Bone and non-contractile soft tissue changes following open kinetic chain resistance training and testosterone treatment in spinal cord injury: an exploratory study.

Twenty men with spinal cord injury (SCI) were randomized into two 16-week intervention groups receiving testosterone treatment (TT) or TT combined with resistance training (TT + RT). TT + RT appears to hold the potential to reverse or slow down bone loss following SCI if provided over a longer period. INTRODUCTION: Persons with SCI experience bone loss below the level of injury. The combined effects of resistance training and TT on bone quality following SCI remain unknown. METHODS: Men with SCI were randomized into 16-week treatments receiving TT or TT + RT. Magnetic resonance imaging (MRI) of the right lower extremity before participation and post-intervention was used to visualize the proximal, middle, and distal femoral shaft, the quadriceps tendon, and the intermuscular fascia of the quadriceps. For the TT + RT group, MRI microarchitecture techniques were utilized to elucidate trabecular changes around the knee. Individual mixed models were used to estimate effect sizes. RESULTS: Twenty participants completed the pilot trial. A small effect for yellow marrow in the distal femur was indicated as increases following TT and decreases following TT + RT were observed. Another small effect was observed as the TT + RT group displayed greater increases in intermuscular fascia length than the TT arm. Distal femur trabecular changes for the TT + RT group were generally small in effect (decreased trabecular thickness variability, spacing, and spacing variability; increased network area). Medium effects were generally observed in the proximal tibia (increased plate width, trabecular thickness, and network area; decreased trabecular spacing and spacing variability). CONCLUSIONS: This pilot suggests longer TT + RT interventions may be a viable rehabilitation technique to combat bone loss following SCI. CLINICAL TRIAL REGISTRATION: Registered with clinicaltrials.gov : NCT01652040 (07/27/2012).

Lessons learned from a single institution's retrospective analysis of emergent cesarean delivery following external cephalic version with and without neuraxial anesthesia.

OBJECTIVES: To evaluate the risk of emergent cesarean delivery with the use of neuraxial anesthesia for external cephalic version in a single practice. BACKGROUND: Randomized trials have shown increased external cephalic version success when neuraxial anesthesia is used, without additional risk. We hypothesized that in our actual clinical practice, outside the confines of randomized trials, neuraxial anesthesia could be associated with an increased risk of emergent cesarean delivery. METHODS: This retrospective cohort study included all women who underwent external cephalic version at a single institution with and without neuraxial anesthesia. The primary outcome was the incidence of emergent cesarean delivery (defined as delivery within 4hours of version). Secondary outcomes were version success and ultimate mode of delivery. RESULTS: A total of 135 women underwent external cephalic version procedures; 58 with neuraxial anesthesia (43.0%) and 77 without (57.0%). Location of the procedure, tocolytic therapy, and gestational age were different between groups. An increased rate of emergent cesarean delivery was found in procedures with neuraxial anesthesia compared to procedures without (5/58 (8.6%) compared to 0/77 (0.0%); 95% CI for difference, 1.4 to 15.8%; P=0.013). CONCLUSION: In this single hospital's practice, patients who may be at higher risk of complications and have a lesser likelihood of success were provided NA for ECV. As a result, the use of neuraxial anesthesia for external cephalic version was associated with a higher rate of emergent cesarean delivery. Obstetric and anesthetic practices should evaluate their patient selection and procedure protocol for external cephalic version under neuraxial anesthesia.

Tomographic physical phantom of the newborn child with real-time dosimetry I. Methods and techniques for construction.

A tomographic phantom representing a newborn female patient was constructed using tissue-equivalent materials previously developed at the University of Florida. This phantom was constructed using contoured images from an actual patient data set, a whole-body computed tomography of a newborn cadaver previously described by Nipper et al. [Phys. Med. Biol. 47, 3143-1364 (2002)]. Four types of material are incorporated in the phantom: soft tissue, bone tissue, lung tissue, and air. The phantom was constructed on a slice-by-slice basis with a z-axis resolution of 5 mm, channels for dosimeters (thermoluminescent dosimeter (TLD), metal-oxide-semiconductor field-effect transistor, or gated fiber-optic-coupled dosimeter (GFOC)) were machined into slices prior to assembly, and the slices were then fixed together to form the complete phantom. The phantom will be used in conjunction with an incorporated dosimetry system to calculate individual organ and effective doses delivered to newborn patients during various diagnostic procedures, including, but not limited to, projection radiography and computed tomography. Included in this paper are images detailing the construction process, and images of the completed phantom.

Enzootic Babesia microti in Maine.

Human babesiosis in the northeastern United States caused by Babesia microti (Apicomplexa: Piroplasmida) is mainly reported from coastal New England sites, where deer ticks (Ixodes dammini) are common. However, the piroplasm has been detected in microtine rodents elsewhere in association with I. angustus or other nidicolous ticks, suggesting that the agent is widely distributed but zoonotically significant only where a human-biting "bridge" vector is present. To determine whether this piroplasm may be enzootic in areas where I. dammini is absent, we surveyed small mammals collected from 2 sites in Maine, where I. angustus or I. muris is common but I. dammini is not. Of 43 chipmunks, voles, deer mice, and shrews examined, 3 (6.9, 95% confidence interval 0 to 14.5) were parasitemic, as determined by blood smear or polymerase chain reaction targeting a piroplasm-specific portion of the 18S ribosomal DNA gene. Phylogenetic analysis of the sequenced amplification products demonstrates the presence of 2 forms of B. microti. We conclude that B. microti may be enzootic in the absence of I. dammini but that human risk relates to dense infestations of this human-biting tick.

CD40 regulates the processing of NF-kappaB2 p100 to p52.

The nf-kb2 gene encodes the cytoplasmic NF-kappaB inhibitory protein p100 from which the active p52 NF-kappaB subunit is derived by proteasome-mediated proteolysis. Ligands which stimulate p100 processing to p52 have not been defined. Here, ligation of CD40 on transfected 293 cells is shown to trigger p52 production by stimulating p100 ubiquitylation and subsequent proteasome-mediated proteolysis. CD40-mediated p52 accumulation is dependent on de novo protein synthesis and triggers p52 translocation into the nucleus to generate active NF-kappaB dimers. Endogenous CD40 ligation on primary murine splenic B cells also stimulates p100 processing, which results in the delayed nuclear translocation of p52-RelB dimers. In both 293 cells and primary splenic B cells, the ability of CD40 to trigger p100 processing requires functional NF-kappaB-inducing kinase (NIK). In contrast, NIK activity is not required for CD40 to stimulate the degradation of IkappaBalpha in either cell type. The regulation of p100 processing by CD40 is likely to be important for the transcriptional regulation of CD40 target genes in adaptive immune responses.

Systemic treatment with anti-CD40 antibody stimulates Langerhans cell migration from the skin.

Epidermal Langerhans cells (LCs) play a pivotal role in the initiation of cutaneous immune responses. The maturation of LCs and their migration from the skin to the T cell areas of draining lymph nodes are essential for the delivery and presentation of antigen to naïve T cells. CD40, which acts as a costimulatory molecule, is present on LCs and the basal layer of keratinocytes in the skin. We show here that systemic treatment of mice with anti-CD40 antibody stimulates the migration of LCs out of the epidermis with a 70% reduction in LC numbers after 7 days, although changes in LC morphology are detectable as early as day 3. LC numbers in the epidermis returned to 90% of normal by day 21. As well as morphological changes, LC showed up-regulated levels of Class II and ICAM-1, with only minimal changes in CD86 expression 3 days following anti-CD40 treatment. Despite increased levels of Class II and ICAM-1, epidermal LC isolated from anti-CD40 treated mice were poor stimulators of a unidirectional allogeneic mixed leucocyte reaction (MLR), as were epidermal LC isolated from control mice. These results indicate that CD40 stimulation is an effective signal for LC migration, distinct from maturation of immunostimulatory function in the epidermis, which is not altered. These observations may have important implications for the mechanism of action of agonistic anti-CD40 antibodies, which have been used as an adjuvant in models of infection and experimental tumours and the primary immunodeficiency Hyper IgM syndrome caused by deficiency of CD40 ligand.

Chaos and stability of the solar system.

Over the last two decades, there has come about a recognition that chaotic dynamics is pervasive in the solar system. We now understand that the orbits of small members of the solar system-asteroids, comets, and interplanetary dust-are chaotic and undergo large changes on geological time scales. Are the major planets' orbits also chaotic? The answer is not straightforward, and the subtleties have prompted new questions.

Vav is required for cyclin D2 induction and proliferation of mouse B lymphocytes activated via the antigen Receptor.

B lymphocytes from mice null for the Rho-family guanine-nucleotide exchange factor, Vav, are defective in their ability to proliferate in response to BCR cross-linking, but are able to proliferate normally in response to LPS. In addition, they have a depletion of CD5(+) (B1) lymphocytes and defective IgG class switching. This phenotype is reminiscent of that observed in mice null for the cell cycle regulatory protein, cyclin D2. We demonstrate here that the inability of vav(-/-) B cells to proliferate in response to BCR ligation is due to an inability to induce cyclin D2. In addition, we show that the proliferative defect of these cells occurs after the cells have entered early G1 phase. Analyses of potential down-stream signaling intermediates revealed differential activation of the stress-activated MAP kinases in the absence of Vav, normal activation of the ERK, MAPK, and phosphatidylinositol 3-kinase pathways, and defective intracellular calcium mobilization. We further demonstrate that intracellular calcium homeostasis is required for cyclin D2 induction, implicating a possible link with the defective calcium response of vav(-/-) B cells and their inability to induce cyclin D2.

Discovery of 12 satellites of Saturn exhibiting orbital clustering.

The giant planets in the Solar System each have two groups of satellites. The regular satellites move along nearly circular orbits in the planet's orbital plane, revolving about it in the same sense as the planet spins. In contrast, the so-called irregular satellites are generally smaller in size and are characterized by large orbits with significant eccentricity, inclination or both. The differences in their characteristics suggest that the regular and irregular satellites formed by different mechanisms: the regular satellites are believed to have formed in an accretion disk around the planet, like a miniature Solar System, whereas the irregulars are generally thought to be captured planetesimals. Here we report the discovery of 12 irregular satellites of Saturn, along with the determinations of their orbits. These orbits, along with the orbits of irregular satellites of Jupiter and Uranus, fall into groups on the basis of their orbital inclinations. We interpret this result as indicating that most of the irregular moons are collisional remnants of larger satellites that were fragmented after capture, rather than being captured independently.

The role of chaotic resonances in the Solar System.

Our understanding of the Solar System has been revolutionized over the past decade by the finding that the orbits of the planets are inherently chaotic. In extreme cases, chaotic motions can change the relative positions of the planets around stars, and even eject a planet from a system. Moreover, the spin axis of a planet-Earth's spin axis regulates our seasons-may evolve chaotically, with adverse effects on the climates of otherwise biologically interesting planets. Some of the recently discovered extrasolar planetary systems contain multiple planets, and it is likely that some of these are chaotic as well.

Laparoscopic-assisted renal biopsy: an alternative to open approach.

An open renal biopsy frequently is performed when the conventional percutaneous approach is contraindicated. Although many of the surgical procedures, previously performed by a traditional open technique, are now successfully accomplished by laparoscopic technique, there remains a paucity of reports on laparoscopic kidney biopsy. We describe the use of laparoscopic technique in performing native kidney biopsy in three patients and review the potential safety and accuracy of this approach. To date, laparoscopic-assisted renal biopsy has been reported in six patients. The average length of stay in our small series was 1.3 days, and there were no major or catastrophic complications. Adequate numbers of glomeruli for confirmation of microscopic diagnosis were obtained in all cases. The review of literature, in addition to our encouraging preliminary results of a small group of patients, shows a possible role of laparoscopic-assisted renal biopsy in place of an open renal biopsy.

Attempt to control ticks (Acari: Ixodidae) on deer on an isolated island using ivermectin-treated corn.

We report an attempt by an offshore island community to control the vector tick of Lyme disease by providing ivermectin-treated corn to an isolated herd of free-ranging white-tailed deer, Odocoileus virginianus Zimmerman. Medicated corn was supplied in troughs within the island village and from automatic feeders at remote sites during 5 consecutive fall and spring adult tick questing seasons. Acaricide consumption was monitored by assaying its presence in fresh deer pellets and its concentration in deer sera. Its effectiveness was evaluated by recording the number of adult ticks collected from the hides of deer, the number of females becoming sufficiently engorged to oviposit, and the success of subsequent oviposition and eclosion. Entomologic risk was monitored by collecting immature ticks from hosts and adult ticks from vegetation. Estimates based on a subsequent deer reduction program indicated that up to twice as many deer had been present during the project as originally presumed. For this and other reasons related to deer behavior, target levels of serum ivermectin were achieved in a minority of deer. Nevertheless, > 90% control of female tick infestation, subsequent oviposition, and larval eclosion was obtained in those 8 of 16 sampled deer with serum ivermectin levels of > or = 15 ng/ml. In addition, the ratio of females to males, the numbers of females engorging > 10 mg body weight, and the numbers of those eventually hatching, were all significantly less among ticks from island deer in comparison with ticks from untreated deer. No consistent changes in the numbers of ticks found on immature-stage hosts or removed from vegetation were noted within 3 yr of the cessation of treatment.

Anti-CD40 antibody enhances responses to polysaccharide without mimicking T cell help.

Protection against infection with encapsulated bacteria is mediated by IgG antibodies against the capsular polysaccharides. Production of such antibodies is impaired during infancy, when susceptibility to bacterial meningitis is greatest. Recent studies have proposed the use of anti-CD40 antibody to increase responsivenesses to polysaccharide antigens. We show here that the IgG response to a model polysaccharide antigen is greatly increased, but retains thymus-independent characteristics--switching continues to be mainly to IgG3 and neither germinal centers nor memory B cells are formed. Furthermore, anti-CD40 causes striking splenomegaly in mice, which is accompanied by dramatic cellular redistribution and proliferation of dendritic cells, macrophages, T cells and endothelium, as well as B cells. These findings raise the possibility that the anti-CD40 effect is due mainly to increased activity of accessory cells that affect plasmablast growth and differentiation rather than mimicry of T cell help.

Interaction of B cells with activated T cells reduces the threshold for CD40-mediated B cell activation.

CD154-CD40 interactions are of central importance for the induction of antibody responses to T-dependent antigens. Since most anti-CD40 mAb are only weak B cell mitogens, it is believed that under physiological conditions, signals through CD40 synergize with those from other receptors on B cells to induce B cell activation. We show here that the interaction of either normal B cells, or those from CBA/N (xid) mice, with CD3-activated primary T cells in whole spleen cell cultures markedly reduces the threshold for B cell activation via CD40. Hence, these pre-activated cells undergo vigorous proliferation when stimulated with either optimal or suboptimal concentrations of weakly mitogenic anti-CD40 mAb, or with soluble CD40 ligand. Blocking experiments indicate that the establishment of this priming effect requires stimulation via CD40 itself, plus T cell-derived IL-2. In support of this concept, only CD3/CD28-pre-activated, but not CD3-pre-activated T cells induce this effect, unless the co-cultures of B cells with the latter T cells are supplemented with IL-2. Although B cells activated in this fashion do express higher levels of CD40 than naive cells, we believe that this is insufficient to explain the observed dramatic effects on their proliferative capacity. Rather we propose that T cell-dependent B cell activation induces fundamental changes in the signalling machinery invoked by ligation of CD40. It is likely that this amplification loop could play an important role during the initiation of antibody responses to T-dependent antigens, when activated CD4 T cells only express low levels of CD154.