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The application of new commercial and industrial technologies in the fields of dosimetry and medical physics is of great interest to the scientific community, both to validate existing protocols and to develop new methodologies. The popularization of 3D printing techniques has been analyzed as a great advantage in quality control in complex treatment techniques, such as radiotherapy and the development of patient simulators. Portable dosimetry systems such as Landauer MicroStar OSL system are versatile and their use in quality control is of great importance. The aim of this paper is to compare two of the most used dose calculation algorithms used in Varian Eclipse TPS – AAA and Acuros XB – for treatment planning of multiple brain metastases using a 3D printed anthropomorphic phantom and the OSL InLight system for experimental dosimetry validation. A 3D printed anthropomorphic skull phantom was submitted to a CT scan and planed five target volumes. In order of comparison, two dose calculations were performed in the Varian Eclipse 13.6 TPS with "Alabama technique", using the Varian’s AAA and AXB algorithms, and treatment delivered with 6 MV photon beam of a Varian TrueBeam linear accelerator. Landauer nanoDot dosimeters were positioned inside each of the five target volumes planned and the experimental dosimetric results were compared with the algorithms’ calculated doses. The findings of this work indicate that ACUROS XB calculates more accurate doses compared with AAA, with all the experimental agreements better than 96.0 %, probably because of the heterogeneity corrections. The uncertainty analysis of the InLight system device is enough to sustain the dosimetric uncertainties below 3.0 %, validating the results.

The Total Skin Electron Beam (TSEB) irradiation is a radiotherapeutic technique that aims to provide the patient's skin surface with a more homogeneous dose, in order to treat cutaneous T-cell lymphomas, both for curative and palliative purposes. Electron irradiation penetrates a few millimeters into the skin, reaching the affected parts completely, without penetrating the internal organs. In vivo dosimetry has become an important role for the treatment of total skin irradiation within a rigorous quality assurance program that should be an integral part of the radiotherapy departments. The use of TLDs in vivo can identify variations in the prescribed dose because its measurement accuracy and great precision. The LiF:Mg,Ti is the most used TL material and widely studied in radiotherapy dosimetry due to near tissue-equivalence of the material, along with its overall reliability. The dosimeters of μLiF:Mg,Ti have been gaining considerable importance in the radiotherapy departments. These detectors allow measurements in vivo with great advantages due to their minimum dimensions of 1 × 1 × 1 mm3. This paper reports a comparative study of the TL responses of both materials to dose evaluation in TSEB treatments. The TL response of both materials in several TSEB parameter tests and in clinical application were evaluated, analyzing the dose distribution in a treatment simulation using AldersonRando anthropomorphic phantom. The results showed that the μLiF:Mg,Ti presented greater variation of the response in relation to LiF dosemeters in some parameters analyzed, due to the small dimensions and to evaluate doses absorbed in the surface over a large area in the treatment plan.

Rare Earth doped-phosphate glasses have received a great deal of attention on research because of their applications in biomaterial engineering, however, little to no attention has been given to potential luminescent properties from “heating” these materials when exposed to ionizing radiation. This paper aims to presents results on investigations of Thermoluminescent (TL) and Optically Stimulated Luminescence (OSL) properties of the Er3+-doped phosphate glasses produced at the Physics Department of Federal University of Juiz de Fora on a characterization for beta radiation dosimetry. It was used a RISO TL/OSL reader and its coupled 90Sr/90Y beta source. The experimental findings indicate that the material presents linear responses of thermo (TL) and optically stimulated luminescence (OSL) over the absorbed dose range of 2 to 20Gy. Its emitted TL and OSL signal is more intense and with extended linearity range compared with undoped phosphate glass, probably caused by two absorption bands on 350–380 nm from Er3+. Further investigations are being carried out on its applications to other types and qualities of radiation.

The commissioning and quality assurance The Total Skin Electron Beam (TSEB) irradiation treatment is based on the AAPM's report 23, which describes the six-dual-field (Standford) technique, and the Hospital Israelita Albert Einstein (HIAE) follows this recommended guidance. The Dosimetric Materials Laboratory of the Instituto de Pesquisas Energeticas e Nucleares (IPEN-LMD) has tradition in research related to thermoluminescent materials and its clinical applications. Thus, aiming to apply the LiF:Mg,Ti, the most common TLD material, and CaSO4:Dy + Teflon produced at IPEN as easy-to-use alternatives to electron beams dosimetry and its parameters applied to TSEB, this paper reports a comparative study of the TL responses of both materials to dose evaluation in TSEB treatments. The TL response of both materials was evaluated in several TSEB parameter tests such as clinical field homogeneity, Monitor Units (MU) calculation, absorbed doses over the reference line and throughout the surface of the skin in a treatment simulation using AldersonRando anthropomorphic phantom. Results show that the field homogeneity measurements remained within ± 8% acceptance limit from AAPM Report 23, little to no energy dependency over the range of 4 o 9 MeV electron beams and, for clinical measurements and MU calculations, both TLDs present compatible results and can be used as alternative tools in TSEB dosimetry.

The mammography is the most important and simple tool in the diagnosis of breast diseases in women. In digital mammography, the process of image acquisition, display and storage are separated which allows optimization of each. Despite the innumerous advantages of this technique, such as an accurate diagnosis for women with dense breast, it was noticed an increase of radiation doses to obtain the images by this system. As with any examination that includes x-rays, there is always a small stochastic risk of inducing cancer, it is therefore important to evaluate the risk from the dose delivered to the patient during the screening process. The mean glandular dose within the breast is the recommended quantity to evaluate the risk from radiation to the breast. To guarantee proper conditions of protection for patients, the radiation dose should be as low as reasonably achievable possible and simultaneously compatible with image quality requirements. Thus, this work proposes the use of the thermoluminescent (TL) CaSO4:Dy sintered discs, produced at IPEN, widely used in individual, environmental and area monitoring in Brazil, and Al2O3:C optically stimulated luminescence (OSL) ‘dot’ dosimeters, manufactured by Landauer® Inc., as application as easy-to-use and low cost alternative dosimeters to evaluate the entrance skin doses (ESD) delivered to patients, the half value layer (HVL) and the mean glandular doses (MGD) in a mammographic digital unit, comparing these two techniques with the results obtained using an All-in-one QC meter. The results obtained demonstrated that the TL and OSL dosimetry systems and the CaSO4 and Al2O3 dosimeters used are able to evaluate the entrance skin dose as well as mean glandular doses in a digital mammographic unit accurately within the requirements, and they can be considered a practical, simple, easy-to-use and low cost tools for verification of these items in a Quality Assurance Program.

Purpose To test the association between death and both qualitative and quantitative CT parameters obtained visually and by software in coronavirus disease (COVID-19) early outbreak. Methods The study analyzed retrospectively patients underwent chest CT at hospital admission for COVID-19 pneumonia suspicion, between February 21 and March 6, 2020. CT was performed in case of hypoxemia or moderate-to-severe dyspnea. CT scans were analyzed for quantitative and qualitative features obtained visually and by software. Cox proportional hazards regression analysis examined the association between variables and overall survival (OS). Three models were built for stratification of mortality risk: clinical, clinical/visual CT evaluation, and clinical/software-based CT assessment. AUC for each model was used to assess performance in predicting death. Results The study included 248 patients (70% males, median age 68 years). Death occurred in 78/248 (32%) patients. Visual pneumonia extent > 40% (HR 2.15, 95% CI 1.2–3.85, P = 0.01), %high attenuation area – 700 HU > 35% (HR 2.17, 95% CI 1.2–3.94, P = 0.01), exudative consolidations (HR 2.85–2.93, 95% CI 1.61–5.05/1.66–5.16, P < 0.001), visual CAC score > 1 (HR 2.76–3.32, 95% CI 1.4–5.45/1.71–6.46, P < 0.01/P < 0.001), and CT classified as COVID-19 and other disease (HR 1.92–2.03, 95% CI 1.01–3.67/1.06–3.9, P = 0.04/P = 0.03) were significantly associated with shorter OS. Models including CT parameters (AUC 0.911–0.913, 95% CI 0.873–0.95/0.875–0.952) were better predictors of death as compared to clinical model (AUC 0.869, 95% CI 0.816–0.922; P = 0.04 for both models). Conclusions In COVID-19 patients, qualitative and quantitative chest CT parameters obtained visually or by software are predictors of mortality. Predictive models including CT metrics were better predictors of death in comparison to clinical model. Supplementary Information The online version contains supplementary material available at 10.1007/s10140-020-01867-1.

Purpose Chest computed tomography (CT) is considered a reliable imaging tool for COVID-19 pneumonia diagnosis, while lung ultrasound (LUS) has emerged as a potential alternative to characterize lung involvement. The aim of the study was to compare diagnostic performance of admission chest CT and LUS for the diagnosis of COVID-19. Methods We included patients admitted to emergency department between February 21-March 6, 2020 (high prevalence group, HP) and between March 30-April 13, 2020 (moderate prevalence group, MP) undergoing LUS and chest CT within 12 h. Chest CT was considered positive in case of “indeterminate”/“typical” pattern for COVID-19 by RSNA classification system. At LUS, thickened pleural line with ≥ three B-lines at least in one zone of the 12 explored was considered positive. Sensitivity, specificity, PPV, NPV, and AUC were calculated for CT and LUS against real-time reverse transcriptase polymerase chain reaction (RT-PCR) and serology as reference standard. Results The study included 486 patients (males 61 %; median age, 70 years): 247 patients in HP (COVID-19 prevalence 94 %) and 239 patients in MP (COVID-19 prevalence 45 %). In HP and MP respectively, sensitivity, specificity, PPV, and NPV were 90–95 %, 43–69 %, 96−72 %, 20–95 % for CT and 94−93 %, 7–31 %, 94−52 %, 7–83 % for LUS. CT demonstrated better performance than LUS in diagnosis of COVID-19, both in HP (AUC 0.75 vs 0.51; P

Background While mucosal (MH) and transmural healing (TH) predict relevant clinical outcomes in Crohn’s disease (CD), little is known about the real significance and clinical impact of deep remission (DR). The aim of this study was to better explore the concept of DR, towards a direct correlation between MH, TH and biomarkers. Methods A real-world observational longitudinal study was performed to evaluate the rate of clinical remission (CR), MH and TH, and the fecal calprotectin (FC)/C-reactive protein (CRP) levels in all consecutive patients with CD undergoing maintenance treatment with biologics. A ROC curve was constructed to define the best FC and CRP cut-offs associated with MH and TH. Finally, CD patients achieving CR, MH and TH, in association with the target FC and CRP values, were considered in DR. Results Among, 118 CD patients, CR, MH and TH were achieved in, 74 (62.7%), 52 (44.1%) and, 38 patients (32.2%), respectively. After, 2 years, the mean FC levels decreased from, 494 ±, 515.4 μg/gr to, 260 ±, 354.9 μg/gr (p Conclusion A FC cut-off of, 94 μg/gr and a normal CRP could be included in the definition of DR in association with CR, MH and TH. Thus, DR can be achieved in approximately, 30% of CD patients during maintenance treatment with biologics.

Thermoluminescent dosimeters (TLDs) play an important role in radiotherapy for the dosimetry of ionizing radiation. This type of dosimeter presents advantages that makes them a useful tool for measurements in anthropomorphic phantoms and in vivo dosimetry. Several dosimetric materials have been used in the radiotherapy sectors such as LiF, µLiF, CaSO4:Dy. The OSL dosimetry has also been widely applied using Aluminum Oxide (Al2O3:C). These dosimeters have advantages over TLDs due to their high sensitivity, extensive linearity in response to the dose, faster reading, possibility of multiple readings and the need to perform the heat treatment of the samples. The aim of this work was to compare and characterize, using TL and OSL techniques, different luminescent dosimeters (LiF, µLiF, CaSO4:Dy and Al2O3:C) to be applied in clinical electron beam used to TSEB treatments. Measurements were performed in order to study the applicability of these detectors as easy-to-take alternatives to calibration and measurements of TSEB treatments. Parameters such as dose-response curves; average sensitivity to radiation, intrinsic efficiency and energy and angular dependences were evaluated. The results show good agreement within CaSO4:Dy and TLD-100 measurements and, applying energy and angle dependence factors over the other two materials, all the four detectors can be applied as alternative easy-to-take dosimetric tools for commissioning and quality assurance of 6 MeV clinical electron beams used in TSEB treatments.

This paper aims to evaluate the performance of the commercial OSL Landauer InLight System to be applied in dosimetric measurements in a Volumetric Modulated Arc (VMAT) brain tumor planning treatment using a Stereotactic End-To-End Verification Phantom Patient ( STEEV™ – CIRS), comparing its results with CaSO 4 :Dy TLD pellets manufactured and marketed by the Laboratory of Dosimetric Materials/IPEN, PTW PinPoint™ ion chamber and Eclipse 10.0 planning system. The results of commercial InLight™ System using the nanoDot dosimeters showed good reproducibility and stability in both laboratory and clinical measurements. The experimental dose values obtained by all dosimetric techniques varied less than ±1.0% from prescribed by Eclipse 10.0. The intrinsic precision and uncertainty of the OSL reading device were found fair enough, providing good experimental results for VMAT dosimetry.

3D printing techniques and materials have become widely available in the last couple of decades and remains an important topic of research as the equipments and supplements gets chipper. This study aims to evaluate the attenuation behaviour of several commercially available 3D printing filaments (ABS and PLA-based filaments and other polymers blends) over standard X-ray beams ranging from ~30 keV - to ~50 keV and comparing the experimental results with theoretical data of Cortical Bone, Soft Tissue and PMMA. It was used the transmission method to obtain experimental attenuation coefficients to all materials. HVL for the materials were also calculated. Results show that PLA-based printing filaments mixed with metals (Al, BRASS and Cu) has higher attenuation than pure PLA. Comparing the experimental data with theoretical cross section of Soft Tissue, Cortical Bone and PMMA, it was possible to observe that with the increase of beam energy, ABS-based and other blends’ attenuation behaviour agree with PMMA/Soft tissue. None of the studied materials showed agreement of attenuation with Cortical Bone. Some variations of PLA (SILK, Black and Bone) and some of the other blends of PETG and TPU showed good agreement with Soft Tissue/PMMA since about 30 keV and it can be concluded that these filaments can be used as substitute of PMMA for mimetizing soft tissue in 3D printed phantoms.

With the popularization of 3D printing technologies, it is now possible to develop patient specific simulators and various other accessories using this technology in medical physics and dosimetry. This work aims to evaluate the electronic equilibrium of 3D printed phantoms using PLA and ABS filaments compared to PMMA for 137Cs gamma rays using OSL dosimetry. A Landauer microStar ii commercial OSL system was commissioned and it was used nanoDot dosimeters. Phantom plates with 2.5, 3.0 and 5.0 mm thickness were used to obtain electronic equilibrium for 137Cs gamma rays. Measurements were compared with PMMA measurements at standard conditions. Results show that measurements with ABS and PLA thicknesses of 2.5 and 3.0 mm presents dosimetry results within irradiation uncertainty. More accuracy is obtained using 3.0 mm for both PLA and ABS phantoms, with differences in less than 0.5%. It can be concluded that PLA and ABS 3D phantom plates has similar properties of PMMA for 137Cs gamma rays dosimetry and can be used for developing dosimetry accessories for this energy photon beam.

The aim this paper is characterize materials for 3D printed with different infill percentages for 137Cs gamma rays. The RAISE 3D PRO2 printer was used to print PLA and ABS plates. Using a 137Cs source, the attenuation coefficient was obtained by the transmission method and results compared with PMMA. The readings were performed by a Radcal ionization chamber, model 10X6-6. The results of attenuation coefficients show that the PLA filament demonstrated a equivalent behavior to PMMA. The PLA plates exhibits an increase in radiation transmission when reduces the infilling, and ABS printing achieved same results for all infills.

3D printing techniques and materials have become widely available in the last couple of decades and remains a hot topic of study as new materials can lead to new applications. This study aims to evaluate the attenuation behaviour of GMASS over photon beams ranging from 29.7 up to 661.7keV, comparing with pure ABS and using theoretical data of pure lead as reference. It was used the transmission method to obtain experimental attenuation coefficients to all materials and theoretical data. HVL and TVL calculations were also performed. Results show that ABS+W has higher attenuation than ABS+Bi and pure ABS. Using the lead theoretical reference data it can be concluded that although ABS+Bi and ABS+W attenuates less than pure lead, the 3D printing filaments can be used to create shielding tolls depending on radiation energy and application.

Organic acidurias are inherited metabolic diseases due to the deficiency of an enzyme or a transport protein involved in one of the several cellular metabolic pathways devoted to the catabolism of amino acids, carbohydrates or lipids. These deficiencies result in abnormal accumulation of organic acids in the body and their abnormal excretion in urine. More than 65 organic acidurias have been described; the incidence varies, individually, from 1 out of 10,000 to >1 out of 1000,000 live births. Collectively, their incidence approximates 1 out of 3000 live births. Among these disorders, methyl malonic aciduria, propionic aciduria, maple syrup urine disease and isovaleric aciduria are sometimes referred to as classical organic acidurias. In this review, we focused on the basic GC–MS-based methodologies employed in the diagnosis of classical organic acidurias and provided updated reference values for the most common involved organic acids. We also attempted to provide the most recent updates on the pathogenetic bases of these diseases.

The aim of this paper is to characterize 3D printed phantoms and printing set-ups with different infill percentages for imaging energy X-ray beams attenuation. 3D printing performance was studied using the fused filament fabrication (FFF) technique with PLA (Polylactic Acid) and ABS (Acrylonitrile Butadiene Styrene) filaments. Phantom plates were printed and, using the Pantak Seifert X-ray system with different beam qualities in the diagnostic range, the attenuation coefficients were obtained experimentally with the transmission method and results compared with PMMA used as reference and theoretical data. Different percentages of infill of printed phantoms were also evaluated and transmission characterized. The attenuation coefficients were determined for the different beam qualities and results show that the variation in the values of attenuation coefficients decreases as the infill quality increases. Attenuation characteristics evaluated indicates the suitable equivalence of PLA to PMMA for 3D printing water/tissue equivalent most complex geometry phantoms. The different printing modes characterized together with their attenuation coefficients for the X-ray beams will be studied and used in the development of new 3D printed phantoms in our institute.

The Total Skin Electron Beam (TSEB) therapy is a technique that aims to provide skin surface homogeneous absorbed dose in order to treat cutaneous T-cell lymphomas, both for curative and palliative purposes with electron beams penetrating a few millimeters into the skin, reaching the affected parts without affecting internal organs. In vivo dosimetry has become an important role for the treatment of total skin irradiation within a rigorous quality assurance. The luminescent dosimeters, such as TLDs and OSLDs, have proven to be very useful for the verification of the dose distribution and prescribed for the patient as the dose may differ from place to place due to patient body geometry, overlapping of structures and asymmetries of the radiation field. Other routine in vivo dosimetry tool is the DIODEs and they as well help validating radiation therapy dosimetry. Al2O3:C OSL pellets manufactured and marketed by REXON Components and TLD Systems have already been characterized for TSEB applications. The aim of this work is to compare the performance of Al2O3:C OSL pellets from REXON to in vivo TSEB dosimetry with silicon DIODEs QEDTM detectors from Sun Nuclear (EUA) using an anthropometric phantom. Dosimeters and DIODEs were previously characterized for 6 MeV HDTSe- electron beams and then placed over an Anderson Rando® anthropomorphic phantom, evaluating the body dose distribution. The reference point of measurement was the umbiculous as recommended by formalism. The results showed that the Al2O3:C OSL pellets presented acceptable results, but some greater variation of the response in relation to silicon DIODEs were found due to its considerable rotational dependency.

3-Methylcrotonylglycinuria is an organic aciduria resulting from deficiency of 3-methylcrotonyl-CoA carboxylase (3-MCC), a biotin-dependent mitochondrial enzym carboxylating 3-methylcrotonyl-CoA to 3-methylglutaconyl-CoA during leucine catabolism. Its deficiency, due to mutations on MCCC1 and MCCC2 genes, leads to accumulation of 3-methylcrotonyl-CoA metabolites in blood and/or urine, primarily 3-hydroxyisovaleryl-carnitine (C5-OH) in plasma and 3-methylcrotonyl-glycine (3-MCG) and 3-hydroxyisovaleric acid (3-HIVA) in the urine. The phenotype of 3-MCC deficiency is highly variable, ranging from severe neurological abnormalities and death in infancy to asymptomatic adults. Here we report the biochemical and molecular characterization of an Italian asymptomatic girl, positive for the newborn screening test. Molecular analysis showed two mutations in the MCCC2 gene, an already described missense mutation, c.691A > T (p.I231F), and a novel splicing mutation, c.1150-1G > A. We characterized the expression profile of the splice mutation by functional studies.

Background: Glycogen storage disease type I (GSDI) is an inborn error of carbohydrate metabolism caused by mutations of either the G6PC gene (GSDIa) or the SLC37A4 gene (GSDIb). GSDIa patients are at higher risk of developing insulin-resistance (IR). Mitochondrial dysfunction has been implicated in the development of IR. Mitochondrial dysfunction can demonstrate abnormalities in plama acylcarnitines (ACs) and urine organic acids (UOA). The aim of the study was to investigate the presence of mitochondrial impairment in GSDI patients and its possible connection with IR. Methods: Fourteen GSDIa, seven GSDIb patients, 28 and 14 age and sex-matched controls, were enrolled. Plasma ACs, UOA, and surrogate markers of IR (HOMA-IR, QUICKI, ISI, VAI) were measured. Results: GSDIa patients showed higher short-chain ACs and long-chain ACs levels and increased urinary excretion of lactate, pyruvate, 2-ketoglutarate, 3-methylglutaconate, adipate, suberate, aconitate, ethylmalonate, fumarate, malate, sebacate, 4-octenedioate, 3OH-suberate, and 3-methylglutarate than controls (p < 0.05). GSDIb patients showed higher C0 and C4 levels and increased urinary excretion of lactate, 3-methylglutarate and suberate than controls (p < 0.05). In GSDIa patients C18 levels correlated with insulin serum levels, HOMA-IR, QUICKI, and ISI; long-chain ACs levels correlated with cholesterol, triglycerides, ALT serum levels, and VAI. Discussion: Increased plasma ACs and abnormal UOA profile suggest mitochondrial impairment in GSDIa. Correlation data suggest a possible connection between mitochondrial impairment and IR. We hypothesized that mitochondrial overload might generate by-products potentially affecting the insulin signaling pathway, leading to IR. On the basis of the available data, the possible pathomechanism for IR in GSDIa is proposed.

A dosimetria opticamente estimulada (OSL) tem ganhado destaque em aplicacoes clinicas e academicas no Brasil. Nesse trabalho, sao apresentados resultados da caracterizacao OSL dos dosimetros de Al 2 O 3 :C (TLD-500) fabricados pela Rexon™ Components and TLD Systems em uma leitora RISO, modelo TL/OSL-DA-20 para dosimetria de feixes de fotons de energias altas. Todos os parâmetros da leitora, e suas variacoes foram avaliados.

O tratamento utilizando Radioterapia em Arco Modulado Volumétrico é a modalidade mais moderna de radioterapia conformacional de forma que, com superposição de vários campos, as distribuições de dose forneçam uma perfeita conformação ao tumor, diminuindo a probabilidade de complicações nos tecidos normais adjacentes. Nesse sentido, muitos esforços estão sendo investidos para melhorar a conformidade de distribuição de dose, bem como a integração de técnicas de imagem para rastreamento de tumores e correção de variações inter e intrafração. Para isso, um intenso acompanhamento da qualidade dos processos e um programa de garantia de qualidade são fundamentais para a segurança dos pacientes e o cumprimento da legislação vigente; além do uso de diferentes metodologias de dosimetria para inter comparação e validação dos resultados. Este trabalho tem por objetivo avaliar e comparar o desempenho dos dosímetros OSL de óxido de alumínio (Al2O3:C) fabricados pela Landauer Inc. com os fabricados pela Rexon™ na dosimetria de feixes clínicos de fótons de energias altas empregados em radioterapia com tratamento em arco modulado volumétrico (VMAT) utilizando diferentes objetos simuladores. Os dosímetros foram caracterizados para radiação gama do 60Co e para feixes clínicos de fótons de 6 MV típicos de tratamentos por VMAT em condições de equilíbrio eletrônico e de dose máxima respectivamente. Testes de desempenho das leitoras TL e OSL utilizadas e repetibilidade das amostras foram avaliadas. Após realizados todos os testes, os dosímetros foram irradiados na simulação de diferentes tratamentos radioterápicos por VMAT e suas respostas comparadas ao sistema de planejamento. Todos os tipos de dosímetros apresentaram resultados satisfatórios na verificação das doses desse tipo de simulação de planejamento. Os dosímetros de Al2O3:C apresentaram resultados compatíveis entre si e validados pelos outros dosímetros e câmara de ionização. Em relação a melhor técnica, o sistema comercial OSL InLight apresenta maior praticidade e versatilidade para uso e aplicação na rotina clínica. Treatment using Volumetric Modulated Arc Radiation Therapy is the most modern modality of conformational radiotherapy so that, with the overlapping of several fields, the dose distributions provide a perfect conformation to the tumor, reducing the probability of complications in adjacent normal tissues. In this sense, many efforts are being invested to improve dose distribution compliance as well as the integration of imaging techniques for tumor screening and correction of inter and intrafraction variations. To this end, an intensive monitoring of the quality of the processes and a quality assurance program are fundamental for patient safety and compliance with current legislation; besides the use of different dosimetry methodologies for intercomparison and validation of the results. The aim of this study is to evaluate and compare the performance of aluminum oxide (Al2O3:C) OSL dosimeters manufactured by Landauer Inc. with those produced by Rexon™ in the dosimetry of high energy photon clinical bundles used in arcuate treatment Modulated volumetric (VMAT) using different simulating objects. The dosimeters were characterized for gamma radiation of the 60Co and for clinical photon beams of 6 MV typical of treatments by VMAT under conditions of electronic equilibrium and maximum dose respectively. Performance tests of the TL and OSL readers used and repeatability of the samples were evaluated. After all tests, the dosimeters were irradiated in the simulation of different radiotherapy treatments by VMAT and their responses compared to the planning system. All types of dosimeters presented satisfactory results in verifying the doses of this type of planning simulation. The Al2O3:C dosimeters presented compatible results and validated by the other dosimeters and ionization chamber. Regarding the best technique, the OSL InLight commercial system presents greater practicality and versatility for use and application in the clinical routine.

Congenital Hyperinsulinemic Hypoglycemia (CHH) is a rare metabolic disease (prevalence T (p.R236*) in HADH gene, at homozygous state, while both parents were heterozygous for the mutated allele. The patient started diazoxide treatment at the maximum dose of 10 mg/kg/day, which resulted in adverse drug reactions (hypertrichosis, peripheral edemas and persistent hypertension) gradually solved with antihypertensive regimen. Diazoxide was progressively titrated to 2 mg/kg/ day with good results in glycemic control and no hypertensive crisis. Low organic aciduria was followed.In conclusion, when the metabolic profile suggests a CHH disorder, the molecular analysis is necessary for the precise diagnosis and the appropriate counseling to the parents, also for the possibility of a prenatal diagnosis. In this setting, the definitive diagnosis of CHH, due to M/SCHAD deficiency, may suggest also the most appropriate therapeutic intervention to avoid both risk of worsening or adverse drug effect.

In the last years tandem mass spectrometry (MS/MS) has become a leading technology used for neonatal screening purposes. Newborn screening by MS/MS on dried blood spot samples (DBS) has one of its items in methionine levels: the knowledge of this parameter allows the identification of infant affected by homocystinuria (cystathionine β-synthase, CBS, deficiency) but can also lead, as side effect, to identify cases of methionine adenosyltransferase (MAT) type I/III deficiency.We started an expanded newborn screening for inborn errors of metabolism in Campania region in 2007. Here we report our ten years experience on expanded newborn screening in identifying patients affected by hypermethioninemia. During this period we screened approximately 77,000 infants and identified two cases: one case of classical homocystinuria and one patient affected by defect of MAT I/III. In this paper we describe these patients and their biochemical follow-up and review the literature concerning worldwide newborn screening reports on incidence of CBS and MAT deficiency. Keywords: Newborn screening, Hypermethioninemia, MAT I/III deficiency, CBS deficiency

Background Aggressive behaviour represents a frequent symptom in people with intellectual disability (PWID). Despite uncertain evidence of effectiveness, the use of antipsychotics (APs) drugs to treat aggressive behaviour is very common. Antipsychotic medication of aggressivity in PWID has recently become one of the most debated issues in mental health and the need of further research is persistently stressed by most researchers. Aim The present study was firstly aimed at evaluating the effectiveness (efficacy on target behaviour, safety and persistence on treatment) of new generation APs, in particular, olanzapine and risperidone in treating aggressive behaviour in PWID for who previous medication with first generation APs (FGAs) were not effective. Methods 62 subjects with intellectual disability underwent to a 2-arm, parallel group pragmatic trial of olanzapine and risperidone with balanced randomisation and blind assessment of outcome at 4, 8, 12, 16, 20 and 24 weeks after a switch (cross-tapering) from a 24-week treatment with FGAs. Aggressive behaviours were assessed by Overt Aggression Scale (OAS) and clinical outcome by Clinical Global Impression Scale. Side effects were assessed with Dosage Record and Treatment Emergent Symptoms Scale, other symptom-specific scales, laboratory and instrumental tests. Results Both risperidone and olanzapine resulted to be more effective than FGAs in reducing aggressive behaviour. Repeated-measures analysis of covariance revealed that treatment groups differed for cumulative number of aggressive episodes during the FGAs treatment, which was higher for olanzapine. Conclusion Our findings seem to confirm that olanzapine and risperidone can be effective in reducing aggressive behaviour in PWID. Both compounds resulted to be well tolerated, with side effects similar to those encountered in other patient populations.

Total-skin electron beam (TSEB) irradiation is used to deliver a homogeneous dose distribution over the entire skin surface of a patient. TSEB dosimetry is quite complex as to the evaluation and measurement of absorbed dosage in the cutaneous region. This paper evaluates the performance of different dosimetric materials, using TL and OSL dosimetry, in the extremity-dose assessment of TSEB treatments using the six-dual-field technique and an anthropomorphic phantom. Dosimeters were selected with repeatability better than [Formula: see text] and calibrated to 6-MeV electron-beam dosimetry. Measurements were conducted in the abdominal region as a reference point and on the extremities. Results show expected deviations ranging up to [Formula: see text] in the dose received in the extremities and good results in dose assessment using all dosimetric materials tested.

Sacral nerve stimulation is a safe and effective procedure for fecal incontinence. We investigated whether its efficacy is maintained long term.Sixty patients with fecal incontinence underwent permanent sacral nerve stimulation. Patients' data were prospectively recorded in the national registry of the Italian Group of sacral nerve stimulation. The severity of fecal incontinence was evaluated by the Wexner score, and data were collected in a bowel function diary. Quality of life was evaluated by the Italian version of the Medical Outcomes Survey Short Form (SF-36) questionnaire.Fifty-two patients were available for long-term follow-up lasting at least 5 years. Compared with baseline, the Wexner score decreased significantly after definitive implantation (from 15 +/- 4 to 5 +/- 5, P0.001). At least 50 percent improvement in continence was achieved in 74 percent of the patients, and at least 70 percent improvement (median value) was achieved in 50 percent. The mean number of solid/liquid incontinence episodes decreased significantly from 0.5 (+/-0.5) to 0.1 (+/-0.3) per day (P = 0.004). Quality of life improved in all domains. The overall mean improvement in SF-36 scores was 39.8 percent. Both mean resting and squeeze anal pressures increased significantly, and maximum volume tolerated decreased significantly.Sacral nerve stimulation maintains its efficacy long term, not only in regard to control of symptoms but also regarding quality of life.

This study was designed to assess the safety and outcomes achieved with stapled transanal rectal resection vs. biofeedback training in obstructed defecation patients.A total of 119 women patients who suffered from obstructed defecation with associated rectocele and rectal intussusception were randomized to stapled transanal rectal resection or biofeedback training. Stapled transanal rectal resection was performed by using two circular staplers to produce transanal full-thickness rectal resection. Primary outcome was symptoms of obstructed defecation resolution at 12 months; secondary outcomes included safety, change in quality of life score, and anatomic correction of rectocele and rectal intussusception.Fourteen percent (8/59) stapled transanal rectal resection and 50 percent (30/60) biofeedback training patients withdrew early. Eight (15 percent) patients treated with stapled transanal rectal resection and 1 (2 percent) biofeedback patient experienced adverse events. One serious adverse event (bleeding) occurred after stapled transanal rectal resection. Scores of obstructed defecation improved significantly in both groups as did quality of life (both P0.0001). Successful treatment was observed in 44 (81.5 percent) stapled transanal rectal resection vs. 13 (33.3 percent) evaluable biofeedback training patients (P0.0001). Functional benefit was observed early and remained stable during the study.In this controlled trial, stapled transanal rectal resection was well tolerated, was more effective than biofeedback training for the resolution of obstructed defecation symptoms, and improved quality of life, with minimal risk of impaired continence. Thus, stapled transanal rectal resection offers a new treatment alternative for obstructed defecation after failure of conservative measures including biofeedback training, a noninvasive approach.

Inborn errors of metabolism are genetic disorders due to impaired activity of enzymes, transporters, or cofactors resulting in accumulation of abnormal metabolites proximal to the metabolic block, lack of essential products or accumulation of by-products. Many of these disorders have serious clinical consequences for affected neonates, and an early diagnosis allows presymptomatic treatment which can prevent severe permanent sequelae and in some cases death. Expanded newborn screening for these diseases is a promising field of targeted metabolomics. Here we report the application, between 2007 and 2014, of this approach to the identification of newborns in southern Italy at risk of developing a potentially fatal disease. The analysis of amino acids and acylcarnitines in dried blood spots by tandem mass spectrometry revealed 24 affected newborns among 45,466 infants evaluated between 48 and 72 hours of life (overall incidence: 1 : 1894). Diagnoses of newborns with elevated metabolites were confirmed by gas chromatography-mass spectrometry, biochemical studies, and genetic analysis. Five infants were diagnosed with medium-chain acyl CoA dehydrogenase deficiency, 1 with methylmalonic acidemia with homocystinuria type CblC, 2 with isolated methylmalonic acidemia, 1 with propionic acidemia, 1 with isovaleric academia, 1 with isobutyryl-CoA dehydrogenase deficiency, 1 with beta ketothiolase deficiency, 1 with short branched chain amino acid deficiency, 1 with 3-methlycrotonyl-CoA carboxylase deficiency, 1 with formimino-transferase cyclodeaminase deficiency, and 1 with cystathionine-beta-synthase deficiency. Seven cases of maternal vitamin B12 deficiency and 1 case of maternal carnitine uptake deficiency were detected. This study supports the widespread application of metabolomic-based newborn screening for these genetic diseases.

The Sanfilippo type A syndrome, one of the most frequent forms of mucopolysaccharidosis III, is characterized by severe mental retardation, progressive neurological degeneration, and mild somatic changes. It is due to a deficiency of heparan-N-sulfatase (sulfamidase) activity and consequent excretion of heparan sulfate in the urine. The disease is transmitted through an autosomal recessive mechanism, and more than 60 gene mutations have been identified. Up to now, only 10 cases of attenuated form of Sanfilippo type A syndrome have been described, and the specific mutation has been identified only in two of them. We report here on a female patient, 20 years old, with Sanfilippo type A syndrome presenting with a mild clinical phenotype characterized essentially by a moderate nonevolving mental retardation. The genetic analysis demonstrated that the patient is homozygous for mutation R206P; presence of polymorphism R456H was also found. This study places R206P as a mild mutation underlying Sanfilippo type A disease.

Mucopolysaccharidosis type IIIA, also known as Sanfilippo A disease, results from mutations in the sulfamidase gene. To date, a total of 62 mutations have been described underlying this lysosomal disorder. Expression studies on missense mutations have shown that each alteration was disease-causing and helped to clarify the genotype-phenotype correlation. In this report we describe a large pedigree where the mutations have been identified in two second cousins: one with severe disease (E369K/R433Q) and the other with a mild form of the illness (E369K/P128L). This study places R433Q as a severe mutation underlying Sanfilippo A disease.

Mucopolysaccharidosis type IIIB (MPS IIIB; or Sanfilippo syndrome type B) is a lysosomal disease, due to glycosaminoglycan storage caused by mutations on the α-N-acetylglucosaminidase (NAGLU) gene. The disease is characterized by neurological dysfunction but relatively mild somatic manifestations. No effective treatment is available for affected patients. In the present study, we evaluated the role of a lentiviral vector as the transducing agent of NAGLU cDNA in MPS IIIB fibroblasts. The vector expressed high transduction efficiency and high levels of enzymic activity, 20-fold above normal levels, persisting for at least 2 months. PCR experiments confirmed the integration of the viral vector into the target genome. The NAGLU activity restored by virus infection was sufficient to normalize glycosaminoglycan accumulation, which is directly responsible for the disease phenotype. Metabolic labelling experiments on transduced fibroblasts exhibited, in the medium and in cellular lysates, polypeptide forms of 84 and 80kDa respectively related to the precursor and mature forms of the enzyme. The enzyme secreted by transduced MPS IIIB fibroblasts was endocytosed in deficient cells by the mannose 6-phosphate system. Thus we show that lentiviral vectors may provide a therapeutic approach for the treatment of MPS IIIB disease.

Mucopolysaccharidosis type I (MPS I) results from a deficiency in the enzyme alpha-L-iduronidase (IDUA), and is characterized by skeletal abnormalities, hepatosplenomegaly and neurological dysfunction. In this study, we used a late generation lentiviral vector to evaluate the utility of this vector system for the transfer and expression of the human IDUA cDNA in MPS I fibroblasts. We observed that the level of enzyme expression in transduced cells was 1.5-fold the level found in normal cells; the expression persisted for at least two months. In addition, transduced MPS I fibroblasts were capable of clearing intracellular radiolabeled glycosaminoglycan (GAG). Pulse-chase experiments on transduced fibroblasts showed that the recombinant enzyme was synthesized as a 76-kDa precursor form and processed to a 66-kDa mature form; it was released from transduced cells and was endocytosed into a second population of untreated MPS I fibroblasts via a mannose 6-phosphate receptor. These results suggest that the lentiviral vector may be used for the delivery and expression of the IDUA gene to cells in vivo for treatment of MPS I.

Leukotriene (LT) A(4) hydrolase is a dual function enzyme that is essential for the conversion of LTA(4) to LTB(4) and also possesses an aminopeptidase activity. SC-57461A (3-[methyl[3-[4-phenylmethyl)phenoxy]propyl]amino]propanoic acid HCl) is a potent inhibitor of human recombinant LTA(4) hydrolase (epoxide hydrolase and aminopeptidase activities, K(i) values = 23 and 27 nM, respectively) as well as calcium ionophore-induced LTB(4) production in human whole blood (IC(50) = 49 nM). In the present study, we investigated its action in several animal models. Oral activity was evident from the ability of the compound to inhibit mouse ex vivo calcium ionophore-stimulated blood LTB(4) production with ED(50) values at 1.0 and 3.0 h of 0.2 and 0.8 mg/kg, respectively. A single oral dose of 10 mg/kg SC-57461A blocked mouse ex vivo LTB(4) production 67% at 18 h and 44% at 24 h, suggesting a long pharmacodynamic half-life. In a rat model of ionophore-induced peritoneal eicosanoid production, SC-57461 inhibited LTB(4) production in a dose-dependent manner (ED(50) = 0.3-1 mg/kg) without affecting LTC(4) or 6-keto-prostaglandin F(1alpha) production. Oral pretreatment with SC-57461 in a rat reversed passive dermal Arthus model blocked LTB(4) production with an ED(90) value of 3 to 10 mg/kg, demonstrating good penetration of drug into skin. Plasma level of intact SC-57461 (3 h after oral gavage dosing with 3 mg/kg) was 0.4 microg/ml, which corresponds to >80% inhibition of dermal LTB(4) production. Oral or topical pretreatment with SC-57461A 1 h before challenge with arachidonic acid blocked ear edema in the mouse. SC-57461A is a competitive, selective, and orally active inhibitor of LTA(4) hydrolase in vivo, making it useful to explore the contribution of LTB(4) to a number of inflammatory diseases.

Mucopolysaccharidosis type II (Hunter syndrome; OMIM 309900) is a rare X-linked recessive lysosomal storage disorder caused by the deficiency of the enzyme iduronate-2-sulfatase (IDS; EC 3.1.6.13). Different alterations at the IDS locus, mostly missense mutations, have been demonstrated, by expression study, as deleterious, causing significant consequences on the enzyme function or stability. In the present study we report on the results of the transient expression of the novel K347T, 533delTT, N265I and the already described 473delTCC (previously named ΔS117) mutations in the COS 7 cells proving their functional consequence on IDS activity. This type of information is potentially useful for genotype–phenotype correlation, prognosis and possible therapeutic intervention.

Sanfilippo syndrome type B (mucopolysaccharidosis IIIB) is a rare autosomal recessive disorder characterized by the inability to degrade heparan sulfate because of a deficiency of the lysosomal enzyme alpha-N-acetylglucosaminidase (NAGLU). We performed mutation screening in a group of 20 patients, identyifing 28 mutations, 14 of which were novel (L35F, 204delC, 221insGCGCG, G82D, W156C, 507delC, IVS3+1G--A, E336X, V501G, R520W, S534Y, W649C, 1953insGCCA, 2185delAGA). Four of these mutations were found in homozygosity and only one was seen in two different patients, showing the remarkable molecular heterogeneity of the disease. Mutation IVS3+1G--A produces aberrant RNA splicing: it represents a base substitution from G to A of the invariant GT dinucleotides at the splicing donor site of intron 3 resulting in the skipping of exon 3 and both exons 2 and 3. Transient transfection of COS cells, by DNA mutagenized with NAGLU mutations, produced enzymatic molecules without activity, demonstrating the deleterious nature of the defects. Metabolic labeling of transfected mutants suggested a normal synthesis of the involved polypeptide for missense alterations, whereas increased protein or mRNA instability was shown for nonsense and most of the frameshift mutations.

Sanfilippo syndrome type A or mucopolysaccharidosis IIIA (MPS IIIA) results from the deficiency of the enzyme heparan N-sulfatase (NS, EC 3.10.1.1), required for the degradation of heparan sulfate. Molecular defects of 24 Italian MPS IIIA patients were recently reported by our group. We report here two novel mutations: 1040insT and Q365X and the expression studies on 15 of the identified defects. Transient expression of COS cells by cDNA mutagenized to correspond to heparan N-sulfatase mutations Y40N, A44T, 166delG, G122R, P128L, L146P, R150Q, D179N, R182C, R206P, P227R, 1040insT, 1093insG, E369K, R377C did not yield active enzyme, demonstrating the deleterious nature of the mutations. Western blot analysis and metabolic labeling experiments revealed, for cells transfected with wild-type enzyme, a precursor 62-kDa form and a mature 56-kDa form. Western blot resulted, for 11 mutations, in the presence of both forms, indicating a normal maturation of the mutant enzyme. Western blot, metabolic labeling and immunofluorescence experiments suggested, for mutations 166delG, L146P, 1040insT and 1093insG, an increased degradation of the mutant enzymes. (C) 2000 Published by Elsevier Science B.V.