piRNA pathway gene expression in the malaria vector mosquito Anopheles stephensi.

The ability of transposons to mobilize to new places in a genome enables them to introgress rapidly into populations. The piRNA pathway has been characterized recently in the germ line of the fruit fly, Drosophila melanogaster, and is responsible for downregulating transposon mobility. Transposons have been used as tools in mosquitoes to genetically transform a number of species including Anopheles stephensi, a vector of human malaria. These mobile genetic elements also have been proposed as tools to drive antipathogen effector genes into wild mosquito populations to replace pathogen-susceptible insects with those engineered genetically to be resistant to or unable to transmit a pathogen. The piRNA pathway may affect the performance of such proposed genetic engineering strategies. In the present study, we identify and describe the An. stephensi orthologues of the major genes in the piRNA pathway, Ago3, Aubergine (Aub) and Piwi. Consistent with a role in protection from transposon movement, these three genes are expressed constitutively in the germ-line cells of ovaries and induced further after a blood meal.

[Analysis of neutrophil gelatinase-associated lipocalin in the critical patient]. / Análisis de la lipocalina asociada a la gelatinasa de neutrófilos en el paciente crítico.

OBJECTIVE: To determine if NGAL value exceeding 150 ng/mL is a good diagnostic test for acute renal failure in critically ill patients. DESIGN: Prospective, observational cohort. SETTING: Intensive Care Unit and Cardiac Surgery Intensive Care Service at Hospital Germans Trias I Pujol. PARTICIPANTS: Patients admitted to the Intensive Care department the Designated days in the studio. INTERVENTIONS: Analysis of serum creatinine blood given from 7 days prior to the start of the study, and daily during 4 weeks and by determination of NGAL urine test in frozen sample, analyzer ARCHITECT (Abbott Diagnostics) determined by immunoassay the day baseline and 2 times a week for 4 weeks, analysis of the stay and mortality. RESULTS: A total of 529 NGAL samples were obtained from 46 patients. 37% of patients had a value of NGAL>150 ng/mL. The Sensivity of the test to diagnose acute renal failure was 69%, Specifity was 75,7%. However, the Positive Predictive Test Value was 53%, which means that 47% of patients with high NGAL did not develop AKI. A NGAL >150 mg/dL was associated with a significantly higher SOFA and a longer stay in the ICU. The mortality of patients with elevated NGAL was 58.8%. CONCLUSIONS: A NGAL>150 ng/mL does not seem to be an excellent test for AKI in critically ill patients but is associated with a worse prognosis.

Identification of soluble forms of vascular endothelial growth factor receptors, sVEGFR-1 and sVEGFR-2, in bovine dominant follicles.

The development of dominant follicles requires the parallel growth of a vascular network, regulated by VEGF and its receptors VEGFR-1 and VEGFR-2. Here, we demonstrate the presence of mRNA for the soluble forms of VEGFR-1 and VEGFR-2 by RT-PCR and the respective proteins by Western blot, in bovine dominant follicles. The 3' end of the mRNA coding region and the deduced C-terminal amino acid sequence of the bovine VEGFR soluble forms were similar to those previously described in human and mice. The relative abundance of sVEGFR-1 was higher in dominant follicles of day 4, decreasing on day 6 and further on day 9 of the cycle. In contrast, sVEGFR-2 expression was low on day 4 follicles and increased as the cycle advanced, becoming greater on day 9. The changes of sVEGFR-1 and sVEGFR-2 with the age of the bovine dominant follicle indicate a physiological role in its growth and atresia.

The experience of obstetric nursing students in an innovative maternal care programme in Chiapas, Mexico: a qualitative study.

In Mexico, over the last decade, more non-physician medical professionals have been participating in birth care according to recent federal regulations. So far, very few sites have been able to implement birth care models where midwives and obstetric nurses participate. We describe the experience of a group of intern obstetric nurses participating in a model that provides respectful birth care to rural populations, managed by an international NGO in partnership with the Ministry of Health of Chiapas, Mexico. We conducted a case study including individual interviews and focus group discussions with obstetric nurse interns participating in the Compañeros En Salud programme over four years from 2016 to 2019. We applied targeted content analysis to the qualitative data. There were 28 participants from 4 groups of interns. Informants expressed their opinions in four areas: (a) training as a LEO, (b) training experience at CES, (c) LEO role in health care delivery; and (d) LEOs' perspectives about respectful maternity care. Interns identified gaps in their training including a higher load of theoretical content vs practical experience, as well as little supervision of clinical care in public hospitals. Their adaptation to the health services model has increased over time, and recent classes acknowledge the difficulties that earlier ones had to confront, including the challenging interactions with hospital staff. Interns have incorporated the value of respectful birth care and their role to protect this right in rural populations. Findings could be useful to call for the expansion of the model in public birth centres.

[External validity of a relevant model for Irritable Bowel Syndrome (IBS) using chronic stress by water avoidance in Wistar rats]. / Validez externa de un modelo experimental para síndrome de intestino irritable (SII) mediante estrés crónico por evitación al agua en ratas Wistar.

BACKGROUND: Development of animal models has been one of the most remarkable achievements for Irritable Bowel Syndrome (IBS) research. These models need to exhibit face validity, construct and predictive validity, as well as internal (replicability) and external validity (generalizability). Among these models, chronic stress induced by water avoidance exposure (WA) has been validated in rats through increasing visceral hypersensitivity, motility impairment, anxiety and, colonic immune activity, all related to IBS. OBJECTIVE: To assess the external validity of WA indirectly on colonic motility in Wistar rats. METHOD: Ten male-Wistar rats were exposed to WA and compared with ten Wistar rats not exposed (controls). At the end of each exposure, the quantity of fecal pellets were determined and considered as a sign of autonomic regulation of colonic motility. Data was analyzed with a general linear model for repeated measures. RESULTS: Rats exposed to WA had higher number or pellets than controls: 7.46 ± 0.45 (95%CI: 6.51, 8.41) vs. 2.88 ± 0.45 (1.93, 3.83), p < 0.001. The higher number of pellets was related to WA exposure as there were no other significant interactions. In both groups, the number of pellets was higher during the first day and then decreased progressively. CONCLUSIONS: Chronic stress induced through WA in Wistar rats, exhibits external validity as an experimental model for IBS research and our findings of increased number of fecal pellets coincide with the appearance hypermotility related to IBS. The model is optimum for research studies on this disorder.

Squamous cell carcinoma over pilonidal chronic disease. A new therapeutic approach.

INTRODUCTION: Pilonidal sinus is a very common disease. Malignant transformation occurs in 0,1% of patients. We present a case of squamous cell carcinoma arised from recurrent pilonidal disease, managed by multimodal treatment. PRESENTATION OF CASE: We present a 70-year-old man with chronic pilonidal sinus. Inflammation had worsened in previous months and exploration revealed a large ulcerative mass which biopsy showed a squamous cell carcinoma. CT scan and MRI imaging showed tumoral invasion of the coccyx and both gluteus major muscles. Neoadjuvant radiotherapy, chemotherapy as radiosensitizer and surgery with intraoperative radiotherapy was decided in the multidisciplinary tumor committee. Post neoadjuvant therapy MRI showed partial response with a decrease of the mass but persistence of the coccyx infiltration. Surgery consisted in en-bloc resection of the tumor with presacral tissues, coccyx and partial gluteal resection. Intraoperative radiotherapy was administered over the sacrum and in the bed of the coccyx resection. One week later, reconstructive surgery was practiced using a latissimus dorsi free flap, advancement of gluteal flaps and skin graft. Histological examination showed no residual tumor. The patient is currently asymptomatic and he has a satisfactory quality of life. DISCUSSION: Although squamous cell carcinoma is rare, it must be suspected in patients with recurrent pilonidal disease. Diagnosis is done by histological examination of biopsies. This type of tumors have a high local recurrence rate. CONCLUSION: We propose a multimodal treatment that includes neoadjuvant radiotherapy and chemotherapy as radiosensitizer and surgery plus intraoperative radiotherapy with the aim to decrease local recurrence rate.

Multidisciplinary management of liver metastases in patients with colorectal cancer: a consensus of SEOM, AEC, SEOR, SERVEI, and SEMNIM.

Colorectal cancer (CRC) has the second-highest tumor incidence and is a leading cause of death by cancer. Nearly 20% of patients with CRC will have metastases at the time of diagnosis, and more than 50% of patients with CRC develop metastatic disease during the course of their disease. A group of experts from the Spanish Society of Medical Oncology, the Spanish Association of Surgeons, the Spanish Society of Radiation Oncology, the Spanish Society of Vascular and Interventional Radiology, and the Spanish Society of Nuclear Medicine and Molecular Imaging met to discuss and provide a multidisciplinary consensus on the management of liver metastases in patients with CRC. The group defined the different scenarios in which the disease can present: fit or unfit patients with resectable liver metastases, patients with potential resectable liver metastases, and patients with unresectable liver metastases. Within each scenario, the different strategies and therapeutic approaches are discussed.

100% peer review in radiation oncology: is it feasible?

PURPOSE: Peer review has been proposed as a strategy to ensure patient safety and plan quality in radiation oncology. Despite its potential benefits, barriers commonly exist to its optimal implementation in daily clinical routine. Our purpose is to analyze peer-review process at our institution. METHODS AND MATERIALS: Based on our group peer-review process, we quantified the rate of plan changes, time and resources needed for this process. Prospectively, data on cases presented at our institutional peer-review conference attended by physicians, resident physicians and physicists were collected. Items such as time to present per case, type of patient (adult or pediatric), treatment intent, dose, aimed technique, disease location and receipt of previous radiation were gathered. Cases were then analyzed to determine the rate of major change, minor change and plan rejection after presentation as well as the median time per session. RESULTS: Over a period of 4 weeks, 148 cases were reviewed. Median of attendants was six physicians, three in-training-physicians and one physicist. Median time per session was 38 (4-72) minutes. 59.5% of cases presented in 1-4 min, 32.4% in 5-9 min and 8.1% in ≥ 10 min. 79.1% of cases were accepted without changes, 11.5% with minor changes, 6% with major changes and 3.4% were rejected with indication of new presentation. Most frequent reason of change was contouring corrections (53.8%) followed by dose or fractionation (26.9%). CONCLUSION: Everyday group consensus peer review is an efficient manner to recollect clinical and technical data of cases presented to ensure quality radiation care before initiation of treatment as well as ensuring department quality in a feedback team environment. This model is feasible within the normal operation of every radiation oncology Department.

Time for radioimmunotherapy: an overview to bring improvements in clinical practice.

Harnessing the patient's own immune system against an established cancer has proven to be a successful strategy. Within the last years, several antibodies blocking critical "checkpoints" that control the activation of T cells, the immune cells able to kill cancer cells, have been approved for the use in patients with different tumours. Unfortunately, these cases remain a minority. Over the last years, radiotherapy has been reported as a means to turn a patient's own tumour into an in situ vaccine and generate anti-tumour T cells in patients who lack sufficient anti-tumour immunity. Indeed, review data show that the strategy of blocking multiple selected immune inhibitory targets in combination with radiotherapy has the potential to unleash powerful anti-tumour responses and improve the outcome of metastatic solid tumours. Here, we review the principal tumours where research in this field has led to new knowledge and where radioimmunotherapy becomes a reality.

Effects of cryopreservation on head morphometry and its relation with chromatin status in brown bear (Ursus arctos) spermatozoa.

The Cantabrian brown bear (Ursus arctos) is a highly endangered species in Spain and basic studies are necessary in order to bank its germplasm. Sperm heads are mainly made up of chromatin, thus their shape depends partly on chromatin structure. Thawed semen from 10 bears was used to analyze chromatin status by sperm chromatin structure assay (SCSA) and head morphometry by the computer-assisted sperm morphology assessment (CASMA) system. Morphometry was analyzed before and after freezing-thawing in order to evaluate the effects of cryopreservation on sperm heads. Each spermatozoon was measured for four primary parameters (length, L; width, W; area, A; perimeter, P) and derived parameters (ellipticity: L/W, circularity: 4piA/ P2, elongation: (L-W)/(L+W), regularity: piLW/ 4A). All the derived parameters significantly differed between bears. Likewise, cryopreservation affected head morphometry by reducing its size. Clustering based on morphometric parameters separated three subpopulations, one of them being significantly more influenced by the cryopreservation process. We obtained high correlations between head morphometry and SCSA parameters: standard deviation of DNA fragmentation index (SD-DFI) was correlated with perimeter and area (r=0.75 and r=0.62, respectively) and DFIm and DFIt (moderate and total DNA fragmentation index) were correlated with perimeter (r=0.65 and r=0.67, respectively). Nevertheless, classification of males according to SCSA or head morphometry did not completely agree so the two assays might explain male variability differently. We conclude that cryopreservation affected morphometry at least in a subset of spermatozoa. These results might improve future application of sperm banking techniques in this species.

Practical aspects of planning, building, and interpreting tissue microarrays: the Cooperative Prostate Cancer Tissue Resource experience.

This is a review of several new approaches developed at or adopted by the Cooperative Prostate Cancer Tissue Resource (CPCTR) to resolve issues involved in tissue microarray (TMA) construction and use. CPCTR developed the first needle biopsy TMA, allowing researchers to obtain 200 or more consecutive cancer sections from a single biopsy core. Using radiographs of original paraffin blocks to measure tissue thickness we developed a method to produce TMAs with a larger number of usable sections. The modular approach to plan TMA construction is also a novel concept wherein TMAs of different types, such as tumor grade TMAs, metastasis TMA and hormone refractory tumors TMA can be combined to form an ensemble of TMAs with expanded research utility, such as support for tumor progression studies. We also implemented an open access TMA Data Exchange Specification that allows TMA data to be organized in a self-describing XML document annotated with well-defined common data elements. It ensures inter-laboratory reproducibility because it offers information describing the preparation of TMA blocks and slides. There are many important aspects that may be missed by both beginners and experienced investigators in areas of TMA experimental design, human subjects protection, population sample size, selection of tumor areas to sample, strategies for saving tissues, choice of antibodies for immunohistochemistry, and TMA data management.

Extender osmolality and sugar supplementation exert a complex effect on the cryopreservation of Iberian red deer (Cervus elaphus hispanicus) epididymal spermatozoa.

We have carried out two experiments to study the cryobiology of red deer epididymal spermatozoa and to improve freezing extenders: (1) effect of extender (Tris-citrate-fructose) osmolality (300-600 mOsm/kg), and (2) effect of sugar (0.4M) supplementation to the extender (no sugar, glucose, fructose, mannose, sucrose, maltose, threalose and raffinose). Sperm quality was assessed pre-freezing, post-thawing, and after 2h at 37 degrees C post-thawing: sperm motility index (SMI), acrosome integrity and membrane integrity (HOS test) were assessed subjectively; mitochondrial activity (JC-1) and membrane stability (merocyanine 540) were assessed by flow cytometry. In experiment 2, DNA status was assessed using acridine orange and flow cytometry. To find an optimal osmolality, we fitted the data to a quadratic curve. Four hundred Osmolal per kilogram rendered better results pre-freezing and post-thawing. However, post-thawing viability and most parameters after 2h incubation fitted a linear model. Osmolalities above 425 mOsm/kg were deleterious (P<0.05). In experiment 2, fructose had a positive effect respect to control after 2h of incubation at 37 degrees C post-thawing. Di and trisaccharides were deleterious. Trehalose showed impaired DNA status after 2h incubation. In conclusion, the osmolality of the extenders should be around 400 mOsm/kg, although the change from quadratic to lineal may indicate a complex effect that must be further studied. Monosaccharides may enhance red deer epididymal sperm cryopreservation, especially fructose, whereas di and trisaccharides may not be adequate.

Does prostate volume correlate with vitamin D deficiency among men undergoing prostate biopsy?

OBJECTIVES: Recent studies demonstrate vitamin D is inversely correlated with BPH and prostate cancer (PCa) incidence. We aim to clarify the associations of vitamin D with prostate volume. METHODS: This is an observational study investigating the associations of serum PSA, PSA density and prostate volume with serum 25-hydroxyvitamin D (25-OH D) in PCa patients and men with negative biopsies seen in outpatient urology clinics in Chicago, IL, USA. There were 571 men (40-79 years old) with elevated PSA or abnormal digital rectal examination with available prostate volume recorded from initial biopsy. The primary outcomes were the unadjusted associations of serum 25-OH D deficiency with prostate volume. The secondary outcomes were the adjusted associations using linear and logistic regression analysis. RESULTS: On univariate analysis, serum 25-OH D<20 ng ml-1 inversely correlated with prostate volume among all men undergoing transrectal ultrasonography (P=0.02), and this relationship remained significant for men with negative biopsy on stratified analysis. In adjusted models, controlling for age, serum PSA, 5-α reductase inhibitors use, obesity and PCa diagnosis, prostate volume was inversely associated with vitamin D (P<0.05) using serum vitamin D as a continuous and categorical variable. Logistic regression model also demonstrated an inverse association between vitamin D (continuous and categorical) and prostate volume ⩾40 grams. CONCLUSION: Serum 25-OH D levels are inversely associated with overall prostate volume and enlarged prostate gland (⩾40 grams), especially in men with benign prostatic disease. Given the largely non-toxic effect of supplementation, consideration should be given to assessing vitamin D levels in men with benign prostatic disease in addition, to malignant prostatic disease.

Improvement strategies in ovine artificial insemination.

Artificial insemination in ram is scarcely widespread comparing with other domestic species. This has been due not only to fertility results being irregular and low but also because of the difficulty in the application of enhancements such as the use of frozen-thawed sperm. Although there is a lot of information on the use of different options to improve these AI results (such as transcervical application, the use of thawed sperm, etc.) commercial programmes can be classified on two general categories: those using refrigerated semen (15 degrees C) by superficial intracervical deposition (vaginal), and, more restricted, those using thawed sperm by intrauterine deposition (laparoscopy). In the present work, we have summarized our viewpoint on three general research lines for the improvement of AI results in sheep: semen preservation, AI procedures and semen assessment. Briefly, in ram it is necessary to develop a medium term methodology of sperm refrigeration (3-5 days), which would allow the distribution of sperm doses to a widespread area. Nevertheless, it is also necessary to develop an intrauterine transcervical AI technique, which allows thawed semen to be applied by vaginal insemination. Besides, the low predictive value of classic assessment techniques limits the ability to adjust the number of spermatozoa per dose according to its actual fertility.

Spanish Society of Radiation Oncology clinical guidelines for stereotactic body radiation therapy in lymph node oligometastases.

Data in the literature support the existence of a state of limited metastases or oligometastases. Favorable outcomes have been observed in selected patients with such oligometastases that are treated with local ablative therapies, which include surgical extirpation, stereotactic body radiation therapy (SBRT), and radiofrequency ablation. The role of SBRT in the setting of lymph node oligometastases is still emerging but the early results for local control are promising. However, the biggest challenge is to identify patients who will benefit from treatment of their oligometastatic disease with local aggressive therapy. Patients are initially categorized based upon examination of the initial biopsy, location, stage, and previous treatments received. Appropriate patient management with SBRT requires an understanding of several clinicopathological features that help to identify several subsets of patients with more responsive tumors and a good tolerance to SBRT. In an effort to incorporate the most recent evidence, here the Spanish Society of Radiation Oncology presents guidelines for using SBRT in lymph node oligometastases.

Clasped-thumb mental retardation (MASA) syndrome: confirmation of linkage to Xq28.

We describe a 5-generation Hispanic family with 13 males and 1 female affected with MASA syndrome. The proposita, a 17-year-old female, and her affected male relatives shared many of the cognate manifestations--mental retardation (14/14), aphasia or delayed speech (13/13), shuffling gait (8/13), adduction of thumbs (14/14)--as well as scoliosis (2/13) and increased deep tendon reflexes in the lower extremities (10/13). Southern analysis with the polymorphic DNA probes DXS14 (Xp11), DXS72 (Xq21), and F8C (Xq28) confirmed linkage to the Xq28 region with a maximum lod score of 3.01 for this family.

Recognition hypermnesia with repeated trials: initial evidence for the alternative retrieval pathways hypothesis.

The alternative retrieval pathways (ARP) hypothesis of hypermnesia is here proposed. This hypothesis predicts hypermnesia (net improvements in recall or recognition after initial learning) whenever alternative retrieval pathways are provided leading to the original episodic trace. Initial evidence for this hypothesis was obtained in two experiments testing a non-obvious prediction of its format transformation assumption, namely that hypermnesia would be obtained in recognition and would not occur in recall if the former, but not the latter, condition requires obligatory format transformations between item encoding and retrieval. In the first experiment the same participants, exposed to identical items and having analogous encoding and retrieval conditions, showed recognition and did not show recall hypermnesia. With a between-participant design, the second experiment replicated the recognition hypermnesia findings, using a different recognition procedure and three instead of two test trials, whereas recall hypermnesia remained absent. Results are discussed comparing the heuristic value of ARP hypothesis to that of other current theories. It is concluded that recognition hypermnesia using individual words and pictures is a reliable phenomenon, provided ceiling effects can be prevented, and access to the original episodic information takes place using alternative retrieval pathways.

Initial experience with stereotactic body radiation therapy for localized prostate cancer using helical tomotherapy.

PURPOSE: Single-institution single-arm prospective study. Endpoint: To assess whether there are more than 5 % of men having grade 3 GU or any grade 3 GI acute toxicity during stereotactic body radiation therapy (SBRT) for prostate cancer using helical tomotherapy. METHODS: Since May 2012, 17 prostate cancer patients were treated with helical tomotherapy. The exclusion criteria used are the following: Gleason score ≥8, PSA >20 ng/ml, cT3b-4, IPSS ≥20 and history of acute urinary retention. CTV included the prostate gland and 1 cm of seminal vesicles in the low-risk group (LR) or the seminal vesicles completely in the intermediate (IR) and high-risk (HR) NCCN groups. CTV margins ranged from 2 to 8 mm, while PTV margins were 2 to 9 mm. Patients received eight fractions of 5.48 Gy (LR) or 5.65 Gy (IR, HR) on alternate days. Total equivalent doses at 2 Gy per fraction are 87.4 for LR and 92.3 Gy for IR-HR using an α/ß value of 1.5. Correspondent figures for a α/ß of 3 are 74.3 Gy and 78.2 Gy, respectively. Megavoltage CT (MVCT) for on-line correction was taken before every fraction. RESULTS: The patient distribution by risk group is 29, 47 and 24 % for LR, IR and HR, respectively. 82 % received neoadjuvant-concomitant hormonal therapy. Acute GU toxicity grade 1, 2 and 3 was found in 70, 6 and 0 % of men. GI toxicity was observed in 50, 0 and 0. After 136 MVCT, the standard deviation of the mean individual corrections in the anterior-posterior direction was 2.5 mm. CONCLUSION: SBRT for prostate cancer using helical tomotherapy is feasible. Initial results show an early toxicity profile no worse than SBRT delivered with robotic radiosurgery or conventionally fractionated radiotherapy.

Prognostic factors for acute toxicity in prostate cancer patients treated with high-dose hypofractionated radiotherapy.

PURPOSE: To prospectively study acute genitourinary (GU) and gastrointestinal (GI) toxicity during hypofractionated radiotherapy. PATIENTS AND MATERIALS: One-hundred and seventy-one consecutive men with cT1-T3cN0cM0 prostate cancer were treated at 2.6 Gy/fraction to a total dose of 67.6 for low risk (EQD2 = 79 Gy) and 70.2 Gy for intermediate-high risk (EQD2 = 82 Gy) over 5.2-5.4 weeks (α/ß 1.5). Acute toxicity was scored according to RTOG/EORTC toxicity extended criteria after completing a 22-item questionnaire (basal, weekly, at 6 months). RESULTS: Minimum and median follow-up were 36 and 54.2 months, respectively. GU toxicity grades 0, 1, 2 and 3 were found in 30.4, 37, 32 and 0.6 % of patients, respectively. The figures for grades 0, 1, 2 and 3 GI toxicity were 66, 24, 10 and 0 %. The highest degree of acute reactions was reached at 4-5 weeks. At 6 months, 15 % of patients had GU toxicity (11 % grade 1, 4 % grade 2) and 5.8 % GI toxicity (5.3 % grade 1, 0.5 % grade 2). Multivariate analysis shows that bladder volume receiving ≥65 Gy (V 65) is associated with an increased risk of GU complications (p = 0.017, HR = 1.143, 95 % CI = 1.025-1.276), while history of TURP is linked to lower risk (p = 0.002, HR = 0.310, 95 % CI 0.004-0.370). Mean rectal dose (p = 0.013, HR = 1.089, 95 % CI 1.018-1.116) and total dose (p = 0.019, HR = 0.734, 95 % CI 0.567-0.950) are significantly related to GI toxicity. CONCLUSIONS: This 5-week dose-escalation hypofractionated radiotherapy schedule that uses 3D-conformal radiotherapy without IGRT has resulted in <1 % grade 3 acute complications. Our study suggests that reducing the mean rectal dose and the bladder V 65 helps prevent acute toxicity. TURP before radiotherapy was associated with lower acute GU toxicity.