Publications by authors named "Francesco Carinci"

277 Publications

Non-syndromic Cleft Palate: An Overview on Human Genetic and Environmental Risk Factors.

Front Cell Dev Biol 2020 20;8:592271. Epub 2020 Oct 20.

Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum - University of Bologna, Bologna, Italy.

The epithelial and mesenchymal cells involved in early embryonic facial development are guided by complex regulatory mechanisms. Any factor perturbing the growth, approach and fusion of the frontonasal and maxillary processes could result in orofacial clefts that represent the most common craniofacial malformations in humans. The rarest and, probably for this reason, the least studied form of cleft involves only the secondary palate, which is posterior to the incisive foramen. The etiology of cleft palate only is multifactorial and involves both genetic and environmental risk factors. The intention of this review is to give the reader an overview of the efforts made by researchers to shed light on the underlying causes of this birth defect. Most of the scientific papers suggesting potential environmental and genetic causes of non-syndromic cleft palate are summarized in this review, including genome-wide association and gene-environment interaction studies.
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http://dx.doi.org/10.3389/fcell.2020.592271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606870PMC
October 2020

Drug-Induced Gingival Overgrowth: A Pilot Study on the Effect of Diphenylhydantoin and Gabapentin on Human Gingival Fibroblasts.

Int J Environ Res Public Health 2020 11 7;17(21). Epub 2020 Nov 7.

Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy.

Introduction: The administration of several classes of drugs can lead to the onset of gingival overgrowth: anticonvulsants, immunosuppressants, and calcium channel blockers. Among the anticonvulsants, the main drug associated with gingival overgrowth is diphenylhydantoin.

Materials And Methods: In this study, we compared the effects of diphenylhydantoin and gabapentin on 57 genes belonging to the "Extracellular Matrix and Adhesion Molecule" pathway, present in human fibroblasts of healthy volunteers.

Results: Both molecules induce the same gene expression profile in fibroblasts as well as a significant upregulation of genes involved in extracellular matrix deposition like COL4A1, ITGA7, and LAMB3. The two treatments also induced a significant downregulation of genes involved in the expression of extracellular matrix metalloproteases like MMP11, MMP15, MMP16, MMP24, and transmembrane receptor ITGB4.

Conclusions: Data recorded in our study confirmed the hypothesis of a direct action of these drugs at the periodontium level, inducing an increase in matrix production, a reduction in its degradation, and consequently resulting in gingival hyperplasia.
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http://dx.doi.org/10.3390/ijerph17218229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664415PMC
November 2020

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

Orthod Craniofac Res 2021 May 15;24(2):251-260. Epub 2020 Oct 15.

Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.

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.
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http://dx.doi.org/10.1111/ocr.12427DOI Listing
May 2021

The Association between Periodontitis and Human Colorectal Cancer: Genetic and Pathogenic Linkage.

Life (Basel) 2020 Sep 18;10(9). Epub 2020 Sep 18.

Department of Medicine, Surgery and Dentistry "Schola Medica Salernitana", University of Salerno, Via S. Allende, 84081 Baronissi (Salerno), Italy.

Periodontitis has been associated with an increased risk of and mortality associated with human colorectal cancer (CRC). Current evidence attributes such an association to the direct and indirect effects of virulence factors belonging to periodontal pathogens, to inflammatory mediators and to genetic factors. The aims of the study were to assess the existence of a genetic linkage between periodontitis and human CRC, to identify genes considered predominant in such a linkage, thus named leader genes, and to determine pathogenic mechanisms related to the products of leader genes. Genes linking periodontitis and CRC were identified and classified in order of predominance, through an experimental investigation, performed via computer simulation, employing the leader gene approach. Pathogenic mechanisms relating to leader genes were determined through cross-search databases. Of the 83 genes linking periodontitis and CRC, 12 were classified as leader genes and were pathogenically implicated in cell cycle regulation and in the immune-inflammatory response. The current results, obtained via computer simulation and requiring further validation, support the existence of a genetic linkage between periodontitis and CRC. Cell cycle dysregulation and the alteration of the immuno-inflammatory response constitute the pathogenic mechanisms related to the products of leader genes.
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http://dx.doi.org/10.3390/life10090211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555596PMC
September 2020

Titanium Implants Coated with a Bifunctional Molecule with Antimicrobic Activity: A Rabbit Study.

Materials (Basel) 2020 Aug 15;13(16). Epub 2020 Aug 15.

Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Via dei Vestini, 31 66100 Chieti, Italy.

Background: Various surface treatments have been tested for titanium implants aiming at increasing their surface biocompatibility and their biological characteristics, but also the efficiency of the implant surface will have to be improved to drastically decrease peri-implantite and mucosite. In fact, the peri-implantitis and peri-implant mucositis have a high incidence in clinical practice. The nanofabrication techniques that offer the possibility to achieve the implant surface that reduces bacterial colonization could influence the osteointegration. The aim of this research was to evaluate the bone response to titanium implants coated with a bifunctional molecule with antimicrobic activity consisting of a combination of silver ions covalently bound to titanium dioxide nanoparticles.

Methods: A total of 36 implants were inserted into 18 older New Zealand white male rabbits. They had two different surfaces. The implants Control group was characterized by an acid-etched and sandblasted surface treatment, and the Test implants had an acid-etched and sandblasted surface coated with a silver ion covalently bound to titanium dioxide nanoparticles in the solution.

Results: No statistically significant difference of the bone density was evidenced between Control and Test implants at two weeks (-value = 0.623), four weeks (-value = 0.339), and eight weeks (-value = 0.461). Moreover, no statistically significant difference of the bone-implant contact percentage was evidenced between Control and Test implants at two weeks (-value = 0.938), four weeks (-value = 0.307), and eight weeks (-value = 0.294). The effectiveness of the present investigation demonstrated no adverse effects on osseointegration, and no statistically significant differences were observed in the bone density and percentage of bone-implant contact between Test and Control implants at all the experimental time points (two, four, and eight weeks).

Conclusions: Titanium implants coated with the silver-anatase solution bind very well to the bone and did not have an adverse effect on the bone tissue in a rabbit model. These facts suggest possible clinical applications for the silver composition.
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http://dx.doi.org/10.3390/ma13163613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475867PMC
August 2020

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

Aesthetic Plast Surg 2020 12 6;44(6):2277-2285. Epub 2020 Aug 6.

Department of Medical, Oral and Biotechnological Sciences and CAST, University of Chieti-Pescara, Via Dei Vestini 31, 66100, Chieti, Italy.

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 .
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http://dx.doi.org/10.1007/s00266-020-01891-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683462PMC
December 2020

Drug-Induced Gingival Overgrowth: The Effect of Cyclosporin A and Mycophenolate Mophetil on Human Gingival Fibroblasts.

Biomedicines 2020 Jul 17;8(7). Epub 2020 Jul 17.

Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy.

Drug-induced gingival overgrowth may occur after a chronic administration of three classes of systemic drugs: Anticonvulsants, immunosuppressants, and calcium channel blockers. This study aimed to investigate how cyclosporin A and mycophenolate mophetil (immunosuppressive drugs) could interfere with human gingival fibroblasts functions, leading to gingival enlargement. Human gingival fibroblasts derived from the tissue of a 60-year-old female were cultured in a DMEME medium. A stock solution with 1 mg/mL of mycophenolate and 1 mg/mL of cyclosporine were prepared and dissolved in a DMEM medium to prepare a serial dilution at the concentrations of 5000, 2000, 1000, 500, and 100 ng/mL, for both treatments. Cell viability was measured using the PrestoBlue™ Reagent Protocol. Quantitative real-time RT-PCR was performed in order to analyze the expression of 57 genes coding for gingival fibroblasts "Extracellular Matrix and Adhesion Molecules". Mycophenolate and cyclosporine had no effect on fibroblast cell viability at 1000 ng/mL. Both the treatments showed similar effects on the expression profiling of treated cells: Downregulation of most extracellular matrix metalloproteases genes (, , , , ) was assessed, while , , , , , and were recorded to be upregulated in fibroblasts treated with immunosuppressive drugs. It has been demonstrated that gingival overgrowth can be caused by the chronic administration of cyclosporin A and mycophenolate mophetil. However, given the contrasting data of literature, further investigations are needed, making clear the possible effects of immunosuppressive drugs on fibroblasts.
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http://dx.doi.org/10.3390/biomedicines8070221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400382PMC
July 2020

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

J Clin Periodontol 2020 10 7;47(10):1268-1280. Epub 2020 Aug 7.

Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.

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.
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http://dx.doi.org/10.1111/jcpe.13345DOI Listing
October 2020

Saliva is a reliable tool to detect SARS-CoV-2.

J Infect 2020 07 14;81(1):e45-e50. Epub 2020 Apr 14.

Laboratory of Clinical Microbiology, ASST dei Sette Laghi, Department of Medicine and Surgery, University of Insubria, Varese, Italy.

Objectives: This study analyzed salivary samples of COVID-19 patients and compared the results with their clinical and laboratory data.

Methods: Salivary samples of 25 COVID-19 patients were analyzed by rRT-PCR. The following data were collected: age, sex, comorbidities, drugs. Lactate dehydrogenase (LDH) and ultrasensitive reactive C protein (usRCP) values were registered on the same day when a salivary swab was collected. Prevalence of positivity in saliva and association between clinical data and the cycle threshold as a semiquantitative indicator of viral load were considered.

Results: Twenty-five subjects were recruited into this study, 17 males and 8 females. The mean age was 61.5 +/- 11.2 years. Cardiovascular and/or dysmetabolic disorders were observed in 65.22% of cases. All the samples tested positive for the presence of SARS-CoV-2, while there was an inverse association between LDH and Ct values. Two patients showed positive salivary results on the same days when their pharyngeal or respiratory swabs showed conversion.

Conclusions: Saliva is a reliable tool to detect SARS-CoV-2. The role of saliva in COVID-19 diagnosis could not be limited to a qualitative detection of the virus, but it may also provide information about the clinical evolution of the disease.
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http://dx.doi.org/10.1016/j.jinf.2020.04.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194805PMC
July 2020

Nanomaterials for Periodontal Tissue Engineering: Chitosan-Based Scaffolds. A Systematic Review.

Nanomaterials (Basel) 2020 Mar 25;10(4). Epub 2020 Mar 25.

Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy.

. Several biomaterials are used in periodontal tissue engineering in order to obtain a three-dimensional scaffold, which could enhance the oral bone regeneration. These novel biomaterials, when placed in the affected area, activate a cascade of events, inducing regenerative cellular responses, and replacing the missing tissue. Natural and synthetic polymers can be used alone or in combination with other biomaterials, growth factors, and stem cells. Natural-based polymer chitosan is widely used in periodontal tissue engineering. It presents biodegradability, biocompatibility, and biological renewability properties. It is bacteriostatic and nontoxic and has hemostatic and mucoadhesive capacity. The aim of this systematic review is to obtain an updated overview of the utilization and effectiveness of chitosan-based scaffold (CS-bs) in the alveolar bone regeneration process. . During database searching (using PubMed, Cochrane Library, and CINAHL), 72 items were found. The title, abstract, and full text of each study were carefully analyzed and only 22 articles were selected. Thirteen articles were excluded based on their title, five after reading the abstract, twenty-six after reading the full text, and six were not considered because of their publication date (prior to 2010). Quality assessment and data extraction were performed in the twelve included randomized controlled trials. Data concerning cell proliferation and viability (CPV), mineralization level (M), and alkaline phosphatase activity (ALPA) were recorded from each article All the included trials tested CS-bs that were combined with other biomaterials (such as hydroxyapatite, alginate, polylactic-co-glycolic acid, polycaprolactone), growth factors (basic fibroblast growth factor, bone morphogenetic protein) and/or stem cells (periodontal ligament stem cells, human jaw bone marrow-derived mesenchymal stem cells). Values about the proliferation of cementoblasts (CB) and periodontal ligament cells (PDLCs), the activity of alkaline phosphatase, and the mineralization level determined by pure chitosan scaffolds resulted in lower than those caused by chitosan-based scaffolds combined with other molecules and biomaterials. . A higher periodontal regenerative potential was recorded in the case of CS-based scaffolds combined with other polymeric biomaterials and bioceramics (bio compared to those provided by CS alone. Furthermore, literature demonstrated that the addition of growth factors and stem cells to CS-based scaffolds might improve the biological properties of chitosan.
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http://dx.doi.org/10.3390/nano10040605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221778PMC
March 2020

The Impact of Implant-Abutment Connection on Clinical Outcomes and Microbial Colonization: A Narrative Review.

Materials (Basel) 2020 Mar 3;13(5). Epub 2020 Mar 3.

Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy.

Introduction: Osseointegration are often suffering from oral conditions, especially, the micro gap at the implant-abutment connection represents a site for bacterial plaque aggregation, leading to increased inflammatory cells and causing peri-implantitis.

Aim: The aim of this narrative review was to describe the different kinds of implant-abutment connections and their ability to reduce bacterial leakage and thus prevent peri-implantitis.

Materials And Methods: The following databases were consulted: Pubmed, Scopus, Cochrane Library, and Research gate and a total of 528 articles were found. After reading the abstract and titles, 473 items were excluded. The remaining articles (n = 55) were assessed for full-text eligibility. Thirty-three studies were included in the review.

Results And Conclusions: We selected 22 clinical trials and 11 reviews, examining a total sample of 2110 implants. From the review, it was clear that there exists a relationship between the implant-abutment interface and bacterial leakage. All the connections presented an amount of micro-gap and bacterial micro-leakage, though conical and mixed connection systems seemed to behave better. Moreover, both connections seemed to have a better load distribution and the mixed system also had anti-rotational properties which are very useful during the positioning of the prosthesis.
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http://dx.doi.org/10.3390/ma13051131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7085009PMC
March 2020

Oral Manifestations in HIV-Positive Children: A Systematic Review.

Pathogens 2020 Jan 31;9(2). Epub 2020 Jan 31.

Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy.

The number of pediatric patients affected by HIV still remains high, mainly in developing countries, where the main cause of infection is vertical transmission from the mother. Even today, a large number of these children do not have access to treatment, and, without proper care, they die in the first few years of life. The aim of our review was to assess the prevalence of oral hard and soft tissue lesions in HIV-positive pediatric patients by identifying the most common manifestations and the overall impact that they may have on the children's quality of life. A systematic review of the articles in the English language in PubMed and Scopus was conducted in March 2019 in order to identify the main epidemiological and cross-sectional studies on the topic. Oral diseases are still one of the most common manifestations in HIV-positive pediatric patients, and they often represent the first form in which immunosuppression shows itself. An analysis of the literature shows that candidiasis is the most common oral lesion found in HIV-positive children. A significant incidence of gingivitis and gingival disease is also evident, though not strictly correlated to HIV infection. However, thanks to the introduction of new antiretroviral therapies, the incidence of HIV-related oral lesions is decreasing. An HIV-positive children care program should also include dental protocols, as oral disease negatively influences the quality of life, affecting both functional and social aspects.
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http://dx.doi.org/10.3390/pathogens9020088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168689PMC
January 2020

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

Int J Mol Sci 2020 Jan 16;21(2). Epub 2020 Jan 16.

Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy.

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 , which codes for the cell adhesion protein E-cadherin, showed up-regulation. Almost all the extracellular matrix metalloproteases showed down-regulation (, , , , , ). The administration of cyclosporine A was followed by down-regulation of other genes: , the transmembrane receptors and , and the basement membrane constituents and .

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.
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http://dx.doi.org/10.3390/ijms21020595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7014429PMC
January 2020

Oral Health Status and Need for Oral Care in an Aging Population: A Systematic Review.

Int J Environ Res Public Health 2019 11 18;16(22). Epub 2019 Nov 18.

Interdisciplinary Department of Medicine, University of Bari, 70121 Bari, Italy.

Background: The world population is aging. This phenomenon is accompanied by an increase in the number of elderly with dementia, whose oral hygiene care is a challenge.

Objective: This paper presents a literature review of oral health status and the need for oral care in people with dementia, as compared to people without dementia and also of the relationship between periodontal disease and cognitive impairment.

Methods: A systematic review was conducted in PubMed, CINAHL, and the Cochrane Library. Fifty-six articles met the inclusion criteria and were consequently included for quality assessment and data extraction.

Results: No significant differences were found between both groups with regard to the number of present teeth, DMFT Index, edentulousness/use of denture, and orofacial pain. Coronal/root caries and retained roots were more common in people with dementia than in those without dementia. Most of the participants with dementia presented gingival bleeding or inflammation and they suffered from the periodontal disease more than people without dementia.

Conclusions: Poor oral health is a common condition among the elderly with dementia. The education process of caregivers might improve the oral health status of people with dementia. Finally, periodontal disease might contribute to the onset or progression of dementia.
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http://dx.doi.org/10.3390/ijerph16224558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888624PMC
November 2019

ROCK1 is associated with non-syndromic cleft palate.

J Oral Pathol Med 2020 Feb 24;49(2):164-168. Epub 2019 Nov 24.

Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.

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.
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http://dx.doi.org/10.1111/jop.12973DOI Listing
February 2020

Accuracy of the Cone Beam Computed Tomography in the Detection of Bone Invasion in Patients with Oral Cancer: A Systematic Review.

Eurasian J Med 2019 Oct;51(3):298-306

Department of Biomedical, Surgical and Dental Sciences, Maxillo-Facial and Dental Unit, Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico Milan, University of Milan, Italy.

This review article aims to analyze the diagnostic accuracy of the cone beam computed tomography (CBCT) with respect to other imaging methods in detection of bone tissue invasion by oral squamous cell carcinoma (OSCC). The review was carried out of English language studies in PubMed Search, National Library of Medicine, between 1990 and 2017. For each study, sensitivity, specificity, and positive (LR+) and negative (LR-) likelihood ratio, as well as the diagnostic accuracy, and positive and negative predictive values were calculated. Of the 62 collected articles, 7 fulfilled the inclusion criteria. Tests and respective articles included were computed tomography (CT, four studies), magnetic resonance imaging (MRI, five studies), C (two studies), single-photon emission tomography (SPECT, two studies), multi-slice computed tomography (MSCT, two studies), and panoramic radiography (PR, two studies). The analytic data show values of LR+ were 14.4 (CT), 37.9 (MRI), 27.8 (CBCT), 25.5 (SPECT), 37.0 (MSCT), 4.8 (PR), respectively. The values of LR- were 0.35 (CT), 0.24 (MRI), 0.10 (CBCT), 0.06 (SPECT), 0.31 (MSCT), and 0.36 (PR), respectively. The positive and negative predictive values for bone tissue invasion by OSCC were 90.31%-74.91% (CT), 90.63%-78.69% (MRI), 80.05%-89.83% (CBCT), 72.97%-95.53% (SPECT), 87.44%-73.74% (MSCT), and 84.245%-69.18% (PR), respectively. The level of scientific evidence available today is weak. To better define the impact of CBCT on clinical decision-making, further studies with uniform methodological approach are needed.
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http://dx.doi.org/10.5152/eurasianjmed.2019.18101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6812923PMC
October 2019

Evaluation of IL6, IL10 and VDR alleles distribution in an Italian large sample of subjects affected by chronic periodontal disease.

Int J Immunopathol Pharmacol 2019 Jan-Dec;33:2058738419840844

Paediatric Dentistry, Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.

In recent decades, the role played by the immune response to bacteria in the pathogenesis of chronic periodontal disease (PD) has long been studied. Although from the clinical point of view, adequate oral hygiene is essential to ensure a satisfactory response of the host to infections, modulation of the reaction of immune system could be influenced by genetic factors. The aim of the present study was to investigate the distribution of alleles of polymorphisms relevant for chronic periodontitis in a sample of adult subjects affected by chronic PD. The present study was conducted with sample collected in Italian private practice offices from January 2013 to December 2017. The sample included 744 adult patients diagnosed with chronic periodontitis. The inclusion criteria were as follows: age > 18 years, diagnosis of chronic PD. The diagnosis of chronic periodontitis was based on the criteria established by the American Academy of Periodontology. No significant difference in allele distribution among patients from different Italian regions was found. Results, supporting absence of population heterogeneity for the investigated polymorphisms in Italy, suggest similar effect in periodontitis etiology.
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http://dx.doi.org/10.1177/2058738419840844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822182PMC
March 2020

Non-syndromic cleft palate: Association analysis on three gene polymorphisms of the folate pathway in Asian and Italian populations.

Int J Immunopathol Pharmacol 2019 Jan-Dec;33:2058738419858572

Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.

Periconceptional folic acid supplementation can reduce the risk of inborn malformations, including orofacial clefts. Polymorphisms of MTHFR, TCN2, and CBS folate-related genes seem to modulate the risk of cleft lip with or without cleft palate (CL/P) in some populations. CL/P and cleft palate only (CPO) are different malformations that share several features and possibly etiological causes. In the present investigation, we conducted a family-based, candidate gene association study of non-syndromic CPO. Three single nucleotide polymorphisms, namely, rs1801133 of MTHFR, rs1801198 of TCN2, and rs4920037 of CBS, were investigated in a sample that included 129 Italian and 65 Asian families. No evidence of association between the three genotyped polymorphisms and CPO was found in the Italian and Asian cases, indeed the transmission disequilibrium test did not detect any asymmetry of transmission of alleles. This investigation, although with some limitation, further supports that CL/P and CPO diverge in their genetic background.
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http://dx.doi.org/10.1177/2058738419858572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822179PMC
March 2020

Copy number variation analysis of twin pairs discordant for cleft lip with or without cleft palate.

Int J Immunopathol Pharmacol 2019 Jan-Dec;33:2058738419855873

Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.

Non-syndromic cleft lip with or without cleft palate (nsCL/P) is a frequent orofacial malformation. The comparison of concordance rate observed in monozygotic and dizygotic twins supports high level of heritability and a strong genetic component. However, phenotype concordance for orofacial cleft in monozygotic twins is about 50%. The aim of the present investigation was to detect postzygotic events that may account for discordance in monozygotic twins. High-density SNP microarrays hybridization was used to genotype two pairs of monozygotic twins discordant for nsCL/P. Discordant SNP genotypes and copy number variants were analyzed to identify genetic differences responsible of phenotype discrepancy. A number of differences were observed, none involving known nsCL/P candidate genes or genomic regions. Considering the limitation of the study, related to the small sample size and to the large-scale investigation method, the results suggest that the detection of discordant events in other monozygotic twin pairs would be remarkable and warrant further investigations.
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http://dx.doi.org/10.1177/2058738419855873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822181PMC
March 2020

Association between oral cleft and transcobalamin 2 polymorphism in a sample study from Nassiriya, Iraq.

Int J Immunopathol Pharmacol 2019 Jan-Dec;33:2058738419855571

Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.

Orofacial clefts are common congenital defects whose prevalence differs between geographical regions and ethnic groups. The inheritance is complex, involving the contribution of both genetic and environmental factors. The involvement of genes belonging to the folate pathway is still matter of debate, with strong evidences of association and conflicting results. After demonstrating the contribution, for a sample from the Italian population, of common mutations mapping on three genes of the folate pathway, our group tried to unravel their contribution in independent sample studies with different ethnicity. In the present investigation a set of 34 triads with oral cleft from Nassiriya, Iraq, has been genotyped for rs1801133 of MTHFR, rs1801198 of TCN2, and rs4920037 of CBS polymorphisms. Association analysis evidenced a decreased risk of cleft for children carrying the 667G allele at TCN2 gene ( = 0.02). This evidence further supported the relationship between polymorphisms of folate related genes and oral clefts, and outlined the relevance of studying populations having different ethnicity.
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http://dx.doi.org/10.1177/2058738419855571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822189PMC
March 2020

Periauricular wrinkles removed with voltaic arc dermabrasion (Atmospheric Plasma technique).

J Cosmet Dermatol 2020 Jul 26;19(7):1709-1714. Epub 2019 Oct 26.

Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Chieti, Italy.

Background: In recent literature, different approaches have been proposed to improve the long-lasting treatment of age-related alterations on the human face with decreased invasiveness and side effects such as scar tissue. Voltaic arc dermabrasion is a minimally painful procedure that does not create discomfort to the patient and requires no anaesthesia.

Aims: The aim of this investigation was to evaluate the voltaic arc technique for the treatment of skin wrinkles in the periauricular area.

Methods: A total of 80 patients were treated in this study, 56 females and 24 males. The population was visited at 1 week, 1 month, and 2 months postoperative follow-ups to evaluate the healing of the treated regions.

Results: All subjects showed evidence of tissue contraction related to the skin of the periauricular region with a cosmetic reduction of wrinkles in the treated area. No scars, complications, or pigmentary alterations were reported. At 1 month, all treated areas showed complete healing.

Conclusions: The voltaic arc dermabrasion can be considered a useful tool for a noninvasive treatment of wrinkles related to the periauricular skin, with no discomfort for the patient or complications related to the procedure.
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http://dx.doi.org/10.1111/jocd.13204DOI Listing
July 2020

Aging and Oral Care: An Observational Study of Characteristics and Prevalence of Oral Diseases in an Italian Cohort.

Int J Environ Res Public Health 2019 10 7;16(19). Epub 2019 Oct 7.

Interdisciplinary Department of Medicine, University of Bari, 70121 Bari, Italy.

: Poor oral health is a common condition in patients suffering from dementia. Several aspects of this systemic pathology contribute to causing oral problems: cognitive impairment, behavior disorders, communication and, motor skills deterioration, low levels of cooperation and medical-nursing staff incompetency in the dental field. : The objectives of this study were to evaluate the prevalence and the characteristics of oral pathology in a demented elderly population, as well as to check the association between the different degree of dementia and the oral health condition of each patient. : In this observational study (with cross-sectional design) two groups of elderly patients suffering from dementia, living in two different residential care institutions were recruited. The diagnosis of dementia of each included patient was performed using the Clinical Dementia Rating Scale. In order to evaluate the oral health condition of the included subjects, each patient underwent a physical examination of the oral cavity, during which different clinical parameters were analyzed (number of remaining teeth, oral mucosa, periodontal tissues, bone crests). To each parameter, a score was assigned. Spearman's Rho test was used. : Regarding the prevalence of oral pathology in elderly suffering from dementia, it emerged that 20.58% of the included patients had mucosal lesions and/or new mucosal formations (in most cases undiagnosed and therefore untreated). The prevalence of periodontal disease was equal to 82.35% and a marked clinically detectable reabsorption of bone crests was found in almost all patients (88.23%). 24.13% of patients, who underwent the oral examination, had totally edentulous maxillae and/or with retained roots, without prosthetic rehabilitations. The correlation index r showed the presence of a linear correlation (inverse relationship) between the degree of dementia and the state of health of the oral cavity of each patient. : Several factors contribute to poor oral health in the elderly suffering from dementia: cognitive functions deterioration, behavioral disorders and inadequate medical-staff nursing training on oral hygiene. This study also demonstrated that the lower the dementia degree is, the lower tends to be the oral health status. In order to guarantee a complete assistance to these patients, residential care institutions should include in their healthcare program specific dental protocols.
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http://dx.doi.org/10.3390/ijerph16193763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801690PMC
October 2019

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

Periodontol 2000 2019 10;81(1):41-47

Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.

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.
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http://dx.doi.org/10.1111/prd.12281DOI Listing
October 2019

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

Int J Mol Sci 2019 Aug 9;20(16). Epub 2019 Aug 9.

Department of Oral Science, Nano and Biotechnology and CeSi-Met University of Chieti-Pescara, 66100 Chieti, Italy.

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) ( < 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.
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http://dx.doi.org/10.3390/ijms20163897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6720572PMC
August 2019

Prevalence of Oral Lesions and Correlation with Intestinal Symptoms of Inflammatory Bowel Disease: A Systematic Review.

Diagnostics (Basel) 2019 07 15;9(3). Epub 2019 Jul 15.

Interdisciplinary Department of Medicine, University of Bari, 70121 Bari, Italy.

Background: Extra-intestinal manifestations of inflammatory bowel disease (IBD) are widely studied. Oral manifestations are manifold, miscellaneous, and hardly detected by general practitioners and gastroenterologists.

Objectives: The main purpose of this systematic review is to find all the possible correlations between inflammatory bowel disease and the oral cavity in order to underline the importance of multidisciplinary cooperation with dental care providers, and to secure better treatments for patients.

Materials And Methods: Articles were searched up to June 2019 through Ebsco's, Google Scholar, and PubMed databases. The search terms included IBD, oral manifestations of inflammatory bowel disease, oral manifestations of Crohn's disease or Ulcerative colitis, an extra-intestinal manifestation of IBD, oral Crohn's disease, and paediatric inflammatory bowel disease.

Discussion: The prevalence of the oral manifestation of IBD ranges from 0.7% to 37% in adults and from about 7% to 23% in children. They can be divided into specific manifestations (cobblestoning mucosa, mucosal tags, cheilitis granulomatosa, pyostomatitis vegetans) and nonspecific manifestations (halitosis, dysphagia, aphthous ulcerations, deep oral fissuring, cheilitis angularis, taste changes, lichen planus). Moreover, the link between IBD and the higher prevalence of dental caries and periodontitis have also been studied.

Conclusions: The presence of oral manifestations that precede or follow intestinal symptoms of IBD, must be taken into serious consideration from both gastroenterologists and dentists in order to allow for early diagnosis and improve patients' quality of life.
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http://dx.doi.org/10.3390/diagnostics9030077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787704PMC
July 2019

Intraoral confocal microscopy of suspicious oral lesions: a prospective case series.

Int J Dermatol 2019 Jul 9. Epub 2019 Jul 9.

Multidisciplinary Department of Medical-Surgical and Dental Specialties, University of Campania Luigi Vanvitelli, Naples, Italy.

Background: Oral squamous cell carcinoma (OSCC) accounts for more than 90% of oral epithelial malignancies and often arises from precursor lesions, whose diagnosis is based on biopsy and histopathology. In vivo reflectance confocal microscopy (RCM) images the vital tissues at microscopic resolution, well correlating with conventional histopathology, but it is poorly investigated in oral oncology. The present work aims to describe RCM cytoarchitectural findings in oral mucosae affected by OSCC and its precursors.

Materials And Methods: A series of clinically suspected oral lesions underwent RCM imaging before conventional biopsy and histopathological assessment in order to identify features suggestive of tumoral changes. Sensitivity (SE), specificity (SP), positive and negative predictive values (PPV and NPV) of RCM compared to histopathology were calculated.

Results: Totally, 30 sites in 20 patients were considered and clinically classified into 16 "leukoplakia"/" traumatism", nine erosive-ulcerative lesions, three verrucous lesions, and two healthy mucosae, as control. The histopathological "positivity," due to the presence of various degrees of dysplasia and/or neoplasia, was found in 11 lesions; the RCM "positivity" was referred to nine lesions reporting the RCM detection of polymorphism, multinucleated cells, irregular cellular maturation, altered nuclear/cytoplasm ratio, and abnormal blood vessels. After excluding three verrucous lesions from the RCM analysis, due to the low laser penetration through the hyperkeratotic layers, the results well correlated with histopathology, reporting 1.000 (SE), 0.933 (SP), 0.909 (PPV), and 1.000 (NPV).

Conclusion: RCM can reveal dysplastic/neoplastic signs occurring in oral lesions, thus supporting their diagnostic pathway.
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http://dx.doi.org/10.1111/ijd.14574DOI Listing
July 2019

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

Int J Mol Sci 2019 Apr 25;20(8). Epub 2019 Apr 25.

Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy.

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. (, , , , , , , ) except for , , , and , 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.
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http://dx.doi.org/10.3390/ijms20082047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514768PMC
April 2019

Clinical Management of Oral Lichen Planus: A Systematic Review.

Mini Rev Med Chem 2019 ;19(13):1049-1059

Department of Medicine and Surgery, Centre of Neuroscience of Milan, University of Milano-Bicocca, 20126 Milan, Italy.

Aim: The clinical management of OLP represents a considerable challenge for the oral physician. The aim of this review is to assess the main intervention used in the management of OLP and the efficacy of every type of treatment.

Materials And Methods: We searched and analyzed PubMed database for articles on OLP management. Only randomized controlled trials, comparing an active treatment with placebo, or between different active treatments, were considered in this systematic review. Only patients with symptomatic OLP were included and interventions of all types were considered (topical treatment, systemic drugs, non pharmacological intervention).

Results: A total of 25 randomized controlled trials were examined and included in this review. Steroids are the most frequently employed drug in the treatment of OLP and their efficacy and safety are demonstrated. Also calcineurin inhibitors and photo-dynamic therapy are used in different studies for OLP management, with positive results.

Conclusion: Topical steroids remain the first-line treatment for symptomatic OLP, however, many different pharmacological and non-pharmacological therapies would represent a valid alternative for its management, but, nowadays they require further investigations.
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http://dx.doi.org/10.2174/1389557519666190301144157DOI Listing
October 2019

Reuterinos as adjuvant for peri-implant treatment: A pilot study.

Int J Immunopathol Pharmacol 2019 Jan-Dec;33:2058738419827745

5 Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.

The objective of this study was to evaluate the effects of lozenges-containing Lactobacillus reuteri as an adjuvant treatment of peri-implant mucositis and to detect the level of L. reuteri colonization in the peri-implant tissues of treated patients. A total of 10 patients were selected. Subjects with at least one implant affected by peri-implant mucositis, with gingival index (GI) of ⩾2 in each quadrant, evaluated at the buccal aspect of all teeth. Patients included in the study were partially edentulous and had implants with mucositis or peri-implantitis. Implants with radiographic bone loss of ⩾5 mm and/or ⩾50% of the implant length were excluded, and only one implant per patient was included. Each patient received L. reuteri-containing lozenges. Microbiological sampling was performed at baseline and on day 28 and analysed by polymerase chain reaction (PCR). Our results indicate that the use of the probiotic did not influence the peri-implant microbiota in a statistically significant way, although there was a reduction in the number of periodontal and peri-implant species. The lack of statistically significant microbiological changes could be explained either by the small sample population or by the short evaluation period. Therefore, the poor colonization of L. reuteri in the peri-implant pockets can be explained by the different anatomical and histological characteristics of the interface of the dental-gingival unit with respect to the periodontal sulcus. The administration of a daily lozenge of L. reuteri for 4 weeks had a limited effect on the microbiological analysis. Probiotics provide an alternative therapeutic approach to consider in the prevention and treatment of peri-implant diseases, but further long-term prospective studies with standardized variables are needed.
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http://dx.doi.org/10.1177/2058738419827745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365990PMC
June 2019