Return to work predictors after traumatic brain injury in a welfare state.

OBJECTIVE: To identify predictors of return to work (RTW) and stable labour market attachment (LMA) after severe traumatic brain injury (TBI) in Denmark. MATERIALS & METHODS: Patients aged 18-64 years, admitted to highly specialized neurorehabilitation after severe TBI 2004-2012 were included and followed up for ≤6 years. Weekly LMA data were retrieved from a national register of public assistance benefits. Weeks without or with supplemental public assistance benefits were defined as LMA weeks. Time of RTW was defined as first week with LMA. Stable LMA was defined as weeks with LMA ≥75% first year after RTW. Multivariable regressions were used to identify predictors of RTW and stable LMA among preinjury characteristics, injury severity, functional ability and rehabilitation trajectories. RESULTS: For the analyses of RTW and stable LMA, 651 and 336 patients were included, respectively. RTW was significantly associated with age (adjusted subhazard ratio 0.98, 95% CI 0.97-0.99), education (1.83, 95% CI 1.16-2.89), supplemental benefits (3.97, 95% CI 2.04-7.71), no benefits (4.86, 95% CI 2.90-8.17), length of stay in acute care (0.77, 95% CI 0.60-0.99) and time period of injury (1.56, 95% CI 1.15-2.10). The only significant predictor of stable LMA was age (adjusted odds ratio 0.97, 95% CI 0.95-0.99). CONCLUSION: RTW after severe TBI was associated with several socio-economic factors, whereas maintaining LMA depended on age only. We suggest that RTW rates could be improved by extensive rehabilitation targeting people that are older and low-educated, as these were less likely to RTW.

Reliability of surface electromyography measurements from the suprahyoid muscle complex.

Assessment of swallowing musculature using motor evoked potentials (MEPs) can be used to evaluate neural pathways. However, recording of the swallowing musculature is often invasive, uncomfortable and unrealistic in normal clinical practice. To investigate the possibility of using the suprahyoid muscle complex (SMC) using surface electromyography (sEMG) to assess changes to neural pathways by determining the reliability of measurements in healthy participants over days. Seventeen healthy participants were recruited. Measurements were performed twice with one week between sessions. Single-pulse (at 120% and 140% of the resting motor threshold (rMT)) and paired-pulse (2 ms and 15 ms paired pulse) transcranial magnetic stimulation (TMS) were used to elicit MEPs in the SMC which were recorded using sEMG. ≈50% of participants (range: 42-58%; depending on stimulus type/intensity) had significantly different MEP values between day 1 and day 2 for single-pulse and paired-pulse TMS. A large stimulus artefact resulted in MEP responses that could not be assessed in four participants. The assessment of the SMC using sEMG following TMS was poorly reliable for ≈50% of participants. Although using sEMG to assess swallowing musculature function is easier to perform clinically and more comfortable to patients than invasive measures, as the measurement of muscle activity using TMS is unreliable, the use of sEMG for this muscle group is not recommended and requires further research and development.

Effect of transcranial direct current stimulation on neuroplasticity in corticomotor pathways of the tongue muscles.

The aim of this study is to investigate effects of transcranial direct current stimulation (tDCS) on neuroplasticity in corticomotor pathways related to tongue muscles evoked by a training task using the tongue drive system (TDS). Using a crossover design, 13 healthy participants completed two sessions of tDCS while performing 30 min of TDS training. Sessions were spaced at least 2 weeks apart and participants randomly received anodal and sham tDCS stimulation in the first session and the other condition in the second session. Single and paired pulse transcranial magnetic stimulation was used to elicit motor evoked potentials (MEPs) of the tongue at three time-points: before, immediately after and 30 min after training. Participant-based reports of fun, pain, fatigue and motivation, level of difficulty and effort were evaluated on numerical rating scales. There was no consistent significant effect of anodal and sham stimulation on single or paired pulse stimulation MEP amplitude immediately or 30 min after TDS training. Irrespective of tDCS type, training with TDS induced cortical plasticity in terms of increased MEP amplitudes for higher stimulus intensities after 30 min compared with before and immediately after training. Participant-based reports revealed no significant difference between tDCS conditions for level of fun, fatigue, motivation, difficulty and level of effort but a significant increase in pain in the anodal condition, although pain level was low for both conditions. In conclusion, tongue MEP amplitudes appear to be sensitive to training with the tongue using TDS; however, anodal tDCS does not have an impact on training-evoked neuroplasticity of tongue corticomotor pathways.

Assessment of Newcastle disease-specific T cell proliferation in different inbred MHC chicken lines.

In this study, we have described the establishment of an antigen-specific T cell proliferation assay based on recall stimulation with Newcastle disease (ND) antigen; further, we have described the results obtained after recall stimulation of animals containing different major histocompatibility complex (MHC) haplotypes, vaccinated against ND. First optimization of the assay was performed to lower unspecific proliferation and to enhance antigen-specific T cell proliferation. These two issues were achieved using ethylene diamine tetra acetic acid as stabilizing agent in blood samples and autologous immune serum in culture medium. The optimized assay was used to screen chickens with different MHC haplotypes for their ability to perform T cell proliferation. Results showed that the antigen-specific response of CD4(+) and CD8(+) T cells from B12 chickens was generally low, whereas B13, B130 and B201 chickens were medium in CD4(+) or CD8(+) T cell responses. High responses were seen only in few animals of each haplotype and not in general. A polymorphism in the chicken CD8α gene was found in our experimental chicken lines, resulting in incapability to detect CD8α(+) T cells using antibodies from the CT8 clone. Screening chickens with alternative antibodies showed that antibodies from the 2-398 clone were able to discriminate all CD8α(+) cells from CD8α(-) cells, and consequently this antibody was used in a second vaccination experiment performed with chickens of the haplotypes B13 and B130. This experiment showed a significant difference in antigen-specific proliferation of CD4(+) T cells between the two lines, but not in CD8α(+) T cell proliferation.

Flow cytometric assessment of chicken T cell-mediated immune responses after Newcastle disease virus vaccination and challenge.

The objective of this study was to use flow cytometry to assess chicken T cell-mediated immune responses. In this study two inbred genetic chicken lines (L130 and L133) were subjected to two times vaccination against Newcastle disease (ND) and a subsequent challenge by ND virus (NDV) infection. Despite a delayed NDV-specific antibody response to vaccination, L133 appeared to be better protected than L130 in the subsequent infection challenge as determined by the presence of viral genomes. Peripheral blood was analyzed by flow cytometry and responses in vaccinated/challenged birds were studied by 5-color immunophenotyping as well as by measuring the proliferative capacity of NDV-specific T cells after recall stimulation. Immunophenotyping identified L133 as having a significantly lower CD4/CD8 ratio and a lower frequency of gammadelta T cells than L130 in the peripheral T cell compartment. Furthermore, peripheral lymphocytes from L133 exhibited a significantly higher expression of CD44 and CD45 throughout the experiment. Interestingly, also vaccine-induced differences were observed in L133 as immune chickens had a significantly higher CD45 expression on their lymphocytes than the naïve controls. Immune chickens from both lines had a significantly higher frequency of circulating gammadelta T cells than the naïve controls both after vaccination and challenge. Finally, the proliferative capacity of peripheral CD4+ and CD8+ cells specific for NDV was addressed 3 weeks after vaccination and 1 week after infection and found to be significantly higher in L133 than in L130 at both sampling times. In conclusion, we found the applied flow cytometric methods very useful for the study of chicken T cell biology.

Comparison of the pharmacokinetics of tacrolimus and cyclosporine at equivalent molecular doses.

Even though calcineurin inhibitors, namely Tacrolimus (FK) and Cyclosporine (CsA) share similar physicochemical properties and a common mechanism of action, their pharmacokinetics (pk) are different and unpredictable. Both drugs are metabolized by cytochrome P450-3A4 isoforms in the liver and in the mucosa of the upper gastrointestinal tract. FK in clinical practice is given in doses up to 50-fold lower than those of CsA due to its greater potency. It is often assumed that the diverse dosing contributes to the observed pharmacokinetic differences between the two drugs. The objective of the present study was to compare single-dose pk profiles of the two drugs, following oral and intravenous administration, on the basis of equivalent molecular dosing, thus ruling out the quantitative factor. Five healthy volunteers and 14 dialysis patients (7 hemodialysis, 7 peritoneal dialysis) were included in the study. Comparing the pharmacokinetic parameters obtained from the drugs, it appeared that cyclosporine has an greater primary volume of distribution and clearance rate compared to tacrolimus. No other statistically significant differences were observed regarding bioavailability, absorption rate, or elimination rate. The only significant correlation between the pk values of the drugs was in primary volume of distribution. We conclude that even at equivalent molecular doses the pk of each drug remains unique and unpredictable. Furthermore our data fail to reveal significant correlations between the bioavailability, clearance, absorption, and elimination rates of the two drugs.

Dose-effect relations of loop- and thiazide-diuretics on calcium homeostasis: a randomized, double-blinded Latin-square multiple cross-over study in postmenopausal osteopenic women.

BACKGROUND: Thiazide diuretics (TDs) reduce whereas loop diuretics (LDs) increase urinary calcium. We studied the effects of different doses of a TD and LD on electrolytes, calcitropic hormones and biochemical bone markers. SUBJECTS AND METHODS: In a five-period crossover study, comparing four active doses with placebo, 40 postmenopausal women with osteopenia were treated with different doses of LD bumetanide (n = 20, 0.5-2.0 mg per day) or TD bendroflumethiazide (n = 20, 2.5-10 mg per day). Each treatment period lasted 1 week. RESULTS: Urinary calcium decreased dose-dependently in response to the bendroflumethiazide. The best hypocalciuric effect was achieved by 5 mg day-1 of bendroflumethiazide. Total plasma calcium levels increased, whereas ionised calcium at ambient pH-values decreased because of increased pH-values in response to the bendroflumethiazide. Plasma PTH levels did not change, whereas a slight dose-dependent increase occurred in plasma 1,25(OH)2D levels. As a marker of bone formation, plasma osteocalcin levels increased. Conversely, bumetanide dose-dependently increased renal calcium losses with a concomitant increase in plasma PTH and 1,25(OH)2D levels. Plasma osteocalcin levels increased and bone-specific alkaline phosphatase levels decreased dose-dependently. CONCLUSION: Whether a LD or TD is chosen as diuretic therapy affects calcium homeostasis. The effects of LDs are potentially harmful to bone. Further studies are needed to evaluate whether long-term treatment with LDs causes osteoporosis. Until then, we suggest using, if possible, a TD rather than a LD as diuretic therapy in order not to risk deleterious effects on bone metabolism.

Exocrine pancreatic secretion is stimulated in piglets fed fish oil compared with those fed coconut oil or lard.

An experiment was conducted to study the effect of feeding diets containing fat sources with different fatty acid composition (fish oil, coconut oil or lard, 10 g/100 g diet) on exocrine pancreatic secretion in piglets after weaning. A total of 16 barrows were weaned at 4 wk of age; 3 d later, they were surgically fitted with a catheter in the pancreatic duct for continuous collection of pancreatic juice. Collections of pancreatic juice were made every other day starting 4 d postsurgically. Piglets fed the fish oil diet secreted a significantly greater volume of pancreatic juice than piglets fed the coconut oil or lard diets. The output [U/(h. kg(0.75))] of lipase was higher in piglets fed fish oil than in piglets fed lard or coconut oil. The output of colipase was greater in piglets fed fish oil and coconut oil than in those fed lard. The dietary treatments did not affect the output of carboxylester hydrolase. The output of trypsin was significantly lower in piglets fed lard than in piglets fed fish oil or coconut oil diets and the output of carboxypeptidase B was greater in those fed the fish oil diet. Protein, chymotrypsin, carboxypeptidase A, elastase and amylase outputs did not differ among the dietary treatment groups. The apparent digestibilities of nutrients and energy were measured in feces and did not differ among groups. Thus, the greater output of lipase in fish oil-fed piglets did not result in a greater digestibility of fat in this diet.

The Danish PET/depression project: PET findings in patients with major depression.

BACKGROUND: It is hypothesized from previous positron emission tomography (PET) studies of patients with major depression that dysfunction of regions of the limbic system and the frontal lobes in close connection with the basal ganglia is involved in the pathophysiology of major depression. METHODS: By means of PET and 15O labelled radioactive water we determined an index of the neuronal activity by mapping the cerebral blood flow distribution of 42 unselected in-patients suffering from moderate to severe depression and 47 healthy controls controlling for age and gender. The PET maps were co-registered to magnetic resonance images of the anatomy of the brain. RESULTS: The functions-of-interest analysis revealed significant gender differences in cerebral blood flow and changes in the relative distribution of the blood with increasing age. The patients had increased activity of the hippocampus and the cerebellum compared to the healthy controls when corrected for these confounders and the influence of antidepressant medication. Furthermore, data in the Danish Psychiatric Central Register showed that the patients studied were representative of the population of depressed patients admitted to the hospital during the study period. CONCLUSION: Our main finding is increased blood flow to the hippocampus, even when controlling for a number of confounders. This is in accordance with a rapidly expanding literature suggesting an important role for this structure in major depression.

Activity of Toluene-degrading Pseudomonas putida in the early growth phase of a biofilm for waste gas treatment.

A biological trickling filter for treatment of toluene-containing waste gas was studied. The overall kinetics of the biofilm growth was followed in the early growth phase. A rapid initial colonization took place during the first three days. The biofilm thickness increased exponentially, whereas the incease of active biomass and polymers was linear. In order to investigate the toluene degradation, various toluene degraders from the multispecies biofilm were isolated, and a Pseudomonas putida was chosen as a representative of the toluene-degrading population. A specific rRNA oligonucleotide probe was used to follow the toluene-degrading P. putida in the multispecies biofilm in the filter by means of number and cellular rRNA content. P. putida appeared to detach from the biofilm during the first three days of growth, after which P. putida was found at a constant level of 10% of the active biomass in the biofilm. Based on the rRNA content, the in situ activity was estimated to be reduced to 20% of cells grown at maximum conditions in batch culture. The toluene degraded by P. putida was estimated to be a minor part (11%) of the overall toluene degradation.

Activity and three-dimensional distribution of toluene-degrading Pseudomonas putida in a multispecies biofilm assessed by quantitative in situ hybridization and scanning confocal laser microscopy.

As a representative member of the toluene-degrading population in a biofilter for waste gas treatment, Pseudomonas putida was investigated with a 16S rRNA targeting probe. The three-dimensional distribution of P. putida was visualized in the biofilm matrix by scanning confocal laser microscopy, demonstrating that P. putida was present throughout the biofilm. Acridine orange staining revealed a very heterogeneous structure of the fully hydrated biofilm, with cell-free channels extending from the surface into the biofilm. This indicated that toluene may penetrate to deeper layers of the biofilm, and consequently P. putida may be actively degrading toluene in all regions of the biofilm. Furthermore, measurements of growth rate-related parameters for P. putida showed reduced rRNA content and cell size (relative to that in a batch culture), indicating that the P. putida population was not degrading toluene at a maximal rate in the biofilm environment. Assuming that the rRNA content reflected the cellular activity, a lower toluene degradation rate for P. putida present in the biofilm could be estimated. This calculation indicated that P. putida was responsible for a significant part (65%) of the toluene degraded by the entire community.