Randomised trial of glutamine, selenium, or both, to supplement parenteral nutrition for critically ill patients

Peer reviewedPublisher PD

Levetiracetam-loaded biodegradable polymer implants in the tetanus toxin model of temporal lobe epilepsy in rats

Approximately one-third of people with epilepsy receive insufficient benefit from currently available anticonvulsant medication, and some evidence suggests that this may be due to a lack of effective penetration into brain parenchyma. The current study investigated the ability of biodegradable polymer implants loaded with levetiracetam to ameliorate seizures following implantation above the motor cortex in the tetanus toxin model of temporal lobe epilepsy in rats. The implants led to significantly shorter seizures and a trend towards fewer seizures for up to 1 week. The results of this study indicate that drug-eluting polymer implants represent a promising evolving treatment option for intractable epilepsy. Future research is warranted to investigate issues of device longevity and implantation site

In-beam gamma-ray spectroscopy of 35Mg and 33Na

Excited states in the very neutron-rich nuclei 35Mg and 33Na were populated in the fragmentation of a 38Si projectile beam on a Be target at 83 MeV/u beam energy. We report on the first observation of gamma-ray transitions in 35Mg, the odd-N neighbor of 34Mg and 36Mg, which are known to be part of the "Island of Inversion" around N = 20. The results are discussed in the framework of large- scale shell-model calculations. For the A = 3Z nucleus 33Na, a new gamma-ray transition was observed that is suggested to complete the gamma-ray cascade 7/2+ --> 5/2+ --> 3/2+ gs connecting three neutron 2p-2h intruder states that are predicted to form a close-to-ideal K = 3/2 rotational band in the strong-coupling limit.Comment: Accepted for publication Phys. Rev. C. March 16, 2011: Replaced figures 3 and 5. We thank Alfredo Poves for pointing out a problem with the two figure

Blockade of collagen-induced arthritis post-onset by antibody to granulocyte-macrophage colony-stimulating factor (GM-CSF): requirement for GM-CSF in the effector phase of disease

There is mounting evidence for a role of the growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) in inflammatory disease, including arthritis. In the present study, we examined the effectiveness of treatment of collagen-induced arthritis (CIA) with a neutralizing mAb to GM-CSF. DBA/1 mice were immunized for the development of CIA and treated at different times, and with different doses, with neutralizing mAb to GM-CSF or isotype control mAb. Anti-GM-CSF mAb treatment prior to the onset of arthritis, at the time of antigen challenge, was effective at ameliorating the ensuing disease. Modulation of arthritis was seen predominantly as a reduction in overall disease severity, both in terms of the number of limbs affected per mouse and the clinical score of affected limbs. Importantly, anti-GM-CSF mAb treatment ameliorated existing disease, seen both as a reduction in the number of initially affected limbs progressing and lower numbers of additional limbs becoming affected. By histology, both inflammation and cartilage destruction were reduced in anti-GM-CSF-treated mice, and the levels of tumor necrosis factor-a and IL-1? were also reduced in joint tissue washouts of these mice. Neither humoral nor cellular immunity to type II collagen, however, was affected by anti-GM-CSF mAb treatment. These results suggest that the major effect of GM-CSF in CIA is on mediating the effector phase of the inflammatory reaction to type II collagen. The results also highlight the essential role of GM-CSF in the ongoing development of inflammation and arthritis in CIA, with possible therapeutic implications for rheumatoid arthritis

Dietary supplementation with vitamin E modulates avian intestinal immunity

The effect of dietary vitamin E on immunoglobulin A (IgA) antibody production, which acts as the first line of defence at the intestinal mucosa, has not been evaluated in chickens. In the present study the impact of the inclusion of supplementary levels of vitamin E to the diet, on total and antigen-specific IgA antibody titres, T-cell subsets and Ia+ cells, was assessed. From hatching, chickens received a maize-based diet which was supplemented with either 25, 250, 2500 or 5000 mg dl-alpha-tocopherol acetate/kg. Primary immunisation with tetanus toxoid (T. toxoid) emulsified in a vegetable oil-in-water adjuvant was administered by the intraperitoneal route at 21 d of age. At 35 d of age all birds received an oral booster vaccination of T. toxoid. Significantly higher total IgA antibody titres were present in the day 42 intestinal scrapings of birds receiving the 5000 mg/kg vitamin E-supplemented diet (VESD) (P=0.05) and a notable increase was observed in birds receiving the 250 mg/kg VESD (P=0.06). At days 21 and 42 total serum IgA antibody titres of birds receiving the 250 mg/kg VESD was significantly higher (

Issues in the determination of “responders” and “non‐responders” in physiological research

As a follow-up to our 2015 review, we cover more issues on the topic of “response heterogeneity”, which we define as clinically-important individual differences in the physiological responses to the same treatment or intervention that cannot be attributed to random within-subjects variability. We highlight various pitfalls with the common practice of counting the number of “responders”, “non-responders” and “adverse responders” in samples that have been given certain treatments/interventions for research purposes. We focus on the classical parallel-group randomised controlled trial (RCT) design and assume typical good practice in trial design.We show that sample responder counts are biased because individuals differ in terms of pre-to-post within-subjects random variability in the study outcome(s) and not necessarily treatment response. Ironically, sample differences in responder counts may be explained wholly by sample differences in mean response, even if there is no response heterogeneity at all. Sample comparisons of responder counts also have relatively low statistical precision. These problems do not depend on how the response threshold has been selected, e.g. on the basis of a measurement error statistic, and are not rectified fully by the use of confidence intervals for individual responses in the sample

Spectroscopy of the odd-odd fp-shell nucleus 52Sc from secondary fragmentation

The odd-odd fp-shell nucleus 52Sc was investigated using in-beam gamma-ray spectroscopy following secondary fragmentation of a 55V and 57Cr cocktail beam. Aside from the known gamma-ray transition at 674(5)keV, a new decay at E_gamma=212(3) keV was observed. It is attributed to the depopulation of a low-lying excited level. This new state is discussed in the framework of shell-model calculations with the GXPF1, GXPF1A, and KB3G effective interactions. These calculations are found to be fairly robust for the low-lying level scheme of 52Sc irrespective of the choice of the effective interaction. In addition, the frequency of spin values predicted by the shell model is successfully modeled by a spin distribution formulated in a statistical approach with an empirical, energy-independent spin-cutoff parameter.Comment: accepted for publication in PR

Population of bound excited states in intermediate-energy fragmentation reactions

Fragmentation reactions with intermediate-energy heavy-ion beams exhibit a wide range of reaction mechanisms, ranging from direct reactions to statistical processes. We examine this transition by measuring the relative population of excited states in several sd-shell nuclei produced by fragmentation with the number of removed nucleons ranging from two to sixteen. The two-nucleon removal is consistent with a non-dissipative process whereas the removal of more than five nucleons appears to be mainly statistical.Comment: 5 pages, 6 figure