The consistency of invasive and non-invasive arterial blood pressure for the assessment of dynamic cerebral autoregulation in NICU patients

BackgroundStudies of the clinical application of dynamic cerebral autoregulation show considerable variations, and differences in blood pressure devices may be one of the reasons for this variation. Few studies have examined the consistency of invasive and non-invasive arterial blood pressure for evaluating cerebral autoregulation. We attempted to investigate the agreement between invasive and non-invasive blood pressure methods in the assessment of dynamic cerebral autoregulation with transfer function analysis.MethodsContinuous cerebral blood flow velocity and continuous invasive and non-invasive arterial blood pressure were simultaneously recorded for 15 min. Transfer function analysis was applied to derive the phase shift, gain and coherence function at all frequency bands from the first 5, 10, and 15 min of the 15-min recordings. The consistency was assessed with Bland–Altman analysis and intraclass correlation coefficient.ResultsThe consistency of invasive and noninvasive blood pressure methods for the assessment of dynamic cerebral autoregulation was poor at 5 min, slightly improved at 10 min, and good at 15 min. The values of the phase shift at the low-frequency band measured by the non-invasive device were higher than those measured with invasive equipment. The coherence function values measured by the invasive technique were higher than the values derived from the non-invasive method.ConclusionBoth invasive and non-invasive arterial blood pressure methods have good agreement in evaluating dynamic cerebral autoregulation when the recording duration reaches 15 min. The phase shift values measured with non-invasive techniques are higher than those measured with invasive devices. We recommend selecting the most appropriate blood pressure device to measure cerebral autoregulation based on the disease, purpose, and design

A Strategy for Discovery and Verification of Candidate Biomarkers in Cerebrospinal Fluid of Preclinical Alzheimer’s Disease

Alzheimer’s disease (AD), a progressive neurodegenerative disease, is characterized by the accumulation of senile plaques, neurofibrillary tangles, and loss of synapses and neurons in the brain. The pathophysiological process of AD begins with a long asymptomatic phase, which provides a potential opportunity for early therapeutic intervention. Therefore, it is crucial to define putative biomarkers via reliable and validated methods for early diagnosis of AD. Here, we characterized candidate biomarkers by discovery proteomics analysis of cerebrospinal fluid (CSF), revealing that 732 and 704 proteins with more than one unique peptide were identified in healthy controls and preclinical AD patients, respectively. Among them, 79 and 98 proteins were significantly altered in preclinical AD for women and men, respectively, many of which have been demonstrated with consistent regulation pattern in patients with mild cognitive impairment or AD dementia. In-house developed 5-plex isotopic N,N-dimethyl leucine (iDiLeu) tags were further utilized to verify candidate biomarkers, neurosecretory protein VGF (VGF) and apolipoprotein E (apoE). By labeling peptide standards with different iDiLeu tags, a four-point internal calibration curve was constructed to allow for determination of the absolute amount of target analytes in CSF through a single liquid chromatography-mass spectrometry run

Molecular Programming of Biodegradable Nanoworms via Ionically Induced Morphology Switch toward Asymmetric Therapeutic Carriers

Engineering biodegradable nanostructures with precise morphological characteristics is a key objective in nanomedicine. In particular, asymmetric (i.e., nonspherical) nanoparticles are desirable due to the advantageous effects of shape in a biomedical context. Using molecular engineering, it is possible to program unique morphological features into the self-assembly of block copolymers (BCPs). However, the criteria of biocompatibility and scalability limit progress due to the prevalence of nondegradable components and the use of toxic solvents during fabrication. To address this shortfall, a robust strategy for the fabrication of morphologically asymmetric nanoworms, comprising biodegradable BCPs, has been developed. Modular BCPs comprising poly (ethylene glycol)-block-poly(caprolactone-gradient-trimethylene carbonate) (PEG−PCLgTMC), with a terminal chain of quaternary ammonium-TMC (PTMC-Q), undergo self-assembly via direct hydration into well-defined nanostructures. By controlling the solution ionic strength during hydration, particle morphology switches from spherical micelles to nanoworms (of varying aspect ratio). This ionically-induced switch is driven by modulation of chain packing with salts screening interchain repulsions, leading to micelle elongation. Nanoworms can be loaded with cytotoxic cargo (e.g., doxorubicin) at high efficiency, preferentially interact with cancer cells, and increase tumor penetration. This work showcases the ability to program assembly of BCPs and the potential of asymmetric nanosystems in anticancer drug delivery

First detection of Cryptosporidium spp. in red-bellied tree squirrels (Callosciurus erythraeus) in China

Cryptosporidium spp. are opportunistic pathogens that cause diarrhea in a variety of animal hosts. Although they have been reported in many animals, no information has been published on the occurrence of Cryptosporidium spp. in red-bellied tree squirrels (Callosciurus erythraeus). A total of 287 fecal specimens were collected from Sichuan province in China; the prevalence of Cryptosporidium spp., measured by nested-PCR amplification of the partial small-subunit (SSU) rRNA gene, was 1.4% (4/287). Three different Cryptosporidium species or genotypes were identified: Cryptosporidium parvum (n = 1), Cryptosporidium wrairi (n = 1), and Cryptosporidium rat genotype II (n = 2). The present study is the first report of Cryptosporidium infection in red-bellied tree squirrels in China. Although there is a relatively low occurrence of Cryptosporidium, the presence of C. parvum and C. wrairi, which were previously reported in humans, indicates that red-bellied tree squirrels may be a source of zoonotic cryptosporidiosis in China

A Strategy for Discovery and Verification of Candidate Biomarkers in Cerebrospinal Fluid of Preclinical Alzheimer’s Disease

Alzheimer’s disease (AD), a progressive neurodegenerative disease, is characterized by the accumulation of senile plaques, neurofibrillary tangles, and loss of synapses and neurons in the brain. The pathophysiological process of AD begins with a long asymptomatic phase, which provides a potential opportunity for early therapeutic intervention. Therefore, it is crucial to define putative biomarkers via reliable and validated methods for early diagnosis of AD. Here, we characterized candidate biomarkers by discovery proteomics analysis of cerebrospinal fluid (CSF), revealing that 732 and 704 proteins with more than one unique peptide were identified in healthy controls and preclinical AD patients, respectively. Among them, 79 and 98 proteins were significantly altered in preclinical AD for women and men, respectively, many of which have been demonstrated with consistent regulation pattern in patients with mild cognitive impairment or AD dementia. In-house developed 5-plex isotopic N,N-dimethyl leucine (iDiLeu) tags were further utilized to verify candidate biomarkers, neurosecretory protein VGF (VGF) and apolipoprotein E (apoE). By labeling peptide standards with different iDiLeu tags, a four-point internal calibration curve was constructed to allow for determination of the absolute amount of target analytes in CSF through a single liquid chromatography-mass spectrometry run

Accurate Characterization of the Properties of the Rare-Earth-Doped Crystal for Laser Cooling

We present a method for calibrating a commercial thermal camera adopted to accurately measure the temperature change of the sample in a laser-induced temperature modulation spectrum (LITMoS) test, which is adopted for measuring two crucial parameters of the external quantum efficiency ηext and the background absorption coefficient αb for assessing the laser cooling grade of the rare-earth-doped materials. After calibration, the temperature resolution of the calibrated thermal camera is better than 0.1 K. For the cooling grade Czochralski-grown 5% Yb3+:LuLiF4 crystal, the corresponding values of ηext and αb are LITMoS = measured to be ηext=99.4 (±0.1)% and αb=1.5 (±0.1)×10−4 cm−1, respectively

Accurate Characterization of the Properties of the Rare-Earth-Doped Crystal for Laser Cooling

We present a method for calibrating a commercial thermal camera adopted to accurately measure the temperature change of the sample in a laser-induced temperature modulation spectrum (LITMoS) test, which is adopted for measuring two crucial parameters of the external quantum efficiency ηext and the background absorption coefficient αb for assessing the laser cooling grade of the rare-earth-doped materials. After calibration, the temperature resolution of the calibrated thermal camera is better than 0.1 K. For the cooling grade Czochralski-grown 5% Yb3+:LuLiF4 crystal, the corresponding values of ηext and αb are LITMoS = measured to be ηext=99.4 (±0.1)% and αb=1.5 (±0.1)×10−4 cm−1, respectively

Supersaturation induced by Itraconazole/Soluplus® micelles provided high GI absorption in vivo

To investigate the effect of supersaturation induced by micelle formation during dissolution on the bioavailability of itraconazole (ITZ)/Soluplus® solid dispersion. Solid dispersions prepared by hot melt extrusion (HME) were compressed into tablets directly with other excipients. Dissolution behavior of ITZ tablets was studied by dissolution testing and the morphology of micelles in dissolution media was studied using transmission electron microscopy (TEM). Drug transferring from stomach into intestine was simulated to obtain a supersaturated drug solution. Bioavailability studies were performed on the ITZ tablets and Sporanox® in beagle dogs. The morphology of micelles in the dissolution media was observed to be spherical in shape, with an average size smaller than 100 nm. The supersaturated solutions formed by Soluplus® micelles were stable and no precipitation took place over a period of 180 min. Compared with Sporanox®, ITZ tablets exhibited a 2.50-fold increase in the AUC(0–96) of ITZ and a 1.95-fold increase in its active metabolite hydroxyitraconazole (OH-ITZ) in the plasma of beagle dogs. The results obtained provided clear evidence that not only the increase in the dissolution rate in the stomach, but also the supersaturation produced by micelles in the small intestine may be of great assistance in the successful development of poorly water-soluble drugs. The micelles formed by Soluplus® enwrapped the molecular ITZ inside the core which promoted the amount of free drug in the intestinal cavity and carried ITZ through the aqueous boundary layer (ABL), resulting in high absorption by passive transportation across biological membranes. The uptake of intact micelles through pinocytosis together with the inhibition of P-glycoprotein-mediated drug efflux in intestinal epithelia contributed to the absorption of ITZ in the gastrointestinal tract. These results indicate that HME with Soluplus®, which can induce supersaturation by micelle formation, may be of great assistance to the successful development of poorly water-soluble drugs