Description and validation of an improved method to feed solitary bees (Osmia spp.) known amounts of pesticides.

Pesticide exposure is an important driver of bee declines. Laboratory toxicity tests provide baseline information on the potential effects of pesticides on bees, but current risk assessment schemes rely on one species, the highly social honey bee, Apis mellifera, and there is uncertainty regarding the extent to which this species is a suitable surrogate for other pollinators. For this reason, Osmia cornuta and Osmia bicornis have been proposed as model solitary bee species in the EU risk assessment scheme. The use of solitary bees in risk assessment requires the development of new methodologies adjusted to the biology of these species. For example, oral dosing methods used with honey bees cannot be readily applied to solitary bees due to differences in feeding behaviour and social interactions. In this study, we describe the "petal method", a laboratory feeding method, and validate its use in acute and chronic exposure oral tests with Osmia spp. We conducted five experiments in which we compared the performance of several artificial flowers combining visual and olfactory cues against the petal method, or in which variations of the petal method were confronted. We then use the results of these experiments to optimize the feeding arenas and propose standardized methods for both acute and chronic exposure tests. The petal method provides high levels of feeding success, thus reducing the number of bees needed. It works with a wide variety of petal species and with both female and male Osmia spp., thus ensuring reproducibility across studies. To validate the use of the petal method in ecotoxicology tests, we assess the toxicity of a standard reference insecticide, dimethoate, in O. cornuta adults and determine LD50 values for this species. The petal method should facilitate the inclusion of solitary bees in risk assessment schemes therefore increasing the protection coverage of pesticide regulation.

The Financial Impact on Reimbursement of Moderately Hypofractionated Postoperative Radiation Therapy for Breast Cancer: An International Consortium Report.

AIMS: Moderately hypofractionated breast irradiation has been evaluated in several prospective studies, resulting in wide acceptance of shorter treatment protocols for postoperative breast irradiation. Reimbursement for radiation therapy varies between private and public systems and between countries, impacting variably financial considerations in the use of hypofractionation. The aim of this study was to evaluate the financial impact of moderately hypofractionated breast irradiation by reimbursement system in different countries. MATERIALS AND METHODS: The study was designed by an international group of radiation oncologists. A web-questionnaire was distributed to representatives from each country. The participants were asked to involve the financial consultant at their institution. RESULTS: Data from 13 countries from all populated continents were collected (Europe: Denmark, France, Italy, the Netherlands, Spain, UK; North America: Canada, USA; South America: Brazil; Africa: South Africa; Oceania: Australia; Asia: Israel, Taiwan). Clinicians and/or departments in most of the countries surveyed (77%) receive remuneration based on the number of fractions delivered to the patient. The financial loss per patient estimated resulting from applying moderately hypofractionated breast irradiation instead of conventional fractionation ranged from 5-10% to 30-40%, depending on the healthcare provider. CONCLUSION: Although a generalised adoption of moderately hypofractionated breast irradiation would allow for a considerable reduction in social and economic burden, the financial loss for the healthcare providers induced by fee-for-service remuneration may be a factor in the slow uptake of these regimens. Therefore, fee-for-service reimbursement may not be preferable for radiation oncology. We propose that an alternative system of remuneration, such as bundled payments based on stage and diagnosis, may provide more value for all stakeholders.

Importance of 68Ga-PSMA PET/CT in hospital practice. View of the radiation oncologist. / PET/TC con 68Ga-PSMA, importancia en la práctica hospitalaria. Visión del oncólogo radioterápico.

Radiotherapy is a treatment with curative intent, both in patients with primary diagnosis of prostate cancer (PCa) and in patients presenting with biochemical recurrence after radical prostatectomy (RP). Moreover, the use of stereotactic body radiotherapy as a metastasis directed therapy in patients with oligometastatic PCa has significantly increased in the recent years. Conventional imaging techniques, including transrectal ultrasound, computed tomography (CT), morphologic magnetic resonance and bone scintigraphy have traditionally played a minor role in all those clinical scenarios due to its low diagnostic accuracy. The recent development of the positron emission tomography (PET) radiotracer 68Ga-PSMA binding to the prostate specific membrane antigen (PSMA), a transmembrane glycoprotein overexpressed in PCa cells, has shown promising results. Detection rates for PCa lesions are higher than CT and higher than the best technique available, the PET/CT with choline. Its superiority has been demonstrated even at very low PSA levels (<1 ng/ml). This increase in diagnostic accuracy represents a potential impact on patient management, especially in radiotherapy. Even if this imaging technique is already available for routine clinical practice in some European countries, in Spain, unfortunately, there is very limited access. In this review, we analyze the main studies that investigate the usefulness of 68Ga-PSMA PET/CT in patients with PCa and its potential impact on radiotherapy treatments. In addition, we compared the 68Ga-PSMA PET/CT, with the multiparametric magnetic resonance imaging and the PET/CT with choline, in the different clinical scenarios.

Multiparametric MRI for prostate cancer: a national survey of patterns of practice among radiation oncologists in Spain.

PURPOSE: To investigate patterns of practice among Spanish radiation oncologists in the use of multiparametric magnetic resonance imaging (mpMRI) for the treatment of prostate cancer (PCa). We evaluated (1) access to mpMRI, (2) current clinical practices, and (3) physician expectations of mpMRI. METHODS: Cross-sectional survey of 118 radiation oncologists at 75 Radiation Oncology (RO) departments in Spain. RESULTS: A total of 55 radiation oncologists from 52 RO departments (52/75; 69%) completed the survey. Prostate mpMRI is performed at 94.5% of the centres that provided data. The most common indications for mpMRI in routine clinical practice were: (1) detection/localization of the tumour prior to second biopsy (82.7%), (2) cancer staging (80.8%), and (3) detection of recurrence after definitive treatment (80.8%). Most respondents (72.7%) reported modifying the primary radiotherapy treatment when mpMRI findings indicate a more advanced T stage with a resultant change in the risk group. Most respondents (90.5%) treat macroscopic local recurrence after prostatectomy with high doses, ranging from 71 to 83 Gy; in 37.7% of cases, the full dose is delivered to the entire prostate bed. In pelvic nodal recurrence, more than half (59.3%) of the respondents reported performing elective pelvic radiotherapy, including the prostate bed, with a boost to the involved nodes. CONCLUSIONS: This survey shows that prostate mpMRI is routinely used by radiation oncologists in Spain in a wide range of clinical scenarios. The findings reported here underscore the need to standardize treatment protocols for definitive and salvage radiotherapy in patients evaluated with mpMRI.

Pelvic MRI findings in relapsed prostate cancer after radical prostatectomy.

PURPOSE/OBJECTIVE: Little is known about the clinical impact of using multiparametric MRI to plan early salvage radiotherapy after radical prostatectomy. We aimed to evaluate the incidence and location of recurrence based on pelvic multiparametric MRI findings and to identify clinical variables predictive of positive imaging results. MATERIALS AND METHODS: We defined radiological criteria of local and lymph node malignancy and reviewed records and MRI studies of 70 patients with PSA recurrence after radical prostatectomy. We performed univariate and multivariate analysis to identify any association between clinical, pathological and treatment-related variables and imaging results. RESULTS: Multiparametric MRI was positive in 33/70 patients. We found local and lymph node recurrence in 27 patients and 7 patients, respectively, with a median PSA value of 0.38 ng/ml. We found no statistically significant differences between patients with positive and negative multiparametric MRI for any variable. Shorter PSADT was associated with positive lymph nodes (median PSADT: 5.12 vs 12.70 months; p: 0.017). CONCLUSIONS: Nearly half the patients had visible disease in multiparametric MRI despite low PSA. Positive lymph nodes incidence should be considered when planning salvage radiotherapy, particularly in patients with a short PSADT.

Infrastructures, treatment modalities, and workload of radiation oncology departments in Spain with special attention to prostate cancer.

AIM: The purpose of the study was to describe infrastructures, treatment modalities, and workload in radiation oncology (RO) in Spain, referred particularly to prostate cancer (PC). METHODS: An epidemiologic, cross-sectional study was performed during 2008-2009. A study-specific questionnaire was sent to the 108 RO-registered departments. RESULTS: One hundred and two departments answered the survey, and six were contacted by telephone. Centers operated 236 treatment units: 23 (9.7 %) cobalt machines, 37 (15.7 %) mono-energetic linear accelerators, and 176 (74.6 %) multi-energy linear accelerators. Sixty-one (56.4 %) and 33 (30.5 %) departments, respectively, reported intensity-modulated radiation therapy (IMRT) and image-guided RT (IGRT) capabilities; three-dimensional-conformal RT was used in 75.8 % of patients. Virtual simulators were present in 95 departments (88.0 %), 35 use conventional simulators. Fifty-one departments (47.2 %) have brachytherapy units, 38 (35.2 %) perform prostatic implants. Departments saw a mean of 24.9 new patients/week; the number of patients treated annually was 102,054, corresponding to 88.4 % of patients with a RT indication. In 56.5 % of the hospitals, multidisciplinary teams were available to treat PC. CONCLUSIONS: Results provide an accurate picture of current situation of RO in Spain, showing a trend toward the progressive introduction of new technologies (IMRT, IGRT, brachytherapy).

Application of continuous positive airway pressure in the delivery room: a multicenter randomized clinical trial

This study evaluated whether the use of continuous positive airway pressure (CPAP) in the delivery room alters the need for mechanical ventilation and surfactant during the first 5 days of life and modifies the incidence of respiratory morbidity and mortality during the hospital stay. The study was a multicenter randomized clinical trial conducted in five public university hospitals in Brazil, from June 2008 to December 2009. Participants were 197 infants with birth weight of 1000-1500 g and without major birth defects. They were treated according to the guidelines of the American Academy of Pediatrics (APP). Infants not intubated or extubated less than 15 min after birth were randomized for two treatments, routine or CPAP, and were followed until hospital discharge. The routine (n=99) and CPAP (n=98) infants studied presented no statistically significant differences regarding birth characteristics, complications during the prenatal period, the need for mechanical ventilation during the first 5 days of life (19.2 vs 23.4%, P=0.50), use of surfactant (18.2 vs 17.3% P=0.92), or respiratory morbidity and mortality until discharge. The CPAP group required a greater number of doses of surfactant (1.5 vs 1.0, P=0.02). When CPAP was applied to the routine group, it was installed within a median time of 30 min. We found that CPAP applied less than 15 min after birth was not able to reduce the need for ventilator support and was associated with a higher number of doses of surfactant when compared to CPAP applied as clinically indicated within a median time of 30 min.

Mycotoxins: occurrence, toxicology, and exposure assessment.

Mycotoxins are abiotic hazards produced by certain fungi that can grow on a variety of crops. Consequently, their prevalence in plant raw materials may be relatively high. The concentration of mycotoxins in finished products is usually lower than in raw materials. In this review, occurrence and toxicology of the main mycotoxins are summarised. Furthermore, methodological approaches for exposure assessment are described. Existing exposure assessments, both through contamination and consumption data and biomarkers of exposure, for the main mycotoxins are also discussed.

Occurrence and exposure assessment of aflatoxins in Catalonia (Spain).

The main objective of this study was to assess the exposure of Catalonian (Spain) population to AFs. Thus, two sub-objectives were considered: (1) to assess the occurrence of AFs in food marketed in Catalonia, and (2) to assess the consumption of those foods susceptible to AFs contamination by Catalonian population. AFs were analysed in a total of 603 samples considering special commodities as free-gluten, ethnic or baby foods. Analytical method consisted of an extraction and clean-up of aflatoxins step using immunoaffinity columns, and determination by HPLC with post-column photochemical derivatization and fluorescence detection. Food dietary intake was assessed using a food frequency questionnaire, administered to 1387 individuals by trained interviewers. Contamination and consumption raw datasets were combined by means of a direct method and a stochastic method, building the pseudo-parametric bootstrap confidence intervals of the main outputs. Margins of exposure (MoE) and cancer incidence were estimated for the different collectives. The highest percentages of positive samples were found in red pepper, pistachios and peanuts. Considering our results, the most exposed group was the celiac sufferer collective followed by the adolescents; however health concern should not be expected in the population groups.

Occurrence of fumonisins in Catalonia (Spain) and an exposure assessment of specific population groups.

Fumonisin B1 (FB1) and B2 (FB2) are mycotoxins produced by Fusarium verticillioides and F. proliferatum and common contaminants of cereal crops. The objectives of this study were to (1) study the occurrence of fumonisins in Catalonia (north-eastern region of Spain) and (2) assess the exposure of the Catalonian population to these mycotoxins. Contamination data was provided by a wide survey where 928 individual samples were pooled to analyse 370 composite samples. Fumonisins were extracted and purified using immunoaffinity columns and determined by HPLC with fluorescence detection. The raw consumption data came from a nutritional study specifically designed to assess the dietary intake of the main foodstuffs related to fumonisin contamination for all population age groups. In addition, two specific groups were selected with respect to maize consumption: immigrants and celiac sufferers. Contamination and consumption data were combined by simulation using an essentially parametric-parametric (P-P) method. The P-P method draws sampling values from distribution functions fitted to consumption and contamination datasets. Moreover, to quantify the accuracy and reliability of the statistical estimates, we built related confidence intervals using a Pseudo-Parametric bootstrap method. The results of this study show that fumonisins are commonly found in some commodities on the Catalonian market, such as beer, corn snacks and ethnic foods; however, the values were well below the permitted maximum EU levels. The most exposed group were infants followed by immigrants but, in all cases, they were below the TDI of 2 µg/kg bw/day.

Occurrence of zearalenone, an oestrogenic mycotoxin, in Catalonia (Spain) and exposure assessment.

The objectives of this study were to assess the occurrence of zearalenone (ZEA) in food in Catalonia (Spain); to assess the consumption of the main food items contaminated with ZEA; and finally, to estimate the dietary exposure of the Catalonian population to the mycotoxin. Therefore 1187 samples were collected from the Catalonian market and pooled to obtain 485 analytical samples (composites) of the commodities most susceptible to ZEA contamination and commonly consumed in the region. Extraction and clean-up was performed using immunoaffinity columns and ZEA was detected and quantified by high performance liquid chromatography (HPLC) and fluorescence detection. A specific food frequency questionnaire (FFQ) was administered to 1264 individuals by trained interviewers to estimate the consumption of the relevant foods. The results showed that the occurrence of ZEA in food marketed in Catalonia was infrequent. Sliced bread, corn snacks and sweet corn were the commodities where it was most often present. In considering the contamination levels and food consumption estimates, the dietary intake of ZEA by the Catalonian population was estimated to be considerably lower than the temporary tolerable daily intake (TDI) of 200 ng ZEA kg(-1) bw day(-1).

Current management of muscle-invasive bladder cancer.

Management of muscle-invasive bladder cancer (MIBC) has changed little in the last twenty years. The gold standard treatment is still cystectomy, but it has a significant negative impact on quality of life. Bladder-preservation strategies can be used in some cases but patient selection for this approach remains unclear. New chemotherapy and biologic agents in combination with surgery or radiotherapy could improve results and these possibilities are currently under investigation.

Ochratoxin A and its metabolite ochratoxin alpha in urine and assessment of the exposure of inhabitants of Lleida, Spain.

Ochratoxin A (OTA) as well as its metabolite ochratoxin α (OTα) were detected in human urine in order to assess the exposure to OTA of a group of 72 adult inhabitants of the city of Lleida (Spain). Urine samples were enzymatically treated; OTA and OTα were separated by liquid-liquid extraction, and detected by HPLC-fluorescence. Exposure to OTA was also evaluated by the estimation of its daily intake from food contamination data from the literature and from food consumption data provided by the participants, who filled in a food frequency questionnaire (FFQ) and a three-day food consumption record (3DR). OTA occurrence (12.5%, limit of detection=0.034 ng/mL) was lower than OTα occurrence (61.1%, limit of detection=0.023 ng/mL). The range of concentrations was 0.057-0.562 ng/mL and 0.056-2.894 ng/mL for OTA and for OTα, respectively. It could be observed for positive samples that the FFQ data were related to the OTA concentration in urine, whereas the 3DR data were related to the OTα levels in urine. The OTA estimated daily intake of the participants was lower than 30% of the latest provisional tolerable daily intake of 14 ng/kg body weight/day in the worst cases of exposure.

Renal toxicity after allogeneic bone marrow transplantation: the combined effects of total-body irradiation and graft-versus-host disease.

PURPOSE: To evaluate retrospectively the cumulative risk probability and factors correlated with renal dysfunction after allogeneic bone marrow transplantation (BMT). PATIENTS AND METHODS: From October 1984 to July 1994, 84 patients with malignant hematopoietic diseases received allogeneic BMT after conditioning with high-dose chemotherapy and total-body irradiation (TBI). Seventy-nine patients with normal renal function before conditioning are included in this study. Conditioning included high-dose cyclophosphamide without (n = 46) or with (n = 33) other agents (daunorubicin, busulfan, cytarabine, and thiotepa) followed by TBI. The TBI dose prescribed to the center of the abdomen was 10 Gy for 24 patients, 12 Gy for 32, and 13.5 Gy for 23. In vitro T-cell depletion was undertaken in 48 cases. The post-BMT nephrotoxicity of aminoglycosides, vancomycin, amphotericin, and cyclosporine was assessed. Time to renal dysfunction was defined as the time to a persistent increase of serum creatinine (SCr) level greater than 110 mumol/L. The potential influence of sex, age, diagnosis, chimerism, and graft-versus-host disease (GvHD) on renal dysfunction was also assessed. RESULTS: The 18-month probability of renal dysfunction-free survival (RDFS) for the whole group was 77%. Only TBI dose and presence of GvHD were significantly correlated with renal dysfunction by multivariate analysis. The 18-month probabilities of RDFS were 95%, 74%, and 55% for the patients conditioned with 10, 12, and 13.5 Gy, respectively. The 18-month RDFS probabilities were 88% and 61% for patients without and with GvHD, respectively. Combining both variables, we have defined two risk categories: low-risk (ie, 10 Gy TBI with/without GvHD and 12 Gy TBI without GvHD) and high-risk (ie, 12 Gy TBI with GvHD and 13.5 Gy TBI with/without GvHD). The predicted 18-month RDFS rates were 93% and 52% for the low- and high-risk groups, respectively. CONCLUSION: Renal dysfunction after allogeneic BMT is strongly related to the delivered TBI dose (and dose per fraction) and to the presence of GvHD. Renal shielding should be recommended if a TBI dose greater than 12 Gy (fractionated twice daily over 3 days) is to be prescribed. Furthermore, in those cases with a high risk of developing GvHD (eg, unrelated allogeneic BMT, absence of T-cell depletion), these data suggest that kidney doses greater than 10 Gy should be avoided.

[Dermatomyositis and head and neck neoplasia]. / Dermatomiositis y neoplasia de cabeza y cuello.

The incidence of malignant disease appears to be increased in patients with dermatomyositis, although the relationship between dermatomyositis and cancer is still controversial. The most frequently associated tumors are not different from the tumors observed in the general population. There are very few cases of head and neck cancer associated with myositis reported in the medical literature despite the high incidence of these tumors in western countries. Two new cases are reported and the relationship between myositis and cancer is discussed.

Trenbolone acetate induced changes in the genital tract of male pigs.

Eleven entire and twelve castrated male pigs were implanted with trenbolone acetate and the effects of the treatment on genital tract macro- and microscopical modifications were evaluated and compared to non-implanted animals. In entire male pigs a reduction of testicular weight and size was observed as a consequence of the treatment (< 0.001), but no important modifications were found in bulbourethral gland and seminal vesicles macroscopically. Castrated non-implanted males had bulbourethral gland atrophy (P < 0.01), while castrated implanted ones showed similar development to entire males. As for vesicular glands there were no significant differences among the four groups under study. Histological study of prostate has demonstrated structural modifications. As a consequence of the treatment glandular lumen was increased (P < 0.05), and most parenchyma was occupied by polymorphous cysts.