the cell adhesion protein E-cadherin, showed up-regulation. Almost all the extracellular matrix metalloproteases showed down-regulation (MMP8, MMP11, MMP15, MMP16, MMP24, MMP26). The administration of cyclosporine A was followed by down-regulation of other genes: COL7A1, the transmembrane receptors ITGB2 and ITGB4, and the basement membrane constituents LAMA2 and LAMB1. CONCLUSION: Data collected demonstrate that cyclosporine inhibits the secretion of matrix proteases, contributing to the accumulation of extracellular matrix components in the gingival connective tissue, causing gingival overgrowth. Patients affected by gingival overgrowth caused by cyclosporine A need to be further investigated in order to determine the role of this drug on fibroblasts.

Molecular tools for preventing and improving diagnosis of peri-implant diseases.

Peri-implantitis is an inflammatory disease of tissues surrounding osseointegrated dental implants. Inflammation affecting soft and hard peri-implant tissues can cause alveolar bone resorption and subsequent implant loss. Clinical surveillance and early diagnosis are of paramount importance to reduce clinical failures and improve implant survival. Current diagnosis of implants is based on clinical and radiological signs. Molecular tests are an emerging diagnostic methodology, which potentially can help to detect and prevent early peri-implantitis and monitor the efficacy of therapy as well. A plethora of potential biomarkers are potentially available to support the clinical diagnosis of peri-implantitis. However, conflicting diagnostic conclusions have been reached, probably related to weak statistical results due to limited sample size or disease heterogeneity. The present paper reviews candidate diagnostic biomarkers for peri-implantitis, including infective agents, genetic susceptibility factors, and key proteins related to inflammation and tissue remodeling.

Eradication of hairy mouth after oncological resection of the tongue and floor mouth using a diode laser 808 nm. Postoperative pain assessment using thermal infrared imaging.

OBJECTIVES: Vascularized soft tissue flaps are often harvested from hair-bearing areas, such as the radial forearm or anterolateral thigh, making their use in oral reconstruction problematic due to postoperative hair growth. The presence of intact hair follicles in free tissue transfer and continued hair growth at the recipient site can result in difficulties with oral hygiene, intraoral irritation, food trapping, and patient distress. This study was to evaluate the intraoral efficacy and safety of a diode laser 808 nm when used for hair removal. MATERIALS AND METHODS: Sixteen male patients, between 2010 and 2017, were referred for intraoral hair eradication with a history of squamous cell carcinoma of the tongue or floor mouth resection. An 808 nm diode laser (Stark 808, Plume s.r.l., Rome, Italy) was used to remove the intraoral hair. Each patient received a total of six treatments at 4-week intervals. Perifollicular pain was quantified by the physician using visual analog scales. Follow-up visits were scheduled at 1, 4, and 6 days to check the state of the tissues. The recall program included assessments of VAS, erythema, and perifollicular temperature. Patients were followed up for long-term assessments at 6 and 12 months after the final treatment session. RESULTS: All patients presented well with no occurrence of symptoms, indicating possible perifollicular inflammation. Based on the VAS scores, very mild discomfort during laser irradiation was recorded in all patients, with average pain score of 10.98 ± 1.42. No pain or discomfort was recorded 1, 4, and 6 days after the procedure. After the third pulse of light was applied, the average temperature with standard deviation of the hair tip with both the dark and light skin was 74.4 ± 11.7°C. The difference in temperature before the procedure (basal measurement 37.5 ± 2.8°C) and immediately after laser irradiation was 36.9 ± 3.7°C. The difference in temperature disappeared after 0.29 seconds, and no temperature increase was recorded on days 1, 4, or 6. In all the patients, the hair clearance between baseline and the 6th treatment, the 6-month follow-up, and the 12-month follow-up rated as significant P < 0.05. The mean percentage of hair reduction was 97.3% at 12 months. CONCLUSION: In conclusion, the clinical findings demonstrate the safety and efficacy of the 808 nm diode laser system for intraoral hair removal Lasers Surg. Med. 51:516-521, 2019. © 2019 Wiley Periodicals, Inc.

A New Strategy Against Peri-Implantitis: Antibacterial Internal Coating.

The bacterial biofilm formation in the oral cavity and the microbial activity around the implant tissue represent a potential factor on the interface between bone and implant fixture that could induce an inflammatory phenomenon and generate an increased risk for mucositis and peri-implantitis. The aim of the present clinical trial was to investigate the bacterial quality of a new antibacterial coating of the internal chamber of the implant in vivo at six months. The PIXIT implant (Edierre srl, Genova Italy) is prepared by coating the implant with an alcoholic solution containing polysiloxane oligomers and chlorhexidine gluconate at 1%. A total of 15 healthy patients (60 implants) with non-contributory past medical history (nine women and six men, all non-smokers, mean age of 53 years, ranging from 45-61 years) were scheduled to receive bilateral fixed prostheses or crown restorations supported by an implant fixture. No adverse effects and no implant failure were reported at four months. All experimental sites showed a good soft tissue healing at the experimental point times and no local evidence of inflammation was observed. Real-Time Polymerase Chain Reaction (PCR) analysis on coated and uncoated implants showed a decrease of the bacterial count in the internal part of the implant chamber. The mean of total bacteria loading (TBL) detected in each PCR reaction was lower in treated implants (81038 units/reaction) compared to untreated implants (90057 units/reaction) (p < 0.01). The polymeric chlorhexydine coating of the internal chamber of the implant showed the ability to control the bacterial loading at the level of the peri-implant tissue. Moreover, the investigation demonstrated that the coating is able to influence also the quality of the microbiota, in particular on the species involved in the pathogenesis of peri-implantitis that are involved with a higher risk of long-term failure of the dental implant restoration.

Molecular Aspects of Drug-Induced Gingival Overgrowth: An In Vitro Study on Amlodipine and Gingival Fibroblasts.

Gingival overgrowth is a serious side effect that accompanies the use of amlodipine. Several conflicting theories have been proposed to explain the fibroblast's function in gingival overgrowth. To determine whether amlodipine alters the fibrotic response, we investigated its effects on treated gingival fibroblast gene expression as compared with untreated cells. MATERIALS AND METHODS: Fibroblasts from ATCC® Cell Lines were incubated with amlodipine. The gene expression levels of 12 genes belonging to the "Extracellular Matrix and Adhesion Molecules" pathway was investigated in treated fibroblasts cell culture, as compared with untreated cells, by real time PCR. RESULTS: Most of the significant genes were up-regulated. (CTNND2, COL4A1, ITGA2, ITGA7, MMP10, MMP11, MMP12, MMP26) except for COL7A1, LAMB1, MMP8, and MMP16, which were down-regulated. CONCLUSION: These results seem to demonstrate that amlodipine has an effect on the extracellular matrix of gingival fibroblast. In the future, it would be interesting to understand the possible effect of the drug on fibroblasts of patients with amlodipine-induced gingival hyperplasia.

Salivary flow and xerostomia in patients with type 2 diabetes.

BACKGROUND: Saliva is secreted by the major and minor salivary glands. There are a number of physiological factors that can reduce this secretion such as age, sex, body weight, number of teeth present in the mouth or time of day. This decrease may also be caused by the use of certain drugs, radiotherapy for head and neck cancer, chronic rheumatic diseases such as Sjögren's syndrome and other systemic disorders such as diabetes mellitus (DM). Objective of this study was to investigate the effect of type 2 DM on salivary secretion and its relation to the sensation of xerostomia. METHODS: Forty-seven patients with type 2 DM and 46 healthy individuals, aged 40-80, participated in the study. Samples of saliva were collected, at rest and after stimulation, at baseline and after the administration of a meal. A questionnaire of 10 items was used to define the patients' sensations of xerostomia. For statistical analysis, the Mann-Whitney test was used to assess the difference in salivary flow between the two groups and the relationship between the response to each of the questions and salivary flow levels. The degree of the patients' sensation of xerostomia was analysed by the Fisher test. RESULTS AND CONCLUSIONS: There was a significant decrease in total saliva levels at rest in patients with type 2 DM compared to the control group. The study group also experienced higher levels of dryness at night and on waking as well as a greater sensation of lingual burning compared to the control group.

Possible effect of SNAIL family transcriptional repressor 1 polymorphisms in non-syndromic cleft lip with or without cleft palate.

OBJECTIVE: Orofacial development is a complex process subjected to failure impairing. Indeed, the cleft of the lip and/or of the palate is among the most frequent inborn malformations. The JARID2 gene has been suggested to be involved in non-syndromic cleft lip with or without cleft palate (nsCL/P) etiology. JARID2 interacts with the polycomb repressive complex 2 (PRC2) in regulating the expression patterns of developmental genes by modifying the chromatin state. MATERIALS AND METHODS: Genes coding for the PRC2 components, as well as other genes active in cell differentiation and embryonic development, were selected for a family-based association study to verify their involvement in nsCL/P. A total of 632 families from Italy and Asia participated to the study. RESULTS: Evidence of allelic association was found with polymorphisms of SNAI1; in particular, the rs16995010-G allele was undertransmitted to the nsCL/P cases [P = 0.004, odds ratio = 0.69 (95% C.I. 0.54-0.89)]. However, the adjusted significance value corrected for all the performed tests was P = 0.051. CONCLUSIONS: The findings emerging by the present study suggest for the first time an involvement of SNAI1 in the nsCL/P onset. CLINICAL RELEVANCE: Interestingly, SNAI1 is known to promote epithelial to mesenchymal transition by repressing E-cadherin expression, but it needs an intact PRC2 to act this function. Alterations of this process could contribute to the complex etiology of nsCL/P.

Upper Eyelid Blepharoplasty With Voltaic Arc Dermabrasion.

The aging to the upper eyelid complex includes skin laxity, resulting in rhytids, orbicularis oculi hypertrophy, and pseudohermitian of orbital fat and nowadays a high number of patients seeking cosmetic surgery. Excess and laxity of upper eyelid skin affect more than 90% of women, the impact of these problems on the patient's self-esteem can become important enough to affect quality of life in psychological and sociocultural terms.The aim of the study was to evaluate the clinical efficacy of blepharoplasty with an electrosurgical technology for treatment of skin laxity of upper eyelid, which produced a lid retraction and an elevation of the upper lid without complications.This retrospective evaluation was conducted from October 2008 to July 2015, where 80 patients (56 female and 24 male) were treated for excess and laxity of upper eyelid skin with voltaic arc dermabrasion.The outcome was that all patients displayed some aspects of tissue contraction that stretched the lax skin of the upper eyelids, resulting in cosmetic improvement.In conclusion this technique was predictable and useful to remove the laxity of upper eyelid skin minimal recurrence rates, and acceptable aesthetics.

Intense, Instantaneous, and Shooting Pain During Local Anesthesia for Implant Surgery.

Administration of local anesthetics is daily routine for most dental practitioners. Normally, the effect is achieved, and no adverse effects are seen. In this article, the authors describe the complications of immediate, intense and shooting pain, numbness, and marked pallor of the cheek, which occurred during infiltration of a local anesthetic in buccal vestibule infiltration. The patients moved suddenly because of pain and marked pallor of the cheek near the root of the nose and lower eyelid pallor was observed. The pain was very short and the injection was performed again after a few minutes. Two patients also reported an alteration of vision or paralysis of the extra-ocular muscles and drooping eyelid due to paralysis of the levator palpebrae superioris muscle and signs of numbness in the infraorbital area on the same side as the anesthesia. While 3 patients were also apprehensive and started to scare with heart palpitations, as they did not understand what was happening. Probably the anesthetic solutions were injected into an intravascular artery and passed from the extraosseous branch of posterior superior alveolar artery through to the infraorbital artery, which could produce the clinical signs observed in the present study. At the same time, the inoculation of anesthetic in the artery could be grounds for legal disputes for the dentist. In fact, in the absence of vascular disease, anomalies documented by the dentist, they would, however, respond to professional liability and be liable for damages caused to the patient. In conclusion, despite the fact that this condition requires no treatment, it could lead to the recognition of clinical signs in patient with injection of local anesthesia into the artery. At the same time, the inoculation of anesthetic in the artery could be grounds for legal disputes for the dentist.

Tarsal Strip Versus Tarsal Belt in Ectropion Correction: A Statistical Evaluation.

Two surgical procedures for ectropion correction are compared: the widespread "lateral tarsal strip" and the more recently introduced "tarsal belt" techniques. A retrospective interventional patient series of 40 patients with mono or bilateral ectropion are investigated.Distances of lower lid margin from interpupillary line before surgery and after 1, 6, 12, and 24 months in tarsal belt and lateral tarsal strip surgical procedure are compared. The postoperative distance is reduced in both the groups of patients, but as regard the tarsal belt the amount of correction is greater and more stable over time and this difference is statistically significant.The ideal surgical technique for ectropion's correction must be focused simultaneously on the lid and on the canthal region because it is mandatory to tight and elevate the lower lid, rotate the tarsal plate, lift the lateral canthal ligament fixing it in a sure fashion. The tarsal strip technique can result in a more vulnerability to relapse. In fact, all the lower eyelid is maintained through the little strip that is assured with a single stitch to the orbital rim periosteum.The tarsal belt technique allows a more uniform distribution of the tissue excess. The suture, with its multiple intratarsal stitches, produces a real reinforcement of the eyelid. The double passage is an added value because it is the element that assures a precise regulation of the tarsal plate rotation. Thus, the tarsal belt technique guarantees a better result over time.

Tear Trough Deformity: Study of Filling Procedures for Its Correction.

The aim of this work is to discuss the anatomy of the tear trough region with relative danger areas, and to describe 2 different options to correct this deformity.The tear trough is a concave deformity of the orbital fat that is noticeable as a result of inherited anatomic differences and aging. However, the periorbital region is a complex area with its own septa and ligaments, fat compartments, muscles, vascularization, and lymphatic drainage and presents anatomic characteristics that must be taken into account in order to achieve good results and avoid complications.The use of hyaluronic acid gel or autologous fat for soft tissue correction is a good option.A total of 96 patients with periorbital hollowing were divided into 2 groups; each group received a different treatment, from December of 2013 to December of 2015, with hyaluronic- or lipo-filling.

Treatment of the Crooked Nose: The Final Steps to Perfection.

Perfection is sometimes approached in treatment of the crooked nose today but not fully achieved due to the continued existence of flaws. While the traditional surgical algorithm envisages the use of 2 series of procedures to straighten the nasal bones and cartilaginous septum, the addition of a third appears very useful with a view to obtaining truly excellent results, above all in the case of marked deviation. The authors present their experience in the use of certain procedures designed to correct asymmetry of the upper lateral and lower lateral cartilages, as well as the soft covering tissues where necessary.A retrospective study was carried out on 105 patients treated for crooked nose over a 3-year period, 90% of the patients being due to trauma and the remaining 10% to congenital malformation. All the patients involved severe deviation of the nasal pyramid.The mean follow-up period was 18 months (range: 8-36 months). The use of these additional surgical procedures made it possible to obtain excellent final results in 83 (97.6%) patients with crooked nose of traumatic origin and in 17 (85%) patients with crooked nose due to congenital malformation. No major complication was registered, although 3 patients did present minor complications not connected with the nasal deviation.In conclusion, more modern approach to correction of the crooked nose should involve not only realignment of the osteocartilaginous axis but also treatment of the neighboring structures.

Replication analysis of 15 susceptibility loci for nonsyndromic cleft lip with or without cleft palate in an italian population.

BACKGROUND: Nonsyndromic cleft lip with or without cleft palate (nsCL/P) is one of the most common congenital malformations in humans. Its average global incidence is 1.7 per 1000 live births, with wide variation according to geographical location and ethnicity. Its etiology involves both genetic and environmental factors. The aim of the present study was to confirm genetic association of a selection of 15 candidate nsCL/P loci using an independent sample of the Italian population. METHODS: At least one single-nucleotide polymorphism (SNP) for each locus was genotyped in 380 nuclear trios. RESULTS: Transmission disequilibrium analysis revealed significant associations for three variants at two loci (8q24 and 1p22). Two SNPs at 8q24 showed the strongest level of association, the rs987525 (PTDT = 6.81 × 10(-6) ; homozygous relative risk = 3.60 [95% confidence interval, 2.12-6.13]), and the rs17241253 (PTDT = 1.03 × 10(-5) ; homozygous relative risk = 3.75 [95% confidence interval, 2.10-6.67]). Four additional loci (at 1q32, 3q12, 8q21, and 10q25) achieved nominally significant p-values. Two SNPs at 1p36 achieved p-values of < 0.1. The present data suggest that 6 of the 15 analyzed nsCL/P risk loci contribute significantly to nsCL/P risk in the Italian population. These include the 1p22 locus, which previous research has implicated predominantly in Asian populations. CONCLUSION: Different loci, including 8q24 and 1p22 have been found associated with nsCL/P in multiple populations. Further efforts are needed to identify causative variants and transfer knowledge to clinical application, such as personal genetic risk assessment.