Publications by authors named "Manoela Domingues Martins"

124 Publications

Impact of photobiomodulation in a patient-derived xenograft model of oral squamous cell carcinoma.

Oral Dis 2021 Jul 17. Epub 2021 Jul 17.

Oral Diagnosis Department, Piracicaba Dental School, University of Campinas, Piracicaba-SP, Brazil.

Background: Photobiomodulation therapy (PBMT) is an effective method for the prevention of oral mucositis. However, the effects of PBMT on oral squamous cell carcinoma (OSCC) have not yet been fully elucidated. This study aimed to evaluate the impact of PBMT in an OSCC-patient-derived xenograft (OSCC-PDX) model.

Methods: BALB/c nude mice with OSCC-PDX models were divided into Control, without PBMT (n=8); Immediate irradiation, PBMT since one week after tumor implantation (n=6); and Late irradiation, PBMT after tumors reached 200mm (n=6). OSCC-PDX were daily irradiated (660nm; 100mW; 6J/cm ; 0,2J/point) for 12 weeks. The tumors were collected and submitted to volumetric, histological, immunohistochemistry, and cell cycle analysis.

Results: No significant differences in the volumetric measurements (p=0.89) and in the histopathological grade (p>0.05) were detected between the groups. The immunohistochemical analysis of Ki-67 (p=0.9661); H3K9ac (p=0.3794); and BMI1 (p=0.5182), and the evaluation of the cell cycle phases (p>0.05) by flow cytometry also did not demonstrate significant differences between the irradiated and non-irradiated groups.

Conclusion: In this study, PBMT did not impact the behavior of OSCC-PDX models. This is an important preclinical outcome regarding safety concerns of the use of PBMT in cancer patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/odi.13967DOI Listing
July 2021

Immunohistochemical expression of OCT4 and CD44 in major and minor salivary gland neoplasms.

Braz Oral Res 2021 16;35:e073. Epub 2021 Jun 16.

Universidade Federal do Rio Grande do Norte - UFRN, Department of Dentistry, Natal, RN, Brazil.

The aim of this study was to identify tumor parenchyma cells exhibiting immunohistochemical profile of stem cells by evaluating the immunoreactivity of OCT4 and CD44 in a number of cases of salivary gland neoplasms. The sample consisted of 20 pleomorphic adenomas, 20 mucoepidermoid carcinomas, and 20 adenoid cystic carcinomas located in major and minor salivary glands. The expression of OCT4 and CD44 was evaluated by the percentage of positive cells and the intensity of expression. All studied cases showed positive expression of OCT4 and CD44 and higher values than the control groups. For OCT4, luminal and non-luminal cells were immunostained in the case of pleomorphic adenomas and adenoid cystic carcinomas. Moreover, the immunoreactivity of CD44 was particularly evident in the non-luminal cells of these lesions. In mucoepidermoid carcinomas, there was immunoreactivity for both markers in squamous and intermediate cells and absence of staining in mucous cells. For both markers, a significantly higher immunostaining was verified in neoplasms located in the major salivary glands compared with lesions in minor salivary glands (p<0.001). In the total sample and in minor salivary glands, malignant neoplasms exhibited higher immunoreactivity for OCT4 than pleomorphic adenoma. A significant moderate positive correlation (r = 0.444 and p ≤ 0.001) was found between OCT4 and CD44 immunoexpression in the total sample. The high expression of OCT4 and CD44 may indicate that these proteins play an important role in identifying tumor stem cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1590/1807-3107bor-2021.vol35.0073DOI Listing
June 2021

Analysis of referrals to the stomatology service in a Southern Brazilian hospital: a retrospective study.

Braz Oral Res 2021 16;35:e072. Epub 2021 Jun 16.

Universidade Federal do Rio Grande do Sul - UFRGS, School of Dentistry, Department of Oral Pathology, Porto Alegre, RS, Brazil.

This paper intends to describe the demand for referrals to the stomatology service requested by the medical teams for inpatients in a reference hospital in the south of Brazil. This research is a retrospective cross-sectional descriptive study focusing on data collection and assessment of information about referrals to the stomatology unit carried out from January 2008 to December 2018. All information was obtained from the hospital management software database, then transferred and analyzed individually for descriptive statistics. A total of 4433 cases were referred to the stomatology team, with an average of 403 cases by year. Hematology/hemato-oncology (37.3%) was the specialty asking for the majority of the referrals, followed by Oncology (20.4%) and Pneumology (8.2%). The mean patients' profile was males (55.5%), receiving a diagnosis of oral mucositis (43.5%), and with the first and second decades of life being the most prevalent ones (34.9%), with a mean age of 34.8±22.3 years. The most common treatment performed by the stomatology team was the photobiomodulation therapy (44.8%). This retrospective study demonstrated the important profile of the stomatological care in hospitalized patients from a specific hospital, especially referred by the hematology/hemato-oncology team. These results evidenced the importance of the stomatology specialty in the hospital environment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1590/1807-3107bor-2021.vol35.0072DOI Listing
June 2021

Mantle cell lymphoma, malt lymphoma, small lymphocytic lymphoma, and follicular lymphoma of the oral cavity: An update.

J Oral Pathol Med 2021 Jul 1;50(6):622-630. Epub 2021 Jul 1.

Department of Oral Diagnosis, Piracicaba Dental School, University of Campinas, Piracicaba, Brazil.

Background: Although uncommon, mature small B-cell lymphomas may arise in the oral/maxillofacial area and oral pathologists must be aware of the key characteristics of these neoplasms to perform an accurate diagnosis. In this manuscript, we attempted to integrate the currently available data on the clinicopathological features of follicular lymphoma (FL), mantle cell lymphoma (MCL), extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT-L), and chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/SLL) affecting these anatomical regions.

Methods: An updated descriptive literature review was carried out and a detailed electronic search was done in multiple databases to gather all cases affecting the oral/maxillofacial region and palatine tonsils.

Results: We observed that MALT-L was the most frequently reported subtype, followed by FL, MCL, and CLL/SLL. The palate was affected in a high proportion of cases and the most usual clinical presentation was an asymptomatic swelling. MALT-L and CLL/SLL neoplastic cells were strongly associated with small salivary glands. FL showed no gender preference, while MCL and CLL/SLL were more prevalent in males and MALT-L in females. Overall, cases were more common in elderly individuals. Patients' treatment and outcome varied, with MCL being the most aggressive neoplasm with a dismal prognosis in comparison to FL and MALT-L.

Conclusion: Despite the poor documentation in many of the cases available, especially regarding the microscopic and molecular features of tumors, this review demonstrated that the oral mature small B-cell lymphomas investigated share similar clinical presentation, but carry different prognostic significance, demanding an accurate diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jop.13214DOI Listing
July 2021

Oral and oropharyngeal lymphomas: A multi-institutional collaborative study.

J Oral Pathol Med 2021 Jul 30;50(6):603-612. Epub 2021 Jun 30.

Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

Background: Lymphomas in the oral and oropharyngeal regions are relatively uncommon, and their diagnosis is challenging and complex due to the myriad histopathological subtypes. Herein, we report a large series of oral and oropharyngeal lymphomas and compare our data with the currently available literature.

Methods: All cases diagnosed as lymphomas affecting the oral and oropharyngeal regions were retrospectively retrieved from seven Brazilian institutions. Clinicodemographic data and histopathological features were evaluated and described, while a comprehensive literature review was undertaken in order to compare our findings.

Results: A total of 304 cases of oral and oropharyngeal lymphomas were obtained, mostly affecting individuals aged 60-69 years (n = 68) with a mean age at diagnosis of 54.2 ± 20.1 years. Males and females were equally affected. Mature B-cell neoplasms (87.2%) were the most common group, followed by mature T- and NK-cell neoplasms (11.2%) and precursor lymphoid neoplasms (1.6%). The most frequent subtypes in each group were diffuse large B-cell lymphomas, not otherwise specified (n = 99), extranodal NK/T-cell lymphomas, nasal type (n = 12), and B-lymphoblastic leukaemia/lymphomas, not otherwise specified (n = 4). The most commonly involved sites were the palate (26.3%), mandible (13%), and maxilla (10.5%).

Conclusion: Diffuse large B-cell lymphoma, not otherwise specified, remains the most common subtype of lymphomas in the oral and oropharyngeal region. Older patients are the most affected, with no gender predilection and the palate and jaw are usually affected.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jop.13211DOI Listing
July 2021

Mature T/NK-Cell lymphomas of the oral and maxillofacial region: A multi-institutional collaborative study.

J Oral Pathol Med 2021 Jul 29;50(6):548-557. Epub 2021 Jun 29.

Department of Oral Diagnosis and Pathology, School of Dentistry, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

Background: The diagnosis of oral and maxillofacial mature T/NK-cell neoplasms is challenging because of their rarity, morphological heterogeneity and complex immunophenotype with scarce available data describing their clinical and microscopic aspects. Therefore, in this study, we investigated a series of mature T/NK-cell neoplasms affecting this anatomical region and provided an updated literature review.

Methods: Cases diagnosed as mature T/NK-cell lymphomas affecting the oral and maxillofacial region were retrospectively retrieved from six pathology files and their diagnoses were confirmed using haematoxylin and eosin-stained slides, immunohistochemical reactions and in situ hybridization for Epstein-Barr virus (EBV) detection. Patients' clinical data were collected from their pathology forms.

Results: A total of 22 cases were included in this study. Eleven (50%) consisted of extranodal NK/T-cell lymphomas, nasal type; eight (36.4%) were peripheral T-cell lymphomas, NOS; two (9.1%) were adult T-cell leukaemia/lymphomas, and one (4.5%) was an ALK-positive anaplastic large cell lymphoma. Overall, males predominated, with a mean age of 55.7 years. The palate was the most affected site (50%), and tumours usually presented as destructive and painful ulcers. EBV was present in all cases of extranodal NK/T-cell lymphoma nasal type but was absent in the other subtypes.

Conclusion: Among mature T/NK-cell lymphomas of the oral and maxillofacial region, extranodal NK/T-cell lymphoma, nasal type and peripheral T-cell lymphoma, NOS predominated. Older men were the most affected patients, and this heterogeneous group of neoplasms has a very aggressive clinical behaviour.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jop.13205DOI Listing
July 2021

Oral lymphangioma-like Kaposi sarcoma: a Brazilian case report in a scenario of a still high number of HIV infections.

Oral Maxillofac Surg 2021 Jun 5. Epub 2021 Jun 5.

Oral Diagnosis Department, Piracicaba Dental School, University of Campinas (UNICAMP), Av. Limeira, Areão, Piracicaba, São Paulo, Brazil.

We present a challenging case of HIV-related lymphangioma-like Kaposi sarcoma (LLKS) affecting the oral cavity. A 54-year-old Brazilian male patient was referred to our center complaining of bleeding lesions affecting the oral cavity for 2 months. Interestingly, these oral lesions were the first clinical manifestation of HIV infection. Clinically, multiple erythematous nodular and patch lesions were observed. An incisional biopsy was performed, revealing numerous microscopic angled and irregular vascular channels lined with flattened endothelial cells. More cellularized and solid areas consisting of more fusiform cells with little pleomorphism and with slit-like vascular channels were noted. Based on immunoreactivity for CD31, CD34, D2-40, and HHV-8, the final diagnosis was oral LLKS. Highly active antiretroviral therapy (HAART) was initiated with dolutegravir, tenofovir, and lamivudine. During follow-up, the patient showed KS metastases to other sites and a chemotherapeutic protocol was initiated. Regression of the oral lesion was clearly noted by the clinicians 1 year after the KS diagnosis. Dentists should be able to recognize systemic diseases that affect the oral cavity such as KS in order to make an early diagnosis of its oral manifestations and to implement effective therapeutic measures to ensure a better prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10006-021-00974-8DOI Listing
June 2021

Direct costs associated with the management of mucositis: A systematic review.

Oral Oncol 2021 Jul 29;118:105296. Epub 2021 Apr 29.

Oral Diagnosis Department, Piracicaba Dental School, University of Campinas (UNICAMP), Av. Limeira, 901, Bairro Areião, 13414-903 Piracicaba, São Paulo, Brazil; Dental Oncology Service, São Paulo State Cancer Institute (ICESP-FMUSP), Av. Dr. Arnaldo, 251, Cerqueira César, 01246-000 São Paulo, São Paulo, Brazil. Electronic address:

Mucositis is one of the more frequent and costly adverse events following cancer treatment. To evaluate and report the direct economic outcomes associated with the management of mucositis across several cancer treatments we conducted a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Scopus, MEDLINE/PubMed, and Embase were searched electronically and a total of 37 relevant studies were included. The costs attributable to mucositis in the hematopoietic stem cell transplantation setting ranged from 1124,47 US dollars (USD) to 299 214,14 USD per patient. The radiotherapy/chemoradiotherapy/radiotherapy plus molecular targeted therapy accounted for mucositis costs that ranged from 51,23 USD to 33 560,58 USD per patient. Costs for mucositis in the chemotherapy setting ranged from 4,18 USD to 31 963,64 USD per patient. When the cancer treatment was not specified, costs of mucositis ranged from 565,85 USD to as high as 20 279, 12 USD per patient. Mucositis costs from multimodal therapy ranged from 12,42 USD to 5670,46 USD per patient. The molecular targeted therapy setting included only one study and depending on the healthcare providers' perspective of each country evaluated, mucositis' costs ranged from 45,78 USD to 3484,91 USD per patient. Mucositis is associated with increased resource use, consultations, hospitalizations and extended hospitalizations, leading to a substantial incremental cost that exacerbates the economic burden on the patient, health plan and health system across several cancer treatments and diagnosis. More studies with a prospective evaluation of the economic costs associated with mucositis management are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.oraloncology.2021.105296DOI Listing
July 2021

Intraoral versus extraoral photobiomodulation therapy in the prevention of oral mucositis in HSCT patients: a randomized, single-blind, controlled clinical trial.

Support Care Cancer 2021 Apr 27. Epub 2021 Apr 27.

Stomatology Department, A.C. Camargo Cancer Center, Sao Paulo, Brazil.

To compare the efficacy of intraoral and extraoral photobiomodulation (PBM) protocols for the prevention of oral mucositis (OM) in hematopoietic stem cell transplantation (HSCT) patients. A total of 60 patients was randomized into intraoral PBM (IOPBM) and extraoral PBM (EOPBM) groups. Both PBM protocols were well tolerated and no side effects were observed. EOPBM session times were one fourth of IOPBM durations. Of 60 patients, 35 (58.3%) developed ulcerated OM between day +3 and day +12. No intergroup difference was observed in OM healing times (p = 0.424). The lateral border of the tongue was the most common site affected in both groups. However, the incidence of mucositis on buccal mucosa was significantly reduced in the EOPBM group (p = 0.021). Young patients (OR.5.35, 95%CI 0.94-30.4, p = 0.058) and those who had received myeloablative conditioning (OR.55.1, 95%CI 2.69-1129.3, p = 0.009) were more likely to develop ulcerated OM, whereas autologous HSCT recipients (OR 0.079, 95% CI 0.009-0.67, p = 0.021) had a lower probability of developing ulcerated OM independent of PBM protocol. EOPBM protocol was as effective as IOPBM in the management of OM in HSCT patients, with the advantage of shorter treatment sessions. Trial registration number: RBR-7nww56. Date of trial registration submission: 30th September 2019.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00520-021-06228-3DOI Listing
April 2021

Incidence and risk factors for oral mucositis in pediatric patients receiving chemotherapy.

Support Care Cancer 2021 Apr 12. Epub 2021 Apr 12.

Department of Oral Pathology, School of Dentistry, Federal University of Rio Grande do Sul, Rua Ramiro Barcelos, 2492, sala 503, CEP: 90035-003 Santana, Porto Alegre, RS, Brazil.

Purpose: To investigate the incidence and risk factors for oral mucositis (OM) in patients with childhood cancer undergoing chemotherapy.

Methods: Eight hundred and twenty-nine cycles of chemotherapy were evaluated in 112 patients with childhood cancer undergoing chemotherapy. Chemotherapy protocol, hematological, hepatic, and renal function parameters were collected and compared to presence and severity of OM, as graded by the World Health Organization (WHO) scale. Patients received counseling on oral hygiene and those who presented with OM (grade ≥1) received photobiomodulation therapy (PBMT).

Results: Age ranged from 0 to 17 years (mean/SD, 8.58 ± 5.05) and fifty-one patients (45.54%) were females. The most common baseline diseases were leukemia (51%) followed by sarcomas (23%) and lymphomas (18%). Eight hundred and twenty-nine cycles of chemotherapy were evaluated, and OM was diagnosed in 527 cycles (63.57%). Higher incidence and severity of OM was observed in protocols using high-dose methotrexate (MTX-HD), MTX-HD cyclophosphamide/doxorubicin combination, and MTX-HD combined with cyclophosphamide (p <0.001). Patients with severe OM had lower levels of leukocytes (p = 0.003), hemoglobin (p = 0.005), platelets (p = 0.034), and higher levels of total bilirubin (p = 0.027), alanine aminotransferase (ALT) (p = 0.001), and creatinine (p = 0.007).

Conclusion: The study contributes to the elucidation of the risk factors for OM in pediatric cancer patients. Chemotherapy protocols using MTX-HD, MTX-HD associated with doxorubicin and cyclophosphamide, and MTX-HD and cyclophosphamide a have higher incidence of severe grades of OM. Other toxicities such as hematological, hepatic, and renal also developed in patients with OM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00520-021-06199-5DOI Listing
April 2021

Risk factors associated with the development of oral mucositis in pediatric oncology patients: Systematic review and meta-analysis.

Oral Dis 2021 Mar 28. Epub 2021 Mar 28.

Department of Oral Pathology, School of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.

Objectives: Oral mucositis (OM) is an acute toxicity related to cancer treatment. This systematic review aimed to identify potential risk factors associated with the development of OM in pediatric cancer patients.

Methods: A search was performed in four electronic databases to identify studies that analyzed risk factors for OM in pediatric cancer patients.

Results: Nineteen articles were included. The incidence of OM ranged from 20% to 80.4%. Chemotherapeutic agents were potential risk factors for OM in eight (42%) studies. Hematological, hepatic, and renal parameters were also considered in eight (42%) studies, while specific individual factors were reported in five (26.3%) studies. Baseline disease, oral microbiota, genetic profile, and biomarkers were reported in four (21.5%) studies each. Meta-analysis showed that groups submitted to high-risk chemotherapy for OM had a 2.79-fold increased risk of OM.

Conclusions: Identifying risk factors for OM is essential in order to allow individualized and early prevention treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/odi.13863DOI Listing
March 2021

Effects of photobiomodulation in salivary glands of chronic kidney disease patients on hemodialysis.

Lasers Med Sci 2021 Aug 20;36(6):1209-1217. Epub 2021 Mar 20.

Universidade Nove de Julho (UNINOVE), R. vergueiro, 235 Liberdade, São Paulo, SP, Brazil.

This randomized placebo-controlled trial evaluates the impact of photobiomodulation (PBMT) on the salivary flow and biochemistry of patients with chronic kidney disease (CKD) on hemodialysis. Forty-four patients on hemodialysis self-responded two questionnaires for oral health and salivary gland function perception. The subjects were evaluated for function of salivary glands and randomly allocated to two groups: PBMT group (three irradiations at 808 nm, 100 mW, 142 J/cm, and 4 J per site); and placebo group. Patients were submitted to non-stimulated and stimulated sialometry and after the treatment at baseline and 14 days. Salivary volume and biochemical of the saliva were analyzed. At baseline, most subjects had self-perception of poor oral health (52.6%) and salivary dysfunction (63.1%). Clinical exam revealed that 47.3% of subjects presented dry mucosa. PBMT promoted increase of the non-stimulated (p = 0.027) and stimulated saliva (p = 0.014) and decrease of urea levels in both non-stimulated (p = 0.0001) and stimulated saliva (p = 0.0001). No alteration was detected in total proteins and calcium analysis. Patients with kidney disease can present alteration in flow, concentrations, and composition of saliva, affecting oral health, but our findings suggest that PBMT is effective to improve hyposalivation and urea levels in saliva of patients with CKD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10103-020-03158-0DOI Listing
August 2021

Fully digital pathology laboratory routine and remote reporting of oral and maxillofacial diagnosis during the COVID-19 pandemic: a validation study.

Virchows Arch 2021 Mar 13. Epub 2021 Mar 13.

Oral Diagnosis Department, Semiology and Oral Pathology Areas, Piracicaba Dental School, University of Campinas (UNICAMP), Av. Limeira, 901, Bairro Areião, Piracicaba, SP, 13414-903, Brazil.

The role of digital pathology in remote reporting has seen an increase during the COVID-19 pandemic. Recently, recommendations had been made regarding the urgent need of reorganizing head and neck cancer diagnostic services to provide a safe work environment for the staff. A total of 162 glass slides from 109 patients over a period of 5 weeks were included in this validation and were assessed by all pathologists in both analyses (digital and conventional) to allow intraobserver comparison. The intraobserver agreement between the digital method (DM) and conventional method (CM) was considered almost perfect (κ ranged from 0.85 to 0.98, with 95% CI, ranging from 0.81 to 1). The most significant and frequent disagreements within trainees encompassed epithelial dysplasia grading and differentiation among severe dysplasia (carcinoma in situ) and oral squamous cell carcinoma. The most frequent pitfall from DM was lag in screen mirroring. The lack of details of inflammatory cells and the need for a higher magnification to assess dysplasia were pointed in one case each. The COVID-19 crisis has accelerated and consolidated the use of online meeting tools, which would be a valuable resource even in the post-pandemic scenario. Adaptation in laboratory workflow, the advent of digital pathology and remote reporting can mitigate the impact of similar future disruptions to the oral and maxillofacial pathology laboratory workflow avoiding delays in diagnosis and report, to facilitate timely management of head and neck cancer patients. Graphical abstract.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00428-021-03075-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955219PMC
March 2021

Effects of osteoporosis on alveolar bone repair after tooth extraction: A systematic review of preclinical studies.

Arch Oral Biol 2021 May 23;125:105054. Epub 2021 Jan 23.

Department of Oral Pathology, School of Dentistry, Federal University of Rio Grande do Sul, R. Ramiro Barcelos, 2492, CEP: 90035-003, Porto Alegre, RS, Brazil; Oral Diagnosis Department, Piracicaba Dental School, University of Campinas, Av. Limeira, 901, CEP: 13414-903, Piracicaba, SP, Brazil. Electronic address:

Objective: This systematic review aimed to address whether the alveolar socket repair after a tooth extraction is impacted by an osteoporotic phenotype and propose methodological observations.

Design: A search strategy in MEDLINE/PubMed, EMBASE, Web of Science, and Scopus databases was performed. Quality assessment was carried out through the SYRCLE Risk of Bias tool.

Results: Out of the 1147 potentially relevant records, 25 met the inclusion criteria. Most of the studies were performed in rats, and ovariectomy (OVX) was the most frequent osteoporosis induction method. Histomorphometry, micro-computed tomography (microCT), and immunohistochemistry were the main bone repair evaluation methods. Most of the included studies (88 %) presented negative impacts of osteoporosis on the alveolar socket repair. Only three studies (12 %) showed no statistical differences among groups. Overall, most of the quality assessment categories presented a high percentage of unclear risk of bias due to insufficient information in the studies.

Conclusions: The results indicated that an osteoporotic phenotype seems to impair alveolar socket repair after tooth extraction. However, there is still a lack of information and standardization. Therefore, further studies should consider the proposed methodological aspects regarding animal characteristics, OVX associated with a low calcium diet, waiting 8 weeks to osteoporosis induction, maxillary molars as the best option for tooth extraction, confirming and reporting OVX and osteoporosis success, and an appropriate method of repair analysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.archoralbio.2021.105054DOI Listing
May 2021

Osteoblastoma of the mandible in a male patient: a case report.

Gen Dent 2021 Mar-Apr;69(2):60-63

Osteoblastoma is a rare benign osteoblastic tumor accounting for less than 1% of all bone tumors; approximately 10% to 12% of cases occur in the maxillofacial skeleton. This case report describes the clinical, imaging, and histopathologic findings of an atypical osteoblastoma occurring in the mandible of a 60-year-old man. The characteristics of the lesion and the differential diagnosis from other bone pathoses are reviewed.
View Article and Find Full Text PDF

Download full-text PDF

Source
March 2021

The impact of the COVID-19 pandemic on hospitalizations for oral and oropharyngeal cancer in Brazil.

Community Dent Oral Epidemiol 2021 06 1;49(3):211-215. Epub 2021 Mar 1.

Faculty of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.

Timely diagnosis and treatment of oral and oropharyngeal cancers are central for the patient's survival. Our objective was to document the impact of the COVID-19 pandemic on the rate of hospitalizations due to these cancers in Brazil's National Health System (SUS). The number of hospitalizations by these cancers during the first periods of the pandemic-and between the same period of 2016 to 2019-was retrieved from the SUS Hospital Information System. We compared hospitalization rates between pre- and pandemic periods, by State. The hospitalization rate for oral and oropharyngeal cancer during the pandemic was lower than that of the same period of previous years. The decline between 2019 and 2020 was of 49.3%, reaching 60% in the North. The reduction in hospitalization during an extended period suggests that oral and oropharyngeal cancer care will be postponed, with potentially detrimental impact on survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cdoe.12632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013296PMC
June 2021

Oral and oropharyngeal diffuse large B-cell lymphoma and high-grade B-cell lymphoma: A clinicopathologic and prognostic study of 69 cases.

Oral Surg Oral Med Oral Pathol Oral Radiol 2021 Apr 20;131(4):452-462.e4. Epub 2020 Nov 20.

Private Pathology Service, Natal, Rio Grande do Norte, Brazil.

Objective: The objective of this study was to describe the clinicopathological, molecular, and prognostic features of oral/oropharyngeal diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma.

Study Design: All cases were retrieved from 7 Brazilian institutions. Immunohistochemical reactions were performed to confirm the diagnoses and to categorize the tumors. In situ hybridization was used to detect Epstein-Barr virus (EBV) and fluorescence in situ hybridization was used to identify gene rearrangements.

Results: Most cases involved the oral cavity (76.8%). Males and females, with a mean age of 60 years, were evenly affected. Tumors mostly presented as painful swellings. Forty cases represented germinal center B-cell type (58%). Five cases presented double-hit translocation and 3 harbored rearrangement for MYC/BCL2/BCL6. EBV was detected in 3 cases (4.3%). The 5-year overall survival was 44.4%. Female sex, presence of pain and ulcer, microscopic "starry sky pattern" and necrosis, co-expression of c-Myc/Bcl2, and translocation of MYC were associated with a lower survival in univariate analysis (P = .05, P = .01, P = .01, P = .03, P = .05, P = .006, P = .05, respectively).

Conclusion: Patients affected by oral/oropharyngeal DLBCL have a low survival rate. High-grade B-cell lymphoma (17.7%) and EBV-positive DLBCL, not otherwise specified (4.3%) account for a small number of cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.oooo.2020.11.005DOI Listing
April 2021

Effectiveness of phytotherapeutics in the prevention and treatment of 5-fluorouracil-induced oral mucositis in animal models: A systematic review.

Arch Oral Biol 2021 Mar 18;123:104998. Epub 2021 Jan 18.

Post Graduate Program in Dental Sciences, Federal University of Rio Grande do Norte, Natal, RN, Brazil. Electronic address:

Objectives: This systematic review evaluated the effect of phytotherapeutics in the treatment and prevention of 5-fluorouracil (5-FU)-induced oral mucositis (OM) in animal models.

Design: A search was performed in PubMed/Medline, CENTRAL (The Cochrane Library), EMBASE, and Web of Science, including studies published up to January 2020. Only articles investigating the chemoinduction of OM by 5-FU in animal models were included. Eligibility was evaluated and data were extracted from the eligible studies following the predefined PICO questions. The Cochrane Collaboration Risk of Bias Assessment tool was used to evaluate the quality of the included studies.

Result: A total of 503 articles were retrieved and 13 were included. The hamster was the animal model used in all included studies. The treatment method ranged from the topical application of ointment (n = 3), gel (n = 5) and extract (n = 3) to the oral ingestion of the phytotherapeutics (n = 3). Chamomilla recutita L. (n = 3) and Pistacia atlantica (n = 3) were the most used therapeutic agents. Although all studies were classified as high risk of bias, all of them reported promising results regarding the use of phytotherapeutics in the management of OM, including lower clinical and histopathological scores as well as healing, anti-inflammatory, antimicrobial, and antioxidant activities.

Conclusion: Despite the high risk of bias of the studies, phytotherapy is a promising alternative for the treatment of 5-FU-induced OM, showing interesting results in terms of tissue healing and anti-inflammatory, antimicrobial and antioxidant activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.archoralbio.2020.104998DOI Listing
March 2021

Clinicopathological analysis of oral and maxillofacial acinic cell carcinoma: A systematic review.

J Oral Pathol Med 2021 Jan 17. Epub 2021 Jan 17.

Oral Diagnosis Department, Piracicaba Dental School, Universidade Estadual de Campinas, Piracicaba, SP, Brazil.

Background: The aim of the present systematic review was to analyze the available data regarding acinic cell carcinoma of the oral and maxillofacial region.

Methods: A search strategy was performed using PubMed, Web of Science, Scopus, and Embase electronic databases.

Results: Available data revealed a slight female preference (54.73%) and a mean age at diagnosis of 47.51 ± 19.85 years. The parotid glands (67.72%) were most frequently affected, and most cases were asymptomatic (69.54%). A microcystic histopathological pattern was reported in 21.56% of the cases, and the Periodic acid-Schiff was the staining method most frequently used, after the hematoxylin and eosin staining, in the tumors analyzed. The lesions were mainly treated by surgical removal (72.32%). Recurrence was reported in 81 cases (27.83%) and metastasis in 100 (42.91%). Statistical data analysis revealed that tumors located in major salivary glands and exhibiting high-grade histology were associated with local recurrence (P = .01). In addition, the patients older than 57 years, lesions with bone involvement, the high-grade tumors and the cases with a history of recurrence and metastasis were associated with a lower overall survival (P < .05).

Conclusion: By assembling all eligible cases in the literature, the present systematic review determined the most common clinicopathological profile of acinic cell carcinoma and the most relevant prognostic factors in a distinctly representative sample. The survey demonstrated the importance of considering the histopathological grading in order to better define the treatment for each case.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jop.13159DOI Listing
January 2021

Oral pigmented lesions in syndromic individuals: A systematic review.

Oral Dis 2021 Jan 4. Epub 2021 Jan 4.

Diagnostic Center for Oral Diseases, School of Dentistry, Universidade Federal de Pelotas, Pelotas, Brazil.

Objective: To systematically integrate the available data published in the literature on oral pigmented lesions (OPL) associated with syndromes, summarizing the clinical and demographic features of the individuals.

Materials And Methods: An electronic search was undertaken in six databases. Eligibility criteria were articles in English, Spanish, and Portuguese describing case reports or case series of OPL associated with syndromes. Data were aggregated and statistically evaluated.

Results: About 108 articles reporting 149 cases of individuals with syndromes were identified. Among the affected individuals, nine syndromes were reported. The mean age at diagnosis was 35.93 years (0.41 to 83 years), with a predilection for white (n = 85/85.86%) female (n = 102/68.46%) individuals. As regards the number of lesions, 109 (73.15%) were multiple and 40 (26.85%) were single. Lip represented the anatomical location more affected (122 cases/38.01%), followed by the buccal mucosa (100 cases/31.15%). Brownish lesions accounted for 82 (69.49%) cases. The mean time of evolution was 10.52 years (0.16 to 56 years). OPL preceding diagnosis of the syndrome was observed in 111 (74.50%) cases.

Conclusions: Although these syndromes are uncommon, dentists should be able to recognize their manifestations, since oral manifestations can represent an important aspect in early diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/odi.13769DOI Listing
January 2021

Management of oral care related to oncological treatment. A proposal for the "new normal".

Photodiagnosis Photodyn Ther 2021 Mar 31;33:102166. Epub 2020 Dec 31.

Stomatology Department - A.C. Camargo Cancer Center, Sao Paulo, Brazil; Stomatology Department - School of Dentistry, Sao Paulo University, Sao Paulo, Brazil. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pdpdt.2020.102166DOI Listing
March 2021

Clinicopathological analysis and survival outcomes of primary salivary gland tumors in pediatric patients: A systematic review.

J Oral Pathol Med 2021 May 8;50(5):435-443. Epub 2021 Jan 8.

Department of Oral Diagnosis, Piracicaba Dental School, State University of Campinas, Piracicaba, Brazil.

Background: Salivary gland tumors are a diverse group of uncommon neoplasms that are rare in pediatric patients. The aim of this study was to evaluate the clinicopathological profile and survival outcomes of pediatric patients affected by salivary gland tumors.

Materials And Methods: An extensive search was carried out using the MEDLINE/PubMed, EMBASE, Scopus databases, and grey literature. The risk of bias was available in all papers included.

Results: A total of 2,830 articles were initially retrieved with 54 remaining for data extraction, resulting in 2,937 cases. This comprised forty-five case series' and nine cohort studies. These tumors were slightly more prevalent in females (57.4%). The patients' age ranged from 0.3 to 19 years old, with a mean age of 13.3 years. Parotid was the most affected site (81.9%), and 99.2% of cases clinically exhibited a swelling. Presence of pain/tenderness was reported in 13.5% of the cases, with an average duration of 12.6 months for the appearance of symptoms. Most of the reported cases were malignant tumors (75.4%), with mucoepidermoid carcinoma the most common tumor of all tumors (44.8%), followed by pleomorphic adenoma (24.1%). Surgery alone was the leading treatment choice in 74.9% cases, and the 5-year overall survival rate of patients was 93.1%. Patients with symptoms (P = .001), local recurrence (P < .001), metastasis (P < .001), and those not undergoing surgery or surgery combined with radiotherapy (P < .001) showed lower survival rates.

Conclusion: The pediatric patients present a high frequency of malignant salivary neoplasms and a high overall survival rate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jop.13151DOI Listing
May 2021

Immunoexpression of BDNF, TrkB, and p75NTR receptors in peripheral neural lesions of the head and neck.

J Oral Pathol Med 2021 May 30;50(5):492-501. Epub 2020 Dec 30.

Department of Oral Pathology, School of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.

Background: Brain-derived neurotrophic factor (BDNF) and neurotrophin receptors have been recognized as fundamental regulators of normal brain development, homeostasis, and plasticity. They have also been studied in the behavior of central nervous system tumors. Here, we studied the pattern of BDNF, TrkB and p75NTR immunoexpression in peripheral benign and malignant neural lesions in head and neck.

Methods: This cross-sectional analytical study included 79 cases of head and neck neural lesions. Nineteen cases of traumatic neuromas (TN), 20 cases of granular cell tumors (GCT), 16 cases of neurofibromas (NF), 20 cases of schwannomas (SC), and 4 malignant peripheral nerve sheath tumor (MPNST) were submitted to immunohistochemistry with BDNF, TrkB, and p75NTR antibodies. A semi-quantitative analysis was performed.

Results: The analysis of BDNF demonstrated a high percentage of positive cells in TN, GCT and SC with a decrease in cases of NF and MPNST. TrkB presented a lower significant immunoexpression in GCT in relation to the TN, NF, SC, and MPNST (P < .0001); and TN showed less percentage of positive cell compared to SC (P = .0017). Regarding p75NTR, the percentage of positive cell was significantly reduced in MPNST compared GCT (P = .009), NF (P = .0138) and SC (P = .0069). Also, a decrease in TN compared to GCT (P = .007) was observed.

Conclusions: Our results showed the immunoreactivity of BDNF, TrkB, and p75NTR in head and neck peripheral neural lesions. Reduction of BDNF and p75NTR in MPNST might suggest down-regulation during the acquisition of malignant phenotype.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jop.13145DOI Listing
May 2021

Binge-Like Exposure During Adolescence Induces Detrimental Effects in Alveolar Bone that Persist in Adulthood.

Alcohol Clin Exp Res 2021 01 22;45(1):56-63. Epub 2020 Dec 22.

Laboratory of Functional and Structural Biology, (DS-M, MKMF, RRL), Biological Science Institute, Federal University of Pará, Belém, Pará, Brazil.

Background: Alcohol (EtOH) intake during adolescence has become an important public health issue. Although the detrimental effects of EtOH intake on the musculoskeletal system are well known, only a few studies have investigated its impact on the stomatognathic system of adolescents. This study aimed to investigate the effect of EtOH binge drinking on the alveolar bone and the long-term consequences after abstinence.

Methods: Adolescent female Wistar rats (35 days old) were exposed to 4 cycles of EtOH binge drinking (3 g/kg/d; 3 days On-4 days Off) or distilled water (control group). Alveolar bone micromorphology and vertical bone distance were evaluated at 1, 30, and 60 days after that last EtOH intake through X-ray computed microtomography. The mineral:matrix ratio was assessed through Raman spectroscopy.

Results: A decrease in both trabecular thickness and volume ratio, and an increase in trabecular separation were observed at the 1-day evaluation (immediate withdrawal). After 30 and 60 days, the alveolar bone parameters were found similar to control, except for the mineral:matrix ratio in the long-term abstinence.

Conclusions: EtOH binge drinking during adolescence results in alveolar bone damage that may persist in adulthood, even after abstinence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/acer.14501DOI Listing
January 2021

Methylmercury-Induced Toxicopathologic Findings in Salivary Glands of Offspring Rats After Gestational and Lactational Exposure.

Biol Trace Elem Res 2021 Aug 3;199(8):2983-2991. Epub 2020 Oct 3.

Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Para, Rua Augusto Corrêa n° 1, Campus do Guamá, Belém, Pará, 66075-110, Brazil.

Methylmercury (MeHg) is one of the main global pollutants. The vulnerability of fetus and newborn to MeHg-induced changes is extensively reported, making relevant investigation possible for alternative sample matrix for human biological monitoring for at this stage of life. This study aimed to characterize tissue change effects of environmental-experimental MeHg on salivary glands of offspring rats after pre- and postnatal exposure. For this, pregnant Wistar rats were orally exposed to MeHg (40 μg/kg BW/day) or only vehicle (control group), from the gestational period to the end of the lactation period. Salivary glands (SG) were collected from the offspring to analyze possible Hg levels and main findings by histopathological evaluations and CK19 and α-SMA immunostaining. The results indicated that Hg levels in SG of intoxicated offspring were associated with histologic abnormalities, such as acinar atrophy and an increase in the intercellular matrix among the acini, as well as damages in the architecture of epithelium and myoepithelial cells, evidenced by a decrease in immunostaining area. Thus, this is the first study to show in the literature the toxicopathologic findings on SG of offspring after pre- and postnatal exposure to MeHg. Moreover, it presents the SG as an attractive target to futures studies, mainly in children exposed to environmentally relevant doses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12011-020-02409-zDOI Listing
August 2021

Prevalence of p16 expression in oropharyngeal squamous cell carcinoma in southern Brazil.

Oral Surg Oral Med Oral Pathol Oral Radiol 2020 12 26;130(6):681-691. Epub 2020 Aug 26.

Integrated Oncology Center of Ana Nery Hospital, Santa Cruz do Sul, RS, Brazil.

Objective: Our aim was to evaluate the prevalence of human papillomavirus (HPV)-positive tumors in a cohort of patients with oropharyngeal squamous cell carcinoma (OPSCC) at a single center in southern Brazil and determine the short-term prognostic factors in this sample.

Study Design: Ninety-one consecutive patients with newly diagnosed primary OPSCC between January 2017 and December 2019 were retrospectively included. Demographic, clinical, pathologic, and survival data were collected. HPV status was determined by using p16 immunohistochemistry.

Results: The overall prevalence of HPV-positive (HPV+) OPSCC was 20.9%. Patients with HPV+ tumors presented a nodal metastasis as the first clinical sign (P = .02); reported less alcohol (P < .001) and tobacco use (P < .001); exhibited lower tumor stages (P < .001) and higher microscopic grades (P = .01); and had higher chances of having resectable tumors (P = .008). p16-negative status (P = .01); unresectable/inoperable tumors (P < .001); presence of nodal metastasis (P = .005); and higher American Joint Committee on Cancer (AJCC) stage (P = .002) were significantly associated with worse disease-specific survival.

Conclusions: The prevalence of HPV+ OPSCC in southern Brazil is relatively low, and p16-positive status was associated with Better prognosis. Higher AJCC stage, nodal metastasis, and unresectability/inoperability were associated with the highest hazard ratios for death resulting from OPSCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.oooo.2020.08.021DOI Listing
December 2020

Oral mucositis in childhood cancer patients receiving high-dose methotrexate: Prevalence, relationship with other toxicities and methotrexate elimination.

Int J Paediatr Dent 2021 Mar 11;31(2):238-246. Epub 2020 Oct 11.

Department of Oral Pathology and Oral Medicine, School of Dentistry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.

Background: Oral mucositis (OM) is one of the main adverse effects of the chemotherapeutic agent methotrexate (MTX).

Aim: To evaluate the relationship of OM with MTX metabolism time and other toxicities in childhood, cancer patients receiving high-dose of methotrexate (HD-MTX).

Design: Seventy-seven childhood patients receiving HD-MTX for treatment of leukaemia, osteosarcoma or lymphoma were evaluated. MTX serum level, hepatic and renal function parameters, and presence and intensity of OM were analysed.

Results: The patients were submitted to 255 cycles of chemotherapy. OM was diagnosed in 191 (74.9%) cycles. Of these, 119 (46.6%) presented ulcerative lesions. Lymphoma was associated with severe OM (P = .01). OM was associated with higher serum levels of aspartate aminotransferase (P = .006), alanine aminotransferase (P = .04) and creatinine (P = .008). Increase of one unit of total bilirubin and indirect bilirubin associated, respectively, with 11% and 39% higher prevalence of OM. For each increase of one unit of creatinine serum level, it was observed a 37% higher prevalence of OM in patients with lymphoma. No association was found between delayed excretion of MTX and OM development.

Conclusions: OM is a prevalent complication of childhood cancer patients receiving HD-MTX. Renal and hepatic toxicity could be considered risk factors for OM, especially in patients with lymphoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ipd.12718DOI Listing
March 2021

Prolonged caffeine intake decreases alveolar bone damage induced by binge-like ethanol consumption in adolescent female rats.

Biomed Pharmacother 2020 Oct 9;130:110608. Epub 2020 Aug 9.

Laboratory of Functional and Structural Biology, Biological Science Institute, Federal University of Pará, Belém, Pará, Brazil.

Ethanol consumption has been reported to negatively impact on periodontal disease. In particular, oral cavity disorders occur upon ethanol exposure during adolescence, a life period associated with particular patterns of short and intense ('binge-like') ethanol consumption that is most deleterious to oral health. The hazardous central effects of ethanol have been linked to the overfunction of adenosine receptors, which are antagonized by caffeine, a bioactive substance present in numerous natural nutrients, which can also modify bone metabolism. The aim of this study was to investigate the effects of caffeine on alveolar bone damage induced by an ethanol binge drinking paradigm during adolescence. Female Wistar rats (35 days old; n = 30) were allocated to six groups: control (vehicle), ethanol (3 g/kg/day; 3 days On-4 days Off challenge), caffeine (10 mg/kg/day), caffeine plus ethanol, SCH58261 (0.1 mg/kg/day, an antagonist of A receptors), and SCH58261 plus ethanol. Bone micromorphology and vertical bone loss were analyzed by computed microtomography. Our data showed that ethanol binge drinking reduced alveolar bone quality, with repercussion on alveolar bone size. This ethanol-induced alveolar bone deterioration was abrogated upon treatment with caffeine, but not with SCH58261. This shows that caffeine prevented the periodontal disorder caused by ethanol binge drinking during adolescence, an effect that was not mediated by adenosine A receptor blockade.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopha.2020.110608DOI Listing
October 2020

Ethanol binge drinking exposure affects alveolar bone quality and aggravates bone loss in experimentally-induced periodontitis.

PLoS One 2020 30;15(7):e0236161. Epub 2020 Jul 30.

Laboratory of Functional and Structural Biology, Institute of Biological Sciences, Federal University of Pará (UFPA), Belém, Pará, Brazil.

Background: Periodontitis is a multifactorial inflammatory disease of tooth supporting tissues caused by oral biofilms, influenced by environmental and genetic factors, among others. Ethanol consumption has been considered a factor that enhances alveolar bone loss, especially in high doses. The present study aims to investigate the changes promoted by ethanol binge drinking per se or associated with ligature-induced periodontal breakdown on alveolar bone loss.

Materials And Methods: Thirty-two Wistar rats were randomly allocated into four groups: control (C), ethanol (3g/kg/day; 3 days On-4 days Off protocol by gavage for 28 days, EtOH), experimental periodontitis (EP) and experimental periodontitis plus ethanol administration (EP+EtOH). On day 14th, periodontitis was induced by ligatures that were placed around the lower first molars. On day 28th, the animals were euthanized and mandibles were submitted to stereomicroscopy for exposed root area analysis and micro-computed tomography (micro-CT) for the evaluation of alveolar bone loss and microstructural parameters.

Results: The results revealed that ligature-induced alveolar bone loss is aggravated by ethanol binge drinking compared to controls (1.06 ± 0.10 vs 0.77 ± 0.04; p<0.0001). In addition, binge drinking per se altered the alveolar bone quality and density demonstrating a reduction in trabecular thickness, trabecular number parameter and bone density percentual. Periodontal disorder plus ethanol binge drinking group also demonstrated reduction of the quality of bone measured by trabecular thickness.

Conclusions: In conclusion, intense and episodic ethanol intake decreased alveolar bone quality in all microstructural parameters analyzed which may be considered a modifying factor of periodontitis, intensifying the already installed disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236161PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392256PMC
September 2020