Longitudinal decline in pulmonary diffusing capacity among nitrate fertilizer workers.

BACKGROUND: This study is part of a 3-year follow-up of lung function among nitrate fertilizer production workers. AIMS: To study the possible adverse effects of occupational exposure to aerosols and gases on pulmonary diffusing capacity. METHODS: A longitudinal study of a cohort of fertilizer workers who performed single-breath carbon monoxide diffusing capacity (DLco) tests and spirometry in 2007 and 2010. The workers completed a questionnaire on respiratory symptoms and smoking habits. Exposure to mineral dust, acid aerosols and inorganic gases was measured. The overall median inhalable and thoracic aerosol mass concentrations were 1.1mg/m(3) (min-max: <0.93-45) and 0.21mg/m(3) (min-max: <0.085-11), respectively. RESULTS: There were 308 participants in 2007 with 168 returning subjects in 2010. Overall, we found a statistically significant decline in the DLco of 0.068 mmol/min/kPa/year, adjusted for gender, age, height, weight, smoking status and doctor-diagnosed asthma during the 3-year follow-up (P < 0.01). The change in DLco did not vary significantly between the various job groups. Subjects with respiratory symptoms did not show a larger decline in DLco than those without symptoms. CONCLUSIONS: This study indicates a larger than expected decline in the DLco of fertilizer workers during a 3-year follow-up. However, the decline was not related to specific exposures at work, or to possible covariates of exposure.

Evaluating the properties of the coefficient of multiple correlation (CMC) for kinematic gait data.

When assessing reliability of three dimensional gait analysis, the coefficient of multiple correlation (CMC), a measure of similarity of waveforms, is frequently used. Several shortcomings of the method have been reported. It is strongly related to the range of motion (ROM); it is supposed to take values from 0 to 1, but is known to obtain complex values and break down. Removing offset before calculations appears to make it insensitive to apparent differences in gait. In the present work we use stochastic simulations to demonstrate why all of this happens, and the consequences thereof. We also demonstrate other, lesser-known, issues with the method, such as the strong dependency on number of subjects and test situations. The results are demonstrated on real data from an inter-rater repeatability study. We conclude that the CMC in its current form is generally unsuitable as a tool for assessing reliability in kinematic gait data.

Photoplethysmographic and pulse pressure variations during abdominal surgery.

BACKGROUND: Respiratory variations in pulse pressure (ΔPP) predict fluid responsiveness during mechanical ventilation. Variations in pulse oximetry plethysmography amplitude (ΔPOP) are proposed as a non-invasive alternative. Large variations in ΔPOP and poor agreement between ΔPP and ΔPOP are found in intensive care unit patients. General anaesthesia is suggested to reduce variability of ΔPOP and improve agreement between the variables. We evaluated the variability of the agreement between and the diagnostic values of ΔPP and ΔPOP during ongoing open abdominal surgery. The variability of diagnostic methods in specific clinical conditions is important, as this reflects the stability over time during which clinical decisions are made. METHODS: Observational study during open abdominal surgery in general anaesthesia. ΔPP and ΔPOP were calculated semi-automatically from recording periods of approximately 5 min both before and after fluid challenges. Fluid responsiveness was evaluated by changes in stroke volume (oesophageal Doppler) after 250 ml colloid. RESULTS: Thirty-four fluid challenges were performed in 25 patients. Variance both within registration periods and between patients were significantly larger for ΔPOP than for ΔPP (54.1% vs. 22.1% and 69.6% vs. 22.6%, respectively, both P < 0.001). Limits of agreement with a regression-based correction were ± 13.9%. Areas under receiver operating characteristics curves for fluid responsiveness were 0.67 for ΔPP and 0.72 for ΔPOP. CONCLUSIONS: Analysis of raw signals during open abdominal surgery documents that the variance of ΔPOP is larger than of ΔPP, with wide limits of agreement between ΔPP and ΔPOP. The diagnostic values of ΔPP and ΔPOP are relatively poor.

Cytoprotective effects of growth factors: BDNF more potent than GDNF in an organotypic culture model of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by a preferential loss of dopaminergic (DAergic) neurons of the substantia nigra pars compacta (SNpc). Both glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) play key roles in maintaining the DAergic phenotype and exert a cytoprotective effect on these neurons in vivo and in vitro. However, controversy still exists regarding the relative potency of the two factors and the extent to which they act synergistically. In this study, we used a refined version of organotypic cultures as a model for PD. The neurotoxin 6-hydroxydopamine (6-OHDA) was applied unilaterally in slices of rat mesencephalon, allowing for internal controls and enabling a precise comparison between the two sides of the midbrain. We evaluated the cytoprotective and regenerative effects of BDNF, GDNF and the combination of these in terms of surviving tyrosine hydroxylase positive (TH+) cells and TH mRNA expression. Pre-, co-, or post-treatment with neurotrophic factors clearly protects DAergic neurons from cell death. Cell survival is particularly pronounced in cultures pre-treated with BDNF and is not further increased when BDNF is applied in combination with GDNF in equimolar dose. On the lesion side, surviving TH+ cells exposed to neurotrophic factors showed extensive sprouting, and BDNF treatment resulted in a two-fold increase in TH mRNA. Such effects were not seen in the absence of toxin exposure. Thus, we observed that BDNF induced an upregulation of the DAergic phenotype, which suggest a cytoprotective and regenerative effect.

A twelve-year longitudinal study of hearing thresholds among professional divers.

In this prospective study over twelve years, we have studied 30 young professional divers. The aim of the study was to see if changes in hearing thresholds were related to cumulative diving exposure. The study started at the beginning of the divers' education to become professional divers. Over the follow-up period the divers performed air-dives to shallow sea levels with a median number of 477 dives (range: 40-4458). The examination was performed by measuring air conduction thresholds in a sound treated booth. During follow-up, a significant reduction in auditory function was found at 0.25, 0.5, 2, 3 and 6 kHz for the right ear and 3, 4 and 6 kHz for the left ear. A reduction in hearing function associated with diving was found at 4 and 8 kHz (p < 0.01) both ears combined. Hearing impairment among this group of professional divers, with possible noise exposure, shows that hearing impairment is associated with their profession.

Protein interacting with C kinase 1 (PICK1) and GluR2 are associated with presynaptic plasma membrane and vesicles in hippocampal excitatory synapses.

AMPA receptors have been identified in different populations of presynaptic terminals and found to be involved in the modulation of neurotransmitter release. The mechanisms that govern the expression of presynaptic AMPA receptors are not known. One possibility is that pre- and postsynaptic AMPA receptors are regulated according to the same principles. To address this hypothesis we investigated whether protein interacting with C kinase 1 (PICK1), known to interact with AMPA receptors postsynaptically, also is expressed presynaptically, together with AMPA receptors. Subfractionation and high-resolution immunogold analyses of the rat hippocampus revealed that GluR2 and PICK1 are enriched postsynaptically, but also in presynaptic membrane compartments, including the active zone and vesicular membranes. PICK1 and GluR2 are associated with the same vesicles, which are immunopositive also for synaptophysin and vesicle-associated membrane protein 2. Based on what is known about the function of PICK1 postsynaptically, the present data suggest that PICK1 is involved in the regulation of presynaptic AMPA receptor trafficking and in determining the size of the AMPA receptor pool that modulates presynaptic glutamate release.

Neuronal enriched endosomal protein of 21 kDa colocalizes with glutamate receptor subunit GLUR2/3 at the postsynaptic membrane.

Functional evidence suggests that neuronal enriched endosomal protein of 21 kDa (NEEP21) takes part in facilitating transport of AMPA receptors (AMPAR) in the synapse. To explore the anatomical basis for a role in this synaptic trafficking, we investigated the ultrastructural localization of NEEP21 in rodent brain. Using immunogold electron microscopy, we show that NEEP21 is colocalized with the AMPAR subunits GluR2/3 in postsynaptic spines. Quantitative analysis of gold particle distribution along an axis perpendicular to the postsynaptic specialization indicated that NEEP21 occurs in the postsynaptic membrane but also in the interior of the spines. NEEP21 positive endosomes/multivesicular bodies were found throughout cell bodies and dendrites. In light microscopical preparations, the NEEP21 antibody produced a labeling pattern in the neocortex, hippocampus and cerebellum that mimicked that of GluR2/3 and not that of GluR1 or 4. Our findings are consistent with a role for NEEP21 in facilitating vesicular transport of GluR2 between intracellular compartments and the postsynaptic plasma membrane.

Subcellular localization of the glutamate transporters GLAST and GLT at the neuromuscular junction in rodents.

The vertebrate neuromuscular junction (NMJ) is known to be a cholinergic synapse at which acetylcholine (ACh) is released from the presynaptic terminal to act on postsynaptic nicotinic ACh receptors. There is now growing evidence that glutamate, which is the main excitatory transmitter in the CNS and at invertebrate NMJs, may have a signaling function together with ACh also at the vertebrate NMJ. In the CNS, the extracellular concentration of glutamate is kept at a subtoxic level by Na(+)-driven high-affinity glutamate transporters located in plasma membranes of astrocytes and neurons. The glutamate transporters are also pivotal for shaping glutamate receptor responses at synapses. In order to throw further light on the potential role of glutamate as a cotransmitter at the NMJ we used high-resolution immunocytochemical methods to investigate the localization of the plasma membrane glutamate transporters GLAST (glutamate aspartate transporter) and GLT (glutamate transporter 1) in rat and mice NMJ regions. Confocal laser-scanning immunocytochemistry showed that GLT is restricted to the NMJ in rat and mouse skeletal muscle. Lack of labeling signal in knock-out mice confirmed that the immunoreactivity observed at the NMJ was specific for GLT. GLAST was also localized at the NMJ in rat but not detected in mouse NMJ (while abundant in mouse brain). Post-embedding electron microscopic immunocytochemistry and quantitative analyses in rat showed that GLAST and GLT are enriched in the junctional folds of the postsynaptic membrane at the NMJ. GLT was relatively higher in the slow-twitch muscle soleus than in the fast-twitch muscle extensor digitorum longus, whereas GLAST was relatively higher in extensor digitorum longus than in soleus. The findings show--together with previous demonstration of vesicular glutamate, a vesicular glutamate transporter and glutamate receptors--that mammalian NMJs contain the machinery required for synaptic release and action of glutamate. This indicates a signaling role for glutamate at the normal NMJ and provides a basis for the ability of denervated muscle to be reinnervated by glutamatergic axons from the CNS.

Creatine supplementation improves sprint performance in male sprinters.

The object of this study was to evaluate the effect of creatine (Cr) supplementation in well trained male sprinters. The study was performed as a single blind test on 18 sprinters at a local competition level. During the last two years a substantial part of their training had consisted of a series of maximal sprints with short rest periods to improve their fatigue resistance. The participants consumed either 20 g Cr+20 g glucose per day (Cr group, n=9) or 40 g glucose per day (placebo group, n=9), divided into 4 equal dosages. The effect of Cr on sprint performance was evaluated in two tests, 1 x 100 m sprint and an intermittent 6x60 m sprint. Cr supplementation increased the 100 m sprint velocity (11.68+/-0.27 s vs 11.59+/-0.31 s) and reduced the total time of 6 intermittent 60 m sprints (45.63+/-1.11 s vs 45.12+/-1.1 s), whereas no changes were observed in the placebo group. The sprint velocity was significantly increased in 5 out of 6 intermittent 60 m sprints. Venous blood was drawn 5 min after finishing the final intermittent 60 m run. Plasma lactate, Cr and serum creatinine (Crn) were all increased in the Cr group compared to presupplementation values; no changes were observed in the placebo group. The improved sprint performance suggests an increased availability of energy substrate for performing work, possibly as a result of increased skeletal muscle creatine phosphate (PCr).