Disrupted sleep-wake regulation in the MCI-Park mouse model of Parkinson's disease.

Disrupted sleep has a profound adverse impact on lives of Parkinson's disease (PD) patients and their caregivers. Sleep disturbances are exceedingly common in PD, with substantial heterogeneity in type, timing, and severity. Among the most common sleep-related symptoms reported by PD patients are insomnia, excessive daytime sleepiness, and sleep fragmentation, characterized by interruptions and decreased continuity of sleep. Alterations in brain wave activity, as measured on the electroencephalogram (EEG), also occur in PD, with changes in the pattern and relative contributions of different frequency bands of the EEG spectrum to overall EEG activity in different vigilance states consistently observed. The mechanisms underlying these PD-associated sleep-wake abnormalities are poorly understood, and they are ineffectively treated by conventional PD therapies. To help fill this gap in knowledge, a new progressive model of PD - the MCI-Park mouse - was studied. Near the transition to the parkinsonian state, these mice exhibited significantly altered sleep-wake regulation, including increased wakefulness, decreased non-rapid eye movement (NREM) sleep, increased sleep fragmentation, reduced rapid eye movement (REM) sleep, and altered EEG activity patterns. These sleep-wake abnormalities resemble those identified in PD patients. Thus, this model may help elucidate the circuit mechanisms underlying sleep disruption in PD and identify targets for novel therapeutic approaches.

Influence of Spectroscopic Techniques on the Estimation of the Degree of Conversion of Bulk-fill Composites.

OBJECTIVES: To compare the degree of conversion (DC) of different flowable and sculptable bulk-fill composites (BFC), at 0- and 4-mm depths from the surface, by Fourier transform infrared (FTIR), attenuated total reflection FTIR (ATR-FTIR), and FT-Raman spectroscopic techniques. METHODS AND MATERIALS: Six BFC were investigated, including three sculptable composites (Admira Fusion [Voco], Aura Bulk Fill [SDI], and X-tra Fill [Voco]) and three flowable composites (Venus Bulk Fill [Heraeus], Filtek [3M], and X-tra Base [Voco]). Three molds of each composite were light cured as specified by the manufacturer. For each mold, slices corresponding to 0-mm (surface) and 4-mm depth were analyzed by spectroscopic techniques: ATR-FTIR, FTIR, and FT-Raman. The spectra of uncured composite material were used as an analytical control for background subtraction of the treated composite. The area and amplitude of the reference peaks (1607 and 1637 cm-1) were obtained to calculate the DC percentage at 0- and 4-mm depth. A Kruskal-Wallis nonparametric test was used for materials, and paired comparisons were made using Mann-Whitney nonparametric test. Wilcoxon's rank test was used for comparison between spectroscopic methods and between 0- and 4-mm depth in each composite. Significance was accepted at p<0.05. RESULTS: FTIR showed significantly lower DC values, both in areas and amplitudes of the peaks, when compared with the results reported by different BFC. Differences between the surface and 4-mm depth were detected more precisely by FT-Raman. ATR-FTIR obtained DC values significantly higher than those obtained by FTIR. CONCLUSIONS: The vibrational spectroscopy method significantly influenced DC measurements of the flowable and sculptable BFC explored.

Porous Layered Double Hydroxides Synthesized using Oxygen Generated by Decomposition of Hydrogen Peroxide.

Porous magnesium-aluminium layered double hydroxides (LDH) were prepared through intercalation and decomposition of hydrogen peroxide (H2O2). This process generates oxygen gas nano-bubbles that pierce holes in the layered structure of the material by local pressure build-up. The decomposition of the peroxide can be triggered by microwave radiation or chemically by reaction with iodide (I-) ions. The carbonate LDH version [Mg0.80Al0.20(OH)2](CO3)0.1∙mH2O was synthesized by microwave-assisted urea coprecipitation and further modified by iodide or H2O2 intercalation. High resolution Scanning Electron Microscopy (HR-SEM) and Brunauer-Emmet-Teller (BET) analysis were used to assess the morphology and surface area of the new porous materials. The presence of H2O2 in the interlayer region and later decomposition triggered by microwave radiation generated more pores on the surface of the LDH platelets, increasing their specific surface area from initially 9 m2/g to a maximum of 67 m2/g. X-Ray Diffraction showed that the formation of the pores did not affect the remaining crystal structure, allowing possible further functionalization of the material.

Hypoxic induction of T-type Ca(2+) channels in rat cardiac myocytes: role of HIF-1α and RhoA/ROCK signalling.

T-type Ca(2+) channels are expressed in the ventricular myocytes of the fetal and perinatal heart, but are normally downregulated as development progresses. Interestingly, however, these channels are re-expressed in adult cardiomyocytes under pathological conditions. We investigated low voltage-activated T-type Ca(2+) channel regulation in hypoxia in rat cardiomyocytes. Molecular studies revealed that hypoxia induces the upregulation of Cav 3.2 mRNA, whereas Cav 3.1 mRNA is not significantly altered. The effect of hypoxia on Cav 3.2 mRNA was time- and dose-dependent, and required hypoxia inducible factor-1α (HIF-1α) stabilization. Patch-clamp recordings confirmed that T-type Ca(2+) channel currents were upregulated in hypoxic conditions, and the addition of 50 µm NiCl2 (a T-type channel blocker) demonstrated that the Cav 3.2 channel is responsible for this upregulation. This increase in current density was not accompanied by significant changes in the Cav 3.2 channel electrophysiological properties. The small monomeric G-protein RhoA and its effector Rho-associated kinase I (ROCKI), which are known to play important roles in cardiovascular physiology, were also upregulated in neonatal rat ventricular myocytes subjected to hypoxia. Pharmacological experiments indicated that both proteins were involved in the observed upregulation of the Cav 3.2 channel and the stabilization of HIF-1α that occurred in response to hypoxia. These results suggest a possible role for Cav 3.2 channels in the increased probability of developing arrhythmias observed in ischaemic situations, and in the pathogenesis of diseases associated with hypoxic Ca(2+) overload.

A new water absorbable mechanical Epidermal skin equivalent: the combination of hydrophobic PDMS and hydrophilic PVA hydrogel.

Research on human skin interactions with healthcare and lifestyle products is a topic continuously attracting scientific studies over the past years. It is possible to evaluate skin mechanical properties based on human or animal experimentation, yet in addition to possible ethical issues, these samples are hard to obtain, expensive and give rise to highly variable results. Therefore, the design of a skin equivalent is essential. This paper describes the design and characterization of a new Epidermal Skin Equivalent (ESE). The material resembles the properties of epidermis and is a first approach to mimic the mechanical properties of the human skin structure, variable with the length scale. The ESE is based on a mixture of Polydimethyl Siloxane (PDMS) and Polyvinyl Alcohol (PVA) hydrogel cross-linked with Glutaraldehyde (GA). It was chemically characterized by XPS and FTIR measurements and its cross section was observed by macroscopy and cryoSEM. Confocal Microscope analysis on the surface of the ESE showed an arithmetic roughness (Ra) between 14-16 µm and contact angle (CA) values between 50-60°, both of which are close to the values of in vivo human skins reported in the literature. The Equilibrium Water Content (ECW) was around 33.8% and Thermo Gravimetric Analysis (TGA) confirmed the composition of the ESE samples. Moreover, the mechanical performance was determined by indentation tests and Dynamo Thermo Mechanical Analysis (DTMA) shear measurements. The indentation results were in good agreement with that of the target epidermis reported in the literature with an elastic modulus between 0.1-1.5 MPa and it showed dependency on the water content. According to the DTMA measurements, the ESE exhibits a viscoelastic behavior, with a shear modulus between 1-2.5MPa variable with temperature, frequency and the hydration of the samples.

Robust depth selectivity in mesoscopic scattering regimes using angle-resolved measurements.

We study optical imaging of tissues in the mesoscopic scattering regime in which light multiply scatters in tissues but is not fully diffusive. We use the radiative transport equation to model light propagation and an ℓ1-optimization method to solve the inverse source problem. We show that recovering the location and strength of several point-like sources that are close to each other is not possible when using angle-averaged measurements. The image reliability is limited by a spatial scale that is on the order of the transport mean-free path, even under the most ideal conditions. However, by using just a few angle-resolved measurements, the proposed method is able to overcome this limitation.

Application of statistical experimental design to study the formulation variables influencing the coating process of lidocaine liposomes.

In this paper, we have used statistical experimental design to investigate the effect of several factors in coating process of lidocaine hydrochloride (LID) liposomes by a biodegradable polymer (chitosan, CH). These variables were the concentration of CH coating solution, the dripping rate of this solution on the liposome colloidal dispersion, the stirring rate, the time since the liposome production to the liposome coating and finally the amount of drug entrapped into liposomes. The selected response variables were drug encapsulation efficiency (EE, %), coating efficiency (CE, %) and zeta potential. Liposomes were obtained by thin-layer evaporation method. They were subsequently coated with CH according the experimental plan provided by a fractional factorial (2(5-1)) screening matrix. We have used spectroscopic methods to determine the zeta potential values. The EE (%) assay was carried out in dialysis bags and the brilliant red probe was used to determine CE (%) due to its property of forming molecular complexes with CH. The graphic analysis of the effects allowed the identification of the main formulation and technological factors by the analysis of the selected responses and permitted the determination of the proper level of these factors for the response improvement. Moreover, fractional design allowed quantifying the interactions between the factors, which will consider in next experiments. The results obtained pointed out that LID amount was the predominant factor that increased the drug entrapment capacity (EE). The CE (%) response was mainly affected by the concentration of the CH solution and the stirring rate, although all the interactions between the main factors have statistical significance.