Countermovement Jump Performance with Increased Training Loads in Elite Female Rugby Athletes.

Countermovement jump (CMJ) performance is typically analyzed through single-point concentric-based variables (e. g., peak power or force and height). However, methodological approaches examining movement strategies may be more sensitive to neuromuscular fatigue. 12 elite female rugby sevens athletes undertook weekly CMJ testing throughout a 6-week training block involving progressively increased training loads. Athletes self-reported training load (TRIMP) and wellness daily. 22 CMJ variables were assessed, incorporating analyses of force, velocity, power and time measured during eccentric and concentric jump phases. Differences over time were examined using the magnitude of change (effect sizes; ES) compared to baseline. Pearson correlations examined relationships between CMJ variables, wellness and TRIMP. TRIMP displayed large increases (mean ES; weeks 2-6: 2.47). Wellness decreased in week 3 (-0.41), with small reductions following (weeks 4-6: -0.34). Flight time (weeks 3-6: -1.84), peak displacement (weeks 2-6: -2.24), time to peak force (weeks 3-6: 2.58), force at zero velocity (F@0V) (weeks 5-6: -1.28) displayed multiple changes indicative of diminished neuromuscular function. Wellness scores and max rate of force development (mean; r=0.32), F@0V (r=0.28) and flight time (r=0.34) displayed positive correlations. Intensified training decreased CMJ output and altered CMJ mechanics. Longitudinal neuromuscular fatigue monitoring of team-sport athletes appears improved through CMJ mechanics analysis.

High-magnification Faraday rotation imaging and analysis of X-pinch implosion dynamics.

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.

Optimization of switch diagnostics on the MAIZE linear transformer driver.

The MAIZE Linear Transformer Driver consists of 40 capacitor-switch-capacitor "bricks" connected in parallel. When these 40 bricks are charged to ±100-kV and then discharged synchronously, the MAIZE facility generates a 1-MA current pulse with a 100-ns rise time into a matched load impedance. Discharging each of the capacitors in a brick is carried out by the breakdown of a spark-gap switch, a process that results in the emission of light. Monitoring this output light with a fiber optic coupled to a photomultiplier tube (PMT) and an oscilloscope channel provides information on switch performance and timing jitter-whether a switch fired early, late, or in phase with the other switches. However, monitoring each switch with a dedicated detector-oscilloscope channel can be problematic for facilities where the number of switches to be monitored (e.g., 40 on MAIZE) greatly exceeds the number of detector-oscilloscope channels available. The technique of using fibers to monitor light emission from switches can be optimized by treating a PMT as a binary digit or bit and using a combinatorial encoding scheme, where each switch is monitored by a unique combination of fiber-PMT-oscilloscope channels simultaneously. By observing the unique combination of fiber-PMT-oscilloscope channels that are turned on, the prefiring or late-firing of a single switch on MAIZE can be identified by as few as six PMT-oscilloscope channels. The number of PMT-oscilloscope channels, N, required to monitor X switches can be calculated by 2N = X + 1, where the number "2" is selected because the PMT-oscilloscope acts as a bit. In this paper, we demonstrate the use of this diagnostic technique on MAIZE. We also present an analysis of how this technique could be scaled to monitor the tens of thousands of switches proposed for various next generation pulsed power facilities.

Evaluation of cerebrospinal fluid uPA, PAI-1, and soluble uPAR levels in HIV-infected patients.

To evaluate the potential role of the uPAR/uPA/PAI-1 system in HIV-induced blood-brain-barrier (BBB) disruption, CSF uPA-dependent plasminogen activation (PdPA) was analyzed by casein zymography, and CSF protein levels of all three molecules were measured by ELISA. CSF uPAR, but not uPA, PAI-1, or PdPA levels was significantly increased in neurologically compromised HIV+ patients. Only individual patients with severe AIDS dementia complex had increased levels of uPA (but not PAI-1) which fell upon initiation of antiretroviral therapy. The levels of all three molecules did not correlate with the CSF to serum albumin ratio suggesting not an important role in HIV-induced BBB disruption.

L-arginine-induced regional cerebral blood flow increase is abolished after transient focal cerebral ischemia in the rat.

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.

Contraversive eye deviation during deep brain stimulation of the globus pallidus internus.

Clinical signs help determine correct electrode positioning during stereotactic implantation for chronic high-frequency pallidal stimulation in Parkinson's diease (PD). The authors describe a patient who had marked, sustained, contraversive eye deviation caused by stimulation during pallidal surgery. The underlying mechanism is probably an excitation of fibers in the internal capsule by volume-conducted current spread. Such conjugate eye deviation is thus not necessarily an indication of incorrect electrode placement.

Human immunodeficiency virus type-1 Nef protein induces blood-brain barrier disruption in the rat: role of matrix metalloproteinase-9.

We recently showed that MMP-9 activity was detectable in the cerebrospinal fluid (CSF) of about half of neurologically symptomatic HIV-infected patients. Using an experimental animal model, we detected MMP-9 activity in CSF samples from rats that had been injected intracisternally with recombinant HIV-1 Nef protein, but not after injection of heat-treated Nef, gp120, gp160 or PBS. Nef also induced a breaching of the blood-brain barrier (BBB), which could be inhibited by pretreatment with the matrix metalloproteinase (MMP) inhibitor batimastat. In vitro Nef only slightly induced MMP-9 activity in freshly isolated human peripheral blood mononuclear cells and in the murine macrophage cell line RAW 264.7, but not in endothelial, neuronal or astroglial cell lines. Taken together, our findings indicate that HIV-1 Nef protein can induce BBB disruption in the rat - presumably via MMP induction.

Identification of a T cell chemotactic factor in the cerebrospinal fluid of HIV-1-infected individuals as interferon-gamma inducible protein 10.

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.

Increased levels of soluble Fas receptor and Fas ligand in the cerebrospinal fluid of HIV-infected patients.

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.

A proposed model for examining the interference phenomenon between concurrent aerobic and strength training.

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 tower 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.

Reproducibility of a laboratory based 20-km time trial evaluation in competitive cyclists using the Velotron Pro ergometer.

The purpose of this study was to evaluate the reliability of a 20-km cycling time trial using the Velotron cycle ergometer in competitive cyclists. Twenty male cyclists (V.O (2max) = 68.5 +/- 3.6 ml . kg (-1) . min (-1); peak power (P (peak)) = 469 +/- 33 W) participated in this study. Each subject performed a V.O (2max) test and 3 separate 20-km time trials (TT1, TT2, and TT3). Data from trials were compared using a one-way ANOVA. Coefficients of variation (CV) and 95 % confidence intervals (CI) were calculated between trials. Values are mean +/- SD unless otherwise noted. Performance time T (tot) (30.03 +/- 1.24, 30.12 +/- 1.21, and 30.14 +/- 1.21 min) and mean absolute power (P (mean)) (326 +/- 35, 323 +/- 35, 322 +/- 34 Watts) were not significantly different across TT1 - TT3. P (mean) was highly related between TT1 - TT2 (r = 0.96; p < 0.01) and TT2 - TT3 (r = 0.97; p < 0.01). A low CV was also demonstrated between trials for P (mean) (TT1 - TT2 = 2.1 %, CI = 1.6 % to 3.1 %; TT2 - TT3 = 1.9 %, CI = 1.4 % to 2.8 %). P (peak) and P (mean) were both correlated to T (tot) in TT1 with P (mean) accounting for most of the variance in T (tot) (R (2) = 0.993). These data show that performance in a 20-km time trial using the Velotron ergometer is highly reproducible in competitive cyclists. Furthermore, the CV variance demonstrated between trials is comparable to that expected during actual performance in elite athletes.

Evaluation of CSF glial fibrillary acidic protein (GFAP) as a putative marker for HIV-associated dementia.

BACKGROUND: The involvement of the central nervous system (CNS) is a prominent feature of infection with human immunodeficiency virus type-1 (HIV-1). One of the neuropathological hallmarks of HIV-1-associated dementia (HAD) is the proliferation of astrocytes (astrogliosis). The major structural protein of astrocytes is glial fibrillary acidic protein (GFAP) and its increased expression has been reported in disorders characterized by astrogliosis. PATIENTS AND METHODS: In order to determine whether CSF GFAP may be a putative marker for HAD, we measured CSF GFAP levels of HIV-infected patients with (n = 11) and without (n = 21) HAD, and, additionally, of HIV-infected patients with opportunistic CNS diseases (n = 13) and HIV negative control patients (n = 20) using an immuno flourescent sandwich immunoassay. RESULTS: CSF GFAP levels and the frequency of increased GFAP levels did not significantly differ between the three groups of HIV-infected patients. CONCLUSION: Our data suggest that CSF GFAP is not a sensitive laboratory marker for HAD.

Vascular endothelial growth factor (VEGF) is increased in serum, but not in cerebrospinal fluid in HIV associated CNS diseases.

Vascular endothelial growth factor (VEGF) is a potent angiogenic and mitogenic peptide, which also induces several mediators that may play a role in HIV induced CNS damage. VEGF levels were determined in cerebrospinal fluid (CSF) and serum samples from patients with (n = 8) and without (n = 19) directly HIV associated CNS disorders and HIV negative control patients (n = 18). VEGF serum but not CSF levels were significantly increased in HIV infected patients with (381.1 (78.9) pg/ml) HIV associated CNS diseases compared with those without (120.8 (13.1) pg/ml) and HIV negative control patients (133.1(14.8) pg/ml). Serum samples from patients with untreated HIV associated encephalopathy (HIVE, n = 3) contained the highest VEGF levels (583.9 (71.5) pg/ml). In two patients VEGF serum levels were reduced during antiretroviral therapy. However, regardless of effective viral suppression, patients with HIVE still had higher levels compared with HIV infected patients without HIVE. A relevant increase of serum VEGF was not observed in patients without HIVE though high HI viral load. We conclude that HIVE is associated with increased serum VEGF levels. Further studies are warranted to elucidate the role of VEGF in HIVE.

Pharmacologic interference with NF-kappaB activation attenuates central nervous system complications in experimental Pneumococcal meningitis.

This study assessed the effects of 2 different inhibitors of NF-kappaB activation on central nervous system complications and clinical symptoms in an advanced stage of experimental pneumococcal meningitis: the calpain inhibitor I N-acetyl-leucinyl-leucinyl-norleucinal (ALLN), which interferes with IkappaB proteolysis, and BAY 11-7085, which inhibits IkappaB phosphorylation. Pneumococcal meningitis was associated with an increase in NF-kappaB activity, as determined by immunohistochemistry and Western blot analysis of rat brains 24 h after infection. Treatment with ALLN or BAY 11-7085 improved the clinical scores of infected rats, compared with those of untreated infected rats. This beneficial effect was parallelled by a significant reduction of the increase in intracranial pressure, blood-brain barrier permeability (as measured by the Evans blue-extravasation technique), cerebrospinal fluid (CSF) pleocytosis, CSF interleukin-6 levels, and impairment of cerebrovascular CO(2) reactivity and autoregulation. Thus, pharmacologic interference with NF-kappaB activation might be a possible target for adjunctive therapy in bacterial meningitis.

Matrix metalloproteinases contribute to the blood-brain barrier disruption during bacterial meningitis.

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.

Presence of matrix metalloproteinase-9 activity in the cerebrospinal fluid of human immunodeficiency virus-infected patients.

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.

HIV type 1 Nef protein is a viral factor for leukocyte recruitment into the central nervous system.

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.