Successful kinetic impact into an asteroid for planetary defence.

Although no known asteroid poses a threat to Earth for at least the next century, the catalogue of near-Earth asteroids is incomplete for objects whose impacts would produce regional devastation1,2. Several approaches have been proposed to potentially prevent an asteroid impact with Earth by deflecting or disrupting an asteroid1-3. A test of kinetic impact technology was identified as the highest-priority space mission related to asteroid mitigation1. NASA's Double Asteroid Redirection Test (DART) mission is a full-scale test of kinetic impact technology. The mission's target asteroid was Dimorphos, the secondary member of the S-type binary near-Earth asteroid (65803) Didymos. This binary asteroid system was chosen to enable ground-based telescopes to quantify the asteroid deflection caused by the impact of the DART spacecraft4. Although past missions have utilized impactors to investigate the properties of small bodies5,6, those earlier missions were not intended to deflect their targets and did not achieve measurable deflections. Here we report the DART spacecraft's autonomous kinetic impact into Dimorphos and reconstruct the impact event, including the timeline leading to impact, the location and nature of the DART impact site, and the size and shape of Dimorphos. The successful impact of the DART spacecraft with Dimorphos and the resulting change in the orbit of Dimorphos7 demonstrates that kinetic impactor technology is a viable technique to potentially defend Earth if necessary.

[Correlation between unilateral internal carotid artery stenosis and asymmetric distribution of enlarged perivascular spaces in patients with acute cerebral infarction].

Objective: To explore the correlation between unilateral internal carotid artery (ICA) stenosis and asymmetrical distribution of enlarged perivascular spaces (EPVS) in patients with acute cerebral infarction. Methods: Acute cerebral infarction patients with unilateral ICA stenosis hospitalized in Changzhou Second People's Hospital from October 2020 to December 2021 were collected. Routine cranial MRI and CT angiography were completed for each patient. The 3D Slicer software was used to quantitatively analyze the volume of patient's EPVS. Patients were divided into moderate stenosis group and severe stenosis/occlusion group according to the degree of ICA stenosis. Baseline data were compared between the two groups. Patients were further divided into three groups: moderate stenosis, severe stenosis and occlusion groups, and the ipsilateral and contralateral EPVS volume of ICA stenosis patients was compared. The asymmetry index (AI) was calculated for EPVS in the basal ganglia region (BG-EPVS) and EPVS in the centrum semiovale (CSO-EPVS). Patients with AI≥0.2 were included in the EPVS asymmetry group, while the rest were in the EPVS symmetry group, and the degree of unilateral ICA stenosis was compared between the two groups. Multivariate logistic regression model was used to analyze the relationship between ICA severe stenosis/occlusion and the asymmetric distribution of BG-EPVS. Results: A total of 122 patients (96 males and 26 females) were enrolled, aged (70±10) years, with 81 cases in the unilateral ICA severe stenosis/occlusion group (46 cases of severe stenosis and 35 of occlusion) and 41 cases in the moderate stenosis group. Patients in the unilateral ICA severe stenosis/occlusion group had greater BG-EPVS volume [(4.08±0.76) mm3]and proportion of asymmetric distribution of BG-EPVS [75.3%(61/81)] than those of the moderate stenosis group [(3.12±0.85) mm3 and 39.0% (16/41)], with statistically significant differences (both P<0.001). The BG-EPVS volumes of the ipsilateral side of the stenosis in the severe stenosis group and the occlusion group [(3.34±0.86) mm3 and (3.93±0.60) mm3] were significantly greater than those of the contralateral side [(2.65±1.28) mm3 and (3.21±0.88) mm3], with statistically significant differences (both P<0.001). Correlation analysis indicated that the degree of unilateral ICA stenosis was positively correlated with the BG-EPVS volume on the stenosis side (r=0.62, P<0.001). Further comparison of the degree of unilateral ICA stenosis between the EPVS symmetric and asymmetric groups showed that the proportion of unilateral ICA severe stenosis/occlusion in the BG-EPVS asymmetry group was higher than that in the symmetric group [79.2%(61/77) vs 44.4%(20/45),P<0.001]. Multivariate logistic regression analysis showed that unilateral ICA severe stenosis/occlusion (OR=4.280, 95%CI: 1.743-10.508, P =0.002) and age (OR=1.055, 95%CI: 1.001-1.112, P=0.044) were risk factors for asymmetric distribution of BG-EPVS. Conclusions: The severe stenosis/occlusion of the unilateral ICA and age are the risk factors for the asymmetric distribution of the BG-EPVS in patients with acute cerebral infarction. The ipsilateral EPVS volume of unilateral ICA stenosis is larger than that of the contralateral side, and the degree of ICA stenosis is positively correlated with the severity of BG-EPVS.

[Correlation between total cerebral small vessel disease score and retinal vessel diameters in patients with mild stroke].

Objective: To explore the relationship between the total cerebral small vessel disease (CSVD) score and retinal vessel diameters in patients with mild stroke. Methods: The patients with mild stroke who were hospitalized in the Second People's Hospital of Changzhou, Nanjing Medical University from March to December 2019 were continuously collected (National Institutes of Health Stroke Scale score≤3 points). All patients completed the head magnetic resonance imaging and retinal fundus photography examination, and then the retinal arteriovenous diameter was measured semi-automatically based on the pictures. According to the total CSVD score (0-4 points), the patients were divided into 5 groups. The baseline characteristics of the patients were compared. Moreover, the correlation of total CSVD with retinal blood vessel diameters were analyzed by spearman and linear regression. Results: A total of 206 patients were enrolled. There were 69, 51, 41, 30, and 15 patients with 0, 1, 2, 3, and 4 points, respectively. In CSVD subgroups, there were significant differences in age, duration of hypertension and diabetes (all P<0.05). The central retinal artery equivalent (CRAE), (CSVD scores 0-4 were (126±12) µm, (118±11) µm, (108±11) µm, (99±8) µm, (90±7) µm, P<0.001) and arteriole-to-venule ratio (AVR) (CSVD scores 0-4 were 0.65±0.05, 0.60±0.04, 0.56±0.04, 0.49±0.03, 0.44±0.02, P<0.001) were different in CSVD subgroups. With the increase of CSVD score, the diameter of artery and AVR became smaller. The total CSVD was significantly correlated with AVR by Spearman correlation analysis (r= 0.818, P<0.001). By constructing a linear regression equation model, the coefficient of determination of the total CSVD score (R2=0.694) was higher than that of lacunes, white matter hyperintensities, cerebral microbleeds and enlarged perivascular space. After adjusting for age, course of hypertension and diabetes, and different types of CSVD, further multiple linear regression analysis revealed that the total CSVD score was still an independent related factor of AVR (ß=-0.039, P<0.001, 95%CI=-0.051--0.028). Conclusions: Total CSVD score is negatively correlated with retinal artery diameters and AVR. Additionally, the total CSVD score can better reflect the degree of cerebral microvascular lesions than single type CSVD.

Calhm2 governs astrocytic ATP releasing in the development of depression-like behaviors.

This corrects the article DOI: 10.1038/mp.2017.229.

Depth extraction with offset pixels.

Numerous depth extraction techniques have been proposed in the past. However, the utility of these techniques is limited as they typically require multiple imaging units, bulky platforms for computation, cannot achieve high speed and are computationally expensive. To counter the above challenges, a sensor with Offset Pixel Apertures (OPA) has been recently proposed. However, a working system for depth extraction with the OPA sensor has not been discussed. In this paper, we propose the first such system for depth extraction using the OPA sensor. We also propose a dedicated hardware implementation for the proposed system, named as the Depth Map Processor (DMP). The DMP can provide depth at 30 frames per second at 1920 × 1080 resolution with 31 disparity levels. Furthermore, the proposed DMP has low power consumption as for the aforementioned speed and resolution it only requires 290.76 mW. The proposed system makes it an ideal choice for depth extraction systems in constrained environments.

[Influence of intravenous thrombolysis on prognosis of acute ischemic stroke in patients with moderate to severe leukoaraiosis].

Objective: To investigate the influence of intravenous thrombolysis on prognosis of acute ischemic stroke in patients with moderate to severe leukoaraiosis and to analyze influencing factors of the clinical prognosis. Methods: We consecutively included acute ischemic stroke patients with middle cerebral artery occlusion (n=101) from Department of Neurology or Emergency, and patients were divided into two groups according to whether on intravenous thrombolysis therapy (IVT) or not. The Fugl-Meyer scale score (FMS) was used to assess motor function outcome and the National Institutes of Health Stroke Scale (NIHSS) score was used to assess neurologic function. Clinical data were obtained and compared between the two groups. Patients were followed up for 90 days, the primary clinical endpoint events included stroke recurrence and death, and the key secondary endpoint events included other vascular events after IVT. Multivariate linear regression analysis was used to analyze the relevant factors influencing the motor function 90 days later. Results: Among the 101 enrolled patients, 37 (36.6%) were classified as IVT group and 64 (63.4%) as no IVT group. In IVT group, hemorrhagic transformation and symptomatic intracranial hemorrhage were observed in 32.4% (12/37) and 13.5% (5/37) of the patients, which were higher than those in the no IVT group (9.4% (6/64) and 1.6% (1/64) , respectively) (χ(2)=8.511, P=0.004; χ(2)=5.993, P=0.014). And there was no significant difference between the two groups in NIHSS score and FMS score at any time point. In addition, there was no significant increase in 90-day FMS score in the two groups compared with the FMS score on admission (83±9 vs 80±12; 86±8 vs 80±10). After followed up for 90 days, the primary clinical endpoints were obtained in 32 patients (32/101; 31.9%), including 18 cases of stroke recurrence (18/101; 17.8%) and 14 cases of death (14/101; 13.9%). No significant difference was found in primary clinical endpoints between the two groups. Multivariate linear regression analysis revealed that symptomatic intracranial hemorrhage (t=-2.318; P=0.023), baseline NIHSS score (t=-4.263; P=0.000), recurrent stroke (t=-9.114; P=0.000) and hemorrhage transformation (t=-2.121; P=0.037) were risk factors of poor 90-day motor function recovery, but not application of intravenous thrombolysis therapy (t=0.328; P=0.744). Conclusions: Acute ischemic stroke patients with moderate to severe LA have higher risk of hemorrhagic transformation and symptomatic intracranial hemorrhage after intravenous thrombolysis. However, there is no association of intravenous thrombolysis therapy with motor function recovery.

Assessment of apple core collections constructed using phenotypic and genotypic data.

Several types of information can be used to select core collections, including passport data, agronomic data, and molecular data. However, little is known about the ability of core collections to retain the genetic diversity and structure of the whole collection for characters that were not considered during the selection, particularly when molecular markers are used. In this study, two core subsets were established for the apple (Malus spp) germplasm bank curated at the Apple Research Station, National Institute of Horticultural and Herbal Science, Korea, based upon genetic diversity estimated with 14 simple sequence repeat markers, and phenotypic diversity based on 23 traits. Comparisons between these two subsets and with the whole collection were used to determine the effect of the data used in the selection on phenotypic and genetic diversity, and population structure. The two subsets had a similar diversity and did not differ from the original collection, according to the Nei and Shannon diversity indices. Allele and class frequencies were also maintained in the two subsets. Overall, the type of data used to construct the core collection had little influence on the phenotypic and genetic diversity retained. Therefore, in the case of apple collections, the use of molecular markers is preferable, because they allow rapid and reliable characterization.

Melatonin prevents gentamicin-induced testicular toxicity and oxidative stress in rats.

This study investigated the protective effects of melatonin (MT) against gentamicin (GM)-induced testicular toxicity and oxidative damage in rats. GM (100 mg kg(-1) ) was injected intraperitoneally (i.p.) to rats for 6 days. MT (15 mg kg(-1) ) was administered i.p. to rats for 6 days at 1 hr after the GM treatment. GM caused a decrease in prostate and seminal vesicle weights, sperm count and sperm motility. Histopathological examination showed various morphological alterations in the testis, characterised by degeneration of spermatogonia/spermatocytes, decrease in the number of early spermatogenic cells and vacuolisation. In addition, an increased malondialdehyde concentration and decreased glutathione content and glutathione reductase, catalase and glutathione-S-transferase activities were found in the testis. In contrast, MT treatment significantly attenuated the testicular toxicity of GM, including decreased reproductive organ weights, sperm count, and sperm motility and increased histopathological alterations. MT also had an antioxidant benefit by decreasing the lipid peroxidative product malondialdehyde and increasing the level of the antioxidant glutathione and the activities of antioxidant enzymes in the testis. These results indicate that MT prevents testicular toxicity induced by GM in rats, presumably due to its potent antioxidant activity, and its ability to inhibit lipid peroxidation, and restore antioxidant enzyme activity.

Radiomics approach to distinguish between benign and malignant soft tissue tumors on magnetic resonance imaging.

Objective: To build a radiomics signature based on MRI images and evaluate its capability for preoperatively identifying the benign and malignant Soft tissue neoplasms (STTs). Materials and methods: 193 patients (99 malignant STTs and 94 benign STTs) were at random segmented into a training cohort (69 malignant STTs and 65 benign STTs) and a validation cohort (30 malignant STTs and 29 benign STTs) with a portion of 7:3. Radiomics features were extracted from T2 with fat saturation and T1 with fat saturation and gadolinium contrast images. Radiomics signature was developed by the least absolute shrinkage and selection operator (LASSO) logistic regression model. The receiver that operated characteristics curve (ROC) analysis was used to assess radiomics signature's prediction performance. Inner validation was performed on an autonomous cohort that contained 40 patients. Results: A radiomics was developed by a total of 16 radiomics features (5 original shape features and 11 were wavelet features) achieved favorable predictive efficacy. Malignant STTs showed higher radiomics score than benign STTs in both training cohort and validation cohort. A good prediction performance was shown by the radiomics signature in both training cohorts and validation cohorts. The training cohorts and validation cohorts had an area under curves (AUCs) of 0.885 and 0.841, respectively. Conclusions: A radiomics signature based on MRI images can be a trustworthy imaging biomarker for identification of the benign and malignant STTs, which could help guide treatment strategies.

Predicting stroke risk after sepsis hospitalization with new-onset atrial fibrillation.

BACKGROUND: New-onset atrial fibrillation (AF) during sepsis is common, but models designed to stratify stroke risk excluded patients with secondary AF. We assessed the predictive validity of CHA2DS2VASc scores among patients with new-onset AF during sepsis and developed a novel stroke prediction model incorporating presepsis and intrasepsis characteristics. METHODS: We included patients ≥40 years old who survived hospitalizations with sepsis and new-onset AF across 21 Kaiser Permanente Northern California hospitals from January 1, 2011 to September 30, 2017. We calculated the area under the receiver operating curve (AUC) for CHA2DS2VASc scores to predict stroke or transient ischemic attack (TIA) within 1 year after a hospitalization with new-onset AF during sepsis using Fine-Gray models with death as competing risk. We similarly derived and validated a novel model using presepsis and intrasepsis characteristics associated with 1-year stroke/TIA risk. RESULTS: Among 82,748 adults hospitalized with sepsis, 3992 with new-onset AF (median age: 80 years, median CHA2DS2VASc of 4) survived to discharge, among whom 70 (2.1%) experienced stroke or TIA outcome and 1393 (41.0%) died within 1 year of sepsis. The CHA2DS2VASc score was not predictive of stroke risk after sepsis (AUC: 0.50, 95% confidence interval [CI]: 0.48-0.52). A newly derived model among 2555 (64%) patients in the derivation set and 1437 (36%) in the validation set included 13 variables and produced an AUC of 0.61 (0.49-0.73) in derivation and 0.54 (0.43-0.65) in validation. CONCLUSION: Current models do not accurately stratify risk of stroke following new-onset AF secondary to sepsis. New tools are required to guide anticoagulation decisions following new-onset AF in sepsis.

Towards virtual histology with X-ray grating interferometry.

Breast cancer is the most common type of cancer worldwide. Diagnosing breast cancer relies on clinical examination, imaging and biopsy. A core-needle biopsy enables a morphological and biochemical characterization of the cancer and is considered the gold standard for breast cancer diagnosis. A histopathological examination uses high-resolution microscopes with outstanding contrast in the 2D plane, but the spatial resolution in the third, Z-direction, is reduced. In the present paper, we propose two high-resolution table-top systems for phase-contrast X-ray tomography of soft-tissue samples. The first system implements a classical Talbot-Lau interferometer and allows to perform ex-vivo imaging of human breast samples with a voxel size of 5.57 µm. The second system with a comparable voxel size relies on a Sigray MAAST X-ray source with structured anode. For the first time, we demonstrate the applicability of the latter to perform X-ray imaging of human breast specimens with ductal carcinoma in-situ. We assessed image quality of both setups and compared it to histology. We showed that both setups made it possible to target internal features of breast specimens with better resolution and contrast than previously achieved, demonstrating that grating-based phase-contrast X-ray CT could be a complementary tool for clinical histopathology.

Advantages of a synchrotron bending magnet as the sample illuminator for a wide-field X-ray microscope.

In this paper the choice between bending magnets and insertion devices as sample illuminators for a hard X-ray full-field microscope is investigated. An optimized bending-magnet beamline design is presented. Its imaging speed is very competitive with the performance of similar microscopes installed currently at insertion-device beamlines. The fact that imaging X-ray microscopes can accept a large phase space makes them very well suited to the output characteristics of bending magnets which are often a plentiful and paid-for resource. There exist opportunities at all synchrotron light sources to take advantage of this finding to build bending-magnet beamlines that are dedicated to transmission X-ray microscope facilities. It is expected that demand for such facilities will increase as three-dimensional tomography becomes routine and advanced techniques such as mosaic tomography and XANES tomography (taking three-dimensional tomograms at different energies to highlight elemental and chemical differences) become more widespread.

Proteomics analysis of the nucleolus in adenovirus-infected cells.

Adenoviruses replicate primarily in the host cell nucleus, and it is well established that adenovirus infection affects the structure and function of host cell nucleoli in addition to coding for a number of nucleolar targeted viral proteins. Here we used unbiased proteomics methods, including high throughput mass spectrometry coupled with stable isotope labeling by amino acids in cell culture (SILAC) and traditional two-dimensional gel electrophoresis, to identify quantitative changes in the protein composition of the nucleolus during adenovirus infection. Two-dimensional gel analysis revealed changes in six proteins. By contrast, SILAC-based approaches identified 351 proteins with 24 proteins showing at least a 2-fold change after infection. Of those, four were previously reported to have aberrant localization and/or functional relevance during adenovirus infection. In total, 15 proteins identified as changing in amount by proteomics methods were examined in infected cells using confocal microscopy. Eleven of these proteins showed altered patterns of localization in adenovirus-infected cells. Comparing our data with the effects of actinomycin D on the nucleolar proteome revealed that adenovirus infection apparently specifically targets a relatively small subset of nucleolar antigens at the time point examined.

Systematic optimization of targeted and multiplexed MS-based screening workflows for protein biomarkers.

Background: The capability of targeted MS-based methods to simultaneously measure multiple analytes with high selectivity and sensitivity greatly facilitates the discovery and quantitation of novel biomarkers. However, the complexity of biological samples is a major bottleneck that requires extensive sample preparation. Results: This paper reports a generic workflow to optimize surrogate peptide-based protein biomarker screening for seven human proteins in a multiplexed manner without the need for any specific affinity reagents. Each step of the sample processing and LC-MS methods is systematically assessed and optimized for better analytical performance. Conclusion: The established method is used for the screening of multiple myeloma patient samples to determine which proteins could be robustly measured and serve as potential biomarkers of the disease.

Quantitative nucleolar proteomics reveals nuclear re-organization during stress- induced senescence in mouse fibroblast.

BACKGROUND: Nucleolus is the most prominent mammalian organelle within the nucleus which is also the site for ribosomal biogenesis. There have been many reports indicating the involvement of nucleolus in the process of aging. Several proteins related to aging have been shown to localize in the nucleolus, which suggests the role of this organelle in senescence. RESULTS: In this study, we used quantitative mass spectrometry to map the flux of proteins into and out of the nucleolus during the induction of senescence in cultured mammalian cells. Changes in the abundance of 344 nucleolar proteins in sodium butyrate-induced senescence in NIH3T3 cells were studied by SILAC (stable isotope labeling by amino acids in cell culture)-based mass spectrometry. Biochemically, we have validated the proteomic results and confirmed that B23 (nucleophosmin) protein was down-regulated, while poly (ADP-ribose) polymerase (PARP) and nuclear DNA helicase II (NDH II/DHX9/RHA) were up-regulated in the nucleolus upon treatment with sodium butyrate. Accumulation of chromatin in the nucleolus was also observed, by both proteomics and microscopy, in sodium butyrate-treated cells. Similar observations were found in other models of senescence, namely, in mitoxantrone- (MTX) treated cells and primary fibroblasts from the Lamin A knockout mice. CONCLUSION: Our data indicate an extensive nuclear organization during senescence and suggest that the redistribution of B23 protein and chromatin can be used as an important marker for senescence.

Pharmacokinetic study of the phase III, randomized, double-blind, multicenter trial (TRIBUTE) of paclitaxel and carboplatin combined with erlotinib or placebo in patients with advanced Non-small Cell Lung Cancer (NSCLC).

PURPOSE: To assess the pharmacokinetics and evaluate potential drug-drug interactions between erlotinib, paclitaxel and carboplatin. EXPERIMENTAL DESIGN: 1,079 previously untreated patients with advanced NSCLC were enrolled and randomized in a phase III trial (TRIBUTE) to receive either erlotinib or placebo in combination with paclitaxel 200 mg/m2 IV over 3 h and carboplatin at a calculated dose to achieve an AUC 6 mg∙min/mL. To determine possible drug-drug interaction with this combination, a subset of 24 (12 erlotinib, 12 placebo) patients were enrolled onto an intensive pharmacokinetic (IPK) substudy group at a single site. All IPK patients received either erlotinib 150 mg/day or placebo-controlled tablets. Analyses were completed using validated analytical methodologies. Non-compartmental modeling was utilized to estimate PK parameters. RESULTS: Complete blood sampling for pharmacokinetic analysis was obtained in 21 of 24 patients. Mean AUC(0-τ) for erlotinib and the OSI-420 metabolite were 29,997 ng∙h/mL and 3,020 ng∙h/mL, respectively. Mean (SD) paclitaxel clearances (L/h/M(2)) were 11.7 (3.4) and 12.7 (6.7) in the placebo and erlotinib treatment groups, respectively. The resultant paclitaxel AUC(0-∞) (ng∙h/mL) was 18,400 (5,300) for the placebo group and 17,800 (5,500) for the erlotinib group. For carboplatin, the mean (SD) clearances (L/h) were 16.8 (3.9) and 16.1 (4.4) for the placebo and erlotinib groups, respectively. The resultant carboplatin AUC(0-∞) (ng/mL∙h) were 49,900 (9,700) for the placebo group and 48,400 (11,900) for the erlotinib group. No significant differences were observed in these paclitaxel or carboplatin pharmacokinetic group comparisons. CONCLUSIONS: The addition of erlotinib to a standard chemotherapy regimen for NSCLC did not alter the systemic exposures (AUC(0-∞)) of paclitaxel (p = 0.80) and carboplatin (p = 0.756) when erlotinib-treated patients were compared to placebo-treated patients. The pharmacokinetics of erlotinib and its metabolite OSI-420 did not appear to be altered by the concomitant administration of paclitaxel and carboplatin.

Nucleolar proteome dynamics.

The nucleolus is a key organelle that coordinates the synthesis and assembly of ribosomal subunits and forms in the nucleus around the repeated ribosomal gene clusters. Because the production of ribosomes is a major metabolic activity, the function of the nucleolus is tightly linked to cell growth and proliferation, and recent data suggest that the nucleolus also plays an important role in cell-cycle regulation, senescence and stress responses. Here, using mass-spectrometry-based organellar proteomics and stable isotope labelling, we perform a quantitative analysis of the proteome of human nucleoli. In vivo fluorescent imaging techniques are directly compared to endogenous protein changes measured by proteomics. We characterize the flux of 489 endogenous nucleolar proteins in response to three different metabolic inhibitors that each affect nucleolar morphology. Proteins that are stably associated, such as RNA polymerase I subunits and small nuclear ribonucleoprotein particle complexes, exit from or accumulate in the nucleolus with similar kinetics, whereas protein components of the large and small ribosomal subunits leave the nucleolus with markedly different kinetics. The data establish a quantitative proteomic approach for the temporal characterization of protein flux through cellular organelles and demonstrate that the nucleolar proteome changes significantly over time in response to changes in cellular growth conditions.

Experimental solubility profiling of marketed CNS drugs, exploring solubility limit of CNS discovery candidate.

We determined the experimental solubility of CNS marketed drugs. Of the 98 drugs measured, greater than 90% had solubility >10 µM in pH 7.4 buffer. Only seven drugs had solubility <10 µM. Using these data, we established a solubility criterion to support CNS discovery. The implication of poor solubility with potential safety concerns and undesirable side effects are discussed.

Autonomic changes in preoperative uncomplicated diabetic patients with postural changes.

Diabetic autonomic neuropathy is a critical complication frequently encountered in anaesthetic and surgical practice. Power spectral analysis is a noninvasive tool for monitoring frequency analysis of heart rate variability (HRV) and autonomic control of the heart. This study examined HRV changes in preoperative diabetic patients without overt signs of autonomic dysfunction and in matched controls (n=18 per group). HRV values at -15 degrees, 0 degrees, 15 degrees, 45 degrees and sitting positions were compared between groups and for each position. HRV in diabetic patients was lower than in controls at all positions (absolute units). Low-frequency power (normalized units) and the low-frequency/high-frequency ratio increased significantly at 45 degrees and in sitting positions in controls but not in diabetic patients. Pre-existing autonomic derangements in diabetic patients without overt clinical symptoms can be aggravated by high-degree tilting or sitting positions. Consequently, great care should be taken during the intra- and perioperative management of these patients.

Microenvironmental topographic cues influence migration dynamics of nasopharyngeal carcinoma cells from tumour spheroids.

Tumour metastasis is a complex process that strongly influences the prognosis and treatment of cancer. Apart from intracellular factors, recent studies have indicated that metastasis also depends on microenvironmental factors such as the biochemical, mechanical and topographical properties of the surrounding extracellular matrix (ECM) of tumours. In this study, as a proof of concept, we conducted tumour spheroid dissemination assay on engineered surfaces with micrograting patterns. Nasopharyngeal spheroids were generated by the 3D culture of nasopharyngeal carcinoma (NPC43) cells, a newly established cell line that maintains a high level of Epstein-Barr virus, a hallmark of NPC. Three types of collagen I-coated polydimethylsiloxane (PDMS) substrates were used, with 15 µm deep "trenches" that grated the surfaces: (a) 40/10 µm ridges (R)/trenches (T), (b) 18/18 µm (R/T) and (c) 50/50 µm (R/T). The dimensions of these patterns were designed to test how various topographical cues, different with respect to the size of tumour spheroids and individual NPC43 cells, might affect dissemination behaviours. Spreading efficiencies on all three patterned surfaces, especially 18/18 µm (R/T), were lower than that on flat PDMS surface. The outspreading cell sheets on flat and 40/10 µm (R/T) surfaces were relatively symmetrical but appeared ellipsoid and aligned with the main axes of the 18/18 µm (R/T) and 50/50 µm (R/T) grating platforms. Focal adhesions (FAs) were found to preferentially formed on the ridges of all patterns. The number of FAs per spheroid was strongly influenced by the grating pattern, with the least FAs on the 40/10 µm (R/T) and the most on the 50/50 µm (R/T) substrate. Taken together, these data indicate a previously unknown effect of surface topography on the efficiency and directionality of cancer cell spreading from tumour spheroids, suggesting that topography, like ECM biochemistry and stiffness, can influence the migration dynamics in 3D cell culture models.