Remodelling surgery with 3D printed patient specific surgical guides in patients with chronic diffuse sclerosing osteomyelitis/tendoperiostitis of the mandible, a case series.

BACKGROUND: Patients with chronic diffuse sclerosing osteomyelitis/tendoperiostitis (DSO/TP) of the mandible may complain about facial asymmetry as a result of mandibular deformity, one of the characteristics of DSO/TP of the mandible. If the disease is fully extinguished, remodelling surgery could be performed to treat complaints of facial asymmetry. This study reports the results of remodelling surgery with three-dimensional (3D) designed- and -printed patient-specific surgical guides. MATERIAL AND METHODS: 3D printed guides were designed and manufactured by using mirroring of the contralateral non-affected mandible. Subsequently, the surgical procedure was performed under general anaesthesia using these surgical guides. RESULTS: Four patients (all female) aged 15 (±2.8) years were included. They all complained about facial asymmetry and were planned for surgery with patient-specific surgical guides. Three of those surgeries were performed, of which two patients were satisfied with the result and the other patient is planned for re-surgery because of persistent aesthetical complaints. The last patient cancelled her surgery, because she eventually accepted her asymmetry with the help of a psychologist. CONCLUSIONS: The use of patient-specific surgical guides in remodelling surgery of the mandible could enable a more predictable and symmetrical outcome, which could minimise the chance for re-surgery and could increase patient satisfaction. Furthermore, it could minimise the chance of iatrogenic damage to the inferior alveolar nerve.

In vitro assessment of the mutagenic and genotoxic potential of a pure stilbene extract.

Stilbenes are secondary metabolites of great interest produced by many plant species due to their important bioactive properties. These phytochemicals have become of increasing interest in the wine industry as a natural alternative to sulphur dioxide, which has been associated with human health risks. However, there is still little toxicological information on stilbenes and the results thus far have been contradictory. Considering the key role of genotoxicity in risk assessment and the need to offer safe products in the market, the aim of this study was to assess the mutagenic and genotoxic potential of a stilbene extract with 99% purity (ST-99 extract). A complete series of different in vitro tests (Ames test, micronucleus (MN) test, and standard and enzyme-modified comet assays) was performed before its use as a preservative in wines. The ST-99 extract induces a significant increase of binucleated cells with micronuclei only in presence of the metabolic fraction S9 at the highest concentration assayed. Neither the Ames test nor the comet assay revealed the extract's genotoxic potential. Further studies are necessary, including in vivo assays, to ensure consumer safety before it can be used.

Dental implants as risk factors for patients with medication-related osteonecrosis of the jaws (MRONJ).

An increasing number of patients with medication-related osteonecrosis of the jaws (MRONJ) has recently been reported. It is still being debated whether the presence or placement of dental implants can lead to MRONJ, so the aim of this study was to find out whether dental implants are a risk factor for MRONJ. From January 2003-January 2019 180 patients with MRONJ were seen at the Leiden University Medical Center. Luxating moments for the onset of MRONJ were calculated retrospectively. We collected clinical data and details of antiresorptive medication and found 22 patients with both dental implants and MRONJ. In 18 patients the implants were in the region of the MRONJ and they were included in this study, 14 who had had implants before using antiresorptive drugs and four who had had antiresorptive drugs before or at the time that the implants were placed. The median times between the placement of implants and the diagnosis of MRONJ in these two groups were 24 months and 6 months, respectively. Among the 47 implants, 30 were located in the necrotic region, and all 30 were either lost spontaneously or had to be removed during treatment of MRONJ. Our results show an increased risk for developing MRONJ in patients with dental implants. Both peri-implantitis around previously placed implants, and insertion of dental implants, are risk factors. Prevention of peri-implantitis and caution when inserting dental implants in patients who take antiresorptive medication are therefore important.

Outcome of different treatments for chronic diffuse sclerosing osteomyelitis of the mandible: a systematic review of published papers.

Treating chronic diffuse sclerosing osteomyelitis (DSO) is challenging and many treatments have been reported. However, we know of no standard protocol or guidelines. In this systematic review of relevant publications we provide an overview of the different treatments used. We made an electronic search of PubMed, Medline, Embase, Web of Science, and the Cochrane Library databases, for papers that described the treatment of DSO of the mandible. The search yielded 48 papers that applied to all inclusion criteria, resulting in 16 case reports, 13 case series, 18 retrospective clinical cohort studies, and one randomised controlled trial. Reported treatment options included different operations; the use of antibiotics, anti-inflammatories, and antiresorptive medication; conservative treatment; and hyperbaric oxygen. Surgical treatment resulted in a low success rate and was associated with higher morbidity than other treatments. Conservative treatment, and that of bisphosphonates, yielded more promising results, so conservative treatment and bisphosphonates seem to be the most promising therapeutic options. However, because of the high risk of bias, no firm conclusions can be drawn, and larger studies with clear inclusion criteria and specified endpoints are needed.

Dose-dependent antioxidant responses and pathological changes in tenca (Tinca tinca) after acute oral exposure to Microcystis under laboratory conditions.

The effects of cyanobacterial cells containing microcystins (MCs), toxins from cyanobacteria, on oxidative stress biomarkers from liver and kidney of Tenca fish (Tinca tinca) were investigated under laboratory conditions. Moreover, a histopathological study of liver, kidney, heart and intestine tissues was performed. Fish were orally exposed to cyanobacterial cells dosing 0, 5, 11, 25 and 55 microg MC-LR/fish mixed with the food. Results showed a dose-dependent decrease of superoxide dismutase (SOD) activity, and also of catalase (CAT) in the liver. Glutathione levels and protein oxidation, however, were not altered by the exposure to the cyanobacterial material. The microscopic study revealed tissue alterations even at the lower cyanobacterial cells doses. Onion-like hepatocytes in the liver, glomerulopathy in the kidney, loss of myofibrils in the heart and vacuolated enterocytes in the gastrointestinal tract were the main changes observed. These findings suggest that this fresh water fish can be adversely affected by cyanobacterial blooms in their natural habitats.

New integrated imaging high intensity focused ultrasound probe for transrectal prostate cancer treatment.

The present study proposes a new integrated imaging (II) high-intensity focused ultrasound (HIFU) probe intended as an improvement to the Ablatherm prostate cancer treatment. Because of a perforation in the center of the II probe, the expected lesion differs from the one obtained for the original Ablatherm probe. In this paper, the new geometry and the strategy followed to establish the treatment parameters are presented. The original probe has a 40-mm focal length, a 50-mm aperture and is truncated at 31 mm. The II probe has a 45-mm focal length, a 61-mm aperture, a central perforation of 25 mm and is truncated at 31 mm. Both probes operate at 3 MHz. A mathematical model for lesion prediction was used for setting the treatment parameters for the II probe. These parameters should ensure equivalence between the lesions obtained with the original and II probes. Simulation-obtained parameters were validated by in-vitro and in-vivo (on liver of 70 New Zealand rabbits) experiments. The new II probe was used clinically to treat 30 patients. The mean age was 70.9 +/- 5.3 years (SD), the mean prostate volume 26.9 +/- 7.7 mL and the mean serum prostate specific antigen (PSA) concentration before treatment was 9.2 +/- 5.5 ng/mL. Simulations showed that for the II probe acoustical power and duration when the transducer is inactive should be reduced of 14% and 1s. In-vitro and in-vivo experiments confirmed the equivalence between the lesions obtained with the two probes. The lesion volume obtained under in-vitro conditions (for a traversed tissue depth of 16 mm to the focus) was 5 +/- 0.4 cm(3) and 5.1 +/- 0.5 cm(3) for the original and II probes, respectively. Under in-vivo conditions, the lesion volume (for a traversed tissue depth of 18 mm) was 5.3 +/- 1.1 cm(3) and 5.1 +/- 1.1 cm(3) for the original and II probes, respectively. During the clinical trial, a correction of + 1s in the exposure time was required to recreate the same degree of efficacy observed with the original probe (p = 0.97): 66.7 % of negative biopsies and 75% of patients with PSA at 3 mo < or =1 ng/mL. The morbidity observed was minimal and identical to that observed with the original probe.

Acute and subacute toxic effects produced by microcystin-YR on the fish cell lines RTG-2 and PLHC-1.

Approximately 80 microcystins (MCs) variants have been isolated in surface water worldwide. The toxicity of the most frequently MCs are encountered, MC-LR and MC-RR, has been extensively studied in humans and animals. However, studies dealing with MC-YR toxicity are still scarce. In this work, the toxic effects of MC-YR were investigated in the fish cell line PLHC-1, derived from a hepatocellular carcinoma of the topminnow Poeciliopsis lucida, and RTG-2 fibroblast-like cells derived from the gonads of rainbow trout Oncorhynchus mykiss. After 48 h, morphological and biochemical changes (total protein content, neutral red uptake and methylthiazol tetrazolium salt metabolization) were determined. The most sensitive endpoint for both cell lines was the reduction of total protein content, with EC(50) values of 35 microM for PLHC-1 cells and 67 microM for the RTG-2 cell line. Lysosomal function and methylthiazol tetrazolium salt metabolization were stimulated at low concentrations, while they decreased at high doses. Increase of piknotic cells, rounding effects, reduction in cell number and cell size, hydropic degeneration, and death mainly by necrosis but also by apoptosis were observed in the morphological study. Furthermore, PLHC-1 cells are more sensitive than RTG-2 cells to MC-YR exposure. These results were similar to those obtained when both cell lines were exposed for 24h to a Microcystis aeruginosa isolated strain extract containing MC-LR.

A subchronic 90-day oral toxicity study of Origanum vulgare essential oil in rats.

Oregano essential oil (Origanum vulgare L. virens) (OEO) is being used in the food industry due to its useful properties to develop new active packaging systems. In this concern, the safety assessment of this natural extract is of great interest before being commercialized. The European Food Safety Authority requests different in vivo assays to ensure the safety of food contact materials. One of these studies is a 90 days repeated-dose oral assay in rodents. In the present work, 40 male and 40 female Wistar rats were orally exposed to 50, 100 and 200 mg/kg body weight (b.w.) OEO during 90 days following the OECD guideline 408. Data revealed no mortality and no treatment-related adverse effects of the OEO in food/water consumption, body weight, haematology, biochemistry, necropsy, organ weight and histopathology. These findings suggest that the oral no-observed-adverse-effect level (NOAEL) of this OEO is 200 mg/kg b.w. in Wistar rats, the highest dose tested. In conclusion, the use of this OEO in food packaging appears to be safe based on the lack of toxicity during the subchronic study at doses 330-fold higher than those expected to be in contact consumers in the worst scenario of exposure.

Pyrolysis-gas chromatography-isotope ratio mass spectrometry for monitoring natural additives in polylactic acid active food packages.

Compound-specific isotope analysis (CSIA) usually requires preparative steps (pretreatments, extraction, derivatization) to get amenable chromatographic analytes from bulk geological, biological or synthetic materials. Analytical pyrolysis (Py-GC/MS) can help to overcome such sample manipulation. This communication describe the results obtained by hyphenating analytical pyrolysis (Py-GC) with carbon isotope-ratio mass spectrometry (IRMS) for the analysis of a polylactic acid (PLA) a based bio-plastic extruded with variable quantities of a natural plant extract or oregano essential oil. The chemical structural information of pyrolysates was first determined by conventional analytical pyrolysis and the measure of δ13C in specific compounds was done by coupling a pyrolysis unit to a gas chromatograph connected to a continuous flow IRMS unit (Py-GC-C-IRMS). Using this Py-CSIA device it was possible to trace natural additives with depleted δ13C values produced by C3 photosystem vegetation (cymene: -26.7‰±2.52; terpinene: -27.1‰±0.13 and carvacrol: -27.5‰±1.80 from oregano and two unknown structures: -23.3‰±3.32 and -24.4‰±1.70 and butyl valerate: -24.1‰±3.55 from Allium spp.), within the naturally isotopically enriched bio-plastic backbone derived from corn (C4 vegetation) starch (cyclopentanones: -14.2‰±2.11; lactide enantiomers: -9.2‰±1.56 and larger polymeric units: -17.2‰±1.71). This is the first application of Py-CSIA to characterize a bio-plastic and is shown as a promising tool to study such materials, providing not only a fingerprinting, but also valuable information about the origin of the materials, allowing the traceability of additives and minimizing sample preparation.

[The role of thiazides in the prophylaxis of recurrent calcium lithiasis]. / Papel de las tiazidas en la profilaxis de la litiasis cálcica recidivante.

OBJECTIVE: To show the prolonged efficacy of thiazides in the prophylaxis and treatment of recurrences in patients with calcium oxalate and phosphate lithiasis. METHODS: A randomised prospective study is conducted, with a three-year follow-up, in 150 patients diagnosed with recurrent calcium lithiasis. The patients are divided into three groups: A) 50 cases subject to observation with no treatment, B) 50 cases treated with 50 mg/day of hydrochlorothiazide, and C) 50 cases treated with 50 mg of hydrochlorothiazide and 20 mlEq of potassium citrate/day. Each group is subject to a renal study with imaging techniques and a urinary metabolic study at baseline, 12, 24 and 36 months. RESULTS: The patients treated with thiazides (Groups B and C) obtain a significant reduction in lithiasis recurrence compared with the control group (Group A). The most common abnormality found in the metabolic study was hypercalciuria, 52% of cases; 16% present a mixed lithogenic pattern. The number of recurrences and need for new sessions of extracorporeal lithotripsy in patients with hypercalciuria treated with thiazides is significantly smaller than in Group A (p=0.003). CONCLUSIONS: We observe a significant relation between lithogenic pattern and lithiasis recurrence. Thiazides help us to control lithogenic factors and recurrences in patients with calcium lithiasis. This effect is prolonged and significant in patients with hypercalciuria.

Toxicological evaluation of an Allium-based commercial product in a 90-day feeding study in Sprague-Dawley rats.

Proallium AP(®) is a commercial Allium extract intended to be used in active food packaging as the antibacterial and antioxidant effects of some organosulfur compounds are well known. However, there is little information on its toxicity and the Scientific Committee on Food (UE) requires the safety assessment of substances used in food contact materials. Thus, the aim of this study was to conduct for the first time a subchronic oral toxicity study of Proallium AP(®) with groups of 10 males and 10 females Sprague-Dawley rats fed a diet containing 0, 25, 100, 400 mg/kg/d for 90 days. No treatment-related clinical signs or mortality were noted. Besides, no treatment-related effects with regard to any of the toxicological biomarkers considered were observed, including biochemical, haematological and histopathology parameters. In conclusion, the non-observed-adverse-effect-level (NOAEL) for Proallium AP(®) in rats was determined to be a dietary dose of 400 mg/kg/d under the present experimental conditions, a value 500-fold higher than the exposure derived from its potential use in active packaging.

Development of PLA films containing oregano essential oil (Origanum vulgare L. virens) intended for use in food packaging.

Consumers' concerns about the environment and health have led to the development of new food packaging materials avoiding petroleum-based matrices and synthetic additives. The present study has developed polylactic acid (PLA) films containing different concentrations of essential oil from Origanum vulgare L. virens (OEO). The effectiveness of this new active packaging was checked for use in ready-to-eat salads. A plasticising effect was observed when OEO was incorporated in PLA films. The rest of the mechanical and physical properties of developed films did not show much change when OEO was included in the film. An antioxidant effect was recorded only for films containing the highest percentages of the active agent (5% and 10%). In addition, films exhibited in vitro antibacterial activity against Staphylococcus aureus, Yersinia enterocolitica, Listeria monocytogenes, Enterococcus faecalis and Staphylococcus carnosus. Moreover, in ready-to-eat salads, antimicrobial activity was only observed against yeast and moulds, where 5% and 10% of OEO was the most effective.

Acid and alkaline phosphatase activities and pathological changes induced in Tilapia fish (Oreochromis sp.) exposed subchronically to microcystins from toxic cyanobacterial blooms under laboratory conditions.

The effects of microcystins (MCs) from cyanobacterial cells on the enzymatic activities of acid and alkaline phosphatases (ACP and ALP) from liver, kidney and gill tissues, and the histopathological changes in freshwater Tilapia fish (Oreochromis sp.) were investigated under laboratory conditions. Fish were exposed to cyanobacterial cells (60.0 microg MC-LR/fish per day) through their diet at different exposure times (14 and 21 days). The cells were fed to the fish in two types of oral administration: mixed with a commercial fish food or crushed into a commercial fish food so that the toxins were released. ACP and ALP activities changed in response to MCs in a time-dependent manner, and these changes were more prominent in liver and kidney. The way the MCs were administered had no influence on the biochemical parameters. Similarly, the most severe histopathological changes were observed in the same two organs, although the gills and intestines were also affected. The parenchymal architecture of the liver was dissolved, and round hepatocytes with the appearance of pyknotic nuclei were detected. Kidney lesions consisted of the dilation of Bowman's space and necrotic epithelial cells with pyknotic nuclei in the tubules. These findings suggest that low and repeated doses of MC-LR from cyanobacterial cells induce toxicity in tilapia fish although no adverse effects were detected.

Antioxidant enzyme activity and lipid peroxidation in liver and kidney of rats exposed to microcystin-LR administered intraperitoneally.

The effect of acute exposure of intraperitoneal injection of microcystin-LR (MCLR) on antioxidant enzymes and lipid peroxidation has been studied in liver and kidney of rats. Rats were treated with two doses, i.e. 100 and 150 microg of pure MCLR/kg body weight or saline solution. The enzyme activities of glutathione peroxidase (GSH-Px), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT) in the liver were significantly decreased in MCLR-treated rats. The decrease of GR activity in the liver was 60%, followed by GSH-Px, SOD and CAT. Similarly, a decrease in the antioxidant enzymes was found in the kidney of MCLR-treated rats, such as GSH-Px (27-31%), GR (22%), SOD (42%) and CAT (25-28%). Concomitantly, significant increases in lipid peroxidation levels were recorded in liver (121 and 196% for 100 and 150 microg/kg, respectively) and kidney (48 and 58% for 100 and 150 microg/kg, respectively) from MCLR-treated rats. In conclusion, acute exposure to MCLR results in a decrease in the antioxidant enzymes and an increase in lipid peroxidation in liver and kidney rats, suggesting the oxidative stress as an important role in the pathogenesis of MCLR-induced toxicity. Antioxidant enzymes were significantly consumed in the liver and a minor decrease was found in kidney, confirming the organ-specific effects of MCLR.

The use of the fish cell lines RTG-2 and PLHC-1 to compare the toxic effects produced by microcystins LR and RR.

Cyanobacterial toxins, especially microcystins (MC), are found in eutrophied waters through the world. Acute poisonings of animals and humans has been reported following MC exposure. In the present study, two fish cell lines, PLHC-1 and RTG-2, were evaluated after exposure to the cyanobacterial toxins MC-LR and MC-RR. The effects of different concentrations of the toxins were investigated in both cell lines at morphological and biochemical levels (total protein content, lactate dehydrogenase leakage, lysosomal activity and succinate dehydrogenase activity). The results obtained showed a decrease in protein content and no relevant increase in cell disruption, except for MC-LR in PLHC-1 cells. Morphological changes produced by microcystins were cellular swelling, blebbling, rounding, reduction in the cell number and increase in the number and size of lysosomal bodies. In addition, steatosis was produced in hepatoma PLHC-1 cells, particularly with MC-RR. Furthermore, the fish PLHC-1 cell line was more sensitive than RTG-2 cells to the cyanobacterial toxins compared, being the stimulation of the lysosomal function and the induction of steatosis the most specific changes detected.

Genotoxicity assessment of propyl thiosulfinate oxide, an organosulfur compound from Allium extract, intended to food active packaging.

Essential oils from onion (Allium cepa L.), garlic (Allium sativum L.), and their main components, such as propyl thiosulfinate oxide (PTSO) are being intended for active packaging with the purpose of maintaining and extending food product quality and shelf life. The present work aims to assess for the first time the potential mutagenicity/genotoxicity of PTSO (0-50 µM) using the following battery of genotoxicity tests: (1) the bacterial reverse-mutation assay in Salmonella typhimurium (Ames test, OECD 471); (2) the micronucleus test (OECD 487) (MN) and (3) the mouse lymphoma thymidine-kinase assay (OECD 476) (MLA) on L5178YTk(+/-), cells; and (4) the comet assay (with and without Endo III and FPG enzymes) on Caco-2 cells. The results revealed that PTSO was not mutagenic in the Ames test, however it was mutagenic in the MLA assay after 24 h of treatment (2.5-20 µM). The parent compound did not induce MN on mammalian cells; however, its metabolites (in the presence S9) produced positive results (from 15 µM). Data from the comet assay indicated that PTSO did not induce DNA breaks or oxidative DNA damage. Further in vivo genotoxicity tests are needed to confirm its safety before it is used as active additive in food packaging.

Experimental evaluation of lesion prediction modelling in the presence of cavitation bubbles: intended for high-intensity focused ultrasound prostate treatment.

The accuracy of high-intensity focused ultrasound (HIFU) lesion prediction modelling was evaluated for a truncated spherical transducer designed for prostate cancer treatment The modelling adapted the bio heat transfer equation (BHTE) to take into account the activity of cavitation bubbles generated during HIFU exposure. This modelling was used to predict the lesions produced by three different transducer geometries: fixed-focus, concentric-ring and 1.5D phased-array. Lesions were predicted for different ultrasound exposure conditions close to those used in prostate cancer treatment. Twenty-one in vitro and nine in vitro experiments were performed on pig liver to validate the accuracy of the predictions. A good match was found between the predicted and experimental lesion shapes. Lesion dimensions (maximum depth and length, area at the centre of the lesion or central surface area) were measured on experimental and predicted lesions. The central surface area was predicted by the model with a range of error of 0.15-6.5% for in vitro tests and 0.97-9% in vivo. For comparison, BHTE without bubbles had a range of error of 0.4-55.5% (in vitro) and 9-25.5% (in vivo). The model should be accurate enough to predict HIFU lesions under ultrasound exposure conditions used in prostate cancer treatment.

[Leiomyosarcoma of the bladder. Report of a new case and review of the literature]. / Leiomiosarcoma de vejiga. Aportación de un nuevo caso y revisión de la literatura.

Contribution of a new case of bladder leiomyosarcoma due to the rarity of its presentation. There are barely one hundred cases reported in the medical literature. Clinico-pathological, therapeutic and prognostic assessment of this type of bladder sarcoma and discussion on the convenience of complementary therapy after surgery.

[Malignant fibrohistiocytoma of the spermatic cord]. / Fibrohistiocitoma maligno del cordón espermático.

A malignant fibrous histiocytoma (MFH) of the spermatic cord is presented and a review of the literature has been performed. The patient here presented survived for eight years and is probably cured of his tumour. In general, MFHs of the spermatic cord have a good prognosis, even when they attain a big size. They have a worse evolution when satellite nodules are present. Although more experience is needed. It is our feeling, that a spermatic MFH smaller than 8 cm, without any satellite nodule and less than 25% nuclei positive to MIB-1 (cell proliferation marker), may have a conservative therapy, including only tumorectomy.

Marble game with optimal ferroelectric switching.

A low coercivity and, consequently, low hysteresis loss are desired properties for ferroelectric materials used in high-power and high-frequency actuators. The coercive field required for the onset of ferroelectric switching is shown to develop a strong directional anisotropy due to peculiarities of an energy surface associated with the polarization rotation. It is found that the ferroelectric anisotropy exhibits 'hard' and 'easy' switching axes similar to magnetic materials. The hard axis corresponds to 180° polarization reversal, whereas the easy axis favors 90° switching. Our results suggest that the intrinsic low coercivity and the full polarization reversal may not be achieved at the same time under uniaxial excitation. A rotating electric field excitation is proposed in order to circumvent this limitation and to guide the polarization switching along a curved path.