Comparison of FAST and Stroke-112: A randomized study in Taiwan.

BACKGROUND/PURPOSE: FAST and Stroke-112 are two campaigns to reduce the emergency room arrival time of stroke patients. No study has compared the effectiveness of these campaigns. This study aimed to compare recalling capacity of people in these two campaigns. METHODS: A prospective, open-label randomized study was conducted in 2019. Recall ability for the items of the two campaigns on the 5th and 30th days post-education was compared using non-parametric methods. Subject characteristics including age, education level, presence of stroke in co-residents, and habitual language were evaluated using multiple ordered logistic regression. RESULTS: There were 202 participants in FAST group and 193 participants in Stroke-112 group who completed the study. No differences were observed between the two groups in recall ability, either on day 5 or day 30 after receiving education. For both campaigns, recall ability was better for signs in the face (FAST: 87.1%, Stroke-112: 86.5%) and the arm (FAST: 87.1%, Stroke-112: 88.1%) than for abnormality in speech (FAST: 78.7%, Stroke-112: 76.7%) on day 5. Recall ability on day 30 remained the same only for the arm item (FAST: 86.1%, Stroke-112: 88.6%). The recall ability was correlated to education level equal or more than 7 years in FAST group, and was inversely correlated to age and being a stroke patient in Stroke-112 group. CONCLUSION: We found no difference in recall ability between the 2 campaigns. Education level was associated with recallability of FAST, and age and stroke history were associated with recallability of Stroke-112.

Protective Effects of Fucoxanthin on Hydrogen Peroxide-Induced Calcification of Heart Valve Interstitial Cells.

Cardiovascular diseases such as atherosclerosis and aortic valve sclerosis involve inflammatory reactions triggered by various stimuli, causing increased oxidative stress. This increased oxidative stress causes damage to the heart cells, with subsequent cell apoptosis or calcification. Currently, heart valve damage or heart valve diseases are treated by drugs or surgery. Natural antioxidant products are being investigated in related research, such as fucoxanthin (Fx), which is a marine carotenoid extracted from seaweed, with strong antioxidant, anti-inflammatory, and anti-tumor properties. This study aimed to explore the protective effect of Fx on heart valves under high oxidative stress, as well as the underlying mechanism of action. Rat heart valve interstitial cells under H2O2-induced oxidative stress were treated with Fx. Fx improved cell survival and reduced oxidative stress-induced DNA damage, which was assessed by cell viability analysis and staining with propidium iodide. Alizarin Red-S analysis indicated that Fx has a protective effect against calcification. Furthermore, Western blotting revealed that Fx abrogates oxidative stress-induced apoptosis via reducing the expression of apoptosis-related proteins as well as modulate Akt/ERK-related protein expression. Notably, in vivo experiments using 26 dogs treated with 60 mg/kg of Fx in combination with medical treatment for 0.5 to 2 years showed significant recovery in their echocardiographic parameters. Collectively, these in vitro and in vivo results highlight the potential of Fx to protect heart valve cells from high oxidative stress-induced damage.

Integrated Medicine for Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of typical chemotherapeutics among cancer survivors. Despite the recent progress, the effective prevention and treatment strategies for CIPN remain limited. Better understanding of the pathogenesis of CIPN may provide new niches for developing a new ideal therapeutic strategy. This review summarizes the current understanding of CIPN and current recommendations along with completed/active clinical trials and aims to foster translational research to improve the development of effective strategies for managing CIPN.

MHz-ultrasound generation by chirped femtosecond laser pulses from gold nano-colloidal suspensions.

Strong absorption of femtosecond laser pulses in Au nano-colloidal suspensions was used to generate coherent ultrasound signals at 1-20 MHz frequency range. The most efficient ultrasound generation was observed at negative chirp values and was proportional to the pulse duration. Maximization of a dimensionless factor A ≡ αc0tp defined as the ratio of pulse duration tp and the time required for sound at speed c0 to cross the optical energy deposition length (an inverse of the absorption coefficient α) given by 1/(αc0). Chirp controlled pulse duration allows effective enhancement of ultrasound generation at higher frequencies (shorter wavelengths) and is promising for a high spatial resolution acoustic imaging.

Regioisomeric effects on the electronic features of indenothiophene-bridged D-π-A'-A DSSC sensitizers.

Two D-π-A'-A regioisomers (A-IDT-D and D-IDT-A) featuring 4,4'-di-p-tolyl-4 H-indeno[1,2-b]-thiophene as a π linker (π) between the diarylamino donor (D) and the pyrimidine-cyanoacrylic acid acceptor (A'-A) have been successfully synthesized and characterized as efficient sensitizers for the dye-sensitized solar cells (DSSCs). The different arrangements of the D and A'-A blocks on the unsymmetrical indenothiophene (IDT) core render the dipole of IDT being along (A-IDT-D) or opposite (D-IDT-A) to the direction of intramolecular (donor-to-acceptor) charge transfer, and thus induce variations in the physical properties. The experimental observations correlated well with the theoretical analyses, clearly revealing the trade-off between the molar extinction coefficient (ε) and the S0 →S1 transition energy. As a result, a superior ε value was observed for D-IDT-A, whereas a bathochromic shift in the absorption occurred in A-IDT-D. The larger ε value of D-IDT-A together with its more favorable energy level relative to TiO2 led to a higher power conversion efficiency of 7.41 % for the D-IDT-A-based DSSC, retaining approximately 95 % of the N719-based DSSC efficiency. This work manifests the clear structure-property relationship for the case of donor and acceptor components being connected by an unsymmetrical π linker and provides insights for molecular engineering of organic sensitizers.

Unilateral non-lesional temporal lobe epilepsy presenting as isolated ictal vertigo: a case report.

Temporal lobe epilepsy is the most common focal epilepsy syndrome and has a broad spectrum of presentations. Nevertheless, isolated vestibular symptoms without other symptoms typical of temporal lobe seizures are relatively rare. Here, we report one female patient who suffered from chronic refractory vertigo and had inappropriate pharmacotherapy for several years. Eventually, epileptic vertigo and dizziness (ictal vertigo) were accurately diagnosed by detailed history taking and serial examinations assisted by sphenoid electroencephalography. Awareness of this unique syndrome is important in the diagnosis of patients with epileptic vertigo and dizziness.

Organic dyes containing a coplanar indacenodithiophene bridge for high-performance dye-sensitized solar cells.

A series of new organic dyes exploiting coplanar indacenodithiophene as the central π-spacer of the classical donor-(π-spacer)-acceptor configuration were synthesized and characterized for dye-sensitized solar cells. The coplanarity of the indacenodithiophene core facilitates efficient donor to acceptor charge transfer, imparting the new organic dyes significant bathochromic shifts and remarkable power conversion efficiencies of up to 6.7% (DTInDT) under AM 1.5G radiation.

Echocardiographic parameters and indices in 23 healthy Maltese dogs.

BACKGROUND: Echocardiography is a primary tool used by veterinarians to evaluate heart diseases. In recent years, various studies have targeted standard echocardiographic values for different breeds. Reference data are currently lacking in Maltese dogs and it is important to fill this gap as this breed is predisposed to myxomatous mitral valve disease, which is a volume overload disease. OBJECTIVES: To establish the normal echocardiographic parameters for Maltese dogs. METHODS: In total, 23 healthy Maltese dogs were involved in this study. Blood pressure measurements, thoracic radiography, and complete transthoracic echocardiography were performed. The effects of body weight, age and sex were evaluated, and the correlations between weight and linear and volumetric dimensions were calculated by regression analysis. RESULTS: The mean vertebral heart size was 9.1 ± 0.4. Aside from the ejection fraction, fractional shortening, and the left atrial to aorta root ratio, all the other echocardiographic parameters were significantly correlated with weight. CONCLUSION: This study describes normal echocardiographic parameters that may be useful in the echocardiographic evaluation of Maltese dogs.

Organic dyes containing coplanar diphenyl-substituted dithienosilole core for efficient dye-sensitized solar cells.

Two new organic dyes adopting coplanar diphenyl-substituted dithienosilole as the central linkage have been synthesized, characterized, and used as the sensitizers for dye-sensitized solar cells (DSSCs). The best DSSC exhibited a high power conversion efficiency up to 7.6% (TP6CADTS) under AM 1.5G irradiation, reaching approximately 96% of the ruthenium dye N719-based reference cell under the same conditions.

A multifunctional Ni-doped iron pyrite/reduced graphene oxide composite as an efficient counter electrode for DSSCs and as a non-enzymatic hydrogen peroxide electrochemical sensor.

Nickel-doped FeS2/rGO composites were synthesized as multifunctional materials via a facile hydrothermal method. The synthesized materials were characterized with XRD, FESEM, XPS, and TEM-SAED for structural, morphological and chemical studies. To study their electrochemical properties, all the synthesized composites were subjected to cyclic voltammetry tests. The optimum composite revealed high catalytic activity with high peak current density, limiting current, and efficiency of 7.60% for DSSC, which surpassed that of a platinum-based counter electrode (6.69%). The efficiency of the DSSC was significantly supported by interfacial studies and electron lifetime studies, and it exhibited lower charge transfer resistance and higher electron lifetime, respectively. Moreover, the fabricated DSSCs with high efficiency were subjected to transient photo-response studies and showed a stable current response with multiple photo-ON and OFF cycles for a period of 600 s. To broaden the application of the synthesized material, it was used as an electrochemical sensor for the efficient sensing of hydrogen peroxide (H2O2). The sensing electrode was modified with the optimum Ni-doped FeS2/rGO composite, and voltammetric detection was carried out in the hydrogen peroxide concentration range of 4-100 µM. Thus, the synthesized material can be applied in DSSCs and as an electrochemical H2O2 sensor.

Transcranial focused ultrasound pulsation suppresses pentylenetetrazol induced epilepsy in vivo.

BACKGROUND: Epilepsy is a neurological disorder characterized by abnormal neuron discharge, and one-third of epilepsy patients suffer from drug-resistant epilepsy (DRE). The current management for DRE includes epileptogenic lesion resection, disconnection, and neuromodulation. Neuromodulation is achieved through invasive electrical stimulus including deep brain stimulation, vagus nerve stimulation, or responsive neurostimulation (RNS). As an alternative therapy, transcranial focused ultrasound (FUS) can transcranially and non-invasively modulate neuron activity. OBJECTIVE: This study seeks to verify the use of FUS pulsations to suppress spikes in an acute epileptic small-animal model, and to investigate possible biological mechanisms by which FUS pulsations interfere with epileptic neuronal activity. METHODS: The study used a total of 76 Sprague-Dawley rats. For the epilepsy model, rats were administered pentylenetetrazol (PTZ) to induce acute epileptic-like abnormal neuron discharges, followed by FUS exposure. Various ultrasound parameters were set to test the epilepsy-suppressing effect, while concurrently monitoring and analyzing electroencephalogram (EEG) signals. Animal behavior was monitored and histological examinations were conducted to evaluate the hazard posed by ultrasound exposure and the expression of neuronal activity markers. Western blotting was used to evaluate the correlation between FUS-induced epileptic suppression and the PI3K-mTOR signaling pathway. RESULTS: We observed that FUS pulsations effectively suppressed epileptic activity and observed EEG spectrum oscillations; the spike-suppressing effect depended on the selection of ultrasound parameters and highly correlated with FUS exposure level. Expression level changes of c-Fos and GAD65 were confirmed in the cortex and hippocampus, indicating that FUS pulsations deactivated excitatory cells and activated GABAergic terminals. No tissue damage, inflammatory response, or behavioral abnormalities were observed in rats treated with FUS under these exposure parameters. We also found that the FUS pulsations down-regulated the S6 phosphorylation and decreased pAKT expression. CONCLUSION: Our results suggest that pulsed FUS exposure effectively suppresses epileptic spikes in an acute epilepsy animal model, and finds that ultrasound pulsation interferes with neuronal activity and affects the PTZ-induced PI3K-Akt-mTOR pathway, which might help explain the mechanism underlying ultrasound-related epileptic spike control.

Low-frequency dual-frequency ultrasound-mediated microbubble cavitation for transdermal minoxidil delivery and hair growth enhancement.

Ultrasound (US) has been found to rejuvenate and invigorate the hair follicles, increase the size of hair shafts, and promote new hair growth. Our present study found that dual-frequency US-mediated microbubble (MB) cavitation significantly enhanced minoxidil (Mx) delivery in both in vitro and in vivo models, while increasing the hair growth efficacy compared to single-frequency US sonication. The in vitro experiments showed that cavitation activity was enhanced more significantly during dual-frequency sonication than single-frequency sonication in higher concentration of MBs. The pigskin penetration depth in the group in which dual-frequency US was combined with MBs was 1.54 and 2.86 times greater than for single-frequency US combined with MBs and in the control group, respectively; the corresponding increases in the release rate of Mx at 18 hours in in vitro Franz-diffusion-cell experiments were 24.9% and 43.7%. During 21 days of treatment in C57BL/6J mice experiments, the growth rate at day 11 in the group in which dual-frequency US was combined with MBs increased by 2.07 times compared to single-frequency US combined with MBs. These results indicate that dual-frequency US-mediated MB cavitation can significantly increase both skin permeability and transdermal drug delivery. At the same US power density, hair growth was greater in the group with dual-frequency US plus MBs than in the group with single-frequency US plus MBs, without damaging the skin in mice.

A frontier Zn- and N-rich complex grafted onto reduced graphene oxide for the electrocatalysis of dye-sensitized solar cells.

This paper proposes a novel µ-hydroxo-bridged dinuclear macrocyclic zinc complex, {[Zn(C10H20N8)]2(OH)}(BF4)3. The structure was determined by X-ray crystallography: Monoclinic, C2/c, a = 25.4632(6), b = 10.9818(3), c = 15.7522(4) Å, Z = 8, R1 = 0.0233, wR2 = 0.0557, based on reflections I > 2σ(I). The complex was successfully reacted with graphene oxide to form a µ-hydroxo-bridged dinuclear macrocyclic Zn complex/reduced graphene oxide composite. To evenly disperse the Zn- and N-rich complex onto the surface of the reduced graphene oxide, and to enhance the electrocatalytic property of the graphene composites, a soluble molecular grafting method was used here. The graphene-based composites were applied as the counter electrodes (CEs) of dye-sensitized solar cells. Current density-voltage measurements revealed that the conversion efficiency of the GO/Zn (1 : 10) sample was 7.78%, which was better than that of Pt CE (7.49%). GO/Zn (1 : 10) CE exhibited the lowest impedance (RCE = 9.90 Ω), which was better than that of Pt CE (RCE = 66.1 Ω), showing that GO/Zn CEs can reduce the impedance at the CE/electrolyte interface. The proposed method is simple, and the composite materials can potentially replace conventional Pt, optimizing efficiency and reducing production cost.

Focused ultrasound-induced blood brain-barrier opening enhanced vascular permeability for GDNF delivery in Huntington's disease mouse model.

BACKGROUND: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the gene encoding the huntingtin (Htt) protein, which results in a protein containing an abnormally expanded polyglutamine (polyQ) sequence. The expanded polyQ in the Htt protein is toxic to brain cells. No therapy exists to delay disease progression. METHODS: This study describes a gene-liposome system that synergistically applied focused ultrasound (FUS)-blood-brain barrier (BBB) opening for rescuing motor and neuropathological impairments when administered from pre to post-symptomatic transgenic mouse models of HD. DPPC liposomes (LPs) are designed to carry glia cell line-derived neurotrophic factor (GDNF) plasmid DNA (GDNFp) to form a GDNFp-liposome (GDNFp-LPs) complex. Pulsed FUS exposure with microbubbles (MBs) was used to induce BBB opening for non-viral, non-invasive, and targeted gene delivery into the central nervous system (CNS) for therapeutic purposes. RESULTS: FUS-gene therapy significantly improved motor performance with GDNFp-LPs + FUS treated HD mice equilibrating longer periods in the animal behavior. Reflecting the improvements observed in motor function, GDNF overexpression results in significantly decreased formation of polyglutamine-expanded aggregates, reduced oxidative stress and apoptosis, promoted neurite outgrowth, and improved neuronal survival. Immunoblotting and histological staining further confirmed the neuroprotective effect from delivery of GDNF genes to neuronal cells. CONCLUSIONS: This study suggests that the GDNFp-LPs plus FUS sonication can provide an effective gene therapy to achieve local extravasation and triggered gene delivery for non-invasive in vivo treatment of CNS diseases.

Bioresorption behavior of tetracalcium phosphate-derived calcium phosphate cement implanted in femur of rabbits.

One primary focus of the present study was to clarify the crucial resorption-location relationship of a recently developed single-phase TTCP-derived calcium phosphate cement (CPC) implanted in rabbit femur in a systematic and quantitative way. Gross examination of retrieved CPC/bone composite samples indicated that the CPC implant did not evoke inflammatory response, necrosis or fibrous encapsulation in surrounding bony tissues. Histological examination revealed excellent CPC-host bone bonding. At 4 weeks, the resorption-induced voids between terminals of bone defects and implants were largely filled with new bone. CPC resorption, new blood vessels, osteocytes, osteons and osteoblast-like cells lining up with active new bone were observed at remodeling sites. At 12 weeks, a new bone network was developed within femoral defect, while CPC became islands incorporated in the new bone. At this stage, crevices filled with lamellar new bone structure were frequently observed. At 24 weeks, bone ingrowth and remodeling activities became so extensive that the interface between residual cement and new bone became less identifiable. In general, at all implant locations the resorption ratio values increased with implantation time, while at all implantation times the resorption ratios decreased from the exterior (cortical site) to the interior (cancellous site) of implants. At the end of 24 weeks, CPC was almost completely resorbed and bone remodeling almost finished at the cortical site.

Safety evaluation of frequent application of microbubble-enhanced focused ultrasound blood-brain-barrier opening.

Focused ultrasound (FUS) with the presence of microbubbles induces blood brain barrier (BBB) opening in targeted areas and facilitates drug delivery. However, recent studies have indicated that FUS-BBB opening with excessive exposure levels may be associated with inflammatory response and cellular/tissue damage. Multiple weekly FUS exposures have been shown to be safe for human subjects. However the effect of more frequent FUS exposures is still unknown. This study examines whether frequent focused ultrasound blood brain barrier opening is associated with aggravated behavioral, histopathologic change or brain tissue damage. Two protocols of focused ultrasound blood brain barrier opening were devised using different microbubble doses (0.15 µl/kg and 0.4 µl/kg). Focused ultrasound exposure at a threshold level of BBB-opening, below-threshold level, or above level for intracerebral hemorrhage were delivered every 2 days. Animal behavioral and physiological changes were examined and recorded. Brain tissue was examined for hemorrhage and apoptosis. Results indicate that frequent exposure of excessive focused ultrasound (1.4 mechanical index) produced minor and short-term behavioral changes despite significant tissue damage, while frequent BBB opening with threshold or below-threshold FUS exposure (0.33-0.8 mechanical index) did not cause behavioral or histological change. Immunofluorescent examination of rat brain tissue indicated that excessive doses of microbubble administration induce an apparent cellular apoptotic response, which may be exacerbated by intracerebral hemorrhage. Experimental results suggest that frequent focused ultrasound blood brain barrier opening with sufficient ultrasound exposure level and a microbubble dose can be safe and pose minimal risk to brain tissue.

Metabolomic assessment of arsenite toxicity and novel biomarker discovery in early development of zebrafish embryos.

CONTEXT: Arsenic poisoning commonly occurs through exposure to water contaminated with arsenic and causes long-term symptoms. Of all the arsenic derivatives, arsenite is the one of the most toxic compounds. However, the toxicity of arsenite during developmental stages is still unclear. OBJECTIVE: In this study, we performed a metabolomic analysis of arsenite responses in embryonic zebrafish. MATERIALS AND METHODS: Embryonic zebrafish were used as an animal model in this study. They were exposed to sodium arsenite under different concentrations (0.5, 1.0, 2.0, and 5.0 mg/L) in 24 h, 48 h and 72 h post fertilization. Changes in morphology were observed through a light microscope. Changes in metabolomics were identified using an ultraperformance liquid chromatography quadrupole time-of-flight system. RESULTS: The IC50 range was 0.75 ±â€¯0.25 mg/L. Compared with the control group, the embryonic lethality rate decreased to 33.3% under 1.0 mg/L of arsenite treatment, whereas it decreased to 20.0% under 2.0 mg/L of arsenite treatment. Numerous body axis curvatures were also observed under treatment with 2.0 and 5.0 mg/L of arsenic. Pericardium and yolk sac edema were randomly discovered and found to worsen over time. Moreover, the 10 metabolites with the highest variable importance in projection score were identified as potential biomarkers for arsenic exposure. CONCLUSION: Arsenic exposure not only leads to a change in the morphology of embryonic zebrafish but also disturbs the metabolism of zebrafish in early developmental stages.

Image-Guided Focused-Ultrasound CNS Molecular Delivery: An Implementation via Dynamic Contrast-Enhanced Magnetic-Resonance Imaging.

Focused ultrasound (FUS) exposure with microbubbles can transiently open the blood-brain barrier (BBB) to deliver therapeutic molecules into CNS tissues. However, delivered molecular distribution/concentration at the target need to be controlled. Dynamic Contrast-Enhanced Magnetic-Resonance Imaging (DCE-MRI) is a well-established protocol for monitoring the pharmacokinetic/pharmacodynamic behavior of FUS-BBB opening. This study investigates the feasibility of using DCE-MRI to estimate molecular CNS penetration under various exposure conditions and molecule sizes. In the 1st stage, a relationship among the imaging index Ktrans, exposure level and molecular size was calibrated and established. In the 2nd stage, various exposure levels and distinct molecules were applied to evaluate the estimated molecular concentration discrepancy with the quantified ones. High correlation (r2 = 0.9684) between Ktrans and transcranial mechanical index (MI) implies Ktrans can serve as an in vivo imaging index to mirror FUS-BBB opening scale. When testing various molecules with the size ranging 1-149 kDa, an overall correlation of r2 = 0.9915 between quantified and predicted concentrations was reached, suggesting the established model can provide reasonably accurate estimation. Our work demonstrates the feasibility of estimating molecular penetration through FUS-BBB opening via DCE-MRI and may facilitate development of FUS-induced BBB opening in brain drug delivery.

Design and Implementation of a Transmit/Receive Ultrasound Phased Array for Brain Applications.

Focused ultrasound phased array systems have attracted increased attention for brain therapy applications. However, such systems currently lack a direct and real-time method to intraoperatively monitor ultrasound pressure distribution for securing treatment. This study proposes a dual-mode ultrasound phased array system design to support transmit/receive operations for concurrent ultrasound exposure and backscattered focal beam reconstruction through a spherically focused ultrasound array. A 256-channel ultrasound transmission system was used to transmit focused ultrasonic energy (full 256 channels), with an extended implementation of multiple-channel receiving function (up to 64 channels) using the same 256-channel ultrasound array. A coherent backscatter-received beam formation algorithm was implemented to map the point spread function (PSF) and focal beam distribution under a free-field/transcranial environment setup, with the backscattering generated from a strong scatterer (a point reflector or a microbubble-perfused tube) or a weakly scattered tissue-mimicking graphite phantom. Our results showed that PSF and focal beam can be successfully reconstructed and visualized in free-field conditions and can also be transcranially reconstructed following skull-induced aberration correction. In vivo experiments were conducted to demonstrate its capability to preoperatively and semiquantitatively map a focal beam to guide blood-brain barrier opening. The proposed system may have potential for real-time guidance of ultrasound brain intervention, and may facilitate the design of a dual-mode ultrasound phased array for brain therapeutic applications.

Gamma-radiation-induced changes in structure and properties of tetracalcium phosphate and its derived calcium phosphate cement.

The purpose of the present study was to investigate the gamma-radiation effect on the structure and properties of the single-phase tetracalcium phosphate (TTCP) powder and its derived calcium phosphate cement (CPC). Experimental results show that low-dosed (0-30 kGy) CPC has a setting time of 10-12 min, while high-dosed (40-120 kGy) CPC has a setting time of 8-10 min. The low dose gamma-radiation does not significantly change porosity volume fraction or compressive strength of the CPC. The pH values of all CPC samples fell in a relatively narrow band, with a band width of 8.5-9.1 (in terms of pH value). With a dose of 10 or 20 kGy gamma-radiation, the TTCP-apatite conversion ratio does not change much. With 30 kGy the conversion ratio significantly increases and reaches a maximum value. With further increases in dose, the conversion ratio quickly declines. With increasing gamma-ray dose, the CPC morphology becomes more porous/loose and apatite particles become larger in size. When exposed to a high dose (120 kGy) of gamma-radiation, TTCP structure is radiation-damaged, and gamma-ray-induced formation of apatite is confirmed by transmission electron microscopic/selected-area diffraction/lattice imaging analyses.