Transcriptional cyclin dependent kinases (CDKs) regulate RNA polymerase II initiation and elongation as well as co-transcriptional mRNA processing. In this report, we describe an important role for CDK12 in the epidermal growth factor (EGF)-induced c-FOS proto-oncogene expression in mammalian cells. This kinase was found in exon junction complexes (EJCs) together with SR proteins and was thus recruited to RNA polymerase II. In cells depleted of CDK12 or eIF4A3 from the EJC, EGF induced fewer c-FOS transcripts. In these cells, phosphorylation of serines at position 2 in the C-terminal domain (CTD) of RNA polymerase II, as well as levels of cleavage stimulating factor 64 (Cstf64) and 73-kDa subunit of cleavage and polyadenylation specificity factor (CPSF73), was reduced at the c-FOS gene. These effects impaired 3' end processing of c-FOS transcripts. Mutant CDK12 proteins lacking their Arg-Ser-rich (RS) domain or just the RS domain alone acted as dominant negative proteins. Thus CDK12 plays an important role in co-transcriptional processing of c-FOS transcripts.
In order to resolve the problem of poor permeability of sewage sludge compost (SSC) which was used as the substitution of peat, perlite was used to regulate the permeability of the sewage. The pure SSC was used as control. The proportions of perlite in the mixtures with SSC were 20%, 40%, 60%, 80% and 100% (V/V), respectively. The effects of different perlite ratios on the physical and chemical properties and the growth of Tagetes patula were studied. The bulk density, water holding porosity and water holding porosity to aeration porosity decreased, but the total porosity and aeration porosity increased with the increasing addition of perlite to the SSC. For the chemical properties, the pH increased, and the EC and nutrient contents decreased with the increasing addition of perlite to the SSC. The aboveground biomass and flowers of T. patula were the highest in the 60% perlite treatment, and the lowest in the pure SSC treatment. The root morphology and activity were the best in the 40%, 60% and 80% perlite treatments. Aeration was the strongest factor to impact the maximum root length and average root diameter. Perlite promoted the growth of T. patula mainly through impacting the physical properties of the SSC. The addition of 60% perlite to the SSC could significantly improve the poor aeration and decrease the high salinity greatly in the SSC and regulate the growth of the root and aboveground of T. patula.
To assess the efficacy of Yishen Jiejing Decoction (YJD) in treating poststroke shoulder-hand syndrome (SHS) patients of yin deficiency yang hyperactivity with blood stasis stagnation collaterals syndrome.
Electronic medical records with encoded entries should enhance the semantic interoperability of document exchange. However, it remains a challenge to encode the narrative concept and to transform the coded concepts into a standard entry-level document. This study aimed to use a novel approach for the generation of entry-level interoperable clinical documents.
Phytochemical investigation of the roots of Syringa pinnatifolia has resulted in the isolation of a new lignan, pinnatifolin A (1), together with seven known compounds (2-8). The structures were elucidated on the basis of extensive spectroscopic methods, including NMR, MS, UV and IR spectra. The seven lignans were screened for their antioxidant activity (DPPH assay), and most of them showed potent antioxidant activity.
Ambiguity in malignant transformation of glioma has made prognostic diagnosis very challenging. Tumor malignant transformation is closely correlated with specific alterations of the metabolic profile. Exploration of the underlying metabolic alterations in glioma cells of different malignant degree is therefore vital to develop metabolic biomarkers for prognosis monitoring.
Neuronal production in the mammalian cortex depends on extensive mitoses of radial glial progenitors (RGPs) residing in the ventricular zone (VZ). We examined the function of centrioles in RGPs during cortical neurogenesis in mice by conditional removal of SAS-4, a protein that is required for centriole biogenesis. SAS-4 deletion led to a progressive loss of centrioles, accompanied by RGP detachment from the VZ. Delocalized RGPs did not become outer subventricular zone RGPs (oRGs). Although they remained proliferative, ectopic RGPs, as well as those in the VZ, with a centrosomal deficit exhibited prolonged mitosis, p53 upregulation and apoptosis, resulting in neuronal loss and microcephaly. Simultaneous removal of p53 fully rescued RGP death and microcephaly, but not RGP delocalization and randomized mitotic spindle orientation. Our findings define the functions of centrioles in anchoring RGPs in the VZ and ensuring their efficient mitoses, and reveal the robust adaptability of RGPs in the developing cortex.
Seasonal variation of heavy metal contents in leaves and their relationships with soil heavy metal pollution levels were studied through measuring and analyzing the leaves of the common tree species in Beijing and soil heavy metal contents, to detect heavy metal accumulation ability of plant leaves. The results showed that: (1) the contents of Cu, Pb, Zn in plant leaves first decreased and then increased, again declined with changing the seasons (from spring to winter). Cr concentration showed the trend of first increase and then decrease from spring to winter, and the highest in the autumn; the accumulation capacities of Cu for Babylonica and Japonica were higher in the spring, summer and autumn, while Tabuliformis was in winter; the higher accumulation capacities for Cr, Pb were Japonica and Platycladus, and in winter were Platycladus and Bungeana; the higher accumulation capacities for Zn were Babylonica and Bungeana, while Platycladus in winter; (2) the pollution degree of four kinds of heavy metals (Cu, Cr, Pb, Zn) from downtown to suburbs showed that: Jingshan (C =2.48, C is contamination factor) > Olympic (C = 1.27) > Songshan (C = 1.20) > Shuiguan (C = 1. 18); (3) the heavy metals concentration of same plant leaves in the water of the Great Wall changed larger, but those in the other three areas showed that: Jingshan > Olympic > Songshan; the ability of same species leaf to absorb different sorts of heavy metals showed that: Zn >Cu >Pb >Cr; the difference between Zn content and Cr content was significant (P <0.01); (4) the relationship between heavy metal content in plant leaves and soil heavy metal pollution levels presented a quadratic polynomial relation; the significant correlation was found between other three heavy metal contents of plant samples and soil samples, but they were not the case for the Cu, and the correlation coefficients were above 0. 9.
Hexagonal NaYbF4:Tm(3+) upconversion nanoparticles hold promise for use in high contrast near-infrared-to-near-infrared (NIR-to-NIR) in vitro and in vivo bioimaging. However, significant hurdles remain in their preparation and control of their morphology and size, as well as in enhancement of their upconversion efficiency. Here, we describe a systematic approach to produce highly controlled hexagonal NaYbF4:Tm(3+) nanoparticles with superior upconversion. We found that doping appropriate concentrations of trivalent gadolinium (Gd(3+)) can convert NaYbF4:Tm(3+) 0.5% nanoparticles with cubic phase and irregular shape into highly monodisperse NaYbF4:Tm(3+) 0.5% nanoplates or nanospheres in a pure hexagonal-phase and of tunable size. The intensity and the lifetime of the upconverted NIR luminescence at 800 nm exhibit a direct dependence on the size distribution of the resulting nanoparticles, being ascribed to the varied surface-to-volume ratios determined by the different nanoparticle size. Epitaxial growth of a thin NaYF4 shell layer of ?2 nm on the ?22 nm core of hexagonal NaYbF4:Gd(3+) 30%/Tm(3+) 0.5% nanoparticles resulted in a dramatic 350 fold NIR upconversion efficiency enhancement, because of effective suppression of surface-related quenching mechanisms. In vivo NIR-to-NIR upconversion imaging was demonstrated using a dispersion of phospholipid-polyethylene glycol (DSPE-PEG)-coated core/shell nanoparticles in phosphate buffered saline.
Mutations of SDCCAG8 are associated with nephronophthisis and Bardet-Biedl syndrome, as well as schizophrenia; however, the function of SDCCAG8 remains largely unknown. Here, we show that SDCCAG8 regulates centrosomal accumulation of pericentriolar material and neuronal polarization and migration in the developing mouse cortex. Sdccag8 expression is selectively elevated in newborn neurons prior to their commencement of radial locomotion, and suppression of this expression by short-hairpin RNAs or a loss-of-function allele impairs centrosomal recruitment of ?-tubulin and pericentrin, interferes with microtubule organization, decouples the centrosome and the nucleus, and disrupts neuronal migration. Moreover, SDCCAG8 interacts and cotraffics with pericentriolar material 1 (PCM1), a centriolar satellite protein crucial for targeting proteins to the centrosome. Expression of SDCCAG8 carrying a human mutation causes neuronal migration defects. These results reveal a critical role for SDCCAG8 in controlling centrosomal properties and function, and provide insights into the basis of neurological defects linked to SDCCAG8 mutations.
The spatial and temporal variations and sources of polychlorinated biphenyls (PCBs) in sediment of tidal flat from Haizhou Bay, China were investigated. PCBs concentrations in surface sediments ranged from 1.33 to 6.27ngg(-1) dry weight. Low-chlorinated PCBs, dominated by the tri-PCB homologs, were identified as the prevalent contaminate of surface sediments. These results were in agreement with the fact that tri-PCB homologs are the dominant contaminants in China. In surface sediment, the highest level appeared in the estuary, and it decreased with distance from the Linhong River estuary. PCBs concentrations started to rise from the mid-1950s, and reached a maximum in 2005. PCBs in sediment might originate from surface runoff and discharges of local source as well as slight atmospheric deposition, based on PCA. Additionally, the PCBs levels in the sediments were considered to rarely pose hazard to the aquatic and human health, based on Sediment Quality Guidelines (SQGs).
Brain activity associated with attention sustained on the task of safe driving has received considerable attention recently in many neurophysiological studies. Those investigations have also accurately estimated shifts in drivers' levels of arousal, fatigue, and vigilance, as evidenced by variations in their task performance, by evaluating electroencephalographic (EEG) changes. However, monitoring the neurophysiological activities of automobile drivers poses a major measurement challenge when using a laboratory-oriented biosensor technology. This work presents a novel dry EEG sensor based mobile wireless EEG system (referred to herein as Mindo) to monitor in real time a driver's vigilance status in order to link the fluctuation of driving performance with changes in brain activities. The proposed Mindo system incorporates the use of a wireless and wearable EEG device to record EEG signals from hairy regions of the driver conveniently. Additionally, the proposed system can process EEG recordings and translate them into the vigilance level. The study compares the system performance between different regression models. Moreover, the proposed system is implemented using JAVA programming language as a mobile application for online analysis. A case study involving 15 study participants assigned a 90 min sustained-attention driving task in an immersive virtual driving environment demonstrates the reliability of the proposed system. Consistent with previous studies, power spectral analysis results confirm that the EEG activities correlate well with the variations in vigilance. Furthermore, the proposed system demonstrated the feasibility of predicting the driver's vigilance in real time.
Islet transplantation is a therapeutic option for type 1 diabetes, but its long-term success is limited by islet allograft survival. Many factors imperil islet survival, especially the adverse effects and toxicity due to clinical immunosuppressants. Compound (Cpd) K is a synthesized analog of highly unsaturated fatty acids from Isatis tinctoria L. (Cruciferae). Here we investigated the therapeutic effect of Cpd K in diabetic mice and found that it significantly prolonged islet allograft survival with minimal adverse effects after 10 days. Furthermore, it reduced the proportion of CD4(+) and CD8(+) T cells in spleen and lymph nodes, inhibited inflammatory cell infiltration in allografts, suppressed serum interleukin-2 and interferon-? secretion, and increased transforming growth factor-? and Foxp3 mRNA expression. Surprisingly, Cpd K and rapamycin had a synergistic effect. Cpd K suppressed proliferation of naïve T cells by inducing T-cell anergy and promoting the generation of regulatory T cells. In addition, nuclear factor-?B signaling was also blocked. Taken together, these findings indicate that Cpd K may have a potential immunosuppressant effect on islet transplantation.
Preserving periodontally compromised abutments in patients who are actively undergoing oral and intravenous bisphosphonate treatment for osteoporosis provides an alternative to tooth extraction and dental implants, both of which put patients at risk for bisphosphonate-related osteonecrosis of the jaw. This case report describes how a CAD/CAM-fabricated cobalt-chromium telescopic prosthesis was placed on periodontally compromised abutments of a 74-year-old woman actively undergoing oral and intravenous bisphosphonate treatment for osteoporosis.
We sought to clarify the prognostic value of CD44 in survival of patients with non-small cell lung cancer (NSCLC). We performed a meta-analysis of relevant literature to aggregate the available survival results, using studies published in English until March 2014. Eligible studies dealt with CD44, CD44 standard form (CD44s) and CD44 variant 6 (CD44v6), assessment in NSCLC patients on primary lesions and reported survival data according to CD44 and CD44 isoforms expression. We aggregated 10 trials (5 trials for CD44v6, 3 trials for CD44, and 2 trials for CD44s) comprising 1,074 patients, in this meta-analysis. The combined hazard ratio (HR) with CD44v6 and CD44s was 2.39 (95 % confidence interval (CI) 1.69-3.37) and 1.64 (95 % CI 1.06-2.52), respectively. It associated high CD44v6 and CD44s expression with poor survival in NSCLC patients. However, CD44 overexpression did not significantly correlate with survival in patients with NSCLC (HR 1.44; 95 % CI 0.72-2.89). Our meta-analysis shows that CD44v6 and CD44s overexpression indicates poor prognosis for NSCLC patients. However, the high CD44 expression is not significantly correlated with survival for patients with NSCLC.
The genetic variation in HIV-1 in patients is due to the high rate of viral replication, the high viral load, and the errors made during viral replication. Some of the mutations in reverse transcriptase (RT) that alter the deoxynucleoside triphosphate (dNTP)-binding pocket, including those that confer resistance to nucleoside/nucleotide analogs, affect dNTP selection during replication. The effects of mutations in RT on the spectrum (nature, position, and frequency) of errors made in vivo are poorly understood. We previously determined the mutation rate and the frequency of different types of mutations and identified hot spots for mutations in a lacZ? (the ? complementing region of lacZ) reporter gene carried by an HIV-1 vector that replicates using wild-type RT. We show here that four mutations (Y115F, M184V, M184I, and Q151M) in the dNTP-binding pocket of RT that had relatively small effects on the overall HIV-1 mutation rate (less than 3-fold compared to the wild type) significantly increased mutations at some specific positions in the lacZ? reporter gene. We also show that changes in a sequence that flanks the reporter gene can affect the mutations that arise in the reporter. These data show that changes either in HIV-1 RT or in the sequence of the nucleic acid template can affect the spectrum of mutations made during viral replication. This could, by implication, affect the generation of drug-resistant mutants and immunological-escape mutants in patients.
The treatment of acute myocardial infarction (AMI) is thought to restore antegrade blood flow in the infarct-related artery (IRA) and minimize ischemic damage to the myocardium as soon as possible. The present study aimed to identify possible clinical predictors for no-reflow in patients with AMI after primary percutaneous coronary intervention (PCI).
In this work, we report on efficient visible and near-IR upconversion emissions in colloidal hexagonal-phase core/shell NaYF4:Er(3+)/NaYF4 nanoparticles (?38??nm) under IR laser excitation at 1523 nm. Varying amounts of Er(3+) dopants were introduced into the core NaYF4:Er(3+) nanoparticles, revealing an optimized Er(3+) concentration of 10% for the highest luminescent efficiency. An inert epitaxial shell layer of NaYF4 grown onto the core of the NaYF4:Er(3+) 10% nanoparticle increased its upconversion emission intensity fivefold due to suppression of surface-related quenching mechanisms, yielding the absolute upconversion efficiency to be as high as ?3.9±0.3% under an excitation density of 18??W/cm(2). The dependence of the intensity of upconversion emission peaks on laser excitation density in the core/shell nanoparticle displayed "saturation effects" at low excitation density in the range of 1.5-18??W/cm(2), which again demonstrates high upconversion efficiency.
This dental technique report describes a digital workflow with digital data acquisition at the implant level, computer-aided design and computer-aided manufacturing fabricated, tissue-colored, anodized titanium framework, individually luted zirconium oxide restorations, and autopolymerizing injection-molded acrylic resin to fabricate an implant-supported, metal-ceramic-resin fixed complete dental prosthesis in an edentulous mandible. The 1-step computer-aided design and computer-aided manufacturing fabrication of titanium framework and zirconium oxide restorations can provide a cost-effective alternative to the conventional metal-resin fixed complete dental prosthesis.
Herein, we report the effect of parecoxib on the structure and function of human serum albumin (HSA) by using fluorescence, circular dichroism (CD), Fourier transforms infrared (FTIR), three-dimensional (3D) fluorescence spectroscopy, and molecular docking techniques. The Stern-Volmer quenching constants K(SV) and the corresponding thermodynamic parameters ?H, ?G, and ?S have been estimated by the fluorescence quenching method. The results indicated that parecoxib binds spontaneously with HSA through van der Waals forces and hydrogen bonds with binding constant of 3.45 × 10(4) M(-1) at 298 K. It can be seen from far-UV CD spectra that the ?-helical network of HSA is disrupted and its content decreases from 60.5% to 49.6% at drug:protein = 10:1. Protein tertiary structural alterations induced by parecoxib were also confirmed by FTIR and 3D fluorescence spectroscopy. The molecular docking study indicated that parecoxib is embedded into the hydrophobic pocket of HSA.
This clinical report demonstrated the use of an implant-supported fixed dental prosthesis fabricated with a contemporary digital approach. The digital diagnostic data acquisition was completed with a digital diagnostic impression with an intraoral scanner and cone-beam computed tomography with a prefabricated universal radiographic template to design a virtual prosthetically driven implant surgical plan. A surgical template fabricated with computer-aided design and computer-aided manufacturing (CAD/CAM) was used to perform computer-guided implant surgery. The definitive digital data were then used to design the definitive CAD/CAM-fabricated fixed dental prosthesis.
A better understanding of changes in HIV-1 population genetics with combination antiretroviral therapy (cART) is critical for designing eradication strategies. We therefore analyzed HIV-1 genetic variation and divergence in patients' plasma before cART, during suppression on cART, and after viral rebound. Single-genome sequences of plasma HIV-1 RNA were obtained from HIV-1 infected patients prior to cART (N?=?14), during suppression on cART (N?=?14) and/or after viral rebound following interruption of cART (N?=?5). Intra-patient population diversity was measured by average pairwise difference (APD). Population structure was assessed by phylogenetic analyses and a test for panmixia. Measurements of intra-population diversity revealed no significant loss of overall genetic variation in patients treated for up to 15 years with cART. A test for panmixia, however, showed significant changes in population structure in 2/10 patients after short-term cART (<1 year) and in 7/10 patients after long-term cART (1-15 years). The changes consisted of diverse sets of viral variants prior to cART shifting to populations containing one or more genetically uniform subpopulations during cART. Despite these significant changes in population structure, rebound virus after long-term cART had little divergence from pretherapy virus, implicating long-lived cells infected before cART as the source for rebound virus. The appearance of genetically uniform virus populations and the lack of divergence after prolonged cART and cART interruption provide strong evidence that HIV-1 persists in long-lived cells infected before cART was initiated, that some of these infected cells may be capable of proliferation, and that on-going cycles of viral replication are not evident.
Organic field-effect transistors (OFETs) are used to directly "touch" the movement and dynamics of polymer chains, and then determine Tg. As a molecular-level probe, the conducting channel of OFETs exhibits several unique advantages: 1) it directly detects the motion and dynamics of polymer chain at Tg; 2) it allows the measurement of size effects in ultrathin polymer films (even down to 6?nm), which bridges the gap in understanding effects between surface and interface. This facile and reliable determination of Tg of polymer films and the understanding of polymer chain dynamics guide a new prospect for OFETs besides their applications in organic electronics and casting new light on the fundamental understanding of the nature of polymer chain dynamics.
Enhanced H2 evolution efficiency is achieved via manipulating the spatial location of oxygen vacancies in niobates. The ultrathin K4 Nb6O17 nanosheets which are rich in surface oxygen vacancies show enhanced optical absorption and band gap narrowing. Meanwhile, the fast charge separation effectively reduces the probability of hole-electron recombination, enabling 20 times hydrogen evolution rate compared with the defect-free bulk counterpart.
We propose a method (EXIA2) of catalytic residue prediction based on protein structure without needing homology information. The method is based on the special side chain orientation of catalytic residues. We found that the side chain of catalytic residues usually points to the center of the catalytic site. The special orientation is usually observed in catalytic residues but not in noncatalytic residues, which usually have random side chain orientation. The method is shown to be the most accurate catalytic residue prediction method currently when combined with PSI-Blast sequence conservation. It performs better than other competing methods on several benchmark datasets that include over 1,200 enzyme structures. The areas under the ROC curve (AUC) on these benchmark datasets are in the range from 0.934 to 0.968.
The hippocampus, as part of the cerebral cortex, is essential for memory formation and spatial navigation. Although it has been extensively studied, especially as a model system for neurophysiology, the cellular processes involved in constructing and organizing the hippocampus remain largely unclear. Here, we show that clonally related excitatory neurons in the developing hippocampus are progressively organized into discrete horizontal, but not vertical, clusters in the stratum pyramidale, as revealed by both cell-type-specific retroviral labeling and mosaic analysis with double markers (MADM). Moreover, distinct from those in the neocortex, sister excitatory neurons in the cornu ammonis 1 region of the hippocampus rarely develop electrical or chemical synapses with each other. Instead, they preferentially receive common synaptic input from nearby fast-spiking (FS), but not non-FS, interneurons and exhibit synchronous synaptic activity. These results suggest that shared inhibitory input may specify horizontally clustered sister excitatory neurons as functional units in the hippocampus.
Autophagy is classified as type II programmed cell death and may participate in tumorigenesis. However, changes in autophagy-lysosome signaling and the relationship between the apoptotic cascade and gastric cancer cells have not been fully elucidated. The present study investigated the induction of autophagy in poorly differentiated human gastric adenocarcinoma. Immunoblotting revealed markedly induced autophagy in low grade differentiated gastric adenocarcinoma, indicated by elevation of microtubule-associated protein 1 light chain 3-I/II conversion and Beclin 1 in human gastric carcinomas. In addition, the diffuse (poorly differentiated) subtype showed significantly elevated Lamp2 and cathepsin B protein levels. Concomitantly, significant induction of anti-apoptotic events were indicated by changes in B-cell lymphoma 2 (Bcl-2) and X-linked inhibitor of apoptosis protein levels. Notably, confocal laser microscope data indicated co-expression of Bcl-2 and Beclin 1 in poorly differentiated human gastric adenocarcinoma. Results of this study indicate that the autophagy-lysosome signaling participates in poorly differentiated human gastric adenocarcinoma and there are intracellular links between autophagic signaling and the apoptotic cascade.
This report describes a technique that uses an acrylic resin verification device and polyvinyl siloxane impression to verify and correct the analog position in a milled polyurethane definitive cast with removable periimplant soft tissue replica for a nonsegmental implant restoration in an edentulous jaw.
This aim of the present study was to evaluate the effects of dexmedetomidine (DEX) on the intraoperative monitoring of somatosensory-evoked potentials (SEPs) and motor-evoked potentials (MEPs) in patients undergoing spinal surgery. A total of 36 patients who received spinal surgery under general anesthesia were randomly divided into two groups (n=18 per group), group C, the test group and group D, the control group, and these groups were subjected to a matching anesthesia induction. In brief, the anesthesia was administered via injection of etomidate and fentanyl; once the patients were unconscious, a laryngeal mask airway (LMA) was inserted, SEPs and MEPs were monitored and the collected data were considered to be basic data. Cisatracurium was subsequently injected and an endotracheal tube (7#) was inserted to replace the LMA. The following procedures were conducted for anesthesia maintenance: Group C, the anesthesia was maintained via target-controlled infusion of etomidate and intermittent injection of fentanyl; and group D, DEX (0.5 ?g/kg) was injected over a duration of 10 min and then pumped at a rate of 0.5 ?g/kg/h. In the two groups, all of the other drugs used were the same and a muscle relaxant was not administered. The bispectral index was maintained between 45 and 55 during surgery, and the SEPs and MEPs were monitored continuously until the surgery was completed. No significant difference in duration and amplitude of the SEPs (P15-N20) was identified between group C and D (P>0.05). Furthermore, the MEPs were monitored in the two groups at specific durations and no significant difference was observed between the two groups (P>0.05). The SEPs and MEPs were maintained in the patients who were administered with the DEX-etomidate-fentanyl combined anesthesia during spinal surgery.
We compared our clinical experience with currently available reference oxygen saturation level (SpO2) values from the American Academy of Pediatrics/American Heart Association (AAP/AHA) neonatal resuscitation program guidelines.
Remakes, or the refabrication of dental prostheses, can occur as a result of inherent inaccuracies in both clinical and laboratory procedures. Because dental schools manage large numbers of predoctoral dental students with limited familiarity and expertise as related to clinical prosthodontic techniques, it is likely these schools will experience an elevated incidence of laboratory remakes and their ramifications. The University of Louisville School of Dentistry, not unlike other dental schools, has experienced remakes associated with both fixed and removable prosthodontic procedures. Limitations in faculty standardization and variable enforcement of established preclinical protocols have been identified as variables associated with the high percentage of remakes documented. The purpose of this study was to introduce the implementation of a new multidepartmental quality assurance program designed to increase consistency and quality in both information provided to commercial dental laboratories and the prostheses returned. The program has shown to be advantageous in terms of cost-effectiveness and treatment outcomes. A statistically significant decrease in remake percentages has been recorded from inception of this program in December 2010 until December 2012. Furthermore, this program has resulted in more consistent communication between the dental school and commercial dental laboratories, among faculty members, and between faculty and students.
Sterol regulatory element-binding protein (SREBP) transcription factors are central regulators of cellular lipogenesis. Release of membrane-bound SREBP requires SREBP cleavage-activating protein (SCAP) to escort SREBP from the endoplasmic reticulum (ER) to the Golgi for cleavage by site-1 and site-2 proteases. SCAP then recycles to the ER for additional rounds of SREBP binding and transport. Mechanisms regulating ER-to-Golgi transport of SCAP-SREBP are understood in molecular detail, but little is known about SCAP recycling. Here, we have demonstrated that SCAP Golgi-to-ER transport requires cleavage of SREBP at site-1. Reductions in SREBP cleavage lead to SCAP degradation in lysosomes, providing additional negative feedback control to the SREBP pathway. Current models suggest that SREBP plays a passive role prior to cleavage. However, we show that SREBP actively prevents premature recycling of SCAP-SREBP until initiation of SREBP cleavage. SREBP regulates SCAP in human cells and yeast, indicating that this is an ancient regulatory mechanism.
The growth arrest and DNA-damage-inducible protein 45 gamma (Gadd45g) is known to play a major role in embryonic development and sex determination. In this study, two Gadd45g genes were isolated from half-smooth tongue sole (Cynoglossus semilaevis). Using chromosomal fluorescence in situ hybridization (FISH), Gadd45g1 and Gadd45g2 were located on the W and Z chromosomes, respectively. The full-length cDNA sequences of Gadd45g1 (1270bp) and Gadd45g2 (1181bp) were predicted to contain a 480-bp coding sequence that could encode a protein of 159 amino acids residues. A phylogenetic tree showed that the predicted Gadd45g1 and Gadd45g2 amino acid sequences clustered closely in one branch. It is proposed that Gadd45g1 and Gadd45g2 are paralogous genes derived from the divergence of the sex chromosome. Ka/Ks ratios indicated that Gadd45g1 and Gadd45g2 may have undergone a high number of mutations and have a divergence time of only about 68,000years, although Gadd45g homologs are highly conserved. The qRT-PCR demonstrated that Gadd45g1 and Gadd45g2 were highly expressed in ovary, and negligibly expressed in testis of male and neo-male. During development of the ovary (from 80 to 150days), the expression levels of both genes reached high levels. Gadd45g1 was also highly expressed at 50days, the stage just before gonad differentiation in C. semilaevis. All these findings imply functional divergence of the two Gadd45g homologs; Gadd45g1 may be necessary for sex differentiation in the early stage of gonad development, and then Gadd45g1 and Gadd45g2 maintain ovary development and the female character of half-smooth tongue sole.
Transport of PEGylated silica nanoparticles (PSiNPs) with diameters of 100, 50, and 25 nm across the blood-brain barrier (BBB) was evaluated using an in vitro BBB model based on mouse cerebral endothelial cells (bEnd.3) cultured on transwell inserts within a chamber. In vivo animal experiments were further performed by noninvasive in vivo imaging and ex vivo optical imaging after injection via carotid artery. Confocal fluorescence studies were carried out to evaluate the uptake of PSiNPs by brain endothelial cells. The results showed that PSiNPs can traverse the BBB in vitro and in vivo. The transport efficiency of PSiNPs across BBB was found to be size-dependent, with increased particle size resulting in decreased efficiency. This work points to the potential application of small sized silica nanoparticles in brain imaging or drug delivery.
Lymantria dispar asiatica (Vnukovskij) (Lepidoptera: Lymantridae) is one of three gypsy moth subspecies found in East Asia. Understanding the diapause and postdiapause phases of its eggs is important in characterizing its life cycle. The effects of different constant temperatures for different lengths of times on field-collected, postdiapause eggs were tested during the first year. In the second year, the effects of the same treatments on laboratory-raised eggs in diapause were investigated. The effects of temperature on percent egg hatching, time to hatching, and hatching duration were determined. When field-collected eggs were held at 0 and 5°C, they terminated postdiapause within 11 days. The percent hatching tended to decline with an increased duration of exposure at temperatures greater than 5°C. Diapause terminated slowly (> 37 days) and with a high percentage of hatching for postdiapause eggs held at 10°C. There was a positive correlation between temperature and the speed of postdiapause development for field-collected eggs held at constant temperatures between 10 and 25°C. However, the number of days to the first hatch was significantly longer than for eggs treated with lower temperatures before being transferred to 25°C. Freshly oviposited eggs treated at a constant 0 or 5°C for 200 days were unable to develop into pharate larva. However, eggs treated at a constant 20 or 25°C for 200 days developed into pharate larva but did not hatch even after a subsequent chill. This result suggests why L. dispar asiatica is not found in tropical areas and helps us to predict the distribution of the gypsy moth in China.
This clinical report presents the treatment of a maxillary central incisor with class III invasive cervical resorption and a compromised ferrule. Nonsurgical endodontic therapy combined with periodontal surgery was provided for debridement. Direct light-polymerizing resin-modified glass ionomer cement and a zirconia crown were used to repair the defect. Symptomatic endodontic complication was diagnosed with localized cone beam computed tomography at 6-month follow-up, and periapical microsurgery was rendered. The patient was followed-up for 30 months after treatment and had no further complications.
Estimating viral diversity in infected patients can provide insight into pathogen evolution and emergence of drug resistance. With the widespread adoption of deep sequencing, it is important to develop tools to accurately calculate population diversity from very large datasets. Current methods for estimating diversity that are based on multiple alignments are not practical to apply to such data. In this study, the authors report a novel method (Pairwise Alignment Positional Nucleotide Counting, PAPNC) for estimating population diversity from 454 sequence data. The diversity measurements determined using this method were comparable to those calculated by average pairwise difference (APD) of multiply aligned sequences using MEGA5. Diversities were estimated for 9 patient plasma HIV samples sequenced with Titanium 454 technology and by single-genome sequencing (SGS). Diversities calculated from deep sequencing using PAPNC ranged from 0.002 to 0.021 while APD measurements calculated from SGS data ranged proximately from 0.001 to 0.018, with the difference being attributable to PCR error (contributing background diversity of 0.0016 in a control sample). Comparison of APDs estimated from 100 sets of sequences drawn at random from 454 generated data and from corresponding SGS data showed very close correlation between the two methods with R(2) of 0.96, and differing on average by about 1% (after correction for PCR error). The authors have developed a novel method that is good for calculating genetic diversities for large scale datasets from next generation sequencing. It can be implemented easily as a function in available variation calling programs like SAMtools or haplotype reconstruction software for nucleotide genetic diversity calculation. A Perl script implementing this method is available upon request.
Clodronate liposome injection is an effective approach to selectively and specifically depleting macrophages. Macrophages play a crucial role in cutaneous wound healing and are associated with excessive scar formation. Use of clodronate liposomes to enhance cutaneous wound healing and reduce scar formation could represent a major advance in wound therapy and hypertrophic scar treatment. This study aimed to investigate the effects of subcutaneous or intraperitoneal injection of clodronate liposomes on cutaneous wound healing and scar formation. A burn injury mouse model was used. Mice were treated with subcutaneous or intraperitoneal injection of clodronate liposomes. Wound healing time was analyzed and scar tissues were harvested for hematoxylin and eosin (HE) staining, reverse transcription polymerase chain reaction (RT-PCR) and Western blot analyses. Wound healing time in treated mice was extended. HE showed that the basal layer of the epidermis in treated scars was flattened, the dermis layer was not significantly thickened, and collagen fibers were well arranged, with few cells and micro vessels. RT-PCR and Western blot analyses showed that the levels of TGF-?1 and collagen I-?2 were decreased in treated mice. Clodronate liposomes reduce excessive scar formation and delay cutaneous wound healing possibly by reducing collagen deposition and macrophage-derived TGF-?1 expression.
Mounting evidence has shown the toxic effects of anesthesia to neonatal hippocampus. We used an in vivo mouse model to explore the role of microRNA 34a (miR-34a) in regulating anesthesia-induced hippocampal neurotoxicity.
CELLO2GO (http://cello.life.nctu.edu.tw/cello2go/) is a publicly available, web-based system for screening various properties of a targeted protein and its subcellular localization. Herein, we describe how this platform is used to obtain a brief or detailed gene ontology (GO)-type categories, including subcellular localization(s), for the queried proteins by combining the CELLO localization-predicting and BLAST homology-searching approaches. Given a query protein sequence, CELLO2GO uses BLAST to search for homologous sequences that are GO annotated in an in-house database derived from the UniProt KnowledgeBase database. At the same time, CELLO attempts predict at least one subcellular localization on the basis of the species in which the protein is found. When homologs for the query sequence have been identified, the number of terms found for each of their GO categories, i.e., cellular compartment, molecular function, and biological process, are summed and presented as pie charts representing possible functional annotations for the queried protein. Although the experimental subcellular localization of a protein may not be known, and thus not annotated, CELLO can confidentially suggest a subcellular localization. CELLO2GO should be a useful tool for research involving complex subcellular systems because it combines CELLO and BLAST into one platform and its output is easily manipulated such that the user-specific questions may be readily addressed.
We sequenced HIV-1 in 70 CSF and 29 plasma samples and the corresponding pre-therapy samples from 17 subjects on suppressive therapy. More of the CSF sequences were hypermutants than plasma sequences. We generated on-therapy sequences from both CSF and plasma from two subjects; in one we found genetically distinct sequences in CSF and plasma indicating that they came from two different compartments, one potentially the CNS, during suppressive therapy. In addition, there was little evidence of viral evolution in the CSF during therapy, suggesting that continuous virus replication is not the major cause of viral persistence in the CNS.
Purpose: This article describes the preliminary findings of the mechanical properties of functionally graded titanium with controlled distribution of porosity and a reduced Youngs modulus on the basis of a computeraided design (CAD) file, using the rapid-prototyping, direct metal laser sintering (DMLS) technique. Materials and Methods: Sixty specimens of Ti-6Al-4V were created using a DMLS machine (M270) following the standard for tensile testing of metals. One group was fabricated with only 170 W of laser energy to create fully dense specimens (control group). The remaining specimens all featured an outer fully dense "skin" layer and a partially sintered porous inner "core" region. The outer "skin" of each specimen was scanned at 170 W and set at a thickness of 0.35, 1.00, or 1.50 mm for different specimen groups. The inner "core" of each specimen was scanned at a lower laser power (43 or 85 W). Results: The partially sintered core was clearly visible in all specimens, with somewhat greater porosity with the lower laser power. However, the amount of porosity in the core region was not related to the laser power alone; thinner skin layers resulted in higher porosity for the same power values in the core structure. The lowest Youngs modulus achieved, 35 GPa, is close to that of bone and was achieved with a laser power of 43 W and a skin thickness of 0.35 mm, producing a core that comprised 74% of the total volume. Conclusion: Additive manufacturing technology may provide an efficient alternative way to fabricate customized dental implants based on a CAD file with a functionally graded structure that may minimize stress shielding and improve the long-term performance of dental implants.
The source and dynamics of persistent HIV-1 during long-term combinational antiretroviral therapy (cART) are critical to understanding the barriers to curing HIV-1 infection. To address this issue, we isolated and genetically characterized HIV-1 DNA from naïve and memory T cells from peripheral blood and gut-associated lymphoid tissue (GALT) from eight patients after 4-12 y of suppressive cART. Our detailed analysis of these eight patients indicates that persistent HIV-1 in peripheral blood and GALT is found primarily in memory CD4(+) T cells [CD45RO(+)/CD27((+/-))]. The HIV-1 infection frequency of CD4(+) T cells from peripheral blood and GALT was higher in patients who initiated treatment during chronic compared with acute/early infection, indicating that early initiation of therapy results in lower HIV-1 reservoir size in blood and gut. Phylogenetic analysis revealed an HIV-1 genetic change between RNA sequences isolated before initiation of cART and intracellular HIV-1 sequences from the T-cell subsets after 4-12 y of suppressive cART in four of the eight patients. However, evolutionary rate analyses estimated no greater than three nucleotide substitutions per gene region analyzed during all of the 4-12 y of suppressive therapy. We also identified a clearly replication-incompetent viral sequence in multiple memory T cells in one patient, strongly supporting asynchronous cell replication of a cell containing integrated HIV-1 DNA as the source. This study indicates that persistence of a remarkably stable population of infected memory cells will be the primary barrier to a cure, and, with little evidence of viral replication, this population could be maintained by homeostatic cell proliferation or other processes.
Abstract Objectives. The objectives of this study are to develop a discrete-event simulation (DES) model for the Singapore Emergency Medical Services (EMS), and to demonstrate the utility of this DES model for the evaluation of different policy alternatives to improve ambulance response times. Methods. A DES model was developed based on retrospective emergency call data over a continuous 6-month period in Singapore. The main outcome measure is the distribution of response times. The secondary outcome measure is ambulance utilization levels based on unit hour utilization (UHU) ratios. The DES model was used to evaluate different policy options in order to improve the response times, while maintaining reasonable fleet utilization. Results. Three policy alternatives looking at the reallocation of ambulances, the addition of new ambulances, and alternative dispatch policies were evaluated. Modifications of dispatch policy combined with the reallocation of existing ambulances were able to achieve response time performance equivalent to that of adding 10 ambulances. The median (90th percentile) response time was 7.08 minutes (12.69 minutes). Overall, this combined strategy managed to narrow the gap between the ideal and existing response time distribution by 11-13%. Furthermore, the median UHU under this combined strategy was 0.324 with an interquartile range (IQR) of 0.047 versus a median utilization of 0.285 (IQR of 0.051) resulting from the introduction of additional ambulances. Conclusions. Response times were shown to be improved via a more effective reallocation of ambulances and dispatch policy. More importantly, the response time improvements were achieved without a reduction in the utilization levels and additional costs associated with the addition of ambulances. We demonstrated the effective use of DES as a versatile platform to model the dynamic system complexities of Singapores national EMS systems for the evaluation of operational strategies to improve ambulance response times.
Abstract This study evaluates alginate-poly-l-lysine-alginate Bifidobacterium longum subsp. infantis ATCC 15697-loaded microcapsules to enrich the human gut microbiota. The cell survival of alginate-poly-l-lysine-alginate microencapsulated B. infantis ATCC 15697 in gastric acid, bile, and through human gastrointestinal transit was investigated, as well as the formulations effect on the gut microbiota. Results show that microencapsulation increases B. infantis ATCC 15697 cell survival at pH1.0 (33.54?±?2.80% versus <1.00?±?0.00%), pH1.5 (41.15?±?2.06% versus <1.00?±?0.00%), pH2.0 (60.88?±?1.73% versus 36.01?±?2.63%), pH3.0 (75.43?±?1.23% versus 46.30?±?1.43%), pH4.0 (71.40?±?2.02% versus 47.75?±?3.12%) and pH5.0 (73.88?±?3.79% versus 58.93?±?2.26%) (p?0.05). In addition, microencapsulation increases cell survival at 0.5% (76.85?±?0.80% versus 70.77?±?0.64%), 1.0% (59.99?±?0.97% versus 53.47?±?0.58%) and 2.0% (53.10?±?1.87% versus 44.59?±?1.52%) (p?0.05) (w/v) bile. Finally, daily administration of alginate-poly-l-lysine-alginate microencapsulated B. infantis ATCC 15697 in a human gastrointestinal model induces a significant enrichment of B. infantis within the ascending (184.51?±?17.30% versus 53.83?±?17.82%; p?0.05), transverse (174.79?±?25.32% versus 73.17?±?15.30%; p?0.05) and descending (94.90?±?25.22% versus 46.37?±?18.93%; p?>?0.05) colonic microbiota.
Helicobacter pylori (H. pylori) infection might initiate and contribute to the progression of lymphoma from gastric mucosa-associated lymphoid tissue (MALT). Increasing evidence shows that eradication of H. pylori with antibiotic therapy can lead to regression of gastric MALT lymphoma and can result in a 10-year sustained remission. The eradication of H. pylori is the standard care for patients with gastric MALT lymphoma. Cytotoxin-associated gene A (CagA) protein, one of the most extensively studied H. pylori virulence factors, is strongly associated with the gastric MALT lymphoma. CagA possesses polymorphisms according to its C-terminal structure and displays different functions among areas and races. After being translocated into B lymphocytes via type IV secretion system, CagA deregulates intracellular signaling pathways in both tyrosine phosphorylation-dependent and -independent manners and/or some other pathways, and thereby promotes lymphomagenesis. A variety of proteins including p53 and protein tyrosine phosphatases-2 are involved in the malignant transformation induced by CagA. Mucosal inflammation is the foundational mechanism underlying the occurrence and development of gastric MALT lymphoma.
Abstract Objectives: This retrospective study investigated the association between hypoglycemic events (HEs) and depression events (DEs) in patients with diabetes mellitus (type 1 and type 2). Methods: Analyzed data were from health care claims for individuals with employer-sponsored primary or Medicare supplemental insurance from the Thomson Reuters Market Scan database during the years 2008 and 2009. A baseline period (January 2008 to December 2008) was used to identify eligible patients and collect baseline clinical and demographic characteristics. Eligible patients were aged ?18 years with diabetes (ICD-9-CM codes: 250.00, 250.01, 250.02, 250.03) who had not experienced any HEs or DEs and were not on antidepressant therapy during the baseline period. We studied the relationships between the DEs and HEs before and after adjusting for the covariates. Results: Of the 923,024 patients meeting the inclusion criteria, 22,735 (2.46%) patients had HEs (ICD-9-CM coded: 251.0, 251.1, 251.2, 250.8) and 6164 (0.67%) patients had DEs (ICD-9-CM: 311) during the evaluation period. Patients reporting HEs had 78% higher odds of experiencing depression than patients without HEs before adjusting for the covariates. Similarly, after adjusting for the covariates, data indicated that patients with HEs had higher odds of experiencing depression (OR?=?1.726; 95% CI?=?1.52-1.96). Similar analyses in different age categories showed that the OR monotonically increases with age regardless of whether the other covariates are included in the model. Conclusions: ICD-9-CM-coded HEs were independently associated with an increased risk of DEs in patients with diabetes, and this incidence increased with the patients age. Key limitations: A key limitation to this study is that only those HEs that resulted in health care provider contact and subsequent claims coding indicative of hypoglycemia were included. It is likely that many cases of mild hypoglycemia, particularly those not severe enough to warrant medical attention, were not captured in this study.
This report describes the use of a multipurpose template stabilized with existing implants to provide accurate information for immediate implant placement, to facilitate impression making, and to record maxillomandibular relationships for the fabrication of an interim immediate implant-supported fixed prosthesis.
KYKZL-1, a newly synthesized compound with COX/5-LOX dual inhibition, was subjected to the inhibitory activity test on Hep G2 growth. We found that KYKZL-1 inhibited the growth of Hep G2 cells via inducing apoptosis. Further studies showed that KYKZL-1 activated caspase-3 through cytochrome c release from mitochondria and down regulation of Bcl-2/Bax ratio and reduced the high level of COX-2 and 5-LOX. As shown in its anti-inflammatory effect, KYKZL-1 also exhibited inhibitory effect on the PGE2 and LTB4 production in Hep G2 cells. Accordingly, exogenous addition of PGE2 or LTB4 reversed the decreases in cell viability. In addition, KYKZL-1 caused cell cycle arrest at the S-G2 checkpoint via the activation of p21(CIP1) protein and down-regulation of cyclin A expression. These data indicate that the growth inhibitory effect of KYKZL-1 is associated with inhibition of AA metabolites and caspase-3 pathway and cell cycle arrest. Combined with our previous findings, KYKZL-1 exhibiting COX/5-LOX inhibition may be a promising potential agent not only for inflammation control but also for cancer prevention/therapy with an enhanced gastric safety profile.
The digital workflow in this clinical report describes a maxillary rehabilitation with an articulator-free and definitive cast-free treatment protocol for computer-aided design and computer-aided manufacturing (CAD/CAM) fabricated long-term interim and anatomic contour monolithic lithium disilicate definitive restorations.
Both inhalable particulate matter (PM10) and fine particulate matter (PM2.5) are not only one of the main causes of air pollution, but also the primary pollutants in most cities. Based on the analysis of the impacts of PM10 and PM2.5 on the environment and human health, this paper summarized the components, sources, and mass concentration variations of PM10 and PM2.5 and related affecting factors, and introduced the network layout of PM10 and PM2.5 monitoring and its principles and features. The research methods on the removal of PM10 and PM2.5 by forests, the removal rates of PM10 and PM2.5 by different forests, and the related affecting mechanisms were summed up at regional and individual scales, and the existed problems in this research field were discussed. Due to the lack of the comparable observation studies on the atmospheric PM10 and PM2.5 along different gradients and in background areas, the joint effects of multiple factors on the PM10 and PM2.5 concentrations are not revealed. It was suggested that to make a rational network layout of PM10 and PM2.5 monitoring, to correctly select proper monitoring methods, and to compare and calibrate the observed results from classical manual methods would be the bases to guarantee the validity of PM10 and PM2.5 monitoring data. At present, there are few reports about the PM2.5 removal by forests, and its not clear about the physiological processes and ecological mechanisms of PM10 and PM2.5 removal at cell, tissue, organ, and individual level.
Hepatobiliary cystadenoma and cystadenocarcinoma are rare cystic lesions of the liver. The aim of the study was to discuss the clinical features, diagnostic methods and surgical treatment of hepatobiliary cystadenoma and cystadenocarcinoma in our hospital.
Coastal zone could be considered as an important sink of regional source to sink and preserve historical records of environmental evolution. Four sediment cores, collected from tidal flat at Haizhou Bay near Lianyungang City, were examined for concentrations of heavy metals including Cd, Cr, Cu, Mn, Pb and Zn in core sediments to investigate the historical input of trace metals. In addition, sediment rates of cores LH3 and LH4 were determined based on radionuclide 210Pb. The results showed that grain size control effect was not the main factor that influenced the distribution of heavy metals. Heavy metals concentrations in the surface sediments were higher than these regional background values. Furthermore, Al element as a proxy of grain size was selected for normalization and calculation of metal enrichment factor (EF) and anthropogenic heavy metal fluxes. The results revealed that heavy metals in tidal flats were continuously enriched in the past decades, meanwhile, tidal flats have been significantly subjected to contaminations due to anthropogenic activities. Moreover, the depth profiles of heavy metals fluxes correspond to scenario of social-economy development of Lianyungang, which is an important urban area near Haizhou Bay. From 1950s to 2005, anthropogenic fluxes of metals increased with fluctuations, whereas, since 2005 anthropogenic fluxes declined, which may be correlated to the adjustment of industrial structure as well as the strengthened environmental regulation.
Carbon nanotube (CNT) possesses excellent properties as a drug carrier. To overcome the challenge of drug functionalization with CNT, we have developed a lipid-drug approach for efficient drug loading onto CNT, in which a long chain lipid molecule is conjugated to the drug molecule so that the lipid-drug can be loaded directly onto CNT through binding of the lipid tail in the drug molecule to CNT surfaces via hydrophobic interactions. In a proof-of-concept study, drug paclitaxel (PTX) was conjugated with a non-toxic lipid molecule docosanol for functionalization with CNT. Folic acid was also conjugated to CNT for targeted drug delivery. High level of drug loading onto SWNT could be achieved by lipid-drug approach. Conjugation of FA to SWNT-lipid-PTX led to an increase in cell penetration capacity, and the targeted SWNT-lipid-PTX showed much improved drug efficacy in vitro in comparison to free drug Taxol and non-targeted SWNT-lipid-PTX at 48 h (78.5% vs. 31.6% and 59.1% in cytotoxicity respectively, p < 0.01). In vivo analysis using a human breast cancer xenograft mice model also confirmed the improved drug efficacy. The targeted SWNT-lipid-PTX was found non-toxic as evaluated by biochemical analysis using blood samples, and by histological analysis of major organs.
Genetic recombination contributes to the diversity of human immunodeficiency virus (HIV-1). Productive HIV-1 recombination is, however, dependent on both the number of HIV-1 genomes per infected cell and the genetic relationship between these viral genomes. A detailed analysis of the number of proviruses and their genetic relationship in infected cells isolated from peripheral blood and tissue compartments is therefore important for understanding HIV-1 recombination, genetic diversity and the dynamics of HIV-1 infection. To address these issues, we used a previously developed single-cell sequencing technique to quantify and genetically characterize individual HIV-1 DNA molecules from single cells in lymph node tissue and peripheral blood. Analysis of memory and naïve CD4(+) T cells from paired lymph node and peripheral blood samples from five untreated chronically infected patients revealed that the majority of these HIV-1-infected cells (>90%) contain only one copy of HIV-1 DNA, implying a limited potential for productive recombination in virus produced by these cells in these two compartments. Phylogenetic analysis revealed genetic similarity of HIV-1 DNA in memory and naïve CD4(+) T-cells from lymph node, peripheral blood and HIV-1 RNA from plasma, implying exchange of virus and/or infected cells between these compartments in untreated chronic infection.
A customized impression coping is often used in conjunction with conventional implant impression techniques to transfer a well-defined periimplant soft tissue profile resulting from an implant-supported interim restoration to the definitive cast with a removable gingival replica and achieve the desired esthetic outcome of the definitive restorations. However, a direct line of sight between the intraoral scanner and the periimplant soft tissue is needed during the data acquisition of the digital impression techniques, and it is not possible to use customized scannable impression copings to support periimplant soft tissue. This study describes a clinical technique with implant-supported interim restorations to transfer desired periimplant soft tissue profiles to the milled definitive polyurethane cast with a removable periimplant soft tissue replica to maximize the esthetic outcome of the definitive restorations.
HIV infection is characterized by rapid and error-prone viral replication resulting in genetically diverse virus populations. The rate of accumulation of diversity and the mechanisms involved are under intense study to provide useful information to understand immune evasion and the development of drug resistance. To characterize the development of viral diversity after infection, we carried out an in-depth analysis of single genome sequences of HIV pro-pol to assess diversity and divergence and to estimate replicating population sizes in a group of treatment-naive HIV-infected individuals sampled at single (n = 22) or multiple, longitudinal (n = 11) time points. Analysis of single genome sequences revealed nonlinear accumulation of sequence diversity during the course of infection. Diversity accumulated in recently infected individuals at rates 30-fold higher than in patients with chronic infection. Accumulation of synonymous changes accounted for most of the diversity during chronic infection. Accumulation of diversity resulted in population shifts, but the rates of change were low relative to estimated replication cycle times, consistent with relatively large population sizes. Analysis of changes in allele frequencies revealed effective population sizes that are substantially higher than previous estimates of approximately 1,000 infectious particles/infected individual. Taken together, these observations indicate that HIV populations are large, diverse, and slow to change in chronic infection and that the emergence of new mutations, including drug resistance mutations, is governed by both selection forces and drift.
Retropancreatic retroperitoneal tumors (RRTs) are seldom encountered in clinical practice. The lack of characteristics on clinical presentation and imaging make preoperative diagnosis difficult and surgical management remains a challenge. This retrospective report surveys the presenting diagnosis and surgical management of 38 patients with RRTs presenting at our center between August 1981 and May 2012. Six patients were misdiagnosed on the basis of computerized tomography and one each by magnetic resonance imaging and magnetic resonance cholangiopancreatography. Tumors were localized posterior to the pancreatic head and uncinate process (n = 18); posterior to the neck and body of the pancreas (n = 9); or posterior to the body and tail of the pancreas (n = 11). Thirty-three patients underwent surgical resections. Operative approaches were chosen on the basis of tumor size and localization. The tumors were mostly commonly originating from neurogenic tissue (n = 16). There were 25 benign neoplasms (65.8%), 10 malignant tumors (26.3%), and three undefined tumors. The morbidity of postsurgical complications was 21 per cent (eight of 38). The number of patients who underwent follow-up was 21, and the mean follow-up time was 35 months (range, 2 to 90 months). Three patients died during follow-up. The morbility of local recurrence was 10.5 per cent (four of 38). Definitive diagnosis of RRTs is made at laparotomy. Complete resection remains the fundamental objective of disease management. Different operative approaches should be used according to tumor localization and size.
The heavy metal inventory and the ecological risk of the tidal flat sediments in Haizhou Bay were investigated. Results show that the average concentrations of heavy metals in the surface sediments exceeded the environment background values of Jiangsu Province coastal soil, suggesting that the surface sediments were mainly polluted by heavy metals (Cd, Cr, Cu, Mn, Pb and Zn). In addition, the profiles of heavy metals fluxes can reflect the socio-economic development of Lianyungang City, and heavy metals inputs were attributed to anthropogenic activities. Cr, Cu, Pb and Zn were mainly present in the non-bioavailable residual form in surface sediments, whereas Cd and Mn were predominantly in the highly mobile acid soluble and reducible fractions. The ecological risk of the polluted sediments stemmed mainly from Cd and Pb. According to the Sediment quality guidelines (SQGs), however, the adverse biological effects caused by the heavy metals occasionally occurred in tidal flat.
This report describes the fabrication of customized abutments consisting of prefabricated 2-piece titanium abutments and customized anatomic lithium disilicate structures for cement-retained implant restorations in the esthetic zone. The heat-pressed lithium disilicate provides esthetic customized anatomic structures and crowns independently of the computer-aided design and computer-aided manufacturing process.
KYKZL-1, a newly synthesized compound with COX/5-LOX dual inhibition, was subjected to the anti-inflammatory activity test focusing on its modulation of inflammatory mediators as well as intracellular MAPK and NF-?B signaling pathways. In acute ear edema model, pretreatment with KYKZL-1 (p.o.) dose-dependently inhibited the xylene-induced ear edema in mice with a higher inhibition than diclofenac. In a three-day TPA-induced inflammation, KYKZL-1 also showed significant anti-inflammatory activity with inhibition ranging between 20% and 64%. In gastric lesion test, KYKZL-1 elicited markedly fewer stomach lesions with a low index of ulcer as compared to diclofenac in rats. In further studies, KYKZL-1 was found to significantly inhibit the production of NO, PGE2, LTB4 in LPS challenged RAW264.7, which is parallel to its attenuation of the expression of iNOS, COX-2, 5-LOX mRNAs or proteins and inhibition of phosphorylation of p38 and ERK MAPKs and activation of NF-?B. Taken together, our data indicate that KYKZL-1 comprises dual inhibition of COX and 5-LOX and exerts an obvious anti-inflammatory activity with an enhanced gastric safety profile via simultaneous inhibition of phosphorylation of p38 and ERK MAPKs and activation of NF-?B.
Gut-derived lipopolysaccharides (LPS) are critical to the development and progression of chronic low-grade inflammation and metabolic diseases. In this study, the effects of probiotics Lactobacillus and Bifidobacterium on gut-derived lipopolysaccharide and inflammatory cytokine concentrations were evaluated using a human colonic microbiota model. Lactobacillus reuteri, L. rhamnosus, L. plantarum, Bifidobacterium animalis, B. bifidum, B. longum, and B. longum subsp. infantis were identified from the literature for their anti-inflammatory potential. Each bacterial culture was administered daily to a human colonic microbiota model during 14 days. Colonic lipopolysaccharides, and Gram-positive and negative bacteria were quantified. RAW 264.7 macrophage cells were stimulated with supernatant from the human colonic microbiota model. Concentrations of TNF-alpha, IL-1beta, and IL-4 cytokines were measured. Lipopolysaccharide concentrations were significantly reduced with the administration of B. bifidum (-46.45 +/- 5.65%), L. rhamnosus (-30.40 +/- 5.08%), B. longum (-42.50 +/- 1.28%), and B. longum subsp. infantis (-68.85 +/- 5.32%) (p < 0.05). Cell counts of Gram-negative and positive bacteria were distinctly affected by the probiotic administered. There was a probiotic strain-specific effect on immunomodulatory responses of RAW 264.7 macrophage cells. B. longum subsp. infantis demonstrated higher capacities to reduce TNF-alpha concentrations (-69.41 +/- 2.78%; p < 0.05) and to increase IL-4 concentrations (+16.50 +/- 0.59%; p < 0.05). Colonic lipopolysaccharides were significantly correlated with TNF-alpha and IL-1beta concentrations (p < 0.05). These findings suggest that specific probiotic bacteria, such as B. longum subsp. infantis, might decrease colonic lipopolysaccharide concentrations, which might reduce the proinflammatory tone. This study has noteworthy applications in the field of biotherapeutics for the prevention and/or treatment of inflammatory and metabolic diseases.
This report described the fabrication of a customized anatomic abutment and zirconia restoration in the esthetic zone with a digital pathway. The implant level impression was made with a scannable impression coping and intraoral digital scanner. The milled definitive polyurethane cast with corresponding implant analog, customized anatomic abutment, and definitive zirconia restoration were made with a computer-aided design and computer-aided manufacturing (CAD/CAM) process.
Identification of recent HIV infection within populations is a public health priority for accurate estimation of HIV incidence rates and transmitted drug resistance at population level. Determining HIV incidence rates by prospective follow-up of HIV-uninfected individuals is challenging and serological assays have important limitations. HIV diversity within an infected host increases with duration of infection. We explore a simple bioinformatics approach to assess viral diversity by determining the percentage of ambiguous base calls in sequences derived from standard genotyping of HIV-1 protease and reverse transcriptase. Sequences from 691 recently infected (?1 year) and chronically infected (>1 year) individuals from Sweden, Vietnam and Ethiopia were analyzed for ambiguity. A significant difference (p<0.0001) in the proportion of ambiguous bases was observed between sequences from individuals with recent and chronic infection in both HIV-1 subtype B and non-B infection, consistent with previous studies. In our analysis, a cutoff of <0.47% ambiguous base calls identified recent infection with a sensitivity and specificity of 88.8% and 74.6% respectively. 1,728 protease and reverse transcriptase sequences from 36 surveys of transmitted HIV drug resistance performed following World Health Organization guidance were analyzed for ambiguity. The 0.47% ambiguity cutoff was applied and survey sequences were classified as likely derived from recently or chronically infected individuals. 71% of patients were classified as likely to have been infected within one year of genotyping but results varied considerably amongst surveys. This bioinformatics approach may provide supporting population-level information to identify recent infection but its application is limited by infection with more than one viral variant, decreasing viral diversity in advanced disease and technical aspects of population based sequencing. Standardization of sequencing techniques and base calling and the addition of other parameters such as CD4 cell count may address some of the technical limitations and increase the usefulness of the approach.
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