Improved nutrition in adolescents and young adults after childhood cancer - INAYA study.

BACKGROUND: Multimodality treatment improves the chance of survival but increases the risk for long-term side effects in young cancer survivors, so-called" Adolescents and Young Adults"(AYAs). Compared to the general population AYAs have a 5 to 15-fold increased risk of cardiovascular morbidity. Thus, improving modifiable lifestyle risk factors is of particular importance. METHODS: The INAYA trial included AYAs between 18 and 39 years receiving an intensified individual nutrition counseling at four time points in a 3-month period based on a 3-day dietary record. At week 0 and 12 AYAs got a face-to-face counseling, at week 2 and 6 by telephone. Primary endpoint was change in nutritional behavior measured by Healthy Eating Index - European Prospective Investigation into Cancer and Nutrition (HEI-EPIC). RESULTS: Twenty-three AYAs (11 female, 12 male, median age 20 years (range 19-23 years), median BMI: 21.4 kg/m2 (range: 19.7-23.9 kg/m2) after completion of cancer treatment for sarcoma (n = 2), carcinoma (n = 2), blastoma (n = 1), hodgkin lymphoma (n = 12), or leukemia (n = 6) were included (median time between diagnosis and study inclusion was 44 month). The primary endpoint was met, with an improvement of 20 points in HEI-EPIC score in 52.2 % (n = 12) of AYAs. At baseline, median HEI-EPIC score was 47.0 points (range from 40.0 to 55.0 points) and a good, moderate and bad nutritional intake was seen in 4.3, 73.9 and 21.7 % of AYAs. At week 12, median HEI-EPIC improved significantly to 65.0 points (range from 55.0 to 76.0 points) (p ≤ 0.001) and a good, moderate and bad nutritional intake was seen in 47.8, 52.2 and 0 % of AYAs. No change was seen in quality of life, waist-hip ratio and blood pressure. CONCLUSION: Intensified nutrition counseling is feasible and seem to improve nutritional behavior of AYAs. Further studies will be required to demonstrate long-term sustainability and confirm the results in a randomized design in larger cohorts. TRIAL REGISTRATION: Clinical trial identifier DRKS00009883 on DRKS.

Participation in patient support groups among cancer survivors: do psychosocial and medical factors have an impact?

A better understanding of the role of psychosocial resources and factors associated with participating in patient support groups appears to be important for the development and implementation of cancer survivorship care plans. We therefore investigated the frequency of participation in and satisfaction with patient support groups after completion of a rehabilitation programme and aimed to examine differences in demographic, medical and psychosocial characteristics between group participants and non-participants. We further aimed to identify predictors of participation in patient support groups. A total of 1281 eligible patients (75.5% participation rate) were recruited on average 11 months post diagnosis and assessed at the beginning (t1 ), at the end (t2 ) and 12 months after rehabilitation (t3 ). Study participants completed self-report measures assessing support-group participation and satisfaction, psychosocial distress (anxiety, fear of cancer recurrence, depression), social support, coping, quality of life, pain and treatment-related characteristics. Sixty-seven patients (7.6%) participated in a patient self-help group. Being unemployed, undergoing an increased number of overall treatments, and a higher active emotion-oriented coping style significantly predicted self-help group participation; the predictive power of the multivariate logistic regression model was rather weak (Nagelkerke's R(2) = 0.07). Our data provide evidence that self-help group participation in cancer patients may be largely related to other factors than medical or psychosocial distress.

Laser-accelerated electron beams at 1 GeV using optically-induced shock injection.

In recent years, significant progress has been made in laser wakefield acceleration (LWFA), both regarding the increase in electron energy, charge and stability as well as the reduction of bandwidth of electron bunches. Simultaneous optimization of these parameters is, however, still the subject of an ongoing effort in the community to reach sufficient beam quality for next generation's compact accelerators. In this report, we show the design of slit-shaped gas nozzles providing centimeter-long supersonic gas jets that can be used as targets for the acceleration of electrons to the GeV regime. In LWFA experiments at the Centre for Advanced Laser Applications, we show that electron bunches are accelerated to [Formula: see text] using these nozzles. The electron bunches were injected into the laser wakefield via a laser-machined density down-ramp using hydrodynamic optical-field-ionization and subsequent plasma expansion on a ns-timescale. This injection method provides highly controllable quasi-monoenergetic electron beams with high charge around [Formula: see text], low divergence of [Formula: see text], and a relatively small energy spread of around [Formula: see text] at [Formula: see text]. In contrast to capillaries and gas cells, the scheme allows full plasma access for injection, probing or guiding in order to further improve the energy and quality of LWFA beams.

[Long-term sequelae of cancer survivors]. / Therapiefolgen bei Krebs-Langzeitüberlebenden.

Multimodal treatment modalities enable an increasing number of patients with malignant diseases to become candidates for a curatively intended treatment strategy. Furthermore, for numerous patients with incurable cancer disease, new therapeutic developments (including molecular "targeted" agents) allow control of further progression of tumor growth for months up to years - and therefore, even those patients may be regarded as having a "chronic" disease. Taken together, both patient groups increase the number of "long-term cancer survivors" markedly. However, complex interdisciplinary therapeutic strategies and the increasing number of options for sequential treatments also result in higher rates of acute and chronic toxicities and sequelae. Even years after completion of the initial treatment, many cancer survivors still suffer from sequelae of both malignant disease and therapy. This refers to both psychosocial and somatic involvement. In consequence, a focus of (future) oncology care - beyond successful oncology treatment rates - is to carefully investigate the somatic and psychosocial aspects of long-term sequelae in order to treat them, or - using appropriate preventative measures - to limit or even prevent their occurrence.

Phase II trial of vinorelbine and trastuzumab in patients with HER2-positive metastatic breast cancer. A prospective, open label, non-controlled, multicenter phase II trial (to investigate efficacy and safety of this combination chemotherapy).

The purpose of this study was to evaluate the efficacy (progression free survival (PFS) and response rate) and safety of vinorelbine and trastuzumab combination chemotherapy in patients with HER2-overexpressing, metastatic breast cancer as a first line chemotherapy regimen. Patients with histologically confirmed, HER2-positive (immunohistochemistry (ICH) 3+, or 2+ and FISH+) metastatic breast cancer who had nor received prior vinorelbine or anti-HER2 therapy in the adjuvant setting, received at least eight weeks of vinorelbine i.v. (25 mg/g weekly) and trastuzumab (4 mg/kg on day 1 followed by 2 mg/kg weekly). Forty-one women from six participating centers were enrolled into the trial. The overall response rate, was 43.9% (18 of 41 patients), (CI 28-60.3%), 30% of patients were progression free after 1 year. Four patients reached complete remission, 14 partial remission and five had stable disease for at least 18 weeks. Six patients developed primary progression. 35 patients (85%) experienced progression after a median time of 235 days. Therapy was in general well-tolerated. There were two CTC grade 4 infusion syndromes and two patients experienced cardiotoxicity at least grade 2. This phase II trial of vinorelbine and trastuzumab demonstrated an effective and well-tolerated regimen with a favourable safety profile.

Atrophin-1, the dentato-rubral and pallido-luysian atrophy gene product, interacts with ETO/MTG8 in the nuclear matrix and represses transcription.

Dentato-rubral and pallido-luysian atrophy (DRPLA) is one of the family of neurodegenerative diseases caused by expansion of a polyglutamine tract. The drpla gene product, atrophin-1, is widely expressed, has no known function or activity, and is found in both the nuclear and cytoplasmic compartments of neurons. Truncated fragments of atrophin-1 accumulate in neuronal nuclei in a transgenic mouse model of DRPLA, and may underlie the disease phenotype. Using the yeast two-hybrid system, we identified ETO/MTG8, a component of nuclear receptor corepressor complexes, as an atrophin-1-interacting protein. When cotransfected into Neuro-2a cells, atrophin-1 and ETO/MTG8 colocalize in discrete nuclear structures that contain endogenous mSin3A and histone deacetylases. These structures are sodium dodecyl sulfate-soluble and associated with the nuclear matrix. Cotransfection of ETO/MTG8 with atrophin-1 recruits atrophin-1 to the nuclear matrix, while atrophin-1 and ETO/MTG8 cofractionate in nuclear matrix preparations from brains of DRPLA transgenic mice. Furthermore, in a cell transfection-based assay, atrophin-1 represses transcription. Together, these results suggest that atrophin-1 associates with nuclear receptor corepressor complexes and is involved in transcriptional regulation. Emerging links between disease-associated polyglutamine proteins, nuclear receptors, translocation-leukemia proteins, and the nuclear matrix may have important repercussions for the pathobiology of this family of neurodegenerative disorders.

HIGH-ENERGY ASTROPHYSICS: Gamma Ray Bursts May Pack a One-Two Punch.

Most astrophysicists puzzling over what causes gamma ray bursts--short, intense explosions of high-energy photons that occur deep in space--now agree that the answer is a hypernova, the blast of energy released when a supermassive star collapses into a black hole. Two papers in this issue of Science (pp. 953 and 955), reporting on new x-ray observations of two gamma ray bursts, argue that the hypernova model tells only half of the story. On its way to becoming a black hole, the authors propose, the supermassive star actually collapses twice.

HIGH-ENERGY ASTROPHYSICS: X-ray Satellites Seek Clues to Bursts.

Last month the High Energy Transient Explorer 2, the first satellite dedicated to spotting gamma ray bursts, rocketed successfully into orbit, bolstering a handful of x-ray satellites whose instruments are trained on the mysterious explosions. But some researchers say setbacks to the fleet have left unfortunate gaps in coverage.

ASTRONOMY: The Virtual Observatory Moves Closer to Reality.

Data from decades of observations by dozens of instruments may soon be accessible over the Internet, changing the way that astronomy is done around the world. The National Virtual Observatory will be an electronic web that gives astronomers access to terabytes of celestial data with the click of a mouse. The virtual observatory promises to make possible new analyses of the heavens by weaving together information from facilities around the world--and in space.

ASTRONOMY: Watch This Space!

Later this year, a site called SkyServer hopes to put the sky at your fingertips at www.skyserver.org. Initially aimed at a more general audience, SkyServer might become part of a National Virtual Observatory.

PLANETARY SCIENCE: Imaging Spat Pits Amateur Against Pros.

A long-running dispute over who should get credit for first reporting landmarks on Mercury's uncharted hemisphere burst into public view on 26 May, when a Boston University press release claimed honors for a BU team without mentioning the contributions of an erstwhile collaborator, amateur astronomer Ron Dantowitz. The row, which has left both sides bitter and unwilling to work with each other, "was the opposite of how a collaboration between amateurs and professionals should be," says one of the scientists involved.

ASTRONOMY: Neighborhood Gamma Ray Burst Boosts Theory.

Titanic explosions that emit powerful flashes of energetic gamma rays are one of astronomy's hottest mysteries. Now an analysis of the nearest gamma ray burst yet detected has added weight to the popular theory that they are expelled during the death throes of supermassive stars.

ASTROPHYSICS: Neutron Stars Imply Relativity's a Drag.

A new finding, based on x-rays from distant neutron stars, could be the first clear evidence of a weird relativistic effect called frame dragging, in which a heavy chunk of spinning matter wrenches the space-time around it like an eggbeater. Using data from NASA's Rossi X-ray Timing Explorer, three astronomers in Amsterdam found circumstantial evidence for frame dragging in the flickering of three neutron stars in binary systems. They announced their results in the 1 September issue of The Astrophysical Journal.

Lymphocyte apoptosis: mediation by increased type 3 inositol 1,4,5-trisphosphate receptor.

B and T lymphocytes undergoing apoptosis in response to anti-immunoglobulin M antibodies and dexamethasone, respectively, were found to have increased amounts of messenger RNA for the inositol 1,4,5-trisphosphate receptor (IP3R) and increased amounts of IP3R protein. Immunohistochemical analysis revealed that the augmented receptor population was localized to the plasma membrane. Type 3 IP3R (IP3R3) was selectively increased during apoptosis, with no enhancement of type 1 IP3R (IP3R1). Expression of IP3R3 antisense constructs in S49 T cells blocked dexamethasone-induced apoptosis, whereas IP3R3 sense, IP3R1 sense, or IP3R1 antisense control constructs did not block cell death. Thus, the increases in IP3R3 may be causally related to apoptosis.

Widespread expression of Huntington's disease gene (IT15) protein product.

Huntington's Disease (HD) is caused by expansion of a CAG repeat within a putative open reading frame of a recently identified gene, IT15. We have examined the expression of the gene's protein product using antibodies developed against the N-terminus and an internal epitope. Both antisera recognize a 350 kDa protein, the predicted size, indicating that the CAG repeat is translated into polyglutamine. The HD protein product is widely expressed, most highly in neurons in the brain. There is no enrichment in the striatum, the site of greatest pathology in HD. Within neurons, the protein is diminished in nuclei and mitochondria and is present in the soluble cytoplasmic compartment, as well as loosely associated with membranes or cytoskeleton, in cell bodies, dendrites, and axons. It is concentrated in nerve terminals, including terminals within the caudate and putamen. Thus, the normal HD gene product may be involved in common intracellular functions, and possibly in regulation of nerve terminal function. The product of the expanded allele is expressed, consistent with a gain of function mechanism for HD at the protein level.

Huntington's disease gene (IT15) is widely expressed in human and rat tissues.

Huntington's Disease (HD) is notable for selective neuronal vulnerability in the basal ganglia and cerebral cortex. We have investigated in human and rodent tissues the expression of the gene (IT15) whose mutation causes HD. IT15 is widely expressed, with highest levels of expression in brain, but also in lung, testis, ovary, and other tissues. Within the brain, expression is widespread with a neuronal pattern and is not enriched in the basal ganglia. Expression of IT15 is not reduced in the brain of HD patients when corrected for actin (though it is slightly decreased in the striatum when uncorrected, consistent with neuronal loss). Thus, the widespread distribution of IT15 expression does not correspond with the restricted distribution of neuropathologic changes in HD. We suggest that pathophysiology may relate to abnormal cell type-specific protein interactions of the HD protein.

Nuclear accumulation of truncated atrophin-1 fragments in a transgenic mouse model of DRPLA.

Dentatorubral and pallidoluysian atrophy (DRPLA) is a member of a family of progressive neurodegenerative diseases caused by polyglutamine repeat expansion. Transgenic mice expressing full-length human atrophin-1 with 65 consecutive glutamines exhibit ataxia, tremors, abnormal movements, seizures, and premature death. These mice accumulate atrophin-1 immunoreactivity and inclusion bodies in the nuclei of multiple populations of neurons. Subcellular fractionation revealed 120 kDa nuclear fragments of mutant atrophin-1, whose abundance increased with age and phenotypic severity. Brains of DRPLA patients contained apparently identical 120 kDa nuclear fragments. By contrast, mice overexpressing atrophin-1 with 26 glutamines were phenotypically normal and did not accumulate the 120 kDa fragments. We conclude that the evolution of neuropathology in DRPLA involves proteolytic processing of mutant atrophin-1 and nuclear accumulation of truncated fragments.

Investigating the temporal course, relevance and risk factors of fatigue over 5 years: a prospective study among patients receiving allogeneic HSCT.

Although allogeneic hematopoietic stem cell transplantation (HSCT) features severe physical and psychological strain, no previous study has prospectively investigated fatigue beyond 3 years after transplantation. We investigated the temporal course of fatigue over 5 years, compared patients with the general population (GP) and tested for treatment- and complication-related risk factors. Patients were assessed before conditioning (T0, N=239) and at 100-day (T1, N=150), 1-year (T2, N=102) and 5-year (T3, N=45) follow-up. We measured fatigue with the Multidimensional Fatigue Inventory-20. Patients were compared with the GP at T0 and at T3. Global fatigue increased from T0 to T1 (t=3.85, P<0.001), decreased from T1 to T2 (t=-2. 92, P=0.004) and then remained stable (t=0.45, P=0.656). No difference in global fatigue was found between T0 and T3 (t=0.68, P=0.497). Compared with the GP, patients showed higher global fatigue at T0 (t=-6.02, P<0.001) and T3 (t=-2.50, P=0.014). These differences reached meaningful effect sizes (d⩾0.5). Acute and chronic GvHD predicted global fatigue at T1 (γ=0.34, P=0.006) and T2 (γ=0.38, P=0.010), respectively. To conclude, fatigue among allogeneic HSCT patients improves with time, finally returning to pretransplantation levels. However, even after 5 years, the difference from the GP remains relevant. Patients with GvHD are at risk for increased fatigue.

Resolution of etodolac and antiinflammatory and prostaglandin synthetase inhibiting properties of the enantiomers.

Etodolac, 1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid, a clinically effective analgesic and antiinflammatory agent, has been resolved via a chromatographic separation of its diastereoisomeric esters with (-)-borneol. The effects of the enantiomers were studied in vitro on prostaglandin synthetase and on adjuvant-induced arthritis in rats. The biochemical and pharmacological results show that virtually all of the effects of etodolac are due to the (+) enantiomer.