In patients with ischemic stroke, DWI lesions can occasionally be reversed by reperfusion therapy. This study aimed to ascertain the relationship between ADC levels and DWI reversal in patients with ...acute ischemic stroke who underwent recanalization treatment.
We conducted a retrospective cohort study in patients with acute ischemic stroke who underwent endovascular mechanical thrombectomy with successful recanalization between April 2017 and March 2021. DWI reversal was assessed through follow-up MR imaging approximately 24 hours after treatment.
In total, 118 patients were included. DWI reversal was confirmed in 42 patients. The ADC level in patients with reversal was significantly higher than that in patients without reversal. Eighty-three percent of patients with DWI reversal areas had mean ADC levels of ≥520 × 10
mm
/s, and 71% of patients without DWI reversal areas had mean ADC levels of <520 × 10
mm
/s. The mean ADC threshold was 520 × 10
mm
/s with a sensitivity and specificity of 71% and 83%, respectively. In multivariate analysis, the mean ADC level (OR, 1.023; 95% CI, 1.013-1.033;
< .0001) was independently associated with DWI reversal. Patients with DWI reversal areas had earlier neurologic improvement (NIHSS at 7 days) than patients without reversal areas (
< .0001).
In acute ischemic stroke, the ADC value is independently associated with DWI reversal. Lesions with a mean ADC of ≥520 × 10
mm
/s are salvageable by mechanical thrombectomy, and DWI reversal areas regain neurologic function. The ADC value is easily assessed and is a useful tool to predict viable lesions.
MDMA (Ecstasy) is an illicit drug used by young adults at hot, crowed "rave" parties, yet the data on potential health hazards of its abuse remain controversial. Here, we examined the effect of MDMA ...on temperature homeostasis in male rats under standard laboratory conditions and under conditions that simulate drug use in humans. We chronically implanted thermocouple microsensors in the nucleus accumbens (a brain reward area), temporal muscle, and facial skin to measure temperature continuously from freely moving rats. While focusing on brain hyperthermia, temperature monitoring from the two peripheral locations allowed us to evaluate the physiological mechanisms (i.e., intracerebral heat production and heat loss via skin surfaces) that underlie MDMA-induced brain temperature responses. Our data confirm previous reports on high individual variability and relatively weak brain hyperthermic effects of MDMA under standard control conditions (quiet rest, 22-23°C), but demonstrate dramatic enhancements of drug-induced brain hyperthermia during social interaction (exposure to male conspecific) and in warm environments (29°C). Importantly, we identified peripheral vasoconstriction as a critical mechanism underlying the activity- and state-dependent potentiation of MDMA-induced brain hyperthermia. Through this mechanism, which prevents proper heat dissipation to the external environment, MDMA at a moderate nontoxic dose (9 mg/kg or ~1/5 of LD50 in rats) can cause fatal hyperthermia under environmental conditions commonly encountered by humans. Our results demonstrate that doses of MDMA that are nontoxic under cool, quiet conditions can become highly dangerous under conditions that mimic recreational use of MDMA at rave parties or other hot, crowded venues.
Synthetic exendin-4 (EX4, exenatide), is a GLP-1 receptor agonist used clinically to treat glycemia in Type-2 diabetes mellitus. EX4 also promotes weight loss and alters food reward-seeking behaviors ...in part due to activation of GLP-1 receptors in the mesolimbic dopamine system. Evidence suggests that GLP-1 receptor activity can directly attenuate cue-induced reward seeking. Here, we tested the effects of EX4 (0.6, 1.2, and 2.4 μg/kg, i.p.) on incentive cue (IC) responding, using a task where rats emit a nosepoke response during an intermittent reward-predictive IC to obtain a sucrose reward. EX4 dose-dependently attenuated responding to ICs and increased the latencies to respond to the IC and enter the sucrose reward cup. Moreover, EX4 dose-dependently decreased the total number of active port nosepokes for every cue presented. There was no effect of EX4 on the number of reward cup entries per reward earned, a related reward-seeking metric with similar locomotor demand. There was a dose-dependent interaction between the EX4 dose and session time on the responding to ICs and nosepoke response latency. The interaction indicated that effects of EX4 at the beginning and end of the session differed by the dose of EX4, suggesting dose-dependent pharmacokinetic effects. EX4 had no effect on free sucrose consumption behavior (i.e., total volume consumed, bout size, number of bouts) within the range of total sucrose volumes obtainable during the IC task (~3.5 ml). However, when rats were given unrestricted access for 1 h, where rats obtained much larger total volumes of sucrose (~30 ml), we observed some dose-dependent EX4 effects on drinking behavior, including decreases in total volume consumed. Together, these findings suggest that activation of the GLP-1 receptor modulates the incentive properties of cues attributed with motivational significance.
New therapeutic modalities are needed for ovarian cancer, the most lethal gynecologic malignancy. Recent clinical trials have demonstrated the impressive therapeutic potential of adoptive therapy ...using chimeric antigen receptor (CAR)-redirected T cells to target hematological cancers, and emerging studies suggest a similar impact may be achieved for solid cancers. We sought determine whether genetically-modified T cells targeting the CE7-epitope of L1-CAM, a cell adhesion molecule aberrantly expressed in several cancers, have promise as an immunotherapy for ovarian cancer, first demonstrating that L1-CAM was highly over-expressed on a panel of ovarian cancer cell lines, primary ovarian tumor tissue specimens, and ascites-derived primary cancer cells. Human central memory derived T cells (TCM) were then genetically modified to express an anti-L1-CAM CAR (CE7R), which directed effector function upon tumor antigen stimulation as assessed by in vitro cytokine secretion and cytotoxicity assays. We also found that CE7R+ T cells were able to target primary ovarian cancer cells. Intraperitoneal (i.p.) administration of CE7R+ TCM induced a significant regression of i.p. established SK-OV-3 xenograft tumors in mice, inhibited ascites formation, and conferred a significant survival advantage compared with control-treated animals. Taken together, these studies indicate that adoptive transfer of L1-CAM-specific CE7R+ T cells may offer a novel and effective immunotherapy strategy for advanced ovarian cancer.
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Flowing gases of hydrocarbon molecules were irradiated by tightly focused ns and fs laser, and the products were captured in hexane solution. In the case of ns laser irradiation, short polyynes up to ...C12H2 were produced efficiently from all the hydrocarbons, propane, hexane, octane, benzene, and toluene. The yields vary significantly among the products from different target molecules, extending beyond the effects of difference in the vapor pressures. With an aid of the visible emission spectra of the focused spot, polyyne forming reaction is discussed. In the case of fs laser irradiation of hexane, polyynes were produced efficiently much more than the ns-laser case, whereas for the toluene target, polyynes were not produced. Such a variation in the polyyne yield suggests there would be more suitable molecules for formation of polyynes, or any other carbon-rich materials, by gas-phase laser irradiation method.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
1 Ernest Gallo Clinic and Research Center, University of California, San Francisco, Emeryville 94608
2 Graduate Program in Neuroscience, University of California, San Francisco 94143
3 Departments of ...Neurology and Physiology, and Wheeler Center for the Neurobiology of Addiction, University of California, San Francisco, California 94143
Submitted 9 July 2003;
accepted in final form 20 November 2003
The nucleus accumbens (NAc) has long been thought of as a limbic-motor interface. Despite behavioral and anatomical evidence in favor of this idea, little is known about how NAc neurons encode information about motivationally relevant environmental cues and use this information to affect motor action. We therefore investigated the firing of these neurons during the performance of a discriminative stimulus (DS) task using simultaneous multiple single-unit recordings in rats. In this task, two stimuli are randomly presented to the animal: a DS, which signals the availability of a sucrose reward contingent on an operant response, and a similar but nonrewarded stimulus (NS). Subpopulations of NAc neurons increased or decreased their firing in association with several distinct components of the task. In this paper, we investigate cue- and operant-responsive neurons. Neurons excited and inhibited by cues showed larger firing changes in response to the DS than the NS and larger changes when the animal made an operant response to the cue than when the animal failed to respond. Excitations during operant responding were not modulated by the information contained by the cue, whereas inhibitions during operant responding were somewhat larger if the operant response occurred during the DS and somewhat smaller if they occurred in the absence of a cue. These results are consistent with the hypothesis that the firing of subpopulations of NAc neurons encode both the predictive value of environmental stimuli and the specific motor behaviors required to respond to them.
Address for reprint requests and other correspondence: S. Nicola, Ernest Gallo Clinic and Research Center, University of California, San Francisco, 5858 Horton St., Ste. 200, Emeryville, CA 94608 (E-mail: nicola{at}phy.ucsf.edu ).
High‐speed data transfer and high‐performance imaging can be realized by using radio‐waves in high‐frequency bands, such as millimeter‐waves and THz‐waves, where wide frequency bands are available. ...However, the cell size would be smaller than a few hundred meters, due to large free space propagation loss and large atmospheric attenuation. Thus, many base stations, which are connected by networks, are required to offer nationwide or global network services by such high‐frequency radio‐bands. The networks would be constructed by various transmission media including optical fibers and fixed wireless links, where many media converters are required. This paper reviews various technologies for seamless bridges between radio and optical links. For the time being, congestion of radio spectrum in THz bands is not significant. However, if we look at the history of radio‐wave technologies, spectral congestion has been high even in newly developed high frequency bands. In active radio services in millimeter‐wave or THz‐wave bands, interference mitigation with passive services such as radio astronomy and Earth observation satellites is an important issue, as of now. This paper describes research trends of THz‐wave technologies from the point of view of a figure of merit defined by a product of the carrier frequency and spectral efficiency, to discuss the significance of spectral efficiency enhancement in the high‐frequency region. Analysis of power consumption of short‐distance radio systems is also shown to discuss expected performance of THz‐wave links.
Key Points
Seamless networks consisting of high‐speed wireless and wired links can offer nationwide or global high‐performance radio services
Multimode radio‐over‐fiber can be used for short‐distance waveform transfer in future mobile networks
Interference mitigation is an important issue even in THz bands
High‐speed wireless links can offer low‐power consumption data transfer
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
High-grade serous ovarian cancers (HGSCs) display a high degree of complex genetic alterations. In this study, we identified germline and somatic genetic alterations in HGSC and their association ...with relapse-free and overall survival. Using a targeted capture of 557 genes involved in DNA damage response and PI3K/AKT/mTOR pathways, we conducted next-generation sequencing of DNA from matched blood and tumor tissue from 71 HGSC participants. In addition, we performed the OncoScan assay on tumor DNA from 61 participants to examine somatic copy number alterations (SCNA).
Approximately one-third of tumors had loss-of-function (LOF) germline (18/71, 25.4%) or somatic (7/71, 9.9%) variants in the DNA homologous recombination repair pathway genes BRCA1, BRCA2, CHEK2, MRE11A, BLM, and PALB2. LOF germline variants also were identified in other Fanconi anemia genes and in MAPK and PI3K/AKT/mTOR pathway genes. Most tumors harbored somatic TP53 variants (65/71, 91.5%). Using the OncoScan assay on tumor DNA from 61 participants, we identified focal homozygous deletions in BRCA1, BRCA2, MAP2K4, PTEN, RB1, SLX4, STK11, CREBBP, and NF1. In total, 38% (27/71) of HGSC patients harbored pathogenic variants in DNA homologous recombination repair genes. For patients with multiple tissues from the primary debulking or from multiple surgeries, the somatic mutations were maintained with few newly acquired point mutations suggesting that tumor evolution was not through somatic mutations. There was a significant association of LOF variants in homologous recombination repair pathway genes and high-amplitude somatic copy number alterations. Using GISTIC analysis, we identified NOTCH3, ZNF536, and PIK3R2 in these regions that were significantly associated with an increase in cancer recurrence and a reduction in overall survival.
From 71 patients with HGCS, we performed targeted germline and tumor sequencing and provided a comprehensive analysis of these 557 genes. We identified germline and somatic genetic alterations including somatic copy number alterations and analyzed their associations with relapse-free and overall survival. This single-site long-term follow-up study provides additional information on genetic alterations related to occurrence and outcome of HGSC. Our findings suggest that targeted treatments based on both variant and SCNA profile potentially could improve relapse-free and overall survival.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Rat intravenous self-administration is a widely-used animal model in the study of substance use disorders. Rats are tethered to a drug delivery system usually through a port or button that interfaces ...the drug delivery system with a chronic indwelling jugular vein catheter. These buttons can be purchased commercially but are costly, presenting a significant economic barrier for many researchers. Many researchers manufacture buttons in-house from a combination of individual custom made and commercially available components, resulting in large variation in terms of how the animals are handled and the longevity of catheter patency. We have developed a jugular catheter button that uses a split septum port to provide snap-on entry of a blunt cannula allowing for quick and easy attachment of the i.v. tubing. The port is constructed from commercially available split septum ports, surgical mesh and small metal cannula. The system is “needleless” which decreases the risk of infection and improves safety. The split-septum buttons are easily sterilized in-house adding to the reliability and decreases in the risk of infection. We have used this easily constructed, and inexpensive button for i.v. self-administration experiments in which 80 % of the rats maintained patency for a minimum of 35 days.•Inexpensive method to construct a self-administration backport button.•Utilizes inexpensive components already found in a research laboratory or commercially available.•Can be sterilized in-house without degrading glue or components.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Failures of machines having rotating parts are mostly caused by damage to bearings and there exist increasing demands for detecting damaged bearings at an early stage. However, conventional ...diagnostic methods, such as measuring temperature and observing vibration, have found difficulties in performing the early detection, so that more advanced diagnosis is necessary. This study therefore applies an ultrasonic technique as an advanced diagnostic method to bearing life tests. Ultrasonic wave pulses (UWP) emitted from a piezoelectric UWP generator can partially reflect from the interfaces of contact zones within the housing and the bearing with regard to the different acoustic impedance between a solid-to-solid contact and a contact dominated by some fluid layers. Hence, the intensity of the resultant UWP echoes can be determined by the real contact area formed at the interfaces. The experimental results of UWP echoes under the different operating conditions have demonstrated that the time intervals between peaks of UWP echoes varied in accordance with the movement of rolling balls and the lubricating phenomena in bearings. This behavior has further suggested the possibility of the early detection of abnormalities in ball bearings by using the variation in UWP echoes.
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