Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic pain due to bone metastases (Trans-Tasman Radiation Oncology Group, TROG 96.05)

Background and purpose: Despite numerous randomized trials investigating radiotherapy (RT) fractionation schedules for painful bone metastases, there are very few data on RT for bone metastases causing pain with a neuropathic component. The Trans-Tasman Radiation Oncology Group undertook a randomized trial comparing the efficacy of a single 8 Gy (8/1) with 20 Gy in 5 fractions (20/5) for this type of pain. Materials and methods: Eligible patients had radiological evidence of bone metastases from a known malignancy with no change in systemic therapy within 6 weeks before or anticipated within 4 weeks after RT, no other metastases along the distribution of the neuropathic pain and no clinical or radiological evidence of cord/cauda equina compression. All patients gave written informed consent. Primary endpoints were pain response within 2 months of commencement of RT and time to treatment failure (TTF). The hypothesis was that 8/1 is at least as effective as 20/5 and the planned sample size was 270 patients. Results: Between February 1996 and December 2002, 272 patients were randomized (8/1:20/5 = 137:135) from 15 centres (Australia 11, New Zealand 3, UK 1). The commonest primary cancers were lung (31%), prostate (29%) and breast (8%); index sites were spine (89%), rib (9%), other (2%); 72% of patients were males and the median age was 67 (range 2989). The median overall survival (95% CI) for all randomized patients was 4.8 mo (4.2-5.7 mo). The intention-to-treat overall response rates (95% Cl) for 8/1 vs 20/5 were 53% (45-62%) vs 61% (53-70%), P = 0.18. Corresponding figures for complete response were 26% (18-34%) vs 27% (19-35%), P = 0.89. The estimated median TTFs (95% CI) were 2.4 mo (2.0-3.3 mo) vs 3.7 mo (3.1-5.9 mo) respectively. The hazard ratio (95% Cl) for the comparison of TTF curves was 1.35 (0.99-1.85), log-rank P = 0.056. There were no statistically significant differences in the rates of re-treatment, cord compression or pathological fracture by arm. Conclusions: 8/1 was not shown to be as effective as 20/5, nor was it statistically significantly worse. Outcomes were generally poorer for 8/1, although the quantitative differences were relatively small. (c) 2004 Elsevier Ireland Ltd. All rights reserved.

Whole brain irradiation following surgery or radiosurgery for solitary brain metastases: Mature results of a prematurely closed randomized Trans-Tasman Radiation Oncology Group trial (TROG 98.05)

We evaluated the effect of adjuvant whole brain irradiation (WBI) after surgery or radiosurgery for solitary brain metastases in a Phase III multicentre trial with randomization to 30-36 Gy WBI or observation. The study was closed early due to slow accrual after 19 patients (WBI 10, observation 9). There was no difference in CNS failure-free survival or overall survival between the arms. There was a trend to reduced CNS relapse with WBI (30% versus 78%, P = 0.12). Limited analysis of quality of life and neurocognitive function data revealed no evidence of difference between the arms. Our results are not inconsistent with two larger randomized trials and support the use of upfront WBI to decrease brain recurrence in this setting. (c) 2006 Elsevier Ireland Ltd. All rights reserved.

Transformações químicas, caracterizações e estudo de modelagem molecular do clerodano bioativo trans-desidrocrotonina

In this work it were developed synthetic and theoretical studies for clerodane-type diterpenes obtained from Croton cajucara Benth which represents one of the most important medicinal plant of the Brazil amazon region. Specifically, the majoritary biocompound 19-nor-clerodane trans-dehydrocrotonin (t-DCTN) isolated from the bark of this Croton, was used as target molecule. Semi-synthetic derivatives were obtained from t-DCTN by using the followed synthetic procedures: 1) catalytic reduction with H2, 2) reduction using NaBH4 and 3) reduction using NaBH4/CeCl3. The semi-synthetic 19-nor-furan-clerodane alcohol-type derivatives were denominated such as t-CTN, tCTN-OL, t-CTN-OL, t-DCTN-OL, t-DCTN-OL, being all of them characterized by NMR. The furan-clerodane alcohol derivatives t-CTN-OL and tCTN-OL were obtained form the semi-synthetic t-CTN, which can be isolated from the bark of C. cajucara. A theoretical protocol (DFT/B3LYP) involving the prevision of geometric and magnetic properties such as bond length and angles, as well as chemical shifts and coupling constants, were developed for the target t-DCTN in which was correlated NMR theoretical data with structural data, with satisfactory correlation with NMR experimental data (coefficients ranging from 0.97 and 0.99) and X-ray diffraction data. This theoretical methodology was also validated for all semi-synthetic derivatives described in this work. In addition, topological data from the Quantum Theory of Atoms in Molecules (QTAIM) showed the presence of H-H and (C)O--H(C) intramolecular stabilized interactions types for t-DCTN e t-CTN, contributing to the understanding of the different reactivity of this clerodanes in the presence of NaBH4.

The effects of trans-generational exposure to ocean warming and acidification on life history and physiological traits in a marine polychaete

Human-assisted, trans-generational exposure to ocean warming and acidification has been proposed as a conservation and/or restoration tool to produce resilient offspring. To improve our understanding of the need for and the efficacy of this approach, we characterised life history and physiological responses in offspring of the marine polychaete Ophryotrocha labronica exposed to predicted ocean warming (OW: + 3 °C), ocean acidification (OA: pH -0.5) and their combination (OWA: + 3 °C, pH -0.5), following the exposure of their parents to either control conditions (within-generational exposure) or the same conditions (trans-generational exposure). Trans-generational exposure to OW fully alleviated the negative effects of within-generational exposure to OW on fecundity and egg volume and was accompanied by increased metabolic activity. While within-generational exposure to OA reduced juvenile growth rates and egg volume, trans-generational exposure alleviated the former but could not restore the latter. Surprisingly, exposure to OWA had no negative impacts within- or trans-generationally. Our results highlight the potential for trans-generational laboratory experiments in producing offspring that are resilient to OW and OA. However, trans-generational exposure does not always appear to improve traits, and therefore may not be a universally useful tool for all species in the face of global change.

Outcome of the Public Consultation on the Draft Opinion of the Scientific Panel on Dietetic Products, Nutrition, and Allergies (NDA) on Dietary Reference Values for Fats, Including Saturated Fatty Acids, Polyunsaturated Fatty Acids, Monounsaturated Fatty Acids, Trans Fatty Acids, and Cholesterol

On 2 July 2009, the EFSA Panel on Dietetic products, Nutrition and Allergies (NDA) endorsed a draft Opinion on Dietary Reference Values for fats to be released for public consultation. This Scientific Report summarises the comments received through the public consultation and outlines how these were taken into account in the final opinion. EFSA had received contributions from 40 interested parties (individuals, non-governmental organisations, industry organisations, academia and national assessment bodies). The main comments which were received during the public consultation related to: the availability of more recent data, the nomenclature used, the use of a non-European food composition data base, the impact of genetic factors in modulating the absorption, metabolism and health effects of different fatty acids, the definition of “nutritionally adequate diet”, the use of Dietary Reference Values in the labelling of foods, the translation of advice into food-based dietary guidelines, nutrient goals and recommendations, certain risk management issues, and to Dietary Reference Values of fats, individual fatty acids, and cholesterol. All the public comments received that related to the remit of EFSA were assessed and the Opinion on Dietary Reference Values for fats has been revised taking relevant comments into consideration.

Pre-Discharge Screening Trans-Cutaneous Bilirubinometry in Healthy Newborns in Mahdieh Hospital, Tehran

Background: Incidence of jaundice is high in newborn infants. Since well appearing newborns are rapidly and routinely discharged from hospital, performing an inexpensive noninvasive pre-discharge screening test for evaluation of jaundice seems to be necessary. Objectives: This study was conducted to compare the accuracy of cutaneous v/s serum bilirubin measurements in this regard. Patients and Methods: This was a prospective cross sectional study conducted in Mahdieh hospital, Tehran. 613 neonates weighing ≥ 1,800 g with gestational age of ≥ 35 weeks were enrolled. A pre discharge transcutaneous bilirubin test (TcB) was performed in all. Serum samples were taken from neonates with TcB ≥ 5 mg/dL in first and > 8 mg/dL in second 24 hours. Decision for treatment or recheck of bilirubin level after discharge was made based on serum bilirubin results. Results: Based on the study protocol, among 613 studied neonates, 491 (80%) revealed high TcB, of them 240 (49%) cases showed TBC ≥ 5 mg/dL in first and 251 (51 %) in second pre-discharge 24 hours. TcB ranged 3.3 - 17.1, mean TcB in first 24 hours was 6.9 ± 1 .7 (mode 6) and in second 24 hours 9.1 ± 2.1 (mode 10). Of 491 neonates with high TcB, capillary serum sample was taken as the second step and 398 neonates revealed high total serum bilirubin (TsB) with the same protocol for TcB. 108 (27.1%) neonates showed TsB ≥ 5 mg/dL in first and 290 (72.9%) in second 24 hours. According to the study results TcB has a 81% positive predictive value (PPV) in diagnosis of hyperbilirubinemia. Correlation coefficient of TcB and TsB in highest rate is equal to 72% (P value < 0.001). Conclusions: TcB is an inexpensive, noninvasive and precise pre-discharge screening test for evaluation of hyperbilirubinemia, with a high PPV. It is highly recommended to be performed routinely due to high incidence of hyperbilirubinemia in neonates.

¡Porque ni putas, ni peluqueras, ni nada… somos ciudadanas!’: Reflexiones sobre ciudadanía desde un grupo trans en la ciudad de Bogotá

‘¡Porque ni putas, ni peluqueras, ni nada… somos ciudadanas!’. Se pregunta por cómo se puede entender la ciudadanía desde las acciones comunitarias que llevaron a cabo un grupo de mujeres trans en la ciudad de Bogotá . Según informes nacionales y a nivel Latinoamérica son las mujeres trans pertenecientes al sector LGBT las que dijeron sentir, en mayor número, vulnerados sus derechos entorno a trabajo, salud y educación en la capital del país en comparación a la población LGB. La causa de tal vulneración pareció coincidir con su identidad de género, por ejemplo, al no poder encontrar trabajo por las expresiones de género que utilizaban. Por ende era necesario abordar cómo se entiende la ciudadanía desde corporalidades que no han tenido un óptimo acceso a la ciudad teniendo como referencia sus experiencias personales. Siendo el tránsito un proceso que se hace a lo largo del tiempo.

Detection of human interchromosomal trans-splicing in sequence databanks.

Trans-splicing is a common phenomenon in nematodes and kinetoplastids, and it has also been reported in other organisms, including humans. Up to now, all in silico strategies to find evidence of trans-splicing in humans have required that the candidate sequences follow the consensus splicing site rules (spliceosome-mediated mechanism). However, this criterion is not supported by the best human experimental evidence, which, except in a single case, do not follow canonical splicing sites. Moreover, recent findings describe a novel alternative tRNA mediated trans-splicing mechanism, which prescinds the spliceosome machinery. In order to answer the question, ?Are there hybrid mRNAs in sequence databanks, whose characteristics resemble those of the best human experimental evidence??, we have developed a methodology that successfully identified 16 hybrid mRNAs which might be instances of interchromosomal trans-splicing. Each hybrid mRNA is formed by a trans-spliced region (TSR), which was successfully mapped either onto known genes or onto a human endogenous retrovirus (HERV-K) transcript which supports their transcription. The existence of these hybrid mRNAs indicates that trans-splicing may be more widespread than believed. Furthermore, non-canonical splice site patterns suggest that infrequent splicing sites may occur under special conditions, or that an alternative trans-splicing mechanism is involved. Finally, our candidates are supposedly from normal tissue, and a recent study has reported that trans-splicing may occur not only in malignant tissues, but in normal tissues as well. Our methodology can be applied to 5'-UTR, coding sequences and 3'-UTR in order to find new candidates for a posteriori experimental confirmation.