CNS involvement in CMTX1 caused by a novel connexin 32 mutation: a 6-year follow-up in neuroimaging and nerve conduction.

X-linked Charcot-Marie-Tooth disease, type 1 (CMTX1) is one of the most common inherited neurological disorders. Obvious CNS involvement is relatively rare in CMTX1 patients. A 24-year-old male with CMTX1 presented with three transient stroke-like attacks, and was followed up regularly for 6 years with brain MRI and electrophysiological examination. Transient symmetrical high signals on T2 imaging and restricted diffusion were found in bilateral deep white matter. Electrophysiological measurement revealed a sensorimotor peripheral neuropathy with slightly reduced nerve conduction velocities. A novel thymine to cytosine mutation at nucleotide position 445 in the connexin 32 allele of the GJB1 gene was identified. During the 6-year longitudinal study, patient's motor and sensory function did not worsen; radiological abnormalities correlated with episodes of CNS dysfunction and resolved after clinical recovery; electrophysiological records showed no obvious change. Little change in the patient's clinical, radiological and electrophysiological results over the follow-up reflected a slow disease progression.

Poly (dextrogyr-levogyr) lactide acid-triiodothyronine scaffold for peripheral nerve regeneration.

OBJECTIVES: To evaluate the poly(dextrogyr-levogyr) lactide acid-triiodothyronine (PDLLA-T3) seeded with Schwann cells conduit for repairing sciatic nerve defect. MATERIALS & METHODS: The rats were divided into three groups: autologous nerve transplantation (Group A), PDLLA-T3 + Schwann cells (Group B) and PDLLA + Schwann cells (Group C). RESULTS: Myelin sheath thickness was significantly greater in Group A compared with Group B and Group C. The regenerated nerves had nearly normal structure in Group A, and in Groups B and C nerve tissues filled in the anastomotic site and angiogenesis was noted. The mean number of myelinated nerve fibers and neurons in Group B was greater than in Group C. CONCLUSIONS: PDLLA-T3 is superior to PDLLA alone for repairing nerve defects.

Anti-Escherichia coli O157:H7 properties of purple prairie clover and sainfoin condensed tannins.

Condensed tannins (CT) from purple prairie clover (PPC; Dalea purpurea Vent.) and sainfoin (SF; Onobrychis viciifolia) were assessed for anti-Escherichia coli activity by comparing their ability to react with proteins and liposome, cause cell aggregation, and alter outer membrane (OM) morphology and permeability. The PPC CT had greater (P < 0.01) protein-precipitating capacity than SF CT using either bovine serum albumin or ribulose 1,5-disphosphate carboxylase as model proteins. Minimum inhibitory concentration of PPC CT for two strains of E. coli and five strains of E. coli O157:H7 was four to six times lower than that of SF CT. E. coli exposed to 10 µg/mL of both CT had higher (P < 0.05) OM permeability than controls and was greater (P < 0.05) for PPC than for SF CT. Addition of both CT at 50 and 200 µg/mL caused cell aggregation which was more evident (P < 0.05) for PPC than for SF CT. Transmission electron microscopy showed electron dense material on the cell surface when cells were exposed to 50 µg/mL of PPC CT. The greater anti-E. coli activity of PPC than SF CT was due to its enhanced ability to precipitate protein that increased OM permeability and promoted cell aggregation.

[Abundances and Morphology Patterns of Microplastics Under Different Land Use Types on the Loess Plateau].

As an emerging pollutant to the environment, microplastics have received widespread attention worldwide. The Loess Plateau, as one of the major agricultural production areas in China, has various land use types, but how the abundance and morphological patterns of microplastics differ among soils under different land use types remains unclear. In this study, we collected soils from three different land use types:croplands, apple orchards, and landfills in the Wangdonggou Catchment. Microplastics were separated and extracted using a modified density centrifugation method, and the abundance, composition, and morphological characteristics of the soil were analyzed and characterized using a laser infrared imaging system. The results showed that the average abundance of microplastics in the Wangdonggou Catchment was 4715 n·kg-1, mainly composed of PET, PU, and alkyd varnish(ALK), respectively accounting for 30.39%, 29.58%, and 8.42%. More than 80% of the microplastics were fragmented, and more than 60% of the microplastics were of a size ≤ 50 µm. The average abundance of microplastics varied significantly among land use types:cropland soil (7550 n·kg-1)>apple orchard soil (3440 n·kg-1)>landfill soil (2283 n·kg-1). The average area, width, height, eccentricity, circularity, and other morphological characteristics of microplastics in apple orchard soil were significantly different from those in the cropland and landfill soil.

A novel mutation of gap junction protein ß 1 gene in X-linked Charcot-Marie-Tooth disease.

INTRODUCTION: In this study we report a novel mutation in the gap junction protein beta 1 (GJB1) gene of a Chinese X-linked Charcot-Marie-Tooth disease (CMTX1) family, which has specific electrophysiological characteristics. METHODS: Twenty members in the family were studied by clinical neurological examination and GJB1 gene mutation analysis, and 3 patients were studied electrophysiologically. The proband and his mother also underwent sural nerve biopsy. RESULTS: All patients have the CMT phenotype, except for 2 asymptomatic carriers. Electrophysiological examinations showed non-uniform slowing of motor conduction velocities and partial motor conduction blocks and temporal dispersion. Sural nerve biopsy confirmed a predominantly demyelinating neuropathy, and an Asn2Lys mutation in the amino-terminal domain was found in 9 members of this family, but not in 25 normal controls in the family. CONCLUSIONS: This family represents a novel mutation in the GJB1 form of CMTX1. The mutation in the amino-terminus has an impact on the electrophysiological characteristics of the disease.

[Chemical Characteristics and Causes of Groups Water in Niangziguan Spring].

Discharge in Niangziguan Spring is 7.19 m3·s-1, which is the main water supply source for Yangquan City and Pingding County. Every year, Yangquan municipal government take water from the mouth of Niangziguan Spring to supply drinking water to urban residents at a rate of approximately 1.7 m3·s-1. It is of great significance to determine the characteristics and causes of variations in spring water flow conditions for the appropriate utilization of water resources and pollution prevention. Here, sample collection and hydrochemical isotope analyses were undertaken for the Niangziguan Spring area to chemically characterize the water environment and genesis. The pH of the karst spring is 7.2-7.5 with an average of 7.36; the calcium content of the water is 112.1-135.2 mg·L-1 with a mean value of 131.4 mg·L-1; the concentration of magnesium ions is 34.8-42.3 mg·L-1 with an average of 40.8 mg·L-1; the concentration of K++Na- ions is 41.6-46.7 mg·L-1 with an average of 45.2 mg·L-1; and the sulfate ion concentration is 185.6-271.8 mg·L-1 with a mean value of 255.4 mg·L-1. The hydrochemical type of the aquifer is classified as HCO3·SO4-Ca·Mg. The spring water is characterized by high Ca2+, Mg2+, and SO42- concentrations, and low Na+, K+, and Cl- concentrations. The supply path of Chengxi Spring is shortest followed by Wulong Spring. The supply paths of the remaining five spring are much longer. The Niangziguan Spring water environment is characterized by increasing pollution from coal mine acid drainage alongside decreasing inputs from domestic sewage. Environmental isotope tracing shows that sulfate in Chengxi Spring mainly derives from precipitation and gypsum dissolution, and the concentrations of sulfate in Wulong Spring are increasing. These changes are mainly driven by the amount of coal mine acid water pollution in the area.

Microarray analysis using disiloxyl 70mer oligonucleotides.

DNA microarray technology has evolved dramatically in recent years, and is now a common tool in researchers' portfolios. The scope of the technique has expanded from small-scale studies to extensive studies such as classification of disease states. Technical knowledge regarding solid phase microarrays has also increased, and the results acquired today are more reliable than those obtained just a few years ago. Nevertheless, there are various aspects of microarray analysis that could be improved. In this article we show that the proportions of full-length probes used significantly affects the results of global analyses of transcriptomes. In particular, measurements of transcripts in low abundance are more sensitive to truncated probes, which generally increase the degree of cross hybridization and loss of specific signals. In order to improve microarray analysis, we here introduce a disiloxyl purification step, which ensures that all the probes on the microarray are at full length. We demonstrate that when the features on microarrays consist of full-length probes the signal intensity is significantly increased. The overall increase in intensity enables the hybridization stringency to be increased, and thus enhance the robustness of the results.

A Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer.

PURPOSE: Platinum resistance in ovarian cancer is associated with epigenetic modifications. Hypomethylating agents (HMA) have been studied as carboplatin resensitizing agents in ovarian cancer. This randomized phase II trial compared guadecitabine, a second-generation HMA, and carboplatin (G+C) against second-line chemotherapy in women with measurable or detectable platinum-resistant ovarian cancer. PATIENTS AND METHODS: Patients received either G+C (guadecitabine 30 mg/m2 s.c. once-daily for 5 days and carboplatin) or treatment of choice (TC; topotecan, pegylated liposomal doxorubicin, paclitaxel, or gemcitabine) in 28-day cycles until progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS); secondary endpoints were RECIST v1.1 and CA-125 response rate, 6-month PFS, and overall survival (OS). RESULTS: Of 100 patients treated, 51 received G+C and 49 received TC, of which 27 crossed over to G+C. The study did not meet its primary endpoint as the median PFS was not statistically different between arms (16.3 weeks vs. 9.1 weeks in the G+C and TC groups, respectively; P = 0.07). However, the 6-month PFS rate was significantly higher in the G+C group (37% vs. 11% in TC group; P = 0.003). The incidence of grade 3 or higher toxicity was similar in G+C and TC groups (51% and 49%, respectively), with neutropenia and leukopenia being more frequent in the G+C group. CONCLUSIONS: Although this trial did not show superiority for PFS of G+C versus TC, the 6-month PFS increased in G+C treated patients. Further refinement of this strategy should focus on identification of predictive markers for patient selection.

[Clinical study of lumbar fusion by hybrid construct of stem cells technique and biodegradable material].

OBJECTIVE: To explorer the effectiveness of enriched bone marrow stem cells technique for lumbar fusion. METHODS: With the randomization and control principles, 2 graft materials [Enrichment bone marrow mesenchymal stem cells hybridized with beta-tri calcium phosphate (composite graft group), autologous iliac crest bone graft (autograft group)] were compared in posterior lumbar fusion procedures. 56 patients with degenerative disc disease, lumbar instability or spinal stenosis, were included. The volume of cells suspension in pre- and post-enrichment and the number of nucleated cells (NCs) were identified. The number of osteoprogenitor cells was estimated by counting the colony-forming units which express alkaline phosphatase (CFUs/ALP+). Then the efficiency of the enrichment was evaluated. Clinical follow-up with roentgenogram and Oswestry scale scores was performed for outcome evaluation. RESULTS: (249 +/- 31) ml bone marrow per patient from bilateral iliac crests was aspirated peri-operatively. About (43 +/- 11) ml enriched bone marrow was collected. The number of NCs was concentrated from (15.9 +/- 3.3) x 10(6)/ml to (44.1 +/- 10.8) x 10(6)/ml, CFUs/ALP+ was significantly increased from (118 +/- 86)/ml to(486 +/- 305)/ml. The follow-up was about (26.3 +/- 7.5) months. There was no significant differences in age, gender, disease and fusion segments between the two groups. The fusion rate was 93.3% and 96.2% for composite graft group and autograft group, respectively (chi2 = 0.2146, P = 0.6432). There was no difference in operation time between the two group (t = 0.5243, P = 0.6022), but blood loss in composite graft group was more than that in autograft group (t = 6.4664, P < 0.01). Cell salvage for auto-transfusion could transfuse back half of the blood loss during operation. No hematoma or chronic soreness in the bone marrow donor sites of composite graft group occurred, but a little exudation or moderate swelling in the wound happened in 4 cases which disappeared under medical treatment. Meanwhile, 15.4% patients had hematoma in the iliac bone donor site and 26.9% patients had chronic soreness, but no case had wound problem in autograft group. As for Oswestry scale scores, there was no significant difference between the two groups. CONCLUSIONS: The enrichment technique of autologous bone marrow stem cells can greatly increase the concentration of MSCs. It is a rapid and safe method used peri-operatively. The composite material of enriched MSCs and porous beta-TCP is a good bone substitute in posterior spinal fusion.

Maxillary sinus floor elevation with a tissue-engineered bone composite of deciduous tooth stem cells and calcium phosphate cement in goats.

The study aimed to assess the effect of maxillary sinus floor elevation with tissue-engineered bone constructed from deciduous tooth stem cells (DTSCs) and calcium phosphate cement (CPC). The stem cells from goat deciduous teeth (SGDs) were isolated and transfected by means of the adenovirus with an enhanced green fluorescent protein gene (AdEGFP). As many as 18 bilateral maxillary sinuses of nine goats were randomly allocated into three groups (n = 6/group): group A (SGDs-CPC compound), group B (CPC alone) and group C (autogenous bone obtained from an iliac crest). All the samples were evaluated by computed tomography (CT), histology and histomorphometric analysis. Furthermore, the fate of implanted SGDs was traced using an immunohistochemical staining method in the decalcified samples. SGDs might be differentiated into osteoblasts in an osteogenic medium. In the present study, three-dimensional CT analysis showed that the volume of newly formed bone in group A was greater than that in the other two groups. After a healing period of 3 months, sequential analyses of triad-colour fluorescence labelling, histology and histomorphology indicated that the SGDs-CPC compound primarily promoted bone formation and mineralization at 2 and 3 months after the operation. Moreover, the areas of new bone formation in elevated sinuses were 41.82 ± 6.24% in the SGDs-CPC group, which was significantly higher than the 30.11 ± 8.05% in the CPC-alone group or the 23.07 ± 10.21% in the autogenous bone group. Immunohistochemical staining revealed that GFP and OCN were both expressed in the new bone tissue for the samples with eGFP, which suggested that the implanted SGDs might have contributed to new bone formation on the elevated sinus floor. SGDs can promote new bone formation and maturation in the goat maxillary sinus, and the tissue-engineered bone composite of SGDs and CPC might be a potential substitute for existing maxillary sinus floor elevation methods. Copyright © 2014 John Wiley & Sons, Ltd.

Effects of site-specific polyethylene glycol modification of recombinant human granulocyte colony-stimulating factor on its biologic activities.

BACKGROUND: Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is a long-chain cytokine that is administered to stimulate the production of white blood cells (WBCs) to reduce the risk of serious infection in immunocompromized patients. However, to achieve sustained stimulation of WBC production, rhG-CSF must be administered frequently, thus limiting its clinical use. METHODS: We conjugated rhG-CSF with linear monomethoxy-polyethylene glycol (PEG) maleimide at amino acid residue Cys(17) to test our hypothesis that this could extend the in vivo half-life of rhG-CSF in blood. RESULTS: The mono-PEG rhG-CSF became more stable to pH, temperature, and enzyme degradation in vitro, and had granulopoietic activity that was superior to the unmodified form in vivo. The granulopoietic activity of PEG-G-CSF was 2.82-fold greater than that of unmodified G-CSF. CONCLUSIONS: These results indicate that the thiol-specific PEGylation remarkably prolonged the half-life of rhG-CSF and represents a novel strategy to address the more clinically acceptable therapeutic application of hemopoietic growth factor.

Materials and surface modification for tissue engineered vascular scaffolds.

Although vascular implantation has been used as an effective treatment for cardiovascular disease for many years, off-the-shelf and regenerable vascular scaffolds are still not available. Tissue engineers have tested various materials and methods of surface modification in the attempt to develop a scaffold that is more suitable for implantation. Extracellular matrix-based natural materials and biodegradable polymers, which are the focus of this review, are considered to be suitable materials for production of tissue-engineered vascular grafts. Various methods of surface modification that have been developed will also be introduced, their impacts will be summarized and assessed, and challenges for further research will briefly be discussed.

Block copolymer lithography of rhodium nanoparticles for high temperature electrocatalysis.

We present a method for forming ordered rhodium nanostructures on a solid support. The approach makes use of a block copolymer to create and assemble rhodium chloride nanoparticles from solution onto a surface; subsequent plasma and thermal processing are employed to remove the polymer and fully convert the nanostructures to metallic rhodium. Films cast from a solution of the triblock copolymer poly(styrene-b-2-vinyl pyridine-b-ethylene oxide) dissolved in toluene with rhodium(III) chloride hydrate were capable of producing a monolayer of rhodium nanoparticles of uniform size and interparticle spacing. The nanostructures were characterized by scanning electron microscopy, X-ray photoelectron spectroscopy, and atomic force microscopy. The electrocatalytic performance of the nanoparticles was investigated with AC impedance spectroscopy. We observed that the addition of the particles to a model solid oxide fuel cell anode provided up to a 14-fold improvement in the anode activity as evidenced by a decrease in the AC impedance resistance. Examination of the anode after electrochemical measurement revealed that the basic morphology and distribution of the particles were preserved.

[Preliminary study of akermanite's effect on stem cells from goat deciduous teeth in proliferation and osteogenic differentiation].

PURPOSE: To explore the characters of attachment, proliferation and osteogenic differentiation of stem cells from goat deciduous teeth (SGDs) cultured on akermanite ceramic. METHODS: SGDs were collected with enzyme digestion, and cultured. Under culture condition in growth medium, actin filament labeling and CCK-8 analysis were used to reveal attachment and proliferation. Expression level of alkaline phosphatase (ALP) and osteogenic differentiation genes (ALP, COL I, OPN and OCN) were examined by pNPP method and real-time PCR. The data was analyzed using SPSS 13.0 software package. RESULTS: Compared with ß-TCP, SGDs seeded on akermanite ceramic not only spread out better, but also grew faster since day 4. In osteogenic medium, cells of akermanite group had stronger ALP activity at day 4 and 7. The gene expression of akermanite was more than the ß-TCP group. The gene OCN expression level increased significantly at day 7 (P<0.01). CONCLUSIONS: SGDs can attach and grow well on akermanite ceramic. Compared with ß-TCP, akermanite ceramic shows an advantage in osteogenic differentiation of SGDs.

Entrapment and release difference resulting from hydrogen bonding interactions in niosome.

In this study the influence of hydrogen bonding interaction between niosomal membrane and solutes on the drug loading and release was investigated. Salicylic acid (SA) and p-hydroxyl benzoic acid (p-BA) were selected as models. Niosomes were prepared with 1:1 molar ratios of various surfactants and cholesterol by film hydration technique, and the corresponding formulation variables were optimized to achieve the maximum entrapment efficiencies (EE%). The EE% of different formulations followed the trend Span 60>Span 40>Span 20>Span 80. Additionally, it was also found that the EE% of p-BA was much higher than that of SA. This difference may be due to the formation of hydrogen bond between p-BA and niosomal membrane, and the corresponding interaction diagram has been proposed and confirmed indirectly by UV spectroscopy method. The quantitative analysis of hydrogen binding interaction between solutes and niosome has been finished firstly, and the corresponding entrapment equilibrium constant K has been calculated as well. Moreover, in vitro the release of both drugs from niosomes was examined in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF), respectively. The results indicated that the release of p-BA in SIF was much slower than that in SGF, and the release rate of SA in SGF is apparently slower than that in SIF. The possible mechanism was given as well.

[Experimental study on stem cells from goat deciduous teeth compounded with porous calcium phosphate cement for ectopic osteogenesis].

PURPOSE: To observe the biocompatibility and ectopic bone-like tissue formation of stem cells from goat deciduous teeth (SGDs) with porous calcium phosphate cement (pCPC). METHODS: The expression of STRO-1 on SGDs was measured with flow cytometry (FCM); the 4th passage SGDs were cultured in induced-mineralization medium in vitro for 7 days. Combined with pCPC, the adhesion and growth of the compounds were observed with scanning electron microscopy (SEM); the ectopic bone-like tissue formation was observed 8 weeks after the compounds implanted subcutaneously into the nude mice. RESULTS: On the third day of SGDs compounded with pCPC, SEM verified that the cells adhered closely and tightly with pCPC, protruded pseudopods and secreted matrix. 8 weeks after the compounds implanted in ectopic sites, HE staining confirmed the formation of bone-like tissue; Immunohistochemistry showed the strongly positive expression of OCN protein in the implanted materials. CONCLUSIONS: SGDs may differentiate into osteoblast and are potential to induce bone matrix formation; combined with pCPC, the compounds may generate bone-like tissue.

[Application of multislice helical computed tomography in maxillofacial distraction osteogenesis].

OBJECTIVE: To develop the method and investigate the value of the application of multislice helical computed tomography (CT) in the maxillofacial distraction osteogenesis. METHODS: Twelve cases of maxillofacial distraction osteogenesis (3 in zygoma, 2 in maxilla, and 7 in mandible) were scanned by the multislice helical CT, then the reconstruction of three dimensional and fault image and the relative measurement were carried out to study the effect of distraction and osteogenesis. RESULTS: The three dimensional image provided clear and high resolution stereoscopic view that the effect of distraction osteogenesis could be evaluated easily and exactly. The fault image could be set up in private computer by Mimics and the measurements, such as distance, thickness and density, could be performed as expected. The effect of 12 cases was satisfied, and the average distracted distance was 16.73 mm. CONCLUSION: Basing on multislice helical CT scanning, the high resolution image reconstruction and relative measurement data could be obtained which could meet the need of clear and direct observation. Its application in the maxillofacial distraction osteogenesis is expecting and promising.