Pressure Time Dose as a Representation of Intracranial Pressure Burden and Its Dependency on Intracranial Pressure Waveform Morphology at Different Time Intervals.

Intracranial pressure (ICP) burden or pressure time dose (PTD) is a valuable clinical indicator for pending intracranial hypertension, mostly based on threshold exceedance. Pulse frequency and waveform morphology (WFM) of the ICP signal contribute to PTD. The temporal resolution of the ICP signal has a great influence on PTD calculation but has not been systematically studied yet. Hence, the temporal resolution of the ICP signal on PTD calculation is investigated. We retrospectively analysed continuous 48 h ICP recordings with high temporal resolution obtained from 94 patients at the intensive care unit who underwent neurosurgery due to an intracranial haemorrhage and received an intracranial pressure probe (43 females, median age: 72 years, range: 23 to 88 years). The cumulative area under the curve above the threshold of 20 mmHg was compared for different temporal resolutions of the ICP signal (beat-to-beat, 1 s, 300 s, 1800 s, 3600 s). Events with prolonged ICP elevation were compared to those with few isolated threshold exceedances. PTD increased for lower temporal resolutions independent of WFM and frequency of threshold exceedance. PTDbeat-to-beat best reflected the impact of frequency of threshold exceedance and WFM. Events that could be distinguished in PTDbeat-to-beat became magnified more than 7-fold in PTD1s and more than 104 times in PTD1h, indicating an overestimation of PTD. PTD calculation should be standardised, and beat-by-beat PTD could serve as an easy-to-grasp indicator for the impact of frequency and WFM of ICP elevations on ICP burden.

The time-resolved atomic, molecular and optical science instrument at the Linac Coherent Light Source.

The newly constructed time-resolved atomic, molecular and optical science instrument (TMO) is configured to take full advantage of both linear accelerators at SLAC National Accelerator Laboratory, the copper accelerator operating at a repetition rate of 120 Hz providing high per-pulse energy as well as the superconducting accelerator operating at a repetition rate of about 1 MHz providing high average intensity. Both accelerators power a soft X-ray free-electron laser with the new variable-gap undulator section. With this flexible light source, TMO supports many experimental techniques not previously available at LCLS and will have two X-ray beam focus spots in line. Thereby, TMO supports atomic, molecular and optical, strong-field and nonlinear science and will also host a designated new dynamic reaction microscope with a sub-micrometer X-ray focus spot. The flexible instrument design is optimized for studying ultrafast electronic and molecular phenomena and can take full advantage of the sub-femtosecond soft X-ray pulse generation program.

No Gender Differences in Pain Perception and Medication after Lumbar Spine Sequestrectomy-A Reanalysis of a Randomized Controlled Clinical Trial.

BACKGROUND: Gender issues have received increasing attention in clinical research of the past years, and biological sex has been introduced as a moderating variable in experimental pain perception. However, in clinical studies of acute pain and gender, there are conflicting results. In particular, there are limited data on the impact of gender differences after spinal sequestrectomy. The aim of this work is to examine gender differences in postoperative pain and pain medication consumption in an inpatient clinical setting. METHODS: Data of a completed double-blind RCT was subdivided by gender and reanalyzed by means of an analysis of variance in repeated measures. Outcomes included pain severity measured on a VAS, affective (SES-A) and sensory pain perception (SES-S) and morphine equivalent doses (MED) of analgesics after spinal sequestrectomy. RESULTS: In total, 42 female (47.73%) and 46 male (52.27%) patients were analyzed. No differences in pain severity (VAS: Gender × Time F = 0.35; (df = 2, 86); p = 0.708), affective and sensory pain perception (SES-A: Gender × Time F = 0.08; (df = 2, 86); p = 0.919; SES-S: Gender × Time F = 0.06; (df = 2, 86); p = 0.939) or post-operative opioid use between men and women (MEDs: Gender × Time F = 1.44; (df = 2, 86); p = 0.227) could be observed. CONCLUSIONS: This reanalysis of an RCT with respect to gender differences is to our knowledge the first attempt to investigate the role of gender in pain perception and medication after lumbar spine sequestrectomy. In contrast to other studies, we were not able to show significant differences between male and female patients in all pain-related outcomes. Apart from well-established pain management, psychological reasons such as gender-specific response biases or the observer effect might explain our results. TRIAL REGISTRATION: The study was registered as a regulatory phase IV study at the German Clinical Trials Register (DRKS), an open-access online register for clinical trials conducted in Germany (Reg-No: DRKS00007913).

Attosecond coherent electron motion in Auger-Meitner decay.

In quantum systems, coherent superpositions of electronic states evolve on ultrafast time scales (few femtoseconds to attoseconds; 1 attosecond = 0.001 femtoseconds = 10-18 seconds), leading to a time-dependent charge density. Here we performed time-resolved measurements using attosecond soft x-ray pulses produced by a free-electron laser, to track the evolution of a coherent core-hole excitation in nitric oxide. Using an additional circularly polarized infrared laser pulse, we created a clock to time-resolve the electron dynamics and demonstrated control of the coherent electron motion by tuning the photon energy of the x-ray pulse. Core-excited states offer a fundamental test bed for studying coherent electron dynamics in highly excited and strongly correlated matter.

Comparison of Two Algorithms Analysing the Intracranial Pressure Curve in Terms of the Accuracy of Their Start-Point Detection and Resistance to Artefacts.

OBJECTIVES: For further insight into the possibly predictive quality of the intracranial pressure (ICP) waveform morphology a definite and reliable identification of its components is a prerequisite but presents the problem of artefacts in physiological signals. METHODS: ICP and electrocardiogram (ECG) data were recorded to depict not only their numerical value but also their respective waveforms and were analysed by two algorithms, which were then compared for their artefact resistance.The algorithms in question identify the start point of every ICP wave, one (AR[SA]) by scale analysis, the other (AR[ECG]) by analysing the ICP wave linked to the ECG. RESULTS: Start-point identification accuracy in rhythmic patients showed sensitivity of 95.14% for AR[SA] and 99.99% for AR[ECG], with a positive predictive value (ppv) of 98.30% for AR[SA] and 99.76% for AR[ECG].In arrhythmic patients sensitivity was 98.05% for AR[SA] and 99.73% for AR[ECG], with a ppv of 100% for AR[SA] and 99.78% for AR[ECG]. CONCLUSIONS: AR[ECG] has proven to be more resistant to artefacts than AR[SA], even in cases such as cardiac arrhythmia. It facilitates reliable, three-dimensional visualisation of long-term changes in ICP-wave morphology and is thus suited for analysis in cases of more complex or irregular vital parameters.

Loss of KDM6A confers drug resistance in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aggressive hematologic neoplasm resulting from the malignant transformation of myeloid progenitors. Despite intensive chemotherapy leading to initial treatment responses, relapse caused by intrinsic or acquired drug resistance represents a major challenge. Here, we report that histone 3 lysine 27 demethylase KDM6A (UTX) is targeted by inactivating mutations and mutation-independent regulation in relapsed AML. Analyses of matched diagnosis and relapse specimens from individuals with KDM6A mutations showed an outgrowth of the KDM6A mutated tumor population at relapse. KDM6A expression is heterogeneously regulated and relapse-specific loss of KDM6A was observed in 45.7% of CN-AML patients. KDM6A-null myeloid leukemia cells were more resistant to treatment with the chemotherapeutic agents cytarabine (AraC) and daunorubicin. Inducible re-expression of KDM6A in KDM6A-null cell lines suppressed proliferation and sensitized cells again to AraC treatment. RNA expression analysis and functional studies revealed that resistance to AraC was conferred by downregulation of the nucleoside membrane transporter ENT1 (SLC29A1) by reduced H3K27 acetylation at the ENT1 locus. Our results show that loss of KDM6A provides cells with a selective advantage during chemotherapy, which ultimately leads to the observed outgrowth of clones with KDM6A mutations or reduced KDM6A expression at relapse.

Photothermal Ablation of Cancer Cells Using Folate-Coated Gold/ Graphene Oxide Composite.

OBJECTIVE: A new tumor targeted polymer-coated gold/graphene hybrid has been developed for achieving simultaneously thermoablation and chemoterapy of folate receptor-positive cancer cells. METHODS: The gold/graphene hybrid was prepared by depositing gold nanospheres onto graphene oxide and coating it with an inulin-folate conjugate. Paclitaxel was loaded by sonication. The hybrid was characterized by UV-Vis spectroscopy, DSC analysis and SEM microscopy. The cytotoxicity, thermoablation and anticancer activity were evaluated in vitro on MCF-7 and 16 HBE. RESULTS: In vitro tests showed that the paclitaxel-loaded hybrid improved the effectiveness of the drug especially after photothermal treatments. CONCLUSION: On the whole, while gold/graphene composite provided an excellent time-dependent photothermal effect, the loading of paclitaxel allowed a suitable chemotherapy, thus killing cancer cells both via a selective laser beam thermoablation and hyperthermia-triggered chemotherapy.

Influence of shift work in nursing on sleep and circadian blood pressure and rhythm / 心血管康复医学杂志

Objective: To explore influence of shift work in nursing on sleep and circadian blood pressure and rhythm. Methods: A total of 29 shift nurses, who worked in our hospital for a long period, were enrolled as shift nurse group. Another 32 day shift nurses were regarded as day shift nurse control group（control group）. Both groups received Pittsburgh sleep quality index (PSQI) assessment and 24h ambulatory blood pressure monitoring (ABPM). Results: Compared with control group, PSQI assessment showed that most factor scores and PSQI total score [(8.67±2.16) scores vs. (11.98±3.30) scores] significantly increased in shift nurse group（P<0.05~0.01）; 24h ABPM showed that mean nighttime SBP [(106.51±12.94) mmHg vs. (115.74±13.72) mmHg] and nighttime DBP [(71.23±9.76) mmHg vs. (74.96±10.68) mmHg] significantly rose in shift nurse group, P<0.05; Mean SBP decreasing rate [(7.84±1.52)% vs. (3.66±1.47)%] and mean DBP decreasing rate [(6.55±1.39)% vs. (2.83±0.51)%], SBP dipper percentage (59.38% vs. 31.03%) and DBP dipper percentage (68.75% vs. 27.59%) significantly reduced, SBP non-dipper percentage (40.63% vs. 68.97%) and DBP non-dipper percentage (31.25% vs. 72.41%) significantly rose in shift nurses group, P<0.05~0.01.Conclusions: There exists definite somnipathy and significant change of circadian blood pressure and rhythm in shift nurses.

Therapeutic effect of chemokine SLC combined with immune adjuvant CpG-ODN in treatment of implanted mouse melanoma / 中国肿瘤生物治疗杂志

Objective: To study the therapeutic effect of secondary lymphoid tissue chemokine (SLC) combined with CpG oligodeoxynucleotide (CpG-ODN) in treatment of implanted mouse melanoma and the possible mechanism. Methods: SLC-Fc fusion protein was prepared and its chemotaxis of lymphocytes was detected by chemotaxis assay. Implanted melanoma mouse models were established and randomly divided into 4 groups: control group, SLC-Fc group, CpG-ODN group, and SLC-Fc+CpG-ODN group. The growth of implanted tumors in each group was observed after treatment. Subtype and infiltration of lymphocytes in implanted tumor tissues were examined by flow cytometry. Results: SLC-Fc protein was successfully prepared, and it dose-dependently attracted lymphocytes (0.03, 0.3, and 3 μg/L). Intra-tumor injection SLC-Fc and CpG-ODN alone or in combination significantly inhibited growth of B16-implanted tumors. Tumor size in SLC-Fc+CpG-ODN group was significantly smaller than that in control group (P<0.01), and animals in SLC-Fc+CpG-ODN group survived longer. Tumor-infiltrated CD4~+ T, CD~8+ T, and dendritic cells (DCs) in SLC-Fc+CpG-ODN group were markedly increased as compared with those in control group (P<0.05), and tumor draining lymph nodes were dramatically enlarged. Conclusion: SLC combined with CpG-ODN can inhibit the growth of implanted melanoma by attracting CD4~+ T and CD8~+ T and promoting proliferation of DCs.