Investigation of mixed ion fields in the forward direction for 220.5 MeV/u helium ion beams: comparison between water and PMMA targets.

Currently there is a rising interest in helium ion beams for radiotherapy. For benchmarking of the physical beam models used in treatment planning, there is a need for experimental data on the composition and spatial distribution of mixed ion fields. Of particular interest are the attenuation of the primary helium ion fluence and the build-up of secondary hydrogen ions due to nuclear interactions. The aim of this work was to provide such data with an enhanced precision. Moreover, the validity and limits of the mixed ion field equivalence between water and PMMA targets were investigated. Experiments with a 220.5 MeV/u helium ion pencil beam were performed at the Heidelberg Ion-Beam Therapy Center in Germany. The compact detection system used for ion tracking and identification was solely based on Timepix position-sensitive semiconductor detectors. In comparison to standard techniques, this system is two orders of magnitude smaller, and provides higher precision and flexibility. The numbers of outgoing helium and hydrogen ions per primary helium ion as well as the lateral particle distributions were quantitatively investigated in the forward direction behind water and PMMA targets with 5.2-18 cm water equivalent thickness (WET). Comparing water and PMMA targets with the same WET, we found that significant differences in the amount of outgoing helium and hydrogen ions and in the lateral particle distributions arise for target thicknesses above 10 cm WET. The experimental results concerning hydrogen ions emerging from the targets were reproduced reasonably well by Monte Carlo simulations using the FLUKA code. Concerning the amount of outgoing helium ions, significant differences of 3-15% were found between experiments and simulations. We conclude that if PMMA is used in place of water in dosimetry, differences in the dose distributions could arise close to the edges of the field, in particular for deep seated targets.

Helium ions at the heidelberg ion beam therapy center: comparisons between FLUKA Monte Carlo code predictions and dosimetric measurements.

In the field of particle therapy helium ion beams could offer an alternative for radiotherapy treatments, owing to their interesting physical and biological properties intermediate between protons and carbon ions. We present in this work the comparisons and validations of the Monte Carlo FLUKA code against in-depth dosimetric measurements acquired at the Heidelberg Ion Beam Therapy Center (HIT). Depth dose distributions in water with and without ripple filter, lateral profiles at different depths in water and a spread-out Bragg peak were investigated. After experimentally-driven tuning of the less known initial beam characteristics in vacuum (beam lateral size and momentum spread) and simulation parameters (water ionization potential), comparisons of depth dose distributions were performed between simulations and measurements, which showed overall good agreement with range differences below 0.1 mm and dose-weighted average dose-differences below 2.3% throughout the entire energy range. Comparisons of lateral dose profiles showed differences in full-width-half-maximum lower than 0.7 mm. Measurements of the spread-out Bragg peak indicated differences with simulations below 1% in the high dose regions and 3% in all other regions, with a range difference less than 0.5 mm. Despite the promising results, some discrepancies between simulations and measurements were observed, particularly at high energies. These differences were attributed to an underestimation of dose contributions from secondary particles at large angles, as seen in a triple Gaussian parametrization of the lateral profiles along the depth. However, the results allowed us to validate FLUKA simulations against measurements, confirming its suitability for 4He ion beam modeling in preparation of clinical establishment at HIT. Future activities building on this work will include treatment plan comparisons using validated biological models between proton and helium ions, either within a Monte Carlo treatment planning engine based on the same FLUKA code, or an independent analytical planning system fed with a validated database of inputs calculated with FLUKA.

Dosimetric verification in water of a Monte Carlo treatment planning tool for proton, helium, carbon and oxygen ion beams at the Heidelberg Ion Beam Therapy Center.

The introduction of 'new' ion species in particle therapy needs to be supported by a thorough assessment of their dosimetric properties and by treatment planning comparisons with clinically used proton and carbon ion beams. In addition to the latter two ions, helium and oxygen ion beams are foreseen at the Heidelberg Ion Beam Therapy Center (HIT) as potential assets for improving clinical outcomes in the near future. We present in this study a dosimetric validation of a FLUKA-based Monte Carlo treatment planning tool (MCTP) for protons, helium, carbon and oxygen ions for spread-out Bragg peaks in water. The comparisons between the ions show the dosimetric advantages of helium and heavier ion beams in terms of their distal and lateral fall-offs with respect to protons, reducing the lateral size of the region receiving 50% of the planned dose up to 12 mm. However, carbon and oxygen ions showed significant doses beyond the target due to the higher fragmentation tail compared to lighter ions (p and He), up to 25%. The Monte Carlo predictions were found to be in excellent geometrical agreement with the measurements, with deviations below 1 mm for all parameters investigated such as target and lateral size as well as distal fall-offs. Measured and simulated absolute dose values agreed within about 2.5% on the overall dose distributions. The MCTP tool, which supports the usage of multiple state-of-the-art relative biological effectiveness models, will provide a solid engine for treatment planning comparisons at HIT.

RADIATION DOSE MEASUREMENTS FOR HIGH-INTENSITY LASER INTERACTIONS WITH SOLID TARGETS AT SLAC.

A systematic study of photon and neutron radiation doses generated in high-intensity laser-solid interactions is underway at SLAC National Accelerator Laboratory. These laser-solid experiments are being performed using a 25 TW (up to 1 J in 40 fs) femtosecond pulsed Ti:sapphire laser at the Linac Coherent Light Source's (LCLS) Matter in Extreme Conditions (MEC) facility. Radiation measurements were performed with passive and active detectors deployed at various locations inside and outside the target chamber. Results from radiation dose measurements for laser-solid experiments at SLAC MEC in 2014 with peak intensity between 1018 and 7.1 × 1019 W cm-2 are presented.

Modifiable and non-modifiable risk factors affecting walking recovery after hip fracture.

UNLABELLED: Modifiable and non-modifiable predictors of mobility recovery were analyzed on a sample of 774 hip fracture patients according to pre-fracture abilities. Overall predictors were mostly non-modifiable factors related to frailty of patients with the exception of 25-hydroxyvitamin D concentration which significantly affected walking recovery, especially in patients with higher pre-fracture performance. INTRODUCTION: This study aims to investigate mobility changes after hip fracture with the aim of identifying modifiable and non-modifiable predictors of mobility recovery according to different pre-fracture abilities. METHODS: This is a prospective inception cohort study of consecutive older patients, admitted with a fragility hip fracture in three Hospitals of Emilia Romagna (Italy). A sample of 774 patients alive at the sixth month was divided into three groups according to pre-fracture ambulation ability (group 1: mobile outdoors; group 2: mobile indoors; and group 3: mobile with help). The relationship between baseline characteristics of patients and the odds of walking recovery was analyzed using multivariate regression analysis. RESULTS: Mortality differed significantly among the three groups and was the highest in patients needing help to walk. Among the survivors, only 50.3 % of patients recovered walking ability. In a multivariate analysis, independent risk factors were different among the three groups. In group 1, older age, comorbidities, the use of walking devices before fracture, and low albumin level acted as negative factors while male gender, a pre-fracture high functional status, and higher 25-hydroxyvitamin D levels increased the probability of full recovery. In group 2, only pre-fracture functional status and 25-hydroxyvitamin D concentration were related to the recovery of walking ability. Pre-fracture functional status was also the only significant predictor for patients in group 3. CONCLUSIONS: Several baseline characteristics of patients are related to the likelihood of recovering walking ability after hip fracture. The 25-hydroxyvitamin D level seems to be the only relevant modifiable factor even if the effectiveness of its supplementation has yet to be demonstrated.

Effects of a blend of essential oils and an enzyme combination on nutrient digestibility, ileum histology and expression of inflammatory mediators in weaned piglets.

The aim of this study was to test the hypothesis of an improved gut environment of post-weaning piglets when administered a blend of essential oils (EO; thymol and cinnamaldehyde) and an enzyme combination (xylanase and ß-glucanase (XB)) either alone or in combination. To assess the effect of dietary treatments, faecal nutrient digestibility and microbial counts, as well as ileum histology and gene expression of inflammatory mediators were evaluated. One hundred and ninety-two weaned piglets were allocated into four experimental treatments, and fed the basal diet (CTRL) either without or with EO, XB or their combination (EO+XB) for a 42-day period. The experiment concerning digestibility was designed with two periods (period I: days 15 to 21; period II: days 29 to 35) and the faeces were collected on days 20, 21, 34 and 35. On day 42, six piglets from each treatment were slaughtered. It was found that EO, XB and EO+XB supplementation did not affect (P>0.05) the growth performance of the piglets from days 0 to 42. Moreover, no dietary effect on faecal score was observed. Faecal digestibility of dry matter, organic matter, ash, dietary fibre, lipid, CP and NDF were increased from period I to period II (P<0.01 to P=0.06), while no effect (P>0.05) of EO, XB or their combination on the faecal digestibility was observed at both periods. Compared with the CTRL diet, dietary XB reduced the faecal Lactobacillus and Escherichia coli counts but increased the Lactobacillus to Coliforms ratio on day 42 (P=0.02, 0.03 and 0.03, respectively), and all the additives supplementations decreased the counts of faecal Coliforms on day 42 (P<0.01). XB supplementation increased the villus to crypt ratio (P=0.04) and reduced the mucosal macrophages number (P<0.01) in the ileum compared with the CTRL group, and dietary EO or EO+XB decreased the number of lymphatic follicles (P=0.01 and P<0.01, respectively) and mucosal macrophages (P=0.02 and P<0.01, respectively). In addition, the interleukin (IL)-1α was downregulated in piglets treated with EO+XB compared with the EO group (P=0.02). In conclusion, the administration of EO, XB or their combination was effective in improving ileum histology, and EO+XB supplementation might benefit the modulation of the expression of ileum inflammatory cytokines in piglets.

Comprehensive care.

Comprehensive care (CC) represents the basic approach of orthogeriatric comanaged care with the overall objectives of improving results regarding physical and psychological functions and reducing hospitalization, long-term care placement and mortality. It is a two-stage process that includes the Comprehensive Geriatric Assessment (CGA) and the development and implementation of an interdisciplinary treatment plan based on priority interventions and unmet needs. In older hip fracture patients CC has to face crucial issues such as treatment choice and surgical options, clinical stabilization of patients before surgery and the prevention and treatment of complication in the postoperative phase. The main aim are to avoid inappropriate surgical delays and reduce the overall number of days of immobility endorsing an early ambulation with full weight bearing as tolerated. Multiprofessional CC must also ensure uninterrupted care for transition between the different care levels that patients need after fracture before returning home. Therefore another important issue is a structured discharge plan tailored to the individual patient identifying subjects that could benefit from a skilled or more intensive rehabilitation, identifying patients and family that will probably need a higher level of care even after rehabilitation, determining timing of discharge, defining the continuing care that needs to be provided and finally ensuring the patient has access to available services and resources. However, the implementation of a comprehensive and multidisciplinary co-care model in an orthopedic unit is a difficult task because it is necessary a great effort to change cultural attitudes related to traditional model of care.

Oral supplementation with a nutraceutical containing Echinacea, methionine and antioxidant/immunostimulating compounds in patients with cutaneous viral warts.

AIM: The aim of thos paper was to determine the effect of oral supplementation (OS) with a nutraceutical, containing methionine, Echinacea, zinc, probiotics and other antioxidant and immunostimulating compounds, on the response of cutaneous warts to conventional standard therapy (CST). METHODS: This was an open-label study in adults and adolescents aged 14 years or more and with a body weight ≥40 kg, who had at least one cutaneous viral wart. Eligible patients were consecutively allocated to CST (topical therapy with a preparation containing salicylic acid and lactic acid or liquid nitrogen cryotherapy) alone or CST combined with nutraceutical OS for 4 months. RESULTS: A total of 172 patients were enrolled: 83 received CST alone and 89 CST+OS. During the 6-month observation period, a statistically significant reduction of the mean number of warts was obtained in each treatment group and subgroup. The addition of nutraceutical OS was associated with a significantly lower number of warts at 6 months as compared to CST alone. Complete remission was obtained in 54.5% and 86% of patients in the CST group and CST+OS arm, respectively (P<0.001). The influence of the nutraceutical on the response rate appeared to be more prominent in the subgroup of patients treated with topical therapy. The development of new warts during the study period occurred significantly less frequently with CST+OS compared to CST (9% versus 25%; P=0.004). No adverse events possibly related to the nutraceutical administration were observed. CONCLUSION: Our pilot experience seems to suggest that nutraceutical OS is safe and beneficial in patients with cutaneous warts, and capable of enhancing the response to CST.

Effect of selenium source and dose on selenium status of mature horses.

This study was conducted to determine the effects of either dietary Se source or dose on the Se status of horses. Twenty-five mature horses were blocked by BW and randomly allocated to 1 of 5 dietary treatments that comprised the same basal diet that differed only in Se source or dose. Treatments were as follows: negative control (0.085 mg of Se/kg of DM), 3 different dietary concentrations of supplemental organic Se (Se yeast; 0.2, 0.3, and 0.4 mg of total Se/kg of DM), and positive control (0.3 mg of total Se/kg of DM) supplemented with Na selenite. Horses initially received the control diet (6 kg of grass hay and 3 kg of concentrate per horse daily) for 56 d to allow diet adaptation. After the period of diet adaptation, horses were offered their respective treatments for a continuous period of 112 d. Jugular venous blood samples were collected before the morning feed on d 0, 28, 56, 84, and 112. Whole blood and plasma were analyzed for total Se, glutathione peroxidase activity in whole blood (GPX-1) and plasma, and thyroid hormones (thyroxine and triiodothyronine) in plasma. The proportion of total Se as selenomethionine (SeMet) or selenocysteine in pooled whole blood and plasma samples was determined on d 0, 56, and 112. Data were analyzed as repeated measures. Total Se in blood and plasma and GPX-1 activity were greater in all supplemented horses (P < 0.001, except P < 0.01 for GPX-1 in horses supplemented with the least dose of Se yeast) with a linear dose effect of Se yeast for whole blood and plasma Se (P < 0.001) and a quadratic dose effect (P < 0.05) for whole blood GPX-1 activity. A plateau for total Se in plasma was achieved within 75 to 90 d, although this was not observed in blood total Se or GPX-1 activity. On d 84 and 112, horses supplemented with Se yeast showed greater total Se in blood (P < 0.05) compared with horses supplemented with Na selenite, and a source effect (P < 0.05) was observed in the relationship between total blood Se and GPX-1 activity. Selenocysteine (the predominant form of Se in whole blood and plasma) increased in all horses supplemented with Se. The SeMet content of whole blood and plasma increased in horses supplemented with Se yeast, but it was not observed in those supplemented with selenite. The rate of increase in SeMet over time was greater in whole blood (P < 0.05) and plasma (P = 0.10) with the Se yeast product. In conclusion, Se yeast was more effective than Na selenite in increasing total Se in blood, mainly as consequence of a greater increase of the proportion of Se comprised as SeMet, but it did not modify GPX-1 activity.

Development of functionalized superparamagnetic iron oxide nanoparticles for interaction with human cancer cells.

Our goal is to develop, characterize and optimize functionalized super paramagnetic iron oxide nanoparticles (SPION) demonstrating the capacity to be internalized by human cancer cells. SPION (mean diameter 9nm) were coated with various ratios to iron oxide of either polyvinyl alcohol (PVA), carboxylate-functionalized PVA, thiol-functionalized PVA and amino-functionalized PVA (amino-PVA). The interaction with cells and cytotoxicity of the SPION preparations were determined using human melanoma cells. From the four functionalized SPION preparations, only the amino-PVA SPION demonstrated the capacity to interact with, and were not cytotoxic to, human melanoma cells. This interaction with melanoma cells was dependent on the amino-PVA to iron oxide ratio, was an active and saturable mechanism displayed by all cells in a culture. These functionalized SPION were characterized by transmission electron microscopy and electrophoretic mobility. The physical comportment of SPION changed at specific PVAs to iron oxide ratios, and this ratio corresponded to the ratio of optimal interaction with cells. In conclusion, the successful development of functionalized SPION displaying potential cellular uptake by human cancer cells depends both on the presence of amino groups on the coating shell of the nanoparticles and of its ratio to the amount of iron oxide.

Lactobacilli for prevention of urogenital infections: a review.

Urogenital infections are a worldwide shared problem that represent the most common reason for a woman to decide to visit to gynaecologist or urologist. The origin of the uropathogens in uncomplicated urinary tract infection and bacterial vaginosis is the fecal flora. Key element of pathogenesis namely the ability of the pathogens to survive exposure to the microflora that exists on the external urogenitalia, in which lactobacilli predominate. Some health food appear to contain > or = 1 common Lactobacillus strain; L. rhamnosus GR-1 was found to be the best of a group of 34 Lactobacillus strains isolated from dairy, poultry, health food. Recently has been reported the first clinical evidence that probiotic lactobacilli can be delivered to the vagina following oral intake. These L. strains possess the ability to adhere to and colonize tissues and the capacity to inhibit the pathogenesis of disease-causing organisms that make them effective probiotic agents. In particularly, two strains, Lactobacillus GG and Lactobacillus rhamnosus GR-1 appear to be effective at colonizing and protecting the intestine and urogenital tract, respectively, against microbial infection. Treating and preventing urogenital infection by instillating probiotic organisms has great appeal to patients and caregivers. The ability to administer orally L. rhamnosus GR-1 and L. fermentum RC-14, which colonize the intestine and vagina, provides a major step in the right direction for patients as it potentially allows for the self administration of therapy.

Standard case management of pneumonia in hospitalized children in Uruguay, 1997 to 1998.

OBJECTIVE: To report the results of the use of antimicrobial guidelines for the management of children with community-acquired bacterial pneumonia. METHODS: Admittance and discharge criteria and algorithms for diagnosis and treatment were established. The decision to treat with antibiotics was based on radiologic findings in pneumonia with pulmonary consolidation and left to the attending physician's criteria in the remaining cases. The use of antibiotics was limited to penicillin and derivatives (ampicillin, amoxicillin) and macrolides. RESULTS: Of the 1163 children treated as bacterial pneumonia, hospitalized in public and private health facilities in Montevideo from September, 1997, through September, 1998, standard case management was applied in 1082 (93%). Age distribution was: <1 month, 1%; between 1 and 11 months, 29%; between 1 and 5 years, 50%; >5 years, 20%. Chest radiography showed evidence of pulmonary consolidation in 843 children (73%). Bacteria were detected in blood culture and/or pleural fluid of 57 children (5%). In 51 the identified microorganism was Streptococcus pneumoniae, susceptible to penicillin in 30, intermediate in 6 and resistant in 5 (maximum MIC, 4 microg/ml); in 10 cases etiologic diagnosis was made by antigen detection. Empyema was present in 62 children (5.3%); 38 (3.27%) required treatment in an intensive care unit; and 5 (0.4%) died. CONCLUSIONS: Compliance with standard case management was highly satisfactory. Outcome of children treated with penicillin and derivatives was good, including children with empyema and pneumatocele and two patients with penicillin-resistant S. pneumoniae. At the present time S. pneumoniae resistant to penicillin is not an important problem in children with pneumonia in Uruguay. Surveillance of identified microorganisms and their antimicrobial susceptibility must continue.

Human albumin enhances expression of vascular endothelial growth factor in cultured human luteinizing granulosa cells: importance in ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) is a severe complication of ovarian stimulation for assisted reproductive techniques. Clinical manifestations are massive extravascular fluid accumulation and haemoconcentration. Vascular endothelial growth factor (VEGF) has been demonstrated to mediate the development of OHSS. Intravenous albumin at the time of oocyte aspiration has been suggested as an effective prophylactic treatment against the occurrence of severe OHSS. Here it is reported that in cultured human luteinizing granulosa cells, VEGF mRNA expression was enhanced by human albumin and maximum expression was observed in cultured granulosa cells obtained from patients with serum oestradiol concentrations >2000 pg/ml on the day of human chorionic gonadotrophin injection (P < 0. 05).

Treatment of childhood post-irradiation sarcoma of bone in cancer survivors.

PATIENTS AND METHODS: This is a retrospective review of five children with post-irradiation bone sarcoma (PIS). Age at PIS onset ranged between 10 and 17 years (median 11). They were treated with a chemotherapy regimen, similar to that in use for primary osteogenic sarcoma, consisting of vincristine and high-dose methotrexate alternated with cisplatinum and ifosfamide, given for 12 months. RESULTS: In all children chemotherapy induced a complete clinical remission. Four of them were alive in continuous complete remission at 1, 2, 4, and 12 years from the diagnosis of bone sarcoma. One girl recurred 3 years from PIS diagnosis and was salvaged by repeating the same chemotherapy program: she remained alive in second complete remission 8 years from relapse. CONCLUSIONS: In spite of an intensive treatment previously given for the primary tumor, this drug schedule proved to be feasible and short-term side effects were manageable. Chemotherapy alone, using an intensive regimen effective for primary osteogenic sarcoma, may be an adequate therapy for childhood post-irradiation sarcoma.

Effects of long-term treatment with naltrexone on hepatic enzyme activity.

The influence of naltrexone on liver function in heroin addicts was studied, with respect to the metabolizing function by using the antipyrine clearance and to cellular damage by monitoring plasma levels of hepatic enzymes. The clearance of antipyrine was not affected by naltrexone treatment, and, during the study period, the use and withdrawal of benzodiazepines and alcohol did not change this parameter; moreover, there was no relationship between changes in plasma hepatic enzymes and antipyrine half-life. Mean plasma levels of hepatic enzymes did not show significant modification in the course of treatment with naltrexone.

Characterization of a novel mouse reticular cell sarcoma M5076 subline resistant to cisplatin.

A novel murine tumor resistant to cis-diamminedichloroplatinum (cisplatin, DDP) was obtained (M5/DDP) after 22 passages in which mice bearing the ovarian reticular cell sarcoma M5076 (M5) were treated with DDP. Although DDP conserved some inhibitory activity on growth of M5/DDP, it was much less effective than on M5. Treatment with DDP did not prolong the survival time of mice with M5/DDP, whereas it markedly prolonged survival of M5-bearing mice. M5 and M5/DDP tumors shared many biological and biochemical features. They were similar histologically, they metastasized reproducibly to the liver and were poorly immunogenic. Their growth rates were comparable; their DNA index, percentage of cells in S phase and intra-cellular glutathione content were also similar. In both tumors, DDP caused an accumulation of cells in S late-G2-M within 24 hr after drug treatment. However, this was efficiently reversed in M5/DDP, whereas it worsened and persisted longer in M5. Cross-resistance was observed between DDP and its analogues carboplatin and iproplatin, but tetraplatin retained marginal activity on M5/DDP tumor. Several alkylating agents tested [L-phenyalanine mustard (L-PAM); cyclophosphamide (CTX); chlorambucil (CLB); 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and dacarbazine (DTIC)] were not totally cross-resistant to DDP, but showed greater activity on M5 than on M5/DDP. Other non-alkylating anti-neoplastic drugs showed a similar degree of activity on M5 and M5/DDP. 5-Aza-2'-deoxycytidine (Aza-d-Cyd) was very effective on both tumors, etoposide (VP-16) and cytosine arabinoside (Ara-C) had no activity and Adriamycin (ADR) was weakly effective.

Tratamento de pacientes portadores de dispepsia alta ou de úlcera peptica com preparaçöes de Espinheira-santa (Maytenus ilicifolia) / Treatment of Patients of High Dyspepsia or Peptic Ulcers with Maytenus ilicifolia Preparations

Em esquema duplo-cego, vinte e três pacientes diagnosticados como portadoes de dispepsia alta näo-ulcerosa foram alocados para receber, durante 28 dias, duas cápsulas contendo 200 mg cada de liofilizado de abafo de espinheira-santa (treze pacientes) ou cápsulas contendo açucar mascavo como placebo (onze pacientes). Apenas um paciente do grupo espinheira-santa näo terminou o tratamento contra cinco desistências do grupo placebo, sendo a diferença estatisticamente significante. O grupo espinheira-santa também apresentou melhora estatisticamente significante, em relaçäo ao grupo placebo, no que diz respeito a sintomatologia dispéptica global, e, particularmente, nos sintomas de azia e dor. Näo houve queixas de efeitos colaterais produzidos pela espinheira-santa. Vinte pacientes com úlceras pépticas, diagnosticadas endoscopicamente, passaram a receber, em esquema duplo-cego, duas cápsulas diárias com 200 mg de liofilizado de espinheira-santa (dez pacientes) ou cápsulas de palcebo (dez pacientes). Dado o número de desistências (cinco e quatro, respectivamente) e das cicatrizaçöes de úlceras terem ocorrido também no grupo placebo, os resultados näo diferiram estatisticamente