Quercetin improves and protects Calu-3 airway epithelial barrier function.

Introduction: In light of the impact of airway barrier leaks in COVID-19 and the significance of vitamin D in COVID-19 outcomes, including airway barrier protection, we investigated whether the very common dietary flavonoid quercetin could also be efficacious in supporting airway barrier function. Methods: To address this question, we utilized the widely used airway epithelial cell culture model, Calu-3. Results: We observed that treating Calu-3 cell layers with quercetin increased transepithelial electrical resistance while simultaneously reducing transepithelial leaks of 14C-D-mannitol (Jm) and 14C-inulin. The effects of quercetin were concentration-dependent and exhibited a biphasic time course. These effects of quercetin occurred with changes in tight junctional protein composition as well as a partial inhibition of cell replication that resulted in decreased linear junctional density. Both of these effects potentially contribute to improved barrier function. Quercetin was equally effective in reducing the barrier compromise caused by the pro-inflammatory cytokine TNF-α, an action that seemed to derive, in part, from reducing the elevation of ERK 1/2 caused by TNF-α. Discussion: Quercetin improved Calu-3 barrier function and reduced TNF-α-induced barrier compromise, mediated in part by changes in the tight junctional complex.

Comparative studies of the sensitivities of sparse and full geometries of Total-Body PET scanners built from crystals and plastic scintillators.

BACKGROUND: Alongside the benefits of Total-Body imaging modalities, such as higher sensitivity, single-bed position, low dose imaging, etc., their final construction cost prevents worldwide utilization. The main aim of this study is to present a simulation-based comparison of the sensitivities of existing and currently developed tomographs to introduce a cost-efficient solution for constructing a Total-Body PET scanner based on plastic scintillators. METHODS: For the case of this study, eight tomographs based on the uEXPLORER configuration with different scintillator materials (BGO, LYSO), axial field-of-view (97.4 cm and 194.8 cm), and detector configurations (full and sparse) were simulated. In addition, 8 J-PET scanners with different configurations, such as various axial field-of-view (200 cm and 250 cm), different cross sections of plastic scintillator, and multiple numbers of plastic scintillator layers (2, 3, and 4), based on J-PET technology have been simulated by GATE software. Furthermore, Siemens' Biograph Vision has been simulated to compare the results with standard PET scans. Two types of simulations have been performed. The first one with a centrally located source with a diameter of 1 mm and a length of 250 cm, and the second one with the same source inside a water-filled cylindrical phantom with a diameter of 20 cm and a length of 183 cm. RESULTS: With regards to sensitivity, among all the proposed scanners, the ones constructed with BGO crystals give the best performance ([Formula: see text] 350 cps/kBq at the center). The utilization of sparse geometry or LYSO crystals significantly lowers the achievable sensitivity of such systems. The J-PET design gives a similar sensitivity to the sparse LYSO crystal-based detectors while having full detector coverage over the body. Moreover, it provides uniform sensitivity over the body with additional gain on its sides and provides the possibility for high-quality brain imaging. CONCLUSION: Taking into account not only the sensitivity but also the price of Total-Body PET tomographs, which till now was one of the main obstacles in their widespread clinical availability, the J-PET tomography system based on plastic scintillators could be a cost-efficient alternative for Total-Body PET scanners.

Efficiency determination of J-PET: first plastic scintillators-based PET scanner.

BACKGROUND: The Jagiellonian Positron Emission Tomograph is the 3-layer prototype of the first scanner based on plastic scintillators, consisting of 192 half-metre-long strips with readouts at both ends. Compared to crystal-based detectors, plastic scintillators are several times cheaper and could be considered as a more economical alternative to crystal scintillators in future PETs. JPET is also a first multi-photon PET prototype. For the development of multi-photon detection, with photon characterized by the continuous energy spectrum, it is important to estimate the efficiency of J-PET as a function of energy deposition. The aim of this work is to determine the registration efficiency of the J-PET tomograph as a function of energy deposition by incident photons and the intrinsic efficiency of the J-PET scanner in detecting photons of different incident energies. In this study, 3-hit events are investigated, where 2-hits are caused by 511 keV photons emitted in [Formula: see text] annihilations, while the third hit is caused by one of the scattered photons. The scattered photon is used to accurately measure the scattering angle and thus the energy deposition. Two hits by a primary and a scattered photon are sufficient to calculate the scattering angle of a photon, while the third hit ensures the precise labeling of the 511 keV photons. RESULTS: By comparing experimental and simulated energy distribution spectra, the registration efficiency of the J-PET scanner was determined in the energy deposition range of 70-270 keV, where it varies between 20 and 100[Formula: see text]. In addition, the intrinsic efficiency of the J-PET was also determined as a function of the energy of the incident photons. CONCLUSION: A method for determining registration efficiency as a function of energy deposition and intrinsic efficiency as a function of incident photon energy of the J-PET scanner was demonstrated. This study is crucial for evaluating the performance of the scanner based on plastic scintillators and its applications as a standard and multi-photon PET systems. The method may be also used in the calibration of Compton-cameras developed for the ion-beam therapy monitoring and simultaneous multi-radionuclide imaging in nuclear medicine.

[Clinical research in radiation oncology: how to move from the laboratory to the patient?] / Recherche clinique en oncologie radiothérapie : comment passer du laboratoire au patient ?

Translational research in radiation oncology is undergoing intense development. An increasingly rapid transfer is taking place from the laboratory to the patients, both in the selection of patients who can benefit from radiotherapy and in the development of innovative irradiation strategies or the development of combinations with drugs. Accelerating the passage of discoveries from the laboratory to the clinic represents the ideal of any translational research program but requires taking into account the multiple obstacles that can slow this progress. The ambition of the RadioTransNet network, a project to structure preclinical research in radiation oncology in France, is precisely to promote scientific and clinical interactions at the interface of radiotherapy and radiobiology, in its preclinical positioning, in order to identify priorities for strategic research dedicated to innovation in radiotherapy. The multidisciplinary radiotherapy teams with experts in biology, medicine, medical physics, mathematics and engineering sciences are able to meet these new challenges which will allow these advances to be made available to patients as quickly as possible.

Radiation therapy of cutaneous cancers.

We present the update of the recommendations of the French society of oncological radiotherapy on radiotherapy of cutaneous cancers. The indications of radiotherapy for skin cancers are not clearly defined because of the lack of randomized trials or prospective studies. For basal cell carcinomas, radiotherapy frequently offers a good local control, but a randomized trial showed that surgery is more efficient and less toxic. Indications of radiotherapy are contra-indications of surgery for patients older than 60, non-sclerodermiform histology and located in non-sensitive areas. Adjuvant radiotherapy could be proposed to squamous cell carcinomas, in case of poor prognostic factors. Dose of 60 to 70Gy are usually required, and must be modulated to the size of the lesions. Adjuvant radiotherapy seems beneficial for desmoplastic melanomas but not for the other histological types. Prophylactic nodal irradiation (45 to 50Gy), for locally advanced tumors (massive nodal involvement), decreases the locoregional failure rate but do not increase survival. Adjuvant radio- therapy (50 to 56Gy) for Merkel cell carcinomas increases also the local control rate, as demonstrated by meta-analysis and a large epidemiological study. Nodal areas must be included, if there is no surgical exploration (sentinel lymph node dissection). Kaposi sarcomas are radiosensitive and could be treated with relatively low doses (24 to 30Gy). Also, cutaneous lymphomas are good indications for radiotherapy: B lymphomas are electively treated with limited fields. The role of total skin electron therapy for T-lymphomas is still discussed; but palliative radiotherapy is very efficient in case of cutaneous nodules.

Hepatic tumours and radiotherapy.

We present the update of the recommendations of the French society of oncological radiotherapy on hepatic tumours. Recent technological progress led to develop the concept of focused liver radiation therapy. We must distinguish primary and secondary tumours, as the indications are restricted and must be discussed as an alternative to surgical or medical treatments. The tumour volume, its liver location close to the organs at risk determine the irradiation technique (repositioning method, total dose delivered, dose fractionation regimens). Tumour (and liver) breathing related motions should be taken into account. Strict dosimetric criteria must be observed with particular attention to the dose-volume histograms of non-tumoral liver as well as of the hollow organs, particularly in case of hypofractionated high dose radiotherapy "under stereotaxic conditions". Stereotactic body radiotherapy is being evaluated and is often preferred to radiofrequency for primary or secondary tumours (usually less than 5cm). An adaptation can be proposed, with a conformal fractionated irradiation protocol with or without intensity modulation, for hepatocellular carcinomas larger than 5cm.

ROV assessment of mesophotic fish and associated habitats across the continental shelf of the Amathole region.

Understanding how fish associate with habitats across marine landscapes is crucial to developing effective marine spatial planning (MSP) in an expanding and diversifying ocean economy. Globally, anthropogenic pressures impact the barely understood temperate mesophotic ecosystems and South Africa's remote Amathole shelf is no exception. The Kei and East London region encompass three coastal marine protected areas (MPAs), two of which were recently extended to the shelf-edge. The strong Agulhas current (exceeding 3 m/s), which runs along the narrow shelf exacerbates sampling challenges. For the first time, a remotely operated vehicle (ROV) surveyed fish and their associated habitats across the shelf. Results indicated fish assemblages differed between the two principle sampling areas, and across the shelf. The number of distinct fish assemblages was higher inshore and on the shelf-edge, relative to the mid-shelf. However, the mid-shelf had the highest species richness. Unique visuals of rare Rhinobatos ocellatus (Speckled guitarfish) and shoaling Polyprion americanus (wreckfish) were collected. Visual evidence of rhodolith beds, deep-water lace corals and critically endangered endemic seabreams were ecologically important observations. The ROV enabled in situ sampling without damaging sensitive habitats or extracting fish. This study provided information that supported the Amathole MPA expansions, which extended protection from the coast to beyond the shelf-edge and will guide their management. The data gathered provides baseline information for future benthopelagic fish and habitat monitoring in these new MPAs.

[Combination radiotherapy-immunotherapy in genitourinary cancer]. / Combinaison radiothérapie-immunothérapie en cancérologie génito-urinaire.

Immunotherapy occupies a growing place in urologic oncology, mainly for kidney and bladder cancers. On the basis of encouraging preclinical work, the combination of immunotherapy with radiotherapy aims to increase the tumor response, including in metastatic tumors, which raises many hopes, which this article reviews.

Perineal recurrence of prostate cancer along a brachytherapy needle track: A case report.

Metastatic recurrence in an atypical site, such as the perineum, can occur after prostatectomy, cryotherapy, or brachytherapy, but is uncommon. To our knowledge, this is only the third case of perineal recurrence of prostatic cancer along a low dose rate brachytherapy needle track. A 64-year-old man was referred to an urologist with an increased PSA of 6.9ng/mL in December 2008. There were no urinary symptoms. Prostatic biopsies revealed a Gleason 6 adenocarcinoma (3+3), and he was treated with low dose rate brachytherapy in May 2009. Sixty-seven seeds of iodine 125 were loaded under ultrasound control, and the PSA subsequently fell to a nadir of 1.19ng/mL in November 2015. Eight years (May 2017) after the initial treatment, the PSA rose to 5.2ng/mL. Pelvic MRI and choline PET revealed a nodule in the region of the left internal obturator muscle. Nodule biopsies confirmed prostatic origin. This perineal recurrence is thus most likely related to seeding of tumour cells along the track of a brachytherapy needle. To our knowledge, this is only the fourth case of perineal recurrence of prostatic cancer along a low-dose rate brachytherapy needle track. Perineal recurrence of prostatic cancer along a LDR brachytherapy needle track can occur. Improved imaging techniques may help to identify this type of recurrence earlier and optimise treatment.

Multiple Perianal Ulcers Related to Use of a Hemorrhoidal Ointment With the Active Ingredients Triamcinolone Acetonide, Lidocaine, and Pentosan Polysulfate Sodium: A Series of 11 Spanish Patients. / Múltiples úlceras perianales en relación con el uso de una pomada antihemorroidal con acetónido de triamcinolona, lidocaína y pentosano polisulfato sódico como principios activos: una serie de 11 pacientes españoles.

The development of perianal ulcers related to the use of a hemorrhoidal ointment has not been reported in the literature. We describe a series of 11 patients who were treated for perianal ulcers in 10 Spanish hospitals after they used the same ointment containing the active ingredients triamcinolone acetonide, lidocaine, and pentosan polysulfate sodium. No prior or concomitant conditions suggesting an alternative cause for the condition could be identified, and after the patients stopped using the ointment, their ulcers cleared completely in 8 weeks on average. This case series shows the damage that can be caused by an over-the-counter pharmaceutical product used without medical follow-up. It also illustrates the need to ask patients with perianal ulcers about any topical agents used before the lesions appeared.

Soft matter dynamics: A versatile microgravity platform to study dynamics in soft matter.

We describe an experiment container with light scattering and imaging diagnostics for experiments on soft matter aboard the International Space Station (ISS). The suite of measurement capabilities can be used to study different materials in exchangeable sample cell units. The currently available sample cell units and future possibilities for foams, granular media, and emulsions are presented in addition to an overview of the design and the diagnostics of the experiment container. First results from measurements performed on ground and during the commissioning aboard the ISS highlight the capabilities of the experiment container to study the different materials.

The prevalence of Achilles and patellar tendon injuries in Australian football players beyond a time-loss definition.

Little is known about the prevalence and associated of morbidity of tendon problems. With only severe cases of tendon problems missing games, players that have their training and performance impacted are not captured by traditional injury surveillance. The aim of this study was to report the prevalence of Achilles and patellar tendon problems in elite male Australian football players using the Oslo Sports Trauma Research Centre (OSTRC) overuse questionnaire, compared to a time-loss definition. Male athletes from 12 professional Australian football teams were invited to complete a monthly questionnaire over a 9-month period in the 2016 pre- and competitive season. The OSTRC overuse injury questionnaire was used to measure the prevalence and severity of Achilles and patellar tendon symptoms and was compared to traditional match-loss statistics. A total of 441 participants were included. Of all participants, 21.5% (95% CI: 17.9-25.6) and 25.2% (95% CI 21.3-29.4) reported Achilles or patellar tendon problems during the season, respectively. Based on the traditional match-loss definition, a combined 4.1% of participants missed games due to either Achilles or patellar tendon injury. A greater average monthly prevalence was observed during the pre-season compared to the competitive season. Achilles and patellar tendon problems are prevalent in elite male Australian football players. These injuries are not adequately captured using a traditional match-loss definition. Prevention of these injuries may be best targeted during the off- and pre-season due to higher prevalence of symptoms during the pre-season compared to during the competitive season.

Prognostic factors for parotid metastasis of cutaneous squamous cell carcinoma of the head and neck.

BACKGROUND: Cutaneous squamous cell carcinoma (CSCC) develops on the head in 80% of cases. Parotid metastasis (PM) is rare, but treatment, which associates surgery and radiation therapy, is heavy and prognosis poor. MATERIAL AND METHODS: All cases of parotidectomy for PM of CSCC of the head and neck between 2005 and 2015 were studied retrospectively. Epidemiologic, oncologic and therapeutic data were analyzed. Overall and specific survival were calculated following Kaplan-Meier. Log-rank and Cox models were used to identify prognostic factors for PM. OBJECTIVES: The principal study objective was to identify factors for survival in PM from CSCC of the head and neck. RESULTS: Thirty-five patients were included. Mean time to onset of PM was 13months. Overall 1-, 2- and 5-year survival was respectively 70, 66 and 59%. Independent prognostic factors comprised immunodepression, age at treatment, positive CSCC margins, macroscopic facial nerve involvement, and metastatic cervical adenopathies. CONCLUSION: The study confirmed an association of several independent prognostic factors at the stage of parotid lymph-node metastasis, related to patient, primary CSCC and PM. Complete primary resection is essential to reduce the risk of PM. Intensified radiologic and clinical surveillance should enable early diagnosis.

Otras caras de la enfermedad de Darier / Other faces of darier disease

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[Radiotherapy of oligometastatic pelvic node relapses in patients with prostate cancer]. / Rechutes oligométastatiques ganglionnaires pelviennes au cours des cancers de la prostate : rôle de la prise en charge par radiothérapie.

The Oligopelvis 2 studies is based on the assumption that salvage pelvic radiotherapy may prolong the interval between the first and the second intermittent hormone therapy sequence in pelvic lymph node oligometastatic prostate cancer. This phase 3 study will compare intermittent hormone therapy (standard arm) alone or combined with salvage pelvic radiotherapy (experimental arm).

[Stereotactic body radiation therapy for hepatic malignancies: Organs at risk, uncertainties margins, doses]. / Radiothérapie stéréotaxique hépatique : organes à risque, marges d'incertitudes, doses.

Stereotactic body radiation therapy for primary and metastatic hepatic malignancies can be performed in association and/or as an alternative to surgery and radiofrequency. The consequences of the great number of techniques available are heterogeneity in contouring, dose prescription and in determination of dose constraints for organs at risk. The objective of this paper is to improve the quality and safety and to help the diffusion of this technique for a majority of patients. In 2016, the French Society of Radiation Oncology (SFRO) published guidelines for external radiotherapy and brachytherapy ("Recorad"). This paper is an update of these recommendations considering recent publications.

[Clinical to target volume margins determination in radiotherapy for anal cancers]. / Détermination des marges du volume cible anatomoclinique au volume cible prévisionnel pour la radiothérapie des cancers du canal anal.

There are very few data on the expansion from the clinical target volume (CTV) to the planning target volume (PTV) in the anal cancer treatment. This article aims to collect the different elements needed for the construction of a PTV from scientific data based on a literature analysis. We reviewed the articles published in the medical literature from the last 20years. They concerned setup errors and internal organ mobility of the different volumes of patients treated by conformational radiotherapy and intensity-modulated radiotherapy (anal canal, meso-rectum, common, intern and extern, inguinal and pre-sacral lymph nodes). CTV to PTV margins admitted in the guidelines and atlas of consensus groups (SFRO, RTOG, AGITG) are from 0.7 to 1cm in all directions, based on expert's opinions but not on scientific data. There are no specific studies on the canal anal mobility. Most of the data are from other pelvis cancers (gynecologic, rectum and prostate). Setup errors can be reduced by daily imaging. Patient repositioning and immobilization modalities are mostly local habits rather than scientific consensus. A three-dimensional 1cm margin is generally admitted. Margins reduction must be careful and has to be assessed.

[Role of radiotherapy in the management of node-positive prostate cancer]. / Place de la radiothérapie dans la prise en charge des cancers de prostate avec atteinte ganglionnaire pelvienne initiale sans métastase à distance.

Node-positive prostate cancer patients represent a small proportion of all prostate cancers for whom limited prospective information is available. Most retrospective or cohort data strongly suggest however that radiotherapy combined with androgen-depriving therapies is the preferable treatment in this setting. Only randomized clinical trials would be able to better define both radiotherapy (dose? volume? fractionation?) and androgen-depriving therapies (duration? role of novel androgen-depriving therapy?) modalities.