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An X-pinch load driven by an intense current pulse (> 100 kA in ∼100 ns) can result in the formation of a small radius, runaway compressional micro-pinch. A micro-pinch is characterized by a hot (>1 keV), current-driven (> 100 kA), high-density plasma column (near solid density) with a small neck diameter (1–10 µm), a short axial extent (< 1 mm), and a short duration (≲1 ns). With material pressures often well into the multi-Mbar regime, a micro-pinch plasma often radiates an intense, sub-ns burst of sub-keV to multi-keV x rays. A low-density coronal plasma immediately surrounding the dense plasma neck could potentially shunt current away from the neck and thus reduce the magnetic drive pressure applied to the neck. To study the current distribution in the coronal plasma, a Faraday rotation imaging diagnostic (1064 nm) capable of producing simultaneous high-magnification polarimetric and interferometric images has been developed for the MAIZE facility at the University of Michigan. Designed with a variable magnification (1–10×), this diagnostic achieves a spatial resolution of ∼35 µm, which is useful for resolving the ∼100-μm-scale coronal plasma immediately surrounding the dense core. This system has now been used on a reduced-output MAIZE (100–200 kA, 150 ns) to assess the radial distribution of drive current immediately surrounding the dense micro-pinch neck. The total current enclosed was found to increase as a function of radius, r, from a value of ≈ 50 ± 25 kA at r ≈ 140 µm (at the edge of the dense neck) to a maximal value of ≈ 150 ± 75 kA for r ≥ 225 µm. This corresponds to a peak magnetic drive pressure of ≈ 75 ± 50 kbar at r ≈ 225 µm. The limitations of these measurements are discussed in the paper. [ABSTRACT FROM AUTHOR]

A review of the current research on the interference phenomenon between concurrent aerobic and strength training indicates modest support for the model proposed in this article. However, it is clear that without a systematic approach to the investigation of the phenomenon there is lack of control and manipulation of the independent variables, which makes it difficult to test the validity of the model. To enhance the understanding of the interference phenomenon, it is important that researchers are precise and deliberate in their choice of training protocols. Clear definition of the specific training objectives for strength (muscle hypertrophy or neural adaptation) and aerobic power (maximal aerobic power or anaerobic threshold) are required. In addition, researchers should equate training volumes as much as possible for all groups. Care needs to be exercised to avoid overtraining individuals. There should be adequate recovery and regeneration between the concurrent training sessions as well as during the training cycle. The model should be initially tested by maintaining the same protocols throughout the duration of the study. However, it is becoming common practice to use a periodised approach in a training mesocycle in which there is a shift from high volume and moderate intensity training to lower volume and higher intensity. The model should be evaluated in the context of a periodised mesocycle provided the investigators are sensitive to the potential impact of the loading parameters on the interference phenomenon. It may be that the periodised approach is one way of maintaining the training stimulus and minimising the amount of interference. The effects of gender, training status, duration and frequency of training, and the mode of training need to be regarded as potential factors effecting the training response when investigating the interference phenomenon. Other experimental design factors such as unilateral limb training or training the upper body for one attribute and the lower body for another attribute, may help establish the validity of the model. [ABSTRACT FROM AUTHOR]

Reveals that pharmacologic interference with necrosis factor-kappaB activation attenuates central nervous system complications in experimental pneumococcal meningitis. Treatment with calpain inhibitor I N-acetyl-leucinyl-leucinyl-norleucinyl (ALLN) and BAY 11-7085; Reduction of increase of intracranial pressure, blood-brain barrier permeability, cerebrospinal fluid (CSF) pleocytosis and CSF interleukin-6 levels.

Presents a letter to the editor referencing articles and topics on a case of HIV-infected patient with chorea, published in previous issues.

Previous studies have shown improved shorter duration (∼1 h) performance with carbohydrate (CHO) mouth rinsing (WASH), especially in overnight fasted/non-fuelled subjects., Purpose: To determine the effect of WASH on cycling time trial (TT) performance and muscle activity (EMG) after 2 h of submaximal cycling while receiving CHO (FED)., Methods: In a double-blind, placebo-controlled crossover design, 10 well-trained males cyclists (V˙O2max: 65 mL·kg·min) completed two experimental trials. Each trial consisted of a standardized pretrial snack (2 h prior) followed by 120 min of steady-state (SS) cycling (∼60% V˙O2max) followed by an approximately 30-min TT, randomized as follows: 1) 30 g CHO·h during SS + WASH during TT (every 20% of TT) (FEDWASH); 2) 30 g CHO·h during SS + placebo (PLA) wash during TT (FEDPLA)., Results: Although FEDWASH was not significantly different than FEDPLA (P = 0.51), there was a 1.7% (90% confidence interval, +6.4% to -3.2%; ES, 0.21) decrease in TT time (35 s) for FEDWASH compared with FEDPLA, with qualitative probabilities of a 60% positive and 23% trivial outcome. For EMG, soleus showed significant increase, whereas medial gastrocnemius showed significant decrease in muscle recruitment from the beginning 20% TT segment to the last 20% only in the FEDPLA condition, which coincided with a slower (P = 0.01) last 20% of the TT in FEDPLA versus FEDWASH., Conclusions: Contrary to previous studies, this investigation utilized conditions of high ecological validity including a pretrial snack and CHO during SS. Significant changes in muscle recruitment and time over the last 20% of the TT, along with an average 1.7% improvement in TT time, suggest CHO mouth rinse helps maintain power output late in TT compared with placebo. Although marginal gains were achieved with a CHO mouth rinse (35 s), small performance effects can have significant outcomes in real-world competitions.

Purpose: To examine the reliability and magnitude of change after fatiguing exercise in the countermovement-jump (CMJ) test and determine its suitability for the assessment of fatigue-induced changes in neuromuscular (NM) function. A secondary aim was to examine the usefulness of a set of alternative CMJ variables (CMJ-ALT) related to CMJ mechanics., Methods: Eleven male college-level team-sport athletes performed 6 CMJ trials on 6 occasions. A total of 22 variables, 16 typical (CMJ-TYP) and 6 CMJ-ALT, were examined. CMJ reproducibility (coefficient of variation; CV) was examined on participants' first 3 visits. The next 3 visits (at 0, 24, and 72 h postexercise) followed a fatiguing high-intensity intermittent-exercise running protocol. Meaningful differences in CMJ performance were examined through effect sizes (ES) and comparisons to interday CV., Results: Most CMJ variables exhibited intraday (n = 20) and interday (n = 21) CVs of <10%. ESs ranging from trivial to moderate were observed in 18 variables at 0 h (immediately postfatigue). Mean power, peak velocity, flight time, force at zero velocity, and area under the force-velocity trace showed changes greater than the CV in most individuals. At 24 h, most variables displayed trends toward a return to baseline. At 72 h, small increases were observed in time-related CMJ variables, with mean changes also greater than the CV., Conclusions: The CMJ test appears a suitable athlete-monitoring method for NM-fatigue detection. However, the current approach (ie, CMJ-TYP) may overlook a number of key fatigue-related changes, and so practitioners are advised to also adopt variables that reflect the NM strategy used.

Many sports incorporate training at altitude as a key component of their athlete training plan. Furthermore, many sports are required to compete at high altitude venues. Exercise at high altitude provides unique challenges to the athlete and to the sport medicine clinician working with these athletes. These challenges include altitude illness, alterations in training intensity and performance, nutritional and hydration difficulties, and challenges related to the austerity of the environment. Furthermore, many of the strategies that are typically utilized by visitors to altitude may have implications from an anti-doping point of view.This position statement was commissioned and approved by the Canadian Academy of Sport and Exercise Medicine. The purpose of this statement was to provide an evidence-based, best practices summary to assist clinicians with the preparation and management of athletes and individuals travelling to altitude for both competition and training.

Seventy-nine cytokines, chemokines, and growth factors were measured by protein array analysis in the cerebrospinal fluid of patients with meningitis and controls. Several factors were found to be regulated, which have not been studied in the CNS before, e.g., macrophage inflammatory protein-1delta (CCL15) and neutrophil-activating peptide-2 (CXCL7). In pneumococcal meningitis, other new observations were an increase of macrophage migration inhibitory factor, monocyte chemoattractant protein-2 (CCL8), pulmonary and activation-regulated chemokine (CCL18), and macrophage inflammatory protein-3alpha (CCL20), and a sustained upregulation of several growth factors. In viral meningitis, new findings were an elevation of CCL8, thrombopoietin, and vascular endothelial growth factor.

Thrombosis of the deep venous system presenting with bilateral thalamic infarction or edema is a common finding, but unilateral venous thrombosis presenting with unilateral thalamic edema is extremely rare. We report a case of a patient with this unusual condition presenting with nonspecific clinical signs and symptoms. CT and MR imaging revealed a unilateral thalamostriate lesion. The imaging sign that was most helpful in establishing the diagnosis, however, was the MR finding of a thrombus in a single internal cerebral vein.

Fas (CD95) and Fas ligand (FasL, CD95L) have been implicated to be involved in the acute inflammatory response by attracting neutrophils and regulating their survival. Increased levels of soluble Fas and FasL are found in cerebrospinal fluid (CSF) samples of patients with bacterial meningitis but not in controls. Functional FasL (gld)- or Fas (lpr)-deficient mice were used to assess their role in the pathophysiology of pneumococcal meningitis. Induction of meningitis in wild-type (WT) mice caused an increase in CSF white blood cell (WBC) count, intracranial pressure (ICP), and vessel permeability, paralleled by a worse clinical status at 24 h. The inflammatory response was accompanied by elevated levels of IL-1beta, MMP-2, and MMP-9 in the brain. Neither gld- nor lpr-mice showed significant differences in the above-mentioned pneumococci-induced pathophysiological alterations. These results indicate that Fas and FasL are not essential in the regulation of the acute inflammatory response during pneumococcal meningitis.

The CX(3)C chemokine fractalkine is suggested to play an important role in inflammatory brain diseases, for example, because of its chemotactic properties. To investigate the release of soluble fractalkine in HIV-induced brain diseases fractalkine levels were determined in cerebrospinal fluid (CSF) and serum samples of HIV-infected patients with (n = 10) and without (n = 23) HIV-induced CNS complications, using semiquantitative Western blot analysis. Fractalkine CSF levels were significantly elevated (p < 0.05) in HIV-infected patients with CNS diseases compared with those without, and compared with HIV-negative controls (n = 23). Fractalkine serum concentrations did not differ between the two groups of HIV-infected patients, but were significantly elevated (p < 0.05) in HIV-infected patients with CNS complications compared with HIV-negative controls. Levels of fractalkine did not correlate with the CSF and serum HIV load and other CSF parameters. In one patient with HIV-associated dementia and myelopathy CSF fractalkine levels decreased on initiation of antiretroviral therapy and subsequent clinical improvement. In conclusion, intrathecal fractalkine release was observed in the majority of patients with HIV infection. The highest levels of soluble fractalkine were detected in CSF (and serum) samples of patients with HIV-induced CNS disorders. These results suggest a dysregulation of brain soluble fractalkine release during HIV infection.

Analyses of serum samples and blood cells have revealed a dysregulation of the Fas/Fas ligand (FasL) system during HIV infection, which may be related to disease progression. As Fas and FasL have been suggested to participate in brain injury in a variety of CNS disorders, the aim of this study was to determine (1) whether soluble Fas and FasL can be detected in cerebrospinal fluid (CSF) samples from HIV-infected patients, (2) whether levels of these molecules are related to disease progression, and (3) whether levels of sFasL are related to other laboratory findings. Soluble Fas was detected in 38 of 56 (68%) and soluble Fas ligand in 17 of 56 (30%) CSF samples from HIV-infected patients. CSF levels of both molecules correlated neither with the CSF-to-serum albumin ratio nor with corresponding serum concentrations. This finding suggests that they are at least in part produced intrathecally. Levels of both CSF sFas and sFasL correlated significantly and inversely with the blood CD4+ cell counts, suggesting that the intrathecal release of both molecules is increased during progression to advanced immunodeficiency.

Recombinant HIV-1 Nef protein, but not Tat, gp120, and gp160, provoked leukocyte recruitment into the CNS in a rat model. The strong reduction of bioactivity by heat treatment of Nef, and the blocking effect of the mAb 2H12, which recognizes the carboxy-terminal amino acid (aa) residues 171-190 (but not of mAb 3E6, an anti-Nef Ab of the same isotype, which maps the aa sequence 168-175, as well as a mixture of mAbs to CD4) provided evidence for the specificity of the observed Nef effects. Using a modified Boyden chamber technique, Nef exhibited chemotactic activity on mononuclear cells in vitro. Coadministration of the anti-Nef mAb 2H12, as well as treatment of Nef by heat inhibited Nef-induced chemotaxis. Besides soluble Nef, chemotaxis was also induced by a Nef-expressing human astrocytoma cell line, but not by control cells. These data suggest a direct chemotactic activity of soluble Nef. The detection of elevated levels of IL-6, TNF-alpha, and IFN-gamma in rat cerebrospinal fluid 6 h after intracisternal Nef injection hint at the additional involvement of indirect mechanisms in Nef-induced leukocyte migration into rat CNS. These data propose a mechanism by which HIV-1 Nef protein may be essential for AIDS neuropathogenesis, as a mediator of the recruitment of leukocytes that may serve as vehicles of the virus and perpetrators for disease through their production of neurotoxins.

Central nervous system (CNS) involvement is a prominent feature of human immunodeficiency virus (HIV-1) infection. Monocytes and CD4+ T cells traverse the blood brain barrier (BBB), and serve as vehicles for the virus and perpetrators for brain pathology by their production of neurotoxins. In the present study cerebrospinal fluid (CSF) samples from HIV-1-infected patients were analyzed for the presence of chemotactic factors. All 36 CSF samples from the patients were positive for the CXC chemokine interferon-gamma inducible protein (IP-10), which was not detected in CSF samples of 14 controls. The IP-10 concentrations were higher in HIV-1-infected patients with HIV-1 associated neurologic disorders than in those without neurological deficits. In contrast to IP-10, other chemotactic factors including the CC chemokines MCP-1, MIP-1alpha, MIP-1beta and RANTES and the cytokines IL-15 and IL-16 were either not detected or increased in only less than 30% of the patients. Unlike the CSF samples of controls, all CSF samples from HIV-1-infected patients induced chemotaxis of T cells activated with IL-2. The significance of IP-10 as a T cell chemotactic cytokine in HIV-1-infected CSF is shown by (1) the correlation of the IP-10 levels with the extent of T cell chemotaxis, (2) the neutralization of T cell chemotaxis by anti-IP-10 antibodies and (3) the correlation of the chemotactic response of CSF samples on activated T cells and the CSF white cell count in the patients. Our data provide evidence that IP-10 contributes to the accumulation of activated T cells in the CSF compartment in HIV-1-infected individuals.

In this study, we investigated the involvement of matrix metalloproteinases (MMPs) in the pathophysiology of bacterial meningitis. By using an enzyme immunoassay, high concentrations of MMP-9 were detected in the cerebrospinal fluid (CSF) of adult patients with bacterial meningitis but not in controls, and in patients with Guillain-Barré syndrome. Moreover, we observed significantly elevated concentrations of the tissue inhibitor of metalloproteinase-1 (TIMP-1) in the CSF of patients with bacterial meningitis, compared with controls. In a rat model of meningococcal meningitis, intracisternal injection of heat-killed meningococci caused a disruption of the blood-brain barrier (BBB), an increase in intracranial pressure, and CSF pleocytosis paralleled by the occurrence of MMP-9 activity in the CSF 6 hours after meningococcal challenge. The MMP inhibitor batimastat (BB-94) significantly reduced the BBB disruption and the increase in intracranial pressure irrespective of the time of batimastat administration (15 minutes before and 3 hours after meningococcal challenge) but failed to significantly reduce CSF white blood cell counts. In conclusion, our results suggest that MMPs are involved in the alterations of BBB permeability during experimental meningococcal meningitis.

To determine whether matrix metalloproteinase (MMP)-9 is a potential mediator involved in the frequently detected blood-brain barrier leakage in human immunodeficiency virus (HIV)-infected patients, zymography was used to detect MMP-9 activity in cerebrospinal fluid (CSF) samples of 80 HIV-infected patients and of 10 control patients. CSF MMP-9 activity was detected in 40% of HIV-infected patients (but not in controls) and was significantly more frequent in HIV-infected patients than in those without neurologic deficits (50% vs. 13.6%). The frequency of CSF MMP-9 activity did not significantly differ between neurologically symptomatic HIV-infected patients with or without opportunistic central nervous system disease (51.6% vs. 48.1%). Additionally, the presence of CSF MMP-9 activity in HIV-infected patients was associated with an increased CSF white blood cell count and an elevated CSF-to-serum albumin ratio, suggesting that it may play a role in blood-brain/CSF barrier leakage in HIV-infected patients.

We investigated the L-arginine-induced, regional cerebral blood flow (rCBF) enhancement after different durations of transient focal cerebral ischemia in the rat to determine if L-arginine increases rCBF after transient focal cerebral ischemia. Focal ischemia (5 minutes and 20 minutes) followed by 90 minutes of reperfusion was induced in a normotensive rat suture-model. Regional cerebral blood flow in both hemispheres was measured by laser-Doppler-flowmetry. Reactivity of rCBF to L-arginine (300 mg/kg) was measured 45 minutes after reperfusion, and hypercapnia 90 minutes after reperfusion. The effect of D-arginine and pretreatment with the nitric oxide (NO) synthase inhibitor N(omega)-nitro-L-arginine (L-NA) (10 mg/kg) was examined in additional groups. Hypercapnia and L-arginine increased rCBF in sham operated controls and on the nonischemic hemispheres. D-arginine did not. Twenty-minute long ischemia significantly reduced the response to L-arginine (control side: 115 +/- 5.9%; ischemic side: 107 +/- 6.1%, n = 7) and hypercapnia, 5 minutes of ischemia did not. N(omega)-nitro-L-arginine pretreatment partly restored the L-arginine-induced rCBF increase. Thus, rCBF increase caused by L-arginine in the reperfusion period was unaffected by 5 minutes of ischemia, but reduced by 20 minutes of ischemia. The restoration after pretreatment with L-NA may be caused by attenuated production of cytotoxic substances, e.g., NO and related compounds.