Thermoradiotherapy optimization strategies accounting for hyperthermia delivery uncertainties.

INTRODUCTION: The combined effect of hyperthermia and radiotherapy can be quantified by an enhanced equivalent radiation dose (EQDRT). Uncertainties in hyperthermia treatment planning and adjustments during treatment can impact achieved EQDRT. We developed and compared strategies for EQDRT optimization of radiotherapy plans, focusing on robustness against common adjustments. METHODS: Using Plan2Heat, we computed pre-planning hyperthermia plans and treatment adjustment scenarios for three cervical cancer patients. We imported these scenarios into RayStation 12A for optimization with four different strategies: (1) Conventional radiotherapy optimization prescribing 46 Gy to the planning target volume (PTV), (2) Nominal EQDRT optimization using the pre-planning scenario, targeting uniform 58 Gy in the gross tumor volume (GTV), keeping organs at risk (OAR) doses as in plan (1), (3) Robust EQDRT optimization, as (2) but adding adjusted scenarios for optimization, (4) Library of Plans (four plans), with strategy (2) criteria but optimizing on one adjusted scenario per plan. We calculated for each radiotherapy plan EQDRT distributions for pre-planning and adjusted scenarios, evaluating for each combination GTV coverage and homogeneity objectives. RESULTS: EQDRT95% increased from 49.9-50.9 Gy in strategy (1) to 56.1-57.4 Gy in strategy (2) with the pre-planning scenario, improving homogeneity in ∼10%. Strategy (2) demonstrated the best overall robustness, with 62% of all GTV objectives within tolerance. Strategy (3) had higher percentage of coverage objectives within tolerance than strategy (2) (68% vs 54%), but lower percentage for uniformity (44% vs 71%). Strategy (4) showed similar EQDRT95% and homogeneity for adjusted scenarios than strategy (2) for pre-planning scenario. D0.1% for OARs was increased by strategies (2-4) by up to ∼6 Gy. CONCLUSIONS: EQDRT optimization enhances EQDRT levels and uniformity compared to conventional optimization. Better overall robustness is achieved optimizing on the pre-planning hyperthermia plan. Robust optimization improves coverage but reduces homogeneity. A library of plans ensures coverage and uniformity when dealing with adjusted hyperthermia scenarios.

Cystic fibrosis: desensitization in delayed hypersensitivity reactions to elexacaftor/tezacaftor/ivacaftor.

Background: Cystic fibrosis transmembrane conductance regulator modulators are the only available treatment for cystic fibrosis. Although elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) is well-tolerated, rash has been reported as very frequent. In severe rashes, ELX/TEZ/IVA withdrawal is necessary, leading to clinical deterioration. The objective of the study is to increment the experience of ELX/TEZ/IVA desensitization. Methods: Adult patients who developed a delayed hypersensitivity rash to ELX/TEZ/IVA between December 2021 and February 2023 and required withdrawal due to ineffective rescue medication were included. Skins test for ELX/TEZ/IVA and IVA were conducted to establish hypersensitivity mechanism. Balijepally ELX/TEZ/IVA desensitization protocol was selected. In cases where desensitization had to be discontinued due to rash, an extended desensitization was proposed. Clinical and health-related quality of life parameters were collected before ELX/TEZ/IVA and after desensitization. Results: 162 patients (81 women, 31.2 [23.8-42.5] years) started ELX/TEZ/IVA, developing rash 12 of them (7.4%, six women). Six patients (five women) required stopping ELX/TEZ/IVA and were selected for desensitization. Skin tests indicated delayed type-IV hypersensitivity in one patient. Two patients presented adequate tolerance to desensitization; while, four patients developed rash. Three of these patients, successfully concluded extended desensitization (one patient declined participation). No significant clinical deterioration or quality of life worsening was observed during desensitization; in fact, there was an improvement in practically all mesured parameters. All five patients who resumed ELX/TEZ/IVA are currently receiving therapy with good tolerance. Conclusion: Desensitization to ELX/TEZ/IVA could be a successful and safe strategy for reintroducing this essential treatment in cases of a delayed hypersensitivity rash.

Improving hybrid image and structure-based deformable image registration for large internal deformations.

Objective.Deformable image registration (DIR) is a widely used technique in radiotherapy. Complex deformations, resulting from large anatomical changes, are a regular challenge. DIR algorithms generally seek a balance between capturing large deformations and preserving a smooth deformation vector field (DVF). We propose a novel structure-based term that can enhance the registration efficacy while ensuring a smooth DVF.Approach.The proposed novel similarity metric for controlling structures was introduced as a new term into a commercially available algorithm. Its performance was compared to the original algorithm using a dataset of 46 patients who received pelvic re-irradiation, many of which exhibited complex deformations.Main results.The mean Dice Similarity Coefficient (DSC) under the improved algorithm was 0.96, 0.94, 0.76, and 0.91 for bladder, rectum, colon, and bone respectively, compared to 0.69, 0.89, 0.62, and 0.88 for the original algorithm. The improvement was more pronounced for complex deformations.Significance.With this work, we have demonstrated that the proposed term is able to improve registration accuracy for complex cases while maintaining realistic deformations.

Inter-laboratory method validation of CD34+ flow-cytometry assay: the experience of Turin Metropolitan Transplant Centre.

The Turin Metropolitan Transplant Centre (CIC 305) includes four flow-cytometry laboratories assessing quality control on hematopoietic stem cells (HSC) with different instruments and operators. Therefore, the CD34+ enumeration assay should be validated on a regular basis. We describe here the validation plan to test the inter-laboratory reproducibility of CD34+ enumeration assay, based on the risk analysis. Stabilized blood samples were analysed using Stem-Kit reagent according to manufacturer's instructions and acquired using the Beckman Coulter Navios at Regina Margherita Children's' Hospital (305-1), Beckman Coulter FC500 at Candiolo Cancer Institute FPO-IRCCS (305-2), BD Biosciences FACSLyric™ at S. Luigi Hospital (305-3), and Beckman Coulter Navios EX at Mauriziano Hospital (305-4). The ISHAGE guidelines were followed for estimating % and absolute number of CD34+ cells in single-platform method. For each sample repeatability limit (r), reproducibility error, uncertainty of reproducibility error and coefficient of variation (CV) were reported. The repeated measurements from each laboratory or instrument have a variability, expressed as reproducibility error, lower than the repeatability limit for that single parameter. The corrected reproducibility error is always lower than the repeatability limit except for the percentage value of the "low" count. The analysis of inter-laboratory variance is within the maximum acceptable variance value, and the CV of all measurements for each parameter is less than 8%, indicating low measurement variability among laboratories. Evaluating the overall data, we can conclude that the four laboratories are perfectly aligned and the results are reproducible.

External Beam Radiotherapy in Western Africa: 1969-2019.

AIMS: We describe the absolute and per capita numbers of megavoltage radiotherapy machines (MVMs) in Western Africa from 1969 to 2019. MATERIALS AND METHODS: Western Africa was defined in accordance with the United Nations' delineation and inclusive of 16 countries. A literature search for publications detailing the number of cobalt-60 machines (COs) and linear accelerators (LINACs) in radiotherapy centres was carried out. Population data from the World Bank Group and crude cancer rates from the International Agency for Research on Cancer were used to calculate ratios of million persons per MVM and MVMs per 1000 cancer cases. RESULTS: The numbers of MVMs in Western Africa in 1969, 1979, 1989, 1999 and 2009 were zero, two, three, six and nine, respectively. In 2019 there were 22 MVMs distributed across Ghana (five), Côte d'Ivoire (two), Mali (one), Mauritania (two), Nigeria (nine) and Senegal (three). Nine countries (56.3%) had no history of external beam radiotherapy (EBRT). The largest increase in absolute EBRT capacity occurred from 2017 to 2019, during which 13 MVMs were commissioned. The largest decrease in EBRT capacity occurred from 2015 to 2017, during which four LINACs and three COs were rendered non-operational. The ratio of million persons per MVM improved from 67.0 in 1979 to 17.8 in 2019. As of 2019, there was 0.09 MVM per 1000 cancer cases. CONCLUSIONS: Western African nations have experienced an increase in the absolute number of MVMs and per capita radiotherapy capacity during the last 50 years, especially in the last decade. As non-functional LINACs contributed to a temporary decline in the EBRT infrastructure, dual use of CO/LINAC technologies may act to promote the availability of EBRT treatment in centres with capacity for multiple MVMs.

Aluminum oxides as alternative building blocks for efficientlayer-by-layerblocking layers in dye-sensitized solar cells.

All inorganic layer-by-layer (LbL) thin films composed by TiO2nanoparticles and [Al(OH)4]-anions (TiO2/AlOx) as well as Al2O3and Nb2O5nanoparticles (Al2O3/Nb2O5) have been deposited to fluorine-doped tin-oxide coated glass (FTO) surfaces and applied as blocking layers in dye-sensitized solar cells (DSCs). Structural and morphological characterization of the LbL films by different techniques reveal that inTiO2/AlOxassembly, aluminate anions undergo condensation reactions on the TiO2surface leading to the formation of highly homogeneous films with unique optical properties. After 25 depositions transmittance losses below 10% in relation to the bare FTO substrate are observed. Electrochemical impedance spectroscopy shows thatTiO2/AlOxlayers impose an effective barrier for the charge recombination at FTO/electrolyte interface with an electron exchange time constant 50-fold higher than that for bare FTO. As a result, an improvement of 85% in the overall conversion efficiency of DSCs was observed with the employment of TiO2/AlOxblocking layers.Al2O3/Nb2O5LbL films can also work as blocking layers in DSCs but not as efficient, which is associated with the poor homogeneity of the film and its capacitive behavior. The production of cost-effective blocking layers with a low light scattering in the visible region is an important feature toward the application of DSC in other Building-integrated photovoltaic applications.

Clinical practice update of antifungal prophylaxis in immunocompromised children.

Due to the rise in the number and types of immunosuppressed patients, invasive fungal infections (IFI) are an increasing and major cause of morbidity and mortality in immunocompromised adults and children. There is a broad group of pediatric patients at risk for IFI in whom primary and/or secondary antifungal prophylaxis (AFP) should be considered despite scant evidence. Pediatric groups at risk for IFI includes extremely premature infants in some settings, while in high-risk children with cancer receiving chemotherapy or undergoing haematopoietic stem cell transplantation (HCT), AFP against yeast and moulds is usually recommended. For solid organ transplanted, children, prophylaxis depends on the type of transplant and associated risk factors. In children with primary or acquired immunodeficiency such as HIV or long-term immunosuppressive treatment, AFP depends on the type of immunodeficiency and the degree of immunosuppression. Chronic granulomatous disease is associated with a particular high-risk of IFI and anti-mould prophylaxis is always indicated. In contrast, AFP is not generally recommended in children with long stay in intensive care units. The choice of AFP is limited by the approval of antifungal agents in different age groups and by their pharmacokinetics characteristics. This document aims to review current available information on AFP in children and to provide a comprehensive proposal for each type of patient.

Introducing FDG PET/CT-guided chemoradiotherapy for stage III NSCLC in low- and middle-income countries: preliminary results from the IAEA PERTAIN trial.

PURPOSE: Patients with stage III non-small-cell lung cancer (NSCLC) treated with chemoradiotherapy (CRT) in low- and middle-income countries (LMIC) continue to have a poor prognosis. It is known that FDG PET/CT improves staging, treatment selection and target volume delineation (TVD), and although its use has grown rapidly, it is still not widely available in LMIC. CRT is often used as sequential treatment, but is known to be more effective when given concurrently. The aim of the PERTAIN study was to assess the impact of introducing FDG PET/CT-guided concurrent CRT, supported by training and quality control (QC), on the overall survival (OS) and progression-free survival (PFS) of patients with stage III NSCLC. METHODS: The study included patients with stage III NSCLC from nine medical centres in seven countries. A retrospective cohort was managed according to local practices between January 2010 and July 2014, which involved only optional diagnostic FDG PET/CT for staging (not for TVD), followed by sequential or concurrent CRT. A prospective cohort between August 2015 and October 2018 was treated according to the study protocol including FDG PET/CT in treatment position for staging and multimodal TVD followed by concurrent CRT by specialists trained in protocol-specific TVD and with TVD QC. Kaplan-Meier analysis was used to assess OS and PFS in the retrospective and prospective cohorts. RESULTS: Guidelines for FDG PET/CT image acquisition and TVD were developed and published. All specialists involved in the PERTAIN study received training between June 2014 and May 2016. The PET/CT scanners used received EARL accreditation. In November 2018 a planned interim analysis was performed including 230 patients in the retrospective cohort with a median follow-up of 14 months and 128 patients in the prospective cohort, of whom 69 had a follow-up of at least 1 year. Using the Kaplan-Meier method, OS was significantly longer in the prospective cohort than in the retrospective cohort (23 vs. 14 months, p = 0.012). In addition, median PFS was significantly longer in the prospective cohort than in the retrospective cohort (17 vs. 11 months, p = 0.012). CONCLUSION: In the PERTAIN study, the preliminary results indicate that introducing FDG PET/CT-guided concurrent CRT for patients with stage III NSCLC in LMIC resulted in a significant improvement in OS and PFS. The final study results based on complete data are expected in 2020.

Photocatalytic oxidation of diuron using nickel organic xerogel under simulated solar irradiation.

In this study, a nickel organic xerogel (X-Ni) was used as semiconductor photocatalyst for the degradation of the herbicide diuron (DRN) in aqueous solution. The main objective of this work was to analyze and compare the effectiveness of solar irradiation to remove DRN from water both by direct photolysis and photocatalytic degradation. We examined the influence of the initial concentration of the herbicide, the solution pH, the presence of different ions in the medium, the chemical composition of the water, and the presence of a photocatalyst, after 240 min of irradiation. Direct photolysis achieved a low percentage of DRN degradation but was favored: i) by a reduction in the initial concentration of the herbicide (from 35.6% to 79.0% for 0.150 × 10-3 mol/L and 0.021 × 10-3 mol/L of DRN, respectively) and ii) at solution pHs at which diuron is positively charged (78.6% for pH 2 and 50.4% for pH 7), as suggested by DFT calculations carried out for DRN and its protonated form (DRN-H+). The corresponding mono-demethylated DRN derivative, 1-(3,4-dichlorophenyl)-3-methylurea (DCPU), was identified as a DRN degradation byproduct. In addition, the presence of certain anions in the medium significantly affected the overall degradation process by direct photolysis, due to the additional generation of HO radicals. We highlight that the presence of X-Ni considerably improved the photodegradation process under solar irradiation. The photocatalytic degradation rate constant was directly proportional to the xerogel concentration, because an increase in catalyst dose produced an increase in surface active sites for the photodegradation of DRN, enhancing the overall efficiency of the process. Thus, when 4167 mg/g of X-Ni was added, the DRN removal rate was 3-fold higher and both percentage of degradation and mineralization increased 88.5% with respect to the results obtained by direct photolysis.

Residuos sólidos en viviendas de interés social / Solid waste in social interest housing

Objetivo. Determinar el conocimiento y actitud, acerca del manejo de los residuos sólidos domiciliarios, que tienen los habitantes de unas viviendas de interés social del municipio de Montería. Materiales y métodos. Estudio descriptivo, cuantitativo, transversal, coninformación recolectada mediante aplicación de un cuestionario, que evaluó aspectos relacionados con el conocimiento y actitud de las personas acerca del manejo de los residuos sólidos domiciliarios. Se realizó en 24 torres de apartamentos de viviendas de interés social; se tomó una muestra aleatoria de 175 apartamentos, en donde se aplicó un cuestionario a los jefes de hogar para la recolección de la información, la cual fue recolectada en físico y procesada en SPSS. Resultados. Los hallazgos indican que el 68% de los jefes de hogar manifiestan que tienen conocimiento de algunas técnicas de reciclaje; el 60% refieren que no separan los residuos; el 70% no separa los desechos tecnológicos; 65,7% no tiene claridad acerca de cuáles son los llamados residuos sólidos; el 63,5% no conoce el código de colores que permite una clasificación adecuada de los residuos. Conclusiones. En las viviendas objeto de estudio, es necesario implementar estrategias para mejorar el conocimiento de los habitantes que contribuya a una adecuada separación en la fuente de los residuos sólidos domiciliarios, para favorecer la reducción en la producción de basura y el desarrollo de una conciencia del cuidado al ambiente.

Objective. Determine the knowledge of and attitude to ward the management of solid house hold waste that the inhabitants of social housing have in the municipality of Monteria. Materials and methods. This was a descriptive, quantitative, and cross-sectional study with information collected through the application of a question naire, which evaluated aspects related to the knowledge of and attitude of people toward the man agement of solid house hold waste. The study was carried out in 24 apartment towers of social-interes thousing. Arandom sample of 175 apartments was chosen, and a questionn aire was administered to the heads of house holds forthe collection of the information, which was collected inphysical formand process edin SPSS. Results. The finding sindicated that 68% of heads of households have knowledge of somere cycling techniques; 60% reported that they do not separate the waste; 70% of them did not separate technological waste; 65.7 % of the respondents were not cleara bout what is called solid waste; and 63.5% of them did not know the color code that allows an adequate classification ofwaste. Conclusion. In the home sunder study, it is necessary to implement strategies to improve the knowledge of the inhabitants that contribute to an adequate separation in the source of the household solid waste to favor the reduction in the production of garbage and the development of anawareness of the care for the environment.

Global Access to Radiotherapy in Low- and Middle-income Countries.

Over the last 60 years, the International Atomic Energy Agency (IAEA) has been working to introduce, expand and improve radiotherapy services, working with partners such as the World Health Organization (WHO) to improve cancer diagnosis, treatment, care and control through collective action in low- and middle-income countries (LMICs). The Lancet Oncology Commission on radiotherapy published a report that defined five calls for action to expand global access to radiotherapy, drawing on the previous work of the Global Taskforce on Radiotherapy for Cancer Control. The IAEA supports LMICs in the development of the required national infrastructure and regulatory authority for radiation and nuclear safety and in the training of human resources necessary for the provision of high-quality effective and safe radiation medicine services for the diagnosis, treatment and palliative care of cancer patients, helping in this way to address the different priorities outlined in the Lancet Commission report.

Recommendations of the Spanish Brachytherapy Group of SEOR for HDR endoluminal treatments. Part 1: Oesophagus.

The endoesophageal brachytherapy technique provides good results in the treatment of oesophageal cancer, when indicated. In a consensus meeting, the Spanish Brachytherapy Group of SEOR and the Spanish Society of Medical Physics (SEFM) agreed on the indications, dose, fractionation schedule, prescription and reporting to be performed in endoesophageal brachytherapy. The results of this consensus are presented here as recommendations for medical practice.

[The use of therapeutic apheresis in neurological diseases and comparison between plasma exchange and immunoadsorption]. / Utilizzo dell'aferesi terapeutica in corso di patologie neurologiche comparazione tra plasmaexchange ed immunoadsorbimento.

The use of plasmapheresis in neurological diseases with immune-mediated pathogenesis is widely certified. In recent years, the technological evolution of the dialysis membranes allowed to accompany the classical plasma exchange (PEX) treatment of apheresis by means of selective adsorption (IA). It has proved to be of equal therapeutic efficacy and, at the same time, devoid of most of the PEX side effects. The recent guidelines of the American Society for Apheresis (ASFA) and, later, the American Academy of Neurology, outlined directions and diagrams for the application of the method that has found wide use in many neurological diseases on the basis of auto-antibodies; in particular in Myasthenia Gravis, Guillain-Barre Syndrome, Multiple Sclerosis and Chronic Demyelinating Polyradiculoneuropathy. We add our experience in the treatment of 13 patients suffering from Myasthenia Gravis, treated over a four years period with filters containing tryptophan immunoadsorption in polyvinyl alcohol gel. The results confirm the achievement of a rapid regression of clinical symptoms, together with the rapid fall in the levels of antibody against acetylcholine-receptor. Therefore, the method of AI is to be considered of equal therapeutic efficacy of PEX, providing greater security in its use.

Intraoperative radiotherapy-containing multidisciplinary management of trunk-wall soft-tissue sarcomas.

PURPOSE: A joint analysis of data from centers within the intraoperative radiotherapy (IORT)-Spanish cooperative initiative was performed to investigate the main contributions of IORT to the multidisciplinary treatment of trunk-wall soft-tissue sarcoma (TW-STS). MATERIALS AND METHODS: Patients with a histologic diagnosis of TW-STS (primary tumor 53 %; locally recurrent 47 %) with absence of distant metastases, undergoing surgery with radical intent and IORT (median dose 12.5 Gy) were considered eligible for participation in this study. In addition, all primary tumors received external-beam radiotherapy (median dose 50 Gy). RESULTS: From 1986 to 2012, a total of 68 patients were analyzed in the study from three Spanish institutions. With a median follow-up time of 53 months (range 4-316), 5-year local control (LC) was 58 %. Five-year IORT in-field control, disease-free survival (DFS) and overall survival were 70, 45 and 51 %, respectively. On multivariate analysis, only microscopically involved margin (R1) resection status retained significance in relation to LC (HR 3.97, p < 0.001). In regard to IORT in field control, incomplete resection (HR 3.23, p = 0.008) and recurrent disease status (HR 2.52, p = 0.04) retained a significant association in multivariate analysis. CONCLUSION: From this joint analysis emerges the fact that margin and disease status influences local and central control, but DFS remains modest, given the high risk of distant metastases. Intensified local treatment needs to be tested in the context of more efficient concurrent, neo-, and adjuvant systemic therapy.

Chromosome 16 abnormalities in embryos and in sperm from a male with a fragile site at 16q22.1.

Two fragile sites, FRA16B and FRA16C, are located in the chromosome band 16q22.1. Neither of them is associated with any specific clinical condition. We report the development and outcome of a clinically applied PGD cycle in a couple who had difficulty in achieving pregnancy. The woman was a carrier of a balanced reciprocal translocation, t(11;22)(q23;q11.2), and the man presented high expression of the fragile site 16q22.1 (FRA16B/C) in peripheral blood lymphocytes. Gains and losses of chromosome 16 fragments were detected in sperm and embryos. To our knowledge, this is the first documented case suggesting a link between FRA16B/C and chromosome 16 abnormalities in embryos and sperm from a carrier.

Retreatment with radiotherapy for symptomatic bone, brain or visceral metastases.

BACKGROUND: The need for reirradiation in the metastatic disease appears when other modalities of treatment lose their efficacy. The aim of reirradiation in the metastatic disease is mainly palliative to control a particular symptom. However, this theoretical benefit must be confronted against the risk of an undesirable toxicity. MATERIALS AND METHODS: Experience with reirradiation for symptomatic bone, brain or visceral metastases are reviewed. Twenty-two patients were found to have a second palliative radiotherapy on the same location. Locatión of metastases were visceral in 5 (23 %) patients, brain in 4 (18 %) patients, spine in 1 (4.5 %) patient and bone metastasis other than spine in 12 (54.5 %) patients. Median dose delivered in the first treatment was 30 Gy (range 20-30 Gy) and 20 Gy for the second treatment (range 6-32.4 Gy). RESULTS: A good symptomatic response after first irradiation (complete response or disappearance of >50 % of symptoms) was reached in 21 (95.5 %) of the 22 patients analyzed. After second irradiation, 82 % (18 patients) achieved a good response, 3 (14 %) patients had a moderate response (relief of symptoms <50 %) whereas no response was observed in 1 (4 %) patient. Acute toxicity was limited to grade 1-2 proctitis in 2 and 3 patients after the first and second irradiation, respectively. No cases of late toxicity after the first or second irradiation were recorded. CONCLUSION: A second treatment with palliative radiotherapy is feasible and well tolerated and offers the possibility of symptomatic relief in a high percentage of patients with symptomatic metastases.

Pilot study of feasibility and dosimetric comparison of prone versus supine breast radiotherapy.

PURPOSE: The aim of this study was to demonstrate feasibility and analyze dosimetric differences in prone and supine position breast cancer radiotherapy in women with large or pendulous breast. METHODS: Ten post-lumpectomy breast cancer patients underwent supine and prone computed tomography-based treatment plan. On each data set, the whole breast, the ipsilateral lung and the heart were outlined. Multisegment tangential-fields plans were generated for each position. Target coverage, homogeneity, overdosage outside breast and organ at risk sparing were analyzed and compared for supine and prone position. RESULTS: Coverage and dose homogeneity of the PTV measured by D 90 and V(95)% were similar for both plans although breast maximum dose was higher in the supine plan (p = 0.017). Prone position reduced the percentage of ipsilateral lung receiving 20 Gy (V(20Gy)) from 26.5 to 2.9 % (p = 0.007), medium lung dose, as well as the percentage of the heart receiving 35 Gy heart (V(35Gy)) from 3.4 to 1.2 % (p = 0.038). Overdosage of areas outside breast PTV was also consistently reduced with prone position (p = 0.012). In addition, average number of segments and monitor units needed was reduced in prone position. CONCLUSIONS: Prone position in large breast women appears to favor normal tissue sparing in breast radiotherapy as compared to supine position, without diminishing the target coverage.

First successful double-factor PGD for Lynch syndrome: monogenic analysis and comprehensive aneuploidy screening.

Preimplantation genetic diagnosis (PGD) has been applied worldwide for a great variety of single-gene disorders over the last 20 years. The aim of this work was to perform a double-factor preimplantation genetic diagnosis (DF-PGD) protocol in a family at risk for Lynch syndrome. The family underwent a DF-PGD approach in which two blastomeres from each cleavage-stage embryo were biopsied and used for monogenic and comprehensive cytogenetic analysis, respectively. Fourteen embryos were biopsied for the monogenic disease and after multiple displacement amplification (MDA), 12 embryos were diagnosed; 5 being non-affected and 7 affected by the disease. Thirteen were biopsied to perform the aneuploidy screening by short-comparative genomic hybridization (CGH). The improved DF-PGD approach permitted the selection of not only healthy but also euploid embryos for transfer. This has been the first time a double analysis of embryos has been performed in a family affected by Lynch syndrome, resulting in the birth of two healthy children. The protocol described in this work offers a reliable alternative for single-gene disorder assessment together with a comprehensive aneuploidy screening of the embryos that may increase the chances of pregnancy and birth of transferred embryos.

BDNF gene therapy induces auditory nerve survival and fiber sprouting in deaf Pou4f3 mutant mice.

Current therapy for patients with hereditary absence of cochlear hair cells, who have severe or profound deafness, is restricted to cochlear implantation, a procedure that requires survival of the auditory nerve. Mouse mutations that serve as models for genetic deafness can be utilized for developing and enhancing therapies for hereditary deafness. A mouse with Pou4f3 loss of function has no hair cells and a subsequent, progressive degeneration of auditory neurons. Here we tested the influence of neurotrophin gene therapy on auditory nerve survival and peripheral sprouting in Pou4f3 mouse ears. BDNF gene transfer enhanced preservation of auditory neurons compared to control ears, in which nearly all neurons degenerated. Surviving neurons in treated ears exhibited pronounced sprouting of nerve fibers into the auditory epithelium, despite the absence of hair cells. This enhanced nerve survival and regenerative sprouting may improve the outcome of cochlear implant therapy in patients with hereditary deafness.