Nonspherical ultrasound microbubbles.

Surface tension provides microbubbles (MB) with a perfect spherical shape. Here, we demonstrate that MB can be engineered to be nonspherical, endowing them with unique features for biomedical applications. Anisotropic MB were generated via one-dimensionally stretching spherical poly(butyl cyanoacrylate) MB above their glass transition temperature. Compared to their spherical counterparts, nonspherical polymeric MB displayed superior performance in multiple ways, including i) increased margination behavior in blood vessel-like flow chambers, ii) reduced macrophage uptake in vitro, iii) prolonged circulation time in vivo, and iv) enhanced blood-brain barrier (BBB) permeation in vivo upon combination with transcranial focused ultrasound (FUS). Our studies identify shape as a design parameter in the MB landscape, and they provide a rational and robust framework for further exploring the application of anisotropic MB for ultrasound-enhanced drug delivery and imaging applications.

Correlation Between the Peripheral Neuropathy and Levels of hs-CRP, IL-1ß and IL-6 in Senile Parkinson's Disease Patients.

This study was carried out to investigate the correlation between the onset of peripheral neuropathy and levels of hypersensitive C-reactive protein (hs-CRP), interleukin 1ß (IL-1ß) and IL-6 in senile Parkinson's disease (PD) patients. For this purpose, a total of 60 PD patients and 60 age-matched healthy subjects were enrolled in this study and received the assessment for peripheral nerves by using the quantified method. Besides, levels of hs-CRP, IL-1ß and IL-6 in serum were determined to analyze the correlation between the clinical features, including the severity of PD and cognitive decline, and the levels of hs-CRP, IL-1ß and IL-6. Results showed that PD patients had more cases of peripheral neuropathy than those in the healthy control group. Levels of hs-CRP, IL-1ß and IL-6 in the serum of PD patients were much higher than those in the healthy control (P<0.05). Besides, PD patients had lower scores of MMSE and MoCA but higher CNPI scores when compared to the healthy control group. As a result, we found that the severity of peripheral neuropathy was in a positive correlation with the levels of hs-CRP, IL-1ß and IL-6. It was concluded that PD patients generally have peripheral neuropathy that may correlate with the increases in the levels of hs-CRP, IL-1ß and IL-6, and early intervention may mitigate the development and progression of peripheral neuropathy.

Capability of phytoremediation of glyphosate in environment by Vulpia myuros.

Glyphosate is an herbicide extensively used worldwide that can remain in the soil. Phytoremediation to decontaminate polluted water or soil requires a plant that can accumulate the target compound. Vulpia myuros is an annual fescue that can be used as a heavy mental phytoremediation strategy. Recently, it has been used to intercrop with tea plant to prohibit the germination and growth of other weeds in tea garden. In order to know whether it can be used an decontaminating glyphosate' plant in water or soil, in this study, glyphosate degradation behavior was investigated in Vulpia myuros cultivated in a hydroponic system. The results showed that the concentration of glyphosate in the nutrient solution decreased from 43.09 µg mL-1 to 0.45 µg mL-1 in 30 days and that 99% of the glyphosate molecules were absorbed by V. myuros. The contents of glyphosate in the roots reached the maximum (224.33 mg kg-1) on day 1 and then decreased. After 3 days, the content of glyphosate in the leaves reached the highest value (215.64 mg kg-1), while it decreased to 156.26 mg kg-1 in the roots. The dissipation dynamics of glyphosate in the whole hydroponic system fits the first-order kinetic model C = 455.76e-0.21 t, with a half-life of 5.08 days. Over 30 days, 80% of the glyphosate was degraded. The contents of the glyphosate metabolite amino methyl phosphoric acid (AMPA), ranged from 0.103 mg kg-1 on day 1-0.098 mg kg-1 on day 30, not changing significantly over time. The Croot/solution, Cleaf/solution and Cleaf/root were used to express the absorption, transfer, and distribution of glyphosate in V. myuros. These results indicated that glyphosate entered into the root system through free diffusion, which was influenced by both the log Kow and the concentration of glyphosate in the nutrient solution, and that glyphosate was either easily transferred to the leaves through the transpiration stream, accumulated, or degraded. The degradation of glyphosate in V. myuros indicated that it has potential as a remediating plant for environmental restoration.

Bioaccumulation and biomagnification effects of nano-TiO2 in the aquatic food chain.

The increasing production of nano-TiO2 has attracted extensive concerns about the ecological consequence and health risk of these compounds in natural ecosystem. However, little is known about its toxicity on zooplankton, especially its possibility to access to the food chain via dietary exposure. To address this concern, the toxic and cumulative effects of nano-TiO2 on an aquatic food chain were explored through two trophic levels independently or jointly including producer and consumer. The results revealed that exposure to suspensions of nanomaterials had negative effects on both producers and consumers. Specifically, nanoparticles reduced the density of algal cells in a concentration-dependent way, and hatching life expectancy, average lifespan, net reproductive rate, and population intrinsic growth rate of rotifers decreased significantly with the concentration of nanomaterials increased (P < 0.05). Notably, nanoparticles accumulated in algal cells and were transferred to consumers through dietary exposure. Biomagnification of nano-TiO2 was observed in this simplified food chain, as many of the biomagnification factor (BMF) values in this study were >1. Exposure concentration, exposure time and their interactions play a strong part in the accumulation of nanoparticles in algae and rotifers. Overall, the present findings confirmed that nano-TiO2 was deleterious to plankton, posing a significant environmental threat to aquatic ecosystems. Graphical abstract.

Identification of functional lncRNAs based on competing endogenous RNA network in osteoblast differentiation.

Adult human mesenchymal stem cells have the potential to differentiate into osteoblast, which plays crucial roles in bone regeneration and repair. Some transcriptional factors (TFs), such as BMP-2 and RUNX2, have been demonstrated to control the differentiation processes. It is important to discover more key regulators in osteoblast differentiation. Recently, some studies found long noncoding RNAs (lncRNAs) participating in osteoblast differentiation, such as MALAT1, DANCR, and ANCR. In this study, we performed a network-based computational analysis to investigate the lncRNA-messenger RNA (mRNA) crosstalks via integrating microRNA (miRNA)-RNA interactions, gene coexpression, and protein-protein interactions. First, multiple topology analyses were performed to osteoblast-differentiation-related lncRNA-mRNA network (ODLMN). Several lncRNAs with central topology structures were identified as key regulators. Results showed that these lncRNAs participated in osteoblast differentiation via phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase, and Ras signals. Previous studies have demonstrated that lncRNAs exert functions by involving in close modules. Second, after performing module searching in ODLMN, two functional modules were identified, which played crucial roles through involving in PI3K/protein kinase B, cyclic adenosine 3',5'-monophosphate, and hypoxia-inducible factor 1 pathways. Third, a subset of core lncRNA-TF crosstalks that might form feedback loops to control the biological processes in osteoblast differentiation was identified. These core lncRNA-TF feedback loops showed more TF binding affinity than other lncRNAs. All these results can help us to uncover the molecular mechanism and provide new targets for bone regeneration and repair.

Shock Exfoliation of Graphene Fluoride in Microwave.

An unprecedented microwave-based strategy is developed to facilitate solid-phase, instantaneous delamination and decomposition of graphite fluoride (GF) into few-layer, partially fluorinated graphene. The shock reaction occurs (and completes in few seconds) under microwave irradiation upon exposing GF to either "microwave-induced plasma" generated in vacuum or "catalyst effect" caused by intense sparking of graphite at ambient conditions. A detailed analysis of the structural and compositional transformations in these processes indicates that the GF experiences considerable exfoliation and defluorination, during which sp2 -bonded carbon is partially recovered despite significant structural defects being introduced. The exfoliated fluorinated graphene shows excellent electrochemical performance as anode materials in potassium ion batteries and as catalysts for the conversion of O2 to H2 O2 . This simple and scalable method requires minimal energy input and does not involve the use of other chemicals, which is attractive for extensive research in fluorine-containing graphene and its derivatives in laboratories and industrial applications.

Closed-loop control of targeted ultrasound drug delivery across the blood-brain/tumor barriers in a rat glioma model.

Cavitation-facilitated microbubble-mediated focused ultrasound therapy is a promising method of drug delivery across the blood-brain barrier (BBB) for treating many neurological disorders. Unlike ultrasound thermal therapies, during which magnetic resonance thermometry can serve as a reliable treatment control modality, real-time control of modulated BBB disruption with undetectable vascular damage remains a challenge. Here a closed-loop cavitation controlling paradigm that sustains stable cavitation while suppressing inertial cavitation behavior was designed and validated using a dual-transducer system operating at the clinically relevant ultrasound frequency of 274.3 kHz. Tests in the normal brain and in the F98 glioma model in vivo demonstrated that this controller enables reliable and damage-free delivery of a predetermined amount of the chemotherapeutic drug (liposomal doxorubicin) into the brain. The maximum concentration level of delivered doxorubicin exceeded levels previously shown (using uncontrolled sonication) to induce tumor regression and improve survival in rat glioma. These results confirmed the ability of the controller to modulate the drug delivery dosage within a therapeutically effective range, while improving safety control. It can be readily implemented clinically and potentially applied to other cavitation-enhanced ultrasound therapies.

Experimental investigation of large-scale flow structures in an aircraft cabin mock-up.

The purpose of this study was to investigate the influence of large-scale circulation on the flow field in a cabin mockup. The velocity was measured by ultrasonic anemometers (UA). Then, this study analyzed the turbulence kinetic energy spectra of the velocity fluctuation signal. The turbulence kinetic energy spectra of the measurement points reflect the flow characteristic of the large-scale circulation in the cabin mockup. The results contribute to the understanding of the role of the thermal plume on the large-scale circulation in the cabin. The large-scale circulation's impact on air quality was also investigated, and the contaminant distribution was measured using tracer gas in the cabin. The two large-scale circulation interactions made the air flow mixing approximately uniform.

The neurovascular response is attenuated by focused ultrasound-mediated disruption of the blood-brain barrier.

Focused ultrasound (FUS)-induced disruption of the blood-brain barrier (BBB) is a non-invasive method to target drug delivery to specific brain areas that is now entering into the clinic. Recent studies have shown that the method has several secondary effects on local physiology and brain function beyond making the vasculature permeable to normally non-BBB penetrant molecules. This study uses functional MRI methods to investigate how FUS BBB opening alters the neurovascular response in the rat brain. Nine rats underwent actual and sham FUS induced BBB opening targeted to the right somatosensory cortex (SI) followed by four runs of bilateral electrical hind paw stimulus-evoked fMRI. The neurovascular response was quantified using measurements of the blood oxygen level dependent (BOLD) signal and cerebral blood flow (CBF). An additional three rats underwent the same FUS-BBB opening followed by stimulus-evoked fMRI with high resolution BOLD imaging and BOLD imaging of a carbogen-breathing gas challenge. BOLD and CBF measurements at two different stimulus durations demonstrate that the neurovascular response to the stimulus is attenuated in both amplitude and duration in the region targeted for FUS-BBB opening. The carbogen results show that the attenuation in response amplitude, but not duration, is still present when the signaling mechanism originates from changes in blood oxygenation instead of stimulus-induced neuronal activity. There is some evidence of non-local effects, including a possible global decrease in baseline CBF. All effects are resolved by 24 h after FUS-BBB opening. Taken together, these results suggest that FUS-BBB opening alters that state of local brain neurovascular physiology in such a way that hinders its ability to respond to demands for increased blood flow to the region. The mechanisms for this effect need to be elucidated.

Modulation of brain function by targeted delivery of GABA through the disrupted blood-brain barrier.

The technology of transcranial focused ultrasound (FUS) enables a novel approach to neuromodulation, a tool for selective manipulation of brain function to be used in neurobiology research and with potential applications in clinical treatment. The method uses transcranial focused ultrasound to non-invasively open the blood-brain barrier (BBB) in a localized region such that a systemically injected neurotransmitter chemical can be delivered to the targeted brain site. The approach modulates the chemical signaling that occurs in and between neurons, making it complimentary to most other neuromodulation techniques that affect the electrical properties of neuronal activity. Here, we report delivering the inhibitory neurotransmitter GABA to the right somatosensory cortex of the rat brain during bilateral hind paw electrical stimulation and measure the inhibition of activation using functional MRI (fMRI). In a 2 × 2 factorial design, we evaluated conditions of BBB Closed vs BBB Open and No GABA vs GABA. Results from fMRI measurements of the blood oxygen level-dependent (BOLD) signal show: 1) intravenous GABA injection without FUS-mediated BBB opening does not have an effect on the BOLD response; 2) FUS-mediated BBB opening alone significantly alters the BOLD signal response to the stimulus, both in amplitude and shape of the time course; 3) the combination of FUS-mediated BBB opening and GABA injection further reduces the peak amplitude and spatial extent of the BOLD signal response to the stimulus. The data support the thesis that FUS-mediated opening of the BBB can be used to achieve non-invasive delivery of neuroactive substances for targeted manipulation of brain function.

Geographical traceability of Chinese green tea using stable isotope and multi-element chemometrics.

RATIONALE: Deliberate and fraudulent origin mislabeling of Chinese green tea motivated by large price differences often brings significant food safety risks and damages consumer trust. Currently, there is no reliable method to verify the origin of green tea produced in China. Stable isotope and multi-element analyses combined with statistical models are widely acknowledged as useful traceability techniques for many agro-products, and could be developed to confirm the geographical origin of Chinese green tea and, more importantly, combat illegal green tea mislabeling and fraud. METHODS: An analytical strategy combining elemental analyzer/isotope ratio mass spectrometry (EA/IRMS) and inductively plasma coupled mass spectrometry (ICP-MS) with chemometrics tools was used to confirm the origin of green tea grown in the main tea production provinces around China. Stable C, N, H, O isotope ratios and twenty elements were measured to build mathematical discriminant models using unsupervised principal component analysis (PCA) and supervised linear discriminant analysis (LDA). Two main problems: (i) tracing the origin of Chinese green tea from different tea growing provinces (Zhejiang, Shandong, and other provinces); (ii) authentication of high-value Westlake Longjing tea from the Westlake region and surrounding areas in Zhejiang province, were investigated and assessed. RESULTS: The results demonstrated that PCA and follow-up LDA based on stable isotope and multi-element signatures can verify the geographical origin of Chinese green tea from different provinces, and even localized zones in the same province could be distinguishable, with discrimination accuracies higher than 92.3% and 87.8%, respectively. CONCLUSIONS: Geochemical fingerprinting techniques coupled with chemometric tools offer an accurate and effective verification method for the geographical origin of Chinese green tea, providing a promising tool to combat fraudulent mislabeling of high-value green tea.

Influence of leaf age, species and soil depth on the authenticity and geographical origin assignment of green tea.

RATIONALE: Stable isotope fractionation occurring during leaf growth provides internal characteristics for identifying the geographical origin, traceability and authentication of tea. Studying the influence of leaf age, species and the relationship with the cultivated soil may reveal previously undocumented stable isotope fractionation mechanisms, and provide a deeper understanding of the physiological isotopic effects on the tractability and authentication accuracy of green tea to combat mislabeling and fraudulent conduct. METHODS: A total of 36 pairs of young (one bud with one leaf) and mature growth (older leaf) samples from two species of Longjing tea (Longjing #43 and Colonial cultivar) and corresponding cultivation soil samples from two different depth layers (0-20 cm and 20-40 cm) were collected in Westlake district, Hangzhou, Zhejiang province, China. Four stable isotope ratios (δ13 C, δ15 N, δ2 H, and δ18 O values) were measured using an elemental analyzer coupled with an isotope ratio spectrometer. Linear correlation and one-way analysis of variance (ANOVA) statistical analyses were performed to investigate isotopic fractionation mechanisms during plant growth, and reflect the dynamic physiological processes from soil to leaf. RESULTS: The carbon and nitrogen isotope ratios (δ13 C and δ15 N values) reflected the absorption, migration and fractionation of carbon dioxide and nitrogenous nutrients during photosynthesis, nutrient uptake, nitrogen fixation and leaf respiration. The water isotope ratios (δ2 H and δ18 O values) reflected the use and fractionation of water by tea plants at different growth stages. CONCLUSIONS: Considerable differences were found for hydrogen and oxygen isotope ratios according to leaf age, revealing complex isotopic fractionation mechanisms and possible interference factors. Leaf maturity effects should be considered, as they will influence the precision and accuracy of models when assigning the geographical origin, traceability and authentication of tea.

Focused ultrasound induced opening of the blood-brain barrier disrupts inter-hemispheric resting state functional connectivity in the rat brain.

Focused ultrasound (FUS) is a technology capable of delivering therapeutic levels of energy through the intact skull to a tightly localized brain region. Combining the FUS pressure wave with intravenously injected microbubbles creates forces on blood vessel walls that open the blood-brain barrier (BBB). This noninvasive and localized opening of the BBB allows for targeted delivery of pharmacological agents into the brain for use in therapeutic development. It is possible to use FUS power levels such that the BBB is opened without damaging local tissues. However, open questions remain related to the effects that FUS-induced BBB opening has on brain function including local physiology and vascular hemodynamics. We evaluated the effects that FUS-induced BBB opening has on resting state functional magnetic resonance imaging (rs-fMRI) metrics. Data from rs-fMRI was acquired in rats that underwent sham FUS BBB vs. FUS BBB opening targeted to the right primary somatosensory cortex hindlimb region (S1HL). FUS BBB opening reduced the functional connectivity between the right S1HL and other sensorimotor regions, including statistically significant reduction of connectivity to the homologous region in the left hemisphere (left S1HL). The effect was observed in all three metrics analyzed: functional connectivity between anatomically defined regions, whole brain voxel-wise correlation maps based on anatomical seeds, and spatial patterns from independent component analysis. Connectivity metrics for other regions where the BBB was not perturbed were not affected. While it is not clear whether the effect is vascular or neuronal in origin, these results suggest that even safe levels of FUS BBB opening have an effect on the physiological processes that drive the signals measured by BOLD fMRI. As such these effects must be accounted for when carrying out studies using fMRI to evaluate the effects of pharmacological agents delivered via FUS-induced BBB opening.

An innovative personalized displacement ventilation system for airliner cabins.

In airliner cabins, mixing ventilation systems with gaspers are not efficient in controlling contaminant transport. To improve the cabin environment, this investigation proposed an innovative ventilation system that would reduce contaminant transport and maintain thermal comfort. We manufactured and installed the proposed ventilation system in an occupied seven-row, single-aisle aircraft cabin mockup. Air velocity, air temperature, and contaminant distribution in the cabin mockup were obtained by experimental measurements. The investigation used the experimental data to validate the results of CFD simulation. The validated CFD program was then used to study the impact of the locations and number of exhausts on contaminant removal and thermal comfort in a one-row section of a fully occupied Boeing-737 cabin. Although the diffusers in the proposed system were close to the passengers' legs, the air velocity magnitude was acceptable in the lower part of the cabin and the leg area. The proposed system provided an acceptable thermal environment in the cabin, although passengers could feel cold when placing their legs directly in front of the diffusers. The four-exhaust configuration of the new ventilation system was the best, and it decreased the average exposure in the cabin by 57% and 53%, respectively, when compared with the mixing and displacement ventilation systems.

Cross-resistance patterns to acetolactate synthase (ALS)-inhibiting herbicides of flixweed (Descurainia sophia L.) conferred by different combinations of ALS isozymes with a Pro-197-Thr mutation or a novel Trp-574-Leu mutation.

Acetolactate synthase (ALS) is the common target of ALS-inhibiting herbicides, and target-site ALS mutations are the main mechanism of resistance to ALS-inhibiting herbicides. In this study, ALS1 and ALS2 genes with full lengths of 2004bp and 1998bp respectively were cloned in individual plants of susceptible (S) or resistant (R) flixweed (Descurainia sophia L.) populations. Two ALS mutations of Pro-197-Thr and/or Trp-574-Leu were identified in plants of three R biotypes (HB24, HB30 and HB42). In order to investigate the function of ALS isozymes in ALS-inhibiting herbicide resistance, pHB24 (a Pro-197-Thr mutation in ALS1 and a wild type ALS2), pHB42 (a Trp-574-Leu mutation in ALS1 and a wild type ALS2) and pHB30 (a Trp-574-Leu mutation in ALS1 and a Pro-197-Thr mutation in ALS2) subpopulations individually homozygous for different ALS mutations were generated. Individuals of pHB30 had mutations in each isozyme of ALS and had higher resistance than pHB24 and pHB42 populations containing mutations in only one ALS isozyme. Moreover, the pHB24 had resistance to SU, TP and SCT herbicides, whereas pHB24 and pHB42 had resistance to these classes of herbicides as well as IMI and PTB herbicides. The sensitivity of isolated ALS enzyme to inhibition by herbicides in these populations correlated with whole plant resistance levels. Therefore, reduced ALS sensitivity resulting from the mutations in ALS was responsible for resistance to ALS-inhibiting herbicides in flixweed.

High-resolution renal perfusion mapping using contrast-enhanced ultrasonography in ischemia-reperfusion injury monitors changes in renal microperfusion.

Alterations in renal microperfusion play an important role in the development of acute kidney injury with long-term consequences. Here we used contrast-enhanced ultrasonography as a novel method for depicting intrarenal distribution of blood flow. After infusion of microbubble contrast agent, bubbles were collapsed in the kidney and postbubble destruction refilling was measured in various regions of the kidney. Local perfusion was monitored in vivo at 15, 30, 45, 60 minutes and 24 hours after 28 minutes of bilateral ischemia in 12 mice. High-resolution, pixel-by-pixel analysis was performed on each imaging clip using customized software, yielding parametric perfusion maps of the kidney, representing relative blood volume in each pixel. These perfusion maps revealed that outer medullary perfusion decreased disproportionately to the reduction in the cortical and inner medullary perfusion after ischemia. Outer medullary perfusion was significantly decreased by 69% at 60 minutes postischemia and remained significantly less (40%) than preischemic levels at 24 hours postischemia. Thus, contrast-enhanced ultrasonography with high-resolution parametric perfusion maps can monitor changes in renal microvascular perfusion in space and time in mice. This novel technique can be translated to clinical use in man.

Assessment of heavy metal pollution in vegetables and relationships with soil heavy metal distribution in Zhejiang province, China.

There are increasing concerns on heavy metal contaminant in soils and vegetables. In this study, we investigated heavy metal pollution in vegetables and the corresponding soils in the main vegetable production regions of Zhejiang province, China. A total of 97 vegetable samples and 202 agricultural soil samples were analyzed for the concentrations of Cd, Pb, As, Hg, and Cr. The average levels of Cd, Pb, and Cr in vegetable samples [Chinese cabbage (Brassica campestris spp. Pekinensis), pakchoi (Brassica chinensis L.), celery (Apium graveolens), tomato (Lycopersicon esculentum), cucumber (Colletotrichum lagenarium), cowpea (Vigna unguiculata), pumpkin (Cucurbita pepo L.), and eggplant (Solanum melongena)] were 0.020, 0.048, and 0.043 mg kg(-1), respectively. The Pb and Cr concentrations in all vegetable samples were below the threshold levels of the Food Quality Standard (0.3 and 0.5 mg kg(-1), respectively), except that two eggplant samples exceeded the threshold levels for Cd concentrations (0.05 mg kg(-1)). As and Hg contents in vegetables were below the detection level (0.005 and 0.002 mg kg(-1), respectively). Soil pollution conditions were assessed in accordance with the Chinese Soil Quality Criterion (GB15618-1995, Grade II); 50 and 68 soil samples from the investigated area exceeded the maximum allowable contents for Cd and Hg, respectively. Simple correlation analysis revealed that there were significantly positive correlations between the metal concentrations in vegetables and the corresponding soils, especially for the leafy and stem vegetables such as pakchoi, cabbage, and celery. Bio-concentration factor values for Cd are higher than those for Pb and Cr, which indicates that Cd is more readily absorbed by vegetables than Pb and Cr. Therefore, more attention should be paid to the possible pollution of heavy metals in vegetables, especially Cd.

[Research Progress on Forensic Toxicology of Z-drugs].

The Z-drugs (zolpidem, zopiclone, and zaleplon), as the innovative hypnotics, have an improvement over the traditional benzodiazepines in the management of insomnia. Z-drugs have significant hypnotic effects by reducing sleep latency and improving sleep quality, though duration of sleep may not be significantly increased. As benzodiazepines, Z-drugs exert their effects through increasing the transmission of γ-aminobutyric acid. Z-drugs overdose are less likely to be fatal, more likely would result in poisoning. Z-drugs can be detected in blood, urine, saliva, and other postmortem specimens through liquid chromatography-mass spectrometry techniques. Zolpidem and zaleplon exhibit significant postmortem redistribution. Z-drugs have improved pharmacokinetic profiles, but incidence of neuropsychiatric sequelae, poisoning, and death may prove to be similar to the other hypnotics. This review focuses on the pharmacology and toxicology of Z-drugs with respect to their adverse effect profile and toxicity and toxicology data in the field of forensic medicine.

Association of variants in KCNK17 gene with ischemic stroke and cerebral hemorrhage in a Chinese population.

BACKGROUND: KCNK17 (potassium channel, subfamily K, member17) has a role in the pathogenesis of stroke. We reported previously that rs10947803 single-nucleotide polymorphism (SNP) in KCNK17 is associated with cerebral hemorrhage in a Chinese population. The aim of the present study was to examine other SNPs in the KCNK17 gene that are associated with cerebral hemorrhage and other subtypes of stroke in the Chinese population. METHODS: A total of 1356 subjects with stroke and 1225 control patients were examined by a case-control methodology. The SNPs (rs12214600, rs12195376, rs2758912, and rs10807204) in KCNK17 gene were genotyped with the TaqMan real-time polymerase chain reaction assay. RESULTS: rs12214600 SNP in KCNK17 was significantly associated with cerebral hemorrhage (unadjusted odds ratio = .55, 95% confidence interval = .35-.86, P = .008, q = .0328) under the allele model. After adjusting for age, sex, and hypertension, we found that the association remained significant (odds ratio = .56, 95% confidence interval = .35-.90, P = .0158). There was no association detected for other SNPs in KCNK17 with cerebral hemorrhage, and none of the SNPs in KCNK17 had an association with ischemic stroke. CONCLUSIONS: The T carrier of an SNP (rs12214600) is associated with reduced risk of cerebral hemorrhage in the Chinese population, together with previous findings that SNPs rs10947803 and rs12214600 in the KCNK17 gene are associated with hemorrhagic stroke, but none of the SNPs tested had an association with ischemic stroke. KCNK17 may be important in the pathogenesis of cerebral hemorrhage.

The impact of pulse repetition frequency on microbubble activity and drug delivery during focused ultrasound-mediated blood-brain barrier opening.

Objective.Pulsed focused ultrasound (FUS) can deliver therapeutics to the brain by using intravenous microbubbles (MBs) to open the blood-brain barrier (BBB). MB emissions indicate treatment outcomes, like BBB opening (harmonics) and damage (broadband). Typically, a pulse repetition frequency (PRF) of 1 Hz is used, but the effect of PRF on MBs is not fully understood. We investigated the effect of PRF on MB activity and tracer delivery.Approach.The effect of PRF (0.125, 0.25, 0.5, 1, and 2 Hz) on MB activity was monitored through harmonic and wideband emissions during FUS sonications of the rat brain at 274.3 kHz. BBB opening was quantified through fluorescence imaging to estimate the concentration of Trypan Blue (TB) dye following a 75-pulse FUS exposure for PRFs of 1 and 0.25 Hz.Main results.At a fixed acoustic pressure, the percentage change in maximum harmonic amplitude compared to the control (PRF = 1 Hz) decreased with increasing PRF, with a median change of 73.8% at 0.125 Hz and -38.3% at 2 Hz. There was no difference in the pressure threshold for broadband emissions between PRFs of 0.25 and 1 Hz. PRF = 0.25 Hz, led to a 68.2% increase in the mean concentration of TB measured after FUS, with a 53.9% increase in the mean harmonic sum, compared with PRF = 1 Hz. Harmonic emissions-based control at PRF = 0.25 Hz yielded similar TB delivery, with less damage at histology, compared with 1 Hz.Significance.For a fixed number of FUS pulses, reducing the PRF was shown to increase the magnitude of harmonic emissions and TB delivery, but not the threshold for broadband emissions. While further research is necessary to understand the mechanisms involved, these results may be useful to improve clinical safety margins and sensitivity to detecting small harmonic signals from cavitating MBs.