A technique for the quantification of the 3D connectivity of thin articulations in Bony sutures

The anatomy and development of cranial and facial sutures have been studied in detail using histological sections, 2D radiographs and more recently CT imaging. However, little attention has been paid to evaluating and quantifying the connectivity of these thin cortical bone articulations. More recent technological advances such as micro-CT imaging has the potential to be used to provide quantitative measurements of 3D connectivity in bony articulations. This study presents a new technique for quantifying the connectivity of bony projections inside cranial and facial sutures using a combination of skeletonization, thinning algorithms and 3D intensity mapping. The technique is demonstrated in five sutures through semi-automated analysis and image processing of μCT scans. In the sagittal, coronal and frontozygomatic sutures an average bone connectivity of 6.6–11.6% was found with multiple bony projections providing an interlocking structure between adjacent bones. Much higher bone connectivity was present in the zygomaticotemporal and zygomaticomaxillary sutures (22.7–37.4%) with few bony projections. This method combining μCT scanning and image processing techniques was successfully used to quantify the connectivity of thin bone articulations and allowed detailed assessment of sutural fusion in 3D. The wider application of this technique may allow quantification of connectivity in other structures, in particular fracture healing of long bones.     

SMER28 Attenuates Dopaminergic Toxicity Mediated by 6-Hydroxydopamine in the Rats via Modulating Oxidative Burdens and Autophagy-Related Parameters

Parkinson’s disease is the second most common neurodegenerative disease that occurs due to cellular autophagy deficiency and the accumulation of alpha-synuclein in the dopaminergic neurons of the substantia nigra pars compacta (SNc) of the brainstem. The SMER28 (also known as 6-Bromo-N-prop-2-enylquinazolin-4-amine) is an autophagy inducer. In this study, the neuroprotective effects of SMER28 were evaluated on autophagy induction, antioxidant system activation, and microgliosis attenuation. The Parkinson’s disease model was developed in the male Wistar rats by injection of 6-OHDA into the left striatum. Apomorphine-induced behavior assessment test and SNc cell counting were performed to investigate the neuroprotective effects of SMER28. This study examined the pharmacological roles of SMER28, especially by focusing on the autophagy (p62/ SQSTM1 and LC3II/LC3I ratio where LC3 is microtubule-associated protein 1A/1B-light chain 3), inhibiting free radicals, and activating the antioxidant system. The levels of malondialdehyde (MDA), reactive oxygen species (ROS), glutathione (GSH), GSH/glutathione peroxidase (GP_X), superoxide dismutase (SOD) activity and nuclear factor-erythroid 2-related factor-2 (Nrf2) were measured to evaluate the antioxidant activity of SMER28. Moreover, Iba-1 (ionized calcium binding adaptor molecule, indicating microgliosis) and tyrosine hydroxylase immunoreactivities were evaluated in the SNc. In the behavioral assessment, SMER28 (50 µg/kg) attenuated damages to the SNc dopaminergic neurons, characterized by improved motor function. The tissue observations revealed that SMER28 prevented the destruction of SNc neurons and attenuated microgliosis as well. It also reduced MDA and ROS production and increased GSH, GP_X, SOD, and Nrf2 activities by inducing autophagy (decreasing p62 and increasing LC3II/LC3I ratio). Consequently, possibly with further studies, it can be considered as a drug for neurodegenerative diseases with proteinopathy etiology.     

Effect of Endobronchial Valve Therapy on Pulmonary Perfusion and Ventilation Distribution

Introduction

Endoscopic lung volume reduction (ELVR) is an emerging therapy for emphysematous COPD. However, any resulting changes in lung perfusion and ventilation remain undetermined. Here, we report ELVR-mediated adaptations in lung perfusion and ventilation, as investigated by means of pulmonary scintigraphy.

Methods

In this observational study, we enrolled 26 patients (64.9±9.4 yrs, 57.7% male) with COPD heterogeneous emphysema undergoing ELVR with endobronchial valves (Zephyr, Pulmonx, Inc.). Mean baseline FEV1 and RV were 32.9% and 253.8% predicted, respectively. Lung scintigraphy was conducted prior to ELVR and eight weeks thereafter. Analyses of perfusion and ventilation shifts were performed and complemented by correlation analyses between paired zones.

Results

After ELVR, target zone perfusion showed a mean relative reduction of 43.32% (p<0.001), which was associated with a significant decrease in target zone ventilation (p<0.001). Perfusion of the contralateral untreated zone and of the contralateral total lung exhibited significant increases post-ELVR (p = 0.002 and p = 0.005, respectively); both correlated significantly with the corresponding target zone perfusion adaptations. Likewise, changes in target zone ventilation correlated significantly with ventilatory changes in the contralateral untreated zone and the total contralateral lung (Pearson’s r: −0.42, p = 0.04 and Pearson’s r: −0.42, p = 0.03, respectively). These effects were observed in case of clinical responsiveness to ELVR, as assessed by changes in the six-minute walk test distance.

Discussion

ELVR induces a relevant decrease in perfusion and ventilation of the treated zone with compensatory perfusional and ventilatory redistribution to the contralateral lung, primarily to the non-concordant, contralateral zone.     

Long bone mesenchymal stem cells (Lb-MSCs): clinically reliable cells for osteo-diseases

Mesenchymal stem cells (MSCs) have been designated as the most reliable cells in clinics to treat osteo-diseases because of their versatile nature. MSCs, isolated from long bone (Lb-MSCs) are rarely reported and named as RIA-MSCs because of the reamer–irrigator–aspirator (RIA) device. The potential of these cells in the treatment of non-union bone fractures made them the ideal candidates to be studied for clinical practices. In this work, effect of cryopreservation on the proliferation and differentiation capabilities of long bone MSCs (Lb-MSCs) has been studied. For this purpose, Lb-MSCs were isolated via RIA device and characterized using flow cytometry and differentiation assays. Cells were cryopreserved for 3, 6 and 12 months and thereafter were characterized using differentiation assays and genetic markers specific for osteogenic, chondrogenic, and adipogenic potential quantitatively by qRT-PCR. Lb-MSCs were found expressing MSC characteristic markers defining their identity. The population doubling time (PDT) was about 2.5 ± 0.5 days and colonies appeared after 7–10 days. Differentiation potential and gene expression of 3, 6 and 12 months cryopreserved Lb-MSCs were unaltered. The results show that cryopreservation did not have an effect on the differentiation potential of human Lb-MSCs. Therefore, our work offers Lb-MSCs as clinically cells for treating osteo-diseases.     

Clustering-neural network models for freeway work zone capacity estimation

Two neural network models, called clustering-RBFNN and clustering-BPNN models, are created for estimating the work zone capacity in a freeway work zone as a function of seventeen different factors through judicious integration of the subtractive clustering approach with the radial basis function (RBF) and the backpropagation (BP) neural network models. The clustering-RBFNN model has the attractive characteristics of training stability, accuracy, and quick convergence. The results of validation indicate that the work zone capacity can be estimated by clustering-neural network models in general with an error of less than 10%, even with limited data available to train the models. The clustering-RBFNN model is used to study several main factors affecting work zone capacity. The results of such parametric studies can assist work zone engineers and highway agencies to create effective traffic management plans (TMP) for work zones quantitatively and objectively.     

Distribution of Metals (Cu,Zn, Pb,and Cd) in Sediments of the Anzali Lagoon,North Iran

Concentrations of four metals (Cu, Zn, Pb, and Cd) in the sediments of the Anzali Lagoon in the northern part of Iran were determined to evaluate the level of contamination and spatial distribution. The sediments were collected from 21 locations in the lagoon. At each lagoon site a core, 60 cm long, was taken. The ranges of the measured concentrations in the sediments are as follows: 17–140 mg kg^?1 for Cu, 20–113 mg kg^?1 for Zn, 1–37 mg kg^?1 for Pb and 0.1–3.5 mg kg^?1 for Cd in surficial (0-20 cm) and 16–87 mg kg^?1 for Cu, 28.5–118 mg kg^?1 for Zn, 3–20 mg kg^?1 for Pb and 0.1–3.5 mg kg^?1 for Cd in deep (40–60 cm) sediments. The results of the geoaccumulation index (I_geo) show that Cd causes moderate to heavy pollution in most of the study area. Environmental risk evaluation showed that the pollution in the Anzali Lagoon is moderate to considerable and the ranking of the contaminants followed the order: Cd > Cu > Pb > Zn. Some locations present severe pollution by metals depending on the sources, of which sewage outlets and phosphate fertilizers are the main sources of contaminants to the area.     

Molecular cytotoxic mechanisms of catecholic polychlorinated biphenyl metabolites in isolated rat hepatocytes

Polychlorinated biphenyl (PCB) and PCB metabolites are highly lipophilic and accumulate easily in the lipid bilayer and fat deposits of the body. The molecular cytotoxic mechanisms of these metabolites are still not understood. The aim of the present study was to compare the cytotoxicity and toxicological properties of six dihydroxylated metabolites using isolated rat hepatocytes. All of the metabolites were more cytotoxic than 4-chlorobiphenyl (4-ClBP) and less cytotoxic than phenyl hydroquinone (PHQ). The order of cytotoxic effectiveness of catecholic metabolites expressed as LC(50) (2h) was 3',4'-diCl-2,3-diOH-biphenyl>PHQ>4'-Cl-2,5-diOH-biphenyl, 4'-Cl-2,3-diOH-biphenyl>2',5'-diCl-3,4-diOH-biphenyl>2',3'-diCl-3,4-diOH-biphenyl>3',4'-diCl-3,4-diOH-biphenyl>4'Cl-3,4-diOH-biphenyl>4'-Cl-biphenyl; showing that the positions of hydroxyl and chlorine groups were important for their hepatotoxicity and that the two 2,3-diOH congeners were the most cytotoxic. Cytotoxicity for 3,4-diOH metabolites correlated with the number and position of chlorine atoms with the more chlorine atoms being more cytotoxic. The cytotoxic order of metabolites with two chlorine atoms being 2',5'>2',3'>3',4'. Borneol, an uridine diphosphate glucuronosyltransferases (UGT) inhibitor, increased the cytotoxicity of all tested metabolites; suggesting that glucuronidation was a major mechanism of elimination of these compounds. On the other hand entacapone, a catechol-O-methyl transferase (COMT) inhibitor, only increased the cytotoxicity of 3',4'-diCl-3,4-diOH-biphenyl, 3',4'-diCl-2,3-diOH-biphenyl and 4'-Cl-2,3-diOH-biphenyl. Hepatocyte GSH was depleted (oxidized and conjugated) by these metabolites before cytotoxicity ensued in a similar order of effectiveness to their cytotoxicity with PHQ being the most effective. Hepatocyte mitochondrial membrane potential also decreased before cytotoxicity ensued with a similar order of effectiveness as their cytotoxicity. These results suggest that catecholic cytotoxicity can be attributed to mitochondrial toxicity and oxidative stress. Semiquinone or benzoquinone species were also important in the cytotoxicity of catecholic metabolites.