477 research outputs found
Management of Obstructive Hydrocephalus Associated with Pineal Region Cysts and Tumors and Its Implication in Long-Term Outcome
BACKGROUND: Different treatment options have been proposed for obstructive hydrocephalus associated with pineal lesions. We discuss the obstructive hydrocephalus management associated with pineal region tumors and cysts in Helsinki Neurosurgery. METHODS: In this article, hydrocephalus treatment by tumor-cyst removal (n = 40), shunt surgery (n = 25), and endoscopic ventriculostomies (n = 3) is evaluated in 68 patients with obstructive hydrocephalus among 136 patients with pineal region tumor and cyst. Multivariate statistical analysis was followed by univariate and multivariate regression models of last functional status, last tumor-free imaging, and disease-specific mortality of the study population. RESULTS: Preoperative hydrocephalus was linked to higher World Health Organization tumor grades, poor functional status, higher mortality, and incomplete resection of pineal region cysts and tumors. Preoperative hydrocephalus remained a predictor of poor last functional status after multivariate regression. Pineal lesion removal with the posterior third ventricle opening as primary hydrocephalus treatment resulted in better last functional status, fewer postoperative shunts, fewer hydrocephalus related procedures, and fewer postoperative infections than in the shunt-treatment group. Multivariate regression analysis linked higher World Health Organization tumor & nbsp;grade, poor immediate functional status, postoperative complications, and incomplete surgical resection as independent predictors of disease mortality in patients with hydrocephalus. Same variables (except immediate modified Rankin Scale score) and higher number of shunt surgeries became independent predictors of poor last functional status at multivariate analysis. Incomplete resection was the only independent predictor of tumor-free magnetic resonance imaging at the last evaluation. CONCLUSIONS: Direct removal of pineal lesions with the opening of the posterior third ventricle could represent effective and reliable management of the associated obstructive hydrocephalus. Further research is required to generalize our inferences.Peer reviewe
Carbon Dioxide Inhalation Induces Dose-Dependent and Age-Related Negative Affectivity
BACKGROUND: Carbon dioxide inhalation is known to induce an emotion similar to spontaneous panic in Panic Disorder patients. The affective response to carbon dioxide in healthy subjects was not clearly characterized yet. METHODOLOGY/PRINCIPAL FINDINGS: Sixty-four healthy subjects underwent a double inhalation of four mixtures containing respectively 0, 9, 17.5 and 35% CO(2) in compressed air, following a double blind, cross-over, randomized design. Affective responses were assessed according to DSM IV criteria for panic, using an Electronic Visual Analogue Scale and the Panic Symptom List. It was demonstrated that carbon dioxide challenges induced a dose dependent negative affect (p<0.0001). This affect was semantically identical to the DSM IV definition of panic. Older individuals were subjectively less sensitive to Carbon Dioxide (p<0.05). CONCLUSIONS/SIGNIFICANCE: CO(2) induced affectivity may lay on a continuum with pathological panic attacks. Consistent with earlier suggestions that panic is a false biological alarm, the affective response to CO(2) may be part of a protective system triggered by suffocation and acute metabolic distress
ORIGIN: Metal Creation and Evolution from the Cosmic Dawn
ORIGIN is a proposal for the M3 mission call of ESA aimed at the study of metal creation from the epoch of cosmic dawn. Using high-spectral resolution in the soft X-ray band, ORIGIN will be able to identify the physical conditions of all abundant elements between C and Ni to red-shifts of z=10, and beyond. The mission will answer questions such as: When were the first metals created? How does the cosmic metal content evolve? Where do most of the metals reside in the Universe? What is the role of metals in structure formation and evolution? To reach out to the early Universe ORIGIN will use Gamma-Ray Bursts (GRBs) to study their local environments in their host galaxies. This requires the capability to slew the satellite in less than a minute to the GRB location. By studying the chemical composition and properties of clusters of galaxies we can extend the range of exploration to lower redshifts (z approx. 0.2). For this task we need a high-resolution spectral imaging instrument with a large field of view. Using the same instrument, we can also study the so far only partially detected baryons in the Warm-Hot Intergalactic Medium (WHIM). The less dense part of the WHIM will be studied using absorption lines at low redshift in the spectra for GRBs. The ORIGIN mission includes a Transient Event Detector (coded mask with a sensitivity of 0.4 photon/sq cm/s in 10 s in the 5-150 keV band) to identify and localize 2000 GRBs over a five year mission, of which approx.65 GRBs have a redshift >7. The Cryogenic Imaging Spectrometer, with a spectral resolution of 2.5 eV, a field of view of 30 arcmin and large effective area below 1 keV has the sensitivity to study clusters up to a significant fraction of the virial radius and to map the denser parts of the WHIM (factor 30 higher than achievable with current instruments). The payload is complemented by a Burst InfraRed Telescope to enable onboard red-shift determination of GRBs (hence securing proper follow up of high-z bursts) and also probes the mildly ionized state of the gas. Fast repointing is achieved by a dedicated Controlled Momentum Gyro and a low background is achieved by the selected low Earth orbit
Localization of an accessory helicase at the replisome is critical in sustaining efficient genome duplication
Genome duplication requires accessory helicases to displace proteins ahead of advancing replication forks. Escherichia coli contains three helicases, Rep, UvrD and DinG, that might promote replication of protein-bound DNA. One of these helicases, Rep, also interacts with the replicative helicase DnaB. We demonstrate that Rep is the only putative accessory helicase whose absence results in an increased chromosome duplication time. We show also that the interaction between Rep and DnaB is required for Rep to maintain rapid genome duplication. Furthermore, this Rep–DnaB interaction is critical in minimizing the need for both recombinational processing of blocked replication forks and replisome reassembly, indicating that colocalization of Rep and DnaB minimizes stalling and subsequent inactivation of replication forks. These data indicate that E. coli contains only one helicase that acts as an accessory motor at the fork in wild-type cells, that such an activity is critical for the maintenance of rapid genome duplication and that colocalization with the replisome is crucial for this function. Given that the only other characterized accessory motor, Saccharomyces cerevisiae Rrm3p, associates physically with the replisome, our demonstration of the functional importance of such an association indicates that colocalization may be a conserved feature of accessory replicative motors
Blunted endogenous opioid release following an oral amphetamine challenge in pathological gamblers
Pathological gambling is a psychiatric disorder and the first recognized behavioral addiction, with similarities to substance use disorders but without the confounding effects of drug-related brain changes. Pathophysiology within the opioid receptor system is increasingly recognized in substance dependence, with higher mu-opioid receptor (MOR) availability reported in alcohol, cocaine and opiate addiction. Impulsivity, a risk factor across the addictions, has also been found to be associated with higher MOR availability. The aim of this study was to characterize baseline MOR availability and endogenous opioid release in pathological gamblers (PG) using [(11)C]carfentanil PET with an oral amphetamine challenge. Fourteen PG and 15 healthy volunteers (HV) underwent two [(11)C]carfentanil PET scans, before and after an oral administration of 0.5 mg/kg of d-amphetamine. The change in [(11)C]carfentanil binding between baseline and post-amphetamine scans (ΔBPND) was assessed in 10 regions of interest (ROI). MOR availability did not differ between PG and HV groups. As seen previously, oral amphetamine challenge led to significant reductions in [(11)C]carfentanil BPND in 8/10 ROI in HV. PG demonstrated significant blunting of opioid release compared with HV. PG also showed blunted amphetamine-induced euphoria and alertness compared with HV. Exploratory analysis revealed that impulsivity positively correlated with caudate baseline BPND in PG only. This study provides the first evidence of blunted endogenous opioid release in PG. Our findings are consistent with growing evidence that dysregulation of endogenous opioids may have an important role in the pathophysiology of addictions
Inter- and intrachromosomal asynchrony of cell division cycle events in root meristem cells of Allium cepa: possible connection with gradient of cyclin B-like proteins
Alternate treatments of Allium cepa root meristems with hydroxyurea (HU) and caffeine give rise to extremely large and highly elongated cells with atypical images of mitotic divisions, including internuclear asynchrony and an unknown type of interchromosomal asynchrony observed during metaphase-to-anaphase transition. Another type of asynchrony that cannot depend solely on the increased length of cells was observed following long-term incubation of roots with HU. This kind of treatment revealed both cell nuclei entering premature mitosis and, for the first time, an uncommon form of mitotic abnormality manifested in a gradual condensation of chromatin (spanning from interphase to prometaphase). Immunocytochemical study of polykaryotic cells using anti-β tubulin antibodies revealed severe perturbations in the microtubular organization of preprophase bands. Quantitative immunofluorescence measurements of the control cells indicate that the level of cyclin B-like proteins reaches the maximum at the G2 to metaphase transition and then becomes reduced during later stages of mitosis. After long-term incubation with low doses of HU, the amount of cyclin B-like proteins considerably increases, and a significant number of elongated cells show gradients of these proteins spread along successive regions of the perinuclear cytoplasm. It is suggested that there may be a direct link between the effects of HU-mediated deceleration of S- and G2-phases and an enhanced concentration of cyclin B-like proteins. In consequence, the activation of cyclin B-CDK complexes gives rise to an abnormal pattern of premature mitotic chromosome condensation with biphasic nuclear structures having one part of chromatin decondensed, and the other part condensed
Effects of tryptophan depletion and tryptophan loading on the affective response to high-dose CO2 challenge in healthy volunteers
It has been reported that in panic disorder (PD), tryptophan depletion enhances the vulnerability to experimentally induced panic, while the administration of serotonin precursors blunts the response to challenges. Using a high-dose carbon dioxide (CO2) challenge, we aimed to investigate the effects of acute tryptophan depletion (ATD) and acute tryptophan loading (ATL) on CO2-induced panic response in healthy volunteers. Eighteen healthy volunteers participated in a randomized, double-blind placebo-controlled study. Each subject received ATD, ATL, and a balanced condition (BAL) in separate days, and a double-breath 35% CO2 inhalation 4.5 h after treatment. Tryptophan (Trp) manipulations were obtained adding 0 g (ATD), 1.21 g (BAL), and 5.15 g (ATL) of l-tryptophan to a protein mixture lacking Trp. Assessments consisted of a visual analogue scale for affect (VAAS) and panic symptom list. A separate analysis on a sample of 55 subjects with a separate-group design has also been performed to study the relationship between plasma amino acid levels and subjective response to CO2. CO2-induced subjective distress and breathlessness were significantly lower after ATD compared to BAL and ATL (p <0.05). In the separate-group analysis, Delta VAAS scores were positively correlated to the ratio Trp:I LNAA pound after treatment (r = 0.39; p <0.05). The present results are in line with preclinical data indicating a role for the serotonergic system in promoting the aversive respiratory sensations to hypercapnic stimuli (Richerson, Nat Rev Neurosci 5(6):449-461, 2004). The differences observed in our study, compared to previous findings in PD patients, might depend on an altered serotonergic modulatory function in patients compared to healthy subjects
EURECA: European-Japanese microcalorimeter array
The EURECA project aims to demonstrate technological readiness of a micro-calorimeter array for application in future X-ray astronomy missions, like Constellation-X, EDGE, and XEUS. The prototype instrument consists of a 5 × 5 pixel array of TES-based micro-calorimeters read out by two SQUID-amplifier channels using frequency-domain-multiplexing (FDM) with digital base-band feedback. The detector array is cooled by a cryogen-free cryostat consisting of a pulse tube cooler and a two stage ADR. Initial tests of the system at the PTB beam line of the BESSY synchrotron showed stable performance and an X-ray energy resolution of 1.5 eV at 250 eV for read-out of one TES-pixel only. Next step is deployment of FDM to read-out the full array. Full performance demonstration is expected end 2008.This work was financially supported by the Dutch Organization for Scientific Research
(NWO).Peer Reviewe
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Hospital Readmissions Among Persons With Human Immunodeficiency Virus in the United States and Canada, 2005–2018: A Collaboration of Cohort Studies
BackgroundHospital readmission trends for persons with human immunodeficiency virus (PWH) in North America in the context of policy changes, improved antiretroviral therapy (ART), and aging are not well-known. We examined readmissions during 2005-2018 among adult PWH in NA-ACCORD.MethodsLinear risk regression estimated calendar trends in 30-day readmissions, adjusted for demographics, CD4 count, AIDS history, virologic suppression (<400 copies/mL), and cohort.ResultsWe examined 20 189 hospitalizations among 8823 PWH (73% cisgender men, 38% White, 38% Black). PWH hospitalized in 2018 versus 2005 had higher median age (54 vs 44 years), CD4 count (469 vs 274 cells/μL), and virologic suppression (83% vs 49%). Unadjusted 30-day readmissions decreased from 20.1% (95% confidence interval [CI], 17.9%-22.3%) in 2005 to 16.3% (95% CI, 14.1%-18.5%) in 2018. Absolute annual trends were -0.34% (95% CI, -.48% to -.19%) in unadjusted and -0.19% (95% CI, -.35% to -.02%) in adjusted analyses. By index hospitalization reason, there were significant adjusted decreases only for cardiovascular and psychiatric hospitalizations. Readmission reason was most frequently in the same diagnostic category as the index hospitalization.ConclusionsReadmissions decreased over 2005-2018 but remained higher than the general population's. Significant decreases after adjusting for CD4 count and virologic suppression suggest that factors alongside improved ART contributed to lower readmissions. Efforts are needed to further prevent readmissions in PWH
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