Background and purpose
High blood pressure (BP) at presentation is associated with poor outcomes in acute ischaemic stroke, but serial BP measurements may better delineate the clinical implications ...of BP. The aim was to investigate the association between various BP parameters and functional outcomes in acute ischaemic stroke patients treated with endovascular thrombectomy (EVT).
Methods
This study reports a retrospective analysis of a prospective registry of a comprehensive stroke centre. Patients treated with EVT due to large vessel occlusion in the anterior circulation were enrolled. BP was measured hourly during the first 24 h after admission. Associations of various BP parameters, including BP variability, with functional outcomes at 3 months, including good outcomes (modified Rankin Scale score of 0–2), were analysed.
Results
Of the 378 enrolled patients (mean age 70 ± 11 years, male 54.2%), 313 (82.8%) achieved successful reperfusion after EVT, and 149 (39.4%) had good outcomes at 3 months. Higher mean systolic BP each 10 mmHg increase, odds ratio 0.82 (0.69–0.97) and higher systolic successive variation (SV) each 10% increase, odds ratio 0.37 (0.18–0.76) were associated with a reduced likelihood of achieving good outcomes. In addition, reperfusion status after EVT moderated the influence of higher systolic SV on good outcomes (Pint = 0.05).
Conclusion
The results showed that a higher mean systolic BP and systolic SV during the first 24 h of EVT reduced the likelihood of good outcomes at 3 months. The effects of these parameters on outcomes are more substantial amongst patients with successful reperfusion after EVT, suggesting that different BP control strategies should be employed according to reperfusion status.
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We present a background model for dark matter searches using an array of NaI(Tl) crystals in the COSINE-100 experiment that is located in the Yangyang underground laboratory. The model includes ...background contributions from both internal and external sources, including cosmogenic radionuclides and surface
210
Pb contamination. To build the model in the low energy region, with a threshold of 1 keV, we used a depth profile of
210
Pb contamination in the surface of the NaI(Tl) crystals determined in a comparison between measured and simulated spectra. We also considered the effect of the energy scale errors propagated from the statistical uncertainties and the nonlinear detector response at low energies. The 1.7 years COSINE-100 data taken between October 21, 2016 and July 18, 2018 were used for this analysis. Our Monte Carlo simulation provides a non-Gaussian peak around 50 keV originating from beta decays of bulk
210
Pb in a good agreement with the measured background. This model estimates that the activities of bulk
210
Pb and
3
H are dominating the background rate that amounts to an average level of
2.85
±
0.15
counts/day/keV/kg in the energy region of (1–6) keV, using COSINE-100 data with a total exposure of 97.7 kg
·
years.
The specific role of endogenous glutathione in response to neuronal degeneration induced by trimethyltin (TMT) in the hippocampus was examined in rats. A single injection of TMT (8mg/kg, i.p.) ...produced a rapid increase in the formation of hydroxyl radical and in the levels of malondialdehyde (MDA) and protein carbonyl. TMT-induced seizure activity significantly increased after this initial oxidative stress, and remained elevated for up to 2 weeks post-TMT. Although a significant loss of hippocampal Cornus Ammonis CA1, CA3 and CA4 neurons was observed at 3 weeks post-TMT, the elevation in the level of hydroxyl radicals, MDA, and protein carbonyl had returned to near-control levels at that time. In contrast, the ratio of reduced to oxidized glutathione remained significantly decreased at 3 weeks post-TMT, and the glutathione-like immunoreactivity of the pyramidal neurons was decreased. However glutathione-positive glia-like cells proliferated mainly in the CA1, CA3, and CA4 sectors and were intensely immunoreactive. Double labeling demonstrated the co-localization of glutathione-immunoreactive glia-like cells and reactive astrocytes, as indicated by immunostaining for glial fibrillary acidic protein. This suggests that astroglial cells were mobilized to synthesize glutathione in response to the TMT insult. The TMT-induced changes in glutathione-like immunoreactivity appear to be concurrent with changes in the expression levels of glutathione peroxidase and glutathione reductase. Ascorbate treatment significantly attenuated TMT-induced seizures, as well as the initial oxidative stress, impaired glutathione homeostasis, and neuronal degeneration in a dose-dependent manner. These results suggest that ascorbate is an effective neuroprotectant against TMT. The initial oxidative burden induced by TMT may be a causal factor in the generation of seizures, prolonged disturbance of endogenous glutathione homeostasis, and consequent neuronal degeneration.
To identify predictive markers for responders in lapatinib-treated patients and to demonstrate molecular changes during lapatinib treatment via cell-free genomics.
We prospectively evaluated the ...efficacy of combining lapatinib with capecitabine and oxaliplatin as first line neoadjuvant therapy in patients with previously untreated, HER2-overexpressing advanced gastric cancer. A parallel biomarker study was conducted by simultaneously performing immunohistochemistry and next-generation sequencing (NGS) with tumor and blood samples.
Complete response was confirmed in 7/32 patients (21.8%), 2 of whom received radical surgery with pathologic-confirmed complete response. Fifteen partial responses (46.8%) were observed, resulting in a 68.6% overall response rate. NGS of the 16 tumor specimens demonstrated that the most common co-occurring copy number alteration was CCNE1 amplification, which was present in 40% of HER2+ tumors. The relationship between CCNE1 amplification and lack of response to HER2-targeted therapy trended toward statistical significance (66.7% of non-responders versus 22.2% of responders harbored CCNE1 amplification; P=0.08). Patients with high level ERBB2 amplification by NGS were more likely to respond to therapy, compared with patients with low level ERBB2 amplification (P=0.02). Analysis of cfDNA showed that detectable ERBB2 copy number amplification in plasma was predictive to the response (100%, response rate) and changes in plasma-detected genomic alterations were associated with lapatinib sensitivity and/or resistance. The follow-up cfDNA genomics at disease progression demonstrated that there are emergences of other genomic aberrations such as MYC, EGFR, FGFR2 and MET amplifications.
The present study showed that HER2+GC patients respond differently according to concomitant genomic aberrations beyond ERBB2, high ERBB2 amplification by NGS or cfDNA can be a positive predictor for patient selection, and tumor genomic alterations change significantly during targeted agent therapy.
Two common general anaesthetic methods are total i.v. anaesthesia (TIVA) and inhalation anaesthesia, but it is unclear whether this affects the patient's perception of their quality of recovery. The ...Quality of Recovery-40 questionnaire (QoR-40) is a valid and reliable method to evaluate the extent of functional recovery after surgery with general anaesthesia. This study therefore compared patient recovery using the QoR-40 in surgical patients who received TIVA with those who received desflurane anaesthesia.
Eighty females (20–65 years old) undergoing thyroid surgery were prospectively recruited and randomized to either the TIVA (effect-site target controlled infusion using propofol and remifentanil) or DES (desflurane inhalation with manual infusion of remifentanil) groups. The QoR-40 was administered by an investigator blind to group allocation before surgery, and postoperative days 1 and 2 (POD1 and POD2). Additional data including the incidence of nausea or vomiting, the consumption of antiemetic and analgesic agents in the post-anaesthesia care unit, and the duration of the hospital stay, were collected in all cases.
The QoR-40 score on POD1 was significantly higher in the TIVA group compared with the DES group (174 vs 161, respectively; P=0.004), indicating a better quality of recovery in the TIVA group. Among the five dimensions of the QoR-40, physical comfort and physical independence were significantly better on POD1 and POD2 in the TIVA group.
This study demonstrates that the quality of recovery for female thyroid surgery patients is significantly better with TIVA compared with desflurane anaesthesia.
www.clinicaltrials.org; ref.: NCT01760018.
Mutations in the mitofusin 2 (MFN2) gene, which encodes a mitochondrial GTPase mitofusin protein, have recently been reported to cause both Charcot–Marie–Tooth 2A (CMT2A) and hereditary motor and ...sensory neuropathy VI (HMSN VI). It is well known that HMSN VI is an axonal CMT neuropathy with optic atrophy. However, the differences between CMT2A and HMSN VI with MFN2 mutations remained to be clarified. Therefore, we studied the phenotypic characteristics of CMT patients with MFN2 mutations. Mutations in MFN2 were screened in 62 unrelated axonal CMT neuropathy families. We calculated CMT neuropathy scores (CMTNSs) and functional disability scales (FDSs) to quantify disease severity. Twenty-one patients with the MFN2 mutations were studied by brain MRI. Ten pathogenic mutations were identified in 26 patients from 15 families (24.2%). Six of these mutations had not been reported, and de novo mutations were observed in five families (33.3%). The electrophysiological patterns of affected individuals with the MFN2 mutations were typical of axonal CMT; however, the clinical and electrophysiological characteristics were markedly different in early (<10 years) and late disease-onset (≥10 years) groups. All patients with an early onset had severe CMTNS (≥21) and FDS (6 or 7), whereas most patients with late onset had mild CMTNS (≤10) and FDS (≤3). We identified two HMSN VI families with the R364W mutation in the early onset group; however, two other families with the same mutation did not have optic atrophy. In addition, two early onset families with R94W mutations, previously reported for HMSN VI, did not have visual impairment. Interestingly, eight patients had periventricular and subcortical hyperintense lesions by brain MRI. In the late-onset group, three patients had sensorineural hearing loss and two had bilateral extensor plantar responses. We found that MFN2 mutations are the major cause of axonal CMT neuropathy, and that they are associated with variable CNS involvements. Phenotypes were significantly different in the early and late disease-onset groups. Our findings suggest that HMSN VI might be a variant of the early onset severe CMT2A phenotype.
Networks of sensors placed on the skin can provide continuous measurement of human physiological signals for applications in clinical diagnostics, athletics and human-machine interfaces. Wireless and ...battery-free sensors are particularly desirable for reliable long-term monitoring, but current approaches for achieving this mode of operation rely on near-field technologies that require close proximity (at most a few centimetres) between each sensor and a wireless readout device. Here, we report near-field-enabled clothing capable of establishing wireless power and data connectivity between multiple distant points around the body to create a network of battery-free sensors interconnected by proximity to functional textile patterns. Using computer-controlled embroidery of conductive threads, we integrate clothing with near-field-responsive patterns that are completely fabric-based and free of fragile silicon components. We demonstrate the utility of the networked system for real-time, multi-node measurement of spinal posture as well as continuous sensing of temperature and gait during exercise.
Mood disorders and antidepressant therapy involve alterations of monoaminergic and glutamatergic transmission. The protein S100A10 (p11) was identified as a regulator of serotonin receptors, and it ...has been implicated in the etiology of depression and in mediating the antidepressant actions of selective serotonin reuptake inhibitors. Here we report that p11 can also regulate depression-like behaviors via regulation of a glutamatergic receptor in mice. p11 directly binds to the cytoplasmic tail of metabotropic glutamate receptor 5 (mGluR5). p11 and mGluR5 mutually facilitate their accumulation at the plasma membrane, and p11 increases cell surface availability of the receptor. Whereas p11 overexpression potentiates mGluR5 agonist-induced calcium responses, overexpression of mGluR5 mutant, which does not interact with p11, diminishes the calcium responses in cultured cells. Knockout of mGluR5 or p11 specifically in glutamatergic neurons in mice causes depression-like behaviors. Conversely, knockout of mGluR5 or p11 in GABAergic neurons causes antidepressant-like behaviors. Inhibition of mGluR5 with an antagonist, 2-methyl-6-(phenylethynyl)pyridine (MPEP), induces antidepressant-like behaviors in a p11-dependent manner. Notably, the antidepressant-like action of MPEP is mediated by parvalbumin-positive GABAergic interneurons, resulting in a decrease of inhibitory neuronal firing with a resultant increase of excitatory neuronal firing. These results identify a molecular and cellular basis by which mGluR5 antagonism achieves its antidepressant-like activity.
A
bstract
Limits on the cross section for weakly interacting massive particles (WIMPs) elastic scattering on nuclei in NaI(Tl) detectors at the Yangyang Underground Laboratory are obtained from a ...2967.4 kg·day data exposure. The nuclei recoiling from the scattering process are identified by the pulse shape of the scintillation light signals that they produce. The data are consistent with a no nuclear-recoil hypothesis, and WIMP-mass-dependent 90% confidence-level upper-limits are set on WIMP-nuclei elastic scattering cross sections. These limits partially exclude the DAMA/LIBRA allowed region for WIMP-sodium interactions with the same NaI(Tl) target material. The 90% confidence level upper limit on the WIMP-nucleon spin-independent cross section is 3.26×10
−4
pb for a WIMP mass of 10 GeV/c
2
.
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