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1.
Article in English | MEDLINE | ID: mdl-33904270

ABSTRACT

This paper aims to describe the biochemical interactions between teeth and the oral environment that occur during the caries process, hence it covers all the steps related to physico-chemical reactions, including the most up-to-date theoretical basis in the clinical application for the prevention and treatment of caries. The terms 'demineralization' and 'remineralization' that characterise this process were analysed, as well as the role of the microbiota in its interaction with the hard surface of the teeth. The biochemical mechanisms that lead to the onset of carious lesions and those that occur during the healing and repair of such lesions are listed.


Subject(s)
Microbiota , Tooth Remineralization
2.
J Biol Regul Homeost Agents ; 35(2 Suppl. 1): 295-302, 2021.
Article in English | MEDLINE | ID: mdl-34281326

ABSTRACT

The occlusal trauma has been defined as an injury to the periodontium resulting from occlusal forces that exceeds the reparative capacity of the attachment apparatus. Currently, the effects of occlusal trauma on tooth support tissues, the onset and the progression of periodontal disease are still debated. In fact, researchers started evaluating the possible effects of occlusal discrepancies on incidence, progression, and treatment outcomes of periodontitis, but all the results underlined the more significant role played by microbiological flora. The results of this study show that after 60 days of treating the occlusal trauma, a significant reduction was achieved in the periodontal bacterial flora.


Subject(s)
Dental Occlusion, Traumatic , Microbiota , Periodontal Diseases , Periodontitis , Humans , Periodontium
3.
J Biol Regul Homeost Agents ; 35(2 Suppl. 1): 227-240, 2021.
Article in English | MEDLINE | ID: mdl-34281321

ABSTRACT

White spot lesions (WSL) are demineralizations of the enamel found on the tooth surfaces. WSL are considered incipient non-cavitated caries caused by bacterial plaque activity. Subjects with malocclusion such as dental crowding and fixed orthodontic appliances have a greater number of retention sites and consequently difficulty in cleaning and greater predisposition to caries. In fact, WSL are a frequent side effect of orthodontic fixed treatments. The prevention and resolution of this problem is the goal of any orthodontist because untreated WSL can lead to the formation of deeper dental caries and restorative treatment with consequent compromise of patient satisfaction with the aesthetic result obtained at the end of the orthodontic treatment. This review is intended not only for orthodontists but also for general and pediatric dentists who want to learn how to correctly prevent, and treat this unsightly problem. On the market there are many products sold to achieve this goal, some of them can be managed independently by the patient at home, others require the intervention of the dentist. The purpose of this literature review is to understand how these substances work, to identify with which of the currently most widespread the best results have been obtained and then to provide useful information to guide the clinician in choosing the most suitable one for the patient.


Subject(s)
Dental Caries , Orthodontics , Cariostatic Agents , Child , Dental Care , Dental Caries/etiology , Dental Caries/prevention & control , Dentists , Humans
4.
J Biol Regul Homeost Agents ; 35(2 Suppl. 1): 241-251, 2021.
Article in English | MEDLINE | ID: mdl-34281322

ABSTRACT

The research is aiming to obtain at room temperature a new ceramic material containing partially stabilized zirconia with different oxides after sintering used for dental and other technological purposes. Our research proposes a new method based on the use of stabilized zirconia with other oxides to obtain optimized dental material with a lower cost price and / or improved properties to allow wider use of these products to an increased number of patients in dental offices. X-ray diffraction, SEM analysis. FTIR spectroscopy, UVVis and density measurements were accomplished for the three ceramic systems. The correlation between the microstructure and the spectroscopic properties of zirconium stabilized by FTIR spectroscopy, UV-Vis helps understanding the mechanisms associated with the formation of high (tetragonal and / or cubic) temperature zirconia. Along with the simple, less costly preparation method and high purity of the ceramic products our study offers a highly desirable product for technological applications.


Subject(s)
Ceramics , Zirconium , Humans , Materials Testing , Surface Properties , X-Ray Diffraction
5.
J Biol Regul Homeost Agents ; 35(2 Suppl. 1): 253-269, 2021.
Article in English | MEDLINE | ID: mdl-34281323

ABSTRACT

The diabetes and osteoporotic metabolic diseases are characterized by a wide prevalence of the population worldwide and correlated to alteration of the bone tissues. Several cofactors could influence the clinical course and the biochemistry of the pathologies such as human microbiome, nutrition characteristics, gut microbiota activity and interactions with vitamin K and D across IGF/GH and TP53 signaling pathways and the glucose/energy as mechanism for bone tissue health. Moreover, also the calories and sugar consumption seem to be correlated to an increased inflammatory state with several consequences for hematopoiesis and host tissues response. The aim of the present literature review was to highlight the role of osteoporotic diseases and diabetes type 2 link for the bone metabolism. The literature cases showed that a correlation between bone-gut-kidney-heart-CNS-Immunity crosstalk seems to be linked with bone metabolism and health regulation. Moreover, also the aging process could represent a valuable co-factor for the sustaining of the metabolic disorders upon a multi-systemic level.


Subject(s)
Diabetes Mellitus, Type 2 , Gastrointestinal Microbiome , Metabolic Diseases , Bone and Bones , Hematopoiesis , Humans
6.
J Biol Regul Homeost Agents ; 35(2 Suppl. 1): 271-281, 2021.
Article in English | MEDLINE | ID: mdl-34281324

ABSTRACT

Anterior open bite is one of the most complex malocclusions to manage. The interaction of skeletal, dental, and soft tissue effects can contribute to develop an anterior open bite. The skeletal open bite requires a more complex approach of treatment to reach function, aesthetics, and stability. The approaches vary depending on the causative factors and the age of patients. Treatment approaches for open bite patients differ when dealing with adults and growing patients. The aim of this descriptive review was to summarize the main existing treatment strategies for anterior open bite, from the noninvasive behavioural shaping to the orthodontic intrusion with skeletal anchorage.


Subject(s)
Malocclusion , Open Bite , Adult , Dentition, Mixed , Dentition, Permanent , Humans , Malocclusion/therapy , Open Bite/therapy
7.
J Biol Regul Homeost Agents ; 35(2 Suppl. 1): 283-294, 2021.
Article in English | MEDLINE | ID: mdl-34281325

ABSTRACT

Resorption of alveolar ridge after tooth extraction often compromises dental implant placement and esthetic. Alveolar ridge preservation is a common procedure performed in order to preserve the pontic site for a prosthetically ideal position. This procedure has already become an indisputable need. Tooth matrix as bone substituted material poses osteoconduction and osteoinduction properties and as autologous graft, this material is free of antigenic reaction. This biomaterial allows the threedimensional reconstruction of the bone, is easy to prepare and has a low cost. The aim of this review is to summarize and put in evidence the properties of tooth as bone substitute and its use in alveolar ridge preservation. Keyword: autologous tooth, autologous graft, bone regeneration, bone substitute, alveolar ridge preservation, alveolar ridge augmentation, socket preservation.


Subject(s)
Alveolar Bone Loss , Alveolar Ridge Augmentation , Bone Substitutes , Alveolar Bone Loss/prevention & control , Alveolar Process/surgery , Bone Transplantation , Humans , Tooth Extraction , Tooth Socket/surgery
8.
J Biol Regul Homeost Agents ; 35(2 Suppl. 1): 303-321, 2021.
Article in English | MEDLINE | ID: mdl-34281327

ABSTRACT

The aim of the present investigation was to evaluate the essential physiological functions of the skin microbiota in human health and diseases. The main characteristics of the normal microbiota in the different anatomical sites have been reported in relation to the main factors, such as the effect of age, on its composition and stability for the eubiosis condition. Moreover, the present overview analyzed the functions and composition and the correct functionality of the skin microbiota in the light of current knowledge. According to several evidence is important preserving the eubiosis of the commensal microbes of the microecosystem (symbiotic and pathogenic), and probiotics are able to counteract the conditions of dysbiosis. Also, it has been shown that there is a crosstalk between gut and skin microbiota that affects human health and is still being studied, and its relationship to the current pandemic SARS-CoV-2.


Subject(s)
COVID-19 , Gastrointestinal Microbiome , Microbiota , Probiotics , Dysbiosis , Humans , Integumentary System , SARS-CoV-2
9.
J Biol Regul Homeost Agents ; 35(2 Suppl. 1): 365-377, 2021.
Article in English | MEDLINE | ID: mdl-34281334

ABSTRACT

Treatments with removable appliances are widely used in Europe to correct dento-skeletal dysgnatia in the growth phase that is a period of poor cooperation of the patients. Adherence to the wear-time prescription is often not achieved and it represent the main argument against the use of removable devices. Suspected non-compliant behavior with the wear time prescription is often the subject of medico-legal disputes, which can deteriorate doctor-patient relationship. The use of microchips allows to document objectively and clarify the patient's behavior. To conduct a systematic review of the orthodontic literature to identify the factors associated with compliance in orthodontic treatment. We conduct a systematic review that aimed to identity the factors associate with compliance in orthodontic treatment. The main purpose was to assess the objective levels of time of use of the removable appliances and the self-reported levels. A literature search was conducted by the electronic databases PubMed and Cochrane Library. The following search terms were used: compliance functional removable orthodontic appliance. Randomized and nonrandomized controlled trials, prospective cohort studies, case series, qualitative and mixed-methods studies objectively assessing compliance levels were included in the study. A total of 94 articles were identified by PubMed and 14 articles by Cochrane. The papers selected were included for the qualitative analysis and categorized according to the subjects age, the clinical appliance, compliance factors, wear time and monitoring. Removable appliances are an important part of orthodontic treatment, used in growth phase of the patient. Collaboration with removable functional devices determines success / failure in treatment.


Subject(s)
COVID-19 , Pandemics , Child , Europe , Humans , Patient Compliance , Physician-Patient Relations , Prospective Studies , SARS-CoV-2
10.
J Biol Regul Homeost Agents ; 34(3): 747-756, 2020.
Article in English | MEDLINE | ID: mdl-32456403

ABSTRACT

Orthopedic temporomandibular joint (TMJ) instability is very common among children and adults. It is often associated with pain in the cervicofacial region, and muscle contraction. To investigate whether muscle contraction can cause permanent posterior rotation of the head and whether treatment with splint and kinetotherapy is efficient, a literature review was carried out of patients with pain in the cervicofacial area. Additionally, the case of a 15-year old patient presenting with permanent posterior rotation of cra¬nium, with no movement between the first two vertebra and pain in the cervicofacial area was reported. Kinetotherapy followed by rapid maxillary expansion improved the function of cervical vertebrae and re¬duced the cervicofacial pain within the first two weeks. Kinetotherapy, rapid maxillary expansion, and or¬thodontic treatment with a stable joint position could be a good therapy to control occipital-atlas function.


Subject(s)
Joint Instability/complications , Palatal Expansion Technique , Temporomandibular Joint Disorders , Adolescent , Cervical Vertebrae , Humans , Occlusal Splints , Pain , Pain Management , Pain Measurement , Temporomandibular Joint Disorders/therapy
11.
J Biol Regul Homeost Agents ; 33(3): 1011-1013, 2019.
Article in English | MEDLINE | ID: mdl-31056888

ABSTRACT

Skin cancer basal cell carcinoma (BCC) is a quite common lesion with a worldwide annual incidence between 3% and 8%. Tissue reconstruction should be biologically driven: nowadays, the naso-genial flap is one of the safest and usable flaps for the reconstruction of the labial and nasal region after invasive surgery aimed at a full BCC excision. In fact, the proximity of this flap to the area to be treated, the similar colour of the skin and the technical possibility to perform a single surgery to both harvest the flap and remove the lesion in the area to be then reconstructed, make it highly preferred by surgeons. In order to prevent the most severe swelling, the Authors started to use a novel method consisting in the use of the small-diameter cannula for lipoaspiration technique (SDCL). The correct use of SDCL allows to aspirate the adipose tissue, thus obtaining an available adipose-based scaffold, highly compatible with the area in which the flap is to be placed.


Subject(s)
Cannula , Carcinoma, Basal Cell/surgery , Plastic Surgery Procedures/instrumentation , Plastic Surgery Procedures/methods , Skin Neoplasms/surgery , Esthetics , Humans , Surgical Flaps
12.
Article in English | MEDLINE | ID: mdl-31056889

ABSTRACT

Dental biofilm is a complex, organized microbial community that is the primary etiologic factor for plaque, the most frequently occurring oral contamination for gingivitis, dental caries and periodontal diseases. In dentistry, calculus is a form of hardened dental plaque, caused by precipitation of calcium (Ca) and phosphorous (P) ions deposited from saliva and gingival crevicular fluid. Although the dental biofilm cannot be eliminated, it can be controlled with comprehensive mechanical and chemotherapeutic oral hygiene practices. Chemotherapeutic agents have difficulty penetrating the polysaccharide matrix to reach and affect the microorganisms. The purpose of the present study was to evaluate the anti-calculus efficiency of a mouthwash containing an association of sodium tripolyphosphate, tetrapotassium pyrophosphate, sodium bicarbonate and citric acid in patients affected with gingivitis.


Subject(s)
Dental Calculus/prevention & control , Gingivitis/therapy , Mouthwashes/therapeutic use , Dental Caries/prevention & control , Dental Plaque/prevention & control , Humans
13.
J Biol Regul Homeost Agents ; 33(6 Suppl. 2): 155-169. DENTAL SUPPLEMENT, 2019.
Article in English | MEDLINE | ID: mdl-32425036

ABSTRACT

The rarely diagnosed persistent trigeminal artery (PTA) originates from the posterior bend or lateral wall of the intracavernous carotid artery and is the most common occurring type of remnant primitive fetal arteries. Even if PTA is uncommon, information and awareness about it could be of great help for clinicians dealing with cranial vascular imaging and operating this region. In addition, it could give a supporting response to the presence of a wide range of idiopathic and unresponsive disturbs that sometimes are erroneously interpreted and treated. There are very few published scientific reports of coexisting PTA and unilateral trigeminal neuralgia and migraine-cephalgia (MC). In this review we describe few reported and unreported cases regarding the manifestation of unresponsive trigeminal neuralgia and migraine due to the presence of PTA. Patients usually present with a clinical symptomatology with unstable blood hypertension, pain of typical trigeminal neuralgia and MC that cover unilaterally the occipital area over the second and third divisions of the nerve. The outbreaks may often become more severe during physical exertion, stress and hypertension. Angio-MRI may reveal the PTA with an occasional occurrence of parietal cavernoma. We also describe a case of chronic left MC case associated with an adjacent PTA close to the trigeminal nerve position. The size and location of the PTA was confirmed by a CT-Angiography. The MC was safely treated by bio-identical testosterone, human placenta extract (HPE), b-nicotinamide adenine dinucleotide (NADH) and low dose amlopidine. It is hypothesized that these types of primitive anastomose arteries that fully belong to the intracranial arterial vascular system do not perform any supportive functional activity. Nevertheless, they undergo the normal biological decay caused by the aging process and metabolic dysfunctions. Therefore, such primitive fetal arteries as PTA might be subjected not only to a faster structural deterioration but they would actively contribute to a series of mechanisms causing a variety of idiopathic intracranial vascular and structural symptoms. Consequently, this would change the primary therapeutic approach to solve this problem, today represented by surgical removal. Anatomic implications related to treatment procedure are also discussed.


Subject(s)
Arteries/pathology , Inflammation/therapy , Migraine Disorders/therapy , Trigeminal Neuralgia/therapy , Arteries/innervation , Humans , Trigeminal Nerve
14.
J Biol Regul Homeost Agents ; 33(6 Suppl. 2): 59-67. DENTAL SUPPLEMENT, 2019.
Article in English | MEDLINE | ID: mdl-32425025

ABSTRACT

The aim of this literature review article is to evaluate the new surgical technique "Surgery-First" and compare it with the conventional orthognathic surgery in terms of treatment length, patient satisfaction and post-surgical stability. The goal is to compare the pro and cons of the two techniques and to determine which technique can offer more efficient results.


Subject(s)
Orthognathic Surgical Procedures/methods , Humans , Patient Satisfaction
15.
J Biol Regul Homeost Agents ; 33(6 Suppl. 2): 23-29. DENTAL SUPPLEMENT, 2019.
Article in English | MEDLINE | ID: mdl-32425021

ABSTRACT

Persistent trigeminal artery (PTA) originates from the posterior bend or lateral wall of the intra-cavernous carotid artery and is the most common occurring type of remnant primitive fetal arteries. In literature, there is limited number of reports on migraine-cephalgia (MC) associated with coexisting PTA. The primitive anastomose arteries that fully belong to the intracranial arterial vascular system are not supposed to perform any supportive functional activity; usually they are subjected to normal biological decay caused by the aging process and metabolic dysfunctions. The hypothesis suggests that these primitive fetal arteries such as PTA may not undergo a fast and structural deterioration but they might be active contributors to a series of mechanisms that can cause a variety of idiopathic complaints. Consequently this would bring a different therapeutic approach other than their surgical removal, which is the accepted option today as a solution for these problems. In this case report, a chronic unilateral MC due to coexisting PTA adjacent to trigeminal nerve is presented. The caliber and location of the PTA was confirmed by a CT-Angiography. The MC treatment was achieved by administration of bio-identical testosterone, human placenta extract (HPE), b-nicotinamide adenine dinucleotide (NADH) and low dose amlopidine.


Subject(s)
Carotid Artery, Internal/pathology , Migraine Disorders/etiology , Migraine Disorders/therapy , Carotid Arteries , Carotid Artery, Internal/innervation , Computed Tomography Angiography , Headache/etiology , Headache/therapy , Humans , Trigeminal Nerve
16.
J Biol Regul Homeost Agents ; 33(6 Suppl. 2): 143-154 DENTAL SUPPLEMENT, 2019.
Article in English | MEDLINE | ID: mdl-32425035

ABSTRACT

Osseo-degeneration is a disorder related to several factors, that may lead to the disruption of several skeletal regions providing support, such as the femur head, the vertebrae and the alveolar bone. The functional condition can be restored by means of grafting procedures, using different materials: calcium powder, xenografts, ceramics and metals. Such procedures aim at reforming an adequate bone volume and strength, that is necessary to support loading forces. Bone regeneration requires that the basic biological principles of osteogenesis, osteoinduction, osteoconduction and biocompatibility are followed. The success of regenerative procedures may depend on the inner structural, mechanical and metabolic condition of the host's bone on which implants should be inserted, on the surgical technique, and on the biomaterial used. Among these, the aging process of the patient appears to be relevant. It can be associated with metabolic disease leading to systemic functional decay, which involves a gradual steady decline of hormonal, immune function and osteo-metabolic activity. The latter can affect the positive outcomes of bone reconstruction and implant therapy. This review will analyze the biological and physiological factors involved in the bone tissue break-down, such as the influences from gut microbiome unbalance and the consequent metabolic, endocrine, immune dysfunctions, the surgery procedures and the quality of the grafting material used. The decline of bone architecture and strength should be corrected by using an appropriate clinical regenerative approach, based on a bio-endocrine, metabolic and immunologic know-how. The final characteristics of the regenerated bone must be able to support the loading forces transmitted by the implants, independent of the body location, and should be individualized according to the different condition of each patient.


Subject(s)
Bone Diseases/therapy , Bone Substitutes , Bone Regeneration , Bone Transplantation , Bone and Bones , Ceramics , Gastrointestinal Microbiome , Humans , Osteogenesis
17.
J Biol Regul Homeost Agents ; 33(6 Suppl. 2): 31-39. DENTAL SUPPLEMENT, 2019.
Article in English | MEDLINE | ID: mdl-32425022

ABSTRACT

Our group recently developed an innovative maxillary sinus augmentation technique without the need of sinus membrane elevation, termed as "IPG" DET protocol. This technique utilizes autologous platelet concentrates (including platelet rich plasma (PRP), platelet rich fibrin (PRF), growth factors (GFs) and CD34+ stem cells), together with bone grafting materials positioned through intentionally perforated Schneider's membrane for flapless implant placement. This study aimed at evaluating the performance of "IPG" DET protocol in terms of new bone formation and implant stability at 8 months post-op. This prospective study consisted of forty-eight patients with a mean age of 52.8 years. A total of eighty-five implants were placed with "IPG" DET protocol in combination with autologous platelet concentrates. CBCT (cone beam computed tomography) was performed at two different time points: pre-operatively and at 8 months post-op. CBCT images were then compared by an intensity-based image algorithm to assess the newly formed bone in terms of gray scale values. Additionally, implant stability quotient (ISQ) was used to estimate implant osseointegration and success rate. The average new bone formation was 5.9 ± 0.9 mm2 per implant. All implants successfully osseointegrated, and ISQ ranged 62.3-71.7. According to the results of this study, "IPG" DET protocol in combination with autologous platelet concentrates is a successful technique for implant-supported rehabilitation of the edentulous posterior maxilla without the need of sinus floor elevation.


Subject(s)
Dental Implants , Platelet-Rich Fibrin , Sinus Floor Augmentation , Spiral Cone-Beam Computed Tomography , Bone Transplantation , Humans , Maxillary Sinus/diagnostic imaging , Maxillary Sinus/surgery , Middle Aged , Prospective Studies
18.
J Biol Regul Homeost Agents ; 32(5): 1323-1328, 2018.
Article in English | MEDLINE | ID: mdl-30334433

ABSTRACT

Oral bacteria that degrade sulphur-containing amino acids (cysteine, cystine, and methionine) produce volatile sulphur compounds (VSCs = hydrogen sulphide, methyl mercaptan, and dimethyl sulphide) highly correlated with halitosis. When these bacteria are given the right environment, i.e. periodontal disease, cariogenic biofilm or food source they can grow in number very quickly and will start to convert proteins to VSC that, together with volatile fatty acids are largely responsible for oral malodor. Recently, the prevention of dental caries and periodontal diseases using various probiotics has been attempted. The purpose of this study was to investigate the effects of probiotics based on in vitro analysis, such as antibacterial activity, and to evaluate the neutralizing effect of probiotics on halitosis, the levels of VSCs were measured by gas chromatography. .


Subject(s)
Halitosis/diet therapy , Halitosis/microbiology , Periodontal Diseases/diet therapy , Periodontal Diseases/microbiology , Probiotics/therapeutic use , Sulfur Compounds/analysis , Chromatography, Gas , Halitosis/metabolism , Humans , In Vitro Techniques , Odorants/analysis , Odorants/prevention & control , Periodontal Diseases/metabolism
19.
J Biol Regul Homeost Agents ; 32(5): 1329-1334, 2018.
Article in English | MEDLINE | ID: mdl-30334434

ABSTRACT

Dental plaque-related diseases (cavities, gingivitis, periodontitis and halitosis) have been traditionally controlled by mechanical non-specific removal of plaque. However, many novel treatment approaches aim to inhibit the growth of pathogenic bacteria or to remove their toxins. Probiotics are viable microorganisms which, when administered in adequate amounts, provide a health benefit to the host. Recently, probiotics have been applied as new tools for the improvement of dental health. They have been used to substitute existing antibiotic treatments due to increased resistant bacteria. Probiotics not only have antibacterial activity, but they also have inhibitory effects on the reappearance of oral pathogenic bacteria. The aim of this study was to assess the clinical effect of the administration of probiotics agents in the treatment of mild to moderate periodontitis.


Subject(s)
Oral Health , Periodontal Diseases/diet therapy , Periodontal Diseases/microbiology , Probiotics/therapeutic use , Humans , Probiotics/administration & dosage
20.
J Biol Regul Homeost Agents ; 31(2): 529-534, 2017.
Article in English | MEDLINE | ID: mdl-28685563

ABSTRACT

Acrylates and methacrylates are a large group of chemically reactive monomers that are polymerized into acrylic plastics. These have very broad applications in glues, coatings and various plastic materials. Allergic contact dermatitis (ACD) caused by acrylates can be occupational, mainly in dentistry workers during the manufacturing and implantation of dental prosthesis, and in nail technicians during the sculpturing and application of artificial nails. The clinical manifestations vary according to the location of the contact. In non-occupational ACD, hand eczema, pulpitis and stomatitis are more frequent. We conducted a study to investigate the frequency of sensitization to acrylates, determining the most frequently sensitizing acrylates and assessing the possible role of 2-hydroxyethyl methacrylate (2-HEMA) as a screening allergen. From January 2013 to December 2014, 217 patients with a personal history and symptoms suggestive of contact dermatitis were patch tested with an extended series of acrylates at the Dermatology and Allergology Units of the University Hospital of Bari. Seven patients (3.2%) had positive reactions. The reactions were related to artificial nails in 2 patients (28.6%), both beauticians, and dental material in 5 patients (71.4%) with dental prosthesis. 2-HEMA detected 100%of sensitized patients to acrylates.


Subject(s)
Acrylates/toxicity , Dental Prosthesis , Dermatitis, Allergic Contact/diagnosis , Dermatitis, Allergic Contact/epidemiology , Occupational Exposure/adverse effects , Adult , Aged , Female , Humans , Male , Middle Aged
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