Design, In Vitro Evaluation and In Vivo Biocompatibility of Additive Manufacturing Three-Dimensional Printing of ß beta-Tricalcium Phosphate Scaffolds for Bone Regeneration.

The reconstruction of bone deficiencies remains a challenge due to the limitations of autologous bone grafting. The objective of this study is to evaluate the bone regeneration efficacy of additive manufacturing of tricalcium phosphate (TCP) implants using lithography-based ceramic manufacturing (LCM). LCM uses LithaBone TCP 300 slurry for 3D printing, producing cylindrical scaffolds. Four models of internal scaffold geometry were developed and compared. The in vitro studies included cell culture, differentiation, seeding, morphological studies and detection of early osteogenesis. The in vivo studies involved 42 Wistar rats divided into four groups (control, membrane, scaffold (TCP) and membrane with TCP). In each animal, unilateral right mandibular defects with a total thickness of 5 mm were surgically performed. The animals were sacrificed 3 and 6 months after surgery. Bone neoformation was evaluated by conventional histology, radiology, and micro-CT. Model A (spheres with intersecting and aligned arrays) showed higher penetration and interconnection. Histological and radiological analysis by micro-CT revealed increased bone formation in the grafted groups, especially when combined with a membrane. Our innovative 3D printing technology, combined with precise scaffold design and efficient cleaning, shows potential for bone regeneration. However, further refinement of the technique and long-term clinical studies are crucial to establish the safety and efficacy of these advanced 3D printed scaffolds in human patients.

Spatial and temporal dynamics and potential pathogenicity of fecal coliforms in coastal shallow groundwater wells.

Access to water through shallow groundwater wells is a common practice in coastal settlements. This, coupled with a lack of planning for wastewater disposal promotes fecal contamination of groundwater and poses a threat to human health. Here, the spatial and temporal dynamics of groundwater fecal contamination was evaluated during summer and winter (2013 and 2014) in a coastal protected area having a high touristic relevance (Cabo Polonio, Uruguay). Fecal coliforms (FC) abundance in groundwater was significantly higher during summer, related to an influx of ~ 1000 tourists per day. A significant spatial autocorrelation was found in 2014, when the abundance of FC in a well was influenced by its three nearest wells (Moran and Geary tests). The applied statistical models (mixed models) indicated that total phosphorus and organic matter were the variables significantly explaining FC abundance. The risk for human health was estimated using groundwater-extracted DNA and qPCR of genes encoding for E. coli virulence factors (stx1, stx2, and eae). Potential Shiga toxin-producing enteropathogenic and enterohemorrhagic pathotypes were detected, even at FC abundances ≤ 1 CFU (100 mL-1). Moreover, we found that contaminated groundwater reached the beach, being the presence of FC in sand detected even in winter and showing its highest frequency nearby groundwater wells consistently having high FC abundance (hot spots). Altogether, the results show that fecal contamination of shallow groundwater in Cabo Polonio involves a risk for human health that intensifies during summer (associated to a significant increase of tourists). This contamination also impacts the beach, where FC can remain through the whole year.

Comparative analysis of plasma-derived albumin scaffold, alveolar osteoblasts and synthetic membrane in critical mandibular bone defects: An experimental study on rats.

Repair of bone deficiencies in the craniofacial skeleton remains a challenging clinical problem. The aim of this study was to evaluate and compare the effects of a plasma-derived albumin scaffold, alveolar osteoblasts and synthetic membrane implanted into experimental mandibular defects. Bilateral mandibular defects were created in twelve immunodeficient rats. The bone defect was filled with serum scaffold alone in left sides and scaffold combined with human alveolar osteoblast in right side defects. Implanted areas were closed directly in Group 1 (n = 6) and covered by a resorbable polyglycolic-polylactic acid membrane in Group 2 (n = 6). Bone regeneration was determined at 12 weeks as measured by and exhaustive multiplanar computed tomography analysis and histological examination. No significant differences in bone density were observed between defects transplanted with scaffold alone or scaffold seeded with osteoblasts. The use of membrane did not result in a determining factor in the grade of bone regeneration between Groups 1 and 2. Based on these results, it could be concluded that the albumin scaffold alone has osteoinductive capacity but presence of seeded ostogenic cells accelerates defect repair without being significantly influenced by covering the defect with a resorbable membrane.

Trophic assessment in South American Atlantic coastal lagoons: Linking water, sediment and diatom indicators.

Within two coastal shallow lagoons, trophic state was assessed by integrating water and sediment chemical indicators such as the TRIX and the benthic biopolymeric carbon (BPC) trophic indicator, altogether with biological environmental indicators (diatom species characterization). Spatial and temporal behavior of TRIX and BPC indices suggest that water column trophic indicators reflect rather short-term variations in water quality changes, while benthic trophic indicators rather reflect consistent long-term trends which make them useful as enduring indicators of eutrophication. Canonical Correspondence Analysis (CCA) showed that both sediment and transitional water trophic state indices increased eutrophic conditions with a decreasing salinity and increasing total nutrients. Diatom species associated with elevated eutrophic condition such as Staurosirella martyi, Staurosira breviestriata, Amphora copulata, Amphora veneta, Nitzschia sp., and Bacillaria paradoxa, showed a positive correlation with both trophic indices. We highlight the need for considering sediment eutrophication indicators towards in monitoring programmes within shallow coastal lagoons.

Regeneration of mandibular osteoradionecrosis with autologous cross-linked serum albumin scaffold.

Osteoradionecrosis is one of the most severe complications of radiotherapy administered for head and neck tumors. We present the first two cases of advanced and refractory mandibular osteoradionecrosis treated by application of a novel autologous cross-linked 3D serum matrix. Patients were followed clinically and radiographically up to 24 months. Complete wound healing and intact mucosal cover were achieved in both cases. At 12 months, the radiographic values showed an almost complete regeneration of the bone defect, which continued a favourable progression increased to the maximum by 24 months after surgery. The use of an autologous serum-derived scaffold proved to be a quick, predictable, cost-effective and safe adjunct to the conservative surgical treatment of this pathology.

Basin-scale monitoring and risk assessment of emerging contaminants in South American Atlantic coastal lagoons.

Emerging contaminants (ECs) such as pharmaceuticals, personal care products, drugs of abuse and polar pesticides are under particular attention due to their high consumption, frequent detection in the environment and reported ecotoxicological risk. This study investigates the occurrence and distribution of multiclass of ECs in surface waters at basin scale of two Atlantic coastal lagoons of Uruguay, South America. For this purpose, a target screening approach covering up to 362 compounds was employed using nanoflow liquid chromatography - high resolution mass spectrometry (nanoLC/HRMS). 56 compounds were identified including five banned pesticides in the European Union: atrazine, carbendazim, chlorpyrifos ethyl, diazinon, and ethion. Pharmaceuticals, hormones and drugs of abuse showed maximum detection frequencies and concentrations downstream cities. The highest occurrence of pesticides was found in lagoons and streams with neighboring agricultural activity. ECs were also found in coastal sea. Environmental risk assessment revealed that the hormones 17α-ethinylestradiol and 17-ß-estradiol showed the highest risk to aquatic organisms in these basins. This study represents the first basin- scale monitoring of ECs in superficial waters encompassing streams, lagoons, and coastal seas in Uruguay, South America.

Temperature and precipitation shape the distribution of harmful cyanobacteria in subtropical lotic and lentic ecosystems.

Cyanobacterial blooms are expected to become more frequent in freshwaters globally due to eutrophication and climate change effects. However, our knowledge about cyanobacterial biogeography in the subtropics, particularly in lotic ecosystems, is still very limited and the relationship of blooms to temperature and precipitation remains unclear. We took advantage of a comprehensive database of field data compiled over several years (1997 to 2015) to compare cyanobacteria biomass and distribution between lentic and lotic subtropical freshwaters (36 ecosystems, 30°-35°S) and to investigate the role of water temperature and precipitation as significant predictors in eutrophic ecosystems. A filamentous Nostocales, Dolichospermum (Anabaena), was the most widely distributed and frequent genus in the region of the study, followed by the colonial Microcystis, supporting observations of a global latitudinal pattern. Similar total cyanobacteria biovolumes (TCB) were found in lentic and lotic ecosystems, but the proportion of Dolichospermum was higher in lotic ecosystems. Using generalized linear models (GLMs), we found that temperature and rainfall explained 27% of the variation in TCB in lotic ecosystems, while temperature explained 19 and 28% of Dolichospermum and Microcystis biovolume, respectively. In lentic ecosystems, accumulated rainfall explained 34% of the variation of Microcystis biovolume while temperature explained 64%. Our results imply that the increase in extreme meteorological events and temperature predicted by climate models will promote increasingly severe cyanobacterial blooms in eutrophic subtropical freshwaters. Our analysis provides new information about the occurrence of bloom-forming cyanobacteria for southeastern South America and thus fills an important knowledge gap for subtropical freshwaters.

Sentinel node biopsy versus elective neck dissection. Which is more cost-effective? A prospective observational study.

OBJECTIVE: The aim of this prospective not randomized observational study was to determine the costs and outcomes of sentinel lymph node biopsy (SNB) vs elective neck dissection (END) among patients with early oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Seventy-three consecutive patients were divided according to neck staging method. Patients took the decision themselves after receiving detailed information of both suggested treatment tools. False negative (FN) and negative predictive value (NPV) were assessed. Log-rank test was used to compare disease-free survival (DFS) and overall survival (OS). Only direct costs were analysed. Cost information derived from volumes for hospital stay, surgery and neck outcome were obtained from an internal database of tertiary health care center. RESULTS: Thirty-two patients underwent SNB and 41 underwent an END (levels I-III). Average follow-up time was 48.2 months (range 7-80). Five neck recurrences were recorded in the SNB group (range 11-21). Seven neck recurrences occurred in the END group (range 9-16). No significant differences were found in DFS or OS. True negative patients in SNB group incurred in 42% less costs than END group. FN regardless of radiotherapy, was also lower in the SNB group. However, pN+ patients generated 23% more costs in the SNB group. CONCLUSION: In this not randomized observational study with an average follow-up period of 48.2 months, SNB appear to confer less cost than END, with similar prognosis.

Repair of segmental mandibular bone defects in sheep using bone marrow stromal cells and autologous serum scaffold: a pilot study.

AIM: The aim of this study was to evaluate effective bone regeneration using an autologous serum scaffold (alone or seeded with autologous bone marrow-mesenchymal stem cells, BM-MSCs), when implanted in a 30 mm length segmental mandibular defect in sheep. MATERIALS AND METHODS: The bone defect was filled either with serum scaffold alone (control group; n = 5) or combined with BM-MSCs (experimental group; n = 10). Bone regeneration was determined at 12 (T12; 2 control sheep and 4 experimental sheep) and 32 weeks (T32; 3 control and 6 experimental sheep), as measured by computed and microcomputed tomography and histological examination. RESULTS: Two sheep of the Experimental group died after surgery. While complete bone union in the control group was only observed at T32, it was observed both at T12 (1/4 sheep) and T32 (3/4 sheep) in the experimental group. When properties/characteristics of new bone where compared, a better bone quality, similar to native bone, was observed in the scaffold combined with BM-MSCs. CONCLUSIONS: Based on these results, we conclude that the serum scaffold can promote efficient repair of large bone defects, but the combination with BM-MSCs accelerates this process, increasing significantly the amount and quality of bone formed.

Epidemiología, farmacología y caracterización clínica de la osteonecrosis de los maxilares. Un estudio retrospectivo de 70 casos / Epidemiology, pharmacology and clinical characterization of bisphosphonate-related osteonecrosis of the jaw. A retrospective study of 70 cases

Introducción y objetivos: Los bisfosfonatos son fármacos con un amplio espectro de indicaciones cuya principal capacidad es la inhibición de la función osteoclástica. En el año 2003 se ha descrito una complicación asociada a su empleo, la osteonecrosis de los maxilares por bisfosfonatos (ONMB). Los objetivos del presente estudio son identificar los casos recogidos de ONMB en un hospital de tercer nivel durante 8 años, evaluando las principales variables en relación con la enfermedad, el bisfosfonato empleado y los factores de riesgo locales o generales que pudieran actuar como desencadenante en la patogénesis de la ONMB. Material y método: Se procedió a la selección los pacientes diagnosticados de ONMB en un centro de referencia para una población de 1.100.000 habitantes. Las variables analizadas se dividieron en 3 grupos: pacientes, fármaco (incluyendo el análisis de la dosis aplicada y la ponderación dosis/potencia) y osteonecrosis. Resultados: Se recogieron 70 casos (44 mujeres y 26 varones), con una media de 66,8 años. Dieciocho pacientes habían recibido un aminobisfosfonato oral y 52 por vía intravenosa. El tiempo medio de administración fue de 26,53 meses. En el 67,1% de los pacientes se pudo identificar un factor local desencadenante, siendo el más frecuente la exodoncia (48,6%). Aunque la exposición ósea estaba presente en el 75,7% de los casos, 8 enfermos padecieron una osteonecrosis sin exposición, manifestando la presencia de dolor y/o fístula crónica. El 58,6% experimentaron una resolución completa con un tiempo medio de control de 16,28 meses. Conclusiones: El 25% de las ONMB en nuestra serie se relacionaron con la administración de un bisfosfonato oral, especialmente el alendronato. El ácido zoledrónico es el agente que menos miligramos precisa para desarrollar la enfermedad. La exposición ósea solitaria fue el dato clínico más habitual, afectando especialmente a sectores posteriores mandibulares en pacientes con enfermedad metastásica (AU)

Background and objectives: Bisphosphonates are widely prescribed drugs whose principal capacity is inhibiting the osteoclast function. In 2003 a complication related to their administration, bisphosphonate-related osteonecrosis of the jaw (BRONJ), was described. The objectives of this study were to identify diagnosed cases of BRONJ in a third-level hospital over 8 years, evaluating the main features in relation to the disease, the bisphosphonate and the presence of local or general risk factors that could trigger the BRONJ. Material and method: Patients diagnosed with BRONJ in a centre of reference for a population of 1,100,000 inhabitants were selected. Variables analysed were classified into 3 groups: patients, bisphosphonate (focusing on dose and weighting dose/potency) and osteonecrosis. Results: Seventy cases were studied —44 women and 26 men—, with a mean age of 66.8 years. Eighteen patients received bisphosphonates orally and 52, intravenously. The mean time of administration was 26.53 months. In 67.1% of the patients it was possible to identify a local trigger, with the most common being tooth extraction (48.6%). Bone exposure was present in 89.2% of the cases, while 12 patients developed BRONJ without exposed bone, with only pain and/or chronic sinus tracts. Complete resolution was achieved in 58.6% of the patients, with a mean time of control of 16.28 months. Conclusions: 25% of the BRONJ cases were related to the administration of oral bisphosphonates, especially alendronate. Zoledronic acid was the bisphosphonate that required the fewest milligrams to induce osteonecrosis. Single bone exposure was the most common clinical finding, especially in the molar mandibular region in patients with metastatic disease (AU)

Epidemiology, pharmacology and clinical characterization of bisphosphonate-related osteonecrosis of the jaw. A retrospective study of 70 cases.

BACKGROUND AND OBJECTIVES: Bisphosphonates are widely prescribed drugs whose principal capacity is inhibiting the osteoclast function. In 2003 a complication related to their administration, bisphosphonate-related osteonecrosis of the jaw (BRONJ), was described. The objectives of this study were to identify diagnosed cases of BRONJ in a third-level hospital over 8 years, evaluating the main features in relation to the disease, the bisphosphonate and the presence of local or general risk factors that could trigger the BRONJ. METHODS: Patients diagnosed with BRONJ in a centre of reference for a population of 1,100,000 inhabitants were selected. Variables analysed were classified into 3 groups: patients, bisphosphonate (focusing on dose and weighting dose/potency) and osteonecrosis. RESULTS: Seventy cases were studied -44 women and 26 men-, with a mean age of 66.8 years. Eighteen patients received bisphosphonates orally and 52, intravenously. The mean time of administration was 26.53 months. In 67.1% of the patients it was possible to identify a local trigger, with the most common being tooth extraction (48.6%). Bone exposure was present in 89.2% of the cases, while 12 patients developed BRONJ without exposed bone, with only pain and/or chronic sinus tracts. Complete resolution was achieved in 58.6% of the patients, with a mean time of control of 16.28 months. CONCLUSIONS: 25% of the BRONJ cases were related to the administration of oral bisphosphonates, especially alendronate. Zoledronic acid was the bisphosphonate that required the fewest milligrams to induce osteonecrosis. Single bone exposure was the most common clinical finding, especially in the molar mandibular region in patients with metastatic disease.

Sinus mucosal thickening in bisphosphonate-related osteonecrosis of the jaws: a case-control study.

Osteonecrosis of the jaws is a clinically significant complication of bisphosphonate (BP) medications. Otherwise, the effects of BPs on oral soft tissue or cells remain unknown. The main objective of the present study was to determine whether the presence of sinus mucosal thickening was significantly related to BP-related osteonecrosis of the jaw (BRONJ). A case-control study was conducted on 32 patients who underwent treatment of BRONJ with conventional radiological investigations (panoramic radiographs) and computed tomography. The results indicated that patients with BRONJ had a 5.57-fold greater probability of presenting sinus mucosal thickening than controls. Although the existence of this thickening was more common in patients with advanced-stage disease or low levels of C-telopeptide-cross-linked type I collagen, no significant difference was observed between cases and controls. While considering the limitations inherent in the design and number of cases analyzed in our study, patients with osteonecrosis of the jaw were found to have a 5.57-fold greater probability of presenting sinus mucosal thickening (>3 mm) than healthy subjects.

Alternative treatments for oral bisphosphonate-related osteonecrosis of the jaws: A pilot study comparing fibrin rich in growth factors and teriparatide

OBJECTIVES: The aim of this study is to describe and compare the evolution of recurrent bisphosphonate-related osteonecrosis of the jaws (BRONJ) in patients treated with plasma rich in growth factors or teriparatide. MATERIAL AND METHODS: Two different types of treatments were applied in patients diagnosed of recurrent BRONJ in a referral hospital for 1.100.000 inhabitants. In the group A, plasma rich in growth factors was applied during the surgery. In the group B, the treatment consisted in the subcutaneous administration of teriparatide. All the cases of BRONJ should meet the following conditions: recurrent BRONJ, impossibility of surgery in stage 3 Ruggiero classification and absence of diagnosed neoplastic disease. Clinical and radiographic evolution of the patients from both groups was observed. RESULTS: Nine patients were included, 5 in group A and 4 in group B. All the patients were women on oral bisphosphonate therapy for primary osteoporosis (5 patients) or osteoporosis-related to the use of corticosteroids (4 patients). Alendronate was the most common oral bisphosphonate associated with BRONJ in our study (four patients in group A and two in group B). The mean age was 72,8 years in the group A and 73,5 years in the group B. All the patients from group A showed a complete resolution of their BRONJ. Only one patient in the group B showed the same evolution. CONCLUSIONS: In our series, the plasma rich in growth factors showed better results than the teriparatide in the treatment of recurrent BRONJ

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Primary tuberculosis of the palate.

Tuberculosis (TB) is a life-threatening infectious disease with a high world incidence. However, TB with oral expression is considered rare. The importance of recognising this entity lies in its early diagnosis and treatment, as it can be easily confused with neoplastic or traumatic ulcers. We present a case of a primary TB located in the hard palate and gingiva in an 88-year-old woman.

Bisphosphonate-related osteonecrosis associated with dental implants: a microcomputed tomography study.

PURPOSE: The aims of this study were to quantify bone mineral density (BMD) and trabecular architecture of sequestra in patients with bisphosphonate-related osteonecrosis of the jaw (BRONJ) associated with dental implants and to assess if there are differences between trabecular bone in "implant loading-triggered" and "implant surgery-triggered" BRONJ. MATERIALS AND METHODS: Bone sequestra of 2 patients diagnosed with BRONJ associated with dental implants were scanned using high-resolution microcomputed tomography (microCT). Images were obtained at a voltage of 50 kV and 800 µA, and the specimens were scanned at 180 degrees with a single rotation step of 0.3, 1-mm aluminum filter, and a pixel size of 12 µm. The morphometric parameters examined were: BMD, ratio of bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), connectivity density (Conn.D, mm), degree of anisotropy, and the structural model index. RESULTS: BMD and BV/TV were higher in bone sequestration than in healthy bone. Tb.Sp was lower and Tb.N and Tb.Th were higher in the BRONJ group. Conn.D and Tb.N values were significantly high in implant surgery-triggered sequestrum but substantially low in sequestra caused by loading as compared with those of the control sample. CONCLUSIONS: MicroCT is useful for assessing bone sequestration of BRONJ associated to dental implants. The necrotic bone is similar to that described in conventional BRONJ.

Alternative treatments for oral bisphosphonate-related osteonecrosis of the jaws: a pilot study comparing fibrin rich in growth factors and teriparatide.

OBJECTIVE: The aim of this study is to describe and compare the evolution of recurrent bisphosphonate-related osteonecrosis of the jaws (BRONJ) in patients treated with plasma rich in growth factors or teriparatide. MATERIAL AND METHODS: Two different types of treatments were applied in patients diagnosed of recurrent BRONJ in a referral hospital for 1.100.000 inhabitants. In the group A, plasma rich in growth factors was applied during the surgery. In the group B, the treatment consisted in the subcutaneous administration of teriparatide. All the cases of BRONJ should meet the following conditions: recurrent BRONJ, impossibility of surgery in stage 3 Ruggiero classification and absence of diagnosed neoplastic disease. Clinical and radiographic evolution of the patients from both groups was observed. RESULTS: Nine patients were included, 5 in group A and 4 in group B. All the patients were women on oral bisphosphonate therapy for primary osteoporosis (5 patients) or osteoporosis-related to the use of corticosteroids (4 patients). Alendronate was the most common oral bisphosphonate associated with BRONJ in our study (four patients in group A and two in group B). The mean age was 72,8 years in the group A and 73,5 years in the group B. All the patients from group A showed a complete resolution of their BRONJ. Only one patient in the group B showed the same evolution. CONCLUSION: In our series, the plasma rich in growth factors showed better results than the teriparatide in the treatment of recurrent BRONJ.

Inflammatory myofibroblastic tumor of the lung and the maxillary region: a benign lesion with aggressive behavior.

Inflammatory myofibroblastic tumor (IMT) is a rare mass-forming lesion characterized by fibroblastic or myofibroblastic spindle cell proliferation with varying degrees of inflammatory cell infiltration. Although it has been reported in virtually every organ in the body, the lung is the most common site of involvement. Extrapulmonary IMTs, although rare, have been reported and are characterized by different, more aggressive behavior. We report an extremely rare case of maxillary metastases of pulmonary IMT. Lung IMT was initially misdiagnosed, and oral lesion mimicked clinically and radiologically a radicular cyst. On histologic examination, cells exhibited diffuse and intense immunoreactivity for α -smooth muscle actin and vimentin whereas both pulmonary and oral IMTs presented absence of cellular atypia and lack of expressivity of oncogenic determinants. Distant metastases of lung IMT are extremely unusual, and this is the first report to our knowledge with this particular clinical course. Despite the possibility that the present case could also represent a metachronous multifocal IMT, with pulmonary and extrapulmonary lesions, similar histopathological and immunohistochemical patterns in lung and maxillary region suggest a metastatic course.

Bilateral carcinoma in situ of Wharton's duct after chronic obstructive sialadenitis: inflammation as the cause of malignancy?

A case of bilateral carcinoma in situ of Wharton's duct after chronic sialadenitis is reported. The patient, a 54-year-old man, complained of recurrent pain and swelling in the left lower submandibular region. Computed tomography showed large stones in the hilar area of both submandibular glands. The patient underwent bilateral submandibular excision. Histologic and immunohistochemical examination revealed squamous metaplasia with areas of carcinoma in situ in both right and left ducts adjacent to the calculus. To the best of our knowledge, this is the first case report in the literature describing an association between obstructive sialadenitis and carcinoma in situ of Wharton's duct. We discuss etiologic factors and chronic inflammation as a possible cause of malignancy.