Feasibility of unilateral hemilaminectomy utilizing a Williams retractor for the resection of intradural-extramedullary spinal neoplasms.

BACKGROUND: While open approaches have historically been used in the surgical treatment of intradural-extramedullary spine tumors, minimally-invasive surgical (MIS) techniques are frequently applied to minimize post-operative complications associated with open surgery. Tubular retractor systems in particular have been employed in combination with the unilateral hemilaminectomy (UHL) approach. Here we describe the use of a Williams retractor as a safe and effective minimally-invasive alternative to tubular retractor systems with similar post-operative outcomes. METHODS: We retrospectively reviewed a cohort of eight patients who underwent unilateral hemilaminectomy using a Williams retractor for the minimally-invasive resection of intradural-extramedullary neoplasms at a large tertiary academic center from 2017 to 2019. Patient demographics, pathologic specimens, radiographic studies, and intraoperative parameters were collected and analyzed. RESULTS: In our series, gross total resection was achieved in all cases. Average operative time was 158±40minutes, the mean estimated blood loss (EBL) was 44.4±30.4mL, and mean length of stay was three days. All patients reported symptomatic improvement at follow-up as reported by Visual Analog Scale scores. CONCLUSION: A Williams retractor yields similar outcomes with respect to post-operative pain, operative time, and EBL as it maintains the advantages of the UHL approach in the resection of intradural-extramedullary spine tumors while enhancing feasibility and providing significant cost savings.

Experimental capabilities of 0.4 PW, 1 shot/min Scarlet laser facility for high energy density science.

We report on the recently completed 400 TW upgrade to the Scarlet laser at The Ohio State University. Scarlet is a Ti:sapphire-based ultrashort pulse system that delivers >10 J in 30 fs pulses to a 2 µm full width at half-maximum focal spot, resulting in intensities exceeding 5×1021 W/cm2. The laser fires at a repetition rate of once per minute and is equipped with a suite of on-demand and on-shot diagnostics detailed here, allowing for rapid collection of experimental statistics. As part of the upgrade, the entire laser system has been redesigned to facilitate consistent, characterized high intensity data collection at high repetition rates. The design and functionality of the laser and target chambers are described along with initial data from commissioning experimental shots.

Microengineering Laser Plasma Interactions at Relativistic Intensities.

We report on the first successful proof-of-principle experiment to manipulate laser-matter interactions on microscales using highly ordered Si microwire arrays. The interaction of a high-contrast short-pulse laser with a flat target via periodic Si microwires yields a substantial enhancement in both the total and cutoff energies of the produced electron beam. The self-generated electric and magnetic fields behave as an electromagnetic lens that confines and guides electrons between the microwires as they acquire relativistic energies via direct laser acceleration.

Spherical quartz crystals investigated with synchrotron radiation.

The quality of x-ray spectra and images obtained from plasmas with spherically bent crystals depends in part on the crystal's x-ray diffraction across the entire crystal surface. We employ the energy selectivity and high intensity of synchrotron radiation to examine typical spherical crystals from alpha-quartz for their diffraction quality, in a perpendicular geometry that is particularly convenient to examine sagittal focusing. The crystal's local diffraction is not ideal: the most noticeable problems come from isolated regions that so far have failed to correlate with visible imperfections. Excluding diffraction from such problem spots has little effect on the focus beyond a decrease in background.

Resection of an obstructive neonatal cardiac myxoma of the infundibulum.

Myxoma, the most common primary cardiac tumor in adults, is rare in neonates. We describe a myxoma arising from the infundibulum of the right ventricle causing significant outflow tract obstruction in an otherwise normal newborn. Serial echocardiograms revealed an increasing gradient across the right ventricular outflow tract prompting surgery. The patient underwent successful excision of the myxoma with an uneventful recovery.

Association between socioeconomic status and adiposity in urban Cameroon.

BACKGROUND: As the relation between socioeconomic status (SES) and obesity may depend on the stage of development of a country, this relation is assessed in adults from urban Cameroon. METHODS: A sample comprising 1530 women and 1301 men aged 25 years and above, from 1897 households in the Biyem-Assi health area in the capital of Cameroon, Yaoundé, were interviewed about their household amenities, occupation, and education. Weight, height, and waist circumference were measured and subjects were classified as obese if their BMI>or=30 kg/m2 or overweight if BMI was between 25.0 and 29.9 kg/m2. Abdominal obesity was defined by a waist circumference>or=80 cm in women and>or=94 cm in men. RESULTS: Of the sample studied 33% of women and 30% of men were overweight (P<0.08), whereas 22% of women and 7% of men were obese (P<0.001). Abdominal obesity was present in 67% of women and 18% of men (P<0.001). After adjusting for age, leisure time physical activity, alcohol consumption, and tobacco smoking, the prevalence of overweight+obesity, obesity, and abdominal obesity increased with quartiles of household amenities in both genders and with occupational level in men. CONCLUSION: SES is positively associated with adiposity in urban Cameroon after adjusting for confounding factors.

Poststroke hyperglycemia: natural history and immediate management.

BACKGROUND AND PURPOSE: Poststroke hyperglycemia (PSH) is a frequent finding for which there is currently no evidence to justify routine treatment. The United Kingdom Glucose Insulin in Stroke Trial (GIST-UK) is the only trial of glucose modulation in acute stroke from which evidence can be derived for the immediate management of PSH. Using safety-monitoring data from the trial we aimed to describe the immediate recovery of PSH in treated and control patients, thus providing evidence for the use of glucose/potassium/insulin (GKI) infusions as a means of maintaining euglycemia. METHODS: GIST-UK is a multicenter randomized controlled trial of GKI or saline infusions in acute stroke patients presenting with mild to moderate hyperglycemia (admission plasma glucose, 6.0 to 17 mmol). We analyzed the capillary BM and plasma glucose values in the 2 treatment groups to describe the recovery of PSH and the effectiveness of the GIST treatment regimen in maintaining euglycemia. RESULTS: The majority of patients have only moderate PSH (mean plasma glucose, 8.37+/-SD 2.13). Without specific intervention, mean plasma glucose levels decline spontaneously. Treatment with the GIST GKI regimen rapidly achieved euglycemia at significantly lower levels than with saline hydration alone. Euglycemia was achieved with a median of 2 changes to the GKI regimen and a low risk of hypoglycemia. CONCLUSIONS: GKI infusions as described in the GIST trial are a safe and effective means of correcting PSH and maintaining euglycemia in the acute phase of stroke. The clinical benefits of routine management of hyperglycemia remain to be determined.

A Mycobacterium ulcerans toxin, mycolactone, causes apoptosis in guinea pig ulcers and tissue culture cells.

Mycobacterium ulcerans is the causative agent of Buruli ulcer, a tropical ulcerative skin disease. One of the most intriguing aspects of this disease is the presence of extensive tissue damage in the absence of an acute inflammatory response. We recently purified and characterized a macrolide toxin, mycolactone, from M. ulcerans. Injection of this molecule into guinea pig skin reproduced cell death and lack of acute inflammatory response similar to that seen following the injection of viable bacteria. We also showed that mycolactone causes a cytopathic effect on mouse fibroblast L929 cells that is characterized by cytoskeletal rearrangements and growth arrest within 48 h. However, these results could not account for the extensive cell death which occurs in Buruli ulcer. The results presented here demonstrate that L929 and J774 mouse macrophage cells die via apoptosis after 3 to 5 days of exposure to mycolactone. Treatment of cells with a pan-caspase inhibitor can inhibit mycolactone-induced apoptosis. We demonstrate that injection of mycolactone into guinea pig skin results in cell death via apoptosis and that the extent of apoptosis increases as the lesion progresses. These results may help to explain why tissue damage in Buruli ulcer is not accompanied by an acute inflammatory response.

The inhibitory action of Mycobacterium ulcerans soluble factor on monocyte/T cell cytokine production and NF-kappa B function.

Buruli ulcer is a chronic and progressive necrotizing ulcer for which there is no medical treatment. Historically, a soluble toxin (factor) derived from the causative Mycobacterium ulcerans was found to induce the massive necrosis of skin and s.c. tissue seen in this condition. However, the persistence of the disease is thought to be caused by a lack of any immune response. We therefore investigated whether the factor was related to immunosuppression. A protocol to partially purify the factor was developed, and its effects on immune competent cells were tested. The factor produced >95% inhibition of LPS-induced release of TNF and IL-10 from human monocytes and caused a loss of adherence of these cells without cell death. The factor also blocked the production of IL-2 from activated T lymphocytes. The factor had no effect on TNF-induced cytotoxicity, but abrogated TNF-induced NF-kappa B activation. Surprisingly, a synergy was observed between the factor and phorbol ester-directed NF-kappa B activation. The factor had no effect on IL-1- or LPS-induced NF-kappa B activity, indicating selective activity of the factor. The factor did not inhibit the degradation of I kappa B alpha induced by TNF, indicating that the target for its activity lies within an undefined part of the TNF signaling mechanism. The data indicate that the localized immunosuppression associated with Buruli ulcer relates to the activity of the released factor, and this may provide a target for future therapeutic strategies for this intractable disease.

Mycolactone: a polyketide toxin from Mycobacterium ulcerans required for virulence.

Mycobacterium ulcerans is the causative agent of Buruli ulcer, a severe human skin disease that occurs primarily in Africa and Australia. Infection with M. ulcerans results in persistent severe necrosis without an acute inflammatory response. The presence of histopathological changes distant from the site of infection suggested that pathogenesis might be toxin mediated. A polyketide-derived macrolide designated mycolactone was isolated that causes cytopathicity and cell cycle arrest in cultured L929 murine fibroblasts. Intradermal inoculation of purified toxin into guinea pigs produced a lesion similar to that of Buruli ulcer in humans. This toxin may represent one of a family of virulence factors associated with pathology in mycobacterial diseases such as leprosy and tuberculosis.

Partial purification and characterization of biological effects of a lipid toxin produced by Mycobacterium ulcerans.

Organisms in the genus Mycobacterium cause a variety of human diseases. One member of the genus, M. ulcerans, causes a necrotizing skin disease called Buruli ulcer. Buruli ulcer is unique among mycobacterial diseases in that the organisms at the site of infection are extracellular and there is little acute inflammatory response. Previous literature reported the presence of a toxin in the culture supernatant of M. ulcerans which causes a cytopathic effect on the mouse fibroblast cell line L929 in which the adherent cells round up and detach from the tissue culture plate. Here we report partial purification of a lipid toxin from the culture supernatant of M. ulcerans which is capable of causing the cytopathic effect on L929 cells. We also show that this cytopathic effect is a result of cytoskeletal rearrangement. The M. ulcerans toxin does not cause cell death but instead arrests cells in the G1 phase of the cell cycle.

Differential trafficking of live and dead Mycobacterium marinum organisms in macrophages.

We characterized the Mycobacterium marinum phagosome by using a variety of endocytic markers to follow the path of the bacteria through a mouse macrophage cell line. Using a laser confocal microscope, we found that the majority of viable M. marinum cells were in nonacidic vacuoles that did not colocalize with the vacuolar proton ATPase (V-ATPase), the calcium-independent mannose-6-phosphate receptor (CI-M6PR), or cathepsin D. In contrast, heat-killed organisms and latex beads were in acidic vacuoles which contained the V-ATPase, the CI-M6PR, and cathepsin D. A population of vesicles that contained live M. marinum labeled with the lysosomal glycoprotein LAMP-1, but the percentage of vacuoles that labeled was lower than for heat-killed organisms or latex beads. When testing live and heat-killed Mycobacterium tuberculosis, we found levels of colocalization with LAMP- and cathepsin D comparable to those for the M. marinum isolate. We conclude that M. marinum, like M. tuberculosis, can circumvent the host endocytic pathway and reside in an intracellular compartment which is not acidic and does not fuse with lysosomes. In addition, we describe a system for sampling a large population of intracellular organisms by using a laser confocal microscope.

The biosynthesis of cyclopropanated mycolic acids in Mycobacterium tuberculosis. Identification and functional analysis of CMAS-2.

The major mycolic acid produced by Mycobacterium tuberculosis contains two cis-cyclopropanes in the meromycolate chain. The gene whose product cyclopropanates the proximal double bond was cloned by homology to a putative cyclopropane synthase identified from the Mycobacterium leprae genome sequencing project. This gene, named cma2, was sequenced and found to be 52% identical to cma1 (which cyclopropanates the distal double bond) and 73% identical to the gene from M. leprae. Both cma genes were found to be restricted in distribution to pathogenic species of mycobacteria. Expression of cma2 in Mycobacterium smegmatis resulted in the cyclopropanation of the proximal double bond in the alpha 1 series of mycolic acids. Coexpression of both cyclopropane synthases resulted in cyclopropanation of both centers, producing a molecule structurally similar to the M. tuberculosis alpha-dicyclopropyl mycolates. Differential scanning calorimetry of purified cell walls and mycolic acids demonstrated that cyclopropanation of the proximal position raised the observed transition temperature by 3 degrees C. These results suggest that cyclopropanation contributes to the structural integrity of the cell wall complex.

Violence, solace, and ritual: a case study from island Southeast Asia.

Most headhunting traditions in island Southeast Asia link ritual violence to grief and mourning. Some of the more persuasive analyses of these practices pivot on notions of rage and catharsis, arguing that turbulent emotions motivate persons to take up cleansing acts of violence. This paper seeks a more complex understanding of how ritual may connect bereavement and violence through a look at case materials from highland Sulawesi (Indonesia). Ritual practices there suggest that the resolution of communal mourning is more significant than personal catharsis in motivating violence; that individual affect is refigured collectively as "political affect;" and that varied discursive forms, such as vows, songs, and noise mediate the ways in which people put grief behind them and resume their lives. Indeed, such discursive forms appear to be generative sites for violence and solace.

Differential regulation of transcription factor gene expression and phenotypic markers in developing sympathetic neurons.

We have examined the regulation of transcription factor gene expression and phenotypic markers in developing chick sympathetic neurons. Sympathetic progenitor cells first express the bHLH transcriptional regulator Cash-1 (a chicken achaete-scute homologue), followed by coordinate expression of Phox2, a paired homeodomain protein, and GATA-2, a zinc finger protein. SCG10, a pan-neuronal membrane protein, is first detected one stage later, followed by the catecholaminergic neurotransmitter enzyme tyrosine hydroxylase (TH). We have used these markers to ask two questions: (1) is their expression dependent upon inductive signals derived from the notochord or floor plate?; (2) does their sequential expression reflect a single linear pathway or multiple parallel pathways? Notochord ablation experiments indicate that the floor plate is essential for induction of GATA-2, Phox2 and TH, but not for that of Cash-1 and SCG10. Taken together these data suggest that the development of sympathetic neurons involves multiple transcriptional regulatory cascades: one, dependent upon notochord or floor plate-derived signals and involving Phox2 and GATA-2, is assigned to the expression of the neurotransmitter phenotype; the other, independent of such signals and involving Cash-1, is assigned to the expression of pan-neuronal properties. The parallel specification of different components of the terminal neuronal phenotype is likely to be a general feature of neuronal development.

GATA factor activity is required for the trophoblast-specific transcriptional regulation of the mouse placental lactogen I gene.

The molecular determinants governing tissue-specific gene expression in the placenta are at present only poorly defined, particularly with respect to the regulation of specific hormone genes whose products are vital to embryonic development and the maintenance of a nurturing maternal environment. In continuing our analysis of the trophoblast-specific expression of the mouse placental lactogen I gene, we now demonstrate that the transcription factors GATA-2 and GATA-3 regulate the activity of this gene promoter. These factors are expressed in placental trophoblast cells, with peak levels of the GATA-2, GATA-3 and placental lactogen I mRNAs each accumulating at midgestation. Analysis of a region of the placental lactogen I gene promoter, previously shown to be sufficient for directing trophoblast-specific transcription, revealed the presence of three consensus binding sites for GATA-2 or GATA-3. Both GATA-2 and GATA-3 bind to these sites in vitro and mutation of these sites results in a significant decrease in promoter activity as assayed by transient transfection into the choriocarcinoma-derived cell line Rcho-1, which expresses endogenous GATA-2 and GATA-3. Furthermore, overexpression of GATA factors in Rcho-1 cells stimulates transcription from a co-transfected placental lactogen I gene promoter. Most significantly, expression of GATA-2 or GATA-3 was found to induce transcription from this promoter in transfected non-trophoblast (fibroblast) cells. These data indicate that GATA factors are both limiting and required transcriptional regulatory molecules in placental trophoblasts, and that the tissue specificity of the placental lactogen I gene is determined, at least in part, by GATA-2 and/or GATA-3.

Embryonic expression and cloning of the murine GATA-3 gene.

We describe the embryonic expression pattern as well as the cloning and initial transcriptional regulatory analysis of the murine (m) GATA-3 gene. In situ hybridization shows that mGATA-3 mRNA accumulation is temporally and spatially regulated during early development: although found most abundantly in the placenta prior to 10 days of embryogenesis, mGATA-3 expression becomes restricted to specific cells within the embryonic central nervous system (in the mesencephalon, diencephalon, pons and inner ear) later in gestation. GATA-3 also shows a restricted expression pattern in the peripheral nervous system, including terminally differentiating cells in the cranial and sympathetic ganglia. In addition to this distinct pattern in the nervous system, mGATA-3 is also expressed in the embryonic kidney and the thymic rudiment, and further analysis showed that it is expressed throughout T lymphocyte differentiation. To begin to investigate how this complex gene expression pattern is elicited, cloning and transcriptional regulatory analyses of the mGATA-3 gene were initiated. At least two regulatory elements (one positive and one negative) appear to be required for appropriate tissue-restricted regulation after transfection of mGATA-3-directed reporter genes into cells that naturally express GATA-3 (T lymphocytes and neuroblastoma cells). Furthermore, this same region of the locus confers developmentally appropriate expression in transgenic mice, but only in a subset of the tissues that naturally express the gene.

Murine and human T-lymphocyte GATA-3 factors mediate transcription through a cis-regulatory element within the human T-cell receptor delta gene enhancer.

A family of transcriptional activators has recently been identified in chickens; these transcriptional activators recognize a common consensus motif (WGATAR) through a conserved C4 zinc finger DNA-binding domain. One of the members of this multigene family, cGATA-3, is most abundantly expressed in the T-lymphocyte cell lineage. Analysis of human and murine GATA-3 factors shows a striking degree of amino acid sequence identity and similar patterns of tissue specificity of expression in these three organisms. The murine and human factors are abundantly expressed in a variety of human and murine T-cell lines and can activate transcription through a tissue-specific GATA-binding site identified within the human T-cell receptor delta gene enhancer. We infer that the murine and human GATA-3 proteins play a central and highly conserved role in vertebrate T-cell-specific transcriptional regulation.